Iap Speciality Series on Pediatric Cardiology [2 ed.] 9789350903643, 9350903644

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IAP SPECIALTY SERIES ON Pediatric Cardiology

IAP SPECIALTY SERIES ON Pediatric Cardiology Second Edition Founder Editor Dr Nitin K Shah Editors Dr R Krishna Kumar

Chief Pediatric Cardiologist Amrita Institute of Medical Sciences and Research Center Cochin, Kerala, India

Dr Shakuntala S Prabhu

Dr M Zulfikar Ahamed

Professor and Head Department of Pediatrics Chief, Division of Pediatric Cardiology Bai Jerbai Wadia Hospital for Children Mumbai, Maharashtra, India

Professor of Pediatric Cardiology Department of Pediatrics Medical College Thiruvananthapuram, Kerala, India

Co-ordinating Editor Dr Sailesh Gupta Honorary Secretary General Indian Academy of Pediatrics Kailash Darshan, Kennedy Bridge Mumbai, Maharashtra, India



Dr CP Bansal



IAP President 2013

Foreword

Dr Rohit Agrawal IAP President 2012

IAP National Publication House, Gwalior ®

Jaypee Brothers Medical Publishers (P) Ltd New Delhi • London • Philadelphia • Panama

®

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Pediatric Cardiology First Edition: 2008 Second Edition: 2013 ISBN 978-93-5090-364-3 Printed at

Dedicated to Our Teachers who shaped our life and destiny 1. Professor R Tandon, a role model beyond compare; as a clinician, as a teacher, as an academician and as a human being. 2. Dr NC Joshi, A Senior Pediatrician with special interest in Pediatric Cardiology, a master teacher and an astute clinician. 3. Dr MS Valiathan, Cardiac Surgeon by rank, master builder by vocation and mentor by choice. 4. The support of our families and our parents whose faith in us made us what we are today.

Contributors

Abhay Divekar

Harinder Singh

Clinical Associate Professor University of Iowa Children’s Hospital Lowa City, United Satate of America

Division of Cardiology The Carman and Ann Adams Department of Pediatrics Children’s Hospital of Michigan Michigan, United State of America

Abhijit Raut Consultant in Radiology Seven Hills Hospital Mumbai, Maharashtra, India

Alpana Ohri Assistant Professor BJ Wadia Hospital for Children Mumbai, Maharashtra, India

Amar Taksande Lecturer of Pediatrics Mahatma Gandhi Institute of Medical Sciences Wardha, Maharashtra, India

Anita Saxena Professor of Cardiology All India Institute of Medical Sciences New Delhi, India

Bharat Dalvi Consultant Cardiologist Glenmark Cardiac Center Mumbai, Maharashtra, India

Hemant B Telkar Director Infinity Medical Center Mumbai, Maharashtra, India

Krishna S Iyer Executive Director Pediatric and Congenital Heart Surgery Fortis-Escorts Heart Institute New Delhi, India

Mahesh K Assistant Professor of Pediatric Cardoiology Amrita Institute of Medical Sciences and Research Center Cochin, Kerala, India

M Zulfikar Ahamed Professor of Pediatric Cardiology Department of Pediatrics Medical College Thiruvananthapuram, Kerala, India

NC Joshi

Consutant Jankharia Imaging Center Mumbai, Maharashtra, India

Ex Dean and Professor Emeritus BJ Wadia Hospital for Children Consultant Pediatrician and Neonatologist Dr Balabhai Nanavati Hospital Mumbai, Maharashtra, India

BRJ Kannan

Nitin Rao

Bhavin Jankharia

Assistant Professor of Pediatric Cardiology Amrita Institute of Medical Sciences and Research Center Kochi, Kerala, India

Consultant Cardiologist Child Care Hospital Hyderabad, Andhra Pradesh, India

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Pediatric Cardiology

Pooja Hingorani

Sona A Pungavkar

Quintiles Cardiac Safety Services Mumbai, Maharashtra, India

Consultant MRI Center Dr Balabhai Nanavati Hospital Mumbai, Maharashtra, India

Rakhi B Assistant Professor in Anesthesia Amrita Institute of Medical Sciences and Research Center Cochin, Kerala, India

Richard A Humes Chief of Division of Pediatric Cardiology and Professor of Pediatrics Children’s Hospital of Michigan Michigan, United State of America

R Krishna Kumar Chief Pediatric Cardiologist Amrita Institute of Medical Sciences and Research Center Cochin, Kerala, India

Sankar VH Additional Professor and Consultant Geneticist Department of Pediatrics SAT Hospital Thiruvananthapuram, Kerala, India

Savitri Shrivastava Director Pediatric and Congenital Heart Disease Fortis Escorts Heart Institute New Delhi, India

Shakuntala S Prabhu Head, Department of Pediatrics Chief, Division of Pediatric Cardiology Bai Jerbai Wadia Hospital for Children  Mumbai, Maharashtra, India

Shantanu Deshpande Consultant Cardiologist Quintiles Cardiac Safety Services Mumbai, Maharashtra, India

Sheetal Deshmukh Quintiles Cardiac Safety Services Mumbai, Maharashtra, India

Shreepal Jain Consultant Pediatric Cardiologist Glenmark Cardiac Center Mumbai, Maharashtra, India

Sreekanthan Sundararaghavan American Board Certified in Pediatrics and Pediatric Cardiology Consultant Pediatric Cardiologist Apollo Children’s Heart Hospital Hyderabad, Andhra Pradesh, India

S Sivasankaran Professor Sree Chitra Tirunal Institute of Medical Sciences and Technology Thiruvananthapuram, Kerala, India

Sumitra Venkatesh Assistant Professor Department of Pediatrics and Pediatric Cardiology BJ Wadia Children’s Hospital Mumbai, Maharashtra, India

Suresh G Nair Professor and Head Department of Anesthesia Amrita Institute of Medical Sciences and Research Center Cochin, Kerala, India

S Vijay Junior Consultant Pediatric and Congenital Heart Surgery Fortis-Escorts Heart Institute New Delhi, India

Swati Garekar Consultant Pediatric Cardiologist Kokilaben Dhirubhai Ambani Hospital  Mumbai, Maharashtra, India

Uma Shankar Ali Ex-Dean and Chief of Nephrology Division and PICU BJ Wadia Hospital for Children Consultant Pediatrician Lilavati Hospital and Research Center Mumbai, Maharashtra, India

Usha S Krishnan

Assistant Professor of Pediatric Cardiology Medical College Thiruvananthapuram, Kerala, India

Dip American Board of Pediatrics and Pediatric Cardiology Assistant Professor Department of Pediatrics and Pediatric Cardiology New York Medical College New York, United State of America

Snehal Kulkarni

Yash Lokhandwala

S Lakshmi

Pediatric Cardiologist, Consultant Pediatric Cardiologist Kokilaben Dhirubhai Ambani Hospital  Mumbai, Maharashtra, India

Consultant Cardiologist and Arrhythmia Specialist Arrhythmia Associates Mumbai, Maharashtra, India

Foreword

Dear Reader, The book that you hold is the fulfilment of the dreams of the doyens of Indian Academy of Pediatrics (IAP). For many years, the need for good Indian books in every specialty of pediatrics was felt. The Indian Academy of Pediatrics has no dearth of great teachers and writers in the various subspecialties to author these books. Their dedicated and diligent labor has created the beautiful and eminently readable book that you hold. An Indian book by Indian authors will appropriately suit the needs of the readers in India and in countries with similar geographical and sociocultural milieus. Although the first editions of the IAP subspecialty series were published in 2006, we proudly present to you a second, completely revised and updated edition. The IAP specialty series books serve the purpose of providing evidence based, authentic and uniform information to IAP members, other pediatricians, and students of pediatrics in the country. Guidelines and established protocols on disease management will be very helpful for pediatricians in their everyday practice. Creating a book is such as the birth of a baby. Right from conception to delivery, there is a long and complex process. It is very labor intensive and time- consuming work that involves considerable financial expense too. To streamline the entire process from writing to editing to publishing to distribution and sales of books, it was envisioned to have an additional wing of IAP, and which is established as “IAP National Publication House (IAP NPH)” at Gwalior. Knowledge has no limits and seekers of knowledge can access the subject from anywhere in the world. We understand that books published by IAP NPH will be read and referred not only in India but also in many parts of the world. Objective of IAP NPH, therefore, is to provide standardized content and world class quality. With this objective, printed books are to be made available throughout the globe and distribution will also be done through online editions. Publishing 7 books at a time is a mammoth task and for this we collaborated with the second largest medical publisher in the world, i.e. M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India.

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What you are reading, the world is also reading. Our writers are getting worldwide exposure and readers are getting world class books at reasonable cost. It needs to be mentioned here that all authors and editors have dedicated the royalty from sale of books to IAP and have thereby done a selfless service for our mother organization. By buying this book, you are also contributing to IAP in a significant manner. Finally, we express our pride and happiness in being associated with this project and in reaching this valuable book to you. We wish you a happy and contented reading.

CP Bansal IAP President 2013

Rohit Agrawal IAP President 2012

Preface to the Second Edition

The rapid pace of progress in medicine is a motivation to update knowledge, gather new information and continue the process of learning. We the editors acknowledge the difficulty in competing with large books composed by many expert authors. The format of this book has not changed and remains clinically focused. The purpose of this new second edition is to incorporate the latest scientific advances. More than 90% of physicians taking care of children with cardiac disorders are not cardiologists and hence must have the knowhow of interpreting and arriving at a clinical diagnosis and a fair knowledge of pharmacologic, interventional and surgical therapy. They obviously do not require much information on invasive and noninvasive cardiac testing, neither of which they are called on to perform. This makes the task of extracting essential and vital information from available large volume textbooks difficult and also impractical for the busy clinician. This book is aimed to cover important aspects of clinical pediatric cardiology as seen in office practice and sufficient enough to equip the primary care physicians and postgraduates to approach various cardiac disorders systematically. A number of experts in the field of pediatric cardiology have contributed to this book and we would like to thank all of them for their valuable time and effort in preparing these chapters. We thank the Indian Academy of Pediatrics for the opportunity to edit this important book and we welcome the feedback from our readers to help us improve the quality of the subsequent editions.

R Krishna Kumar Shakuntala S Prabhu M Zulfikar Ahamed

Preface to the First Edition

Impressive advances have occurred in Pediatric Cardiac Care in India over the last decade. Several new programs have been established and the quality of care has progressively improved. Infant heart surgery is now becoming increasingly available in many Indian centers. Pediatric cardiology is now recognized as a distinct subspecialty and dedicated fellowship training programs have been initiated in selected centers in India. However, several challenges continue to exist. The number of centers is not enough to take care of the number of affected children and cost of care continues to be prohibitive for the average Indian family. Large parts of India still do not have access to pediatric heart care because there are no centers even in many larger states. Most postgraduate training programs in India are in centers which do not offer specialized pediatric cardiac services. As a result the average Indian pediatric postgraduate trainee receives very little systematic exposure in pediatric cardiology. While it is absolutely clear that early recognition and timely intervention is the key to successful outcome of children with heart disease, the average pediatrician in India has limited opportunities to improve his/her understanding in diagnosis of pediatric heart disease. This book attempts to bridge this gap and aims to provide basic information required for a practising pediatrician and a postgraduate student in pediatrics. The entire text throws light on clinical approach and seeks to examine relatively common problems encountered by practising pediatricians. The text begins with the diagnostic tools required to identify heart disease and the chapters include clinical examination, X-ray, ECG, echocardiography and diagnostic catheterization. Common clinical problems such as chest pain, syncope and arrhythmias are dealt with in the next set of chapters. Congenital heart diseases are described under conventional categories. Specific congenital heart conditions are not dealt with in great detail and readers will need to refer to comprehensive textbooks for details on individual conditions. Acquired conditions such as rheumatic fever, Kawasaki disease, myocardial and pericardial diseases and endocarditis are all described in separate chapters. The final set of chapters includes a variety of special issues relating to pediatric heart care. A chapter on Follow-up of Children Following Cardiac Surgery and Percutaneous Interventions is specifically included.

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We thank all contributors who made this book possible and the Indian Academy of Pediatrics for giving us the opportunity to write this textbook. We also wish to specially acknowledge the editorial assistance of Dr Sumitra Venkatesh and Dr BRJ Kannan. Given the fact that this is the first edition, we recognize that there will be considerable scope for improvement. We sincerely solicit feedback from our readers. We would use them to improve the quality of next edition.

R Krishna Kumar Shakuntala S Prabhu M Zulfikar Ahamed

Acknowledgments

Dr R Krishna Kumar’s contributions was supported in part by funding from Children’s Heartlink, Minneapolis, Minnesota (www.childrensheartlink.org). We are thankful to Shri Jitendar P Vij (Group Chairman), Mr Ankit Vij (Managing Director) and Mr Tarun Duneja (Director-Publishing) of M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India in helping us to bring out this edition on time.

Contents

1. Clinical Assessment of a Child with Heart Disease

Shakuntala S Prabhu, Sumitra Venkatesh



Gestational and natal history  1;  Maternal conditions  2;   Birth history and weight 2;  Family history 2;  Postnatal history 3;  Physical examination 6; Cardiovascular assessment  8;  Precordial examination  12

2. X-ray Chest for Evaluation of Pediatric Heart Diseases

Savitri Shrivastava



X-ray chest in left-to-right (L to R) shunts  30;  Obstructive lesions  31; Cyanotic heart disease  33

3. The ECG: A Practical Approach to the Pediatric Electrocardiogram

BRJ Kannan



Basics of recording and interpretation  40

4. Imaging in Pediatric Cardiology

1

26

40

54

A. Echocardiography

BRJ Kannan, R Krishna Kumar



Basics of echocardiography  54

B. Role of CT, MRI and Radionuclide Scans in Pediatric Cardiopulmonary Disease

Hemant Telkar, Bhavin Jhankharia, Abhijit Raut, Sona Pungavkar



Role of 64 slice MDCT  63;  MRI in congenital heart disease  66;  Role of cardiac MR in fetal cardiology  71;  Radionuclide imaging in pediatric cardiology 73



5. Diagnostic Cardiac Catheterizations in Children Snehal Kulkarni



75

Precatheterization assessment  77;  Premedication and sedation  77; Transport of neonate or sick infant to the catheterization laboratory  80; Imaging  80;  Specific cardiovascular diseases and cardiac catheterization and angiography  80;  Complications of cardiac catheterization  83

6. Heart Failure in Children

Sreekanthan Sundararaghavan, R Krishna Kumar



Management of CHF  91

86

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7. Systemic Hypertension in Children

Uma S Ali, Alpana Ohri



Measurement of blood pressure  96;  Causes  97;  Investigations  100

8. Pulmonary Hypertension in Children

Usha Krishnan



Definition and classification  109;  Persistent pulmonary hypertension of the newborn  110;  Childhood pulmonary hypertension  111;  Pathobiology of pulmonary hypertension  111;  Diagnosis and investigations  112;  Treatment  114

9. Syncope in the Young

S Deshmukh, P Hingorani, S Deshpande, Y Lokhandwala



Definition  119;  Epidemiology  119;  Evaluation of a patient with syncope  124; Management of syncope  127;  Prevention of syncope on long-term basis  128

10. Chest Pain in Childhood

M Zulfikar Ahamed, S Lakshmi



Causes of chest pain  133;  Specific types of chest pain  135;  Laboratory Evaluation (Investigations)  136;  Management  140

11. Arrhythmias in Children

BRJ Kannan, R Krishna Kumar



Classification of arrhythmias  142;  Presentation of cardiac arrhythmias  144;  Diagnosis and management of tachyarrhythmias  146

12. Congenital Heart Disease Introduction, Epidemiology and Classification

Nitin Rao



Congenital heart disease prevalence—the Indian scenario  155;  Epidemiology  157 Maternal factors  158;  Classification of CHD  162;  A clinical classification of congenital heart disease general  163;  Cyanotic  164

13. Left-to-Right Shunts

R Krishna Kumar, Abhay Divekar



Definition of terms  168;  Perinatal changes in vascular resistances influencing; Left-to-right shunting  171;  Factors determining magnitude of left-to-right shunts 171;  Pathophysiology 172;  Hemodynamics 173;  Clinical features 173; The untreated large left-to-right shunt lesions  175;  Management of patients with left to right shunts  175

14. Cyanotic Congenital Heart Disease

Swati Garekar, Richard A Humes



Total anomalous pulmonary venous return  181;  Tricuspid atresia  183;  Ebstein’s anomaly  185;  Tetralogy of Fallot  187;  Tetralogy of Fallot with pulmonary atresia  189;  Pulmonary atresia with intact ventricular septum  192;  Double-outlet right ventricle  194;  Hypoplastic left heart syndrome  195; Transposition of the great arteries  197;  L-transposition of the great vessels  199; Truncus arteriosus  200;  Univentricular atrioventricular connection  202



15. Obstructive Acyanotic Congenital Heart Diseases

Snehal Kulkarni



Left sided obstructions  205;  Right sided obstructions  215

16. Miscellaneous Congenital Cardiac Conditions

Amar Taskande



Aortopulmonary septal defect  221;  Aneurysm of the sinus of valsalva  222; Arteriovenous fistula, coronary  222;  Arteriovenous fistula, pulmonary  223;

95

109

119

133

142

153

168

180

205

221

Contents

xix

Arteriovenous fistulas, systemic  223;  Anomalous origin of the left coronary artery from the pulmonary artery  224;  Congenital pericardial defect  224; Cervical aortic arch  225;  Cor triatriatum  225;  Congenital mitral stenosis  226;  Congenital mitral insufficiency  226;  Common atrium  227;  Congenital anomalies of vena caval connection  227;  Double-chambered right ventricle  228;  Diverticulum of the left ventricle  229;  Ectopia cordis  229;  Hemitruncus arteriosus  229;  Idiopathic dilatation of the pulmonary artery  230;  Kartagener’s syndrome  230;  Pulmonary artery stenosis  230;  Patent foramen ovale  231;  Pseudocoarctation of the aorta  231;  Rubella syndrome  231;  Scimitar syndrome  232;  Taussig-bing anomaly  232

17. Timing of Surgical or Catheter Intervention in Congenital Heart Disease

R Krishna Kumar



Predicting the natural history of congenital heart disease  235; Spontaneous closure of defects  238;  Procedural outcome  239;  Guidelines for individual lesions  240

18. Rheumatic Fever and Rheumatic Heart Diseases in Children

M Zulfikar Ahamed, NC Joshi



Historical perspective  245;  Epidemiology  246;  Carditis  251;  Chorea  254 Investigations 256;  Dilemma in evaluation 264;  Treatment 265; Prophylaxis  269;  Anaphylaxis  269;  Chronic rheumatic valvular disease  271; Mitral regurgitation  271;  Mitral stenosis  273;  Correlation between valve area and mean MV gradient  275;  Rationale of drug therapy  276;  Aortic stenosis 277;  Aortic regurgitation 280

19. Myocardial Disease

R Krishna Kumar



Dilated cardiomyopathy  287;  Diagnostic approach for dilated cardiomyopathy in children  289;  Treatment  296

20. Pericardial Disease

Harinder R Singh



Anatomy and physiology  303

235

245

287

303

21. Infective Endocarditis in Children

317

22. Kawasaki Disease: Diagnosis and Management

328



Anita Saxena



M Zulfikar Ahamed



Historial perspective: a brief history of Kawasaki disease  328;  Epidemiology  328; Etiopathogenesis  330;  Laboratory evaluation  334;  Terminologies in KD 337; Other investigations  338;  Standard protocol followed in our institution  340; Kawasaki disease—other modalities of therapy  341;  Long-term management  343

23. Cardiac Manifestations in Systemic Illness

Sumitra Venkatesh, Shakuntala S Prabhu, Mahesh K



Storage disorders  346;  Collagen vascular diseases (connective tissue diseases, rheumatic diseases)  350;  Endocrine and metabolic conditions  355; Hematological conditions  358;  Neuromuscular diseases  359;  Disorders of collagen synthesis  361

24. Fetal Cardiology

Shakuntala Prabhu, Sumitra Venkatesh



Fetal echocardiography  365;  Importance of fetal echocardiography  365; Optimal timing of screening  366;  Intrauterine interventions  374

346

365

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25. Diagnosis and Initial Management of Heart Disease in the Newborn

R Krishna Kumar



Diagnosis of heart disease in the newborn  376;  Circulatory support and inotropes  383; Transportation of sick newborn infants with heart disease  384

26. Cardiac Implications of Changing Lifestyle: Prevention of Adult Cardiovascular Disease

S Sivasankaran



Magnitude and definition of the problem  390

27. Genetics of Congenital Heart Disease

Sankar VH



Importance of identifying the genetic basis of CHD 402;  Chromosomal disorders  403;  Microdeletion syndrome and fish  404;  Single gene disorders  406 Evaluation for genetic basis in children with CHD  408;  Genetic counseling in genetic syndromes with CHD 409



28. Catheter-based Interventions in Children

Shreepal Jain and Bharat Dalvi



Atrial septostomy procedures  413;  Balloon valve dilatations  414;  Transcatheter closure of intracardiac shunts 422;  Cardiac interventions in complex congenital heart disease  426;  Intravascular stents in congenital heart disease  427

29. Surgery for Common Congenital Cardiac Defects

Krishna S Iyer, S Vijay



General aspects of cardiovascular surgery  434

30. Pediatric Cardiac Postoperative Intensive Care

Rakhi B, Suresh G Nair, R Krishna Kumar



Specific aspects of cardiac surgery that impact patient care  451;  Mechanical ventilation  456;  Sedation, paralysis and pain management  458;  Fluid and electrolyte management  460;  Nutrition  463;  Management issues associated with specific surgeries  465;  Corrective procedures  468;  Common postoperative problems after pediatric cardiac surgery  476;  End organ injury  486

31. Follow-up of Children Following Cardiac Surgery and Percutaneous Interventions

BRJ Kannan



Patent ductus arteriosus (PDA) interruption (surgical or transcatheter intervention)  502;  Atrial septal defect  502;  Valvar pulmonary stenosis  503; Valvar aortic stenosis 504;  Coarctation of aorta  504;  Blalock-taussig shunt (systemic artery to pulmonary artery)  505;  Tetralogy of Fallot  505;  D-transposition of great arteries  506;  Operations requiring the use of conduits  507;  Pulmonary artery banding  507;  Bidirectional Glenn shunt  507;  Fontan procedure  508;  Children on oral anticoagulation  508

32. Drug Dosages

Shakuntala Prabhu

376

388

402

413

433

451

501

510

Index 531

1

Clinical Assessment of a Child with Heart Disease

Shakuntala Prabhu, Sumitra Venkatesh

“Listen to what patients are saying Because they are telling you the diagnosis”

The history, physical examination, electrocardiogram and chest radiography are the keystones for the diagnosis of cardiac problems in children. With each technique, different aspects of the cardiovascular system are viewed, and by combining the data derived, a fairly accurate assessment of the patient’s condition can be obtained.1 More sophisticated techniques, such as echocardiography and cardiac catheterization, permit detailed patient evaluation. Symptoms of congenital cardiac disease are protean, sometimes subtle and may manifest anytime from fetal period to adulthood (Table 1.1). Many aspects of the history are age specific and therefore, historical information should be obtained from both parents and the child.

GESTATIONAL AND NATAL HISTORY Exposure to possible teratogens may provide important etiological clues (Table 1.2). Increasingly, infants are being born having a fetal cardiac scan and one must always enquire into the indication with special emphasis given to an abnormal scan. Complications such as toxemia, birth asphyxia, fetal distress, and low

Table 1.1: Presentation of cardiac problems Fetus (diagnosis by fetal echocardiography) Abnormal ultrasound screening Hydrops fetalis Arrhythmias Cardiomegaly Parent or previous sibling with congenital heart defect Neonate and Infant Heart failure (tachypnea, feeding difficulty) Cyanosis Circulatory failure, or collapse Abnormal heart rate/rhythm Prominent precordial pulsations Murmur Weak femoral pulses Dysmorphism (trisomy 21, 18 and 13, catch 22, other chromosomal and single gene disorders) Noncardiac congenital abnormalities Failure to gain weight Older child Murmur Heart failure Fatigue on effort Multisystem disease (e.g. rheumatic fever, Kawasaki’s disease) Chest pain Palpitations Fainting (syncope and presyncope) Syndromes (Turner’s, Marfan’s, and Noonan’s) Hypertension Family history

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Pediatric Cardiology Table 1.2: Known teratogens for congenital heart disease

Teratogens Most frequent cardiac malformation Phenytoin Septal defects and/or transposition Carbamazepine ASD/PDA Trimethadione Transposition/TOF Sodium valproate TOF/VSD Lithium Ebstein’s anomaly Warfarin Various septal defects Antimalignancy TOF, Dextrocardia Viruses (especially rubella) PDA, peripheral pulmonary stenosis Alcohol Septal defects and/or transposition of great vessels (Abbreviations: ASD, Artial septal defect; PDA, Patent ductus arteriosus; TOF, Tetralogy of fallot; VSD, Ventricular septal defect)

birth weight may result in perinatal insult to the myocardium and persistent pulmonary hypertension. Clinical differentiation from CHD may be difficult and usually requires an echocardiographic evaluation.2

MATERNAL CONDITIONS There is a high incidence of reversible ventricular hypertrophy in infants born to diabetic mothers. Additionally, these babies have structural heart diseases such as transposition (TGA), ventricular septal defect (VSD) and patent ductus arteriosus (PDA). Systemic lupus erythematosus (SLE) and mixed connective tissue disorders in the mother increase the risk of congenital complete heart block. However, most mothers of infants born with congenital complete heart block have no symptoms of SLE. A history of frequent abortions in previous pregnancies may be obtained. Maternal history of congenital heart disease increases the incidence of CHD in offspring from 1 to 15%.

BIRTH HISTORY AND WEIGHT Prematurity is a clue more to presence of noncardiac especially respiratory disease, but may point to cardiac disease (PDA). Prematurity influences the rate of regression of pulmonary vasculature and premature infants with left-to-right shunts tend to present with heart failure at a relatively younger age. Birth weight can alert to a syndrome, for example, in congenital rubella the child is small for gestational age and in maternal diabetes the child is large for gestational age. Birth asphyxia is associated with both persistent pulmonary hypertension and myocardial dysfunction.

FAMILY HISTORY A family history of sudden death and a structural or functional cardiac abnormality in a first degree relative may have diagnostic relevance. Family history is also important to prognosticate recurrence risks and also that many inherited or genetically determined conditions have cardiac components, e.g. Noonan’s syndrome, Familial long QT-interval or Duchenne’s dystrophy. In hypertrophic cardiomyopathy, there is evidence of more than 20% higher incidence

Clinical Assessment of a Child with Heart Disease

3

of inheritance in first degree relatives, thus, meriting consideration of an echocardiographic screening of relatives. The family history should identify the presence of early myocardial infarction and hypercholesterolemia that may prompt cholesterol screening.

POSTNATAL HISTORY The time at which signs and symptoms of heart disease begin may indicate the type of cardiac lesion. Most newborns are asymptomatic at birth and as perinatal changes are completed, symptoms specific to physiology of the defect becomes evident, e.g. ductal dependent left or right sided obstructive lesions present in the first week of life as the ductus arteriosus closes. In the former group of lesions this results in decrease in cardiac output and signs of shock children. Commonly, murmurs detected in the neonatal period are because of atrioventricular valve (AV) regurgitation. The significant left-to-right shunts present around 4 weeks of age, when pulmonary vascular resistance decreases and heart failure ensues. The three most common postnatal presentations are cyanosis, respiratory difficulty and murmur.

Cyanosis, “Cyanotic Spells” and Squatting Cyanosis is a bluish or purplish color of the skin, lips or mucous membrane caused by the presence of at least 5 g/dL of reduced hemoglobin. Central cyanosis must be distinguished from peripheral or acrocyanosis; the latter is usually confined to nail beds and perioral skin and occurs when the child is exposed to hypothermia. A distinctive feature of central cyanosis is that it worsens with activity and increasing cardiac output while acrocyanosis often improves. Cyanosis in association with cardiac murmur strongly suggests a structural heart lesion. Children in shock may also appear cyanosed because of venous stasis. Episodic central cyanosis may be a sign of cardiac disease as in hypercyanotic spell or of respiratory or neurological disorders such as asthma, apnea and fits. The true hypercyanotic spells are seen in infants with TOF and require immediate attention. The precipitating factors, duration of spell and its frequency should be enquired into. In a true spell, the child would be breathing fast as compared to a child with breath holding spell that would be apneic. A typical spell is characterized by a sudden increase in intensity of the cyanosis, at times associated with loss of consciousness. Special enquiry must be made as to whether the child squats when tired or has a favorite position of comfort (knee-chest) when tired. In this position, the systemic arterial resistance rises, the right-to-left shunt decreases and patient becomes less desaturated.3

Tachypnea, Dyspnea The infant’s breathing patterns should be documented which may be: (1) tachypnea with abnormally rapid respirations. This is often seen in cyanotic heart disease with low cardiac output and usually associated with a compensatory rapid respiratory rate, particularly on exertion, because of diminished peripheral oxygenation or (2) grunting and dyspnea with difficult breathing. Dyspnea or labored breathing is also often present in patients with pulmonary congestion from either left sided cardiac failure; conditions raising the pulmonary venous pressure or from marked hypoxia. Increased pulmonary venous pressure causes

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Pediatric Cardiology

increased stiffness of the pulmonary vessels and transudation of fluid into the interstitial tissue, making the lungs less compliant. The child works harder to breathe. Wet, stiff lungs encourage secondary infection; respirations become rapid, the accessory muscles come into use, and subcostal indrawing is observed. Older children complain of shortness of breath. Occasionally, wheezing or cough could suggest CHF. Tachypnea also leads to poor feeding and weight gain. A sleeping respiratory rate more than 40/min in children and 60/min in neonates is significant.

Frequent Respiratory Infections Congenital heart with large left-to-right shunts and increased pulmonary blood flow predispose to frequent lower respiratory tract infections (LRTIs). Compression of the airways by plethoric vessels may contribute to stasis and atelectasis and predispose children to LRTIs.

Weight Gain, Development and Feeding Pattern In young infants, metabolic demands are usually greatest during feeds. The infant with poor peripheral oxygenation because of low cardiac output will tire easily during feeds, the equivalent of exercise in older children. As a result of fatigue, the infant is unable to take a full feed. In addition, rapid respiration diminishes the time available for swallowing. This combination of factors results in failure to gain weight. In the baby with a large left-to-right shunt, the process is exaggerated by the increased caloric needs of an overworked myocardium. Increased sympathetic activity causes excessive perspiration—often a valuable diagnostic feature. Any baby with this clinical presentation of suck-rest-suck cycle has congestive heart failure until proved otherwise. When a young baby tires rapidly, sweats during feedings, and has subcostal indrawing, always think of the possibility of left sided cardiac failure.4

Exercise Intolerance Decreased exercise intolerance is usually seen in large left-to-right shunt lesions, cyanotic defects, valvular stenosis or regurgitation and arrhythmias. Enquiries regarding exercise intolerance should be age relevant and in very small infants should include feeding patterns, easy fatigability or resting after minimal feeding may give a clue to CHF. In older infants history must include the ability to climb stairs or walk for extended periods. In older children, a comparison with peer sporting interactions, level of function in physical education, and index of aerobic ability should be sought.

Puffy Eyelids and Peripheral Edema Puffy eyelids and sacral edema are signs of systemic venous congestion. Ankle edema is not usually found in infants. Pretibial and presacral edema are late developments in the child’s congestive circulatory failure picture, apparently because of difference in tissue turgor. When peripheral edema because of heart failure does develop in an infant, it first appears periorbitally, usually preceded by other manifestations such as tachypnea, tachycardia, dyspnea, and liver enlargement and suggests right heart failure.

Clinical Assessment of a Child with Heart Disease

5

Heart Murmur An enquiry into the timing of discovery of heart murmur may be relevant. Aortic stenosis, pulmonary valvular stenosis, small VSDs, PDAs and atrioventricular regurgitation manifest with murmur a few hours to a few days after birth. Many instances of tetralogy of Fallot (TOF) are often identified soon after birth because of a systolic murmur. These infants are often initially pink and cyanosis appears later as the pulmonary stenosis worsens. The murmur of large left-to-right shunts usually presents beyond 4 weeks with regression of pulmonary pressures. A febrile illness usually unmasks a heart murmur.5,6

Chest Pain Chest pain is a benign symptom in older children and adolescents. Chest pain rarely occurs with cardiovascular disease and the common noncardiac causes are musculoskeletal, gastroesophageal reflux, anxiety and respiratory causes (asthma, pleuritis, bronchitis, pneumonia). Cardiac conditions that may cause chest pain include severe aortic and pulmonary stenosis, pulmonary vascular obstructive diseases, mitral valve prolapse, pericarditis, myocarditis and Kawasaki’s disease. Chest pain may also be experienced with very rapid paroxysmal tachycardias and has been recognized in infants with an aberrant left coronary artery (ALCAPA). 7

Palpitations Palpitations is the subjective feeling of rapid or forceful heartbeats or irregular heartbeats and is common in school aged child and adolescents. Palpitations usually occur concurrently with chest pain. In children with MVP, palpitations may be the presenting symptom. Neurologic Symptoms Syncope: Transient loss of consciousness and muscle tone that result from inadequate cerebral perfusion. Dizziness is the most common prodromal symptom of syncope. These complaints could represent a serious cardiac condition that may result in sudden death because of lifethreatening arrhythmias or conditions such as MVP, hypertrophic cardiomyopathy or severe aortic stenosis. Syncope could be because of noncardiac causes (such as benign vasovagal syncope), neuropsychiatric conditions, and metabolic disorders. Left ventricular outflow tract obstruction (e.g. aortic stenosis or hypertrophic cardiomyopathy) commonly causes effort syncope, whereas syncopal episodes because of dysrhythmias can occur either at rest or during activity. A history of stroke suggests embolization or thrombosis, secondary to cyanotic CHD with polycythemia or infective endocarditis. A history of headache may be a manifestation of cerebral hypoxia with cyanotic heart disease, severe polycythemia, or brain abscess. Hypertension with or without coarctation rarely causes headache in children.8 Medications Physicians should note the timing, dosage, compliance and duration of cardiac and noncardiac medications. Tachycardia may be produced by aminophylline, antihistamines and related drugs.

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Joint Joint pains, swelling may be seen in children with rheumatic fever, systemic diseases, infective endocarditis and children with Eisenmenger’s syndrome. Disease Impact History of disease impact on child especially growth and development, schooling, sports, sibling and family is also important. Previous Evaluations and Records It is important to ascertain whether the patient was evaluated previously for suspected heart disease. Previous records may provide important insights into the natural history of the underlying condition. For example, a subpulmonic VSD may progress to have aortic valve prolapse and aortic regurgitation at a later age. Age at presentation of clinical signs gives a clue to underlying CHD.9 1. If congestive cardiac failure develops solely because of CHD then symptoms usually arise before 3 months. Heart failure is rarely present at birth as the fetal circulation is in parallel and there are communications between the two sides. When there is obstruction on one side, blood flows easily to the other. As the fetal lungs are collapsed, increased pulmonary blood flow does not occur in utero. 2. Heart failure that develops during the first week of life, especially in the first 3 days, is usually because of an obstructive lesion or to persistent pulmonary hypertension. 3. Heart failure that develops at 4 to 6 weeks of age is invariably due to left-to-right shunting through a defect (volume overload). Pulmonary resistance usually nadirs at around 4 weeks of age, allowing left-to-right shunting to reach a maximum. 4. If heart failure develops after 3 months of age, additional causes must be kept in mind, such as myocarditis, cardiomyopathy, or paroxysmal tachycardia. 5. Central cyanosis because of congenital heart disease may be present at birth or may appear first when the ductus closes off, usually by 5 days of age. In tetralogy of Fallot, it may develop later (2 months of age or older) when the infundibular stenosis becomes more severe, increasing the volume of right-to-left shunting.

PHYSICAL EXAMINATION Developing an organized routine in the performance of cardiac examination is necessary so as to not miss the important signs. The cardiac examination consists of vital signs assessment by inspection, palpation and auscultation.

Overall Appearance A general assessment would reveal the child to be well or sick. The sick infants often appear anxious, fretful, diaphoretic, pale, or breathless and are seldom consolable. An assessment of child’s overall growth, appearance and state of distress serve to guide the urgency of further investigations and management. The height and weight should be measured

Clinical Assessment of a Child with Heart Disease

7

and plotted on a standard growth chart that would aid in determining the presence of failure to thrive. Different patterns of growth impairment are seen in various types of CHD. 1. Acyanotic patients, particularly those with a large left-to-right shunt, with or without pulmonary edema and/or ventricular dysfunction tend to have cardiac malnutrition with weight being more affected than height and degree of weight impairment proportional to the size of the shunt. 2. Acyanotic children with pressure overload lesions without intracardiac shunts grow normally. 3. Cyanotic patients have disturbances in both (usually height more evident than weight). Infants should gain about 20 g/day; Those with impaired growth would need adjustment of medications (diuretics, digoxin, correction of anemia if present) and use of caloricsupplemented food. If these methods are insufficient, surgical catheter interventions may be necessary. It should be remembered that poor growth in a child with a mild cardiac anomaly or failure of catch-up weight gain after repair of the defect may indicate failure to recognize certain genetic syndromes or associated noncardiac deformities. Evidence of pallor, clubbing, edema, pattern of respiration, sweating and dysmorphic features must be looked for in general examination. Clinical cyanosis is evident only when the oxygen saturation is below 85%. The presence of cyanosis should therefore be ascertained with pulse oximeter in all with suspected CHD. If cyanosis is present, the degree and distribution should be additionally noted. In differential cyanosis, the upper half of the body is pink and the lower half blue, or vice versa. Systemic-level pulmonary vascular resistance and a patent ductus arteriosus need to be present for this phenomenon to occur. The oxygen saturation can be higher in the upper extremity in patients with normally related great arteries if there is rightto-left shunting at the level of the ductus arteriosus (as seen in infants with either persistent pulmonary hypertension of the newborn, severe coarctation of the aorta, or interrupted aortic arch). The differential effect is reduced if there is also right-to-left shunting at the level of the foramen ovale, or if there is left-to-right shunting across a coexisting ventricular septal defect.10 The lower portion of the body can be more cyanotic than the upper segment in older patients with Eisenmenger syndrome caused by a persistent large patent ductus arteriosus. Clubbing: Reddening and shininess of the terminal phalanges are seen in the early stages of clubbing and most noticeably in the thumb. Presence of clubbing represents chronic arterial desaturation of at least 3 months duration. When fully developed, clubbing is characterized by a widening and thickening of the ends of the fingers and toes as well as by convex finger nails and loss of angle between the nail and nail bed. With marked clubbing, the terminal phalange becomes bulbous. Clubbing may also be associated with lung disease (e.g. abscess), cirrhosis of the liver, and subacute bacterial endocarditis. Occasionally, clubbing without cyanosis occurs in healthy people, as seen in familial clubbing.

Edema Pitting edema indicates systemic congestion and is unusual in children with CHD. In older children edema can be caused by cardiac dysfunction or may be noted after Fontan procedure

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because of protein-losing enteropathy, a complication that occurs with high venous pressure. Swelling of the face, neck, and arms can occur with superior vena cava obstruction, postpalliative surgery for CHD, intravascular thrombosis associated with an indwelling central venous catheter, or obstructing mediastinal mass. Obstruction of the inferior vena cava or iliac or femoral veins occasionally occurs secondary to in utero thrombosis or as a complication of catheterization and can produce edema of the abdomen and lower extremities. Nonpitting swelling of the hands and feet represents lymphedema and may be seen in infants with Turner’s syndrome. Extracardiac anomalies should be looked for in all children with congenital heart disease.  Multiple syndromes have characteristic facies. A webbed neck and short stature suggest Turner’s syndrome. Arachnodactyly, pectus deformity, scoliosis, and arm span exceeding height are features of Marfan syndrome. Radial dysplasia is a component of HoltOram syndrome.

Heart Failure Children with CHD with a low cardiac output and high pulmonary venous pressure would have sufficient underlying hemodynamic disturbances to have clinical manifestations. The precordial bulge noted in these children is because of underlying cardiac enlargement of at least 3 months duration. Additionally, tachycardia, tachypnea, dyspnea, poor weight gain, flaring of the inferior rib cage with subcostal indrawing and Harrison’s groove (line of depression in the bottom of the rib cage along the attachment of the diaphragm) could be noted and indicate poor lung compliance of long duration as seen with large left-to-right shunt lesions. Infants with CHF often have a cold sweat on the forehead and represents a heightened sympathetic activity as a compensatory mechanism for decreased cardiac output.11

CARDIOVASCULAR ASSESSMENT Vital Sign Assessment Vital signs should be recorded for each patient.

Pulse Characteristics The pulse is examined with respect to rate, rhythm, volume and character. Sinus tachycardia occurs in a variety of conditions, including anxiety, fever, pain, anemia, large left-to-right shunts, decreased cardiac contractility, cardiac tamponade, sepsis, pulmonary disease, or hyperthyroidism. Supraventricular tachycardia in infants or children typically occurs at a rate that is too rapid to count by an observer (more than 220 beats/minute). Bradycardia is seen in athletes, hypothyroidism, or heart block. Normal resting heart and respiratory values for age are presented in Table 1.3. Table 1.3: Normal values of respiratory and heart rates in children Rate Respiratory Heart

Birth–6 weeks 45–60/min 125 ± 30/min

6 weeks–2 year 40/min 115 ± 25/min

2–6 years 30/min 100 ± 20/min

6–10 years 25/min 90 ± 15/min

Over 10 years 20/min 85 ± 15/min

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Rhythm: A phasic variation related to the respiratory cycle (faster during inspiration) is characteristic of sinus arrhythmia. Occasional premature beats can represent atrial, ventricular, or junctional premature beats. Nonconducted atrial premature beats are the most common cause of a “pause” in the neonatal period and usually resolve during the first month of life. Isolated ventricular premature beats are common in adolescence; resolution with exercise suggests a benign etiology. Volume: The dynamic character of the pulse may provide information about the cardiac output. Clinical information of cardiac output includes the warmth of the digits and measured capillary refill time that is usually 2 to 3 seconds. Bounding pulses are present in febrile states, hyperthyroidism, exercise, anxiety, severe anemia and with aortic runoff lesions that produce increased pulse pressure (aortic regurgitation, patent ductus arteriosus, arteriovenous malformations, aortopulmonary window, truncus arteriosus). The prominent pulse which is classically associated with aortic regurgitation has been termed Corrigan’s pulse or water hammer pulse. This high runoff conditions produce visible ebbing and flowing of the capillary pulse that can be observed by partially compressing the nail bed, a phenomenon termed Quincke’s sign. Generalized decreased intensity of pulses is associated with low cardiac output. This can be caused by acquired heart disease such as myocarditis, cardiomyopathy or obstructive lesions, pericardial tamponade or constrictive pericarditis. Pulses may be absent or decreased in Takayasu’s arteritis, that is a rare form of vasculitis affecting the large arteries (also termed as pulseless disease). A weak, thready pulse is found in cardiac failure or circulatory shock. The radial and brachial pulses should be assessed simultaneously in the upper limb. By palpating the pulse on two sites and altering the pressure applied by the palpating fingers, a more accurate assessment of the rate of arterial pressure rise, volume and contour may be obtained. The radial pulse should also be compared with the femoral to feel for any delay that may be seen in coarctation of the aorta. The presence of a palpable femoral pulse may not always rule out coarctation because collateral vessels may perfuse the lower limbs. Previous arterial instrumentation, injury or congenital variability may account for a reduction in palpable peripheral pulses. In Takayasu’s arteritis, segmental affection of aorta may result in differences in volume of extremity pulses depending on site of affection. A systemic–to–pulmonary artery shunt (either classic Blalock-Taussig shunt or modified Gore-Tex shunt) or subclavian flap angioplasty for repair of COA may result in an absent or weak pulse in the arm affected by surgery. Variation: In pulsus paradoxus, an exaggerated decrease in inspiratory systolic pressure of more than 10 mm Hg is noted and is seen with pericardial tamponade or severe respiratory distress. Pulsus alternans consists of a decrease in systolic pressure on alternate beats and indicates severe left ventricular dysfunction and can be easily appreciated observing intravascular blood pressure recordings. Pulsus bisferiens consists of a pulse with two peaks separated by a plateau and can occur in patients with either hypertrophic obstructive cardiomyopathy or large left ventricular stroke volume.

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Venous Examination The jugular venous pulse is generally difficult or impossible to assess in infants and young children. In them, the liver character and size are more reliable indicators of systemic congestion. The congested liver margin is rounded, firm and tender. In a cooperative child or adolescent, venous pressure can be estimated by examination of the jugular vein. When the patient is sitting or reclining at a 45° angle, the jugular vein should not be visible above the level of the clavicle. Measuring the difference in the height of the jugular vein with a parallel line drawn through the level of the manubrium yields central venous pressure. Prominent jugular venous waves are present in normal atrial contraction into a stiff right ventricle or against a closed tricuspid valve (tricuspid atresia; complete heart block, tricuspid regurgitation, pericardial disease (pericardial tamponade, constrictive pericarditis), vein of Galen malformation and superior vena cava obstruction. Splenic enlargement in CHF is unusual.

Blood Pressure Measurement Blood pressure measurement can be difficult and time-consuming, but is an essential part of cardiovascular system assessment. It is recommended that the bladder width of the blood pressure cuff is approximately 40% and the bladder length is approximately 80% of the arm circumference midway between the olecranon and the acromion. The inflatable bag should thus ideally cover two-thirds of the full length of the arm. The equipment necessary to measure blood pressure in children 3 years of age through adolescence includes pediatric cuffs of different sizes. For newborn—premature infants, a cuff size of 4 × 8 cm is recommended; for infants, 6 × 12 cm; and for older children, 9 × 18 cm. A standard adult cuff, a thigh cuff for leg blood pressure measurement and cuffs for use in children with very large arms are also available.13 In general, blood pressure obtained by palpation or flush technique is significantly less accurate than auscultation. The systolic pressure is recorded as the first audible Korotkoff sound, with the diastolic pressure correlating best with muffling phases or fourth Korotkoff sound. Increasingly, automated oscillometric methods allowing digital print outs of systolic, mean and diastolic pressures are being used for blood pressure measurements. The upper and lower limb blood pressures should be recorded at least on one occasion in child’s life. The calf cuff application to the thigh and Doppler assessment of popliteal systolic pressure can be easily performed. The lower extremity systolic pressure can be 5 to 10 mm Hg greater than the upper extremity value because of the standing wave effect, with successive heartbeats adding to the pressure downstream. If systolic pressure in the upper extremity is more than 10 mm Hg than in the lower extremity, it strongly suggests presence of coarctation of the aorta. The blood pressure measured should be compared with normal values for age and sex of the child (Figs 1.1A to D). Tables are available that provide the systolic and diastolic blood pressure level at the 95th percentile according to age, sex, and height.14 Hypertension in children and adolescents is defined as systolic and/or diastolic blood pressure that is consistently equal to or greater than the 95th percentile of the blood pressure distribution. The pulse pressure is the difference between systolic and diastolic values. The pulse pressure is increased in conditions associated with bounding pulses and decreased in states associated with diminished pulses. 

Clinical Assessment of a Child with Heart Disease

A

B

C

D

11

Figures 1.1A to D: (A,B) Age-specific percentiles of BP measurements in boys and girls respectively—birth to 12 months of age. (C, D) Age-specific percentiles for BP measurements in boys and girls respectively—1–13 years of age (From National Heart, Lung, and Blood Institute, Bethesda, D: report from second task force on blood pressure control in children, 1987)13

Respiratory Assessment A review of respiratory system should be a part of the assessment of cardiovascular examination. The rate, depth , effort of respiration, evidence of air trapping, increased chest diameter, or

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presence of Harrison’s sulci should be noted. Infants with heart failure often have labored efforts and tend to use their accessory muscles of respiration quite prominently. Tachypnea is present with pulmonary parenchymal disease, pulmonary edema, large leftto-right shunts that elevate pulmonary venous pressure, and conditions causing metabolic acidosis. The normal respiratory rate at different ages is mentioned in table 1.3. Quiet tachypnea is often present in left-to-right shunt lesions, while labored tachypnea is observed with pulmonary disease. Both can be accompanied by intercostal or subcostal retractions, flaring of the alae nasi, or audible wheezing. Orthopnea is pathognomic sign of left ventricular dysfunction or severe elevation in pulmonary venous pressure.

PRECORDIAL EXAMINATION Inspection A visible apical impulse can be seen in left ventricular volume overload lesions, including large left-to-right shunts and significant mitral or aortic regurgitation. A visible parasternal impulse is associated with right ventricular overload lesions, including tetralogy of Fallot, absent pulmonary valve associated with severe pulmonary regurgitation or severe tricuspid regurgitation associated with Ebstein’s anomaly, and large arteriovenous malformations.6 Harrison’s groove, a line of depression in the bottom of the rib cage along the attachment of the diaphragm, indicates poor lung compliance of long duration such as that seen with large left-to-right shunts. Substernal thrust indicates the presence of right ventricular enlargement, whereas, an apical heave is noted with left ventricular hypertrophy. A hyperdynamic precordium suggests a volume load such as that found with a large left-to-right shunt, although it may be normal in a thin patient. A silent precordium with a barely detectable apical impulse suggests pericardial effusion, severe cardiomyopathy, Fallot’s tetralogy or may be normal in an obese patient.

Palpation The chest should be palpated for: apical impulse, point of maximum impulse (PMI), hyperactivity of the precordium, and palpable heart sounds and thrills. In general, if apical impulse is not palpable and if the pulses are of normal volume, then in most probability, the child does not have a serious hemodynamic disturbance.15 a. Apical impulse: The location and character of apical impulse should be noted. The apical impulse is best appreciated using the tips of the index and middle fingers and is normally located in the left midclavicular line in the fourth or fifth intercostal space. The apical impulse is displaced laterally and is more prominent in left ventricular overload lesions such as severe aortic or mitral regurgitation or lesions associated with large leftto-right shunts at the ventricular or great vessel level. The right ventricular impulse is best detected by placing the hand on the chest with the heads of the metacarpals along the left costochondral junctions. A prominent lift indicates right ventricular hypertension or right ventricular volume overload. The right ventricular impulse can also be assessed in the epigastric area under the xiphoid process; the tips of the fingers can easily palpate

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13

the right ventricular impulse. However, the specificity of this pattern is rather limited. Right-sided apical impulses signify dextrocardia, tension pneumothorax, or left-sided thoracic space-occupying lesions (e.g. diaphragmatic hernia), left lobar emphysema, or scimitar syndrome. The character of the apical impulse is a useful guide to the underlying physiology. LV volume overload such as that which occurs with large VSD, mitral or aortic regurgitation results in a hyperdynamic apex. Here the apex is forceful but the outward movement occupies < 50% of the cardiac cycle. Obstructive lesions in the left ventricular outflow result in a sustained heave (> 50% of the cardiac cycle) and are often accompanied by a presystolic impulse (S4) which is slow rising heaving apical impulse. If impulse is well localized and sharp rising, it is called a tap and is noted in mitral stenosis. Heaving apex is classically seen in pressure overload conditions that result in ventricular hypertrophy (aortic stenosis, systemic hypertension, etc.). This is a forceful and sustained apex that is usually localized. Hyperdynamic apex is classically seen in volume overload conditions where there is ventricular dilatation (aortic regurgitation, hyperdynamic circulation, etc.). This is a forceful, but ill-sustained apex that is palpable over a larger area than normal (diffuse), i.e. more than one intercostal space.16 b. Point of Maximal Impulse: Site of maximal impulse helps to determine that of the ventricles are enlarged. With RV dominance, the impulse is maximal at the lower left sternal border or over the xiphoid process and would be heaving in character if the RV systolic pressure is elevated; with LV dominance, the impulse is maximal at the apex. Systolic pulsations in the left second intercostal space suggest pulmonary hypertension or rarely, a L-posed aorta of corrected transposition. Suprasternal pulsations suggest enlargement of the ascending aorta. c. Palpable heart sounds: A palpable second heart sound usually indicates severe pulmonary hypertension but can also be present in conditions in which the aorta has an anterior location, such as transposition of the great arteries. A palpable first heart sound can be present in hyperdynamic states. The third and fourth heart sounds are often better felt than heard because of their low frequencies. d. Precordial Thrills: These are best identified by palpation with the palmar surfaces of the metacarpophalangeal and proximal interphalangeal joints of the examiner’s hand. Thrills are vibratory sensations that represent palpable manifestations of loud, harsh murmurs (grade IV) and are located in the same areas as maximum intensity of the murmur. The timing and location of thrills should be noted. Systolic thrills at the left lower sternal border usually are caused by small ventricular septal defects and occasionally tricuspid regurgitation, if there is right ventricular hypertension. Mitral, aortic, and pulmonary thrills are located at the apex, right upper sternal border, and left upper sternal border, respectively. A thrill in suprasternal notch should arouse suspicion of aortic stenosis, coarctation or less commonly pulmonary stenosis and indicate significant degrees of obstruction. In patent ductus arteriosus or aortic insufficiency, the suprasternal notch is very pulsatile. Although most thrills occur in systole, diastolic thrills can occur at the apex with mitral stenosis, or along the left sternal border with aortic or pulmonary regurgitation.17

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Percussion In general, percussion of the heart in children is of negligible diagnostic value. Auscultation is an art that improves with practice and provides perhaps the most useful diagnostic information. The precordium should be listened to in the four cardinal areas and the back with both bell and diaphragm, the former better suited for detecting low-frequency events, while the diaphragm selectively picks up high frequency events. It is important to be systematic so that all available data are collected and a reliable diagnosis is made. It is also important to listen to one sound at a time. The components to be evaluated include the heart sounds (S1, S2, S3, S4), ejection click, opening snap, pericardial rub, and murmurs (systolic, diastolic, continuous). The patient should be evaluated in more than one position, including supine, sitting, and standing, depending on the diagnosis, because some heart sounds change or are more easily appreciated with different patient posture.18 1. Heart rate and regularity: Extremely fast or slow rates or irregularity in the rhythm should be evaluated by an ECG and a long rhythm strip. 2. Heart sounds: Intensity and quality of the heart sounds, especially the second heart sound (S2) should be evaluated. Abnormalities of first, third and presence of gallop rhythm or the fourth sound (S4) should be noted. Systolic or diastolic sounds (e.g. an ejection click in early systole and midsystolic click) provide important clues to diagnosis. 3. Heart murmurs: Heart murmurs are caused either by turbulence in blood or tissue vibration.

Heart Sounds First heart sound (S1): This represents closure of the mitral and tricuspid valves and occurs when the ventricular pressure exceeds the atrial pressure at the onset of systole. Splitting of the first sound is normal as mitral valve closes earlier than the tricuspid. The intensity of first heart sound is decreased in low cardiac output states, prolonged atrioventricular conduction and in myocardial diseases. It is accentuated with increased blood flow across atrioventricular valve as in left-to-right shunts or in high cardiac output states and in mitral stenosis. Patients with complete heart block have variable intensity of S1. Second heart sound (S2): S2 is produced by closure of the semilunar valves and is typically best appreciated at the left upper sternal border. The quality of S2 yields important information on cardiac physiology, particularly in a child with cardiac malformation. The second heart sound has two components that represent the asynchronous closure of the aortic and pulmonary valves and signal the end of ventricular ejection. Aortic closure (A2) normally precedes the closure of pulmonary valve (P2) because right ventricular ejection is longer. The time interval between the components varies with respiration, i.e. with inspiration, the degree of splitting increases and with expiration, it shortens. This variation is because of greater volume of blood that returns to the heart during inspiration, and longer time taken for ejection of this augmented volume of blood. Detecting splitting of S2 is always challenging. If the split is easily detected, the split is often wide. In infants with tachycardia and tachypnea, correlating S2 with the respiratory cycle is impossible. The best the examiner can do is to detect variability with a split present in some beats and not in others. Table 1.4 shows the conditions with abnormal S2.

Clinical Assessment of a Child with Heart Disease

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A widely fixed split S2  occurs with right ventricular volume overload lesions, the most common of which is atrial septal defect and less with total or partial anomalous pulmonary venous connection or large arteriovenous malformation. In these conditions, the persistent right ventricular volume overload delays pulmonary valve closure so that the split is wider. Wide inspiratory splitting can also be noted with right bundle branch block, pulmonary stenosis, or idiopathic dilation of the main pulmonary artery due to prolonged contraction of the right ventricle and also with significant mitral regurgitation (due to earlier closure of the aortic valve). Paradoxical splitting is uncommon in children and difficult to appreciate. The intensity of S2 depends on the pressure closing the semilunar valves and the anteriorposterior position of the great arteries. The most common cause of a loud S2  is pulmonary hypertension. Pulmonary hypertension can be caused by increased pulmonary flow or elevated pulmonary vascular resistance; evaluation of murmurs often helps to distinguish between these two mechanisms, with the former being associated with diastolic rumbles across the atrioventricular valve that receives increased flow. Increased intensity of S2 is also present in patients with transposition of the great arteries because of the anterior location of the aorta, and often in tetralogy of Fallot. S2 is single in patients with severe pulmonary hypertension and when there is atresia of one the semilunar valves. Third heart sound (S3): This is normally heard in many children and is accentuated in pathological states and best heard with the bell of the stethoscope. This sound occurs early in diastole and represents the transition from rapid to slow filling phases. Cardiac diseases associated with a third heart sound include myocardial dysfunction or volume overload conditions as seen with an increased blood flow across either the mitral valve ( as in VSD or MR) or through tricuspid valve (as in atrial septal defect ). A third heart sound produced by the left ventricle is detected in the apical region, whereas that from the right ventricle is noted at the left lower sternal border. A gallop rhythm found in congestive cardiac failure often represents exaggeration of the third heart sound in the presence of tachycardia. Left ventricular enlargement and dysfunction that accompanies cardiomyopathy, anomalous coronary artery from pulmonary artery (ALCAPA) characteristically has a prominent S3 and is accompanied by a soft S1. Fourth heart sound (S4): This is abnormal and is produced by atrial contraction in late diastole and is best heard with the bell of the stethoscope. S4 is seen in conditions with decreased ventricular compliance so that increased atrial contractile force is required to fill the ventricle as occurs with myocardial fibrosis, hypertrophic cardiomyopathy, systemic hypertension, and valvar aortic or pulmonary stenosis. When both an S3 and S4 are present, there is a quadruple rhythm. In such a situation, if there is tachycardia and resulting shortening of diastole, the two extra sounds may become superimposed and create a summation gallop.19

Heart Murmurs Heart murmurs should be evaluated in terms of intensity, timing, location, transmission and quality.20 a. Intensity (loudness): The intensity of a murmur is graded on a scale of 1 through 6. Murmurs grade 4 or greater are associated with a palpable thrill. The loudness depends on both the

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pressure gradient and the volume of blood flowing across the site creating the murmur. Murmur is graded as follows: Grade 1 : Heard only with intense concentration Grade 2 : Faint but heard immediately Grade 3 : Easily heard, of intermediate intensity Grade 4 : Easily heard and loud (associated with a thrill) Grade 5 : Very loud, thrill present and audible with the stethoscope barely on the chest Grade 6 : Audible with the stethoscope off the chest. The difference between 2 and 3 or grades 5 and 6 may be somewhat subjective. b. Timing: The relative position within the cardiac cycle and with relationship to S1 and S2. Systolic (occurring between the first and second heart sounds), diastolic (between the second sound and the first sound), or continuous (present continuously through the cardiac cycle). c. Location and transmission: It should be noted where the murmur on the chest wall is heard loudest and the other areas where the murmur is audible (extent of radiation) (Fig. 1.2). Aortic valve stenosis has maximal intensity at the right upper sternal border and may radiate to the suprasternal notch and carotid arteries. Aortic valve regurgitation is most easily detected at the left upper sternal border with the patient sitting, leaning forward, in expiration. Pulmonary stenosis and regurgitation are maximal at the left upper sternal border. The severity of aortic or pulmonary regurgitation correlates with the amount of radiation. The systolic murmur of peripheral pulmonary stenosis is common in infancy and is maximal at the left upper sternal border and radiates to the infraclavicular, axillary regions and to the back. Systolic murmurs at the left lower sternal border usually represent a ventricular septal defect but can be associated with tricuspid regurgitation. The murmur of tricuspid regurgitation usually increases during inspiration. Mitral valve disease is best

Figure 1.2: Location of common murmurs

Clinical Assessment of a Child with Heart Disease

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heard at the apex with the patient in the lateral decubitus position. Mitral regurgitation typically radiates to the axilla. Sites other than the precordium need to be auscultated as well. Coarctation is best heard in the intrascapular region on the back. Long-standing severe coarctation can produce collateral circulation audible as continuous murmur over the ribs where the intercostals arteries course. Arteriovenous malformations may be audible over the affected body region in the cranium for vein of Galen malformations or right upper quadrant for hepatic source. d. Duration: The time of the murmur from beginning to end. e. Pitch: The frequency range of the murmur. f. Quality: Harsh murmurs are characteristic of murmurs caused by ventricular outflow tract obstruction or hyperdynamic states. Blowing murmurs are typical of valve regurgitation. A rumbling quality is a feature of diastolic turbulence across atrioventricular valves. A vibratory, musical, or humming property is associated with the innocent Still’s murmur.

Classification of Heart Murmurs Based on the timing of the heart murmur to the S1 and S2, the heart murmur may be classified into three types.21

Systolic Murmur Systolic murmurs also are classified by their dynamic mechanism, of which there are four types (Fig. 1.3). 1. Regurgitation (backward flow of blood) 2. Obstruction to forward flow 3. Vibration of tissues in heart chamber 4. Excessive flow of blood through a normal orifice or vessel. Thus, the systolic murmurs may be: (i) Holosystolic murmurs when they begin with S1 and continue at the same intensity to S2. These occur when a regurgitant atrioventricular valve is present (tricuspid or mitral) or in association with a majority of ventricular septal defects and each is associated with a high systolic pressure gradient. The murmur of mitral regurgitation is heard loudest at the apex and radiates toward the axilla. The murmur of ventricular septal defect is heard best along the left sternal border, over the right ventricular area. The murmur of tricuspid regurgitation is unique in that it increases in intensity during inspiration because of increased right ventricular filling. Usually pansystolic murmurs are harsh or blowing murmurs. (ii) Ejection murmurs; crescendo-decrescendo or diamond shaped murmur that may arise from narrowing of the semilunar valves or outflow tracts. The velocity and volume of blood passing through the valve is greatest toward the center of systole, and thus the murmur will be loudest in mid-systole creating a crescendo-decrescendo, “diamond shaped” type of murmur. These loud coarse murmurs generally occur over the pulmonary or aortic valve. The murmur of aortic coarctation tends to be higher in pitch, but it is heard in a different area, being maximal high in the precordium, in the left axilla, and over the left side of the back. Generally, obstructive murmurs are coarse and they tend to radiate in the direction of blood flow, e.g. murmur of aortic stenosis is well heard over the carotid arteries. (iii) Vibratory murmur: A medium-

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Pediatric Cardiology

pitched musical murmur would sound like a hum. Because vibration occurs in tissue, it often transmits in the same tissue plane. Thus, the common still’s murmur is a vibratory murmur arising in the left ventricular outflow tract will transmit through the left ventricular tissue toward the apex or through the aortic wall up toward the aortic area. Merely detecting a musical quality of the murmur in children means that the chances of the murmur being innocent are high. (iv) Flow murmurs are generated by the turbulence associated with an increased stroke volume. Systolic flow murmurs occur in the outflow tract of either the left or right ventricle and accordingly are usually heard maximally at the left or right sternal border in the second interspace. Invariably, when the patient is examined in a standing position, the systolic flow murmur greatly diminishes in intensity or totally disappears, because of the decrease in stroke volume that occurs in the standing position. The characteristics of the second sound become extremely important in trying to interpret the significance of flow murmurs. Unfortunately, the mechanism of an atrial septal defect murmur, which is actually a flow murmur arising in the right ventricular outflow tract, is similar to that of the innocent functional flow murmur heard in normal individuals, and the two murmurs may be indistinguishable on auscultation. The key distinguishing feature is a characteristic wide and fixed splitting of the second sound that occurs with most atrial septal defects. With atrial septal defect, blood ejected from the right ventricle is constant in volume both in inspiration and in expiration; hence, splitting of the second sound is fixed, meaning it does not change with respiratory phase. Other features (easily palpable right ventricular impulse, mid-diastolic murmur in tricuspid area) may help in the diagnosis of atrial septal defect. (v) Mid to late systolic murmurs: begin midway through systole and are often heard in association with the mid-systolic clicks in insufficiency of mitral valve prolapse (Fig. 1.3). The “whoop” that occurs with mitral valve prolapse is best heard with the patient standing. It occupies the mid-late portion of systole and may be exceedingly loud, sometimes audible without a stethoscope. Whoops are usually evanescent, being loud at one time and absent at another. The patient is usually tall asthenic and frequently has a thoracic bony abnormality such as pectus excavatum. Mitral valve prolapse may be familial due to a congenital conective tissue defect.

Figure 1.3: Types of systolic murmurs

Clinical Assessment of a Child with Heart Disease

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Diastolic Murmurs These are further classified as early diastolic, mid-diastole or presystolic. Usually seen with regurgitation of the semilunar valves, stenosis of atrioventricular valve or an increased flow across the atrioventricular valve. Early diastolic murmurs are decrescendo in nature and arise either from aortic or pulmonary valve insufficiency. Mid-diastolic murmurs are diamond shaped and occur either because of an increased flow across a normal tricuspid or mitral valve or normal flow across an obstructed or stenotic tricuspid or mitral valve.22 All diastolic murmurs are organic. Diastolic murmurs are classified similarly to systolic murmurs and may be early, beginning with the second sound, mid, or mid-late or presystolic. The mechanisms are the same, and the murmurs that are produced, are therefore regurgitant, obstructive, flow, or vibratory. Regurgitant diastolic murmurs imply either aortic or pulmonary valve regurgitation. As with systolic regurgitant murmurs, the murmur begins with the closure of that portion of the second heart sound caused by the closure of either the pulmonary or aortic valve. The murmur of aortic regurgitation will be high pitched because of the high-pressure gradient between the aorta and the left ventricle in diastole, and it will be heard maximally along the left sternal border. The murmur of pulmonary regurgitation with normal pulmonary artery pressure is low pitched because of the low-pressure gradient; it is heard in the same area as the aortic regurgitation murmur. When the child has pulmonary hypertension, the murmur, known as the Graham-Steell murmur, is of high pitch, because of the high-pressure gradient between the pulmonary artery and the right ventricle in diastole. Obstructive murmurs are caused by mitral or tricuspid stenosis of usually, chronic rheumatic carditis. Decrescendo-crescendo in shape related to flow velocity, the murmur will be low pitched, and it will not begin until the mitral valve opens; therefore, there will be a pause between the second sound and the start of the murmur. With mitral valve stenosis, the murmur occurs in the left ventricle and is loudest at the apex. A diastolic flow murmur also is noted with lesions such as moderate to large ventricular septal defect, atrial septal defect, and mitral or tricuspid regurgitation. Its presence indicates that flow volume across the AV valve is at least twice normal. Mid-diastolic in timing, of short duration, and medium pitch, it is heard maximally in either the apical or tricuspid areas, according to which valve generates the turbulence.

Continuous Murmurs Flow through vessels or channels distal to the semilunar valves begin in systole and persist through S2  into early, mid, or all of diastole. Continuous murmurs are generally pathologic except the continuous murmur of venous hum. Of the many causes of continuous murmurs, only two are of major importance. The venous hum is seen in children whose circulation is hyperkinetic, continuous turbulence is audible over the jugular veins, usually loudest in the right supraclavicular fossa. This murmur, usually heard only in the sitting or upright position, varies considerably in intensity with movement of the child’s head and its intensity may be influenced by light pressure on either jugular vein.The turbulence may also be palpated with light pressure on the jugular vein.

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The other important continuous murmur is that of a patent ductus, heard maximally on the left side of the thorax, usually just below the clavicle, or between the left sternal border and the midclavicular line in the second interspace. Flow through a patent ductus of average size increases aortic runoff and left ventricular stroke volume. Accordingly, the pulse will be bounding and left ventricular activity is readily palpable. The ductus murmur has a “machinery” quality. The other causes of continuous murmurs are: 1. Systemic and pulmonary arterial circulations: Surgically created Blalock-Taussig, Waterston, Potts, or central shunts, patent ductus arteriosus, aortopulmonary collaterals, aortopulmonary window, anomalous left coronary artery arising from the main pulmonary artery 2. Systemic arteries and veins: Arteriovenous malformation 3. Systemic arteries and cardiac chambers: Coronary arteriovenous fistula, ruptured sinus of Valsalva aneurysm 4. Disturbed flow in arteries: Collateral circulation associated with severe coarctation 5. Disturbed flow in veins: Venous hum. In a coronary AV fistula the continuous murmur is best heard low along the left sternal border. A continuous murmur is distinguished from a to-and-fro murmur, which consists of two murmurs, one that occurs in systole and the other that occurs in diastole. A to-andfro murmur does not continue through S2 but instead has peak intensity earlier in systole. Examples include patients with combined aortic stenosis and aortic regurgitation (as can occur after balloon dilation of a stenotic bicuspid valve), combined pulmonary stenosis and pulmonary regurgitation (as can occur after repair of tetralogy of Fallot), or ventricular septal defect, prolapsed aortic cusp, and aortic regurgitation.

Additional Sounds a. The terms, clicks and snaps are a continual source of confusion. Valve opening is quiet in health and signals the end of the period of isovolemic contraction or relaxation. When a sound is heard at the time of the opening of any heart valve, it is abnormal.20-22 A sound heard at the time of opening of the pulmonary or aortic valve is called an ejection click; when mitral or tricuspid opening is heard, the term opening snap is used. The “clicks” signal the beginning of ejection into a dilated great vessel; the “snaps” signal the commencement of diastolic flow into the ventricle.

Opening Snap: An opening snap is a high-frequency sound associated with mitral stenosis. As the degree of mitral stenosis progresses, the opening snap occurs earlier in diastole because of elevated atrial pressures and becomes softer because of decreased leaflet mobility.

Clicks: Ejection clicks are brief, high-frequency, sharp sounds that have a quality distinct from S1 and S2. They usually are associated with abnormal valve structure. Evaluation of location, timing (early versus mid-systolic), and nature (constant versus variable) enables the examiner to determine the affected valve. In patients with mitral valve prolapse, the click may be associated with a murmur of mitral regurgitation that is only present or

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louder in the standing than supine position because of reduced left ventricular volume that produces a greater degree of prolapse. The click associated with aortic stenosis or bicuspid aortic valve is best detected at the apex rather than the aortic valve region at the right upper sternal border. At times, it is difficult to distinguish a split S1 (normal variant) from an aortic valve ejection click, and echocardiography is needed for differentiation. The click associated with pulmonary stenosis is located at the left upper sternal border and is variable and louder in expiration because of greater systolic valve excursion in this phase of the respiratory cycle.  Clicks associated with semilunar valve stenosis become softer as the degree of obstruction progresses because of reduced valve mobility. Ebstein’s anomaly of the tricuspid valve can be associated with a systolic click at the left lower sternal border. Clicks occasionally occur in conditions associated with dilation of the aorta or pulmonary artery. The latter can occur with pulmonary hypertension, patent ductus arteriosus, or idiopathic dilation of the main pulmonary artery. In neonates with left-to-right shunting across a patent ductus arteriosus, there may be multiple systolic clicks at the left upper sternal border. Clicks can also be produced by membranous ventricular septal defects associated with aneurysm of the ventricular septum and are located at the left lower sternal border. b. Pericarditis and mediastinal emphysema: Two other auscultatory findings of significance are the pericardial friction rub of pericarditis and the mediastinal crunch of mediastinal emphysema. Pericardial friction occurs most frequently after operation in patients undergoing cardiac surgery, or in the so-called postpericardiotomy syndrome, which characteristically occurs 3 to 6 weeks after operation. In a nonoperative situation, it may be a sign associated with pericarditis from any cause, but usually viral. Most clinicians identify a friction rub easily because of its characteristic scratchy quality. The sound is not present if there is a moderate to large pericardial effusion because the two surfaces of the pericardium cannot rub together. Pericardial rubs may be heard anywhere on the left side of the chest but are usually best heard along the sternal border with the patient sitting and leaning forward and often has inspiratory accentuation.They generally have three phases, related to atrial filling, ventricular ejection, and the rapid phase of ventricular filling giving a triple cadence. The mediastinal crunch has much the same quality as pericardial friction, and although it may have a to-and-fro rhythm, it will not have a three-phase cadence. More often, its rhythm will be chaotic, at times systolic and at times phasic with respiration.23 Relative timings of heart sounds and added sounds on auscultation are shown in (Fig 1.4).

Innocent Murmurs of Childhood24,25 Innocent heart murmurs also called as functional murmurs arise from cardiovascular structure in the absence of anatomical abnormalities. More than 80% of children have innocent murmurs sometime during childhood, usually beginning around 3 to 4 years of age. All innocent murmurs are accentuated or brought out in a high output state, usually during a febrile illness. A left ventricular false tendon is often found in children and adults with innocent heart murmurs. When one or more of the following are present, the murmur is more likely pathologic

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Figure 1.4: Relative positions of heart sounds and added sounds in auscultation. Sounds in red are high pitched. A2: aortic component of second heart sound; EC: ejection click; MSC: mid-systolic click; OS: opening snap; P2: pulmonary component of second heart sound; S1–S4: heart sounds.22 Table 1.4: Common innocent heart murmurs26 Type (timing) Classical vibratory murmur

Description of murmur Maximal at mid or left lower sternal border or apex

Age group 3–6 years

(Still’s murmur) Systolic

Grade 2 to 3/6 Low-frequency vibratory “twanging” groaning or musical murmur

Occasionally in infancy

Pulmonary ejection murmur (systolic)

Maximal at upper left sternal border, Transmits well to left and right chest, axilla and back, grade 1–2/6

Premature and full term, disappears by 3–6 months

Venous hum

Maximal at right or left supra or infraclavicular areas, grade 1–3/6 in intensity and changes with rotation of head and compression of jugular vein

3–6 years

Carotid bruit

Right supraclavicular area and over the carotids, grade 2–3/6 with occasional thrill over carotid

and requires cardiac consultation, i.e. symptoms, abnormal cardiac size or silhouette or abnormal pulmonary vascularity on chest X-ray, abnormal ECG, diastolic murmur, a systolic murmur that is loud (with a thrill), cyanosis, abnormally strong or weak pulse and abnormal heart sounds11,12,27 (Table 1.4). An underlying fear that a cardiac abnormality is present may negatively affect a child’s self-image and subtly influence personality development and a 2D echocardiogram may allay this anxiety.

Chest Examination Chest Deformity Congenital heart disease associated with cardiomegaly can produce prominence of the left chest because of the effects of cardiac contraction against an elastic rib cage. Pectus carinatum is a feature of Marfan syndrome. Pectus excavatum is associated with mitral valve prolapse; the mitral valve prolapse often improves after surgical correction of the chest wall deformity. An

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asymmetric precordial bulge can also be seen in pulmonary conditions, including atelectasis, pneumothorax, emphysema, and diaphragmatic hernia. Chest pain in children frequently has a musculoskeletal basis, including costochondritis, slipping rib syndrome, or myodynia. The diagnosis of musculoskeletal pain can be confirmed by an ability to reproduce a similar quality of discomfort by palpation of the chest. The examination should include palpation of the costochondral junctions, the insertion site of the pectoralis major muscle group by grasping the head of the muscle between the examiner’s fingers and thumb, the inframammary area, and other regions of the chest where pain is reported. Although one would expect the right and left costochondral junctions to be equally affected, the left-sided junctions are more typically involved.  In patients with slipping rib syndrome, the examiner can perform the “hooking” maneuver by placing fingers around the lower costal margin and lifting anteriorly to elicit a click and reproduce pain. The demonstration of pain reproduction and an explanation of the anatomic basis are reassuring to the family and patient and help allay concerns about the heart.28

Pulmonary Auscultation Lesions associated with excessive pulmonary flow or left-sided dysfunction or obstruction can be associated with inspiratory rales or expiratory wheezing. These features are also present in patients with reactive airway disease or pneumonia.

Abdomen Examination Palpation of the liver yields information about visceral situs and central venous pressure. A right-sided liver indicates normal situs of the abdominal viscera, a left-sided liver indicates situs inversus, and a midline liver indicates the presence of situs ambiguous and heterotaxy. Hepatomegaly is present in conditions associated with elevated central venous pressure. Percussion of the liver size helps to distinguish patients with “false” hepatomegaly caused by inferior displacement by a flattened diaphragm caused by hyperinflation. Palpation of the liver is easier when the abdomen is soft. Flexing the knees can relax the abdominal musculature. In infants, the liver can normally be palpated about 2 cm below the costal margin in the midclavicular line. In children, the liver can be palpated 1 cm below the right costal margin. An engorged liver is usually tender to palpation. A pulsatile liver is palpated in patients with elevated right atrial pressure, most commonly associated with significant tricuspid regurgitation. In infants, a spleen tip can normally be palpated under the costal margin. Location of the spleen also aids in determination of visceral situs. Elevated central venous pressure usually does not produce splenomegaly. An enlarged spleen is a feature of bacterial endocarditis, and in a known cardiac patient with fever or new regurgitant murmur, this physical finding should prompt thorough evaluation of that complication. Thus, equipped with data from history and clinical examination data, the clinician can arrive at an appropriate clinical diagnosis. With a systematic approach, the physician can develop the skills and confidence that will allow to make correct decisions on most children. Best classification and a simplistic approach is the one proposed by the legend, late Dr Paul wood29 and are based on answering the following basic questions:

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Q1. Does the child have a CHD? Q2. Is the child cyanotic or acyanotic? Q3. Is the pulmonary arterial blood flow increased or not? Q4. Does the malformation originate from the right side or left side of the heart? Q5. Which is the dominant ventricle? Q6. Is pulmonary hypertension present or not? The clinical findings have to be interpreted in terms of the underlying hemodynamic disturbance and conclude by noting the severity of lesion and complications, if any.

SUMMARY A good clinical assessment can spare many children with cardiovascular complaints from unnecessary or inappropriate investigative procedures. The key element is a systematic approach that always interprets each symptom and sign in terms of the underlying hemodynamic disturbance.

REFERENCES 1. Zoneraich S, Spodick DH. Bedside science reduces laboratory art. Circ. 1995;91:2089–92. 2. Gillian M Blue, Edwin P Kirk, Gary F Sholler, et al. Congenital heart disease: Current knowledge about causes and inheritance. Med J Aust. 2012;197(3):155–9. 3. John F Keane, Donald C Fyler, James E Lock. History. Physical examination and laboratory tests. In: Fyler DC (2nd edition) Nadas ‘Pediatric Cardiology St. Louis. Mosby. 2006. 4. Emmanouildes GC, Reemenschneider TA, Alien HD, et al. Moss and Adams Heart Diseases in Infants, Children, and Adolescents. Including Fetus and Young adult. 5th edition Baltimore, Williams & Wilkins. 1995. 5. Mc Connell ME, Adkins SB, Hannon DW. Heart Murmurs in Pediatric Patients: When Do You Refer? Am Fam Physician. 1999;60(2):558–64. 6. Pelech AN. Evaluation of the pediatric patient with a cardiac murmur. Pediatr Clinic of North Am. 1999;46:167–87. 7. Surendranath R. Veeram Reddy, Harinder RS. Chest Pain in Children and Adolescents. Pediatrics in review. 2010;31(1). pp. e1–e9. 8. Martin K, Bates G, Whitehouse WP. Transient loss of consciousness and syncope in children and young people: What you need to know. Arch Dis Child Educ Pract Ed. 2010;95:66–72. 9. Yun SL , Jae SB, Bo Sang K, Gi BK, et al. Pediatric Emergency Room Presentation of Congenital Heart Disease. Korean Circ J. 2010;40(1):36–41. Published online 2010 January 27. 10. Rao PS. Diagnosis and management of cyanotic congenital heart disease: part I. Indian J Pediatr. 2009;76(1):57–70. Epub 2009 Apr 18. 11. Erin M , Michael Silberbach. Heart Failure in Infants and Children. Pediatrics in review. 2010;31(1). pp. 4–12. 12. National High Blood Pressure education Program Working Group on Hypertension Control in Children and adolescents. Update on the 1987 Task Force Report on High Blood Pressure in children and Adolescents: A Working Group. Report from the National High Blood Pressure Education Program. Pediatrics. 1996;98:649–58. 13. National High Blood Pressure Education Program Working Group. The Fourth report on the diagnosis, evaluation and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114:555–76.

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14. Duff DF, McNamara DG. History and physical examination of the cardiovascular system. In Garson A, Bricker JT, McNamara DG (Eds). The Science and Practice of Pediatric Cardiology. Philadelphia, Lea and Febiger. 1990;671–90. 15. Gaskin, PR, Owens A, Talner SN, et al. Clinical Auscultation Skills in Pediatric Residents. Pediatrics. 2000;105:1184–87. 16. Michael S, David Hannon. Presentation of Congenital Heart Disease in the Neonate and Young Infant. Pediatrics in review. 2007;28(4). pp. 123–31. 17. Taggart NW, Cetta F. Overview of Congenital Heart Disease. Epocrates Online: BMJ Group. [Internet] 2011 [updated 2010 Nov 30; cited 2011 Mar 6]. 18. Uazman Alam, Omar Asghar, Sohail Q Khan, et al. Cardiac auscultation: an essential clinical skill in decline. Br J Cardiol. 2010;17(1). pp. 8–10. 19. Dhuper S, Vashist S, Shah N, Sokal M. Improvement of cardiac auscultation skills in pediatric residents with training. Clin Pediatr (Phila). 2007;46:236–40. 20. Haney I, Ipp M, Feldman W, McCrindle B. Accuracy of clinical assessment of heart murmurs by office based (general practice) paediatricians. Arch Dis Child. 1999;81:409–12. 21. Asprey DP. Evaluation of children with heart murmurs. Lippincot’s Primary Care Practice 1998;2(5):505–13. 22. Pelech AN. The cardiac murmur. Pediatr Clin North Am. 1998;45:107–22. 23. Maisch B, Seferovic PM, Ristic AD, et al. Guidelines on the diagnosis and management of pericardial diseases executive summary: The Task Force on the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology. Eur Heart J. 2004;25:587–610. 24. Rosenthal A. How to distinguish between innocent and pathologic murmurs in childhood. Pediatr Clin North Am. 1984;31:1229–40. 25. Biancaniello T. Innocent Murmurs. Circulation. 2005;111:20–22. 26. Sapin SO. Recognizing Normal Heart Murmurs: A Logic-based Mnemonic. Pediatrics. 1997;99: 616–18. 27. Satou GM, Halnon NJ. Pediatric Congestive Heart Failure. eMedicine: WebMD. [Internet] 2011 [updated 2009 Mar 19; cited 2011 Mar 6]. 28. Shamberger RC. Cardiopulmonary effects of anterior chestwall deformities. Chest Surgery Clinics of North America. 2000;10(2):245–52. 29. Somerville J. Congenital heart disease—changes in form and function. Br Heart J. 1979;41(1):1–22. [PMC free article] [PubMed]

2

X-ray Chest for Evaluation of Pediatric Heart Diseases

Savitri Shrivastava

INTRODUCTION In spite of numerous advances and increasing availability of sophisticated imaging tools, the chest X-ray continues to play an important role in initial evaluation as well as follow-up of children with heart diseases. It is also useful in postoperative evaluation, long-term follow-up after surgery or catheter intervention. The information provided by the chest X-ray includes visceral situs, cardiac size, position and configuration, pulmonary vasculature, pulmonary arterial and venous hypertension and associated pulmonary pathology. Although the X-ray is not used to arrive at the exact anatomic diagnosis of congenital heart disease, the chest X-ray continues to contribute vital information for decision making in many children.1 It is usual practice to evaluate the heart size in posteroanterior view but rarely the cardiac enlargement may be better evaluated in lateral view as the heart may enlarge in anteroposterioraxis. For the assessment of cardiac position, situs and associated lung pathology; chest X-ray is the main tool of evaluation. The interpretation of a chest X-ray should not be separated from clinical context. A good quality X-ray is obtained at end inspiration with adequate exposure, and proper centering. The interpretation of the chest X-ray should not be separated from its clinical context.2

What is a Good X-ray Chest? Correct centering without rotation: If the centering is correct both clavicles should be at the same level. The shadow of the spine should not be rotated. The medial ends of the clavicles should have the same distance from the center of the spine. In the postoperative patient, the sternal wires should overlap the spine. Correct exposure: In adults and older children, the space between 2nd and 3rd intervertebral vertebra should be visible if the penetration and exposure is adequate. If the whole spine is clearly seen, the chest X-ray is over-penetrated and the pulmonary vascularity is likely to be underestimated. On the contrary, if the spine is not at all seen the chest X-ray is

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under-penetrated and under-exposed. The changes in pulmonary vascularity may be overestimated in such an X-ray. The spine is visible in most young children even with correct exposure. Proper inspiratory film: A proper end-inspiratory film should have diaphragm at the level of 9th posterior intercostal space. If the film is taken when the inspiration is not complete the level of the diaphragm will be higher and the cardiac size maybe overestimated.3,4

Alterations in Cardiac Position One should always remember to look for extraneous causes to explain the altered cardiac position. Diaphragmatic hernia and conditions such as pneumothorax, hyperinflation or pleural effusion result in shifts to the opposite side. Collapse or lung hypoplasia results in a shift to the same side. The following general information can be obtained from the X-ray chest. 1. Situs 2. Cardiac configuration 3. Cardiac borders 4. Cardiac size 5. Chamber size i. Left atrium ii. Right atrium iii. Left ventricle iv. Right ventricle 6. Pulmonary vascular changes 7. Pulmonary pathology (not being discussed in this chapter).

Diagnosis of Situs a. In normal situs, i.e. situs solitus the gas bubble in stomach is seen on left side and the liver shadow is seen on the right side. The right dome of the diaphragm being higher than the left dome. If the stomach gas bubble is seen on the right side and the liver shadow with the higher diaphragm is seen on the left side it will indicate that one is dealing with situs inversus (Fig. 2.1). The liver is often in the midline in situs ambiguous, (Fig. 2.2). This indicates the presence of either right or left isomerism (asplenia or polysplenia syndrome) and should alert the physician of the possibility of complex congenital heart disease.

Figure 2.1: X-ray chest PA view showing situs inversus. Note the presence of stomach bubble on the right side and liver shadow on the left side. The pattern of bronchial bifurcation is also suggestive of situs inversus

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b. Bronchial division can sometimes be seen on routine chest X-ray and this can give a clue to the situs. The left main bronchus is longer and has a more acute angle with trachea as compared to the right main bronchus. If the right and left bronchi are lateralized normally it indicates normal situs and if vice versa, i.e. inversely lateralized it will indicate situs inversus (70 to 80% correct prediction). If both the bronchi are like right-sided bronchus it well indicate right isomerism or asplenia syndrome. If both the bronchi are like left-sided bronchus, it will indicate possibility of left isomerism or polysplenia syndrome. Bronchial arrangements are better seen on filtered beam X-ray chest (rarely used these days).

Figure 2.2: X-ray chest showing large midline liver with dextrocardia. This should immediately alert the physician for presence of complex congenital heart disease associated with isomerism

Cardiac Configuration The sensitivity of alterations in cardiac configuration for diagnosis of chamber enlargements is quite limited. Some of these alterations are listed below. When the apex of the heart is down and out with rounded configuration it suggests left ventricular enlargement. If the apex is lifted up and rounded, it suggests right ventricular enlargement. However, these are not very specific. If the right heart border, which is formed by the right atrium, is enlarged it suggests right atrial enlargement. When right atrium is enlarged the contour of the right heart border usually occupies more then 2½ intercostals spaces. The other sign, which could be useful, is to see the distance between the maximum right atrial curve to the right atrial-superior vena cava (SVC) junction, which normally is greater than the distance between the former and the cardiophrenic angle. The reverse will happen if the right atrium is enlarged. Enlargement of left atrium is best judged by seeing the carinal angle. Normally it is less than 70° and is increased with left atrial enlargement. If the carinal angle is 90° or more it is more specific for left atrial enlargement. Additional signs of left atrial enlargement are “double shadow” or “shadow in shadow” of the left atrial border that is often seen close to the lower half of the right border.

Heart Size5,6 For the assessment of heart size, cardiothoracic (CT) ratio is calculated. The cardiac dimension is measured from middle of the spine to maximum shadow on right and left side. The widest thoracic dimension is usually measured at the level of upper level of dome of diaphragm. A cardiothoracic ratio of more than 60% in neonates, 55% in infants and 50% in children indicate cardiac enlargement. These ratios are considered valid for the posterior-anterior (PA) view and

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not the anterior-posterior (AP) view. While calculating this ratio it is necessary that the chest X-ray is well-centered and good inspiratory film. Expiratory film causes false increase in CT ratio. Also in neonates and infants one should remember not to include thymic shadow in the heart borders.

Vascularity A good quality chest X-ray is a very useful to assess the vascularity. This helps the clinician to categorize the patient belonging to increased or decreased pulmonary blood flow group and to assess the presence and severity of pulmonary arterial or venous hypertension.7 •• Increased pulmonary vascularity: The main pulmonary artery is prominent with normally related great vessels. The hilar pulmonary arteries are also prominent and the pulmonary arteries can be traced till the lateral third of the lung fields (Fig. 2.3). Additionally more than four end-on vessels are seen in each lung field (the end vessel being more than twice the size of accompanying bronchus). Evidence of increased vascularity on X-ray often tips the decision towards operability in patients with left to right shunts and increased vascularity.8 •• Decreased vascularity: With decreased vascularity the main pulmonary artery is not prominent and hilar branches appear small. The peripheral pulmonary vessels are thinned out (stringy vasculature). The overall lung fields appear dark. Patients with VSD and pulmonary atresia with collaterals have numerous small “end-on” vessels seen all over the lung fields including the outer-most regions. This does not necessarily qualify as increased pulmonary blood flow because these vessels are typically quite small. •• Pulmonary arterial hypertension (PAH): The main pulmonary artery dilates with the increase in the pulmonary artery pressures and this can be seen on a chest X-ray, if the

A

B

Figures 2.3A and B: X-ray chest from patients with different degree of shunt at atrial level. (A) The X-ray chest shows presence of mild cardiomegaly with prominent main pulmonary artery (MPA) segment and right atrial (RA) enlargement. Pulmonary vasculature is also prominent, indicating perhaps a moderate atrial level shunt. (B) The X-ray chest shows moderate cardiomegaly with enlargement of MPA segment and RA. Also notice prominent hilar PA with evidence of increased pulmonary blood flow indicative of large shunt at atrial level

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great vessels are normally related. In addition, the proximal right and left pulmonary arteries are also enlarged. Right pulmonary artery diameter of more than trachea indicates significant PAH. If the PAH is severe, with prominent hilar vessels there is sudden tapering of the vessels called as pruning. Pruning means that more than a 50% reduction in vessel diameter at any branching level. It is generally clearly seen at the junction of medial and middle third of lung fields. It is important to remember that X-ray changes are not evident early in the course of conditions that result in PAH. Pulmonary venous hypertension (PVH): The X-ray features of pulmonary venous hypertension are better seen in adults and older children and when the disease is of a relatively short duration. For young children and in short-standing disease PVH may not be evident on the X-ray. In the initial stages with mild elevation of pulmonary venous pressures the upper lobe vessels dilate with constriction and blurring of the lower zone vessels. With further increase in pulmonary venous pressures the interstitial lung water increases leading to increased lymphatic drainage resulting in cuffing of fluid around bronchi, background haze, Kerley’s lines, septal and interstitial edema. Very severe elevation of pulmonary venous pressures results in collection of edema fluid towards the hilum resulting in “Bat’s wing” appearance.

X-RAY CHEST IN LEFT-TO-RIGHT (L TO R) SHUNTS The chest X-ray can be useful in deciding the site of shunt, quantifying it and to some extent assessing severity of pulmonary arterial hypertension and presence of pulmonary venous hypertension. The L to R shunts can be at pre-tricuspid (i.e. atrial shunts) or post-tricuspid (ventricular or aortopulmonary) level.9 All the lesions causing left to right shunt will result in increased pulmonary blood flow; the heart size correlates with the degree of shunt. The larger the shunt quantum the larger will be the heart size (provided that there is no other reason for increase in heart size—like anemia). The presence of pulmonary arterial and venous hypertension should be assessed as discussed earlier. In presence of shunt at atrial level, the right atrium (RA) and right ventricle (RV) are dilated and the aortic shadow is inconspicuous. The atrial level shunts are mostly due to atrial septal defect (ASD) (Fig. 2.3). The shunt at ventricular level will result in enlargement of left atrium (LA) and left ventricle (LV) (Fig. 2.4). In shunts at aortopulmonary level (PDA or aortopulmonary window), the aorta is also dilated in addition to LA and LV (Fig. 2.5).10-12

Special Diagnostic Features of Some Shunts 1. LV-RA shunt: LV-RA shunt is often small and does not result chamber enlargement. If the shunt is large enough, it will result in enlargement of all four chambers. 2. Scimitar syndrome: Anomalous drainage of the right pulmonary vein to inferior vena cava (IVC) can produce a typical X-ray picture of a Turkish sword “scimitar” in the right lower lung. This is usually associated with varying grades hypoplasia of right lung and pulmonary arteries causing shift of the cardiac shadow to the right side.

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A

B

31

C

Figures 2.4 A to C: X-ray chest from patients with different degree of shunt at ventricular level. (A) X-ray chest showing normal sized heart, MPA segment is not prominent and pulmonary vasculature is within normal limits suggestive of less than 2:1 shunt. (B) X-ray chest shows mild cardiomegaly with mild prominence of MPA segment. Pulmonary vasculature is also prominent. This is suggestive of moderate shunt. (C) X-ray chest shows cardiomegaly (LV type apex) with enlargement of MPA segment. Pulmonary vasculature is markedly increased. The aortic shadow is not prominent. It is indicative of large shunt at ventricular level

A

B

C

Figures 2.5 A to C: X-ray chest from patients with different degree of shunt at ductal level. (A) Small shunt (B) Moderate shunt (C) Large shunt. Notice the enlarged aorta and left ventricular configuration in all of them. The degree of cardiac enlargement and pulmonary vasculature increases with increasing level of shunt

OBSTRUCTIVE LESIONS The chest X-ray helps in the diagnosis of the site of obstruction but does not help in evaluating its severity. It is of very limited value in infants with critical obstructive lesions because poststenotic dilation is not often severe enough to cast a shadow in the X-ray.

Valvular Pulmonary Stenosis (PS) Dilated main pulmonary artery (MPA) and left pulmonary artery (LPA) are the hallmark for the diagnosis of pulmonary valve stenosis in the older child. The MPA and LPA dilation is not so remarkable with dysplastic pulmonary valve. The heart size is usually normal. If very critical,

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Figure 2.6: X-ray chest of patient with critical PS with severe tricuspid regurgitation. Note the presence of massive cardiomegaly with prominent MPA and RA enlargement. The pulmonary vascular markings are diminished

Figure 2.7: Characteristic X-ray findings in patient with valvular aortic stenosis with preserved left ventricular function. Note the presence of normal heart size with dilated ascending aorta suggestive of the diagnosis

pulmonary stenosis with significant tricuspid regurgitation is present, cardiac enlargement occurs with prominent RA and SVC (Fig. 2.6).13,14

Valvular Aortic Stenosis (AS) Dilated ascending aorta is typical of aortic valve stenosis in the older child (Fig. 2.7). Normally ascending aorta does not form the right border of the heart. If the ascending aorta dilates, it will result in a convex shadow to the right of the spine above the RA. If the aortic stenosis is severe the cardiac configuration became left ventricular in type. Cardiac enlargement with evidence of pulmonary venous hypertension is seen with associated congestive heart failure.

Coarctation of Aorta The ascending aorta and the left subclavian artery are prominent. Aortic arch may or may not be prominent depending on the associated arch hypoplasia. At times in classical coarctation of aorta without arch hypoplasia a notch at the site of coarctation may be seen on chest X-ray between the dilated proximal and distal segments—‘3 sign’ (Fig. 2.8A). Before the era of echocardiography, this sign was very useful in the diagnosis of coarctation and was confirmed by Barium Swallow causing indentation on barium filled esophagus by the dilated segment of aorta, proximal and distal to the area of coarctation the so-called ‘E/reversed 3 sign’ (Fig. 2.8B). After the age of 4 to 5 years, rib notching can be seen from 3 to 8th rib as wavy indention at the lower border of the rib due to collaterals (Fig. 2.8C). If the left subclavian artery arises below the coarctation, the rib notching is seen only on the right side. In case there is aberrant right subclavian artery below

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B

A

C

Figures 2.8A to C: Characteristic radiologic findings in patient with coarctation of aorta. (A) This X-ray chest showing characteristic ‘3 sign’ (arrow at the site of coarctation). (B) Barium swallow showing ‘E or reversed 3 sign’. (C) Findings of rib notching (arrow) in presence of long standing coarctation of aorta

the coarctation the rib notching is seen on left side. Rarely both subclavian arteries may arise below the coarctation segment, then no rib notching will be seen.15,16

CYANOTIC HEART DISEASE Patients presenting with cyanosis and congestive heart failure, the chest X-ray can help in categorizing if the pulmonary blood flow is increased, decreased, normal or if there is severe pulmonary venous hypertension. This helps in categorizing the patient in different disease groups. It is not advisable to depend on the X-ray to arrive at an anatomic diagnosis.

Cyanosis with Increased Pulmonary Blood Flow Most of the patterns described below are better seen beyond infancy. It is important to recognize that, in the newborn or young infant, the chest X-ray has very little sensitivity and often very limited specificity in identifying the specific condition. D-Transposition of Great Arteries (DTGA) If the X-ray chest shows increased pulmonary blood flow, cardiac enlargement with right ventricular configuration and narrow pedicle giving the typical appearance of “egg on side”, the most likely diagnosis is complete transposition of great vessels (Fig. 2.9). In some of these cases, there may be differential increase in the pulmonary blood flow in the right upper lobe of the lung due to abnormal orientation of the subpulmonary outflow.

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Figure 2.9: Characteristic ‘Egg on side’ appearance in d-transposition of great arteries. Note presence of cardiomegaly with narrow pedicle and increased pulmonary vascular markings

The majority of newborns with DTGA do not have a typical or diagnostic X-ray. It is difficult to assess vascularity and the cardiac configuration may not acquire the typical egg-on-side appearance.

Persistent Truncus Arteriosus The chest X-ray will show left ventricular configuration, increased heart size, prominent aorta, and absence of main pulmonary artery shadow with increased vasculature. Some cases may show higher shadow of the hilar pulmonary arteries causing the waterfall appearance. In 30 to 40% case a right aortic arch may be seen.17 Total Anomalous Pulmonary Venous Connection (TAPVC) The chest X-ray shows enlarged right heart chambers with increased pulmonary blood flow. If the anomalous pulmonary veins drain via the left vertical vein, then typical “figure of 8” or “snowman appearance” (Fig. 2.10) is produced due to dilated left and right vena cava and innominate vein forming upper part and enlarged right sided chambers the lower part of the “figure of 8”. This sign is only seen in the relatively older survivors of natural history and is not characteristic of infants with supracardiac TAPVC to the left vertical vein. If the drainage is directly to the right superior vena cava (RSVC) then only RSVC is dilated with other features of atrial shunt. Other types of TAPVC will show evidences of large atrial shunt only. When the chest X-ray shows a hazy ground glass appearance, obstructed TAPVC (often of the infra-diaphragmatic type should be suspected), as it is usually associated with severe obstruction of the common pulmonary venous channel resulting in severe PVH (Fig. 2.11). This X-ray may be mistaken for hyaline membrane disease and the clinical picture may be quite similar as well. It is useful to consider an echocardiogram at a very low threshold for such situations to ensure that this serious but often correctable condition is not missed.18 Cyanosis with Heart Failure and Decreased Pulmonary Blood Flow There are two important differential diagnoses.

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Figure 2.10: Characteristic ‘Snow Man appearance’ or ‘Figure of 8’ in patient with supracardiac TAPVC draining into left innominate vein through vertical vein. Upper part of figure of 8 is formed by ascending vertical vein, dilated innominate vein and dilated SVC and the lower part of figure ‘8’ by the cardiac shadow. The pulmonary vasculature is increased

Figure 2.11: Obstructed total anomalous pulmonary venous connection. Note the ground glass appearance of the lung parenchyma that results from severe pulmonary venous hypertension. This can be mistaken for hyaline membrane disease

Severe Pulmonary Stenosis with Tricuspid Regurgitation The chest X-ray shows enlarged right atrium and right ventricle with enlarged main and left pulmonary artery and decreased pulmonary blood flow (Fig. 2.6). The cyanosis in these cases is due to presence of atrial right to left shunt. Severe Ebstein’s Anomaly of Tricuspid Valve The classical features being cardiomegaly with right ventricular configuration, right atrial enlargement, main pulmonary artery segment not prominent, giving an appearance of pencil sharp outline with decreased pulmonary blood flow (Fig. 2.12).19, 20

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Figure 2.12: Typical X-ray chest findings in patients with Ebstein’s Anomaly of tricuspid valve showing presence of cardiomegaly with absent MPA shadow, gross RA enlargement with diminished pulmonary vascular markings

Cyanotic CHD with Decreased Pulmonary Blood Flow Tetralogy of Fallot (TOF) The cardiac size is usually normal with right ventricular configuration (lifted, upturned and rounded apex). The aorta is usually enlarged and in the area of main pulmonary artery concavity may be seen—called “pulmonary bay” (Fig. 2.13). In some cases with tight isolated infundibular stenosis this area may show a little prominence (at the site of infundibulum, i.e. a little below anatomical site of main pulmonary artery). This is due to the dilated infundibular chamber.21 The hilar vessels are small with thinned out pulmonary vasculature. One-third of these patients have a right-sided aortic arch that is identified by the indentation on the right border of tracheal shadow. Similar X-ray findings can be Figure 2.13: X-ray chest in patient with tetralogy seen in patients with double outlet right ventricle of Fallot showing normal heart size, RV type with VSD and pulmonary stenosis, d-transposition apex, presence of pulmonary bay and diminished pulmonary vascular markings. Right aortic arch is with VSD and pulmonary stenosis or pulmonary also seen atresia with VSD.22,23 As stated earlier in tetralogy and similar conditions, the heart size is normal. Heart size may enlarge if there is associated anemia, valvular regurgitations, bacterial endocarditis or any other severe infection. In selected patients with very tetralogy, pulmonary atresia and very large collaterals, cardiac enlargement may also be seen.

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A variant of Tetralogy of Fallots—TOF with absent pulmonary valve syndrome may produce characteristic X-ray picture due to marked dilation of both pulmonary arteries, right and/or left pulmonary artery (Fig. 2.14). The other rare association of TOF is absent left or right pulmonary artery. This may produce hypoplasia and/or markedly decreased vasculature on the side with absent pulmonary artery. Rarely one of the pulmonary artery may arise directly from the aorta then there will be plethoric lung field on the side with ectopic aortic origin of pulmonary artery.

Corrected (L) Transposition with VS and PS The X-ray appearance may be characteristic because of an enlarged left sided (L-malposed) aorta causing a smooth shoulder on upper left heart border. The heart size is normal with decreased pulmonary blood flow (Fig. 2.15).24

Figure 2.14: Characteristic X-ray chest finding in tetralogy of Fallot with absent pulmonary valve syndrome. Notice the markedly enlarged hilar pulmonary arteries. Rest of features is same as tetralogy of Fallot

Figure 2.15: X-ray chest showing smooth shoulder at left upper heart border, characteristic of L-malposed aorta with normal heart size and decreased pulmonary vasculature

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Eisenmenger’s Syndrome Severe pulmonary arterial hypertension with right to left shunt at atrial, ventricular or aortopulmonary level. The X-ray chest shows the main pulmonary artery and hilar branches are markedly dilated with pruning and oligemic peripheral lung fields (Fig. 2.16). End-on vessels may still be seen in lung fields as described for L to R shunts. In atrial level right to left shunt with severe PAH, there may be cardiac enlargement (right sided) due to tricuspid regurgitation, which is mostly associated with these lesions. In ventricular and aortopulmonary level right to left shunt with severe PAH, the heart size is usually normal. There is no left atrial or left ventricular enlargement. The aorta may be prominent in ductal level shunts.25

Figure 2.16: Characteristic X-ray findings in patient with Eisenmenger’s syndrome— normal heart size with markedly enlarged MPA and hilar pulmonary arteries, abrupt ‘cut off’ at proximal PA level and oligemic peripheral lung fields

CONCLUSIONS The X-ray today complements other modalities for evaluation of patients with congenital heart disease. The information on lung vascularity is of particular value. Heart size and chamber enlargement are also of additive value in specific situations. It is extremely important to evaluate a chest X-ray with the clinical picture in mind and correlate it with the other data. It is important to understand that many “typical” X-ray patterns that point to the specific diagnosis are not frequently seen. Their valve is particularly limited in young infants and newborns. However, it is useful to recognize them as they may help fine-tune the diagnostic process.

ACKNOWLEDGEMENT I am thankful to Dr. Kashyap Sheth, MD (Ped), Fellow in Pediatric Cardiology; for his help in preparing the manuscript.

REFERENCES 1. Elliott LP and Schiebler GL. X-ray Diagnosis of congenital heart disease. Springfield Ill, Charles C Thomas, 1968. 2. Elliott LP: Cardiac imaging in infants, children and adults, J.B. Lippincott Co., Philadelphia, 1991. 3. Steiner RM and Levin DC: Radiology of the heart in Heart Disease edited by Raunwald E, W B Saunders Co. (5th edn). 1997. pp. 204–39. 4. Sharma S, Gurpreet G: Imaging of CHD in Diagnostic Radiology Chest & Cardiovascular. (2nd edn). Berry M, Suri S, Chowdhury V, Mukhopadhyay S (eds), Jaypee Brothers Medical Publishers (P) Ltd, New Delhi. 2003;285–95.

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5. Tonkin IL, Kelley MJ, Bream PR and Elliot LP. The Frontal chest film as a method of suspecting transposition complexes. Circulation. 1976;53:1016. 6. Moes CAF: Analysis of the chest in the neonate with congenital heart disease. RCNA. 1975;13: 251–76. 7. Coussement AM: Objective radiographic assessment of pulmonary vascularity in children. Radiology 1973;109:649–54. 8. Campbell M and Gardner FE: Radiological features of enlarged bronchial arteries. Br Heart J. 1950;12:183. 9. Roberts WC: Radiologic differentiation of common anomalies. In: Adult congenital heart disease 1988;191–219. 10. Dimich I, Steinfield L and Park SC. Symptomatic atrial septal defect in infants. Am. Heart J. 1973;85:601. 11. Vickers CW, Kincaid OW, Dushane JW and Kirklin JW. Ventricular septal defect and severe pulmonary arterial hypertension: Radiologic consideration in selection of patients for surgery. Radiology. 1960;75:69. 12. Steinberg I. Roentgenography of patent ductus arteriosus. Am J Cardiol. 1964;13:698. 13. Abrahams DG and Wood P. Pulmonary stenosis with normal aortic rood. Br Heart J. 1951;13:519. 14. Chang CH. The normal roentgenographic measurement of the right descending pulmonary artery in 1085 cases. AJR. 1962;87:929–35. 15. Bjoork, L and Friedman R. Routine roentgenographic diagnosis of coarctation of the aorta in the child. Am J Roentgen. 1965;95:636. 16. Drexler CJ, Stewart JR and Kincaid OW. Diagnostic implications of rib notching. Am J Roentgen 1964;91:1064. 17. Danelius G. Absence of hilar shadow. Diagnostic sign in rare congenital cardiac malformations. (Truncus arteriosus soliterius with heterotropic pulmonary blood supply). Am J Roentgen. 1942; 47:870. 18. Grishman A, Poppel MH, Simpson R and Sussman ML. Roentgenographic and angiocardiographic aspects of (1) aberrent insertion of pulmonary veins associated with interatrial septal defect and (2) Congenital arteriovenous aneurysm of lung. Am J Roentgen. 1949;62:500. 19. Amplatz K, Lester RG, Schiebler GL, Adams P Jr and Anderson RC. Roentgenologic features of Ebstein’s anomaly of the tricuspid valve. Am J Roentgen. 1959;81:788. 20. Kieffer SA and Carey LS. Tricuspid Atresia with normal aortic root. Roentgen- anatomic correlation: Radiology. 1963;80:605. 21. Walgein, DE and Singleton EB: Tetralogy of Fallot. Radiological evaluation before and after surgical treatment. Radiology. 1963;81:760. 22. Hallerman FJ, Davis GD, Ritter RD and Kincaid OW. Roentgenographic features of common ventricle. Radiology. 1966;87:409. 23. Dayem MK, Preger L, Goodwin JF and Steiner RE. Double outlet right ventricle with pulmonary stenosis. Br Heart J. 1967;29:64. 24. Carey LS and Ruttenberg HD. Roentgenographic features of congenital corrected transposition of great vessels. Am J Roentgen. 1964;92:623. 25. Sharma S. Proceedings of symposium and workshops in cardiovascular and interventional radiology. Springer-Verlag, Singapore, 1997.

3

The ECG: A Practical Approach to the Pediatric Electrocardiogram BRJ Kannan

Electrocardiogram (ECG) is a simple and useful investigation that is often under utilized. It records changes in the electrical activity of the heart and the information provided by ECG is not readily obtained by any other method. Apart from ischemia detection, ECG plays an important role in arrhythmia detection and management. Its role is somewhat limited in the diagnosis of structural heart disease. However, it does provide important clues regarding the changes in cardiac chambers and supplements information required for diagnosis along with clinical examination and chest radiography. Some of the limitations of pediatric electrocardiography are as follows: • Age dependent changes occur, therefore, single set of criteria cannot be applied to children in various age groups • Absence of specific guidelines for chest lead placement • ‘Borrowed’ criteria for chamber hypertrophy from adult experience • Poor sensitivity, i.e. a child with large VSD might not have large LV forces • Complexity of congenital heart diseases with very few lesion specific changes Nonetheless, ECG has an important role to play and this chapter will address its practical utility in the diagnosis and management of children with heart diseases.

BASICS OF RECORDING AND INTERPRETATION While recording ECG in a small child, limb lead electrodes should be placed more proximally to reduce motion artifacts. The usual ‘12 lead ECG’ is not enough; additional V3R or V4R leads have to be recorded in children with heart suspected congenital heart disease. Standard gain (10 mm/mV) is used. If the QRS voltages are very large, then the gain might be halved. The ECG is recorded at a paper speed of 25 mm per second. The time or duration of a wave is measured in milliseconds or seconds. Each small square represents 40 milliseconds (0.04 second). The voltage is measured in small squares or millivolts (mV). Each small square represents 0.1mV. Intervals should be hand measured, as the computerized systems are often inaccurate, especially in the neonates. Intervals in children increase with age, reaching the

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adult normal values by 7 to 8 years of age. The PR interval is measured from the onset of the P wave to the Q wave or R wave if no Q wave is present. It is often best measured in lead II. The duration of QRS complex is measured in the lead with an initial Q wave. The QT interval is often best measured in leads II, V5 and V6 and the longest value should be used. Corrected QT (QTc) is calculated using Bazett’s formula. Corrected QT = QT interval/ √RR For example, if there are 15 small squares between two consecutive R’s, then the heart rate is 100/min (1500/15).

Axis Detection Select leads aVF and I. Determine if the net QRS voltage is positive or negative in these leads. For example, if the R wave height is 10 mm (above the isoelectric line) and S wave height is 3 mm (below the isoelectric line), then the net QRS voltage is positive (+7). If the R wave is short and S wave is longer, the net QRS voltage would be negative (Fig. 3.1). The QRS axis can be located using the following simple rule: Lead I Positive Negative Positive Negative

Lead aVF Positive Positive Negative Negative

Interpretation Normal axis Right axis deviation Left axis deviation North-west axis

Comment Abnormal in infancy Normal in neonates Abnormal at any age Abnormal at any age

neonates and early and in early infancy

Normal Variations and Related Abnormalities Many tables of ECG standards for various measurements are available.1,2 However, the practical utility of these tables is limited. The salient age related changes that one needs to know are as follows:

Figure 3.1: The four quadrants representing various axes have been shown. The arrow shows a normal QRS vector. Similarly, by determining the net voltage of P wave, one can locate the ‘P axis’

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1. Normal HR in the neonates vary between 120 to 230/min, it increases further by first or second month of life and gradually decreases over the next 6 months. Resting heart rate is about 120 beats/min at 1 year, 100 at 5 years and reaches adult values by 15 years.2 2. Appearance of secondary r waves (r’ or R’) in right chest leads is normal in neonates. 3. At birth, right axis deviation of mean QRS vector is the rule. The axis becomes normal by 1 year of age. Hence, normal or leftward QRS axis is abnormal in the neonatal period and early infancy. Common conditions with leftward axis of QRS vector are tricuspid atresia and AV canal defects. 4. Dominant R in right precordial leads can persist up to 6 months to 8 years; in the majority, the R/S ratio in lead V1 becomes less than 1 by 4 years. 5. Q waves are normally seen in leads II, III, aVF, V5 and V6. • If Q waves are seen in other leads, it is abnormal. • Presence of Q wave in inferior leads (II, III and aVF) is due to clockwise loop of initial QRS vector. This finding is seen in majority of congenital heart diseases also. • When Q waves are absent in inferior leads but are seen in Leads I and aVL, it is due to counterclockwise loop of the initial QRS vector. This is a feature of tricuspid atresia, AV canal defects and inlet VSD. • Deep Q waves in lateral leads might point towards underlying anomalous origin of left coronary artery from pulmonary artery. 6. QT interval is highly variable in the first 3 days of life. If the corrected QT is more than 0.44 seconds (440 ms), it is abnormal3 (Fig. 3.2). • Hypokalemia, hypocalcemia, hypothermia, and cerebral injury are common causes of prolonged QT interval. • Drug induced QT prolongation has to be ruled out and the drugs commonly implicated are macrolide antibiotics, trimethoprim, cisapride, etc.

Figure 3.2: QT prolongation: The measured QTc was 680 ms with deep inverted T waves in multiple leads. This was secondary to the administration of Azithromycin

The ECG: A Practical Approach to the Pediatric Electrocardiograme



7.

8.

9.

10. 11.

12.

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• Consider Long QT syndrome, if clinically relevant. A comprehensive discussion on congenital long QT syndromes and the management flow chart is available in the guidelines given by European society of cardiology.4 T wave in lead V1 can be upright at birth and it inverts by 7 days and typically remains inverted until 7 years of age. • Upright T waves in right precordial leads (V1-V3) between ages 7 days and 7 years usually indicate right ventricular hypertrophy even if the voltage criterion is not fulfilled. Atrial and ventricular extra systoles are common and are typically abolished with exercise. Also, sinus arrhythmia is very common and there could be irregularly irregular rhythm (Fig. 3.3). The heart rate slows in expiration and speeds up in inspiration. Some children would present with significant sinus bradycardia. Both these conditions are due to excessive vagal tone. Exercise consistently increases the heart rate and the rhythm becomes regular in these children. Sinus pauses as long as 800 to 1000 ms can be seen especially during feeding, sleep, defecation or other times of increased vagal tone. At times, periods of junctional rhythm, i.e. narrow QRS complexes without preceding P waves can be seen. Wandering pacemaker: Change in P wave axis and morphology in different beats due to the shift of pacemaker from the sinus node to other sites. It is a non-pathological finding. Early repolarization: Some children especially in the adolescent age group would show ST segment elevation of 1 to 4 mm with the concavity facing upwards (Fig. 3.3). They can also have terminal T wave inversion. Premature children, especially those born before 28 weeks gestation, may not show RV dominance. Chest leads may show LV dominance and QRS axis can be normal or leftward even at birth.

Figure 3.3: There is significant irregularity of the rhythm. However, all QRS complexes are preceded by P waves with constant PR interval. This is due to sinus arrhythmia. Note the ST segment elevation with concavity facing upwards due to early repolarization. Both the findings are normal in children

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Analysis of P Wave • •

•

P wave amplitude varies very little with age. Unlike QRS axis, P wave axis is normal (positive in both lead I and aVF) from birth due to sinus nodal origin of the atrial impulse If the P axis is different, it indicates ectopic atrial rhythm, i.e. the atrial impulse arises from some other site. Low atrial origin of the rhythm is common in congenital heart disease where the P waves are typically negative in inferior leads (II, III and aVF) In children with situs inversus, right axis deviation of the P wave is seen (Fig. 3.4).

Right Atrial Enlargement • •

P wave amplitude is increased to more than 0.25 mV (2.5 mm) with a relatively normal P wave duration (tall and peaked P waves). The changes are best visualized in lead II. Tricuspid atresia, pulmonary atresia with intact ventricular septum and severe pulmonary stenosis are commonly associated with right atrial enlargement.

Left Atrial Enlargement •

•

The changes are best visualized in lead V1 where the terminal negative deflection is increased (> 0.1 mV) and prolonged (> 40 ms). Prolonged P wave duration with increased notching can be seen in lead II due to left atrial enlargement but it is less specific Mitral atresia and post-tricuspid shunts (VSD, PDA, aorto pulmonary window) show left atrial enlargement.

Figure 3.4: There is right axis deviation of P wave (black arrows) as it is negative in lead I and positive in lead aVF. This is consistent with atrial situs inversus. The chest leads show progressive reduction of the QRS size without the normal progression of R wave, which is suggestive of dextrocardia

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Analysis of PR Segment PR segment reflects the time taken by the depolarization impulse to travel across the atrium and the atrioventricular node. AV block results in prolongation of the PR interval. • First degree block: Prolonged AV interval. • Second degree block, Mobitz Type I (Wenkebach type): With each successive beat, the PR interval lengthens resulting in a ‘dropped’ QRS. This could be a normal finding and does not usually indicate an adverse prognosis. • Second degree block, Mobitz Type II: The PR interval is normal or mildly prolonged but it is constant in successive beats. There is sudden, intermittent loss of conduction resulting in ‘dropped’ QRS. This is always pathological, carries high-risk to progress to complete AV block. • Third degree AV block: This is also called as complete heart block (CHB) where no atrial impulse is conducted to the ventricles. Atrial rate would be higher than the ventricular rate with complete AV dissociation (Fig. 3.5). If the escape rhythm originates near the His bundle, the resulting QRS would be narrow. If the escape focus is lower down, the resultant QRS complex would be broad. Congenital complete heart block is often not associated with any underlying congenital heart disease. About 2–5% of mothers with autoimmune antibodies have children with CHB and this condition carries a high mortality risk especially in the first 3 months of age.7 CHB can be also seen in children with congenitally corrected transposition of great arteries and AV canal defects. Acquired CHB can be seen in myocarditis, digitoxicity, following cardiac surgery and rarely, after interventional procedures such as catheter closure of the membranous VSD.

Figure 3.5: Complete heart block: Atrial rate is 90/min and the ventricular rate is 45/min. Arrows indicate the P waves. Though apparently P wave is seen before each QRS complex, there is PR interval that is not constant suggestive of AV dissociation

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Causes of Short PR Interval Common causes are Wolff Parkinson White syndrome (WPW syndrome), ectopic atrial pacemaker from the low right atrium, mannosidosis, Fabry’s disease and Pompe’s disease.

WPW Syndrome (Preexcitation) It is because of premature conduction of atrial impulses to ventricles through accessory pathways resulting in delta wave and a fusion complex in the ECG (Fig. 3.6). The preexcitation may be subtle and only detected in the mid precordial leads. The prevalence in children has been estimated to be 0.15 to 0.3%, higher in those with structural heart disease.5 Congenital heart diseases with higher prevalence of WPW syndrome are: Ebstein’s anomaly of tricuspid valve, congenitally corrected transposition of great arteries, hypertrophic cardiomyopathy and cardiac rhabdomyoma. WPW syndrome is the commonest cause of paroxysmal supraventricular tachycardia in children. The incidence of sudden death has been estimated to be as high as 0.5% and cardiac arrest may be the initial presentation.6 Hence, it is very important to identify this electrical abnormality. Digoxin and Verapamil have to be avoided in this condition and beta blocker therapy is the ideal choice.

Figure 3.6: WPW syndrome: Short PR interval is seen. The slurring of initial portion of R wave (delta wave) is seen in all leads, especially II, III, aVF, V5 and V6 (black arrows)

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Analysis of QRS Complex Bundle Branch Blocks Intraventricular conduction abnormalities due to bundle branch blocks (BBB) are uncommon in normal children. BBB result in wide QRS duration of > 0.14 sec or more. Right BBB is diagnosed if V1 shows tall wide notched R (rSR′ pattern) and the lateral oriented leads (lead I, V5 and V6) show notched wide S wave (Fig. 3.7). In left BBB, the lateral leads show tall notched R wave and V1 shows wide notched QS or rS complex. Right BBB is commonly seen following open-heart surgery.

Right Ventricular Hypertrophy •

• •

Many congenital heart diseases are associated with right ventricular hypertrophy. Tall R in V1 (R/S >1), deep S in V6 and upright T wave in right precordial leads indicate the presence of right ventricular hypertrophy. Conditions with pressure overload of right ventricle, e.g. valvar pulmonary stenosis show small q and tall R pattern or only tall R could be seen (Fig. 3.8). Conditions with volume overload of right ventricle, e.g. atrial septal defect show rSR’ pattern.

Left Ventricular Hypertrophy It produces increased voltages in the left sided leads and manifest as tall R wave in leads V5, V6 and deep S wave in lead V1 (Fig. 3.9). No definite criteria based on the voltages are available to diagnose ventricular hypertrophy in children. Another important clue for the presence of left ventricular hypertrophy is the presence of T wave abnormalities in leads V5 and V6.

Figure 3.7: Right bundle branch block: Broad QRS complexes with rsR′ pattern in V1. The ST-T changes are secondary to the bundle branch block. This is a common finding in children following open-heart surgery

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Figure 3.8: Right ventricular hypertrophy: There is right axis deviation of QRS. Tall R wave, ST depression and T inversion in leads V1-3 is suggestive of right ventricular hypertrophy with pressure overload strain

Figure 3.9: Left ventricular hypertrophy: Tall QRS complexes in the lateral leads with ST depression and T inversion due to pressure overload of LV

The ECG: A Practical Approach to the Pediatric Electrocardiograme

• • •

•

49

Tall T waves would indicate underlying volume overloading condition (VSD, PDA) ST depression and T inversion in lateral leads could result from pressure overloading of left ventricle (aortic stenosis, coarctation of aorta) Peculiarly, neonates with coarctation of aorta have ECG features of right ventricular hypertrophy (and not left ventricular hypertrophy) as the right ventricle receives a greater proportion of systemic venous return from the SVC and faces the systemic vascular resistance in the fetal period through the ductus arteriosus. In children with post-tricuspid shunts, large amplitude equi-phasic QRS complexes could be seen in the mid precordial leads suggestive of biventricular hypertrophy (Katz-Wachtel phenomenon).

Cardiac Position Related QRS Changes In levocardia, the major portion of the ventricles is positioned to the left of the midline with the apex pointing to the left. The chest leads show a progressive change from a dominant S wave in lead V1 to a dominant R wave in leads V5 and V6. In children with dextrocardia where the major portion of the ventricles is to the right of midline, this normal progression is not seen. Instead, there is progressive reduction in the amplitude of QRS from V2–V6 (see Fig. 3.4). In these children, right-sided leads are commonly taken in the positions corresponding to the left sided leads that would show ‘normal’ progression of QRS complexes. However, further interpretation of the right-sided leads regarding chamber enlargement is not possible.

Analysis of ST Segment ST segment elevation is commonly because of early repolarization as mentioned above. The next common cause is pericarditis. Other causes are: Hyperkalemia, intracranial hemorrhage, pneumothorax or pneumopericardium. Structural anomalies that can cause ST segment elevation are anomalous origin of left coronary artery from pulmonary artery and Kawasaki’s disease related coronary arteritis. The former more commonly presents with deep Q waves in leads I, aVL, V5 and V6 with associated T wave inversion. Brugada syndrome is a genetic disorder associated with a high incidence of sudden death due to ventricular fibrillation. ECG in this condition shows ST segment elevation with RBBB pattern in the right precordial leads. ST segment depression is seen secondary to pressure over load strain. In right ventricular strain, ST depression is seen in right precordial leads while it is seen in left precordial leads in left ventricular strain.

Analysis of T Wave In children, T wave is inverted in V1 to V3 between 7 days to 7 years. At times, T remains inverted in older children and adolescents (persistent juvenile T). As mentioned above, upright T wave in V1 would indicate right ventricular hypertrophy even in the absence of high amplitude R wave. • T wave inversion in lateral leads represent relative or absolute ischemia and is a feature of ventricular pressure overload strain, ALCAPA and Kawasaki’s disease with coronary involvement

50 •

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Tall T wave is one of the ECG manifestations of hyperkalemia. Other manifestations of hyperkalemia are disappearance of P wave, broadening of QRS wave, ST segment disappearance resulting in sine wave In hypokalemia, there is gradual reduction in the amplitude of T wave with eventual disappearance of T wave while U wave appears.

Some Disease Specific ECG Changes Most of the common congenital heart diseases like tetralogy of Fallot, D-transposition of great arteries, total anomalous pulmonary venous connection, truncus arteriosus, pulmonary atresia, hypoplastic left heart syndrome show Q waves in inferior leads (leads II, III and aVF), RVH and right axis deviation of the QRS vector. The ECG pattern does not help distinguish one condition from the other. However, absence of above mentioned features point towards some other diagnosis. Tricuspid atresia (Fig. 3.10): Q wave in leads I and aVL Left axis deviation of QRS Right atrial enlargement Dominant LV forces in the chest leads Common AV canal defect: Q wave in leads I and aVL Left axis deviation of QRS

Figure 3.10: Tricuspid atresia: Left axis deviation of QRS, Q waves in leads I and aVL and absence of RV forces in right sided leads

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Both right ventricular and left ventricular forces are seen (biventricular hypertrophy pattern)

Corrected Transposition of Great Arteries Normally, interventricular septum is depolarized from left to right that results in Q waves in lateral leads (leads V5 and V6). In this condition, as the ventricles are inverted, the septal depolarization is also reversed. Hence q waves are absent in V5 and V6, but can be seen in right precordial leads (V3R, V1).

Ebstein’s Anomaly (Fig. 3.11) Giant P waves, RBBB pattern, low voltage complexes (especially in limb leads). Look for the presence of delta wave, as WPW syndrome is commonly associated. The accessory pathway is usually right sided and hence V1 will show deep S wave.

Pompe’s Disease (Fig. 3.12) This condition produces apparent hypertrophy of the ventricles due to accumulation of glycogen. Short PR interval Very tall QRS complexes in multiple leads

Figure 3.11: Ebstein’s anomaly: Tall P waves because of right atrial enlargement. Broad and bizarre QRS complexes of RBBB morphology typically seen in this condition

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Figure 3.12: Pompe’s disease: Very tall QRS complexes in all the leads with relatively short PR interval

Dilated Cardiomyopathy In idiopathic dilated cardiomyopathy, ECG may be normal or show broad QRS complexes in sick patients. However, in any case of cardiomyopathy, two common treatable causes that need to be ruled out are ALCAPA and Tachycardiomyopathy. ECG signs of ALCAPA are ST depression and Q waves in lateral leads (leads V5, V6, I and aVL) (Fig. 3.13). Persistent high heart rate should make one to suspect the ongoing tachycardia. Even when the suspicion is small, it is useful to administer adenosine and record the effect on the rhythm (see chapter on Arrhythmias).

Arrhythmias in Children In any child presenting with tachycardia, it is important to document the rhythm with a 12 lead ECG unless the child is hemodynamically compromised. It is particularly useful to record the effects of administration of medications such as adenosine because important clues to the underlying arrhythmia are unraveled. Supraventricular tachycardia (SVT) is much more common than ventricular tachycardia (VT). QRS complex is narrow and similar to that of sinus rhythm in SVT. If the QRS complex is different from sinus, VT should be diagnosed even if the QRS is relatively narrow (4). Any wide QRS tachycardia should be considered as VT until proved otherwise (see chapter on Arrhythmias).

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Figure 3.13: ALCAPA: Note the deep Q waves in leads I, aVL, V5 and V6. These leads also show ST depression and T wave inversion

REFERENCES 1. Davignon A, Rautaharju P, Boisselle E, Soumis F, Megelas M, Choquette A. Normal ECG standards for infants and children. Pediatr Cardiol. 1979;1:123–52. 2. Goodacre S, McLeod K. ABC of clinical electrocardiography: Pediatric electrocardiography. BMJ. 2002;324:1382–85. 3. Schwartz PJ, Stramba-Badiale M, Segantini A, et al. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J med. 1998;338:1709–14. 4. Schwartz PJ, Garson A, Paul T, et al. Guidelines for the interpretation of the neonatal electrocardiogram. European Heart J. 2002;23:1329–44. 5. Sorbo MD, Buja GF, Miorelli M, et al. The prevalence of the Wolff Parkinson White syndrome in a population of 116542 young males. G Ital Cardiol. 1995;25:681–7. 6. Munger TM, Packer DL, Hammill SC, et al. A population study of the natural history of Wolf Parkinson White syndrome in Olomsted County, Minnesota, 1953-89. Circulation. 1993;87:866–73. 7. Buyon JP, Hiebert R, Copel J, et al. Autoimmune associated congenital heart block: long term outcome of children and immunogenetic study. J Am Coll Cardiol. 1998;31:1658–66.

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Imaging in Pediatric Cardiology

A. ECHOCARDIOGRAPHY

BRJ Kannan, R Krishna Kumar

Echocardiography refers to the evaluation of cardiac structure and function with images and recordings produced by ultrasound. It is the most cost-effective investigation in pediatric cardiology. While the clinical examination and chest radiograph give important clues regarding the underlying physiology, echocardiography helps in arriving accurate anatomical diagnosis upon which further management depends. Additionally, the information on physiology is refined considerably. In the vast majority of the cases, surgery or transcatheter intervention is planned solely based on echocardiography and the diagnostic cardiac catheterization has been limited to a very small group of conditions. It is essential for the person performing echocardiography to have a sound knowledge of anatomy and hemodynamics of congenital heart diseases. While performing the echocardiography, one has to correlate the anatomical features identified with the expected changes in the chambers and other structures to arrive at the correct diagnosis. A detailed description of echocardiography for congenital and other structural heart diseases can occupy an entire textbook. Only a brief outline will be presented here.

BASICS OF ECHOCARDIOGRAPHY There are four basic modes: B mode, M mode, Doppler and color flow imaging. B (brightness) mode is also called as 2D echo where the images are displayed real time in various shades of grey depending on their echo reflectance. Doppler’s mode helps to evaluate the velocity of blood across valves and in the blood vessels. Color flow imaging uses the Doppler’s principles where the direction of the blood is easily identified by color coding. If the blood flows towards the transducer, it is coded red and if it moves away, it is coded blue (Blue Away Red Towards—‘BART’). Color flow imaging also demonstrates whether the flow

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is laminar or turbulent (disturbed). M mode refers to recording of the movement of cardiac structures at a particle plane in single dimension. It is the least commonly performed mode in pediatric echocardiography. Each mode is not mutually exclusive but complementary to each other. Higher the frequency of the ultrasound, higher is the resolution power and lower is the tissue penetration capacity. Most of the children with thin chest wall have good echo window and hence a transducer frequency of 8  to 12 MHz is ideal. For older or obese children, a transducer with lower frequency is selected.

Sedation Protocol A well sedated or a quite child is essential for complete assessment. In neonates and young infants (< 2–3 months age), pharmacological sedation is seldom necessary. Feeding itself is good enough to keep the child quiet in majority of cases. In older infants and children, oral chloral hydrate is a safe and effective drug for sedation. It is administered at a dose of 50 to 100 mg/kg, maximum dose being 1.5 g. It takes 20 to 40 minutes for the onset of action and children remain sedated for 45 to 90 minutes. Over dosage can result in paradoxical excitement. Midazolam is the next commonly used drug. It can be administered intranasally for rapid onset of action at a dose of 0.2 to 0.3 mg/kg. An occasional child might need intravenous midazolam, administered at a dose of 0.1 mg/kg. The hypotensive effect of midazolam can precipitate an episode of cyanotic spell and hence intravenous administration should be avoided in a child suspected to have TOF like situation. The echocardiography laboratory should be equipped with wall suction and oxygen. Noninvasive blood pressure monitoring and oxygen saturation monitoring should be available.

Standard Transducer Positions (Fig. 4.1) Systematic segmental analysis has to be done irrespective of the underlying diagnosis. Generally, the echo evaluation is started with the subxiphoid (SX) view. Then, apical four chamber view (A4CV) is obtained followed by parasternal long axis view (PLAV), parasternal short axis view (PSAV), high parasternal and suprasternal views. At times, an apprehensive child might not allow SX view to be performed and hence one can start with apical view. Suprasternal view can result in mild tracheal compression that can wake up a sleeping child and hence it has to be done at the last. In the PSLV, the pointer of the transducer should be facing the right shoulder. In all other views, the pointer should be facing to the left. Even if the child has dextrocardia, this rule has to be followed. In each location, the evaluation should not be limited to one particular

Figure 4.1: Transducer positions in levocardia. The small circle indicates the position of the marker on the transducer

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sector of the heart. The transducer has to be swept in horizontal and vertical planes to assess the relation between various structures. In the screen, the image is displayed as a sector. The tip of sector is the site of the transducer and conventionally, it is at the 12 O’ clock position. In parasternal and suprasternal views, the same display is maintained in pediatric echocardiography also. However in A4CV, the ventricles are displayed above and atria are displayed below with the conventional display. Anatomically correct image is obtained if the image is rotated so that the tip of the sector is at the 6 O’ clock position. Assessment of chambers and vessels is easier with this modification. Similarly, the image has to be rotated in subxiphoid view. In each view, one should optimize the gain and keep the color sector smallest to the region of interest.

Measurements Standard M-mode left ventricle, left atrium and aorta measurements are taken in the PSLV. LV measurements are taken at a plane just at the tip of the mitral valve. Though traditionally ejection fraction is calculated in this view using Teicholtz formula, it has been found to be inaccurate especially when the geometry of the ventricle is altered. Hence, it is not necessary to routinely record LV parameters and EF in a child with CHD. It is appropriate to record in children with cardiomyopathy and dilated heart due to any cause (valvar regurgitation, postoperative LV dysfunction etc) in whom follow up echocardiograms need to be compared with the previous one. In these situations, ejection fraction is best calculated in the A4CV using the modified Simpson’s method. Standard charts are available with which the measurements of various structures are compared and z score value is obtained. If the z value is –3 or less, then the structure is considered abnormally small.1 Annulus of semilunar valve is measured in end systole and annulus of atrioventricular valves is measured in end diastole, i.e. with the valves in fully open position. Tricuspid annulus is measured in the A4CV, mitral annulus is measured both in A4CV and PSLV. Aortic annulus is measured in PSLV and pulmonary annulus is best measured in tilted PSLV or PSAV. Septal defects should be measured in more than one view. In ostium secundum atrial septal defects and ventricular septal defects complete enface reconstruction is possible by multiple measurements taken from various views in relation to the various structures around the defects.2 In sinus venosus defect, the superior extent is ill-defined and in primum defect, the inferior extent is ill-defined. Hence, in these conditions, an accurate measurement cannot be given. In patent ductus arteriosus, the pulmonary artery end is generally the narrowest and is mentioned as the size of the duct. The length of the PDA and the size at aortic end would help one to assess the suitability for coil closure or device closure.3 Branch pulmonary arteries are measured at the hilum. For right pulmonary artery, suprasternal coronal view is the best. Left pulmonary artery is generally measured in the left parasternal view. If it is not satisfactory, tilted suprasternal view can be used. In arch anomalies, ascending aorta, various segments of arch and descending aorta need to be measured accurately.

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Situs Identification This is best done in the subxiphoid view. In the short axis view, normally aorta is seen as a round structure over the vertebra just to the left of the midline while the inferior vena cava is seen to its right (Fig. 4.2). This is consistent with situs solitus. When these vessels are traced upwards, once can see the inferior vena cava (IVC) entering the right atrium while the aorta can be imaged crossing the diaphragm. In situs inversus, the above said relation would be reversed (Fig. 4.3). If both the great vessels are seen lying very close to each other in the same side or positioned anteroposteriorly, then it would favor the diagnosis of situs ambiguous. In many of these patients (especially those in polysplenia type heterotaxy), the suprahepatic portion of IVC is interrupted. Hence, when the venous channel is imaged upwards, it would be seen crossing the diaphragm and ascending upwards. If it lies to the right of aorta, then it is azygos continuation of IVC which opens into superior vena cava (SVC). If it lies to the left of the aorta, then it is hemiazygos continuation of IVC which opens into the innominate vein. The location of the atria depends on the situs, i.e. right atrium

A

D

B

A

B

Figures 4.2A and B: Arrangements of the abdominal viscera and great vessels in situs solitus. On the left is a picture of a cross section of the abdomen. On the right is a equivalent ultrasound image. Ao: Aorta, IVC: Inferior vena cava, Sp: Spine

C

Figures 4.3A to D: Coronal sweep in situs inversus. Images have been obtained by progressively sweeping upwards: Aorta, IVC: Inferior vena cava, Sp: Spine, RA: Right atrium, HV: hepatic veins

  

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is on the right side in situs solitus and it is on the left side in situs inversus, irrespective of the arrangement of the ventricles or great vessels.

Cardiac Position (Fig. 4.4) It refers to the orientation of the ventricles. When the apex of the heart is to the left, it is called levocardia. When it faces the right, it is called dextrocardia. Mesocardia refers to a heart with its apex in the midline. This naming is irrespective of whether the apex forming ventricle is right ventricle or left ventricle. When the apex faces the left but major portion of the heart is seen in the right thorax, it is usually secondary to lung pathology. It is referred to as ‘pseudodextrocardia’.

Chamber Identification IVC draining atrium is generally taken as right atrium and pulmonary vein draining atrium is taken as left atrium. Right atrium has broad based short appendage and left atrium has long finger like appendage. Though atrial appendages are said to be useful in differentiating right vs left atrium, it is not very helpful echocardiographically. Generally, the anterior ventricle is right ventricle. The tricuspid valve is more apically displaced as compared to mitral valve. Presence of moderator band and significant trabeculations would help one to identify the right ventricle. The most important and specific finding is the identification of septal attachment of the tricuspid valve (septophilic AV valve). Left ventricle is identified by its nontrabeculated smooth septal surface with the chordae and papillary muscles attached to the lateral wall (septophobic AV valve). Interventricular relation is mentioned with letters D and L based on the embryological rotation of bulboventricular loop. D refers to dextro loop where the morphological RV is to the right of LV. L refers to levo loop where the morphological RV is to the left of LV.

Imaging the Great Vessels There are no definite echocardiographic features to identify a great vessel as aorta or pulmonary artery. An early branching vessel is generally pulmonary artery. The vessel giving off the coronary arteries is aorta. Pulmonary artery confluence can be best imaged in the PSAV and suprasternal coronal view. The great artery relationship is mentioned based on the positions of the aortic and pulomonary valves/annului and it does not refer to the ascending aorta and main pulmonary artery relationship. Normally, PA is anterior and to the left of aorta.

Figure 4.4: Positions of the heart. Images have all been obtained in the subxiphoid coronal view

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If aorta is anterior, then it is malposed. If it is placed anterior and to the right of PA, it is called D-malposed aorta. If it is placed anterior and to the left of aorta, it is called L-malposed aorta. One has to remember that the PA cannot be positioned anterior and to the right of aorta in a situs solitus situation.

Imaging Pulmonary Veins Right upper pulmonary vein is best imaged in SX long axis view. After viewing the superior vena cava, the transducer is slightly swept to the right to image the right upper pulmonary vein. Other pulmonary veins can be seen in parasternal short axis view. After imaging the main pulmonary artery and its bifurcation, the transducer is tilted posteriorly when the pulmonary veins would be seen entering the left atrium. A4CV commonly shows up right lower pulmonary vein and left upper pulmonary vein. One needs to look for additional pulmonary veins that might drain directly into superior vena cava or innominate vein.

Limitations of Echocardiography It is important to recognize that there are situations where echocardiography has major limitations. Alternative imaging modalities are required in these situations. In general, ultrasound tends to get scattered by air. It cannot, therefore be used to see vascular structures inside lungs. The reliability of echocardiogram is critically dependent on the presence of a good “window”. A solid tissue in close proximity with the heart allows good transmission and provides an excellent window. The liver and thymus are examples of organs that provide acoustic windows and enable acquisition of good images. Table 4.1 lists the key limitations of echocardiography and how they can be overcome. Common Sources of Error and How to Avoid Them Echocardiography is a powerful tool and has the potential of identifying most forms of CHD with great precision. However, it is important to respect the following core principles to get the best of this extremely useful modality: 1. Echo should be performed after a clinical evaluation except in dire emergencies. This ensures that the clinical question is answered. 2. The correct transducer and equipment should used. Failing to use a high frequency transducer can result in serious errors when high resolution is required. Evaluation of the aortic arch in a newborn, coronary arteries in infants and children require high resolution and therefore, high frequency transducers. Table 4.1 Limitation

Basis

Alternative imaging modality

Vascular structures inside lungs (branch pulmonary arteries and veins, aortopulmonary collaterals)

Ultrasound gets scattered by air

Computerized tomography (CT), magnetic resonance imaging (MRI), angiography

Postoperative state

Absence of the thymic window

Transesophageal echocardiography (TEE), CT and MRI

Older patients

Thick chest wall, deeper structures

TEE, CT, MRI

Coronary artery branches

Small size of vessels

CT, coronary angiography

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3. The results of the echo should be interpreted in context of the clinical situation and should not be viewed in isolation. 4. The echocardiographic diagnosis should be internally consistent. For example, a small VSD cannot coexist with severe pulmonary hypertension unless there is an alternative explanation (such as a large PDA). 5. The echocardiographic diagnosis should be comprehensive (as in the checklist above) irrespective of the clinical indication for doing an echocardiogram. This is because congenital heart lesions often do not conform to predictable stereotypes. Surprises are commonplace. 6. It is important recognize limitations of echo and seek alternative modes of imaging when key questions cannot be answered with satisfaction through echo.

The Checklist for Comprehensive Echocardiography A complete checklist of items to be looked for in an echocardiogram for congenital heart disease should be included in the report. An endeavor should be made to complete the checklist irrespective of the lesions identified. The list is as follows:   1. Visceral and atrial situs.   2. Location of the heart.   3. Sequential chamber relationship.   4. Systemic and pulmonary veins, atria and atrial septum.   5. AV valve morphology, attachments of the valve tissue and function.   6. The ventricles: Size and function.   7. The ventricular septum: Location of the VSD, size of the VSD.   8. The conotruncus: This includes the outflow tracts that lead to the great vessels and the great vessel origins including the semilunar valves. The presence or absence of obstruction in either of the outflow tracts, the nature of obstruction if present, the severity of obstruction. The sizes of the aortic and pulmonary valve annuli.   9. The status of the branch pulmonary arteries and areas of narrowing if any. 10. The presence or absence of PDA. 11. The aortic arch: Side, branching and the presence or absence of coarctation. 12. Coronary artery anatomy. 13. Physiological consequences of defects found (ventricular size and function, pulmonary artery pressure, etc.). The above list may be tailored to suit individual lesions and specific surgical issues that may arise. Some common congenital heart diseases and the important echocardiographic features are given below:

Atrial Septal Defects (Fig. 4.5) Secundum ASDs with adequate margins are amenable for transcatheter device closure. Echocardiography plays a crucial role in the case selection for this procedure. SX long axis view images the SVC and IVC rims. A4CV helps in the assessment of mitral rim and inferoposterior rim and the PSSA view is useful in assessing the retroaortic rime and corresponding posterior rim of the ASD. The measurement of the defect should be mentioned in all the planes. Associated mitral valve prolapse and mitral regurgitation has to be looked for.

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A

B

C

Figures 4.5A to C: Various types of atrial septal defects. All images are in the sagittal plane and have been obtained in the subxiphoid view

In ostium primum defects, the mitral rim is altogether absent and one can see both the atrioventricular valves attached at the same level. It is always associated with a cleft in the anterior mitral leaflet with or without mitral regurgitation. In a patient with clinical features of ASD, if the A4CV fails to show the defect, one should suspect sinus venosus defect or partial anomalous pulmonary venous drainage. Sinus venosus defects are visualized only in SX view in most of the patients. The defect is seen in the superior aspect of the interatrial septum bordered above by the superior vena cava. Anomalous drainage of right upper pulmonary vein is seen in nearly 95% of cases. Persistent left superior vena cava is also a common association of this defect.

Ventricular Septal Defects (Fig. 4.6) Depending on the location, VSDs are divided into four types. Perimembranous defects are bordered by aortic and tricuspid annuli. These defects are commonly but incorrectly labeled as subaortic defects. If the defect is bordered by aortic and pulmonary annuli, it is referred to as subpulmonic or doubly committed VSD. Inlet VSDs are located just below the AV valve. When the defect is entirely bordered by septal musculature, then it is termed as muscular VSD. Presence of aortic valve prolapse and or aortic regurgitation should be noted. In large unrestrictive VSD, color Doppler often would show some right to left shunt during some phases of diastole which does not signify inoperability. The pres- Figure 4.6: Picture of the ventricular septum showsure gradient across the VSD should be ing various parts of the septum enface

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evaluated with continuous wave Doppler. In unrestrictive defects, the gradient is usually < 20 mm Hg. In small restrictive VSDs, it is > 60 mm Hg. Moderate sized defects would have a gradient of 30–50 mm Hg.

Patent Ductus Arteriosus High parasternal and suprasternal views are useful in assessing PDA. The adequacy of the ampulla for coil or device closure should be assessed. The peak systolic and end diastolic pressure gradient across the PDA should be recorded. In small restrictive ducts, both the systolic and diastolic gradients would be high. Large unrestrictive ducts will have a small systolic gradient and negligible diastolic gradient. Even in large ducts, if the ampulla is adequately long, it would offer resistance to the flow in systole that would result in significant systolic gradient. However, the diastolic gradient would remain low. If flow reversal is seen in the descending aorta, it signifies a large duct.

Tetralogy of Fallot Large malaligned unrestrictive VSD can be imaged from multiple views. The overriding of the aorta can vary from 30–70%. The degree of overriding would differ in the same patient depending on the view. The important details needed are: Sites of right ventricular outflow obstruction, size of the pulmonary annulus, size of the main pulmonary artery and its branches, presence of any origin stenosis and if any coronary artery crossing the right ventricular outflow tract near the pulmonary annulus. Right arch is commonly associated, identified in suprasternal views. One should look for the presence of aortopulmonary collaterals. Echocardiography cannot image the collaterals well and if their presence is suspected based on clinical grounds, multislice computerized tomographic angiography or invasive catheter angiography should be performed. In children with pulmonary atresia where presence of PDA or aortopulmonary collaterals is the rule, angiography is invariably performed.

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B. ROLE OF CT, MRI AND RADIONUCLIDE SCANS IN PEDIATRIC CARDIOPULMONARY DISEASE Hemant Telkar, Bhavin Jankharia, Abhijit Raut, Sona Pungavkar

INTRODUCTION 2 D Doppler imaging is first line of imaging for pediatric cardiology diagnosis. The role of MRI has been known for more than a decade in pediatric cardiology. Diagnostic cardiac catheterization, which has a small but recognized risk, is usually performed if echocardiography fails to provide confident evaluation of the lesions. With advancement in CT scanners and now 64 slice MDCT scanners being available, MDCT CT scans can also be used for pediatric cardiopulmonary problems.

ROLE OF 64 SLICE MDCT This chapter will address the scope of the technique in demonstrating cardiopulmonary pathologies.

Technical Considerations The preprocedural requirement is 2 hours fasting for kids less than 1 year and 3 hours fasting for others. PediclorylTM (Triclofos) syrup is given in necessary dose to all those whose weight is less than 15 kg. Short anesthesia is given to others. Contrast used is nonionic contrast according to weight (1 mL/kg body weight) at rate of 0.2 to 0.5 mL/sec using single phase mode injector with intravenous access in arm or leg. Contrast related artifacts is an issue around SVC and therefore leg vein can be used for injection. Scanning parameters are chosen to give the least amount of mAs and kV in order to minimize radiation and not compromise on image quality. Nongated technique with scan time less than 10 seconds without breath hold are used and with data sets of 0.6 mm with 50% overlap are used to reconstruct MIP and VRT images. Postprocedure patient is allowed to leave CT suite after 15 minutes (as observation period) with necessary instruction. Pulmonary vasculature is primarily screened by 2D echocardiography. If there is possibility of pulmonary stenosis or if visualization of branch PAs is difficult, then CT angiogram can be used to demonstrate them (Fig. 4.7). MAPCAs are well-demonstrated using volume rendering technique with precise measurement (Fig. 4.8). The distal course of MAPCAs can be difficult to trace if they are smaller than 1.5 mm and merge Figure 4.7: Absent right pulmonary with simultaneously opacified pulmonary veins. artery

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Figure 4.8: This rare case of RIMA contributing to pulmonary supply

Segmental lobar supply by MAPCAs cannot be assessed. Aortic abnormalities like coarctation (Fig. 4.9) or aortic interruption (Fig. 4.10) or small rudimentary LV (Fig. 4.11) are well-demonstrated. This is one area where CT angiogram consistently demonstrates accurate detailing in all cases. In complex cardiac anomaly like hypoplastic left heart syndrome (see Fig. 4.5), though CMR is of help. CT scan is useful to demonstrate branch PAs and aortic abnormalities.1 Postoperative follow-up for patency of BT and BQ shunts can be used if 2D Doppler cannot assess it. Fallacy in CTA in slow flow is erroneous diagnosis of thrombus. Assessment of homograft (RV to PA) is possible (Fig. 4.12). Evaluation of pulmonary (Fig. 4.13) and SVC stents (Figs 4.14A and B) can be done accurately. For suspected aortoarteritis, CTA can screen long segment of the aorta and its branches using multiclice CT angiogram. Evaluation of proximal coronary artery in suspected cases of Kawasaki’s (Figs 4.15A and B) can be attempted (non-gated) when echo window is not good.

Figure 4.9: Coarctation of Aorta (MIP)

A

B

Figures 4.10A and B: Interruption of aortic arch: Ascending aorta (1) is interrupted with descending aorta, (2) seen as continuation of PDA

Limitation 1. CT angiogram has a limitation of the inability to show the pattern of flow, i.e ante or retrograde flow. Pressure measurements and knowing gradient across the stenosis is not possible on CTA.

Figure 4.11: Small rudimentary (*) LV

Imaging in Pediatric Cardiology

Figure 4.12: RV to PA patent homograft

A

65

Figure 4.13: Poststenting of PA in same case as (Fig. 4.12), pulmonary stent patent but ‘waist’ in mid segment

  

B

Figures 4.14A and B: (A) SVC stenosis; (B) Stent in SVC

A

  

B

Figures 4.15A and B: (A) CTA showing left main and left anterior descending artery dilation; (B) Corresponding 2D echo picture

2. Assessment of quantification of blood flow through MAPCAs and exact segmental flow cannot be assessed. 3. Simultaneous opacification of pulmonary veins hampers proper assessment of distal pulmonary artery.

Disadvantages Radiation exposure is an issue which needs to be addressed. Hence, cardiac MRI is more and more being used unless CT angiogram is mandatory.

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Advantages 1. 2. 3. 4.

Very short time for scanning. Majority of patients do not require anesthesia. Less motion artifact. Good spatial resolution.

Future The technical and clinical feasibility of MDCT in complex congenital heart disease in neonates is confirmed. After initial assessment with echocardiography, MDCT could probably replace diagnostic cardiac catheterization for further anatomical clarification in neonates.2 Though CT scan has a distinct advantage over MRI and Doppler due to the short time of acquisition, the reduced need for anesthesia, and better spatial resolution in aortopulmonary anomalies, ionizing radiation and intravenous contrast agents are an issue. Evaluation of chambers and their complex anomalies is still difficult on present scanners.2 However, newer hardware and software are there on the horizon to overcome these limitations.

MRI IN CONGENITAL HEART DISEASE Principles Cardiac MRI (CMR) is an excellent technique for the evaluation of structure and function in the heart. It has numerous indications including viability imaging, stress perfusion imaging, evaluation of cardiomyopathies and constrictive pericarditis as well as valvular diseases. CMR has been used in congenital heart disease (CHD) for well over 20 years.3 In the early years, its use was restricted to the depiction of anatomy, mainly for deciphering complex congenital anatomy. With the advent of better gradient strengths and faster machines, it was then possible to obtain functional information, initially starting with simple cine sequences and then flow information to now perfusion studies.4

Hardware and Software For performing good quality CMR studies, a 1.5 T scanner is a basic requirement, with gradient strengths at least better than 23 mT and rise times better than 150 ms. Sequences that allow fast anatomic imaging, cine imaging and flow analysis are essential, alongwith software for evaluating the consequent functional information obtained.

Techniques and Sequences Children less than 5 to 6 years old often require sedation. Older children can be scanned without sedation, if cooperative. All studies are ECG-gated and if the child cooperates, breath-hold is also used. However cine studies can be performed without breathhold, as well. Most studies, irrespective of the indication, follow this order: 1. HASTE black-blood anatomy sequences, 1 image per heart beat (Fig. 4.16). 2. TrueFISP (balanced gradient) white blood anatomy sequences.

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A

B

C

D

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Figures 4.16A to D: Corrected transposition of the great vessels. There is normal systemic (1 – SVC) and pulmonary (4 – pulmonary vein) drainage. There is atrial situs (2 – right atrium and 3 – left atrium). The right ventricle (6) is to the left of the left ventricle (5) and can be identified by the presence of the infundibulum (7 in C). There is consequent atrioventricular discordance. The aorta (8) however arises from the LV and the pulmonary trunk (9) from the RV, leading to ventriculararterial discordance. This is thus classic corrected transposition

3. TrueFISP cine sequences in the four-chamber, two-chamber and short-axis views as well other views, such as LVOT, RVOT, inlet and outlet, valvular transaxial, etc. (Fig. 4.17). 4. Phase-encoded gradient sequences for flow information across valves or stenotic areas.

Contraindications As with most MRI studies, the presence of electromagnetic devices, which if they stop or malfunction can hurt or kill the patient, are contraindications. These include pacemakers and cochlear implants. Intracranial aneurysm clips are a contraindication, as are mobile foreign bodies within the eyeball, orbit or chest and abdominal cavities. Stents, valves, implants, wires, and other orthopedic hardware are not contraindications.

Indications Before the advent of multislice CT (MSCT), virtually all congenital examinations were performed with CMR. However, with the advent of MSCT, especially 64-slice CT scanners, it is possible to obtain exquisite images of the intrathoracic vessels. Though CMR is very useful for the indications listed below, 64-slice MSCT is better and hence pathologies relate to the evaluation of the pulmonary arteries, veins and aorta are now performed using MSCT, rather than CMR. These include:

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A

B

Figures 4.17A to B: Ebstein’s anomaly. The 4-chamber cine view in diastole (A), and systole (B) shows the abnormal distal position of the tricuspid valve (arrow) as compared to the mitral valve. The atrialized RV (portion between white arrowheads) is well seen. There is good function and this patient can be conserved and followed-up with no active management

•• Pulmonary vascular pathology—venous and arterial •• Extracardiac postoperative shunts—Glenns and Fontans •• MAPCAs •• Coronary arteries •• Coarctation. The indications where CMR is extremely useful are as follows: •• Anatomy of complex CHD •• Functional significance of lesions •• Pulmonary valvular and RV pathology and function •• Shunt evaluation—ASD, postoperative.

Anatomy of Complex CHD Using simple HASTE images as well as TrueFISP bright-blood images, it is usually possible to get an understanding of a complex CHD. The approach involves evaluation of the following parameters: •• Veins—systemic and pulmonary drainage •• Atria—situs •• AV connections—concordance/discordance •• Ventricles •• VA connections—concordance/discordance. Once the exact anatomy is established, it is relatively easy to arrive at a specific diagnosis and understanding of the complex CHD (Fig. 4.16). Functional Significance of Lesions Once a congenital anomaly is known, it is often necessary to understand its functional significance, especially with pathologies involving the right side of the heart. For example, in patients with Ebstein’s anomaly (Fig. 4.17), CMR is an excellent tool for assessing the extent of atrialization of the right ventricle (RV) as well as RV and RA function.

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Pulmonary Valvular and RV Function In patients with tetralogy of Fallot (TOF) and other complex congenital anomalies, especially in older children5, CMR is an excellent tool for the depiction of: •• Pulmonary stenosis (Fig. 4.18) •• Pulmonary regurgitation (Fig. 4.19) •• Double-chamber RV •• Sub-PS pathologies (Fig. 4.20).

A

B

Figures 4.18A and B: Postoperative TOF with pulmonary stenosis. In this 20 year-old patient, operated at the age of one year, the CMR shows severe pulmonary stenosis (arrow in B), with virtually no contractility and thickening of the RV walls (A – diastole, B – systole), with an RV ejection fraction of 5%

A

B

Figures 4.19A and B: Postoperative TOF with pulmonary regurgitation and stenosis. This patient shows moderate to severe pulmonary regurgitation (arrow) in diastole (A); as well as pulmonary stenosis (arrow) in systole (B). There is significant dyskinesia of the RV segments

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A

B

Figures 4.20A and B: Sub-PS. This 21 years old man was diagnosed to have pulmonary hypertension. The CMR reveals a subpulmonic membrane (arrow), well seen in diastole (A), and systole (B). The pulmonary valve is well seen (arrowheads). In systole, the severe jet due to the sub-PS is wellvisualized (black arrow in B)

RV function can also be very well-assessed, qualitatively and quantitatively and this is extremely useful, especially in patients of postoperative TOF1, where it is necessary to assess the presence/absence of pulmonary regurgitation and RV function, for deciding further management.

Shunts Intracardiac: ASD (Fig. 4.21) CMR is an excellent tool for the depiction of atrial septal defects (ASDs). It approximates the role of a transesophageal echocardiogram and with CMR it is possible to evaluate the size of the defect, the distance from the sinus venosus and SVC, etc. information required to plan management.

Figure 4.21: ASD. The diastolic image shows the defect well (arrow) with dilatation of the RV, in this 32 years old woman, who was diagnosed late in life with this condition, having presented with pulmonary hypertension

Postoperative Intracardiac-Mustard (Fig. 4.22): In patients with transposition of the great vessels (TGV), in the earlier days, atrial switch surgeries were often performed. The Mustard operation consists of a baffle that is created at the atrial level, that connects the RA to the LV and the LA to the RV. In older children, often there are complications with respect to the baffle and these are best depicted using CMR.

Conclusion In the era of 64-slice MSCT, the use of CMR has undergone further refinement. For information related to the heart and its chambers, CMR is the gold standard. However, for the pulmonary

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B

Figures 4.22A and B: Postmustard surgery. In this patient with transposition, the pulmonary veins (1) drain into the RA (3) and the SVC (2) and IVC (5) into the LA (4), thus switching the systemic and pulmonary venous drainage at the atrial level. This is achieved with the means of a surgically created baffle (arrow in A). This patient had edema feet, which was a result of severe stenosis at the level of the IVC drainage into the LA (arrowhead in B). 6 – RV, 7 – LV

veins, arteries and aorta, MSCT is now supplanting CMR as has been described elsewhere in this chapter. The best role of CMR today is the evaluation of RV function as well as the RVOT and pulmonary valve.

ROLE OF CARDIAC MR IN FETAL CARDIOLOGY (FIGS 4.23 TO 4.27) Fetal magnetic resonance imaging (FMRI) has gained considerable interest during the last decade. MRI was first used in prenatal diagnosis in the early 1980’s. It became obvious that MRI allowed for greater resolution of the fetus as compared to the commonly used ultrasound. MRI is the ideal choice because of lack of ionizing effect, multiplanar capability and inherent soft tissue contrast. Also, no harmful effect has been documented in the fetus.6 However, it is avoided in the first trimester which covers the period of organogenesis. Although seen as a promising technique, fetal MR studies were limited by long image acquisition times, that necessitated sedation of the otherwise moving fetus.7 Technical advances of the early 1990’s produced fast MR techniques, better coils and gradients. This paved the way for meaningful imaging of a fetus without Figure 4.23: Sagittal ssFSE T2 image the need for maternal sedation or fetal curarization. through the thorax of 30 weeks fetus. Single-shot fast spin echo (ssFSE) sequences are used The heart is seen as a dark ovoid structure against the hyperintense lungs and to obtain high-resolution of the fetus in between two hypointense hepatic parenchyma. Note movements. However, fetal motion at times can be a the isointense structure superior to the limiting factor in obtaining good quality images, as it heart which represents the thymus

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results in blurring. This problem is usually countered with repetition of the sequence and/or a repeat study at another time resulting in satisfactory evaluation of the fetal brain, spine, chest and abdomen most of the times. However, cardiac motion poses an additional limitation to the assessment of the fetal heart. Fetal MR scans are not gated for cardiac motion and hence assessment of the cardiac chambers and the outflow tracts is not adequate obtained with the current technology.8 Figure 4.24: Axial ssFSE T2 image in The fetal heart appears as a dark ovoid structure the same fetus as Fig. 20A. The heart is in the center of the chest flanked by high signal seen seen as an oval dark structure extendfrom the lungs on both sides. The size and shape of ing anteriorly upto the anterior chest the heart and the orientation of the cardiac axis can wall. Fluid-filled esophagus is identified as a rounded hyperintensity posterior to be assessed reliably after 25 weeks. As the fetal age the heart and anterior to the descending increases, the chambers, aorta and inferior vena cava aorta which is seen as a round signal are better delineated. However, it is difficult to provide void. The vertebra is seen as a hyponreliable diagnosis. Work is on to assess the role of real- tense triangular area posterior to the time MRI in evaluation of the fetal heart in comparison aorta. Note the spina bifida defect with a myelocele at this level to fetal echocardiography. Yet, MRI has been found to be useful in better characterization in cases of heterotaxy syndromes, e.g. visualization of polysplenia and azygous continuation of the inferior vena cava. MRI has a role in supplementing sonography by displaying features of congenital heart disease in cases of hypoplastic left heart syndrome, poststenotic dilatation in a case of aortic stenosis, truncus arteriosus, single ventricle and cooractation of the aorta.9 Levine et al have also demonstrated rhabdomyomas in the heart. However, the role of MRI in evaluation of the fetal heart is not currently well defined. Advances in MRI technology may enhance its capabilities in the future.

Figure 4.25: Axial ssFSE T2 image in 28 weeks fetus. Herniated bowel loops are seen in the thorax causing shift of the ipsilateral lung as well as the heart

Figure 4.26: Coronal ssFSE T2 image in 26 weeks fetus—a large anterior mediastinal mass (white arrow) causing posteroinferior and left lateral displacement of the heart

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Figure 4.27: Sagittal ssFSE T2 image in 16 weeks fetus. The heart is blurred even on this sagittal image. Descending thoracic and part of the abdominal aorta are seen as a linear signal void in the prevertebral region. Thymic tissue is seen anteriorly

RADIONUCLIDE IMAGING IN PEDIATRIC CARDIOLOGY Radionuclide angiography maybe used to detect and quantify shunts and to analyze the distribution of blood flow to each lung. This technique is particularly useful in quantifying the volume of blood flow distribution between the two lungs in patients with abnormalities of the pulmonary vascular tree, after a shunt operation (Blalock-Taussig or Glenn), or to quantify the success of balloon angioplasty and intravascular stenting procedures. Gated blood pool scanning can be used to calculate hemodynamic measurements, quantify valvular regurgitation, and detect regional wall motion abnormalities. Thallium imaging can be performed to evaluate cardiac muscle perfusion. These methods can be used at the bedside of seriously ill children and can be performed serially, with minimal discomfort and low radiation exposure.8–10

REFERENCES 1. Lipshultz SE, Easley K, Orav EJ, et al. The reliability of multicenter pediatric echocardiographic measurements of left ventricular structure and function. Circulation. 2001;104:310–16. 2. Sivakumar K, Anil SR, Rao SG, Shivaprakash K, Kumar RK. Closure of Muscular Ventricular Septal Defects Guided by En-face Reconstruction of the Right Ventricular Septal Surface Using Two Dimensional Echocardiography, Annals of Thoracic Surgery. 2003;76:158–66. 3. Kumar RK, Anil SR, Philip A, Sivakumar K, Bioptome-assisted coil occlusion of moderate-large patent arterial ducts in infants and small children, Catheterization and Cardiovascular Interventions. 2004;62:266-71.

Multidetector CT Scan 3. Gilkrson RC Multidetector CT evaluation of congenital heart disease in pediatric and adult patient. AJR. 2003;180:973. 1. Hypoplastic left heart syndrome/Norwood operation. The Heart Centre Encyclopedia. 2. Using multidetector-row CT in neonates with complex congenital heart disease to replace diagnostic cardiac catheterization for anatomical investigation: Initial experiences in technical and clinical feasibility. Paed Card. 2006. 4. Gutierrez FR. Magnetic resonance imaging of congenital heart disease. Top Magn Reson Imaging. 1995;7:246–57. 5. Boechat MI, Ratib O, Williams PL, Gomes AS, Child JS, Allada V. Cardiac MR imaging and MR angiography for assessment of complex tetralogy of Fallot and pulmonary atresia. Radiographics 2005;25:1535–46.

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6. Levine Deborah (ed). Atlas of fetal MRI. Taylor & Francis. 2005. 7. Stark David D, Bradley William G (Eds). Magnetic resonance Imaging. 3rd edn. Mosby. 1999. 8. Sty JR, Starshak RJ. Thallium-201 myocardial imaging in children. J Am Coll Cardiol. 1985;5(1): 128S-39S. 9. Didier D, Higgins CB, Fisher MR, et al. Congenital heart disease: Gated MR imaging in 72 patients. Radiology. 1986;158:227. 10. Hurwitz RA: Quantitation of aortic and mitral regurgitation in the pediatric population: Evaluation by radionuclide angiography. Am J Cardiol. 1983;51:252.

5

Diagnostic Cardiac Catheterizations in Children

Snehal Kulkarni

Since 1947, when the use of the cardiac catheterization began in children, technical improvements in the catheter design and materials, the quality and type of imaging, and the type of contrast materials used for imaging have lead to an improved quality and safety of the cardiac catheterization and angiography even in neonates and small infants. In the mid20th century cardiac catheterization was used as a means of ascertaining accurate anatomic and physiologic diagnosis. With newer echocardiographic equipments and availability of high frequency transducers, the cardiac imaging in children, especially in neonates and infants is excellent. All the anatomic details of heart structures can be easily identified. The remarkable diagnostic precision of echocardiographic tool has essentially eliminated the need for preoperative diagnostic cardiac catheterization in many of the common congenital lesions such as ventricular septal defect (VSD), tetralogy of fallot (TOF), total anomalous pulmonary venous return(TAPVR), endocardial cushion defects.1 Few children have difficult imaging due to poor acoustic windows especially in postoperative situations. Cardiac magnetic resonance imaging (CMRI) and multislice CT (MSCT) have come a long way to help in these situations to give more information regarding the anatomic details. Cardiac MRI does not involve radiation and iodinated contrast reagents. In contrast, multislice CT involves radiation and iodinated contrast agents, but the examination can be performed in few seconds which is very useful in a very sick child especially in a postoperative situation. In this era of newer echocardiography machines, transesophageal echocardiography, cardiac MRI and multislice CT, the role of diagnostic cardiac catheterization in children is diminishing. It is mainly limited to resolving questions remaining unanswered from a less invasive technique or a noninvasive test. It still has a significant role in hemodynamic assessment of intracardiac lesions, measuring the pulmonary arterial pressure, pulmonary vascular resistance and ventricular end diastolic pressures. Calculation of intracardiac shunts and pulmonary vascular resistance is important for determining the operability in older children with large left to right shunts. There is a definite role of cardiac catheterization if an intervention is required in addition to acquiring diagnostic details. Over the period of years,

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the number of procedures done in a pediatric catheterization laboratory has almost remained the same, but the proportion undergoing interventional procedures continues to increase.

Indications for Cardiac Catheterization in Children 1. Estimation of pulmonary arterial pressure and pulmonary vascular resistance in children with left to right shunt with severe pulmonary arterial hypertension to decide operability. 2. Measurement of pulmonary arterial pressure, pulmonary vascular resistance and ventricular end diastolic pressure prior to univentricular repair. 3. Patients with pulmonary atresia with or without ventricular septal defects (VSD) to delineate the major aortopulmonary collaterals and measure the pressure in distal collateral vessels. 4. Preoperative assessment of patients undergoing palliation for complex single ventricle repairs especially pre-Glenn and pre-Fontan repairs.

Derived Hemodynamic Variables 1. Intracardiac shunts : Difference in the oxygen saturation at various sites on the right side of the heart would give information regarding the presence and magnitude of left to right shunt. 2. Qualitative assessment of shunts. 3. Quantitative assessment of shunts : With the use of Fick principle, it is possible to measure pulmonary and systemic blood flow. 4. Vascular resistances: Assessment of pulmonary vascular resistance is one of the commonest indication of cardiac catheterization in children. 5. Valve areas: Gorlin and Gorlin presented a method for calculation of valve orifice size based on the physical properties of flow through a circular orifice and relationship between pressure gradient and velocity of flow.10, 11

Special Procedures 1. Transseptal left heart catheterization: This technique is used to measure left ventricular pressure in the presence of aortic valve prosthesis but rarely used in children due to the risk of transseptal puncture. 2. Selective coronary angiography: In general, ventriculography and aortography are sufficient to identify major proximal coronary arteries in patients with tetralogy of Fallot or d-transposition of great vessels. Selective coronary angiography is needed for patients with Kawasaki disease, coronary cameral fistulae, pulmonary atresia with intact ventricular septum to see for right ventricle dependent coronary circulation and frequently when origin of left anterior descending artery from right coronary artery is suspected. 3. Pulmonary venous wedge angiography : It is essential to identify the pulmonary artery before the corrective surgical procedure but in some patients, either as a result of congenital defect or prior cardiac surgery one of the pulmonary arteries cannot be visualized by routine angiographic methods. A balloon tip end hole catheter is placed in

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the pulmonary vein. With the balloon inflated, up to 0.3 mL/kg of nonionic contrast agent is injected followed by equal volume of saline. The parenchymal vessels are usually well visualized with back filling. 4. Endomyocardial biopsy: Frequent endomyocardial biopsies are usually needed after cardiac transplant. The great majority of procedures involve right ventricular biopsy. It is usually done through right internal jugular, subclavion or femoral venous access. 5. Electrophysiological studies and therapy.

PRECATHETERIZATION ASSESSMENT One of the essential elements of cardiac catheterization is accurate precatheterization assessment of the cardiac problem to plan catheterization procedure.2 Catheterization procedures should be meticulously planned to get essential details necessary to ascertain nature of the problem relevant for the current medical and future therapeutic procedures. This should include: •• A complete physical examination and assessment of vitals, hydration status, oxygen saturation, adequacy of the peripheral circulation. •• Review of routine laboratory investigations. •• Evaluate need for endotracheal intubation, inotropic support, diuretics or prostaglandins prior to the catheterization. •• An electrocardiogram to define arrhythmias which will have to be controlled before the catheterization. •• Recheck the hemoglobin and hematocrit which should be corrected using Gidding’s regression equation—the appropriate hemoglobin (g/dL) = 38–(0.25 × SaO2). Adjust hemoglobin level to have oxygen content of at least 15 mL of oxygen per 100 mL of blood (Hb g/dL × 1.36 mL O2 /g Hb × O2 saturation). •• Review current two-dimensional echocardiogram to assess the basic anatomy of the heart to avoid excessive use of contrast material. •• Ascertain if any systemic venous anomalies exists which will help in planning out the venous access route. •• Written informed consent is obtained in all procedures. •• The older patients are kept nil per oral for 5 hours and infants are given clear liquids upto 3 hours prior to the procedure. •• Patients with hematocrit more than 50% are given adequate hydration via intravenous fluids. •• All children must have an intravenous line before coming to the laboratory. A written plan of the catheterization procedures is necessary which would help both the operator as well as the catheterization laboratory staff.

PREMEDICATION AND SEDATION Usually sedatives are not routinely used as premedication in small children, as they are very vulnerable to the central nervous system depressant effects of these drugs. Opioids should be cautiously used in sick children to avoid low cardiac output from bradycardia (vagal effect)

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and venous dilation. Sedation should always be administered under the supervision of a well trained staff or the attending physician in the catheterization laboratory.3 We routinely use oral chloral hydrate at a dosage of 50–75 mg/kg 30 to 45 minutes prior to cardiac cauterization. Alternatively Lytic cocktail regimen consisting of intramuscular injection of Meperidine (1.5 to 2.0 mg/kg), promethazine (1.0 mg/kg), and chlorpromazine (1.0 mg/kg) can also be used. It’s use should be avoided in patients with ventricular outflow tract obstruction or pulmonary vascular disease due to its propensity to cause systemic vasodilatation and hypotension which may induce cyanotic spells. It also causes pulmonary vasoconstriction which would alter the pulmonary hemodynamics in a sick child. Approximately, 80 to 90% of diagnostic cardiac catheterization procedures are performed under sedation and local anaesthesia. About 10–20% of very sick children need general anesthesia for diagnostic procedures. Ketamine at a dosage of 2 mg/kg IM or 0.5 to 1 mg/kg intravenously can be effectively used as an anesthetic and analgesic agent with preservation of the pharyngeal and laryngeal reflexes reducing the chances of aspiration. It dose not significantly alter the systemic or pulmonary hemodynamics. It does not lower systemic resistance and does not produce vasoconstriction and can therefore be safely used for patients with reduced pulmonary blood flow and those without pulmonary arterial hypertension. Ketamine is associated with excessive salivation and should be used along with the atropine or an antihistamine agent. Midazolam can be added as a sedative at a dose of 0.1mg/kg or fentanyl (at a dosage of 1 to 2 micrograms/kg) can be supplemented with ketamine. Continuous intravenous infusion of propofol also can be used safely for the diagnostic procedures.

Monitoring During Catheterization •• •• •• •• ••

Routine monitoring of the heart rate, electrocardiogram, blood pressure, temperature, respiratory rate, chest movement, air entry and infusion site is done. Appropriate body temperature is maintained in neonates and infants using warming devices. Adjustments of endotracheal tube position can be carried out with or without the use of fluoroscopy. Respiratory depression is quite common with these sedatives and frequent blood gas monitoring is mandatory. A defibrillator is charged and kept ready during all the procedures.

Catheterization Study Many a times most of the lesions are identified by noninvasive techniques before the studies. During cardiac catheterization it is not necessary to prove the existence of already known diagnosis. It is important to target the study to the specific objectives for which the study is conducted.

Femoral Cannulation The percutaneous femoral route is the preferred approach for diagnostic catheterization in patients with congenital heart disease.4 Special short beveled 21-gauge needles or Jelco are used for easy insertion of guide wires. Vascular sheath is then inserted over the guide wire and

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dilator at the mid point between the superior iliac crest and the pubic tubercle at the symphysis pubis in infants and children and at the medial one third of this line in adolescents. Vessel entry is just below the inguinal ligament in infant and about 1 to 2  cm below this in larger children. Smallest possible sheaths are used which can give all the necessary information.

Retrograde Left Heart Catheterization Essential steps of the cannulation are same as the femoral venous cannulation except that the femoral arterial puncture is guided by the femoral pulse. Intravenous heparin is given at a dosage of 50 to 100 IU/Kg and activated clotting time (ACT) is maintained above 200 sec during the study. Heparin is repeated after 45 minutes if the procedure time is prolonged. The initial phase of the procedure is aimed at gathering physiological data. Right sided heart catheterization is performed by measuring oxygen saturation and pressure measurement of superior vena cava, upper, mid and lower right atrium, inferior vena cava, inflow and outflow portions of right ventricle, main, right and left pulmonary arteries and pulmonary capillary wedge position. An arterial catheter is used to record pressure and oxygen saturation in descending, ascending aorta and left ventricle. All this information is required for calculation of intracardiac shunts and pulmonary vascular resistance.

Oxygen Consumption There are two widely used methods for measuring oxygen consumption— Douglass bag method and Polarographic method. Because of the difficulty in measuring oxygen consumption in the cardiac catheterization laboratory, assumed values are frequently used, based on the formulas of Lafarge and Meittinen.5 Most of the laboratories assume oxygen consumption as 125 mL/m2 or 110/m2 of body surface area for older children. Cardiac output can be calculated if needed with the thermodilution method.6 The next phase of the study consists of angiography. Emphasis needs to be given to appropriate patient positioning for optimum visualization of specific cardiac anatomy.7 The renal shadows should be viewed at the end of procedure to see for dye excretion through the kidneys. The catheters and sheaths are removed and bleeding at the entry site is controlled in 10 to 15 minutes. Usually nonionic contrast material is used for angiography. The maximum permissible contrast dose is 5 mL/kg of body weight. With the availability of biplane catheterization laboratories, the requirement of dye for angiography is significantly less.

Other Vascular Entry Sites i. Umbilical vessels: Umbilical venous access is possible upto 3 days after birth in neonates. Umbilical vein is usually used for balloon atrial septostomy. Umbilical arterial catheterization is used to monitor arterial pressure and saturation and in rare cases for aortography. ii. Transhepatic venous route: This approach is increasingly used for patients in whom femoral veins are occluded or in patients with interrupted inferior vena cava for diagnostic and occasionally for intervention procedures.8,9

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iii. Internal jugular vein: This approach is usually used for right ventricular endomyocardial biopsy and study of patients with bidirectional Glenn shunt or electrophysiological study. This route is often used for intervention procedures especially transcatheter closure of ventricular septal defects. iv. Subclavian vein: This approach is occasionally used in cases of thrombosis of femoral or iliac veins or interruption of inferior vena cava. It is also used to study the Glenn shunts in the postoperative situations. v. Vascular cut down: Incisional exposure of vessels for catheter entry is virtually never required except after prolonged fruitless puncturing in a sick patient.

TRANSPORT OF NEONATE OR SICK INFANT TO THE CATHETERIZATION LABORATORY Checklist before Shifting •• •• •• •• •• •• •• ••

The hemodynamic status of the patient should be stabilzed. Blood volume replacement if required is given before transport. Inotropic and other cardiovascular support drugs are given at a stable infusion rate. Intravenous lines are secured and infusion pumps are stabilized for safe transport. A stable thermal environment such as an incubator or warming stand or appropriate covering is available to prevent rapid heat loss during transport. For an intubated and ventilated patient appropriate bag, mask and oxygen connection is available and ventilator settings are set up in the catheterization laboratory before transport. Electorcardiogram and pulse oximetry monitoring are available during transport. The catheterization laboratory is warmed to an ambient temperature of 80 to 85° F if possible.

IMAGING Biplane fluoroscopy and cineangiography are preferred for angiography of cardiovascular defects in children. A high quality videotape or digital recorder is necessary for immediate and delayed review of the angiograms. Digital angiography techniques with a high resolution video camera convert the light intensity into a voltage value, depending on the intensity of the light which are read and stored by computer). Frame rate is kept at 60 frames/ second for pediatric angiography which produces 154 MB/second of digital data.

SPECIFIC CARDIOVASCULAR DISEASES AND CARDIAC CATHETERIZATION AND ANGIOGRAPHY Atrial Septal Defect By and large atrial septal defects rarely need to be catheterized except in older children with severe pulmonary artery hypertension (PAH) to assses feasibility of surgery.

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Ventricular Septal Defect Isolated ventricular septal defects rarely need to be catheterized except in older children with severe pulmonary artery hypertension to ascertain feasibility of surgery.

Patent Ductus Arteriosus/Aortopulmonary Window Isolated Patent ductus arteriosus (PDA) need to be catheterized only in older children with severe pulmonary artery hypertension to decide feasibility of surgery. Balloon occlusion of the PDA may be needed in large ductus to ascertain if the patient will tolerate the surgical or trans catheter closure of PDA.

Coarctation of Aorta Postoperative residual coarctation and uncertain native coarctation may need diagnostic cardiac catheterization. Need for catheterization in these subgroups is significantly decreasing due to availability of excellent imaging of cardiac MRI and multislice CT.

Double Chamber Right Ventricle Double chamber right ventricle may occasionally need cardiac catheterization to ascertain the site of the anomalous obstructive muscle bundle if the echocardiography windows are poor and to assess the severity of obstruction.

Truncus Arteriosus Truncus arteriosus needs to be catheterized only in older children with severe pulmonary artery hypertension, or if there is branch pulmonary artery stenosis or unilateral agenesis of the pulmonary artery to delineate the source of the blood supply the respective lung.

Transposition of Great Arteries Children with transposition of great arteries with regression of left ventricle may need catheterization for estimation of LV pressures to assess the suitability for arterial switch operation.

Total Anomalous Pulmonary Venous Return Total anomalous pulmonary venous return needs to be catheterized only in children with severe pulmonary artery hypertension. The anatomical details can be very well identifed on echocardiography, CT or MRI techniques.

Tetralogy of Fallot Tetralogy of Fallot needs to be catheterized only in older children with suboptimal windows or in those with branch pulmonary artery stenosis or unilateral agenesis of the pulmonary artery to define the source of the blood supply to the respective lung. Additionally unusual coronary anatomy and presence of systemic pulmonary collaterals may merit cardiac catheterization.

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Pulmonary Atresia, Intact Ventricular Septum Pulmonary atresia, intact IVS will need cardiac catheterization to define native pulmonary artery anatomy and to rule out the right ventricular dependant coronary circulation.

Pulmonary Atresia with VSD Pulmonary atresia with VSD needs catheterization to define native pulmonary artery anatomy and major aortopulmonary collaterals.

Single Ventricle Physiology All patients with single ventricle physiology where biventricular repair is not feasible (Tricuspid atresia with pulmonary stenosis (PS)/Pulmonary atresia, Mitral atresia, Double outlet right ventricle with non-committable VSD, PS, double inlet left ventricle with PS) need cardiac catheterization to ascertain native pulmonary artery anatomy, measurement of pulmonary artery pressures and resistance, ventricular enddiastolic pressures and define major aortopulomnary collaterals.

Cardiac Catheterization in the Immediate Postoperative Period This is helpful to define residual shunts, residual RVOT or LVOT obstruction, anastamotic site narrowing, evaluation of the branch PA stenosis and adequacy of PA plasty.

Issues During Cardiac Catheterization Hemostasis The use of hemostasis or bleed-back valves on percutaneous sheaths minimizes blood loss during catheter exchanges. Anticoagulants Retrograde arterial catheterization requires heparinization. A dose of 50 to 100 U/kg should be administered which should be repeated based on activated clotting time (ACT) every 30 to 60 minutes. Patients with marked polycythemia may have accelerated clotting and consumptive coagulopathy if the hematocrit is over 60%. Phlebotomy with plasma replacement is remedial measure. Polycythemia and Anemia Polycythemic patients have a marked elevation of blood viscosity with the hematocrit of above 65%. If the precatheterization hemoglobin is above 20 g/dL, a centrifuge hematocrit is obtained using venous blood to measure the true packed cells volume and partial phlebotomy is done.

Observed hematocrit – desired hematocrit



Observed hematocrit

Blood volume to withdraw = Weight (kg) × 100 ×

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COMPLICATIONS OF CARDIAC CATHETERIZATION The incidence of complications and mortality from cardiac catheterization have decreased significantly over past few decades due to improvement in the catheterization techniques, the catheters used, quality and type of imaging, safe and better anesthetic and cardiovascular support drugs and availability of nonionic contrast agents.12-14 The mortality and morbidity are no longer related to the age and weight of the child. The underlying cardiopulmonary disease as well as the general condition is the major determinant.

Mortality Mortality for routine diagnostic cardiac catheterization is very less . The sick, acidotic, hypoxic children with poor perfusion who do not respond to precatheterization medications and management have poor outcome and they are also likely to have complex or inoperable cardiopulmonary defects. Mortality during cardiac catheterization is high in these subsets of patients. Patients with the highest mortality are the ones who are critically ill or at high-risk and are catheterized while still acidotic (pH below 7.1), hypoxemic (PO2 below 25 mm Hg) with poor peripheral perfusion and requiring ventilation.

Perforation of the Heart Perforation of the heart has become less common with the use of balloon-tipped catheters. These catheters should be carefully manipulated without balloon inflation as the catheter tip is sharply pointed when the balloon is deflated and the risk of cardiac perforation is high.

Blood Loss Blood loss is an important problem in neonates and small children. In such cases blood withdrawal for arterial blood gas measurement and oxygen saturation should be carefully measured and cumulative blood loss should be replaced. Use of a percutaneous sheath with a bleed back or hemostasis valve minimizes the blood loss during catheter exchanges and should be employed.

Hypotension Neonates and smaller children with pre-existing low blood volume can have sub clinical dehydration with the use of diuretic, fluid restriction, and excess loss during the blood sampling. These children are prone for profound hypotension and bradycardia following angiogram with contrast agent. Checking atrial filling pressures before angiography, use of calcium chloride and replacing blood loss would minimize the risk. The degree and incidence of hypotension have been reduced with the introduction of nonionic contrast material in the past few years.

Arterial Complications Since the introduction of percutaneous sheath techniques, major arterial complications are very less. Minor complications involving decreased femoral or peripheral pulses with

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pallor and coolness of the limb still occur, but their frequency have been reduced by systemic heparinization during arterial catheterization.15-17 Most of the problems from arterial cannulation improve within 24 hours and rarely require surgical embolectomy and arterioplasty. Streptokinase or Urokinase is helpful in opening up occluded femoral arteries if 24 hours of systemic heparinization does not improve the circulation.

Arrhythmias Transient supraventricular tachycardia, atrial flutter or fibrillation, ventricular tachycardia / fibrillation, and 2nd and 3rd degree heart block are the most common arrhythmias occurring during cardiac catheterization. These are usually transient and resolve spontaneously after withdrawal of the catheter stimulation. Fast ventricular rates are usually tolerated well by neonates and infants who become more cyanotic with tachycardia except by those with Tetralogy of Fallot physiology. On the other hand, bradycardia is less well tolerated by infants who relay on increasing heart rate to increase cardiac output.

CONCLUSION Last few decade have seen tremendous modifications in technique and approach to cardiac catheterization in congenital heart disease. Significant improvements have occurred in the diagnosis and management of the critically ill patient with congenital heart disease. The cardiac catheterization has evolved as a technology that is increasingly used when the information is lacking or further precision of the data obtained by two dimensional echocardiography and color flow imaging is required. The modernization of technique has increased the ease and safety of the procedure. Being the most reliable and direct method of delineating the physiological derangements caused by the congenital cardiovascular diseases, the cardiac catheterization and angiography will continue to play important role even with the advent of newer and better imaging modalities.

REFERENCES 1. Huhta JC, Glassgow P, Murphy D J Jr, et al. Surgery without catheterization for congenital heart defects: management of 100 patients. J Am Coll Cardiol. 1987;9:823. 2. Lock JE, Evaluation and management prior to catheterization in: Lock JE, Keane JF, Fellows KE (eds), Diagnostic and Interventional Catheterization in Congenital Heart Disease. Boston: Martinus Nijhoff pup., 1987;1–8. 3. Ruckman RN, Keane JF, Freed MD, et al. Sedation for cardiac catheterization: a controlled study. Pediatr Cardiol. 1980;1:263. 4. Keane JF, Lock JE, Vessel entry and catheter manipulation. In: Lock JE, Keane JF, Fellows KE (eds), Diagnostic and Interventional Catheterization in Congenital Heart Disease. Boston, Martinus, Nijhoff, 1987. 5. Lafarge CG, Miettinen OS. The estimation of oxygen consumption. Cardiovasc Res 1970;4:23–30. 6. Freed MD, Keane JF, Cardiac output by thermodilution in infants and children. J Pediatr. 1978;92:39. 7. Fellows KE, Keane JF, Freed MD. Angled views in cineangiography of congenital heart disease. Circulation. 1977;56:485.

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8. Shim D, Lloyd TR, Chok J, et al. Transhepatic cardiac catheterization in children  ; evaluation of efficacy and safety. Circulation. 1995;92:1526. 9. Wallace MJ, Hovsepian Dm, Balzer Dt. Transhepatic venous access for diagnostic and interventional cardiovascular procedures. J Vasc Interv Radiol. 1996;74:57. 10. Gorlin R Gorlin G. Hydraulic formula for calculation of area of stenotic mitral valve, other cardiac valves and central circulatory shunts. AM Heart J. 1995;4:1–29. 11. Cacabello BA, Grossman W, Calculation of stenotic valve orifice area. In; Gossman W, Baim D, (eds). Cardiac Catheterization Angiography and Interventions, 4th ed. Philadelphia; Lea and Febige 1991;152–65. 12. Stranger P, Heymann MA, Tarnoff H, Rudolf AM. Complications of cardiac catheterization of neonates, infants and children: a three year study. Circulation. 1974;50:595–698. 13. Fellows KE, Radtke W, Keane JF, Lock JE. Acute complications of catheter therapy for congenital heart disease. Am J Cardiol. 1987;60:679–83. 14. Cassidy SC, Schmidt KG, VanHare GF, Stanger P, Teitel DF. Complications of pediatric cardiac cathetrizations: a 3 years study. J Am Coll Cardiol 1992;19:1285–93. 15. Cahill JL, Talbert JL, Otteson DE, Rowe RD, Haller JA Jr. Arterial complications following cardiac catheterization in infants and children. J Pediatr Surg. 1967;2:134–43. 16. Bulbul ZR, Galal MO,Mahmoud E, Narden B,Solymar L, Chaudhary MA, Al Halees ZY. Artrial complications following cardiac catheterization in children less than 10 kg. Asian Cardiovasc Thorac Ann. 2002;10:129–32. 17. Snehal Kulkani, Renuka Naidu. Use of vascular ultrasound imaging to study immediate postcathetrization vascular complications in children Catheterization & Cardiovascular Interventions (In press).

6

Heart Failure in Children

Sreekanthan Sundararaghavan, R Krishna Kumar

Heart failure is a clinical syndrome resulting from the inability of the heart to meet the metabolic demands of the body. However, the description of heart failure needs to encompass the physiological, metabolic, molecular and clinical aspects. A good understanding of the physiology is essential to diagnose and manage heart failure whether it is in children or adults. This clinical state may arise from excessive work load (high output), decreased myocardial performance (low output) or a combination of these two. Physiologically this may be categorized as a state wherein the systolic phase, diastolic phase or both may be affected. Pathologically this may be associated with ventricular dilatation (thinning) or hypertrophy (thickening) of the ventricular muscle. However, the current knowledge of heart failure encompasses not only altered organ function and the functional changes but also the fundamental changes happening at the biochemical and molecular level. Although, the fundamentals of heart failure remain the same between adults and children, there are differences in the etiology, physiology, clinical presentations and management, which will be addressed in this chapter. The etiology of heart failure in children can be age specific (Table 6.1). Interestingly, most of the children with heart failure present during infancy and thereafter the incidence decline dramatically. With the advances in understanding of fetal abnormalities, heart failure is being increasingly diagnosed earlier in gestation. Of course, fetal loss remains a major end result in this population and heart failure has clearly emerged as an indicator of poor prognosis and hence survival. The specific individual congenital heart conditions responsible for heart failure at various ages is listed in table 6.2. The age of onset of heart failure in CHD is an important clue to the possible underlying conditions. For example when a newborn with a diagnosis large ventricular septal defect presents with heart failure at 2 weeks age, it is important to carefully examine the aortic arch by echocardiography for an associated coarctation that may have been missed. The time of onset of heart failure in common left to right shunts at the ventricular level (VSD) of great artery level (PDA) is closely related to the drop in pulmonary vascular resistance (PVR).

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Table 6.1: Age at presentation for various forms of heart failure in children Newborns and Infants 1. Congenital heart disease: Acyanotic L-R Shunts, Cyanotic heart disease with increased pulmonary blood flow and severe obstructive lesions (severe aortic stenosis, coarctation) 2. Myocardial disease: Myocarditis, metabolic causes of ventricular dysfunction, 3. Rhythm disorders (tachyarhythmias and bradyarhythmias) 4. Pulmonary hypertension (persistent pulmonary hypertension of the newborn, idiopathic pulmonary hypertension, pulmonary hypertension secondary to hypoxia from conditions such as upper airway obstruction) 5. Hypocalcemia 6. Neonatal asphyxia (as a result of myocardial dysfunction and pulmonary hypertension) Children 1. Rheumatic fever and rheumatic heart disease 2. Congenital heart disease complicated by anemia, infection or endocarditis 3. Systemic hypertension (renal disease, aortoarteritis) 4. Myocarditis and primary myocardial disease 5. Late complication of Kawasaki disease with coronary occlusion 6. Pulmonary hypertension (primary and secondary)

Table 6.2: Age of onset of congestive failure for various congenital heart defects Age Birth-1 week

1-4 weeks

4-8 weeks

2-6 months

Lesion Critical left ventricular outflow obstruction (hypoplastic left heart syndrome, critical aortic stenosis, severe coarctation, arch interruption) Total anomalous pulmonary venous return (obstructed), congenital mitral and tricuspid valve regurgitation Patent ductus (preterms), ventricular septal defect (VSD) with coarctation, transposition with large ventricular septal defect or patent ductus, persistent truncus arteriosus, single ventricle physiology with unrestrictive pulmonary blood flow, severe coarctation, critical aortic stenosis, congenital mitral or tricuspid valve regurgitation, Transposition with VSD or PDA, endocardial cushion defects, ventricular septal defect, patent ductus arteriosus, severe coarctation, Total anomalus pulmonary venous return, anomalous left coronary artery from pulmonary artery, single ventricle physiology with unrestrictive pulmonary blood flow VSD, PDA, Endocardial cushion defect. Anomalous left coronary artery from the pulmonary artery, coarctation, single ventricle physiology with unrestrictive pulmonary blood flow

The elevated PVR at birth does not permit excessive pulmonary blood flow initially. With time the PVR fall and pulmonary blood flow progressively rises. Tachypnea and feeding difficulties, therefore, typically starts between 4–8 weeks. In preterm infants the decline in PVR is much faster and therefore they can present earlier. The elevated PVR is also responsible preserving the coronary blood flow in newborns with anomalous left coronary artery from the pulmonary artery (ALCAPA). The left coronary artery is reasonably perfused when the PVR (and therefore the PA pressures) is high. With drop in PVR and PA pressures there is a decline in flow in the anomalous left coronary artery with resultant myocardial ischemia and infarction. There are certain physiological principles that are unique to pediatric heart failure. The Frank-Starling mechanism and pressure volume loops are helpful in understanding the basic mechanism of heart failure (Figs 6.1 and 6.2). The animal studies done by Rudolf and colleagues have exemplified these mechanisms in great detail. Increase in ventricular preload increases stroke volume by stretching the myocardial cells. Changes in afterload and inotropy

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Figure 6.1: Frank-Starling mechanism. Increasing venous return to the left ventricle increases left ventricular end-diastolic pressure (LVEDP) and volume, thereby increasing ventricular preload. This result in an increase in stroke volume (SV). The “normal” operating point is at a LVEDP of ~8 mm Hg and a SV of ~70ml/beat

Figure 6.2: Effects of ventricular failure (decreased inotropy) on the force-velocity relationship. Decreased inotropy decreases velocity of fiber shortening at any given afterload

also shift the Frank-Starling curves up or down and thereby results in changes in stroke volume (Fig. 6.3). However, cardiac output which is a quotient of heart rate and stroke volume, also changes accordingly. Interestingly in adults, most of the coping in the heart during strain and stress happens with changes in stroke volume primarily by altering the Frank-Starling mechanics (Figs 6.4 and 6.5). However, in children the majority of the cardiac output is primarily dependent on the chronotropy (increased heart rates). The primary response to cope with excess volume overload such as in left to right shunt is by increasing the heart rate. Since the pediatric heart is already compromised due to poor filling volume and hence stroke volume, their reserve is poor. However, their body is accustomed to rapid heart rates and hence may not be clinically evident. Eventually all compensatory mechanisms are overcome and the patient then deteriorate rapidly. Hence, the clinical conundrum of an apparently well looking infant, suddenly decompensating.

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Figure 6.3: Family of Frank-Starling curves. Changes in after-load and inotropy shift the FrankStarling curve up or down

Figure 6.4: The Frank-Starling relationship showing the effects of heart failure on stroke volume, (left ventricular end-diastolic pressure - LVEDP). Point A: control point, Point B: ventricular failure

Clinical Features of Heart Failure Symptoms: Poor weight gain is a consistent hallmark of heart failure in infants and young children. It is related to poor intake because of easy fatigability and wasted consumption of calories by the increased work of breathing. Uncommonly, there may be an unusual weight gain from fluid accumulation when right heart failure predominates with associated facial puffiness or edema on the feet. The common complaint is that the baby does not take more than one to two ounces of milk at a time and is hungry soon after feeds. Shortness of breath or fatigue from feeding results in the baby accepting only small amounts of milk at a time. A few minutes rest relieves the baby and since hunger persists, the result is an irritable infant crying all the time. Mothers may volunteer that the baby is more comfortable and breathes better when held against the shoulder (equivalent of orthopnea). In children with heart failure,

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Figure 6.5: Pathophysiology of CHF

syncope may be very serious and needs to be evaluated immediately. Appetite may be poor when heart failure is severe and weight loss or lack of weight gain can be seen even in older children (cardiac cachexia). Older children with congestive heart failure  are beyond the time of rapid growth and therefore do not have major growth problems like infants. Their symptoms are usually related to their inability to tolerate exercise. They become dyspneic rapidly when compared to their peers and are effort intolerant more akin to the adults. Dyspnea can occur even with minimal exertion, such as climbing stairs or taking a walk if the heart failure is severe. These children will have fatigue on effort when compared to their friends, although this may be harder to determine because all children have different levels of energy.

Signs of Heart Failure Persistent tachypnea, tachycardia, cough that increases on lying down and wheeze are all signs of lung congestion associated with left sided heart failure. The lungs are often clear and crepitations or rales are seldom heard. Right heart failure is indicated by hepatomegaly and facial puffiness. Examination of the jugular venous pressure or pulsations in small babies is seldom helpful. Common to both left and right sided failure is the presence of cardiac enlargement, third sound gallop and poor peripheral pulses with or without cyanosis. Several clues to the underlying specific heart disease can be evident on examination. Perhaps it is prudent to mention the significance of feeling femoral pulsations in any infant being evaluated for heart failure because coarctation is often missed clinically.

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Investigations The purpose of investigations for heart failure can be classified as follows: 1. Confirmation of diagnosis of heart failure: In certain circumstances it may be difficult to distinguish heart failure from respiratory conditions such as bronchial asthma. Sometimes the two of them may co-exist. Obtaining a chest X-ray or an echocardiogram usually reveals the underlying cardiac cause. Rarely, it may be necessary to measure BNP levels. Elevated BNP levels may help in circumstances where the clinical picture is very clouded. 2. Identification of etiology: While a comprehensive echocardiogram is often the definitive test to identify the etiology in congenital and structural heart disease, additional tests are needed when there is just ventricular dysfunction identified on the echocardiogram. The work up of a child with severe ventricular dysfunction is described in the chapter on myocardial disease. The purpose of this work up is to identify possible of “treatable cardiomyopathy”. Hypocalcemia, anomalous coronary artery from pulmonary artery, persistent tachyarrhythmia and other selected metabolic conditions are all examples of ventricular dysfunction that may reverse completely with specific treatment. The importance of ECG lies in the clues it may provide to identifying treatable causes. These clues include prolonged QTc interval (hypocalcemia), evidence of lateral wall infarction or ischemia (ALCAPA) or tachycardia with an abnormal ‘p’ wave axis (tachycardiomyopathy). 3. Assessment of co-morbidities: Blood work up for anemia is mandatory. Occasionally in acutely ill children, it may be necessary to assess end-organ injury. Compromised liver and renal function is seen after prolonged hypotension and they impact subsequent decisions on management. CRP levels best identify associated infections. The threshold for obtaining bacteriologic cultures should be low for infants and children with CHF. 4. Monitoring effects of treatment: A baseline serum electrolytes must be obtained in all patients hospitalized for management of CHF. Serum sodium and potassium levels need to be monitored after intense diuresis and renal functions should be monitored especially when angiotensin converting enzyme inhibitors are administered especially in the very young.

MANAGEMENT OF CHF The traditional management of CCF is based on the following core principles: 1. Correcting the underlying cause 2. Supportive measures 3. Reducing Preload 4. Reducing Afterload 5. Improving myocardial contractility 6. Managing co-morbidity 1. Identifying and Correction of Underlying Cause: It must be recognized that identification of cause is perhaps the most important priority because it has a direct bearing on survival. Other measures are all supportive. Echocardiography allows identification of

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the cause in the vast majority of children with suspected heart disease. Many of these are tackled by curative or palliative operations. A diagnostic label of idiopathic dilated cardiomyopathy mandates careful exclusion of all conditions that are known to cause ventricular dysfunction. The commonest conditions likely to be missed are sustained tachyarrhythmias, coarctation of the aorta and obstructive aortitis, anomalous origin of the left coronary artery from pulmonary artery and hypocalcemia. It is important to look out for subtle evidence of sustained tachyarrhythmias on the ECG. The heart failure is readily corrected once the tachyarrhythmia is taken care of and this may require completely different approach (e.g using beta blockers). The treatment approaches for tachyarrhythmias is written in the section on arrhythmias. Anomalous origin of the left coronary artery is treated surgically with rewarding results. Many myocardial diseases do not have specific treatment. However they may improve with supportive measures. 2. Supportive Measures: The work of the heart is reduced by restricting the patient’s activities, sedatives, treatment of fever, anemia, obesity, and by vasodilators. Mechanical ventilation helps when heart failure is severe by eliminating the work of breathing. Infants should be handled minimally. An incline of about 30° allows pooling of edema fluid in the dependent areas, reduces the collection of fluid in lungs, thus reducing the work of breathing. Humidified oxygen improves impaired oxygenation secondary to pulmonary congestion, thus reducing the work of heart by reducing requirements of cardiac output. If the infant or the child is restless or dyspneic, sedation may help by reducing anxiety and lowering endogenous catecholamine secretion. 3. Reducing Preload: Diuretics are the mainstay in managing CHF. They provide symptom relief through removing excess lung water. Diuretics reduce the blood volume, decrease venous return and ventricular filling. This tends to reduce the heart size. The larger the heart, the more the wall tension and the poorer is its performance. With reduction in heart size and volume, the myocardial function and the cardiac output improve. Diuretics are the first line of management in congestive failure. The action of orally administered frusemide starts within 20 minutes. Frusemide interferes with the diluting mechanism in the distal cortical tubules and sodium transport in loop of Henle or the ascending limb. Frusemide interferes with the sodium reabsorption mechanism in descending limb of loop of Henle. Patients on frusemide should be given potassium supplement. With the use of potent diuretics like frusemide it is necessary to have frequent checks of the serum electrolytes to prevent serious electrolyte imbalance. It may be preferable to combine frusemide with a potassium sparing diuretic such as triamterene, spironolactone or amiloride. 4. Reducing Afterload: Vasodilators reduce cardiac work by reducing the afterload. Increased afterload is the result of increased systemic vascular resistance, from overcompensated sympathetic drive. The use of ACE inhibitors (enalapril) is now well established as vasodilators in infants and children. Besides being vasodilators, ACE inhibitors have other useful effects in congestive failure. They suppress renin angiotensin/ aldosterone system, thus reducing vasoconstriction as well as sodium and water retention. They prevent potassium loss and hence reduce arrhythmias. Persistent cough is a side effect and may necessitate the use of angiotensin receptor blockers such as losartan. Initially it is

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necessary to monitor the renal function—urinalysis, serum creatinine, and blood urea— once a week for six to eight weeks after starting ACE inhibitors. First dose should be one quarter of the calculated dose to avoid “first dose hypotension”. 5. Improving Myocardial Contractility: The use of agents to improve contractility is of value mainly for the acute care setting and during postoperative care. Digoxin was once the mainstay of treatment. There is a trend to limit the use of drugs such as digoxin because of absence of any major survival or symptom benefit. Digitalis decreases heart rate and increases myocardial contractility. The strength and velocity of myocardial contraction is increased due to a direct action on the myocardium, whether it is normal or failing. Infants tolerate digitalis well. In a hospitalized patient full digitalization should be sought to maximize benefit. Digitalis is used with caution preterm infants. 6. Managing co-morbidity: Fever, anemia or infection also increase the work of the heart. Lung infections are particularly common and merit aggressive management. Anemia imposes stress on the heart and its correction reduces cardiac work. Typically packed cell volumes of 15–20 mL/kg are required to correct severe anemia. A single dose of frusemide (1mg/kg) should be given intravenously prior to transfusion. The role of beta blockers in children with heart failure is controversial. Beta blockers have gained importance in treating CHF related to pump failure in adults. They have shown increase in stroke work index, decrease in LV chamber size and decrease in heart rates. Recently they have been used with some success even in the pediatric population also with primary myocardial dysfunction. Metoprolol which is a selective B-1 blocker has been studied in children and have shown benefit in improving the cardiac function and the clinical functional class. They have shown benefit in patients with cardiomyopathies and some moderate to severe CHF. However, some nonselective beta blockers such as Carvedilol have not shown such clear benefits among pediatric population although some studies have shown a favorable response. However, due to its additional effects such as peripheral and pulmonary vasodilatory reponses, it has still been tried in certain cardiomyopathies and as a bridge to transplantation. In one such randomized placebo controlled trial use of Carvedilol did not show any changes in mortality

Acute CHF Perhaps the most important consideration while managing infants with acute CHF is to recognize that mechanical ventilation which often provides the greatest benefit among all the measures instituted in the ICU because it dramatically eliminated the work of breathing.

Inotropic Agents in the Acute Care Setting Inotropic agents belong to two groups: i. Catecholaminic inotropic agents like dopamine, dobutamine; and adrenaline ii. Phosphodiesterase inhibitors like milrinone. These agents combine the inotropic effects with peripheral vasodilation. The specific indications for the use of include, acute mitral or aortic regurgitation, ventricular dysfunction resulting from myocarditis, anomalous coronary artery from pulmonary artery and in the early postoperative setting. In the acute care setting sodium nitroprusside is often used as a vasodilator when

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contractility ids reserved and blood pressures are normal or elevated. It has effects on both the venous as well as the arterial systems. If the blood pressure is low, dopamine should be used. Dopamine is given as an intravenous infusion. At a dose of less than 5 mg/kg/min it causes peripheral vasodilation and increases myocardial contractility. The renal blood flow improves, resulting in natriuresis. In higher doses it results in peripheral vasoconstriction. Dobutamine has certain advantages over dopamine. It does not need to be administered via a central line. The dose of dobutamine is 2.5 to 15 mg per kg/min. It should be increased gradually till the desired response is achieved.

SUGGESTED READING 1. Balaguru D, Artman M, Auslender M. Management of heart failure in children. Curr Probl Pediatr. 2000;30(1):1–35. 2. Blume ED, Canter CE, Spicer R, et al. Prospective single-arm protocol of carvedilol in children with ventricular dysfunction. Pediatr Cardiol. 2006;27(3):336–42. 3. Bruns LA, Chrisant MK, Lamour JM, et al. Carvedilol as therapy in pediatric heart failure: an initial multicenter experience. J Pediatr. 2001;138(4):505–11. 4. Erickson LC: In: Burg FD, Polin RA, Ingelfinger JR, Wald ER, eds. Congestive Heart Failure in Current Pediatric Therapy. Philadelphia, Pa: WB Saunders. 1997;16. 5. Erickson LC. Medical issues for the cardiac patient. In: Critical Care of Infants and Children 1996; 259–62. 6. Freed MD: Congestive heart failure. In: Nadas’ Pediatric Cardiology. 1994;63–72.

7

Systemic Hypertension in Children Uma S Ali, Alpana Ohri

Systemic hypertension is not uncommon in children. Its reported prevalence in developed countries is about 1–3% with an increase in recent times to 4.5% largely due to the epidemic of obesity and insulin resistance.1-3 This makes it as common as antenatally detected hydronephrosis or urinary tract infections in infancy. However, it is recognized far less frequently. Hypertension is mostly silent except when severe and hence likely to be missed unless measuring blood pressure becomes part of routine pediatric practice as is growth monitoring and immunizations.

Definitions,Staging and Classification of Hypertension In adults definition of blood pressure is based on approximate level of BP that marks an increase in cardiovascular events and death. However in children the definition continues to be based on the upper segment of the normal BP distribution and not on outcome data.4 Blood pressure can be considered normal if both systolic and diastolic blood pressure is less than 90th centile for age, gender and height. Hypertension is diagnosed when either the systolic or diastolic blood pressure is above the 95th centile. Stage I hypertension is diagnosed when systolic or diastolic blood pressure is above 95th centile but not greater than 5 mm above the 99th centile. Stage II hypertension is diagnosed when systolic or diastolic blood pressure is more than 5 mm above the 99th centile. Prehypertension is said to exist when the blood pressure is above the 90th centile but less than the 95th centile. Severe hypertension has not been as rigorously defined but usually denotes BP 20 mm Hg above the 95th percentile. Severe hypertension has been traditionally divided into hypertensive emergencies and hypertensive urgencies.The former is associated with life threatening symptoms and/or target organ injury in the form of hypertensive encephalopathy, left ventricular failure, retinopathy or acute renal failure. Hypertensive urgencies can be defined as severe hypertension without acute target organ injury but with a high-risk of developing the same.

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Before making a diagnosis of hypertension at least three readings of blood pressure should be taken and the mean of the three readings should be considered as the representative value. When asymptomatic hypertension is diagnosed the additional measurements can be taken at weekly intervals. However, if Stage II hypertension is diagnosed the second and third readings should be taken at the same visit to confirm the diagnosis. White coat hypertension (WCH) refers to hypertension detected in the physician’s office but not present when measured in the patient’s usual surroundings. Masked hypertension also referred to as reverse white-coat HTN is said to exist when blood pressure measured in the clinic is not high but is high in the patient’s usual surroundings. Home blood pressure monitoring or ambulatory blood pressure monitoring may be needed to confirm these diagnoses. White coat hypertension may not be entirely innocuous and may represent a prehypertensive state. Both WCH and masked hypertension are not uncommon having a prevalence of 20% and 10%respectively in adults and may be associated with left ventricular hypertrophy, an independent predictor of cardiovascular morbidity.5

Screening for Hypertension The awareness that essential hypertension has its origin in childhood has resulted in increased emphasis on screening. All children more than 3-year-old, who are seen in clinics or hospital settings should have annual measurement of blood pressure.6 Blood pressure should also be measured in at-risk younger children with: (i) history of prematurity, very low birth weight or interventions in NICU; (ii) congenital heart disease; (iii) recurrent urinary tract infections, known renal or urological diseases, hematuria or proteinuria; (iv) family history of congenital renal disorders; (v) malignancy, post organ transplant; (vi) conditions associated with hypertension, e.g., neurofibromatosis, tuberous sclerosis and ambiguous genitalia. Blood pressure should be measured in patients who present with features of kidney or heart disease, seizures, altered sensorium and headache or visual complaints. Accurate techniques for measurement of blood pressure are necessary for its diagnosis, staging and follow-up.

MEASUREMENT OF BLOOD PRESSURE Measuring blood pressure requires a little time and attention to the right method. It also requires the use of appropriate reference standards to detect and stage the blood pressure appropriately as milder case of hypertension are likely to go unrecognized especially in younger children if not referenced to age appropriate charts. The sphygmomanometer remains the gold standard for measuring blood pressure. It requires the use of appropriate sized cuffs. The width of the cuff bladder should be 40% of the arm circumference midway between the olecranon and the acromion and its length 80–100% of the arm circumference. The patient should be seated or supine with the arm at heart level. Blood pressure should be measured in the right arm once the child has rested for 5–10 minutes. The first Koratkoff sound should be taken as the systolic blood pressure and the diastolic blood pressure is the level at which sounds disappear totally. However in infants and preadolescent children, the fifth Korotkoff sound may not disappear until the pressure is very low so that the first and fourth Korotkoff sounds(muffling of sounds) represent the SBP and DBP.7

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Besides mercury sphygmomanometer,other BP measurement devices include oscillometric devices,aneroid devices and ambulatory blood pressure monitoring(ABPM). Oscillometry based devices are popular in infants where auscultation is difficult and in intensive care settings where frequent blood pressure measurements are needed. Aneroid devices require frequent calibration and validation and should be avoided.6 ABPM is being increasingly recognized as a valuable tool in the investigation of pediatric hypertension. It involves repetitive noninvasive BP measurements using portable devices in outpatients over an entire day and maintaining a patient diary to account for times of physical activity,sleep and drug intake. It reflects true blood pressures more accurately and correlates better with target organ damage. It is also useful for identifying white coat hypertension,isolated nocturnal hypertension and characterizing BP patterns and assessing response to therapeutic interventions. The results are interpreted as the mean BP (in day,night or over 24 hours),BP load(percentage of measurements more than 95th percentile limit and BP patterns (nocturnal dip). Despite the obvious advantages of ABPM its widespread use is limited in children because of lack of availability of pediatric instruments and normative standards.8 The reference standards to be used for children between 1–17 years of age are the published charts by the fourth task force, which depend on age, gender and height.9 The systolic and diastolic norms depend on the height percentile for age. For neonates a standardized protocol for blood pressure measurement using an automated oscillometric device should be followed and the normative data published by the second task force should be used.10 Direct arterial puncture monitoring or umbilical artery catheterization is used in sick neonates.11

CAUSES Secondary Hypertension Childhood hypertension is usually secondary hypertension especially when it occurs below 10 years of age. In more than 90% of the cases there is an underlying renal problem that may be parenchymal or renovascular in nature. Cardiac and endocrine diseases form a smaller but significant subgroup with distinct therapeutic implications.

Primary Hypertension Primary hypertension is increasingly being recognized in children especially in older children and adolescents. A careful exclusion of secondary causes needs to be considered before making a diagnosis of primary hypertension. Genetic influences undoubtedly play a role in the development of primary hypertension in many patients. However these influences are modified by body habitus and the lifestyle of the individual. Dietary habits decreased physical activity, obesity, smoking and stress may be some of the contributory factors. High sodium and low potassium intake may favour the development of hypertension in a predisposed individual. Low birth weight and administration of antenatal steroids for fetal lung maturation to prevent respiratory distress syndrome are considered as important risk factors.11 In children primary hypertension tends to be milder but is not entirely innocuous. Essential hypertension often tracks into adulthood and is an important contributor to increased cardiovascular morbidity.12,13

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Clinical Features Most hypertension is clinically silent. Non-specific features in younger children include irritabily, excessive sweating, feeding problems and failure to thrive. Infants may present with cardiac failure. Severe or sudden rise of hypertension may manifest with headache, vomiting, altered sensorium, convulsions, facial palsy or hemiparesis. Presentation as dilated cardiomyopathy is encountered occasionally. The cardiac dysfunction leads to a fall in blood pressure that may sometimes lead to a missed diagnosis or underestimation of the severity of the hypertension. Examination for stigmata of collagen vascular disease and neurocutaneous syndromes should be done in all children with hypertension. Taking blood pressure in all 4 limbs and palpation of all peripheral pulses should be always done. Abdominal auscultation for bruit should not be forgotten. Anthropometric evaluation including calculation of body mass index is an important part of clinical examination. Children with BMI > 95th centile for age are more likely to have higher blood pressures. Clues to the presences of the original disease should be looked for (Table 7.1).

Renal Parenchymal Disorders These account for 70 to 80% of cases of childhood hypertension. Focal segmental glomerulosclerosis, chronic glomerulonephritis, hemolytic uremic syndrome (HUS), lupus nephritis, Henoch-Schonlein purpura and other renal vasculitis are some important causes of hypertension. Children with these glomerular diseases often have edema and oliguria. Joint pains, skin rashes, abdominal pain, anemia and extrarenal involvement may be present in the vasculitic disorders. Hemolytic uremic syndrome especially the nondiarrheal variety is known to cause very severe hypertension during the acute phase which often persists even when HUS activity resolves. Abnormal urinalysis with proteinuria and/or hematuria is a constant accompaniment of glomerular disorders. Non-glomerular disorders such as reflux nephropathy, obstructive uropathy, dysplastic kidneys, and polycystic kidneys may be totally asymptomatic or may have clinical stigmata of chronic renal disease in the form of anemia, short stature, failure to thrive and rickets. Children with reflux nephropathy may have a past history of recurrent UTI in the form of fever, vomiting, loin pain, and dysuria. Not uncommonly serious reflux nephropathy may exist in the absence of any such history. Chronic renal failure of any

Table 7.1: Causes of secondary hypertension Renal causes 1. Renal parenchymal Glomerulonephritis Reflux nephropathy Vasculitis Renal dysplasia Ask upmark kidney Polycystic kidney diseases Chronic renal failure 2. Renovascular Renal artery stenosis Fibromuscular dysplasia Aortoarteritis/Takayasu’s arteritis 3. Endocrine Catecholamine excess Pheochromocytoma Neuroblastoma Paraganglioma Corticosteroid excess Exogenous steroids Cushing’s syndrome/disease Congenital adrenal hyperplasia 11B hydroxylase deficiency 17 alpha hydroxylase deficiency Primary hyperaldosteronism Adenoma Adrenal hyperplasia Monogenic defects Apparent mineralocorticoid excess Liddle syndrome Glucocorticoid remediable aldosteronism Gordon syndrome 4. Cardiac causes Coarctation of aorta

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etiology is an important cause of hypertension. Occasionally a renin-secreting tumor such as Wilm’s tumor or tumor of the juxta glomerular apparatus may be the cause of hypertension.

Renovascular Disease These account for approximately 10% of all cases of childhood hypertension. Aortoarteritis is the commonest cause of renovascular hypertension in Indian children and may have a tubercular etiology. Renal artery stenosis and fibromuscular dysplasia are other important causes of renovascular hypertension in children. Renal vein thrombosis and renal artery thrombosis are important neonatal causes of hypertension and may be the sequelae of umbilical vessel cannulation. Children with neurofibromatosis or William’s syndrome may have associated renovascular cause for hypertension.

Endocrine Some endocrine causes have obvious clinical clues such as cushingoid facies in Cushing’s syndrome and ambiguous genitalia or virilization in congenital adrenal hyperplasia. Only two defects producing CAH result in hypertension. These include the more common 11B hydroxylase defect and the rare 17 alpha hydroxylase defect. Children with 17 alpha hydroxylase deficiency are not virilized and hence go unrecognized till an older age when hypertension and hypogonadism may be the clinical features. Boys may have external genitalia of the female phenotype. Catecholamine producing tumours like pheochromocytoma,neuroblastoma and paraganglioma can present with severe hypertension without any other associated symptoms. Episodic rise of BP, excessive sweating, tachycardia or palpitations are not always found in children. Hence children with stage II hypertension without an apparent renal cause should have a screening for urinary vanyl mandelic acid (VMA) and catecholamine studies. Rare endocrine causes include primary hyperaldosteronism that may be characterized by early onset hypertension, hypokalemia and metabolic alkalosis. The hormonal profile is characterized by elevated aldosterone with low renin levels. Primary hyperaldosteronism may be due to adrenocortical adenoma or hyperplasia. Monogenic defects of sodium excretion or reabsorption at the level of the cortical collecting tubule are inherited in a Mendelian fashion. They are rare causes of early onset hypertension and include four different conditions—apparent mineralocorticoid excess, Liddle’s syndrome, glucocorticoid remediable aldosteronism and Gordon’s syndrome.13,14

Cardiac Causes Coarctation of aorta remains the most important cardiac cause of hypertension. It is easily missed if routine palpation of lower limb pulses is not done. Upper limb BP that is more than 10 mm Hg higher than the lower limb BP is a characteristic feature. In infancy it may be associated with other cardiac anomalies and may present with cardiac failure. In older children it is usually an isolated anomaly. Intermittent claudications, notched ribs on X-ray are some clinical and investigative clues. Their absence does not exclude the diagnosis. Children with Turner’s syndrome have a higher incidence of coarctation.

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INVESTIGATIONS Investigations can be characterized into those done for detecting the cause of hypertension and tests to detect target organ damage.

Tests to Identify the Cause Initial Investigations All children diagnosed to have hypertension should undergo initial investigations with urinalysis, tests for renal excretory function, serum electrolytes and ultra-sonography of the kidneys, ureters and bladder as listed in Table 7.2. As the majority of pediatric hypertension is due to renal parenchymal disorders the initial tests are designed to identify these. Most renal parenchymal disorders can be identified by a combination of these tests. The presence of proteinuria and/or hematuria is a characteristic feature of glomerular disorders. Urinalysis may be totally normal in non-glomerular disorders especially the structural defects. These are identified on USG. Kidney sizes should be carefully assessed and compared to normative data based on age and length in order to identify slightly smaller kidneys that may give a clue to the existence of scarred kidneys. The presence of marginally smaller kidneys may be the only clue on initial investigations to indicate the pres- Table 7.2: Investigations in a child with hypertension ence of renovascular problems or reflux A. Investigations for cause Initial investigations nephropathy. Urinalysis Children with chronic renal failure will BUN, S Creatinine have elevated BUN and serum creatinine S electrolytes levels and may have associated hyper- USG of kidneys Second line investigations kalemia and metabolic acidosis. DMSA renal scan The main role of electrolyte estima- Serology for ANA, ANCA, C3, C4 tion however is to look for the presence of Doppler evaluation of renal vasculature hypokalemic metabolic alkalosis which Urinary VMA, catecholamines Confirmatory tests although very rare gives a valuable clue to Renal biopsy for glomerular disease the presence of primary or secondary hy- MCU for VUR peraldosteronism. Electrolytes need to be Selective Renal arteriography for RAS MR angiography RAS evaluated before starting any drug therapy. Spiral CT renal angiography RAS

Confirmatory Tests Renal Parenchymal Disorders Children suspected to have a glomerular pathology can be characterized further by appropriate serological tests such as antinuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), anti-neutrophil cytoplasmic antibodies (ANCA ), C3 levels as indicated. Renal biopsy may be needed in most of these cases.

CT scan for tumors Special tests for endocrine hypertension Hormonal profile Serum cortisol, catecholamines, peripheral renin activity, aldosterone When primary hypertension is suspected Fasting blood sugar Lipid profile Uric acid B. For target organ damage Opthalmic evaluation 2D echocardiography Microalbuminuria

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Structural problems may require additional imaging studies to define the anomalies. Reflux nephropathy needs to be excluded in apparently clueless hypertension by a DMSA scan which may demonstrate scarring.

Renovascular Hypertension Evaluation for renovascular hypertension should be undertaken when there are obvious clinical clues to suggest the presence of renovascular disease. In the absence of such clinical clues, investigations for renovascular hypertension should be undertaken in children who have difficult to control severe hypertension after reflux nephropathy and renal parenchymal causes have been ruled out. Doppler ultrasonography evaluation of the aorta and main renal arteries is a good screening test for renovascular hypertension. The detection of flow abnormalities is a good pointer to the presence of renal artery stenosis but the absence of abnormalities does not exclude a renovascular cause. Doppler studies may not delineate abnormalities in accessory renal arteries and intrarenal vasculature which are the common sites of involvement in children. Selective renal arteriography with or without digital subtraction remains the gold standard for identifying renal artery stenosis and abnormalities of intrarenal vasculature. Although invasive, with risks of contrast administration and high radiation it is the investigation of choice and can be combined with transluminal balloon angioplasty at the same setting. With technological advancements magnetic resonance angiography gives good delineation of the renal vasculature, aorta and its other branches without the risks of radiation and contrast administration and can be the investigation of choice when intervention is not planned. Spiral CT renal angiography gives excellent visualization but at the cost of high radiation exposure and risks of contrast administration. It can be utilized when selective renal arteriography or MR angiography is not feasible or available.15,16 Primary Hypertension Older children with mild to moderate hypertension who have normal initial investigations and no target organ damage are likely to have primary hypertension. They need to have their fasting lipid levels and uric acid levels assessed. Obese or overweight hypertensive adolescents should also have their fasting blood sugar estimated.

Investigations for Target Organ Damage These should be done in all cases. Target organ damage may be seen in the form of retinopathy, increase in left ventricular mass and diastolic dysfunction, microalbuminuria(more than 300 micrograms per gram of creatinine), intimal and medial changes in blood vessels.Target organ damage is not uncommon and may be seen with even stage I hypertension. The choice of investigations as well as the rapidity of evaluation is entirely dependent on the age of the child, the clinical clues, the severity of hypertension and the presence or absence of target organ damage.

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Transient Hypertension A significant number of hypertension in children may be transient. However its transient nature does not make it any less serious. The common causes of transient hypertension include •• Acute glomerulonephritis •• Genitourinary surgery •• Colloid infusions •• Drugs.

Treatment Hypertensive Emergencies Severe hypertension that occurs acutely may lead to end organ injury and manifest as emergencies in the form of hypertensive encephalopathy, left ventricular failure, retinopathy or renal failure. The severity of the hypertension as well as the rate of rise of BP may determine the occurrence of the damage. This requires emergency reduction of blood pressure in a controlled manner. The goal should be to reduce the blood pressure by 25% over one hour and then to lower it gradually to about the 95th centile for age by 24 hours (Flow chart 7.1). Levels below 95th centile should be achieved by 48 hours. Rapid reduction to normal levels may cause hypoperfusion and ischemic damage to organs such as the brain, retina, myocardium and the kidney. When managing patients with hypertensive emergencies,two IV lines should be maintained, one for infusion of antihypertensive and the other for saline infusion (if the blood pressure were to fall precipitously). Loss of pupillary reflex to light is an early indicator of retinal vascular ischemia, requiring immediate infusion of normal saline.6 Long-acting oral medications should be started after early so that they may become effective when parenteral therapy is being tapered.Prolonged use of IV anti-hypertensive agents is avoided because it may result in sodium and water retention and tachyphylaxis. IV nitroprusside is the most widely used drug for hypertensive emergencies in children. (Table 7.3). It acts rapidly and the dose can be titrated every few minutes to achieve the desired fall in BP but needs to be light protected as it is photosenstive. It is both an arterial and venodilator, reduces pre-load and after-load and is very useful in congestive heart failure Table 7.3: Drugs for hypertensive emergencies Drug Route Dosage

Class

Nitroprusside IV infusion 0.5–8 ug/kg/min Vasodialtor Nicardapin IV infusion 1–3 ug/kg/min CCB Labetalol IV Bolus 0.2–1 mg/kg/dose Alpha& B-Blocker IV infusionn max 40 mg/dose 0.25–3 mg/kg/hr Esmolol IV Bolus Bolus 100–500 mcg B Blocker over 1 min; then 25–100 mcg/kg/min; Increase to 500 mcg/kg/min Hydralazine IV Bolus 0.1–0.5 mg/kg/dose. Vasodilator 4–6 hours

Comments Monitor for cyanide toxicity if used for >72 hours in patient in renal failure Avoid in asthma and heart failure Can cause reflex tachycardia

Can cause CHF, bradycardia, bronchospasm contraindicated in cocaine toxicity Tachycardia, flushing, lupus like syndrome

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Flow chart: 7.1 Proposed algorithm for initial management of children with severe hypertension

CHF Congestive heart failure, IV intravenous, PO oral *Drug of choice but not available in India.

induced by hypertensive crisis. Use of the drug for more than 24–48 hours can lead to an accumulation of thiocyanate, especially in the presence of renal and hepatic insufficiency. Thiocyanate poisoning can cause methemoglobinemia, metabolic acidosis, altered mental status, and seizures.7 IV hydralazine has been used in certain situations, particularly in neonates and pregnant teenagers, to control severe hypertension. In very sick and low-birth-weight neonates for whom enteral administration of medications is not possible, IV hydralazine is a good therapeutic option. It is a potent arterial vasodilator with an onset of action within 10 minutes, and its effect lasts for 2–4 hours. It can be administered intramuscularly when immediate IV access is not available. The side-effects of hydralazine are tachycardia and sodium retention. Labetalol is a combined α1 and β-adrenergic blocking agent that can be administered either orally or intravenously. Intravenous labetalol can be administered as a continuous infusion or by bolus injection which can be advantageous when an infusion cannot be started quickly. Adverse reactions are those expected from a beta-adrenergic blocker, including bradycardia, bronchospasm and hyperkalemia especially in presence of renal insufficiency. It is contraindicated in patients with acute left ventricular failure. Severe hypertension from fluid overload in children with ESRD requires emergent ultrafiltration and dialysis. However if the child is in congestive cardiac failure, inotropic agents with vasodilator properties will need to be used to stabilize the patient. Diuretics can be effective in severe hypertension caused by acute glomerulonephritis. IV or transdermal nitroglycerin is generally not used as the first line of therapy and has not been used in children. It is a venodilator and therefore reduces pre-load and cardiac output. It can cause methemoglobinemia, hypoxemia, reflex tachycardia, and tachyphylaxis. It is usually considered in adults as adjunctive therapy for acute coronary syndromes. Sublingual nifedipine has been widely used in setups where hypertensive emergencies occur in the absence of ICU access. It is an effective drug to lower the BP but does so in an

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uncontrolled fashion. Despite the very real dangers of rapid acute reduction in BP it has been widely used with a fairly good safety profile in children.21,22 Other therapeutic options available abroad for hypertensive crisis are IV infusions of Nic ardipine,Esmolol,Fenoldopam,Clevidipine etc. Intravenous nicardipine is a dihydropyridine calcium channel blocker that is considered as the first line of therapy in children with hypertensive crisis abroad. It is very effective antihypertensive, lacks the negative inotropic effect of other calcium channel blockers, can be used for a longer period of time without the fear of cyanide toxicity and is safe even in patients with renal and hepatic failure. However it is not available in India.7,17

Hypertensive Urgency Hypertensive urgencies differ from emergencies in having no evidence of acute target organ damage. Children with hypertensive urgency do not need IV medications; can be treated with oral drugs but controlled reduction of blood pressure over several hours is desirable. However they need to be under close medical supervision as they have the potential to progress into an emergency. Effective oral agents include nifedipine, clonidine, enalapril, isradipine and labetalol. The onset of action of nifedipine (0.25 mg/kg,maximum 10 mg) administered orally is within 5–10 minutes, peaks at 30–60 minutes and lasts for 2–6 hours. While children show reflex tachycardia, the occurrence of serious complications with the use of oral nifedipine in this situation is rare. Oral administration of clonidine (0.05–0.1 mg) is also effective, although the onset of action (30–60 min) and peak effect (2–4 hours) is delayed. Sedation and orthostatic hypotension occurs in many patients. Sublingual or oral administration of captopril (6.25–25 mg) also shows a rapid onset (10–30 min) and peak (1–2 hours), and relatively prolonged duration of action (4–8 hours). Minoxidil is a direct vasodilator that has been shown to be effective in children with severe chronic hypertension refractory to other oral agents , and also in children with chronic hypertension experiencing acute BP elevations. It has well-known side effects of hirsutism and fluid retention that are primarily seen with chronic use.17 Isradipine is a second-generation dihydropyridine calcium channel blocker that has a rapid onset of action, usually producing BP within 1 hour of administration, with its peak effect occurring in 2–3 hours. A liquid formulation is available abroad facilitating precise dosing even in infants and small children. In many centres across the world isradipine has become the drug of choice for oral therapy of severe hypertension. Treatment of Persistent Hypertension The goal of treatment is to achieve sustained reduction of blood pressure below the 95th centile. In children with comorbid conditions such as chronic kidney disease or target organ damage; the aim should be to reduce it to below the 90th centile.

Nonpharmacological Interventions In children with prehypertension, primary hypertension and Stage I hypertension without target organ damage the initial therapy consists of non-pharmacological interventions. These

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consist of lifestyle changes that include dietary modifications, weight reduction, regular exercise and reduction in stress. Sodium intake should be reduced to less than 1.2 gm per day in children below 10 years of age and to less than 1.5 gm per day in older children. Avoiding added salt in the diet and reduction in the intake of baked and canned and processed foods goes along way to reduce the sodium intake. Pickles and papads are significant sources of salt in the Indian diet and should be strictly avoided. Fruits and nuts are rich in potassium and magnesium and may have a beneficial effect in lowering the blood pressure. Reduction in sedentary habits such as watching TV, video and computer games and increase in regular aerobic exercise in the form of play, dancing, swimming, etc. is most beneficial. For all children who are overweight, weight reduction is an important aspect of management. Cessation of smoking is an important consideration in adolescents.18,19 Children with hypertension should be encouraged to have aerobic exercise such as walking, running, swimming, dancing, etc. for 30 to 60 minutes at least 3 to 4 times a week. Besides helping in weight control exercise is beneficial in reduction of BP by producing vasodilatation and reducing peripheral insulin resistance. Children with well controlled hypertension without target organ damage can participate in competitive sports but need BP monitoring at two monthly intervals to see the effect of participation on the BP. Children with target organ damage or poorly controlled hypertension should avoid competitive sports. Anaerobic or static exercises such as weight lifting and body building should be avoided as it increases both systolic and diastolic blood pressure.20

Pharmacological Treatment Pharmacological treatment is required for all children with stage II hypertension and in those children with stage I hypertension that have comorbid conditions, target organ damage or where the hypertension has failed to resolve after 6 months of non-pharmacological therapy. The common initial drugs consist of either angiotensin converting enzyme inhibitors (ACEI) or calcium channel blockers (CCB) (Table 7.4). ACEIs block the conversion of Angiotensin I to angiotensin II — the most potent vasoconstrictor in the body. ACEI are drugs that also have a beneficial effect on proteinuria and are known to be both renoprotective and cardioprotective. They are the preferred drugs for children with chronic kidney disease and those with cardiac dysfunction. Children on ACEI require GFR and K monitoring. ACEI should not be used in children with suspected bilateral renal artery stenosis and in children with GFR < 30 mL/min. A 30% increase in serum creatinine from the baseline requires discontinuation or lowering of the drug dosage. Captopril and enalapril are the two most widely used drugs in this category. Enalapril has the advantage of once or twice daily dosing and hence is more commonly used in childhood hypertension.23 Calcium channel blockers are good first line antihypertensives. They inhibit cellular influx of calcium and produce vascular smooth muscle relaxation. The most widely used drug in this category is nifedipine. Amlodepin has the advantage of a longer duration of action and lends itself well to once daily dosing. Diuretics may serve as first line drugs when salt and water retention in the form of edema forms an important component of the hypertensive child like in a patient with postinfectious

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Pediatric Cardiology Table 7.4: Drugs used in the treatment of childhood hypertension

Agents

Dose;Frequency

Comments

Captopril

0.3–0.6 mg/kg/day;tid

Use cautiously if GFR < 30 mL/m in/1 .73 m 2; avoid in renal artery stenosis Avoid in neonates. Monitor serum potassium, creatinine

Enalapril

0.1–0.6 mg/kg/day;qd

Side effects: hyperkalemia, impaired renal functions; anemia, neutropenia,

Lisinopril

0.06–0.6 mg/kg/day;qd

Dry cough infrequently

Ramipril

6 mg/kg/day

Dose modification is needed in renal failure.

ACE inhibitors

Angiotensin receptor blockers

Same as ACE inhibitors except that cough is not seen and dose modification is not needed in renal failure

Losartan

0.7–1.4 mg/kg/day;qd-bid

Irbesartan

4–5 mg/kg/day

Calcium channel blockers Nifedipine

0.25–3 mg/kg/day;qd-bid

Amlodipine

0.05–0.5 mg/kg/day

Lower extremity edema, erythema

Isradipine

0.15–0.8 mg/kg/day

Liquid formulation is available abroad

Beta blockers Atenolol 0.5–2 mg/kg/day

Extended release nifedepine must be swallowed as a whole Side effects: Headache, flushing, dizziness, tachycardia; at higher doses:

Avoid in asthma, heart failure; Sleep disturbances, hyperlipidemia. Atenolol: decrease dose by 50% at GFR 20 Kg. Another PDE5 inhibitor, Tadalafil has similar pharmacologic effects as sildenafil, but is longer acting requiring only once a day administration is approved for use in adults, but studies in children are awaited.

Adjunctive Therapy Chronic oxygen therapy is indicated in patients who are desaturated at rest or during sleep or with exercise. It is recommended that oxygen administration should be towards a goal of maintaining peripheral oxygen saturations in the low 90% range. It helps preventing hypoxia induced vasoconstriction, and polycythemia from chronic hypoxia, which might lead to

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further complications. Oxygen is recommended during air travel, respiratory infections and during exercise in patients who may be normally saturated at rest. Atrial septostomy is indicated in patients in severe right heart failure with recurrent syncope due to fixed cardiac output. It has been shown to result in improved survival compared to conventional therapy, and is usually used as a bridge to lung transplant.30 Lung or heart-lung transplantations are performed in a few centers worldwide, however, the limited availability of organs, the high rate of rejection and infections make this option the last resort in very sick patients. Multiple other molecules are currently undergoing laboratory and animal as well as limited human trials and there is promise of further improved therapies in the future. Lastly, the genome projects also are leading to exciting discoveries, with the hope of gene therapy, preventing the progression of the disease as well as predicting patients at-risk for the disease.31

CONCLUSION Despite the introduction of multiple new medications into the treatment armamentarium for pulmonary hypertension, this disease still remains a serious and potentially life-threatening illness with multiple management challenges. With increasing understanding of the cellular processes involved in the disease, newer therapies are emerging, specifically targeting these factors and hold great promise for future outlook in this disease.31

REFERENCES 1. D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. results from a national prospective registry. Ann Intern Med. 1991;115:343–9. 2. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: The impact of epoprostenol therapy. Circulation. 2002;106:1477–82. 3. McLaughlin VV, Presberg KW, Doyle RL, et al. Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126:78S–92S. 4. Yung D, Widlitz AC, Rosenzweig EB, Kerstein D, Maislin G, Barst RJ. Outcomes in children with idiopathic pulmonary arterial hypertension. Circulation. 2004;110(6):660–5. 5. Channick RN, Sitbon O, Barst RJ, Manes A, Rubin LJ. Endothelin receptor antagonists in pulmonary arterial hypertension. J Am Coll Cardiol. 2004;43(12 Suppl S):62S–67S. 6. Rosenzweig EB, Widlitz AC, Barst RJ. Pulmonary arterial hypertension in children. Pediatr Pulmonol. 2004;38:2–22. 7. Gaine S. Pulmonary hypertension (grand rounds). JAMA. 2000;284:3160–8. 8. Barst RJ. Recent advances in the treatment of pediatric pulmonary artery hypertension. Pediatr Clin North Am. 1999; 46(2):331–45. 9. McLaughlin VV. Classification and epidemiology of pulmonary hypertension. Cardiol Clin 2004;22:327–41. 10. Simonneau G, Robbins IM, Beghetti M, Channick RN, Denton CP, Elliott GE, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009;54:S43–54. 11. Baquero H, Soliz A, Neira F, Venegas ME, Sola A. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: A pilot randomized blinded study. Pediatrics. 2006;117:1077–83. 12. Calhoun DA, Murthy SN, Bryant BG, Luedtke SA, Bhatt-Mehta V. Recent advances in neonatal pharmacotherapy. Ann Pharmacother. 2006;40(4):710–19.

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13. Cook LN, Stewart DL. Inhaled nitric oxide in the treatment of persistent pulmonary hypertension/ hypoxic respiratory failure in neonates: An update. J Ky Med Assoc. 2005;103(4):138–47. 14. Singh SA, Ibrahim T, Clark DJ, Taylor RS, George DH. Persistent pulmonary hypertension of newborn due to congenital capillary alveolar dysplasia. Pediatr Pulmonol. 2005;40:349–53. 15. Eulmesekian P, Cutz E, Parvez B, Bohn D, Adatia I. Alveolar capillary dysplasia: A six-year single center experience. J Perinat Med. 2005;33:347–52. 16. Wagenvoort CA and Wagenvoort. N. Primary pulmonary hypertension. A pathological study of the lung vessels in 156 clinically diagnosed cases. Circulation. 1970;42:1163–84. 17. Barst RJ, Maislin G, Fishman AP. Vasodilator therapy for primary pulmonary hypertension in children. Circulation. 1999; 99:1197–1208. 18. Fuster V, Steele PM, Edwards WD, Gersh BJ, McGoon MD, Frye RL. Primary pulmonary hypertension: Natural history and the importance of thrombosis. Circulation. 1984;70:580–7. 19. Rosenzweig EB, Barst RJ. Idiopathic pulmonary arterial hypertension in children. Curr Opin Pediatr. 2005;17:372–80. 20. Barst RJ, Rubin LJ, McGoon MD, Caldwell EJ, Long WA, Levy PS. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med. 1994;121:409–15. 21. Berman EB, Barst RJ. Eisenmenger’s syndrome: Current management. Prog Cardiovasc Dis. 2002;45:129–38. 22. Galie N, Torbicki A, Barst R, et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. the task force on diagnosis and treatment of pulmonary arterial hypertension of the European society of cardiology. Eur Heart J. 2004;25:2243–78. 23. Humbert M, Barst RJ, Robbins IM, et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J. 2004;24:353–9. 24. Rosenzweig EB, Ivy DD, Widlitz A, Doran A, Claussen LR, Yung D, Abman SH, Morganti A, Nguyen N, Barst RJ. Effects of long-term bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol. 2005 Aug. 16;46:697–704 25. Takatsuki S, Rosenzweig EB, Zuckerman W, Brady D, Calderbank M, Ivy DD. Clinical safety, pharmacokinetics, and efficacy of ambrisentan therapy in children with pulmonary arterial hypertension. Pediatr Pulmonol. 2012. 26. Galiè N, Hoeper MM, Simon J, Gibbs R, Simonneau G; Task Force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Liver toxicity of sitaxentan in pulmonary arterial hypertension. Eur Heart J. 2011;32:386–7 27. Schulze-Neick I, Hartenstein P and Li J. Intravenous Sildenafil is a potent pulmonary vasodilator in children with congenital heart disease. Circulation. 2003;108:II-167–II-173 28. Madden BP, Allenby M, Loke TK, Sheth A. A potential role for sildenafil in the management of pulmonary hypertension in patients with parenchymal lung disease. Vascul Pharmacol. 2006;44: 372–76. 29. Barst RJ, Ivy DD, Gaitan G, Szatmari A, Rudzinski A, Garcia AE, Sastry BK, Pulido T, Layton GR, Serdarevic-Pehar M, Wessel DL. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation. 2012 Jan 17;125:4–34. 30. Kerstein D, Levy PS, Hsu DT, Hordof AJ, Gersony WM, Barst RJ. Blade balloon atrial septostomy in patients with severe primary pulmonary hypertension. Circulation. 1995; 91:2028–35. 31. Archer SL, Weir EK, Wilkins MR. Basic science of pulmonary arterial hypertension for clinicians: New concepts and experimental therapies. Circulation. 2010;121:2045–66.

Syncope in the Young

9

S Deshmukh, P Hingorani, S Deshpande, Y Lokhandwala

INTRODUCTION Syncope, a transient loss of consciousness, is a common clinical problem. Syncope is derived from the Greek words, ‘syn’ meaning ‘with’ and the verb ‘koptein’ meaning ‘to cut’ or `to interrupt’. Most often syncope occur due to neurocardiogenic causes (61% to 80% of cases),1 while underlying cardiac disease like Wolff-Parkinson-White syndrome, AV block, longQT syndrome (LQTS), Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia, account for 6–8% of cases.1 Syncope may occur at any age; however it is predominantly prevalent in childhood, adolescence and in elderly people. Even though most of the cases are benign, it results in significant distress to patient and relatives, especially when patient is young. Therefore, the attending physician should perform a thorough evaluation of cause and provide emotional reassurance with a goal to improve the quality of the patient’s life and to prevent injury to the patient or others.2

DEFINITION As per European Society of Cardiology Guidelines (2009) syncope is defined as “transient loss of consciousness (T-LOC) due to transient global cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery.”3

EPIDEMIOLOGY The incidence of syncope was 1.7% of all patients seen at neurology clinics4 and 125.8/100,000 population as reported by Driscoll et al5 whereas, it was a chief complaint in 3% of all emergency hospital visits and up to 6% of hospitalizations.1,4 Syncope is common in the pediatric population, with 15–25% of children and adolescents between the ages of 8 and 18 years experiencing at least 1 syncopal event by adulthood.1,6,7 An incidence peak occurs around the age of 15 years, with females having more preponderance than males.5 In children

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and adolescent athletes with sudden death due to cardiac origin (85%), 17% had a history of syncope.1,5,8 The primary purpose of the evaluation of the patient with syncope is to determine whether the patient is at increased risk for death and to find out whether the causative factor of syncope in the patient is of cardiac or non cardiac in origin. (Table 9.1)

Non Cardiac Causes Neurocardiogenic/Reflex Syncope The vasovagal syncope is the most frequent neurocardiogenic syncope and is also known as vasodepressor syncope, neurally mediated syncope, reflex syncope, or the common fainting and it accounts for more than 50–70% of the children with syncope.4,9 Vasovagal syncope is usually a benign condition and the episodes are self-limiting. However, the quality of life of patients with recurrences can be seriously affected.10 Patients classically experience 3 distinct phases during an event: Prodrome, loss of consciousness, and recovery. A good prodrome history can determine the diagnosis. This phase can last seconds to minutes and is usually recalled by the patient.1 Vasovagal syncope is stimulated by physical or emotional stimuli (e.g. pain, fright, sight of blood), and may be preceded by warning symptoms such as pallor, weakness, yawning, lightTable 9.1: Causes of syncope in young patients I.  Noncardiac causes

II.  Cardiac causes

A.  Neurocardiogenic/reflex syncope i. Vasovagal ii. Situational iii. Stretch

A.  Cardiac arrhythmias (Primary cause) i. Ventricular and supraventricular tachycardia (i.e Wolf-Parkinson-White Syndrome) ii. Ion channel abnormalities a.  Long QT syndrome—congenital and or    drug induced b.  Brugada syndrome iii. Atrioventricular conduction block (congenital and acquired) iv. Arrhythmogenic right ventricular disease v. Sinus node dysfunction (including bradycardia/ tachycardia syndrome) vi. Implanted device (pacemaker, ICD) malfunction vii. Sick sinus syndrome

B.   Orthostatic hypotension i. Volume depletion/hemorrhage ii. Anemia iii. Drug (and alcohol)-induced orthostatic syncope iv. Primary autonomic failure syndromes v. Secondary autonomic failure syndromes C.   Neurologic i. Migraines ii. Seizures iii. Subclavian steal D.  Breath holding spells E.  Others i. Hypoglycemia ii. Psychiatric

B.  Structural cardiac or cardiopulmonary disease i. Obstructive cardiac valvular disease ii. Unrepaired tetralogy of fallot iii. Coronary artery anomalies iv. Pulmonary hypertension v. Obstructive cardiomyopathy vi. Left atrial myxoma vii. Acute aortic dissection viii. Pericardial tamponade ix. Pulmonary embolism x. Cardiac tumors

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headedness, nausea, diaphoresis, hyperventilation, blurred vision, decreased hearing, etc. which carry the evidence of decreased systemic and cerebral perfusion.11 It may be characterized by the sudden loss of vasomotor tone with resultant systemic hypotension (the vasodepressor response), accompanied by significant bradycardia or asystole (the cardioinhibitory response) Fig. 9.1. Hunter in 1773 first identified vasodepressor reaction as a cause of syncope.12 A century later, Foster described vagally induced cardioinhibition as a putative cause of syncope.13 Most episodes occur either during a prolonged period of standing or during the rapid change from supine or sitting position to standing. Vasovagal syncope may also include an emotional component. The loss of consciousness does not last for more than one to two minutes. However, the loss of consciousness may be prolonged if the patient tries to return to the upright position too quickly. Prolonged unconsciousness may indicate a diagnosis other than vasovagal syncope. The physiologic mechanism thought to be responsible for vasovagal syncope is an exaggeration of the normal Bezold-Jarisch reflex responsible for maintaining blood pressure during orthostatic stress.9

Orthostatic Hypotension Orthostatic hypotension occurs when the autonomic nervous system fails to maintain a stable blood pressure when there is a sudden change in posture. It happens due to venous pooling and hypovolemia and occurs when one changes to upright posture after a prolonged bed rest. In children, this may occur with acute febrile illness.14 Neurologic Neurological causes of syncope should be considered only if suggested by the history or physical examination. Epileptic seizure is associated with loss of consciousness; however, patents with seizures do not experience the prodrome symptoms of syncope.1 Migraine can too cause syncope; specifically, vertebrobasilar vascular spasm.1 Cardiac causes of syncope can be accompanied by upward gaze deviation, asynchronous myoclonic jerks, and brief automatisms that result from global cerebral hypoperfusion and are not an indication for a neurological evaluation.1

Figure 9.1: Asystole following termination of SVT

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Breath Holding Spell Breath holding spells may be responsible for syncope in a patient with a normal ECG and echocardiogram.15,16 In 2–5% of well patients an emotional upset have been reported to be a cause for breath holding spells.16 Others Hypoglycemia may cause syncope though this is preceded by weakness and sweating. Psychiatric causes of syncope are common in adolescents like malingering, hyperventilation and conversion syncope but rare in children under the age of 10.1

CARDIAC CAUSES Cardiac Arrhythmias Syncope can arise due to multiple factors such as type of arrhythmia (supraventricular or ventricular tachycardias), Wolff-Parkinson-White (WPW) syndrome, sick sinus syndrome, brady-tachy syndrome, atrioventricular (AV) block and sinus node dysfunction. Arrhythmias are the most common cardiac causes of syncope. In supraventricular tachycardias (SVT) a relative anoxia from compromised cardiac output can lead to syncope.6 In WPW syndrome, a delta wave (due to accessory conduction through the Bundle of Kent), and other associated ECG findings can be seen. Most patients with WPW will have symptoms of palpitations caused by accessory pathway mediated atrioventricular reciprocating supraventricular tachycardia—a generally benign form of supraventricular tachycardia17 but rarely atrial fibrillation may cause a very rapid ventricular rate, leading to ventricular fibrillation. In the absence of structural heart disease syncope and sudden death can be caused by inherited cardiac ion channel abnormalities. The two most prevalent ion channel abnormalities are the long-QT syndrome (LQTS) and the Brugada syndrome. Both the conditions should be diagnosed on the basis of careful family history and the analysis of the ECG. Long-QT syndrome: Inherited long QT syndrome (LQTS) refers to the primary electrical diseases of the heart and is characterized by QT prolongation on resting electrocardiogram (ECG) and syncope due to life-threatening ventricular arrhythmias (Fig. 9.2).18 LQTS is characterized by prolongation of the QT interval with a QTc > 450 ms on resting ECG. This prolongation in the QT is caused by a genetic defect in either cardiac potassium (LQT1 and LQT2) or sodium (LQT3) channels. Long QT syndrome type 2 (LQT2) is caused by loss-of-function mutations in KCNH2 (named HERG), the gene that encodes the channel carrying the rapidly activating delayed rectifying potassium current (IKr). Long QT type 2 is the second most frequent phenotype of LQTS, accounting for 35–40% of all patients with LQTS.19 In LQTS patients the lifetime risks of syncope or actual sudden death can be around 5%, 20%, and 50% with a QTc < 440 ms, 460–500 ms, and > 500 ms, respectively. In recent analysis of 3015 Registry LQTS children by Goldenberg, showed that the time-dependent syncope is the most powerful predictor of outcome during childhood among both LQTS males and females.19 Syncope is an ominous finding and is presumably secondary to an episode of torsades de pointes polymorphic ventricular tachycardia (Fig. 9.3) that terminates spontaneously.2

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Figure 9.2: LQT in 4-year-old child

Figure 9.3: Torsades de pointes

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Brugada syndrome: The Brugada syndrome is an inheritable arrhythmogenic disorder of the cardiac sodium channel resulting in ST elevation in the anterior precordial leads, i.e. V1 and V2, and susceptibility to polymorphic ventricular tachycardia and increased risk of sudden cardiac death.20,21 Patients with Brugada syndrome who present with syncope have a 2-year risk of sudden cardiac death of approximately 30%.20 Probst et al studied 30 children under the age of 16 affected with Brugada syndrome of which 11 were diagnosed after a syncopal episode confirming that Brugada syndrome though rare, can manifest at a very young age.21

Structural Cardiac or Cardiopulmonary Disease The structural cardiac or cardiopulmonary causes of syncope are: 1. Left ventricular outflow obstruction (aortic valve stenosis and hypertrophic obstructive cardiomyopathy are the most common examples). 2. Cardiac tumors (such as an atrial myxoma that can obstruct the mitral valve). 3. Obstructed blood vessels (such as a massive pulmonary embolus) and coronary artery anomalies. 4. Restricted cardiomyopathy, which results in, restricted filling and reduced diastolic size of the ventricles. 5. Unrepaired tetralogy of Fallot is a significant cardiac cause of syncope. Due to the right to left shunting across the VSD, an acute fall in arterial saturation occurs resulting in a syncopal attack.

EVALUATION OF A PATIENT WITH SYNCOPE As syncope can be due to variety of causes, it is important to establish a cause so that patients can be risk stratified and managed accordingly. In most patients, the cause of syncope can be determined with great accuracy from a careful history and physical examination, although the mechanism of syncope remains unexplained in 40% of episodes.22 The most important part of the diagnostic evaluation in a patient with syncope is taking a good history and performing a physical examination. In majority of patients their symptoms before and after the syncopal episode, along with an observer’s description of the event plays an important role in evaluating the cause of syncope. An ECG should be used as a screening tool for the unusual cardiac causes and if required a tilt table test, which is a safe diagnostic tool, can be done.23 Holter monitoring, electrophysiological testing, and loop event monitoring are used in the evaluation of patients with syncope. Loop recording (LR) devices have made it possible to capture arrhythmias during recurrent symptoms, thus allowing the diagnosis of arrhythmic syncope to be made with greater certainty. Symptom correlation is generally not possible with electrophysiological testing. Loop monitoring is the test of choice when bradyarrhythmia is a consideration. Implantable loop recorders (ILR) are the diagnostic test of choice to detect bradyarrhythmias in patients with rare recurrent symptoms24 when conventional diagnostic testing, such as electrocardiogram, Holter monitoring, and/or external loop recording (ELR), is inconclusive.25 In case of a genetic disorder such as LQTS or Brugada syndrome detected in children as a cause of syncope the evaluation should be extended to the other family members.2

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In making a diagnosis of syncope it is important to differentiate it from other mimics like seizure, drop attacks, presyncope, and dizziness. These symptoms except seizures can easily be differentiated from syncope because these symptoms do not cause loss of consciousness. Features separating seizure and syncope are precipitants, prodromal symptoms, and complaints during the spell, and symptoms after the episode help in differentiating between seizure and syncope. Loss of consciousness precipitated by pain or occurring after exercise, micturition, defecation, and stressful events is generally due to syncope, whereas aura may precede a seizure. Symptoms such as sweating and nausea during the episode are associated with syncope. A long duration of loss of consciousness (> 5 minutes), disorientation after the event, and slowness of return to consciousness suggest a seizure.26 Syncope can result in seizure-like activity, but when rhythmic movements (such as clonic or myoclonic jerks) are reported, seizure is the likely diagnosis.

ECG Evaluation An ECG is an important screening tool for investigating syncope as it can detect cardiac related causes such as: 1. Arrhythmia related syncope which may be due to: a. Atrioventricular blocks (High grade) b. Sick sinus syndrome c. Sinus bradycardia (< 50 bpm) d. Pre-excited QRS complexes e. Prolonged QT interval f. Ventricular or supraventricular arrhythmias g. LQTS h. Brugada syndrome. 2. Cardiac ischemia. ECG monitoring is indicated only when there is a high pre-test probability of arrhythmia responsible for syncope. Immediately after a syncopal attack, ECG monitoring for a few days is justified and is of value in evaluating the definite cause of syncope.

Echocardiogram In certain instances, the patient history, physical examination and ECG may not be sufficient to provide a diagnosis or detect an underlying cardiac cause. In such cases, an echocardiogram is a helpful screening test. An echocardiogram can be helpful in identifying the fine cardiac abnormalities like valvular disease, pulmonary embolism or right ventricular enlargement. Anomalous coronary artery can also be detected on an echocardiogram that is the most frequent cause of sudden death in the young. If anomalous coronary artery is not visualized on echocardiography, it may be further evaluated with a transesophageal echocardiogram, cardiac MRI or CT, or other imaging modality.2

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Holter Monitoring and Event Recorder Depending on the frequency of the symptoms, the type and duration of ambulatory ECG monitoring is dictated. After a syncopal attack, Holter monitoring (Figs 9.4A and B) is the ideal to detect the episodes that occur at any time of the day and for episodes that occur at least once a month, event recording is suitable. In patients when the symptoms are infrequent, an implantable loop monitor allows the correlation of symptoms with the cardiac rhythm. Traditionally, ambulatory monitoring is carried out for 24 to 48 hours with a Holter monitor. The short duration of the recording limits the diagnostic yield. Event recorders allow ambulatory monitoring for 30 to 60 days. Patient triggering stores the ECG from 1 to 4 minutes before and 30 to 60 seconds after activation. The major limitation of the device is the complexity of its use, which results in patient errors with acquisition and transmission of data.27 The introduction of continuously recording monitors that have both patient-activated and automatic triggers appears to improve the diagnostic yield of event monitors.21

A

 

B

Figures 9.4A and B: A. Ambulatory Holter Monitoring (Mortara instrument H3+™ digital Holter recorder, Milwaukee, WI, USA.), B. Holter attached to the patient

Implantable Loop Recorder (ILR) Implantable loop recorders (Fig. 9.5) inserted subcutaneously under local anesthesia and have a battery life of up to 36 months. Advantages of ILRs include continuous loop high-fidelity ECG recording. Major disadvantage of ILR is the need for a minor surgical procedure and the high

A

B

Figures 9.5A and B: Implantable loop recorder: (A) Device; (B) Position of the device (A) Reveal® implantable loop recorder (Medtronic, Minneapolis, Minn)

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cost of the implantable device with high initial cost. Sometimes due to the presence of underor oversensing memory can be full and in that case it may be difficult to differentiate between supraventricular or ventricular arrhythmias.3 Although, ILR have high initial cost, it has shown to be more cost-effective than a strategy using conventional investigation where symptom– ECG correlation can be achieved in a substantial number of patients during the active life of the device.24,29 Pooled data from nine studies,24,30-37 including 506 patients with unexplained syncope at the end of a complete conventional investigation, show that a correlation between syncope and ECG was found in 176 patients (35%); of these, 56% had asystole (or bradycardia in a few cases) at the time of the recorded event, 11% had tachycardia and 33% had no arrhythmia. In patients with unexplained syncope, use of an implantable loop recorder for one year yielded diagnostic information in more than 90% of patients.28

Head-Up Tilt Test When syncope is not diagnosed by typical history and compatible physical findings tilt table testing is a useful procedure. Tilt-table testing helps in identifying vasodepressor or other reflex-induced syncope. Tilt table test can be performed successfully on children over the age of six years, but also can be performed on younger children, if they are cooperative. Testing should be performed under controlled circumstances by experienced staff.38 Tilt testing has been widely used for investigational and therapeutic purposes. Factors such as angle of tilting, time duration and use of different provocative drugs play an important role in deciding the tilt testing protocols. The end-point of the test is defined as induction of syncope or completion of the planned duration of tilt including drug provocation. The test is considered positive if syncope occurs. The type of response influences the decision to terminate tilting.39 In order to classify the responses correctly, the tilting should be interrupted at the precise occurrence of loss of consciousness with simultaneous loss of postural tone.40 Premature interruption underestimates and delayed interruption overestimates the cardioinhibitory response and exposes the patient to the consequences of prolonged loss of consciousness. However, many of the physicians consider a steady fall in blood pressure accompanied by symptoms to stop the test. However, serious questions about the sensitivity, specificity, diagnostic yield, and dayto-day reproducibility of tilt table testing exist.41-44 The reported sensitivity and specificity of tilt table testing depend on the technique used. The sensitivity ranges from 26–80%, and the specificity is approximately 90%.

MANAGEMENT OF SYNCOPE When treating a patient with syncope, the main aim should be towards preventing any symptom recurrence, avoid any associated injuries (in neurocardiogenic causes), reduce the mortality rate and improve the quality of life. The underlying cause of the symptom is the basis for treating the patients with syncope. The present management of syncope consists of providing the patient with an explanation of the pathophysiology involved and advising him or her to avoid any stimulations. Generally, patients with syncope can be managed on an outpatient basis; however, hospital admission is necessary for rapid diagnostic evaluation in

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cases of serious arrhythmias, sudden death, and newly diagnosed serious cardiac disease (e.g. aortic stenosis, myocardial infarction). Management of syncope primarily depends on the underlying mechanism of the syncope. After evaluation of symptoms patients can be classified in broad three categories. Firstly, most common cause, i.e. neurocardiogenic syncope, secondly patients with underlying heart disease or arrhythmias, thirdly patients without identifiable underlying mechanism. Patients with underlying structural heart disease will need to undergo treatment for the underlying disease. Patients with underlying bradyarrhythmias and syncope will need to undergo pacemaker implantation. Patients with tachyarrhythmias will need to undergo either drug therapy or catheter ablation or ICD implantations. Breath-holding spells generally do not require specific therapy unless connected with longer asystole associated with potential cerebral injury.45,46 Treatment for neurocardiogenic syncope includes patient education; tilt training, drug therapy and pacemaker implantation.

Patient Education First and foremost thing is reassurance regarding relative harmless nature of the syncope. Patient and family should be told about almost nonexistent risk of sudden death.47 As physical injury remains a concern patient should be educated regarding identifying precipitating causes and presyncopal symptoms. This will not only help patients to avoid them but they can also assume certain postures to abort the episode. Assuming supine position or sitting along with lowering head between the knees helps to increase peripheral venous return and increase peripheral vascular resistance.48,49 But these postures draw attention from others. Krediet et al showed that the combination of leg crossing and tensing of the thigh and abdominal musculature is highly effective in aborting syncope in young patients with reflex syncope. Squatting also helps to increase the peripheral arterial resistance.50

PREVENTION OF SYNCOPE ON LONG-TERM BASIS Nonpharmacological Measures The treatment of neurally-mediated syncope in young includes behavior modification,47 increase in salt and fluid intake.47,51 In majority of the cases, behavior modification, is the first line of therapy and proves to be as useful as pharmacological therapy.47 Measures such as increase in salt and fluid intake, exercise and tilt training are helpful and safe. In highly motivated patients with recurrent symptoms, progressively prolonged periods of enforced upright posture or ‘‘tilt training’’ may reduce recurrences.

Pharmacological Therapy This should be reserved for patients with continued symptoms despite non pharmacological measures. One short-term randomized trial and a large number of uncontrolled studies of beta blockers claim effectiveness of these drugs, but several controlled trials did not show

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effectiveness.52-54 European guidelines year 2004 have made Class III recommendation for beta blockers in syncope. Mineralocorticoid, fludrocortisone is used more commonly in young patients. This drug along with increased salt intake increases blood volume and blood pressure and helps to reduce incidence of syncope. Mild fluid retention and occasional hypertension are generally the only significant side effects, making fludrocortisone 51,55 the best tolerated agent in pediatric patients. Other medications include agonists like midodrine or pseudoephedrine to increase the peripheral vascular resistance and venous tone, but the side effects of both medications are often intolerable.

Pacing Permanent cardiac pacing has been reported to be beneficial in some pediatric patients who have failed pharmacologic treatment. In cases of cardioinhibitory syncope with severe asystolic response, rarely a special “rate-drop” dual chamber pacemaker may be needed.56 The efficacy of this therapy is limited. Pacing for vasovagal syncope has been the subject of five major multicenter randomized controlled trials, three gave positive and two negative results. Putting together the results of the 5 trials, 318 patients were evaluated; syncope recurred in 21% (33/156) of the paced patients and in 44% (72/162) of not paced patients (p < 0.001).57-62 However, all the studies have weaknesses and further follow-up studies addressing many of these limitations (particularly the preimplant selection criteria of the patients who might benefit from pacemaker therapy) need to be completed before pacing can considered an established therapy.

CONCLUSION Syncope is a common cardiovascular symptom in young patients. It results in lot of anxiety to patient and family. Neurocardiogenic syncope remains the most common cause. Patients should be evaluated to rule out potentially dangerous disorders such as cardiac dysrrythmias or ventricular outflow tract obstruction. The most important part of the diagnostic evaluation is taking a good history and performing a physical examination. A good history from patient and observer will pinpoint to cause most of the times. ECG should be done in all patients. Further cardiac evaluation should be performed if a cardiac cause is suspected. Event monitor and implantable loop recorder are important investigating tools in syncope or arrhythmias and are likely to increase with respect to many current conventional investigations. Tilt table test is helpful in diagnosing neurocardiogenic cause of syncope. Patient education, behavior modification, increased fluid and salt intake remains the mainstay of therapy of neurocardiogenic syncope. Very rare patient will need drug or pacemaker therapy.

REFERENCES 1. Fischer JW, Cho CS. Pediatric syncope: Cases from the emergency department. Emerg Med Clin North Am. 2010;28:501–16.

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2. Strickberger SA, Benson W, Biaggioni I, Callans DJ, Cohen MI, Ellenbogen KA, et al. AHA/ACCF Scientific statement on the evaluation of syncope. Circulation. 2006;113;316–27. 3. Moya A, Sutton R, Ammirati F, Blanc JJ, Brignole M, Dahm JB, Deharo JC, et al. Task Force for the diagnosis and management of syncope; European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA); Heart Failure Association (HFA); Heart Rhythm Society (HRS). Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J. 2009;21:2631–71. 4. DiMario FJ and Wheeler CS. Castillo clinical categorization of childhood syncope. J Child Neurol. 2011;26:548. 5. Driscoll DJ, Jacobsen SJ, Porter CJ, et al. Syncope in children and adolescents. J Am Coll Cardiol. 1997;29:1039–45. 6. Black KD, Seslar SP, Woodward GA. Cardiogenic causes of pediatric syncope. Clinical Pediatric Emergency Medicine. 2011;12:266–77. 7. Johnsrude CL. Current approach to pediatric syncope. Pediatr Cardiol. 2000;21:522–31. 8. Maron BJ, Shirani J, Poliac LC, et al. Sudden death in young competitive athletes: Clinical, demographic, and pathologic profiles. JAMA 1996;276:199–204. 9. Feit LR. Syncope in the pediatric patient; Advances in pediatrics. Volume 43. 10. Linzer M, Gold DT, Pontinen M, et al. Recurrent syncope as a chronic disease: Preliminary validation of a disease-specific measure of functional impairment. J Gen Intern Med. 1994;9:181–6. 11. Shah JS, Gupta AK, Lokhandwala YY. Neurally-mediated syncope: An overview and approach. J Assoc Phys India. 2003;51:805–10. 12. Hunter J. The works of John Hunter with notes. Palmer JF, ed. London: Longman, Rees, Orme, Brown, and Green; 1837. 13. Foster M. Syncope. In: A Textbook of physiology. 5th ed. London; Macmillan: 1890. 14. Shalem T, Goldman M, Breitbart R, Baram W, Kozer E. Orthostatic hypotension In children with acute febrile illness. The of Emerg Med. 2012. 15. DiMario FJ Jr. Prospective study of children with cyanotic and pallid breath-holding spells. Pediatrics. 2001;107:265–9. 16. Kelly AM, Porter CJ, McGoon MD, Espinosa RE, Osborn MJ, Hayes DL. Breath-holding spells associated with significant bradycardia: Successful treatment with permanent pacemaker implantation. Pediatrics. 2001;108:698–702. 17. Santinelli V, Radinovic A, Manguso F, et al. The natural history of asymptomatic ventricular preexcitation: A long-term prospective follow-up study of 184 asymptomatic children. J Am Coll Cardiol. 2009;53:275–80. 18. Kapoor WN. Syncope. N Engl J Med. 2000;343:1856–62. 19. Goldenberg I, Zareba W, Moss AJ. Long QT syndrome. Curr Probl Cardiol. 2008;33:629–94. 20. Brugada J, Brugada R, Antzelevitch C, Towbin J, Nademanee K, Brugada P. Long-term follow-up of individuals with the electrocardiographic pattern of right bundle branch block and ST segment elevation in precordial leads V1 to V3. Circulation. 2002;105:73–8. 21. Probst V, Denjoy I, Meregalli PG, Amirault JC, Sacher F, Mansourati J, et al. Clinical aspects and prognosis of Brugada syndrome in children. Circulation. 2007;115:2042–8. 22. Kapoor WN. Current evaluation and management of syncope. Circulation. 2002;106:1606–9. 23. Wieling W, Ganzeboom KS, Saul JP. Reflex syncope in children and adolescents. Heart. 2004;90; 1094–1100. 24. Krahn A, Klein GJ, Yee R, Skanes AC. Randomized assessment of syncope trial. Conventional diagnostic testing versus a prolonged monitoring strategy. Circulation. 2001;104:46–51. 25. Rossano J, Bloemers B, Sreeram N, Balaji S, Shah MJ. Efficacy of implantable loop recorders in establishing symptom-rhythm correlation in young patients with syncope and palpitations. Pediatrics. 2003;112:e228–e233. 26. Hoefnagels WA, Padberg GW, Overweg J, et al. Transient loss of consciousness: The value of the history for distinguishing seizure from syncope. J Neurol. 1991;238:39–43.

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27. Linzer M, Pritchett E, Pontinen M, McCarthy E, Divine G. Incremental diagnostic yield of loop electrocardiographic recorders in unexplained syncope. Am J Cardiol. 1990;66:214–9. 28. Assar M, Krahn A, Klein G, Yee R, Skanes A. Optimal duration of monitoring in patients with unexplained syncope. Am J Cardiol. 2003;92:1231–3. 29. Farwell D, Freemantle N, Sulke N. The clinical impact of implantable loop recorders in patients with syncope. Eur Heart J. 2006;27:351–6. 30. Krahn A, Klein G, Norris C, Yee R. The etiology of syncope in patients with negative tilt table and electrophysiologic testing. Circulation. 1995;92:1819–24. 31. Krahn AD, Klein GJ, Yee R, Takle-Newhouse T, Norris C. Use of an extended monitoring strategy in patients with problematic syncope. Reveal Investigators. Circulation. 1999; 26:99:406–10. 32. Moya A, Brignole M, Menozzi C, Garcia-Civera R, Tognarini S, Mont L, Botto G, Giada F, et al. Mechanism of syncope in patients with isolated syncope and in patients with tilt-positive syncope. Circulation. 2001;104:1261–67. 33. Menozzi C, Brignole M, Garcia-Civera R, Moya A, Botto G, Tercedor L, Migliorini R, Navarro X; International Study on Syncope of Uncertain Etiology (ISSUE) Investigators. Mechanism of syncope in patients with heart disease and negative electrophysiologic test. Circulation. 2002;105:2741–45. 34. Brignole M, Menozzi C, Moya A, Garcia-Civera R, Mont L, Alvarez M, Errazquin F, Beiras J, et al. International Study on Syncope of Uncertain Etiology (ISSUE) Investigators. Mechanism of syncope in patients with bundle branch block and negative electrophysiological test. Circulation. 2001;104:2045–50. 35. Nierop P, van Mechelen R, Elsacker A, Luijten RH, Elhendy A. Heart rhythm during syncope and presyncope: Results of implantable loop recorders. Pacing Clin Electrophysiol. 2000;23:1532–1538. 36. Boersma L, Mont L, Sionis A, Garcia E, Brugada J. Value of implantable loop recorder for the management of patients with unexplained syncope. Europace. 2004;6:70–76. 37. Lombardi F, Calosso E, Mascioli G, Marangoni E, Donato A, Rossi S, Pala M, Foti F, et al. Utility of implantable loop recorder (Reveal Plus) in the diagnosis of unexplained syncope. Europace. 2005;7:19–24. 38. Seifer CM, Kenny RA. Head-up tilt testing in children. Eur Heart J. 2001;22:1968–71. 39. Wieling W, van Lieshout JJ, ten Harkel ADJ. Dynamics of circulatory adjustments to head up tilt and tilt back in healthy and sympathetically denervated subjects. Clin Sci. 1998;94:347–52. 40. Brignole M, Menozzi C, Del Rosso A et al. New classification of haemodynamics of vasovagal syncope: Beyond the VASIS classification. Analysis of the pre-syncopal phase of the tilt test without and with nitroglycerin challenge. Europace. 2000; 2:66–76. 41. Sagrista-Sauleda J, Romero-Ferrer B, Moya A, Permanyer-Miralda G, Soler-Soler J. Variations in diagnostic yield of head-up tilt test and electrophysiology in groups of patients with syncope of unknown origin. Eur Heart J. 2001;22:857–65. 42. Fujimura O, Yee R, Klein G, Sharma A, Boahene K. The diagnostic sensitivity of electrophysiologic testing in patients with syncope caused by transient bradycardia. N Engl J Med. 1989;321:1703–1707. 43. Garcia-Civera R, Ruiz-Granell R, Morell-Cabedo S, Sanjuan-Manez R, Perez-Alcala F, Plancha E, Navarro A, Botella S, et al. Selective use of diagnostic tests in patients with syncope of unknown cause. J Am Coll Cardiol. 2003;41:787–90. 44. Sarasin FP, Louis-Simonet M, Carballo D, Slama S, Rajeswaran A, Metzger JT, Lovis C, Unger PF, et al. Prospective evaluation of patients with syncope: A population-based study. Am J Med. 2001;111:177–84. 45. McHarg ML, Shinnar S, Rascoff H, Walsh CA. Syncope in childhood. Pediatr Cardiol. 1997;18:367–71. 46. Lewis DA, Dhala A. Syncope in pediatric patient. Pediatr Clin North Am. 1999;46:205–19. 47. Levine MM. Neurally mediated syncope in children: Results of tilt testing, treatment, and long-term follow-up. Pediatr Cardiol. 1999;20:331–5. 48. Saul JP. Syncope: Etiology, management, and when to refer. J S C Med Assoc. 1999;95:385–7. 49. Wieling W, Van Lieshout JJ, Van Leeuwen AM. Physical maneuvers that reduce postural hypotension in autonomic failure. Clin Autonom Res. 1993;3:57–65.

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50. Krediet CTP, Van Dijk N, Linzer M, et al. Management of vasovagal syncope: Controlling or aborting faints by the combination of legcrossing and muscle tensing. Circulation. 2002;106:1684–9. 51. Perry JC, Garson A Jr. The child with recurrent syncope: Autonomic function testing and betaadrenergic hypersensitivity. J Am Coll Cardiol. 1991;17:1168–71. 52. Mahanonda N, Bhuripanyo K, Kangkagate C, et al. Randomized doubleblind, placebo-controlled trial of oral atenolol in patients with unexplained syncope and positive upright tilt table test results. Am Heart J. 1995;130:1250–3. 53. Sheldon R, Rose S, Flanagan P, et al. Effects of beta blockers on the time to first syncope recurrence in patients after a positive isoproterenol tilt table test. Am J Cardiol. 1996;78:536–39. 54. Madrid A, Ortega I, Rebollo GJ, et al. Lack of efficacy of atenolol for prevention of neurally-mediated syncope in highly symptomatic population: A prospective double-blind, randomized and placebocontrolled study. J Am Coll Cardiol. 2001;37:554–9. 55. Grubb BP, Temesy-Armos P, Moore J, Wolfe D, Hahn H, Elliott L. The use of head-upright tilt table testing in the evaluation and management of syncope in children and adolescents. Pacing Clin Electrophysiol. 1992;15:742–8. 56. Gupta AK, Maheshwari A, Thakur RK, Shah CP, Lokhandwala YY. Can cardiac pacing prevent neurocardiogenic syncope? J Interv Card Electrophysiol. 2001;5(4):411–5. 57. McLeod KA, Wilson N, Hewitt J, et al. Cardiac pacing for severe childhood neurally mediated syncope with reflex anoxic seizures. Heart. 1999;82:721–5. 58. Sutton R, Brignole M, Menozzi C et al. Dual-chamber pacing in treatment of neurally-mediated tiltpositive cardioinhibitory syncope. Pacemaker versus no therapy: A multicentre randomized study. Circulation. 2000;102:294–9. 59. Connolly SJ, Sheldon R, Roberts RS et al. Vasovagal pacemaker study investigators. The North American vasovagal pacemaker study (VPS): A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope. J Am Coll Cardiol. 1999;33:16–20. 60. Ammirati F, Colivicchi F, Santini M et al. Permanent Cardiac Pacing versus medical treatment for the prevention of recurrent vasovagal syncope. A multicenter, randomized, controlled trial. Circulation. 2001;104:52–7. 61. Connolly SJ, Sheldon R, Thorpe KE et al. for the VPS II investigators. Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II). JAMA. 2003;289:2224–9. 62. Giada F, Raviele A, Menozzi C et al. The vasovagal syncope and pacing trial (Synpace). A randomized placebo-controlled study of permanent pacing for treatment of recurrent vasovagal syncope. Pacing Clin Electrophysiol. 2003;26:1016.

10

Chest Pain in Childhood

M Zulfikar Ahamed, S Lakshmi

Chest pain in childhood is not an uncommon problem. Yet it is very uncommon to have cardiovascular cause for the chest pain in childhood. Nevertheless, as chest pain is generally linked to cardiovascular system by both children and parents, it is essential for both Pediatrician and pediatric cardiologist to make a proper assessment in a child with chest pain and offer reassurance and if required, solutions. Chest pain in children can be acute or recurrent. It is more common above ten years but can occur in as early as four years. It is slightly more common in males and forms a small but definite percentage of OPD referral in a teaching hospital; approximately 0.25%. Chest pain in children has to be assessed by assessing the following characteristics: 1. Location 2. Duration 3. Quality 4. Provoking factors 5. Relieving factors. Location can be central, on the left, especially below nipple, on the right and near epigastrium. Duration can be very brief to long—a few seconds to minutes or hours. Generally, it is relatively easy to characterize chest pain in children as anginal or nonanginal. Provoking factors like trauma, breathing, lying down, food intake and of course, exertion have to be evaluated. Relieving factors have to be identified.

CAUSES OF CHEST PAIN 1.

Noncardiac (> 90%) a. From chest wall i. Costochondritis ii. Tietze syndrome iii. Precordial catch syndrome

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iv. Trauma v. Muscle spasm/strain b. Respiratory i. Asthma ii. Bronchitis iii. Pneumonia iv. Pneumothorax v. Pleurisy c. Gastrointestinal tract i. Acute gastritis ii. GERD with esophagitis iii. Acid peptic disease d. Psychogenic e. Miscellaneous i. Varicella-zoster ii. Pleurodynia iii. Breast pain in girls f. Idiopathic chest pain (ICP). Cardiac (< 10%) i. Pericardium—Acute pericarditis ii. Coronary artery disease a. ALCAPA (Anomalous Left Coronary Artery from Pulmonary Artery) b. Anomalous route of Left coronary artery (LCA) c. Muscle bridging d. Coronary ostial stenosis e. Coronary AV fistula f. Type II hyperlipidemia g. Kawasaki disease h. Systemic tupus erythematous (SLE) iii. Myocardium a. Viral myocarditis b. Hypertrophic cardiomyopathy (HCM), Dilatation cardiomyopath (DCM) iv. Valves a. Mitral valve prolapse (MVP) syndrome b. Aortic stenosis c. Mitral stenosis d. Severe pulmonary stenosis (PS) e. Severe pulmonary arterial hypertension (PAH) v. Electrical a. Supraventicular tachycardia (SVT) b. Ventricular tachycardia (VT) c. Long QT (LQTS)/Wolff-Parkinson-White (WPW) syndrome

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SPECIFIC TYPES OF CHEST PAIN Costochondritis It is usually unilateral, can be either costochondral or costosternal. Involves two or more junctions and is sharp, lasting for a few seconds to minutes. It increases on deep breathing and local application of pressure.

Tietze Syndrome It is uncommon in children. Affects one junction with pain, tenderness and swelling.

Precordial Catch Syndrome Brief and localized to the area below left nipple and is often pleuritic.

Idiopathic Chest Pain (ICP) Very common. It is a sharp, brief (seconds–minutes) pain which is felt below left nipple or can be central. It increases on deep breathing.

Benign Adolescent Chest Pain Can occur between 8–16 years and peaks around 12 years, and may recur over months. Children may out grow this brief, sharp, precordial pain. One of the most important causes of cardiac chest pain is ALCAPA. The ALCAPA usually presents in infancy with CHF and episodes of irritability, presumably because of chest pain. Coronary AV fistula can produce coronary steal and cause ischemic pain. In both KD (Kawasaki disease) and SLE, pain could be severe because of acute myocardial infarction because of coronary vasculitis and ensuing thrombosis. Viral myocarditis can cause excruciating pain and often causes ECG changes simulating myocardial infarction. Valvar lesions produce pain because of supply-demand mismatch in oxygen supply. In PAH, pain can be because of RV ischemia, pulmonary infarct or acute dilatation of pulmonary artery. The MVP is a an important cause of chest pain in children. In our institution (Government Medical College, Trivandrum, Department of Pediatrics), chest pain was the leading symptom in MVP. About 2/3rd of MVP were symptomatic, out of which 25 children had chest pain, mostly non-anginal.

Leading Causes of Chest Pain in Children A. Cardiac 1. MVP 2. Pericarditis 3. Vasculitis B. Noncardiac 1. Idiopathic 2. Musculoskeletal 3. Costochondritis.

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Evaluation The purpose of evaluation of chest pain in preadolescent child or adolescent is: 1. To ascertain cause 2. To assess functional status of the heart and if found normal, reassure the child and the parents.

History Family history of cardiovascular risk factors has to be elicited. Sudden cardiac death (SCD) in the family may point to HCM or LQT Syndrome. Previous history of Kawasaki like illness, history suggestive of SLE, previous flu like illness, myocarditis and history of palpitations preceding chest pain have to be ascertained. Certain syndromes have to be looked for in the general examination. Williams syndrome, Marfan syndrome, tuberous sclerosis and Friederich’s syndrome have to be looked for, along with inspection for xanthomas. Pain has to be characterized into nonanginal and anginal type. There is usually a low prevalence of cardiac conditions in children with chest pain, but most of those conditions would require intervention; medically or otherwise. Cardiovascular examination including pulse, BP, JVP and precordial examination may rule out most lesions—valvar, myocardial and pericardial. Coronary abnormalities and electrical abnormalities may be hard to localize unless there is specific marker or markers as in SLE, Type II hyperlipoproteinemia and tuberous sclerosis. Situations that indicate high possibility of cardiac cause are: i. Syncope/presyncope ii. Paroxysmal palpitation iii. Previously diagnosed cardiac defect iv. Previously performed cardiac surgery v. History of SCD in the family vi. Exertional nature of pain.

LABORATORY EVALUATION (INVESTIGATIONS) Blood Counts Could be useful as sternal pain may be because of leukemia, rib pain because of sickle cell anemia and high PCV could be because of severe PAH (Eisenmenger syndrome). Hematological abnormalities occur both in SLE and Kawasaki disease. A very high ESR could be because of KD, SLE, viral myocarditis, bacterial pericarditis.

Chest X-ray It is useful in assessing cardiac status, possible lung pathology, chest wall problems.

Electrocardiography It could be very helpful in looking for left ventricular hypertrophy (LVH), myocardial ischemia including infarction. Right ventricular hypertrophy (RVH), arrhythmias and arrhythmia substrates like WPW and LQTS. It can be used judiciously for reassuring the parents (Figs 10.1–10.3).

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Figure 10.1: Electrocardiography: anomalous left coronary artery from pulmonary artery

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Figure 10.2: Electrocardiography: left ventricular hypertrophy because of aortic stenosis

Figure 10.3: Electrocardiography: long QT syndrome

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Echocardiography It has to be offered to selected patients. It can definitely rule out ALCAPA, coronary artery lesions in KD, anomalous route of LCA, coronary arteriovenous fistula (CAVF), viral myocarditis, HCM and DCM. Both valvar and pericardial diseases can be excluded in the appropriate setting (Figs 10.4–10.6).

Exercise Testing It could be utilized in older children and adolescents to provoke ischemia if any. But the yield in a nonselected group of children with chest pain can be very low (0.5%). Occasionally endoscopy, ultrasound of abdomen and other modalities of cardiovascular imaging may be required.

Figure 10.4: Echocardiography: hypertrophic cardiomyopathy (Abbreviations: IVS, Interventricular septal; LV, Left ventricle)

Figure 10.5: Echocardiography: viral myocarditis (Abbreviations: RV, Right ventricle; LV, Left ventricle; RA, Right artery; LA, left artery)

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Figure 10.6: Echocardiography: pericarditis (Abbreviations: AO, Aorta; LA, Left artery; LV, Left ventricle; RV, Right ventricle; PE, Pulmonary embolism)

MANAGEMENT Specific Causes a. b.

Noncardiac Cardiac Give specific treatment. Chest wall problems may need local heat application, anti-inflammatory drugs and reassurance. Respiratory problems have to be tackled using the standard protocol. Occasionally H2 receptor blockers and proton pump inhibitors may have to be used in gastrointestinal causes. Idiopathic chest pain needs only reassurance (Flow chart 10.1). Flow chart 10.1

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Specific cardiac causes need focused, specific, targeted management. Here, cardiac medications, interventions and surgery will possibly solve the issue.

SUGGESTED READING 1. Coleman W. Recurrent chest pain in children. PCNA. 1984;31:1007–26. 2. Driscoll DJ, Glicklich LB, Gallen WJ. Chest pain in children: A prospective study. Pediatrics 1976;57: 648–51. 3. Braunwald E. The history in Braunwald’s heart disease: In: Zipes Elsevier DP, Libby P. Bonow RD, Braunwald E (eds). Braunwald’s Heart Disease: A Textbook of Cardiorascular Disease, Philadelphia, WB Saunders. 2005. p. 63. 4. Duster MC. Chest pain. In: Garson A, Bricker JT, Fisher DJ, Neish SR. The Science and Practice of Pediatric Cardiology 2nd ed. Williams and Wilkinson. 1999. p. 2213. 5. Rowland TW, Richards MM. The natural history of Idiopathic Chest pain in Children. Clin Pediatr 1986;25:612. 6. Selbst SM, et al. Pediatric chest pain. a prospective study. Pediatrics. 1988;82:319.

11

Arrhythmias in Children

BRJ Kannan, R Krishna Kumar

INTRODUCTION A variety of cardiac arrhythmias can manifest in Abbreviations children that can present at any time from fetal AF — Atrial fibrillation life to adolescence. The reported incidence of AICD — Automatic implantable cardioverter defibrillator supraventricular tachycardia (SVT) in children ranges from 1 in 250 to 1 in 1000.1 Some of the AVNRT — AV nodal re-entrant tachycardia AVRT — Atrioventricular reciprocating tachyarrhythmias are potentially life-threatening and cardia recognition requires high index of suspicion. EAT — Ectopic atrial tachycardia — Junctional ectopic tachycardia Treatment is dictated by the specific arrhythmia JET MAT — Multifocal atrial tachycardia and hence it is important to arrive at a precise PJRT — Permanent junctional reciprocating diagnosis. Fortunately, many will resolve comtachycardia pletely after 12 to 18 months as a consequence RFA — Radiofrequency ablation of myocardial maturation and growth.2,3 In those SVT — Supraventricular tachycardia VT — Ventricular tachycardia with persistent arrhythmia, radiofrequency ablation (RFA) can effect a ‘cure’. While majority of children have structurally normal heart, arrhythmias are frequently encountered in children with underlying operated or unoperated congenital heart disease. Arrhythmias can be broadly classified into bradyarrhythmias and tachyarrhythmias. This chapter will provide an overview of understanding the mechanisms, diagnostic approach and management of common tachyarrhythmias in children. Detailed description of individual arrhythmia is beyond the scope of this chapter. Additional details on basic understanding of the ECG are discussed in a separate chapter.

CLASSIFICATION OF ARRHYTHMIAS Arrhythmias are commonly classified based on the site of origin (atrial, junctional or ventricular). Any tachycardia with its origin above the His bundle is called supraventricular tachycardia (SVT) and all the tachycardias that arise below the His bundle are called ventricular tachycardia (VT). A practical scheme for classification of tachyarrhythmias is

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Flow chart 11.1: AVNRT: AV nodal re-entrant tachycardia; AVRT: Atrioventricular reciprocating tachycardia, PJRT: Paroxysmal junctional reciprocating tachycardia

shown in Flow chart 11.1. The behavior and management depends on the mechanism by which the arrhythmia is produced. Two mechanisms commonly involved are increased automaticity and reentrant mechanism. The third mechanism is because of ‘triggered activity’.

Increased Automaticity Normally, sinus node automaticity is higher than other cardiac tissues. It produces impulses at a rate varying between 60 to 200/min depending on the physiological needs. Hence, it is called as the pacemaker of the heart. If another automatic focus develops in the atrium that fires at a rate faster than sinus rate, then it would result in ectopic atrial tachycardia (EAT). If there are multiple automatic foci, then the resulting tachycardia is called as multifocal atrial tachycardia (MAT). If an automatic focus develops in the junctional tissue (near His bundle), it would cause ‘junctional ectopic tachycardia’ (JET) and a similar focus in the ventricle will result in automatic VT.

Re-entrant Mechanism Here, an abnormal electrical circuit is formed where some portion of the circuit conducts fast and the other portion conducts slowly (Fig. 11.1). When an impulse encounters this circuit, it travels along both slow and fast pathways. By the time the impulse passes through

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A

B

C

Figure 11.1A to C: (A) A premature atrial complex (PAC) occurs and is blocked in a fast pathway, but it can propagate down the slower pathway; (B) By the time the electrical signal reaches the end of the slow pathway, the fast pathway has repolarized, and retrograde conduction of the wave occurs; (C) The wave then returns down the slow pathway, setting up a closed circuit that is self-sustaining

the slow pathway, the fast pathway is repolarized and is ready to conduct the impulse retrogradely. The wave then returns down the slow pathway setting up a closed circuit that is self-sustaining. The tachycardias caused by this mechanism and the associated re-entrant circuits are given in Table 11.1.

Triggered Activity

Figure 11.2: EAD: Early after depolarization; DAD: Delayed after depolarization

This occurs during the repolarization phase of the cardiac cycle. If the trigger occurs in phase 3 of ventricular depolarization, it is called early after-depolarization (Fig.  11.2). If the trigger occurs in phase 4, it is called delayed afterdepolarization. Long QT syndrome and digoxin toxicity related tachycardias are associated with this mechanism. The behavior of the tachycardias differs depending on the mechanisms involved as given in Table 11.2.

PRESENTATION OF CARDIAC ARRHYTHMIAS There is no specific symptom or sign that would help the clinician to diagnose arrhythmia. 1. Heart rate inappropriate for the clinical condition: Many a times, tachycardia is diagnosed on routine assessment while the child would be asymptomatic. Parent would notice ‘excessive neck pulsations’ and bring the child for evaluation. 2. Unexplained heart failure: a. This is relatively common in infants and young children who have poor symptom expression. The incessant arrhythmia would result in cardiac dilatation and heart failure and could be wrongly labeled as dilated cardiomyopathy. The underlying tachycardia as the cause may be easily missed and requires a high index of suspicion. b. Recent worsening or onset of new symptoms in a child with underlying corrected or uncorrected congenital heart disease should arouse the suspicion of tachycardia.

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Table 11.1: Re-entrant tachyarrhythmias Tachycardia Sinus node re-entry Intra-atrial re-entrant tachycardia (IART) Atrial flutter

Atrial fibrillation AV nodal re-entrant tachycardia (AVNRT) Atrioventricular reciprocating

Ventricular tachycardia (VT)

Re-entry circuit Small re-entry circuit within or very close to sinus node Common after cardiac surgeries where the re-entrant circuits form around the atrial incisions It is a macrore-entry where impulse passes up along the atrial septum and down along the right atrial free wall. At times, the direction of the impulse can be reversed. The zone of slow conduction is at the ‘isthmus’ between the IVC and coronary sinus openings in the right atrium Multiple small circuits usually located at the pulmonary vein-left atrial junctions Small circuit present within the AV node This is mediated by the presence of accessory conduction pathway (bypass tracts). The tachycardia (AVRT) atrial impulse travels down through AV node to the ventricles and ascends up through the bypass tract back to the atrium, thus forming a macroreentry. Rarely, the direction can be reversed with the impulse descending down the bypass tract. If the basal ECG shows delta wave suggestive of accessory pathway, then it is called WPW syndrome. If no delta wave is seen, it is called ‘concealed accessory pathway’ The re-entrant circuit seen in right ventricular outflow tract or it is formed by the fascicles of left bundle branch

Table 11.2: Features of automatic versus re-entrant tachycardia Automatic tachycardia Varying heart rates At the onset of tachycardia, the rate gradually accelerates to its peak level (‘warm up’ phenomenon). When the tachycardia reverts, the rate gradually decelerates to normal level (‘cool down’ phenomenon) Cardioversion ineffective Overdrive pacing ineffective Vagal maneuvers produce no change or can slow the rate that gradually returns to original rate

Re-entrant tachycardia Fixed heart rate Sudden increase and sudden fall in the heart rates (no warm up or cool down phenomenon)

Tachycardia is terminated Tachycardia can be terminated Can terminate AV nodal dependent re-entrant tachycardias

3. Episodic pallor, sweating or lethargy. 4. Palpitations and chest discomfort: This is one of the common symptoms with which older children and adolescents present. 5. Syncope, breath holding attacks or seizures: These are more common with bradyarrhythmias and are uncommon with SVT. However, malignant VT can present with cardiovascular collapse. In a child with suspected tachyarrhythmia, the following history should be obtained: a. Is there any precipitating event like exercise or emotion? b. How do the palpitations go off—spontaneously or by some maneuvers like coughing, sneezing or induced vomiting? If these vagal maneuvers abort the tachycardia, that would indicate the presence of AV nodal dependent tachycardia (AVNRT and AVRT).

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c. Family history of syncope or sudden death can suggest inherited disorders associated with arrhythmias like prolonged QT syndrome, arrhythmogenic right ventricular cardiomyopathy or hypertrophic cardiomyopathy d. Sensorineural deafness (prolonged QT syndrome) e. Previous cardiac surgery f. Drug intake: Certain drugs like macrolide antibiotics can cause QT prolongation and VT. Tricyclic antidepressants and digoxin can cause various arrhythmias. Supraventricular tachycardia accounts for 95% of tachyarrhythmias while ventricular tachycardia accounts for less than 5% in children. Most children with SVT have structurally normal heart. AV nodal dependent tachycardias form approximately 90% of all SVT in children.4 Common arrhythmias according to the age are as follows: 1. Neonatal period and early infancy: Atrial flutter, ectopic atrial tachycardia and bypass tract related tachycardias. These SVTs have 30% chance of complete resolution by 12 months and 50% of them resolve by 18 to 24 months.2,3 2. Infancy and early childhood: WPW syndrome and other bypass tract related tachycardias. Cardiovascular collapse can be the first presenting symptoms in older children with WPW syndrome but this is rare.5 There is a 2% incidence of sudden cardiac death in adolescents and young adults with WPW syndrome and hence it is not a benign disorder as it was considered earlier.6 Permanent junctional reciprocating tachycardia (PJRT), which is a form of bypass-tract related tachycardia and ectopic atrial tachycardia are known their incessant nature and causing tachycardiomyopathy. These children present with symptoms of heart failure. WPW syndrome is associated with Ebstein’s anomaly, corrected transposition of great arteries and cardiac rhabdomyomas. 3. Older children and adolescents: Even in this age group, WPW syndrome and other bypass tract related tachycardias form majority of SVTs. The next common SVT is AV nodal re-entrant tachycardia (ANVRT), constituting 30% of SVT in adolescents.4 A child with VT can present with syncope or can be completely asymptomatic. Significant number of these children has structurally abnormal heart. Cardiac surgery is one of the most common causes of VT in children. 15% of patients with congenital heart defects develop VT and 5 to 10% experience sudden death.7 In children with structurally normal hearts, there are two primary electrical abnormalities that result in malignant VT: prolonged QT syndrome and Brugada syndrome. The latter is characterized by right bundle branch block pattern with ST segment elevation in leads V1 to V3. Right ventricular outflow tract VT and left ventricular septal VT are also seen in structurally normal hearts and are relatively benign. Arrhythmogenic right ventricular cardiomyopathy is a condition where the myocardium of right ventricle is replaced with fibrofatty tissue and resulting in VT and sudden death. In infants, up to 40% have significant associated medical disorders like electrolyte imbalance, drug toxicity, myocarditis, cardiomyopathy, etc. Some forms of VT are catecholamine dependent (catecholaminergic VT) and brought on by emotion or exercise.

DIAGNOSIS AND MANAGEMENT OF TACHYARRHYTHMIAS A combined strategy that simultaneously addresses both diagnosis and treatment is appropriate. Extreme hemodynamic instability is relatively rare in childhood arrhythmias,

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particularly in the absence of structural heart disease. Children tolerate a wide range of heart rates. An infant or a child may appear quite comfortable with heart rates exceeding 240/min. In those who present with instability, synchronized DC cardioversion should be performed at a dose of 0.5 to 2 Joules/kg. Unless there is hemodynamic compromise; the important initial step is to record a 12 lead ECG and rhythm strip during tachycardia. One should follow the following steps to arrive at proper diagnosis of the tachycardia.

Is the QRS Complex Narrow or Broad? If the QRS complexes are narrow, it is suggestive of SVT (Fig. 11.3) and if it is broad, VT (Fig. 11.4) has to be diagnosed. A small percentage of SVT can present with broad QRS complexes. It is rare in children. If a child has bundle branch block pattern in the basal ECG, then any SVT in this child will have the same broad QRS complexes. Hence, it is important to compare the tachycardia ECG complexes with that of the basal ECG. This is especially important in children after cardiac surgery, as right bundle branch block pattern is quite common in this subset of children. In neonates and infants, even VT can have relatively narrow complexes. If the morphology and axis of QRS complexes is grossly different from that of basal ECG, one should suspect VT even if the QRS duration appears relatively narrow.

Is the Heart Rate Regular or Irregular? Tachycardias with irregular rhythm include, atrial fibrillation, atrial flutter or ectopic atrial tachycardia with varying block, and multifocal atrial tachycardia. In patients with WPW syndrome and atrial fibrillation, the rate will be irregular and QRS complexes would be wide because of conduction through accessory pathway. Other important cause for irregular wide QRS complex tachycardia is polymorphic ventricular tachycardia, which is a medial emergency. All the other tachycardias usually have regular RR intervals.

Figure 11.3: Narrow QRS tachycardia at a rate of around 300/min. Arrows show the inverted P waves on the ST segment suggestive of AVRT

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Figure 11.4: Broad QRS tachycardia of left bundle branch block morphology at a rate of 150/min. Arrows show P waves with AV dissociation suggestive of ventricular tachycardia

Is the P Wave Seen? The next most important step is to identify the P waves, which would give clues to the diagnosis of the rhythm disorder: •• If atrium and ventricles are simultaneously depolarized (AVNRT, JET), P wave would be submerged within QRS and hence no obvious P wave will be seen •• If T waves are tall and peaked, one should consider the superimposition of P wave on the T wave •• If the ST segment is depressed, especially in the inferior leads, it could be secondary to retrograde negative P wave falling on the ST segment •• In atrial fibrillation, no P waves are seen and the isoelectric line is replaced with fibrillatory waves •• In atrial flutter, the isoelectric line is replaced with continuous P waves giving rise to saw tooth appearance (Fig. 11.5).

If P Wave is Seen, What is its Relation with QRS? •• •• ••

If P waves are seen prior to each QRS complex, then the tachycardia is of atrial origin i. Normal P axis: Sinus tachycardia or sinus node reentrant tachycardia ii. Abnormal P axis (different P morphology): Ectopic atrial tachycardia (Fig. 11.7) If P waves are seen prior to each QRS but inverted in the inferior leads, the possibilities are: EAT, paroxysmal junctional reciprocating tachycardia and atypical AVNRT. If the P waves are seen after the QRS complex, generally it would be inverted in leads II, III and aVF. This is because of retrograde activation of atria from the ventricles. i. AVNRT: Inverted P wave is seen on the terminal portion of QRS or just after QRS complex. This is also seen in JET with 1:1 retrograde conduction. ii. AVRT (WPW syndrome): Inverted P is seen on the ST segment

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Figure 11.5: Atrial flutter. Note that the isoelectric line is replaced by the flutter wave with a ‘sawtooth’ appearance. The heart rate is irregular because of variable conduction

Figure 11.6: Narrow QRS tachycardia at a rate of 150/min: There are inverted P waves (arrow) seen in II, III and aVF. There is 2:1 AV block. The atrial rate is approximately 300 per minute. The possibilities include either atrial flutter or ectopic atrial tachycardia

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If P waves are seen with no consistent relation with QRS complexes, it indicates AV dissociation. If this occurs in the context of a narrow QRS tachycardia, it is diagnostic of JET. This is also a feature of VT where the QRS complexes would be broad.

What is the Effect of Vagal Maneuvers or Administration of Adenosine? Adenosine administration can be both diagnostic (Table 11.3) as well as therapeutic. It causes marked slowing of AV node conduction and the effect lasts few seconds only. Hence, the side effects (flushing, chest pain, dyspnea) are also short lived. It is imperative to obtain an ECG record during adenosine administration. Ideally, it should be given through a central line. Recommended dose is 50 to 300 mcg/kg. It should be followed by a rapid push of normal saline bolus. It is imperative to record the response to adenosine (Fig. 11.7). If adenosine is not available, vagal maneuvers can be attempted. For infants and young children, an ice filled plastic bag placed on the face is the most effective vagal maneuver. Older children can be encouraged to perform the Valsalva maneuver or carotid sinus massage can be done. Eyeball compression is unsafe to elicit vagal response and hence to be avoided. Table 11.3: Response of various tachycardias to adenosine Tachycardia Sinus tachycardia Ectopic atrial tachycardia Atrial flutter AV node dependent tachycardias (AVNRT and AVRT) Junctional ectopic tachycardia

Response to adenosine Gradual slowing of sinus rate and gradual return to the original level Ventricular rate slows, P waves unmasked Ventricular rate slows, flutter waves seen better Tachycardia terminates

No effect. AV dissociation might become prominent

Figure 11.7: Recording the effect of adenosine to diagnose tachyarrhythmia: A single lead (lead II) is shown here. The tachycardia is at the rate of 220 per minute with inverted P waves (small arrows) that appear between two QRS intervals (long R-P interval). Following the administration of adenosine (block arrow) there is abrupt slowing of heart rate resulting from termination of the tachycardia. Upright P waves (tall arrows) appear. They are not followed by QRS complexes initially. Later however, the P waves are followed by QRS complexes and isolated inverted P waves that are initially blocked. After an interval these inverted P waves are followed by single QRS complexes and eventually the tachycardia resumes. This response to adenosine is characteristic of permanent junctional re-entrant tachycardia (PJRT)

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Subsequent management depends on the diagnosis of the rhythm disorder. Though a variety of antiarrhythmic drugs have been recommended, many of them are either not available in our country or safety has not been tested in children. The common antiarrhythmic drugs and their doses are given in Table 11.4. If the child reverts from SVT to sinus rhythm either spontaneously or with adenosine, maintenance therapy has to be started. Beta blockers are the preferred drugs and any of the drugs mentioned in the Table 11.4 can be used. If the tachycardia does not respond to adenosine or recurs within seconds to minutes, then repeat administration of adenosine will not be useful. Start IV beta blocker therapy, esmolol, propranolol or metoprolol. This can either result in termination of tachycardia or control of the ventricular rate. Aim at a ventricular rate of < 120/min and start the maintenance therapy accordingly. This strategy would suffice in majority of children. Some children will still continue to remain in tachycardia despite IV beta blockade. The next step is to administer loading dose of IV digoxin. In older children, IV verapamil therapy can be tried. Extreme caution is needed during administration of verapamil in a child who has already received beta blocker therapy. An occasional child will be resistant to both beta blocker and digoxin and will need IV amiodarone infusion. If VT is diagnosed, then the maintenance therapy would be IV beta blocker therapy to IV amiodarone, depending on the clinical situation. Subsequently, the same drug is continued orally as maintenance therapy. Some tachycardias like right ventricular outflow tract tachycardia seen in children with no structural heart disease, generally respond well to beta blocker therapy. RFA is considered in older children and adolescents. Some tachycardias like arrhythmogenic right ventricular cardiomyopathy do not respond to any medical therapy. Similarly, VT occurring in patients with structural heart disease, e.g. operated tetralogy of Table 11.4: Drug treatment of tachyarrhythmia after the initial event Drug Dose Digoxin 40 mg/kg loading over 24 hours, then 10 mg/kg OD Esmolol IV – 0.5 mg/kg over 1 min, then 50–200 mg/kg/ min infusion

Propranolol Metoprolol Atenolol

IV – 0.1 mg/kg over 5 min, can be repeated every 5 min to max 3 doses Oral—2–5 mg/kg/day in three divided doses IV – 0.1 mg/kg over 5 min, can be repeated every 5 min to a max 3 doses Oral—2–4 mg/kg/day in 2 doses Oral—2–4 mg/kg/day OD

Verapamil

IV— 0.1–0.2 mg/kg over 10 min Oral—3–6 mg/kg/day in 3 doses

Amiodarone

IV—5 mg/kg over 1 hour, then 10–15 mg/kg over the next 24 hours. Maintenance: IV or oral—2.5–5 mg/kg/day

Comment Serum level increases if given along with amiodarone. Hence, the dose of digoxin has to be halved Short acting beta blocker, ideal in situations where prolonged beta blockade is undesirable, like reactive airway disease and LV dysfunction Ideal maintenance therapy in infants and small children as dose adjustments are easy Reasonable and less expensive substitute for Esmolol. Alternative to propranolol for maintenance (once a day dosage) Contraindicated in infants. If significant hypotension develops, give 1–2 ml/kg of Ca gluconate Associated with multiple side effects. Basal CXR, liver function test and pulmonary function tests need to be done and repeated half-yearly

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Fallot, can be life-threatening. In these children, implantation of automatic cardioverter defibrillator (AICD) is considered to be the most effective treatment.

Follow-up Care after the Arrhythmic Event Most childhood arrhythmias warrant evaluation by a pediatric cardiologist for follow-up care and to plan definitive treatment. This would often include an echocardiogram to rule out structural heart disease. Children are discharged on maintenance drug(s) to prevent recurrences. If the child is on amiodarone, one should attempt to reduce the dose to the minimum and later substitute with another antiarrhythmic drug, usually a beta-blocker. In the absence of recurrence, withdrawal of the drug can be tried at around 1½ to 2 years. In case of recurrence, the drug needs to be restarted and continued for few more years till the child becomes suitable for electrophysiological study and radiofrequency ablation. This modality offers a prospect of “cure” by permanently modifying the arrhythmic substrate. It has been successfully applied for a variety of arrhythmias (both SVT and VT) in children with structurally normal and abnormal hearts.8 The success rate of radiofrequency ablation in AVNRT and AVRT is more than 95%. Because of long-term concerns, radiofrequency ablation therapy is usually reserved for older children (> 4 years). For younger children RF ablation is reserved for refractory situations.9

REFERENCES 1. Garson A Jr, Ludomirsky A. Supraventricular tachycardia. In Garson A Jr, Bricker JT, McNamara DG (Eds): The Science and Practice of Pediatric Cardiology. Philadelphia: Lea & Gebiger. 1990;1809–48. 2. Nadas AS, Daeschner CW, Roth A, et al. Paroxysmal tachycardia in infants and children. Study of 41 cases. Pediatrics. 1952;9:167–81. 3. Lubbers WJ, Losekoot TG, Anderson RH, et al. Paroxysmal supraventricular tachycardia in infancy and childhood. Eur J Cardiol. 1974;2:91–99. 4. Ko JK, Deal BJ, Strasburger JF, et al. Supraventricular tachycardia mechanisms and their age distribution I pediatric patients. Am J Cardiol. 1992;69:1028–32. 5. Vignati G, Balla E, Mauri L, Lunati M, Figini A. Clinical and electrophysiologic evolution of the WolffParkinson-White syndrome in children: impact on approaches to management. Cardiol Young. 2000;10:367–75. 6. Pietersen AH, Andersen ED, Sandoe E. Atrial fibrillation in the Wolff-Parkinson-White syndrome. Am J Cardiol. 1992;70:38A–43A. 7. Vetter VL. What every pediatrician needs to know about arrhythmias in children who have had cardiac surgery. Pediatr Ann. 1991;20:378–85. 8. Anguera I, Brugada J, Roba M, Mont L, Aguinaga L, Geelen P, et al. Outcomes after radiofrequency catheter ablation of atrial tachycardia. Am J Cardiol. 2001;87:886–90. 9. Erikson CC, Walsh EP, Triedman JK, Saul JP. Efficacy and safety of radiofrequency ablation in infants and young children R shunts the S2 may be paradoxically split. Large PDAs are associated with wide pulse pressure because of the “diastolic steal” of blood in to the pulmonary circulation.

Aorto Pulmonary (AP) Window This is an uncommon malformation consists of a communication, usually large, between the adjacent walls of the ascending aorta and pulmonary trunk. The pathophysiology of AP window is similar to that of a large PDA. A restrictive AP window generates a continuous murmur, but this is rare. In most instances, the murmur is systolic because of the equalization of pressures in diastole. Infants with AP window present early and need surgical closure in the first few months of life.

PERINATAL CHANGES IN VASCULAR RESISTANCES INFLUENCING LEFT-TO-RIGHT SHUNTING3 Gas exchange in the fetus is a placental function; consequently there is little PBF and high pulmonary vascular resistance (PVR). The majority of right ventricular output is diverted through the ductus arteriosus into the descending aorta. The low resistance placental circuit reduces SVR. After birth, physical expansion of the lung and increase in arterial PaO2 drive a fall in PVR mediated by arteriolar dilation and increase in cross sectional area. This is needed to accommodate a full cardiac output. Pulmonary artery pressure (PAP) however still remains elevated (refer to section on hemodynamics) as smooth muscle regression and a postnatal increase in cross-sectional area of the pulmonary vascular bed allows for progressive reduction in PVR; substantially over the initial 8–12 weeks and then continuing until 4–5 years of age. Elimination of the low resistance placental circuit increases systemic vascular resistance (SVR) promoting left–to–right shunting. Time course of perinatal of changes in vascular resistances in the perinatal period dictate onset of clinical symptoms and hemodynamically significant left-to-right shunting at approximately 8–12 weeks.

FACTORS DETERMINING MAGNITUDE OF LEFT-TO-RIGHT SHUNTS1,4,5 Defect size is the primary determinant of the magnitude of shunting, larger defects allowing larger shunts. Left-to-right shunt physiology allows access to both the systemic and pulmonary circulations. Blood will preferentially flows to the site of least resistance. For larger defects (e.g. VSD) PVR is the most important determinant of left-to-right shunting. In the presence of a VSD, left ventricular blood can flow either into the aorta or the pulmonary artery. For the same sized defect, lower PVR promotes and a higher PVR impedes magnitude of left-to-right shunting. Higher SVR will promote and lower SVR will reduce left-to-right shunting.

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• • •

Size of the communication –  Larger defect—larger shunt Vascular resistances –  Lower relative (to SVR) or absolute PVR—higher magnitude of shunt –  Higher relative (to SVR) or absolute PVR—lower magnitude of shunt Ventricular stiffness (compliance) –  Decreased right ventricular stiffness (increased compliance)—larger shunt –  Increased left ventricular stiffness (decreased compliance)—larger shunt

For pretricuspid lesions (e.g. ASD) ventricular stiffness (compliance) rather than resistances determines the magnitude of shunting. The lower the absolute or relative (compared to left ventricle) stiffness of the right ventricle larger is the shunt. Typically right ventricular stiffness decreases with age (regression of fetal right ventricular hypertrophy). Left ventricular stiffness increases with age especially in adults: Left ventricular hypertrophy from systemic hypertension or myocardial infarction. Both promote left-to-right shunting. Vascular resistances indirectly influence ventricular stiffness.

PATHOPHYSIOLOGY Left-to-right shunting increases PBF without changing EPBF (re-circulation of already oxygenated blood). Increased PBF increases pulmonary hydrostatic pressure; there is also increase in pulmonary venous return, which in turn increases left atrial and left ventricular end-diastolic pressure. These changes in Starling’s forces at the pulmonary capillaries promote net transudation of fluid into the lung interstitium.1 Pulmonary interstitial edema increases lung stiffness and airway resistance. Adequate lung inflation now requires generation of more negative intrathoracic pressure. This is accomplished by increased effort by the diaphram and use of accessory muscles of respiration. In infants with compliant chest walls, clinically manifest as subcostal and intercostal in drawing.1,6 There is also need for higher end-expiratory pressure (greater than critical airway closing pressure) to prevent airway collapse. Exhalation against a closed glottis (grunting) generates higher end-expiratory pressure. A number of compensatory mechanisms attempt to reduce PBF by increasing PVR. This is accomplished by vasoconstriction (short-term), neointimal and smooth muscle proliferation and hypertrophy (intermediate-term) and fibroproliferative changes (long-term). Short and intermediate term compensation is reversible, on the other had long term compensation is typically irreversible. Systemic steal or low cardiac output is often under appreciated.1 To understand systemic steal, let us take the example of a large VSD. A certain proportion of left ventricular stroke volume is diverted to the pulmonary circulation (left-to-right shunt). This amount is “stolen” from what would have been cardiac output (Systemic blood flow or SBF) triggering compensatory sympatho-adrenal stimulation. This results in salt and water retention and peripheral vasoconstriction (increased SVR) to maintain tissue perfusion. Blood diverted to the pulmonary circuit is returned to the left ventricle as increased preload. All these compensatory changes (compensated steal) at least initially maintain SBF.1 At a certain

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Table 13.2: Increased PBF • Pulmonary interstitial edema • Partial compensation: Increased WOB, intercostal and subcostal retractions, grunting • Uncompensated: Respiratory • Failure

• Systemic steal • Partial compensation: Salt and water retention, increased SVR cold clammy skin, diaphoresis grayish/mottled appearance • Uncompensated: Cardiogenic • Shock

critical magnitude of left-to-right shunt, left ventricle is no longer able to maintain SBF (uncompensated steal) decreasing systemic perfusion and oxygen delivery. This is clinically evident during the compensated stage as cold clammy extremities, diaphoresis, and grayish peripheral discoloration and circulatory shock during the uncompensated stage.1

HEMODYNAMICS1 In order to understand the terms pulmonary artery hypertension, PVR, and pulmonary vascular disease, which are often but inappropriately, used interchangeably one needs to understand the relationship between pressure, flow and resistance. According to Ohm’s law, R  = P/Q (where R = resistance, P = pressure drop, Q = flow), it is apparent that pressure is directly proportional to both flow and resistance (P = R × Q). In a patient with a large left-to-right shunt (e.g. large VSD), PAP can be elevated either secondary to high flow or high resistance. Clinical signs of congestive heart failure (CHF), radiographic evidence of cardiomegaly with increased pulmonary vascular markings and/or presence of left ventricular volume overload on an echocardiogram in a patient with a large VSD suggests that elevated PAP is secondary to increased flow. On the other hand minimal or absence of these signs suggests that that elevated PAP is secondary to increased resistance. Cardiac catheterization is the gold standard to calculate PVR. However increasingly echocardiography is the only investigation performed prior to surgical intervention. Echocardiography routinely estimates and reports PAP based on estimated systolic pressures. This is sometimes erroneously understood as increased resistance. During infancy and to a lesser extent in early childhood clinical, roentgenographic or echocardiographic estimation of PBF can be used to predict PVR. In an older child or if there is any doubt invasive hemodynamic assessment is warranted. All patients with large, nonrestrictive, post-tricuspid defects (e.g. large VSD, PDA) have pulmonary artery hypertension; if there is evidence of increased PBF then PVR is very likely in the operable range especially during infancy.

CLINICAL FEATURES Clinical signs and symptoms are related to excessive PBF, systemic steal and compensation.

Symptoms1,6 Typically, initial symptoms occur at 6–8 weeks of age dictated by perinatal changes in vascular resistances. Dyspnea on exertion, unmasked by feeding, is often the first sign. This is associated

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with increased work of breathing (subcostal and intercostal in drawing) and diaphoresis with feeds (especially on the forehead). Increase in time required for feeding and decrease in the amount of milk/formula consumed is progressive and culminates in poor weight gain/failure to thrive. A number of factors contribute to decreased intake: Tachypnea, interference with suck-swallow coordination, and fatigue. Finally dyspnea at rest becomes evident. Increased susceptibility to recurrent respiratory infections is common and may in fact bring the infant to clinical attention. In experienced mothers (no previous children) usually describe the infant as hungry, always wanting to eat, but still not gaining weight. What is actually occurring is that the infant consumes an insufficient amount at each feed (secondary to easy fatigue), prompting early hunger. Experienced mothers (previous children) or grandparents will likely note these findings earlier and consider them problematic. Therefore, it is important that accurate feeding history is important. Poor weight gain or failure to thrive is typical and sometimes the only clinical symptom. It is frequently overlooked; serial weights are more important.

Signs/Clinical Features1,6 Growth parameters typically show poor weight gain or falling off the percentiles. As with other causes of malnutrition, length and head circumference are usually preserved. Etiology for poor weight gain is multi factorial; inadequate intake, increased demands (e.g. increased work of breathing) and decreased supply (systemic steal) are all proposed as possible mechanisms. There is evidence that there is increased total energy expenditure. “Happy tachypnea” is a typical finding; the infant appears comfortable in contrast to tachypnea associated with respiratory illness where the infant is ill appearing. Subcostal and intercostal retractions, grunting, nasal flaring are manifestation of use of accessory muscles of respiration. Even in the presence of frank CHF crepi-tations/rales are conspicuous by their absence. Clinical hallmarks of sympathoadrenal activation include sinus tachycardia, generalized pallor/grayish mottled look secondary to vasoconstriction and cold extremities. Dependent edema is conspicuous by its absence, instead replaced by hepatomegaly. This is probably related to distensibility of the hepatic bed. Certain inadequately appreciated clinical features, which point to a significant left-toright shunt include, increased precordial activity, precordial bulge and prominent pulmonary component of the second heart sound. High pulmonary pressures often can mask the typical harsh quality of the murmur often associated with VSD or PDA. Patients with Down’s syndrome frequently do not have any audible murmur and have a propensity to develop early pulmonary vascular disease (in the first year of life). These secondary signs, poor weight gain, recurrent respiratory infections should prompt search for “occult” left-to-right shunt. In fact features are so atypical in children with Down’s syndrome the American Academy of Pediatric suggests routine echocardiography. Uncomplicated isolated secundum ASD’s usually do not present with CHF in infancy or early childhood. Clinical manifestation of CHF in these patients should prompt exhaustive search for the presence of anomalous pulmonary venous drainage or associated mitral valve disease.

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A small number of patients with initially large defects may improve secondary to a spontaneous reduction in defect size. This should be a diagnosis of exclusion (always rule out high PVR). •• Accurate feeding history is critical •• Poor weight gain in infancy is a manifestation of CHF •• Secondary signs such as tachypnea, poor weight gain, increased precordial activity may be the only manifestations suggestive of a left to right shunt lesion (e.g. child with Down’s syndrome) •• Dependent edema and pulmonary crepitations/rales are conspicuous by their absence •• Murmurs lack their typical expected quality •• Spontaneous improvement should prompt search of increased PVR •• CHF in patient with ASD’s should prompt search for associated cardiac defects.

THE UNTREATED LARGE LEFT-TO-RIGHT SHUNT LESIONS This manuscript does not deal with pulmonary vascular disease and development of Eisenmenger syndrome. It is, however, important to understand that the compensatory changes aimed at reduction in PBF, especially proliferative changes are progressive and at a critical point increase surgical morbidity and mortality. Spontaneous improvement in clinical signs and symptoms, lower or lack of need for previously used antifailure medications is strongly suggestive of increased PVR. At an early stage this may still be reversible with elimination of the shunt albeit with higher morbidity and mortality. Unfortunately for the patient and sometimes the physician, clinical improvement provides a false sense of security often resulting in loss of follow-up, deferral of surgical intervention and the unrelenting progression to pulmonary vascular disease. Established vascular disease now makes an otherwise excellent surgical candidate (hemodynamic cure) with excellent long-term prognosis into a cardiac cripple with the development of Eisenmenger syndrome. Timely intervention can nearly completely eliminated this travesty.

Spontaneous Closure of Left-to-Right Shunts Some of the common lefts-to-right shunts have a natural tendency to close spontaneously. Surgical correction is sometimes deferred in expectation of this fortunate event. The defects known to close spontaneously include fossa ovalis ASDs, muscular and membranous VSDs and selected small PDA. The variables that influence likelihood of spontaneous closure include, age at evaluation (the likelihood of spontaneous closure declines with age and most ASDs and many VSDs are unlikely to close after the first three years of age), size of the defect (smaller defects are more likely to close), location of the defects (fossa ovalis ASDs, membranous and muscular VSDs can close on their own).

MANAGEMENT OF PATIENTS WITH LEFT TO RIGHT SHUNTS General Principles Most patients presenting with clinically significant left-to-right shunting (large VSD, PDA, atrioventricular septal defect) will require intervention to close the defect during early infancy.7, 8

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Attempts at medical management and improving nutrition are important and necessary, but not likely to change natural history. The emphasis in most modern centers including those situated in the developing world, has overwhelmingly shifted towards surgery. As explained earlier in this chapter, pretricuspid shunts seldom require intervention in infancy.

Nutrition Fluid volume can worsen CHF, and this combined with the inability of the infant to consume significant amount of milk/formula is the rationale for increasing caloric density. Careful attention to caloric composition is important to avoid osmotic diarrhea and “malnutrition”. Physical activity (feeding) in infants with a large left-to-right shunt is associated with a very significant increase in total energy expenditure.9 At some point the total energy expenditure cannot be sustained by even appropriate oral intake. Gavage feeds are an interim measure aimed at improving caloric intake and at the same time to reducing total energy expenditure by preventing feeding related physical activity. Iron deficiency anemia tends to be common especially in developing countries. Further changes intake related to CHF may aggravate the problem. Anemia by itself if significant can add to the cardiac workload (anemia is a cause of high output failure). Screening for anemia and prompt treatment once identified is important.

Intercurrent Infections Infants with a large left-to-right shunts show a propensity towards recurrent pulmonary infections.1,6 Frequently, especially recurrent infections, force deferral of surgical intervention and set up a vicious cycle culminating in increased morbidity and mortality. When possible prevention and prompt treatment is crucial. Active immunization against Hemophilus influenza, Streptococcus pneumoniae, and influenza and passive immunization against respiratory syncytial virus should be considered whenever possible.10,11

Medical Therapy Diuretics Sodium and water retention occurs secondary sympathoadrenal activation. As we have seen pulmonary interstitial edema is responsible for a number of clinical manifestations. Administration of diuretics tends to improve these symptoms. A variety of diuretics are available for use, furosemide and thiazide diuretics being the most commonly used. Electrolyte imbalance and hypovolemia are frequent side effects and need to anticipated and looked for. Chronic usually asymptomatic hyponatremia is common and well-tolerated. The urge to supplement sodium should be avoided unless patient is symptomatic. Hypokalemia may be avoided by judicious use of potassium supplements, or a potassium sparing diuretic.1 If a potassium sparing diuretic is used concomitant with an angiotensin converting enzyme (ACE) inhibitor dangerous hyperkalemia can result (both inhibit potassium excretion).12 Afterload Reduction1 Compensatory increase in SVR promotes left-to-right shunting setting up a vicious cycle of increased systemic steal–compensatory sympathoadrenal discharge– increased SVR.

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Administration of ACE inhibitors (more recently angiotensin receptor blockers) should decrease SVR. This would promote forward flow thereby decreasing both PBF and systemic steal. ACE inhibitors when co-administered with diuretics can precipitate renal insufficiency especially in a hypovolemic patient.

Inotropes1,13 Most patients with CHF related to left-to-right shunts have good systolic function mitigating the need for inotropic support. Digoxin was a commonly administered weak inotrope. The neuralmediated effects of digoxin with blunting of high sympathetic tone and thereby reducing tachycardia, improving diastolic filling have been proposed as the mechanism for beneficial effects of digoxin. However, there is growing evidence that digoxin likely produced no or little benefit for patients with left-to-right shunts with normal systolic function. Traditional intravenous inotropes such as dopamine/dobutamine is usually unnecessary. Milrinone a phosphodiesterase-III inhibitor with ability to augment left ventricular stroke volume and reduce afterload is likely to be the most appropriate agent to use in the minority of patients presenting with severe reduction in SBF and requiring intensive care. Beta-Blockade14-17 There is data to suggest that ACE inhibitors do not sufficiently suppress renin-angiotensin and patients do not have the expected clinical improvement. There is also early data to suggest that beta-blockade results in better biochemical and clinical improvement compared to ACE inhibition. This situation is similar to use of beta-blockers in dilated cardiomyopathy. Can Oxygen Therapy be Harmful?1 Patients with CHF or intercurrent respiratory illness can have mild systemic de-saturation. Oxygen is frequently administered. Oxygen is a potent pulmonary vasodilator and can potentiate left-to-right shunting and systemic steal detrimental to the patient. Consideration for permissive systemic hypoxemia (oxygen saturation of 88–92%) should be entertained in appropriate clinical circumstances. Surgical Intervention Corrective surgery for most left-to-right shunts is feasible as early as a few months after birth and should be undertaken if congestive failure cannot be controlled with medical management. With evidence of pulmonary hypertension, the operation should be performed as early as possible. It is unwise to make the sick infants to wait for a certain weight threshold because most infants with large VSDs do not gain weight satisfactorily. Episodes of respiratory tract infections often require hospitalization and are particularly difficult to manage. For very sick infants with pneumonia who require mechanical ventilation, surgery should be considered after initial control of the infection. Most patent arterial ducts can be closed in the catheterization laboratory using coils or occlusive devices Pulmonary artery (PA) banding is used to palliate selected infants who are not suited for a single stage correction (such as multiple apical ventricular septal defects). In spite of all good intentions, PA banding is an inexact science and a significant number of patients can be under or over banded. Banding does not eliminate the need for careful clinical evaluation.

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For example a patient with a large VSD who undergoes PA banding but does not gain weight, has clinical signs of CHF and has an ongoing need for anti-failure therapy is not adequately palliated.

SUMMARY It is imperative that all health care providers understand the pathophysiology and make early diagnosis of left to right shunt lesions especially at the ventricular or great artery level allowing early diagnosis. Medical intervention is appropriate and necessary, but should not unnecessarily prolonged purely for the purpose of achieving a “magic weight” prior to intervention. Poor weight gain is a sign of CHF and treatment is referral for intervention, not deferral. Knowledge of experienced surgical centers is crucial. Most infant with significant post-tricuspid left-toright shunt lesions will require intervention in early infancy. In most patients with hemodynamically significant left-to-right shunts timely intervention and elimination of the shunt can result in hemodynamic cure. Spontaneous “clinical improvement” in a patient with a nonrestrictive post-tricuspid defect (e.g. VSD, PDA) results in loss of follow-up and progression to development of pulmonary vascular disease. This increases morbidity and mortality related to intervention and at times the patient might be inoperable.

REFERENCES 1. Gumbiner CH, Takao A. Ventricular septal defect. In Garson A Jr, Bricker JT, Fisher DJ, Neish SR, (Eds). The science and practice of pediatric cardiology. (2nd edn). Baltimore: Williams and Wilkins 1998;1:1119–40. 2. Talner NS. The physiology of congenital heart disease. In Garson A Jr, Bricker JT, Fisher DJ, Neish SR, (Eds). The science and practice of pediatric cardiology. (2nd edn). Baltimore: Williams and Wilkins. 1998;1:1107–18. 3. Rudolph AM. Prenatal and postnatal pulmonary circulation. Congenital diseases of the heart: Clinical-physiological considerations. (2nd edn), Armonk, NY: Futura Pub. Co. 2001;121–52. 4. Rudolph AM. Ventricular septal defect. Congenital diseases of the heart: Clinical-physiological considerations. (2nd edn), Armonk, NY: Futura Pub. Co. 2001;197–244. 5. Rudolph AM. Atrial septal defect: Partial anomalous drainage of pulmonary veins. Congenital diseases of the heart: Clinical-physiological considerations. (2nd edn). Armonk, NY: Futura Pub. Co. 2001;245–81. 6. Tynan M, Anderson RH. Ventricular Septal Defect. In: Anderson RH, Baker EJ, Macartney FJ, Rigby ML, Shinebourne EA, Tynan M, (Eds). Paediatric cardiology. (2nd edn). London; New York: Churchill Livingstone. 2002;2:983–1014. 7. Vaidyanathan B, Roth SJ, Rao SG, Gauvreau K, Shivaprakasha K, Kumar RK. Outcome of ventricular septal defect repair in a developing country. J Pediatr. 2002;140:736–41. 8. Shrivastava S. Timing of surgery/catheter intervention in common congenital cardiac defects. Indian J Pediatr. 2000; 67:273–77. 9. Ackerman IL, Karn CA, Denne SC, Ensing GJ, Leitch CA. Total but not resting energy expenditure is increased in infants with ventricular septal defects. Pediatrics. 1998;102:1172–77.

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10. Bonnet D, Schmaltz AA, Feltes TF. Infection by the respiratory syncytial virus in infants and young children at high risk. Cardiol Young. 2005;15:256–65. 11. Dooley KJ, Bishop L. Medical management of the cardiac infant and child after surgical discharge. Crit Care Nurs Q. 2002;25:98–104. 12. Perry JC. Drug Formulary. In: Garson A Jr, Bricker JT, Fisher DJ, Neish SR, (Eds). The science and practice of pediatric cardiology. (2nd edn). Baltimore: Williams and Wilkins. 1998;2:2950–56. 13. Hougen TJ. Digitalis use in children: An uncertain future. Prog Pediatr Cardiol. 2000;12:37–43. 14. Buchhorn R, Bartmus D, Siekmeyer W, Hulpke-Wette M, Schulz R, Bursch J. Beta-blocker therapy of severe congestive heart failure in infants with left to right shunts. Am J Cardiol. 1998;81:1366–68. 15. Buchhorn R, Hulpke-Wette M, Hilgers R, Bartmus D, Wessel A, Bursch J. Propranolol treatment of congestive heart failure in infants with congenital heart disease: The CHF-PRO-INFANT Trial. Congestive heart failure in infants treated with propanol. Int J Cardiol. 2001;79:167–73. 16. Buchhorn R, Ross RD, Bartmus D, Wessel A, Hulpke-Wette M, Bursch J. Activity of the reninangiotensin-aldosterone and sympathetic nervous system and their relation to hemodynamic and clinical abnormalities in infants with left-to-right shunts. Int J Cardiol. 2001;78:225–30; discussion 230–31. 17. Buchhorn R, Ross RD, Hulpke-Wette M, Bartmus D, Wessel A, Schulz R, Bursch J. Effectiveness of low dose captopril versus propranolol therapy in infants with severe congestive failure due to left-toright shunts. Int J Cardiol. 2000;76:227–33.

14

Cyanotic Congenital Heart Disease

Swati Garekar, Richard A Humes

INTRODUCTION Cyanotic congenital heart disease (CCHD) is an important group of complex cardiac defects that present to the clinician with decreased oxygenation resulting in clinical cyanosis.1,2 Cyanosis is generally defined as a bluish discoloration of the skin that results when the deoxyhemoglobin levels in the blood rise above 4 gm%. The presentation of this diverse group of defects is highly variable.3 Most of the CCHDs are major structural defects that may be detected prenatally by fetal echocardiography as early as 18–22 of gestational age. A few ductal dependent ones present soon after birth are while others present during infancy. Many of the cyanotic defects discussed in this chapter may not present for clinical attention based solely on the appearance of cyanosis alone. Indeed, many of the “cyanotic” defects are not initially cyanotic that can create confusion among clinicians unfamiliar with the details of the anatomy and physiology. Prostaglandin E1 should be started empirically in any neonate presenting in cardiovascular collapse or cyanosis (Table 14.1). In this scenario, the role of echocardiography to rule out a cardiac defect is irreplaceable. Early diagnosis and early treatment is a guiding principle of therapy for CCHD. Therapeutic options include surgery and/or intervention in the catheterization laboratory. The outcome of any intervention varies from one CCHD to another; but in general a fair quality of life can be expected for most if treated in a timely fashion.

Table 14.1: Prostaglandin infusion table. Take 500 mg (1mL of standard available vial) and add to 49 mL of D5 water. So the concentration is 500 mg/50 mL or 10 mg/mL. Now follow the guidelines below for a dose of 0.1 mg/kg/min. This can easily be titrated up or down as required Weight of neonate 2 kg 2.5 kg 3 kg

Infusion rate 1.2 mL/h 1.5 mL/h 1.8 mL/h

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Further Comments •• All ‘cyanotic’ CHDs may not appear cyanotic to the observer. The cyanosis is more apparent in those cyanotic CHDs that have low pulmonary blood flow. The cyanosis is less apparent in those cyanotic CHDs that have pulmonary overcirculation. An infant with Tetralogy of Fallot appears cyanotic; an infant with total anomalous pulmonary venous return may not appear cyanotic. •• In a pathologic condition with complete mixing of oxygenated and deoxygenated blood (TAPVC, tricuspid atresia, truncus arteriosus, single ventricle states) and no pulmonary stenosis or atresia, if the amount of systemic and pulmonary venous blood flow returning to the heart is equal in quantity, the resultant saturation of the mixed blood will a mathematical mean of the saturations of the two (e.g. 75% and 100%; resultant saturation is 87.5%). So, if in these states, the peripheral saturation recorded is high (e.g. 94%), it is a clue that the amount of pulmonary venous return is high. This will be so if the amount of pulmonary arterial flow to the lungs is high (pulmonary overcirculation). •• Oxygen is a potent pulmonary vasodilator. Administering oxygen to the infant with a cyanotic CHD who has pulmonary overcirculation physiology (TAPVC, truncus arteriosus, single ventricle states without pulmonary stenosis) may worsen the situation. Similarly, sildenafil is contraindicated. This is specially mentioned as the author has observed rampant misuse in this situation.

TOTAL ANOMALOUS PULMONARY VENOUS RETURN Definition Total anomalous pulmonary venous return (TAPVR) is a CCHD where all the pulmonary veins connect to the systemic veins or right atrium instead of draining into the left atrium.

Pathology The TAPVR results when the developing common pulmonary vein becomes atretic early in development. At this stage, the branch pulmonary veins still retain connections with the systemic veins (cardinal, umbilical and vitelline) that disappear during normal embryologic development. These persistent connections constitute the anomalous drainage routes of the pulmonary veins. The connections may have obstructions (intrinsic or extrinsic) at various points. Thus, TAPVR may vary by both site of connection and degree of obstruction of pulmonary venous return. The anomalous drainage may be at the supracardiac (e.g. innominate vein or superior vena cava), cardiac (right atrium directly or coronary sinus) or infracardiac (e.g. portal vein, inferior vena cava) level or may be of a mixed type with more than one anomalous site. Supracardiac TAPVR is the most common type, with pulmonary veins coming together to form a confluence (chamber) and then draining superiorly via a remnant of the left common cardinal vein to the innominate vein. The vein connecting the chamber to the innominate vein is referred to as the vertical vein. The vertical vein may become compressed by surrounding structures or an obstruction develops at its junction with the confluence or the anomalous site.

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Significant obstruction is unusual with supracardiac TAPVR that occasionally will go unnoticed for many months if the cyanosis is relatively mild, which it can be. Obstruction is most likely to occur in infradiaphragmatic type of TAPVR. In infradiaphragmatic TAPVR, the vertical vein from the confluence descends below the diaphragm through the esophageal hiatus and enters the portal vein, ductus venosus, IVC or hepatic veins. The obstruction is usually severe resulting in early presentation and often severe respiratory distress and cyanosis. The third common type of TAPVR is the coronary sinus type. The chamber connects with the coronary sinus via the vertical vein. The coronary sinus opens into the right atrium as usual. This type is least likely to get obstructed. The mixed type of TAPVR is where the pulmonary veins drain into more than one site. For example 3 veins might drain into the coronary sinus and one to the innominate vein. Although the majority of TAPVR occurs as an isolated lesion, approximately 30% of patients have associated complex heart defects. There is also a high association with heterotaxy syndromes especially polysplenia.4

Physiology The anomalous pulmonary venous return must find a way to return to the left atrium to sustain life. A PFO or an ASD is necessary for life. If the ASD/PFO is small, there may be the unfortunate combination of insufficient systemic blood flow and pulmonary over circulation that worsens as the pulmonary vascular resistance rapidly drops in the first few hours of life. In the presence of a large ASD/PFO, there is sufficient systemic blood flow coexisting with pulmonary over circulation.

Natural History Untreated neonates with obstructed TAPVR die within days to a few weeks. In patients with unobstructed TAPVR, cyanosis may be slight because of adequate mixing of systemic and pulmonary venous blood. Pulmonary vascular obstructive disease may develop overtime, increasing the risk of surgical repair.

Presentation The patient with unrestricted flow of the anomalous pulmonary venous blood may present in the neonatal period or in infancy with symptoms of congestive heart failure (sweating, tachypnea, suck-rest-suck cycle with feeds), repeated respiratory infections and failure to thrive. Cyanosis may be slight with systemic saturations in the high 80’s or low 90’s but are never completely normal. The neonate with obstructed TAPVR presents within a few hours of birth with respiratory distress and cyanosis unresponsive to any nonsurgical intervention. The cardiovascular exam shows a prominent left parasternal heave (RV volume overload). The second heart sound may be widely split and fixed with respiration. There is a flow murmur across the pulmonary and mitral valve. An S4 may be present with congestive heart failure. Supracardiac TAPVRs will have a continuous murmur in the infraclavicular area. Hepatomegaly is common with congestive heart failure.

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Evaluation The ECG shows right ventricular hypertrophy as in many newborns. The chest radiograph will show increased pulmonary vascular markings. The ‘snowman’ sign (enlarged superior mediastinum) is seen in supracardiac TAPVR to the left innominate vein in older infants. In neonates with obstructed TAPVR the radiograph resembles that seen in meconium aspiration syndrome/persistent pulmonary hypertension with often dense opacification of both lung fields. Pulmonary venous edema (batwing) may be prominent. An echocardiogram defines the anatomy sufficiently. Special attention should be given to flow in the major systemic veins and a careful search for anomalous drainage into the liver as well as detection of obstruction to flow is important in all echocardiographic studies. Pulmonary hypertension will be severe in obstructed TAPVR.

Therapy In obstructed TAPVR, prostaglandin infusion is contraindicated as it may worsen the obstruction by promoting left-to-right shunting across the ductus and hence increased pulmonary venous return. Prostaglandin also dilates pulmonary arterioles, promoting pulmonary forward flow in the face of obstructed return. If the infusion was started prior to echocardiography, worsening of the neonate’s condition is a clue to the etiology. Other maneuvers to reduce pulmonary hypertension (nitric oxide, sildenafil) are an absolute contraindication as is giving oxygen to the neonate. Cardiac surgery is carried out for relief of pulmonary venous congestion by reanastomosis of the pulmonary venous confluence to the posterior wall of the left atrium. Obstructed TAPVR is a true surgical emergency. Surgical correction may be carried out on a semi-elective basis for unobstructed TAPVR. While awaiting financial arrangements, the infant with unobstructed TAPVR may be placed on decongestive therapy.

Outcome The outcome depends largely upon the anatomic type of TAPVR. Obstructed TAPVR is associated with high (30%) perioperative mortality. Unobstructed TAPVR has a mortality of 5–10%. Late postoperative complications are rare and successful correction is generally curative with a normal life and lifespan. Rare problems include pulmonary vein branch stenosis or stenosis at the site of reanastomosis with the left atrium. The ‘sutureless technique’ of repair is associated with better results.

TRICUSPID ATRESIA Definition The tricuspid valve is absent, obstructing normal flow from the right atrium to the right ventricle.

Pathology The tricuspid valve is replaced by a plate of tissue (Figure 14.1). An atrial septal defect is present resulting in an obligatory right-to-left atrial shunt. A VSD, which is usually present, is

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an important determinant of systemic or pulmonary blood flow quantity (depending on whether the great arteries are normally related or transposed). Please see Table 14.2.

Physiology Systemic venous blood entering the right atrium finds an outlet through the ASD/PFO. There is complete mixing of pulmonary and systemic venous blood in the left atrium. In case of normally related great arteries, pulmonary blood flow is supplied through the VSD. The amount of pulmonary flow will thus be dependent on the size of the VSD. With transposed great arteries, the aorta arises from the right ventricle and systemic flow to the aorta is dependent on the size Figure 14.1: Tricuspid Atresia with normally related great arteries with ASD of the VSD. and VSD

Presentation The neonate with tricuspid atresia will have cyanosis that might be picked up in the first week of life. Cyanosis will be more profound if pulmonary blood flow is restricted. On the other hand, if there is excessive pulmonary blood flow, the peripheral saturations will be on the higher side and cyanosis may be missed. The baby will present with tachypnea, poor feeding skills and will have signs of congestive heart failure and pulmonary overcirculation. The cardiovascular exam shows a prominent apical impulse (LV volume overload). A loud harsh pansystolic murmur due to flow across the VSD may be heard. In case of pulmonary overcirculation, increased flow across the mitral valve produces a mid-diastolic rumble.5

Evaluation The ECG of a patient with tricuspid atresia and normally related great arteries is unusual with a leftward and superior QRS axis (270°–360°). In the presence of transposed great arteries, the Table 14.2: Classification of tricuspid atresia Type Type I Ia Ib Ic Type II IIa IIb IIc Type III

Description Normally related great arteries Intact ventricular septum and pulmonary atresia Small VSD and pulmonary stenosis Large VSD without pulmonary stenosis D-transposition of the great arteries VSD with pulmonary atresia VSD with pulmonary stenosis VSD without pulmonary stenosis L-transposition of the great arteries Associated with complex lesions

Frequency 70–80% rare most common 12–25%

3–6%

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mean QRS axis remains leftward but may be inferior (0°–90°) in half of the cases. The P wave may be tall. An echocardiogram is diagnostic and provides complete information required to execute a treatment plan.

Natural History Patients will have progressive cyanosis as the VSD becomes smaller over time with the most common type of tricuspid atresia, with normally related great arteries and a mildly restrictive VSD. Patients with tricuspid atresia with or without transposition and a large VSD can develop congestive heart failure and subsequent pulmonary hypertension resulting in death in infancy or the late development of pulmonary vascular obstructive disease.

Therapy Despite advances in the field, placing a prosthetic tricuspid valve instead of the atretic plate is not a suitable cure because of multiple reasons. So only palliative surgery is possible for all types of tricuspid atresias. Fontan and Baudet described the Fontan operation for palliation of tricuspid atresia in 1971. The Fontan approach to single ventricle repair has changed over the years. Despite the modifications, the goals remain the same: separation of the systemic and pulmonary circulations and utilization of the single functional ventricle for pumping blood to the systemic circulation. The Fontan palliation is carried out in 3 steps; the first establishes a stable and controlled source of pulmonary blood flow. The subsequent steps route systemic venous return to the pulmonary arteries directly (Figure 14.2).

Outcome A patient who has undergone complete Fontan palliation has a 10 year survival of close to 80%. Freedom from surgical reintervention is 60% at 15 years. Some long-term issues with Fontan include RV dysfunction, protein losing enteropathy, atrial arrhythmias and plastic bronchitis.

EBSTEIN’S ANOMALY Definition Ebstein’s anomaly of the tricuspid valve is characterized by downward displacement of the origin of the tricuspid valve leaflets from the annulus to the RV wall, resulting in tricuspid valve insufficiency, “atrialization” of the right ventricle and resultant loss of right effective Figure 14.2: Repair of tricuspid atresia-s/p modified lateral tunnel fontan: ligation of main ventricular function. pulmonary artery, anastamosis of SVC to RPA, baffling of IVC to RPA through the right atrium

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Pathology The septal and posterior leaflets are most commonly displaced downwards. In addition, they are dysplastic and the leaflets are adherent to the RV wall. The anterior leaflet is typically described as being ‘sail like’ and redundant. The right atrium may be massively enlarged. The RV has a thinned out atrialized portion (above the line of attachment of the displaced leaflets) that is noncontractile; and a functional portion below the line of attachment. The tricuspid valve and hence the RA and RV are affected to a highly variable degree. Associated anomalies include pulmonary valve atresia, ASD and left-sided obstructive lesions. There is a 25% incidence of accessory conduction pathways resulting in an increased likelihood of supraventricular tachycardia.

Physiology Tricuspid valve dysplasia results in insufficiency. In mild cases, this may be minimal. In severe Ebstein’s anomaly, the regurgitant blood from the RV shunts across the PFO/ASD into the left atrium. In addition, the RV in such cases is limited by its atrialized portion in both volume and effective contracting myocardium and may pump very ineffectively. This may lead to functional pulmonary valve atresia in the neonate as the RV is unable to overcome the higher pulmonary vascular resistance of the newborn.

Presentation In the fetus, severe Ebstein’s anomaly can cause heart failure and hydrops in addition to atrial arrhythmias. At birth severe Ebstein’s anomaly presents as a ductal dependent lesion with often severe cyanosis. Pulmonary blood flow is unable to be sustained by the dysfunctional RV. The cyanosis may improve gradually over days or weeks as the PVR drops and makes it easier for the RV to pump blood to the pulmonary arteries. Cyanosis is seen only when an atrial septal defect is present. The heart sounds are often normal. The systolic murmur of tricuspid regurgitation may be associated with a thrill and is best heard at the left lower sternal border. A third heart sound may be present. Moderate Ebstein’s anomaly will manifest as congestive heart failure because of elevated right atrial pressure. Mild cases may go unnoticed lifelong or may present as dyspnea on exertion or a murmur or palpitations in adulthood.

Natural History Untreated, severely cyanotic newborns with Ebstein’s anomaly may die from progressive hypoxia in a few weeks. The cyanosis in the newborn period often resolves as the pulmonary resistance falls. At this time, children can be remarkably well and acyanotic for many years, becoming symptomatic and cyanotic again in later teens and young adulthood. Mild cases may remain undiagnosed till adulthood when they present with SVT or a murmur or heart failure. Relentless RV failure, arrhythmias and sudden cardiac death are the common modes of death in such cases.

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Evaluation The ECG shows Himalayan P waves as manifestations of right atrial enlargement. The PR interval is increased, reflecting the enlarged right atrium. A delta wave in V6 may be seen. The chest radiograph shows variable degrees of cardiomegaly and may display a massively enlarged, “wall to wall” heart, in a severely affected infants. The echocardiogram delineates the anatomy completely.

Treatment The goal of corrective surgery is to restore the tricuspid valve competency and RV size and function if possible. Surgery should only be a last option in the newborn. The available surgical options include tricuspid valve annuloplasty with right ventriculoplasty or tricuspid valve replacement. A two ventricle repair may not be feasible in some cases that are recalcitrant to usual medical therapy. The Starne’s approach is to close the tricuspid valve with a pericardial patch and then place an aortopulmonary shunt followed by the Fontan palliation or variations of this approach in a staged fashion.

Outcome Neonatal Ebstein’s anomaly has a poor prognosis in the presence of the following risk factors: cardiothoracic ratio of > 0.85 on the chest radiograph, large and noncontractile RV with the anterior leaflet of the tricuspid valve tethered or adherent to the RV wall, severe cyanosis and severe tricuspid regurgitation. Mild Ebstein’s anomalies have an excellent prognosis.

TETRALOGY OF FALLOT Definition The four components of tetralogy of Fallot (TOF) are ventricular septal defect, aortic override of the ventricular septum, right ventricular outflow tract obstruction (RVOTO) and right ventricular hypertrophy.

Pathology Embryologically, anterior deviation of the ventricular septum causes a malalignment VSD and also intrudes into the RV outflow tract, thereby narrowing it. The RV muscles hypertrophy in response to the narrowed outflow region. Deviation of the conal ventricular septum also results in overriding of the aorta over the septum. There are important associated cardiac anomalies in tetralogy of Fallot, many of which have important implications for the treatment plan. Five percent of cases have anomalous origin of the Table 14.3: Cyanotic congenital heart defects left anterior descending coronary artery (LAD) associated with chromosome 22q11 deletion % cases with from the right coronary artery. Other associated CCHD the deletion anomalies include valvar pulmonic stenosis Interrupted aortic arch type B 70% in 60% cases, a right aortic arch in 25% cases Truncus arteriosus 33% and an ASD in 15% cases. Deletion of the short Tetralogy of Fallot with pulmo23–40% arm of chromosome 22 (22q11del) is present in nary atresia Tetralogy of Fallot 8–23% 8–23% of patients with tetralogy (Table 14.3).

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Physiology The physiology of TOF is predominantly determined by the degree of right ventricular outflow tract obstruction. If the obstruction is severe, there will be insufficient pulmonary blood flow, creating a ductal dependent pulmonary circulation. Systemic venous blood entering the RV will exit more easily through the VSD into the LV, thereby causing systemic desaturation and cyanosis. If the obstruction is mild, there may be a normal amount of pulmonary blood flow. Flow across the VSD will be left-to-right in most cases. The amount of clinical hypoxemia and cyanosis will be determined by the amount of pulmonary blood flow that is in turn controlled by the degree of right ventricular outflow obstruction.

Evaluation The ECG shows right ventricular hypertrophy and right axis deviation. The chest radiograph may show a boot shaped heart, although this is not uniformly true. The lung fields on chest X-ray reflect the relative amount of pulmonary blood flow at the moment and may be oligemic or normal. An echocardiogram provides detailed and complete information. Rarely a coronary angiogram is required to delineate the origin of the left anterior descending coronary.

Presentation The presentation, as with the physiology, varies with the degree of severity of right ventricular outflow tract obstruction. With mild obstruction, a murmur might be all that is apparent (pink tetralogy). With severe obstruction, cyanosis will be the presenting symptom. On cardiovascular exam, there is a prominent left lower parasternal heave. The second heart sound is loud and often single because of the anterior position of the aorta and soft closure of the pulmonary valve respectively. The sub-RV outflow tract obstruction produces a harsh ejection systolic murmur best heard in the left mid-parasternal area. The intensity of the murmur is more if the obstruction is milder and inversely, severe obstruction often produces a less intense murmur. This is because blood in the RV exits through the VSD if it encounters severe RV outflow tract obstruction. This implies less blood flowing out through the RVOT and hence the murmur is less intense. During a hypercyanotic spell the murmur almost disappears as most of the blood in the RV shunts through the VSD instead of going through the RV outflow tract. A murmur is not produced by flow across the VSD in tetralogy because the VSD is invariably large and nonrestrictive.6

Hypercyanotic or TET Spell A TET spell is characterized by severe cyanosis and deep rapid breathing (hyperpnea). It may occur regardless of the degree of resting cyanosis. A spell is produced by an abrupt increase in right-to-left shunt across the VSD secondary to a drop in the SVR and a rise in the PVR. A spell is most likely to be seen in a child less than 2 years old, upon waking up in the morning and following a crying episode. The principles of management are aimed at restoring the VSD shunt direction from right-to-left, to predominantly left-to-right by manipulating an increase in the systemic vascular resistance and a decrease in pulmonary resistance. Calm the child in an effort to decrease the hyperpnea. Place the patient in a knee-chest position or have him squat if he is older. These postures compress the femoral vessels and increase SVR (femoral

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artery) and decrease systemic venous return (femoral vein). Give supplemental oxygen to the child to decrease the PVR. Consider intramuscular ketamine (1 mg/kg) or subcutaneous/ intravenous (IV) morphine (0.1 mg/kg). These cause sedation, reduce breathing effort and increase peripheral venous pooling. Intravenous fluids to replace volume and correction of acid base abnormalities are also helpful. Persistent severe cyanosis is an indication for intramuscular or subcutaneous phenylephrine (0.1 mg/kg/dose) or IV (0.02 mg/kg/dose) to raise systemic resistance. An esmolol drip (500 mg/kg bolus followed by 100–300 mg/kg/ min IV infusion) may slow the heart rate and affect the sequence of events causing the spell. Intravenous propranolol bolus is also used. Intubation and mechanical ventilation is the next resort; followed by emergency surgery (BT shunt or complete repair).7

Natural History Untreated patients have a median age of death of 9 years (11 days to 60 years). Cerebral abscesses from septic emboli, cerebral thromboses from polycythemia and dehydration and bacterial endocarditis may occur.

Treatment Surgical correction is accomplished by patch closure of the VSD and RV muscle bundle resection with or without a transpulmonary valve annulus patch or pulmonary valvotomy. Although each case is unique, in India, surgical repair is recommended between 6–12 months of life. In the presence of anomalous origin of the left anterior descending (LAD) coronary from the right coronary artery, the LAD courses across the RVOT in the area where the surgeon often incises the RVOT, precluding adequate dissection in the area in some cases. In such cases, a modified approach is required. A Blalock-Taussig shunt is indicated as a palliative procedure when the branch pulmonary arteries are hypoplastic regardless of the associated anomalies. This is later followed by complete intracardiac repair and takedown of the shunt.

Outcome Survival rate to age 10 years is 90% overall. Important postoperative issues relate to the style of repair and the fate of the pulmonary valve. If a transanular patch has been used, there is frequently free and severe pulmonary insufficiency. This physiology is well-tolerated in childhood, but may produce late long-term problems because of progressive right ventricular dilation and dysfunction leading to need for late pulmonary valve replacement. Ventricular arrhythmias, also probably related to right ventricular dysfunction, contribute to the incidence of sudden cardiac death in adulthood. Severe QRS duration prolongation on ECG remains an important predictor of adverse outcome after repair.

TETRALOGY OF FALLOT WITH PULMONARY ATRESIA Definition This is an extreme form of tetralogy. Tetralogy of Fallot with pulmonary atresia is often referred to as “pulmonary atresia with VSD”. This designation separates this group of patients from

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other tetralogy patients on functional grounds, even though the intracardiac anatomy is quite similar, since the surgical management and outcomes can be very different.

Pathology The right ventricle is hypertrophied. The right ventricular outflow tract ends in a blind sac. The pulmonary valve and the proximal pulmonary artery are replaced by elastic tissue. The branch pulmonary artery anatomy is highly variable and determines the extreme variability of this complex anatomy. The left and right pulmonary arteries may share a common origin that is supplied by the ductus arteriosus or by a collateral artery (aortopulmonary (AP) collateral) arising from the aorta. The left and right pulmonary arteries may arise separately and may be fed by single or multiple aortopulmonary collaterals. The native branch pulmonary arteries may be severely hypoplastic in which case all of the AP collaterals run to the lung segments directly. The VSD is perimembranous and malaligned as in other cases of tetralogy of Fallot. An atrial septal defect or patent foramen ovale is present in 50% of cases. A right aortic arch is present in up to 50% cases.

Physiology The systemic venous blood entering the RV shunts through the VSD to the LV where there is complete mixing of oxygenated and deoxygenated blood. Pulmonary blood flow is maintained by the various collaterals or the ductus arteriosus from the systemic circulation. Collaterals tend to develop stenosis overtime, decreasing the pulmonary blood flow and increasing the amount of cyanosis. There may or may not be ductal dependent pulmonary circulation depending upon the relative contribution of the ductus or the AP collateral arteries (Figure 14.3).

Natural History The lifespan depends on the quantity and supply source of pulmonary blood flow. The median age at death has been reported to be 11 months (range 9 days to 30 years).8

Presentation The neonate presents with cyanosis that may worsen with ductal closure. In case pulmonary blood flow is through ductal independent collaterals, the presentation may be delayed till infancy, when somatic growth exceeds the capacity of the AP collaterals to provide sufficient pulmonary blood flow. In either case, these children are hypoxemic, but the degree of hypoxemia and cyanosis depends upon the pulmonary blood flow that varies greatly between patients. On Figure 14.3: TOF/Pulmonary atresia cardiovascular exam, there is a prominent left lower with multiple aorto-pulmonary collaterparasternal heave. The second heart sound is loud als (MAPCAs)

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and single. Continuous murmurs of the AP collaterals may be heard in the back, although this is an unusual newborn finding.

Evaluation The ECG shows right ventricular hypertrophy and right axis deviation. The chest radiograph may show a boot shaped heart. The normal pulmonary vasculature pattern is replaced by a nonuniform appearance. Detailed angiography, done by an experienced pediatric cardiologist is essential to evaluate the various sources of pulmonary blood flow. The less invasive CT angiography, in experienced hands provides this information in addition to detailing non-vascular thoracic structures.

Treatment The goal of treatment is to perform a biventricular repair. In order to accomplish this, the pulmonary arteries and or the various AP collaterals are mobilized and unifocalized (brought together). This point of unifocalization is then connected to the right ventricle via a valved conduit (Figure 14.4). Successful unifocalization depends on the anatomy of the AP collaterals: their number, size, site of origin and also on the anatomy of the true pulmonary arteries. The surgical goal is to bring as much of the lung vasculature together as possible with a minimum of at least one complete lung.9 The repair is often carried out in separate surgeries. There are several variations in the approach including initial placement of a modified BT shunt or a central shunt (aorta to pulmonary artery); fenestrated closure of the VSD or ASD. Successful biventricular repair depends on anatomy of the RV, state of unifocalization and timing of the repair. Occasionally, the AP collaterals are so numerous and individually hypoplastic, that complete unifocalization is impossible. In these instances, the patient may have to settle for palliation without VSD closure, chronic cyanosis and a shortened life expectancy.

Outcome At best, early mortality is 11% and the 4 year survival is 74%. Freedom from reintervention is 42% at 5 years. Important postoperative issues are the need for conduit ballooning and/or stenting for stenosis; and multiple conduit replacements to accommodate somatic growth.

Figure 14.4: Repair of ToF/Pulmonary atresia with MAPCAs, s/p unifocalization of MAPCAs, s/p placement of RV to PA conduit, s/p patch closure of VSD and ASD

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PULMONARY ATRESIA WITH INTACT VENTRICULAR SEPTUM Definition This defect is created by an imperforate pulmonary valve with an intact ventricular septum resulting in variable degrees of hypoplasia and hypertrophy of the right ventricle.

Pathology In membranous pulmonary atresia, the pulmonary valve leaflets are fairly well-formed but have commissural fusion. Muscular valvar atresia is associated with a muscular and atretic right ventricular infundibulum. The right ventricle may be severely hypoplastic. The tricuspid often has severely hypoplastic and dysplastic leaflets. There is often significant tricuspid valve regurgitation resulting in secondary right atrial enlargement. The main pulmonary artery and the branch pulmonary arteries may have mild to moderate hypoplasia (Figure 14.5).

Figure 14.5: Pulmonary atresia, intact ventricular septum, PDA

Physiology The only way for blood in the RV to egress is back through the tricuspid valve into the RA. An adequate sized ASD is, therefore, essential for survival. The right ventricle is frequently under very high (suprasystemic) pressure because of “trapping” of blood in it. This high pressure may force blood in a retrograde fashion from the right ventricle into the coronary artery system. This leads to a disrupted coronary artery anatomy since this exists in utero as well. The impact on the coronary artery anatomy may be such that aortic sinuses may be disconnected from the coronary arteries. This has been called a right ventricular dependent coronary circulation.

Presentation The newborn presents with severe progressive cyanosis after ductal closure. The apical impulse is prominent. The second heart sound is single. Tricuspid regurgitation produces a holosystolic murmur that is best heard at the left lower sternal border.

Evaluation A chest radiograph may show significant cardiomegaly. An echocardiogram should easily define the basic anatomy. However, echocardiography will not be sufficient to identify coronary artery abnormalities that are important in therapeutic planning. Therefore, cardiac catheterization is often required for delineation of these finer points and to perform balloon atrial septostomy if the ASD is restrictive. A right ventricular angiogram and an ascending

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aortogram are essential to plan further management. Angiograms that identify a right ventricular dependant coronary are seen in 10–20% of cases of PA/IVS.

Therapy This is a ductal dependent lesion and prostaglandin should be initiated to maintain ductal patency. This defect has a highly variable set of treatment options that will be dictated by the anatomy. The most desirable option is eventual two ventricle repair. The size of the right ventricle and tricuspid valve annulus is the major determining factor for this. The choice of therapy may vary from center to center depending upon the skills of the clinicians and surgeon. An initial management strategy would be to decrease right ventricular pressure by opening up the pulmonary valve. This is not done in the presence of a right ventricular dependent coronary Figure 14.6: Repair of pulmonary circulation as this may compromise coronary perfusion atresia, Intact ventricular septum, s/p pressure resulting in myocardial ischemia and death. pulmonary valvotomy, s/p modified BT For PA/IVS without a right ventricular dependent shunt placement, s/p ASD patch clocoronary circulation, the pulmonary valve may be sure opened either surgically or in the catheterization laboratory. Patients with membranous pulmonary atresia are amenable to percutaneous valvotomy in the catheterization lab. The neonate will need to be supported with PGE1 for some days after wire perforation as the RV compliance improves slowly. Pulmonary blood flow may need to be augmented with a BlalockTaussig shunt following either style of valvotomy (Figure 14.6). Other surgical strategies for pulmonary atresia with an intact ventricular septum are ‘one and half ventricle’ repair and Fontan palliation. A recent advancement in palliation to provide a stable source of pulmonary blood flow is transcatheter stenting of the PDA. According to the American Heart Association Guidelines (2011) for indications for cardiac catheterization and interventions in pediatric cardiac disease, it might be reasonable to stent an anatomically suitable PDA in an infant with cyanotic CHD whose sole source of pulmonary blood flow is the ductus (class IIB Level of Evidence: C). Class IIa indication for ductal stenting is stenting the PDA in an infant with cyanotic CHD who has >1 source of pulmonary blood flow (e.g. antegrade pulmonary blood flow or collateral blood flow) but who requires additional pulmonary blood flow from the stented ductus for a relatively short period of time (3–6 months) (Level of Evidence: B).10

Outcome A two ventricle repair can be achieved in approximately 50% of cases. Most of the remaining patients undergo Fontan palliation. Survival is improving in recent years. It is 75% at 1 year and 67% at 5 years.

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DOUBLE-OUTLET RIGHT VENTRICLE Definition This is a complex set of anomalies that is defined by origin of both great arteries from the right ventricle.

Pathology The great arteries arise from the right ventricle with variable relation to each other (normally related, malposed, anterior-posterior or side-by-side relationship). The left ventricle’s outlet is a VSD that may be located below the origin of either artery (subpulmonic or subaortic) or may be remote. The most common type is DORV with side-by-side great arteries and a subaortic VSD. There may be a variable amount of subpulmonic stenosis with a subaortic VSD and variable degrees of left-sided obstructions with a subpulmonary VSD. Other associated defects include atrioventricular canal defect, atrial septal defect and total anomalous pulmonary venous return. The Taussig-Bing anomaly is a form of DORV with side-by-side great arteries and a subpulmonic VSD. Fifty percent of Taussig-Bing anomalies are associated with left-sided obstructive lesions (subaortic stenosis, coarctation).

Physiology The physiology resembles either that of a large VSD, tetralogy of Fallot or transposition of the great arteries. The major determinants of the presentation are the location of the VSD and the great artery position. In general, a DORV with a subaortic VSD will present with the physiology of a large VSD. A DORV with subaortic VSD and pulmonic stenosis may resemble tetralogy of Fallot in presentation. Double-outlet right ventricle with a subpulmonic VSD may mimic the physiology of transposition of the great arteries. In addition, associated lesions such as coarctation or mitral atresia will also significantly affect the presentation and the physiology.

Presentation The clinical features of double-outlet right ventricle will vary with the physiology. With TOF or transposition physiology, there is a varying degree of cyanosis. In addition, the subpulmonic stenosis produces an ejection systolic murmur. With large VSD physiology, the infant presents with failure to thrive and congestive heart failure.11

Evaluation The ECG shows RV hypertrophy and right axis deviation. The chest radiograph varies according to the anatomy of the DORV and should reflect the degree of pulmonary blood flow. The echocardiogram should be diagnostic.

Treatment The primary treatment goal of DORV is similar to other forms of congenital heart disease. An attempt should be made to achieve normal four chamber cardiac anatomy. In the most common type of DORV, with side-by-side great arteries and subaortic VSD (Figure 14.7), the

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Figure 14.7: DORV with side-by-side great arteries and subaortic VSD

Figure 14.8: Repair of DORV, s/p VSD patch closure, s/p Baffle from aorta to left ventricle

VSD is closed to direct left ventricular blood to the aorta (Figure 14.8). Other types of DORV may require more complex surgeries including arterial switch operation, or a Rastelli operation with the use of a prosthetic conduit to the pulmonary arteries. In some complex cases, the relative position of the VSD and great arteries precludes a two-ventricle repair and a Fontan palliation must be employed.

Outcome The outcome of DORV patients is reflective of the variety of the anatomy, with the presence of a concomitant restrictive VSD, inlet VSD, straddling tricuspid valve, hypoplastic LV or arch defects producing less satisfactory results. For the DORV with side-by-side great arteries and a subaortic VSD, survival at 15 years is 96% and freedom from reoperation is estimated at 87%.

HYPOPLASTIC LEFT HEART SYNDROME Definition Hypoplastic left heart syndrome (HLHS) is comprised of multiple obstructive abnormalities in the left heart resulting in the inability of the left ventricle to adequately provide systemic blood flow.

Pathology There are variable degrees of hypoplasia of the left ventricle that may also have endocardial fibroelastosis. Other features include severe stenosis or atresia of the aortic valve, mitral valve stenosis or atresia and hypoplastic aortic arch with coarctation of the aorta. An ASD is present in 90% of cases.

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Physiology Poor egress of pulmonary venous blood through the mitral valve and left heart requires an adequate ASD to “decompress” the left atrium. In some of the cases, a restrictive atrial septal defect causes raised pulmonary venous pressure and congestion. The systemic circulation is ductal dependent. With aortic atresia, coronary perfusion is through retrograde flow of blood from the aortic arch.

Presentation Diminished systemic blood flow results in poor perfusion, hypotension and shock. The neonate presents in the first 1–3 days of life when the ductus arteriosus closes. There is a prominent left lower parasternal heave on cardiovascular exam. The second heart sound is single and loud. A soft ejection systolic flow murmur across the pulmonary valve may be heard at the left upper sternal border.

Evaluation The ECG shows sinus tachycardia and right ventricular hypertrophy, which may appear normal for a newborn. There may be Q-waves in lead V1. There is often an absence of left-sided forces. Diffuse ST-T wave changes are sometimes seen. The echocardiogram should provide sufficient details of the anatomy to determine further management.

Natural History Death is generally imminent once the ductus arteriosus closes.

Therapy There is no cure for HLHS. Cardiac transplantation and Norwood surgery or a hybrid approach are the palliative options available. Prostaglandin E1 should be initiated immediately after birth to maintain ductal patency. A balloon atrial septostomy is indicated in patients with a restrictive ASD. The Norwood procedure was first reported in 1981 as an initial palliation for HLHS. The goal of the Norwood procedure is to use the right ventricle to support the systemic arterial circulation. It is performed in three stages to allow adaptation of the vasculature to the changing hemodynamics. The first stage, that is carried out in the neonatal period, has four components: (1) construction of the neoaorta from the pulmonary artery, (2) repair of the hypoplastic arch, (3) atrial septectomy, (4) modified Blalock-Taussig shunt. Norwood palliation may not be a viable option if there is moderate to severe tricuspid valve regurgitation. The BT shunt may be replaced by a conduit from the right ventricle to the pulmonary artery (Sano modification). Norwood stage I may also be carried out as a hybrid procedure (combined effort in the cardiac catheterization laboratory and the operating room resulting in placement of a stent across the ASD; stent across the PDA and bilateral branch pulmonary artery banding). The final two stages (Glenn and extracardiac Fontan), performed at 4–6 months and 4–5 years ( or 18–24 months for a lateral tunnel Fontan) respectively, rely on the passive flow of systemic venous blood to the lungs for pulmonary arterial circulation. This requires a low pressure, low resistance pulmonary circulation that is hopefully produced by the first stage procedure.12

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Outcome The Norwood stage I operation has the highest mortality of all the stages in the correction of HLHS. Mortality is reduced if the Norwood operation is performed within first 10 days of birth. Long-term concerns of the right ventricle failing in the 2nd–3rd decade of life remain. Heart transplant for this is an elusive answer even in the best of economies.

TRANSPOSITION OF THE GREAT ARTERIES Definition The aorta and pulmonary arteries arise from the wrong ventricles resulting in deoxygenated blood from the right ventricle being delivered to the body and oxygenated blood from the left ventricle circulating back to the lungs (Figure 14.9).

Pathology The majority of transposition of the great arteries (TGA) (75%) occurs with an intact ventricular septum. A VSD is the most common associated anomaly, occurring in 25% cases. It may be perimembranous or muscular. Fixed left ventricular outflow obstruction (LVOTO) is seen 30% of TGA/VSD cases. Dynamic LVOTO is common, though usually mild. The coronary arteries normally arise from the aortic sinuses that face the pulmonary artery. The most common coronary artery anomaly is origin of the left circumflex artery from the right coronary artery.

Physiology In order to survive, there has to be mixing of blood between the systemic and pulmonary circulations. The ideal place for exchange to occur is at the atrial level through an atrial septal defect. A patent ductus arteriosus or a VSD may also provide some amount of mixing, but generally both lead to flow of blood from the high resistance systemic circuit to the low resistance pulmonary circuit. The right ventricle fails to undergo the normal involution of hypertrophy after birth as it pumps to the high pressure systemic circulation. The left ventricle will undergo this involution rapidly in the absence of a large high pressure shunt such as a VSD or PDA.

Presentation The newborn with transposition and intact ventricular septum usually presents within the first 24 hours of life with cyanosis that is

Figure 14.9: D-transposition of the great arteries

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often severe. The severity of the cyanosis is dependent upon the amount of mixing of blood between the systemic and pulmonary circulations. The systemic arterial PO2 may be as low as 15–25 mm Hg. Reverse differential cyanosis is the hallmark of TGA with intact ventricular septum: the pulse oximeter will show a significantly lower saturation in the right hand (preductal) than in the foot. In the presence of a VSD, cyanosis will occasionally be unnoticed and the infant may present in early infancy with congestive heart failure from pulmonary overcirculation and failure to thrive because of the VSD. A ventricular septal defect does not always result in improved saturations or lessened cyanosis.

Evaluation The ECG findings vary according to the presence or absence of a VSD and associated fixed LVOTO. The newborn ECG will generally be normal for the newborn condition. Right ventricular hypertrophy or biventricular hypertrophy may be evident. The chest radiograph shows a mildly enlarged egg shaped heart with a narrow base (as the great arteries lie on top of each other) and increased pulmonary vascular markings. The echocardiogram provides sufficient details of the anatomy to guide further management.

Therapy/Intervention Infants with TGA will generally be stable with a peripheral saturation above 70%. If the peripheral saturation is less than 60%, balloon atrial septostomy should be performed to improve atrial level mixing. Immediately after septostomy, saturations should rise to >70%. Increasingly, pediatric cardiac centers are opting for early arterial switch bypassing the need for balloon atrial septostomy. The corrective surgery for TGA is the arterial switch operation. In this procedure the aorta and pulmonary arteries are transected above their roots and reanastomosed to the anatomically correct roots. In addition, the coronary arteries must be moved to the new aortic root. The operation is most successful when performed in the early neonatal period ( 80 nary artery mm Hg) obstruction should undergo intervention to relieve the stenosis of the pulmonary valve (Fig. 15.8). After relieving the stenosed pulmonary valve, they can have normal activity levels. Patients with signs of right ventricular failure should be promptly treated with decongestive measures, including digitalis and diuretics, and immediate relief of obstruction after initial stabilization. Prompt balloon or surgical intervention should be undertaken. Right ventricular function may not recover completely if intervention is withheld for too long and if myocardial damage sets in. BPV is associated with excellent short-term and long-term outcome.14 Surgical valvotomy is indicated in children with dysplastic pulmonary valve with severe stenosis that are usually resistant to balloon dilatation and those with failed BPV.

Follow-up Evaluation Clinical, ECG, and Doppler echocardiographic evaluations are generally recommended at 1, 6 and 12 months after the procedure and yearly thereafter. Regression of right ventricular hypertrophy, as revealed on ECG is well known. The Doppler gradient generally reflects residual obstruction and is a useful and reliable noninvasive monitoring tool.

Critical Pulmonary Stenosis in the Neonate The term critical PS with intact ventricular septum is applied to severe valvular pulmonary obstruction resulting in suprasystemic right ventricular systolic pressure, tricuspid insufficiency and right-to-left shunt across the interatrial septum, and often a PDAdependent pulmonary circulation. Prostaglandin infusion may be needed in a sick neonate to keep the ductal patency and maintain pulmonary blood flow. Transcatheter balloon dilatation of pulmonary valve is the treatment of choice (Fig. 15.9).15

Figure 15.9: Inflated balloon with waist at stenotic valve in a patient under going balloon pulmonary valvuloplasty

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Infundibular Pulmonary Stenosis Isolated infundibular PS is an uncommon defect and accounts for approximately 5% of all cases of right ventricular outflow tract obstruction. It is usually associated with ventricular septal defect. Surgical resection of the fibrotic area or hypertrophic muscle is the treatment.

Double Chambered Right Ventricle Double chambered riht ventricle (DCRV) is caused by anomalous bands of muscles that divide the right ventricular cavity into a proximal high pressure chamber and a distal low pressure chamber. Treatment of double chambered right ventricle with significant obstruction is surgical resection of hypertrophied muscle bundle in right ventricle.

Branch Pulmonary Artery Stenosis It presents as supravalvar or bilateral or unilateral branch pulmonary artery narrowing. It may be a part of Rubella syndrome, Noonan, Alagille (arteriohepatic dysplasia), Ehlers Danlos, cutis Laxa, Leopard, Silver and William syndrome. The later is associated with supravalvar aortic stenosis, multiple branch pulmonary arterial stenosis, elfin facies and mental retardation.

Clinical Manifestations These may be masked by the other associated cardiac defects. Mild to moderate arterial obstruction are asymptomatic, whereas those with severe stenosis may have dyspnea on exertion, easy fatigability and occasionally right sided heart failure. The first heart sound and second heart sounds are normal. A click is usually absent unless pulmonary valve stenosis is associated. A continuous murmur may be present in up to 10% of patients and indicates that the diastolic gradient across the obstruction is significant. Diagnosis Diagnosis is established with the help of echocardiography and Doppler studies. Cardiac catheterization is helpful in diagnosis as well as in planning the management strategy. Treatment Natural history of isolated pulmonary artery stenosis is generally benign. Multiple and peripheral stenosis carry a potentially poor prognosis. The disease is associated with poor surgical results. The main stay of therapy is catheter based interventions, i.e. balloon dilatation of pulmonary artery with stent implantation if possible in older children. The stenosis relief, however, may be limited by accelerated intraluminal stent restenosis which may require rediatation and mandates long-term follow-up.16

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REFERENCES 1. Moore P, Adatia I, Spevak PJ, Keane JF, Perry SB, Castaneda AR, et al. Severe congenital mitral stenosis in infants. Circulation. 1994;89:2099–106. 2. Brauner RA, Laks H, Drinkwater DC, Scholl F, McCaffery S. Multiple left heart obstructions (Shone’s anomaly) with mitral valve involvement: long-term surgical outcome. Ann Thorac Surg. 1997;64: 721–9. 3. Breinholt JP, Hawkins JA, Minich LA, Tani LY, Orsmond GS, Ritter S, et al. Pulmonary vein stenosis with normal connection: associated cardiac abnormalities and variable outcome. Ann Thorac Surg. 1999;68:164–8. 4. Mendelsohn AM, Bove EL, Lupinetti FM, et al. Intraoperative and percutaneous stenting of congenital pulmonary artery and vein stenosis. Circulation. 1993;88:210–7. 5. Mendeloff EN, Spray TL, Huddleston CB, Bridges ND, Canter CB, Mallory GB. Lung transplantation for congenital pulmonary vein stenosis. Ann Thorac Surg. 1995;60:903–6. 6. Detter C, Fischlein T, Feldmeier C, Nollert G, Reichart B. Aortic valvotomy for congenital valvular aortic stenosis: A 37-year experience. Ann Thorac Surg. 2001;71:1564–71. 7. Borghia A, Agnolettia G, Valsecchia O, Carminatib M. Aortic balloon dilatation for congenital aortic stenosis: report of 90 cases (1986–98). Heart.1999;82:10. 8. Elkins RC, Knott-Craig CJ, Ward KE, Lane MM. The Ross operation in children: 10-year experience. Ann Thorac Surg. 1998;65:496–502. 9. Rohliceka C V, Font del Pinoa S, Hoskingb M, Miroc J, Côtéd J-M, Finle J. Natural history and surgical outcomes for isolated discrete subaortic stenosis in children. Heart. 1999;82:708–13. 10. Hamdan MA, Maheshwari S, Fahey JT, Hellenbrand WE. Endovascular stents for coarctation of the aorta: initial results and intermediate-term follow-up. J Am CollCardiol. 2001;38:1518–23. 11. Celoria GC, Patton RB. Congenital absence of the aortic arch. Am Heart J. 1959;58:407–13. 12. Krishnamoorthy KM. Balloon dilatation of isolated congenital tricuspid stenosis. Int J Cardiol. 2003;89:119–21. 13. Gikonyo BM, Lucas RV, Edwards JE. Anatomic features of congenital pulmonary valvar stenosis. Pediatr Cardiol. 1987;8:109–16. 14. Jarrar M, Betbout F, Farhat MB, et al. Long-term invasive and noninvasive results of percutaneous balloon pulmonary valvuloplasty in children, adolescents, and adults. Am Heart J. 1999;138:950–4. 15. Jureidini SB, Rao PS. Critical pulmonary stenosis in the neonate: role of transcatheter management. J Invasive Cardiol. 1996;8:326–31. 16. Fogelman R, Nykanen D, Smallhorn JE, McCrindle BW, Freedom RM, Benson LN. Endovascular stents in the pulmonary circulation: clinical impact on management and medium-term follow-up. Circulation. 1995;92:881–5.

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Amar Taskande

AORTOPULMONARY SEPTAL DEFECT Aortopulmonary septal defect or Aortopulmonary window (APW) is an uncommon malformation consists of a communication, usually nonrestrictive, between adjacent walls of the ascending aorta and pulmonary trunk. This condition results from the failure of the spiral septum to completely divide the embryonic truncus arteriosus. The associated cardiac lesions, including aortic origin of the right pulmonary artery, type A interruption of the aortic arch, tetralogy of Fallot and anomalous origin of the right or left coronary artery from the pulmonary artery and right aortic arch. Three types of aortopulmonary connection, i.e. Type I: Proximal defect, midway between the semilunar valves and the pulmonary bifurcation Type II: Distal defect, with posterior border absent, and aortic origin of right pulmonary artery Type III: Total defect, incorporating defect present in both types I and II. The clinical features are not specific but are those of a large left-to-right shunt, and clinically this lesion often mimics either a VSD or a PDA or both. Signs of congestive heart failure (tachypnea, diaphoresis, failure to thrive and recurrent respiratory difficulty) usually begin in the first weeks of life. Peripheral pulses are bounding. On auscultation, either a loud systolic ejection murmur at the left upper sternal border or a machinery-type murmur similar to that found with a PDA. Patient with very small defect may be asymptomatic. Congestive heart failure and pulmonary hypertension appear in early infancy. The chest X-ray film shows cardiomegaly with prominent pulmonary vascular marking. The aortic knuckle usually is not prominent. ECG may show right ventricular hypertrophy usually, or combined ventricular hypertrophy, if defect is large. Doppler echocardiography reveals abnormal, continuous forward flow in the pulmonary arteries indicates the presence of an aortopulmonary communication. With current echocardiographic techniques, cardiac catheterization usually is not required. Surgical closure of the defect is indicated in all patients with APW. Successful closure of APW using various catheter-delivered devices has also been reported.

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ANEURYSM OF THE SINUS OF VALSALVA The sinuses of Valsalva are three small outpouchings in the wall of the aorta immediately above the attachments of each aortic cusp. Aneurysm of sinus of Valsalva (SVA) or Aneurysm of the aortic sinus is a localized weakness of the wall of a sinus of Valsalva, leads to aneurysmal bulging and even rupture. About 90 to 95% originate in the right or noncoronary sinus and project into the right ventricle or right atrium, leaving less than 5% that originate in the left coronary sinus. Rupture into the pericardium is rare. The aneurysm may be isolated or associated with ventricular septal defect (VSD), bicuspid aortic valve, coarctation of aorta (COA), atrial septal defect (ASD) and tetralogy of Fallot (TOF). It is rarely associated with, Marfan syndrome, but may also result from Ehlers-Danlos syndrome, atherosclerosis, syphilis, cystic medial necrosis, chest injury, or infective endocarditis. These aneurysms do not always rupture but may cause symptoms by obstructing the right ventricular outflow tract, distorting the aortic valve and causing aortic incompetence, compressing the left coronary artery and causing myocardial ischemia, or causing conduction disturbances or even complete heart block by compressing the conduction system. The acute rupture of a large sinus of Valsalva aneurysm is characterized by sudden onset of chest pain, dyspnea, continuous murmur over the right or left sternal border and bounding peripheral pulses. Severe congestive heart failure eventually develops. Chest X-ray films shows cardiomegaly and increased pulmonary vascularity. The ECG may show combined ventricular hypertrophy. 2D and pulsed Doppler echocardiography may detect the walls of the aneurysm and disturbed flow within the aneurysm or at the site of perforation. Urgent surgical repair is recommended in all patients with ruptured SVA, especially with intracardiac shunting.

ARTERIOVENOUS FISTULA, CORONARY A congenital fistula (coronary-cameral fistula) may exist between a coronary artery and an atrium, ventricle (especially right), or pulmonary artery. In the majority of cases, the fistula arises from the right coronary artery (60%). The left coronary artery is the site of aneurysm in about 30% of cases, with the remainder arising from both right and left coronary arteries or from a single coronary artery. Coronary arteriovenous fistulas are arising as a persistence of sinusoidal connections between the lumens of the primitive tubular heart that supply myocardial blood flow in the early embryologic period. Over 90% of congenital coronary arterial fistula drains into the right side of the heart, i.e. 40% in RV, 25% in RA, 15% in PA, 7% in coronary sinus and most rarely in the SVC. Patients usually are asymptomatic. Physical appearance, the arterial pulse and jugular venous pulse are usually normal. A continuous murmur, like PDA is audible over the precordium, rather than in the left infraclavicular area. Chest X-ray films show a normal heart size. The ECG usually is normal but may show RVH or LVH if the fistula is large. The anatomic abnormality is usually demonstrable by color flow Doppler echocardiography and, during catheterization, by injection of contrast medium into the ascending aorta. Small fistula may be hemodynamically insignificant and may even close spontaneously. If the shunt is large, treatment consists of either transcatheter coil embolization or, for lesions not amenable to catheter intervention, surgical closure of the fistula.

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ARTERIOVENOUS FISTULA, PULMONARY In pulmonary arteriovenous fistula, there is a communication directly between the pulmonary artery and pulmonary vein bypassing the pulmonary capillary circulation. The fistula can be solitary or multiple, unilateral or bilateral, or minute or diffuse throughout both lungs. Approximately 75% of congenital pulmonary arteriovenous fistula involve the lower lobes or right middle lobes. Desaturated blood in the pulmonary artery is shunted through the fistula into the pulmonary vein, thus bypassing the lungs and then enters the left side of the heart. Large fistulas are associated with dyspnea, cyanosis, clubbing, a continuous murmur, and polycythemia. Features of the Osler-Weber-Rendu syndrome are seen in about 50% of patients and include recurrent epistaxis and gastrointestinal tract bleeding. Soft systolic or continuous murmurs may be audible over the site of the fistula. Occasional complication includes stroke, brain abscess, rupture of the fistula with hemoptysis or hemothorax and infective endocarditis. Roentgenographic examination of the chest may show one or more rounded opacities of variable sizes may present in the lung fields produced by large fistulas. The ECG show normal. Selective pulmonary arteriography demonstrates the site, extent, and distribution of the fistulas. Treatment consisting of excision of solitary or localized lesions by lobectomy or wedge resection.

ARTERIOVENOUS FISTULAS, SYSTEMIC In systemic arteriovenous fistula, there is direct communication (either a vascular channel or angiomas) between the artery and a vein without the interposition of the capillary bed. Arteriovenous fistulas may be limited to small cavernous hemangiomas or may be extensive. The most common sites in infants and children are within the cranium, in the liver, in the lung, in the extremities, and in vessels in or near the thoracic wall. Clinical symptoms occur only in association with large arteriovenous communications when arterial blood flows into a low-pressure venous system; local venous pressure is increased, and arterial flow distal to the fistula is decreased. Systemic arterial resistance falls because of the runoff of blood through the fistula. Compensatory mechanisms include tachycardia and increased stroke volume so that cardiac output rises. Physical examination reveals a systolic or continuous murmur over the affected organ. An ejection systolic murmur may be present over the precordium because of increased blood flow through the semilunar valves. The peripheral pulses may be bounding during the highoutput state but weak when CHF develops. Chest X-ray films show cardiomegaly and increased pulmonary vascular markings. The ECG may show hypertrophy of either or both ventricles. Injection of contrast material into an artery proximal to the fistula confirms the diagnosis. Most patients with large cerebral arteriovenous fistulas and CHF die in the neonatal period, and surgical ligation of the affected artery to the brain is rarely possible without infarcting the brain. Surgical treatment of hepatic fistulas is often impossible because they are widespread throughout the liver.

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ANOMALOUS ORIGIN OF THE LEFT CORONARY ARTERY FROM THE PULMONARY ARTERY Anomalous origin of the left cornary artery from the pulmonary artery (ALCAPA) is a rare but serious congenital anomaly (Bland-White-Garland syndrome). It may result from (1) abnormal septation of the conotruncus into the aorta and pulmonary artery, or from (2) persistence of the pulmonary buds together with involution of the aortic buds that eventually form the coronary arteries. This anomaly is usually isolated but has been associated with PDA, VSD, TOF, or COA. Patients usually asymptomatic in the newborn period until the pulmonary artery pressure fall to a critical level after birth. The direction of blood flow is from the right coronary artery, through intercoronary collaterals to the left coronary artery and into the pulmonary artery. This result in LV (left ventricle) insufficiency or infarction. The LV becomes dilated, and localized aneurysms may also develop in the LV free wall. Occasional patients have adequate myocardial blood flow during childhood and, later in life, a continuous murmur and a small left-to-right shunt via the dilated coronary system. Evidence of heart failure becomes apparent within the 1st few months of life, and it is often precipitated by respiratory infection. Recurrent attacks of discomfort, restlessness, irritability, sweating, dyspnea and pallor with or without mild cyanosis occur and probably represent angina pectoris. Cardiac enlargement is moderate to massive. A gallop rhythm is common. If a gallop is present, murmurs may be of the nonspecific, ejection type or may be holosystolic because of mitral insufficiency. During adolescence, they may experience angina during exercise. Chest X-ray shows marked cardiomegaly, predominantly of the left atrium and ventricle and evidence of pulmonary edema. The ECG resembles the anterolateral infarction pattern consisting of wide and deep Q waves, inverted T waves, and an ST-segment shift in leads I and aVL and the precordial leads V4 to V6. Color Doppler ultrasound examination may demonstrate retrograde flow in the left coronary artery, an enlarged right coronary artery, regional left ventricular wall motion abnormalities and mitral regurgitation, increased echogenicity of the papillary muscle and adjacent endocardium because of fibrosis and fibroelastosis. Untreated, death often occurs from heart failure within the 1st 6 months. Surgical revascularization of the left coronary artery system is usually necessary. Establishing revascularization by creating a two coronary artery system via either (1) a left subclavian artery— coronary artery anastomosis, (2) a saphenous vein bypass graft, (3) Takeuchi procedure (creation of an aortopulmonary window and an intrapulmonary tunnel extending from the anomalous ostium to the window), or (4) direct reimplantation.

CONGENITAL PERICARDIAL DEFECT Congenital pericardial defect includes partial or total absence of the pericardium. It represents defective formation of the pleuropericardial membrane or, if diaphragmatic, defective formation of the septum transversum.The majority of these cases occur on the left side (85%), and they are more often complete (65%) than partial. Associated congenital heart disease (PDA, ASD, mitral stenosis) or congenital pulmonary anomalies (sequestration, bronchogenic cyst and diaphragmatic defect) is present in 30% of cases. Partial absence of pericardium is often symptomatic and may even allows herniation of the portions of the heart through

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the defect or torsion of the great vessels, with potentially life-threatening hemodynamic consequences. Herniation and strangulation of the left atrial appendage also can occur. Obstruction of the superior vena cava can be associated with a right-sided pericardial defect secondary to herniation of the right lung into the pericardial space. Many patients with isolated pericardial defect are asymptomatic. Nonspecific symptoms, consisting of vague left chest discomfort, recurrent pulmonary infection, palpitations, and occasionally dizziness and syncope. A complete defect may produce vague positional discomfort in the supine or left lateral position. Occasionally, chest X-ray film may show a prominence of the left hilum or the PA caused by herniation of these structures. Complete absence of the left pericardium may be characterized by leftward displacement of the heart and aortic knob or a prominent PA. The ECG reveals an incomplete right bundle branch block. Echocardiography reveals paradoxical septal motion and right ventricular enlargement. CT or MRI imaging should be employed to establish a definitive diagnosis. Complete absence of the pericardium is usually asymptomatic and requires no treatment. Only partial forms of pericardial defect (left-sided, right-sided, or diaphragmatic) require surgical treatment. Surgical treatment like partial pericardiectomy, primary closure, partial appendectomy (of the left atrial appendage), and pericardioplasty with pleural flaps, Teflons or porcine pericardium is recommended for symptomatic patients.

CERVICAL AORTIC ARCH Cervical aortic arch is a rare anomaly in which the arch is found above the level of the clavicle (as high as the C-2 vertebral body). There are two main subcategories of cervical arch: i. Those with anomalous subclavian artery and vascular ring with either descending aorta contralateral to the arch or retroesophageal diverticulum. ii. Those with a virtual normal branching pattern. In infants, prior to the appearance of a mass, the presenting sign may be stridor, dyspnea, or repeated lower respiratory infections. A pulsating mass with associated thrill is present in the right supraclavicular fossa. In the presence of a pulsatile neck mass, a presumptive diagnosis can be made by notation of loss of femoral pulses during brief compression of the mass. Chest X-ray shows the presence of a widened upper mediastinum, absence of the aortic knob and evidence of anterior deviation of the trachea. An aortogram may assist in making an accurate diagnosis. Treatment is necessary if cervical arch is complicated by arch hypoplasia, symptomatic vascular ring, or, rarely aneurysm of the cervical arch itself.

COR TRIATRIATUM Cor triatriatum is a congenital anomaly in which the left atrium (cor triatriatum sinistrum) or right atrium (cor triatriatum dextrum) is divided into 2 parts by a fibromuscular band. Classically, the proximal portion of the corresponding atrium receives venous blood, whereas the distal portion is in contact with the atrioventricular valve and contains the atrial appendage and the true atrial septum that bears the fossa ovalis. This anomaly may be associated with major congenital cardiac lesions such as TOF, double outlet right ventricle (DORV), COA, partial anomalous pulmonary venous connection (PAPVC), persistent left superior vena cava with unroofed coronary sinus, VSD, endocardial cushion defect, and common atrioventricular

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canal. Embryologically, cor triatriatum sinistrum results from failure of incorporation of the embryonic common pulmonary vein into the LA whereas in cor triatriatum dextrum there is complete persistence of the right sinus valve of embryonic life results in separation of the smooth and trabeculated portions of the right atrium. Most patients with classic cor triatriatum have onset of symptoms within the first few years of life. Usually, the patients present with a history of breathlessness, frequent respiratory infections, and pneumonia. The signs of pulmonary hypertension, including loud pulmonary component of the second heart sound, right ventricular heave, and pulmonary systolic ejection click, are most characteristic. The usual cardiac murmur is a soft, blowing, systolic murmur along the left sternal border. Rightsided heart failure is usual. Pulmonary rales are frequent. The ECG shows sinus rhythm, frequent atrial premature complexes, left or right atrial abnormality, right axis deviation, right ventricular hypertrophy and strain pattern in cor triatriatum sinistrum whereas there are no pathognomonic ECG findings in isolated cor triatriatum dextrum. Chest X-ray films shows evidence of pulmonary venous congestion or pulmonary edema, prominent PA segment, and right-sided heart enlargement. Echocardiography is the most commonly used imaging technique for the diagnosis of cor triatriatum. Surgical resection of the cor triatriatum membrane under cardiopulmonary bypass is the effective treatment of choice.

CONGENITAL MITRAL STENOSIS Congenital mitral stenosis is a rare anomaly that can be isolated or associated with aortic stenosis or coarctation of aorta. It is characterized by variable combinations of anomalies, including thickened, rolled leaflet margins, shortened and thickened chordae tendineae, fibrous obliteration of the interchordal spaces, abnormal chordal insertions, papillary muscle hypoplasia, and decreased interpapillary muscle distance or fusion. Other mitral valve anomalies include parachute mitral valve, caused by a single papillary muscle, and doubleorifice mitral valve. Symptoms usually appear within the 1st 2 years of life. These infants are underdeveloped and generally have obvious dyspnea secondary to heart failure. Physical examination reveals an increased right ventricular impulse and an apical mid-diastolic murmur. Other findings include presystolic accentuation, loud S1 and opening snap. Roentgenograms usually show LA and RV enlargement and pulmonary congestion. ECG reveals RVH with bifid, or spiked P waves indicative of LA enlargement. The 2D echocardiogram shows thickened mitral valve leaflets, a diminished E-F slope on the M-mode, and an enlarged LA with a normal or small left ventricle. Doppler studies demonstrate a mean pressure gradient across the mitral orifice. For severe obstruction, surgical relief by closed or open valvotomy or placement of mitral valve prosthesis may be indicated but carries significant mortality and morbidity. Transcatheter balloon valvuloplasty has been used as a palliative procedure, depending on the anatomy of the valve and the papillary muscles.

CONGENITAL MITRAL INSUFFICIENCY Congenital mitral insufficiency may be isolated but is more often associated with other congenital cardiac defects, connective tissue disorders and metabolic or storage diseases. Secondary or

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acquired mitral regurgitation may be seen following trauma, acquired inflammatory conditions such as infectious myocardium, rheumatic fever, endocarditis, Kawasaki disease and collagen vascular disorders. Acute insufficiency leads to rapid rise of atrial pressure and pulmonary edema. When mitral insufficiency is chronic and gradual in onset, the left atrium becomes highly compliant, and gradual atrial enlargement and venous hypertension occur. Resistance to ventricular ejection is consequently reduced, leading to an early appearance of increased left ventricular ejection. A regurgitant holosystolic murmur is audible at the apex with radiation to the left axilla and left back. An apical rumble and a loud S3 may be present. The ECG and chest X-ray films may show hypertrophy and enlargement of LA and LV. Medical management should be tried initially. In patients unresponsive to medical management, mitral valvuloplasty or annuloplasty should be attempted to preserve the valve. If this is not possible, valve replacement is performed.

COMMON ATRIUM Common atrium is characterized by near absence of the atrial septum. In the presence of two ventricles, it always associated with an atrioventricular septal defect (AVSD). It may have anomalies of cardiac and abdominal situs and asplenia. Mainly patients present with symptoms of excess pulmonary blood flow, fatigue, tachypnea and failure to thrive. The precordium is hyperactive with a prominent right ventricular impulse. The second heart sound is widely split and fixed with respiration. A systolic ejection murmur is present over the upper left sternal border and radiates to the axillae and to the back. The ECG shows left anterior hemiblock (“superior” QRS axis), as in endocardial cushion defect, and an rsR’ pattern in the right precordial leads, as in ASD. 2D echocardiography shows the absence of the atrial septum and associated abnormalities. It require surgical repair that should be done early in life because the patient usually has symptoms and is at risk for developing pulmonary vascular obstructive disease.

CONGENITAL ANOMALIES OF VENA CAVAL CONNECTION Anomalous vena caval connections represent a wide range of malformations that vary from minor to major and that occur either in isolation or with coexisting congenital heart disease. The congenital anomalies of vena caval connection are: 1. Left superior vena cava – connected to coronary sinus – connected to left atrium 2. Right superior vena cava – connected to left atrium absent 3. Bilateral superior vena cava 4. Inferior vena cava – connected to left atrium – interruption with azygous continuation 5. Superior and Inferior venae cavae both connected to left atrium. Persistent left superior vena cava does not produce symptom or signs. Cardiac examination is entirely normal. It is suspected in the X-ray by a shadow that emerges from beneath the

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middle third of the left clavicle and passes downward toward the left upper border of the aortic arch. Echocardiography with color Doppler and echocontrast confirm the diagnosis and determine whether the caval connection is to the coronary sinus or to the left atrium. A left SVC-to-coronary sinus connection is often first suspected on echocardiography because of dilatation of the coronary sinus. Treatment is not necessary. Isolated superior vena cava connection to the left atrium is a form of cyanotic CHD with a dominant left ventricle that is palpable at the apex without a palpable right ventricle. Cyanosis dates from birth or early life, but cardiac symptoms are absent or mild even when cyanosis is conspicuous. The ECG shows normal adult left ventricle dominance. Echocardiography with color Doppler and echocontrast identifies the left superior vena cava entering the left atrium. A dilated coronary sinus effectively excludes direct connection of a left superior vena cava to the left atrium. Complex defects such as cor biloculare, conotruncal abnormalities and asplenia syndrome, are commonly found. Surgical correction is always necessary. Inferior vena cava connecting to the left atrium is an extremely rare condition in which the IVC receives the hepatic veins, curves toward the left atrium and makes a direct connection with the chamber. It is accompanied by conspicuous cyanosis unless a large azygos vein preferentially channels inferior vena caval return into the right atrium. The inferior vena caval shadow is absent from the expected location in the lateral chest X-ray. Contrast echocardiography with injection into the femoral vein opacifies the left atrium. Inferior venae caval interruption with azygous continuation is rare as an isolated malformation. The IVC below the level of renal veins is normal, but the hepatic portion of Inferior vena cava (IVC) is absent. Instead of receiving the hepatic veins and entering the right atrium, the IVC drains via an enlarged azygos system into the right SVC and eventually to the RA. The hepatic vein connects directly to the RA. It is associated with complex cyanotic heart defects, such as polysplenia syndrome, double-outlet RV, cor biloculare and anomalies of pulmonary venous return. This venous anomaly does not require surgical correction. Anomalous connection of either vena cava to the left atrium is rare enough, but connection of the right superior vena cava and the inferior vena cava to the left atrium (total anomalous systemic venous connection) is even rare. Survival depends on adequate mixing through an interatrial communication.

DOUBLE-CHAMBERED RIGHT VENTRICLE Double–chambered right ventricle is characterized by aberrant hypertrophied muscle bands that divide the RV cavity into a proximal high-pressure chamber and a distal low-pressure chamber. It is frequently associated with VSD, pulmonary valve stenosis, and discrete subaortic stenosis. Clinically, patients with double-chambered right ventricle (DCRV) and no VSD resemble patients with isolated pulmonary valve stenosis. When a VSD is present, the clinical picture relates to a VSD. A holosystolic ejection murmur that peaks in intensity near midsystole, with greatest intensity at mid-left and upper-left precordial areas, characterizes DCRV. Usually, the patient is diagnosed with a VSD or pulmonary outflow tract obstruction and, subsequently,

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may show signs of progression of the outflow obstruction, such as cyanosis, fatigue, and decreased exercise tolerance. ECG shows evidence of right ventricular hypertrophy, 40% of them demonstrated an upright T wave in V3R. Echocardiography demonstrates the muscle bundles that traverse the RV cavity, with an accompanying gradient starting proximal to the infundibulum. The angiographic demonstrates the filling defect dividing the RV, as well as the absence of infundibular hypoplasia. Early surgical resection of the bundle, as well as repair of other anomalies is indicated in DCRV.

DIVERTICULUM OF THE LEFT VENTRICLE In this rare anomaly, a diverticulum of the left ventricle protrudes into the epigastrium. The lesion may be isolated or associated with complex cardiovascular anomalies. Associated abnormalities include defects of the sternum, abdominal wall, diaphragm and pericardium. A pulsating mass is visible and palpable in the epigastrium. Systolic or systolic-diastolic murmurs produced by blood flow into and out of the diverticulum may be audible over the lower part of the sternum and the mass. Chest X-ray film may or may not show the mass. The ECG shows a pattern of complete or incomplete left bundle branch block. Surgical treatment of the diverticulum and associated cardiac defects can be performed in selected cases.

ECTOPIA CORDIS Ectopia cordis defect is characterized by partial or complete displacement of the heart out of the thoracic cavity. This anomaly is classified into five types: cervical, cervicothoracic, thoracic, abdominal and thoracoabdominal. The two most common forms of ectopia cordis are the thoracic and thoracoabdominal type. The latter is frequently associated with Cantrell’s pentalogy that includes bifid sternum, deficiency of the diaphragm, defect of diaphragmatic pericardium, defect of the anterior abdominal wall and intracardiac defects. Associated intracardiac anomalies like ASD, VSD, TOF and tricuspid atresia are common. Death occurs in the 1st days of life in most, usually from infection, cardiac failure, or hypoxemia. Patients without omphalocele or intracardiac defects may remain largely asymptomatic and can undergo surgical repair later in childhood. Occasional patients with the abdominal type have survived to adulthood. The management of ectopia cordis are: closure of the chest wall defect, including the sternal defect, repair of the associated omphalocele, placement of the heart into the thorax, and repair of the intracardiac defect. However, in more severe cases, most surgical efforts to put the heart into the thorax have failed because of the smallness of the thorax and kinking of the blood vessels.

HEMITRUNCUS ARTERIOSUS In hemitruncus arteriosus, anomalous pulmonary artery (PA) branch usually right PA arising from the ascending aorta in the presence of a main PA. Associated defects such as PDA, VSD, TOF, and APW are present. Hemodynamically, one lung receives blood directly from the aorta, with resulting volume or pressure overload or both, and the other lung receives the entire RV output, resulting in volume overload of that lung.

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The clinical presentation is predominantly that of congestive heart failure in infancy followed by the development of pulmonary vascular disease as early as 6 months of age, if unrepaired. A continuous murmur and bounding pulses may be present. The chest X-ray films show cardiomegaly and increased pulmonary vascular markings and ECG shows combined ventricular hypertrophy. Echocardiography is diagnostic. Treatment consists of surgical division of the anomalously connected pulmonary artery branch and reanastomosis directly, or with a graft, to the main pulmonary artery.

IDIOPATHIC DILATATION OF THE PULMONARY ARTERY In idiopathic dilatation of the pulmonary artery, pulmonary regurgitation is present in the absence of pulmonary hypertension in asymptomatic children or adolescents. A characteristic auscultatory finding is a grade 1–3/6 low frequency, decrescendo diastolic murmur at the upper and mid-left sternal borders. The S2 is normal. Chest X-ray films show a prominent main PA segment with normal peripheral pulmonary vascularity. The ECG usually is normal, but occasionally right bundle branch block is present. The prognosis is generally good, but rightsided heart failure may occur in later life.

KARTAGENER’S SYNDROME Kartagener’s syndrome is an autosomal recessive disorder characterized by the clinical triad of chronic sinusitis, bronchiectasis and situs inversus (dextrocardia). This disorder is inherited as an autosomal recessive pattern. Males and females are equally affected. Patients present with chronic upper and lower respiratory tract disease resulting from ineffective mucociliary clearance. Immotile spermatozoa result in male sterility. Cardiovascular examination demonstrates a point of maximal impulse and the heart sounds are heard best on the right side of the chest. Chest radiographs may reveals bronchial wall thickening as an early manifestation of chronic infection, hyperinflation, atelectasis, bronchiectasis and situs inversus.

PULMONARY ARTERY STENOSIS Single or multiple constrictions along the major PA branchs and may range from mild to severe and from localized to extensive. The stenosis may be confined to trunk or main PA, multiple peripheral involving segmental pulmonary arteries, central and peripheral stenosis. This may be an isolated anomaly or may be seen in association with syndromes (Williams, Alagille, Noonan’s, congenital rubella, cutis laxa, Ehlers-Danlos and Silver’s). Mild stenosis of the PA causes no hemodynamic abnormalities. Patients with mild to moderate stenosis remain stable and rarely progress. PPS of severe degree may be progressive and complications include RV failure, PA thrombosis, poststenotic aneurismal dilatation with pulmonary artery hemorrhage. An ejection systolic murmur grade 2–3/6 is audible at the upper left sternal border, with good transmission to the axilla and back. The S2 is either normal or more obviously split. If the stenosis is severe, the chest radiograph shows cardiomegaly and prominence of the main pulmonary artery and the ECG shows evidence of right atrial and right ventricular hypertrophy. Echocardiography is limited in its ability to visualize the distal branch PAs.

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Peripheral PA stenosis can be demonstrated only by angiography. If peripheral pulmonic stenosis is isolated, it may be treated by catheter balloon dilatation. When peripheral obstruction occurs distally in the intrapulmonary vessels, it is not usually amenable to surgical repair. These obstructions are often multiple and are best treated with repeat balloon angioplasty, although the rate of recurrence is high. The introduction of expandable intravascular stents, placed by catheter in the distal pulmonary arteries and then dilated with a balloon to the appropriate size, may prevent restenosis.

PATENT FORAMEN OVALE Patent foramen ovale (PFO) is a flaplike opening between the atrial septa primum and secundum at the location of the fossa ovalis that persists after age 1 year. In utero, the foramen ovale serves as a physiologic conduit for right-to-left shunting. Functional closure of the foramen ovale occurs postnatally as pressure in the left atrium exceeds that in the right atrium. As a result, the valve of the fossa ovalis is pressed against the limbus and forms a competent seal. During the first year of life, fibrous adhesions may develop between the limbus and valve and thereby produce a permanent anatomic seal and an imperforate atrial septum. It is usually of no hemodynamic significance and is not considered an ASD. However, a PFO may play an important role if other structural heart defects are present. If another cardiac anomaly is causing increased right atrial pressure (e.g. pulmonary stenosis or atresia, tricuspid valve abnormalities, right ventricular dysfunction), venous blood may shunt across the PFO into the left atrium with resultant cyanosis. Most patients with isolated PFO are asymptomatic. Patients may have a history of stroke or transient ischemic event of undefined etiology. Color Doppler imaging detect a small “flame” of color signal may be seen in the middle region of the atrial septum. Contrast echocardiography is usually required to detect small PFO. An isolated PFO does not require surgical treatment, although it may be a risk for paradoxical (right to left) systemic embolization.

PSEUDOCOARCTATION OF THE AORTA Pseudocoarctation of the aorta is a condition in which the distal portion of the aortic arch and the proximal portion of the descending aorta are abnormally elongated and tortuous. Unlike coarctation of the aorta, there is no obstruction of blood flow and no measureable pressure gradient across the area of redundancy/narrowing. Associated congenital cardiac anomalies include bicuspid aortic valve, congenital aortic stenosis, PDA, VSD and corrected transposition. There is a tendency for dilatation and aneurysm formation related to turbulent flow across the kink, and the condition may progress to show a substantial pressure difference between the arms and legs. Physical examination and the ECG are normal. It is a benign condition that requires no treatment. Surgical intervention may be required if dilatation compresses surrounding structures or aneurysm formation.

RUBELLA SYNDROME Congenital rubella syndrome is associated with malformations of multiple organ systems including the central nervous system, cardiac, ocular, and skeletal systems. The triad of this

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syndrome is deafness, cataract and cardiac defect. Damage to the fetus is most likely when maternal infection occurs during the first 2 months of pregnancy. The causative organism is a single-stranded RNA togavirus that is transmitted by means of respiratory droplets. The virus replicates in the nasopharynx and regional lymph nodes, resulting in viremia. The virus then may spread to the skin, CNS, synovial fluid, and transplacentally to a developing fetus. The most common cardiac malformation is PDA and stenosis of pulmonary artery. Other intracardiac defects, such as ASD, VSD, TOF and TGA, are also found in some cases.

SCIMITAR SYNDROME Scimitar syndrome is characterized by partial or complete anomalous pulmonary venous drainage of the right or left lung to the inferior vena cava. Right-sided scimitar syndrome is commonly associated with ipsilateral lung hypoplasia, dextroversion, elevation of ipsilateral diaphragm and ipsilateral pulmonary artery hypoplasia with systemic arterial supply to the lung. The lower portion of the right lung is perfused by systemic arteries from the abdominal aorta. This malformation is associated with other anomalies including hypoplasia of right lung, anomalies of the bronchial system, horseshoe lung, secondary dextrocardia, hypoplasia of the right pulmonary artery, anomalous arterial connection to the right lung from the aorta, and pulmonary sequestration. Additional cardiac anomalies are common, such as VSD, PDA, COA, TOF and DORV. The clinical spectrum of scimitar syndrome ranges from severely ill infants to asymptomatic adults. The anomalous venous channel produces characteristic X-ray findings of a crescent-like shadow in the right lower lung field, designated as the Scimitar syndrome (Shape of a Turkish sword). In symptomatic infants, embolization or ligation of systemic arterial supply to the right lung, if present, may result in improvement in pulmonary hypertension and sign of congestive heart failure. For older children, the total anomalous pulmonary venous return can be redirected to the LA, but in patients with associated with bronchopulmonary sequestration, the involved lobes of the right lung may need to be resectioned.

TAUSSIG-BING ANOMALY Taussig-Bing anomaly is a form of double-outlet right ventricle (DORV) with subpulmonary VSD. In subpulmonary VSD, oxygenated blood from the LV is directed to the PA, and desaturated blood from the systemic vein is directed to the aorta. This results in severe cyanosis. The PBF increases with the fall of the PVR. It resembles complete TGA with nonrestrictive VSD. Pulmonary vascular disease with right-to-left shunt through a nonrestrictive PDA results in distinctive reversed differential cyanosis with finger more cyanotic than toes. The S2 is loud, and a grade 2 to 3/6 systolic murmur is audible at the upper left sternal border. An ejection click and an occasional PR murmur may be audible. Patients experience cardiac failure early in infancy and are at risk for the development of pulmonary vascular disease and cyanosis. The ECG shows right axis deviation and right, left or biventricular hypertrophy. Two-dimensional echo, cardiac catheterization and angiocardiography are required for diagnosis. The surgical management is the creation of an intraventricular tunnel between the VSD and the PA, which is then corrected by the arterial switch operation or Senning operation or Damus-Kaye-Stansel operation and RV-to-PA conduit.

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SUGGESTED READING 1. Alphonso N, Norgaard MA, Newcomb A, et al. Cor triatriatum: presentation, diagnosis and longterm surgical results. Ann Thorac Surg. 2005;80(5):1666–71. 2. Arciniegas E, Farooki ZQ, Hakimi M, Green EW. Management of anomalous left coronary artery from the pulmonary artery. Circulation. 1980;62:I180–9. 3. Balaji S, Burch M, Sullivan ID. Accuracy of cross-sectional echocardiography in diagnosis of aortopulmonary window. Am J Cardiol. 1991;67(7):650–3. 4. Banerjee A, Kohl T, Silverman N. Echocardiographic evaluation of congenital mitral valve anomalies in children. Am J Cardiol. 1995;76:1284–91. 5. Baum D, Khoury GH, Ongley PA, et al. Congenital stenosis of pulmonary artery branches. Circulation. 1964;29:680. 6. Bernstein D. Congenital heart disease. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 17th end. Philadelphia: WB Saunders. 2004;1499–1548. 7. Byerregaard P, Laursen HB. Persistent left superior vena cava. Acta paediatr Scand. 1980;69:105–8. 8. CDC: Centers for Disease Control and Prevention (CDC). Elimination of rubella and congenital rubella syndrome—United States, 1969–2004. Morb Mortal Wkly Rep. Mar 2005 25;54(11):279–82. 9. Chang RR, Allada V. Electrocardiographic and echocardiographic features that distinguish anomalous origin of the left coronary artery from pulmonary artery from idiopathic dilated cardiomyopathy. Pediatr Cardiol. 2001;22:3–10. 10. Chhatriwalla AK, Younoszai A, Latson L, Jaber WA. An 8-month-old girl with an anomalous left coronary artery from the pulmonary artery complicated by myocardial ischemia after surgical reimplantation. J Nucl Cardiol. 2006;13(3):432–6. 11. Daoud G, Kaplan s, Perrin EV, et al. Congenital mitral stenosis. Circulation. 1963;27:185–96. 12. Davachi R, Moller JH, Edward JE. Disease of the mitral valve in infancy: anatomic analysis of 55 cases. Circulation. 1971;43:565–79. 13. Davis WH, Jordaan FR, Snyman HW. Persistent left superior vena cava draining into left atrium as an isolated anomaly. Am Heart J. 1959;57:906–18. 14. Di Segni E, Seigel A, Katzenstein M. Congenital diverticulum of the heart arising from the coronary sinus. Br Heart J. 1986;56:380–84. 15. Donnan GA, Davis SM. Patent foramen ovale and stroke: closure by further randomized trial is required! Stroke. 2004;35(3):806. 16. Fontana GP, Spach MS, Effmann EL, Sabiston DC. Origin of the right pulmonary artery from the ascending aorta. Ann Surg. 1987;102:206. 17. Franch RH, Gay BB Jr. Congenital stenosis of pulmonary artery branches. Am J Med. 1963;35:512. 18. Freedom RM, Mawson JB, Yoo SJ. The divided right ventricle: anomalous right ventricular muscle bundles and other entities. In: Congenital Heart Disease: Textbook of Angiocardiography. Futura Publishing Company, Incorporated. 1997:389–407. 19. Gao Y, Burrows PE, Benson LN, et al. Scimitar syndrome in infancy. J Am Coll Cardiol. 1993;22:873–82. 20. Godoy I, Tantibhedhyangkul W, Karp R, Lang R. Cor triatriatum. Circulation. 1998;98:2781. 21. Goitein KJ, Neches WH, Park SC, et al. Electrocardiogram in double chamber right ventricle. Am J Cardiol. 1980;45(3):604–8. 22. Hagen PT, Scholz DG, Edwards WD: Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc. 1984; 59(1):17–20. 23. Hammoudeh AJ, Kally ME, Mekhjian H. Congenital total absence of pericardium. J Thorac Cardiovasc Surg. 1995;109:805. 24. Hands ME, Lloyds BJ, Hung J. Cross sectional echocardiographic diagnosis of unruptured right sinus of Valsalva aneurysm dissecting into the interventricular septum. Int J Cardiol. 1985;9:380–84. 25. Haughton VM, Fellows KE, Rosenbaum AE. The cervical aortic arches. Radiology. 1975;114:675–81.

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26. Joseph M, Leclerc Y, Hutchinson SJ. Aortic pseudocoarctation causing refractory hypertension. N Engl J Med. 2002;346:784–85. 27. Khalil KG, Shapiro I, Kilman JW. Congenital mitral stenosis. J Thorac Cardiovasc Surg. 1975;70:40–5. 28. Kutsche LM, Van Mierop LH. Anatomy and pathogenesis of aorticopulmonary septal defect. Am J Cardiol. 1987;59(5):443–7. 29. LeWinter MM, Kabbani S. Pericardial diseases. In: Zipes DP, Libby PL, Bonow RO, Braunwald E, (eds). Braunwald’s Heart Disease. 7th end., Philadelphia: Elsevier Saunders. 2005;1779. 30. Menahem S, Venables AW. Anomalous left coronary artery from the pulmonary artery: a 15-year sample. Br Heart J. 1987;58(4):378–84. 31. Mori K, Ando M, Takao A. et al. Distal type of aortopulmonary window. Report of four cases. Br Heart J. 1978;40:681–9. 32. Nash EN, Moore GW, Hutchins GM. Pathogenesis of persistent left superior vena cava with coronary sinus connection. Pediatr Pathol. 1991;11:261–9. 33. Park MK. Pediatric cardiology for Practitioners. 4th end. Mosey, St. Louis. 2004;252–67. 34. Perloff JK. The Clinical Recognition of Congenital Heart Disease. (5th edn), Saunder, Philadelphia. 2003;395–400. 35. Ring WS. Congenital heart surgery nomenclature and database project: aortic aneurysm, sinus of Valsalva aneurysm and aortic dissection. Ann Thorac Surg. 2000;69:S147–63. 36. Ruscazio M, Van Praagh S, Marrass AR, et al. Interrupted inferior vena cava in asplenia syndrome and a review of the hereditary patterns of visceral situs abnormalities. Am J Cardiol. 1998;81:111–6. 37. Seward JB, Tajik AJ, Edward WD, et al. congenital heart disease. In; Two-Dimensional echocardiography Atlas Vol 1. New York: Springer-Verlag, 1987. 38. Sridaromont S, Ritter DG, Fedt RH, et al. Double-outlet right ventricle: anatomic and angiocardiographic correlations. Mayo Clin Proc. 1978;53:555–77. 39. Srivastava D, Preminger T, Lock JE, et al. Hepatic venous blood flow and the development of pulmonary arteriovenous malformations in congenital heart disease. Circulation. 1995; 92:1217–22. 40. Teknos TN, Metson R, Chasse T. New developments in the diagnosis of Kartagener’s syndrome. Otolaryngol Head Neck Surg. 1997;116(1):68–74. 41. Tiraboschi R, Crupi G, Locatelli G, et al. Cervical aortic arch with aortic obstruction: report of two cases. Thorax. 1980;35:26–30. 42. van Son JA, Danielson GK, Schaff HV, et al. Cor triatriatum: diagnosis, operative approach, and late results. Mayo Clin Proc. 1993;68(9):854–9. 43. Velvis H, Schmidt KG, Silverman NH, et al. Diagnosis of coronary artery fistula by two-dimensional echocardiography, pulsed doppler ultrasound, and color flow imaging. J Am Coll Cardiol. 1989;14:968.

17

Timing of Surgical or Catheter Intervention in Congenital Heart Disease

R Krishna Kumar

The timing of surgical or transcatheter intervention for congenital heart disease (CHD) is a critical decision and one of the most important tasks the pediatric cardiologist is asked to perform. Simply stated, the decision about when to intervene requires carefully balancing the results of the procedure with the natural history of the conditions. The extraordinary variety of CHD conditions including unlimited combination of defects complicates the decision making process. Further, during the last 40 years there have been numerous advances in the field of pediatric cardiology and pediatric cardiac surgery. These advances have enabled improved results from operations and transcatheter interventions and have allowed the procedures to be performed early. In addition, we now have information on the natural history of many congenital heart conditions. An increasing number of studies are being published on the longterm results of operations and interventions for congenital heart disease. Because of the wealth of information available to us the decision about “when to intervene in CHD” now involves careful consideration of a number of variables that influence natural history and procedural outcome (Fig. 17.1). There are no simple rules for the numerous CHD conditions and the decision making process has to be individualized for every patient. In this chapter, we propose to outline the various considerations that are involved in making a decision on timing of intervention for CHD. At all times there has to be a careful comparison of immediate and long-term procedural outcome with the natural history.

PREDICTING THE NATURAL HISTORY OF CONGENITAL HEART DISEASE The enormous variety of CHD conditions encountered complicates attempts at predicting the natural history. It is important to gather complete information for every patient and the following requirements must be met: 1. The precise anatomic diagnosis 2. Accurate hemodynamic assessment 3. Thorough clinical evaluation 4. Natural history information.

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Without obtaining complete information it is hazardous to make a statement on the natural history. We have come across numerous examples of patients with Eisenmenger syndrome who were reassured after a clinical evaluation alone in early infancy that their defect would close on its own.

Precise Anatomic Diagnosis Small and apparently trivial variations in the anatomy of a given condition can have an important influence on the natural history. Small differences in the location of a ventricular septal defect (VSD) may make an important difference to the natural history. A subarterial VSD may need closure to prevent aortic valve prolapse via the defect while a small muscular defect has a high likelihood of spontaneous closure. Today, precise anatomic diagnosis is obtained in the vast majority of patients through systematic and thorough echocardiography. Careful attention to seemingly small details while performing an echocardiogram often contributes substantially to correct decision-making in CHD. While performing an echocardiogram additional details may need to be looked for depending on the condition. For example, if a subaortic membrane is identified, it is useful to obtain additional anatomic details such as the distance of the membrane from the aortic valve, thickness of the membrane, nature of attachment to the mitral valve, etc. A thick subaortic membrane close to the aortic valve may have a higher chance of recurrence after resection as compared to a thin membrane situated in the LV outflow at some distance from the aortic valve.

Hemodynamic Assessment The hemodynamic significance of a congenital heart defect essentially involves shunt quantification determination of pulmonary vascular resistance in left-to-right shunts, assessment of severity of obstructive lesions (valve stenosis, outflow obstruction), assessment of severity of valve regurgitation and evaluation of ventricular function. A hemodynamicaly significant lesion often has clinical effects that merit attention. Occasionally, however, decisions to intervene have to be made on basis on hemodynamic evaluation alone in asymptomatic patients. Examples include an occasional patient with a large VSD somewhat elevated but variable pulmonary vascular resistance and severe aortic valve stenosis. The noninvasive tools available to us for hemodynamic evaluation include: history, physical examination, ECG, chest X-ray, echocardiogram. Cardiac catheterization often helps determine the hemodynamic significance of CHD with greater precision that other available tools. However, it is often possible to obtain enough information with the noninvasive methods in order to take a decision without having to resort to cardiac catheterization. Today, in most institutions, catheterization is reserved for the occasional patient where semiquantitative data using the noninvasive tools fails to categorize the patient. Table 17.1 outlines the principles of hemodynamic assessment of a patient with VSD as an example.

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Table 17.1: Hemodynamic assessment in a patient with ventricular septal defect Evaluation tool History Physical examination Chest X-ray ECG Echocardiography

Cardiac Catheterization

Parameters Symptoms of failure to thrive, feeding difficulty, tachypnea, frequent lower respiratory infections Precordial activity, splitting of S2, systolic murmur, apical diastolic murmur Cardiothoracic ratio, lung vasculature Ventricular enlargement or hypertrophy patterns Defect size, flow direction across the defect, predicted PA pressure, LV and LA enlargement, pulmonary acceleration time*, ratio of pulmonary to systemic blood flow (Qp/Qs) estimation** PA pressure, Qp/Qs ratio, pulmonary Vascular resistance

* semi-quantitative measures of pulmonary vascular resistance ** not reliable

Clinical Evaluation The clinical condition is largely dictated by hemodynamics, however, they may independently influence natural history of any CHD condition. The clinical parameters needing consideration include: nutrition, prematurity, respiratory infection and associated conditions involving other organ systems. Chromosomal and genetic conditions may have an important independent influence on the natural history. The presence of lethal conditions such as Trisomy, 13, or 18 can result in a decision not to intervene irrespective of the nature and severity of the cardiac defect. Other conditions such as Trisomy 21 may have an effect on the natural history of the heart defect itself (patients with Trisomy 21 have a relatively rapid rate of increase in pulmonary vascular resistance) and may influence the timing of intervention.

Natural History Information Numerous morbid and fatal events occur in patients with congenital heart disease (Table 17.2). Survival information from published studies on broad categories of lesions provide us with a useful benchmark for comparison with surgical or transcatheter intervention.1,2 Most of these studies have been published before the advent of heart surgery in the very young. Studies have also been published about the adverse neurodevelopment consequences of exposure to hypoxia.3 Serious morbid events affecting the central nervous system such as brain abscess and infarction are quite common in children with uncorrected cyanotic heart disease.4,8 These morbid events have often devastating consequences. Information on development of pulmonary vascular obstructive disease is available from older studies on patients with increased pulmonary blood flow from large left-to-right shunts and admixture lesions.9 Some defects such as transposition with unrestrictive VSD or PDA have a particularly rapid rate of increase in pulmonary vascular resistance (PVR) and can become inoperable during the first 6 months. There is enormous individual variation in the rate of increase in PVR that is largely unexplained (perhaps because of hitherto unidentified genetic influences).

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Lesion category Adverse consequences Duct dependent systemic Systemic hypoperfusion and blood flow in the newborn death with closure of the duct Hypoplastic left heart syndrome Critical coarctation Interrupted aortic arch Critical aortic stenosis Duct dependent pulmonary Fatal hypoxia and death with blood flow in the newborn closure of the ductus Pulmonary atresia intact ventricular septum Pulmonary atresia with other CHD conditions Critical pulmonary stenosis Severe Ebstein’s anomaly Conditions associated with Early: increased pulmonary blood Heart Failure flow Lower respiratory infections that are Left-to-right shunts frequent prolonged and difficult to Admixture lesions with treat increased pulmonary blood Growth retardation flow Late: (Transposition with VSD, Pulmonary vascular obstructive persistent truncus arteriosus, disease and Eisenmenger’s double outlet right ventricle, syndrome tricuspid atresia with Development of valve dysfunction: unrestricted pulmonary blood Aortic regurgitation in VSD flow, single ventricle, etc.) Mitral regurgitation in ASD Conditions with reduced Cyanotic spells pulmonary blood flow and Brain infarction right-to-left shunting in the heart Brain abscess Tetralogy of Fallot’s (TOF) Seizure disorder Other conditions with TOF A variety of adverse long-term (VSD with pulmonic stenosis) neurodevelopmental consequences physiology •  Cognitive impairment •  Lower IQ •  Learning disturbance Problems associated with polycythemia Obstructive Lesions Heart Failure Aortic and pulmonary valve Sudden death stenosis Dysrhythmias Subaortic obstruction Heart Failure Supravalvar aortic stenosis Ventricular dysfunction Isolated infundibular stenosis Dysrhythmias Coarctation Peripheral pulmonic stenosis Congenital valve regurgitation

SPONTANEOUS CLOSURE OF DEFECTS Some defects have a tendency towards spontaneous closure and this can influence the timing of intervention. The defects known to close spontaneously are atrial and ventricular septal defects and during the first few weeks of life, patent arterial ducts. The variables that influence

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likelihood of spontaneous closure include, age at evaluation (the likelihood of spontaneous closure declines with age and most ASDs and many VSDs are unlikely to close after the first three years of age), size of the defect (smaller defects are more likely to close), location of the defects (fossa ovalis ASDs, perimembranous and muscular VSDs can close on their own). Table 17.3 summarizes the variables that influence spontaneous closure.

PROCEDURAL OUTCOME Since at all times a decision to intervene (surgical or transcatheter intervention) requires carefully balancing the natural history with procedural outcome, the physician making an intervention has to have an intimate knowledge of the results of the procedure in the given institution. In the event the procedure is to be performed for the first time the physician should be thoroughly familiar with the institutional capabilities. Needless to say this requires honest communication between the physician making the decision and the person performing the procedure. Procedural outcome can vary substantially from one institution to another. A number of factors influence the outcome of the procedure in a given institution (Table 17.4). There are many components of care in a pediatric cardiac unit performing operative and transcatheter interventions in children. Any weak link in the chain of caregivers may substantially worsen the overall results. As a result of this, inter-institutional variability is common and age and weight threshold for operations may vary substantially from one institution to another. For example, in a 6-month-old child weighing 6 kg with TOF may be advised corrective operation if the institution has good results for TOF repair in young infants it may be wise to advice a corrective operation instead of a palliative procedure such as a Blalock-Taussig shunt. Institutions with poor results for the neonatal arterial switch operation may choose to refer a newborn with transposition to another institution or wait and perform a Senning operation later in infancy. The neurodevelopmental outcome of cardiopulmo­nary bypass and total circulatory arrest has recently become available and has generated considerable interest.10, 11 Impairment on cognitive skills, learning and intelligence has been described in infants undergoing openTable 17.3: Variables that influence likelihood of spontaneous closure Variable Age at evaluation

Effect of likelihood of spontaneous closure Younger patients have a higher likelihood of spontaneous closure of defects. Most ASDs and most VSDs that are destined to close or become very small do so before the age of 3 years. PDAs have a tendency to close in the first 2–4 weeks after which they seldom close, particularly in a preterm infant

Size of the defect

Larger defects have little likelihood of spontaneous closure. ASDs > 8 mm are unlikely to close spontaneously. Similarly large unrestrictive VSDs are also unlikely to close.

Location of the defect

Only fossa ovalis ASDs have a tendency to close Primum and sinus venosus type of ASDs do not close. Muscular VSDs have the highest likelihood of spontaneous closure. Perimembranous VSDs can also close spontaneously. Outlet (sub-pulmonic) VSDs may close by prolapse of the aortic valve with the risk of aortic regurgitation. Inlet VSDs and malalignment type of VSDs (such as those occurring in TOF) rarely close spontaneously



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heart surgery at a very young age.10 These consequences have to be balanced with the adverse long-term effects of uncorrected heart defects. Today the available information clearly favors early correction for most heart defects. However, this may change for specific situations as more information accumulates.12

GUIDELINES FOR INDIVIDUAL LESIONS Guidelines for decision making for common lesions are often sought by pediatricians to guide referral. There are potential difficulties in trying to make generalizations for categories of congenital heart lesions because of numerous individual variations. If echocardiography is available in the hospital, it may improve the quality of information available to the pediatrician. However, it is important that someone who understands congenital heart diseases well performs the echocardiogram. An incorrect echo can result in an erroneous advice. Table 17.5 has guidelines listed for “common” congenital heart lesions. This table is not comprehensive because there are still a number of conditions that cannot be easily categorized. Also the table cannot be used for combination of lesions. Table 17.5 does not relate the recommendations for surgery or catheter intervention to the ratio of pulmonary to systemic (Qp/Qs) blood flows. Traditionally, for VSD or PDA, Qp/Qs ratios of > 2:1 are considered as significant and suggest a large shunt. Typically apical diastolic flow murmurs and other features of large pulmonary blood flow accompany shunts of this magnitude. For ASD shunt ratios in excess of 1.7: 1 are considered important. The Qp/Qs ratios are reliably obtained only through cardiac catheterization. It is important to understand that Qp/Qs ratios obtained by echo are very unreliable and can mislead.  Today cardiac catheterization is not performed for a majority of patients with congenital heart disease because of progressive refinements in echocardiography.  Cardiac catheterization has important morbidity and cost and this is totally avoidable in most situations today.  However, cardiac catheterization is clearly indicated in specific situations. The indications for cardiac catheterization have been spelt out in the Table 17.5. 

CONCLUSIONS The decision about the need and timing of intervention in patients with congenital heart disease is a complex one and has to be individualized for every patient. It requires precise anatomic diagnosis, accurate hemodynamic assessment, and careful clinical evaluation together with intimate knowledge of the natural history of a given condition. This needs to be combined Table 17.4: Factors influencing procedural outcome Parameter Details Diagnostic support Accuracy of noninvasive diagnosis (echocardiography) Surgical and Track record of results for various procedures and experience Interventional skills Intensive care Quality of nursing Equipment Physician cover Anesthesia Availability and expertise of pediatric cardiac anesthesiologists Perfusion Specialized personnel and equipment

Anatomic evaluation Echocardiography (TTE and TEE) provides sufficient anatomic detail in almost all cases. Checklist for evaluation should include pulmonary veins, and mitral valve

Echocardiography is usually sufficient for infants. TEE may be required for the occasional older patient

Echo is often sufficient for anatomic information. TEE is not of additional use. For older patients with limited windows, cardiac catheterization may be required

Diagnosis

Atrial septal defect (ASD) Primum, fossa ovalis and sinus venosus)

Ventricular septal defect (VSD)

Patent ductus arteriosus (PDA), aortopulmonary window

History, physical examination and ECG clues are identical as in VSD. Additional findings favoring operability includes wide pulse pressure, flow reversal in descending thoracic aorta, flow direction across PDA. Transient systolic flow reversal in young children may be compatible with operability, particularly in younger children and infants

Echo: flow directions across the defect, LA and LV enlargement

History: failure to thrive, frequent respiratory infections. Physical examination: active precordium, apical flow rumble. ECG: q in lateral chest leads. Chest X-ray: heart size and lung vascularity

Oxygen saturation and PO2 levels, RV volume overload pattern on echo, flow direction across the ASD

Physiologic evaluation

1. 2.

Suspicion of PVR elevation based on history and physical examination. Significant flow reversal suggested by a lower O2 saturation in lower limbs Catheter closure (coil or device)

(surgery or catheter based) Elective closure for all ASDs with evidence of RV volume overload at preschool (5 to 6) years age if asymptomatic. Closure can be done earlier (if necessary, during infancy) if patient symptomatic

catheterization 1. Suspected pulmonary hypertension, to rule out coronary artery disease. 2. Rare patient with relatively small ASD, to quantify Qp/Qs ratios (> 1.7: 1 may merit closure) 3. Device closure of selected fossa ovalis defects 1. Suspicion of elevation in PVR. (threshold for cardiac catheterization in older children is often lower) 2. Device closure of selected muscular VSDs

Contd...

All large VSDs should ideally be closed electively between 3 to 6 months age and earlier if there are symptoms. The higher possibility of spontaneous closure in muscular VSDs may allow consideration for closure at an older age Small VSDs should be closed only if there is recurrent endocarditis or evidence of aortic valve prolapse All large PDAs should be electively closed after 1-3 months age. Moderate or small PDA can electively closed after 1 year

Indication for intervention

Indications for

Table 17.5: Evaluation and decision making in congenital heart disease

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Echo is usually sufficient.

Echo is often sufficient for anatomic information. Cardiac catheterization and angiography may be required for the occasional older survivor for the purpose of definition of pulmonary venous drainage Echocardiography provides all anatomic information

Echocardiography is usually sufficient except in presence of pulmonary atresia and hypoplastic branch pulmonary arteries or major aortopulmonary collaterals

Transposition with VSD or PDA; DORV with sub-pulmonic VSD (Taussig-Bing anomaly)

Unobstructed total anomalous pulmonary venous return

Cyanotic heart diseases with reduced pulmonary blood flow (two-ventricle repair feasible) Tetralogy of Fallot (TOF), DORV with VSD and PS, TGA with VSD and PS, corrected Transposition with VSD and PS

Obstructed total anomalous pulmonary venous return

Echo provides complete anatomic information including coronary artery anatomy

Transposition—Intact septum

Contd... 1. Balloon atrial septostomy. 2. Rare patient with pulmonary hypertension. PVR calculation prone to er-ror ecause of high PA saturations. Suspicion of elevation in pulmonary vascular resistance (threshold for cardiac catheterization in older children is often lower). However, cardiac catheterization data can be fallacious because of errors in PVR calculation (as in transposition with intact Older patients with evidence of PA pressure elevation (TR jet velocity on echo). Resting saturation < 85%. Cardiac catheterization is rarely required for infants

Presents in neonatal period Cardiac catheterization is and in early infancy. Deep risky and seldom yields cyanosis is frequent and does useful additional not reflect operability information Accurate estimations of Pulmonary atresia, small pulmonary artery pressures or borderline hilar are not crucial for repair pulmonary arteries, Demonstration of a significant suspected major aortogradient across the pulmonary pulmonary collaterals, valve usually suggests that the PA uncertain pulmonary venous pressures are not elevated. anatomy, uncertain coronary anatomy in TOF. The threshold for cardiac catheterization is lower for older patients (> 10 to 15 years) because collaterals are more frequent and

Resting oxygen saturations are valuable. Resting saturation of < 85% often suggest significant PVR elevation and saturation in excess of 90% are typically associated with operable data

Resting oxygen saturations > 85% typically suggest operability. Rest of the physiologic evaluation is similar to that of VSD alone. However, LA and LV enlargement may be present despite PVR elevation to inoperable levels

PVR elevation is rare except in the occasional older survivor

Contd...

Tetralogy of Fallot Considerable institutional variations exist; typically total correction is attempted at 6 months to 1 year. At a younger age a BlalockTaussig Shunt may be used for palliation. Certain forms of DORV or TGA with VSD and PS may have a two-ventricle correctionrequiring conduit. Because

Emergency operation as soon as diagnosis is made

Operation anytime after 1 month

Arterial switch between 1 to 3 months age

Arterial Switch operation in the first 2 to 3 weeks of life before LV regresses. Once LV regresses, two staged arterial switch or atrial switch

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Echo (TTE or TEE) is sufficient

Often sufficient in infants and young children

Obstructive Lesions (valvar or infundibular PS, valvar AS, subaortic stenosis)

Coarctation

Complete assessment requires assessment of ventricular hypertrophy, ventricular function, accurate assessment of gradients across the obstruction

Reasonably accurate gradients can usually obtained by Doppler in most situations Complete assessment requires assessment of ventricular hypertrophy, ventricular function, accurate assessment of gradients across the obstruction

Accurate estimation of PA pressures and PVR is often crucial for repair and can only be obtained through cardiac catheterization

Older children where mid thoracic obstruction cannot be ruled out. Balloon dilation (not suited for neonatal period and infancy) and stent placement (especially for adolescents)

Cardiac catheterization is usually indicated before a Glen shunt (may be occasionally avoided if anatomic definition has been satisfactory and a large gradient is demonstrable across the pulmonary valve) Cardiac catheterization is always indicated prior to a Fontan operation 1. Rare situations where windows are poor and accurate gradients not obtainable through TEE 2. Balloon valvotomy of valvar aortic or pulmonary stenoses

satisfactory demonstration of coronary anatomy is often not feasible

whenever RV systolic reaches systemic levels surgery should be considered. Unless coarctation is mild (gradients < 20 mm Hg) , its presence alone constitutes an indication for relief through surgery or catheter intervention

Valvar PS requires balloon dilation for peak gradients above 50 mm Hg and for valvar AS gradients above 70 mm Hg are considered as an indication for balloon dilation in asymptomatic patients. In the presence symptoms or ventricular dysfunction balloon dilation is indicated at lower gradients. For infundibular PS it is suggested that

of the potential need for conduit revisions with growth corrective operation is often delayed until 3 to 4 years age A Glen shunt can be performed as early as 3 months in many institutions. Fontan operation (definitive operation for single ventricle physiology) should ideally be attempted only after 3 to 4 years

TTE: Transthoracic echocardiography, TEE: Transesophageal echocardiography, ASD: Atrial septal defects, Qp/Qs: Ratio of pulmonary to systemic blood flows, PVR: Pulmonary vascular resistance, DORV: Double outlet right ventricle, PS: Pulmonary stenosis, PA: Pulmonary artery, RV: Right ventricular, TGA: Transposition of great arteries, AS: Aortic stenosis

Echo is sufficient except in older patents and occasional situations where pulmonary venous anatomy is unclear

Cyanotic heart diseases with reduced pulmonary blood flow (two-ventricle repair not feasible)

Contd...

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with a deep understanding of the immediate and long-term surgical results in a given center. The situation is dynamic and age and weight thresholds for various procedures are constantly changing with improved understanding of immediate and long-term procedural outcome.12

REFERENCES 1. Keane JF, Driscoll DJ, Gersony WM, et.al. Second natural history study of congenital heart defects. Circulation. 1993;87. 2. Fyler DC. Report of the New England regional infant cardiac program. Pediatrics. 1980;65:375–461. 3. Newburger J, Silbert A, Buckley L, et al. Cognitive function and age at repair of transposition of great arteries in children. N Engl J Med .1984:310:1495–9. 4. Gilles, Levinton A, Jammes B. Age-dependent changes in white matter in congenital heart disease. J Neuropathol Exp Neurol. 1973:32(Abst):179. 5. O’Dougherty, Wright FS, Loewenson RB, Torres F. Cerebral dysfunction after chronic hypoxia in children. Neurology. 1985;35(1):42–46. 6. Ghosh S, Chandy MJ, Abraham J. Brain abscess and congenital heart disease. J Ind Med Assoc. 1990; 88(11):312–14. 7. Ratnasiri B. Ten year review of brain abscess in Children’s Hospital Bangkok, Thailand. J Med Assoc Thai. 1995;78(1):37–41. 8. Takeshita M, Kagawa M, Yonetani H, et al. Risk factors for brain abscess in patients with congenital cyanotic heart disease. Neurol Med Chir (Tokyo). 1992;32(9):667–70. 9. Perloff JK. Congenital Heart Disease in Adults in Heart Disease, Braunwald E (ed), 5th edition, WB Saunders. 1997;963–87 (vol. 2). 10. Newburger J, Jonas R, Wernovsky G, et al. A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery. N Engl J Med. 1993;329:1057–64. 11. Clarkson P. Macarthur B, Barrat-Boyes B, et al. Developmental progress after cardiac surgery in infancy using deep hypothermia and circulatory arrest. Circulation. 1980;62:855–61. 12. Benson D. Changing profile of congenital heart disease. Pediatrics. 1989;83(5):790–91.

18

Rheumatic Fever and Rheumatic Heart Diseases in Children

M Zulfikar Ahamed, NC Joshi

Rheumatic Fever (RF) is a disease which licks the joints, bites the heart and stings the brain. The bite on the heart may be very severe sometimes and that is what makes us afraid of RF. It is the delayed, non suppurative sequel of upper respiratory tract infection by Group AB hemolytic Streptococci (GABHS) that can be often recurrent. It’s clear link to the preceding streptococcal infection of the throat is well defined. Though its incidence has declined in the developed countries, it still continues to remain as a major public health problem along with Rheumatic Heart Disease (RHD) in India especially in the young. RF is also one of the challenging diseases where accurate diagnosis still eludes the clinician sometimes; particularly to those whose training has had less exposure to RF/RHD.

HISTORICAL PERSPECTIVE The first description of RHD probably derives from Vieussens who did the first autopsies of valvar lesions in 1715. ‘Rheumatism’ as a term was coined by Baillie in 1797. Pitcain, in 18th century discerned a link between acute rheumatism and heart disease and in 1812, Wells published his treatise on “Rheumatism of the Heart”. Latham in the early 19th century described rheumatic endocarditis and pericarditis. The hall mark article which clearly defined ‘pancarditis’ concept in RF was by Boullard who is considered the father of RF/RHD. In India, the first description of RF/RHD came in 1938 by Stolt. Roy from India is credited with the term ‘Juvenile MS’. History of RF/RHD in the 20th century is punctuated by experience from Sanatoria treatment in USA and UK in the pre-penicillin era and use of steroids and penicillin in the treatment in the 2nd half of the century. 1944 saw the first T Ducket Jones criteria for diagnosis of RF, which was later adopted by American Heart Association and was revised several times, last of which was in 1992. 2002 saw a new WHO perspective on RF and its diagnosis that reinforces the application of 1992 Jones criteria. World Heart Foundation has recently (2011) come out with echocardiographic features of RF/RHD.

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EPIDEMIOLOGY The attack rate of RF is 3/1,000 school children. (3 out Prevalence studies in India of 1,000 who get streptococcal throat infection will Year Agency Rate develop RF). During an epidemic, it may go up to 3 per 1972 Berry 2/1000 100, possibly because of increased virulence of bacteria. 1970 ICMR 2.2 to 11.0/1000 Global prevalence of RF/RHD varies appreciably and 1981 Koshy 4.9/1000 ranges from 14/1,000 to 0.04/1,000 (Fig. 18.1). In the 1991 KS Reddy 1.8/1000 USA prevalence is 2/100,000. In India it ranges from 2002 AIMS 0.05/1000 0.9 to 6.4 per 1,000. In Kochi, India it was estimated to be as low as 0.05/1,000 (Fig. 18.2). Globally 5 lac children get RF annually and the total burden is 15–20 million. A conservative estimate puts the figure of total RF/RHD burden in India as 1 to 2 million and the incidence, approximately 50,000 per year. In Kerala the prevalence may be around 1/1,000. In SAT Hospital, Trivandrum, RF still continues to be the most common acquired cardiac illness, closely followed by Kawasaki disease (Figs 18.3 to 18.5). Even after the near elimination of RF in USA, there had been much resurgence there, which probably indicate that there may be a cyclic fall and rise in RF in developed nations also.

Figure 18.1: Epidemiology RF World

Figure 18.2: Epidemiology RF India

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Figure 18.3: Epidemiology RF SATH

Figure 18.4: Epidemiology RF/KD SATH

Figure 18.5: Epidemiology RF/KD SATH

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General Epidemiology Agent Group AB hemolytic streptococci (GABHS) are responsible for RF even though group G and C can cause throat infection. Some strains of GABHS are rheumatogenic–1, 3, 6, 18 and 49. Cardiovirulence may be related to the strain. Skin infection by streptococci does not cause RF. However, repeated skin infection may amplify the immune response to GABHS infection of the throat, especially in tropical countries. Virus had been implicated as a causative agent in RF in the 1980s. However, the link remains not established. Concomitant viral infection may be a priming or amplifying factor in the pathogenesis of RF. Host Rhevmatoid fever (RF) occurs commonly between 5 and 15 years and is a disease of school children. It is rare before 5 years and virtually unheard of below 3 years. The first attack of RF may occur as late as 30 years and recurrence 40 years. The male: female ratio is nearly equal. RF bites the heart at a young age and maims it during young adulthood (Fig. 18.6). Familial incidence of RF may point to either an enB Cell Allo Antigen vironmental factor or genetic factor. Many studies have Normal Control 14% shown that certain HLA types have been linked to RF, RF / RHD 99% e.g. DR-4, DR-3, DR-1 and DW-10. The genetic susceptibility also been highlighted by the presence of B cell Allo Antigen in children with RF/RHD (Fig. 18.7). Environment Overcrowding, lack of sanitation and poverty have been implicated as predisposing factors. In India, RF still remains as a disease of lower socioeconomic strata. Climatic and seasonal variations are not distinct in India unlike in the west, where RF is more common in the spring.

Rheumatic Fever—Possible Causes of Decline a. b. c. d. e.

Improved environmental and social conditions Increased antibiotic use in URT infections Better housing and easier access to medical care Possibly Decreased virulence of bacteria Impact of secondary prophylaxis.

Pathogenesis (Flow chart 18.1) The currently accepted theory of genesis of RF is that of immune mimicry, by which, it is proposed that certain streptococcal antigens share immunological properties of heart valves and cell membrane and antibodies produced against streptococcal antigens cross react with cardiac and other tissues producing damage. Initial theories such as infection theory and toxin theory have been discarded. Virus may be involved, causing amplification of immune process, not directly.

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Figure 18.6: Rheumatic fever major criteria SATH

Figure 18.7: Epidemiology—Comparative (Abbreviations: RF, Rheumatic fever; RHD, Rheumatic heart disease) Flow chart 18.1: Pathogenesis of rheumatic fever

Tissue inflammation occurs mostly in the heart, synovial membrane, and subcutaneous tissue and in brain. In the heart the inflammation essentially involves all the three layers— endocardium, myocardium and pericardium. This is called pancarditis. And yet the principal target is endocardium. Clinical evidence of myocardial element is rather scarce, cell necrosis is rare and Troponin test is negative, however, interstitial myocarditis is found in Endomyocardial biopsy.

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There are three phases of RF process. 1. Exudative phase - 2–3 weeks 2. Proliferative phase - Months 3. Fibrotic phase - Months, years The exudative phase is influenced by NSAIDs and steroids and proliferative phase is possibly influenced by steroids. No drug influences the fibrotic/scarring phase. The biotransformation from exudative and proliferative phases to fibrotic phase may be helped by T cell products. Hence, there is a belief that Acute RF is predominantly caused by B cell activity and RHD is possibly influenced and mediated by T cell immunity.

Clinical Features The clinical picture can be dramatic and acute with fever, arthritis, carditis with CHF or be silent with silent carditis. On an average, 70–80% children report a previous sore throat. The latent period can be from 7 days to 35 days (mean 2–3 weeks). In chorea, latency may be long (2–6 months) (Figs 18.8 and 18.9).

Figure 18.8: Rheumatic fever—in 1985 (then) and 2003 (now)

Figure 18.9: Rheumatic fever and the valves

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Rheumatic fever is a disease with no diagnostic gold standard either clinically or by investigation. Hence, in order to make the diagnosis easy and accurate, Ducket Jones in 1944 proposed criteria. It has been modified several times and the last modification was in 1992. It is to be remembered that the criteria are based on a construct rather than a gold standard. Later on, WHO proposed diagnostic criteria in 2004. Now, the diagnosis of RF—both primary and recurrence, depends on a sound frame work provided by AHA 1992 criteria (Jones) and WHO 2004 criteria. WHO Criteria 2004 1. Primary RF 2. Recurrence RF No valve involvement 3. Recurrence RF. Valvar heart disease pre-existing 4. Chorea Insidious carditis

AHA recommendations : 2 major or 1 major and 2 minor and antecedent streptococcal infection Same as above 2 Minor Antecedent streptococcal infection Other major criteria not required

Modified Jones Criteria 1992 Major

Minor

Supporting evidence of GABHS

Carditis Polyarthritis Chorea Subcutaneous nodules Erythema marginatum Fever Polyarthralgia Elevated acute phase reactants – ESR CRP Prolonged PR interval Positive throat culture / ASO / Rapid antigen positive

Terminology in Rheumatic Fever 1.

Recurrence

:

2.

Rebound

:

3.

Relapse

:

A new episode of RF following another GABHS infection; occurring 8 weeks after stopping treatment. Manifestations of RF occurring within 4–6 weeks of stopping therapy or on tapering drugs. Worsening of RF while under treatment and often with carditis.

CARDITIS Carditis is the most specific of all major criteria. The incidence is approximately 50–75% clinically and is an early presentation and sometimes may not be symptomatic. Being a pancarditis, it may present with varying combination of endocarditis, myocarditis and pericarditis. Approximately 80% of carditis occurs within 2 weeks of the illness (Fig. 18.10).

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Clinical picture of first episode of rheumatic carditis 1

Endocarditis (Valve)

2

Myocarditis

3

Pericarditis

Apical pansystolic murmur Apical mid-diastolic murmur Basal early diastolic murmur Unexplained cardiomegaly CHF Soft S1 S3 gallop Tachycardia Chest pain Rub

Clinical picture of recurrence (Carditis) 1

Endocarditis

2

Myocarditis

3

Pericarditis

Change in murmur New murmur Worsening of cardiomegaly Development of CHF Rub

Figure 18.10: Rheumatic fever carditis clinical picture

Apical Pansystolic Murmur Apical, pansystolic, high pitched murmur; may conduct to axilla, and also called seagull murmur. This is due to MR. Apical Mid-diastolic Murmur Apical, low pitched, mid-diastolic murmur with no presystolic accentuation. It is named after Carey Coombs. Due to valvulitis and thickening. Aortic Early Diastolic Murmur Basal, high pitched early diastolic murmur due to AR.

Practical Points •

Myocarditis without valvulitis is unlikely to be rheumatic

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• • • •

Pericarditis without murmur of valvulitis unlikely to be rheumatic Carditis lasts for 8–12 weeks in 95% of cases Involvement of mitral valve is 95–100%, aortic valve 20%, tricuspid under 5% and pulmonary valve under 1%. Isolated AR without MR is virtually unknown; could be < 5%.

Congestive Heart Failure in Carditis The major contribution to CHF is mechanical, mostly because of MR or added AR. Interstitial myocarditis is a minor contributor to CHF. Cardiomegaly may be because of effect of valvar involvement, myocardial involvement and mild pericardial effusion. Pericarditis in RF does not lead to constrictive pericarditis.

Indolent Carditis Has insidious onset with nonspecific symptoms of lethargy, fever, anorexia, etc. Cardiac findings of valvulitis and myocarditis will be found. The indolent carditis may be found in 10–15% of carditis.

Chronic Carditis Carditis lasting for more than 12 weeks can occur in 5%. They can be indolent also.

Fulminant Carditis Rarely child presents with severe refractory CHF and in pulmonary edema. They usually will have acute MR because of either chordal rupture or acute annular dilatation. Mortality is very high in this subgroup, which fortunately is rare in India. Clinical Presentation in Rheumatic Carditis Sree Avittom Thirunal Hospital data CHF occurs in 15% of carditis. Death is rare in modern times, probably less than 0.05%. In our hospital, there has been no death in acute Rheumatic carditis for the past 15 years. Author/Center Bland Sanyal Arora Carapetis SAT Hospital

No 1000 102 450 555 100

Polyarthritis 41 33 42 55 61

Major manifestations of RF% Carditis Chorea Nodules 65 52 9 67 21 2 30 3 6 55 28 30 mm/h is arbitrarily taken as cut off point for normal. If untreated with anti-inflammatory drugs it can remain high up to 6–10 weeks. Abnormal ESR > 30 mm/1 h Usual values in RF > 60 mm /1 h CRP It is another acute phase reactant. It is not affected by CHF or anemia and may be suited in those clinical situations where diagnostic dilemma of acute rheumatic activity exists on account of nondiagnostic ESR. Normal CRP Value: A value more than 6 mg/dL is diagnostic. CRP is also a nonspecific test. There can be mild polymorphonuclear leukocytosis. Anemia of mild severity exists that is because of: i. Depressed erythropoeisis ii. Increased plasma volume. The ESR can be relatively low in acute RF in the presence of CHF. However, it will not be normal. It is a good indicator of rheumatic activity and can be used for monitoring the response also. The CRP is not affected by CHF. It is not used to monitor the response as it rapidly comes down.

Anti-streptococcal Antibodies 1. Anti-streptolysin-O (ASO) 2. Anti-DNAase B 3. Anti-streptodornase 4. Anti-DPNase 5. Anti-streptokinase 6. Anti-hyaluronidase The commonly employed ones are: ASO —peaks at 3–6 weeks after streptococcal throat infection Anti-DNAase —Peaks at 6–8 weeks after streptococcal throat infection.

ASO (Figs 18.11 and 18.12) Usually a single measurement of ASO is done during suspected RF. If single value is taken, the diagnostic value is: ≥ 240 in adult ≥ 320 in children. The ASO is usually positive in 70–80% of children with ARF. It can also be positive in Rheumatic Chorea, though in less number (20–40%). If the titer is not of diagnostic level, it can be repeated after 5 days and a rising titer is said to be diagnostic.

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ADNase 85%

ASO Values in SATH Both 95%

Clinical All RF Carditis Chorea

% 73 70 30

Year 2003 1995 2001

Serial ASO are not routinely indicated because, it should be positive in the acute polyarthritis phase of ARF. If serial titers are done, samples are taken at 2–4 weeks intervals and should demonstrate rising titer. Natural History of ASO Appears : 7–10 days Peaks : 2–3 weeks Positive at 3 months 75% Positive at 6 months 20%

Figure 18.11: Rheumatic fever carditis clinical picture

Figure 18.12: ASO natural history

Identification of Organism 1.

Throat culture: It is positive only in 20–30%. Even if positive, it may still mean only a carrier state as GAS carrier state can be as high as 15%

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Nonculture techniques: Rapid antigen detection using coagulation, Latex agglutination and ELISA techniques. These tests may be of more help in primary prevention of RF.

Electrocardiography in Rheumatic Fever (Figs 18.13 to 18.15) About 1° AV Block (prolonged PR interval) is a minor criterion in ARF. It is essentially a functional abnormality and need not indicate Carditis. 2° AV block can occur uncommonly. Complete Heart Block occurs, but is quite exceptional. Other ECG changes are junctional rhythm, ST-T changes and occasional VPC.

Chest X-ray Chest X-ray may reveal cardiomegaly in the presence of carditis. LA enlargement in used. PVH may occur. Acute MR can occasionally produce acute pulmonary edema.

Figure 18.13: X-Rays: Moderate cardiomegaly in severe MR

Figure 18.14: Mild mitral regurgitation

Figure 18.15: Acute pulmonary edema

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Echocardiography in Acute Rheumatic Carditis Sine qua non of rheumatic carditis is Mitral valve involvement. Echocardiography has probably revolutionized the diagnosis and management of congenital heart disease (CHD). It has been limited to the evaluation of only chronic RHD so far. In chronic RHD, echocardiography, coupled with Doppler and color flow mapping (CFM) has been utilized for assessing. 1. Severity of valvar involvement—stenosis and regurgitation 2. Chamber function and enlargement 3. Coexisting PAH 4. Presence of clots 5. The timing and mode of interventions. Recently World Heart Foundation has come out with diagnostic criteria for echocardiographic diagnosis of RHD. These criteria are further divided into two age groups. For people below 20 years and for people above 20 years. According to the criteria that were published in 2011, echocardiographic findings may be classified into: 1. Definite RHD 2. Borderline RHD 3. Normal. These are based on both morphological and Doppler findings of mitral and aortic valve.

Echocardiography in Acute Rheumatic Fever (Figs 18.16 to 18.25) In acute rheumatic carditis, Echocardiography is useful in: 1. Assessing severity and bi valvar (Mitral and Aortic) involvement 2. Diagnosis of subclinical carditis 3. Occasionally resolving diagnostic dilemmas 4. Ruling out nonrheumatic conditions. Mitral valve is almost always involved in carditis. Aortic valve involvement is present in 20–25%. Isolated aortic valve involvement is very rare.

Figure 18.16: Valvar involvement in echocardiography in carditis

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Figure 18.17: Morphology of AML in carditis

Figure 18.18: Morphology of PML in carditis

Figure 19.19: Echocardiography in RF

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Figure 18.20: Mitral valve—Involvement in carditis (Abbreviations: LV, Left ventricle; LA, Left artery)

Figure 18.21: Mitral valve—Involvement in carditis (Abbreviations: AO, Aorta; AML, Anterior mitral leaflet; LA, Left artery)

Figure 18.22: Mitral valve—Involvement in carditis (Abbreviations: AO, Aorta; IV, Intravenous; LA, Left artery; RV Right ventricle)

Rheumatic Fever and Rheumatic Heart Diseases in Children

Figure 18.23: Mild mitral regurgitation (Abbreviations: LV, Left ventricle; LA, Left artery)

Figure 18.24: Mild—moderate mitral regurgitation (Abbreviations: LV, Left ventricle; LA, Left artery; AO, Aorta)

Figure 18.25: Severe mitral regurgitation (Abbreviations: LV, Left ventricle; LA, Left artery; AO, Aorta)

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The classical echocardiographic findings of mitral valve involvement in acute RF are: 1. Thickening of AML and PML 2. Annular dilatation 3. Chordal thickening and elongation 4. AML/PML Prolapse 5. Posterolateral jet of MR. Aortic valve can also be thickened with associated AR. There can be prolapse and restricted mobility also.

DILEMMA IN EVALUATION The laboratory evaluation consists of: 1. Acute phase reactants (APR) ESR CRP TLC, DC. 2. Evidence for previous streptococcal infection ASO Throat culture Rapid antigen test Anti-DNAse Anti-carbohydrate antibody Anti-hyaluronidase Streptozyme 3. Chest X-ray, ECG 4. Echocardiography 5. Others.

Dilemmas in Acute Phase Reactants An ESR above 30 mm/h is considered significant. However, ESR is nonspecific and can be elevated because of concomitant throat infection or respiratory infection. It can be elevated because of a recent Benzathine Penicillin injection. It can be falsely low in severe CHF or use of NSAID. However, even severe carditis with CHF will not bring down ESR to normal values. CRP above 6–8 mgm/mL is considered abnormal. It is less affected by anemia or CHF.

Dilemmas in Evidence of Previous Streptococcal Infection Marketing Elevated ASO in a child is a value of > 320 IU. It is, however, present in only 70–80% of RF. The percentage may come down with use of early antibiotics and steroids. If we do ADNase B also, the yield will become 95%. Two major dilemmas in ASO are: i. Persistently elevated ASO titer ii. Isolated elevation of ASO.

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Normally ASO becomes positive by 7–10 days of streptococcal throat infection and reaches a peak by 2–3 weeks. It remains in diagnostic range in 75% up to 3 months and in 20% by 6 months. So, even if RF is properly treated, ASO may remain elevated even at 3 months and need not be considered abnormal and does not imply continuing rheumatic activity. Isolated elevated value of ASO has to be considered as an evidence of a previous unrecognized streptococcal infection. A diagnosis of RF based on this phenomenon alone is untenable. Newer modalities like MRI, Radionuclide imaging and Endomyocardial biopsy have minimal role in routine evaluation of RF and hence do not pose dilemmas. However, these modalities may occasionally be useful to differentiate myocarditis or DCM from RF.

Dilemmas In Echocardiography As of now, echocardiography is not considered as a criterion—major or minor in diagnosis of (Jones criteria) RF. However, echo is being increasingly used to make the diagnosis of RF more accurate and complete. Its uses are: i. In detecting valvar lesions and quantifying them. ii. In picking up subclinical carditis (10–15%). iii. In differentiating rheumatic carditis from infective endocarditis and myocarditis. iv. In ruling out innocent murmurs or CHD, which may mimic rheumatic carditis. v. It is also useful in making a reasonable diagnosis of etiology of MVP in children— nonrheumatic or rheumatic. As a major morphological abnormality (> 50%) of mitral valve in rheumatic carditis is MVP, MVP need not be always non rheumatic as previously believed. In echocardiographic mitral valve leaflet morphology, chordal pathology and features of MR jet are all important in characterizing MVP intorheumatic and nonrheumatic. Still dilemma exists occasionally. From our experience in Trivandrum, we feel that there is a strong case for including echocardiography as a minor criterion in DJ criteria. In our series of 100 consecutive children with RF, seven had murmurs suggestive of carditis but with normal echo, stressing the role of echo in ruling out carditis and thus avoiding over diagnosis. 17 children had no murmur but had significant MR on echo, indicating the importance of picking up subclinical carditis. Finally another major diagnostic dilemma in RF is in retrospective diagnosis of RF. If one is asked to decide or judge on a previously established diagnosis of RF, one is virtually impossible to make a scientific decision, unless there is either clinical or echocardiographic evidence of rheumatic valvar involvement. Hence, the primary contact physician should apply WHO/ Jones criteria and make or unmake a diagnosis of RF.

TREATMENT Principles 1. 2. 3. 4.

General measures Treatment of group A streptococcal (GAS) infection Control of inflammation-Anti-inflammatory drugs (AID) Treatment of complications.

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Rest Guidelines Clinical Polyarthritis Carditis- No CHF/CE Carditis- CHF0 /CE + Carditis CHF+/CE+

Rest 2 weeks 4 weeks 6 weeks 6 weeks

Ambulation > 2 weeks > 4 weeks > 6 weeks > 6 weeks

Schooling 6 weeks 6–12 weeks 12 weeks 4 weeks-post stopping

Treatment of GAS Infection a.

Benzathine Penicillin

1.2 million units (> 30 kg) IM single dose 0.6 million unit(< 30 Kg) IM single dose. b. Penicillin V 250 mg 4 times × 10 days c. Erythromycin 40 mg/kg/day in 4 divided doses × 10 days Other drugs which can eradicate streptococci are: a. Amoxicillin 50 mgm/kg/day tid × 10 days b. Azithromycin 12.5 mgm/kg/day od × 5 days c. First generation cephalosporins 50 gm/kg/day qid × 10 days Tetracyclines and Sulfa drugs are not to be used in the treatment of GAS

Cost of Drugs Penicillin V Erythromycin Azithromycin Cephalexin

Rs 135 Rs 135 Rs 65 Rs 220

Control of Inflammation Agents used:

Aspirin Steroids

Suggested regimens are:

Polyarthritis; No Carditis Aspirin

100 mg/kg/day in 4 divided doses × 2–3 weeks 75 mg /kg/day, when ESR reaches normal value. Total duration of therapy can be around 4–6 weeks depending on clinical response. The serum level of aspirin is to be around 20 mg/dl. The serum level estimation is not absolutely needed.

Carditis; Mild Aspirin

100 mg/kg/day in 4 divided doses × 2–3 weeks . 75 mg/kg/day once ESR is normal × 6–8 weeks

When to Switch from Aspirin to Steroids When do we switch from Aspirin to steroids? 1. No response within 3–4 days*

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New cardiac findings develop; Child develops CHF/Cardiomegaly Child not to tolerating Aspirin**

Carditis; Moderate – Severe Steroids Prednisolone - 2 mgm/kg/day in 4 divided doses × 2–3 weeks Start tapering at the end of 2 weeks and do it over 2–3 weeks to avoid a rebound. The steroids may be given on twice daily basis also. Maximum dose of steroids is 80mg/day. Aspirin 75 mg/kg/day is to be added once the steroids are being tapered off. Note: Prednisolone is tapered by removing 5 mg from the total dose every third day. Total duration of AID therapy will be around 8–12 weeks. What is Severe Carditis? Decision on the severity of Carditis is based on the presence of: i. Cardiomegaly ii. CHF iii. Both aortic and mitral valve involvement and iv. Clinically evident pericarditis. Even if only one of them is present, Carditis is considered moderate/severe and steroids are to be administered.

Treatment of Rheumatic Fever in Adult Polyarthritis/Mild Carditis Aspirin 4–6 g/day 4 divided doses for 2 weeks followed by 50 mgm/kg/day or 75% initial dose for 4–6 weeks Significant Carditis Prednisolone

80 mgm/day/ in 4 divided doses × 2 weeks Taper off steroids Add Aspirin 50 mg/kg/day × 6–8 weeks Steroids are definitely superior to aspirin in acute carditis. However, its superiority in preventing residual RHD has not been fully established. Steroids may have specific theoretical advantages in severe carditis such as influencing the proliferative phase, diminishing biotransformation to RHD by acting against T cell activation. Methyl Prednisolone can be sometimes used in life-threatening cases. The dose is 30 mg/ m2/daily.

* One must exclude other causes of non responding arthropathies, including leukemia ** One can switch to Naproxen or Ibuprofen also if carditis is not present

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Algorithm for Rheumatic Fever Treatment

Treatment of Complications CHF: Diuretics (loop) are initiated first which control CHF and Digoxin should be given in lower doses, if needed. Digoxin: (30 mcg/kg) total digitalizing dose (TDD) (7.5 mcg/kg) maintenance dose (MD). In severe valvar regurgitation in ARF, vasodilators can be used, e.g. ACE inhibitors (ACEI). Captopril: 2–3 mg/kg/day in 3 divided doses. Start with small dose of Captopril (0.5 mg/kg) and build up to 2–3 mg/kg in the hospital. Enalapril is used in the dose of 0.1 mg/kg dose for two doses. Chorea: It is a self-limiting disease and mild chorea can be treated with diazepam. Severe chorea is treated with; i. Haloperidol: 0.25–0.5 mg/kg day tid up to 2.5 mg tid. ii. Diazepam: 0.25–0.5 mgm/kg/day iii. Valproate: 15 mg/kg/day (in resistant cases) Intravenous immunoglobulin (IVIG) has been tried both in chorea and carditis. It has no superiority over either aspirin or steroids and presumed as over kill. Treating chorea, subcutaneous nodules or erythema marginatum with aspirin may not influence the development of RHD.

Surgical Therapy Surgery is not contraindicated severe carditis. In fact, it may save a life. In fulminant rheumatic carditis one may resort to surgical valve replacement or repair. The mortality is around 10%. Prevention in RF Primordial Primary Secondary Tertiary

Preventing Strep throat—Vaccine? Treating Strep throat infection Preventing rheumatic recurrence by chemoprophylaxis Treating RHD

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PROPHYLAXIS i. Primary prophylaxis

:

ii. Secondary prophylaxis

:

Eradication of streptococcal infection so that RF does not occur. Prevention of streptococcal infection of the throat, after RF has occurred so that recurrence of RF does not occur.

Secondary Prophylaxis One can choose from: 1. Injection Benzathine Penicillin 2. 3.

: :

Oral Penicillin (Penicillin-V) : Erythromycin :

12 lacs (BPG) IM every 3 weeks [WHO recommends 6 lacs of BPG for < 27 kg] 250 mg BD daily 250 mg BD daily

Recommended Schedule (Duration) Rheumatic fever

No carditis

Rheumatic fever attack Rheumatic fever

carditis RHD

5 years after the last attack or till 18/21 years of age (whichever is later) 10 years after the last or till 25 years of age (whichever is later) Ideally life-long; at least till 40 years of age

ANAPHYLAXIS There is an unjustified fear of anaphylaxis and death associated with benzathine penicillin. The risk is present, but in a very small percentage. The following is the incidence of untoward reactions to BPG.

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1. 2. 3.

Minor reactions 3.2% Anaphylaxis : 1:10,000 injections Death : 1:30,000 injections. Anaphylaxis is more common in older patients and patients who have multivalvular disease and are sick. • Dropout rate of secondary prophylaxis is between 7% and 29% • During pregnancy either BPG or oral penicillin should be given. Sulfa drugs are not advocated in pregnancy • Prophylaxis should be given even after valve surgery • BPG is painful and may be less appreciated in adolescence. And as time goes by, the risk of recurrence comes down; one may perhaps switch over from injectable penicillin to oral penicillin in adolescence.

Primary Prophylaxis 1.

Diagnosis of streptococcal throat infection is very crucial in making primary prophylaxis a success. Clinical criteria are very important and are easy to follow.

Clinical Diagnosis of “Strep Throat” 1. 2. 3.

Fever - >101°F Red throat with exudates Anterior cervical adenopathy. Throat culture can be falsely negative or falsely positive (carrier state) and can take time. Rapid antigen testing may bring about rapid diagnosis and early treatment. 1. Genetic susceptibility is an important factor in the genesis of RF. Ideally children can be screened for B-cell marker but it quite expensive and not widely available 2. Many children do not complete the course of antibiotics for 10 days. Both the physician and parents should be educated about the importance of strict compliance 3. Another approach in making primary prophylaxis a success is to treat all ‘sore throat’ irrespective of cause, by BPG- The “sledge hammer” approach 4. Vaccines may be help in preventing RF. Not much success has been achieved in this area so far.

Natural History of RF Rheumatic fever (RF) is a disease which licks the joints, bites the heart and stings the brain. The bite on the heart may be very severe at times. Though the incidence of rheumatic fever varies from 0.3–0.5 per 100 documented streptococcal sore throat, during epidemics of streptococcal infections albeit from virulent strains the incidence has risen to 3%.Though these cases show clinical evidence of carditis in 50% of the instances, the echocardiographic evidence may be as high as 70–90%.The cardiac involvement may be a simple tachycardia in basal conditions or it may be clinically obvious valvulitis, myocarditis, pericarditis or an unexplained cardiomegaly (myocarditis?). Mortality in these children vary from 0.3 to1.6%. Within 3–5 years, 30–40% of these children develop permanent cardiac lesions, mitral valve being the commonly involved

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(90%), the other valves to be involved are aortic (12%), tricuspid (5–8%) and pulmonary valve ( 45 mm (> 28 mm/m2) Symptomatic, severe MR a. NYHA III and IV b. NYHA II with EF < 60% ESD > 45 mm ( > 28 mm/m2) or c. Worsening symptoms.

Surgical Treatment It could be either mitral valve repair or mitral valve replacement. 1. Mitral valve repair involves valve repair and reconstruction, subvalvar procedure and/or annular procedure (annuloplasty). A rigid or flexible ring is used for annuloplasty. Young children should have valve repair as far as possible as it retains the anatomy of the valvular apparatus and obviates the need for anticoagulation therapy. Surgical mortality is less than 1%. 2. Mitral valve replacement is done where mitral valve reconstruction is not possible or successful. Generally the mechanical low profile valves are preferred in children. The most popular valves are Medtronic, St Jude and Chitra TTK valves. Surgical mortality is less than 2%. Children should be put on long-term anticoagulation therapy following surgery.

MITRAL STENOSIS Mitral Stenosis (MS) is a common RHD. The usual latent period between RF and MS varies from 3–5 years in India. At least in 40% MS, there is no history of RF. Mitral stenosis is the narrowing of Mitral Valve Orifice (MVO). The normal MVO is 4–6 cm2 in adult. The corresponding value for the child is 4 cm2/m2. When it is < 2.5 cm2, MS exists. Mitral stenosis is graded into mild, moderate and severe as per the MVO. Thus, it is

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mild MS if MVO is 1.5–2.5 cm2; moderate if the MVO is 1.0–1.5 cm2 and severe if it is < 1.0 cm2. 99% of the MS is acquired and most often it is because of rheumatic process. Other rare causes include SLE, JRA and Carcinoid syndrome. Congenital MS occurs in 1% of children and is often associated with other CHD and is present in the very young.

Pathophysiology Pathology involves primarily leaflets, commissures and chordae. MS causes a gradient across mitral valve in diastole. If the gradient is more than 2 mm of Hg, MS exists. This will lead to elevation of LA pressure to maintain flow across stenosed mitral valve. Elevated LA pressure leads to PVH and subsequently PAH. RVH will occur due to long standing PAH. Later there is a reduction in forward flow, leading to low cardiac output.

Clinical Presentation Significant MS is symptomatic. The most common symptom is dyspnea. Varying grades of dyspnea can occur, including PND and acute pulmonary edema. Hemoptysis can occur. Fatigue and chest pain can occur rarely. Palpitation is uncommon. Pulse : Normal or low volume. Can be irregular if there is AF. BP : Can be normal or low JVP : Is normal unless there is significant PAH or RHF. There is minimal or no cardiomegaly. Tapping apex is evident. Diastolic thrill is common. LPH is common. P2 may be palpable. S1 is characteristically loud. S2 will feature loud P2. S3 is absent. Opening snap can be heard medial to apex indicating a pliable mitral valve. A rumbling mid-diastolic, low pitched murmur is the hallmark of MS. There is a presystolic accentuation. In severe PAH, there could be murmur of TR and PR. Features that indicate severity of MS are presence of significant symptoms, low volume pulse, diastolic thrill, long MDM, presence of PAH, short A2 -OS interval, etc.

Investigations X-ray Chest Cardiac size on PA view is normal or near normal. LA enlargement is common. RA enlargement is rare and it occurs late with significant MR and RVH with failure. RV enlargement is appreciable on lateral CXR. Occasionally calcification of mitral valve can be seen and is quite rare in children. Pulmonary artery will be prominent. The changes in the lung fields reflect pulmonary venous pressure changes and interstitial fluid collection. Electrocardiography Children with MS have normal sinus rhythm with mild sinus tachycardia. Left atrial enlargement (LAE) will be seen in 75% of the patients. PR interval can be prolonged. QRS axis shifts to right as MS progresses and is a reliable indicator of the severity of the disease. Right ventricular hypertrophy (RVH) is found in severe MS. LV enlargement depends on associated MR.

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Echocardiography Transthoracic echo is quite adequate in children to pick up, characterize, and quantify MS and the additional lesions. All modalities of echo are utilized—M Mode, 2D and Doppler including color Doppler. The following is looked for: 1. MV morphology—Wilkins scoring system: (to assess MV before balloon mitral valvuloplasty) a. Thickness b. Mobility c. Subvalvar pathology d. Calcification. 2. MV area by 2D, Doppler 3. MV gradient by Doppler

CORRELATION BETWEEN VALVE AREA AND MEAN MV GRADIENT Area cm2 > 2.5 1.5–2.5 1.0–1.5 < 1.0

Gradient (mean) mm Hg 50 mm Hg) iv. Repeated episodes of AF.

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It may be noted that children with mild-moderate MS (MVA 1–1.5 cm2/m2) who develop a significant PAH (PASP > 60 mm Hg) and those who develop pulmonary artery wedge pressure (PAWP) > 25 mm Hg during exertion, may have to undergo Valvotomy. Balloon mitral valvotomy is the procedure of choice in most children having valve apparatus suitable for BMV. On an average after the procedure MVA is increased by 1.0 cm2. The average MVA will be 1.7–2.2 cm2 and MV gradient is < 5 mm Hg. The success rate is 95%. Procedural death is near zero. 10 year survival is 95%. The CMV is the alternative which is not preferred now. CMV is still being used in the developing nations as it is less costly than BMV and equally effective. Direct vision Valvotomy is preferred in the developed world. Mitral valve replacement is done in conditions where significant MS is associated with poor valve morphology and hence not suitable for BMV/CMV. It is also the procedure of choice if there is associated significant MR achieved. Operative mortality for CMV is less than 1.0% and for BMV, it is also similar. Mitral Valvotomy—either balloon or closed surgical is essentially a palliative procedure. True restenosis occur in 10% at 6 years, 20% at 10 years and 30% at 14 years. The long-term results of MS valve interventions are given below: Years

Redo

Restenosis

5 years/10 years/15 years

10%/60%/70–80%

10%/20%/30%

Most patients who have a BMV or IMV maintain reasonably good clinical status for 10–15 years. This is more crucial in MS of the children as more and more young adults may require redo.

AORTIC STENOSIS Aortic stenosis (AS) in children is most often of congenital origin. Significant AS below 10 years is unlikely to be of rheumatic etiology. But in adolescents AS can be rheumatic in origin. Many children with AS are asymptomatic. If symptoms develop, they are dyspnea, chest pain and syncope. Sudden death is a major (5%) complication of severe AS. Physical findings in AS include a low volume pulse, narrow pulse pressure, heaving LV apex and a systolic thrill at the base of heart. ST is normal, S2 is variable and S3 can be prominent. The murmur is a loud, long, ejection systolic murmur heard both at apex and base, followed sometimes by an ejection click. Occasionally AR murmur can be heard. Rheumatic AS has invariably an accompanying AR.

Investigations 1.

2. 3.

X-Ray Chest: Usually a normal sized heart is found with evidence of pulmonary venous hypertension (PVH). Aortic calcification is rare in children. In LV dysfunction, there is cardiomegaly with LA enlargement. ECG: 80% of severe AS will show LVH with ST-T changes. 10% will have normal ECG. Presence of AF indicates MV involvement (Figs 18.26 to 18.30). Echocardiography: All modalities of echo can be useful in assessing aortic valve disease.

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Figure 18.26: Mitral regurgitation (Abbreviations: LA, Left artery; AO, Aorta)

Figure 18.27: Mitral stenosis—Doming MV (Abbreviations: LV, Left ventricle; LA, Left artery; RV Right ventricle)

Figure 18.28: MV area showing MS (Abbreviations: LV, Left ventricle; MV, Mitral valve)

Figure 18.29: Doppler gradient in MS (Abbreviations: MV, Mitral valve)

AS is graded into: Mild Moderate Severe

- peak gradient - peak gradient - peak gradient

< 50 mm Hg 50–75 mm Hg < 75 mm Hg

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Figure 18.30: Aortic regurgitation (Abbreviations: LV, Left ventricle; LA, Left artery)

In children AS can be graded by the AV Area as: Mild AVA > 0.9 cm2/m2 Moderate AVA 0.6–0.9 cm2/m2 Sever AVA < 0.6 cm2/m2 Other tests done are radionuclide studies, catheterization, TMT test, ambulatory ECG, etc.

Natural History Aortic stenosis (AS) is a progressive disease 1. Mild AS : At 10 years 85–90% will remain mild; but 10–15% will become moderate or severe 2. Moderate AS : Nearly half of them become severe at 10 years. 3. Severe AS : In the asymptomatic 5 years mortality/after surgery is 50%. In the symptomatic AS the 5 years mortality is 80%.

Management 1. 2.

Medical measures include Infective endocarditis prophylaxis and rheumatic prophylaxis. The plan of action for AS is Mild AS - No drugs; normal activity Moderate AS - No drugs; some limitation of activity severe AS—occasionally drugs and: limitation of activity. Treatment of CHF with digoxin, diuretics. Surgery/Intervention: a. Preferred is: Balloon aortic valvotomy in children and adolescents. b. The next best is : Surgical commissurotomy or repair c. Aortic valve replacement is a last resort, The indications for the interventions are: 1. Severe AS even if there are no symptoms (Gradient more than 75 mm of Hg) 2. Moderate AS: NYHA II or more 3. All symptomatic patients. In children with normal LV function, it is done as soon as possible. In children with impaired LV function with or with out CHF, it is done as an emergency. Mortality of BAV as

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well as is surgical commissurotomy or repair is 60 mm Hg) peripheral signs, cardiomegaly, soft S1, long EDM and Austin first murmur.

Investigations CXR chest will reveal cardiomegaly and prominence of the ascending aorta. In the chronic AR there can be LA enlargement and PVH.

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ECG will reveal LV volume overload with ST-T changes, occasional AV block or bundle branch blocks. Echocardiography is diagnostic for assessing both the etiology and severity of AR. LV dimensions are large; systolic function (EF; FS) are normal; Aorta is dilated with fluttering of AML in M-mode. 2D measures aortic annulus. Doppler and CFM assesses severity of AR and looks at AS and other valve pathology especially that of the mitral valve. Catheterization, radionuclide study and MRI are not routinely required. AR is graded into: 1. Trivial 2. Mild 3. Moderate 4. Severe.

Treatment A careful assessment of the natural history of chronic AR is required before planning therapy. 1. Mild AR: Near normal longevity. Risk of infective endocarditis is always present. It can progress in the severity. 2. Moderate AR: Can progress to severe AR and can later become symptomatic. Death at 10 years follow-up is 15%. 3. Severe AR a. Severe AR: Normal LV function; No symptom. Risk of events i. Death or SCD is 6%/year ii. CHF iii. LV dysfunction b. Severe AR; Impaired LV Function; No symptom. Risk of events (CHF/death; is > 20%/ yr. c. Severe AR; Impaired LV function; symptoms risk of death is 10%/year.

Treatment Plan 1. Infective endocarditis prophylaxis : In all 2. Rheumatic prophylaxis : If AR is due to RHD 3. Activity : Restriction if AR is severe/LV dysfunction 4. Control arrhythmia and keep the heart in sinus rhythm 5. Drugs Mild AR - No drug Moderate AR - Nifedipine ? Severe AR - Nifedipine—long acting Nifedipine: 0.5–1.0 mg/kg/day in divided doses to be given orally. Long acting preparation. NIFEDIPINE is a bipyridine calcium channel blocker. It produces vasodilatation with fall in SVR with some chronotropic (tachycardia) effect. Oral drug has a half-life of 2–3 hours and the preparations are either short acting or long acting (Retard). Syrup is not available. Strength are 5 mg, 10 mg, 20 and 10 mg retard. The dose is 0.5–1 mg/kg/day with maximum of 20 mg/ dose. It has minimal side effects—headache, tachycardia or flushing.

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Severe AR : Symptoms/CHF—(During the waiting period) Normal LV function - Nifedipine Abnormal LV function - Add ACE inhibitor - Digoxin, Diuretic. 1. Follow-up (echo) is done routinely: For the mild AR it is two-yearly and the moderate AR it is yearly and the severe AR half-yearly. It may be further noted that ACE inhibitors are not very useful in chronic severe AR with normal LV function and no symptoms. Moderate AR is generally prescribed long acting Nifedipine.

Surgery Indications 1.

NYHA I (Asymptomatic) a. LV ejection fraction < 50/55% b. Large LV dimensions LVID d > 38 mm/m2 LVID s > 28 mm/m2 LVEDV Index > 150 cmm/m2 2. NYHA II, III, IV (symptomatic) a. Normal LV function - As soon as possible b. Abnormal LV function - Urgent (< 6 months) c. CHF - Emergent (< 3 months) Aortic valve replacement can be done by a prosthetic valve. 1. Ball and Cage—Starr Edwards valve (SEV) 2. More commonly—tilted disk valve—that can be bi leaflet or unileaflet, St Jude valve, Medtronic valve and Chitra TTK valves are commonly used 3. Usually valve replacement is the choice 4. Rarely—Valve repair is done—it is less feasible than MV repair —Ross procedure

Ross Proceudre In severe AR in a child, valve replacement can be avoided by this surgery. Here pulmonary valve is re-implanted at aortic position and a homograft or bioprosthetic valve is placed at pulmonary valve location. It is increasingly becoming popular in children.

Tricuspid Valve Disease Tricuspid regurgitation is common in severe mitral valve disease and is usually functional in origin. It is secondary to pulmonary hypertension, right ventricular dilatation and failure. In right ventricular dilation, the chordae gets retracted downwards with dilation of the valve annulus. Primary tricuspid valve involvement in RF/RHD is rare—5–8%. The organic involvement usually present as TS. Critical TS has a valve area of < 1.3 cm2. It is extremely rare in children as an isolated lesion, but seen occasionally with mitral valve disease. Critical TS has a valve area of < 1.3 cm2. The major symptoms are fatigue and dyspnea. TS is almost always accompanied by mitral

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valve involvement. TR can be usually functional in RHD (due to PAH). The management of TS include balloon valvotomy and diuretic. TV can be repaired in severe TR as part of RHD.

Pulmonary Valve Disease It is extremely rare ( 0.68 = 2.24, 95% CI:1.04, 4.85), and left atrial enlargement at presentation (relative risk for left atrium-to-aorta ratio > 1.7 = 2.02; 95% CI:1.00, 4.22). Female sex was the only multivariate predictor of death.

CONCLUSION From the multitude of investigations and treatment strategies that are recommended for DCM, it is clear that the etiopathogenesis of pediatric DCM is poorly understood. Treatment of pediatric DCM today, continues to be largely supportive and not directed at the cause. Dilated

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cardiomyopathy in children represents an example of a condition where diagnostic work-up and treatment strategies can be tailored to the resources available with perhaps no substantial impact on the population of affected patients as a whole. The prognosis of DCM in children may not improve without further understanding of its etiologies and development of etiologyspecific therapies. The following strategy for investigating a child with DCM in a limited resource environment (as in most developing countries) may be appropriate. 1. Chest X-ray, ECG, echocardiogram. 2. Basic laboratory tests: Hemogram, ESR, basic blood chemistry (glucose, urea, creatinine, liver function tests, electrolytes, calcium and phosphorous), arterial blood gas analysis. 3. Metabolic Screening: Blood lactate (often can be obtained in an blood gas machine), serum ammonia levels, urinary ketones. 4. Muscle Enzymes: Creatinine phosphokinase (CPK) and CPK-MB, cardiac troponin T (if available). 5. Screening of family members—clinical screening and when relevant, echocardiography. The following treatment plan may be reasonable for a child with “idiopathic” DCM in a developing country. 1. Digoxin 2. Diuretic: Frusemide and spironolactone are a reasonable combination to start with. 3. ACE inhibitors: Captopril can be used to initiate therapy and this can be changed to enalapril because it needs to be given less frequently. 4. Carvedilol: This could be considered in absence of overt heart failure, particularly in the presence of tachycardia. 5. Anticoagulation: All children with DCM and severe LV dysfunction (LVEF < 30%) should ideally be anticoagulated. If close monitoring of INR is not feasible, aspirin should be administered. The presence of a LV thrombus on the initial echocardiogram is a strong indication for oral anticoagulation. 6. Carnitine: If the initial metabolic screening suggests the possibility of carnitine deficiency (elevated ammonia levels, high blood lactate or presence of urinary ketones), carnitine should be considered. Cardiac transplantation and the bridging procedures to transplantation are largely unrealistic in India as of now.

REFERENCES 1. Fujioka S, Kitaura Y, Ukimura A, Deguchi H, Kawamura K, Isomura T, et al. Evaluation of viral infection in the myocardium of patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2000;36:1920–26. 2. Kasper ED, Agema WRP, Hutchins GM, et al. The causes of dilated cardiomyopathy: A clinicopathologic review of 673 consecutive patients. J Am Coll Cardiol. 1994;23:586–90. 3. Matitiau A, Perez-Atayde A, Sanders SP, et al. Infantile dilated cardiomyopathy relation of outcome to left ventricular mechanics, hemodynamics and histology at the time of presentation. Circulation. 1994;90:1310.  

Myocardial Diseasee

301

4. Arola A, Jokinene E, Ruuskanen O, et al. Epidemiology of idiopathic cardiomyopathies in children and adolescents: A nationwide study in Finland. Am J Epidemiol. 1997;146:385–93.   5. Daubeney PEF, Nugent A, Davis AM, Wilkinson JL, Weintraub RG, on behalf of the National Australian Cardiomyopathy Study. Incidence and outcome of childhood cardiomyopathy in Australia: Results of a ten-year population-based study [abstract]. J Am Coll Cardiol. 1999;33(suppl A):496A. 6. Towbin JA. Pediatric myocardial disease. Pediatric Clinics of North America. 1999;46:289–312. 7. The consensus trial study group: Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study. N Engl J Med. 1987;316:1429. 8. The SOLVD Investigators: The effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med. 1991;325:293. 9. Gersony WM. Major advances in pediatric cardiology in the 20th century: II. Therapeutics J Pediatr. 2001;139:328–33. 10. Prabhu SS, Dalvi BV. Treatable cardiomyopathies. Indian J Pediatr. 2000;67:279–82. 11. Schwartz ML, Cox GF, Lin AE, et al. Clinical approach to genetic cardiomyopathy in children. Circulation. 1996;94:2021–38. 12. Ichida F, Hamamichi Y, Miyawaki T, et al. Clinical features of isolated noncompaction of the ventricular myocardium: Long-term clinical course, hemodynamic properties, and genetic background. J Am Coll Cardiol. 1999;34:233–40. 13. Barth PG, Wanders RJA, Vreken P. X-linked cardioskeletal myopathy and neutropenia (Barth syndrome)—MIM 302060. J Pediatr. 1999;135:273–6. 14. Nigro G, Comi LI, Politano L, et al. The incidence and evolution of cardiomyopathy in Duchenne muscular dystrophy. Int J Cardiol. 1990;26:271–7. 15. Towbin JA, Hejtmancik F, Brink P, et al. X-linked cardiomyopathy (XLCM): Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. Circulation. 1993;87:854–1865. 16. Lauer B, Niederau C, Kuhl U, et, al. Cardiac troponin T in patients with clinically suspected myocarditis. J Am Coll Cardiol. 1997 1;30(5):1354–9. 17. Kubo N, Morimoto S, Hiramitsu S, et, al. Feasibility of diagnosing chronic myocarditis by endomyocardial biopsy. Heart Vessels. 1997;12:167–70. 18. Pophal SG, Sigfusson G, Booth KL, et, al. Complications of endomyocardial biopsy in children. J Am Coll Cardiol. 1999;34:2105–10. 19. Narayan R, Menahem S, Chow CW, Dennett X. Endomyocardial biopsy in infants and children with cardiomyopathy. Clin Cardiol. 1991;14(11):903–7. 20. Webber SA, Boyle GJ, Jaffe R, Pickering RM, Beerman LB, Fricker FJ. Role of right ventricular endomyocardial biopsy in infants and children with suspected or possible myocarditis. Br Heart J. 1994;72(4):360–63. 21. Mason JW, O’connel JB, Herskowitz A, et al. A clinical trial of immunosuppressive therapy for myocarditis. N Engl J Med. 1995;333:269. 22. Camargo PR, Snitcowsky R, da Luz PL, et al. Favorable effects of immunosuppressive therapy in children with dilated cardiomyopathy and active myocarditis. Pediatr Cardiol. 1995;16:61–68. 23. Kleinert S, Weintraub RG, Wilkinson JL, Chow CW. Myocarditis in children with dilated cardiomyopathy: Incidence and outcome after dual therapy immunosuppression. J Heart Lung Transplant. 1997;16:1248–54. 24. Martin AB, Webber S, Fricker FJ, et al. Acute myocarditis. Rapid diagnosis by PCR in children. Circulation. 1994;90:330–39. 25. Keeling PJ, Gang G, Smith G, et al. Familial dilated cardiomyopathy in the United Kingdom. Br Heart J. 1995;73:417–21. 26. Michels VV, Moll PP, Miller FA, et al. The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy. N Engl J Med. 1992;326:77–82. 27. Mestroni L, Krajinovic M, Severini GM, et al. Familial dilated cardiomyopathy. Br Heart J. 1994;72: 35–41.

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28. Bengur AR, Beekman RH, Rocchini AP, Crowley DC, Schork MA, Rosenthal A. Acute hemodynamic effects of captopril in children with a congestive or restrictive cardiomyopathy. Circulation. 1991;83:523–7. 29. Shaddy RE. Beta-blocker therapy in young children with congestive heart failure under consideration for heart transplantation. Am Heart J. 1998;136:19–21. 30. Bruns LA, Chrisant MK, Lamour JM, et al. Carvedilol as therapy in pediatric heart failure: an initial multicenter experience. J Pediatr. 2001;138:505–11. 31. Gachara N, Prabhakaran S, Srinivas S, Farzana F, Krishnan U, Shah MJ. Efficacy and safety of carvedilol in infants with dilated cardiomyopathy: a preliminary report. Indian Heart J. 2001;53(1):74–78. 32. Karpati G, Carpenter S, Engel AG, et al. The syndrome of systemic carnitine deficiency: clinical, morphologic, biochemical, and pathophysiologic features. Neurology. 1975;25:16–24. 33. Rebouche CJ, Engel AG. Carnitine metabolism and deficiency syndromes. Mayo Clin Proc. 1983;58:533–40. 34. Helton E, Darragh R, Francis P, et al. Metabolic aspects of myocardial disease and a role for L-carnitine in the treatment of childhood cardiomyopathy. Pediatrics. 2000;105:1260–70. 35. Kothari SS, Sharma M. L-carnitine in children with idiopathic dilated cardiomyopathy. Indian Heart J. 1998;50:59–61. 36. Drucker NA, Colan SD, Lewis AB, et al. Gamma-globulin treatment of acute myocarditis in the pediatric population. Circulation. 1994;89:252. 37. Batista RJ. Reduction ventriculoplasty. Z Kardiol. 2001;90:35–7. 38. Gradinac S, Jovanovic I, Dukic M, et al. Partial left ventriculectomy in a two-year-old girl with dilated cardiomyopathy. J Heart Lung Transplant. 1999;18:610. 39. Hosenpud JD, Novick RJ, Breen TJ, Daily OP. The registry of the International Society for Heart and Lung Transplantation: Eleventh official report—1994. J Heart Lung Transplant. 1994;13:561–70. 40. Taliercio CP, Seward JB, Driscoll DJ, et al. Idiopathic dilated cardiomyopathy in the young: Clinical profile and natural history. J Am Coll Cardiol. 1985;6:1126–31. 41. Wiles HB, McArthur PD, Taylor AB, et al. Prognostic features of children with dilated cardiomyopathy. Am J Cardiol. 1991;68:1372–6. 42. Akagi T, Benson LN, Ligthfoot NE, et al. Natural history of dilated cardiomyopathy in children. Am Heart J. 1991;121:1502–6. 43. Lewis AB, Chabot BS. Outcome of infants and children with dilated cardiomyopathy. Am J Cardiol. 1991;68:365–9. 44. Bruch M, Siddiqui, Celermajar DS, et al. Dilated cardiomyopathy in children; determinants of outcome. Br Heart J. 1994;72:246–50. 45. Kumar K, Thatia D, Saxena A, et al. Pediatric dilated cardiomyopathy (DCM): Prognosis in a developing nation is comparable to developed nations [abstract]. J Am Coll Cardiol. 1995;27:187A.

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Harinder R Singh

ANATOMY AND PHYSIOLOGY The pericardium is a fibro-serous sac encasing the heart and the roots of the great vessels. It consists of an outer sac, the fibrous pericardium, and an inner sac, the serous pericardium. The fibrous pericardium blends with the external coats of the great vessels and is continuous with the pre-tracheal layer of the deep cervical fascia. The vessels receiving fibrous prolongations from this membrane are: the aorta, the superior vena cava, the right and left pulmonary arteries, and the four pulmonary veins. The serous pericardium is a closed sac that lines the fibrous pericardium and is invaginated by the heart. It consists of a visceral and a parietal portion. The arterial supply of the pericardium is derived from the internal mammary artery and its musculophrenic branch, and from the descending thoracic aorta. The nerves supplying the pericardium are derived from the vagus nerve, phrenic nerves, and the sympathetic trunks.1 The pericardium is richly supplied by a lymphatic plexus, which returns pericardial fluid and lymph to the venous circulation.2 The pericardial space normally contains less than 30 mL of fluid in adults and even less in infants and children.3 Pericardial fluid resembles an ultrafiltrate of plasma and contains immune factors.4 The pericardium helps to reduce the friction resulting from cardiac motion. It acts as a barrier by protecting the heart from inflammation, infection and malignancy from contiguous structures.5 It also protects the heart from acute overdistension. However the pericardium is a dynamic structure that, when subjected to chronic stretching either due to the gradual accumulation of intrapericardial fluid or to cardiac enlargement will grow to accommodate its contents, such that the working range of pressures between it and the surface of the heart is low.6

Conditions Affecting the Pericardium 1. Congenital • Absence of the pericardium • Defects in the diaphragmatic pericardium • Pericardial cysts

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2. Inflammation (Acute Pericarditis) • Acute infections: Bacterial/Purulent Pericarditis: Staphylococcus aureus  Hemophilus influenzae type B, other gram-positive and gramnegative organisms • Viral pericarditis: Coxsackie A and B, hepatitis, HIV, mumps, measles, varicella, etc. • Tuberculous pericarditis • Others: Fungal, protozoal, rickettsial • Vasculitis and connective tissue diseases: Rheumatoid arthritis, systemic lupus erythematosus, rheumatic fever, Kawasaki disease, etc • Malignancy • Drugs: Anticoagulants, antithrombolytics, hydralazine, procainamide, phenytoin, isoniazid, rifampicin, phenylbutazone, dantrolene, doxorubicin, penicillin • Postprocedural: Postcardiac catheterization, cardiac surgery, cardiac transplant, radiofrequency ablation, central line placement, pacemaker lead placement, radiation. • Miscellaneous: Renal failure, hypothyroidism, trauma. 3. Pericardial effusion/Tamponade 4. Constrictive pericarditis 5. Intrapericardial tumors

Congenital Absence of the Pericardium This is a rare congenital defect described in less than 500 cases in the literature. Absence of the left pericardium is seen in majority of the cases whereas complete absence of the pericardium is seen in only about 20 to 30% of the cases. Congenital absence of the pericardium is thought to occur due to premature atrophy of the left common cardiac vein with insufficient blood supply to the pleuropericardium leading to its agenesis. A large pleural deficiency is seen in about 75% of the cases with complete absence of the pericardium. Associated defects include patent ductus arteriosus, tetralogy of Fallot, atrial septal defect, mitral stenosis, bicuspid aortic valve, pulmonary sequestration, bronchogenic cysts and diaphragmatic hernia in 30% of the patients.7 Most cases are detected incidentally though few may experience chest pain, dyspnea, syncope or dysrhythmias. Chest radiographs may reveal leftward displacement of the heart, interposition of lung between the pulmonary artery and the aorta or between the diaphragm and the base of the heart. Echocardiographic features described are: (a) unusual echocardiographic windows, (b) cardiac hypermobility, (c) abnormal ventricular septal motion, and (d) abnormal swinging motion of the heart.8 Magnetic resonance imaging (MRI) and computed tomography (CT) are highly sensitive in demonstrating pericardial defects. Occasionally thoracoscopy may be performed to confirm the diagnosis. Partial absence of pericardium can be more significant as it can lead to entrapment and strangulation of atria, appendages or parts of the ventricles.9,10 No treatment is needed in asymptomatic patients with an incidental diagnosis. In symptomatic patients, surgery to enlarge the defect (pericardiectomy) or patch closure of the defect (pericardioplasty) may be performed.11

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Defects in Diaphragmatic Pericardium Defects in the pericardium have been described with a constellation of midline defects involving defects in the anterior diaphragm, sternum and omphalocele in patients with Pentalogy of Cantrell. It can be associated with ventricular septal defect, tetralogy of Fallot or diverticulum of the left ventricle.12 Congenital defect of the central tendon of the diaphragm has been reported with intrapericardial herniation of the liver, pulmonary hypoplasia and massive pericardial effusion in 4 neonates.13

Pericardial Cysts Pericardial cysts are rare remnants of defective embryological development of the pericardium and results from failure of fetal lacunae to coalesce into the pericardial coelom.14 They are usually unilocular, thin-walled structures attached intimately or by a pedicle to the pericardium. On MRI, they appear as a non-enhanced, well-circumscribed, round mass adjacent to the pericardium, most commonly in the pericardiophrenic angle on the right side.15 They are usually asymptomatic but can present with cough, chest pain or breathing difficulties. If the patient is symptomatic or the diagnosis is unclear, percutaneous aspiration can be performed. Open resection is rarely indicated.

Acute Pericarditis Pericarditis is the inflammation of the pericardial sac surrounding the heart and the origins of the great vessels. It is termed acute if the onset is within 6 weeks; subacute when the onset is within 6 weeks to 6 months and chronic when it is present for more than 6 months.

Etiology Pericarditis has been described with many conditions and diseases, as described above. Idiopathic pericarditis constitutes up to 80% of the cases of acute pericarditis. When no cause is determined, viral infection with subsequent immunologic reaction is presumed. Viral infections are presumably the most common cause of pericarditis in developed countries.16, 17 Tuberculous (TB) pericarditis accounts for only 4% of the cases in the developed countries but constitutes about 70% of the cases of acute pericarditis in the under-developed and developing countries.18 TB pericarditis is found in about 1% of the autopsied cases of TB and in 1 to 2% of instances of pulmonary TB.19 The incidence of TB pericarditis is increasing with the increasing prevalence of human immunodeficiency virus (HIV) infection.20 Purulent pericarditis is not uncommon in developing countries. It is a life-threatening illness with mortality rates approaching 2 to 20% even with treatment.21, 22 It occurs most frequently (40 to 60% of the cases) in very young children.23 Tamponade is far more likely to occur in purulent pericarditis (42 to 77% of the cases) than in viral pericarditis.24 Primary bacterial pericarditis accounts for about 7 to 14% of the cases of purulent pericarditis.23 Most often purulent pericarditis is a direct or hematogenous extension of existing pulmonary, cardiac, hematologic or subdiaphragmatic infection.25,26 Staphylococcus aureus is the most common bacterial organism causing purulent pericarditis.21 The other organisms causing

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purulent pericarditis are Haemophilus influenzae type B, Neisseria meningitides, and other gram-negative and gram-positive organisms. Pericarditis is a common feature of autoimmune and connective tissue disorders. It can also develop following an injury to the pericardium as a result of invasive procedures, trauma or radiation therapy. Uremia (blood urea nitrogen levels exceeding 60 mg/dL) can cause pericarditis and effusion in 6 to 10% of patients with advanced renal failure.27 Postpericardiotomy syndrome is an inflammatory condition affecting the pericardium after the first postoperative week. It is seen in about 10 to 50% of the postoperative patients.28 The incidence is much lower in children less than 2 years of age.29 It is thought to be due to an autoimmune response provoked by the presence of autologous tissue or blood in the pericardial space.30 It can occur following any surgery involving the myocardium or the pericardium. However it is more commonly seen following repair of atrial septal defects, tetralogy of Fallot, ventricular septal defects and pulmonary stenosis.29, 31, 32 It has been reported to occur in about 2% of the patients post pacemaker implantation.33 It has also been reported following surgery for pectus excavatum,34 following radiofrequency ablation,35 transvenous pacing,36 chest trauma37 and post heart transplantation.38

Pathophysiology Acute inflammation of the pericardium produces serous fluid, purulent fluid or dense fibrinous material. This may resolve spontaneously or require minimal intervention, based on the etiology. Even larger collections of fluid in the pericardial space may not be clinically significant if it occurs gradually. Acute collection of fluid in the pericardial space can cause the intrapericardial pressure to rise, thereby impeding filling of the heart. The pericardium affects the heart primarily during diastole, affecting the right side more than the left side.39 This can result in cardiac tamponade. If the process of inflammation continues and the fluid organizes into a thickened coating around the heart it results in constrictive pericarditis. The patients usually describe a nonspecific prodrome of malaise, fever and chest pain. Chest pain is described in about 80% of the children with acute pericarditis. The chest pain is precordial in location and pleuritic or dull in nature. It is exacerbated by inspiration, cough, motion or recumbent posture, and relieved by leaning forward. The pain may radiate to the left shoulder.40 The patient may have other additional symptoms relating to the cause of pericarditis. Postpericardiotomy syndrome manifests as low grade fever with malaise, chest pain, irritability or decreased appetite. Clinical Features A pericardial friction rub is pathognomic of acute pericarditis. A pericardial rub is a highpitched scratchy sound present during both systole and diastole. Pressing the diaphragm of the stethescope against the chest wall helps in amplifying the rub. It can also be accentuated by inspiration and the patient leaning forward. It is best heard along the line from the lower left sternal border to the apex. Absence of a pericardial rub does not preclude pericarditis as the rub may not be heard in patients with large effusions, or in patients with a murmur that may obscure the rub.41 The heart sounds may be muffled. Tachycardia is an important sign and may indicate impending tamponade. Dullness to percussion in the scapular region due to compression of the left lung may be seen in patients with large effusions (Ewart’s sign).

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Pericarditis should be considered in the differential diagnosis of any patient presenting with fever and chest pain. Cardiomegaly on chest radiography should raise suspicion, especially in the setting of conditions associated with pericarditis.

Investigations Laboratory tests, electrocardiogram (ECG) and echocardiogram are useful in diagnosing pericarditis. Acute phase reactants such as erythrocyte sedimentation rate may be elevated. Complete blood count may reveal features suggestive of infection. Cardiac enzymes may be elevated in the presence of myocarditis. Chest radiography may reveal a water-bottle appearance of the heart with normal pulmonary vascularity. ECG abnormalities are present in about 90% of the patients presenting with pericarditis. They are: (a) low-voltage QRS complexes due to the dampening effect of pericardial fluid between the chest wall and the myocardium, (b) ST segment changes as described below, and (c) electrical alternans, an alternation in amplitude of the complexes with each cardiac cycle resulting from rotational and pendular motion of the heart floating in the pericardial fluid. ECG abnormalities may evolve through four phases: Initially ST segment elevation and upright T waves (stage I). Over a course of several days, the ST segment returns to normal with flattening of the T waves (stage II). This evolves to T-wave inversion (stage III) and finally resolution to baseline (stage IV).42 The ratio of the height of the ST segment-junction to the height of the apex of the T wave in lead V6 of more than 0.25 is suggestive of pericarditis and helps discriminate it from early repolarization43 (Fig. 20.1).

Figure 20.1: ECG changes in acute pericarditis. There is evidence of ST segment elevation with upright T waves (stage I). The ratio of the height of the ST segment-junction (a) to the height of the apex of the T-wave (b) in lead V6 is more than 0.25, suggestive of pericarditis

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Echocardiography is the diagnostic test of choice to accurately diagnose pericardial effusion. The echocardiographic feature of a pericardial effusion is the appearance of an echofree space around the heart (Fig.  20.2). Echogenic matter within the pericardial space may be secondary to adhesions, fibrinous material, clots, fat or metastases. Doppler evaluation is performed to detect changes suggestive of cardiac tamponade, as discussed later. CT scan, MRI and nuclear studies have also been used in the past with no specific advantage. The indications to perform pericardiocentesis are cardiac tamponade, suspected purulent pericarditis, large pericardial effusions unresponsive to pharmacological interventions, unexplained effusions when present for more than 3 months and when tuberculosis is suspected. The characteristic features of pericardial fluid analysis are described in Table 20.1.

Management of Acute Pericarditis Viral pericarditis: It generally resolves spontaneously over 1 month. Bed rest for 1 week and analgesics are recommended. Corticosteroids are rarely indicated. It rarely progresses to tamponade, although recurrences are not uncommon. Tuberculous pericarditis: In developing countries, a pericardial effusion is often considered to be TB in origin unless an alternative etiology is obvious and therefore treatment is initiated even before bacteriologic diagnosis is established. A regimen consisting of rifampicin, isoniazid, pyrazinamide

Figure 20.2: Echocardiogram showing evidence of a large global pericardial effusion

Table 20.1: Characteristic features of Pericardial fluid analysis Etiology

Chemistry

Cytology

Diagnostic tests

1. Viral Pericarditis

Serosanguinous

Predominant lymphocytes

• Viral culture—low yield • PCR • In—situ hybridization

2. Bacterial Pericarditis

Purulent Elevated protein content Reduced glucose

Predominant neutrophils

• Bacterial culture • Bacterial antigen detection—latex agglutination and CIE • Staphylococcal teichoic acid antibody detection.

3. Tuberculous Pericarditis

Serosanguinous/ straw colored/ blood stained Elevated protein content

Predominant lymphocytes

• Auramine-Rhodamine fluorescent stain for AFB – positive in 15 to 42%.19,74 • Mycobacterial culture (about 6 weeks)—positive in 53%. • Mycobacterial DNA–PCR75 • Mycobacterial Ag specific T cells—ELISPOT • ADA > 35 U/L76 • Pericardial lysozyme = 6.5 mcg/dL77 • Interferon - γ > 200 pg/L78

PCR—polymerase chain reaction, CIE—countercurrent immunoelectrophoresis, AFB—acid-fast bacilli, Ag— antigen, ELISPOT—enzyme-linked immunospot test, ADA—adenosine deaminase activity.

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and ethambutol or streptomycin for at least 2 months followed by rifampicin and isoniazid for 6 months has been found to be effective.44 The effectiveness of corticosteroids in TB pericarditis remains controversial. Although steroids may have some beneficial effect on mortality and morbidity, there appears to be no significant beneficial effect of steroids on reaccumulation of pericardial effusion or progression to constrictive pericarditis.45,46 Purulent pericarditis: The principles of treating this life threatening illness are drainage of the pericardial fluid, institution of appropriate antibiotics and intense supportive care. Surgical drainage of pericardial fluid is indicated in most cases of purulent pericarditis if initial pericardial drainage is unsuccessful in relieving tamponade. Initial antibiotics should cover S. aureus and H. influenzae type B and include penicillase-resistant penicillin and a third generation cephalosporin. In areas with high incidence of methicillin-resistant staphylococci, vancomycin with a third generation cephalosporin should be the initial antibiotics of choice. Antibiotics are changed subsequently based on sensitivity patterns. Treatment is continued for 4 weeks in case of staphylococcus infection and for about 3 weeks in cases of other organisms. Constrictive pericarditis is a rare but well-documented complication of purulent pericarditis.47 Postpericardiotomy syndrome: Postpericardiotomy syndrome is a relatively benign, self-limiting condition. Majority of the patients respond to bed rest and anti-inflammatory agents.48 Steroids are recommended for severe cases and cases associated with large pericardial effusions.49 Methotrexate has been reportedly used for chronic postpericardiotomy syndrome with recurrent pericardial effusions.50 Patients with large or rapidly accumulating pericardial effusion may require pericardiocentesis.51

Cardiac Tamponade Cardiac tamponade is a life-threatening, slow or rapid compression of the heart due to accumulation of fluid, blood, clots or gas in the pericardial space leading to significant impairment of ventricular filling.40

Pathophysiology The key elements to develop cardiac tamponade are the rate of fluid accumulation relative to pericardial stretch and the effectiveness of compensatory mechanisms. During tamponade the cardiac chambers compete with each other for space within a relatively fixed intrapericardial space impinging on ventricular filling. The systemic and pulmonary venous pressure rises and as more fluid accumulates, the stroke volume falls. Tachycardia and increase in blood volume compensates this fall in stroke volume. As more fluid accumulates and the initial compensatory mechanisms fail, the peripheral vascular resistance rises to maintain blood pressure and the pulse pressure narrows. Any further increase in fluid accumulation leads to further compromise of the ventricular filling and hypotension.52 The coronary blood flow is also reduced in tamponade but there is no ischemic component, as the coronary blood flow remains proportional to the reduced work and requirements of the heart.53 Clinical Features Cardiac tamponade must be suspected in patients with hypotension preceded by symptoms of pericardial disease, specifically patients with chest wounds that develop hypotension, and

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patients with suspected purulent pericarditis. The symptoms suggestive of cardiac tamponade are dyspnea on exertion, weakness, syncope, and non-specific symptoms such as anorexia, dysphagia and cough. The signs of cardiac tamponade are tachycardia, pulsus paradoxus, jugular venous distension, soft and muffled heart sounds, hypotension, and signs of end-organ hypoperfusion. Pulsus paradoxus is a key diagnostic finding in patients with cardiac tamponade. It is defined as an inspiratory systolic fall in arterial pressure of 10 mm Hg or > 9% of systolic blood pressure during normal breathing.54 Differential diagnosis of pulsus paradoxus includes massive pulmonary embolism, profound hypotension and obstructive lung disease. Pulsus paradoxus may be absent in patients with severe left ventricular dysfunction, hypertrophic cardiomyopathy, pericardial adhesions, positive pressure ventilation, aortic insufficiency and atrial septal defects.55 Pulsus paradoxus can alternatively be determined with the use of pulse oximetry. Large inspiratory falls in the highest value of upper plethysmographic peak of the waveform obtained by pulse oximetry have been shown to correlate with echocardiographic signs of compromised filling.56

Investigations The specific sign on ECG for cardiac tamponade is electrical alternans, especially if it involves both the P waves and QRS complexes.57, 58 Echocardiography with Doppler studies is the diagnostic investigation of choice to detect tamponade. On echocardiogram there is evidence of global fluid collection in the pericardial space with evidence of compressed and collapsing chambers with hyperdynamic cardiac function. The inferior vena cava may appear dilated with little or no change on respiration. On Doppler evaluation, marked variation in transvalvular flow with respirations is seen.59, 60 This represents a Doppler equivalent of pulsus paradoxus (Fig. 20.3). Management Management of cardiac tamponade consists of drainage of the pericardial contents. This is accomplished by needle pericardiocentesis. Surgical drainage may be necessary when needle pericardiocentesis fails, in patients with intrapericardial bleeding, clotted hemopericardium or thoracic conditions that make needle drainage difficult or ineffective. Needle pericardiocentesis is best performed in a controlled setting such as an intensive care unit under the guidance of echocardiogram or in the catheterization laboratory under fluoroscopic guidance. The procedure is performed with continuous heart rate, pulse oximeter, ECG and blood pressure monitoring. After adequate sedation, the patient is placed in a 30° sitting position. The subxiphoid area is prepped and drapped in a sterile manner. After local infiltration Figure 20.3: Pulse Doppler across the with 1% lidocaine, an 18 to 22 gauge long needle mitral valve showing evidence of marked respiratory variations in the transmitral with attached syringe prefilled with sterile saline is flow in a patient with cardiac tamponade inserted and advanced at a 45° angle towards the (For color version see Plate 2)

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left scapular tip with continuous aspiration until fluid is obtained. A 0.0038-inch guidewire is then passed through the needle and the needle is removed. A vascular dilator is then advanced over the guidewire after making a small incision at the site of wire entry. This dilator is then exchanged for a pigtail catheter. The guidewire is removed and the catheter is sutured to the skin and affixed to a closed drainage system. The catheter is removed when the drainage of fluid is less then 1 to 2 mL/kg per day. Complication rates of 7 to 55% have been reported in the adult literature.61 Myocardial injury due to the pericardiocentesis needle manifests as ventricular ectopy, injury pattern on ECG or presence of bloody fluid on aspiration that does not clot. The other complications reported are laceration of the coronary arteries, pneumopericardium and death. Recurrences of pericardial fluid collection and tamponade may require balloon pericardiotomy, which has been reported to be safe and efficacious even in children.62, 63 Medical treatment of acute tamponade is aimed at supporting compensatory mechanisms to reduce the elevated vascular resistance. Thus dobutamine administered to reverse the hypotension is theoretically ideal. Volume infusion is helpful in patients with hypovolemia. Mechanical ventilation should be avoided as this further decreases the cardiac output.

Constrictive Pericarditis Constrictive pericarditis is characterized by a thick non-compliant and adherent pericardium that restricts filling of the ventricle.64

Etiology In children, TB is probably the most common cause of constrictive pericarditis, as 11 to 27% of patients with TB pericarditis develop constriction. The other causes of constrictive pericarditis are idiopathic, pericardial involvement from trauma, surgery or irradiation, acute pericarditis of any etiology, hemopericardium, and rarely associated with metabolic and genetic syndromes like mulibrey nanism.65 Pathophysiology The thick non-compliant and adherent pericardium leads to impaired diastolic filling and elevated diastolic pressures. It impairs the ventricular filling in mid to late diastole. The intrapericardial volume and space is restricted. This leads to elevated central venous pressures and pulmonary capillary wedge pressures. Further progression of constriction leads to further limitation in diastolic volume and a drop in stroke volume. Compensatory tachycardia and peripheral vasoconstriction fail to maintain the cardiac output. The systolic function of the ventricles is though well maintained.64 Clinical Features The presenting symptoms of constrictive pericarditis include exercise intolerance, easy fatigability, dyspnea, and syncope with exertion, pedal edema, and weight gain. The signs of constrictive pericarditis are tachycardia, jugular venous distension, hepatomegaly, ascites, soft heart sounds and signs of low cardiac output. Pericardial knock, an early diastolic filling sound of higher frequency than S3, is pathognomic of constrictive pericarditis. An inspiratory rise in

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the neck vein filling secondary to decreased right heart compliance is called the Kussmaul’s sign.

Investigations ECG may show low-voltage QRS complexes and an intraventricular conduction delay. Chest radiographs may reveal a normal size cardiac shadow, pericardial calcifications or pleural effusions. Echocardiogram with Doppler study may reveal flattening of the left ventricular posterior wall endocardium, abnormal septal motion, premature opening of pulmonary valve, dilated atria, dilated SVC (superior vena cava) and IVC (inferior vena cava) and marked respiratory variation of transvalvular flow profile. Although these findings lack specificity, a normal echocardiogram and Doppler study rules out constrictive pericarditis. CT scan and MRI are sensitive tests to evaluate pericardial thickness.66,67 Cardiac catheterization reveals nearly equal levels of diastolic pressure in all chambers of the heart (within 5 mm Hg), a dip-plateau or square root like waveform in the right ventricular pressure waveform and outof-phase variation of right and left ventricular peak systolic pressure levels with respirations.68 Management Constriction may be transitory and can resolve either spontaneously or with medical management involving analgesics, corticosteroids and antibiotics. Hugo et al reported resolution of constriction without surgery in 60% of the pediatric patients with TB pericarditis.69 Pericardiectomy is the definite treatment for constrictive pericarditis but is unwarranted either in very early constriction or in severe advanced disease when the operative risk of surgery is very high. Complete or radical pericardial resection is desirable but subtotal pericardiectomy may be desirable in some instances. The risk of mortality with pericardiectomy is between 6 to 19%.70

Intrapericardial Tumors Primary malignant neoplasms of the pericardium are rare and include teratoma, mesothelioma, lymphoma and angiosarcoma. Metastatic disease is the most common neoplastic pericardial disease in adults. CT scan and MRI are diagnostic in evaluating intrapericardial lesions. Teratomas are the most common intrapericardial tumor in children. The majority of the teratomas are diagnosed antenatally or immediately after birth. About 50% have hydropic changes or cardiac tamponade in utero. A pericardial teratoma ultrasonically appears as a hyperechoic, well-circumscribed predominantly solid mass, with cystic components and foci of calcifications characteristically located in close proximity to the right atrium, with a fibrous stalk attachment to the root of the ascending aorta.71 A space-occupying lesion within the pericardium, with relatively little compression of the lung spaces, is suggestive of an intrapericardial teratoma. Despite a usually benign tumor, approximately 15% are classified as malignant based on neuroectodermal cell composition.72 The management is based upon the gestational age and presence of hydrops fetalis. If hydrops fetalis develops during pregnancy, antenatal pericardiocentesis is the treatment of choice.73 Postpartum early resection is indicated to prevent the development of neonatal cardiac failure and to prevent metastasis of a potentially malignant solid tumor.

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Key Messages •• ••

•• ••

••

••

••

Pericardium is a fibro-serous sac surrounding the heart, richly supplied by nerves and lymphatics. Pericardium prevents acute overdistension of the heart, acts as a barrier against spread of infection or malignancy from surrounding structures and reduces the friction resulting from cardiac motion. Congenital anomalies of the pericardium are rare and commonly associated with other midline defects. Acute pericarditis is most often idiopathic, presumed to be viral in etiology although in developing countries, tuberculosis still remains the commonest cause. Chest pain is present in about 80% of the patients and pericardial rub is pathognomic of pericarditis. ECG abnormalities are seen in about 90% of the patients with pericarditis. Purulent pericarditis most often presents in the very young patients, frequently associated with cardiac tamponade. Staphylococcus aureus is the most common organism causing purulent pericarditis. Mortality rate approach 2 to 20% inspite of treatment. Cardiac tamponade is a significant ventricular impairment in diastolic filling of the heart caused by accumulation of fluid in the pericardial space. Pulsus paradoxus is a diagnostic finding in patients with tamponade. Echocardiogram with Doppler studies is the investigation of choice. It is relieved by drainage of the fluid by needle or surgical pericardiocentesis. Constrictive pericarditis implies restriction of diastolic filling of the ventricle by thick non-compliant and adherent pericardium. In children, TB is probably the most common cause. Pericardial knock is pathognomic of constrictive pericarditis. Differentiation from restrictive cardiomyopathy can be challenging.

REFERENCES 1. Cardiovascular System. In: Williams P, (ed.) Gray’s Anatomy: The Anatomical Basis of Medicine and Surgery, 38th edn. New York: Churchill Livingstone. 1995;1451–1626. 2. Miller AJ. The study of the lymphatics of the heart: An overview. Microcirc Endothelium Lymphatics. 1985;2(4):349–60. 3. Holt JP. The normal pericardium. Am J Cardiol. 1970;26(5):455–65. 4. Gibson AT, Segal MB. A study of the composition of pericardial fluid, with special reference to the probable mechanism of fluid formation. J Physiol. 1978;277:367–77. 5. Ishihara T, Ferrans VJ, Jones M, Boyce SW, Kawanami O, Roberts WC. Histologic and ultrastructural features of normal human parietal pericardium. Am J Cardiol. 1980;46(5):744–53. 6. Freeman GL. The effects of the pericardium on function of normal and enlarged hearts. Cardiol Clin. 1990;8(4):579–86. 7. Nasser WK. Congenital absence of the left pericardium. Am J Cardiol. 1970;26(5):466–70. 8. Connolly HM, Click RL, Schattenberg TT, Seward JB, Tajik AJ. Congenital absence of the pericardium: Echocardiography as a diagnostic tool. J Am Soc Echocardiogr. 1995;8(1):87–92. 9. Jones JW, McManus BM. Fatal cardiac strangulation by congenital partial pericardial defect. Am Heart J. 1984;107(1):183–85. 10. Robin E, Ganguly SN, Fowler MS. Strangulation of the left atrial appendage through a congenital partial pericardial defect. Chest. 1975;67(3):354–55.

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11. Gatzoulis MA, Munk MD, Merchant N, Van Arsdell GS, McCrindle BW, Webb GD. Isolated congenital absence of the pericardium: Clinical presentation, diagnosis, and management. Ann Thorac Surg. 2000;69(4):1209–15. 12. Cantrell JR, Haller JA, Ravitch MM. A syndrome of congenital defects involving the abdominal wall, sternum, diaphragm, pericardium, and heart. Surg Gynecol Obstet. 1958;107(5):602–14. 13. Davies MR, Oksenberg T, Da Fonseca JM. Massive foetal pericardiomegaly causing pulmonary hypoplasia, associated with intra-pericardial herniation of the liver. Eur J Pediatr Surg. 1993;3(6): 343–47. 14. Bates JC, Leaver FY. Pericardial celomic cysts; presentation of five new cases and five similar cases illustrating difficulty of diagnosis. Radiology. 1951;57(3):330–38. 15. Feigin DS, Fenoglio JJ, McAllister HA, Madewell JE. Pericardial cysts: A radiologic-pathologic correlation and review. Radiology. 1977;125(1):15–20. 16. Permanyer-Miralda G, Sagrista-Sauleda J, Soler-Soler J. Primary acute pericardial disease: A prospective series of 231 consecutive patients. Am J Cardiol. 1985;56(10):623–30. 17. Zayas R, Anguita M, Torres F, et al. Incidence of specific etiology and role of methods for specific etiologic diagnosis of primary acute pericarditis. Am J Cardiol. 1995;75(5):378–82. 18. Reuter H, Burgess LJ, Doubell AF. Epidemiology of pericardial effusions at a large academic hospital in South Africa. Epidemiol Infect. 2005;133(3):393–99. 19. Fowler NO. Tuberculous pericarditis. Jama. 1991;266(1):99–103. 20. Cegielski JP, Ramiya K, Lallinger GJ, Mtulia IA, Mbaga IM. Pericardial disease and human immunodeficiency virus in Dar es Salaam, Tanzania. Lancet. 1990;335(8683):209–12. 21. Cakir O, Gurkan F, Balci AE, Eren N, Dikici B. Purulent pericarditis in childhood: Ten years of experience. J Pediatr Surg. 2002;37(10):1404–8. 22. Cheatham JE, Jr., Grantham RN, Peyton MD, et al. Haemophilus influenzae purulent pericarditis in children: Diagnostic and therapeutic considerations. J Thorac Cardiovasc Surg. 1980;79(6):933–36. 23. Feldman WE. Bacterial etiology and mortality of purulent pericarditis in pediatric patients: Review of 162 cases. Am J Dis Child. 1979;133(6):641–44. 24. Dupuis C, Gronnier P, Kachaner J, et al. Bacterial pericarditis in infancy and childhood. Am J Cardiol. 1994;74(8):807–9. 25. Klacsmann PG, Bulkley BH, Hutchins GM. The changed spectrum of purulent pericarditis: An 86 years autopsy experience in 200 patients. Am J Med. 1977;63(5):666–73. 26. Rubin RH, Moellering RC, Jr. Clinical, microbiologic and therapeutic aspects of purulent pericarditis. Am J Med. 1975;59(1):68–78. 27. Rostand SG, Rutsky EA. Pericarditis in end-stage renal disease. Cardiol Clin. 1990;8(4):701–7. 28. Miller RH, Horneffer PJ, Gardner TJ, Rykiel MF, Pearson TA. The epidemiology of the postpericardiotomy syndrome: A common complication of cardiac surgery. Am Heart J. 1988;116(5 Pt 1):1323–29. 29. Engle MA, Zabriskie JB, Senterfit LB, Gay WA, Jr., O’Loughlin JE, Jr., Ehlers KH. Viral illness and the postpericardiotomy syndrome: A prospective study in children. Circulation. 1980;62(6):1151–58. 30. Lessof MH. Postcardiotomy syndrome: Pathogenesis and management. Hosp Pract. 1976;11(9): 81–86. 31. Joenson JL. Postpericardiotomy syndrome in congenital heart deformities. Am Heart J. 1959;57(5): 643–53. 32. Drusin LM, Engle MA, Hagstrom JW, Schwartz MS. The postpericardiotomy syndrome: A six-year epidemiologic study. N Engl J Med. 1965;272:597–602. 33. Zeltser I, Rhodes LA, Tanel RE, et al. Postpericardiotomy syndrome after permanent pacemaker implantation in children and young adults. Ann Thorac Surg. 2004;78(5):1684–87. 34. Muensterer OJ, Schenk DS, Praun M, Boehm R, Till H. Postpericardiotomy syndrome after minimally invasive pectus excavatum repair unresponsive to nonsteroidal anti-inflammatory treatment. Eur J Pediatr Surg. 2003;13(3):206–8. 35. Rovang KS, Hee TT, Pagano TV, Mohiuddin S. Dressler’s syndrome complicating radiofrequency ablation of an accessory atrioventricular pathway. Pacing Clin Electrophysiol. 1993;16(2):251–53.

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36. Sasaki A, Kobayashi H, Okubo T, Namatame Y, Yamashina A. Repeated postpericardiotomy syndrome following a temporary transvenous pacemaker insertion, a permanent transvenous pacemaker insertion and surgical pericardiotomy. Jpn Circ. J 2001;65(4):343–4. 37. Segal F, Tabatznik B. Postpericardiotomy syndrome following penetrating stab wounds of the chest: Comparison with the postcommissurotomy syndrome. Am Heart J. 1960;59:175–83. 38. Cabalka AK, Rosenblatt HM, Towbin JA, et al. Postpericardiotomy syndrome in pediatric heart transplant recipients. Immunologic characteristics. Tex Heart Inst J. 1995;22(2):170–6. 39. Assanelli D, Lew WY, Shabetai R, LeWinter MM. Influence of the pericardium on right and left ventricular filling in the dog. J Appl Physiol. 1987;63(3):1025–32. 40. Spodick D. Pericardial diseases. In: Braunwald E, Zipes DP, Libby P, eds. Heart disease: A Textbook of Cardiovascular Medicine. 6th ed. Philadelphia: W.B.Saunders; 2001. 41. Spodick DH. Pericardial rub. Prospective, Multiple observer investigation of pericardial friction in 100 patients. Am J Cardiol. 1975;35(3):357–62. 42. Spodick DH. Electrocardiogram in acute pericarditis: Distributions of morphologic and axial changes by stages. Am J Cardiol. 1974;33(4):470–74. 43. Ginzton LE, Laks MM. The differential diagnosis of acute pericarditis from the normal variant: New electrocardiographic criteria. Circulation. 1982;65(5):1004–9. 44. Combs DL, O’Brien RJ, Geiter LJ. USPHS Tuberculosis Short-Course Chemotherapy Trial 21: Effectiveness, toxicity, and acceptability. The report of final results. Ann Intern Med. 1990;112(6):397–406. 45. Strang JI, Kakaza HH, Gibson DG, Girling DJ, Nunn AJ, Fox W. Controlled trial of prednisolone as adjuvant in treatment of tuberculous constrictive pericarditis in Transkei. Lancet. 1987;2(8573):1418–22. 46. Ntsekhe M, Wiysonge C, Volmink JA, Commerford PJ, Mayosi BM. Adjuvant corticosteroids for tuberculous pericarditis: Promising, but not proven. Qjm. 2003;96(8):593–99. 47. Altman CA. Pericarditis & pericardial diseases. In: Arthur Garson Jr TB, David J Fisher, Steven R Neish, (eds). The Science and Practice of Pediatric Cardiology. Baltimore: Williams and Wilkins; 1998:1795-1815. 48. Engle MA, Zabriskie JB, Senterfit LB, Ebert PA. Postpericardiotomy syndrome: A new look at an old condition. Mod Concepts Cardiovasc Dis. 1975;44(11):59–64. 49. Wilson NJ, Webber SA, Patterson MW, Sandor GG, Tipple M, LeBlanc J. Double-blind placebocontrolled trial of corticosteroids in children with postpericardiotomy syndrome. Pediatr Cardiol. 1994;15(2):62–65. 50. Zucker N, Levitas A, Zalzstein E. Methotrexate in recurrent postpericardiotomy syndrome. Cardiol Young. 2003;13(2):206–8. 51. King TE, Jr., Stelzner TJ, Sahn SA. Cardiac tamponade complicating the postpericardiotomy syndrome. Chest. 1983;83(3):500–3. 52. Reddy PS, Curtiss EI, O’Toole JD, Shaver JA. Cardiac tamponade: Hemodynamic observations in man. Circulation. 1978;58(2):265–72. 53. Cohen MV, Greenberg MA, Grose R, Yipintsoi T. Cardiac tamponade in dogs with normal coronary arteries. II. Myocardial flow and metabolism with moderate and severe hemodynamic impairment. Basic Res Cardiol. 1984;79(5):542–50. 54. Fowler NO. Pulsus paradoxus. Heart Dis Stroke. 1994;3(2):68–69. 55. Spodick DH. Acute cardiac tamponade. N Engl J Med. 2003;349(7):684–90. 56. Tamburro RF, Ring JC, Womback K. Detection of pulsus paradoxus associated with large pericardial effusions in pediatric patients by analysis of the pulse-oximetry waveform. Pediatrics. 2002;109(4):673–77. 57. Spodick DH, Usher BW. Electrical alternans. Am Heart J. 1972;84(4):574–75. 58. Niarchos AP. Electrical alternans in cardiac tamponade. Thorax. 1975;30(2):228–33. 59. Burstow DJ, Oh JK, Bailey KR, Seward JB, Tajik AJ. Cardiac tamponade: Characteristic Doppler observations. Mayo Clin Proc. 1989;64(3):312–24.

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Pediatric Cardiology

60. Appleton CP, Hatle LK, Popp RL. Cardiac tamponade and pericardial effusion: Respiratory variation in transvalvular flow velocities studied by Doppler echocardiography. J Am Coll Cardiol. 1988;11(5):1020–30. 61. Selig MB. Percutaneous transcatheter pericardial interventions: Aspiration, biopsy, and pericardioplasty. Am Heart J. 1993;125(1):269–71. 62. Thanopoulos BD, Georgakopoulos D, Tsaousis GS, Triposkiadis F, Paphitis CA. Percutaneous balloon pericardiotomy for the treatment of large, nonmalignant pericardial effusions in children: Immediate and medium-term results. Cathet Cardiovasc Diagn. 1997;40(1):97–100. 63. Palacios IF, Tuzcu EM, Ziskind AA, Younger J, Block PC. Percutaneous balloon pericardial window for patients with malignant pericardial effusion and tamponade. Cathet Cardiovasc Diagn. 1991;22(4):244–49. 64. Shabetai R, Fowler NO, Guntheroth WG. The hemodynamics of cardiac tamponade and constrictive pericarditis. Am J Cardiol. 1970;26(5):480–89. 65. Karlberg N, Jalanko H, Perheentupa J, Lipsanen-Nyman M. Mulibrey nanism: Clinical features and diagnostic criteria. J Med Genet. 2004;41(2):92–98. 66. Frank H, Globits S. Magnetic resonance imaging evaluation of myocardial and pericardial disease. J Magn Reson Imaging. 1999;10(5):617–26. 67. Breen JF. Imaging of the pericardium. J Thorac Imaging. 2001;16(1):47–54. 68. Hancock EW. Differential diagnosis of restrictive cardiomyopathy and constrictive pericarditis. Heart. 2001;86(3):343–49. 69. Hugo-Hamman CT, Scher H, De Moor MM. Tuberculous pericarditis in children: A review of 44 cases. Pediatr Infect Dis J. 1994;13(1):13–18. 70. Seifert FC, Miller DC, Oesterle SN, Oyer PE, Stinson EB, Shumway NE. Surgical treatment of constrictive pericarditis: Analysis of outcome and diagnostic error. Circulation. 1985;72(3 Pt 2): II264–73. 71. Arciniegas E, Hakimi M, Farooki ZQ, Green EW. Intrapericardial teratoma in infancy. J Thorac Cardiovasc Surg. 1980;79(2):306–11. 72. Weber HS, Kleinman CS, Hellenbrand WE, Kopf GS, Copel J. Development of a benign intrapericardial tumor between 20 and 40 weeks of gestation. Pediatr Cardiol. 1988;9(3):153–56. 73. Bruch SW, Adzick NS, Reiss R, Harrison MR. Prenatal therapy for pericardial teratomas. J Pediatr Surg. 1997;32(7):1113–15. 74. Sagrista-Sauleda J, Permanyer-Miralda G, Soler-Soler J. Tuberculous pericarditis: Ten year experience with a prospective protocol for diagnosis and treatment. J Am Coll Cardiol. 1988;11(4):724–28. 75. Brisson-Noel A, Gicquel B, Lecossier D, Levy-Frebault V, Nassif X, Hance AJ. Rapid diagnosis of tuberculosis by amplification of mycobacterial DNA in clinical samples. Lancet. 1989;2(8671): 1069–71. 76. Komsuoglu B, Goldeli O, Kulan K, Komsuoglu SS. The diagnostic and prognostic value of adenosine deaminase in tuberculous pericarditis. Eur Heart J. 1995;16(8):1126–30. 77. Aggeli C, Pitsavos C, Brili S, et al. Relevance of adenosine deaminase and lysozyme measurements in the diagnosis of tuberculous pericarditis. Cardiology. 2000;94(2):81–85. 78. Burgess LJ, Reuter H, Carstens ME, Taljaard JJ, Doubell AF. The use of adenosine deaminase and interferon-gamma as diagnostic tools for tuberculous pericarditis. Chest. 2002;122(3):900–5.

21

Infective Endocarditis in Children

Anita Saxena

INTRODUCTION Infective endocarditis (IE) is defined as an “endovascular microbial infection of cardiovascular structures”.1 Despite advances in diagnosis and management since its first description by William Osler, IE is associated with considerable morbidity and mortality. The mortality ranges from 16 to 25%2-4 and about 20% of patients require emergency surgery.5 Congenital heart disease (CHD) is the most common underlying condition in pediatric population presenting with IE although rheumatic heart disease is not uncommon in India. Rarely IE can occur without underlying heart disease, however, in one series 35.4% of children with IE had no underlying heart disease. 6 Echocardiography plays a very important role in the diagnosis of IE, particularly in cases where blood cultures are negative. This article reviews the epidemiology, clinical features, diagnostic work-up and management strategies in children presenting with features suggestive of IE.

Epidemiology The epidemiology of IE is changing. IE is less common in children than in adults and accounts for 0.8 to 3.3 cases for each 1000 admissions to hospital.7 The frequency of IE among children may be increasing in recent years. This increase may be because of improved survival among children with CHD following cardiac surgery, increasing use of prosthetic tubes, valves at surgery and increased use of indwelling vascular catheters in newborns and infants admitted to intensive care units. Since the incidence of RF has decreased considerably in western world, rheumatic heart disease (RHD) is very rarely the underlying cardiac condition. In developing countries such as India, RHD still forms a significant proportion of cases with IE. In about 10% of cases, IE develops without a previously identifiable heart disease or other risk factors. In general cardiac lesions associated with steep pressure gradients pose a particularly high risk for IE. Jets of blood spurting through a ventricular septal defect, patent ductus arteriosus or left-sided valvular regurgitation are prone for IE. Tetralogy of Fallot and bicuspid aortic valve are other CHD that may be predisposed to endocarditis. In a study by Morris et al,8 highest risk for IE was found in children who had repair or palliation of cyanotic CHD. Lesions such as

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secundum atrial septal defect, where shunting is not associated with high velocity jet are very low risk for IE.

Infective Endocarditis in Neonates Increasing sophistication of resuscitative and supportive techniques including invasive vascular catheters, for the critically ill neonates is creating another growing population that is at high risk for IE.9 In these cases, diagnosis may be particularly difficult and the endocarditis often involves right sided structures of the heart. IE in newborns is associated with a very high mortality rate.

Diagnosis of Infective Endocarditis Clinical diagnosis of IE may be challenging because of the presence of nonspecific clinical features. However, IE should be considered in any child who has unexplained fever and is known to have heart disease. The initial criteria for the diagnosis of IE were given by von Reyn and colleagues.10 These were primarily based on clinical and pathological findings including demonstration of the infection by histopathology or positive blood cultures. Since these criteria were described before the introduction of two dimensional and Doppler echocardiography, von Reyn’s classification does not consider characteristic echocardiographic findings and has a limited role today. The Duke criteria which were proposed by Durack et al in 199411 included echocardiographic findings as major criteria. These criteria have been further modified12 and have been tested in adults and recently in children.13,14 The Duke criteria are outlined in Tables 21.1 and 21.2. Table 21.1: Modified Duke criteria for the diagnosis of infective endocarditis10 Major Criteria 1. Positive blood culture for IE A. Typical microorganism consistent with IE from 2 separate blood cultures as noted below: i. Viridans streptococci, Streptococcus bovis, or HACEK group or ii. Community-acquired Staphylococcus aureus or enterococci, in the absence of a primary focus or B. Microorganisms consistent with IE from persistently positive blood cultures defined as i. > 2 positive cultures of blood samples drawn > 12 h apart or ii. All of 3 or a majority of > 4 separate cultures of blood (with first and last sample drawn > 1 h apart) 2. Evidence of endocardial involvement A. Positive echocardiogram for IE defined as i. Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation, or ii. Abscess, or iii. New partial dehiscence of prosthetic valve or B. New valvular regurgitation (worsening or changing of pre-existing murmur not sufficient) Minor Criteria 1. Predisposition: Predisposing heart condition or IV drug use 2. Fever: Temperature > 38.00C 3. Vascular phenomena: Major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions 4. Immunologic phenomena: Glomerulonephritis, Osler nodes, Roth’s spots, and rheumatoid factor 5. Microbiological evidence: Positive blood culture but does not meet a major criteria as noted above or serological evidence of active infection with organism consistent with IE 6. Echocardiographic findings: Consistent with IE but do not meet a major criterion as noted above

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Infective Endocarditis in Children Table 21.2: Diagnosis of infective endocarditis using the modified Duke criteria Definite Infective Endocarditis • Pathologic evidence of intracardiac or embolized vegetation or intracardiac abscess or • Clinical criteria: Two major, or one major and three minor, or five minor criteria Possible Infective Endocarditis • One major and one minor or three minor criteria Rejected • Firm alternate diagnosis • “IE syndrome” resolved within 4 days of antibiotic therapy • No pathologic evidence of IE at surgery or autopsy within 4 days of antibiotic therapy • Case does not meet “possible IE” criteria

A rapid diagnosis is of critical importance for survival of the affected child. Despite the above mentioned criteria, IE remains a clinical diagnosis. One should not use echocardiography for “exclusion of IE”, if the clinical probability of IE is low.

Clinical Findings

Table 21.3: Presenting signs in 73 children who had 76 Episodes of Infective Endocarditis14

Sign

Number (%)



Fever Petechiae Changing murmur Dental caries Hepatosplenomegaly Congestive heart failure Splenomegaly Splinter hemorrhages Retinal hemorrhages (Roth spots) Osler nodes Arthritis

75 (99) 16 (21) 16 (21) 11 (14) 11 (14) 7 (9) 5 (7) 4 (5) 4 (5) 3 (4) 2 (3)

The clinical presentation is generally subacute with prolonged fever, myalgia, arthralgia, weight loss, anorexia, headache and generalized malaise. The classical signs like Roth spots, Janeway lesions and Osler’s nodes are very rare in children. Almost all patients will have cardiac murmurs, which may change in a small number of cases. The estimated frequency of presenting signs is given in Table 21.3.15 In the series by Liew et al,16 splenomegaly, septic emboli to skin (petechiae or purpuric rashes), microscopic hematuria and a high CRP value of >100 mg/L were important clues to the diagnosis of IE. Sometimes, the presentation may be more acute, the presenting symptom being secondary to embolization of vegetation to one of the cranial or visceral arteries. Patients with right-sided endocarditis may not have specific cardiac signs, instead they may present with primary lung symptoms and signs.

Laboratory Parameters Pathogens Gram-positive cocci are the most likely pathogens, although Gram-negative rods and fungi can also cause IE. Gram-positive cocci have a predilection for subendocardial connective tissue, especially fibronectin, that gets exposed when endocardium is damaged. Common organisms causing IE are Streptococcus viridans and Staphylococcus aureus. Enterococcal endocarditis is less frequent in children compared to adults (Table 21.4). Streptococcus viridans is most common followed by Staphylococcus aureus in children beyond one year of age. However, Staphylococcus is commoner in patients where IE occurs secondary to

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Pediatric Cardiology Table 21.4: Principal etiologic bacterial agents for infective endocarditis

Johnson Martin Stockheim Sharma et al.18 et al.14 et al.12 et al.16 Viridans group streptococci 43 38 32 14 Staphylococcus aureus 33 32 27 4.5 Coagulase-negative 2 4 12 4.5 staphylococci Streptococcus pneumoniae 3 4 7 Not available Fungal Organisms Not available Not Not 9 available available Culture-negative 6% 7 5 63

indwelling vascular catheter (neonates) or prosthetic material. Fungal endocarditis secondary to Candida is also common in this setting. Fungal endocarditis is associated with large, rapidly increasing, friable vegetations with frequent episodes of embolization (Fig. 21.1). In the series by Martin et al,15 S. viridans was the causative agent in 38%, S. aureus in 36%. No organism could be isolated in 7% of cases. However, most series from India have a much lower rate of positive blood cultures17,18 with S. viridans and S. aureus being almost equally responsible causative agents.

Dhawan et al.17 27 18 Not available Not available 3 57

Figure 21.1: Echocardiography in apical four chamber view showing a large fungal vegetation (arrows) on tricuspid valve. LA, Left atrium; LV, Left ventricle; RA, Right atrium; RV, Right ventricle

Blood Cultures As bacteremia in IE is usually continuous, it is not necessary to obtain the cultures during fever only. Usually, three blood cultures are drawn taking the strict aseptic precautions, 2 to 3 mL of blood may be sufficient for each culture. If there is no growth by second day, two more blood cultures may be drawn in case antibiotics have not been started. Unless otherwise suspected, blood cultures are usually performed for aerobic organisms.

Culture-Negative IE Blood cultures may be persistently negative in 5%–7% of cases according to data from USA,13,15,19 however, the percentage is much higher in series reported from India.16,17,20 Potential reasons for culture negativity are: 1. Patient received antibiotics before blood cultures were obtained. This is the most common reason in our setting, as injudicious use of antibiotics is very frequent whenever a child presents with fever. 2. The causative pathogen is difficult to culture, e.g. Fungi, anaerobic organisms. These are much less frequent causes of IE, but often seen in patients with prosthetic material. 3. The volume of blood drawn for culture was insufficient, especially when dealing with newborns and small infants. 4. The lungs may filter bacteria originating from right sided cardiac chambers.

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The diagnosis of culture negative IE depends on a high degree of clinical suspicion and indirect evidence as may be obtained on echocardiography.

Echocardiography Since the first description of valvar vegetation by Dillon and colleagues,21 echocardiography has played a key role in the diagnosis of IE. Echocardiography not only demonstrates the vegetation (Fig. 21.2), but it also provides very important information on Figure 21.2: Echocardiography in the presence and severity of valvular destruction, parasternal long axis view showing vegedegree of valvular regurgitation and presence of tation on aortic valve (arrow). AO, Aorta; LA, Left atrium; LV, Left ventricle complications such as paravalvular leak, myocardial abscess, etc. Because of its immense usefulness, it has been included as a major criterion for IE diagnosis.11 The echocardiographic findings that are considered to be major criteria are: 1. Presence of vegetation, defined as mobile, echodense masses implanted on a valve or mural endocardium in the trajectory of a regurgitant jet or implanted in prosthetic material with no alternative anatomic explanation; 2. Presence of abscesses; or 3. Presence of a new dehiscence of a valvar prosthesis. Other abnormal echocardiographic findings not fulfilling these definitions were considered as minor criteria. The diagnostic yield of echocardiography is influenced by the image quality, size of vegetation (vegetation < 2–3 mm may not be well seen by transthoracic echocardiography), location of vegetation (e.g. vegetation on a prosthetic valve are difficult to visualize) and experience of the echocardiographer. Transthoracic echocardiography (TTE) is more sensitive in children than in adults because of better acoustic windows. The sensitivity of TTE is 85% in children14 and 68% in adults.22 In another study TTE was 97% sensitive in pediatric-sized subjects < 60 kg) but only 70% in adultsized subjects (> 60 kg).23 The specificity is close to 95% in both adults and children. TTE is more likely to identify vegetations in those with simple CHD than in those with complex CHD. Indications for transesophageal echocardiography (TEE) are limited in pediatric population, although it has clear superiority to TTE in adults. TEE is indicated in children under the following conditions: 1. Obese or very muscular patients with poor acoustic window. 2. Patients with prosthetic valves, grafts or conduits. 3. Patients with compromised respiratory function or pulmonary hyperinflation. 4. Patients with aortic valve endocarditis and suspicion of aortic root abscess on TTE. 5. Patients suspected of paravalvular damage and valve dehiscence because of prosthetic valve infection. 6. Patients with a negative TTE but a high clinical suspicion of IE. 7. When suspecting myocardial abscess, fistula or perforations.

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TEE is less valuable for the detection of right-sided vegetations that are not uncommon in children. Limitations of echocardiography must be noted. Absence of vegetation on echocardiography does not rule out IE and conversely presence of an echogenic mass is not necessarily vegetation. Echocardiography may be unable to differentiate active vegetation from an old sterile vegetation.

Management The principles of management are: 1. Antimicrobial drugs 2. Watch for any complications while on therapy 3. Surgical treatment in some cases.

Antimicrobial Drugs If the patient is acutely ill, antibiotics should be started empirically after blood cultures are taken. However, if the patient is relatively stable, one should wait for 48 hours for the report of blood cultures. If cultures are sterile, additional cultures can be done.

Choice of the Antibiotic Antibiotics should be chosen according to the organism grown. When awaiting for results of the culture, antibiotic treatment may be directed at the most common organisms, i.e. streptococci and staphylococci. A standard regimen is penicillin (or vancomycin, if sensitive to penicillin) plus gentamicin. If an organism can be isolated from the blood, its susceptibility should be determined in the lab. Bacteriacidal, rather than bacteriostatic antibiotics should be chosen and therapy must be given intravenously to attain persistently high bacteriacidal concentrations. This will facilitate entry of antibiotic in relatively avascular valve leaflets and in infected thrombi. A prolonged course of therapy is necessary; the usual course is 4 to 6 weeks. Infection of prosthetic valves and tissue may require longer treatment. Although clinical response is generally sufficient to determine the effect of therapy, one should follow these cases with repeat blood cultures and erythrocyte sedimentation rate to assess the adequacy of treatment. American Heart Association has listed the recommendations for antibiotic treatment in adults with IE according to the organism isolated.24 Similar guidelines can be followed for children with IE after dosages are adjusted according to the weight of the child. Newer antibiotics such as linezolid, teicoplanin can also be used in resistant cases. There are some reports of successful use of recombinant tissue plasminogen activator to lyse intracardiac vegetations in severely ill infants.

Fungal Endocarditis Medical therapy with antifungal agents is often not successful in these cases and surgery has to be combined with these drugs. Intravenous amphotericin B is the first line antifungal drug and

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must be given. It is quite nephrotoxic and hence renal parameters must be monitored closely. The therapy is generally given for 6–8 weeks and followed with oral antifungal agents such as fluconazole as long-term suppressive therapy. The total duration of treatment for eradication of fungus is not clear, but could be one year or more. 5-fluorocytosin is another fungicidal drug that may be combined with amphotericin B in cases with fungal endocarditis. However, the superiority of two drug combination over amphotericin B alone has not been proven.

Surgery Indications for surgery during the acute phase of IE are: 1. Continued bacteremia after two weeks of appropriate antibiotic therapy. 2. Worsening heart failure because of valvular regurgitation. 3. Embolic events; systemic, pulmonary, coronary, cerebral. 4. Myocardial or periannular abscess. 5. Fungal endocarditis. 6. Prosthetic valve dysfunction such as valve dehiscence. The goals of surgery are to eradicate the focus of infection, to repair cardiac defects and to prevent development of complications. Echocardiography may be useful to determine the need for surgery as some of the features on echocardiography may indicate higher likelihood of complications such as embolization. Clinical setting where risk of compilations is high are described by Bayer et al and are listed in Table 21.5.25 About one fifth of patients require surgery in acute phase. Surgery should not be deferred because a full course of antibiotics has not been completed. In one study mitral and tricuspid valve repairs were performed during IE with no mortality in 7 children having active IE. 26 Late surgery may be indicated in some patients after the IE has been controlled, e.g. in a patient with small ventricular septal defect with a previous episode of IE.

Complications of IE Complications are more likely to occur in children under two years of age, those with cyanotic CHD and in those with prosthetic heart valves. In addition, fungal and staphylococcal IE are also high-risk for complications. Left-sided endocarditis15 and duration of symptoms > 3 months are also more prone to complications. The list of complications is given in Table 21.6. Congestive heart failure can occur secondary to ruptured leaflets or chordae. Development of a new onset Table 21.6: Complications of infective endocarditis

Table 21.5: Clinical situations considered high-risk for complications of IE 22 • • • • • • • • •

Prosthetic cardiac valves Left-sided IE Staphylococcus aureus IE Fungal IE Previous IE Prolonged clinical symptoms (> 3 months) Cyanotic congenital heart disease Patients with systemic-to-pulmonary shunts Poor clinical response to antimicrobial therapy

• • • • •

Congestive heart failure Embolic events, e.g. cerebral, pulmonary, renal, coronary Persistent bacteremia or fungemia Periannular extension of abscess Prosthetic device dysfunction including valvar dehiscence • Arrhythmia or development of new heart block • Metastatic infection, mycotic aneurysms • Glomerulonephritis/renal failure

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heart block may suggest perivalvular extension of infection and is, therefore, a serious finding. Large (> 10 mm), mobile vegetations are more likely to embolize.27 It is important to note that emboli events can occur even up to 2 to 4 weeks after starting antibiotic therapy.

Prophylaxis Antibiotic prophylaxis was being routinely practiced for many decades to prevent IE. Various guidelines have only varied in the dose, route and indications. IE prophylaxis became acceptable practice without strong evidence. It is increasingly realized that bacteremia arising from daily activities is far more frequent than dental procedures and are more likely to result in IE. Further, an extremely small number of cases of IE might be prevented by antibiotic prophylaxis, even if prophylaxis is 100% effective. The effectiveness of IE prophylaxis regimens is not proven. To date, there are a few animal studies and 6 case control studies are available to assess the usefulness of IE prophylaxis. There is no randomized controlled study available. Raising costs and antibiotic resistance are the other major concerns. In view of the above concerns American Heart Association has recently modified the guidelines for IE prophylaxis.28 The focus has shifted from antibiotic prophylaxis to dental hygiene. There is a significant reduction in the numbers and types of cardiac conditions for which antibiotic prophylaxis is recommended. Only those conditions with the most serious adverse outcomes of IE are advised antibiotic prophylaxis (Table 21.7). There is a significant increase in the types of dental procedures recommended for prophylaxis in at-risk individuals (almost all dental procedures; Table 21.8). Further, there is a minor modification in the Table 21.7: Conditions in which antibiotic prophylaxis is recommended • Prosthetic cardiac valve • Previous infective endocarditis • Selected congenital heart diseases (CHD) – Unrepaired cyanotic CHD, including those with palliative shunts and conduits – Completely repaired CHD with prosthetic material or device either by surgery or catheter intervention during first 6 months after procedure (to allow time for endothelial covering of the material) – Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device that inhibits endothelialization – Except for the conditions listed above, antibiotic prophylaxis is no longer recommended for any other form of CHD • Cardiac transplantation recipients who develop cardiac valvulopathy

Table 21.8: Dental Procedures for which antibiotic prophylaxis is recommended • All dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa • Except the following: – Routine anesthetic injections through noninfected tissue – Taking dental radiographs – Placement of removable prosthodontic or orthodontic appliances – Adjustment of orthodontic appliances – Shedding of deciduous teeth and bleeding from trauma to the lips or oral mucosa

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timing of antibiotic administration (30–60 minutes prior). Antibiotic prophylaxis is also not indicated for procedures involving the upper and lower gastrointestinal tract, genitourinary tract (including urological, gynecological and obstetric procedures, and childbirth), and upper and lower respiratory tract (except incision of mucosa). The regimen of antibiotic prophylaxis recommended is shown in Table 21.9. The applicability of the present guidelines in India is not clear. Since the focus of prophylaxis is based on conditions with poor outcome of IE, all left-sided IE have relatively poor prognosis in India because of delayed diagnosis, improper management, and late/no surgery. In such a scenario, it may be advisable to continue prophylaxis for left-sided lesions. Further, use of antibiotics is a routine practice among dental practitioners in India. Then, if anyway one is using antibiotics, it may be advisable to use in adequate doses for preventing IE also. These new guidelines lay a great emphasis on maintaining good orodental hygiene as poor dental hygiene is responsible for a large proportion of IE cases. Hence, these children must be encouraged to ensure good orodental health and this must be addressed to the patient/parent during each follow-up visit. A recent article has studied the impact of these new changed guidelines on trends in hospitalizations secondary to IE across 37 US children’s hospitals.29 Interestingly, the study found no evidence that release of new antibiotic prophylaxis guidelines was associated with a significant change in IE admissions.

CONCLUSION Infective endocarditis continues to be responsible for considerable morbidity and mortality specially in developing world. The Duke criteria help guide the diagnosis, but a high degree of suspicion in persistently febrile patients is necessary. Echocardiography plays a very important role in diagnosis and prognostication of these cases, especially in culture negative IE. IE can sometimes develop in spite of antibiotic prophylaxis in children with underlying cardiac defects. A more aggressive therapeutic strategy that includes early surgery appears to reduce mortality in these children. There must be close collaboration between the cardiologist, cardiac surgeon and the microbiologist. Table 21.9: Regimen of antibiotic prophylaxis recommended Situation

Agent

Oral

Amoxicillin

Unable to take oral medication

Ampicillin or cefazolin or ceftriaxone Allergic to penicillin Cephalexin or or ampicillin (Oral) Clindamycin or Azithromycin or Clarithromycin Allergic to penicillins or ampicillin Cefazolin or ceftriaxone and unable to take oral medication Clindamycin phosphate

Regimen-single dose 30–60 minutes before procedure Adults Children 2 gm 50 mg/kg 2 gm IM or IV 50 mg/kg IM or IV 1 gm IM or IV 2 gm 50 mg/kg 600 mg 20 mg/kg 500 mg 15 mg/kg 500 mg 15 mg/kg 1 gm IM or IV 50 mg/kg IM or IV 600 mg IM or IV 20 mg/kg IM or IV

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REFERENCES 1. The Task Force on Infective Endocarditis of the European Society of Cardiology: Guidelines on Prevention, Diagnosis and Treatment of Infective Endocarditis. Eur Heart J. 2004;25:267–76. 2. Mylonakis E, Calderwood SB. Infective endocarditis in adults. N Engl J Med. 2001;345:1318–30. 3. Hoen B, Alla F, Selton-Suty C, Béguinot I Bouvet A, Briançon S, Casalta JP, et al. Changing profile of infective endocarditis: Results of a 1-year survey in France. JAMA. 2002;2:75–81. 4. Netzer R, Zollinger E, Seiler C, Cerny A. Infective endocarditis: Clinical spectrum, presentation and outcome: An analysis of 212 cases 1980–1995. Heart. 2000;84:25–30. 5. Castillo JC, Anquita MP, Ramirez A, et al. Long term outcome of infective endocarditis in patients who were not drug addicts: A 10 year study. Heart. 2000;83:523–30. 6. Lin YT, Hsieh KS, Chen YS, Huang IF, Cheng MF. Infective endocarditis in children without underlying heart disease. J Microbiol Immunol Infect. 2012 Jun 22. [Epub ahead of print] 7. Humpl T, McCrindle BW, Smallhoon JF. The relative roles of transthoracic compared with transesophageal echocardiography in children with suspected infective endocarditis. J Am Coll Cardiol. 2003;4:2068–71. 8. Morris CD, Reller MD, Menasch VD. Thirty-year incidence of infective endoarditis after surgery for congenital heart defect. JAMA. 1998;279:599–603. 9. Millard DD Shulman ST. The changing spectrum of neonatal endocarditis. Clin Perinatol. 1988;15:587–608. 10. Von Reyn CF, Levy BS, Arbeit RD, Arbeit RD, Friedland G, Crumpacker CS. Infective endocarditis: an analysis based on strict case definitions. Ann Intern Med. 1981;94:505–18. 11. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: Utilization of specific echocardiographic findings. Am J Med. 1994;96:200–9. 12. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:633–8. 13. Stockheim JA, Chadwick EG, Kessler S, et al. Aretha Duke criteria superior to Beth Israel criteria for diagnosis of infective endocarditis in children? Clin Infect Dis. 1998;27:1451–6. 14. Tissieres P, Gervax A, Beghetti M, Jaeggi ET. Value and limitations of von Reyn, Duke, and modified Duke criteria for the diagnosis of infective endocarditis in children. Pediatrics. 2003;112:e467–71. 15. Martin JM, Neches WH, Wald ER. Infective endocarditis: 35 years of experience at a children’s hospital. Clin Infect Dis. 1997;24:669–75. 16. Liew WK, Tan TH, Wong KY. Infective endocarditis in childhood: A seven-year experience. Singapore Med J. 2004;45:525–9. 17. Sharma M, Saxena A, Kothari SS, Reddy SCB, Venugopal P, Wasir HS. Infectious endocarditis in children: Changing pattern in a developing country. Cardiolo Young. 1997;7:201–6. 18. Dhawan A, Grover A, Marwaha RK, Khattri HN, Anand ID, Kumar L, et al. Infective endocarditis in children: Profile in a developing country. Ann Trop Paediatr. 1993;13:189–94. 19. Johnson DH, Rosenthal A, Nadas AS. A forty-year review of bacterial endocarditis in infancy and childhood. Circulation. 1975;51:581–8. 20. Math RS, Sharma G, Kothari SS, Kalaivani M, Saxena A, Kumar AS. Prospective study of infective endocarditis from a developing country. Am Heart J. 2011;162:633–8. 21. Dillon JC, Feigenbaum H, Konecke LL, et al. Echocardiagraphic manifestations of valvular vegetations. Am Heart J. 1973;6:698–704. 22. Coechi E. Infective endocarditis: Transesophageal echocardiography in all or in selected cases? When is echocardiography highly predictive for complications. Ital Heart J. 2004;5:656–62. 23. Penk JS, Webb CL, Shulman ST, Anderson EJ. Echocardiography in pediatric infective endocarditis. Pediatr Infect Dis J. 2011;30:1109–11. 24. Wilson W, Karchmer AW, Dajani AS, et al. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. JAMA. 1995;274:1706–13.

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25. Bayer A, Bolger A, Taubert K, et al. Diagnosis and management of infective endocarditis and its complications. Circulation. 1998;98:2936–48. 26. Karaci AR, Aydemir NA, Harmandar B, Sasmazel A, Saritas T, Tuncel Z, et al. Surgical treatment of infective valve endocarditis in children with congenital heart disease. J Card Surg. 2012;27:93–8. 27. Saxena A, Aggarwal N, Gupta P, Juneja R, Kothari SS, Math R. Predictors of embolic events in pediatric infective endocarditis. Indian Heart J. 2011;63:237–40. 28. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, et al. Prevention of infective endocarditis: Guidelines from American Heart Association. Circulation. 2007;116:1736–54. 29. Pasquali SK, He X, Mohamad Z, McCrindle BW, Newburger JW, Li JS, et al. Trends in endocarditis hospitalizations at US children’s hospitals: Impact of the 2007 American Heart Association Antibiotic Prophylaxis Guidelines. Am Heart J. 2012;163:894–9.

22

Kawasaki Disease: Diagnosis and Management

M Zulfikar Ahamed

Kawasaki disease (KD) is the one that ‘licks’ the skin (and mucous membranes) and ‘bites’ the coronaries. The first child with this entity was a four-year-old boy, way back in 1961 who was examined by Tomasaku Kawasaki. Child had fever, lymph node enlargement, skin changes and mucous membrane involvement. He was treated with penicillin and steroids empirically and he recovered. Later similar cases emerged and Kawasaki disease was first reported in 1967 by Kawasaki comprising of fifty cases. He called it “a febrile occulo oro-cutaneo-acrodesquamatous syndrome with or without acute nonsuppurative cervical lymphadenitis”. Over the past 4 decades, this disease has been recognized and treated worldwide, but its etiology still remains an enigma. This is a disease that evolves sequentially, may have multiple physicians involved in assessment, can have atypical lesions and lacks specific lab test.

HISTORIAL PERSPECTIVE: A BRIEF HISTORY OF KAWASAKI DISEASE 1961 — Kawasaki encounters one 1967 — First description by Kawasaki 1974 — First English language article by Kawasaki 1980’s —Diagnostic criteria Diagnostic echocardiography IVIG therapy 1990’s — Single dose IVIG treatment 2000’s — Steroids? Newer agents? Etiology?

EPIDEMIOLOGY Kawasaki disease is perhaps most common in Japan, where it is prevalent in 100/100,000 children below 5 years where the disease is notifiable. In USA, the incidence may be 10–15/100,000 and is the most common cause of acquired heart disease in children and in UK the prevalence is around 10/100,000. The incidence in these countries seems to be plateauing.

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In India, the incidence is not known. KD was first reported in India in 1977 by Taneja. The incidence seems to be increasing. The slow emergence of KD may be because of under reporting, misdiagnosis, geographical localization of the disease, nonspecific tests late detection and lack of awareness. The disease now predominantly occurs in certain geographical areas—Kerala, Chandigarh, and Kolkata, etc. Most of the information is based on hospital data. In north India, KD seems to be occurring in older children, has a bimodal seasonal variation and the coronary lesions are less. In India, the approximate prevalence may be 5–10/100,000. KD may be the second commonest cause for acquired heart illness in children in India, after rheumatic fever. The pattern of both RF and KD in our institution over the years ii as follows (Figs 22.1 to 22.3).1,2

Figure 22.1: Kawasaki disease—Time sequence of principal findings

Figure 22.2: Kawasaki disease versus rheumatic fever—SATH

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Figure 22.3: Kawasaki disease versus rheumatic fever—SATH Table 22.1: Comparison of clinical profile EPIDEMIOLOGICAL PROFILE KD UK

USA

Kerala

India

Prevalence

5–10

10–20

5–10

?

Rank in Acq. HD

1

1

2

?

Below 5 years

75%

80%

70%

80%

M. F ratio

1.51

1.5.1

1.5.1

2>1

Peak Age

6–12 Months

18–24 Months

18–30 Months

18–24 Months

Seasonality

0

+

0

?

Boys seem to be more affected than girls (1.5:1). Twins have a higher chance of developing KD (13%). However, the risk for sibling and offspring is negligible. KD is extremely rare in newborn and in adult. Comparative profile of KD in various regions differ (Table 22.1).4

ETIOPATHOGENESIS It is still an enigma. Infectious agents are implicated as there is a clustering of KD, presence of fever as a dominant symptom, some seasonal variation, and involvement of the young age group. KD is uncommon below 6 months when maternally transmitted immunity is present and uncommon beyond 5 years, when infections are less in children. Seasonal variations vary area to area (Fig. 22.4).3 The implicated pathogens are: Bacteria : Staphylococcus Streptococcus Yesinia

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Figure 22.4: Seasonal variation of KD Flow chart 22.1: Pathogenetic model of KD

Virus : Adenovirus Human parvovirus Herpes virus Bacterial super antigens: Are also implicated—staphylococcal in infants and streptococcal in toddlers. There is a role for host susceptibility also as is evidenced by the increasing incidence in Japanese, Asians, and Indians and increased incidence in twins. The possible pathogenetic model is (Flow chart 22.1):5 Unknown infectious agent(s) Genetic susceptible host ← Virus (helper) Immune vasculitis Kawasaki disease Kawasaki disease is a disease of infants and young children predominantly below 5 years. 80% KD occurs below 5 years; more than half (60%), occur before 2 years and peak age is around 1 year. It is more common in boys than girls (1.5:1) and is more commonly expressed in Japanese and Asian children. This disease is particularly common in Kerala, where it is

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probably the second commonest cause of acquired cardiac illness, after rheumatic fever (RF). It occurs throughout the year with occasional seasonal clustering and is not likely to be communicable. The youngest age of KD worldwide is 2 weeks old baby and oldest is in the thirties. However, KD is particularly uncommon beyond 8 years. Etiologically, possible agents postulated include bacteria, viruses, dust mite and certain noninfectious agents such as carpet shampoo, insecticide and mercury. Cardiac pathology in KD passes through four stages—I to IV. They are stages of microvascular angiitis (0 to 10 days), panvasculitis with aneurism development (12 to 25 days), granulation of coronaries (28 to 31 days) and of scarring (40 days to 4 years). The diagnosis of KD is still essentially clinical, supported by laboratory findings and echocardiography. We follow the Japanese Kawasaki Disease Research Committee (JKDRC) fourth revision diagnostic guidelines to diagnose KD. There is also an AHA criteria.

Principal Symptoms 1. Fever 2. Changes in extremities a. Acute—red palm/sole with indurative edema. b. Subacute—desquamation of fingers, toes, sole and palm. 3. Polymorphous exanthem. 4. Bilateral nonpurulent conjunctival congestion. 5. Changes in the lips and oral cavity. 6. Acute nonsuppurative cervical lymphadenopathy.6 If five principal features are present or if four are present with echocardiographic coronary artery lesions (CAL) demonstrated the diagnosis of KD is made (Fig. 22.5).

Figure 22.5: Clinical picture of KD

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Other significant findings include: 1. Cardiovascular : Gallop, murmur, soft Sl, ECG abnormalities, cardiomegaly, myocardial infarction, pericarditis. 2. Gastrointestinal : Vomiting, diarrhea, colic, hydrops of gallbladder. paralytic ileus, mild hepatitis. 3. Hematological : Polymorphonuclear leukocytosis, thrombocytosis, elevated ESR, CRP, hypoalbuminemia, anemia. 4. Urinary : Proteinuria, pyruia, nephrotic syndrome. 5. Respiratory : Pulmonary nodule, cough, pneumonia. 6. Joints : Arthralgia, polyarthritis. 7. Neurological : Aseptic meningitis, seizures. Fever is usually high, usually the chief symptom, abrupt in onset and can spike. It may last for 10 to 14 days. It is not associated with coryza. Conjunctival congestion is nonpurulent, with perilimbal sparing and occurs within 1 to 3 days, oral mucosal changes occur within 2 days causing changes in lips, oral mucosa and a ‘strawberry’ tongue. These changes last for 10 days. There is characteristic redness of mouth and lips, dryness and fissuring and peeling. Extremity changes include palmar and plantar erythema with induration which starts on the 3rd to 5th day with desquamation occurring by 2nd and 3rd week. The indurative edema is on dorsum of hand and feet. Periungual peeling occurs later over toes and fingers. Polymorphous exanthematous rashes occur predominantly on trunk within 3 to 4 days and lasts for 1 week. Lymph node enlargement occurs in 75% and appears within 3 days of illness (Fig. 22.1). Other less common abnormalities include induration at BCG site, anterior uveitis, Reynaud’s phenomenon and sterile pyuria. Cardiac abnormalities are less obvious clinically ( 30,000) is perhaps a risk factor/marker for coronary artery lesions (CAL). A raised ESR is almost always present as is elevated CRP. An ESR beyond 100 mm/1 h or persistently high ESR or CRP could be indicators of development of CAL. Thrombocytosis (platelet count > 500,000) occurs in 60%. This occurs in the second week and may persist for 4 to 6 weeks.

Biochemistry Liver function tests may abnormal in 20%. Raised transaminases can be common without jaundice. Serum albumin is decreased and α€2 globulin level is increased. Hepatitis can occasionally be due to aspirin.

Chest X-ray Chest X-ray can show mild cardiomegaly and incidence can be as high as 10 to 20%.

ECG ECG abnormalities include sinus tachycardia, prolonged PR interval, low voltage QRS, ST-T changes and QTC prolongation. Other less common manifestations include 11° or 111° AV block, ectopics and acute myocardial infarction pattern. Tachy arrhythmias are uncommon (Flow chart 22.2 and Fig. 22.6).

Echocardiography11,12,13,14 It is extremely useful in acute phase, convalescing phase and in late follow-up in KD. In acute phase it can pick up pericardial effusion, LV dysfunction, MR, less commonly AR and of course possible coronary artery lesions (CAL). In our series, LV dysfunction was extremely rare (Figs 22.7 to 22.10). Visualization of coronaries involves careful visualization of both proximal and, if possible, distal segments of both left coronary artery system and right coronary system. The views are parasternal short axis with tilted views, apical four chamber view and subcostal views. The overall sensitivity of echo in picking up CAL is 95% and specificity is nearly 100%. If stenosis is present, sensitivity may be around 85% and specificity 98%. Sensitivity decreases with distal coronary segments but most coronary lesions are in the proximal segments. The echocardiography is done traditionally in the acute phase, at 6 to 8 weeks of illness and at 6 months and 1.0 year in our institution, using a 5 MHz probe.

Kawasaki Disease: Diagnosis and Management Flow chart 22.2: Incomplete KD approach

Figure 22.6: KD profile in Trivandrum

CAL can be: 1. Aneurysms—sacular, fusiform, sacculofusiform and tubular. 2. Dilatation. 3. Stenosis.

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Figure 22.7: Coronary artery lesions in Kawasaki disease

Figure 22.8: CVS in KD

Figure 22.9: Echo—coronary artery lesions

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Figure 22.10: Echo—coronary artery lesions (Abbreviation: AO, Aorta; LAD, Left anterior descending)

What is Abnormal?

Table 22.3: Principal etiologic

According to JKDRC 1987 recommendations, Normal < 2.5 mm at any age a coronary artery is abnormal if the internal Border line 2.5 to 3.0 mm at any age > 3.0 mm at any age diameter of either coronary artery is > 3 mm in Abnormal Or children below 5 years or > 4 mm in children Segment > 1.5 times adjacent segment above 5 years or if a segment measures 1.5 times the adjacent coronary segment; or if the coronary lumen is irregular. This has been widely followed for assigning CAL in KD. These values do not correlate with body surface area (BSA) and may underestimate coronary abnormality. Hence, Z scores for the appropriate BSA may be used; the usual cutoff values may be 2.0 or 2.5 SD above mean value. In our institution, we assessed coronary artery size (internal diameter) in normal healthy infants and children up to 12 years and calculated centiles and normative data. Instead of age, we decided to measure coronary artery size according to body surface area (BSA) and plotted the mean and the 97th centiles. We are using these data to categorize coronary artery segments into normal, border line and abnormal (Tables 22.3 and 22.4). Table 22.4: Coronary artery lesions—classification according to diameter Up to 4 mm—Mild dilatation 4 to 8 mm—Moderate dilatation > 8 mm—Giant aneurysm

TERMINOLOGIES IN KD 1. 2.

Incomplete KD (10%) Has fever, is more common in infants and equally likely to cause CAL. It has 2 to 3 principal features only.9 Atypical KD KD with unusual presentation like seizures, CVA, pneumonia and pleural effusion, etc.

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3. Late KD Presents with history of illness beyond 10 days. 4. Neonatal KD Presents in the newborn. Very rare. Isolated reports are present. 5. Note: Incomplete KD with normal echocardiography 2 to 3 principal features Elevated ESR and CRP with: a. S. albumin < 3 g/dL b. Anemia c. Elevated SGPT d. Platelet count > 4.5 L/am e. TLC > 15,000/am f. WBC in urine.10

OTHER INVESTIGATIONS Coronary Angiogram They are usually indicated in prognostication and therapeutic strategy planning in KD with CAL. The children who need angiography are those with large coronary aneurisms, multiple aneurisms and who have clinical, ECG or scintigraphic evidence of ischemia.

Stress Studies Dobutamine stress echo, stress thallium have been used in assessment of ischemia in children.

Others Include PET, MRI, spiral CT, IVUS, (Intravascular ultrasound) and endomyocardial biopsy). They are limited to mostly research centers.

Predictors of Coronary Artery Lesion 1. Age less than 1.0 year 2. Male sex 3. TLC > 30,000/cm 4. ESR > 100 mm/1 h 5. Persistently high ESR 6. ECG showing Ac MI pattern 7. Low Hb 8. Hypoalbuminemia 9. Late IVIG administration. Muscle enzymes: CPK—MB, could be elevated in KD, especially if an infarct or microinfarct has occurred or if significant myocarditis develops. Trop T and Trop I results in KD are variable and may not be very useful.19 However, it may be useful in picking up possible myocardial

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infarction. Recently, BNP estimation have been touted as marker for risk of developing CAL, as also plasminogen activator inhibitor-I (PAI-1), urinary neopterin and cytokines-IL-6, IL-8 and IL-2. There have been documentation of mildly elevated total cholesterol, LDL-cholesterol and TG and low HDL following KD, especially in convalescence. Lipid abnormalities have been reported in convalescing KD children. They have an atherogenic profile—high total cholesterol, low HDL cholesterol, high LDL cholesterol and high triglycerides. These changes could be a primary phenomenon or a para- phenomenon—due to IVIG induced protein fraction changes in plasma. These changes may persist also. There have been also studies showing increasing BP, adiposity and TG levels following KD which may cause accelerated atherosclerosis. Hence, there is an intriguing possibility of premature CAD in KD survivors due to interplay of multiplicity of factors such as gross coronary artery lesions, endothelial dysfunction, abnormal flow reserve, dyslipidemia and possible adiposity and hypertension (Flow chart 22.3).16 Death in KD is now rare. It was 1 to 3% in the 1970s and now it has become < 0.1%. It occurs due to acute infarction and rarely due to aneurism rupture. Late mortality is again due to infarction or intervention related events. Coronary involvement is usually between 20 to 30%. In our institution the CAL occurred in 28%. Usually CAL regresses within 1 year in 50% children.15 Endothelial dysfunction is near universal in CAL and it could possibly occur in coronaries identified as normal by echocardiography. Hence, accelerated atherosclerosis is a potential risk in KD. In spite of apparently normal looking coronaries. Carotid intima media thickness (CIMT) is altered in KD. Recurrence can occur in KD in 2 to 3%. Recurrent skin peeling with no other clinical and lab abnormalities can occur in 10% and should be differentiated from recurrence.

Treatment Even though etiology is unknown, current therapeutic strategy for KD is more or less standard. The goals are: 1. To treat acute inflammation and prevent CAL. 2. To prevent thrombosis.

Flow chart 22.3: KD and atherogenesis

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IVIG Landmark trials in 1980s in Japan and USA have established the role of IVIG in reducing CAL and current recommendation of administration of 2.0 g/kg/IVIG is based on major trials in the 1990s. IVIG should be administered within 10 days of illness and preferably within 6 days of illness. Very early IVIG may further reduce CAL. IVIG was first given in KD in 1983. IVIG with aspirin can bring down the percentage of CAL at 6 weeks from 25 to 5% that is a five fold reduction. Late administration of IVIG is a risk factor for giant aneurysm formation. Multiple doses are less efficacious. IVIG should be at least given as two doses (1 g/kg/day × 2) if there is a feasibility problem in administration. Aspirin Relatively high doses of aspirin is started once diagnosis is made. AHA recommends a dose of 100 mg/kg/day/4 divided doses till fever subsides, acute symptoms subside and acute phase reactants become normal. We follow this strategy in our institution. However, most centers in Japan give a dose of 60 mg/kg/day. Salicylate induced hepatitis is a cause for concern in KD treated with large dose aspirin with moderately elevated transaminases, vomiting and mild icterus. This could be more common in Japanese or Asians. So, there is a minor debate on what is the optimal dose of aspirin in acute phase. During convalescence the antiplatelet dose of 5 mg/kg is given for 6 to 8 weeks till the next echocardiograph is performed.

Concerns Regarding IVIG Only 20 to 25% of KD develop CAL but all children with KD will receive IVIG, which means that 3/4th of children may be receiving IVIG without a need. Many of the scoring systems for predicting CAL and then administering IVIG are not fool proof. So, we will continue to give IVIG to all. Some of the ‘KD’ may not be genuine KD. Early administration is IVIG gives more benefit, but according to JKDRC at least 5 days’ fever is essential for diagnosing KD and hence the therapeutic window offered is very small. There have been also concerns regarding spread of hepatitis, HIV and also on the efficacy of different commercial preparations of IVIG.

STANDARD PROTOCOL FOLLOWED IN OUR INSTITUTION 1. IVIG 2 g/kg/IV infusion over 12 hours. 2. Aspirin (Enteric coated) 100 mg/kg/day; 4 divided doses till child is: a. Afebrile b. Acute symptoms abate Usually it involves around 5 to 7 days. 3. Subsequent therapy Aspirin 5 mg/kg/day once daily for 6 to 8 weeks. Echocardiography is done at 6 to 8 weeks and If echocardiography is normal, aspirin is discontinued If echocardiography is abnormal aspirin is continued. Indefinitely with follow-up echocardiography.

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4. Recrudescence or persistent symptoms a. Continue full dose aspirin b. IVIG 2 g/kg/single dose. 5. Large aneurism (> 6 m) a. In acute phase i. Low molecular weight heparin × 5 days ii. Add clopidogrel 1.5 mgm/kg once daily b. In convalescent phase: add clopidogrel c. In giant aneurism (> 8 mm) Anticoagulant added to low dose aspirin to keep INR 1.5 to 2.0 with warfarin. 6. Atypical KD: 10% Treat as KD with full complement of IVIG and aspirin if echocardiogram is abnormal or borderline normal/higher number of risk factors present. 7. Late KD: (> 10 days) Full dose aspirin is given IVIG administration individualized, depending on risk factors, cost, etc. 8. Refractory or Resistant KD: 10% children may not respond to IVIG. Such patients will require additional dose(s) of IVIG. If still nonresponsive, IV methylprednisolone is given. IV infliximab, a monoclonal antibody against TNF alpha has also been tried, though it is very expensive.

KAWASAKI DISEASE—OTHER MODALITIES OF THERAPY Steroids Steroids are generally either not indicated or possibly contraindicated in acute KD. This is based on a major initial trial of steroids in KD in the 1980s. However, there have been recent reports of administration of steroids in KD in selected cases. Drug used is methylprednisolone 30 mg/kg/IV for into 3 doses—pulse methyl prednisolone. The indications may be: a. Recrudescent or persistent clinical features. b. IVIG failure and retreatment (10%). In 2003, a randomized controlled trial comparing IVIG alone vs IVIG + methylprednisolone showed reduced fever, shortened duration of illness, rapid reduction of ESR and CRP but no significant difference in coronary dimension. So, steroids are still not be used in the initial treatment of KD. Plasma exchange: There have been reports of successful treatment with plasmapheresis in KD refractory to IVIG. Yet, it is not generally recommended. Ulinastatin: is a human trypsin inhibitor which has been tried in IVIG refractory KD. Abciximab/Tpa/streptokinase: have been used in acute coronary events in children with KD. Abciximab may reduce remodelling of coronaries and can lead to regression of dilatation. Infliximab: a TNF alpha antagonist antibody is being studied and could be useful in resistant KD.

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Antioxidants: A tocopherol and vitamin C may mitigate the clinical features of KD. So far there has been no genuine trial on these. Cyclosporin A: There have been isolated reports of using cyclosporin A in IVIG failure in KD. Oral Prednisolone: Have been used in a few centers with variable success. Tidopidine/clopidogrel could be an alternative to dipyridamole in large CAL especially in giant aneurisms. Revascularization: Surgical revascularization is occasionally indicated in KD children. CABG using arterial grafts are preferred. PTCA have also been done in children as well as adults who had distant KD.

KD; No CAL Initially Strategy is to repeat echocardiography at 6 to 8 weeks and if proximal coronaries are normal, aspirin is discontinued. So far we have not noticed CAL reappearing once initial two echoes are normal. However, in view of potential endothelial dysfunction, potential for atherosclerosis and reported abnormalities of lipid profile some sort of follow-up may be indicted, preferably every year.

KD; CAL Initially If repeat echo is normal, aspirin is discontinued and child is asked to report after 3 to 6 months. A repeat echo is done. Thereafter, child is followed up as in (1). If echocardiographic abnormalities persist, low dose aspirin is continued indefinitely and follow-up is active—every 3 months (Flow charts 22.4 and 22.5). In the current AHA guidelines, a stratification has been lad out to categorize children by their risk of developing CAD. There are 5 risk levels. Level 1: No coronary lesion Level 2: Transient coronary lesions which have resolved Level 3: Small to medium coronary dilatations Level 4: Large aneurisms or multiple complex aneurisms Level 5: Aneurisms with obstructions documented by angiography Flow chart 22.4: Potential mechanisms for premature coronary artery diseases (CAD) following Kawasaki disease (KD)

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Flow chart 22.5: Initial phase of Kawasaki disease (KD)

LONG-TERM MANAGEMENT36 Role of Interventions In significant occlusive coronary lesions CABG is traditionally offered.37 Initially, SVG were used but now current bilateral IMA graft is preferred. Restenosis seems to be earlier in KD children or adults who undergo CABG. PTCA have been used with or without stent in children or adults with distant KD. Restenosis rate may be higher.

SUMMARY Kawasaki disease is emerging as an important acquired heart disease in children, probably next only to RF/RHD. The regional variation occurs at national level also wherein a large number have been reported from Kerala. Even though etiology remains an enigma, effective acute therapy is currently available which can reduce coronary involvement fivefold. Some sort of long-term surveillance in warranted. Occasionally, revascularization may be required. Many features of KD; both mechanical and biochemical, might predispose to accelerated atherosclerosis and hence increased CAD occurrence.41

REFERENCES 1. Burns JC, Kushner HI, Bastian JF, et al. Kawasaki disease: A brief history. Pediatrics. 2000;106:E 27. 2. Kawasaki T, Kosaki F, Okawa S, et al. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics. 1974;54:271–6. 3. Taubert KA. Epidemiology of Kawasaki disease in the United States and worldwide. Prog Pediatr Cardiol. 1997;6:181–5. 4. Stanley TV, Grimwood K. Classical Kawasaki disease in a neonate. Arch Dis Child Fetal Neonatal Ed. 2002;86(2):F135–6. 5. Barron KS. Immune abnormalities in Kawasaki disease: Prognostic implications and insight into pathogenesis. Cardiol Young. 1991;1:206–11. 6. Fujiwara H, Hamashima Y. Pathology of the heart in Kawasaki disease. Pediatrics. 1978;61:100–7.

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7. Research Committee on Kawasaki Disease. Report of Subcommittee on Standardization of Diagnostic Criteria and Reporting of Coronary Artery Lesions in Kawasaki Disease. Tokyo: Ministry of Health and Welfare 1984. 8. Kato H, Ichinose E, Kawasaki T. myocardial infarction in Kawasaki disease: Clinical analysis in 195 cases. J Pediatr. 1986;108:923–7. 9. Neches WH. Kawasaki Disease in Pediatric Cardiology (2nd edn) in Anderson RH, Baker EJ, MaCartney FJ, Rigby ML, Shinebourne EA, Tynan M Eds. Churchill Livingston, London 200;2:1683. 10. Kurotobi S, Nagai T, Kawakami N, Sato T. Coronary diameter in normal infants. 11. Children and patients with Kawasaki disease. Pediatric Int. 2002;44(1):1–4. 12. Akagi T, Kato H, Inoue O, Sato N, Imamura K. Valvular heart disease in Kawasaki syndrome. Incidence and natural history. AHJ. 1990;120:366–72. 13. Satomi G, Nakamura K, Narai S, et al. Systematic visualization of coronary arteries by twodimensional echocardiography in children and infants: evaluation in Kawasaki’s disease and coronary arteriovenous fistulas. Am Heart J. 1984;107:497–505. 14. Suzuki A, Tizard EJ, Gooch V, et al. Kawasaki Disease: Echocardiographic features in 91 cases presenting the UK. Arch Dis Child. 1990;65:1142–46. 15. Arjunan K, Daniels SR, Meyer RA, et al. Coronary artery caliber in normal children and patients with Kawasaki disease but without aneurysms: An echocardiographic and angiographic study. J Am Coll Cardiol. 1986;8:1119–24. 16. Hiracshi S, Misawa H, Takeda N, et al. Transthoracic ultrasonic visualization of coronary aneurism; stenosis and occlusion in KD. Heart. 2000;83:400–5. 17. Suzuki A, Kamiya T, Ono Y, Kinoshita Y, Kawamura S, Kumura K. Clinical Significance of morphological classification of coronary arterial segmental stensosis due to KD. AJC. 1993;71: 1169–73. 18. Gopika S, Zulfikar MZ, Padmamohan S. Coronary artery dimensions in normal infants and children in Kerala. Unpublished data 2002, Pediatric Cardiology Division, Medical College, Trivandrum, Kerala. 19. Takahashi M. Kawasaki syndrome in Moss and Adams Heart Disease InInfants, children and Adolescents (6th edition). Allen HD, Gutgesel HP, Clark EB, Driscoll DJ (Eds). Lippincott Williams and Wilkins, Philadelpia. 2001; p. 1216. 20. Kim M, Kim K. Elevation of Cardiac troponin I in the acute stages of Kawasaki disease. Pediatr Cardiol. 1999;20:184–88. 21. Newburger JW, Burns JC, Beiser AS, et al. Altered lipid profile after Kawasaki syndrome. Circulation. 1991;84:625–31. 22. Takahashi M, Mason W, Lewis A. Regression of coronary artery aneurysms in patients with Kawasaki syndrome. Circulation. 1987;75:387–94. 23. Yamakawa R, Ishii M, Sugimura T, et al. Coronary endothelial dysfunction after Kawasaki disease: Evaluation by intracoronary injection of acetylcholine. J Am Coll Cardiol. 1998;31:1074–80. 24. Silva AA, Macno Y, Hashmi A, et al. Cardiovascular risk factors after Kawasaki disease: A case control study. J Pediatr. 2001;138:400–5. 25. Onouchi Z, Kawasaki T. Overview of pharmacological treatment of Kawasaki disease. Drugs. 1999;58:813–22. 26. Durongpisitkul K, Gururaj VJ, Park JM, Martin CF. The prevention of coronary artery aneurism in Kawasaki disease: A metaanalysis on the efficacy of aspirin and immunoglobulin treatment. Pediatrics. 1995;96:1057–61. 27. Newberger JW, Takahashi M, Beiser AS, et al. A single intravenous infusion of gammaglobulin as compared with four infusions in the treatment of acute Kawasaki syndrome NEJM. 1991;324: 1633–39. 28. Shulman ST. IVGG therapy in Kawasaki disease: Mechanisms of action. Clin Immunol Immunopath. 1989;53:S141–46.

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29. Tse SM, Silverman ED, McCrindle BW, Yeung RS. Early treatment with IVIG in patients with Kawasaki disease. J Pediatrics. 2002;140:450–5. 30. Akagi T, Kato H, Inoue O, Sato N. Salicylate treatment in Kawasaki disease; high dose or low. Eur J Pediatrics. 1991;150:642–6. 31. Sundel RP, Baker AZ, Futton DR, Newburger JW. Cardiosteroids in the initial treatment of Kawasaki disease: Report of a randomized trial. J Pediatrics. 2003;142:611–6. 32. Shen CT, Wang NK. Antioxidants may mitigate the deterioration of coronary arteritis in patients with Kawasaki disease unresponsive to high dose IVIG. Pediatr Cardiol. 2001;22(5):419–22. 33. Dale RC, Saleem MA, Daw S, Dillon MJ. Treatment of severe complicated KD with oral predinosolone and aspirin. J Pediatr. 2000;137:723–6. 34. Williams RV, VM, Tani LY, Minich LL. Does Abciximab enhance regression of coronary aneurisms resulting from KD? Pediatrics. 2002;109(1):E4. 35. Liang CD, Huang SC, Su WJ, Chen HY, Lee CH. Successful IV streptokinase treatment of a child with Kawasaki disease complicated by acute myocardial infarction. Cathet Cardiovasc Diagn. 1995;35:139–45. 36. Akagi T, Ogawa S, Ino T, et.al. Catheter interventional treatment in KD: A report from Japanese Pediatric Interventional Cardiology Investigation group. J Pediatr. 2000;137:181–6. 37. Dajani AS, Taubert KA, Takahashi M, et.al. Guidelines for long-term management of patients with Kawasaki disease. A report from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 1994;89:916–22. 38. Kitamura S. The role of CABG an children with Kawasaki Disease. Coronary Art Dise. 2003;14:95. 39. Akagi T, Rose V, Benson LN, Newman A, Freedom RM. Outcome of coronary artery aneurisms after KD. J Pediatrics. 1992;121:689–94. 40. Tatara K, Kusakawa S. Long-term prognosis of giant coronary aneurysm in Kawasaki disease: An angiographic study. J Pediatr. 1987;111:705–10. 41. Kato H, Sugimura T, Akagi T, et al. Long-term consequences of Kawasaki disease. A 10-21 yr. follow up study of 594 patients. Circulation. 1996;94:1379–85. 42. Kato H, Inoue U, Kawasaki T, et al. Adult CAD probably due to childhood KD. Lancet. 1992;7:340:1127–9. 43. Singh S, Kawasaki T. Kawasaki disease—An Indian Perspective. IP. 2009;46:563–71.

23

Cardiac Manifestations in Systemic Illness

Sumitra Venkatesh, Shakuntala Prabhu, Mahesh K

A wide variety of primary systemic illnesses produce cardiovascular manifestations as a part of their clinico-pathological spectrum. The list of such illnesses includes storage and metabolic disorders, collagen vascular disorders, endocrine diseases, neuromuscular disorders, etc. Often, it is the cardiac manifestation that leads to the diagnosis of these conditions, though in most cases the cardiac disease becomes evident only after the establishment of the primary diagnosis. Thus, recognition of the heart disease has significant diagnostic and prognostic value, and considerable influence on the overall management of these conditions. This chapter briefly discusses the cardiovascular manifestations of selected systemic diseases.

STORAGE DISORDERS Glycogen Storage Disorders This is a group of inheritable disorders occurring due to quantitative or qualitative deficiency of one of the enzymes involved in glycogen metabolism. Perhaps the most illustrative example of a glycogen storage disorder with cardiac manifestation is GSD Type II or Pompe’s Disease (which accounts for roughly 15% of all GSDs). Cardiomyopathy has also been reported with GSD Types III and IV.

Pompe’s Disease: (GSD Type II) Pompe disease is a rare autosomal recessive disorder that results from deficiency of the lysosomal enzyme acid alpha 1,4 glucosidase (‘GAA’ or ‘acid maltase’) which is required for the degradation of lysosomal glycogen. The enzyme defect causes a progressive deposition of normally structured glycogen within lysosome-derived vacuoles in nearly all types of tissues with a predilection for myocardium, skeletal muscle and liver.1 Cellular injury that occurs as a result of the excessive glycogen accumulation leads to enlargement and dysfunction of the entire organ involved, manifesting as hypertrophic cardiomyopathy, weak bulky skeletal muscles, etc.

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Clinical Features The clinical manifestations depend on the severity of the enzyme deficiency. The more severe the deficiency, the earlier the presentation and more relentless the course. Thus, there are three major clinical phenotypes: 1. Infantile 2. Juvenile onset 3. Adult onset Infantile onset (classical Pompe) is the most severe variant, characterized by massive glycogen deposition in heart, liver and skeletal muscles. Apparently normal at birth, these patients usually present within first 6 months of life with history of feeding difficulties, breathing difficulty, hypotonia, weak cry, enlarged protruding tongue, and features of congestive cardiac failure. Only 15% of the patients have cardiac symptoms on presentation viz. cardiac failure or arrhythmia. Gross motor development, usually normal in the initial weeks or months of life, shows retardation as the disease (and the associated hypotonia) progresses. The disease relentlessly progresses to death, usually from cardiac or respiratory failure, usually between 6 months and 2 years of life. A milder subset (late infantile Pompe) has been described, which progresses more slowly, until death ensues few years later from cardiorespiratory failure. Juvenile onset Pompe’s disease presents later in childhood, has slower progression, and is mainly characterized by skeletal muscle weakness. Macroglossia and hepatomegaly are absent; cardiomegaly is variable, but cardiac function is usually normal. They usually succumb to respiratory failure by the second and third decade of life. Adult onset Pompe’s disease presents between second and seventh decade of life with slowly progressive proximal myopathy; death usually results from respiratory failure. Cardiac manifestation of Infantile Pompe’s disease is progressively worsening severe hypertrophic cardiomyopathy and resultant cardiac failure. The diastolic thickness of LV posterior wall and the cardiac weight increase significantly with age. Biochemical investigations may reveal elevated levels of creatine kinase (upto 2000 IU/L), ALT, AST, LDH, and alkaline and acid phosphatase. Chest Roentgenogram Chest roentgenogram shows cardiomegaly and pulmonary congestion (Fig. 23.1). Electrocardiogram Electrocardiogram may show characteristic tall QRS complexes and short PR interval. Supraventricular tachycardias and atrial dysrhythmias have been reported (Fig. 23.2). Echocardiogram Echocardiogram shows severe left ventricular hypertrophy, worsening left ventricular function and increased left ventricular mass index (Fig. 23.3).

Figure 23.1: Chest X-ray PA view showing massive cardiomegaly with CT ratio of 70%

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Figure 23.2:Pompe’s Disease: 12 lead ECG showing a short PR interval with very prominent QRS voltages in all leads

A

B

Figures 23.3A and B: Echocardiographic images in parasternal long axis (A) and parasternal short axis, (B) views showing massive left ventricular hypertrophy involving the entire LV

Confirmation of Diagnosis Confirmation of diagnosis is by demonstration of absent or deficient enzyme (acid maltase) levels in muscle biopsy, cultured skin fibroblasts or peripheral blood lymphocytes. Prenatal diagnosis is possible by determination of the enzyme levels in chorionic villus biopsy sampling or amniocentesis. Management It is principally symptomatic and supportive and includes medical therapy for cardiac and respiratory failure, ventilatory assistance, physiotherapy and rehabilitative training. There are

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anecdotal reports of benefits from dietary management (high protein, low carbohydrate diets, L-alanine supplementation, etc.) and exercise regimens. Recent advances in management include development of a recombinant human acidalpha glucosidase enzyme (MyozymeTM) which has obtained FDA approval in 2006. The objective of enzyme-replacement therapy is to attempt to restore enzyme activity, deplete the accumulated substrate, prevent or slow the re-accumulation, and convert a more severe variant of Pompe’s disease to a milder one. Overall long-term benefits of enzyme-replacement therapy remain to be seen.

Mucopolysaccharidosis (MPS) Mucopolysaccharidosis are a group of rare inherited disorders that result from the deficiency of one or more of the lysosomal enzymes required for glycosaminoglycan (GAG) catabolism. GAGs are complex macromolecules that form a major constituent of connective tissues. Enzyme deficiency therefore results in lysosomal accumulation of excessive amounts of GAGs at various sites including the skeleton, cardiac valves, myocardium and coronaries.

Clinical Features Typically include coarse facial features, corneal clouding, skeletal abnormalities (joint stiffness, dysostosis multiplex), hernias, short stature, deafness and mental subnormality (in certain types), depending upon the specific enzymatic deficiency and the resultant pattern of GAG degradation products. Cardiovascular involvement is not an uncommon feature of this group of disorders and can be found in all types of MPS. Valve distortion due to GAG deposition with resultant stenosis or regurgitation of mitral, aortic and tricuspid valves are the common cardiac manifestation.2 Left sided cardiac involvement is more common. Structural lesions are seen mainly in the older age,whereas all patients show varying degrees of diastolic dysfunction. Primary myocardial involvement and infiltration of the coronary arteries are also known. Cardiac failure associated with endocardial fibroelastosis has also been reported to be a presenting feature.3 Acute infantile cardiomyopathy has been reported with MPS Type VI. Depositions of mucopolysaccharides in the arterial walls produce lesions similar to atherosclerosis. At times, systemic hypertension and very rarely myocardial infarction may occur. Sudden death could occur due to arrhythmias. Investigations Urine can be studied quantitatively and qualitatively for glycosaminoglycan excretion. Specific enzyme deficiency can be demonstrated in cultured fibroblasts or isolated leucocytes. Prenatal diagnosis can be established by amniocentesis. Electrocardiogram Electrocardiogram may show RVH, LVH, LAH and prolonged QT interval. Echocardiogram Reveals the valvular abnormalities and ventricular functions.

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Radiological, opthalmological and other specific systemic evaluations would elucidate the other manifestations of this disorder.

Management It is guided by a multidisciplinary approach aimed at symptomatic and supportive care. Cardiac evaluation and echocardiography is advisable, at least annually. Infective endocarditis prophylaxis should be advised in all patients with valvular abnormalities. There are reports of surgical valve replacement in severely stenosed or regurgitant cardiac valves. Orthopedic and opthalmological surgeries may be required. Recombinant enzyme-replacement therapies are now available for some types of MPS (e.g. AldurazymeTM for MPS Type I and NaglazymeTM for MPS Type VI) which have been shown to improve physical capacity and respiratory functions. There have been reports of cardiac improvement noted in patients with Bone Marrow Transplantation. Mortality and Morbidity Mortality and morbidity depends on the specific enzyme deficiency, the severity of the deficiency, and the extent of specific organ involvements.

COLLAGEN VASCULAR DISEASES (CONNECTIVE TISSUE DISEASES, RHEUMATIC DISEASES) The collagen vascular diseases are a group of diseases that result from abnormally regulated immune responses, leading to inflammation of target organs. They have varied pathogenetic mechanisms, and a wide spectrum of organ involvement and clinical presentation. Cardiac involvement is common, though there is no unified pathobiological mechanism to explain its occurrence.

Systemic Lupus Erythematosus Pediatric SLE is a relatively uncommon disorder with a reported prevalence of 4-250/100,000. It is unusual before 8 years of age, though it has been reported as early as first year of life. There is an overwhelming predilection for female sex with an overall ratio of 6.3:1.

Diagnosis SLE is diagnosed by a combination of clinical criteria and laboratory manifestations. Clinical features include constitutional symptoms of fever, fatigue, malaise, weight loss with joint involvement (pain with/without swelling), skin rash (butterfly/malar rash), oral ulcers, photosensitivity, serositis, hematological derangements (thrombocytopenia, anemia, neutropenia), psychosis, chorea and renal involvement in the form of hypertension. Any four of the above should raise a suspicion of SLE. Investigations Antinuclear Antibody (ANA) is usually positive (>/= 1:160) , though not essential for diagnosis of SLE. Anti-double stranded–DNA, anti-smooth muscle antibody and anti-RNP are more specific for SLE. Hypocomplementinemia provides a measure of disease activity.4 Supportive

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evidence is provided by complete blood count, platelet count, ESR, urinalysis, rheumatoid factor, BUN, creatinine, SGOT, SGPT, GGTP, amylase, lipase, VDRL, Coomb’s test, PT/PTTK. The cardiac manifestations in SLE are seen in about 31% of the children, affecting all layers of the heart including coronaries and the pulmonary arteries.5 Pericarditis is the most common cardiovascular manifestation of SLE, seen in about 25 to 30% of patients with active disease. It may be asymptomatic, or may present with fever, chest pain, pericardial rub and fever. Pericardial effusion is usually present in symptomatic patients, though tamponade is rare ( in less than 1%). Pericardial fluid is often exudative and hypocomplementinemic. Pericarditis is also commonly associated with pleuritis. The pericardium may show patchy areas of inflammatory infiltrates and fibrous adhesions obliterating the pericardial space. Myocarditis is clinically diagnosed in upto 10% of patients. The myocardial abnormality may be in the form of myocardial cell atrophy, mild to moderate infiltrating foci scattered in the interstitium, or vascular lesions like perivasculitis or necrotising vasculitis of intramural arteries. The child usually presents with chest pain, dyspnea, enlarged cardiac shadow on CXR and elevated ST-T wave segment with depressed QRS voltage on ECG. 2D Echocardiography confirms the presence of pericardial effusion. Subclinical myocarditis is a common finding, seen in almost 40% of the cases. This may cause heart failure and arrhythmias. Cardiomyopathy may develop due to accelerated atherosclerosis or platelet aggregation or due to fibrin accumulation causing myocardial ischemia. Myocardium may also be secondarily affected by hypertension or lupus valvulopathy. Valvulitis: The characteristic valvular lesion in SLE is verrucous Liebman-Sacks lesion, which are 2–4 mm, pea sized lesions consisting of proliferative or degenerating valve tissue with clumps of fibrin and platelet thrombi and are located on the ventricular side of the valve and along the chordae tendinae.6 Liebman-Sacks lesions are more common on the mitral valve and are best seen on transesophageal echocardiography. Embolization to coronary or cerebral artery is a rare complication. The other less typical valve afflictions include acute necrotizing valvulitis, valve thickening and fibrosis with occasional calcification and distortion. Conduction system abnormality is seen especially in neonates (on autopsy). AV nodes may be absent or scarred. Fibrosis of SA node and bundle of His have also been noted. Congenital complete heart block has been seen with neonatal lupus. AV block (Ist, IInd, IIIrd degree), bundle branch block, sick sinus syndrome, sinus tachycardia, atrial premature contractions and atrial fibrillation have all been reported in patients with lupus. These may be secondary to vasculitis, focal myocarditis or ischemic injury to the nodal vasculature due to thrombosis or atherosclerosis. Coronary involvement in the form of thrombosis, embolism, accelerated atherosclerosis or combination of these may cause myocardial infarction. Aneurysms in coronaries have also been reported. Antiphospholipid antibodies (APLA) and steroid therapy may play an important role in the development of coronary artery disease. Rarely, pulmonary arterial hypertension has been reported in patients with lupus due to APLA causing pulmonary venous occlusion or lupus-related intrinsic parenchymal lung disease.

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Neonatal Lupus Neonatal lupus is characterized by complete heart block (50% of cases) and transient rash. This is associated with transplacental passage of maternal autoantibodies—anti-SSA and antiSSB or both. These antibodies are usually undetectable after 6 months of age. The damage becomes evident at 22 to 24 weeks of gestation by which time there is damage or destruction of the AV nodal tissue and replacement of normal nodal tissue with fibrotic tissue. This causes fetal bradycardia, which is at times associated with congestive cardiac failure, hydrops fetalis or pericarditis. If fetal myocarditis is recognized in utero, a 2 to 4 weeks course of dexamethasone and/or beta-agonist therapy is recommended (some advocate the same in mothers with SSA positivity and a previously affected child). About 65% of babies born with complete heart block due to neonatal lupus require pacemakers often in the newborn period.7The mortality of 20% is usually due to congestive cardiac failure in infancy. Treatment: Treatment of lupus pericarditis depends on the severity. NSAIDs alone suffice for mild cases. Oral prednisolone at 1 to 2 mg/kg/day for 4 weeks followed by tapering dosage is warranted in moderate or severe pericarditis. If cardiac tamponade is evident, pericardial tap with pulse dexamethasone followed by oral dexamethasone for 4 weeks is the regime. Anticoagulants may be used in cases of vasculitis, thrombosis or pulmonary arterial hypertension occurring due to APLA.

Polyarteritis Nodosa (PAN) This is a necrotising vasculitis affecting the small and medium sized vessels (most commonly those of renal, gastrointestinal tract, muscles and the nervous system). Thrombosis and microaneurysm formation may occur at the site of vessel injury with healing occurring by the proliferation of fibrous tissue (at times causing vessel occlusion). Cardiac involvement includes coronary arteritis, pericardial effusion, myocardial infarction and ventricular hypertrophy. These may manifest as arrhythmias in the form of SVT or AV–nodal arrhythmia, cardiomegaly and congestive cardiac failure.8

Diagnosis Definite diagnosis is difficult and requires either tissue biopsy (muscle, kidney, skin or sural nerve) or angiography of medium or small sized arteries. Treatment Corticosteroid therapy—oral prednisolone 1–2 mg/kg/day for four weeks and subsequent tapering of the dose is the recommended therapy. Cyclophosphamide has also been used for nonresponders and also those developing steroid toxicity.

Takayasu’s Arteritis This is a chronic inflammatory disease that involves the Aorta, the proximal portions of the major branches and the pulmonary arteries, resulting in varying degrees of stenosis, occlusion

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or dilatation of the involved vessels. Predominantly a disease of young adults in their second or third decade of life, it may occur in children, but rarely in infants. It is relatively more common in the Asian and Mexican population. Female: male ratio varies from 9:1 in Japanese population to 1.3:1 in India. Genetic predisposition to Takayasu arteritis has been extensively studied and has revealed association of the disease with HLA B-52 and DR-2 in Japanese population, HLA B-39 in the Mexican population and HLA B-52 and B-5 in the Indian population. Exact pathogenesis of this disease is unknown. Its relationship to tuberculosis has been long debated. Possibly, the pathogenetic mechanism may be related to genetically linked immune responses to an unidentified antigen inciting autoimmune damage by cell-mediated pathways resulting in the disease and its relapses.9 The clinical features have been characterized by two overlapping phases: a. An acute, active inflammatory prepulseless phase. b. A chronic pulseless end-stage phase. Based on angiographic morphology, Takayasu arteritis is divided into Type I (involving aortic arch and its branches), Type II (thoracoabdominal aorta and its branches), Type III (involving lesions both Type I and II) and Type IV (involvement of pulmonary arteries in addition to any of the other types).

Clinical Presentation The child may present with the usual constitutional symptoms in the acute phase with normally palpable peripheral pulses and blood pressure. As the disease progresses into the chronic, pulseless phase, the child may present with claudication, absent or decreased brachial and radial pulses, wide pulse pressure, aortic incompetence, hypertension, congestive cardiac failure and syncope. Hypertension is usually a result of renal artery stenosis or aortic narrowing and aortic fibrosis and may even be severe enough to cause hypertensive encephalopathy or heart failure. Heart failure (resulting from hypertension, coronary involvement, valvar involvement or pulmonary artery involvement) is common in Takayasu arteritis in children and contributes significantly to mortality. Neurological symptoms like headache, visual disturbances, amaurosisfugax, syncope, transient ischemic attacks or cerebrovascular accidents can also be present. Diagnosis Diagnosis is made on the basis of clinical history and the angiographic morphology. Diagnostic criteria have been suggested by Ishikawa10 and the American College of Rheumatology11 (Table 23.1) which have incorporated clinical features (age of onset, blood pressure, peripheral pulses, ESR) and angiographic morphology. Though none of the diagnostic criteria are entirely satisfactory, they aid in arriving at an accurate diagnosis. Diagnosis is easier in the chronic phase by ultrasonography with color Doppler showing mural thickening and a turbulent flow in the aorta and branches. Echocardiography may detect aortic root dilation, aortic regurgitation, mitral regurgitation or coronary artery involvement. CT-angiography and MR-angiography can effectively reveal the thickening and calcification of the aorta and its branches and also the enhancement with inflammation with activity of the disease.

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Criteria Age at disease onset in year  Claudication of extremities  Decreased brachial artery pulse BP difference >10 mm Hg Bruit over subclavian arteries or aorta Arteriogram abnormality 

Definition Development of symptoms or findings related to Takayasu arteritis at age 10 mm Hg in systolic blood pressure between arms  Bruit audible on auscultation over one or both subclavian arteries or abdominal aorta Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal uppper or lower extremities, not due arteriosclerosis, fibromuscular dysplasia, or similar causes: changes usually focal or segmental

Takayasu’s arteritis is diagnosed if at least three of these six criteria are present. BP = blood pressure (systolic) difference between arm

Assessment of Disease Activity The presence of systemic symptoms, raised ESR (> 20 mm/1st hour) and worsening vessel stenosis (claudication, disappearance of pulses, bruit, vascular pain, asymmetric blood pressures, angiographic features) are considered evidence of disease activity. Treatment During the pulseless phase, an elevated ESR or other signs of disease activity warrants oral steroids for four weeks (1 mg/kg/day) followed by slow tapering. Immunomodulation using cyclophosphamide (1 to 2 mg/kg/day), azathioprin (1 to 2 mg/kg/day) or methotrexate (0.15 to 0.35 mg/kg/week) may be tried in resistant cases or in order to facilitate reduction in steroid dose. Duration of treatment is guided by clinical assessment of disease activity. Control of hypertension with antihypertensives and management of cardiac failure is mainstay in therapy. Surgical intervention is required in case of severe arterial damage, when the arteritis is not active or has been adequately suppressed. Transcatheter balloon dilatation with or without stenting of the stenosed vessels has revolutionized the management of Takayasu arteritis.

Juvenile Idiopathic Arthritis (JIA) JIA or Still’s disease is the most common form of chronic arthritis in the pediatric age group. According to the clinical presentation, JIA is classified as—systemic onset, pauciarticular, polyarticular.

Systemic Onset Patients present with persistent fever with an evanescent rash, hepatosplenomegaly and generalized lymphadenopathy. Arthritis may or may not be present. Pericarditis and myocarditis are frequently seen along with pleuritis. Some patients with systemic JIA may develop cardiac tamponade or myocarditis during the acute phase; which may even cause of death. Valvulitis is rare and chronic constrictive pericarditis has not been described with JIA.12

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Pauciarticular JIA affecting four or fewer joints usually with no systemic manifestations. Iridocyclitis is common in pauciarticular JIA. 1/3rd of the patients have pericarditis. Polyarticular JIA involving five or more joints symmetrically with occasional spinal involvement and associated with mild systemic manifestations. Diagnosis Baseline investigations may reveal anemia, leucocytosis, increased ESR. Rheumatic factor and ANA are rarely seen. HLA-B27 histocompatibility is seen in 25% of the cases. Cardiomegaly is noted on chest radiograph. ECG shows nonspecific ST-segment and T-wave changes. 2D-echocardiography has immensely increased the diagnosis of pericardial effusion. Treatment Pericarditis is treated with high dose salicylates or non-steroidal anti-inflammatory drugs and steroids. Steroids are also useful in decreasing the risk of cardiac tamponade. Tamponade is managed with percardiocentesis. Myocarditis warrants high dose steroids and diuretics.

ENDOCRINE AND METABOLIC CONDITIONS Diabetes Mellitus Diabetes mellitus increases the risk of cardiac, cerebral and vascular diseases by two to sevenfold. The annual incidence of juvenile diabetes is 8–10/100,000. Since the cardiac complications occur later in age, the pediatric cardiologist usually gets to manage the infants of diabetic mothers. There is an increased risk of VSD and transposition of great vessels in these babies. Even in the absence of these structural abnormalities, the infants of diabetic mothers have a host of other cardiac problems. Some infants have asymmetric septal hypertrophy.13 These infants are usually macrosomic due to increased body fat and have organomegaly due to increased fetal insulin and synthesis of glycogen, lipids and proteins. They are jittery due to the hypoglycemia secondary to hyperinsulinemia, but some may be lethargic and hypotonic. Cardiomegaly is found in 30% and cardiac failure occurs in 5–10% of these infants. 2D-echocardiography shows thickening of the right ventricular and left ventricular free wall with septal hypertrophy. A spectrum of abnormalities ranging from mild ventricular hypertrophy to hypertrophic obstructive cardiomyopathy (HOCM) may occur in these infants. In case of HOCM, a harsh ejection systolic murmur may be heard due to the obstruction to the left ventricular outflow.

Treatment Children with HOCM need only supportive care and the condition is usually reversible. Cardiac failure is treated with diuretics. Digitalis is avoided in the presence of obstruction.

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Subaortic obstruction improves with propranalol and may regress spontaneously within one to two months as noted on cardiac catheterization.

Hyperaldosteronism This syndrome is associated with chronic hypersecretion of aldosterone. The clinical presentation is mainly in the form of hypertension and edema due to the mineralocorticoid effect on the distal nephron, causing sodium retention. Untreated, the childhood form progresses to chronic renal failure or to premature coronary artery disease in young adults.14

Treatment It includes medical, surgical or combined therapy, depending on the etiology. Those with bilateral adrenal hyperplasia are treated with antihypertensives and potassium-sparing diuretics, while those with aldosterone-secreting adenoma or tumors undergo surgical excision.

Pheochromocytoma This is a catecholamine-secreting tumor, which causes hypertensions as the major cardiovascular manifestation. Fifty percent of the cases have myocardial evidence of focal necrosis with perivascular inflammation and inflammatory infiltration. This may lead to reversible cardiomyopathy. The systolic blood pressure may range from 180 to 260  mm of mercury and the diastolic pressures may range between 120 to 210 mm of mercury.15 Surgery is the treatment of choice and use of alpha and beta-receptor blockers are helpful in those patients in whom the hypertension is refractory to surgery.

Cushing’s Syndrome Majority of cases occur due to increased production of glucocorticoids and androgens secondary to bilateral adrenal hyperplasia. A few occur due to ACTH-secreting tumors. Hyperlipidemia, hypercholesterolemia and hypertension are the most common findings with the former two causing early atherosclerosis.14

Adrenal Insufficiency (Addison’s Disease) This condition most commonly occurs secondary to Tuberculosis in our country. It may also be caused by fungal (histoplasma) infection or due to autoimmune affectation of the adrenal glands. The chief cardiovascular manifestation of this condition is hypotension. An acute crisis is characterized by shock, coma, syncope or profound hypotension.14 Treatment consists of replacement of the deficient glucocorticoid, doses of which need to be increased during periods of stress.

Acromegaly and Gigantism This is a rare disorder occurring due to hypersecretion of growth hormone, secondary to anterior pituitary gland tumors. Cardiovascular manifestations are rare in the juvenile forms, but are seen in the third or fourth decade of life. Cardiac enlargement, hypertension, cardiac

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arrhythmias and development of premature coronary disease are the common manifestations. Myocardial hypertrophy and interstitial fibrosis may cause a type of cardiomyopathy in few of the adult cases.

Thyroid Disorders Thyroid hormone is essential for protein synthesis, growth and development, metabolism of carbohydrates, vitamins and minerals and also increases oxygen consumption by the tissues. It also accelerates the heart rate and myocardial contractility, partly due to the changes in the intracellular calcium levels and partly due to the action on the sympathetic nervous system.

Hypothyroidism This occurs due to deficiency in the production of thyroid hormone or a defect in the thyroid hormone receptors, which may be congenital or acquired. Congenital Hypothyroidism: Children with congenital hypothyroidism may have cardiomegaly mainly due to the thickening of the interventricular septum and left ventricular free wall. Fifty percent of the cases show presence of a slow-filling pericardial effusion, though it does not cause cardiac tamponade. Most studies have highlighted the resolution of the effusion by treatment with L-Thyroxine The infant may present with bradycardia, weak arterial pulses, distant heart sounds, hypotension and peripheral, non-pitting edema. 2D-echocardiography may reveal LV diastolic dysfunction due to the delayed relaxation and at times systolic dysfunction. ECG reveals low-voltage QRS complexes and P-waves with bradycardia. All the above features revert on replacement with thyroid hormone and once the child achieves a euthyroid state.16 Acquired Hypothyroidism: This condition most commonly occurs due to autoimmunity during childhood and adolescence and is also called juvenile hypothyroidism. Acquired hypothyroidism may also result from thyroid surgery, prolonged ingestion of goitrogens or iodides and may also be seen after treatment with amiodarone (antiarrhythmic drug).16 The cardiac features are similar to those seen with congenital hypothyroidism. Laboratory investigations may show hypercholesterolemia, which also reverts on correction of the hypothyroid state.

Hyperthyroidism This occurs due to the excess of tri-iodothyronine (T3) or thyroxine (T4) or both and is most commonly accompanied by a diffuse goiter (Graves’ disease). Congenital Hyperthyroidism: This condition occurs in 1–2% of infants born to mothers with history of hyperthyroidism due to the transplacental passage of the thyroid stimulating immunoglobulin. This condition usually remits spontaneously by six to twelve weeks of postnatal life.16

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The infant is usually premature with an anxious and alert look. He may present with tachycardia, tachypnea, bounding pulses, elevated temperature and occasionally even with episodes of paroxysmal atrial tachycardia. Severe hypertension has also been reported in some. ECG shows evidence of peaked P-waves and chamber hypertrophy, which is reversible on treatment. Echocardiography /CD shows presence of mitral regurgitation in almost 33% of the cases. Therapy consists of Lugol’s solution and propylthiouracil. Propranalol and corticosteroids are indicated in case of severe thyrotoxicity. Digitalis is added in case of congestive cardiac failure. The infant usually improves within the second and third month of life.

Graves’ Disease This is the most common cause of juvenile hyperthyroidism. Incidence is almost five times higher in females especially between 11 and 19 years of age. The patient may experience palpitations with tachycardia, cardiac hyperactivity and dyspnea along with the other constitutional symptoms. Precordium is hyperactive with presence of mid-systolic murmur heard along the left sternal border, most likely due to presence of mitral valve incompetence. Mitral valve prolapse is seen in almost 30% of cases. Almost 15 to 20% of the cases have evidence of atrial fibrillation.16 Definitive therapy includes surgical removal of the gland or irradiation. Treatment of cardiovascular disease is difficult in patients with hyperthyroidism as arrhythmias and congestive cardiac failure may be resistant to the conventional doses of cardiac glycosides. Beta-blockers help in atrial fibrillation by slowing the heart rate, and can be administered orally or intravenously.

Hypoparathyroidism Dilated cardiomyopathy is a known complication in children with hypoparathyroidism (secondary to hypocalcemia). Cases of prolonged QTc have also been reported with hypocalcemia. Patients may be asymptomatic or experience syncope or seizures. Death too has been known due to polymorphic ventricular tachycardia or Long QTc. Aplasia or hypoplasia of the parathyroid gland is also seen in DiGeorge syndrome which is associated with structural heart disease in the form of conotruncal anomalies (e.g. conoventricular VSD, TOF, DORV, interrupted aortic arch, truncus arteriosus).17

HEMATOLOGICAL CONDITIONS Thalessemia Major The hereditary, hemolytic anemia occurring due to deficient synthesis of beta-globin chain is known as beta-thalessemia major and is one of the commonest forms of hemolyticanemias in our country. Regular blood transfusions are necessary to prevent extramedullary erythropoiesis. Hemosiderosis is an obvious complication, unless the patient is on optimal and timely chelation therapy. The major cardiac manifestations in patients with thalessemia are due to iron overload.

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There is cardiac hypertrophy with large quantities of iron deposited in the myocardium and often involves the AV node.18 Pericarditis is seen in about 50% of the unchelated patients, which may appear as acute, self-limiting episodes lasting for 4 to 5 days. Congestive cardiac failure and cardiac arrhythmias may occur due to the myocardial siderosis and may be the cause of death that occurs usually in second or third decade of life. Therapy includes an adequate transfusion program along with early initiation of chelation therapy, which will prevent the above said complications. Digitalis, diuretics and ACEinhibitors are recommended for the treatment of the said complications. Bone marrow/ stem cell transplantation, unfortunately unaffordable for most of our patients is the treatment of choice.

Sickle Cell Anemia This is another relatively common type of hemolyticanemia occurring due to the replacement of fetal hemoglobin by hemoglobin-S. As a result, the erythrocytes become rigid and “sickle” during times of stress, which leads to occlusion of the capillaries. The heart gradually dilates and then hypertrophies due to the increased stroke volume as a compensatory mechanism for anemia. There have been reports of myocardial ischemia occurring during the sickle crises in adult patients. The patients may complain of dyspnea on exertion and palpitations.19There is evidence of wide pulse pressure with brisk arterial pulsations and occasionally a gallop rhythm with apical, systolic thrill. ECG may show Ist degree AV block, left ventricular hypertrophy and nonspecific T-wave changes. Chest radiograph reveals cardiomegaly due to the anemic changes. 2D-echocardiography shows a vigorous left ventricular contraction with LV dilation. Cardiac failure is a known, but late complication.20

NEUROMUSCULAR DISEASES Duchenne’s Muscular Dystrophy This condition occurs due to the defect in the sarcolemmal membrane of the muscular cells causing cellular necrosis. It is X-linked recessive in inheritance and the incidence is one in 3,600 live male infants. Most patients are unable to walk by ten years of age and few survive up to the second decade of life. Deterioration is a continuous process in these cases with the proximal muscles being involved early in the course of the disease. Cardiac involvement is very common mainly affecting the myocardium and is progressive in nature, causing skeletal muscle dysfunction.21 Chest radiograph shows no specific cardiac abnormality. ECG may show presence of tall R-waves in the right precordial leads with narrow and deep Q-waves in the left precordial leads and limb leads. Conduction abnormalities are also commonly noted in these patients. 2D-echocardiography shows systolic and diastolic dysfunction with an increase in the end-systolic and end-diastolic dimensions of the left ventricle.

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Diagnosis Elevated levels of creatine kinase activity and biopsy of the muscle aid in diagnosis of this condition. Electromyography shows a decreased mean action potential voltage and duration with an increase in the number of polyphasic potentials. The gold standard would be the specific molecular genetic diagnosis by demonstration of deficient dystrophin by immunohistochemical staining of the tissue from muscle biopsy or by the DNA analysis of the peripheral blood. Treatment Cardiac dysfunction is treated with decongestive medications and afterload-reduction with ACE-inhibitors. The overall disease progression may be delayed by administration of oral corticosteroids (in experimental stages). Antenatal screening for detection of carriers is necessary for genetic counseling. Death usually occurs due to respiratory tract infections, respiratory insufficiency or cardiac failure and arrhythmias.

Becker Muscular Dystrophy This condition is very similar to Duchenne’s muscular dystrophy, though the onset and progression of the disease is delayed. The patient is unable to walk by the third decade and death occurs in the fifth decade (though the range may vary in individual cases). Management is similar to that of DMD.

Friedreich’s Ataxia This is a rare spinocerebellarneuromyelopathy, transmitted as an autosomal recessive condition with presentation at around 5 to 6 years of age. The neurological presentation includes ataxic gait, positive Romberg’s test, absent tendon reflexes, lower limb weakness, loss of vibration and position sense, muscular atrophy, inco-ordination and dysarthria. Cardiac involvement occurs in many patients in the form of a concentric, symmetrical, progressive hypertrophic cardiomyopathy. Acute dilated cardiomyopathy and hypertrophic obstructed cardiomyopathy have also been rarely noted. These patients may present with dyspnea on exertion, palpitations or angina. At times, soft systolic murmur is heard in the left sternal border and the apex with third and fourth heart sound.22 Diagnosis of this condition is based on the clinical manifestations with nerve conduction studies revealing gross reduction in the sensory conduction. ECG shows nonspecific ST-segment and T-wave changes with signs of ventricular hypertrophy with right or left axis deviation. 2D-echocardiography is imperative in every case, since the clinical, radiographic and electrocardiographical evaluation may be nonspecific in many cases. Echo shows impaired left ventricular function with the systolic function of the posterior wall being more severely affected than the septum along with the other structural changes as described earlier. Delayed mitral valve opening is seen in almost all cases. Cardiac failure in 50% of the cases, cardiac arrhythmias and respiratory complications are the major causes of death in Friedreich’s ataxia.

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Symptomatic therapy with diuretics, judicious use of digoxin and calcium antagonists is the mainstay of treatment in these children.

Spinal Muscular Atrophy (SMA) This is a degenerative disorder of the motor neurons causing programmed cell death or ‘apoptosis,’ beginning in the fetal life and progressing into infancy and childhood. It is autosomal recessive in inheritance. Depending on the age of presentation, severity and clinical course, SMA is divided into three types: Type I (Werdnig-Hoffmann disease): Infantile age. Type II (Kugelberg-Welander disease): Juvenile SMA. Type III: More adult pattern. The children present with weakness and atrophy of the proximal limbs initially and have difficulty in walking, climbing and lifting. Fasciculation is present in about 50% of the cases. Cardiovascular manifestations are more common in type II SMA and is usually in the form of arrhythmias viz. atrial fibrillation, premature beats, atrial flutter or AV block, at times requiring pacemakers. Some cases are also associated with dilated cardiomyopathy.23

DISORDERS OF COLLAGEN SYNTHESIS Marfan’s Syndrome Marfan syndrome is autosomal dominant in inheritance with a prevalence of about 4 to 6 per 100,000. The phenotypic features of this condition are present from birth and the patients manifest with tall stature, arm span more than their height, long and thin fingers (arachnodactyly), chest deformity, kyphoscoliosis, subluxation of lenses and myopia. Ocular abnormalities are seen in almost 75% of the cases. The cardiovascular manifestations of this disorder are mainly in the form of mitral valve prolapse and mitral regurgitation in almost two-thirds of the patients with mitral valve annular dilation and occasional calcification. Aortic root dilation can occur, which progresses with age (Fig. 23.4). This leads to aortic valve non-coaptation and worsening aortic regurgitation, valve rupture and at times even dissection of the diseased aortic wall.24Left ventricle and left atrium undergo progressive dilatation and left ventricular dysfunction ensues.

Diagnosis ECG shows signs of left ventricle and left atrial enlargement in the presence of significant valvar regurgitation. Arrhythmias viz AV block (Ist degree), atrial flutter, fibrillation and ventricular arrhythmias are also common. Echocardiographic Echocardiographic evaluation shows the presence of mitral valve prolapse with the aortic root dilation, LA and LV dilatation and at times the paradoxical motion of the posterior aortic wall. Color Doppler reveals the presence and extent of valvar incompetence. Cardiac MRI in

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children with Marfan’s syndrome has shown decreased aortic distensibility and increased stiffness.

Treatment Presence of aortic and mitral valve regurgitation implies a poor prognosis. Benefit of prophylactic propranalol in children to delay the aortic root dilation is controversial. Diuretic and vasodilators are used to treat cardiac failure. An aggressive surgical approach with aortic root replacement with a composite graft followed by coronary artery implantation and simultaneous mitral valve replacement is the procedure of choice in all symptomatic patients or in those with more than moderate aortic re- Figure 23.4: Typical aortic root in Marfan’s gurgitation. Elective replacement is considered syndrome in those with aortic diameter greater or equal to (Courtesy: Mayo Clinic: www.mayoclinic.org) 5.5 cm. Infective endocarditis prophylaxis with antibiotics is recommended in all cases with valvar incompetence.

Ehlers-Danlos Syndrome The features of this syndrome include flat nasal bridge; epicanthic folds with hyperextensibility of joints and skin, poor wound healing and easy bruising. They may also have other ocular signs like blue sclera, dislocated lens and easy eversion of upper eyelid (Meterier’s sign). Cardiac manifestations include mitral valve prolapse or tricuspid valve prolapse. Rarely, death may also occur due to hemorrhage from arterial or aortic rupture, secondary to minor trauma. Premature death is also known in most severe forms.

Osteogenesis Imperfecta Osteogenesis Imperfecta or brittle bone disease is a generalized connective tissue disorder and the most common genetic cause of osteoporosis. It is autosomal dominant in inheritance with an incidence of 1 in 20,000 live births. Five types have been described of varying severity and all types are caused by structural or quantitative defects in Type I collagen. Fragile/brittle bones is the hallmark of this condition with multiple, subperiosteal fractures. Skull usually consists of wormian bones with frontoparietal bossing. Sclera is blue in most types (except in type IV). Cardiovascular manifestations include aortic and mitral valve incompetence or at times mitral valve prolapse due to ruptured cords. Congenital heart diseases like tetralogy of Fallot and atrial septal defect have also been reported in association with osteogenesis imperfecta.

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Infections Cardiac involvement may also occur in various systemic infections viz. tuberculosis, dengue fever, malaria, Lyme disease, influenza (H1N1), HIV, etc.25 They usually manifest as one or more of the following: 1. Pericarditis 2. Myocarditis 3. Myocardial fibrosis (due to myositis or vasculitis with rhythm and conduction disturbances with systolic or diastolic heart failure) 4. Endocardial involvenment with valvular disease 5. Pulmonary hypertension secondary to concomitant lung disease or recurrent lung embolism 6. Syncope 7. Arterial hypertension Cardiomyopathy is common in several infections due to diffuse myocardial ischemia caused by vasculitis of the small epicardial vessels or by leucocytic infiltration. ECG abnormalities may be present due to myocarditis or pericarditis.

SUMMARY Cardiovascular manifestations are varied and may be seen in association with many systemic illnesses. Often, treatment of the primary disease is therapeutic for the cardiac pathology, though many conditions warrant only symptomatic or supportive therapy. There are many more metabolic conditions, which also have minor cardiovascular changes, viz. alkaptonuria, Bartter’s syndrome, anorexia nervosa, progeria, etc. but are relatively uncommon in our country as well as in our routine office practice.

REFERENCES 1. Hirschhorm R. Glycogen storage disease Type II: Acid alpha-glycosidase (acid maltase) deficiency. In: Scriber CR, Beaudet A L, Sly WS, et al. (Eds). The Metabolic and Molecular Bases of Inherited Disease, (7th edn). New York: McGraw-Hill. 1995:2443–64. 2. Fischer TA, Lehr HA, Nixdorff U, Meyer J. Combined aortic and mitral stenosis in mucopolysaccharidosis type I-S (Ullrich-Scheie syndrome). Heart. 1999;81:97–9. 3. Taylor D, Blaser SI, Burrows PE, Stringer DA, Clarke JTR, Thorner P. Arteriopathy and Coarctation in children with mucopolysaccharidosis: imaging findings. American journal of Roentgenology. 1991;157:819–23. 4. Malleson PN, Sailor M, Mackinnon MJ. Usefulness of antinuclear antibody testing to screen for rheumatic diseases. Arch Dis Child. 1997;77:299–304. 5. Moder KG, Miller TD, Tazelaar HD. Cardiac involvement in systemic lupus erythematosus. Mayo ClinProc. 1999;74:275–84. 6. Galve E, Candell-Riera J, Pigrau C, et al. Prevalence, morphologic types and evolution of cardiac valvular disease in SLE. N Eng J Med. 1988;319:817–23. 7. Buyon JP, Hiebert R, Copel J, et al. Autoimmune associated congenital heart block. J Am Coll Cardiol. 1998;31:1658–66.

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8. Gunal N, Kara N, Cakar N, et al. Cardiac involvement in childhood poly arteritis nodosa. Int J Cardiol. 1997;60:257–62. 9. Kothari SS. Takayasu arteritis in children—a review. Images in Paediatric Cardiology. 2002;9:4–23. 10. Ishikawa K. Diagnostic approach and proposed criteria for the clinical diagnosis of Takayasuarteriopathy. J Am Coll Cardiol. 1988;12:964–72. 11. Arend WP, Michel BA, Bloch DA, Hunder GG, Calobrese IH, Edworthy SM, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheumatism. 1990;33:1129–32. 12. Bernstein B, Takahashi M, Hanson V. Cardiac involvement in juvenile rheumatoid arthritis. J Pediatrics. 1974;85:313–7. 13. Mace S, Hirschfield S, Riggs T, Fanaroff A, Merkatz JR. Echocardiographic abnormality in infants of diabetic mothers. J of Pediatrics. 1979;95:1013–9. 14. DiGeorge AM, Levine LS. Disorders of adrenal glands. In: Behrman RE, Kliegman RM, Arvin AM, (Eds). Nelson Textbook of Pediatrics, (15th edn). Philadelphia: WB Saunders. 1996;1612–28. 15. Loriaux DL. Adrenal cortex. In: Bennett JC, Plum F, (Eds). Cecil Textbook of Medicine, (20th edn). Philadelphia, WB Saunders. 1996;1245–51. 16. DiGeorge AM, La Franchi S. Disorders of the thyroid gland. In: Kleigman RM, Arvin AM, (eds). Nelson Textbook of Pediatrics, Behrman E, (15th edn). Philadelphia: WB Saunders. 1996:1587–605. 17. DiGeorge AM, La Franchi S. Disorders of the parathyroid gland. In: Behrman RE, Kleigman RM, Arvin AM, (Ed). Nelson Textbook of Pediatrics, (15th edn). Philadelphia, WB Saunders, 1996; 1605–12. 18. Shulman LN, Braunwald E, Rosenthal DS. Hematological-oncological disorders and heart disease. In: Braunwald E, (ed). Heart disease. A Textbook of Cardiovascular Medicine, (5th edn). Philadelphia: WB Saunders. 1997:1786–805. 19. Balfour IC, Covitz W, Davis H, Rao PS, Strong WB, Alpert BS. Cardiac size and function in children with sickle cell anemia. Am Heart Journal. 1984;108:345–50. 20. Deneberg BS, Criner G, Jones R, Spann JF. Cardiac function in sickle cell anemia. Am Journal of Cardiology. 1983;51:1674–8. 21. Goldberg SJ, Stern LZ, Feldman L, Sahn DJ, Allen HD, Valdes-Cruz LM. Serial LV wall measurements in Duchenne’s muscular systrophy. J of Am Coll of Cardiol. 1983;136–42. 22. Ackroyd RS, Finnegan JA, Green SH. Friedreich’s Ataxia. A clinical review with neurophysiological and echocardiographic findings. Arch Dis in Childhood. 1984;59:217–21. 23. Tanaka H, Uemeura N, Toyama Y, Kudo A, Ohkatsu Y, Kanehisa T. Cardiac involvement in the KugelWelander syndrome. Am Journal of Cardiol. 1976;38:528–32. 24. Geva T, Sanders SP, Diogenes MS, Rockenmacher S, Van Praagh R. Two-dimensional and Doppler echocardiographic and pathologic characteristics of the Infantile Marfan’s Syndrome. Am Journal of Cardiol. 1990;65:1230–7. 25. Prabhu SS, Taksande A. Cardiac Involvement in Systemic Infections, IJPP. 2011;265–72.

Fetal Cardiology

24

Shakuntala Prabhu, Sumitra Venkatesh

The development of diagnostic ultrasound has opened a window to the womb and in the past few decades, the fetus has been considered as a patient. The advances that have occurred in fetal cardiology are: First a more accurate, noninvasive and early diagnosis by incorporation of the four-chamber view and outflow tracts into routine screening fetal ultrasound evaluation. Second, use of increasingly sophisticated computer processing and imaging technology by three-dimensional ultrasound imaging systems that promise to revolutionize prenatal diagnosis of congenital heart disease. Third, an increasing ability to intervene successfully prenatally for fetal arrhythmias, heart failure and some forms of structural heart disease. Finally, prenatal diagnosis has improved the neonatal outcome for fetuses with congenital heart disease (CHD).1, 2 This chapter reviews the scope and benefits of fetal echocardiography and the management of various congenital heart lesions and arrhythmias when detected prenatally.

FETAL ECHOCARDIOGRAPHY Most cases of CHD occurs in low risk pregnancies. Screening tools commonly used in antenatal scans like nuchal fold thickness, ductal venous flow velocities have very low sensitivity for CHD. Systematic evaluation of fetal heart is the only complete method to rule out significant heart disease. In the present era, early detection of most severe forms of cardiac abnormalities is possible allowing preparedness for the team of physicians caring for the mother and baby.

IMPORTANCE OF FETAL ECHOCARDIOGRAPHY Congenital heart disease (CHD) is the most common severe congenital abnormality with an incidence of 8.8 in 1000 live births. Approximately, half of these are major, requiring intervention in the neonatal period or infancy and are associated with a high degree of mortality and morbidity even when corrected. In the Indian setting, the above figure translates into approximately 75,000 to 1,00,000 children being born with a major CHD every year.

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Lack of availability and affordability of immediate specialized care except in certain pockets and a relative high yield of prenatal diagnosis of CHD make fetal heart screening important in routine obstetric scans during pregnancy. Prenatal diagnosis of congenital heart disease facilitates timely referral of mothers with affected fetuses, i.e. transfer in utero to tertiary care centers where all facilities for neonatal cardiac care are available.

OPTIMAL TIMING OF SCREENING Transvaginal examination of fetal heart is possible as early as 9 to 10 weeks of gestation and impressive views can be obtained because of close proximity of the probe to fetal heart when the lie of fetus is favorable. However, transabdominal fetal cardiac screening is preferred and is possible by 12 weeks onwards. If examination is restricted to high risk groups then only 20% of babies with CHD will be identified. Thus, cardiac screening is done in all obstetric scans by 12–14 weeks and a targeted anomaly scan is done for the high risk group by 16 to 22 weeks. A relook in the mid-second trimester of gestation may be necessary even if an earlier first trimester scan was normal as some of the CHD can develop later, e.g. hypoplasia of a ventricle secondary to inflow or outflow obstruction. It must also be remembered that if an abnormality is detected and the pregnancy is continued, a repeat imaging may be necessary to assess the fetal heart and well-being. 3

Fetal Circulation Understanding the fetal cardiac hemodynamics is essential to have an insight into fetal echocardiography. Essentially, there is a parallel arrangement of systemic and pulmonary circuits in the fetus. The placenta serves as a site of gas exchange being one of low resistance circuit as compared to a high resistance circuit at the pulmonary vascular bed. The unique features of fetal circulation are also the presence of intracardiac and intravascular passages that allow for streaming of blood, i.e. ductus venosus, ductus arteriosus and foramen ovale. Hence, most CHD are well-tolerated in utero except severe atrioventricular regurgitant lesions. The cardiac output is expressed as a combined ventricular output and is dependent on a narrow range of heart rate as compared to children and adults. This explains why arrhythmias are very poorly tolerated in fetal life and results in hydrops.

Equipment Details The equipment used for fetal echocardiography needs to have an excellent B-mode, with a good cine-loop facility so that one can scroll back, to capture the frame of interest. The system should have a color Doppler, pulsed Doppler, and continuous wave Doppler. Generally, high frequency and curvilinear probes are used to achieve a good resolution. A real time imaging is better than still time for assessment. Continuous wave Doppler helps to interrogate high velocity flows such as atrioventricular regurgitation or semilunar valve stenosis. Low scales on color Doppler are preferred for venous flows. It is however; best to avoid color flow mapping and Doppler in the first trimester to prevent any damage to developing fetus.

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The two dimensional imaging is still the commonly employed imaging modality in fetal echocardiography, though more advanced three-dimensional imaging are also available and may provide additional information of clinical value in a small number of cases.

Indications for Fetal Echocardiography Ideally all pregnancies should be screened for congenital heart disease at about 18 weeks of gestation. However, this is not cost effective even in developed countries. A number of risk factors (Table 24.1) have been identified as possible contributory factors in the development of congenital heart defects though it is paradoxically true that majority of fetuses with CHD have no identifiable risk factors.4

Limitations of Fetal Echocardiography Lesions such as small muscular VSDs, atrial septal defect in the region of fossa ovalis, PDA , mild valvular stenosis, mild coarctation of aorta and anomalies of pulmonary veins usually escape detection and are the major limitations of fetal echocardiography. However, it is imperative to stress to the potential parents about the amenability of these lesions to interventional and surgical correction and thus allay their anxiety. Fetal echocardiography is technically difficult beyond 28 to 30 weeks because of increased shadowing by the ribs.7 Additional evaluation: All complex congenital lesions detected antenatally need further evaluation to detect associated chromosomal anomalies and severe noncardiac lesions as the management strategies and prognosis risk greatly varies if they are compounded. Firsttrimester nuchal translucency (NT) measurement is widely used at approximately 10 to 14 weeks of pregnancy as a screening method for fetal chromosomal anomalies and cardiac abnormalities.8 In most cases with multiple cardiac lesions and above mentioned associated factors, the choice of therapeutic termination of pregnancy is offered to the parents (if surgical Table 24.1: Risk factors for congenital heart disease5,6 Fetal: Suspected cardiac anomaly on routine ultrasound – Chromosomal abnormalities –Trisomy’s, DiGeorge syndrome – Extracardiac anatomical abnormalities—commonly neural, renal and GIT – Nonimmune hydrops fetalis – Fetal cardiac arrhythmias/Irregular heart rate – Abnormal cardiac axis – Increased first-trimester nuchal translucency Maternal: Maternal CHD – Metabolic disorders like diabetes and phenylketonuria – Teratogen exposure like anticonvulsants and steroids – Intrauterine infection like rubella – Administration of prostaglandin synthetase inhibitors to mother, e.g. indomethacin – Maternal autoimmune diseases – In vitro fertilization Familial: Previous child with CHD – Paternal CHD – Familial inherited disorders associated with CHD, e.g. Marfan’s, Turner’s syndrome

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correction for that cardiac lesion is not easily available, affordable and where there is a poor prognosis for long-term survival).

Fetal Examinations—Anatomy Four or five transverse sections through the abdomen and chest of the fetus may be sufficient to provide a full examination of the fetal heart. The first view shows the abdominal situs with the aorta to the left of the spine and the inferior cava vein to the right. The normal fetal stomach and heart lie on the left side. The four-chamber view illustrates the chambers of the heart with the left atrium in front of the spine and the right ventricle below the sternum. Normally, both atria are of the same size. The ventricles should also be identical in size, with no evidence of wall thickening. The cardiac axis is the angle the interventricular septum makes with the anteroposterior diameter of the thorax. The normal cardiac axis is 45 ± 15°. The heart is normally deviated to the left. An altered cardiac axis is often associated with outflow tract anomalies. The next image obtained is of the outflow tracts shows the aorta arising centrally in the heart from the left ventricle, and the pulmonary trunk arising from the anteriorly placed right ventricle and crossing to the fetal left over the ascending aorta. The three vessel view which is obtained by sliding the probe, is cephalad from the four-chamber view. The three vessels seen in this view are the pulmonary artery in longitudinal section, seen anteriorly and to the left; the aorta in transverse section, seen in the center; and the superior vena cava (SVC) in transverse section, seen to the right. The last image is that of the arch of aorta and has to be visualized in a sagittal view. It is narrow and round. The great vessels arise from this arch. On Figure 24.1: The ductal arch with color Doppler, the direction of flow can be seen to be descending aorta from the ascending aorta to the arch and then to the descending aorta. The ductal arch is flat and wide and resembles a hockey stick. The peak systolic velocity in the ductus arteriosus can be measured with pulsed Doppler. (Fig. 24.1).9 Thus, with real time imaging as well as simultaneously acquired M-mode, pulse wave and color Doppler interrogation most congenital cardiac anomalies and arrhythmias can be detected antenatally with precision (Fig. 24.2).

Accuracy of Fetal Echocardiography If only a four-chamber view is used, the detection rate of cardiac anomalies is 30 to 50% in low-risk

Figure 24.2: Color flow imaging showing ventricular inflow and spectral Doppler showing the normal flow pattern at mitral valve (For color version see Plate 2)

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Table 24.2: Congenital heart disease easily detected in four chamber and outflow tract views Four chamber view Major septation defects Significant chamber hypoplasia (HLHS/PA/IVS) Major valve lesions Ventricular dysfunction Rhythm abnormalities Pericardial effusion

Four chamber with great vessels TOF/DORV Transposition Truncus Arch abnormalities

pregnancies. If the outflow tracts are also visualized, the detection rate of anomalies increases to 78  to 83% (Figs 24.3 and 24.4) (Table 24.2). There are wellestablished guidelines by the American Society of Echocardiography regarding physicians’ training requirement for performing fetal echocardiography.10,11

Managing the Fetal Patient with Cardiovascular Disease: The Fetal Heart Program

Figure 24.3: Apical four chamber view

With the possibility of advanced imaging technologies and the ability to diagnose complex heart disease in the fetus, a new class of patient has emerged— the fetal heart patient. First, early knowledge of fetal cardiovascular disease offers potential parents the opportunity to consider termination of the pregnancy, if the parents so desire. If the decision is to continue the pregnancy, an intense perinatal and neonatal monitoring and care is advised. During this period, from diagnosis to delivery a variety of educational services should be offered including genetic counsel- Figure 24.4: Apical five chamber view ling. A number of centers have developed fetal heart which includes additionally the left ventricular outflow tract and aorta programs in which these services can be offered in a Abbreviations: LV, Left ventricle; AO, coordinated manner with continuum of care from the Aorta; LA, Left artery womb to the operating room. Management of various groups of structural cardiovascular malformations detected in antenatal period are shown in Flow charts 24.1 and 24.2.12

Atrioventricular Septal Defect This is the commonest of the serious structural abnormality seen on fetal echocardiography. Down’s syndrome is commonly associated and other complex cardiac lesions include left atrial isomerism, complete heart block and nonimmune hydrops. In the complete form, persistent common atrioventricular canal, the tricuspid and mitral valve are fused in a large single atrioventricular valve that opens above into the atria and bridges the two ventricles. The common atrioventricular valve may be incompetent with regurgitation leading to

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Flow chart 24.2: Protocol for management of specific cardiac anomalies detected in fetus

congestive heart failure. The management strategies in most patients with these defects are to advice a normal delivery as surgical repair is easier in term neonates. The prognosis is poor if compounded by chromosomal anomalies and other cardiac and noncardiac anomalies where therapeutic termination of pregnancy may be offered.

Hypoplastic Left and Right Heart Syndrome The second most frequent lesion detected in most series is hypoplastic heart syndrome. Progressive ventricular hypertrophy, endocardial fibroelastosis of the obstructed ventricle leads to cardiac failure and fetal loss. Certain centers in developed countries offer intervention by means of catheter dilation in an attempt to arrest the progressive obstruction to ventricular outflow but with limited success.13,14 Presently in our setting, the best option in a case with

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hypoplastic left heart syndrome is to offer medical termination of pregnancy to the potential parents. In the hypoplastic right heart the pregnancy is continued, with advise to deliver these fetuses in an institution offering specialized and intensive perinatal care and starting prostaglandin infusion immediately after birth to keep the ductus patent. Early surgical intervention and staged palliative repair is offered postnatally. Figure 24.5: Fetal echocardiography Tricuspid Regurgitation with or without showing Ebstein’s anomaly with abnorAssociated Tricuspid Dysplasia mal tricuspid valve and dilated RA It is not uncommon to find mild to moderate tricuspid regurgitation on fetal echocardiography, but most of them are benign and secondary to high pulmonary pressures. The follow-up of these fetuses in neonatal period generally shows regression of right ventricular hypertrophy and tricuspid regurgitation. It is important to distinguish these from the structurally abnormal and dysplastic tricuspid valve conditions like Ebstein’s where the right ventricular cavity is small with associated severe tricuspid regurgitation (Fig. 24.5). Most of these fetuses in addition have Figure 24.6: VSD with over-riding of severe hydrops, heart failure or complete heart block aorta and right ventricular dilatation suggestive of tetralogy of Fallot with a high incidence of fetal or neonatal death.

Conotruncal Anomalies Conotruncal anomalies include transposition of great vessels, double outlet right ventricle, tetralogy of Fallot and its variants and persistent truncus arteriosus (Fig. 24.6). This group of lesions are compatible with normal fetal development and survival. In most lesions, early corrective surgery can be offered postnatally with a fairly good prognosis and a decreased morbidity and mortality. Associated cardiac, noncardiac lesions and chromosomal anomalies have to be ruled out. Transposition of great vessels with intact ventricular septum need prostaglandin infusion in neonatal period to keep the ductus arteriosus patent. Univentricular Hearts These complex forms of cardiac defects are usually associated with fetal losses because of nonimmune hydrops and hence carry poor prognosis. In cases where pregnancy is wished to be continued, a normal delivery is advocated, with staged univentricular repair in infancy.

Management of Fetal Arrhythmias (Flow chart 24.3) Fetal arrhythmia assessment can at times be a challenging task. The routine evaluation of fetal heart rate and rhythm has relied largely on the use of M‐mode and Doppler techniques, which provide information about mechanical activity of the atria and ventricles which reflect indi-

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Pediatric Cardiology Flow chart 24.3: Protocol management of fetus with arrhythmia

rectly the electrophysiological events. Additionally, cardiac dimensions, presence of hydrops and ventricular functions can be assessed to determine the hemodynamic consequences of these arrhythmias on the fetus. Most cases of fetal arrhythmias are benign the commonest being premature atrial or ventricular contractions. More serious arrhythmias include suFigure 24.7: Fetal M-mode echocardipraventricular tachycardia, atrial flutter/fibrillation, ography showing ectopic atrial beats ventricular tachycardia and complete heart block. Some of these arrhythmias may be associated with underlying structural heart disease (Fig. 24.7).15 Fetal tachycardia is defined as sustained heart rate of more than 200 bpm which can lead to fetal cardiac insufficiency and fetal death. The mother should also be advised to avoid caffeine and sympathomimetic drugs. Poor outcome is observed if any three of the seven criteria are present, i.e. fetal HR (> 200 bpm), hydrops, cardiomegaly (heart area/chest area— HA/CA > 0.42), atrioventricular valve regurgitation, fractional shortening (FS)< 25% suggestive

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of ventricular dysfunction, reversal of flow in the IVC and distended hepatic and umbilical veins > 6 mm, warranting fetal therapy. If the fetus is near term with good lung maturity and absence of hydrops, an early delivery with institution of an antiarrhythmic treatment to the neonate is advised. If the fetus is premature with a poor lung maturity and associated hydrops, fetal antiarrhythmic treatment is advised can be achieved through maternally administered medications or a direct instillation into intra-amniotic fluid or umbilical vessels. Fetal bradycardia is defined as sustained heart rate of less than 100 bpm. An associated structurally abnormal fetal heart carries a poor prognosis. If the heart is structurally normal, maternal systemic lupus has to be excluded as the heart block is caused by circulating antibodies, specially anti-Ro and anti-La. These antibodies cross the placenta and damage the fetal conduction tissue producing complete heart block. The bradycardia is generally welltolerated but a small number of fetuses decompensate producing intrauterine heart failure. Fetus with ventricular rate less than 55 bpm and an atrial rates less than 80 bpm with or without hydrops indicate poor prognosis. Maternal therapy with steroids and immunoglobulin has been tried with success in an attempt to arrest the destruction of fetal conduction pathways. In these cases maternal administration of sympathomimetics such as isoproterenol, terbutaline or salbutamol is advocated with an early delivery and postnatal pacemaker implantation.16,17

Fetal Congestive Heart Failure Squeeze of the heart is often a visual impression. Fetal heart failure can be seen with disorders of cardiac rhythm, abnormal peripheral impedances, anemia, valve regurgitation, or myocardial dysfunction. Fetal cardiac functions can be quantified by using traditional M-mode imaging to provide information on wall thickness and ventricular shortening fraction. Cardiomegaly, severe atrio-ventricular valar regurgitation, abnormal venous Doppler tracings and abnormal myocardial functional indices are generally suggestive of fetal heart failure and usually precede the effusions and fetal hydrops state. 18

Impact of Fetal Echocardiography on Postnatal Outcome Early antenatal detection of cardiac anomalies offers the possibility of either termination of pregnancy or transfer of mother with fetus to a setup geared with a better antenatal care, delivery, and postnatal care. This translates to better outcomes for neonates with complex heart diseases requiring immediate interventions or surgery in the neonatal period. Additionally, prenatal detection of cardiac defects has led to a skewed reduction of children born with complex hearts and an increased incidence of neonates diagnosed with cardiovascular defects.19

Benefits of Fetal Echocardiography6 Fetal echocardiography has definite benefits as listed below: 1. A normal fetal scan is very reassuring for a family with a previous child affected with CHD. 2. Counselling and education of the potential parents allows them to be better prepared psychologically at the time of delivery. If a serious defect is detected, such as hypoplastic left heart syndrome, parents can be given a choice of termination of pregnancy.20.21

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3. The fetus can be transported in utero and baby delivered in a center well-equipped with neonatal cardiac care, thus, allowing a smooth transition from pre- to postnatal life. Timely institution of prostaglandin infusion for duct dependent lesions helps in avoiding acidosis and hypoxia. 4. Literature reviews state a better immediate survival rates with improved long-term and neurologic outcome.22 5. Management of arrhythmia in utero can be life-saving and if features of hydrops are present, an early delivery can be undertaken if drug therapy is not effective. 6. Fetal echocardiography will play a major role in future to guide in utero treatment to some cardiac defects which are amenable to surgery and interventions.23

INTRAUTERINE INTERVENTIONS The primary aim of prenatal intervention in congenital heart disease is to reverse the pathological process and to preserve cardiac structure and function, thereby preventing postnatal disease. A secondary aim of prenatal intervention is to modify the severity of the disease to enhance postnatal surgical outcome. Balloon dilatation of the aortic or pulmonary valve has been performed in late-gestation in human fetuses with failing left or right ventricles, but the technical success of such fetal valvuloplasty is currently poor, and the indications for fetal intervention remain limited.20 If antegrade flow could be established earlier in gestation, perhaps normal or near-normal left or right heart growth and function can be ensured.   Neonatal alert in fetuses with duct dependent lesions: The first step in all duct-dependent lesions diagnosed antenatally, such as critical left heart obstructive lesions, transposition of the great arteries and pulmonary atresia, is fetal transport in the mother’s womb with a planned delivery at a site where neonatology, pediatric cardiology, and congenital heart surgery services are readily available. Planning allows for prostaglandin and mechanical ventilation, to be available, if needed while also allowing the mother to remain in close proximity to the infant.24

Counselling Potential Parents For counselling purposes cardiac malformations can be divided into ‘good’—those that are easily treatable and not affecting the child in the long-term, ‘intermediate’—those that can be successfully repaired surgically, but which are likely to affect the long-term survival, and ‘bad’—those lesions likely to have a deleterious effect during childhood and on the chance of reaching healthy adult life.

CONCLUSION Improvements in the antenatal diagnosis of cardiac anomalies have resulted in a significant reduction in neonatal morbidity and mortality.With early diagnosis, a good antenatal and postnatal care can be offered to a baby with a cardiac anomaly and the potential parents can also be prepared emotionally and financially.   In the present era of congenital heart surgery, the whole focus is to repair the cardiac defects early in life, and techniques may eventually advance to the fetal realm. The diagnosis of severe cardiac malformations prenatally may

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prevent postnatal hemodynamic decompensating, lead to better preoperative condition, and potentially result in better overall survival and neurodevelopmental outcome.

REFERENCES 1. Kovalchin JP, Silverman NH, Frank L. The impact of fetal echocardiography. Pediatr Cardiol. 2004; 25:299–306. 2. Rychik J. Frontiers in fetal cardiovascular disease. Pediatr Clin N Am. 2004;51:1489–502. 3. Allan LD. A practical approach to fetal heart scanning. Seem Perinatal. 2000;324–30. 4. Heffner E, Schuler T, Metzenbauer M, Schuchter K, Phillipp K. Increased nuchal translucency and congenital heart defects in a low-risk population. Prenat Diagn. 2003;23:985–89.  5. Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilizaion. N Engl J Med. 2002;346:725–30. 6. Saxena A, Soni NR. Fetal echocardiography: Where are we? Indian J Pediatr. 2005:72:603–08. 7. Forbus GA, Atz AM, Shirali GS. Implications and limitations of an abnormal fetal echocardiogram. Am J Cardiol. 2004;94:688–89. 8. Chasen S, Sharma G, Kalish R, Chervenak F. First-trimester screening for aneuploidy with fetal nuchal translucency in a United States population. Ultrasound Obstet Gynecol. 2003;22(2):149–51. 9. Bronshtein M, Zimmer E. The sonographic approach to the detection of fetal cardiac anomalies at early pregnancy. Ultrasound Obstet Gynecol. 2002;19(4):360–65. 10. Rychik J, Ayres N, Cuneo B, et al. American Society of Echocardiography guidelines and standards for performance of the fetal echocardiogram. J Am Soc Echocardiogr. 2004;17:803–10. 11. Kitchiner D. Antenatal detection of congenital heart disease. Curr Paediatr. 2004;14:39–44. 12. Carvalho J, Mavrides E, Shinebourne E, et al. Improving the effectiveness of routine prenatal screening for major congenital heart defects. Heart. 2002;88(4):387–91. 13. Verheijen P, Lisowski L, Stoutenbeek P, et al. Lactacidosis in the neonate is minimized by prenatal detection of congenital heart disease. Ultrasound Obstet Gynecol. 2002;19(6):552–55. 14. Tworetzky W, Mc Elhinney DB, Reddy VM, et al. Does prenatal diagnosis of  hypoplastic left heart lead to improved surgical outcome? J Am Coll Cardiol. 1998;13:71–5. 15. Lisa K Hornberger. Echocardiographic assessment of fetal arrhythmias. Heart. 2007;93(11):1331–33. 16. Simpson LL. Fetal supraventricular tachycardias: Diagnosis and management. Sem Perinatol 2000;24:360–72. 17. Groves AM, Allan LD, Rosenthal E. Therapeutic trail of sympathomimetics in three cases of complete heart block in the fetus. Circulation. 1995;92:3394–96. 18. Chaubal NG, Chaubal J. Fetal echocardiography. Indian J Radiol Imaging. 2009;19:60–8. 19. Mc Elhinney DB, Lock J, Keane JF, et al. Left heart growth, function, and reintervention after balloon aortic valvuloplasty for neonatal aortic stenosis. Circulation. 2005;111:451–58. 20. Kohl T, Sharland G, Allan LD, Gembruch U, Chaoui R, Lopez LM, et al. World experience of percutaneous ultrasound guided balloon valvuloplasty in human fetus with severe aortic valve obstruction. Am J Cardiol. 2000;85:1230–33. 21. Allan LD, Huggon IC. Counselling following a diagnosis of congenital heart disease. Prenat Diagn. 2004;24:1136–42. 22. Montana E, Khoury MJ, Cragan JD, et al. Trends and outcomes after prenatal diagnosis of cardiac malformations by fetal echocardiography in a well-defined birth population, Atlanta, Georgia. J Am Coll Cardiol. 1990–1994;28:1805–09. 23. Rychik J, Tian T, Cohen MS, Ewing SG, Cohen D, Howell LJ, et al. Acute cardiovascular effects of fetal surgery in the human. Circulation. 2004;110:1549–56. 24. Harrison MR. Fetal surgery: Trials, tribulations, and turf. J Pediatr Surg. 2003;38:275–82.

25

Diagnosis and Initial Management of Heart Disease in the Newborn

R Krishna Kumar

INTRODUCTION The incidence of congenital heart disease (CHD) is estimated at 0.4 to 0.8% in studies from various parts of the world.1-7 Our large population of over one billion clearly underscores the magnitude of the problem of CHD. Many congenital heart defects can now undergo definitive surgical or transcatheter procedures with excellent immediate and long-term results. This is particularly true if we intervene early. For these reasons, the focus of pediatric cardiologists has shifted to the infant and newborn, and many congenital cardiac lesions are now addressed in this age group. The facilities of comprehensive neonatal cardiac care are, in particular, very much limited in India as of now but the situation is likely to change with the establishment of a number of pediatric cardiac centers.8,9 The total numbers of newborns in India with heart disease that receive treatment probably represent a tiny fraction of the total number of newborns with critical CHD (CHD that is usually fatal without early specific intervention) in the country.7 Thus, the vast majority newborns with serious CHD are probably dying before they could be referred to a center with expertize. Heart diseases that manifest during newborn period very often require urgent attention. Prompt treatment can often yield gratifying results and many instances excellent long-term event free survival can be expected. Today, some form of palliative or definitive treatment is feasible for most newborns with CHD. Table 25.1 lists the common cardiac emergencies at birth. Successful management of a newborn with congenital heart disease requires careful attention to a number of steps starting with recognition of heart disease in the newborn to initial resuscitation, transport to a pediatric cardiac center, assessment and detailed diagnosis and palliative or definitive procedure at the pediatric cardiac center. This chapter outlines the principles involved in each of the steps.

DIAGNOSIS OF HEART DISEASE IN THE NEWBORN One of the major reasons for the delay in referral of infants with significant heart disease is failure to suspect heart disease in the newborn baby at initial clinical evaluation. Clinical diagnosis

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Table 25.1: Cardiac emergencies in the newborn Physiologic category

Conditions

Manifestation

Duct dependent systemic blood flow*

Hypoplastic left heart syndrome, critical coarctation, interruption of aortic arch, critical aortic stenosis

Heart failure, shock, circulatory failure, acidosis

Duct dependent pulmonary blood flow*

Pulmonary atresia, critical pulmonary stenosis, Ebstein anomaly

Cyanosis, hypoxia

Obstruction of pulmonary venous return

Obstructed total anomalous pulmonary venous return, mitral atresia with a restrictive patent foramen ovale

Cyanosis, hypoxia, heart failure

Parallel circulation with poor mixing

D-transposition with intact ventricular septum

Cyanosis, hypoxia

Valve regurgitation

Congenital mitral valve regurgitation

Heart failure

High-output state

AV malformations (usually intracranial)

Heart failure

Myocardial dysfunction

Myocardial diseases (inflammatory and metabolic)

Heart failure

Tachyarrhythmia

Atrial flutter, neonatal atrioventricular reentrant tachycardias, ectopic trial tachycardia

Tachycardia, heart failure

Bradyarrhythmia

Complete heart block

Bradycardia, heart failure

*Some of the duct dependent conditions (critical PS, AS, coarctation) manifest with varying severity. The most severe forms manifest early (in the first few days) with absolute dependence on the duct for survival. Others may manifest later in the neonatal period (first few weeks) with heart failure or cyanosis and may not be strictly “duct dependent”.

of heart disease in the newborn can be quite challenging. Manifestations of potentially lifethreatening CHD are often subtle and can be confused with noncardiac conditions. For instance, low cardiac output states resulting from critical aortic stenosis or other left-sided obstructive lesions may be mistaken for sepsis. Unfortunately, the cost of failure to recognize CHD is, not infrequently, death. This is because many forms of CHD that manifest in the early neonatal period are fatal without specific interventions. It is possible to recognize CHD through careful clinical evaluation using the principles outlined below and a few additional tests. The diagnostic strategy for suspected CHD in the newborn is largely dictated by the condition of the newborn.

Clinical Clues Clinical clues are often subtle. However, the trained pediatrician or neonatologist often picks them consistently. Persistent tachypnea (respiratory rate > 60 /min) is a consistent finding in most serious congenital heart defects in newborns. Over a few hours of observation, it is often possible distinguish transient from persistent tachypnea. Evidence of respiratory distress in the form of grunting respiration, intercostal or subcostal retractions, flaring of alae nasae do not consistently accompany tachypnea. Cyanosis of extremities and lips is sometimes not easy to identify. Apart from a trained eye, there is the need for good lighting. Any suspicion of cyanosis should be verified by measurement of oxygen saturation.

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Cardiovascular Examination A thorough and systematic cardiovascular examination provides valuable clues to the presence of heart disease. With practice such an examination can be accomplished in a short time. For the pediatrician, a thorough familiarization with what is normal is a useful initial step. It is useful to answer the following questions that can serve as a checklist for a preliminary cardiac examination. This checklist is not at all comprehensive and is designed primarily for answering the question: Does the patient have heart disease? It can also help, identify the broad physiologic category of heart defect.

Are the Arterial Pulses Normal? •• Is the pulse volume normal or increased? •• Is there a discrepancy of pulsation in any of the four extremities? A careful evaluation of pulses in all extremities should always be a part of physical examination. Coarctation is readily diagnosed when weak femoral pulses are detected in comparison to brachial or radial pulses. While a four extremity blood pressure measurement should ideally accompany clinical evaluation in all children with suspected heart disease, it is not always feasible. Nonetheless, when a discrepancy in pulses is suspected, four extremity blood pressure measurements should be obtained. An automated noninvasive blood pressure instrument is preferred over manual recording for four extremity blood pressure measurements. Does the Precordium Feel Normal? •• Are there visible precordial pulses? •• Is the apex beat displaced, hyperdynamic or heaving? •• Is there a thrill palpable? Are the Heart Sounds Normal? •• Can the two components of the second heart sound be separated? •• Is there an additional heart sound in diastole (such as S3)? •• Are there any additional systolic sounds (ejection clicks)? Is (or are) there a Murmur (or murmurs)? If so: •• Is it systolic or diastolic or both systolic and diastolic (diastolic murmurs always have a structural basis)? •• Is it loud (grade 3 or louder murmurs are seldom innocent)?

Oxygen Saturation In view of relative lack of sensitivity of the routine clinical examination for detection of CHD and the potential implications is not diagnosing critical CHD at birth, recent studies have focused on the use of pulse oxymetry for detection of CHD. Koppel et al reported a sensitivity of 60% and specificity of 99.95%, for pulse oxymetry in detecting significant CHD.10 Similar results have been reported in other studies as well.11,12 Most of these studies have used of cutoff of < 95% saturation as indicative of significant CHD. Hoke et al reported that lower limb saturation less than 92% in room air or 7% lower than that in the upper extremity could suggest critical left heart obstructive disease in the newborn.13

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It is important to pay attention to details while recording oxygen saturations. There should be good correlation between the heart rate recorded in the pulse oximeter and the actual heart rates in the ECG monitor. The measured oxygen saturation has to remain consistent (variations of less than 1 to 3%) over 30 seconds.

ECG and Chest X-ray Beyond the neonatal period, a normal ECG and chest X-ray makes the diagnosis of a hemodynamically significant heart defect unlikely. In newborns, however, ECG and chest X-ray changes, may take a few days to evolve. For the newborn, particularly in the first few days a “normal” ECG and a normal X-ray does not rule out serious heart disease. Notwithstanding this important caveat, important clues can often be obtained from the chest X-ray and ECG. Like in any situation the chest X-ray needs to be looked at systematically. Specific attention needs to be paid to heart size, lung vascularity and, the situs. Although certain conditions are associated with specific cardiac contours (e.g. the “egg on side” contour in transposition), their specificity is very low. The presence of a right aortic arch is a useful clue and may be seen in patients with tetralogy of Fallot’s or persistent truncus arteriosus. In young infants, assessing heart disease is often difficult because of a large thymus. The thymus is characteristically a soft structure in the anterior mediastinum, which imprints the anterior cartilaginous portion of the ribs and creates a characteristic undulating or rippled appearance on the anteroposterior film. Occasionally, a lateral film is necessary to ensure that the structure of the thymus is in the anterior mediastinum and that indeed the heart is not enlarged. On a lateral chest radiograph of a normal child, a line from the trachea to the diaphragm does not usually intersect the heart. On the other hand, when cardiomegaly is present, the heart is posterior to the line. The radiographic assessment of pulmonary blood flow is difficult even for the experienced observer but it is even more difficult in an infant where the arteries and veins are small. Furthermore, pulmonary arterial flow in the neonate may be misleading because the patient may have a patent ductus arteriosus. Pulmonary venous hypertension typically occurs in association with obstructed TAPVC. This conditions often manifests on the chest X-ray as a ground-glass haze that is often mistaken for hyaline membrane disease.

Hyperoxia Test The hyperoxia test is frequently used to rule out critical CHD (conditions that are fatal without specific interventions in the newborn period). Examples of conditions that may be picked up by an abnormal hyperoxia test include transposition of great arteries, obstructed total anomalous pulmonary venous connection (TAPVC), conditions that are dependent on the patent ductus arteriosus for survival such as critical pulmonary stenosis, pulmonary atresia with or without a VSD, interrupted aortic arch, severe coarctation, hypoplastic left heart syndrome and critical aortic stenosis. This test is based on the principle that administration of 100% oxygen can raise the PO2 of the arterial blood to a much higher level in absence of shunting from cardiac causes. It requires estimation of PO2. This can be obtained from an arterial blood gas sample or, if available, a transcutaneous PO2 probe. A cutoff of 300 mm Hg after 10 minutes of 100%

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oxygen administered via a hood (or the endotracheal tube in inubated patients) has been recommended. Values of 300 mm Hg or above virtually rule out CHD. A PO2 of 200 mm Hg or more is also unusual for most forms of CHD, although a few conditions like persistent truncus arteriosus may have marked increase in pulmonary blood flow that can overcome the reduction in PO2 from the admixture physiology. Values below 100 mm Hg strongly suggest congenital heart disease. In conditions like transposition, pulmonary atresia and obstructed TAPVC, PO2 seldom rises above 70 mm Hg. During a hyperoxia test, it is important to include a sample from a “post-ductal” site. Either femoral artery or the umbilical artery can be used for arterial blood gas samples. For a transcutaneous probe the lower quadrant of the abdomen may be used. Absence of adequate standardization is the single biggest limitation of the hyperoxia test. Not uncommonly, PO2 values between 100 and 200 mm Hg are obtained. This constitutes a gray zone where the results need to be viewed in context of other clinical findings.

Echocardiogram When doubts persist whether a patient has CHD or not despite a thorough clinical exam and chest X-ray, ECG, and hyperoxia test, an echocardiogram should be arranged. The threshold for obtaining an echocardiogram is much lower in institutions that have ready access to the investigation. This is especially true if the patient’s condition does not permit adequate clinical evaluation. Such a situation is not infrequent in neonates and in such emergencies, it may be appropriate to bypass obtaining an ECG and chest X-ray. Portable and hand held echocardiography is now feasible and is increasingly being used. It is also now possible to train the pediatricians and neonatologists to perform a basic echocardiography screen for serious congenital heart disease. Initial resuscitation and stabilization of a newborn with suspected heart disease.

Airway and Respiratory Support Like in any other emergency situation a stable airway needs to be established first. Newborns with severe respiratory distress should immediately receive bag and mask ventilation and 100% oxygen may be used for this purpose (although, later the oxygen concentration may need to be reduced). If respiratory distress continues to be profound after the initial resuscitation the newborn should be intubated and mechanical ventilation should be initiated. Neuromuscular blockade, sedation and atropine are recommended prior to intubation. Even in the most emergent situations sufficient time is often available to organize the requirements for performing intubation. It is useful to memorize the following checklist of items required for performing endotracheal intubation expeditiously: 1. Control of the airway and preoxygenation with bag and mask: Make sure that the Ambu bag and mask of appropriate size is available. Test the Ambu bag and make sure that it works well, the bag does not leak and the valve works well. If the physician is alone at the time of intubation, she/he should first take control of the airway and give instructions to ensure that points 2 to 9 listed below are all carried out.

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2. Suction: Choose a suction catheter of appropriate size. Make sure that the suction apparatus works. 3. Access: Ensure that a reliable peripheral or central venous access has been obtained. 4. Monitoring: ECG monitoring and monitoring of oxygen saturation throughout the procedure by pulse oxymeter is required and this should be instituted prior to endotracheal intubation. 5. Medications: All medications required for the intubation should be available. It is strongly recommended in newborns with heart disease that intubation should be performed after sedation and neuromuscular paralysis to avoid unnecessary stress on the cardiovascular system. It is a good idea to standardize a few protocols for drugs and use them for most cases. All dosages should be planned in advance and the drugs should be loaded and kept ready. Medications include atropine (0.02 mg/kg), ketamine 1 to 2 mg/kg bolus dose, (alternatives: Morphine: 0.1 to 0.2 mg/kg IV with or without Midazolam: 0.1 to 0.2 mg /Kg), neuromuscular paralytic agents: (Vecuronium 0.1 to 0.2 mg/kg or succinylcholine 2 mg/kg). 6. The laryngoscope: Straight and curved blades of various sizes. 7. The endotracheal tube and stilette: For newborns, endotracheal tubes (sizes 2.5, 3 and 3.5 mm) should be available and kept ready. Typically for a term newborn size 3 works in most situations. Occasionally, the airways will safely allow the use of a 3.5 mm tube. The 2.5 mm tube may be required for small preterm newborns. 8. Maggil forceps if elective nasotracheal intubation is planned or if an orotracheal position is to be changed to a nasotracheal position. 9. Items required for fixation of the tube. The decision to intubate the newborn and initiate mechanical ventilation electively prior to transport requires consideration of the following variables: condition of the newborn in terms of severity of cyanosis, hemodynamic stability, gestational age and transport distance.

Access A secure peripheral or central intravenous access is very essential. Inotropic agents with vasoconstrictor properties such as dopamine and adrenaline can only be administered via a reliable central access. Extravasation of these agents into the subcutaneous tissue can result in extensive tissue necrosis in the event a peripheral line leaks. In the newborn infant, for the first 3 to 5 days, an umbilical venous line can be easily obtained. Alternatives include a jugular or a subclavian access. Generally, both these routes are somewhat difficult and require some expertize and experience, particularly in centers without an infant or a neonatal surgical program. The femoral route should be avoided at all costs before the cardiac diagnosis is established. This is because the either femoral vein may be required for cardiac catheterization in the immediate or distant future. For the same reason the femoral artery also should not be cannulated and repeated blood sampling should not be attempted from either groin. If central access is unavailable and an inotrope needs to be infused, dobutamine may be a reasonable choice. It may be impractical to obtain arterial access prior to transport and unnecessary arterial punctures for blood gas sampling should be avoided because these sites will be required

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for placement of an arterial line prior to definitive surgery. An arterial sample is, however, necessary for ABG analysis. If the institution where the child is initially resuscitated has a blood gas analysis facility, an umbilical arterial sample should be obtained.

Oxygen The potential dangers of excessive oxygen in a newborn with suspected heart disease include acceleration of closure of the ductus arteriosus and unacceptable decline in the pulmonary vascular resistance. Both these situations can have catastrophic consequences. Duct closure is fatal in duct dependent lesions. A marked decline in pulmonary vascular resistance translates into excessive pulmonary blood flow, often at the cost of reduced systemic blood flow. This is particularly likely to happen in duct dependent conditions. For these reasons, the FiO2 needs to be titrated to maintain an oxygen saturation of 85 ± 5%. In most situations this allows a reasonable balance between pulmonary and systemic blood flows.

Prostaglandin—Availability, Administration and Alternatives Prostaglandin E1 (available in India as Prostin VR) is a very essential drug and should be available in every newborn nursery. It can restore ductal patency in most newborns with closing ducts and is, therefore, life-saving in duct dependent situations. Its effect is usually confirmed by improving saturations in newborns with duct dependent pulmonary circulation and resolution of the circulatory failure and acidosis in newborns with duct dependent systemic circulation. Its efficacy declines somewhat with increasing age particularly after 15 days and it is usually not effective in opening a closed duct after 30 days. The initial dose of prostaglandin is 0.05 to 0.1 mg/kg/min. Once the duct has opened up (this can be confirmed by the clinical response or by echocardiography), the dose may be reduced to as low as 0.01 mg/kg/min. This allows maintenance of ductal patency with minimal adverse effects. Adverse effects of PGE1 infusion include apnea, bradycardia, tachycardia, hypotension, fever, gastric distension and seizures. Leukocytosis frequently accompanies prostaglandin use. Administration over several days may result in increased lung and body water from capillary leak, thrombocytopenia, gastric outlet obstruction and cortical hyperostosis. Prostaglandin is available in most cities in India. Newborn nurseries should endeavor to obtain one or two ampoules of the drug and this should be stored in the refrigerator and replaced when consumed. The drug is expensive (~ Rs. 6000 to 8000). It is, however, possible to extend the use of a single ampoule to about a week by using only small amounts of the drug to prepare the infusion on a daily basis. The remainder of the drug can be aspirated from the ampoule under strict sterile precautions (preferably under a laminar flow system) and stored in a sealed 1-cc syringe for as long as a week. Reducing the maintenance dose to a minimum can also help prolong the availability. In the absence of prostaglandin, atropine 0.02 mg/kg boluses may be used as an alternative. For patients with transposition and intact ventricular septum, an umbilical venous catheter may be passed into the left atrium under fluoroscopic guidance and this could “stent” the atrial septum open to maintain reasonable oxygen saturations until transport to a center for balloon septostomy can be accomplished.

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CIRCULATORY SUPPORT AND INOTROPES Colloid or Crystalloids Hypotension after PGE1 infusion is common. It is the result of relative intravascular volume depletion because of a combination of peripheral vasodilation and increased vascular permeability. It is best treated by administration of 10 to 20 mL/kg of a colloid solution (5% albumin or plasma) as a bolus. If colloid solutions are unavailable, crystalloid solutions may be used in the same volume. Inotropes are likely to be ineffective unless adequate volume replacement is done.

Dopamine This should only be administered via a central line. Doses range from 5 to 15 mg/kg. This is often the first choice in most centers. It has vasoconstrictor as well as inotropic effects and is often the only agent necessary.

Dobutamine Perhaps the only reason to use dobutamine during initial resuscitation is that it done not require a central access. It has a potent inotropic effect and some vasodilatory effects. For this reason, it is not as effective as dopamine in hypotension, particularly if the myocardial contractility is normal.

Adrenaline It has powerful vasoconstrictor and inotropic effects but is seldom required as an infusion prior to or during transportation unless the neonate sustains severe hypotension or a cardiac arrest. Central access is a must and doses range from 0.01 to 0.2 mg/kg/min.

Isoproterenol Newborns with congenital complete heart block can be born with severe bradycardia and infusions of isoproterenol (0.01 to 0.05 mg/kg/min) may be initiated prior to transport to center with facilities for pacemaker implantation.

Basic Laboratory Tests Conditions that compromise systemic circulation (such as hypoplastic left heart syndrome) are likely to have an impact on liver and renal functions. A baseline ABG is very useful. Impaired systemic circulation is likely to result in metabolic acidosis. Conditions such as transposition and duct dependent pulmonary circulation and obstructed TAPVC are like to be associated with significant hypoxia. A septic screen (CBC, CRP, micro-ESR and blood cultures) should be performed at a low threshold. Sepsis in a newborn can have a significant impact on the immediate management strategies after referral.

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TRANSPORTATION OF SICK NEWBORN INFANTS WITH HEART DISEASE Communication The decision to transport a newborn to a tertiary referral center with facilities for specialized care of neonates and infants with heart disease should be a joint one involving the referring pediatrician and the pediatric cardiology team. A thorough communication of important information that is obtained at the referring center helps to reduce problems during transport and helps to prepare the pediatric cardiac center to receive the newborn. Emergency procedures can be planned on arrival with minimal delay. For example, if a newborn is being transported with a diagnosis of transposition, the cath lab can be prepared to perform a balloon septostomy with minimal delay after arrival. The following list could serve as a checklist of points to be communicated by a pediatrician or a neonatologist to the pediatric cardiology center prior to transportation of a newborn with suspected heart disease.

Prenatal Background Term or preterm, birth order, age of mother, important maternal conditions. Birth Mode of delivery, relevant antenatal issues, Apgar scores, birth weight, significant postnatal events if any? Clinical presentation: Why was heart disease suspected? Current condition: Vitals (heart rate, respiratory rate, oxygen saturation, peripheral circulation), lab tests (a baseline arterial blood gas analysis report is valuable, if available), feeding.

Preliminary Diagnosis of the Cardiovascular Condition Results of the physical examination, chest X-ray, ECG and echocardiogram. What has been done so far to resuscitate the newborn? What access has been obtained? Is the child ventilated or breathing spontaneously? What medications have been given (specifically, inotropes, prostaglandin)? Relevant socioeconomic issues: What is the social and economic background of the family? Which family members are likely to accompany the child? How much has been communicated to them? Logistics: Transport distance, mode of transport and transporting personnel? Expected time of departure and arrival?

Personnel for Neonatal Transport Whenever feasible, the newborn should be accompanied by the resident neonatologist or pediatrician taking care of the baby and a nurse. Both the team members should be familiar with the underlying condition and should be aware of the potential problems the newborn may face during transport.

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Monitoring during Transport Ideally, it is necessary to continuously monitor ECG and oxygen saturations during transportation. This may not always be feasible, particularly in our environment. Often it is only realistic to monitor vital signs. Keeping a regular watch on respiration, heart rates and the overall general condition may be all that is feasible. When the newborn reaches the referral center, it is necessary to summarize the condition during transport and indicate important events, if any that occurred during transport. Care of the Newborn during Transport A secure airway and an access are vital. Newborns on prostaglandin can have periods of apnea. For this reason, a number of units in the west would routinely intubate and mechanically ventilate a newborn on prostaglandin infusion during transport. For a number of reasons this is not practical in the Indian scenario. Transportation while on prostaglandin infusion does amount to taking a calculated risk. The physician involved with the transport should be alert to this possibility and be ready to support respiration with a bag and a mask. Excessive oxygen (> 2l/min/ FiO2 > 40%) should be avoided during transport of most newborns with heart disease. This is probably advisable even if PGE1 is used to keep the duct open. High FiO2 reduces pulmonary vascular resistance and can result in excessive pulmonary blood flow at the cost of systemic circulation. This is particularly dangerous in hypoplastic left heart syndrome. Attention to other basic details such as temperature control, fluid balance, avoidance of hypoglycemia and hypocalcemia are all mandatory as in any neonatal transport situations. Asepsis Sepsis frequently complicates the management of newborns with heart disease. The potential for nosocomial sepsis is particularly high for sick newborns that are being transported. A number of caregivers are likely to handle the child and invasion in the form of endotracheal intubation, central and peripheral line insertion are likely to have taken place. Meticulous attention to aseptic precautions is extremely important. All nurses and physicians handling the newborn have to be specifically instructed as many of them may not be routinely used to newborn transport.

Evaluation and Management at the Tertiary Care Center Detailed Diagnostic Evaluation After receiving the newborn and ensuring hemodynamic and respiratory stability, a comprehensive echocardiogram must be performed. This should not be a rushed study. No matter what the initial diagnosis is, the cardiologist performing the echo must pay attention to all components of a comprehensive checklist of items. These include: visceral and atrial situs, systemic and pulmonary veins, the atria, atrial septum, ventricles, ventricular septum, conotruncus, great vessels, aortic arch, and the ductus arteriosus. Once the heart defect(s) is/are identified, the physiology needs to be thoroughly described as well. Patients with tachyarrhythmia in the newborn period should undergo a detailed evaluation that should clearly identify the basic mechanism of the arrhythmia. This allows appropriate treatment (Table 25.2).

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Conditions

Specific Treatment

Comment

Hypoplastic left heart syndrome

Stage I palliation (Norwood operation)

Significant surgical mortality, often not practical in India because of significant long-term problems and requirement of multiple operations

Critical coarctation/ interruption

Primary surgical repair

Surgery is preferred over balloon dilation of aortic arch in coarctation (lower restenosis rates) excellent long-term outcomes

Critical aortic stenosis

Balloon valvotomy

Excellent intermediate—term results. Can be carried out with 90 to 95% success rate

Pulmonary atresia–intact ventricular septum

BT-Shunt, radiofrequency wire puncture of atretic pulmonary valve followed by balloon dilation or surgical restoration by RVOT patch, stenting of the patent arterial duct may also be required in addition

Treatment dictated by precise anatomic issues (extent of RV hypoplasia and tricuspid valve annulus dimension, presence of right ventricle dependent coronary circulation) and experience of the center

Pulmonary atresia with VSD or tetralogy of Fallot

Emergency BT shunt or stenting of the arterial duct

Definitive procedure later in life dictated other defects, “severe” by precise anatomy

Critical pulmonary stenosis

Balloon valvotomy

Excellent long-term outcomes. 5 to 10% immediate mortality

Obstructed total anomalous

Emergency surgical repair pulmonary venous return

Good long-term outcome; surgical mortality of 10 to 30%

D-transposition with intact ventricular septum

Balloon septostomy followed by arterial switch operation

Arterial switch needs to be performed in the first 21 to 28 days, after which a Senning operation is perhaps advisable

Vein of Galen AV fistula, AV malformations (usually intracranial)

Transcatheter coil, embolization

Results with coil embolization are generally poor especially if there are multiple communications

Myocardial diseases (inflammatory and metabolic)

Medical management

Digoxin, diuretics and ACE inhibitors, many patients improve with time

Tachyarrhythmias

Appropriate antiarrhythmic medications

Treatment dictated by precise identification of underlying mechanism of the arrhythmia

Complete heart block implantation

Temporary pacing followed by permanent pacemaker

Permanent pacemaker implantation is feasible in the first few days of life and excellent long-term outcomes can be expected

immediate

Assessment of End-organ Insult Preliminary investigations to identify the extent of end-organ injury must be carried out. These include liver and renal function tests. Typically, conditions presenting with shock or severe hypoxia are associated with varying degrees of liver enzyme and renal parameter elevation. Ideally, these patients are stabilized over the next several days to allow for recovery before definitive treatment is undertaken.

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Ruling out Sepsis It is vital to rule out ongoing sepsis whenever a newborn with suspected heart disease is received in a tertiary care center. A sepsis screen in the form of ESR, C reactive protein estimation, complete blood counts should be performed for all patients irrespective of their condition on arrival. It is reasonable to obtain a blood culture in all such newborns. Prophylactic antibiotics are generally not indicated unless the child shows clinical signs of sepsis. Specific Treatment at the Tertiary Center Specific treatment options in the tertiary center are largely dictated by the precise diagnosis and are listed in Table 25.2.

CONCLUSION It is reasonable to expect a good outcome for most newborns with heart disease after the initial definitive or palliative procedure. Timely detection of heart disease after birth and appropriate referral is the vital initial step. Careful attention to small details during the initial resuscitation and transport is also vital particularly if the newborn is acutely ill. At the referral institution, a detailed and thorough assessment of the heart disease should be followed by institution of the appropriate specific treatment strategy.

REFERENCES 1. Ferencz C, Rubin JD, McCarter RJ, Brenner JI, Neill CA, Perry LW, et al. Congenital heart disease: prevalence at live birth. The Baltimore-Washington Infant Study. Am J Epidem. 1985;12:31–6. 2. Fyler DC. Report of the New England Regional Infant Cardiac Program. Pediatrics. 1980;65:375–461. 3. Carlgren LE. The incidence of congenital heart disease in children born in Gothenburg. 1941–50. Br Heart J. 1959;18:40–50. 4. Hoffman JIE, Christianson R. Congenital heart disease in a cohort of 19,502 births with long-term follow-up. Am J Cardiol. 1978;42:641–7. 5. Feldt RH, Avasthey P, Yoshimasu F, et al. Incidence of congenital heart disease in children born to residents of Olmsted County, Minnesota 1950–1969. Mayo Clin Proc. 1971;46:794–9. 6. Bound JP, Logan WFWE. Incidence of congenital heart disease in Blackpool 1957–1971. Br heart J. 1977;39:445–50. 7. Dickinson DF, Arnold R, Wilkinson JL. Congenital heart disease among 160,480 liveborn children in Liverpool 1960 to 1969. Br Heart J. 1981;46:55–62. 8. Kumar RK. Congenital heart disease in the developing world. Congenital Cardiology Today (North American Edition). 2005;3:1–5. 9. Kumar RK, Tynan MJ. Catheter interventions for congenital heart disease in third world countries. Pediatric Cardiol. 2005;26:1–9. 10. Koppel KS, Druschel CM, Carter T, Goldberg BE, Mehta PN, et al. Effectiveness of pulse oximetry for screening for congenital heart disease in asymptomatic newborns. Pediatrics. 2003;111:451–5. 11. Reich JD, Miller S, Brogdon B, Casatelli J, Gomph T, Huhta JC, et al. The use of pulse oximetry to detect congenital heart disease. Journal of Pediatrics. 2003;142:268–72. 12. Richmond S, Reay G, Abu-Harb M. Routine Pulse oximetry in the asymptomatic newborn. Arch Dis Child Fetal Neonatal Ed. 2002;87(2):F83–8. 13. Hoke TR, Donohue PK, Bawa PK, Mitchell RD, Pathak A, Rowe PC, et al. Oxygen saturation as a screening test for critical congenital heart disease: A preliminary study. Pediatr Cardiol. 2002;23:403–9.

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Cardiac Implications of Changing Lifestyle: Prevention of Adult Cardiovascular Disease

S. Sivasankaran

INTRODUCTION Rapid transitions in nutrition and lifestyle have phenomenally altered the health of Indians, subjecting them to the present wildfire of non-communicable disease epidemic characterized by hypertension, diabetes mellitus, dyslipidemia, and obesity.1 Adult cardiovascular diseases and metabolic syndrome, represent the symptomatic or simultaneous occurrence of these risk factors in the same individual and these occur at least a decade earlier in the Indian subcontinent.2 These clinical syndromes represent only the tip of the iceberg which is the end result of decades of asymptomatic metabolic insult.3 We have clear guidelines to identify those who are obese and at risk of developing the risk factors.4 The challenge we face today in developing countries is to identify those who are not so overweight and succumb to lifestyle related diseases and to postpone the early onset of risk factors.5 For the second time in the history, United Nations held a high level meeting in 2011 to coordinate the preventive strategies against the non-communicable diseases.6 The four behavioral risk factors namely physical inactivity, unhealthy diet, tobacco use and alcohol consumption lead to four major non-communicable diseases namely diabetes, cardiovascular disease, chronic lung disease, and cancer, which account for more than two-third of present day mortality.7 The adverse effects of nutrition and health transition are more adverse in women which formed the basis of ‘Go Red for Women campaign’ by the American Heart Association since 2002.8 The younger age escalation of risk factors is exponential in women in the reproductive age group in India.9 This adverse metabolic profile of pregnant mothers have taken the issue of developmental origin of adult onset diseases beyond the concepts proposed by Barker’s hypothesis.10 There is an urgent need to redefine the mother and child care services so that maternal dysmetabolism is minimized to prevent the in utero programming of adult diseases.11 Adolescence is the last opportunity to achieve a healthy parenthood.

What Drives the Non-Communicable Disease Epidemic? One of the major drivers of chronic non-communicable disease is positive energy balance precipitated by unhealthy diet and physical inactivity especially in children and adolescents.12

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The other two behavioral risk factors like tobacco use and alcohol are initiated usually in the later half of adolescence in India.13 The obesogenic environment thus generated elicits a chronic over stimulation of the insulin-adipogenic axis, leading to the protean manifestations of hyperinsulinemia and or early beta cell failure.3 Lifestyle related diseases are the end result of the chronic stimulation of the insulin adipogenetic system akin to the side effects of chronic stimulation of renin-angiotensin aldosterone system.14 This system is very efficient in promptly maintaining euglycemia in the acute setting, when exposed to the obesogenic or insulinogenic stimuli.15 But chronic or repeated stimulation turns out to be catastrophic manifesting as hyperinsulinemia and metabolic syndrome terminating in overt beta cell failure.16 Three major subsets can be identified. Those who mount appropriate beta cell and adipocyte response to this insulinogenic environment develop high body mass indices (BMI).17 They develop various problems due to morbid obesity like snoring and osteoarthritis before succumbing to the later onset risk factors.Those who have inappropriate adipocyte function but adequate beta cell response develop various risk factors early with sarcopenic adiposity (less muscle more fat) and insulin resistance.18 Beta cell failure and diabetes occur later. Those with both inappropriate beta cell and adipocyte response will remain thin but will be diabetic at lower body mass indices and they develop a variety of secondary risk factors.19 In between this spectrum of lipoatrophic diabetes and morbid obesity we can have a variety of clinical manifestation of insulin resistance and adipocyte inflammation.20,21 In essence, those who develop obesity as well as those who fail to become obese in the obesogenic environment are at risk compared to those who maintain good BMI with adequate physical activity.22 Per-capita energy consumption has increased over the years.23 Per-capita consumption of refined food substance also has substantially increased with drastic decline in physical activity.24 Stress, pollution, and habituations make the process of modernization complete. The metabolic insult of isocaloric but refined food substance is more intense for children and low body mass individuals because of the lower body volume.25 There has been an additional fall in calorie needs of women because of the steady decline in fertility.26 Adipocyte dysfunction in the form of sarcopenic adiposity can be demonstrated in Indian children from in utero life and we perpetuate this during various stages of our life.27 Protecting the beta cell potential from intrauterine life and overcoming the sarcopenic adiposity will be the two major strategies of preventing the early onset of risk factors in Indians, in addition to the established methods of prevention.28 There has been a major decline in physical activity in children in India in the last three decades.29 Skeletal muscle provides ten times more insulin sensitivity than adipose tissue.30 Improving physical activity in children therefore is the optimal solution to sarcopenia induced by variety of in utero risk factors.31 Children are now overfed but are undernourished.32 The steady decline in body nutrients like vitamin B12, folic acid, vitamin D, and maternal dysmetabolism now affects the progeny, directly and by epigenetic mechanisms.11 Many of these deficiencies are evident and many more are hidden.33 The steady increase in obesity in women in the reproductive age group and gestational diabetes are evident.34 The increase in breast cancer incidence in the premenopausal age group and coronary events are now reported.35 Least recognized is the almost universal occurrence of vitamin D deficiency.36 Indian women stand highest risk for osteoporotic fractures.37 At least 45% of the human body needs to be

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exposed to the sun for at least for 2 hours to achieve vitamin D sufficiency.38 Unfortunately for a variety of sociocultural and religious reasons women in India cover their body too much and keep away from outdoor physical activity after adolescence. The sunshine deficit in a tropical country is easily avoidable.39 Pediatric prevention of adult onset diseases therefore needs a major target aimed at minimizing the maternal dysmetabolism which leads to younger age onset of risk factors in the developing world.40

MAGNITUDE AND DEFINITION OF THE PROBLEM Epidemiologic studies conducted in various parts of India have clearly shown that the lifestyle related diseases are on the increase.41 The state of Kerala leads India in terms of economic and health transition and 4 out of 5 adults are affected by lifestyle-related diseases, which develop at a younger age.42 Kerala is now the diabetic capital for India and Kerala.43 Studies from Kerala also has shown features of insulin resistance as a marker of diabetes onset.44 Kerala has the shown the highest increase in per capital calorie consumption over the last three decades and consumes almost double the amount of marketed products than rest of India.45 Kerala children now document the highest records of mean blood pressure which shows a step increase in girls correlating with the onset of puberty.46 Age adjusted cardiovascular mortality in Kerala is twice as that in the United States and thrice as that of Japan and much worse in women.47 The younger age of onset could be because of the earlier onset of risk factors or because of anticipation. Anticipation refers to the occurrence of a disorder at younger age in subsequent generations, and has been documented for lifestyle-related diseases like type 2 diabetes.48 High prevalence of low birth weight children, who harbour the substrate for younger age escalation of risk factors, surviving to adulthood, could be another reason.49 But the persistence of childhood stunting in Kerala, irrespective of good health services and increase in calorie consumption is an important evidence of additional in utero dysmetabolic factors driving the non-communicable disease epidemic in India.50 Additional information from the epidemiologic studies highlights the fact that more than 90% of the cardiovascular epidemic can be explained by 9 simple modifiable risk factors.2 These are six positively correlated risk factors like diabetes, hypertension, dyslipidemia, tobacco use, abdominal obesity and stress. The three risk factors with negative association are the physical activity, alcohol consumption, and vegetable and fruit consumption. But alcohol consumption in India had no protective effect, and was demonstrated to be harmful.51 Urbanization is associated with substantial reduction in physical activity and simultaneous increase in sumptuous consumption of energy dense refined food substances, stress, and habituation to the use of tobacco and alcohol. Children form easy culprits for the urbanization with increasing video screen viewing and susceptibility to peer pressure and industry-driven advertisements (Fig. 26.1). Parents in the developing countries have a misconception that the westernized food portions are healthy and stuff their children with adult portions expecting rapid growth and development.52 Children in urban India are put to tremendous stress in the form of entrance examinations, heavy syllabus and exit exams. They learn at least three languages in addition to the various subjects. Playgrounds are rare in many urban schools and physical education is non-existent

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Figure 26.1: The risks that children in modern societies face. The risks are shown as concentric circles. Proximate causes are shown in the center. In the periphery are societal changes that are responsible for the proximate causes. CVD: Cardiovascular disease

after the 8th grade. Children suffer four levels of teaching to cope up with the syllabus namely the school time, the extra class time, the tuition time, and the entrance coaching sessions, in addition to the bundle of homework and projects. All these positively encroach into the playtime of children and lead to tremendous stress, given the high parental expectation and society pressure. Peculiar sociocultural issues are more damaging to girls who keep their hair long, wear multi-layered uniforms, and avoid taking part in outdoor activities like, sports, cycling or swimming after puberty (Fig. 26.2). The recognition of these modifiable risk factors operating in young children therefore offers a large window, spanning decades to enforce effective preventive strategies. On the other hand, children in the low socioeconomic strata suffer the stress of disrupted families, child labor and childhood infections. Intermittent availability of cheap energy dense food materials and habituation to tobacco adds to the fire generated by stress. The double jeopardy felt by them could be more damaging.53

Figure 26.2: Picture of a 6th grade classroom from Kerala to illustrate the factors which discourage physical activity in girls. (A—illustrates the heavy bags reflecting the academic pressure, B— the long hair, C—multilayered uniforms compare with the simple shirt which boys wear, D—less ventilated classroom in a tropical humid climate. (Additional factors are the social, cultural and religious norms which are not illustrated in this picture which discourage physical activity in girls after puberty)

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Preventive Strategies The time-honoured approaches to prevention for the lifestyle-related disease are classified as secondary, primary and the primordial prevention.54 Secondary prevention targets people who already visit the hospital and aims at preventing further progression of the disease and if possible reversion of the disease process, but this has limitations in the majority, because of the lack of medical insurance and drug side effects.55 Lifestyle modification in this subgroup also shows significant benefits.56 This should be used as a major opportunity to screen and initiate primary preventive programmes to relatives and friends of the affected individual as well.57 Primary preventive programmes include mass screening and health education and initiation of treatment to prevent the onset of cardiovascular events in high-risk subjects. But majority of the asymptomatic individuals refuse to accept that they are abnormal and the currently available investigations and laboratory tests are expensive and do have limitations. Good efforts at health education can achieve reasonable success in this group and theoretically ideal for any population.58 Primordial prevention on the other hand aims at prevention of the development of risk factors as such and can be adopted universally without any screening strategies and is therefore more cost effective. They are proved to be safe as well.59 Developed nations have demonstrated the benefit of the strategies by substantial reduction in death due to stroke and heart attack documented over the past two to three decades.60 Developing countries need additional preventive strategies to combat the increasing prevalence of metabolic syndrome at a younger age. Adipocyte inflammation and insulin resistance are the main pathogenic arms of the metabolic syndrome, which finally leads to the degeneration of the beta cells of the pancreas.20 These phenomena are more common in the Indian babies from the time of conception.27 Genetic ethnic and environmental programming could be a factor in the genesis but the perpetuation by environmental factors offers an excellent opportunity for intervention.61 Fetal origins of adult onset diseases is no longer a hypothesis for the developing world.62 Non- carbohydrate calorie dense food substances like fructose, alcohol milk and fat can also generate adipocyte inflammation by saturating the adipocyte and by their glucose sparing effect.63 Milk is a secretion from a gland for lactation in mammals and the ability to digest lactose is programmed to disappear during weaning.25 Smoking, infection, drugs, and stress are other factors identified for initiating adipocyte inflammation.64 The insulin surge needed to maintain euglycemia once metabolic syndrome sets in, increases to five to six times.65 The beta cells can react by hyperplasia, hypertrophy, or apoptosis.66 Evidence of insulin resistance demonstrated at birth and childhood aggravated by the insulinogenic nutrition leads to hyperfunction of beta cells initially generating early onset risk factors followed by beta cell failure.28 These could be major factors responsible for the “anticipation”, and early onset seen in diabetes and cardiovascular disease in the developing countries. Attempts to preserve the beta cells and to minimize the adipocyte inflammation thus stand out as the additional strategy needed for the prevention.

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Figure 26.3: The spectrum of body response to obesogenic environment across the life cycle. The endocrine metabolic programing is represented by the dark line across the graph connecting the zygote to old age. X axis represents the various types of nutrition from in utero life to energy dense marketed products. Exercise as a major modulation of the response after the first 1000 days and is represented in the Y axis. The major 6 factors which can tip the balance towards Sarcopenia (less skeletal muscle) and metabolic syndrome are depicted by broad curved arrows. They are early life programing; puberty, pregnancy, inflammation/drugs, menopause, and old age. The major five outcomes in the spectrum are represented along the dotted arc labelled with bold italic letters. The best adapted people are the 1) aboriginal people, followed by 2) athletes, and then the 3) obese metabolically healthy people. But the majority of the world population migrates to 4) metabolic syndrome, and those who are abnormally programed in early life evolve into 5) metabolically obese normal weight individuals. Adverse early life programing leads to more Sarcopenia which is perpetuated by the declining physical activity in children and adolescents.

Rationale The cornerstone in understanding the basis of the present cardiovascular disease epidemic is the recognition of the evolution of the glucose insulin adipogenetic system as the survival toolkit for the animals to tide over periods of starvation and famine.67 Glucose, insulin and fat form the three arms of this system. Unhealthy diet and physical inactivity unduly stimulates this system to store the positive energy balance as fat. Accumulation of fat in any other cell other than the adipocyte is abnormal as exemplified by the microvesicular fat accumulation in the liver leading to Rye’s syndrome. Among the adipocyte the accumulation in the gluteofemoral region in the form of a ‘‘pear’’ is metabolically fair, whereas the accumulation in the form of an

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‘‘apple’’ in the visceral tissues portends the beginning of metabolic syndrome.68 The systemic inflammatory state initiated by the adipocyte inflammation has protean manifestations, which can be characterized as the clinical manifestations of metabolic syndrome. 69 The metabolic syndrome has inflammatory components affecting the endothelium, which manifests as hypertension, albuminuria, impaired vasomotor response, and atherosclerotic arterial disease in the long run. The mesodermal inflammation can be recognized as fatty liver, transaminiitis, renal calculi, osteoporosis, and vascular and valvar calcium. The epithelial manifestations are important in that they act as clinical clues to the internal milieu. The manifestations could be innocuous like acne, and male pattern baldness to more specific manifestations like acanthosis nigricans. In short the manifestations of metabolic syndrome can be recognized at various phases in our journey from the womb to tomb. Intrauterine milieu of metabolic syndrome can have two extremes in its spectrum with macrosomia at one end and low birth weight at the other end. During adolescence, acne and polycystic ovarian diseases are classical manifestations.70 In adulthood the metabolic syndrome, renal stones, fatty liver disease, acanthosis nigricans and male pattern baldness are identifiable as markers of metabolic syndrome. In old age senile osteoporosis and metabolic syndrome associated cancers lead the center stage if the individual does not succumb to atherosclerotic arterial disease. There is a gross inter individual and intra individual disparity in the manifestations of metabolic syndrome.71 The INTERHEART study clearly showed the limitation of body mass index to identify the individuals with metabolic syndrome in the Indian subcontinent. 72 Beta cells of the islets of Langerhans are known to show hyperplasia, hypertrophy or undergo apoptosis in response to glycemic insult and the local effects of glucotoxicity and lipotoxicity and oxidative stress.66 It is here the isulinotropic nature of high glycemic isocaloric foods gains the relevance.73 The key points are more refined the food, more is the glycemic insult; more sumptuous the meal, more is the glycemic insult; and smaller the person, more intense is the glycemic response. Many of the manifestations of the metabolic syndrome which can be recognized clinically as thrombotic manifestations, dysglycemia, hypertension, atherogenic dyslipidemia, fatty liver, hyper-uricemia, and vascular calcification are essentially the tip of the iceberg and could mean that more than 70 to 90% of the beta cell reserve is already lost.74 This is the stage when we find the stress induced dysglycemia and the gestational disorders. Those pregnant women with gestational diabetes and hypertension or eclampsia need to be evaluated and managed from this angle depending on the clinical evidence. Physical activity is the nature’s prescription to minimize the hyper-insulinemia.75 Skeletal muscle confers ten times more insulin sensitivity than the adipose tissue.30 Human beings are genetically members of the Palaeolithic era and are yet to adapt to the challenges of civilized life.31 Physical inactivity therefore is now considered as a non-communicable disease risk factor.76 Involvement in sports related physical activity confers a more than 20% reduction in cardiovascular mortality and is now recommended to be assessed as a vital sign.77 Though half and hour of accumulated moderate intensity physical activity at least thrice a week is recommended for cardiovascular health, on the hole 7500 steps are needed on a daily basis.78 The benefits of physical activity in women is almost double that of men.79 Outdoor physical activity in addition achieves adequate vitamin D sufficiency and good bone mineral density.38

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How Indians Perpetuate Sarcopenic Obesity? Sarcopenic obesity refers to the decline in skeletal muscle mass and increasing body fatness compared to an age sex matched control and is an invariable accompaniment of aging and mechanization.80 During various stages of life we perpetuate sarcopenic adiposity. Children exert to their maximum during recreational sports, where as adults try their best, by trying to avoid sweating, especially in tropical environment. Females in India stop exercising at adolescence for sociocultural reasons and are happy with their fat body masses. Puberty, pregnancy and childbirth are other situations associated with substantial increase in body fat in females. This is of great relevance since maternal metabolic abnormalities have been shown to translate into early origin of fatty streaks in fetal life.81 Similarly aging, convalescence from illness, in utero programming and variety of drugs can induce sarcopenic adiposity. Steroids and highly active retroviral therapy are prominent among this.82 Environmental factors like the tropical climate necessitate less calorie requirement for thermogenesis and perpetuate male pattern obesity.83 In addition borderline hypothyroidism and growth hormone deficiency can remain masked in tropical climate.84 Now children are over fed but undernourished.85 Caucasians had a large window of transition to adapt to the stress of civilization.86 This is very much abbreviated in Indians leading to the premature onset of lifestyle-related disease. There is clear evidence for exponential increase in risk factors in women in the reproductive age group, in the form of obesity, dysglycemia, hypertension and dyslipidemia.9 There are good data to suggest micronutrient deficiency in the form of vitamin D, vitamin C and B12.87 All

Figure 26.4: The art and science of perfecting the heart healthy diet plate Ones own had is depicted as the volume measure during a major meal time. The most adapted food substance can be taken as hand full of the rainbow dishes, palm full of energy dense nuts, lean meat and low fat poultry products, fist full of cereals, sprouted grains, and a pinch of ultra-processed modern foods. The calorie count charted is per 100 gm of the food substance

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these factors perpetuate in utero origins of sarcopenia.88 Figure 26.3 illustrates the lifecycle effects of abnormal nutrition and physical inactivity. It can be seen that during the first 1000 days, nutritional deficiency generates the substrate for sarcopenic obesity and physical activity during childhood and adolescence, the best opportunity to reverse this wrong start. This forms the basis for the additional need for intensified preventive strategies for Indian children and adolescents where in we need to reverse the declining out door physical activity.

Plan of Action The recently convened WHO meeting on targets to be achieved in non-communicable disease control, categorically recommends total elimination of partially hydrogenated oils, from food supply and no marketing of food rich in salt sugar and saturated fat in children.89 The modalities of prevention adoptable for the Indian setting has to be worked out given the vast diversity and differences that is present in Indian culture. On a broader note the currently available bakery preparations and feasting are avoidable health hazards. Colas and energy dense fast foods should be kept away from Indian children. Strong recommendations to avoid sugar and salt to infants will go a long way to prevent the development of taste, hypertension and stress to beta cells at that young age.28 There is a need to improve awareness on the risks of rapidly changing lifestyles as a result of urbanization. School-based mass education programs need to be introduced a large scale. Distribution of vegetable oils by ration, strictly enforcing tobacco ban, reducing salt, sugar and fat intake on a large scale with nationwide campaigns and legislation are other active methods to reduce the diet induced metabolic abnormalities. The food pyramid has now evolved into the heart healthy plate. Fresh fruits and vegetables and sprouted grains form the major half of this diet plate as shown in Figure 26.4. Special care should be taken to include fruits and vegetables with the rainbow colors and are not energy dense. Encouragement of physical activity at school, family and social level and strong messages to limit television and video viewing are the key strategies to improve insulin sensitivity. Building good muscles and bones during childhood and adolescence by outdoor physical activity is the best investment. Enabling society which facilitates exercise friendly cloths, and environment is the need of the hour. Mahatma Gandhi represented these principles by his deeds and adherence to cotton Khadi clothes. No wonder, atherosclerosis is not a natural disease of animals, they remain physically active, indulge in natural foods and don’t cover their body from sun.

CONCLUSION The present day epidemic of lifestyle related diseases are the end results of decades of metabolic maladjustment of the thin fat Indian babies. In addition to the well-described strategies, targeted strategies need to be adopted. Mother and child nutrition and adolescent medicine are the three thrust areas. Good antenatal care aimed at minimizing maternal metabolic abnormalities could alter the establishment of metabolic syndrome in utero. Child nutrition should aim at minimizing the calorie and metabolic load to children and encourage more physical activity and avoid the initiation of the use of tobacco. Fasting metabolic abnormalities

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are essentially very specific but are the tip of the iceberg for a major catastrophe hiding in the society. Minimizing the metabolic insult of every meal is essential for preserving the beta cells. Developing a taste in children for regular use of fibre rich fruits and vegetables will go a long way in minimizing the metabolic surge of every meal. Adolescent medicine again targets the avoidance of tobacco and stresses the need to persist with the healthy lifestyle learned from childhood avoiding sweets, salts, tobacco, and alcohol. Revamping of our educational system is needed to substantially reduce the stress suffered by the present day children. Only few of our children can respond appropriately to the modern insulinogenic nutrition with beta cell-adipocyte hyperplasia and hypertrophy and they are the fortunate few who can survive into adulthood with better body mass indices to get their knees and hips replaced by the orthopedics surgeons in old age with probably clean coronaries. The majority succumb to the protean manifestations of metabolic syndrome with early onset of non-communicable disease risk factors and diseases. The wrong start from conception is perpetuated in adolescence to unhealthy parenthood which in turn leads to a vicious cycle propelling the younger age onset of risk factors and diseases. Healthy mother who is proportionate in body size, composition and metabolism, is the single additional key factor for non-communicable disease prevention in India.

REFERENCES 1. Misra A, Singhal N, Sivakumar B, et al. Nutrition transition in India: secular trends in dietary intake and their relationship to diet-related non-communicable diseases. J Diabetes. 2011;3(4):278–92. 2. Goyal A, Yusuf S. The burden of cardiovascular disease in the Indian subcontinent. Indian J. Med. Res. 2006;124(3):235–44. 3. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world: A growing challenge. N. Engl. J. Med. 2007;356(3):213–5. 4. Reaven GM. Importance of identifying the overweight patient who will benefit the most by losing weight. Ann. Intern. Med. 2003;138(5):420–3. 5. Sivasankaran S, Nair MKC, Babu G, Zufikar AM. Need for better anthropometric markers for prediction of cardiovascular risk in nutritionally stunted populations. Indian J Med Res. 2011;133(5):557–9. 6. Beaglehole R, Bonita R, Alleyne G, et al. UN High-level meeting on non-communicable diseases: addressing four questions. Lancet. 2011;378(9789):449–55. 7. Beaglehole R, Bonita R, Horton R, et al. Priority actions for the non-communicable disease crisis. The Lancet. 2011;377(9775):1438–47. 8. Wenger NK. Coronary heart disease in men and women: Does 1 size fit all? No! Clinical Cardiology. 2011;34(11):663–7. 9. Gupta R, Misra A, Vikram N, et al. Younger age of escalation of cardiovascular risk factors in Asian Indian subjects. BMC Cardiovascular Disorders. 2009;9(1):28. 10. Uauy R, Kain J, Corvalan C. How can the Developmental Origins of Health and Disease (DOHaD) hypothesis contribute to improving health in developing countries? The American Journal of Clinical Nutrition. 2011;94(6):1759S–64S. 11. Palinski W, Nicolaides E, Liguori A, Napoli C. Influence of maternal dysmetabolic conditions during pregnancy on cardiovascular disease. J Cardiovasc Transl Res. 2009;2(3):277–85. 12. Prasad DS, Kabir Z, Dash AK, Das BC. Childhood cardiovascular risk factors in South Asians: A cause of concern for adult cardiovascular disease epidemic. Ann Pediatr Cardiol. 2011;4(2):166–71.

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Pediatric Cardiology

13. Anon. ICMR NCD survey Kerala. Available at: http://icmr.nic.in/final/IDSP-NCD%20Reports/ Kerala.pdf. Accessed August 18, 2011. 14. Reaven GM. Compensatory hyperinsulinemia and the development of an atherogenic lipoprotein profile: the price paid to maintain glucose homeostasis in insulin-resistant individuals. Endocrinol. Metab. Clin. North Am. 2005;34(1):49–62. 15. Kopp W. High-insulinogenic nutrition: An etiologic factor for obesity and the metabolic syndrome. Metab. Clin. Exp. 2003;52(7):840–844. 16. Alberti KGMM, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–45. 17. Krachler B, Eliasson M, Stenlund H, et al. Population-wide changes in reported lifestyle are associated with redistribution of adipose tissue. Scand J Public Health. 2009;37(5):545–53. 18. Romero-Corral A, Somers VK, Sierra-Johnson J, et al. Normal weight obesity: A risk factor for cardiometabolic dysregulation and cardiovascular mortality. Eur. Heart J. 2010;31(6):737–46. 19. Bhattarai MD. Three patterns of rising type 2 diabetes prevalence in the world: Need to widen the concept of prevention in individuals into control in the community. JNMA J Nepal Med Assoc. 2009;48(174):173–9. 20. Bays HE. Adiposopathy is “sick fat” a cardiovascular disease? J. Am. Coll. Cardiol. 2011;57(25): 2461–73. 21. Matheson A. From Syndrome to Spectrum: What Evolution Suggests about the Status of the Metabolic Syndrome. Clinical Chemistry. 2007;53(12):2218–19. 22. Yajnik CS, Ganpule-Rao AV. The obesity-diabetes association: What is different in indians? Int J Low Extrem Wounds. 2010;9(3):113–5. 23. Lichtenstein AH, Appel LJ, Brands M, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006;114(1):82–96. 24. Darnton-Hill I, Nishida C, James WPT. A life course approach to diet, nutrition and the prevention of chronic diseases. Public Health Nutr. 2004;7(1A):101–21. 25. Sivasankaran S. The cardio-protective diet. Indian J Med Res. 2010;132(5):608–16. 26. Deaton A, Dreze J. Nutrition in India: Facts and Interpretations. SSRN eLibrary. 2008. Available at: http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1135253. Accessed. April 27, 2010. 27. Yajnik CS, Fall CHD, Coyaji KJ, et al. Neonatal anthropometry: The thin-fat Indian baby. The Pune Maternal Nutrition Study. Int. J. Obes. Relat. Metab. Disord. 2003;27(2):173–80. 28. Sivasankaran S, Thankappan KR. Beta cell protection & metabolic syndrome. Indian J. Med. Res. 2007;125(2):184–5. 29. Swaminathan S, Selvam S, Thomas T, Kurpad AV, Vaz M. Longitudinal trends in physical activity patterns in selected urban south Indian school children. Indian J. Med. Res. 2011;134(2):174–80. 30. Eaton SB, Cordain L, Sparling PB. Evolution, body composition, insulin receptor competition, and insulin resistance. Preventive Medicine. 2009;49(4):283–5. 31. O’Keefe J, Vogel R, Lavie C, Cordain L. Organic Fitness: Physical activity consistent with our huntergatherer heritage. The Physician and Sportsmedicine. 2010;38(4):11–8. 32. Gillis L, Gillis A. Nutrient inadequacy in obese and non-obese youth. Can J Diet Pract Res. 2005;66(4):237–42. 33. Krishnaveni GV, Hill JC, Veena SR, et al. Low plasma vitamin B12 in pregnancy is associated with gestational “diabesity” and later diabetes. Diabetologia. 2009;52(11):2350–58. 34. Seshiah V, Balaji V, Balaji MS, Sanjeevi CB, Green A. Gestational diabetes mellitus in India. J Assoc Physicians India. 2004;52:707–11.

Cardiac Implications of Changing Lifestyle: Prevention of Adult Cardiovascular Disease

399

35. Yeole BB, Kurkure AP. An epidemiological assessment of increasing incidence and trends in breast cancer in Mumbai and other sites in India, during the last two decades. Asian Pac. J. Cancer Prev. 2003;4(1):51–6. 36. Harinarayan CV, Joshi SR. Vitamin D status in India: Its implications and remedial measures. J Assoc Physicians India. 2009;57:40–8. 37. Bandgar TR, Shah NS. Vitamin D and hip fractures: Indian scenario. J Assoc Physicians India. 2010;58:535–37. 38. Marwaha RK, Puri S, Tandon N, et al. Effects of sports training & nutrition on bone mineral density in young Indian healthy females. Indian J Med Res. 2011;134(3):307–13. 39. Bandgar TR, Shah NS. Vitamin D and hip fractures: Indian scenario. J Assoc Physicians India. 2010;58:535–7. 40. Feinstein JA, Quivers ES. Pediatric preventive cardiology: Healthy habits now, healthy hearts later. Curr. Opin. Cardiol. 1997;12(1):70–7. 41. Thankappan KR, Shah B, Mathur P, et al. Risk factor profile for chronic non-communicable diseases: Results of a community-based study in Kerala, India. Indian J. Med. Res. 2010;131:53–63. 42. Peters DH, Rao KS, Fryatt R. Lumping and splitting: The health policy agenda in India. Health Policy Plan. 2003;18(3):249–60. 43. Mohan V, Sandeep S, Deepa R, Shah B, Varghese C. Epidemiology of type 2 diabetes: Indian scenario. Indian J. Med. Res. 2007;125(3):217–30. 44. Menon VU, Kumar KV, Gilchrist A, et al. Acanthosis Nigricans and insulin levels in a south Indian population (ADEPS paper 2). Obesity Research & Clinical Practice. 2008;2(1):43–50. 45. Sivasankaran S. Sree Chitra Tirunal Institute for Medical Sciences & Technology. Broadening waist line of Keralites, the diet link. Available at: http://intranet.sctimst.ac.in/. Accessed April 13, 2010. 46. Raj M, Sundaram R, Paul M, Kumar K. Blood pressure distribution in Indian children. Indian Pediatr. 2010;47(6):477–85. 47. Soman CR, Kutty VR, Safraj S, et al. All-cause mortality and cardiovascular mortality in Kerala state of india: Results from a 5-Year follow-up of 161 942 rural community dwelling adults. Asia Pac J Public Health. 2010. Available at: http://www.ncbi.nlm.nih.gov.proxy.library.emory.edu/ pubmed/20460280. Accessed September 10, 2010. 48. Yaturu S, Bridges JF, Dhanireddy RR. Preliminary evidence of genetic anticipation in type 2 diabetes mellitus. Med. Sci. Monit. 2005;11(6):CR262–5. 49. Adair LS, Prentice AM. A critical evaluation of the fetal origins hypothesis and its implications for developing countries. J. Nutr. 2004;134(1):191–3. 50. Anon. HungamaBKDec11LR.pdf. Available at: http://hungamaforchange.org/HungamaBKDec11LR. pdf. Accessed July 23, 2012. 51. Roy A, Prabhakaran D, Jeemon P, et al. Impact of alcohol on coronary heart disease in Indian men. Atherosclerosis. 2010. Available at: http://www.ncbi.nlm.nih.gov.proxy.library.emory.edu/ pubmed/20226461. Accessed April 25, 2010. 52. Thankappan KR. Some health implications of globalization in Kerala, India. Bull. World Health Organ. 2001;79(9):892–3. 53. Marshall SJ. Developing countries face double burden of disease. Bull. World Health Organ. 2004;82(7):556. 54. Pais P. Preventing ischaemic heart disease in developing countries. Evid Based Cardiovasc Med. 2006;10(2):85–8. 55. Smith SC Jr, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: Endorsed by the National Heart, Lung, and Blood Institute. Circulation. 2006;113(19):2363–72. 56. Capewell S, O’Flaherty M. Rapid mortality falls after risk-factor changes in populations. The Lancet. 27 August;378(9793):752–3.

400

Pediatric Cardiology

57. Libby P. The forgotten majority: Unfinished business in cardiovascular risk reduction. J. Am. Coll. Cardiol. 2005;46(7):1225–28. 58. Liebson PR, Amsterdam EA. Prevention of coronary heart disease. Part I. Primary prevention. Dis Mon. 1999;45(12):497–571. 59. Gidding SS, Dennison BA, Birch LL, et al. Dietary recommendations for children and adolescents: A guide for practitioners: consensus statement from the American Heart Association. Circulation. 2005;112(13):2061–75. 60. Vartiainen E, Laatikainen T, Peltonen M, et al. Thirty-five-year trends in cardiovascular risk factors in Finland. Int. J. Epidemiol. 2010;39(2):504–18. 61. Ludwig DS, Ebbeling CB, Pereira MA, Pawlak DB. A physiological basis for disparities in diabetes and heart disease risk among racial and ethnic groups. J. Nutr. 2002;132(9):2492–3. 62. Robinson R. The fetal origins of adult disease. BMJ. 2001;322(7283):375–6. 63. Lustig RH. Fructose: metabolic, hedonic, and societal parallels with ethanol. J Am Diet Assoc. 2010;110(9):1307–21. 64. Björntorp P. Do stress reactions cause abdominal obesity and comorbidities? Obesity Reviews. 2001;2(2):73–86. 65. Reaven GM. The Metabolic Syndrome: Requiescat in Pace. Clinical Chemistry. 2005;51(6):931–8. 66. Porte D Jr, Kahn SE. beta-cell dysfunction and failure in type 2 diabetes: Potential mechanisms. Diabetes. 2001;50(1):S160–3. 67. Björntorp P. Thrifty genes and human obesity: Are we chasing ghosts? The Lancet. 2001;358(9286): 1006–8. 68. Cameron AJ, Zimmet PZ. Expanding Evidence for the Multiple Dangers of Epidemic Abdominal Obesity. Circulation. 2008;117(13):1624–6. 69. de Ferranti S, Mozaffarian D. The perfect storm: Obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem. 2008;54(6):945–55. 70. Nidhi R, Padmalatha V, Nagarathna R, Amritanshu R. Prevalence of polycystic ovarian syndrome in Indian adolescents. J Pediatr Adolesc Gynecol. 2011;24(4):223–7. 71. Unnikrishnan A. Tissue-specific insulin resistance. Postgrad Med J. 2004;80(946):435. 72. Kragelund C, Omland T. A farewell to body-mass index? Lancet. 2005;366(9497):1589–91. 73. Drucker DJ, Nauck MA. The incretin system: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368(9548):1696–705. 74. Libman IM, Arslanian SA. Prevention and treatment of type 2 diabetes in youth. Horm. Res. 2007;67(1):22–34. 75. Khamseh ME, Malek M, Aghili R, Emami Z. Sarcopenia and diabetes: Pathogenesis and consequences. The British Journal of Diabetes & Vascular Disease. September;11(5):230–4. 76. Prasad D, Das B. Physical inactivity : A cardiovascular risk factor. Indian Journal of Medical Sciences. 2009;63(1):33. 77. Khan KM, Thompson AM, Blair SN, et al. Sport and exercise as contributors to the health of nations. Lancet. 2012;380(9836):59–64. 78. Lucia A, Foster C, Pérez M, Arenas J. What isn’t taught in medical schools: The William Wordsworth lesson. Nat Clin Pract Cardiovasc Med. 2008;5(7):372–4. 79. Sattelmair J, Pertman J, Ding EL, et al. Dose response between physical activity and risk of coronary heart disease: A meta-analysis. Circulation. 2011;124(7):789–95. 80. Roubenoff R. Sarcopenic obesity: The confluence of two Epidemics. Obesity. 2004;12(6):887–8. 81. Napoli C, Glass CK, Witztum JL, et al. Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: Fate of Early Lesions in Children (FELIC) study. Lancet. 1999;354(9186):1234–41. 82. Jevtovi´c D, Dragovi´c G, Salemovi´c D, Ranin J, Djurkovi´c-Djakovi´c O. The metabolic syndrome, an epidemic among HIV-infected patients on HAART. Biomedicine & Pharmacotherapy. 2009;63(5): 337–42.

Cardiac Implications of Changing Lifestyle: Prevention of Adult Cardiovascular Disease

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83. Sniderman AD, Bhopal R, Prabhakaran D, Sarrafzadegan N, Tchernof A. Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis. Int J Epidemiol. 2007;36(1):220–5. 84. Roberts WC. Twenty questions on atherosclerosis. Proc (Bayl Univ Med Cent). 2000;13(2):139–43. 85. Corvalan C, Dangour AD, Uauy R. Need to address all forms of childhood malnutrition with a common agenda. Arch. Dis. Child. 2008;93(5):361–2. 86. Gerstein HC, Waltman L. Why don’t pigs get diabetes? Explanations for variations in diabetes susceptibility in human populations living in a diabetogenic environment. CMAJ. 2006;174(1):25–6. 87. Londhey V. Vitamin D deficiency: Indian scenario. J Assoc Physicians India. 2011;59:695–6. 88. Krishnaveni GV, Veena SR, Winder NR, et al. Maternal vitamin D status during pregnancy and body composition and cardiovascular risk markers in Indian children: The Mysore Parthenon Study. Am. J. Clin. Nutr. 2011;93(3):628–35. 89. Anon. twg_targets_to_monitor_progress_reducing_ncds.pdf. Available at: http://www.wphna.org/ downloadsaug2011/twg_targets_to_monitor_progress_reducing_ncds.pdf. Accessed July 26, 2012.

27

Genetics of Congenital Heart Disease

Dr Sankar VH

Congenital heart disease (CHD) is an important component of pediatric cardiology and cardiac malformations constitute a major percentage of clinically significant birth defects. The estimated prevalence of cardiac malformation is 19 to 75 per 1000 live birth1; of these 40% will be diagnosed in the first year of life. There has been a long standing clinical view that most CHD occurs as isolated cases. Classical studies including Baltimore-Washington Infant Study have found that CHD is multifactorial, due to both genetic predisposition and environmental influences2. Sequencing of the human genome and advanced molecular technology has led to increasing evidence implicating a stronger role for genetic factors. The development of gene targeting technology has led to the generation of a multitude of mouse models with cardiac developmental defects. All these help in the identification of genetic etiologies of CHD and provide evidence that many genes may have etiologic role in CHD. This article summarizes the recent concept on genetics of CHD and importance of evaluating the genetic etiology in the clinical set-up. CHD often occurs in the setting of multiple malformations, abnormal facial features, limb abnormalities, developmental delay or growth abnormalities. CHD occurs in association with other anomalies or as a part of an identified syndrome in 25 to 40% cases3. These multiple malformation syndrome can be chromosomal, microdeletion, single gene disorders or unspecified multiple malformations. The definitive diagnosis is important since risk of recurrence and definitive prenatal diagnosis for each may be different.

IMPORTANCE OF IDENTIFYING THE GENETIC BASIS OF CHD (TABLE 27.1)4 For the clinician caring for a CHD, it is very important to determine whether there is an underlying genetic cause for the following reason: 1. There may be other important organ system involvement 2. There may be prognostic information for clinical outcomes 3. There may be important genetic reproductive risks the family should know about 4. There may be other family members for whom genetic testing is appropriate

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Table 27.1: Common syndromes resulting from aneuploidy and microdeletion4 Syndrome

Cardiac anomalies %with CHD

Other Clinical Features

Trisomy 21 [Down syndrome]

ASD,VSD, AVSD,TOF

40–50%

Hypotonia, hypertelorism, epicanthic folds, developmental delay,

Trisomy 18 [Edwards' syndrome]

AD,VSD,PDA,TOF, DORV,CoA,BAV

90–100%

Rocker bottom feet, hypertonia, severe developmental delay, arthrogryposis, diaphragmatic hernia, omphalocele

Trisomy 13 Patau syndrome

AD,VSD,PDA, HLHS 80%

Microcephaly, holoprosencephaly, scalp defects, severe developmental delay, cleft lip or palate, polydactyly, omphalocele, micropthalmia, genitourinary abnormalities

Monosomy X Turner's syndrome

CoA, BAV,AS, HLHS 25–35%

Short stature, shield chest with widely spaced nipples, webbed neck, lymphedema, primary amenorrhea

47,XXY PDA,ASD, MVP Klinefelter's syndrome

50%

Tall stature, hypogonadism, variable developmental delay

22q11.2 deletion DiGeorge syndrome

IAA type B, AAA, TA, 75% TOF

Thymic and parathyroid hypoplasia, immunodeficiency, facial dysmorphism, speech and learning defects, renal anomalies

7q11.3 deletion Williams-Beuren syndrome

Supravalvular AS PPS

Infantile hypercalcemia, elfin facies, social personality, developmental delay, joint contractures, hearing loss

50–85%

ASD, atrial septal defect; VSD, ventricular septal defect; PDA, patent ductus arteriosus; TOF,tetrology of Fallot; HLH, hypoplastic left heart syndrome; DORV, double outlet right ventricle; CoA, coarctation of aorta; BAV, bicuspid aortic valve; AVSD, atrioventricular septal defect; IAA, interrupted aortic arch; AAA, aortic arch anomalies; AS, aortic stenosis; PPS, peripheral pulmonary stenosis.

CHROMOSOMAL DISORDERS Standard chromosomal analysis revealed chromosomal aberrations in 8 to 13% of neonate with CHD. In contrast, of all children with chromosomal abnormalities, 30% have a congenital cardiac defect4. In case of common trisomy like Down syndrome, 40% will have a CHD ranging from atrial and ventricular septal defects, AVCD and TOF. In trisomy 13, the rate increases to 80% and in case of Trisomy 18, it will reach to almost 100%. Approximately one-third of females with Turner’s syndrome have CHD. These classical chromosomal aneuploidy and major structural aberration in chromosomes can be identified by a conventional karyotype. However this has a resolution of five to ten mega bases and small chromosomal abnormalities like microdeletion cannot be identified by this method. Chromosomes can be analyzed from a number of sources including peripheral blood lymphocytes, skin fibroblasts, amniotic fluid, chorionic villi and bone marrow with peripheral blood commonly used. The sample required is 2 mL of venous blood with heparin as an anticoagulant collected under aseptic precautions. Amniotic fluid cells are the primary means of prenatal chromosomal diagnosis. Chromosomes can be analyzed from any actively dividing cells. Usually peripheral blood lymphocytes are stimulated to undergo multiplication by phytohemagglutinin in a culture bottle. The dividing cells are arrested in metaphase by colchicin, a mitotic inhibitor. These cells are then treated with hypotonic solution to destroy the cell membranes and then fixed

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with fixative made up of methanol and acetic acid. The cell pellet of appropriate quantity is dropped on to glass slides to get ‘metaphases’ (chromosomes from a single cell are usually found in groups). The chromosomes are then ‘banded’ using trypsin and stained by Giemsa to give G-bands, with alternate dark and light bands of various sizes along the length of chromosomes. Several other banding techniques are available, but are used in specific indications. Modifications of the technique permit high resolution banding. Metaphases are then seen under a microscope, imaged, individual chromosomes identified based on their size and band pattern and then arranged to get the ‘karyotype’.

MICRODELETION SYNDROME AND FISH With the development of Fluorescence In Situ Hybridization (FISH) technique, small submicroscopic deletions and duplications causing microdeletion syndromes have been elucidated. Microaberrations (microdeletion and microduplications) are caused by deletion or duplication of genetic material usually involving multiple contiguous genes on a chromosomecontiguous gene syndrome. These aberrations usually involve 2Mb or less in size, cannot be identified by conventional chromosome studies. FISH analysis provides a definite diagnostic test for these conditions. Gene specific probe for the particular deleted or duplicated gene will be used for the test. In case of deletion, there will be only one signal in each metaphase or interphase nuclei. On the contrary in case of duplication, there will be three signals in each cell. For doing FISH for microdeletion, clinical information is very essential to decide which probe to be used. Fluorescence In Situ Hybridization (FISH) is a process whereby chromosomes or portions of chromosomes are vividly painted with fluorescent molecules that anneal to specific regions. In this technique a labeled probe is hybridized to cytological targets such as metaphase chromosomes, interphase nuclei or extended chromatin fibers. Fluorescent-labeled probe and target DNA are denatured using high temperature incubation in a formamaide/salt solution. Then the probe is applied to the target DNA and incubated for hybridization. After that stringent washing is done to remove the excess probe. Probe detection is accomplished by excitement with light of appropriate wavelength of the flurochrome and is observed under fluorescent microscope. Commonly used target DNA is a metaphase spread on a slide. Common microdeletion syndrome associated with congenital heart disease are 22q11 deletion syndrome (DiGeorge syndrome) and Williams-Beuren syndrome. The prevalence of the 22q11 deletion is estimated to be at 1 per 5000 to 6000 live births5. It has been shown that patients with clinical diagnosis of DiGeorge syndrome, Velocardial facial syndrome or conotruncal anomaly face syndrome most often share common genetic origin namely 22q11 deletion. This syndrome is characterized by aplasia or hypoplasia of thymus, aplasia or hypoplasia of the parathyroid glands, cardiac malformations, and facial dysmorphism. Typical facial features include tubular nose, hypoplastic alae nasi, bulbous tip of nose, low set/ dysplastic ears, and myopathic facies. The most common cardiovascular defects associated with a 22q11 deletion are tetrology of Fallot, interrupted aortic branch type B, truncus arteriosus, conoventricular VSDs, and aortic arch anomalies.

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405

Ten to twenty percent of patients Table 27.2: Estimated 22q11 deletion frequency in congenital heart disease4 with DiGeorge syndrome have visible alterations that results in deletion Cardiac defect Estimated deletion frequency (%) identified in conventional karyotype. The Interrupted aortic arch 50-89 chromosomal aberration usually involves VSDs 10 2Mb or less in size, cannot be identified With normal aortic arch 3 by conventional chromosome studies in most (90%) cases. Fluorescent In Situ With aortic arch anomaly 45 Hybridization (FISH) provides a definite Truncus arteriosus 34-41 diagnostic test for these conditions. Gene Tetrology of Fallot 8-35 specific probe for the particular deleted Isolated aortic arch anomalies 24 gene will be used for the test. In case of Double outlet right ventricle 1% of the population. Comparative genomic hybridization (CGH) and a DNA micro-array can detect these submicroscopic CNV. In different

408

Pediatric Cardiology Table 27.3: Non syndromic CHD resulting from ingle gene defects

Cardiac anomalies

Gene

ASD, TOF, atrioventricular conduction delay

NKX2.5

ASD,VSD

GATA4

ASD, hypertrophic cardiomyopathy

MYH6

Cardiac septation defects associated with PHTN

BMPR2

Endocardial cushion defects (AVSD)

CRELD1, ALK2

BAV, early valve calcification

NOTCH1

d-TGA

PROSIT-240

ASD, atrial septal defect; VSD, ventricular septal defect; TOF,tetrology of Fallot; BAV, bicuspid aortic valve; AVSD, atrioventricular septal defect; TGA, transposition of great arteries; PHTN, pulmonary hypertension.

studies in patients with CHD, 17%–25% had causative CNV. These studies demonstrated that CNV are associated with CHD especially in association with developmental delay or other malformations11. In individuals with CHD and neurological anomalies where conventional karyotype is normal, whole genome array CGH can be used to detect diseases associated CNV. Copy number variation is also identified in individual with isolated CHD12. The majority were duplications in contrast to those found in syndromic CHD which are predominantly deletion. In isolated CHD, 44% were familial CNV. In view of significant cost of array CGH and inconclusive result to provide accurate genetic counseling, it is not yet clinically indicated in cases of isolated CHD. Single nucleotide polymorphism (SNP) represents another genetic variation studied in multifactorial disorders. SNP association studies CHD have focused on detecting polymorphism in candidate genes thought to be involved in the development of CHD. The role of folate metabolism in the development of CHD is one area where some association studies were focused. A common polymorphism in the methylenetetrahydro-folate reductase (MTHFR) gene at position 677changes a cytosine to thymine (C677T) causes decreased activity of the enzyme. A recent meta-analysis failed to find an association between the presence of homozygous C677T allele in either or offspring and increased risk of CHD. Similarly another gene where polymorphism were studied was vascular endothelial growth factor (VEGF) failed to demonstrate any association.

EVALUATION FOR GENETIC BASIS IN CHILDREN WITH CHD4 Despite the rapid advances in understanding the genetic basis of CHD, a genetic defect can only be identified through available testing in minority of patients with CHD. The approach to the newly diagnosed patients with CHD should include a detailed accurate medical history and a three generation extended pedigree analysis. A medical history may help to identify teratogenic factor like congenital rubella or exposure to anticonvulsants like sodium valproate. In some form of CHD like Marfan syndrome and Holt-Oram syndrome, the familial nature (autosomal dominant) is well recognized. Specific assessment for physical features is warranted. The physical examination should focus on dysmorphic features, eye and ear abnormalities, limb reduction defects, polydactyly, other skeletal defects, gastrointestinal and

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urologic defects and neurological status. Many of this multiple malformation may indicate a specific clinical phenotype suggestive of a genetic syndrome. Clinicians can refer the standard textbooks or software for syndrome identification. If genetic testing is available for the single gene defect, the testing can be offered. It is better to use an algorithm based on the initial presentation to assess the presence of noncardiac abnormalities . Genetic consultation is recommended in the presence of mental retardation, multiple congenital anomalies or facial dysmorphism. Chromosome analysis and FISH testing for microdeletion is accepted tool for evaluation. In case of normal karyotype, high resolution banding or more advanced cytogenetic techniques (FISH for subtelomeric deletion) is recommended. At present situation, advanced research tools like array CGH and Exome sequencing is not recommended on routine clinical purpose.

Cytogenetic Testing Should be Considered4 1. Any child with phenotypic features of recognizable chromosomal syndrome like Down syndrome. 2. Any CHD combined with a. dysmorphic features, b. growth retardation that cannot be explained by the heart defect, c. developmental delay/MR, d. multiple congenital anomalies. (because all chromosomal abnormalities result in a clinically recognizable syndrome) 3. Child with CHD and family history of multiple miscarriages/ siblings with birth defects. 4. If a major cardiac and/or other visceral malformations are documented by prenatal ultrasound and/or fetal echocardiogram.

Suggested Testing Strategy for a 22q11deletion in the CHD Population4 •• •• •• ••

All newborn/infants with IAA,TA,TOF,VSD with AAA, isolated AAA, Discontinuous branch pulmonary arteries Any newborn/infant/child with CHD and another feature of the 22q11 deletion Any child/adolescent/adult with TOF, TA, IAA, VSD, or AAA not previously tested who has 1 other feature of 22q11 deletion syndrome All fetuses with IAA, TA, TOF, VSD, AAA (if amniocentesis performed for diagnostic purpose)

GENETIC COUNSELING IN GENETIC SYNDROMES WITH CHD When a genetic abnormality is identified, appropriate genetic counseling and evaluation of family members may be undertaken. Genetic counseling is defined as communicative process, which deals with human problems associated with the occurrence and/or recurrence of a genetic disorder in a family. Correct and definitive diagnosis will help to predict the prognosis and recurrence risk precisely.

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Genetic counseling in a case of Down syndrome: Recurrence risk will vary depending on the type of Down syndrome (whether non-disjunction or translocation) and maternal age. •• The chance of recurrence of Trisomy 21 in children of mothers who had one live born affected infant (free trisomy due to non-disjunction): For counseling purposes, the chance of recurrences of Down syndrome can be rounded of to 1%. Trisomy 21 spontaneous or induced abortion has the same recurrence risk consequences as the live birth of an affected infant. •• Previous child with Robertsonian translocation Down syndrome (translocation between 21 and 13/14/15/22 chromosomes): The distinction should be done between de novo and familial forms of translocation Down syndrome is crucial: this distinction is made by chromosomal studies of the parents. For the de novo translocation, a recurrence risk figure of 1% is applicable (similar to non-disjunction trisomy). In the case of familial Robertsonian translocation Down syndrome, the genetic risk for the female carrier is substantial. The risk to have a live born child with translocation Down syndrome is 10–15%. For the male carrier, the risk to have a child with translocation Down syndrome is small, about 1%. In 21/21 translocation Down syndrome with one of the parent having translocation carrier, recurrence risk in next child will be 100%. The confirmatory test to rule out a cytogenetic abnormality in the offspring is the invasive test like amniocentesis and karyotype of the fetus. Amniocentesis is the aspiration of amniotic fluid for various biochemical and genetic tests. Traditionally it is performed at 16–17 weeks of gestation since there will be enough viable amniocytes at this period. Choroinic villus sampling Flow chart 27.1: Clinical approach to a case with CHD to identify genetic etiology

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(CVS) can be done much earlier (at 12 weeks) so that result will be available earlier. This procedure is preferred in prenatal diagnosis of single gene disorders like Noonan syndrome. Invasive diagnostic test is having a procedure related fetal loss of 0.5% to 1%.

KEY MESSAGES ••

••

•• •• ••

Identification of genetic etiology of Congenital Heart disease will help in the management of associated problem, to assess the prognosis and delivering genetic counseling (Flow chart 27.1). Always look for other associated anomalies with CHD to identify chromosomal abnormalities, microdeletion syndrome or syndrome with single gene defect like Alagille syndrome. Karyotype is warranted when CHD is associated with multiple malformations. Fluorescent In Situ Hybridization (FISH) is the investigation of choice in microdeletion syndrome like DiGeorge Syndrome (22q11 deletion syndrome). General recommendation is that routine FISH testing of all newborns/infants with TOF is likely warranted.

REFERENCES 1. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39(12): 1890–900. 2. Ferencz C, Neill CA, Boughman JA, Rubin JD, Brenner JI, Perry LW. Congenital cardiovascular malformations associated with chromosome abnormalities: An epidemiologic study. J Pediatr. 1989;114(1):79–86. 3. Goldmuntz E. The genetic contribution to congenital heart disease. Pediatr Clin North Am. 2004;51(6):1721–37. 4. Pierpont ME, Basson CT, Benson DW Jr, Gelb BD, Giglia TM, Goldmuntz E, McGee G, Sable CA, Srivastava D, Webb CL; American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young. Genetic basis for congenital heart defects: current knowledge: A scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation. 2007;115(23):3015–38. Epub 2007 May 22. 5. Shprintzen RJ. Velo-cardio-facial syndrome: 30 Years of study. Dev Disabil Res Rev. 2008;14(1):3–10. 6. Goldmuntz E, Clark BJ, Mitchell LE, Jawad AF, Cuneo BF, Reed L, McDonald-McGinn D, Chien P, Feuer J, Zackai EH, Emanuel BS, Driscoll DA Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol. 1998;32(2):492–8. 7. Formigari R, Michielon G, Digilio MC, Piacentini G, Carotti A, Giardini A, Di Donato RM, Marino B. Genetic syndromes and congenital heart defects: how is surgical management affected? Eur J Cardiothorac Surg. 2009;35(4):606–14. Epub 2008 Dec 16. 8. Schellberg R, Schwanitz G, Grävinghoff L, Kallenberg R, Trost D, Raff R, Wiebe W. New trends in chromosomal investigation in children with cardiovascular malformations. Cardiol Young. 2004;14(6):622–9. 9. Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM, Puffenberger EG, Hamosh A, Nanthakumar EJ, Curristin SM, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991;352(6333):337–9.

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10. Gelb BD. Genetic basis of congenital heart disease. Curr Opin Cardiol. 2004;19(2):110–5. 11. Thienpont B, Mertens L, de Ravel T, Eyskens B, Boshoff D, Maas N, Fryns JP, Gewillig M, Vermeesch JR, Devriendt K. Submicroscopic chromosomal imbalances detected by array-CGH are a frequent cause of congenital heart defects in selected patients. Eur Heart J. 2007;28(22):2778–84. Epub 2007 Mar 23. 12. Richards AA, Santos LJ, Nichols HA, Crider BP, Elder FF, Hauser NS, Zinn AR, Garg V. Cryptic chromosomal abnormalities identified in children with congenital heart disease. Pediatr Res. 2008;64(4):358–63.

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Catheter-based Interventions in Children

Shreepal Jain and Bharat Dalvi

Pediatric cardiac interventions started in mid 60s, when balloon atrial septostomy was performed by William Rashkind to palliate newborns and infants with transposition of great arteries.1 Following the footsteps of coronary interventions, pediatric cardiac interventions have made a remarkable progress in the last couple of decades. Currently cardiac catheterization is done mainly for therapeutic interventions than for diagnostic purposes. Transcatheter interventions are mainly performed to dilate narrow valves or vessels, close abnormal communications and to create or maintain patency of communications to improve oxygenation. More recently, valves are being replaced with transcatheter techniques. Most of these procedures are being performed in our country with great degree of safety and efficacy. Some of these interventions can palliate or cure the defect by themselves while the others are being used in conjunction with the surgical procedures for more effective and sometimes less morbid palliation.2

ATRIAL SEPTOSTOMY PROCEDURES Balloon Atrial Septostomy Balloon atrial septostomy (BAS), introduced by Rashkind in 1966, is a lifesaving procedure in infants with transposition of the great arteries with intact interventricular septum especially younger than 1 month of age who are not immediately scheduled for surgical correction. Because of septal thickening with age, BAS is not very effective in infants older than 1 month of age.2It is also indicated for palliating newborns in whom all systemic, pulmonary or mixed venous blood must traverse a restrictive interatrial communication to return to the active circulation. These include tricuspid and mitral atresia with hypoplastic right or left ventricles and some instances of total anomalous venous connection. The procedure is usually performed from the femoral vein, although occasionally it has been accomplished successfully via the umbilical vein.3 It is most often done under fluoroscopic guidance, although it can be carried out at the bedside using echocardiographic guidance.3,4 The balloon is inflated in the left atrium and then “jerked” across the interatrial septum, the entire procedure being repeated 3 to 4

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times till there is no resistance to the movement of the balloon. The success of the procedure is indicated by increase in the oxygen saturation and by increase in the size of the interatrial communication on echo. “Fracture” of the septum primum with excessive movement is also an indicator of a good and lasting septostomy. Although during the early years, atrial arrhythmias, tricuspid valve injury and cardiac perforation were described as some of the complications, with increasing experience, echo guidance and improved hardware these have become very rare.

Blade and Balloon Dilatation Atrial Septostomy Blade atrial septostomy is an adjunct to balloon atrial septostomy that was first described by Park and colleagues in 1978.5 This procedure is indicated in those above 1 month of age who may require an atrial septostomy for palliation, where the atrial septum is too tough for a simple BAS to tear. In contrast to BAS, the blade is introduced through a long sheath and withdrawn slowly across the interatrial septum (IAS) in a controlled fashion. This action is repeated a few times with the blade being opened in different directions until there is no resistance to the withdrawal of the fully opened blade (Fig. 28.1). This is usually followed by balloon septostomy using standard dilatation balloons. In most cases an adequate and permanent atrial septal defect is created, palliating the patient until a more definitive solution is available. Stenting of the IAS has been performed in some of these cases to ensure a lasting opening.2

BALLOON VALVE DILATATIONS Significant pulmonary and aortic valve stenoses account for almost 10% of all CHDs.6

Pulmonary Valve Dilatation Severe pulmonic stenosis (PS) can present at any age including adulthood. Data obtained from a sequential follow-up study, suggest that patients with pulmonic stenosis with a gradient across the stenotic valve of more than 50 mm Hg had a better outcome at 20 years follow-up when treated with surgery as compared with no intervention.7 Balloon pulmonary valvuloplasty is currently the procedure of choice for symptomatic as well as asymptomatic

A

B

Figures 28.1 (A and B): Blade atrial septostomy

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but significant valvar PS. The procedure is performed under sedation or general anasthesia. Patients are usually observed in hospital overnight and then discharged home the following day. Postprocedural care is minimal, with exercise restriction for about 48 to 72 hours to allow healing of catheter entry sites. In pulmonic stenosis, balloon dilation is effective in most patients (Fig. 28.2). The main exception is the subset of patients with so-called “dysplastic pulmonary valve”(common in Noonan syndrome), where the valve is thick and adherent to the wall of the main pulmonary artery in part with associated supravalvar narrowing. Calculation of the annulus size on echocardiography and on angiography is extremely important to determine the balloon size needed for adequate dilatation. The balloon diameter chosen is equal to 1.2 times the diameter of the pulmonary annulus but for dysplastic valves one may go upto 1.5 times the annular diameter. To avoid marked drop in systemic blood pressure (common while using large balloons when annulus size is > 20 mm) and to reduce the trauma to the veins at the site of entry, a double balloon technique is occasionally used.2 When using this technique, the combined diameters of the two balloons should equal 1.5 to 1.7 times the measured diameter of the valve annulus. With pure stenosis, the gradient across the valve should reduce to less than 20 mm Hg. In some cases, relief of valvar obstruction unmasks an infundibular obstruction resulting a persistent residual right ventricular outflow gradient. Experience has shown that this infundibular obstruction is usually dynamic and regresses with time. Follow-up for pulmonary valve balloon dilatation now extends to nearly 25 years. Efficacy is long lasting in most cases, although about 8% of individuals require repeat dilatation for restenosis.8 Although dilation results in mild to moderate valvular regurgitation, the physiologic consequences of this regurgitation are rarely significant in childhood and adolescence since it is a low pressure regurgitation. Thus the main long-term issues are observation for the relatively rare cases of restenosis, the continued need for endocarditis prophylaxis and the unknown long-term (e.g. 30 to 60 years) effects of the pulmonary regurgitation.

Critical Pulmonic Stenosis in the Newborn Critical stenosis of pulmonary valve presents in the newborn with cyanosis, cardiac failure or occasionally with sudden cardiovascular collapse following ductal closure. Very little blood

Figure 28.2: Balloon pulmonary valvoplasty—Left frame-predilatation and right frame-postdilatation

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can flow across the valve and majority of the venous return to the heart shunts from right to left across the foramen ovale. Left-to-right shunting at the level of the ductus arteriosus maintains pulmonary blood flow and is life saving. As the normal constriction of the ductus arteriosus occurs, the infant becomes progressively and severely hypoxemic and acidotic. These neonates need to be stabilized in the ICU with IV fluids, prostaglandin E1 (PGE1) infusion to maintain ductal patency, correction of acidosis and electrolyte imbalance and positive inotropes to maintain perfusion. In this group of patients, the procedure is technically more demanding than in older children. In early series technical failures and serious complications were common.9 Refinements in technique and technology (such as use of coronary angioplasty wires and very low profile balloons for those with pin-hole critical stenosis) have resulted in progressively improved outcome. In current practice technical success (i.e. successful dilation of the valve) is achieved in almost all cases. Clinical success, which is defined as relief of significant hypoxemia with no more than mild residual valvular obstruction, occurs in 94% of patients.10 Overall, the prognosis of patients with isolated critical pulmonic stenosis with normally developed right ventricle (i.e. non-hypoplastic) is excellent through childhood, however, long-term sequelae need further follow up. Those with hypoplastic right ventricle may need additional procedure in the form of ductal stenting or a Blalock-Taussig shunt to maintain reliable pulmonary blood flow. It has been our practice to routinely stent the ductus in all newborns belonging to this subset.

Aortic Valve Dilatation Severe aortic stenosis presents with syncope, angina, cardiac failure or cardiogenic shock. Balloon aortic valvotomy is an acceptable palliative procedure that relieves obstruction either by separating fused leaflets or by creating small tears that increase the size of the valve orifice.11 It is common for the procedure to result in some degree of aortic insufficiency. The size of the balloon should preferably not exceed 90% of the size of the annulus and certainly should never be more than the aortic annulus. Attempts to alleviate obstruction completely with the use of larger balloons (exceeding annular diameter) result in an unacceptable amount of regurgitation defeating the very purpose of nonsurgical dilatation. Hence, it has been our policy to accept reduction in the gradient by 60 to 70% or a residual gradient of less than 40 mm Hg. This can usually be accomplished without inducing significant aortic regurgitation. Despite using a conservative approach and a stepwise dilatation, significant residual obstruction or aortic insufficiency occurs in about 10% of patients.12-14 During the early years of BAV, a significant number of patients did not get effective dilatation due to “ping-pong” effect (i.e. inability of the balloon to stabilize itself across the aortic valve during inflation). This is more commonly seen in those with normal left ventricular contractility. With the advent of long balloons (5–6 cm in length) and with the use of rapid ventricular pacing during dilatation, this difficulty has been overcome in majority of the patients. The benefit achieved after aortic valve dilation is for variable duration of time. Intervention-free survival is reported to be 50% to 60% at 10 years after dilation.15 The need for subsequent intervention may result from the development of recurrent obstruction, aortic valve insufficiency or both. In the first case, repeat valve dilation is an option, however, when aortic insufficiency becomes severe surgery is the only modality

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of treatment. Thus follow-up care of patients after intervention for aortic valve disease is quite important. Depending on the severity of residual stenosis and insufficiency, patients may be limited from competitive and contact sports. It is mandatory to evaluate them at regular intervals for assessing their symptomatic status and hemodynamics by echocardiography and color flow mapping. All of them need lifelong infective endocarditis prophylaxis.

Critical Aortic Stenosis in the Newborn Critical aortic stenosis encompasses a spectrum with hypoplastic mitral annulus and/or left ventricle and/or ascending aorta at one end while the other end comprises of those patients with normal sized mitral valve, left ventricle and the ascending aorta. Most of the patients with former anatomical subset have what is essentially a hypoplastic left heart syndrome (HLHS) and will need treatment on those lines. For those belonging to the latter subset, balloon aortic valvuloplasty is a preferred option although some centers practice surgical aortic valvuloplasty.16 In this group of patients, there is a variable affection of left ventricular contractility. Although, the LV function tends to recover in the majority after balloon dilation, in a few of them there is such severe myocyte injury that the ventricle is not recoverable even after successful relief of the narrowing.16 The efficacy of balloon valvotomy in newborn critical aortic stenosis is comparable to that of surgical valvotomy and thus has largely replaced the surgical procedure. Mechanical ventilation, inotropic support and PGE1 infusion are administered to the patient depending on the clinical situation. After balloon aortic valvotomy, some infants need several days of continued intensive care with inotropic support to allow recovery of left ventricular performance. Aortic valve is commonly approached by the “retrograde approach” from the femoral artery. The “prograde” approach from the femoral vein across the interatrial septum into the left atrium and then crossing the aortic valve antegradely is becoming more popular. This procedure however, has a higher incidence of failure in delivering the balloons and a significant incidence of damage to the mitral valve apparatus. Also, this approach is more prone to ventricular arrhythmias which are ill tolerated by some with poor LV contractility. Another option is a trans-carotid approach which gives a direct access to the aortic valve requiring less catheter manipulation, less procedural time and a very minimal complication rate.16 Reported early survival of newborns after balloon dilation of critical aortic stenosis is close to 90% in patients without significant left ventricular hypoplasia. Most deaths were procedure related. Subsequent mortality was negligible when followed for up to 8 years.17 Nowadays, with more experience, the procedural mortality is around 4%, but subsequent intervention remains quiet prevalent. The actuarial freedom from reintervention is only 45% at 3 years.18 If reintervention is needed in childhood, it is likely to be necessary in the first year of life. Recurrent aortic stenosis, severe aortic insufficiency or both necessitate reintervention. Patients with isolated restenosis may benefit from repeat balloon dilation, but many of these patients with predominantly regurgitant lesion will undergo autograft root replacement (Ross procedure). To summarize, aortic valve disease is a lifelong disease, and patients who require dilation of aortic stenosis as newborns are likely to have significant residual disease and on-going cardiovascular concerns. Although all patients with aortic stenosis require cardiac follow-up,

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newborns with critical aortic stenosis require frequent evaluation during growth and are virtually certain to need subsequent aortic valve interventions during infancy, childhood or possibly adulthood. With appropriate follow-up management, however, the majority of these children remain asymptomatic.19,20

Coarctation of the Aorta Coarctation of the aorta occurs in 0.04% of individuals and accounts for 5% of heart defects.6 Like aortic stenosis, critical coarctation presents in the newborn period with severe heart failure or shock when the ductus arteriosus closes. Older patients are most often asymptomatic but sometimes present with hypertension or complication of hypertension pertaining to cerebrovascular or cardiovascular systems. They can come to attention due to a murmur produced by an associated bicommissural valve or by presence of intercostals collaterals. All patients with significant coarctation require treatment. Balloon dilation has been used as a treatment for coarctation since the 1980s. It was first used to successfully dilate post-surgical recurrent coarctation of the aorta. The dense scar tissue surrounding the recurrent coarctation makes repeat surgery difficult and provides support against aortic rupture during balloon dilatation, hence, this mode of treatment has become the preferred approach for tackling recoarctation. As regards native coarctation, however, there is still substantial variation in practice. Surgery is the benchmark against which interventional catheter treatment must be judged. Most agree on the choice of therapeutic approach at the extremes of age. In newborns, the preferred treatment is surgical because there is a high rate of recurrent obstruction after balloon dilation. In infants and older children with coarctation, balloon angioplasty is widely used as the primary form of therapy, but opinion is divided, and surgery continues to remain a common option. The controversy surrounding these options relates to the varying reported rates of recurrence and aneurysm formation at the site of balloon dilatation. For example, the incidence of aneurysm formation (the most worrisome complication of this procedure) has been variously reported as ranging from less than 2 to 40% of cases.19-21 Therefore, clinicians should go by the age of the patient and experience and results of the local institutions. In newborns with coarctation presenting with shock or cardiovascular collapse secondary to severe left ventricular dysfunction, balloon dilatation is the procedure of choice as a salvage therapy. Transcatheter balloon dilatation procedure has been made easier by the use of axillary arterial approach.22 The use of a femoral arterial access has a high-risk of significant vessel damage particularly in a premature neonate suffering from aortic coarctation with impaired flow to the lower part of the body. The advantage of using axillary arterial access is that it is not an end-artery and the arm continues to be perfused by the second intercostal artery as well as by the acromial artery. Morever, the axillary artery is much better felt as compared to the femoral in neonates with coarctation with low cardiac output (Fig.28.3). In patients who present after adolescence and into adulthood, stenting of the coarctation is gaining wide acceptance as first line treatment or at least as an acceptable alternative to surgery. Stents result in effective and predictable relief of the obstruction in the majority of cases. The complications with this procedure are infrequent. At follow-up, recurrent coarctation and aneurysm formation is uncommon23-25 (Fig. 28.4). Although, some groups

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routinely use covered stent for aortic coarctation, specific indications for the use of covered stents include previous balloon related complication (e.g. aneurysm), critical obstruction with lumen diameter 30–40 years), coarctation with irregular aortic wall, previous stent related complications (fracture) and acute arterial wall complications such as pseudoaneurysm or aortic rupture (bail out procedure)

Mitral Valve Dilatation Rheumatic mitral valve stenosis (MS) is still a common lesion in children in India. The pliable leaflets, fusion of commisures, mild subvalvar affection and absence of calcification make these valves most suitable for a dilation procedure, which has been demonstrated to be effective in children. Most of the patients with juvenile MS, have small left atria and severe pulmonary hypertension (PHT). Hence they are unable to tolerate acute mitral regurgitation if it were to occur following the balloon mitral valvotomy (BMV). Hence, it is better to accept a mild

Figure 28.3: Successful balloon dilation of coarctation of aorta via the axillary approach

Figure 28.4: Successful stenting of coarctation of aorta

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residual MS rather than producing acute mitral regurgitation in an effort to achieve complete relief of the stenotic element. The anatomy of congenital mitral stenosis is quite variable and is generally not suitable for balloon dilation, although the procedure has occasionally been effective for this lesion. The procedure can be performed by using standard valvuloplasty balloon catheters. In older children, the specially designed Inoue balloon is found to be safe, simple and effective The decision to proceed with balloon valvuloplasty for congenital mitral stenosis should be based on a complete echocardiographic assessment of mitral valve anatomy. The procedure is less likely to be effective when there is a single papillary muscle or severe shortening or virtual absence of the chordal apparatus (the “arcade-type” mitral valve). In view of suboptimum results with surgery as well as with balloon dilatation for congenital MS, our threshold for any form of intervention in congenital MS is quite high unless the patient is symptomatic despite medical treatment or has progressive worsening of PHT.

Dilation of Branch Pulmonary Artery Stenosis The dilation of all varieties of branch pulmonary artery stenosis is a widely accepted procedure, in large part because most of these lesions (especially those beyond the hilum) are not amenable to surgical repair. The success is usually partial, i.e. some percentage reduction of the gradient or percentage improvement in the measured stenosis rather than actually abolishing the gradient or producing a vessel of normal diameter. The technique for dilation of these stenoses is similar to that for pulmonary valve dilation. The balloon size must be at least 1.5 times the diameter of the “normal’ vessel on each side of the stenosis or three to four times the diameter of the actual narrowing. There is a suggestion that the use of high pressure balloon in these lesions will improve the results: however the data from VACA registry for dilation of branch pulmonary arteries does not show significant difference with high pressure balloons.2 Presence of branch pulmonary artery stenosis in the presence of pulmonary regurgitation (PR) (especially seen after surgical repair of tetralogy of Fallot) can further increase the PR leading to progressive right ventricular dilation and reduced function. These patients are at increased risk of decreased exercise tolerance, arrhythmias and sudden cardiac death. Studies have shown that relief of branch pulmonary artery stenosis reduces insufficiency and improves right ventricular systolic function.26 Although the short-term results are quite gratifying, there is a high incidence of restenosis over a period of time. Less than 20% of these dilated vessels are maintained at near normal diameter with insignificant gradient during the follow-up.2 There is a definite morbidity and even mortality related to the procedure. Since there are no predictors of success, balloon dilation is performed as a therapeutic trial. More recently, cutting balloons have been used with more encouraging results .27 Due to suboptimum results with balloon dilatation, stents are being increasingly used to dilate these obstructions. Since their introduction, intravascular stents have become the primary mode of therapy for branch pulmonary artery stenosis in children beyond 5 years of age. The experience with stents in these lesions has significantly changed the approach to branch pulmonary stenosis. The results are excellent and they virtually eliminate any gradient

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and open the vessel to achieve a normal diameter (Fig. 28.5). The initial results have been sustained over years. In addition, it has been demonstrated that if the appropriate stents are implanted initially, these can be dilated further up to the adult diameter of the vessel. Balloon dilation alone of branch pulmonary stenosis is presently recommended only for patients who urgently require some therapy for their lesion but who are too small for implanting an intravascular stent that can be dilated to adult size at a later date. Recently, there have been isolated reports of biodegradable stents being successfully used in neonates with significant branch PA stenosis.28

Dilation of Systemic Vein Stenosis Dilation of stenosed systemic veins, particularly post-surgical, is acutely successful and carries little risk. The surgical alternative for these lesions is poor. These are usually seen in the venous baffles following Senning’s or Mustard’s operation. The other common postoperative venous stenosis is seen in the superior vena cava (SVC) following repair of sinus venosus atrial septal defect or at the site of SVC cannulation for various open heart procedures. Like pulmonary branch stenosis, the results are not uniform or predictable. As with balloon dilation of other vessels, there is immediate hemodynamic, anatomic, and symptomatic improvement, however, recurrence of the stenosis is almost a rule. The balloon diameter chosen should be equivalent to that of the adjacent normal segment of the vessel or baffle. Due to high rates of restenosis, primary therapy for these venous lesions has become implantation of intravascular stents. The large iliac stents are appropriate for the large central veins, even in adult sized patients. The venous stent delivery procedure is similar to any other intravascular stents. For stent delivery, a single balloon of a diameter not less than that of the adjacent nearest normal vein is used. The results of implantation of stents within systemic veins have been excellent. No adverse reactions or long-term complications of the stents have been reported. Some instent restenosis in the venous location has occurred when the stents were dilated to a diameter significantly larger than the adjacent vessel at the time of implant. In these instances the lumen within the stent ‘remodels’ with neointima to the size of the normal adjacent vessel.

Figure 28.5: Successful stenting of the left pulmonary artery in an operated case of tetralogy of Fallot

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Pulmonary Vein Dilation Pulmonary vein dilation provides only transient relief. The procedure is acutely successful in most cases; however, restenosis has been observed in all attempted cases. Attempted dilation of these lesions may be recommended in an infant or child who is severely symptomatic. High pressure balloons and cutting balloons too have been used in an attempt to improve immediate and long-term results. The experience with intravascular stents in pulmonary vein stenosis to date has had no better results than dilation alone and has been associated with a high percentage of complications, including systemic embolization of the stents. Stents have been placed in pulmonary veins surgically under direct vision with limited short-term success.

TRANSCATHETER CLOSURE OF INTRACARDIAC SHUNTS Atrial Septal Defects Atrial septal defects (ASD) are among the more common defects and account for about 10% of all CHD.1 Most of the children are asymptomatic and are incidentally detected due to murmur. Some may present with repeated respiratory tract infections and failure to thrive usually beyond infancy. A very small minority ( 8 kg) to permit placement of the delivery catheter and in whom location of the VSD allows device placement without valve impingement are candidates for the procedure. Although the devices were originally designed for muscular VSDs, the most common, hemodynamically significant VSDs are perimembranous VSDs (pmVSD). The proximity of these VSDs to the aortic and tricuspid valves precluded device closure of these defects till 2000. The Amplatzer Membranous VSD Occluder (St Jude Medical, Plymouth, MA, USA), was designed specifically for these defects. The success rate of transcatheter closure of pmVSD has increased significantly, whereas complications, such as aortic or tricuspid regurgitation and device embolization, have reduced considerably. Several reports have demonstrated that the procedure is efficacious, reporting

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success rate from 86 to 100%.36-40 These reports include patients with postoperative residual VSDs and some who were considered poor surgical candidates.36-40 However, the incidence of heart blocks after closure of pmVSD has remained high, with complete AVB being the most malignant. Incidence of complete AVB has ranged from 1.1% to 5.7% in various reports.37 In addition, other types of post procedure heart blocks (PPHBs), including RBBB, LBBB, and firstdegree AVB, could progress to high-degree AVB. Yang et al, documented that compared with the patients without PPHB, the patients suffering PPHBs were characterized by a significantly longer distance between the aortic valve and the defect, a shorter distance from the lower rim of the defect to the septal leaflet of the tricuspid valve, and a larger diameter difference between the occluder and ventricular septal defect.37 Devices other than the membranous VSD occluder have been used to close pmVSD. These include the Amplatzer duct occluder I and II (AGA Medical Corporation). ADO I has the advantage that it does not have two discs like the other devices and hence does not impinge on the conduction tissue due to clamp force (Fig. 28.7). Also compared to other devices, it is relatively cheaper. ADO II has the advantage that it requires smaller sheath size and can be deployed from the arterial side thus avoiding the need to form an arterio-venous loop. However, since it is available in sizes upto 6 mm, PMVSDs measuring more than 5.5 mm can not be closed with this device. Due to absence of polyester within the discs and a significantly large separation between the discs, the clamp force exerted by this device is significantly lower and is therefore expected to reduce or even abolish the incidence of complete heart block. Follow-up care of children after device occlusion of VSD is essentially the same as after ASD closure with a special attention on the atrioventricular conduction. In summary, device closure of VSD is currently performed for selected muscular defects and for some of the membranous defects. It is likely that the procedure will become more widespread as experience with these devices grows, and they are approved for general use.

Patent Ductus Arteriosus Patent ductus arteriosus (PDA) accounts of 10% of CHD. Larger PDAs may lead to congestive heart failure or pulmonary vascular disease; however, this condition is uncommon other

Figure 28.7: Transcatheter closure of a moderate sized perimembranous VSD with a ADO I device

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than in the premature neonate. Those with moderate sized shunts may present with repeated respiratory tract infections and failure to thrive. Most often children with a small PDA are asymptomatic, and present with a continuous murmur. Thus, the most common indication for closure of the PDA is the prevention of bacterial endocarditis. Transcatheter closure of PDA has been extensively studied. Smaller PDAs (< 3 mm) can be safely and completely closed with coils. A European registry series reported an overall efficacy of 95% in more than 1200 procedures performed between 1994 and 2001.41 In this series, successful occlusion was less likely in larger PDAs. The Amplatzer PDA device has proven efficacious, with a closure rate of 100% in one report,42 and is particularly useful in the closure of larger PDAs (Fig. 28.8). Some investigators in an attempt to decrease cost (especially in developing countries) have used ingenious techniques to deliver multiple coils in an attempt to close large PDAs. These coils are either delivered using a bioptome or a temporary balloon occlusion technique. The incidence of residual shunts is higher with coils when compared to occlusive devices but the cost benefits are considerable with the former. The second generation PDA device, ADO II, is a versatile device for closure of ducts of various shapes and lengths but upto diameter of 5.5 mms only.43 It requires a smaller delivery sheath size and can also be delivered from the arterial side.

CARDIAC INTERVENTIONS IN COMPLEX CONGENITAL HEART DISEASE Pulmonary Atresia with Intact Intravascular Stents (IVS) Newborns with pulmonary valve atresia present in a fashion identical to those with critical pulmonary stenosis, and the initial medical management is identical. The subsequent management of these patients varies enormously because the disorder is very heterogenous. Some patients are born with a well developed right ventricle, whereas others are born with severe right heart hypoplasia but patent tricuspid valve and may also have communications between the cavity of the right ventricle and the coronary arteries (coronary cameral fistulae). These fistulae are often associated with coronary artery stenosis and the coronary artery

Figure 28.8: PDA closure by Amplatzer device

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flow depends on maintaining a high pressure in the right ventricle. A variety of treatment approaches are used to deal with the heterogeneity of this disorder. When the right heart is well developed, the treatment may be much like the treatment for pulmonary stenosis, but surgical management is required when there is significant underdevelopment of any of the right heart structures. Surgery may be directed at achieving a biventricular repair or toward single ventricle palliation, depending on the severity of anatomic abnormalities. Cardiac catheterization is performed in almost all patients with pulmonary atresia. The first goal of the procedure is to complete the diagnostic assessment: angiography is the only way to determine the extent of coronary artery involvement. Patients with a well-developed right heart are candidates for transcatheter treatment. Innovative strategies have been developed that allow the interventionist to perforate the atretic valve plate safely using radiofrequency energy. 44,45 Thereafter sequential balloon dilation of the valve can be performed. In developing countries where cost considerations play a major role in decision making, perforation of the pulmonary valve with the widely available hard end of the coronary guide wire is used as an effective and cheaper alternative.43 Patient selection is the most important factor determining success of both the techniques. Pericardial tamponade arising from inadvertent perforation of the right ventricular outflow tract remains a major concern with both techniques. Despite adequate relief of outflow obstruction it is not uncommon for patients to require surgical shunt/PDA stent for having a predictable and augmented pulmonary blood flow.44,46,47 It is our practice to routinely stent the PDA in all the patients of pulmonary atresia with intact septum after successful perforation of the pulmonary valve. Follow-up concerns in infants with pulmonary atresia vary depending on initial anatomy and the type of intervention performed. After transcatheter perforation and dilation, oxygen saturation is assessed for evidence of atrial right-to left shunting and degree of pulmonary blood flow. Echocardiography is performed to quantify residual obstruction as well as the direction of the atrial shunt so as to know how well the RV hypertrophy and restriction is involuting following relief of obstruction. In patients without significant residual hypoxemia SaO2> 90 % on room air), the prognosis through childhood tends to be good, although some will require repeat intervention for restenosis. As is true for almost all therapies for CHD, the truly long-term (decades) outcomes are not well known and will require ongoing study.

INTRAVASCULAR STENTS IN CONGENITAL HEART DISEASE As discussed under the individual lesions, the major problems with vascular dilation procedures relate to the need for overdilation of the vessel and to restenosis of the lesions, either acutely with vessel recoil or over the long-term. The use of intravascular stents has provided a definitive solution to this problem. There has been extensive favorable experience and more than 10 years’ follow-up in patients with pulmonary artery branch stenosis and systemic vein stenosis. In the single-center series of Mullins et al at Texas Children’s Hospital, more than 655 stents were implanted in 340 patients with pulmonary artery and systemic veins stenosis. Further dilation of these stents has been successful for as long as 4 years after implant.2 To be used in the growing patients, the stent that is used initially must be capable of being dilated to a full adult-vessel diameter.

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The largest group of patients in this series had lesions involving the central pulmonary arteries in postoperative period and postoperative central systemic vein or systemic venous baffle stenosis. Many of these stenotic veins had a totally occluded initial lumen; some of the venous channels were purposely perforated with a wire or long needle. The mean vessel diameter increased from 5 to 12 mm (with an increase in area from 20 to 113 mm2). The success was lasting, with fewer than 0.5% showing restenosis during the period of follow-up. The number of complications from the procedure or the stents themselves was minimal. Intravascular stents in the branch pulmonary arteries and systemic veins have been demonstrated to provide definitive therapy for these lesions and offer an entirely new outlook for these previously inoperable patients.4 The intravascular stents are now used in many other areas such as the aorta and other intravascular stenosis. Larger stents are already available in Europe for the large adult patient. There are new developments in the area of split, ‘open ring’ stents and biodegradable stents that would make these forms of therapy available for the infants and small children. “Covered” stents have been used in the adult catheterization laboratories for the treatment of ruptured vessels, including aortic aneurysms. In addition, this type of covered stent may be able to be used for transcatheter completion of a lateral tunnel Fontan procedure.

Closure of Abnormal Vascular Communications: Embolization Therapy Embolization of abnormal or persistent arterial or AV structures has been available for more than 30 years. The embolization techniques were developed and perfected primarily by the vascular radiologists working in the abdominal viscera, gastrointestinal areas, and central nervous system, particularly in “end arteries”. Many materials and devices, including the patients’ own clotted blood, gelfoam, colloidal plugs, ‘glues,” detached balloons, and coil occlusion devices, have been used for these peripheral occlusion. The Gianturco (Cook, Inc.) coils are the most commonly used of all these occlusion devices for patients with congenital cardiac defects. These coils are made of spring wire with polyester fibers enmeshed in the coils, which are available in several sizes and multiple diameters and lengths. The coil is introduced into the delivery catheter through a straight metal “loader” as a straight wire. When it is delivered by extrusion out of the distal end of the catheter, it coils like a small “pigtail”. Once delivery with this particular coil has been started, there is no way of withdrawing the coil back into the catheter. The Gianturco coil occludes the vessel by the creation of a mass of fabric and wire in which a thrombus is formed. The coil occlusion device usually is delivered into a vessel with a discrete distal narrowing, where it will fix in place and not migrate further through the vessel. Often, several coils are placed in a single vessel to achieve complete occlusion. The coils are only usable in tubular structures with a distended diameter up to 7 to 8 mm. For larger vessels or vessels without an area of discrete stenosis, coils can be used in conjunction with other intravascular occlusion devices to complete the occlusion of the vessel. Recently, Amplatzer vascular plug is being used to occlude these abnormal communications. It has a smaller and maneuverable delivery system. In addition, the control over the plug, like all other members of Amplatzer family of devices, is far superior than the coils.

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Many abnormal collateral vessels or persistent surgically created systemic to pulmonary artery shunts are associated with complex intracardiac lesions. These vessels need occlusion when systemic flow competes with normal pulmonary flow, particularly when the major defect is corrected, e.g. TOF with pulmonary atresia. These communications traditionally required surgical division during the corrective procedure or as a separate procedure. Other lesions in which these devices may be useful are AV fistulae, including systemic, coronary-cameral, and peripheral as well as pulmonary AV fistulae. In these lesions, it is critical to identify the stenotic or “end” vessel into which the device can be fixed in order to reduce the dangers of migration to vital structure.

Stenting of the PDA in Duct Dependent Circulations Recently, ductal stenting is emerging as an alternative to systemico-pulmonary shunt for palliating duct dependent circulations. Pulmonary atresia with intact ventricular septum, TOF with pulmonary atresia, tricuspid atresia with pulmonary atresia and HLHS are some of the indications for duct stenting. The procedure is usually performed under general anesthesia with IPPR. Intravenous prostaglandin is stopped half to one hour prior to the stent delivery so as to let the duct constrict a little. This prevents migration of the stent during and immediately after the delivery. Most of the children remain on small dose aspirin till such time the presence of the ductus is required. The stenting can be performed from the arterial or the venous side; each having its merits and demerits. Local vascular injury, pulmonary artery obstruction, ductal spasm, stent migration, acute or subacute stent thrombosis and in-stent restenosis are some of the complications reported with this procedure.48

Transcatheter Replacement of Pulmonary Valve Over the last decade, a great deal of experience has been gathered in percutaneous transcatheter replacement of pulmonary valve. Currently, two valves (Medtronic and Edward) 49 are being used for this purpose. Both are stent mounted valves delivered through the femoral vein using long sheaths. Currently, the procedure is being done mainly for those patients with RV-PA conduits who have a free PR or PS with PR due to valve degeneration. In those with a significant PS, the narrowing is relieved by balloon dilation prior to implantation of the valve. This procedure is being performed in adolescents and adults who have almost completed their growth. Recently, Bonhoeffer et al published their data of the first 100 implants (Abstract from World Congress) with no mortality and a very low morbidity such as migration of the stent and vascular injury. There are efforts being made to modify the design so as to suit those with surgically corrected TOF with free PR in whom RV-PA conduit was not used. If this becomes possible, the number of patients benefiting from this procedure will increase exponentially.

Transcatheter replacement of other valves Transcatheter valve implantation in positions other than pulmonary valve have also been reported, although mainly in adults.50 Presently these systems have a larger profile making them unsuitable for pediatric patients. These valves are implanted over failed bioprosthetic valves and hence provide the patient with a favorable less invasive alternative.

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REFERENCES 1. Rashkind WJ, Miller W. Creation of an atrial septal defect without thoracotomy: Pallative approach to complete transposition of the great arteries. JAMA. 1966;196:991–92. 2. Bridges ND, O’Laughlin MP, Mullins CE, Freed MD. From Moss and Adams’ Heart disease in Infants, Children and Adolescents, 6th edn. Philadelphia: Lippincott Williams & Wilkins. 2001;26–324. 3. Ashfaq M, Houston AB, Gnanapragasam JP, Lilley S, Murtagh EP. Balloon atrial septostomy under echocardiographic control: Six years’ experience and evaluation of the practicability of cannulationveia the umbilical vein. Br Heart J. 1991;65:148–51. 4 . Kakadekar AP, Hayes A, Rosenthal E, et al. Balloon atrial septostomy in the intensive care unit under echocardiographic control: Nine years experience. Cardiol in the Young. 1992;2:175–78. 5. Park SC, Neches WH, Zuberbuhler JR, et al. Clinical use of blade atrial septostomy. Circulation. 1978;58:600–06. 6. Hoffman JI, Kaplan S. The incidence of congenital heart disease, J Am Coll Cardiol. 2002:39(12):1890–900. 7. Nugent EW, Freedom RM, Nora JJ, Ellison RC, Rowe RD, Nadas AS. Clinical course of pulmonary stenosis. Circulation. 1977;56(1 suppl):36–71. 8. McCrindle BW. Independent predictors of long-term results after balloon pulmonary valvuloplasty. Valvuloplasty and Angioplasty of Congenital Anomalies (VACA) Registry Investigaors. Circulation. 1994;89(4):1751–59. 9. Zeevi B. Keane JF. Fellows KE Lock JE. Balloon dilation of critical pulmonary stenosis in the first week of life. J Am Coll Cardiol. 1988;11:821–24. 10. Gournay V. Piechaud JF. Delogu A. Sidi D. Kachaner J. Balloon valvotomy for critical stenosis or atresia of pulmonary valve in newborns. J Am Coll Cardiol. 1995;26(7):1725–31. 11. Helgason H, Keane JF, Fellows KE, Kulik TJ. Balloon dilation of the aortic valve: Studies in normal lambs and in children with aortic stenosis. J Am Coll Cadiol. 1987;9(4):816–22. 12. Scoller GF, Keane JF, Perry SB, Sanders SP, Lock JE. Balloon dilation of the congenital aortic valve stenosis: Results and influence of technical and morphological features on outcome. Circulation. 1988;78(2):351–60. 13. Shaddy RE, Boueek MM, Sturtevant JE, Ruttenburg HD, Orsmond HS. Gradient reduction, aortic valve regurgitation and prolapse after balloon aortic valvoplasty in 32 consecutive patients with congenital aortic stenosis. J Am Coll Cardiol. 1990;16(2):451–56. 14. O’Connor BK, Beekman RH, Rocchini AP, Rosenathal A. Intermediate-term effectiveness of balloon valvloplasty for congenital aortic stenosis: A Prospective follow-up study. Circulation 1991;84(2):732–38. 15. Reich O, Tax P, Marek J, et al. Long-term results of percutaneous balloon valvoplasty of congenital aortic stenosis: Independent predictors of outcome. Heart. 2004:90(1):70–76. 16. Rome JJ, Kreutzer J. Pediatric interventional catheterization: Reasonable expectations and outcomes. Pediatr Clin N Am. 2004;51:1589–1610. 17. Egito ES. Moore P.O’Sullivan J, et al. Transvascular balloon dilation for neonatal critical aortic stenosis: Early and midterm results. J Am Coll Cardiol. 1997;29(2):442–7. 18. Schneider HE. Kreutzer J. Cohen MS. Spray TL. Rome JJ. Intermediate-term outcome neonates with critical aortic stenosis after valvotomy in the Ross era. Circulation. 2003;108(17):IV.678. 19. Heggon IC, Qureshi SA, Baker EJ, Tynan M. Effect of introducing balloon dilation of native aortic coarctation on overall outcome in infants and children. Am J Cardiol. 1994;73:799–807. 20. ShaddyRE,Boueck MM, Sturtevant JE. et al. Comparison of angioplasty and surgery for unoperated coarctation of the aorta. Circulation. 1993;87:793–99. 21. Tynan M, Finley JP, Fontes V, Hess J, Kan J. Balloon angioplasty for the treatment of native coarctation: Results of valvuloplasty and angioplasty of congenital anomalies registry. Am J Cardiol. 1990;65:790–92. 22. Michel-Behnke I, Schranz D. Axillary artery access for cardiac interventions in newborns. Ann Pediatr Card. 2008;1(2):126–130.

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23. Thanopoulos BD, Hadjinikolaou L, Konstadopoulon GN, Tsaousis GS, Tripokiadis F, Spirou P. Stent treatment for coractation of the aorta intermediate term follow-up and technical considerations. Heart. 2000;84(1):65–70. 24. Marshall AC, Perry SB, Keane JF, Lock JE. Early results and medium-term follow-up of stent implantation for mild residual or recurrent aortic coarctation. Am Heart J. 2000;139(6):1054–60. 25. Tyagi S. Singh S. Mukhopadhyay S. Kaul UA. Self– and balloon-expandable stent implantation for severe native coarctation of aorta in adults. Am Heart J. 2003;146(5):920–28. 26. Petit CJ, Gillespie MJ, Harris MA, Seymour TL, Liu TY, Khan A, Gaynor JW, Rome JJ. Relief of branch pulmonary artery stenosis reduces pulmonary valve insufficiency in a swine model. J Thorac Cardiovasc Surg. 2009;138:382–9. 27. Bergersen LJ, Perry SB, Lock JE. Effect of cutting balloon angioplasty on resistant pulmonary artery stenosis. Am J of Cardiol. 2003;91(2):185–189. 28. Peters B, Ewert P, Berger F. The role of stents in the treatment of congenital heart disease: Current status and future perspectives. Ann Pediatr Cardiol. 2009;2(1):3–23. 29. Lopez K, Dalvi BV, Balzer D, Bass JL, Momenah T, Cao Q, Hijazi ZM. Transcatheter closure of large secundum atrial spetal defects using the 40 mm Amplatzer Septal occluder.Results of an international registry. Catheter Cardiovasc Interv. 2005;66:580–84. 30. Du ZD, Hijazi ZM, Kleinman CS, Silverman NH, Larntz K, Amplatzer L. Comparison between transcatheter and surgical closure of secundum atrial septal defect in children and adults: Results of a multicentre nonrandomized trial. J Am Coll Cardiol. 2002;39(11):1836–44. 31. Formigari R, Di Donato RM, Mazzera E, et al. Minimally invasive or interventional repair of atrial septal defects in children: experience in 171 cases and comparasion with conventional . JACC. 2001; 37(6):1707–12. 32. Dalvi BV, Pinto RJ, Gupta A. New technique for device closure of large atrial septal defects. Catheter Cardiovasc Interv 2005;64:102–07. 33. Krumsdorf U Keppeler P, Horvth K Zadan E, Schrader R, Sievert H. Catheter closure of atrial septal defects and patent foramen ovale in patients with an atrial septal aneurysm using different devices. J Interv Cardiol. 2001;14(1):49–55. 34. Weidman WH, Blount Jr SG, DuShane JW, Gersony WM, Hayes CJ, Nadas AS. Clinical course in ventricular septal defect. Circulation. 1977;56(1Suppl):156–69. 35. Bacha EA, Hijazi ZM, Cao QL, Abdulla R, Starr JP, Quinones J, Koenig P, Agarwala B. Hybrid pediatric cardiac surgery. Pediatric Cardiology. 2005;26:315–22. 36. Thanopolus BD, Tsaousis GS, Konstadopoulon GN, Zarayelyan AG. Transcatheter closure of muscular ventricular septal defects with Amplatzer Ventricular Septal Defect Occluder: Initial clinical applications in children. J Am Coll Cardiol. 1999;33(5):1395–1459. 37. Yang R, Kong XQ, Sheng YH, Zhou L, Xu D, Yong YH, Sun W, Zhang H, Cao KJ. Risk factors and outcomes of post-procedure heart blocks after transcatheter device closure of perimembranous ventricular septal defect. J Am Coll Cardiol Intv. 2012;5:422–7. 38. Holzer R, Balzer D, Lock K, Hijazi ZM. Device closure of muscular ventricular septal defects using Amplatzer Muscular Ventricular Septal Defect Occluder: Immediate and midterm results of a US registry. J Am Coll Cardiol. 2004;43(7):1257–63. 39. Bridges ND, Perry SB, Keane JF, et al. Preoperative transcatheter closure of congenital muscular ventricular septal defects. N Engl J Med. 1991;324(19):1312–17. 40. Arora R, Trehan V, Thakur AK, Mehta V, Sengupta PP, Nigam M. Transcatheter closure of congenital muscular ventricular septal defect. J Interv Cardiol. 2002;17(2):109–15. 41. Magee AG, Huggon IC, Seed PT, Qureshi SA, Tynan M. Transcatheter coil occlusion of the arterial duct: Results of the European Registry. Eur Heart J. 2001;22(19):18171–72. 42. Ebeid MR, Masura J, Hijazi ZM. Early experience with the Amplatzer ductal occluder for closure of the persistently patent ductus arteriosus. J Interv Cardiol. 2001;14(1):33–36.

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43. Bhole V, Miller P, Mehta C, Stumper O, Reinhardt Z, De Giovanni JV. Clinical evaluation of the new Amplatzer duct occluder II for patent arterial duct occlusion. Catheter Cardiovasc Interv. 2009;74(5):762–9. 44. Humpl T. Soderberg B. MeCrindle BW, et al. Percutaneous balloon valvotomy in pulmonary atresia with intact ventricular septum: Impact on patient care. Circulation. 2003;108(7):826–32. 45. Justo RN. Nykanen DG. Williams WG. Freedom RM. Benson LN. Transcatheter perforation of the right ventricular outflow tract as initial therapy for pulmonary valve atresia and intact ventricular septum in the newborn. Cathet Cardiovase Diagn. 1997;40(4):408–13. 46. Pinto RJ, Dalvi BV. Transcatheter Guidrewire perforation of the pulmonary valve as a palliative procedure in pulmonary atresia with intact interventricular septum. Indian Heart J. 2004;56: 661–63. 47. Ovaert C. Qureshi SA. Rosenthal E. Baker EJ. Tynan M. Growth of the right ventricle after successful transcatheter pulmonary valvotomy in neonates and infants with pulmonary atresia and intact ventricular septum. J Thorac Cardiovase Surg. 1998;115(5):1055–62. 48. Alwi M, Choo KK, Latiff HA, Kandavello G, Samion H, Mulyadi MD. Initial results and mediumterm follow-up of stent implantation of patent ductus arteriosus in duct-dependent pulmonary circulation. J Am Coll Cardiol. 2004;4:438–45. 49. Block PC, Bonhoffer P. Percutaneous approaches to valvular heart disease. Current Cardiology Rep. 2005;(2):108–13. 50. Webb JG, Wood DA, Ye J, Gurvitch R, et al. Transcatheter valve-in-valve implantation for failed bioprosthetic heart valves. Circulation. 2010;121:1848–57.

29

Surgery for Common Congenital Cardiac Defects

Krishna S Iyer, S Vijay

Congenital heart disease remains an important cause of childhood morbidity and mortality. In todays world, most congenital heart defects can be surgically repaired or treated by intervention in the cardiac catheterization laboratory. It is well-accepted now that whenever feasible surgery should be performed earlier than later—before the onset of myocardial dysfunction or secondary organ damage in particular pulmonary vascular disease. Elective cardiac surgery for common defects performed in experienced centres carries a mortality risk of less than 3%. Surgical intervention should therefore be recommended without hesitation, once a diagnosis has been established. This chapter will cover surgical aspects of common congenital heart defects relevant to the practicing pediatrician. For ease of understanding, a surgical classification and approximate incidence of the common congenital cardiac defects are given below:

Acyanotic Left to right shunts: Ventricular septal defect (VSD) Atrial septal defect (ASD) Patent ductus arteriosus (PDA) Atrio-ventricular septal defect (AVSD) Aorto-pulmonary window Left-sided obstructive lesions : Aortic coarctation Congenital aortic stenosis Interrupted aortic arch Congenital mitral stenosis

20 % 10 % 10 % 2–3 % rare 10 % 10 % 1% rare

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Cyanotic Right to left shunts : Tetralogy of Fallot (TOF) Pulmonary stenosis   (with VSD, ASD or single ventricle) Pulmonary atresia (with or without VSD) Tricuspid atresia (TA) Ebstein’s anamoly Complex mixing defects: Transposition of great arteries (TGA) Total anamolous pulmonary venous connection (TAPVC) Truncus arteriosus Hypoplastic left heart syndrome (HLHS)

10 % 10 % 5% 3% 0.5 % 5–8 % 2% 3% 2%

GENERAL ASPECTS OF CARDIOVASCULAR SURGERY Open vs. Closed Heart Surgery Cardiac surgical procedures are broadly categorized into ‘open’ and ‘closed’, the division dating back to the early days of cardiac surgery where open heart surgery referred to situations where the heart chambers were opened and closed heart surgery referred to extra-cardiac operations not involving opening of the heart chambers. Currently open heart surgery generally refers to any procedure in which a heart lung machine (cardio-pulmonary bypass) has been used, and closed heart surgery is one that has been performed without a heart-lung machine. Common closed heart procedures include ligation of patent ductus arteriosus (PDA), repair of coarctation of the aorta, creation of systemic to pulmonary artery shunts and banding of the pulmonary artery.

Cardiopulmonary Bypass (CPB) The temporary transfer of cardiac and pulmonary function in part or whole to a mechanical device is known as cardiopulmonary bypass. Key components of CPB include the heart-lung machine, oxygenator, venous reservoir, circuit tubing, filters, hemoconcentrator, cardioplegia delivery system and temperature control module. During a standard cardiopulmonary bypass, venous blood is drained from the patient through cannulas in the venae cavae into the venous reservoir. This blood is then pumped by a roller pump first into a membrane oxygenator where it gets oxygenated and then onwards through a cannula in the aorta into the patient’s circulation. Carbon dioxide is simultaneously removed from the venous blood in the oxygenator and the blood is cooled or warmed as desired at this point. The system has to be ‘primed’ with a mixture of blood and/or crystalloid solution prior to the onset of CPB. Access to the interior of the heart requires cessation of cardiac activity and this is achieved by injecting cold cardioplegia solution into the coronary arteries through the aortic root. Commonly used cardioplegia solutions have a high concentration of potassium and thus produce diastolic arrest of the heart. Cessation of

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electrical activity and cooling allows preservation of the myocardium for upto 4 hours, during which time complex intracardiac repairs can be performed. Although the safety of CPB has substantially improved in recent years, it remains potentially injurious especially in neonates and low-weight infants. Complications of CPB include—capillary leak syndrome, multi-organ dysfunction, systemic inflammatory response syndrome (SIRS), cerebral embolism, ARDS, sepsis and coagulation disorders.

Deep Hypothermia and Circulatory Arrest Most intracardiac repairs can be performed using standard CPB. Repairs involving the aortic arch or intracardiac repairs in very low weight babies may require cessation of circulation to be successfully performed. This necessitates cooling of the body to deep hypothermia levels (16 to 18°C), to prevent anoxic brain damage. Despite all safety measures, however, deep hypothermic circulatory arrest is still associated with a finite incidence of neurological complications including seizures, choreoathetosis and neurocognitive disturbances and is therefore avoided as far as possible.

Surgical Access to the Heart The standard and most often used approach to the heart is through a midsternotomy incision — a vertical incision extending from the suprasternal notch to the xiphisternum. It provides access to all cardiac structures and is the safest of all approaches to the heart. Operations on the great vessels or the branch pulmonary arteries like PDA ligation or BT shunt are usually performed from the side of the chest — thoracotomy incisions. A cosmetically appealing minimal access approach may be used for simpler lesions like ASD, however these approaches limit access to all areas of the heart, compromise safety and should therefore be judiciously used.

Palliative vs. Corrective Surgery Most congenital cardiac malformations are amenable to surgical correction which means that surgery achieves anatomic and physiologic continuity of the circulatory pathway. In some situations surgery may achieve normal circulation but the anatomy may remain abnormal, e.g. the atrial rerouting operation for transposition of great arteries (Senning procedure). Such procedures are classified as physiologic corrections. Operations where neither anatomic nor physiologic normalcy are achieved are referred to as palliative procedures. These operations are performed to improve hemodynamics in situations where no corrective surgery is feasible. Most palliative procedures today are performed in patients with ‘single ventricle’ physiology as this is the only type of congenital heart disease (CHD) for which no corrective surgery is as yet available.

Valved Conduits Many of the corrective procedures for complex lesions involve the use of what are known as valved conduits. A valved conduit is essentially a tube with a valve incorporated within it. Conduits may be homografts, xenografts or synthetic in nature. Homograft conduits are either aortic homografts (aortic valve and ascending aorta) or pulmonary homografts (pulmonary

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artery with pulmonary valve) which are harvested from human cadavers, sterilized in antibiotic solutions and stored in liquid nitrogen. They require special homograft banks for processing and storage and so are not readily available. Xenograft conduits are generally pulmonary valves harvested from pigs which are processed in glutaraldehyde to make them non-antigenic and durable. These valves are then stitched within a roll of processed bovine pericardium or a tube of crimped Dacron to form the conduits. Xenograft conduits are made commercially and are readily available. Xenograft valves are also made from bovine pericardium. Both homografts and xenografts tend to degenerate and become narrow over course of time, however, properly harvested and processed homografts of larger size are likely to have a better lifespan. Placement of a valved conduit therefore commits the patient to reoperation for eventual conduit replacement The smaller a conduit, the more are the chances of early degeneration and need for reoperation.

Preoperative Considerations Young age and low weight are no bar to cardiac surgery. Open heart surgery is safely possible even in a one day old neonate. Successful open-heart surgery has been reported in preterm babies weighing as little as 700  gm. However the lesser the weight, the greater the postoperative morbidity and therefore the greater the resources required for successful outcome. The outcome of intervention in these very small and young babies depends on the experience and skills of the treating team and the resources available. When there is gross disproportion between weight and age, i.e. significant malnutrition, then surgical morbidity is further increased and also sometimes surgical mortality. Due care needs to be given to nutritional rehabilitation during the presurgical care of the patient. Elective surgery requires that the child be free of any infections especially respiratory tract infections. Common occult infections include urinary tract infection, dental caries and otitis media which need to be carefully looked for. Emergency surgery may be performed even in the presence of infection depending on the need—in which case a more stormy postoperative course should be anticipated. Children with CHD should receive immunization as per normal schedule. Immunization against Hepatitis B is of particular advantage as most surgical procedures require transfusion of blood and blood products. Infants with CHD often have associated syndromic disorders, e.g. Trisomy 21, 22q11.2 deletion syndrome, etc. These have important prognostic implications and it is important for the treating pediatrician to educate and counsel the parents on the special care requirements of these children.

Postoperative Care and Complications Immediate postoperative care is given in an intensive care unit that is appropriately equipped. Neonates and infants weighing less than 4 kg are nursed in an open infant care system with servo-controlled thermoregulation. Continuous monitoring of ECG, arterial blood pressure, left atrial or central venous pressure, oxygen saturation and urine output are routine. Ventilatory support is generally provided for a few hours to a few days depending on the nature of the surgical procedure, presence of pulmonary hypertension and presence or absence of early surgical complications. Patients with preoperative severe pulmonary hypertension benefit

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from an extended period of ventilation postoperatively to allow for normalization of the pulmonary vasculature. Transient low cardiac output is frequent in the postoperative period and is managed by the use of inotropic agents like dobutamine, dopamine and epinephrine or inodilators like milrinone. Vasodilators such as nitroglycerine and sodium nitro-prusside are often used to regulate systemic and pulmonary vascular resistance. Fluid intake is closely regulated and urine output often needs augmentation by use of frusemide infusion. Bed-side echocardiography is performed routinely to assess the adequacy of correction and monitor ventricular function. Hemodynamic supports are gradually weaned off, once cardiovascular stability has been achieved—ventilatory support usually being the first to be withdrawn. The child is sequentially moved from the ICU to a step-down area and then to a ward as the level of supportive care is decreased. Postoperative complications may be related to deleterious effects of cardio-pulmonary bypass, to low cardiac output secondary to myocardial dysfunction and/or residual cardiac defects. Complications related to CPB include capillary leak syndrome also known as the sterile inflammatory response syndrome; pulmonary, hepatic or renal dysfunction; coagulation disorders and CNS disturbances. CNS complications are more likely if circulatory arrest has been utilized. In general these complications are uncommon in routine surgeries requiring CPB of less than two hours duration. Complications are more likely to occur in complex repairs requiring very long CPB, in preterm babies and in low-weight infants where the solid organs are more susceptible to injury. Postoperative infection is a dreaded complication and may take the form of wound infection, mediastinitis, pneumonia, urinary tract infection, generalized sepsis or endocarditis. In infants, infection often results from preoperative colonization in the urinary tract, skin or upper airways. Wound infections are generally caused by Staphylococcus aureus and are often related to preoperative skin colonization with MRSA. Most other infections are caused by gram-negative organisms — Klebsiella, E. coli and Pseudomonas species being most often responsible.

Palliative Procedures Systemic–Pulmonary Artery Shunts These are by far the commonest palliative procedures performed. The essence of these procedures is to shunt some blood from the systemic circuit to the pulmonary circuit to either: (a) augment pulmonary blood flow (in patients with symptomatic cyanosis due to decreased pulmonary blood flow), thereby improving systemic arterial oxygen saturation, or (b) provide a flow and pressure stimulus to augment growth (in patients with hypoplastic pulmonary arteries associated with dereased pulmonary blood flow). The commonest of these shunts is the modified Blalock-Taussig shunt (BT shunt) in which a short segment of PTFE (polytetrafluoroethylene) tube graft is interposed between the subclavian artery and the pulmonary artery of the same side. The size of the graft is decided on the basis of the weight of the patient and the degree of preoperative cyanosis. An undersized graft may result in inadequate relief of cyanosis while a larger than required graft may cause pulmonary over-circulation leading to heart failure or pulmonary vascular disease over time.

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The operation is usually performed through a lateral thoracotomy, but may also be performed through a mid-sternotomy if some other cardiac procedures need to be performed at the same time. When the pulmonary arteries are extremely small, it is better to place a shunt to the main pulmonary artery so that both branch pulmonary arteries receive equal augmentation of blood flow. Such a shunt is called a central shunt. Other forms of shunts like Waterston’s shunt and Pott’s shunt are no longer performed nowadays and are only of historic significance. Common indications for systemic to pulmonary artery shunts are: a. Fallot’s physiology with severe cyanosis in early infancy or with small pulmonary arteries where corrective surgery is either not feasible or expected to carry high risk. b. As a first stage surgery in conditions that require a right ventricle to pulmonary artery conduit for correction of pulmonary stenosis or atresia—to defer the age of correction and allow for placement of a larger conduit. c. As a first stage surgery in single ventricle situations in preparation for an eventual Fontan type circulation. Operative risk is generally less than 5% and is governed by the preoperative status of the patient, age at surgery and nature of cardiac defect.

Pulmonary Artery Banding This procedure is generally performed to retrict excess pulmonary blood flow in situations where a corrective option does not exist. These situations are : a. Multiple muscular VSD’s (so called swiss-cheese septum) b. Single ventricle situation with no pulmonary stenosis The procedure is also occasionally performed to retrain a regressed left ventricle in the setting of transposition of great arteries to make it suitable for an arterial switch operation. The operation is usually carried out through a thoracotomy or a limited mid-sternotomy. The pulmonary artery is isolated and a thin band of siliconized tape or mersilene is passed around it. The band is then tightened to the desired level and secured in place. Hemodynamic adjustment to the band takes some time and as a result the postoperative course can often be stormy. As with other palliative procedures the operative risk is dictated by the preoperative status and the nature of underlying defect.

Corrective Procedures Patent Ductus Arteriosus (PDA) An isolated patent arterial duct is approached through a left postero-lateral thoracotomy incision. After isolation at its origin from the descending thoracic aorta the ductus is either ligated with multiple sutures or divided between clamps and the cut ends oversewn. Controlled systemic hypotension during the procedure reduces the risk of ductal rupture and catastrophic hemorrhage. Ligation has the potential chance of residual ductal patency, however it is a simple and safe procedure. Division of the ductus is an alternative technique which eliminates the chances of residual patency but increases the risk of intra-operative hemorrhage. PDA

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complicated by severe pulmonary hypertension, calcification or endocarditis requires alternative surgical techniques which are beyond the scope of this discussion. When PDA is associated with other intra-cardiac lesions requiring simultaneous correction then it is approached through a midsternotomy incision and the pulmonary artery end is isolated and ligated. Surgical mortality is less than 1%. Specific early complications include thoracic duct injury and chylothorax, recurrent laryngeal nerve injury and lung complications.

Aortopulmonary (AP) Window AP window is a rare congenital heart defect resulting from abnormal septation of the embryonic truncus arteriosus into the aorta and the pulmonary artery. The physiology of AP window is similar to that of a large patent ductus arteriosus , VSD or truncus arteriosus. The magnitude of the left to right shunt is related mainly to the size of the defect and the pulmonary vascular resistance. Because the aorto-pulmonary communication has almost no length even small defects can result in a marked left to right shunt with congestive heart failure, pulmonary hypertension and early development of pulmonary vascular obstructive disease. Surgical repair is, therefore, indicated for all patients with AP window and should be undertaken at the earliest after diagnosis. The procedure of choice is the patch closure of the defect by a technique called as the ’ Anterior sandwich patch technique’. Under standard cardiopulmonary bypass and under cardioplegic arrest the anterior wall of the AP window is opened vertically. A prosthetic patch is sewn to the superior , posterior and inferior rims of the defect . Coronary ostia are visualized and retained in the aortic side of the patch. The incision is then closed incorporating the patch in the anterior suture line. Pulmonary hypertensive crisis can complicate post operative recovery. Surgical mortality should be less than 3 %. Coarctation of Aorta As with a PDA, exposure for coarctation repair is through a left posterolateral thoracotomy. Several techniques repair of coarctation are available depending on the nature of the lesion. In infants and young patients resection of the segment of aorta that is narrowed and direct anastamosis of the normal cut ends (resection and end to end anastamosis) is the preferred mode of treatment. Often the distal arch of the aorta is hypoplastic and in this situation the undersurface of the arch is cut open longitudinally and the distal cut end of the aorta is anastamosed to the undersurface of the arch thereby widening this area (extended aortoplasty). A technique known as subclavian flap aortoplasty was popular a few years ago but is not often performed now. In this procedure the left subclavian artery is divided at its first branch and then cut longitudinally to form a patch which is used to widen the coarctation segment. In older patients balloon dilatation and stent implantation has become the first line of management. However, wherever surgery is required the procedure requires the use of a synthetic graft to either bypass the coarctation segment or to interpose between the cut ends of the aorta after resection. This is so because in older patients the aorta is not pliable enough to be stretched and anastamosed directly after resection. When coarctation exists with other intracardiac lesions like VSD or TGA requiring simultaneous correction then repair is performed through a midsternotomy incision and all lesions are corrected simultaneously.

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The aim of surgery is to relieve the obstruction completely leaving no residual gradient. Surgical mortality is less than 3 % for isolated coarctation. Mortality is higher in the presence of other intra-cardiac lesions requiring simultaneous correction or when the patient presents late with advanced left ventricular dysfunction. Early operative complications are similar to that for PDA surgery. When repair is performed in the neonatal period, there is a potential for recurrent coarctation. The reported incidence of this complication is in the range of 5–20 % .

Atrial Septal Defect (ASD) Non-surgical device closure of ASD in the cardiac catheterisation laboratory has become the norm whenever the size and location is appropriate for this technique. Surgical closure is recommended for the larger defects and those not considered suitable for device closure. Surgically ASD’s are exposed by opening the right atrium under CPB after stopping the heart with cardioplegia. Small secundum defects are closed by directly suturing the edges together. Larger defects are closed using a patch of Dacron cloth or autologous pericardium. Sinus venosus defects are usually associated with anomalous drainage of the right pulmonary veins to the superior vena cava. These defects are always closed with a patch which is sutured in such a way that the pulmonary veins are routed to the left atrium. Defects of the primum variety also have to be closed with a patch. Special attention needs to be paid to the protection of the conduction bundle which runs along the inferior margin of the defect. ASD closure is very low risk surgery and operative mortality approaches 0%. The standard approach is a mid-sternotomy incision but because of the relative simplicity of the procedure many techniques have evolved to reduce the size of the incision and make the operative scar more cosmetically appealing. In older children and adolescents ‘port-access’ surgery and robotically assisted surgery may also be feasible. Ventricular Septal Defect (VSD) VSD’s may be functionally classified into small, moderate and large. Anatomically they may be located in the membranous septum (perimembranous VSD), inlet septum (inlet VSD), trabecular septum (mid-muscular VSD) or in the outlet septum (sub-pulmonic VSD). VSD’s are usually single but may occasionally be multiple. The decision for and timing of surgical intervention is based on symptoms, size of the VSD, its location and age of the patient. Defects in the ventricular septum are approached in different ways depending on the location. Perimembranous defects are approached through the right atrium and accessed by retracting the tricuspid valve. The defects are closed with a patch of Dacron, PTFE or glutaraldehyde treated autologous pericardium. The patch is secured with interrupted sutures or a continuous suture, care being taken to protect the aortic valve along the superior margin and the conduction bundle along the postero-inferior margin. Defects in the mid-muscular septum and the inlet septum are also accessible through the tricuspid valve. Apical muscular VSD’s may require an incision in the apex of the right ventricle for access. Doubly committed sub-arterial VSD’s are most appropriately closed through the pulmonary artery. Aortic valve prolapse often complicates longstanding VSD’s especially those in the subarterial region. In the absence of aortic regurgitation VSD closure alone is sufficient to

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prevent further prolapse of the aortic cusp, however, if significant aortic regurgitation is present then the valve is repaired or replaced depending on the degree of deformity of the cusp. Operative mortality is less than 3%. Postoperative course is generally smooth unless there has been significant pulmonary vascular disease or cardiac cachexia preoperatively. Complete heart block is a potential complication in perimembranous VSD but in skilled hands occurs in less than 1% of the patients.

Atrioventricular Septal Defect (AVSD) AVSD’s may be partial, intermediate or complete. The principles of repair consist of identifying the individual components of the defect and correcting them by appropriate techniques. Patients with complete AVSD are significantly symptomatic in early infancy and should undergo surgery before six months of age. Patients with a partial defect may behave clincally like secundum ASD’s, in the absence of significant mitral regurgitation and may therefore undergo deferred surgery at 2 to 3 years of age. All AVSD’s are repaired through a midsternotomy using standard cardiopulmonary bypass techniques. In the partial variety, the main defect is the ostium primum type of ASD and this is closed with a patch of autologous pericardium. The inferior margin of the defect is formed by the crest of the ventricular septum through which runs the conduction bundle. Injury to the bundle resulting in complete heart block is avoided by placing sutures along the base of the mitral or tricuspid valves which are attached along the crest. The anterior leaflet of the mitral valve is invariably cleft often resulting in mitral regurgitation. The cleft is always closed even when not regurgitant to avoid future onset of regurgitation. In the intermediate variety there are multiple VSD’s between the crest of the interventricular septum and the bridging leaflets of the atrio-ventricular valve. The repair is similar to that for the partial variety with the addition that along the inferior margin, interrupted sutures are placed in such a manner as to close the ventricular septal defects as well. The complete AVSD requires a more complicated surgical repair and precise partitioning of the common atrio-ventricular valve into mitral and tricuspid components is a critical component of the repair. The VSD component is closed with a synthetic patch and the atrial septal defect with a pericardial patch. The bridging leaflets of the atrio-ventricular valve are sandwiched between the two patches at an appropriate plane so as to create competent mitral and tricuspid valves. Additional work may have to be done on the valve leaflets to optimize valve function. Such a repair is called the ‘two-patch repair’ and is the time-tested surgery for this anomaly. Other less used techniques are the ‘single patch repair’ and the ‘modified single patch repair’. Operative mortality is less than 2% for partial AVSD and less than 5 % for the complete type. There is controversy whether the presence of Down’s syndrome adversely affects outcome. Infants with Down’s syndrome are likely to develop pulmonary vascular obstructive disease early and are more likely to have problems related to PAH in the postoperative period. On the other hand they tend to have excess atrio-ventricular valve tissue which lends itself to a better quality of surgical repair. In the long term recurrent or progressive left AV valve (mitral) regurgitation occurs in a significant number of patients and requires re-intervention.

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Total Anomalous Pulmonary Venous Connection (TAPVC) Repair in the neonatal period or in infancy often has to be done as an emergency when the pulmonary venous drainage is obstructed and the child is in respiratory distress. Infradiaphragmatic TAPVC’s are most often obstructed followed in order by the supracardiac variety and the cardiac variety. Usually the obstuction is at the level of the common pulmonary vein but it may also result from a restrictive ASD. In the absence of obstruction elective early surgery is planned. The aim of surgery is to establish a connection between the anomalously draining pulmonary veins and the left atrium, and close the atrial septal defect which is invariably present. In the supracardiac and infracardiac varieties, the pulmonary veins form a confluence behind the left atrium. This confluence is opened under CPB and anastamosed to the opened back wall of the left atrium. The vertical vein is then ligated completing the re-routing of the anomalous veins to the left atrium. The right atrium is then opened and the ASD is closed with a patch ensuring a generous left atrial cavity. In the coronary sinus type of cardiac TAPVC, the wall between the coronary sinus and the left atrium is excised so as to route the pulmonary veins into the left atrium and then the confluent ASD and coronary sinus orifice are closed with one single patch to complete the repair. The postoperative course can be stormy in patients with preoperative obstruction. Ventilatory support is required till the pulmonary function returns to normal which may, sometimes, take several days. Pulmonary hypertensive crises are common in this sub-set and can be fatal unless managed carefully. A pulmonary artery pressure monitoring catheter is often placed in the operating room in such patients to help in postoperative management. Common pulmonary vasodilators used in this setting are nitroglycerine, phenoxybenzamine, inhaled nitric oxide and oral sidenafil. Operative mortality in unobstructed TAPVC is less than 3 %. In the obstructed variety, survival is governed by the preoperative status of the infant. In patients presenting in a collapsed state requiring cardiopulmonary resuscitation mortality may exceed 50%. Tetralogy of Fallot (TOF) In TOF the symptomatic status of the patient is governed by the severity of pulmonary stenosis and the degree of arterial desaturation resulting thereof. Surgery is planned on the basis of symptomatology, pulmonary artery anatomy and age of the patient. Ideally a complete repair (referred to as total correction) is aimed for, if it can be performed at low risk. If risk of total correction is perceived to be high and the patient has significant cyanosis or spells then a palliative BT shunt as described earlier is performed. Usual risk factors are young age (generally less than six months) and hypoplastic branch pulmonary arteries. Sometimes a palliative shunt may be justified in a patient who has severe polycythemia associated with major coagulation abnormalities, or recent cerebrovascular event which would contraindicate the use of CPB. The currently preferred technique of repair of TOF is the transatrial repair. The operation is performed through a mid-sternotomy incision under standard CPB. The VSD is exposed through the retracted tricuspid valve after opening the right atrium and closed with a Dacron

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patch in such a manner as to route the left ventricle to the aorta. The aortic overriding is thereby corrected. The infundibular stenosis is then relieved by excising the hypertrophied parietal and septal bands of muscle. If there is associated pulmonary valvar stenosis then the main pulmonary artery is opened and the stenosis is releived by incising the fused commissures or excising the valve if it is very dysplastic. If the annulus is also hypoplastic then the main pulmonary artery incision is carried across the annulus till an adequate lumen of the right ventricular outflow is achieved. The opened up outflow is then reconstructed by suturing a patch of autologous pericardium to complete the repair. Adequacy of the right ventricular outflow is confirmed by manual sizing and by intraoperative echocardiography at the end of the surgery. The pulmonary artery bifurcation and the right and left pulmonary arteries are sized at this stage and any stenotic areas are identified and repaired by patch augmentation. In certain situations, a monocusp valve made of pericardium may be incorporated to temporarily minimize the effects of pulmonary regurgitation. If the patient has had a previous shunt procedure then the shunt is exposed and ligated or divided as soon as CPB is established. Operative mortality for repair of uncomplicated TOF is less than 3%. Early postoperative problems include bleeding which is more likely to occur in the older polycythemic patient, and right ventricular dysfunction. RV dysfunction often takes the form of diastolic dysfunction and is more likely to occur in patients with severe hypertrophy of the RV or in those who have had a large ventriculotomy. Diastolic dysfunction is readily diagnosed on echocardiography and if not appropriately managed can lead to major morbidity or mortality. The risk of complete heart block necessitating permanent pacemaker implantation is about 1 to 2%. Long-term survival as well as quality of life is excellent in the majority of the patients. Risk factors for adverse longterm outlook are older age at operation, large ventriculotomy, residual lesions after repair and presence of arrythmias. Although pulmonary regurgitation is inevitable in patients who have had a patch augmentation of the pulmonary annulus it is generally well tolerated for several years. Progressive dilatation and dysfunction of the right ventricle however occurs eventually in a significant number and these patients then need to have a pulmonary valve replacement.

TOF with Pulmonary Atresia In the presence of pulmonary atresia the right ventricular outflow cannot be opened up as in a classical TOF. The operation proceeds as for TOF till the VSD is closed. An large opening is then created in the right ventricular outflow (right ventriculotomy) and in the pulmonary artery bifurcation. Right ventricle to pulmonary artery continuity is then established by placing a valved conduit. Because of the need for a conduit, corrective surgery is generally deferred in these patients to 3 to 4 years of age so that a reasonably large conduit can be placed at the first repair, thus minimizing the number of reoperations that the patient would require for conduit replacement. In case the child develops significant cyanosis before this age, a BT shunt is performed as a temporizing measure. TOF, Pulmonary Atresia and Dimunitive Pulmonary Arteries In a subset of patients with pulmonary atresia, there is varying degree of abnormality of the pulmonary arteries ranging from mild hypoplasia to total absence of the central pulmonary arteries. Pulmonary blood supply is usually through multiple aorto-pulmonary collateral

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arteries (MAPCA’s) which generally originate from the descending thoracic aorta. Surgical correction in this situation needs careful planning and is often done in a staged manner. The principles of surgery are: (a) centralizing all pulmonary blood supply to one source by connecting collaterals to central pulmonary arteries (unifocalization), followed by (b) closure of the VSD and a conduit placement between the right ventricle and the unifocalized pulmonary arteries. The surgery may be done in one stage or multiple stages depending on the feasibility in an individual situation.

Double-Outlet Right Ventricle (DORV) Many subtypes of DORV exist depending on the location of the VSD and the relationship of the great arteries. The surgical procedure for DORV depends on the size and location of the VSD and the presence or absence of pulmonary stenosis (PS). If the VSD is sub-aortic in location then repair is carried out by routing the left ventricle to the aorta using a curved patch. If there is associated pulmonary stenosis then it is relieved with an outflow patch as in TOF. If the great vessels are transposed then an outflow patch cannot be placed and a valved conduit has to be interposed between the RV and PA. In DORV with a sub-pulmonic VSD (Taussig-Bing anamoly) the LV is routed to the pulmonary valve to create a transposition and then an arterial switch operation is carried out. In patients with a remote VSD routing of the left ventricle to the aorta through the VSD may not be feasible because of intervening tricuspid valve tissue. A surgical plan similar to that for single ventricle situations, i.e. a Fontan procedure may then have to be adopted. Transposition of Great Arteries (TGA) Transposition complexes broadly fall into three categories which are, in order of frequency : a. TGA with intact ventricular septum (TGA.IVS) b. TGA with ventricular septal defect (TGA.VSD) c. TGA with VSD and pulmonary stenosis (TGA.VSD. PS), and d. TGA with pulmonary stenosis (TGA.IVS.PS). The surgical management of each subtype is unique and is therefore discussed individually. TGA with Intact Ventricular Septum In ideal circumstances, a diagnosis of TGA.IVS is made in the first few days of life. Initial stabilization may require prostaglandin infusion to maintain ductal patency and balloon atrial septostomy to improve inter-atrial mixing. Surgical treatment by means of an arterial switch operation is ideally done before four weeks of age. The arterial switch operation is an anatomical correction and aims to restore normal ventriculoarterial connection. The procedure is performed on CPB with moderate hypothermia. After cardioplegic arrest of the heart, the aorta and pulmonary artery are transected just above the level of the semilunar valves. The two coronary artery origins are then separated from the aortic root and the proximal coronary arteries are freed. Two openings are then made in appropriate locations in the pulmonary artery root and the coronary arteries are sutured to these openings. This is the most delicate and critical part of the operation. Any error here would result in myocardial ischemia and possible perioperative mortality. The transected ascending aorta is then moved

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posterior to the pulmonary artery bifurcation—a step known as the LeCompte maneuver, and anastamosed to the pulmonary artery root. Likewise the transected pulmonary artery which has now been brought anteriorly is anastamosed to the aortic root to complete the operation. The left ventricle is now connected to the aorta, the pulmonary arteries are connected to the right ventricle and the coronary arteries take origin from the base of the aorta. Only the semilunar valves remain reversed, i.e. the embryologic pulmonary valve remains as the aortic valve and the embryologic aortic valve becomes the pulmonary valve. This has however, not been shown to have any detrimental effects at least on intermediate term follow-up. Several coronary artery distribution patterns exist in TGA and a popular classification for these is the Leiden classification. A proper understanding of the coronary artery distribution is key to a successful outcome. Successful outcome is also dependant on the ability of the left ventricle to take on the load of the systemic circulation after the switch procedure. In TGA the left ventricle faces the pulmonary circuit which becomes a low pressure circuit soon after birth. In the face of a decreased afterload, the LV very rapidly begins to regress and beyond four weeks of age may be incapable of taking on the load of the systemic circulation. An arterial switch operation will then fail. Certain factors like the presence of a large PDA or some dynamic left ventricular outflow obstruction may prevent regression of the LV allowing for a delayed arterial switch to be performed. In the event that a patient presents late or the arterial switch cannot be performed in time for unavoidable reasons then the surgical options are either an atrial switch operation or a two-stage arterial switch operation. The atrial switch operation is the time-tested surgical procedure and was the only modality of treatment for TGA for over two decades till the advent of the arterial switch operation. Two versions of this operation exist—the more popular Senning procedure and the less often used Mustard procedure. In both operations, the blood flow is reversed at the atrial level by creating a baffle in such a way that the vena caval return is directed to the mitral valve and the pulmonary venous return to the tricuspid valve. The Senning procedure largely uses atrial wall to create the baffle, hence its popularity over the Mustard procedure which uses pericardium or prosthetic material. In the atrial switch, the circulatory pathway is normalized, however the right ventricle remains the systemic ventricle. While this allows for the operation to be performed at any age without risk of early ventricular failure, there is a risk of systemic ventricular dysfunction and failure in the long-term. The incidence of supraventricular arrhythmias is also higher following the atrial switch procedure and for these reasons an arterial switch operation should be performed whenever feasible. One way of making a regressed left ventricle suitable for arterial switch is by placing a PA band and a BT shunt. This subjects the left ventricle to a pressure and volume load stimulating it to hypertrophy in the course of a few days to weeks. After adequate left ventricular mass has been achieved, an arterial switch can then be performed at a second stage. Although an anatomic repair is thus achieved there is considerable morbidity and higher risk of mortality. In developed countries, all neonates born with TGA are diagnosed soon after birth and undergo an arterial switch procedure and the atrial switch procedure is rarely necessary. However, the

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situation is not so in developing countries where many patients are diagnosed late and the atrial switch operation continues to be of great relevance. Current mortality for the arterial switch operation, in centers doing this procedure frequently, is less than 5%. There is a significant learning curve so mortality can be expected to be higher in low volume centers. Early mortality is related to technical problems with coronary transfer or left ventricular failure in patients operated late. Long-term survival and quality of life is excellent upto at least 20 years of life. As compared to the atrial switch operation the risk of ventricular failure is negligible and the incidence of arrhythmias low. Pulmonary stenosis used to be a frequent complication in the early days but is infrequent with currently employed techniques.

TGA with VSD The presence of a VSD in TGA prevents LV regression because of continued pressure and volume loading. An arterial switch procedure can thus be performed well beyond one month of life unlike in those without a VSD. However, these patients are prone to develop pulmonary vascular disease as early as three months of age and so it is not prudent to wait too long. The operation is thus ideally carried out between two weeks and three months of age. At surgery the VSD is closed first as in an isolated VSD and then an arterial switch procedure is carried out. In TGA.VSD the pulmonary arteries begin to dilate rapidly and so in patients operated late there is significant disproportion between the sizes of the great arteries. This can on occasion lead to technical problems at surgery and therefore becomes another reason for recommending early surgery. Early mortality in TGA.VSD is dependant on the timing of surgery. When done at an appropriate time, the mortality is less than 5%. Chances of left ventricular failure are less in this subset unless there has been a problem with coronary transfer, however, postoperative pulmonary hypertensive crises are a known problem and can cause significant morbidity or lead to mortality in the older patients. Because of the disproportion that generally exists between the aortic root and pulmonary root there is greater chance of neo-aortic root distortion which predisposes to aortic regurgitation in the long-term. TGA,VSD and PS These patients behave functionally like TOF and usually present well beyond the neonatal period. Patients presenting in the neonatal period or early infancy with significant cyanosis are palliated with a BT shunt as in TOF. There are several corrective procedures available for this condition and their details are beyond the scope of this discussion. They are listed here for the sake of completion : a. Rastelli procedure: The LV is routed to the aorta through the VSD with an intra-cardiac tunnel patch and the RV is connected to the PA with an extra-cardiac conduit. b. REV procedure: The LV is routed to the aorta as above, the pulmonary artery is brought forward using the LeCompte maneuver and anastamosed directly to the RV. A monocusp pericardial valve is generally placed in the RV outflow. c. Nikaidoh procedure: This is a complex procedure that involves excision of the aortic root from the RV outflow and transposing it posteriorly to the pulmonary root and reconstructing the pulmonary outflow anteriorly.

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Truncus Arteriosus Infants with truncus arteriosus are symptomatic in early infancy with congestive heart failure and resulting failure to thrive. Surgery is recommended before 3 months of age to prevent early onset of pulmonary vascular disease. The pulmonary artery origin and the quality of the truncal valve need to be assessed preoperatively to plan the surgery. The operation is carried out under routine CPB through a mid-sternotomy incision. The essential components of the surgery are as follows: 1) Separation of the pulmonary artery origin from the common trunk and closure of the resultant defect. The common trunk now functions like the aorta. 2) Creating an opening in the outflow region of the right ventricle and closing the VSD through this hole with a patch in such a way that the left ventricle is connected to the aorta. 3) Placement of a valved conduit between the opening in the right ventricle and the separated pulmonary artery thereby completing the pulmonary circuit. Pulmonary hypertensive crises are a frequent problem in the postoperative period and extended ventilatory support is often required especially in the older infant. Operative mortality is under 10%. The conduit that is placed will become obstructive with time as a result of luminal narrowing, stenosis of the valve or progressive disproportion between the size of the conduit and that of the patient. Replacement of the conduit in course of time is therefore inevtable. Patient growth is maximum in the first 2 years of life and the first conduit change is usually required by 3 to 4 years of age. Surgical Management of Single Ventricle Certain cardiac malformations are not amenable to correction because their ventricular mass is not anatomically separable into separate systemic and pulmonary ventricles containing functional inflow and outflow valves. Such lesions are collectively referred to as single ventricles. Defects included in this group are : a. Tricuspid atresia, mitral atresia b. Double inlet ventricle—LV or RV morphology c. Hypoplastic left heart syndrome d. Hypoplastic right heart syndrome e. AVSD or DORV with unbalanced ventricles f. Straddling mitral or tricuspid valve g. Heterotaxy syndromes h. Severe Ebstein’s malformation. As there is only one functional ventricle, the only way that the systemic and pulmonary circulations can be separated in these patients is by routing the systemic venous return to the lungs directly without the aid of a pump and retaining the single ventricle as the systemic ventricle. This concept was jointly evolved by Fontan from France and Kreutzer from Argentina and is commonly referred to as the Fontan circulation. Certain prerequisites need to be met for a successful outcome after the Fontan procedure. The most important of these are a) normal or less than normal pulmonary vascular resistance b) normal sized pulmonary arteries c) no obstruction to pulmonary venous return or systemic outflow and d) normal ventricular function. Best results are obtained when the Fontan procedure is performed beyond 2 to 3 years of age and when performed in stages. The diagnosis of single ventricle is ideally made

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in the newborn period and the strategy for eventually achieving a good Fontan circulation is worked out at this stage itself. Patients with single ventricle may have decreased or increased pulmonary blood flow depending on the presence or absence of pulmonary stenosis. Patients with significant cyanosis in early infancy need to have a BT shunt for relief of cyanosis. Patients with no PS are usually in heart failure because of increased pulmonary blood flow and need to have a pulmonary artery band placed. Neither of these procedures reliably optimizes pulmonary blood flow and so as soon as these patients are older than 6 to 8 months, they are subjected to a procedure known as the bidirectional Glenn procedure (BD Glenn). In this operation the superior vena cava is divided at its junction with the right atrium and is anastamosed to the right pulmonary artery. The main pulmonary artery is then tied off and any shunt that has been placed previously is occluded. This now results in a circulation where the superior caval return forms the entire pulmonary blood supply and no systemic to pulmonary artery shunting exists. The procedure achieves offloading of the single ventricle allowing optimization of ventricular function for the final Fontan conversion. Pulmonary blood flow is optimized, providing adequate systemic oxygenation with no risk of producing pulmonary vascular disease. The BD Glenn produces adequate relief of cyanosis till about 6 to 7 years of age, however, beyond that age a progressive fall in the relative flow in the superior vena cava results in worsening cyanosis. A long standing Glenn circuit also predisposes to the development of pulmonary arteriovenous malformations presumably due to the lack of a certain hepatic factor which cannot reach the lungs. A conversion to a complete Fontan circuit is therefore planned at any time beyond 3 years of age, preferably before 8 years of age. For completion of the Fontan circuit the inferior vena cava blood is diverted to the pulmonary artery either by creating a passage within the right atrium – lateral tunnel Fontan or by means of an extracardiac tube graft from the divided IVC to the PA – extracardiac Fontan. Sometimes a fenestration is created between this pathway and the left atrium to allow for easier acceptance of the Fontan circulation. This is called a fenestrated Fontan procedure. Once the Fontan circuit is established pulmonary artery flow is driven by the difference in pressure between the systemic veins and the pulmonary veins. Systemic venous pressure therefore has to be maintained at higher levels than normal. Till the tissues get adjusted to these higher pressures, there is seepage of fluid into the extravascular space resulting in pleural effusions, ascitis and peripheral edema. This phase is managed by administering diuretics, colloid infusions and use of vasodilators. If conditions have been right for a Fontan conversion then this phase is short lived and the effusions stop within a few days. However, if the preoperative assessment has not been right then the effusions progressively worsen leading to hemodynamic collapse—a state known as Fontan failure. The only hope for salvage in such situations is immediate re-operation and re-conversion to a bidirectional Glenn circuit. In hypoplastic left heart syndrome, the staging process is more complicated than for other forms of single ventricle because of the absence of a systemic outflow. The first stage of palliation is an extensive procedure called the Norwood procedure where the RV and pulmonary artery are converted into the systemic ventricle and aorta respectively and pulmonary blood flow is established with a BT shunt. In subsequent stages a bidrectional Glenn and Fontan conversion are done as for other single ventricle situations.

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The operative mortality for the Fontan procedure in appropriately selected patients is less than 5%. Most survivors lead a good quality of life for the first few years of life following surgery. There is, however, a steady attrition over the years following surgery due to a host of late complications like ventricular dysfunction, arrhythmias, protein losing enteropathy and thrombo-embolism.

Anomalies of Coronary Arteries The incidence of congenital coronary artery anomalies in the general population is 0.2% to 1.2%, however, the only anamoly which is of clinical significance in infants is—anomalous origin of left coronary artery from pulmonary artery ( ALCAPA). As the name suggests ,the left coronary artery arises anamolously from the main pulmonary artery while the right coronary artery (RCA) arises normally from the aorta. Inter coronary collateral vessels develop to provide retrograde perfusion from the RCA to the left coronary system. As the main pulmonary is a low pressure system, left to right shunting of blood occurs from the right coronary artery through the intercoronary collaterals and left coronary into the main pulmonary artery. Most patients develop marked left ventricular dysfunction and often mitral insufficiency due to papillary muscle infarction. The majority of the patients develop symptoms of failure and ischemia and cardiac failure within days to weeks after birth warranting immediate surgery. In a small group of patients (10–15%) in whom the intercoronary collateral circulation is well developed, symptoms may be delayed for several years. This subset of patients have an estimated 80–90% incidence of sudden cardiac death. Hence surgical therapy is justified as soon as diagnosis is made. Surgical management aims to restore the aortic origin of left coronary artery. Under cardiopulmonary bypass and cardioplegic arrest, the anamolous left coronary artery is harvested along with a button of the sorrounding pulmonary artery and implanted into the aortic root at an appropriate site. If direct implantation is not feasible because of unfavorable coronary artery anatomy or lack of length, a patch of pulmonary artery is used to create a tunnel to provide additional length. Other techniques include left internal thoracic artery grafting of the left coronary after proximal ligation near its origin. Severe mitral regurgitation necessitates mitral valve repair or replacement. Congenital Mitral Valve Lesions Lesions of mitral valve can be stenotic or regurgitant. Stenosis can occur at the valvular level due to a dysplastic valve apparatus or at the supravalvular level due the presence of a ring of fibrous tissue—supramitral ring. Mitral regurgitation often results from clefts in the leaflets or prolapse of the leaflets due to dysplasia or chordal rupture. Mitral valve repair is the preferred approach for valvular stenotic and regurgitant lesions. A supramitral ring is the most correctable of the stenotic lesions because excision of the ring is curative. If repair is not feasible the replacement of the valve with a prosthesis remains the only alternative. Note: The author has attempted to provide concise yet informative descriptions of common surgical procedures that would help pediatricians in the understanding of the management of congenital heart disease and help them advise their patients better. There are a host of congenital cardiac lesions other than those described above that are today amenable to correction, but are beyond the scope of this chapter. The reader is advised to refer to the following publications for more detailed information on these and other lesions.

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SUGGESTED READING 1. Castaneda, Jonas, Mayer and Hanley (eds). Cardiac Surgery of the Neonate and Infant. W.B. Saunders Co. 1994. 2. Kouchoukos, Blackstone, Doty, Hanley and Karp (eds). Kirklin/Barratt-Boyes Cardiac Surgery, 3rd edn. Elsevier Science. 2003. 3. Mavroudis and Backer (eds). Pediatric cardiac surgery. Mosby Inc. 3rd edn. 2003. 4. Garson Jr, Bricker, Fisher and Neish (eds). The Science and Practice of Pediatric Cardiology, 2nd edn. Williams and Wilkins. 1998.

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Pediatric Cardiac Postoperative Intensive Care

Rakhi B, Suresh G Nair, R Krishna Kumar

INTRODUCTION Increased emphasis has been laid on the early primary repair of congenital heart defects in view of the multiple advantages it offers to the infant in terms of growth and development, and also in having as normal a circulation as possible, early in life.1 In this setting, postoperative care of the cardiac surgical patient forms a crucial part of the pediatric cardiac intensive care program. Although the awareness for the need for dedicated pediatric cardiac units has improved in India, only a tiny fraction (< 3%) of infants and newborns with heart disease receive adequate care.2,3 A limited number of centers in India have comprehensive pediatric cardiac programs. Pediatric cardiac intensive care remains an Achilles heel in many of these programs. The quality of intensive care has a strong impact on outcomes following pediatric cardiac surgery. In this article we attempt to highlight important issues in the postoperative care of the cardiac surgical patients that include hemodynamic monitoring, fluid therapy, airway management, nutritional support and aspects of multi-organ dysfunction.

SPECIFIC ASPECTS OF CARDIAC SURGERY THAT IMPACT PATIENT CARE Adverse Effects of CPB Reparative cardiac surgery requires cardiopulmonary bypass (CPB) and periods of myocardial and total body ischemia to provide satisfactory conditions for the procedure. Therefore, knowledge of the systemic effects of bypass is fundamental in understanding the postoperative hemodynamics. Cardiopulmonary bypass has a number of adverse consequences. The duration of CPB is an important determinant of postoperative recovery.

Effects on Heart Myocardial injury occurs not only from ischemia during aortic cross-clamping but also from the subsequent reperfusion. High-energy phosphate depletion and intra-cellular calcium

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accumulation has been recognized as important events in the pathogenesis of ischemia induced myocardial damage and reperfusion.4 Neonatal myocardium compared to the adult myocardium is less compliant and works in a limited range of Starlings curve. It relies heavily on glucose as its major substrate and calcium for excitation contraction coupling. The ischemic tolerance of the immature myocardium may be compromised by cyanosis, hypertrophy or acidosis, which may coexist in the setting of congenital heart disease.5 Increased collateral flow seen in children with chronic cyanosis may increase blood return to the left heart and compromise myocardial protection by warming the heart. Intra-myocardial air has also been suggested as a contributing factor for myocardial dysfunction after pediatric cardiac surgery.6,7 Factors aggravating myocardial injury during CPB include inadequate myocardial protection, ventricular distension, coronary embolism, increased catecholamine levels, aortic crossclamping and reperfusion following periods of ischemia.

Pulmonary Effects Relative ischemia of the lungs due to decreased antegrade flow through the pulmonary artery as well as the inflammatory response to CPB contributes to pulmonary injury.8, 9 Neutrophil and complement activation with cytokine release disturbs the extensive endothelial network of the lung. Generation of reactive oxygen species and elastase will lead to capillary leak from pulmonary endothelial damage. This leads to increased interstitial lung water, impaired pulmonary function and hypoxemia following CPB. In addition, a high left atrial pressure in the post-bypass period will increase the pulmonary capillary hydrostatic pressure with further aggravation of pulmonary edema.

Renal Effects During CPB, there are substantial decreases in renal blood flow, glomerular filtration rate and increases in renal vascular resistance. The non-pulsatile blood flow, increase in circulating catecholamines, inflammatory mediators, macro and micro-embolic insults to the kidney and release of free hemoglobin from traumatized red blood cells contribute to decreased renal function.

Endocrine Effects The stress response to surgery and CPB is characterized by elevation of plasma catecholamine levels lasting for 24 hours into the post CPB period.10,11 Cortisol levels increase during CPB but peak levels are seen on the 1st postoperative day.12 Vasopressin levels increase up to 20 times baseline levels during CPB.13 Hypothermia and CPB also result in a decrease in the level of insulin as well as decreased peripheral response to insulin resulting in hyperglycemia. Thyroid hormones decrease during CPB and into first several days after surgery.14

CNS Effects CNS sequelae following open-heart surgery and CPB are not uncommon. About 40% of patients undergoing open-heart surgery have subtle neurological effects as measured by neuropsychiatric

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testing, preoperatively and postoperatively.15 Intraoperative cerebral embolization of particulate and micro-gaseous elements accounts for majority of the cerebral events in postoperative patients. Intracranial hemorrhage has also been reported after systemic heparinization associated with CPB.16 Global CNS hypoperfusion may result from incorrect cannulae placement, pre-existing cerebrovascular disease or inadequate cerebral perfusion.17

Gastrointestinal Effects Cardiopulmonary bypass (CPB) can be associated with reduced gut blood flow. Gut ischemia of sufficient duration impairs GI barrier function. Studies evaluating gut permeability have shown that CPB is associated with an increase in mucosal permeability and systemic endotoxin concentration.18-20

Effects on Coagulation System Cardiopulmonary bypass (CPB) acts to impair hemostasis. CPB is associated with qualitative and quantitative defects in platelet function. Fibrinogen and fibrin, which adheres to the artificial surfaces of the extracorporeal circuit triggers platelet adhesion and aggregation.21 Clotting factor abnormalities can occur due to dilution of coagulation factors in the circuit prime. Increased fibrinolytic activity arising secondary to the thrombogenic nature of the extracorporeal circuit can also contribute to bleeding following CPB.22,23

Immuno-inflammatory Effects Passage of blood through the extracorporeal circuit, tissue ischemia and reperfusion and nonpulsatile perfusion may trigger a systemic inflammatory response to CPB. This is characterized by activation of complement, platelets, neutrophils, and pro-inflammatory kinins. The mediators, which have been proposed, are TNF α, IL–1, IL–6, IL– 8.4 Reduced number of helper T cells and impaired ability to synthesize IL–2 following cardiac surgery may be responsible for altered cell mediated immune function observed in the postoperative period.24

Deep Hypothermic Circulatory Arrest (DHCA) It involves the complete cessation of perfusion at a core body temperature of less than 18°C. A near bloodless field provides better visualization of small intracardiac structures. At a core temperature of 15 to 18°C, 30 to 45 minutes of DHCA is tolerated by most patients. The safe period of DHCA has not been established with certainty. Recent estimations of cerebral metabolism in adults undergoing DHCA suggest an ischemic tolerance of 30 minutes at 15°C and 40 minutes at 10°C.25 In a study of patients with TGA neuro-developmental outcomes are not adversely affected, if the duration of circulatory arrest does not exceed 41 minutes.26 Average nasopharyngeal temperature used for DHCA in several reported series were 18°C. Periods of DHCA up to 60 minutes with recovery of cerebral metabolism and preservation of neural micro-architecture can be accomplished if the brain is perfused for one minute (25 to 50 mL/kg/min) every 15 to 20 minutes.27,28 As an alternative to DHCA, many surgeons now generally advocate hypothermia with low flow bypass. There is considerable controversy regarding the advantages of low flow bypass

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over DHCA particularly in terms of postoperative neurological outcome and pulmonary function.29-32

General ICU Management Transport from operating room to the ICU is a critical period for the patient. Half an hour before the anticipated transfer, the ICU staff is provided with a concise report of the surgical procedure, bypass and cross-clamp times, current hemodynamic and respiratory status of the patient, medication regimen, significant intraoperative complications, and information regarding the appropriate ventilator settings. Transfer of the infant is carried out with appropriate continuous monitoring and particular attention to prevent hypothermia and hypoxia.

Initial Assessment Upon arrival in ICU, the intensive care physician should perform a rapid initial assessment. This should include the respiratory status, the hemodynamics and the chest drainage. Once the initial assessment is over, blood samples are to be drawn for assessment of basal electrolytes, arterial blood gases and a chest X-ray is ordered. The intensivist should review this at the earliest and make suitable changes in the ventilator settings or electrolyte requirements. The intensive care physician should review the patient’s underlying cardiac defect, history of prior interventions, the extent of surgical repair accomplished, and the concerns of the operating surgeon. This, along with the laboratory and physical examination data thus obtained, are combined to form an impression of the patient’s status and to develop a plan for initial management.

Hemodynamic Monitoring The important clinical signs of inadequate cardiac output are tachycardia, cool periphery with a slightly elevated central temperature, decreased capillary refill and inadequate urine output. If the child is awake, unexplained agitation can be an important physical sign. Intensive hemodynamic monitoring include continuous ECG monitoring, arterial blood pressure monitoring, monitoring of right atrial pressure (RAP) and left atrial filling pressures (LAP) and pulmonary artery pressure (PAP) monitoring. Interpretation of oxygen saturation data from intravascular catheters also provide insight into the adequacy of cardiac output and guide postoperative management.

ECG Monitoring Maintenance of sinus rhythm and AV synchrony is essential for recovery of cardiac function especially in children with a palliated circulation. Continuous surveillance for ischemic changes should be carried out in children who have undergone arterial switch operation or repair of coronary artery anomalies (e.g. ALCAPA repair—anomalous left coronary artery from the pulmonary artery repair). Arrhythmias in the postoperative period may be particularly important after certain procedures like a Fontan repair. Junctional Ectopic Tachycardia in the postoperative period may be distressing. Since neonates and infants have a rate dependent cardiac output bradyarrhythmias should be promptly identified and treated.

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Arterial Pressure Monitoring An indwelling arterial catheter permits continuous real time monitoring of systemic arterial pressure, allows sampling of arterial blood gases and guides the manipulation of vasoactive drugs. The radial, femoral, dorsalis pedis and posterior tibial are the common sites of cannulation. Radial artery is easy to access and has very low complication rate.33 Studies have indicated that radial arterial pressures are often inaccurate during the immediate post-bypass period in both adults and children, the reasons attributed being peripheral vasoconstriction or a decrease in forearm vascular resistance during re-warming from CPB.34 The side for placement of the radial artery catheter depends on whether the blood flow to the arm is expected to be interrupted during the surgery (e.g. left radial artery is preferred for a right modified BT shunt operation). Measurement of pressures in both the upper and lower limbs is required when aortic surgery is involved. The femoral artery is also commonly used for cannulation.

Right and Left Atrial Pressures The RAP and LAP provide valuable information on the preloading conditions of the heart. RAP can be monitored through a percutaneously placed central venous line or an intraoperatively placed right atrial catheter. Right atrial pressure gives a reliable estimate of the right ventricular preload and the right ventricular function.35 An elevated RAP may be seen in a neonate after a right ventriculotomy and may be indicative of right ventricular dysfunction. The LAP reflect the filling pressure of the left ventricle and the LA line is placed intraoperatively. LAP monitoring is invaluable in the management of patients with ventricular dysfunction, coronary artery perfusion abnormalities and mitral valve dysfunction. As a general guideline, the mean LA pressure should not exceed 15 mm Hg to prevent pulmonary edema.36 An elevated LAP indicates either a depressed left ventricular systolic or diastolic function or residual left ventricular outflow obstruction.

Pulmonary Artery Pressure (PAP) Monitoring Pulmonary artery pressure monitoring is indicated in children who are expected to have postoperative pulmonary artery hypertension. For example, endocardial cushion defects, obstructed total anomalous pulmonary venous connection (TAPVC).37 The relationship of the PA pressure to the systemic blood pressure is a more helpful measure than the absolute values. Generally, the mean PA pressure should be less than 50% of the mean systemic blood pressure. If it is greater than 50% of systemic pressures, possible causes and therapeutic measures are to be considered. Although PA catheters suitable for children are available, most surgeons directly place a line into the pulmonary artery at the end of the surgical procedure. PA catheters allow access to mixed venous samples, permitting direct calculation of O2 consumption, oxygen delivery and intrapulmonary shunt. PA oxygen saturation measurements also help to detect residual lesions producing an intracardiac left to right shunt. In patients undergoing intracardiac repair for tetralogy of Fallot (TOF) or ventricular septal defect (VSD) repair, absolute values of PA oxygen saturation greater than 80% within 48 hours of surgery with supplemental oxygen at an FiO2 < 0.5 is a sensitive indicator of significant left to right shunt 1 year after surgery.38

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PA catheters also offer added advantage that pulmonary vasodilator agents can be infused directly into these lines, thus ensuring their maximal effects on the pulmonary vasculature.

Pulse Oximetry Continuous monitoring of arterial oxygen saturation by pulse oximeter allows detection of hypoxemia and permits adjustments of ventilatory parameters. A small decrease in oxygen saturation may be the first sign of an impending pulmonary hypertensive crisis in susceptible patients (AV canal or TAPVC repair, etc.). Trends of falling oxygen saturation level may also be an indicator of decreased cardiac output. Poor peripheral circulation, ambient lighting and presence of abnormal hemoglobin can affect the reliability of the values.39-41

Urine Output Urine output is routinely measured by an indwelling bladder catheter in operations utilizing CPB in even the smallest of pediatric patients. The hourly urine output is an excellent indicator of adequacy of renal perfusion and cardiac output. In the first 2 to 4 hours after surgery most patients who have undergone CPB produce more than 1 mL/kg/h of urine. This is due to intraoperative volume administration, osmotic diuresis secondary to hyperglycemia and intraoperative mannitol administration.42 Thereafter urine output will decrease to < 1 mL/kg/h and continue at lower rates for up to 48 hours. In the initial 12 to 18 hours, kidneys respond poorly to diuretic agents probably due to inappropriate secretion of antidiuretic hormone.42

Temperature Measurement of peripheral as well as core temperature is important in the PICU as the residual effects of hypothermic CPB may persist from the operating room in neonates and small children. Hypothermia has to be promptly identified as it can precipitate arrhythmias as well as prolong neuromuscular blockade in the immediate post-bypass period. In children hypothermia can also increase oxygen consumption and increased metabolic demands by causing shivering. Temperature monitoring also helps to assess the adequacy of peripheral perfusion, by noting the core-peripheral temperature gradient. A core peripheral temperature gradient of more than 2° indicates marked hypoperfusion.33

MECHANICAL VENTILATION Preoperative lung disease, alterations in lung compliance after CPB and anesthesia or unstable postoperative hemodynamies warrant a variable period of mechanical ventilatory support for the children after cardiac surgery. Mechanical ventilation should be targeted at achieving adequate oxygenation and ventilation and optimizing the postoperative cardio-respiratory function till recovery. Ventilator strategies should be tailored to suit the physiology of each patient. Frequent modification of mode and pattern of ventilation may be necessary during recovery with attention to changes in lung volume and compliance. In children with previous left to right

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shunts and severe pulmonary hypertension, postoperative pulmonary vasodilation is required. This requires an arterial oxygen tension (PaO2) between 100 and 150 mm  Hg, respiratory alkalosis with a pH between 7.5 and 7.6 and a PaCO2 between 28 and 35 mm Hg.43 For patients who have a single ventricle physiology and shunt dependent pulmonary blood flow, oxygen tension should be kept at 75 to 80% and PaCO2 at 45 to 50 mm Hg to mildly increase PVR and prevent pulmonary over circulation thus enhancing systemic blood flow.44,45 After a Fontan/Glenn shunt, pulmonary blood flow is passive and PEEP as well as PIP is kept at minimum physiological levels. Early restoration of spontaneous breathing and minimizing peak inspiratory pressure can improve passive pulmonary blood flow in these patients. Sedation and pain relief should be provided throughout the period of mechanical ventilation to avoid patient ventilator asynchrony.

Categories Mechanical ventilator supports in two broad categories.

Pressure Limited Ventilation The decelerating flow pattern in this mode has the advantages of controlled peak and mean airway pressures improved oxygenation, and decreased incidence of barotrauma. Volume Limited Ventilation This provides stable minute ventilation but carries with it the risk of harmful peak airway pressures and barotrauma in patients with decreased lung compliance. A confusing array of ventilatory modes is now available with a variety of features to aid smooth synchronization between the infant and the ventilator. However, no study has shown any specific advantage of one mode over another. It would be more advantageous to understand the underlying pathophysiology and choose the mode which is best adapted for the condition rather than go by the attractive features displayed by the company promoting the machine. It is not within the scope of this chapter to discuss the various modes and their advantages. Positive end expiratory pressure (PEEP) is delivered to virtually all ventilated patients. It promotes alveolar recruitment, expands atelectatic areas, increase lung volume and improve gas exchange. In patients with minimum lung disease, PEEP is initiated at 3 to 5 cm H2O. Low PEEP is advantageous in patients with cavopulmonary shunts.

Weaning After an uncomplicated or simple procedure when cardio-respiratory dysfunction is minimal, early extubation may be considered once child wakes up from anesthesia. Factors that contribute to delayed weaning include younger age, pre-existing lung disease, long bypass time, delayed sternal closure and pulmonary hypertension.46 Requirement for weaning from mechanical ventilation include hemodynamic stability, maintenance of normal electrolyte and satisfactory blood gases, attainment of adequate hemostasis, paucity of secretions and a neurological status consistent with maintenance of a patient airway.

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Weaning is greatly facilitated by use of synchronised intermittent mandatory ventilation (SIMV). The ventilator rate is decreased to incrementally allow more patient initiated ventilation. Spontaneous breaths are supported with pressure support. When patient is able to maintain adequate oxygenation and ventilation with low ventilator rates (< 5–10/min), PS of 5 to 10 cm H2O or less PEEP of 5 cm or less at a FiO2 < 0.40 extubation is considered. In children, crying vital capacity > 15 mL/kg and maximum-inspiratory force > 45 cm H2O was found to predict accurately successful discontinuation of positive pressure ventilation in a study of postoperative infants.47 But clinical judgement and observation of patients breathing pattern, comfort and ability to maintain normal oxygenation and ventilation is the best predictor of success.

SEDATION, PARALYSIS AND PAIN MANAGEMENT (TABLE 30.1) Maintenance of adequate analgesia and sedation after congenital heart surgery has been recognized as an important factor in early postoperative management. The principles of postoperative analgesia in the cardiac patient should include intense analgesia in the early postoperative phase with early extubation, mobilization and elimination of potent analgesic and sedative drugs as early as possible. Individual management should be modified according to the patient’s age and nature of the surgical procedure. The neonate undergoing complex surgery may require an extended period of intensive anesthesia and analgesia for several days while older children having simple procedures can be extubated early.

Rationale for Adequate Analgesia and Sedation in Postoperative Period Adequate analgesia and sedation in the postoperative period can decrease the stress response to cardiac surgery and CPB.11 Analgesia decreases the sympathetic response to pain, and thus the myocardial work and oxygen demand. As most of the patients require mechanical ventilation for a variable period following congenital heart surgery, adequate sedation is critical in maintaining patient-ventilator synchrony. Patients with labile pulmonary artery pressures need adequate sedation and analgesia especially during procedures like ET suction and during emergence from anesthesia to prevent episodes of pulmonary hypertensive crisis. Moreover a number of painful procedures which might be performed in the postoperative period like central line placement, intercostal drain insertion, cardioversion, bronchoscopy and delayed sternal closure also require a quiescent and pain-free patient. Table 30.1: Analgesic doses Drug Acetaminophen Ibuprofen Ketorolac Morphine Fentanyl Sufentanil Ketamine

Dose and Route PO 10–15 mg/kg, 4–6th hourly/PR: 30 mg/kg initially, then 20 mg/kg q 6h 6–10 mg/kg/dose PO, 6–8th hourly 0.5 mg/kg q 6–8th IV IV bolus 0.1– 0.2 mg/kg not to exceed 5 days IV infusion 25–50 mg/kg/h IV bolus 0.5 –1 mg/kg (max 4–5 mg/kg) IV infusion 2–5 mg/kg/h IV bolus 0.1– 0.2 mg/kg IV infusion 0.5–2 mg/kg/h IV bolus 1–2 mg/kg IV infusion 2 mg/kg/h

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Assessment of Pain Response to sedation needs to be continually evaluated during weaning process. Assessment of requirement of analgesia is difficult in a young child who is paralyzed and is on ventilator. A variety of pain scales are available for assessment to pain in small children, the discussion of which is beyond the scope of this chapter. Autonomic signs such as hypertension, tachycardia, pupillary size, diaphoresis and tearing can be used as a guide to pain perception in children. If breathing spontaneously, changes in respiratory pattern like tachypnea, grunting and splinting of the chest wall may be evident. However, quantifying pain in a child remains inexact and highly subjective.

Modes of Pain Management Current trends in pain management employ the combination of drugs or techniques that have different modes of action, thus improving analgesia while reducing the incidence and severity of side effects of individual drugs.

Analgesics Opioids Opioid analgesia remains the mainstay of postoperative analgesia in the pediatric cardiac ICU. The most widely used opioids include fentanyl and morphine. Tolerance development is doseand time-related and can be a significant problem in postoperative patients on large dose opioids. Maintenance of a constant blood analgesic level by a continuous infusion is more appropriate in the postoperative setting to avoid periods of over sedation and under medication. Morphine is given as an infusion at 10 to 40 mcg/kg/h. It facilitates smooth transition from immediate postoperative anesthetic state to the self-ventilated, extubated state with effective analgesia. Fentanyl is given as an infusion of 1 to 5 mcg/kg/h but higher doses up to 10 to 20 mcg/kg/h can be used in sick infants to maintain sedation, reduce metabolic demands and provide hemodynamic stability. Fentanyl has beneficial effects on the pulmonary vasculature and hence may be the choice in children with PAH. Several analogs of Fentanyl have been developed with shorter duration of action including Sufentanil, Alfentanil and Remifentanil. Their indications are predominantly for use in the operating room or for patients who require short-term analgesia with rapid termination of effect before extubation. Acetaminophen and NSAIDs (non-steroidal anti-inflammatory drugs) given enterally reduce opioid requirements and augment analgesia.48 NSAIDs also possess useful antipyretic properties that have a role in children developing postoperative pyrexia as a part of systemic inflammatory response to CPB. Sedatives Midazolam and anesthetics like Propofol, Ketamine are also used to augment the sedative effects of opioids.

Muscle Relaxants Neuromuscular blocking agents are used in pediatric ICU to facilitate intubation and mechanical ventilation in patients with limited cardiorespiratory reserve to decrease myocardial work and

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oxygen demand. Paralysis and deep sedation is particularly important in patients with labile pulmonary hypertension. Prolonged paralysis is not without risks of prolonged ventilatory support, tolerance and muscle weakness in the postoperative period. Agents that are in routine use include non-depolarizing muscle relaxants like pancuronium, vecuronium and atracurium, etc. Depolarizing muscle relaxant succinyl choline is primarily used to facilitate a rapid sequence intubation in patients with risk of potential aspiration. Relaxants can be used as intermittent or continuous infusion. The relaxant infusion may be stopped at regular intervals to assess the adequacy of analgesia and sedation.

Regional Analgesia Use of regional techniques for cardiac surgery in children remains controversial. Concerns related to blind instrumentation of epidural or intrathecal space followed by systemic anticoagulation has been the main objection. The data on use of regional analgesia in post-cardiac surgical children are limited. Single dose caudal epidural blockade with Morphine can provide short-term analgesia after surgery.49

FLUID AND ELECTROLYTE MANAGEMENT (TABLE 30.2) Patients who have undergone CPB have significant salt and water overload from the crystalloid dilution on CPB.50 The total body water and extra-cellular fluid volume increase by about 10% in the first 72 hours after cardiopulmonary bypass and surgery while the intracellular fluid volume tends to decrease.51 This fluid shift can be attributed to increased vascular permeability secondary to the inflammatory response to CPB. The capillary leak syndrome may continue for 24 to 48 hours following surgery. During CPB, optimizing circuit prime hematocrit and oncotic pressure, attenuating the inflammatory response with steroids and serine protease inhibitors like Aprotinin and the use of modified ultrafiltration (MUF) techniques have been recommended to decrease the interstitial fluid accumulation.52 Initial fluid management in the postoperative period should take into consideration the salt and water retention following CPB. Total fluid intake, which includes fluids from every source, is traditionally restricted to 50% of normal maintenance requirements in all patients for the first 24 hours after cardiac surgery.51 Maintenance fluid requirements can be calculated using either the surface area method (1500 Table 30.2: Sedatives and muscle relaxants to 1700 mL/m2/day) or caloric expenditure Drug Dose and Route method {100 mL/kg/day (< 10 kg) + 50 mL/ Midazolam IV bolus 0.05–0.1 mg/kg IV infusion 0.05–0.2 mg/kg/h kg (10 to 20 kg) + 20 mL/kg/day (> 20 kg)}.53 Lorazepam IV bolus 0.05–0.1 mg/kg Subsequent to the first-day after surgery, IV infusion 0.025–0.05 mg/kg/h IV bolus 1.5–3 mg/kg fluid intake should be adjusted according Propofol IV infusion 100–150 mg/kg/min to clinical and laboratory evaluation of the Thiopental IV bolus 3–5 mg/kg patient’s hydration and biochemical status. Succinyl choline IV bolus 2 mg/kg IV bolus 0.1 mg/kg In the absence of systemic or pulmonary Vecuronium IV infusion 0.05–0.2 mg/kg/h edema, fluid intake may be gradually Atracurium IV bolus 0.5 mg/kg increased to achieve full maintenance Pancuronium IV bolus 0.2 mg/kg (intubating dose) IV infusion 0.1 mg/kg/h requirements over 2- to 3-day period.42

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Neonates and young infants who have a decreased ability to maintain blood glucose levels receive an IV solution with a greater glucose concentration, i.e. 10% dextrose with ¼th normal saline whereas older infants and children receive a solution containing less glucose (5% dextrose with ¼ NS). Volume replacement therapy should be titrated to appropriate filling pressures and hemodynamic response. Significant intravascular volume depletion manifests as reduced systemic blood pressure, decreased filling pressures and sinus tachycardia. Patients in whom pulmonary blood flow is dependent on systemic blood pressures (e.g. BT Shunt) systemic desaturation can occur. Treatment consists of an intravenous fluid bolus of 5 to 10 mL/kg at a rate that is titrated to the degree of hemodynamic compromise and filling pressures. The type of fluid depends on the patient’s postoperative physiology, hematocrit and coagulation status. If hematocrit is adequate and bleeding is well-controlled, either a colloid or crystalloid is administered. If patient is anemic but not bleeding, packed red cells are given. If significant bleeding is present, additional blood products like fresh frozen plasma, platelet or cryoprecipitate as dictated by the coagulation profile may be supplemented. Special situations, which require greater maintenance fluid rate, include: 1. Modified BT shunts to decrease the risk of shunt thrombosis from hemoconcentration. 2. Cavopulmonary anastomosis—to provide adequate preload for non-pulsatile blood flow. 3. Closed heart procedures like coarctation repair, PA banding, etc. which do not require CPB. One will also encounter special situations like postoperative pyrexia which will increase the fluid requirement. A practical guide is to allow an increase in water intake by about 10% for each degree rise in temperature above 37.5°C.51 Preterm neonates will require about 25% relatively more fluid than term neonates. Total volume of other fluids that are given as carriers for drug administration must be carefully controlled especially in small babies. All syringe pumps should be used at controlled rates to flush the intravascular cannulae and lines to avoid excessive fluid administration.

Types of Fluids Crystalloids Crystalloid solutions available for intravascular volume replacement include hypotonic, isotonic and hypertonic solution. Isotonic solutions like normal saline, Hartmann’s solution and Ringer’s solution have no direct effect on clotting but remain in vascular compartment only for a short time.54 Large volume infusion of 0.9% saline which contain nonphysiological concentration of chloride may produce dose dependent metabolic acidosis, this does not occur with lactated Ringer’s solution. Colloids HAS: In a recent systematic review of randomized controlled trials, the use of human albumin solution has been found very relevant in cardiac surgery.55 The use of albumin solution is based primarily on the assumption that albumin, whose presence exerts 80% of normal colloid osmotic pressure is retained within the intravascular space. There is little evidence to suggest

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that HAS has any particular advantages over other synthetic colloids, unless the plasma albumin concentrations are very low. HES: Hydroxy ethyl starches have been eyed with caution in the postoperative setting because of reports relating to excessive postoperative bleeding (due to abnormal platelet function).56 A newer low molecular weight HES solution with a low degree of substitution has been developed to minimize this complication.57 HES solution with low substitution has no clinically significant effect on hemostasis or renal function in moderate doses.58

Electrolyte Management Sodium Most patients in the post CPB period are salt overloaded. Sodium overload results from the electrolyte composition of the crystalloid solutions used to prime the bypass circuit. Hyponatremia in the post-bypass period reflects free water excess. Serum sodium level < 125 meq/L may be associated with neurological symptoms and should be managed with water restriction and cautious administration of normal saline solution. Hypernatremia is quite rare and usually occur in patients with renal failure or in infants who have received large amounts of sodium bicarbonate or those who have large free water deficit (due to diuretic therapy). It should be managed with sodium restriction and liberal fluid intake. The amount of fluid that should be given to correct the hypernatremia is as per the formula: + + Change in serum Na = Infusate Na – Serum Na TBW Estimates the effect of 1L of any infusate o the serum Na+. TBW in litres = Body weight × 0.6. The rate of correction should be 1 meq/L/h to avoid complications related to cerebral edema and convulsions. It is generally recommended that the reduction in serum Na should not be more than 8 meq/L on any day.59 Potassium The usual daily requirement of potassium ranges between 2 to 3 meq/kg/day in infants and 1 to 2 meq/kg/day in children. Patients with a serum K+ between 3 and 3.7 meq/L who are hemodynamically stable should have an appropriate dose of potassium added to their maintenance fluid or feeds. Patients with a serum K+ concentration 0.5 meq/kg/h) with continuous ECG monitoring throughout dosing. c. Concentrated KCl should be infused through a dedicated central venous line to avoid venous irritation d. Serum K+ should be checked hourly in a patient receiving continuous infusion. Hyperkalemia occurs less frequently in situations associated with postoperative renal dysfunction, massive blood transfusion or potassium supplementation in IV fluids or TPN

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solutions. Treatment of severe hyperkalemia, if acute or life-threatening arrhythmias coexist, consists of infusion of calcium chloride 0.2 to 0.5 mL/kg of a 10% solution over 2 to 5 min, sodium bicarbonate 2 mEq/kg along with glucose 0.5 g/kg and insulin 0.1 U/kg can be infused over 2 hours.60 If hyperkalemia persists, patient may need urgent dialysis.

Calcium Routine monitoring of ionized calcium levels has become standard in most ICUs. Normal serum ionized calcium levels are 1.14 to 1.30 mmol/L. Avoidance of significant hypocalcemia is important because postoperative cardiac patients commonly have some degree of systolic dysfunction and calcium is a potent positive inotrope.61 Transfusion of large volumes of citrated anticoagulated blood, loop diuretics, which increase excretion of calcium, and acute respiratory alkalosis, are the common causes of hypocalcemia. In neonates, serum calcium levels must be measured frequently and the level maintained by intravenous administration of calcium gluconate 50 to 100 mg/kg every 6 to 8 hours. If multiple intermittent boluses of calcium are required to maintain normal level then a continuous infusion of calcium can be used.42 Magnesium Hypomagnesemia is associated with ventricular dysrhythmias like VT, VF, torsades de pointes, etc. For older children and adults serum magnesium concentration less than 0.7 to 0.8 m mol/L and for neonates serum Mg  10 to 15 mL of residual fluid in the stomach, initial feedings are begun. Human milk is considered ideal for healthy and most sick infants. If human milk is not available appropriately, formulated infant feeds should be used. Advantages of enteral feeding include maintenance of normal milieu of the gut, stimulation of mucosal blood flow and optimization of mucosal nutrition. If full volume enteral feeds are not tolerated, small volume trophic feeds are believed to have beneficial effects in maintaining gastrointestinal integrity. Problems associated with establishing enteral feeds include gastroduodenal paresis in which the gastric emptying is delayed with large residual feed volumes retained in the stomach. Management include decreasing feed volumes, giving more frequent feeds and addition of gastric promotulent drugs like domperidone. Other problems include gastroesophageal reflux and diarrhea. Parenteral nutrition should only be Table 30.3: Recommended daily intake of calories for healthy children used if enteral feedings are absolutely Weight Calorie requirement contraindicated or when enteral feeds fail Age Pre term 130–150 kcal/kg to meet calorie requirements. Parenteral < 1 years 3–10 kg 90–120 kcal/kg nutrition is more expensive, requires 1–6 years 11–20 kg 75–90 kcal/kg 21–40 kg 60–75 kcal/kg central venous access and associated 7–12 years 40–70 kg 25–30 kcal/kg with specific physiological derangements 12–18 years Table 30.4: Increased calorie requirement imposed by critical illness in children Basal Maintenance Minor stress Major stress

% RDI* 55 66 76 98

Comments Basal = Deep sedation, ebb phase injury, mechanical ventilation Maintenance = Mechanical ventilation, enteral feeds, lying quietly Minor stress = skeletal trauma, minor surgery, peritonitis, fever < 39°C Major stress = multiple trauma, large open wound, sepsis, major cardiac surgery

* RDI = Recommended daily intake for growth in healthy children undertaking normal activities

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including cholestasis, gut mucosal atrophy and problems due to central vein catheter residence.43

Infection Control Establishment of robust infection control protocols is vital to the success of a pediatric cardiac ICU. The key components of an infection control system includes ensuring strict and handwashing before patient contact, meticulous care during placement of all forms of invasive lines and a surveillance policy. Frequent education of all health care providers is vital and senior members of the team must set an example in infection control practices.

Antibiotics Antibiotic prophylaxis has become an accepted standard of care for patients undergoing cardiac surgery. The first antibiotic dose is given in the operating room as soon as the intravenous lines have been placed. Prophylactic antibiotic regimens vary between centers but generally do not extend beyond 3 to 4 doses. The choice of antibiotic varies according to institutional protocol. A common regimen which has been recommended by the American heart association uses a third generation cephalosporin together with gentamicin to provide broad spectrum cover. Vancomycin 10 to 15 mg/kg/dose intravenously or clindamycin 10 mg/kg/dose IV Q8H is substituted if patient has known penicillin allergy. For neonates who have relatively incompetent immune system, invasive nature of indwelling lines increases the risk of infection. They are given antibiotics to cover both gram negative and staphylococcal organisms (Table 30.5).43

MANAGEMENT ISSUES ASSOCIATED WITH SPECIFIC SURGERIES Palliative Procedures Palliative procedures correct the physiological defects arising from cardiac anomalies without addressing the anatomical defects. Systemic to pulmonary artery shunts are palliative Table 30.5: Antibiotics Drug Amikacin Ampicillin Cefaclor Ceftriaxone Cephalexin Cephapirin Clindamycin Gentamicin Vancomycin

Dosage and Route 7.5 mg/kg/dose IV/IM 8–12th hourly Mild to moderate infection 50–100 mg/kg/day divided IV/IM 6–8th hourly Severe infection 200–400 mg/kg/day divided IV/IM 4–6th hourly 20–40 mg/kg/day PO divided 8th hourly 50–75 mg/kg/day IV/ IM 12–24 hourly 25–100 mg/kg/day PO divided 12–24 hourly 50–100 mg/kg/day IV/IM divided 6th hourly 15–40 mg/kg/day IV/IM divided 6–8th hourly Systemic infection 7days–5 years : 2.5 mg/kg/dose IM/IV 8–12th hourly >5 years 2–2.5 mg/kg IM/IV 8th hourly 10–15 mg/kg/dose IV 6–8th hourly

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procedures that increase the pulmonary blood flow thereby relieving severe cyanosis, improving functional status and allowing for the diffuse growth of the pulmonary arteries. Blalock-Taussig Subclavian artery to pulmonary artery Modified BT Synthetic shunt from systemic artery (SA) to pulmonary artery (PA) Waterston Ascending aorta to pulmonary artery Potts Descending aorta to (L) pulmonary artery Glenn Right pulmonary artery to superior vena cava (SVC)

Blalock-Taussig (BT) Shunt The classic BT shunt redirects subclavian artery blood into a branch pulmonary artery on the side opposite the aortic arch. Since this involves compromise of the subclavian artery and upper limb blood flow, a modified BT shunt is now preferred using a Gore-Tex synthetic tube graft that is interposed between subclavian artery/innominate artery and pulmonary artery. Important postoperative concern is the incidence of early shunt thrombosis especially in neonates.65 This can be minimized by maintenance of adequate cardiac output and blood pressure in the early postoperative period, inotropic support can be used if needed. Avoid hemoconcentration especially in cyanotic children by maintaining adequate hydration perioperatively. Diuretics should be avoided in early postoperative period as far as possible. Systemic anticoagulation with heparin is used during the creation of shunt and may be continued for 28 to 48 hours, thereafter to prevent early shunt thrombosis.66 Long-term shunt patency may be improved by the use of low dose aspirin 1 mg/kg/day. In patients with systemic to pulmonary artery shunt, the shunt flow is usually restricted by the shunt orifice and the balance between pulmonary and systemic vascular resistance. Appropriately sized shunt results in a balanced circulation, QP/QS 1:1, with peripheral oxygen saturation between 75 and 85%, a normal systolic pressure and a widened pulse pressure. If shunt is too large, excessive pulmonary blood flow will be evident by high arterial oxygen saturation, reduced systemic perfusion with increasing metabolic acidosis, low diastolic blood pressure and pulmonary edema. Increasing the pulmonary vascular resistance (PVR) by controlled hypoventilation and low FiO2 treats pulmonary over circulation. Systemic perfusion can be improved by after load reduction. Occasionally dense opacification of ipsilateral lung may appear in chest radiograph due to hemorrhagic pulmonary edema. It is due to the sudden increase in pulmonary blood flow (PBF) on the abnormal lung of cyanotic patient with tetralogy of Fallot (TOF). If shunt is too small, arterial oxygen saturation will remain low and pulmonary flow will be dependent on normal or increased systemic arterial pressures. Lowering PVR by ventilator adjustments and improving cardiac output by inotropic support and adequate intravascular volume can improve oxygen saturation. If there is evidence of shunt occlusion as per echocardiography, prompt re-operation is indicated. Leaking of serous fluid through the interstices of the fabric of PTFE may result in excessive chest tube drainage in 5 to10% of patients.67 Pulmonary Artery (PA) Banding Pulmonary Artery (PA) banding is done in patients with excessive pulmonary blood flow due to large left-to-right shunt to lessen the symptoms of congestive cardiac failure and to prevent

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the progression of pulmonary vaso-occlusive disease (e.g. tricuspid atresia, children with large VSD/ multiple VSD). It can be used in patients with transposition of great arteries (TGA) to prepare the left ventricle (LV) to face the systemic circulation.68 The appropriate circumferential length of the band required is calculated based on existing formulae. Placement of the band should result in elevation of aortic systolic pressure by 10 to 20 mm Hg. For a patient who will eventually have a two ventricular repair, MPa pressure should be decreased to < 50 % of the measured aortic systolic blood pressure and oxygen saturation should drop to below 90 % (FiO2 0.5). For patients for eventual Fontan, the lowest possible distal main PA pressures that can be achieved with an acceptable oxygen saturation of 80 to 85% is desired (FiO2 0.5).69 According to Trusler and Mustard formula, the circumference of the band in inch should be equal to child’s weight (in kg) + 20.70 Postoperative concerns include the requirement of inotropic support due to an acute increase in RV after load induced by PA banding. Fluids should be restricted along with diuretic therapy in view of pre-existing congestive cardiac failure. Digoxin should be resumed as early as possible postoperatively. Oxygen being a potent pulmonary vasodilator can increase pulmonary flow even in banded patients. Hence, postoperative ventilator strategies should consider a low FiO2 to maintain saturation between 85 to 90% and PaCO2 between 40 and 45 mm Hg.

Fontan Procedure Fontan operation is considered the surgical end point of patients whose cardiac anomalies do not allow a two ventricular repair. The original Fontan operation was performed exclusively in patients with tricuspid atresia, but it is now applied to all forms of univentricular AV connection. All forms of Fontan operation aim to divert the systemic venous return either directly or by alternate pathways to the pulmonary arterial circulation. The focus of post-bypass care of the child with a Fontan procedure is on augmenting the pulmonary blood flow, minimizing pulmonary vascular resistance and optimizing myocardial function.71 This is achieved by optimizing the transpulmonary blood flow. A systemic venous pressure of 10 to 15 mm Hg and a left atrial pressure of 5 to 10 mm Hg (i.e. transpulmonary gradient 5 to 10 mm Hg) are ideal.72 SVC pressure monitoring guides the filling pressure for pulmonary arteries and is of importance in the postoperative period. Right heart return and pulmonary blood flow are maintained through adequate intravascular volume. Patients should be positioned in a 15 to 30° head up tilt to increase SVC drainage. Drainage from inferior vena cava (IVC) may be promoted by the use of cyclically inflated military antishock trouser (MAST)/leg elevation.73 Because of the adverse effect of positive intrathoracic pressure on pulmonary blood flow (PBF), mean airway pressures are kept as low as possible while patient is being ventilated mechanically, with minimal PEEP and should be placed on spontaneous ventilation at the earliest. Early return to spontaneous ventilation is optimal to augment venous return due to negative intra-thoracic pressure. Coagulation abnormalities in these cyanotic children can lead to increased postoperative bleeding and postoperative transfusion requirements. Hematocrit should be maintained at higher levels with packed cells. Sinus rhythm should be maintained to preserve AV synchrony and to maintain atrial contribution to cardiac output. This will also help to maintain a low left atrial pressure, which

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in turn will decrease the pulmonary venous pressure. Late arrhythmias include atrial flutter and sinus node dysfunction. The preferred inotropic agents include, Milrinone and Dobutamine, which dilate the pulmonary vascular bed and lower pulmonary vascular resistance. Low cardiac output state in the presence of elevated LA pressures may reflect systolic and diastolic dysfunction, AV valve regurgitation or loss of sinus rhythm. Arterial oxygen saturation should be followed as an estimate of pulmonary blood flow. Causes of persistent arterial oxygen desaturation include poor cardiac output with low mixed venous oxygen saturation or a large right to left shunt across the fenestration or baffle leak. Incidence of recurrent pleural effusions and ascites has decreased with the use of baffle fenestration.74 Patients with low cardiac output following Fontan procedure are at increased risk for venous thrombosis and central nervous system complications.75 Anticoagulation with heparin or warfarin or antiplatelet medication may be useful in this subgroup of patients. Bidirectional Glenn Shunt (BDGS) is done as a first stage palliation for single ventricular physiology and it includes a superior cavopulmonary anastomosis. It provides obligatory pulmonary blood flow and avoids the LV overload accompanying systemic to PA shunts. BDGS is performed on CPB with mild hypothermia. Postoperatively these patients can be weaned from mechanical ventilation early. Postoperative issues include hypertension, which has been attributed to brainstem mediated mechanisms secondary to increased systemic and central venous pressure. Treatment of hypertension with vasodilators may be necessary. In the event of postoperatively elevated SVC pressures in Glenn, obstruction at anastomotic site, distal pulmonary artery distortion or marked elevation in PVR should be ruled out. Maintenance of low peak airway pressures and early restoration of spontaneous ventilation can improve pulmonary blood flow in these patients. In older children and in those with elevated right atrial pressure anticoagulant therapy with warfarin is indicated from 3rd postoperative day to prevent the incidence of atrial thrombosis. Younger patients may be placed simply on aspirin therapy early postoperatively.

CORRECTIVE PROCEDURES Atrial Septal Defects This accounts for 6 to 10% of all CHD.76, 77 Anatomical types include secundum ASD, primum ASD, sinus venosus ASD and coronary sinus types. Associated lesions which can occur along with ASD include partial anomalous pulmonary venous drainage, pulmonary stenosis and mitral valve abnormalities. Most ASD’s are now closed with a pericardial patch. Catheter based closure of secundum type defects have become popular in the recent era. Early tracheal extubation is routine. These patients rarely require inotropic support. Occasionally low cardiac output after surgery is related to hypovolemia and should be treated with adequate replacement fluids or transfusion of blood products. Postoperative arrhythmias such as atrial flutter, atrial fibrillation, sinus tachycardia and nodal rhythm can occur.78 Only 2% arrhythmias are persistent and may be due to sinus node dysfunction caused by surgical trauma or due to interruption of its blood supply.79

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Patients with large ASD, long standing pulmonary hypertension and ventricular dysfunction preoperatively may require postoperative inotropic support, fluid restriction with diuretic therapy, and longer mechanical ventilation.

Ventricular Septal Defect This is the commonest congenital heart disease. Various classifications based on anatomical and physiological basis has been advocated. Tetralogy of Fallot, double-outlet right ventricle (DORV) and interrupted aortic arch may be associated with VSD. The postoperative course is determined by the preoperative condition, intraoperative course, presence of residual defects, need for ventriculotomy or the success of valve repair if any. Older asymptomatic child who requires little or no inotropic support can be extubated early. In infants with long standing large VSD, persistent elevation of PVR with episodic pulmonary artery hypertensive crisis and right ventricular failure can be anticipated after surgery.80 Such children require continuous monitoring of PA pressures through an intraoperatively placed PA catheter with continued sedation and ventilator support. Use of pulmonary vasodilators and aggressive diuresis may be required for 48 to 72 hours. Ventricular dysfunction can be anticipated in patients with pre-existing congestive cardiac failure, those who required ventriculotomy during repair and infants with persistent elevation of PVR. Inotropic selection should consider the use of agents like Milrinone which lower PVR. Persistently elevated pulmonary artery pressures, low cardiac output state and failure to wean from ventilator raise the possibility of a residual VSD. If significant residual VSD is confirmed, re-operation should be performed without delay. Tachyarrhythmias like supraventricular tachycardia and junctional ectopic tachycardia may be seen in some children after VSD repair. These may be treated by digitalization, controlled hypothermia (as in case of JET) and correction of electrolyte disturbances if any. Heart block can occur in up to 10% of patients after VSD closure. It is more common after closure of perimembranous and AV canal type of VSD.81 Conduction disturbance may be transient due to edema near the sutured areas and may require temporary AV sequential pacing. Persistent heart block that has not resolved in 7 to 14 days requires implantation of permanent pacemaker.

Patent Ductus Arteriosus (PDA) Persistence of the fetal vascular communication between the origin of the left PA and the descending aorta after the first few days of life is called the patent ductus arteriosus. The incidence of isolated PDA is 1 in 2500 live births.82 It can also coexist with anomalies like ASD, VSD, common AV canal and in the duct dependent lesions. Surgical closure of the PDA can be performed either by ligation or division through a thoracotomy incision. Transcatheter closure has become popular as definitive treatment. Double disc devices like Raschkind Occluder are used for large PDA more than 4 mm, and coils for those that are smaller.83

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Children with isolated PDA and no pulmonary vaso-occlusive disease can undergo early extubation in the OT or ICU. Patients with large PDA with persisting cardiac failure, associated PAH and pre-term patients may have difficulty in being weaned off. Judicious use of afterload reducing agents may be beneficial in children with preoperative LV dysfunction. Compression and retraction of ipsilateral lung during the intraoperative period can leave residual areas of atelectasis and produce postoperative pulmonary complications. Possible complications like injury to the phrenic nerve resulting in diaphragmatic palsy, recurrent laryngeal nerve injury leading to vocal cord paralysis and pneumothorax may also need to be addressed occasionally in the pediatric intensive care unit (PICU). Chest radiographs are obtained to rule out lobar collapse and pneumothorax. Since the surgery requires a thoracotomy incision, adequate postoperative analgesia should be ensured to enhance deep breathing and minimize pulmonary complications. Aorta, left pulmonary artery and the left main stem bronchus are all structures that can be mistaken for the ductus and ligated.84 The intensivist should have vigilance to these possibilities and feel for the distal pulses as soon as the patient is brought to the ICU.

Coarctation of Aorta Patients with coarctation of aorta have a narrowing of the descending aorta near the insertion of ductus arteriosus into the aorta. It may be associated with hypoplasia of aortic isthmus, aortic and mitral valve abnormalities and VSD. Surgical repair is achieved by resection and end-to-end anastomosis, patch augmentation of aorta or by a subclavian flap aortoplasty. All techniques require 10 to 25 minutes of aortic cross-clamping above and below the area of coarctation. Continuous intra-arterial pressure monitoring is recommended to facilitate hemodynamic control during anastomosis. Left arm should not be used for pressure monitoring because the left subclavian artery may be involved in the coarctation or may be used for repair. Upper and lower extremity pressures should be monitored to know the distal perfusion during surgery as well as to assess the gradient after repair. Rebound hypertension may be a concern in the postoperative period after removal of cross-clamp. The mechanisms implicated include increased production of catecholamines and renin.85, 86 This needs prompt treatment with vasodilators (SNP, beta-blocker, etc.) as it can increase bleeding from the anastomotic site. ACE inhibitor like captopril may be a useful oral agent for the treatment of persistent hypertension.87 Paraplegia is a rare complication that may occur due to spinal cord ischemia.88 The risk of paraplegia is increased when the collateral circulation is poorly developed and the blood pressure in the distal aorta is lower during aortic clamping.89 Intraoperatively, the temperature of the patient, duration of the aortic cross-clamp and the use of deliberate hypotension can increase the risk of paralysis.90 The importance of neurological examination to rule out this rare complication should be stressed in the postoperative assessment of these patients in the PICU. Clinician should also be wary of the ‘post coarctectomy’ syndrome characterized by abdominal pain and/or distension, ascites, fever and leukocytosis. Reflex mesenteric vasoconstriction secondary to uncontrolled hypertension and splanchnic hypoperfusion has

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been implicated. Nasogastric suction, withholding enteral feeds for 48 hours or more and aggressive management of postoperative hypertension have decreased the frequency of this complication.91 Lung complications secondary to retraction and handling exists as with other thoracotomy procedures. Phrenic nerve injury causing diaphragmatic palsy and recurrent laryngeal nerve injury may create problems during weaning the patient from mechanical ventilation. Chylothorax may be seen in about 5 % of patients. Since the surgery is carried out through a thoracotomy incision postoperative analgesia should be optimized to facilitate early weaning. In neonates and infants who have preoperative LV dysfunction secondary to coarctation, low cardiac output state can persist after coarctation repair. Appropriate inotropic support with judicious use of afterload reducing agents is beneficial in this setting. An ACE inhibitor like Captopril can also be used for afterload reduction when enteral feeds are restored.

Tetralogy of Fallot (TOF) Tetralogy of Fallot (TOF) comprises ventricular septal defect, right ventricular outflow tract obstruction, overriding of aorta and right ventricular hypertrophy. Complete correction of TOF is now performed in infants with lower operative mortality and excellent long term.92 results. The repair includes transatrial closure of VSD with a patch and resection of infundibular tissue. Ventriculotomy is performed at the level of right ventricular outflow tract and may be extended into the pulmonary valve annulus and beyond if necessary. The outflow tract and the pulmonary artery are subsequently enlarged with pericardium or synthetic material to relieve the obstruction. The goal of postoperative management after repair of TOF is to support the right ventricular function and to minimize the afterload on the right ventricle. This is of particular importance in neonates and small infants undergoing early primary repair. While right ventriculotomy, can contribute to systolic dysfunction of the RV, the ‘restrictive‘ physiology due to the reduced compliance of the hypertrophied RV can contribute to diastolic dysfunction also. Inadequate myocardial protection of the hypertrophied ventricle during CPB, residual outflow obstruction, residual VSD and pulmonary regurgitation, can contribute to postoperative RV dysfunction.93 Maintenance of higher right-sided filling pressures is needed to overcome the dynamic outflow obstruction and improve cardiac output. Liberal inotropic support is often required to treat ventricular dysfunction and a phosphodiesterase inhibitor such as Milrinone is beneficial in the setting of RV diastolic dysfunction because of its lusitropic properties.72 Continued sedation and mechanical ventilator support is necessary for the first 24 to 28 hours to minimize stress response and myocardial work. A patent foramen ovale left behind at the time of repair may allow right to left shunt and maintain preload to the left ventricle. A low arterial oxygen tension in the presence of a patent foramen ovale (PFO) shunting right to left may be a subtle evidence of RV dysfunction. High right-sided pressures due to RV dysfunction predispose the patient to pleural effusion, congestive hepatomegaly and ascites. These third space collections should be drained appropriately. Peritoneal dialysis and diuretic therapy can decrease peripheral edema

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in the immediate post-bypass period. Digitalization may be required at the time of weaning off inotropic supports. Another issue that increases the morbidity in postoperative period is the chance of excessive postoperative bleeding in older cyanotic kids. Coagulation defects secondary to long standing polycythemia including factor deficiencies, thrombocytopenia, activation of fibrinolytic system and disseminated intravascular coagulation (DIC) have been reported in these patients. Longer duration of CPB and multiple extra- cardiac suture lines also add to the problem and increase transfusion requirements perioperatively. Maintenance of higher hematocrit >12 g% should be ensured in these cyanotic infants as a sudden drop in hematocrit can decrease systemic vascular resistance and cause hypotension. Right bundle branch block may be typically seen in postoperative ECG.94,95 It may be caused by right ventriculotomy and trauma to right bundle branch or proximal conducting system. JET’s, ventricular ectopics and complete heart block are also reported. Ventricular arrhythmias are a recognized late complication after repair of TOF and is associated with high incidence of sudden death.96, 97

Repair of Partial/complete AV Canal AV canal defects arise from a deficiency in AV septum as a result of incomplete development of superior and inferior endocardial cushion tissue. These defects can be classified into partial, intermediate or complete AV canal defect. These patients have large left to right shunts and therefore increased pulmonary blood flow and congestive cardiac failure. When there is a complete AV canal defect, VSD component is unrestrictive and pulmonary hypertension is often present. In addition, AV valve regurgitation predominantly mitral will exaggerate the left to right shunt and lead to ventricular dilatation. AV canal defects are associated with Down’s syndrome.98 Partial AV canal defects consist of a primum ASD and associated cleft of the mitral valve. Surgical repair aims at closure of the atrial and ventricular septal defect and creation of the two AV valves. In addition, mitral valve may require suture approximation and re-suspension of the separated portions. Commissuroplasty may be required for a dilated mitral annulus. Important postoperative issues that demands attention is the incidence of pulmonary hypertension. This often requires therapy with sedation, mechanical hyperventilation and pulmonary vasodilators including inhaled nitric oxide and Sildenafil. Continuous PA pressure monitoring is invaluable in the postoperative management of these patients. AV valve regurgitation predominantly left sided, may persist even after repair. Selection of inotropic agents like dobutamine and milrinone which decrease the afterload will help to minimize the regurgitant fraction and improve cardiac output. Aggressive volume loading should be avoided to minimize AV valve regurgitation. Pulmonary congestion may result from AV valve regurgitation or fluid overload. Fluid restriction to one half of the maintenance requirements and aggressive diuretic therapy is indicated in these patients. Low cardiac output states should be managed by liberal inotropic support, afterload reduction to minimize AV valve regurgitation and initiation of measures to decrease pulmonary

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vascular resistance. In case of persistent low cardiac output state, residual VSD, if any should be ruled out by transesophageal echocardiogram. Dysrhythmias are common as the surgery involves dissection in the areas of conducting system. SA node dysfunction and complete heart block can complicate the postoperative recovery and may require AV sequential pacing. Ventricular pacing alone should be avoided to minimize AV valve regurgitation. Right bundle branch block is common after repair of complete AV canal defects. Anatomical features like presence of large tongue, subglottic stenosis and upper air way obstruction can lead to airway complications in the immediate post-extubation period.

Total Anomalous Pulmonary Venous Connection (TAPVC) Repair Total anomalous pulmonary venous connection (TAPVC) is a congenital defect in which all of the pulmonary veins drain anomalously to a systemic venous structure rather than directly into the left atrium. Anatomical subtypes include supracardiac, cardiac, infracardiac and mixed types. Surgical repair of the total anomalous pulmonary venous connection requires attachment or redirection of the pulmonary venous confluence to the left atrium. Cardinal postoperative issues include pulmonary hypertension, decreased ventricular function and arrhythmias. Postoperative care is directed towards optimization of cardiac output, peripheral perfusion and respiratory function. Inotropes and afterload reduction are often required. It is important to remember that the LA and LV is small in TAPVC patients and they would not take any volume load. Fluid intake is restricted and diuretics are used as well. Patients with preoperative pulmonary venous obstruction and elevated PA pressures are prone for pulmonary hypertensive crises. Routine precautions to avoid PA crisis should be adopted. It is also prudent to avoid hyperthermia in the postoperative period in children who required repair under tricyclic antidepressant (TCA). Low cardiac output can occur due to the diminished compliance of left heart structures, and increased RV afterload in view of pulmonary hypertension. Several reports suggest that an unligated vertical vein can serve as a left atrial vent during the immediate postoperative period thus allowing time for the left atrial compliance to improve.99 Occasionally fenestration of the atrial patch may be necessary to allow right heart decompression when pulmonary hypertension is present. Delayed sternal closure permits better postoperative RV function until PA pressures settle. Extracorporeal Membrane Oxygenation (ECMO) in such situations will improve survival. Dysrhythmias usually supraventricular occur in 5 to 20% patients following repair of TAPVC.99 Postoperative arrhythmias occur predominantly in patients with cardiac type of TAPVC.100 Children with unobstructed supracardiac TAPVC and cardiac type of TAPVC with no PAH are amenable to early weaning and extubation on first postoperative day. Sick neonates with infra cardiac TAPVC often have a stormy postoperative period with PA crisis and may require longer ventilator support and ICU stay. Partial anomalous pulmonary venous drainage is characterized by anomalous drainage of right pulmonary veins into either SVC or right atrium. It is usually associated with a primum

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ASD. Postoperative period in these children is generally uneventful and early extubation is attempted.

Operations for TGA (Arterial Switch Operation and Senning Operation) TGA accounts for 5 to 7% of all congenital cardiac defects. In TGA, the aorta arises from the anatomic right ventricle and the pulmonary artery from the anatomic left ventricle. Associated anomalies include VSD, coarctation of aorta, interrupted aorta arch, left ventricular outflow tract obstruction (LVOTO) and coronary branching anomalies. Arterial switch operation anatomically corrects discordant ventriculo-arterial connections. This is done in the neonatal period when the PVR and left ventricular pressure have both been high. Immediate postoperative period may be complicated by bleeding from extensive suture lines. Efforts to reduce aortic blood pressure combined with aggressive therapy with blood products may be required. Decreased platelet number and function during bypass and hypothermia may also contribute to bleeding. The clinician should have a high index of suspicion for myocardial ischemia in the immediate postoperative period as the coronary arteries may be stretched or kinked after re-implantation. Coronary air emboli can also precipitate transient myocardial ischemia. Traditional coronary vasodilators like nitroglycerin (NTG) have been used in the setting of myocardial ischemia after arterial switch operation although control studies establishing its efficacy are lacking. Possibility of pulmonary hypertensive crises in patients with preoperative PAH should be borne in mind. Arrhythmias may indicate coronary insufficiency and require prompt diagnosis and treatment. Left ventricle (LV) dysfunction in the immediate postoperative period contributing to a low cardiac output state may result from myocardial ischemia, poor myocardial protection during CPB or afterload mismatch. Mitral regurgitation secondary to papillary muscle dysfunction can also add to this low cardiac output state. Inotropic supports should be liberal and agents which reduce afterload like milrinone are preferred. Volume infusions should be given slowly and in small aliquots as LV may be poorly compliant. LA pressure should remain low (< 12 mm Hg) especially in neonates.101 Acute increases in preload may be followed by significant increase in left arterial pressure, pulmonary edema and fall in colloid ostmotic pressure (COP). Continuous LA pressure monitoring though a catheter inserted perioperatively may be a useful guide to assess left ventricular function and guide volume therapy. If there is myocardial edema, hemodynamic instability or excessive bleeding from suture lines, sternum may be left open and delayed sternal closure is undertaken on 1st or 2nd POD.

Senning Operation This repair involves an atrial switch whereby an atrial level baffle is created which redirects the pulmonary venous blood across the tricuspid valve to the right ventricle and thus to aorta. Systemic venous return is directed across the atrial septum to the mitral valve into the LV and thus to the PA.

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Postoperative concerns include the possibility of systemic or pulmonary venous obstruction in the immediate post bypass period due to the placement of intra atrial baffles. Systemic venous obstruction manifests as SVC syndrome or other signs of systemic venous hypertension. Obstruction to the pulmonary venous baffle will result in pulmonary venous hypertension presenting as pulmonary edema and inadequate gas exchange. Severe pulmonary venous obstruction may be suspected if there is copious amount of blood from the endo-tracheal tube, low cardiac output and poor oxygenation. Extensive atrial sutures may interrupt the conduction system and predispose to arrhythmias. Sinus bradycardia, slow junctional rhythm, supraventricular tachycardia (SVT) and atrial flutter are all encountered in the postoperative period. AV sequential pacing may be required for slow junctional rate. Extubation may be delayed if myocardial dysfunction and low cardiac output state coexists.

Anomalous Left Coronary Artery from the Pulmonary Artery (ALCAPA) This is a rare anomaly in which left coronary artery originates from the pulmonary artery, also known by the name Bland White Garland syndrome. In critically ill small infants, low cardiac output should be anticipated in the first few postoperative days. Tachycardia should be avoided to prevent untoward increases in the myocardial oxygen demand. Cardiac output should be optimized to maintain oxygen delivery to the ischemic myocardium. Monitoring of LA pressure is useful in guiding postoperative fluid management. Mechanical support of the circulation should be available if clinical status dictates its use. Surveillance for ventricular arrhythmias and myocardial ischemia should be continued in the postoperative period. Electrolyte imbalances, which can contribute to ventricular arrhythmias, should be promptly corrected.

Truncus Arteriosus Repair In this anomaly the embryonic truncus fail to separate normally into two great arteries. A single great artery leaves the heart and gives rise to coronary, pulmonary and systemic circulation. Children with this anomaly are at high-risk for developing pulmonary hypertension and pulmonary vaso-occlusive disease. Truncal valve regurgitation can lead to ventricular volume overload. Postoperative concerns are persistent pulmonary hypertension and low cardiac output state secondary to ventriculotomy. Truncal valve regurgitation may complicate postoperative recovery and aggravate the low cardiac output state. Inhaled nitric oxide should be used prophylactically in high-risk cases to decrease pulmonary hypertension. Long-term pulmonary vasodilatation may require oral sildenafil. If myocardial edema is significant in the postoperative period, sternum may be left open to reduce intrathoracic pressure and cardiac compression.102 Mechanical ventilation and judicious inotropic use with afterload reduction should be continued. Residual defects and truncal valve regurgitation should be ruled out. Arrhythmias like atrial tachycardia and JETs should be promptly identified and treated.

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COMMON POSTOPERATIVE PROBLEMS AFTER PEDIATRIC CARDIAC SURGERY Low Cardiac Output State (LCOS) Low cardiac output syndrome is a multifaceted syndrome of inadequate tissue perfusion that is often defined in terms of a cardiac index less than 2 L/min/m2.103 Clinical assessment of cardiac function is inconsistent and often inaccurate. In the PICU, a variety of clinical and laboratory parameters reflect the adequacy of cardiac function and the response to therapy.

Clinical Indicators of Low Cardiac Output Observation of the state of consciousness, hydration and activity level of the child provides valuable diagnostic clues. Anxiety, irritability and lethargy may reflect inadequacy of cardiac output. Respiratory compensation from metabolic acidosis manifest as rapid shallow breathing. A capillary refill time longer than 2 seconds indicates hemodynamic compromise.104 So also a coreperipheral temperature gradient >  2°C indicates marked hypoperfusion.33 Good pedal pulses correlate with adequacy of cardiac output and high probability of survival. Presence of pulsus paradoxus in a spontaneously breathing patient may indicate myocardial decompensation. An increase in pulse volume with mechanical ventilation may indicate impaired contractility while a decrease in pulse volume with a mechanical breath may indicate decreased preload. A urine output of < 0.5 mL should raise concern about the adequacy of renal perfusion. Intensive hemodynamic monitoring to rule out arrhythmia/ischemia, filling pressures of the atria for diagnosing hypovolemia/impaired contractility, analysis of arterial waveform to know stroke volume and contractility will supplement the clinical data. Transesophageal ECHO may reveal systolic and diastolic dysfunction, residual defects, valvar regurgitation, and significant effusions and thus help to pinpoint the cause of low cardiac output state.

Metabolic Indicators of Low Cardiac Output Tissue hypoxemia following inadequate perfusion can lead to high blood lactate levels secondary to anaerobic metabolism. High lactate levels are also associated with hemorhagic or cardiogenic shock, sepsis, CPB and catecholamine administration. Raised concentration of lactate early in the postoperative period is associated with a higher risk of poor outcome.105, 106 A low base deficit early after cardiac surgery is associated with a longer stay in the PICU and major adverse events.107 A low mixed venous oxygen saturation (MVO2) indicates low cardiac output provided the oxygen consumption and oxygen carrying capacity remain constant.108 Mixed venous sample can be obtained from a pulmonary artery catheter (PAC) placed intraoperatively in children. In the absence of PAC sampling from a central vein can be considered a convenient surrogate.109 Mixed venous oxygen saturation > 70% is a measure of good cardiac output.108 Increased AV difference suggests reduced tissue blood flow and increased O2 extraction. Hyperkalemia rising over a 4 hour period with sampling every 2 hours to a level of 5 meq/L is a sensitive indicator of low or falling cardiac output in neonates and infants.110 A rising blood

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urea nitrogen and creatinine will result from hypotension induced decreased renal blood flow and a low glomerular filtration rate (GFR).

Causes of Low Cardiac Output State (LCOS) 1. Preoperative severe LV dysfunction persisting into the postoperative phase 2. Myocardial dysfunction related to intraoperative support techniques (ischemiareperfusion injury, effects of CPB, inadequate myocardial protection, etc.) 3. Complications of surgery or type of surgical technique (e.g. right venticulotomy in TOF repair) 4. Arrhythmias or loss of normal conduction 5. Pulmonary hypertension 6. Residual structural defects 7. Sepsis.

Treatment Management of LCOS is by identifying the cause and optimizing the key determinants of COP namely heart rate, preload, afterload and contractility.

Heart Rate Maintenance of an optimal heart rate is important in preserving adequate COP especially in infants whose ventricles are less compliant and have a rate dependent COP. Very high heart rates will limit ventricular filling time and stroke volume. Lack of AV synchrony also decreases ventricular filling and thus cardiac output. Postoperative tachycardia may be due to pain, agitation or hypovolemia and will respond to specific treatment. Supraventricular tachyarrhythmias may require cardioversion or pharmacological therapy if hemodynamic compromise occurs. Junctional ectopic tachycardia (JET) in the postoperative period may be of concern in surgeries like VSD repair, TOF repair or correction of AV canal defects. Treatment with core cooling to 34°C along with anti-arrhythmic and sedation is often required. Ventricular arrhythmias require correction of electrolyte disturbances, cardioversion or amiodarone therapy. Bradycardia occurs frequently after extensive atrial surgery, TAPVC repair, etc. secondary to sinus node dysfunction. It can also occur due to myocardial dysfunction or hypothermia. Temporary atrial/AV sequential pacing may be required.

Preload Decrease in preload decreases stroke volume and COP. Right and left atrial pressure monitoring if available offers indirect estimate of preload to the corresponding ventricles. Low cardiac output state (LCOS) due to decreased preload will respond to volume administration. Hematocrit should be maintained at 30 to 35% in acyanotic patients. Fluid challenges may be given in boluses of 5 to 10 mL/kg with close monitoring of right and left atrial pressures.

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Afterload In the presence of myocardial dysfunction, increases in systemic vascular resistance (SVR) may be poorly tolerated. Elimination of physiological factors that increase SVR like acidosis, hypoxemia, pain and hypothermia is important in the post CPB period. When SVR is persistently elevated therapy with pharmacological agents like sodium nitroprusside (SNP), nitroglycerin (NTG), beta blockers or angiotensin-converting enzyme (ACE) inhibitors can be initiated. Adequate intravascular volume should be ensured while vasodilator therapy is instituted. Increased pulmonary vascular resistance contributing to increased RV afterload may be managed with hyperventilation and with pulmonary vasodilators like inhaled NO, prostacyclins, sildenafil, etc.

Decreased Afterload Rarely children may develop severe hypotension due to vasodilation in the immediate postbypass period. This hypotension may respond to vasopressin by constant infusion 0.0003 to 0.0024u/kg/min.111

Contractility If the patient cannot maintain adequate CO once HR, rhythm and preload has been optimized, it may indicate impaired contractility and needs therapy with an inotrope. Considerations while selecting the inotrope includes the nature of the lesion and the pathophysiology. Catecholamines are often the first line choice. This includes dopamine, dobutamine, epinephrine, etc. Mild hypotension usually responds to dopamine at an infusion rate of 5 to 10 mg/kg/min. In case of dose dependent tachycardia, dobutamine can be added and dopamine can be reduced. Patients in whom significant myocardial dysfunction is anticipated potent inotropes like epinephrine may be required. Norepinephrine should be avoided due to its predominant vasoconstrictor effect and detrimental effects on organ perfusion. Its use is restricted to patients exhibiting marked vasodilatation.(e.g. septic shock) PDE III inhibitors possess moderate inotropic effects and vasodilatory properties. They reduce systemic, coronary and pulmonary vascular resistance and have beneficial effects on RV function in patients with severe PHT. They have lusiotropic effect which makes them effective in conditions of restrictive RV physiology in TOF patients. Pharmacotherapy alone may be insufficient to maintain adequate COP in the presence of severe ventricular dysfunction. In these circumstances mechanical support of cardiac function may be required. There is limited experience with the use of IABP in children.112 Use of LV assist devices or ECMO can provide successful hemodynamic support and allow recovery.113 Complete discussion of this topic is beyond the scope of this chapter. Other agents which can be used in critically ill patients with myocardial dysfunction include thyroid hormone (T3), glucagon, corticosteroids, etc.114 While all the above measures are indicated for cardiovascular support, supportive measures like continuing mechanical ventilation, sedation and paralysis to decrease stress response and myocardial work, as well as aggressive management of hyperthermia can promote recovery of cardiac function. In the event of low cardiac output (LCOP) and inadequate renal perfusion,

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renal replacement therapy with peritoneal dialysis and diuretic therapy can minimize end organ injury. Resumption of enteral nutrition and ensuring adequate calorie intake can also help the infants to tide over this catabolic state.

Pulmonary Hypertension Pulmonary artery hypertension (PHT) can be defined as a mean pulmonary artery pressure greater than 25 mm Hg after first few weeks of life.115 Four mechanisms are suggested including increased PVR, increased PBF with normal PVR, combination of increased PVR and increased PBF and increased pulmonary venous pressure.

Factors Contributing to Raised PVR PHT is likely to complicate the postoperative course of many children with conditions like truncus arteriosus, complete AV canal defects, TAPVC repair, multiple VSD’s, TGA, etc. The duration of total CPB have been linked to postoperative PHT.116, 117 Transient pulmonary vascular endothelial injury consequent to CPB, microemboli, pulmonary leuco-sequestration, atelectasis, HPV and adrenergic agents have also been suggested to play a role in postoperative PHT.118 Parenchymal lung disease and RDS can cause significant elevation of PVR probably due to alveolar hypoxia. Mechanical ventilation can influence PVR. PVR is minimum when lungs are inflated to its normal FRC. PVR increases both above and below this value.

Diagnosis of Postoperative Pulmonary Hypertension Pulmonary artery pressure that is equal to or greater than systemic arterial pressure and associated with a significant deterioration in systemic blood pressure and arterial desaturation is diagnostic of PHT crises.119 In the presence of PA catheter direct measurement of PA pressure is obtained which can be compared with systemic pressures. In the absence of direct PA measurements unexplained tachycardia, hypotension and desaturation are the cardinal signs. Increased RV afterload leading to RV failure may manifest as high RAP. ECHO may show right ventricular dilation and shift of interventricular septum to the left which can further compromise cardiac output.

Strategies for Prevention and Management of Pulmonary Hypertensive Crisis Hemofiltration during CPB has been an effective strategy which improves pulmonary function. Modified ultrafiltration (MUF) decreases total body water, improves mean arterial pressure and removes inflammatory mediators.120, 121 Postoperatively patients who are likely to have labile pulmonary artery pressures are shown to benefit from prolonged analgesia and sedation. Fentanyl and neuromuscular blocking agents should be continued for first 48 hours. Anesthesia and sedation should be deepened prior to interventions like endotracheal tube (ETT) suctioning and ICD insertion. Hypoxemia, hypercarbia and acidosis should be avoided. Pain control with fentanyl infusion and sedation with a short acting benzodiazepine has been associated with a lower incidence of labile PVR in the postoperative period.122 Mechanical ventilator parameters are adjusted to avoid alveolar hyperinflation or atelectasis. These patients should be kept well oxygenated with a PaO2 > 100 mm Hg and hyperventilated to maintain

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PaCO2 between 25 to 30 mm Hg and pH 7.5 to 7.55. Once the gas exchange and myocardial function are optimized, it is prudent to establish and maintain a diuresis which will help to decrease lung water. The prophylactic use of inhaled NO, nitric oxide donors like SNP, NTG, phosphodiesterase (PDE) III inhibitors like milrinone have also been advocated in patients prone to develop PHT.36 Inhaled nitric oxide has been the single most important advance in the management of pulmonary hypertension. It is a selective pulmonary vasodilator with essentially no systemic side effects.123 Clinical signs that indicate a response to NO include an increase in peripheral oxygen saturation, improved systemic perfusion, decrease in tachycardia and improvement in respiratory symptoms like wheezing and tachypnea. Inhalation of 1 to 80 ppm NO results in significant selective pulmonary vasodilatation, rapid reduction in RV afterload and improving pulmonary oxygenation.124,125 Prophylactic use of iNO at 10 ppm has significantly reduced episodes of postoperative pulmonary hypertensive crises showing 30% decreases without any toxic effects. Concerns during inhaled NO therapy include methemoglobinemia; rebound PHT during withdrawal and contamination by higher oxides of nitrogen leading to environmental pollution. A selective inhibitor of PDE 5, Sildenafil has been demonstrated to attenuate PHT rebound after acute withdrawal of NO and is currently under investigation for long-term treatment of PHT.126

Common Arrhythmias and Heart Blocks During surgery, injury to the conducting system can be caused by direct trauma, ischemia, metabolic abnormalities or by cardioplegia solutions. Postoperative problems like hypothermia, electrolyte disturbances and high levels of circulating catecholamines add to the complexity of the issue. As the pediatric population has a heart rate dependent cardiac output, optimizing heart rate in the postoperative period as well as maintenance of atrioventricular synchrony is vital in maintaining an adequate cardiac output.

Tachyarrhythmias Sinus Tachycardia: In the postoperative setting sinus tachycardia may often be due to hypovolemia, hyperthermia, pain, myocardial ischemia, or due to high level of circulating catecholamine. Treatment is mainly directed at the cause.

Supraventricular Tachycardia (SVT) SVT in the postoperative period can occur in the infant with congenital heart disease especially after surgery at or near the pulmonary veins. Acute hemodynamic compromise may be treated with synchronized cardioversion starting with 0.5 J/kg. If hemodynamic compromise is mild, adenosine is the drug of choice given by fast intravenous injection in a dose of 50 to 250 mcg/kg. Overdrive pacing at 10 to 20% rate faster than the SVT can also break the rhythm. Intravenous digoxin, procainamide and amiodarone may also serve as alternative medications. Junctional Ectopic Tachycardia (JET) Junctional ectopic tachycardia is also a relatively common tachyarrhythmia likely to occur after surgical repairs involving sutures near the bundle of His. This rhythm occurs in the first

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24 to 48 hours after surgery and occur following repair of VSD, AV canal defects, TOF, TGA, TAPVC and modification of Fontan procedure.127 This arrhythmia does not usually respond to adenosine, overdrive pacing or cardioversion. The most useful advance in the treatment of this arrhythmia is the institution of mild hypothermia (around 34°C) which will slow down the rate.128 Patients must be sedated and paralyzed and the dose of catecholamines should be reduced. Serum electrolytes should be normalized. Intravenous amiodarone has been found to be useful in this setting.

Atrial flutter Atrial flutter refers to re-entrant tachycardia involving atrial muscle. Congenital heart lesions that cause significant atrial dilatation (e.g. Ebsteins anomaly, AV canal defects) and surgeries involving extensive atrial suturing (Mustard, Senning, and Fontan) are associated with the highest incidence of atrial flutter.50 Electrical cardioversion and overdrive pacing techniques are highly effective in terminating this arrhythmia. Intravenous adenosine can also terminate the atrial reentry. Once the primary episode is terminated drugs like digoxin, beta-blockers or quinidine can be given to prevent recurrence. Atrial Fibrillation Electrical cardioversion is the usual method of acute conversion and is followed by drug therapy with digoxin, beta-blockers or procainamide/amiodarone to prevent recurrence.

Ventricular Arrhythmias Premature Ventricular Contraction This is characterized by a premature wide QRS complex that has a distinct configuration and is not preceded by a “p” wave. Occurrence of 3 or more consecutive PVC is considered as ventricular tachycardia (VT). Monomorphic VT is due to re-entry within a damaged segment of ventricular tissue. Torsades de pointes is a typical form of VT which has a varying QRS morphology that seems to twist around the isoelectric baseline of the ECG. Torsades de pointes in the perioperative setting can occur with prolongation of QT interval, electrolyte abnormalities and exposure to potent antiarrhythmic drugs. Hemodynamically unstable VT warrants immediate synchronized cardioversion with 0.5 to 1 J/kg. Pharmacological measures include amiodarone, procainamide or lignocaine. After cardioversion a continuous infusion of lignocaine or amiodarone may be needed for maintenance of sinus rhythm.129 Ventricular Fibrillation During VF, CPR should be initiated and defibrillation should be prompt with 2 J/kg, and then increased to 2 to 4 J/kg and then 4 J/kg. If unsuccessful, epinephrine is given and repeated every 3 to 5’. Refractory ventricular arrhythmias may be treated with amiodarone, sotalol or magnesium.

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Bradyarrhythmias In the postoperative setting, this may be due to sinus node dysfunction commonly seen in surgeries involving extensive atrial baffling (Mustard, Senning and Fontan). Conduction system may also be damaged inadvertently in surgeries involving repair around bundle of His and AV node (e.g. VSD, AV canal defects, TOF, etc.) resulting in heart blocks in the postoperative period.

Sinus Bradycardia It is defined as a significant reduction in the heart rate below that expected for the age of the patient. The ECG may show slow and irregular atrial rates with escape rhythms arising from atrial or junctional foci. Temporary atrial pacing is usually required. AV Blocks Varying degrees of AV blocks are encountered in the postoperative period. Complete AV block is a more common cause for postoperative bradyarrhythmia. In complete heart block, there is complete AV dissociation with none of atrial impulses being conducted to the ventricles. QRS duration is usually normal. Temporary sequential pacing is required and a permanent dual chamber pacemaker will need to be implanted if normal conduction does not recover within 10 days.

Residual Lesions These refer to structural defects which persist after corrective surgery for congenital heart disease. These may be evident by echocardiography, intracardiac pressure or waveforms, or from oxygen saturation data from intracardiac catheters. Persistent difficulty in weaning from ventilator or low CO should prompt one to look for residual lesions.

Residual VSD Residual VSDs are not an uncommon complication. A ‘step up’ in oxygen saturation from RA to PA after CPB or in the postoperative period is suggestive of a residual VSD. In a patient with TOF, residual VSD can significantly increase right ventricular pressures and contribute to RV dysfunction and low cardiac output state. Residual right ventricular outflow tract (RVOT) obstruction after repair of TOF can be detected by direct measurement of pressure gradients postoperatively or by TOE. Persistent RVOT gradient after repair of TOF is an indication to widen the annulus with a transannular patch. Residual Aortic Arch Obstruction In repair of aortic arch anomalies a residual pressure gradient between upper limb and lower limb pressure measurements may give a clue to persistence of residual narrowing. Valvular Regurgitation Residual AV valve regurgitation may persist in patients after repair of complete AV septal defect. Similarly mitral valve regurgitation secondary to papillary muscle dysfunction from ischemia

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may occur in neonates following an arterial switch operation or ALCAPA repair. Persistent AV valve regurgitation can contribute to low cardiac output state and hence afterload reduction is required to minimize valvular regurgitation in these patients.

Pulmonary and Airway Complications Respiratory dysfunction after cardiac surgery is multifactorial in origin and results in significant postoperative morbidity. Pulmonary complications arise as a sequelae of cardiopulmonary bypass or from preoperative issues like increased pulmonary blood flow, venous congestion or infection, or due to direct mechanical injury during the surgery itself. Thoracotomy incision and accompanying chest tubes will cause significant postoperative pain, and compromise the respiratory movement. Commonly encountered pulmonary complications are highlighted following:

Pulmonary Edema This can occur secondary to elevated left atrial pressure or due to left ventricular failure. Increased pulmonary blood flow from a residual shunt or pulmonary venous obstruction should be ruled out in the setting of pulmonary congestion. Initiation of positive pressure ventilation to optimize gas exchange and manipulation of PVR to bring down the pulmonary blood flow may help in treatment. Pulmonary edema secondary to fluid overload responds to steady diuresis and digitalis. LVF should be managed with inotropic support. Upper Airway Complications Upper airway obstruction usually presents in the postoperative period after extubation as inspiratory stridor. Risk factors associated with the development of postextubation stridor are patient’s age, traumatic intubation, Down’s syndrome and absence of leak prior to extubation.130,131 Patients with acute upper airway obstruction sometimes present with frank pulmonary edema. Common causes of postextubation stridor include subglottic edema, subglottic stenosis, vocal cord palsy, laryngomalacia or tracheal stenosis. Management strategy includes oxygen supplementation, inhaled racemic epinephrine, noninvasive ventilation by CPAP, and steroids. Role of steroids is disputed. Dexamethasone may prove useful in stridor due to subglottic edema. Re-intubation should be prompted if conservative measures fail. Diaphragmatic Palsy Direct trauma, edema or stretch of the phrenic nerve can occur during surgery causing diaphragmatic palsy in the postoperative period. It usually manifests as respiratory distress as the ventilator support is weaned. Chest radiographs demonstrate elevation of affected hemi-diaphragm, but fluoroscopy which demonstrates paradoxical motion is needed to confirm the diagnosis. Bedside ultrasonography is equally effective in diagnosis. Incidence of phrenic nerve injury is 1.2% in open heart surgeries.132 Treatment is by diaphragmatic plication which allows successful weaning from ventilator.133

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Failure to Wean from Ventilator Success in weaning and discontinuation of ventilator support requires recovery of adequate cardiovascular function along with improvement in pulmonary mechanics and gas exchange. Failed extubation is not uncommon and 10% of postoperative pediatric cardiac patients required reintubation in a recent study. In addition to the above mentioned causes, clinician should also rule out persistent low cardiac output states, inadequate ventilation due to respiratory muscle dysfunction and extrinsic compression of airways by vascular structures or an enlarged left atrium. Until the underlying pathology is corrected ventilator support need to be continued. In those patients who require extended respiratory support, tracheostomy should be considered to minimize complications of prolonged endotracheal intubation.

Common Medication Inotropes These are drugs which improve myocardial contractility. These agents act by modifying calcium handling and calcium-protein interactions. Commonly used inotropes include catecholamines, PDE III inhibitors, and cardiac glycosides. Choice of inotrope is dictated by the patient’s pathophysiology and the relevant hemodynamic goals. Dopamine has action on dopaminergic receptors as well as direct action on alpha and beta-receptors. Inotropic effect is mediated by stimulation of B1 receptors in the heart and indirectly by promoting norepinephrine release at the pre-synaptic terminal. The drug is normally used in ranges between 1 to 10 mcg/kg/min although higher doses up to 20 mg/kg/ min may be used. Indications: It is the most widely used catecholamine to treat systemic hypotension and low cardiac output in neonates, infants and children. Low dose dopamine by stimulation of DA receptors are known to increase renal, mesenteric and coronary blood flow without an appreciable change in myocardial oxygen consumption or cardiac output.134, 135 The role of low dose dopamine as a renal protective agent is disputed. Tachycardia occurs at high doses and can predispose to tachyarrhythmia. Alpha receptor stimulation at high doses can provoke increases in PVR in patients predisposed to pulmonary hypertension.136 Dobutamine is a synthetic catecholamine with predominantly β agonist effects. Inotropic effect is mediated via the b1 receptor of the heart. b2 receptor stimulation promotes pulmonary and systemic vasodilation. Normal dose range include 1 to 10 mcg/kg/min. Doses up to 20 mcg/kg/min may be used. Indications: Dobutamine increases contractility without much tachycardia in patients with myocardial dysfunction.137 It is also a preferred agent for patients with pulmonary hypertension since it does not increase PVR.136 Adverse effect: Hypotension may occur following b2 receptor mediated vasodilation.

Epinephrine This endogenous catecholamine acts via both α and β adrenergic receptors. Predominant effect depends on the dose given. Low doses stimulate b1 receptor and increases contractility.

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High doses can cause alpha receptor mediated vasoconstriction. Normal dose range children is 0.01 to 0.2 mcg/kg/min. Doses above those mentioned does not generally bring any benefit. Indication: Epinephrine is administered as a continuous intravenous infusion in critically ill children with systemic hypotension, myocardial dysfunction or low cardiac output. It is also the first line drug in the management of cardiac arrest. Adverse effects: Administration at very high doses greater than 0.5 mcg/kg/min can cause significant vasoconstriction and compromise end organ perfusion. It can cause glycogenolysis leading to hyperglycemia and hyperkalemia due to its b2 receptor mediated effects.

Norepinephrine It is a potent adrenergic agent that acts primarily on α receptors producing vasoconstriction. Systemic vascular resistance is elevated and perfusion to vital organs may be impaired. Pulmonary vasoconstriction can also occur. The drug should be used in minimal doses to avoid its vasoconstrictive effect on end organs. phosphodiesterase (PDE) III inhibitors: These include Amrinone and Milrinone which act by inhibiting phosphodiesterase III enzyme thereby increasing intracellular cyclic AMP levels and contractility. They also enhance diastolic relaxation of the myocardium by increasing the rate of calcium uptake after systole. Indications: Milrinone after cardiac surgery has been effective in increasing cardiac index and decreasing systemic vascular resistance without a significant increase in myocardial oxygen consumption.138 It is particularly useful in situations of low cardiac output and elevated systemic vascular resistance occurring in post CPB period. They are also being increasingly used in the setting of right heart dysfunction and increased PVR. Lusitropic effect has rendered it useful in the management of right ventricular dysfunction secondary to the ‘restrictive’ RV physiology in children after TOF repair. The drug is normally started as a bolus of 50 mcg/ kg/min over 15 to 20 minutes followed by an infusion of 0.4 to 0.7 mcg/kg/min. The bolus is usually given on CPB to avoid any hypotension. Adverse effect: Hypotension after a loading dose may occur due to its effect on systemic vasculature. Isoproterenol This is a synthetic catecholamine with β effects and no α activity. b1 stimulation increases contractility and automaticity. b2 receptor mediated effects cause vasodilatation of systemic and pulmonary vasculature. Clinical use: Adverse effects of isoproterenol on myocardial oxygen balance limit its use in pediatric intensive care setting. It may be useful in patients with bradycardia and AV block to increase the heart rate and improve A-V conduction, especially in post-transplant patients. It also has a therapeutic role in the treatment of pulmonary hypertension.139 Digoxin This is a cardiac glycoside which exerts its inotropic effect by increasing intracellular calcium by inhibiting sarcolemmal Na-K+ ATPase. Though Digoxin has been used for many decades in the management of congestive cardiac failure, its narrow therapeutic range, slow onset of action and toxic effects make it a poor choice as an inotrope in the acute setting.

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Uses: As an inotrope, it may be started at maintenance dose in the postoperative period when intravenous inotropes are weaned off in those patients with evidence of ventricular dysfunction. As an antiarrhythmic agent it may be effective in SVT, atrial flutter and atrial fibrillation (Table 30.6).

Antiarrhythmic Agents Amiodarone Amiodarone is a very effective antiarrhythmic agent with a wide spectrum of effectiveness against supraventricular and ventricular arrhythmias. Amiodarone prolongs the action potential duration and refractory period and hence it decreases automaticity. It is also suggested to block the cardiac effects of thyroid hormone T3. It is used as an initial bolus of 5 mg/kg over 15 to 30 minutes followed by a continuous infusion of 15 mg/kg over the next 24 hours. Uses: Amiodarone has been widely used in the treatment of refractory ventricular and supraventricular arrhythmias in the intensive care setting. Side effect: Hypotension, pulmonary fibrosis, corneal micro deposits, altered thyroid function have been reported.

Adenosine This is an endogenous nucleoside which has an extremely short half life. Adenosine prolongs A-V conduction by an activation of potassium channels or an inhibition of the slow Ca2+ inward current. It slows sinus rhythm and delays A-V conduction. Uses: Adenosine is the first line therapy for supraventricular tachycardia in children. Because of its extremely short half life, it should be given as a rapid intravenous bolus preferably through a central vein. Adverse effect: Transient bradycardia or sinus arrest may follow rapid administration and reverse promptly (Table 30.7).

END ORGAN INJURY CNS Dysfunction Postoperative neurological sequelae in children with congenital heart disease can be a cause of significant morbidity and mortality in the PICU. These may largely occur as a consequence of processes triggered during the intraoperative period. Randomized control trials have found increased incidence of brain injury in children undergoing corrective surgery under deep hypothermic circulatory arrest (DHCA) and low flow bypass.

Risk Factors for Neurological Dysfunction Developmental cardiac anomalies are associated with an increased prevalence of brain dysgenesis ranging from 10 to 29%.140, 141 Inadequate cerebral perfusion resulting in hypoxemiaischemia/reperfusion injury is the primary pathogenesis implicated in the development of neurological sequelae. Reduction in oxygen delivery to the brain or an increase in cerebral

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Table 30.6: Vasoactive agents Catecholamines Agent Dopamine

Dose range 2–4 mg/kg/min

Peripheral α

b2

0

0

Cardiac D* b1 2+ 0

b2 0

Comment Splanchnic and renal vasodilator Increasing doses produce increasing α effect

4–8 mg/kg/min

0

2+

2+ 1–2+ 1+

Dobutamine

2–10 mg/kg/min

1+

2+

0

Epinephrine

0.03–0.1 mg/kg/min

2+

1–2+ 0

2–3+ 2+

3–4+ 1–2+ Less chronotropy and arrhythmias at lower doses Beta effect with lower doses; used in treatment of severe hypotension and anaphylaxis

0.2–0.5 mg/kg/min

4+

0

0

4+

3+

Norepinephrine

0.1–0.5 mg/kg/min

4+

0

0

2+

0

Increase systemic vascular resistance, may cause renal ischemia

Isoproterenol

0.05–0.5 mg/kg/min

0

4+

0

4+

4+

Strong inotrope and chronotrope, Peripheral and pulmonary vasodilator

Non-Catecholamines Agent

Dose IV

Cardiovascular effects

Digoxin

Pre-term 20 mcg/kg

Inotropic effect, increases peripheral vascular resistance, decreases AV conduction

(Total Digitalizing Dose)

neonates 30 mcg/kg Infant 40 mcg/kg 2–5 years 30 mcg/kg > 5 years 20 mcg/kg

Calcium chloride

10–20 mg/kg/dose

Inotropic effect

Calcium gluconate 50–100 mg/kg/dose

Peripheral vasoconstrictor

Milrinone

50–75 mcg/kg (loading dose)

Systemic and pulmonary vasodilator

0.25–0.75 mcg/kg/min (maintenance)

Lusitropic effect

Vasopressin

0.0003–0.002 U/kg/min

Vasoconstrictor

Thyroid hormone

0.5 mcg/kg loading dose

Nitroprusside

0.05 mcg/kg/h Infusion

Vasodilator, positive inotrope

0.5–5 mcg/kg/min

NO donor, relaxes smooth muscles Pulmonary and systemic vasodilator, decrease afterload

Nitroglycerine

0.5–10 mcg/kg/min

*D – Dopaminergic receptors

Venodilator, coronary and pulmonary vasodilator

488

Pediatric Cardiology Table 30.7: Common antiarrhythmic agents used in children

Drugs effective for SVT Drug Dose and Route Side effects Adenosine 0.1 mg/kg rapid IV bolus, repeat with Transient bradycardia and AV block 0.2 mg/kg if required Digoxin 10–30 mcg/kg load IV in divided doses AV block, arrhythmias, nausea, vomiting over 24 hrs Maintenance: 5 mcg/kg IV bid Verapamil 75–150 mcg/kg IV bolus Hypotension, bradycardia Drugs effective for ventricular arrhythmias Lidocaine 1–1.5 mg/kg IV bolus Infusion:20–50 mcg/kg/min Convulsions, arrhythmias Phenytoin 0.5–1.5 mg/kg IV bolus, may be repeated Rash, Steven-Johnson’s syndrome, neuropathy after 5 min Magnesium sulphate 20–50 mg/kg IV Hypotension Bretylium 5 mg/kg IV bolus Hypotension Drugs effective for both ventricular and supraventricular arrhythmias Amiodarone 5 mg/kg IV over 20–60 min Prolonged QT interval, hypo and Maintenance—15 mg/kg/day infusion hyperthyroidism, over 24 hours Procainamide Infants 5–7 mg/kg slow IV Nausea , vomiting, hypotension Children:7–15 mg/kg slow IV Esmolol 0.5–1 mg/kg loading, slow IV Hypotension, bradycardia Infusion; 50–300 mcg/kg/min

cortical activity without the normal compensatory mechanisms to increase the blood flow, as in the case during CPB can produce ischemia. Occlusion of cerebral circulation by particulate emboli as well as air emboli can lead to local, regional or global ischemic damage depending on the site and size of the embolic trigger. Cerebral hyperthermia which may occur during rewarming and in the PICU can exacerbate neurological injury following DHCA.142 In addition to the above-mentioned etiologies, the inflammatory response to CPB with changes in the microcirculatory level, increased capillary permeability and interstitial edema are also implicated to have a role in the neurological outcome. Metabolic disturbances which are likely to depress the CNS or cause seizure activity include hypoglycemia, hypomagnesemia, and hypocalcemia.

Manifestations of CNS Injury Seizures: Most common manifestation of neurologic dysfunction and a frequency of 4 to 15% following CPB have been reported.17, 143 Clinical signs in young infants are often subtle and may be masked by sedation and anesthesia. Onset is usually in 24 to 48 hours. Motor manifestations may be focal or/multifocal. EEG may be invaluable in directing therapy. Cerebrovascular accidents: In the young infant, stroke often presents as focal seizures or change in mental status, focal neurological deficits, etc.144 Transient or sustained elevation of right heart pressures or CVP predispose to thrombosis in the right atrium and central veins. Prosthetic materials and right to left shunt increase the chance of paradoxical embolization and stroke. Several studies have proven an increased incidence of stroke in children following Fontan procedure.75, 145

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Postoperative movement disorders: A spectrum of dyskinesias is seen in the postoperative period of which choreoathetosis require special mention. Choreoathetosis was associated with pulmonary collaterals arising from the neck which may induce a steal from the cerebral circulation. Patients with aortopulmonary collaterals are suggested to have a higher incidence of neurological abnormalities and choreoathetosis after cardiac surgery. Hypoxemic ischemic encephalopathy and coma are uncommon catastrophes in cardiac intensive care. Severe cases may evolve to brain death. Management: Therapeutic approach includes preventive, pharmacologic and supportive measures.

Cerebral Protection Strategies These revolve around hypothermia, acid-base management and pharmacological agents.

Hypothermia Hypothermia decreases metabolic demands of the brain. Recent experimental publications have demonstrated that profound hypothermia does not cause cerebral injury and is correlated with improved neurological outcome.146, 147 Deep brain temperature correlates well with nasopharyngeal and pump inflow temperatures during CPB and these should be closely followed during rewarming. Reperfusion and rewarming should be conducted slowly to nasopharyngeal temperatures of 36°C in those cases of DHCA to avoid cerebral hyperthermia. Aortic inflow temperatures should not exceed 37°C during rewarming. Hemodilution has been used in conjunction with hypothermia during CPB to counteract increased blood viscosity and red cell rigidity. Though a wide range of protocols for hemodilution were suggested recent available data points to the fact that maintenance of a hematocrit of 25 to 30% during hypothermia is consistent with better neurological scores in the postoperative period.148

Acid-base Management Impact of ABG management during DHCA is still unclear. pH stat management is thought to improve cerebral blood flow and cerebral oxygenation and to effectively cool the brain during CPB.149, 150 But it was also associated with a greater risk of microembolism and free radical injury.151 In a randomized controlled trial (RCT) which showed no difference in neurological outcome between the two groups where pH stat and alpha stat were used, the EEG signal returned sooner among patients assigned to pH stat. Experimental data also suggest that pH stat was associated with a better cerebral metabolic recovery in patients with aortopulmonary collaterals possibly by reducing the steal from the cerebral circulation.148

Pharmacological Agents They act by decreasing cerebral oxygen demand, increasing oxygen delivery and arrest pathological intracellular processes (e.g. barbiturates, volatile agents, benzodiazepines and calcium channel blockers). Attenuation of systemic inflammatory response with methyl

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prednisolone or leukocyte filtration techniques has also shown to confer neuroprotection during circulatory arrest.152,153 Thromboxane A2 and Aprotinin are also suggested to have a role.154

Intermittent Cerebral Perfusion Intermittent systemic reperfusion for 10 minutes period every 20 minutes can prevent cerebral anaerobic metabolism during long periods of circulatory arrest.148 The technique of continuous regional brain perfusion is evolving and technical issues relating to this is yet to be resolved. In spite of correct application of prophylactic measures neurological sequelae do occur. Supportive therapy with emphasis on maintaining a clear airway, ensuring adequate ventilation and a circulation capable of sustaining cerebral perfusion and oxygenation, is important. Seizures should be suppressed with anticonvulsants. Aggravation of cerebral damage should be prevented by appropriate use of position to decrease cerebral venous congestion, (head up tilt of 15 to 30° to improve venous drainage) sedation and analgesia, and prevention of hyperthermia in the PICU.

Renal Failure Postoperative renal failure occurs more frequently after cardiac surgery compared to other surgical procedures. The incidence of renal failure has been reported to be 6.5% following open heart surgery.155

Predisposing Factors Perioperative reduction in cardiac output resulting in low renal blood flow is the most common cause of acute renal failure. Low flows or circulatory arrests during CPB and long duration of CPB with loss of pulsatile renal flow impart additional risk particularly in infants and children. Cyanotic cardiac lesions are associated with increased risk of perioperative renal dysfunction.156 The risk is also associated with left-sided obstructive lesions such as coarctation of aorta, aortic arch interruption and hypoplastic left heart syndrome. Non-cardiac factors like sepsis, DIC, nephrotoxic drugs can pose additional risks. ARF manifests as an abrupt deterioration of renal function impairing the regulation of water, electrolytes and acid-base balance. It presents with oliguria and increasing plasma concentrations of urea and creatinine. Serum electrolytes should be measured every 4 hours, and BUN and creatinine every day for at least 48 hours for early detection of azotemia and hyperkalemia in the postoperative period in sick children. Management Management of oliguria should aim at diagnosis and correcting the underlying cause. Postoperative cardiac function should be optimized and adequate preload should be ensured. Nephrotoxic drugs should be withdrawn or dose optimized in view of falling urine output. Once renal failure is established by clinical and laboratory parameters, fluids should be limited to insensible losses of 300 mL/m2/day plus urine output and other ongoing fluid losses. Potassium must be removed from all intravenous fluids and diet. Nephrotoxic drugs should be withheld. Hyperkalemia should be addressed vigorously. Calcium gluconate, sodium

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bicarbonate, glucose-insulin infusions and ion exchange resins (Kayexalate) can effectively lower serum potassium level until dialysis can be established. If urine output is inadequate after optimizing preload and cardiac output, therapy can be initiated with 0.5–1 mg/kg Frusemide. Continuous infusion is preferred to intermittent bolus doses since it results in a more predictable urine output with a reduced urinary loss of sodium and chloride, cause less fluid shifts and provide better hemodynamic stability.157 Mannitol should be used carefully especially in established ARF in neonates since it can produce a large osmotic load that cannot be excreted by the failing kidney. Persistent or increasing hyperkalemia with anuria warrant prompt peritoneal dialysis or hemodialysis. If anuria and hyperkalemia do not respond to treatment within a few hours, there is a chance of increase in mortality. Therefore peritoneal dialysis or hemodialysis is initiated on an emergency basis. Peritoneal dialysis is usually more efficient in neonates and children due to large surface area of the peritoneum related to body surface area. Peritoneal dialysis is better tolerated hemodynamically, easier to initiate and does not require arterial or venous access. Complications include sepsis, hyperglycemia, hyperosmolality, protein loss and abdominal distension with respiratory compromise. Hemodialysis relies on the same principles as peritoneal dialysis. Rapid fluid shifts and electrolyte changes can cause hemodynamic instability and cardiac arrhythmia. It is technically more complicated and demands trained personnel and equipment. In older children and adults who most commonly develop non-oliguric renal failure conventional hemodialysis may be appropriate when indicated. However, continuous arteriovenous or venovenous hemofiltration may be beneficial in view of advantages in hemodynamically unstable patients.

Hepatic Dysfunction Hepatic dysfunction manifesting as jaundice is seen in 2 to 9% of cases after surgery for congenital heart disease. Important contributing factors include right heart failure, perioperative low cardiac output slates, severe hypoxemia, increased perioperative blood transfusion, hemolysis and use of halothane during CPB.

Manifestations Transient elevation of liver enzymes is common in infants and neonates after cardiac surgery if there was pre-existing cardiac failure. Usually these biochemical derangements settle spontaneously as the general condition improves. Fulminant hepatic failure may manifest with markedly elevated serum transaminase levels, clinical jaundice and hypoalbuminemia. Synthetic, excretory and metabolic functions of the liver are deranged resulting in hypoglycemia, coagulopathy and raised serum ammonia levels. These may occur with/without coma. Management is supportive and aims to minimize metabolic derangements.

Sepsis in Children Sepsis is not an uncommon complication in children who undergo cardiac surgery. Many pediatric literatures defines inclusion of criteria for sepsis as hyperthermia or hypothermia,

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tachycardia, evidence of infection and at least one of the following signs of new onset organ dysfunction—altered mental status, hypoxemia, bounding pulses or increased lactates. However, in the setting of postcardiac surgery, the above-mentioned criteria merge with the changes normally seen in children after CPB. A high degree of suspicion should always be entertained particularly in neonates. On the basis of a number of studies it is accepted that aggressive fluid resuscitation with crystalloids or colloids form the basis of management in septic shock.158,159 In one of these studies 4 different types of intravenous fluid resuscitation in the first hours showed no difference in the outcome.159 Fluid resuscitation is best initiated with boluses of 15 to 20 mL/ kg over 5 to 10 minutes. The initial volume of resuscitation is usually between 40 to 60 mL/ kg.158, 160 Rivers et al, in adult septic shock patients showed that fluid resuscitation aimed at maintaining the superior vena caval oxygen saturation (SCVO2) above 70% was associated with a significant reduction in mortality.161 If during fluid resuscitation the liver becomes palpable, rales are heard or perfusion pressure narrows; more fluid is not advised. Children with fluid and dopamine resistant shock may present with varied hemodynamics including low cardiac output/higher systemic vascular resistance, and high cardiac output/low systemic vascular resistance.162 A variety of inotropes, vasodilators and pulmonary vasodilators should be used diligently to improve the outcome. Therapeutic end points of resuscitation in addition to a SCVO2 > 70% include capillary refill time 1 mL/kg/h, normal mental status and decreased lactate levels. There is no consensus on the role or dosage of steroids used in children. Based on the experience in adult septic shock, a stress dose of hydrocortisone 2 mg/kg bolus followed by an infusion of 2 mg/kg over 24 hours can be recommended.104 Stress dose of steroid is ideally suited for catecholamine resistant shock. Lung protection strategies reduced mortality in adult patients with sepsis and ARDS. Effective tidal volume of 6 to 8 mL/kg with an appropriate PEEP that is titrated against the PaO2/FiO2 ratio seems to be a suitable option in children.104 Human activated protein C has revolutionized the management of sepsis in adults. The first study revealed that infusion dose of 24 mcg/kg/min produces plasma levels similar to that in adults, the study was not able to show any reduction in mortality.163 However, the enthusiasm for the use of APC in children is tempered by the high incidence of intracranial bleeding complications associated with the drug. Hypoglycemia is a constant threat in infants with sepsis. A glucose intake of 4 to 6 mg/kg/ min or a maintenance fluid intake with 10% dextrose in 0.45% NS is advised.160 Recent evidence show that there is a direct correlation between hyperglycemia and mortality.164,165 Srinivasan et al showed that the relative risk of death associated with peak glucose level > 175 mg% was 2.5%. No studies have been performed in children on the effects of stress ulcer prophylaxis. Children should be well-sedated when they are on ventilator. Muscle relaxants are not generally recommended. Antibiotics should be directed to the sensitivity pattern when culture and sensitivity reports are available. Till the antibiotic pattern is available, a broad spectrum antibiotic based on the existing hospital antibiogram and the suspected source of infection can be started.

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In the absence of data it is reasonable to maintain hemoglobin concentration within the normal range for age in children with severe sepsis and septic shock. The role of intravenous immunoglobulin in children with sepsis is doubtful.

REFERENCES 1. Jonas RA. Why Early Primary Repair. In: Jonas RA, DiNardo JA, Laussen PC, Howe RD, LaPierre R, Matte G, (Eds). Comprehensive Surgical Management of Congenital Heart Disease. (1st edn). London: Hodder Arnold Publishers. 2004;3–12. 2. Saxena A. Congenital heart disease in India: A status report. Indian J Pediatr. 2005;72(7):595–8. 3. Kumar RK. Congenital heart disease management in the developing world (letter to editor), Pediatric Cardiology. 2003;24(3):311. 4. Mora-Mangano CT, Chow JL, Kanevsky M. Cardio Pulmonary Bypass and the Anesthesiologist. In Kaplan JA, Reich DL, Lake CL, Konstadt SN, (Eds). Kaplan’s Cardiac Anesthesia. (5th edn). Saunders Elsevier. 2006;893–936. 5. Jaggers J, Ross MU. Cardio Pulmonary Bypass in Infants and Children. In: Mavroudis C, Backer CL, (Eds). Pediatric Cardiac Surgery. (3rd edn). Philadelphia: Mosby. 2003;171–93. 6. Bell C, Rimar S, Barash P. Intraoperative ST-segment changes consistent with myocardial ischemia in the neonate: A report of three cases. Anesthesiology. 1989;71(4):601–4. 7. Greeley WJ, Kern FH, Ungerleider RM, Kisslo JA. Intramyocardial air causes right ventricular dysfunction after repair of a congenital heart defect. Anesthesiology. 1990;73(5):1042–6. 8. Chai PJ, Williamson JA, Lodge AJ, et al. Effects of ischemia on pulmonary dysfunction after cardiopulmonary bypass. Ann Thorac Surg. 1999;67(3):731–5. 9. Kirshbom PM, Page SO, Jacobs MT, et al. Cardiopulmonary bypass and circulatory arrest increase endothelin-1 production and receptor expression in the lung. J Thorac Cardiovasc Surg. 1997;113(4):777–83. 10. Engelman RM, Haag B, Lemeshow S, Angelo A, Rousou JH. Mechanism of plasma catecholamine increases during coronary artery bypass and valve procedures. J Thorac Cardiovasc Surg. 1983;86(4):608–15. 11. Anand KJ, Hansen DD, Hickey PR. Hormonal-metabolic stress responses in neonates undergoing cardiac surgery. Anesthesiology. 1990;73(4):661–70. 12. Firmin RK, Bouloux P, Allen P, Lima RC, Lincoln JC. Sympathoadrenal function during cardiac operations in infants with the technique of surface cooling, limited cardiopulmonary bypass, and circulatory arrest. J Thorac Cardiovasc Surg. 1985;90(5):729–35. 13. Philbin DM, Levine FH, Emerson CW, Coggins CH, Buckley MJ, Austen WG. Plasma vasopressin levels and urinary flow during cardiopulmonary bypass in patients with valvular heart disease: effect of pulsatile flow. J Thorac Cardiovasc Surg. 1979;78(5):779–83. 14. Mitchell IM, Pollock JC, Jamieson MP, Donaghey SF, Paton RD, Logan RW. The effects of cardiopulmonary bypass on thyroid function in infants weighing less than five kilograms. J Thorac Cardiovasc Surg. 1992;103(4):800–05. 15. Govier AV. Central Nervous System Complications After Cardiopulmonary Bypass. In: Tinker JH, (Eds). Philadelphia: W B Saunders Co. 1989;p.41–50. 16. Phornphutkul C, Rosenthal A, Nadas AS, Berenberg W. Cerebrovascular accidents in infants and children with cyanotic congenital heart disease. Am J Cardiol. 1973;32(3):329–34. 17. Brunberg JA, Reilly EL, Doty DB. Central nervous system consequences in infants of cardiac surgery using deep hypothermia and circulatory arrest. Circulation. 1974;50(2 Suppl):II60–8. 18. Perugini RA, Orr RK, Porter D, Dumas EM, Maini BS. Gastrointestinal complications following cardiac surgery. An analysis of 1477 cardiac surgery patients. Arch Surg. 1997;132(4):352–57.

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Pediatric Cardiology

19. Ohri SK, Velissaris T. Gastrointestinal dysfunction following cardiac surgery. Perfusion. 2006;21(4):215–23. 20. Yilmaz AT, Arslan M, Demirkilc U, et al. Gastrointestinal complications after cardiac surgery. Eur J Cardiothorac Surg. 1996;10(9):763–7. 21. Rinder CS, Bohnert J, Rinder HM, Mitchell J, Ault K, Hillman R. Platelet activation and aggregation during cardiopulmonary bypass. Anesthesiology. 1991;75(3):388–93. 22. Umlas J. Fibrinolysis and disseminated intravascular coagulation in open heart sergery. Transfusion. 1976;16(5):460–3. 23. Stibbe J, Kluft C, Brommer EJ, Gomes M, de Jong DS, Nauta J. Enhanced fibrinolytic activity during cardiopulmonary bypass in open-heart surgery in man is caused by extrinsic (tissue-type) plasminogen activator. Eur J Clin Invest. 1984;14(5):375–82. 24. Markewitz A, Faist E, Lang S, Hultner L, Weinhold C, Reichart B. An imbalance in T-helper cell subsets alters immune response after cardiac surgery. Eur J Cardiothorac Surg. 1996;10(1):61–7. 25. Pantin EJ, Cheung AT. Thoracic Aorta. In: Kaplan JA, Reich DL, Lake CL, Konstadt SN, (Eds). Kaplan’s Cardiac Anesthesia. (5th edn). Philadelphia: Elsevier Saunders. 2006;723–64. 26. Wypij D, Newburger JW, Rappaport LA, et al. The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment: THe Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg. 2003;126(5):1397–403. 27. Langley SM, Chai PJ, Miller SE, et al. Intermittent perfusion protects the brain during deep hypothermic circulatory arrest. Ann Thorac Surg. 1999;68(1):4–12. 28. Mault JR, Ohtake S, Klingensmith ME, Heinle JS, Greeley WJ, Ungerleider RM. Cerebral metabolism and circulatory arrest: Effects of duration and strategies for protection. Ann Thorac Surg. 1993;55(1): 57–63. 29. Newburger JW, Jonas RA, Wernovsky G, et al. A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery. N Engl J Med. 1993;329(15):1057–64. 30. Bellinger DC, Wypij D, duDuplessis AJ, et al. Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg. 2003;126(5):1385–96. 31. Bellinger DC, Wypij D, Kuban KC, et al. Developmental and neurological status of children at 4 years of age after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. Circulation. 1999;100(5):526–32. 32. Skaryak LA, Lodge AJ, Kirshbom PM, et al. Low-flow cardiopulmonary bypass produces greater pulmonary dysfunction than circulatory arrest. Ann Thorac Surg. 1996;62(5):1284–8. 33. Heitmiller EH, Wetzel RC. Hemodynamic Monitoring Considerations in Pediatric Critical Care. In: Rogers MC, Nichols DG, (Eds). Textbook of Pediatric Intensive Care. (3rd ed). Baltimore: Williams and Wilkins. 1996;p.607–41. 34. Gallagher JD, Moore RA, McNicholas KW, Jose AB. Comparison of radial and femoral arterial blood pressures in children after cardiopulmonary bypass. J Clin Monit. 1985;1(3):168–71. 35. Castaneda A, Meyer H, Hanley FL. Cardiac Surgery of Neonate and Infant. (2nd edn). Philadelphia: W B Saunders. 1994. 36. George B, Permut LC. Perioperative Care. In: Baue AE, Hammond GS, Laks H, Geha AS, Glenn WWL, Naunheim KS, editors. Glenn’s Thoracic and Cardiovascular Surgery. (6th edn). Stamford: Appleton and Lange. 1996;995–1021. 37. Gold JP, Jonas RA, Lang P, Elixson EM, Mayer JE, Castaneda AR. Transthoracic intracardiac monitoring lines in pediatric surgical patients: a ten-year experience. Ann Thorac Surg. 1986;42(2):185–91. 38. Vincent RN, Lang P, Chipman CW, Castaneda AR. Assessment of hemodynamic status in the intensive care unit immediately after closure of ventricular septal defect. Am J Cardiol. 1985;55(5):526–9. 39. Tobin MJ. Respiratory monitoring. JAMA. 1990;264(2):244–51. 40. Kelman GR, Nunn JF. Clinical recognition of hypoxaemia under fluorescent lamps. Lancet. 1966;1(7452):1400–03.

Pediatric Cardiac Postoperative Intensive Care

495

41. Watcha MF, Connor MT, Hing AV. Pulse oximetry in methemoglobinemia. Am J Dis Child. 1989;143(7):845–7. 42. Roth SJ. Postoperative Care. In: Chang AC, Hanley FL, Wernovsky G, Vessel DL, (Eds). Pediatric Cardiac Intensive Care. (1st ed). Baltimore: Lippincott Williams and Wilkins. 1998;163–87. 43. Backer CL, Baden HP, Costello JM. Perioperative Care. In: Mavroudis C, Backer CL, (Eds). Pediatric Cardiac Surgery. (3rd edn). Philadelphia: Mosby. 2003;119–42. 44. Barnea O, Austin EH, Richman B, Santamore WP. Balancing the circulation: THeoretic optimization of pulmonary/systemic flow ratio in hypoplastic left heart syndrome. J Am Coll Cardiol. 1994;24(5):1376–81. 45. Mosca RS, Bove EL, Crowley DC, Sandhu SK, Schork MA, Kulik TJ. Hemodynamic characteristics of neonates following first stage palliation for hypoplastic left heart syndrome. Circulation. 1995;92(9 Suppl):II267–71. 46. Aronsen LA, Dent CL. Postoperative Respiratory Dysfunction and Management. In: Lake CL, Booker PD, (Eds). Pediatric Cardiac Anesthesia. (4th edn). Philadelphia: Lippincott Willkiams and Wilkins. 2005;682–704. 47. Shimada Y, Yoshiya I, Tanaka K, Yamazaki T, Kumon K. Crying vital capacity and maximal inspiratory pressure as clinical indicators of readiness for weaning of infants less than a year of age. Anesthesiology. 1979;51(5):456–9. 48. Morton NS, O’Brien K. Analgesic efficacy of paracetamol and diclofenac in children receiving PCA morphine. Br J Anaesth. 1999;82(5):715–7. 49. Rosen KR, Rosen DA. Caudal epidural morphine for control of pain following open heart surgery in children. Anesthesiology. 1989;70(3):418–21. 50. Castaneda A, Meyer H, Hanley FL. Cardiac Surgery of Neonate and Infant. (2nd edn). Philadelphia: W B Saunders. 2004. 51. Booker PD. Postoperative Care—General Principles. In: Lake CL, Booker PD, (Eds). Pediatric Cardiac Anesthesia. (4th ed). Philadelphia. 2005;p.633–53. 52. Journois D, Israel-Biet D, Pouard P, et al. High-volume, zero-balanced hemofiltration to reduce delayed inflammatory response to cardiopulmonary bypass in children. Anesthesiology. 1996;85(5):965–76. 53. Holliday Ma, Segar WE. The maintenance need for water in parenteral fluid therapy. Pediatrics. 1957;19(5):823–32. 54. Svensen C, Hahn RG. Volume kinetics of Ringer solution, dextran 70, and hypertonic saline in male volunteers. Anesthesiology. 1997;87(2):204–12. 55. Haynes GR, Navickis RJ, Wilkes MM. Albumin administration—what is the evidence of clinical benefit? A systematic review of randomized controlled trials. Eur J Anaesthesiol. 2003;20(10):771–93. 56. Franz A, Braunlich P, Gamsjager T, Felfernig M, Gustorff B, Kozek-Langenecker SA. The effects of hydroxyethyl starches of varying molecular weights on platelet function. Anesth Analg. 2001;92(6):1402–07. 57. Gallandat Huet RC, Siemons AW, Baus D, et al. A novel hydroxyethyl starch (Voluven) for effective perioperative plasma volume substitution in cardiac surgery. Can J Anaesth. 2000;47(12):1207–15. 58. Boldt J. Hydroxyethylstarch as a risk factor for acute renal failure: Is a change of clinical practice indicated? Drug Saf. 2002;25(12):837–46. 59. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342(21):1581–9. 60. Greenberg A. Hyperkalemia: Treatment options. Semin Nephrol. 1998;18(1):46–57. 61. Opie LH. Regulation of myocardial contractility. J Cardiovasc Pharmacol. 1995;26(Suppl 1):S1–9. 62. Benzing G, III, Francis PD, Kaplan S, Helmsworth JA, Sperling MA. Glucose and insulin changes in infants and children undergoing hypothermic open-heart surgery. Am J Cardiol. 1983;52(1):133–6. 63. Baum D, Dillard DH, Porte D Jr. Inhibition of insulin release in infants undergoing deep hypothermic cardiovascular surgery. N Engl J Med. 1968;279(24):1309–14. 64. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enteral Nutr. 2002;26(1 Suppl):1SA–138SA.

496

Pediatric Cardiology

65. McLaughlin GE, Setzer NA, Schleien CL. Postoperative Management of the Cardiac Surgical Patient. In: Rogers MC, Nichols DG, (Eds). Textbook of Pediatric Intensive Care (3rd edn). Baltimore: Lippincott Williams and Wilkins. 1998;p.85–93. 66. Amato JJ, Marbey ML, Bush C, Galdieri RJ, Cotroneo JV, Bushong J. Systemic-pulmonary polytetrafluoroethylene shunts in palliative operations for congenital heart disease. Revival of the central shunt. J Thorac Cardiovasc Surg. 1988;95(1):62–9. 67. LeBlanc J, Albus R, Williams WG, et al. Serous fluid leakage: A complication following the modified Blalock-Taussig shunt. J Thorac Cardiovasc Surg. 1984;88(2):259–62. 68. Ilbawi MN, Idriss FS, DeLeon SY, et al. Preparation of the left ventricle for anatomical correction in patients with simple transposition of the great arteries. Surgical guidelines. J Thorac Cardiovasc Surg. 1987;94(1):87–94. 69. Backer CL, Mavroudis C. Palliative Operations. In: Mavroudis C, Backer CL, (Eds). Pediatric Cardiac Surgery. (3rd edn). Philadelphia: Mosby. 2003;p.160–70. 70. Trusler GA, Mustard WT. A method of banding the pulmonary artery for large isolated ventricular septal defect with and without transposition of the great arteries. Ann Thorac Surg. 1972;13(4):351–5. 71. Fyman PN, Goodman K, Casthely PA, Griepp RB, Ergin MA, Smith P. Anesthetic management of patients undergoing Fontan procedure. Anesth Analg. 1986;65(5):516–9. 72. Gregory GA. Pediatric Anesthesia. (4th edn). Philadelphia: Churchill Livingstone. 2002. 73. Tobias JD, Schleien CL, Reitz BA. Use of the MAST suit in the postoperative care of patients after the Fontan procedure. Crit Care Med. 1990;18(7):781–2. 74. Bridges ND, Mayer JE Jr, Lock JE, et al. Effect of baffle fenestration on outcome of the modified Fontan operation. Circulation. 1992;86(6):1762–69. 75. Rosenthal DN, Friedman AH, Kleinman CS, Kopf GS, Rosenfeld LE, Hellenbrand WE. Thromboembolic complications after Fontan operations. Circulation. 1995;92(9 Suppl):II287–93. 76. Dickinson DF, Arnold R, Wilkinson JL. Congenital heart disease among 160,480 liveborn children in Liverpool 1960 to 1969. Implications for surgical treatment. Br Heart J. 1981;46(1):55–62. 77. Samanek M, Slavik Z, Zborilova B, Hrobonova V, Voriskova M, Skovranek J. Prevalence, treatment, and outcome of heart disease in live-born children: a prospective analysis of 91,823 live-born children. Pediatr Cardiol. 1989;10(4):205–11. 78. Sealy WC, Farmer JC, Young WG Jr, Brown IW Jr. Atrial dysrhythmia and atrial secundum defects. J Thorac Cardiovasc Surg. 1969;57(2):245–50. 79. Young D. Later results of closure of secundum atrial septal defect in children. Am J Cardiol. 1973;31(1):14–22. 80. Haworth SG. Pulmonary vascular disease in ventricular septal defect: Structural and functional correlations in lung biopsies from 85 patients, with outcome of intracardiac repair. J Pathol. 1987;152(3):157–68. 81. Blake RS, Chung EE, Wesley H, Hallidie-Smith KA. Conduction defects, ventricular arrhythmias, and late death after surgical closure of ventricular septal defect. Br Heart J. 1982;47(4):305–15. 82. Rosen DA, Rosen KR. Anomalies of Aortic Arch. In: Lake CL, Booker PD, (Eds). Pediatric Cardiac Anesthesia. (4th edn). Philadelphia. 2005;381–425. 83. Hillman ND, Mavroudis C, Backer CL. Patent Ductus Arteriosus. In: Mavroudis C, Backer CL, (Eds). Pediatric Cardiac Surgery. (3rd edn). Philadelphia: Mosby. 2003;223–33. 84. Pontius RG, Danielson GK, Noonan JA, Judson JP. Illusions leading to surgical closure of the distal left pulmonary artery instead of the ductus arteriosus. J Thorac Cardiovasc Surg. 1981;82(1):107–13. 85. Rocchini AP, Rosenthal A, Barger AC, Castaneda AR, Nadas AS. Pathogenesis of paradoxical hypertension after coarctation resection. Circulation. 1976;54(3):382–7. 86. Benedict CR, Grahame-Smith DG, Fisher A. Changes in plasma catecholamines and dopamine betahydroxylase after corrective surgery for coarctation of the aorta. Circulation. 1978;57(3):598–602. 87. Casta A, Conti VR, Talabi A, Brouhard BH. Effective use of captopril in postoperative paradoxical hypertension of coarctation of the aorta. Clin Cardiol. 1982;5(10):551–3. 88. Park SC, Neches WH. The neurologic complications of congenital heart disease. Neurol Clin. 1993;11(2):441–62.

Pediatric Cardiac Postoperative Intensive Care

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89. Krieger KH, Spencer FC. Is paraplegia after repair of coarctation of the aorta due principally to distal hypotension during aortic cross-clamping? Surgery. 1985;97(1):2–7. 90. Acute Traumatic Aortic Transection. (3rd edn). Philadelphia: Churchill Livingstone. 2003. 91. Chang AC, Starnes VA. Coarctation of Aorta. In: Chang AC, Hanley FL, Wernovsky G, Vessel DL, (Eds). Pediatric Cardiac Intensive Care. (1st edn). Baltimore: Lippincott Williams and Wilkins. 1998;247–56. 92. Pacifico AD, Bargeron LM Jr, Kirklin JW. Primary total correction of tetralogy of Fallot in children less than four years of age. Circulation. 1973;48(5):1085–91. 93. Chaturvedi RR, Shore DF, Lincoln C, et al. Acute right ventricular restrictive physiology after repair of tetralogy of Fallot: Association with myocardial injury and oxidative stress. Circulation. 1999;100(14):1540-47. 94. Zimmerman HA, Martins de Oliveria J, Nogueira C, Mendelsohn D, Kay EB. The electrocardiogram in open heart surgery; disturbances in the right ventricular conduction. J Thorac Surg. 1958;36(1):12–22. 95. Gelband H, Waldo AL, Kaiser GA, Bowman FO Jr, Malm JR, Hoffman BF. Etiology of right bundle-branch block in patients undergoing total correction of tetralogy of Fallot. Circulation. 1971;44(6):1022–33. 96. James FW, Kaplan S, Chou TC. Unexpected cardiac arrest in patients after surgical correction of tetralogy of Fallot. Circulation. 1975;52(4):691–5. 97. Quattlebaum TG, Varghese J, Neill CA, Donahoo JS. Sudden death among postoperative patients with tetralogy of Fallot: A follow-up study of 243 patients for an average of twelve years. Circulation. 1976;54(2):289–93. 98. Jonas RA. Complete Atrioventricular Canal. In: Jonas RA, DiNardo JA, Laussen PC, Howe RD, LaPierre R, Matte G, (Eds). Comprehensive Surgical Management of Congenital Heart Disease. London: Hodder Arnold Publishers. 2004;p.386–401. 99. Raisher BD, Grant JW, Martin TC, Strauss AW, Spray TL. Complete repair of total anomalous pulmonary venous connection in infancy. J Thorac Cardiovasc Surg. 1992;104(2):443–8. 100. Saxena A, Fong LV, Lamb RK, Monro JL, Shore DF, Keeton BR. Cardiac arrhythmias after surgical correction of total anomalous pulmonary venous connection: Late follow-up. Pediatr Cardiol. 1991;12(2):89–91. 101. Complete Transposition of the Great Arteries. In: Kouchoukos NT, Blackstone EH, Doty DB, Hanley FL, Karp RB, editors. Kirklin/Barratt-Boyes Cardiac Surgery. (3rd edn). Philadelphia: Churchill Livingstone. 2003;1438–1507. 102. Elami A, Permut LC, Laks H, Drinkwater DC Jr, Sebastian JL. Cardiac decompression after operation for congenital heart disease in infancy. Ann Thorac Surg. 1994;58(5):1392–6. 103. Booker PD. Postoperative Cardiac Dysfunction—Pharmacological Support. In: Lake CL, Booker PD, editors. Pediatric Cardiac Anesthesia. (4th edn). Philadelphia. 2005;633–53. 104. Carcillo JA. Pediatric septic shock and multiple organ failure. Crit Care Clin. 2003;19(3):413–40, viii. 105. Charpie JR, Dekeon MK, Goldberg CS, Mosca RS, Bove EL, Kulik TJ. Serial blood lactate measurements predict early outcome after neonatal repair or palliation for complex congenital heart disease. J Thorac Cardiovasc Surg. 2000;120(1):73–80. 106. Munoz R, Laussen PC, Palacio G, Zienko L, Piercey G, Wessel DL. Changes in whole blood lactate levels during cardiopulmonary bypass for surgery for congenital cardiac disease: An early indicator of morbidity and mortality. J Thorac Cardiovasc Surg. 2000;119(1):155–62. 107. Duke T, Butt W, South M, Karl TR. Early markers of major adverse events in children after cardiac operations. J Thorac Cardiovasc Surg. 1997;114(6):1042–52. 108. Vincent JL, Gerlach H. Fluid resuscitation in severe sepsis and septic shock: An evidence-based review. Crit Care Med. 2004;32(11 Suppl):S451–54. 109. Edwards JD, Mayall RM. Importance of the sampling site for measurement of mixed venous oxygen saturation in shock. Crit Care Med. 1998;26(8):1356–60. 110. Postoperative Care. In: Kouchoukos NT, Blackstone EH, Doty DB, Hanley FL, Karp RB, (Eds). Kirklin/ Barratt-Boyes Cardiac Surgery. (3rd edn). Philadelphia: Churchill Livingstone. 2003;195–253.

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111. Rosenzweig EB, Starc TJ, Chen JM, et al. Intravenous arginine-vasopressin in children with vasodilatory shock after cardiac surgery. Circulation. 1999;100(19 Suppl):II182-6. 112. Komea-Agyin C, Kejriwal NK, Franks R, Booker PD, Pozzi M. Intraaortic balloon pumping in children. Ann Thorac Surg. 1999;67(5):1415–20. 113. Dalton HJ, Siewers RD, Fuhrman BP, et al. Extracorporeal membrane oxygenation for cardiac rescue in children with severe myocardial dysfunction. Crit Care Med. 1993;21(7):1020–8. 114. Shime N. Contemporary trends in postoperative intensive care for pediatric cardiac surgery. J Cardiothorac Vasc Anesth. 2004;18(2):218–27. 115. Laussen PC. Pediatric Cardiac Intensive Care. In: Jonas RA, DiNardo JA, Laussen PC, Howe R, LaPierre R, Matte G, editors. Comprehensive Surgical Management of Congenital Heart Disease. London: Hodder Arnold. 2004;p.65–115. 116. Koul B, Willen H, Sjoberg T, Wetterberg T, Kugelberg J, Steen S. Pulmonary sequelae of prolonged total venoarterial bypass: Evaluation with a new experimental model. Ann Thorac Surg. 1991;51(5):794–9. 117. Koul B, Wollmer P, Willen H, Kugelberg J, Steen S. Venoarterial extracorporeal membrane oxygenation—how safe is it? Evaluation with a new experimental model. J Thorac Cardiovasc Surg. 1992;104(3):579–84. 118. Meyrick B, Reid L. Ultrastructural findings in lung biopsy material from children with congenital heart defects. Am J Pathol. 1980;101(3):527–42. 119. Lindberg L, Olsson AK, Jogi P, Jonmarker C. How common is severe pulmonary hypertension after pediatric cardiac surgery? J Thorac Cardiovasc Surg. 2002;123(6):1155–63. 120. Naik SK, Knight A, Elliott M. A prospective randomized study of a modified technique of ultrafiltration during pediatric open-heart surgery. Circulation. 1991;84(5 Suppl):III422–31. 121. Naik SK, Elliott MJ. Ultrafiltration and paediatric cardiopulmonary bypass. Perfusion. 1993;8(1): 101–12. 122. Wessel DL. Hemodynamic responses to perioperative pain and stress in infants. Crit Care Med. 1993;21(9 Suppl):S361–2. 123. Frostell CG, Blomqvist H, Hedenstierna G, Lundberg J, Zapol WM. Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology. 1993;78(3):427–35. 124. Kulik TJ. Inhaled nitric oxide in the management of congenital heart disease. Curr Opin Cardiol. 1996;11(1):75–80. 125. Atz AM, Wessel DL. Inhaled nitric oxide in the neonate with cardiac disease. Semin Perinatol. 1997;21(5):441–55. 126. Atz AM, Wessel DL. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology. 1999;91(1):307–10. 127. Perry JC, Walsh EP. Diagnosis and Management of Cardiac Arrythmias. In: Chang AC, Hanley FL, Wernovsky G, Vessel DL, (Eds). Pediatric Cardiac Intensive Care. (1st edn). Baltimore: Lippincott Williams and Wilkins. 1998;461–81. 128. Bash SE, Shah JJ, Albers WH, Geiss DM. Hypothermia for the treatment of postsurgical greatly accelerated junctional ectopic tachycardia. J Am Coll Cardiol. 1987;10(5):1095–9. 129. Doniger SJ, Sharieff GQ. Pediatric dysrhythmias. Pediatr Clin North Am. 2006;53(1):85–105, vi. 130. Sherry KM. Post-extubation stridor in Down’s syndrome. Br J Anaesth. 1983;55(1):53–5. 131. Kemper KJ, Benson MS, Bishop MJ. Predictors of postextubation stridor in pediatric trauma patients. Crit Care Med. 1991;19(3):352–5. 132. Serraf A, Planche C, Lacour GF, Bruniaux J, Nottin R, Binet JP. Postcardiac surgery phrenic nerve palsy in pediatric patients. Eur J Cardiothorac Surg. 1990;4(8):421–4. 133. Hamilton JR, Tocewicz K, Elliott MJ, de LM, Stark J. Paralysed diaphragm after cardiac surgery in children: Value of plication. Eur J Cardiothorac Surg. 1990;4(9):487–90. 134. Beregovich J, Bianchi C, Rubler S, Lomnitz E, Cagin N, Levitt B. Dose-related hemodynamic and renal effects of dopamine in congestive heart failure. Am Heart J. 1974;87(5):550–7.

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135. Murphy MB, Elliott WJ. Dopamine and dopamine receptor agonists in cardiovascular therapy. Crit Care Med. 1990;18(1 Pt 2):S14–8. 136. Booker PD, Evans C, Franks R. Comparison of the haemodynamic effects of dopamine and dobutamine in young children undergoing cardiac surgery. Br J Anaesth. 1995;74(4):419–23. 137. Habib DM, Padbury JF, Anas NG, Perkin RM, Minegar C. Dobutamine pharmacokinetics and pharmacodynamics in pediatric intensive care patients. Crit Care Med. 1992;20(5):601–08. 138. Chang AC, Atz AM, Wernovsky G, Burke RP, Wessel DL. Milrinone: Systemic and pulmonary hemodynamic effects in neonates after cardiac surgery. Crit Care Med. 1995;23(11):1907–14. 139. Hopkins RA, Bull C, Haworth SG, de Leval MR, Stark J. Pulmonary hypertensive crises following surgery for congenital heart defects in young children. Eur J Cardiothorac Surg. 1991;5(12):628–34. 140. Terplan KL. Patterns of brain damage in infants and children with congental heart disease. Association with catheterization and surgical procedures. Am J Dis Child. 1973;125(2):176–85. 141. Jones M. Anomalies of the brain and congenital heart disease: A study of 52 necropsy cases. Pediatr Pathol. 1991;11(5):721–36. 142. Shum-Tim D, Nagashima M, Shinoka T, et al. Postischemic hyperthermia exacerbates neurologic injury after deep hypothermic circulatory arrest. J Thorac Cardiovasc Surg. 1998;116(5):780–92. 143. Miller G, Eggli KD, Contant C, Baylen BG, Myers JL. Postoperative neurologic complications after open heart surgery on young infants. Arch Pediatr Adolesc Med. 1995;149(7):764–8. 144. Lanska MJ, Lanska DJ, Horwitz SJ, Aram DM. Presentation, clinical course, and outcome of childhood stroke. Pediatr Neurol. 1991;7(5):333–41. 145. du Plessis AJ, Chang AC, Wessel DL, et al. Cerebrovascular accidents following the Fontan operation. Pediatr Neurol. 1995;12(3):230–6. 146. Skaryak LA, Chai PJ, Kern FH, Greeley WJ, Ungerleider RM. Blood gas management and degree of cooling: effects on cerebral metabolism before and after circulatory arrest. J Thorac Cardiovasc Surg. 1995;110(6):1649–57. 147. Gillinov AM, Redmond JM, Zehr KJ, et al. Superior cerebral protection with profound hypothermia during circulatory arrest. Ann Thorac Surg. 1993;55(6):1432–9. 148. Amir G, Ramamoorthy C, Riemer RK, Reddy VM, Hanley FL. Neonatal brain protection and deep hypothermic circulatory arrest: Pathophysiology of ischemic neuronal injury and protective strategies. Ann Thorac Surg. 2005;80(5):1955–64. 149. Hiramatsu T, Miura T, Forbess JM, et al. pH strategies and cerebral energetics before and after circulatory arrest. J Thorac Cardiovasc Surg. 1995;109(5):948–57. 150. Aoki M, Nomura F, Stromski ME, et al. Effects of pH on brain energetics after hypothermic circulatory arrest. Ann Thorac Surg. 1993;55(5):1093–1103. 151. Rehncrona S, Hauge HN, Siesjo BK. Enhancement of iron-catalyzed free radical formation by acidosis in brain homogenates: Differences in effect by lactic acid and CO2. J Cereb Blood Flow Metab. 1989;9(1):65–70. 152. Langley SM, Chai PJ, Jaggers JJ, Ungerleider RM. Preoperative high dose methylprednisolone attenuates the cerebral response to deep hypothermic circulatory arrest. Eur J Cardiothorac Surg. 2000;17(3):279–86. 153. Langley SM, Chai PJ, Tsui SS, Jaggers JJ, Ungerleider RM. The effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest. J Thorac Cardiovasc Surg. 2000;119(6):1262–69. 154. Shum-Tim D, Tchervenkov CI, Laliberte E, et al. Timing of steroid treatment is important for cerebral protection during cardiopulmonary bypass and circulatory arrest: Minimal protection of pump prime methylprednisolone. Eur J Cardiothorac Surg. 2003;24(1):125–32. 155. Brown KL, Ridout DA, Goldman AP, Hoskote A, Penny DJ. Risk factors for long intensive care unit stay after cardiopulmonary bypass in children. Crit Care Med. 2003;31(1):28–33. 156. Krull F, Ehrich JH, Wurster U, Toel U, Rothganger S, Luhmer I. Renal involvement in patients with congenital cyanotic heart disease. Acta Paediatr Scand. 1991;80(12):1214–9.

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157. Luciani GB, Nichani S, Chang AC, Wells WJ, Newth CJ, Starnes VA. Continuous versus intermittent furosemide infusion in critically ill infants after open heart operations. Ann Thorac Surg. 1997;64(4):1133–9. 158. Carcillo JA, Davis AL, Zaritsky A. Role of early fluid resuscitation in pediatric septic shock. JAMA. 1991;266(9):1242–5. 159. Ngo NT, Cao XT, Kneen R, et al. Acute management of dengue shock syndrome: A randomized doubleblind comparison of 4 intravenous fluid regimens in the first hour. Clin Infect Dis. 2001;32(2):204–13. 160. Parker MM, Hazelzet JA, Carcillo JA. Pediatric considerations. Crit Care Med. 2004;32(11 Suppl):S591–4. 161. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368–77. 162. Ceneviva G, Paschall JA, Maffei F, Carcillo JA. Hemodynamic support in fluid-refractory pediatric septic shock. Pediatrics. 1998;102(2):e19. 163. Barton P, Kalil AC, Nadel S, et al. Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis. Pediatrics. 2004;113(1 Pt 1):7–17. 164. Srinivasan V, Spinella PC, Drott HR, Roth CL, Helfaer MA, Nadkarni V. Association of timing, duration, and intensity of hyperglycemia with intensive care unit mortality in critically ill children. Pediatr Crit Care Med. 2004;5(4):329–36. 165. Branco RG, Garcia PC, Piva JP, Casartelli CH, Seibel V, Tasker RC. Glucose level and risk of mortality in pediatric septic shock. Pediatr Crit Care Med. 2005;6(4):470–2.

31

Follow-up of Children Following Cardiac Surgery and Percutaneous Interventions

BRJ Kannan

After care of the children who have undergone cardiac procedures and surgeries is as important, and in some occasions, more important than the actual procedure performed. The primary care pediatrician should be well-versed with the cardiac anatomy and the ongoing physiology following the cardiac surgery. The follow-up of these children depends on the modified natural history of the heart defect. Some general rules applicable to all children following cardiac intervention/surgery are as follows: 1. At the first contact following the cardiac procedure or surgery, check for the lower limb pulses as femoral vessel cannulation is very frequently done both during catheterization procedures or cardiac surgery. 2. Persistence of a short ejection systolic murmur is common despite complete repair and one should make a note of it. Some children might be left with small residual ventricular septal defect (VSD) that would produce loud murmur but is not of major concern. Development of a new murmur or worsening of the pre-existing murmur warrants thorough re-evaluation by the cardiologist. 3. Most children can begin or continue their routine immunizations about one month after their surgery. 4. Restriction of physical activities depends on the underlying uncorrected cardiac lesion and the treating cardiologist should be consulted in this regard. Children are good judge themselves to limiting their own activity. A few weeks after discharge following cardiac surgery, the child can be allowed to play at his or her own pace if total repair had been done with no residual defect. 5. The child can attend the school after 2 to 3 days following percutaneous intervention (e.g. coil or device occlusion of patent ductus arteriosus, device closure of atrial septal defect) or after 1 month following the surgery with no residual defect or lesion (e.g. closure of atrial or ventricular septal defect). Those children with residual lesion can be allowed to attend the school after the first follow-up with the cardiologist.

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6. Proper nutritional advice is important to allow the child to grow normally. There is no specific dietary restriction. A hemoglobin level of 13 to 15 g% is desirable in all cyanotic patients and periodic iron supplementation is essential. 7. The knowledge about the common cardiac medications and its timely modification is important. The dose of most the drugs need to be increased when the child gains weight. Diuretics need to be withheld or reduced in the event of a child developing diarrhea. 8. Infective endocarditis prophylaxis (IE) is recommended for 6 months in children operated for simple left-to-right shunts (ASD, VSD, PDA). IE prophylaxis for the remaining period should be dictated by recent guidelines (see chapter on infective endocarditis). The high risk categories include those who have undergone an aortopulmonary shunt, prosthetic valve placement. Persistent fever for > 4 days without definite localization and not responding to usual treatment warrants prompt cardiac evaluation. 9. All common ailments should be treated as for any other child. Even after complete repair of the cardiac defect, children may develop as many as 3 to 5 episodes of respiratory infections per year, like any other normal child. 10. Late unexpected death is a known complication in any complex congenital heart repair and the majority is because of arrhythmias. Checking the regularity of the rhythm is an important aspect of the follow-up in these children. Follow-up has to be tailored to the individual patient.

PATENT DUCTUS ARTERIOSUS (PDA) INTERRUPTION (SURGICAL OR TRANSCATHETER INTERVENTION) It is a curative procedure. There is a very small possibility of recanalization of the interrupted ductus arteriosus. This can occur with coil closure as well as those who undergo PDA surgical ligation. Hence, a routine echocardiographic evaluation is advisable 3 months following the procedure and another clinical evaluation one year later. The child could then be discharged from the follow-up. If there is a residual flow detected by color Doppler, which is not clinically audible, it should be left alone and these children do not run any increased risk of endarteritis.

ATRIAL SEPTAL DEFECT Following Device Closure As the devices are potentially thrombogenic, the patient runs the risk of developing thrombotic episodes, though the risk is small. These patients receive aspirin (3 to 5 mg/kg/d) for a period of 6 months during which the device would get endothelialized.5 Child can resume normal activities and attend school 2 to 3 days after the procedure. An echocardiography is advised at 3 months to check the position of the device, residual flow and the presence of any pericardial effusion. Thereafter, they need to be seen yearly for 3 to 5 years, especially those who receive large devices. The duration of follow-up is arbitrary, as we do not have long-term follow-up studies in this subset. Recently there has been a significant concern expressed on the small possibility of ASD device eroding into aorta or the right atrial wall. For this reason, follow-up echocardiograms are mandatory at 3 months.

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Following Surgical Closure Residual shunts are rare when the ASD is directly closed by surgical methods. Schooling is allowed 1 month after the procedure. Clinical evaluations at 3 months and at 1 year after surgery would be suffice. Some of these patients would be having associated mitral valve prolapse with mitral regurgitation. Those patients with ostium primum ASD will invariably have a cleft anterior mitral leaflet, which would be addressed at the time of surgical ASD closure. If the mitral regurgitation is more than mild, it can progress, as this complication is not related to the presence or absence of residual ASD. So, these children with moderate regurgitation need regular follow-up for worsening of the regurgitation. A six monthly clinical evaluation and 1 to 2 yearly echocardiographic evaluation is appropriate. Adult patients run the risk of developing atrial arrhythmias especially atrial fibrillation/ flutter despite complete closure of the ASD by device of surgery.6 They warrant yearly or two yearly follow-up for an indefinite period and should be asked to seek medical attention immediately if they develop palpitation or any cardiac complaint.

Ventricular Septal Defect (Device or Surgical Closure) In children who undergo device closure of VSD, aspirin is recommended for 6 months as above. At 3 months following the procedure, they are evaluated by echocardiography. Postsurgical patients, generally do not receive any medication. If there are no issues 1 year after of surgery, these children do not need to follow-up with the cardiologist unless there are specific concerns. In older children, residual pulmonary hypertension is not uncommon. Majority of them have mild to moderate pulmonary hypertension (pulmonary artery systolic pressure between 30 to 70 mm Hg), would not progress, would have normal exercise tolerance and can lead a normal life. Clinical evaluation every 2 to 3 years is sufficient for these children. Some patients would have had significantly elevated preoperative pulmonary vascular resistance. Despite complete closure, 3 to 5% of them would progress to develop severe pulmonary hypertension and right heart failure at 8 to 10 years of follow-up.7 So, echocardiographic evaluation should be done if worsening of the pulmonary hypertension is suspected clinically. Any child with a pulmonary artery systolic pressure of more than 70 mm Hg should be evaluated every 6 months. Addition of pulmonary vasodilators such as Sildenafil could be of help in such children. Complete heart block is known to occur late after device closure of the perimembranous defect and this may be silent or manifest as syncope. It is important, therefore, to obtain an ECG during follow-up evaluations (3 months, 6 months, 1 year and yearly, thereafter).

VALVAR PULMONARY STENOSIS Balloon dilatation is the procedure of choice in this condition. Usually, the residual gradient across the pulmonary valve is small. Persistence of murmur is universal and does not reflect the success of the procedure. This is because of a combination of subvalvar hypertrophied muscles and the presence of poststenotic pulmonary artery dilatation. Long-term outcome is

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extremely good and majority will not need a repeat procedure.13 The subvalvar gradient due to hypertrophied muscles generally decreases with time. Re-evaluations are advised at 3 months and 1 year following the procedure and 2 yearly, thereafter. Those children who present in neonatal and infantile period with critical valvar pulmonary stenosis form a different group. They are further divided into those who had well-developed right ventricle and those who had underdeveloped right ventricle. The former group of patients have good prognosis and are followed up as mentioned above. In the latter group, atrial septal defect or patent foramen ovale is invariably present shunting the blood right to left causing cyanosis. Even after the successful opening of the pulmonary valve, due to smallness of RV cavity, systemic venous blood continues to pass from right atrium to left atrium and hence, persistence of cyanosis is expected. The further outcome depends on the growth of the right ventricle. Repeat balloon dilatation is needed in 6 to 25% of these children. In most of the children, the right ventricle size increases with a parallel reduction in the cyanosis. A small percentage of children with persistent nondeveloped right ventricle will need to undergo bidirectional Glenn shunt, thus, taking away that much load from right ventricle. ASD is closed and the IVC blood is allowed to flow into the RV and hence to pulmonary circulation. This type of surgery is called as “1½ ventricle repair”. Hence, 3 to 6 monthly reviews are needed in these children.

VALVAR AORTIC STENOSIS Unlike valvar pulmonary stenosis, congenital aortic stenosis is a progressive disease and surgical or balloon valvotomy is largely a palliative procedure to reduce the LV strain and sudden death. This allows children grow to an older child or adult when aortic valve replacement would be needed. Various degree of aortic regurgitation is left with following the procedure. Despite good opening of the aortic valve in neonatal and infantile severe aortic stenosis, there is high incidence of death at mid-term follow-up. This is because of associated endocardial fibroelastosis causing severe and persistent left ventricular dysfunction or left ventricular hypoplasia. No single clinical parameter has been found useful to decide on re-intervention. Six monthly echocardiography for the progression of aortic stenosis or regurgitation is probably helpful.

COARCTATION OF AORTA Children presenting in neonatal and infancy period would have undergone surgical repair while older children would have undergone balloon dilatation of the coarctation. In neonates and young infants, the incidence of recoarctation after surgical correction is 14% while it is as high as 57% with balloon angioplasty.14 There are also late complications related to the coarctation itself including hypertension, dissecting, diffuse or false aneurysm of the aorta, stroke, and early coronary artery disease. In a large (571 patients) long-term study from the Mayo clinic15 estimated survival at 10, 20, and 30 years was 91%, 84%, and 76%, respectively in surgically treated patients. Similar study is not available for balloon angioplasty patients, but it is unlikely to be different. Many of these patients have associated bicuspid aortic valves that

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could develop regurgitation or stenosis later during the follow-up. Thus, aortic coarctation is not a benign disease and close follow-up is essential for a long period. Blood pressure measurement is the most important component of the review. It should be recorded in the right upper limb and lower limb and clinical gradient should be noted at the time of first contact following surgery/angioplasty. Three to six monthly follow-up is enough in the majority. In those who have persistent systemic hypertension (20 to 25%), rigorous control of hypertension, well below the 95th centile, is essential. Beta-blockers are the preferred drugs. Increasing difficulty in the control of hypertension may be an indication of recoarctation and would warrant referral to the cardiologist. Also, when the clinical gradient is > 20 mm Hg, an echocardiographic evaluation is indicated.

BLALOCK-TAUSSIG SHUNT (SYSTEMIC ARTERY TO PULMONARY ARTERY) This is performed for a variety of conditions where the pulmonary blood flow is reduced and the anatomy is not suitable for a definitive repair. These patients have to be on aspirin (3 to 5 mg/kg/d) till the time of definitive repair and 3 to 6 monthly review is advocated in this group of children. Shunt blockage is a life-threatening complication and a common preventable cause is dehydration. Worsening cyanosis together with decrease in the intensity or duration of the continuous murmur (murmur becoming only systolic) of the shunt should alert the physician for prompt cardiac evaluation. If recent shunt blockage is suspected in a child, giving a bolus dose of heparin (100 U/kg) and starting on fluids before referral would help the child to reach the referral hospital in a better condition. Gradual and progressive worsening of cyanosis with preservation of the murmur occurs when the child outgrows the size of the shunt. Anemia may also result in worsening oxygen saturation with a well-preserved shunt murmur. All infants and children should receive maintenance iron supplementation after a BT shunt. If anemia is detected therapeutic doses of iron need to be administered. These patients are in the highest risk category for endocarditis and prophylaxis is mandated for dental procedures and whenever transient bacteremia is anticipated.

TETRALOGY OF FALLOT The surgical outcome of this condition is excellent and the 35-year survival rate is 85%, which is just below the normal survival rate.9 Those children who undergo intracardiac repair for TOF can be broadly classified into two groups: THose who have competent pulmonary valve and those who have significant pulmonary regurgitation. The outcome is better with normal life expectancy in those with competent pulmonary valve.10 Significant pulmonary regurgitation is inevitable in those who need transannular patch. The regurgitation is well-tolerated by majority of the children. However, the progressive dilatation of the right ventricle can result in reduce exercise tolerance, right ventricular dysfunction and life-threatening atrial and ventricular arrhythmias. There is a small but significant risk of sudden cardiac death (0.5 to 5%), predominantly because of arrhythmias especially in those with wide QRS duration.11

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For the first few months after tetralogy of Fallot repair, diuretics are often administered together with digoxin. It is advisable to restrict salt intake in these patients early after tetralogy of Fallot repair. The high RV filling pressures results from reduced compliance of the hypertrophied right ventricle together with pulmonary regurgitation. The RV systolic function is often well-preserved. Potential additional problems include residual VSD and residual right ventricular outflow tract. Both these conditions manifest with significant RV failure that requires a relatively higher dose of diuretic for prolonged periods of time. After infancy, yearly review is enough in asymptomatic children. Those who develop symptoms or who have echocardiographic evidence of significant RV dilatation should be followed up more closely as they are the candidates for replacement of the pulmonary valve. ECG evaluation has to be done whenever any pulse irregularity is noted. Although ventricular ectopy is common, its suppression with antiarrhythmic drugs is not indicated. However, if it occurs in those with background QRS duration of > 180 ms, it may warrant a 24-hour ECG monitoring (Holter) and close observation. Considerable data has now accumulated on the long-term implications of persistent pulmonary regurgitation after TOF repair. When echocardiograms suggest RV dilation, a cardiac MRI should be obtained. It is perhaps a good idea to obtain cardiac MRI 10 years after TOF repair where the pulmonary valve has been rendered incompetent. Increased RV enddiastolic (160–170 mL/m2) and end systolic volumes (75–85 mL/m2) are now considered as indications for elective pulmonary valve replacement.

D-TRANSPOSITION OF GREAT ARTERIES Following Arterial Switch Procedure (Jatene) This results in anatomical and physiological correction of D-TGA. Today the 15-year survival probability in excess of 90% can be expected. The possible complications that can occur during follow-up are: Coronary occlusion, development of stenosis of pulmonary artery or the aorta at the site of anastomosis or dilation of the neoaortic root and regurgitation of the neoaortic valve. Obstruction of the translocated coronary arteries is responsible for most deaths and a reasonable number of reoperations.1 Attrition rate is maximum in the first year, decreases substantially thereafter and mortality is unusual after 5 years.2 There should be a 3 monthly follow-up in the first year following surgery and any unexplained symptom should be considered as a manifestation of coronary insufficiency or right ventricular obstruction. Thereafter, 6 monthly follow-up for the next 3 to 4 years and 1 to 2 yearly follow-up for an indefinite period.

Following Atrial Switch Operation (Senning and Mustard) Here, baffles are created to route the SVC and IVC towards mitral valve and LV so that the systemic venous blood reaches the lung. The pulmonary veins are routed to the tricuspid valve and hence to systemic circulation. The 15-year survival is 78 to 90% in children with simple D-TGA.3,4 The quality of life is generally good with mild functional limitation. The possible risks are: Development of obstruction and/or leaks of the baffle, development of rhythm

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abnormalities and dysfunction of the right ventricle that serves as the systemic ventricle. As high as 70% have sinus node dysfunction and 50% have right ventricular dysfunction by 15 years. The time between the occurrence of signs of right ventricular failure and death range from 3 months to 7 years. The use of routine long-term usage of vasodilators to prevent systemic RV dysfunction is controversial. Six-monthly follow-up is adequate in asymptomatic children with no complication. A Holter test should be considered on an annual basis together with echocardiograms to assess RV function. Closer (3 monthly) follow-up is needed for those who develop RV dysfunction or tachy/brady arrhythmia for timely intervention.

OPERATIONS REQUIRING THE USE OF CONDUITS In several conditions the corrective operation often involves connection of the right ventricle to the pulmonary artery by implanting a homograft or allograft conduit. These conduits are explanted from human cadavers or reconstructed from porcine and/or bovine hearts and blood vessels. These conduits (pulmonary homograft or xenografts) do not grow with time and will need to be replaced overtime as it is outgrown. It may become calcified and narrowed or the valve may become leaky overtime. The 5-year survival is around 70% and 80% of them would have required reintervention due to conduit related problems.8 These patients have to be seen at least once in 6 months. Routine echocardiography, probably yearly, is needed even in asymptomatic children.

PULMONARY ARTERY BANDING Two groups of patients undergo this surgery. The first group consists of children with multiple VSDs where complete closure of all defects is not possible. Pulmonary artery (PA) banding, by creating pulmonary stenosis artificially, will prevent excessive pulmonary blood flow and its complications like pneumonia, failure to thrive or cardiac failure. Children are likely to improve and start gaining weight following this procedure. With time, the VSDs might close completely or the multiple small defects would close leaving behind a single defect that can be approached surgically. Surgical debanding with or without VSD closure is done at the age of 3 to 5 years. The second group consists of children with single ventricle physiology with increased pulmonary blood flow and pulmonary hypertension. It is mandatory to reduce the pulmonary pressures to normal levels so that these children would become candidates for future Fontan surgery. PA banding aims to achieve this goal of decreasing the pulmonary pressure. After a period of 4 to 6 months, these children would be subjected to cardiac catheterization procedure followed by bidirectional Glenn shunt.

BIDIRECTIONAL GLENN SHUNT This is the first stage of the Fontan surgery for the patients with single ventricle physiology. Fontan surgery involves connecting the systemic veins (SVC and ICV) directly to pulmonary circulation allowing the only functional ventricle committed to systemic circulation. This is the

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best possible palliation currently done in patients with single ventricle physiology. SVC to right pulmonary artery anastomosis is called as Bidirectional Glenn shunt (BDG). Diaphragmatic palsy and chylothorax are not uncommon with this surgery. As IVC blood is reaching the systemic circulation, persistence of some degree of cyanosis is the rule. As this is an anastomosis between two low-pressure systems, the shunt will not produce any murmur. However, there may be a right ventricular outflow tract murmur if pulmonary artery had not been interrupted at the time of the Glenn operation. The oxygen saturation is an excellent index of the well-being of the patient after a Glenn shunt. If the oxygen saturation exceeds 85%, this usually indicates an adequate anastomosis, a good ventricular function and normal pulmonary vascular resistance. As the child grows, the cyanosis worsens as the relative contribution of the IVC to the systemic venous return increases with age. There is a longterm risk of the development of abnormal arteriovenous malformations in the lung, which causes right-to-left shunt in the lungs. This can worsen the cyanosis. It is felt that these AV malformations can be made to disappear if the hepatic veins are allowed to drain to the lungs, as it will occur with the Fontan procedure.12 Six monthly evaluations are adequate in these patients. Many centers electively do surgical completion of Fontan at 3–5 years of age. We have adopted the policy of waiting till the saturation of the child falls to less than 75% or if the child develops severe polycythemia (Hb > 18–20 g%) and associated effort intolerance.

FONTAN PROCEDURE Some degree of cyanosis would persist if there has been a fenestration in the Fontan circuit. This may worsen with any maneuver that increases pulmonary pressure, e.g. cough, lung infection, etc. These patients run the risk of paradoxical systemic embolism because of the right-to-left shunt across the fenestration. However, routine use of life long anticoagulation in this group is controversial. Oral anticoagulation is indicated if there is history of arrhythmia. The long-term risks involved are: Rhythm abnormalities, failure of the single ventricle, especially if it is of RV type, development or progression AV valve regurgitation and protein losing enteropathy. Recently, “extracardiac Fontan” is favored aiming at reducing the atrial arrhythmias. Six monthly reviews in the initial 2 to 3 years and yearly review, thereafter, is followed here. ECG and/or echocardiographic evaluations are done as and when needed depending on the development of the symptoms.

CHILDREN ON ORAL ANTICOAGULATION Oral anticoagulation is advised for various indications. The common indications are: valve replacement surgery, atrial fibrillation, primary pulmonary hypertension, and Eisenmenger syndrome. Warfarin or Dicoumarol are the two commonly used drugs. Prothrombin time has to be checked every month and dose modification has to be done according to the target INR. Maintaining the target INR may not be easy, as the children are growing with the constant increase in the body mass. It is wise to add low dose aspirin (75 mg/d or 2 to 5 mg/kg/d) in those children who remain below the target levels. When a child receives antibiotics or develops diarrhea, the intestinal bacteria are killed and hence the natural source of vitamin K is lost. The

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need for oral anticoagulation comes down during these events and temporary reduction in the dosage is needed guided by the PT/INR values. It is not unusual for a child to present several months later with unmonitored oral anticoagulation with an INR of > 4.0. These children should be admitted for observation. Parenteral vitamin K should not be administered, as it can result in catastrophic thrombotic occlusion of the mechanical valve. Infuse 10 to 20 mL/kg of fresh frozen plasma and check the prothrombin time 2 hours later. Repeat plasma infusion is needed till the INR value becomes < 3.5. Do liver function test to rule out subclinical unrelated liver dysfunction. Once the INR stabilizes in the desired range, start the oral anticoagulation at a lower dose.

REFERENCES 1. Prêtre R, Tamisier D, Bonhoeffer P, Mauriat P, Pouard P, Sidi D, et al. Results of the arterial switch operation in neonates with transposed great arteries. Lancet. 2001;357:1826–30. 2. Losay J, Touchot A, Serraf A, Litvinova A, Lambert V, Piot JD, et al. Late outcome after arterial switch operation for transposition of the great arteries circulation. 2001;104:I 121–6. 3. Kirjavainen M, Happonen JM, Louhimo I. Late results of Senning operation. J Thorac Cardiovasc Surg. 1999;117:488–95. 4. Helbing WA, Hansen B, Ottenkamp J, Rohmer JJ, Chin JG, Brom AG, et al. Long-term results of atrial correction for transposition of the great arteries: Comparison of Mustard and Senning operations. J Thorac Cardiovasc Surg. 1994;108:363–72. 5. Kannan BRJ, Francis E, Sivakumar K, et al. Transcatheter closure of very large (> 25 mm) atrial septal defects using the Amplatzer septal occluder. Catheter Cardiovasc Interv. 2003;59:522–7. 6. Ghosh S, Chatterjee S, Black E, Firmin RK. Surgical closure of atrial septal defects in adults: Effect of age at operation on outcome. Heart. 2002;88:485–7. 7. Kannan BRJ, Sivasankaran S, Tharakan JA, et al. Long-term outcome of patients operated with large ventricular septal defect with increased pulmonary vascular resistance. Indian Heart J. 2003;55: 161–6. 8. Christian Kreutzer C, De Vive J, Oppido G, Kreutzer J, Gauvreau K, Freed M, et al. Twenty-five years experience with Rastelli repair for transposition of the great arteries. J Thorac Cardiovasc Surg. 2000;120:211–23. 9. Murphy JG, Gersh BJ, Mair DD, Fuster V, McGoon MD, Ilstrup DM, et al. Long-term outcome in patients undergoing surgical repair of tetralogy of Fallot. N Engl J Med. 1993;329:593–9. 10. Nollert G, Fischlein T, Bouterwek T, Böhmer C, Klinner W, Reichart B. Long-term survival in patients with repair of tetralogy of Fallot: 36-Year follow-up of 490 survivors of the first year after surgical repair. J Am Coll Cardiol. 1997;30:1374–83. 11. Gatzoulis MA, Balaji S, Webber SA, Siu SC, Hokanson JS, Poile C, et al. Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: A multicentre study. Lancet. 2000; 356:975–81. 12. Mahle WT, Rychik J, and Rome JJ. Clinical significance of pulmonary arteriovenous malformations after staging bidirectional cavopulmonary anastomosis. Am J Cardiol. 2000;86:239–41. 13. Stanger P, Cassidy SC, Girod DA, et al. Balloon pulmonary valvuloplasty. Results of the valvuloplasty and angioplasty of congenital anomalies registry. Am J Cardiol. 1990;65;775–83. 14. Johnson MC, Canter CE, Strauss AW, et al. Repair of coarctation of the aorta in infancy: Comparison of surgical and balloon angioplasty. Am Heart J. 1993;125:464–8. 15. Cohen M, Fuster V, Steele PM, et al. Coarctation of the aorta. Long-term follow-up and prediction of outcome after surgical correction. Circulation. 1989;80:840–8.

Drug Dosages

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Shakuntala Prabhu

A. Drugs used in the treatment of cardiac failure in children Medication

1.

Class and Mechanism of action

Trade name

Dose/kg Route of Toxicities/Side Administration effects

Supplied

Diuretic agents Mode of action: Loop diuretic, prevents re-absorption of chloride at ascending limb of loop of Henle

Bumex

> 6 mo: PO, IM, IV QD /QOD 0.015–0.1 mg/kg/ dose, (max. dose: 10 mg/24 h)

Hypotension, cramps, dizziness, headache, electrolyte losses (hypokalemia, hypocalcemia, hyponatremia, hypochloremia), metabolic alkalosis

Tab: 0.5, 1, 2 mg Inj: 0.25 mg/mL

Chlorothiazide

thiazide diuretic Mode of action: Inhibits sodium re-absorption in the distal renal tubule

HydroDIURIL, Esidrix, HydroPar, Oretic)

IV 1–2 mg/kg/ dose PO:BID PO 20–40 mg/ kg/24 h, BID Adults–PO: 250–500 mg/dose once a day

May increase serum calcium, ↑ bilirubin, glucose, and uric acid Hypochloremic alkalosis, hypokalemia, hyponatremia, prerenal azotemia, rarely pancreatitis, blood dyscrasias, allergic reactions

Tab: 250, 500 mg Suspension: 250 mg/5 mL Inj: 500 mg (vial, for reconstruction with 18 mL sterile water)

Furosemide

loop diuretic Mode of action: Loop diuretic, prevents re-absorption of chloride at ascending loop of Henle

Lasix, Furomide

IV: 0.5–2 mg/kg/ dose Q 6–12 h, PO: 1–2 mg/kg/ dose 1–3 times/ day prn (maximum 6 mg/kg/dose) 0.1–0.4 mg/kg/h IV infusion Max of PO 40 mg/ dose and IV-80 mg/dose

Hypokalemia, hyperuricemia, prerenal azotemia, ototoxicity, rarely bloody dyscrasias, rash

Oral liquid: 10 mg/mL, 40 mg/5 mL Tab: 20, 40, 80 mg Inj: 10 mg/mL

Diuretics Bumetanide

Contd...

511

Drug Dosages Contd...

2.

Hydrochlorothiazide thiazide diuretic Onset: 1–2 hours Mode of action: Inhibits sodium re-absorption in the distal renal tubule

HydroDIURIL, Esidrix,

PO: 2–4 mg/ kg/24 h in 2 doses

Side effects: Drowsiness, vertigo, headache, hypokalemia, hyperlipidemia, hypochloremic metabolic alkalosis, nausea, muscle cramps, pancreatitis, agranulocytosis, hemolytic anemia, hepatitis, parasthesia, prerenal azotemia, hyperuricemia, hyperglycemia, blood changes, allergic reaction

Tab: 25, 50, 100 mg Caps: 12.5 mg Solution: 10 mg/ mL

Metolazone

Thiazide like diuretic

Zaroxolyn, Diulo, Mykrox

PO: 0.2–0.4 QDBID mg/kg/24 h

Electrolyte imbalance, GI disturbance, hyperglycemia, bone marrow depression, chills, hyperuricemia, hepatitis, rash

Tab: 0.5, 2.5, 5, 10 mg Suspension: 1 mg/mL

Spironolactone

Aldosterone antagonist

Aldactone

PO: 3 mg/kg/day in maximum 200 BID/TID doses mg/day

Hyperkalemia (when given with potassium supplements), GI distress, rash, gynecomastia, agranulocytosis

Tab: 25, 50, 100 mg Suspension: 1, 2, 5, 25 mg/mL

Inotropic and Vasopressor Agents Amrinone

Noncatecholamine Inocor inotropic agent with vasodilator effects Onset: 2–5 minutes Mode of action: Myocardial cAMP phosphodiesterase inhibitor, increase intracellular cAMP resulting in better myocardial function, pulmonary and systemic vasodilation

Children: IV: Loading: 0.5 mg/kg over 2–3 min in ½ NS (not D5W) Maintenance: 5–20 μg/kg/min Adults: IV: Loading: 0.75 mg/kg over 2–3 min Maintenance: 5–10 μg/kg/min

ThrombocytoInj: 5 mg/mL penia, (20 mL) hypotension, tachyarrhythmias, hepatotoxicity, nausea and vomiting, fever Caution: Bleeding disorder, hypertrophic cardiomyopathy, hypotension

Calcium chloride

Onset: rapid Mode of action: Enhances contractility through regulation of action potential

20 mg/kg slow IV bolus, Central line preferred. Max, 2000 mg.

Side effects: (10% solution) Bradycardia, hypotension, peripheral vasodilation, hypercalcemia, hypermagnesemia, hyperchloremic acidosis Contd...

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Contd... Onset: rapid Mode of action: Enhances contractility through regulation of action potential

Caution: Central venous line administration ONLY. Max. conc. is 20 mg/mL infusion, Extravasation may lead to tissue necrosis, use local hyaluronidase if occurs, may precipitate arrhythmia in digitalized patient Contraindication: Hypercalcemia, ventricular fibrillation

Calcium gluconate

Onset: Rapid Mode of action: Enhances contractility through regulation of action potential

PO, IV

Same as calcium chloride

Digoxin

Cardiac glycoside Lanoxin, LanoxiOnset: PO: caps Dixin 1–2 hours, IV: 5–30 minutes Mode of action: Inhibition of Na+K+ pump resulting in increase Ca++ intracellular influx

TDD PO* PT 20 μg/kg; FT:30 μg/kg; CH 1 month– 2 years: 40–50 μg/kg; CH>2 y: 30–40 μg/kg IV: 75%–80% of PO dose Maintenance: 25%–30% of PO in BID-TDD/day Adults: 0.10–0.25 mg/day • Presently Loading dosing is best avoided

AV conduction disturbances, arrhythmias, nausea and vomiting Caution: Renal failure. Cardioversion or calcium infusion may cause VF in patients receiving digoxin (pretreatment with Lidocaine may be helpful). Therapeutic level: 0.8–2 ng/ mL, not reliable in neonates, since they may have falsely elevated levels (due to maternal digoxin like substances in serum) Contraindication: Ventricular arrhythmia, AV block, IHSS, constrictive pericarditis

Elixir: 50 μg/mL (60 mL) Tab: 125, 250,500 μg Caps: 50, 100, 200 μg. Inj: 100, 250 μg/mL

Dopamine

Sympathomimetic Dopastat agent natural Intropin, catecholamine inotropic agent

Children: IV: Effects are dose dependent: 2–5 μg/kg/min— increases RBF and urine output 5–15 μg/kg/ min—increases heart rate,cardiac contractility and cardiac output

Tachyarrhythmias, nausea and vomiting, hypotension or hypertension, extravasation (tissue necrosis). Side effects: Tachyarrhythmias, premature beats, hypertension, headache, nausea

Inj: 40 mg/mL (5 mL), 80 mg/mL (5 mL), 160 mg/ mL (5 mL)

Contd...

513

Drug Dosages Contd... >20 μg/kg/min—αadrenergic effects with decreased RBF (±) (Incompatible with alkali solution) 5–20 µg/kg/ min via CVC

Caution: Correct hypovolemia. Do NOT use discolored solution Contraindication: Infusion through UAC, pheochromocytoma, ventricular fibrillation

Dobutamine

Dobutrex β1-Adrenergic Dobuject,Crdiject stimulator Onset: Rapid Mode of action: stimulates beta adrenergic receptors, resulting in increase myocardial contractility without significant change in heart rate, peripheral resistance and BP

Children: IV: 2–15 μg/kg/ min in D5W or NS (incompatible with alkali solution) Adults: IV: 2.5–10 μg/kg/min (maximum 40 μg/kg/min) 5–20 µg/kg/min

Tachyarrhythmias, Inj: 12.5 mg/mL hypertension, (20 mL vial) nausea and vomiting, headache (contraindicated in IHSS and atrial flutter/ fibrillation) Side effects: Ventricular arrhythmias, hypertrophic cardiomyopathy, tachycardia, hypertension, angina, palpitation, headache Caution: Patient should be euvolemic. Contraindication: IHSS, tachycardia, arrhythmias, hypertension

Epinephrine

Nonselective adr- (Adrenaline) energic stimulator Epinephrine HCl (α-, β1-, and β2-adrenergic stimulator Onset: 1–5 minutes Mode of action: Inotropy: Beta adrenergic receptor stimulation Vasoconstriction: alpha adrenergic receptor stimulation

Children: IV: 1:10,000 sol— begin with 0.1 μg/kg/min; increase to 1 μg/kg/min to achieve desired effect 0.05–1.0 µg/kg/ min

Tachyarrhythmias, hypertension, nausea and vomiting, headache, tissue necrosis (±) Caution: Hyperthyroidisim, hypertension, arrhythmias. Do not use discolored solution. ExtravaIV, ETT Bradycar- sation will cause dia/hypotension: tissue necrosis, 1:10,000, phentolamine 0.1 mL/kg- Q 3–5 should be infilmin trated around the Infusion-1-10 µg/ extravasation to kg/min Q3–5 min minimize necrosis Contraindication: Acute coronary artery disease, angle closure glaucoma

Inj: 0.01 mg/mL (1:100,000 sol, 5 mL) 0.1 mg/mL (1:10,000 sol, 10 mL) 1 mg/mL (1:1000 sol, 1 mL)

Isoproterenol

β1- and β2Adrenergic stimulator

Children: Similar to IV: 0.1–0.5 epinephrine μg/kg/min, titrated to desired effect Adults: IV: 2–20 μg/min, titrated to desired effect (incompatible with alkali solution) 0.05–1.5 µg/kg/h

Inj: 0.2 mg/mL (1:5000 solution: 1.5 mL)

Isuprel

Contd...

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Pediatric Cardiology

Contd...

3

Levosimendan

calcium Simdax sensitization. “Inodilators” Onset of action-5 minutes Peak—10 to 30 minutes of infusion; duration of action 75 hours to 1 week

6–12 ����������� μg��������� /kg loading dose over 10 minutes followed by 0.05 to 0.2 μg/ kg/min as a continuous infusion. PO-4–8 mg daily doses

headache, hypotension, prolongation of QTc, ventricular tachycardia

2.5 mg per 5 mL per ampoule and 10 mL per ampoule

Milrinone

phosphodiesterPrimacor ase inhibitor, noncatecholamine inotropic, vasodilator Side effects: Arrhythmia, headache, hypotension, thrombocytopenia rarely reported. Caution: Renal dysfunction Contraindication: Severe pulmonary or aortic obstructive disease

75 µg/kg bolus,then 0.50–0.75 µg/ kg/min

Arrhythmias, Inj: 1 mg/mL hypotension, hypokalemia, thrombocytopenia

Norepinephrine

α- and β-Adrenergic stimulator Onset: Rapid Mode of action: Stimulates alpha and beta adrenergic receptors (predominantly alpha effect)

Levophed levarterenol

IV: 0.1 μg/kg/min initially; increase dose to attain desired effect Adults: Norepinephrine (Levophed, levarterenol) (α- and β-adrenoceptor stimulant) IV: Add 4 mL levarterenol to 1000 mL D5W, start at 2–3 mL/min (8–12 μg/min) and adjust rate 0.05–1.0 µg/ kg/min

Hypertension, Inj: 1 mg/mL bradycardia (reflex), arrhythmias, tissue necrosis (treat with phentolamine infiltration) Side effects: Arrhythmias, palpitation, hypertension, angina, headache, anxiety, vomiting, uterine contractions, respiratory distress, diaphoresis

Adenosine

Antiarrhythmic Onset: Very rapid with very short t1/2 due to rapid uptake by RBCs and endothelial cells. Mode of action: Slows AV node conduction

Adenocard Adenoject

IV: 50 μg/kg, stat by rapid IV push, Repeat q1–2 min, with increment of 50 μg/kg, to maximum of 250 μg/kg max 12 mg PAH: 50 µg/kg/ min iv infusion into central vein

Tachycardia, Inj: 3 mg/mL Transient AV (2 mL) block in atrial flutter/fibrillation (±) Palpitations, flushing, headache, dyspnea, nausea, chest pain, lightheadedness, bradycardia

Amiodarone

Class III antiarrhythmic Onset: 3 days–3 weeks Mode of action: Class III, inhibits alpha and beta

Cordarone Aldarone Eurythmic

IV (in emergency situation): Loading: 1 mg/ kg, given over a 5–10 min period, 5 doses

Progressive dyspnea and cough (pulmonary fibrosis worsening of arrhythmias, hepatotoxicity,

Antiarrhythmic Agents

Tab: 200 mg Inj: 50 mg/mL Suspension: 5 mg/mL

Contd...

515

Drug Dosages Contd... adrenergic receptors, prolongs action potential and refractoriness (Therapeutic level: 0.5–2.5 mg/L);

May be repeated 30 min later Alternatively, IV infusion at a dose of 10–15 mg/kg/d for 4 hours, then 5–15 µg/kg/min infusion PO: 5–10 mg/ kg/24 h in 2 doses for 10 days If responsive, 3–5 mg/kg once a day May be reduced to 2.5 mg/kg for 5–7 days thereafter Pulseless VF./VT - 5 mg/kg IV over 3–5 min.

nausea and vomiting, corneal microdeposits, hypotension and heart block, ataxia, alteration of thyroid function (hypo- or hyperthyroidism), photosensitivity), Caution: Increases digoxin (reduce dose by 1/2), warfarin, flecanide, procainamide, quinidine and phenytoin serum levels, thyroid disease Therapeutic level: 0.5–2.5 mg/L Contraindications: AV block, sinus node dysfunction, sinus bradycardia

Bretylium

Class III antiarrhythmic Onset: IV: 6–20 min, IM: < 2 h sodium channel blocker, inhibits norepinephrine release

Bretylol

For ventricular fibrillation or tachycardia: Children: IV/IM : 5–10 mg/ kg/dose over 8 min, then 10 mg/ kg/dose q15–30 min (maximum 30 mg/kg)

Hypotension, Inj: 50 mg/mL worsening of (10 mL ampule) arrhythmias, aggravation of digitoxicity, nausea and vomiting. Caution: Pulmonary hypertension, aortic stenosis, renal dysfunction Contraindication: Digitalis induced arrhythmias

Diltiazem

Calcium channel blocker/antihypertensive Maximum antihypertensive effect seen within 2 weeks

Dilacor XR Cardizem Cardizem CD/SR, Tiazac

1 mg/kg 8H, increase if required to 3 mg/kg 8 H oral Slow release - PO: 30–120 mg/ dose, TID-QID. Children: Slow release—120–240 mg/day.

Dizziness, headache, edema, nausea, vomiting, heart block, and arrhythmias Contraindicated in second and thirddegree AV block, sinus node dysfunction

Tab: 30, 60, 90, 120 mg Extended release tab:120, 180, 240 mg Extended release caps: Cardizem SR: 60, 90, 120 mg; Cardizem CD: 120, 180, 240, 300, 360 mg Dilacor XR: 120, 180, 240 mg Tiazac: 120,180, 240, 300, 360, 420 mg Inj: 5 mg/mL

Flecainide

(Class IC anTambocor tiarrhythmic) Onset: Rapid Mode of action: sodium channel blocker, cell membrane depression

For sustained ventricular tachycardia: PO: Initial 1–3 mg/kg/day, q 8 hours. Usual range: 3–6 mg/kg/day, q 8 hours

Worsening of HF, bradycardia, AV block, dizziness, blurred vision, dyspnea, nausea, headache, increased PR and

Tab: 50, 100, 150 mg Suspension: 5, 20 mg/mL

Contd...

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Pediatric Cardiology

Contd... Therapeutic level: 0.2–1 µg/mL

Monitor serum level to adjust dose if needed. Adults: PO: 100 mg, q 12 hours. PO 2–6 mg/kg/ day, divided q 8–12 hours

Mexiletine

(Children: Mexitil (class 1B antiarrhythmic) Therapeutic level: 0.75–2 μg/mL 5–10 mg/kg/day

Lignocaine

Class IB anXylocaine tiarrhythmic Lidocaine Onset: Rapid Mode of action: sodium channel blocker, local anesthetic depressing myocardial irritability Therapeutic level: 2–5 µg/mL Magnesium slows Sulfamag the rate of SA nodal impulse formation

Magnesium sulfate

Phenytoin

Class IB antiarrhythmic Therapeutic level: 5–18 μg/mL for arrhythmias Onset: Minutes Mode of action: Not well-defined

Children: IV: 2–4 mg/kg/ dose over 5–10 min followed by: PO: 2–5 mg/kg/ day in 2–3 doses

QRS duration. Reserve for lifethreatening cases. Caution: Heart failure, heart block, Hepatic impairment, reduce dose by 25–50% in renal failure Contraindication: 2nd or 3rd degree AV block Children: Nausea and Caps: 150, PO: 6–8 mg/kg/day vomiting, CNS 200, 250 mg BID-TID for 2–3 symptoms (headdays, then 2–5 ache, dizziness, mg/kg/dose q 6–8 tremor,ataxia hours. PO paresthesia, mood Increase 1–2 mg/ changes), kg/dose q 2–3 rash, hepatic days until desired dysfunction (±) effect achieved (with food or antacid) Adults: PO: 200 mg q 8 hours for 2–3 days, Increase to 300–400 mg q 8 hours (Usual dose 200–300 mg q 8 hours) divided q 8 hours Children: IV: Seizure, respiraInj: 10 mg/mL Loading: 1 mg/ tory depression, (5 mL ampule), kg/dose q 5–10 anxiety, drowsi20 mg/mL (5,10 min prn ness, arrhythmias, mL ampule) Maintenance: 30 hypotension or μg/kg/min IV drip shock (range 20–50 Caution: Hepatic μg/kg/min) disease, heart failure Contraindication: AV block IV 25–50 mg/kg Flushing, sweating, 2 mL of 50% over 10–20 min. muscle weakness, solution Max dose, 2 g dizziness, drowsiness, slowed/shallow breathing Dilantin Rash, StevensInj: 50 mg/mL Infatab Johnson Suspension: syndrome, CNS 125 mg/5 mL symptoms (ataxia, Chewable dysarthria), lupus tabs: 50 mg such as syndrome, Caps: 100 mg blood dyscrasias, peripheral neuropathy, gingival hypertrophy. Caution: Oral absorption reduced in neonates, serum levels are increased by cimetidine, INH Contd...

517

Drug Dosages Contd... chloramphenicol, sulfonamide, trimethoprim. Rapid injection may cause hypotension and bradycardia Contraindication: Heart block or sinus bradycardia Procainamide

Class IA anProcan SR tiarrhythmic Pronestyl Therapeutic level: 4–10 mg/mL Sodium channel blocker depressing myocardial excitability and conduction Onset: IV: Rapid PO: 2–4 h, IM: 10–30 min Therapeutic level: 4–10 mg/L of procainamide

Children: IV: Loading: 3–6 mg/kg/dose over 5 min repeated q10–30 min (maximum 100 mg) Maintenance: 20–80 (μg/kg/ min by IV infusion (maximum 2g/24 h) PO: 15–50 mg/kg/ day q 3–6 hours (maximum 4 g/24 h) Adults: IV: Loading: 50–100 mg/dose q5 min prn Maintenance: 1–6 mg/min by IV infusion PO: 250–500 mg/dose q3–6 h (usual dose 2–4 g/day). 0.4 mg/kg/min for max 25 min, then 20–80 µg/kg/min infusion(max 2 g/ day).oral: 5–8 mg/ kg 4 h. Level 3–10 µg/mL.

Nausea and vomiting, blood dyscrasias, rash, lupus-like syndrome, hypotension, confusion or disorientation Caution: Toxicity when QRS > 0.2 sec. Contraindication: Myasthenia gravis, complete heart block

Propafenone

Onset: Rapid Rhythmol Mode of acRhythmonorm tion: Class Ic antiarrhythmic agent, also blocks sodium channels and β Blocker effect

PO -2–3 mg/kg tid IV 1–2 mg/kg Infusion 4–8 µg/ kg/min

Side effects: AV 150 mg tablets block, palpitations, bradycardia, CHF, conduction disturbances, dizziness, drowsiness, dry mouth, altered taste, dyspnea, flatulence, blurred vision, dyspepsia Caution: CHF, hepatic or renal dysfunction Contraindication: Cardiogenic shock, bronchospastic disorder, conduction disorder

Quinidine

Class IA anCardioquin tiarrhythmic agent Quinidex, Quinaglute

Children: Test dose for idiosyncrasy: 2 mg/kg once (PO as sulfate; IM/IV as gluconate)

Nausea and vomiting, ventricular arrhythmias, prolonged QRS

Tab: 250, 375, 500 mg Tab, sustained release: 250, 500, 750, 1000 mg Suspension: 6, X50, 100 mg/mL Inj: 100, 500 mg/ mL

Gluconate (62% quinidine): Slow-release tab: 330 mg Inj: 80 mg/mL Contd...

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Contd...

Verapamil

Mode of action: sodium channel blocker, depressing atrial and ventricular excitability. Vagolytic. Therapeutic level: 2–7 mg/L

Therapeutic dose: IV (as gluconate): 2–10 mg/kg/dose, q 3–6 hours, prn PO (as sulfate): 15–60 mg/kg/ 24 hours q 6 hours)

complex > 20 sec), depressed myocardial contractility, blood dyscrasias, symptoms of cinchonism Causes increase of digoxin serum level (reduce digoxin by 1/2). Quinidine’s effect is enhanced by amiodarone or Cimetidine. Quinidine’s effect is reduced by rifampin, phenytoin or barbiturates. Atrial flutter may conduct 1:1 when quinidine is used alone, due to enhancement of AV conduction

Sulfate (83% quinidine): Tab: 200, 300 mg Slow-release tabs: 300 mg Suspension: 10 mg/mL

Class IV anIsoptin tiarrhythmic agent Calan, Verelan (calcium channel blocker, class IV antiarrhythmic agent)

0.1–0.2 mg/kg over10 min IV, then 5 µg/kg/min. Oral: 1–3 mg/kg 8–12 hours For dysrhythmia (SVT): Children: IV: 1–15 years 0. 1–0.3 mg/kg over 2 minutes May repeat same dose in 15 minutes. Max. dose 5 mg first dose;10 mg second dose Adults: IV: 5–10 mg, 10 mg second dose For hypertension: Children: PO: 4–8 mg/kg/24 h in 3 doses

Caution: Extreme caution in infants and in WPW, may cause apnea, bradycardia, or hypotension. Do not use with other negative inotropes (e.g. beta-blockers). To reverse hypotension use calcium, Isoproterenol and IV volume. Reduce digoxin by 1/3 to 1/2. Contraindication: CHF, hypotension, shock, AV block, right to left shunt lesions, atrial fibrillation, sinus bradycardia

Tab: 40, 80, 120 mg Extended release tab:120, 180, 240 mg Suspension: 50 mg/mL Inj: 2.5 mg/mL

Atenolol, Esmolol, Sotalol and Propranolol are detailed under section of beta-blockers 4

Vasodilators Amlodipine

Calcium channel blocker, antihypertensive

Norvasc Amlopres, Amcard, Amlopin

Children: Initial dose 0.1 mg/kg/dose QD-BID May be increased gradually to a maximum of 0.6 mg/kg/24 h. Adults: PO: 5–10 mg/ dose QD (max. 10 mg/24 h)

Edema, dizziness, Tab: 2.5, 5, 10 mg flushing, Suspension: 1 and palpitation. mg/mL Other effects include headache, fatigue, nausea, abdominal pain, somnolence

Contd...

519

Drug Dosages Contd... Hydralazine

Mode of action: Apresoline Peripheral vasoNepresol dilator, antihypertensive Onset: PO: 10–30 min, IV: 5–20 min

Children: IM, IV: 0.15–0.2 mg/kg/dose (for emergency); may be repeated q 4–6 hours PO: 0.75–3 mg/ kg/day,2–4 doses Adults: IM, IV: 20–40 mg/ dose (for emergency); repeat prn PO: Start with 10 mg 4 times/ day for 3–4 days, increase to 25 mg 4 times/day for 3–4 days, then up to 50 mg 4 times/ day

Hypotension, tachycardia and palpitation, lupus-like syndrome with prolonged use (fever, arthralgia, splenomegaly and positive LE-cell preparation), blood dyscrasias

Isradipine

Calcium channel blocker, dihydropyridine agent

DynaCirc

PO: 0.15–0.2 mg/kg/24 h TID QID (max, 0.8 mg/ kg/24 h up to 20 mg/24 h)

Pedal edema, Caps: 2.5, 5 mg headache, dizziness, flushing lightheadedness, asthenia

Nifedipine

Calcium channel blocker Onset: PO 20–30 min, Sublingual 1–5 min

(Procardia, Adalat) For hypertrophic cardiomyopathy: Children: PO: 0.6–0.9 mg/ kg/24 h in 3–4 doses For hypertension: Children: PO: 0.25–0.5 mg/ kg/24 h in 1–2 doses (max. 3 mg/ kg/24 h up to 120 mg/24 h) Adults: Usual dose 10–20 mg 3 times/day; maximum 180 mg/ day) 0.25–0.5 mg/kg 6–8H(caps),0.5–1 mg/kg (tabs) 12H oral/sublingual

Nitroglycerine

peripheral Nitrobid, Tridil, Vasodilator Nitrostat venous more than arterial Onset: Rapid

Children: IV: 0.5–1 μg/kg/ min Increase 1 μg/ kg/min q 20 min to titrate to effect (maximum 6 μg/ kg/min) (Dilute in D5W or NS with final concentration 48 hours and in renal failure) Keep level < 35 mg/L. Contraindication: Reduced cerebral perfusion, coarctation of the aorta, AV shunts

PrazosinHCL

postsynaptic αadrenergic blocker; antihypertensive Onset: 1–3 h

Minipress

For Pulmonary edema – 5 m cg/ kg as test dose, 6–35 µg/kg/(max 15 mg/day) QID Children: PO: 5 μg/kg as a test dose, then 25–150 μg/kg/day in 4 doses Adults: PO: 1 mg 2–3 times/day initially increase to 20 mg/day in 2–4 doses

CNS symptoms Caps: 1, 2, 5 mg (dizziness, headache, drowsiness), palpitation, nausea Caution: “First dose phenomenon”: orthostasis, syncope, usually within 90 min of first dose

Children: PO: Newborn: 0.1–0.4 mg/kg/ 24 h, in QID; Infant: Initially 0.15–0.3 mg/kg/ dose. Titrate upward if needed. Max. dose 6 mg/kg/ 24 h, QDQID. Adolescent and adult: Initially 12.5–25 mg/dose, BID-TID. Increase weekly if needed by 25 mg/ dose to max. dose 450 mg/24 h. Smaller dose in renal impairment

Neutropenia/ agranulocytosi s, proteinuria, hypotension and tachycardia, rash, cough, taste impairment, small increase in serum potassium levels (±) Caution: Adjust with renal dysfunction, administer 1 hour prior to meals. Drug interactions: NSAIDs, e.g. indomethacin, may decrease the antihypertensive effect of captopril. Potassium sparing agents will potentiate hyperkalemic effect

Inj: 50 mg (vial for reconstitution with 2–3 mL D5W)

Angiotensin Converting Enzyme Inhibitors Captopril

Angiotensin con- Capoten verting enzyme Acetan inhibitor, Angiopril antihypertensive, vasodilator Onset: 15–30 min

Tab: 12.5, 25, 50, 100 mg Suspension: 0.75, 1 mg/mL

Contd...

521

Drug Dosages Contd... Enalapril, Enalaprilat

ACE Vasotec inhibitor, Envas, Enam vasodilator Onset: PO: 30–60 min, IV: 10–15 min

Ramipril

6

PO: 0.1 mg/kg/ dose QD or BID (maximum 0.5 mg/ kg/day) Adults: For CHF: PO: Start with 2.5 mg OD/BD (usual range 5–20 mg/ day) For hypertension: PO: Start with 5 mg once a day (usual dose 10–40 mg/day)

Hypotension, dizziness, fatigue, headache, rash, diminishing taste, neutropenia, hyperkalemia, chronic cough Evidence of fetal risk if given during second and third trimesters (same with all other ACE inhibitors) Caution: same as that for captopril

Tab: 2.5, 5, 10, 20 mg Oral suspension: 1 mg/dL Inj: 1.25 mg/mL

Ramiril, Corpril, Cardace

0.05 mg/kg oral daily, may incr over 4–6 week to 0.1–0.2 mg/kg daily

Same with all other ACE inhibitors

Caps. 1.25, 2.5, 5 mg

For hypertension Children: PO: Initial 0.07 mg/kg/day, May increase up to 5 mg/day (max, 0.6 mg/kg/day or 40 mg/day) PO: 0.1–0.5 mg/ kg/dose (max 40 mg) given qd Adults: PO: Initial 10 mg QD. May increase upward as needed to max. 80 mg/day

Dry nonproductive Tab: 2.5, 5, cough, 10, 20, 30, 40 rash, hypotension, mg hyperkalemia, angioedema, rarely marrow depression. Evidence of fetal risk if given during second and third trimesters (same with all other ACE inhibitors)

Lisinopril

ACE inhibitor, antihypertensive)

Zestril, Prinivil, Linvas, Lipril, Lisopril

Losartan

Angiotensin receptor blocker

(Tozaar), Losacar, PO: 0.7 mg/kg/24 Alsartan h, QD-BID, up to 50 mg/24 h

Hypotension, diz- Tab: 25, 50, ziness, nasal con- 100 mg gestion, muscle cramps

Bisoprolol

Cardioselective β blocker

Concor, Corbis

0.2–0.4 mg /kg daily oral

Dizziness, hypotension

Atenolol

Cardioselective β blocker

Aten, Betacard

0.5–1 mg/kg/dose PO: q Day maximum up to 2 mg/ kg/day

Bradycardia, tired- Tab 25, 50, 100 ness, Hypotenmg sion, dizziness, fatigue, dyspnea, nausea, second and third degree heart block, rash, lupus syndrome

Carvedilol

nonselective β-and α1 adrenergic blocker with antioxidant property

Coreg, Coreg Tiltabs, Carvil, Carloc, Carvas

Children: PO: Initial 0.09 mg/kg/ dose, q 12 hours Increase gradually to 0.36 and 0.75 mg/kg as tolerated to adult max. dose of 50 mg/24 h.

Dizziness, hypotension, headache, diarrhea, rarely AV block

B-Blockers Tab 5 mg

Tabs, scored: 1.25 mg, 6.125, 12.5, 25 mg

Contd...

522

Pediatric Cardiology

Contd... Esmolol

β1-selective����� adrenergic blocking agent, antihypertensive. class II antiarrhythmic Onset: Rapid

Brevibloc, Minibloc

IV infusion: Loading dose: 100– 500 μg/kg over 1 min. Maintenance: 25–100 μg/kg/ min as infusion, increase by 50 μg/ kg to a maximum of 300 μg/kg/min rarely given for > 48 hours.

Bronchospasm, Inj: 10, 250 mg/mL CHF, Hypoglyce- (undiluted 10 mg/ mia, hypotension, kg solution) nausea/vomiting, heart block, bradycardia, negative inotropic effect Caution: Skin necrosis may occur with extravasation, max. conc.: 10 mg/mL due to hyperosmolarity. Contraindication: Cardiogenic shock, heart block, severe asthma

Labetolol

(α- and β-adrenergic antagonist)

Normodyne Trandate

Children: Orthostatic hypotension, edema, CHF, bradycardia. PO: Initial 4 mg/ kg/24 h, BID Contraindicated in asthma. Max. 40 mg/ kg/24 h. IV: (for hypertensive emergency) Initial 0.1–1 mg/ kg/dose q10 min, prn (Max. 20 mg/ dose)

Orthostatic hypotension, edema, CHF, bradycardia. Contraindicated in asthma

Metoprolol

Lopressor, β1-adrenoceptor Betaloc, Metolar blocker Onset: 15–30 min

Children >2 years: PO: Initial 0.1–0.2 mg/kg/dose BID Gradually increase to 1–3 mg/ kg/24 h. Adults: PO: 100 mg/day in 1–3 doses initially May increase to 450 mg/24 h in 2–3 doses (Usual dose 100–450 mg/24 h) (Usually used with hydrochlorothiazide 25–100 mg/ day)

CNS symptoms Tab: 50, 100 (dizziness, tiredmg ness, depression), bronchospasm, bradycardia, diarrhea, nausea and vomiting, abdominal pain Caution: In lung disease, heart, hepatic or renal failure. Drug interactions: Barbiturates, rifampin will increase clearance of metoprolol. Metoprolol metabolism decreases with cimetidine, amiodarone, diltiazem, propafenone, quinidine, hydralazine, chlorpromazine, or verapamil. Contraindication: Asthma, heart block with concurrent use of verapamil

Tab: 100, 200, 300 mg Inj: 5 mg/mL Suspension: 10 mg/mL

Contd...

523

Drug Dosages Contd... (β-adrenoceptor blocker, class II antiarrhythmic) Onset: PO: 40–120 min., IV: Rapid

Inderal, Ciplar

Children: PO: 2–4 mg/kg/24 h in 2–4 doses (maximum 16 mg/ kg/24 h) For arrhythmias: Children: IV: 0.01–0.15 mg/ kg/dose over 10 min (maximum 1 mg/dose) PO: 2–4 mg/kg/24 h in 3–4 doses (maximum 16 mg/ kg/24 h) Adults: IV: 1 mg/dose q5 min (maximum 5 mg) PO: 40–320 mg/24 h in 3–4 doses

Hypotension, syncope, bronchospasm, nausea and vomiting, hypoglycemia, lethargy or depression, heart block Caution: In lung disease, heart, hepatic or renal failure. Barbiturates, rifampin or indomethacin will increase clearance, cimetidine, hydralazine, chlorpromazine, or verapamil cause decrease in clearance and enhanced effect. Contraindication: Asthma. cardiogenic shock and heart block

Atropine

Onset: Rapid Mode of action: Blocks acetylcholine activity

Atropine sulfate

IV 0.02 mg/kg Minimum dose, 0.1 mg. Max single dose for child, 0.5 mg, for adolescent = 1 mg. May double for second dose

Side effects: Dry 0.1 mg/mL (Adult) mouth, blurred 0.05 mg/mL vision, tachycar(Pediatric) dia, dry hot skin, restlessness, fatigue, difficult micturition, impaired GI motility, CNS symptoms, hyperthermia, palpitation, delirium, headache, tremor Contraindication: Glaucoma, tachycardia, thyrotoxicosis, GI obstruction, uropathy

Diphenhydramine

Onset: PO: 20–40 Benadryl min, IV: 10–20 min Mode of action: Histamine 1 receptor antagonist

PO, IV, IM 1–2 mg/kg QID max = 50 mg

Side effects: Sedation, drowsiness, insomnia, vomiting, anorexia, constipation, diarrhea, anticholinergic effect, hypotension, palpitation, tachycardia, paradoxical excitement, fatigue, photosensitivity, rash, dry mouth, urinary retention, blurred vision, thickened bronchial secretions

Propanolol

7

Tab: 10, 20,40, 60, 80, 90 mg Extended release caps: 60, 80, 120,160 mg Oral solution: 20, 40 mg/5 mL Concentrated solution: 80 mg/ mL Inj: 1 mg/mL

Drugs Used in Cardiac Emergencies

Capsules: 25 and 50 mg. Tablets: 12.5, 25,50 mg. Elixir, oral solution, liquid: 12.5 mg per teaspoon (5 mL). Injection: 50 mg per mL

Contd...

524

Pediatric Cardiology

Contd... 8

9

Ductal Manipulation For patency of ductus arteriosus: IV: Begin infusion at 0.05–0.1 μg/kg/ min. When desired effect achieved, reduce to 0.05, 0.025, and 0.01 μg/kg/min. If unresponsive, dose may be increased to 0.4 μg/kg/min

Apnea, flushing, Ampule: 500 bradycardia, μg/mL hypotension, fever, hypocalcemia, diarrhea, hypoglycemia, inhibition of platelet aggregation, cortical hyperostosis Caution: Apnea occur in 10–12% of neonates, usually appear in first hour of therapy

Mode of action Indocin Prostaglandin synthesis inhibitor (nonsteroidal antiinflammatory, antipyretic agent

For PDA closure in premature infants: IV: 7 days: 0.2, 0.25, and 0.25 mg/kg/ dose, q12–24 hours 0.5–1 mg/kg 8 H (max 6 H) oral or PR.PDA 0.1 mg/ kg ( = 1kg) day 1, then 0.1 mg/kg daily days 2–7 oral or IV over 1 hour

GI bleeding , Vial: 1 mg ulcers, diarrhea, blood dyscrasias, hypertension, oligurea, renal failure, somnolence, hyperkalemia, hypoglycemia, hepatitis, tinnitus Caution: Monitor renal and hepatic function. Keep urine output > 0.6 ml/kg/h Contraindication: Neonates with BUN > 30 mg/dL, Cr >1.8 mg/dL., recent IVH, NEC, thrombocytopenia, or active bleeding

Mode of action: Brufen Nonsteroidal Ibugesic anti-inflammatory agent (inhibits PG synthesis)

PDA- 10 mg/kg stat, then 5 mg/kg after 24 and 48 hours

Side effects: 100 mg/5 mL Drowsiness, fatigue, headache, GI irritation, inhibition of platelet aggregation, hepatitis, acute renal dysfunction, blood dyscrasias. Caution: CHF, renal disease, hepatic disease Contraindication: Active GI bleeding, GI ulcers, platelet dysfunction

sedative, hypnotic Noctec Onset: 10–20 min. Mode of action: CNS depressant

As sedative: Children: PO, PR: 25 mg/ kg/dose q 8 hours Adults: PO, PR: 250 mg/ dose q 8 hours

Mucous membrane irritation (laryngospasm if aspirated), GI irritation, excitement/delirium (contraindicated in hepatic and renal impairment)

Prostaglandin E1

Vasodilator Onset: 1.5–3 hours Mode of action: Direct effect on vascular smooth muscles causing pulmonary, systemic and ductus arteriosus vasodilation

Indomethecin

Ibuprofen

alprostadil (ProstinVR) Prostin

Sedatives Chloral hydrate

Caps: 500 mg Syrup: 250, 500 mg/5 mL Suppository: 324, 500, 648 mg

Contd...

525

Drug Dosages Contd...

Chlorpromazine

sedative, antiemetic

Thorazine, Largactil

Fentanyl

Onset: Rapid Sublimaze, Mode of action: Duragesic, Semisynthetic opi- Oralet ate analgesic

Diazepam

sedative, Valium antianxiety, antiseizure agent Onset: Rapid Mode of action: CNS depression through enhanced GABA at the limbic system

As hypnotic: Children: PO, PR: 50–75 mg/kg/dose Adults: PO, PR: 500– 2000 mg/dose 20–100 mg/kg (max 2 gm) Q 6–8 hours For sedation or nausea: Children > 6 mo:IM: 0.5 mg/kg/ dose q6–8 h prn PO: 0.5 mg/kg/ dose q4–6 h prn PR: 1–2 mg/kg/ dose q6–8 h prn Adults: IM: 25-mg test dose, then 25–50 mg q3–4 h PO: 10–25 mg q4–6 h PR: 100 mg q6–8 h 0.5–2 mg/kg (max 100 mg) Q 4–6 H oral,0.25–1 mg/kg (usual 50 mg) 6–8 H For sedation: Children: IV: 1–3 year: 2–3 μg/kg/dose; 3–12 year: 1–2 μg/kg/ dose; >12 year: 0.5–1 μg/kg/dose; may repeat q30–60 min PO for sedation:10–15 µg/kg/ dose.(Max. 400 μg/dose) Ventilated: 5–10 µg/kg stat or 50 µg/kg IV infusion over 1 h; infusion 5–10 µg/kg/h For sedation: Children > 6 mo: IM, IV: 0.1–0.3 mg/kg/dose q 2–4 hours (maximum 0.6 mg/kg in 8 hours) PO: 0.2–0.8 mg/ kg/24 h in 3–4 doses, or 1–2.5 mg 3–4 times/ day initially and increase prn Adults: IM, IV: 2–10 mg/ dose q3–4 h prn PO: 2–10 mg/dose q6–8 h prn 0.1–0.4 mg/kg IV or PR.0.04–0.25 mg/ kg Q 8–12 H oral

Hypotension, arrhythmias, first-degree AV block, STT changes, hepatotoxicity, leukopenia or agranulocytosis

Syrup: 10 mg/5 mL (120 mL) Tab: 10, 25, 50, 100, 200 mg Supp: 25, 100 mg Oral concentrate: 30 mg/mL,100 mg/mL. Inj: 25 mg/mL

Respiratory depression, apnea, rigidity, bradycardia

Inj: 50 μg/mL Fentanyl Oralet: 100, 200, 300, 400 μg

Apnea, drowsiness, ataxia, rash, hypotension, bradycardia, hyperexcited state Contraindications: Narrow angle glaucoma Caution: Glaucoma, shock, depression, hypoalbuminemia, hepatic dysfunction. No faster than 1–2 mg/min (IV)

Tab: 2, 5, 10 mg Oral solution: 1 mg/mL, 5 mg/ mL Inj: 5 mg/mL

Contd...

526

Pediatric Cardiology

Contd... Midazolam

Onset: IV: Rapid, Versed, Mezolam IM: 5–15 min, PO/ PR: 15–30 min Mode of action: CNS depression by inducing GABA at limbic system

0.1–0.2 mg/kg IV/ IM (max 0.5 mg/ kg); nasal:0.2 mg/ kg (repeated in 10 mins if required); 1–4 µg/kg/min IV infusion

Side effects: Respiratory depression, hypotension, bradycardia, myclonic jerking in neonates Contraindications: Narrow angle glaucoma, shock, physical dependence. Caution: Lower dose by 25% when used with narcotics, cimetidine or anesthetic agents. Care should be observed in the post-operative open-heart patient, and with hemodynamic instability

Morphine sulfate

(narcotic analDuramorph, Cengesic tin, Astramorph Onset: IV: Rapid, PO: 15–30 min Mode of action: Strongest narcotic analgesic. Unspecified aid with CHF, pulmonary edema and anoxic spells

Children: SC, IM, IV: 0.1–0.2 mg/kg/dose q 2–4 hours (maximum 15 mg/dose) Adults: Morphine sulfate SC, IM, IV: 2.5–20 mg/dose q 2–6 h pm 0.1–0.2 mg/ kg/dose,10–30 µg/ kg/h iv infusion in ventilated neonate, 20–80 µg/ kg/h in children

CNS depression, Inj: 8, 10, 15 respiratory demg/mL pression, nausea and vomiting, hypotension, bradycardia Contraindications: Increase ICP and IOP (unless ventilated), shock. Caution: Hepatic failure, renal failure

Promethazine

(sedative, Phenergan antiemetic) Onset: Rapid Mode of action: Antihistaminic, antiemetic, phenothiazine

For nausea and vomiting: Children: IM, PR: 0.25–0.5 mg/kg q4–6 h prn Adults: IM, PR: 12.5–25 mg q6 h prn: 0.2–0.5 mg/kg 6–8 h IV,IM or oral; 0.5–1.5 mg/kg 6–8 h as hypnotic/ sedative For sedation before surgery: Children: IM, PO, PR: 0.5–1 mg/kg/dose q6 h prn Adults: IM, PO, PR: 25–50 mg q4–6 h prn

CNS stimulation, anticholinergic effects Side effects: CNS depression, anticholinergic effect, antihistaminic effect, photosensitivity, extrapyramidal reaction Contraindications: Increase IOP

1 mg or 5 mg midazolam compounded with 0.8% sodium chloride

Tab: 12.5, 25, 50 mg Syrup: 6.25 mg/5 mL, 25 mg/5 mL Supp: 12.5,25, 50 mg Inj: 25, 50 mg/mL

Caution: Seizure, liver disease, CV disease

Contd...

527

Drug Dosages Contd... 10

Miscellaneous Aspirin

Mode of action: Aspirin, Colsprin, Inhibits prostaDisprin, Ecosprin glandin synthesis which prevents thromboxane A2 formation, leading to decrease platelet aggregation

Antiplatelet: 3–10 mg/kg/day Anti-inflammatory: 15–25 mg/kg/dose

Side effects: Rash, nausea, hepatotoxicity, GI bleeding, bronchospasm, GI distress, tinnitus Caution: Renal dysfunction, erosive gastritis, peptic ulcer or gout Contraindication: Hepatic failure, bleeding disorder, hypersensitivity to other NSAID, children 40 kg: 125 mg BID

Liver dysfunction, decrease in hemoglobin, fluid retention, heart failure, headache

Tab: 62.5, 125 mg

Digoxin immune FAB (Ab)

digoxin antidote serum digoxin (nmol/L) x Wt(kg) x 0.3,or mg ingested x 55,given IV over 30 min

Digibind

IV: 1 vial (40 mg) dissolved in 4 mL H2O, over 30 min

Allergic reaction (rare), hypokalemia, rapid AV conduction in atrial flutter

1 vial -40 mg

Heparin

Anticoagulant

Infants and children Loading dose 75 to 100 units/kg followed by 28 units/ kg/h < 1 year, 20 units/kg/h >1 year and 18 unit/ kg/h in older children. Adjust dose to give PTT 1.5–2.5 times control, 6–8 hours after IV infusion (or 3.5–4 hours after injection)

Bleeding Antidote: protamine sulfate (1 mg per 100 U heparin in previous 4 hours)

Inj: 1000, 2500, 5000, 7500, 10,000 U/mL 1 mg=100 IU

Contd...

528

Pediatric Cardiology

Contd... Enoxaparin sodium (Clexane) Lovenox

SC Infants < 12 mo Treatment- 3 mg/ kg/day q 12 hours Prophylaxis: 1.5 mg/kg/day divided q 12 hours Children and adolescents Treatment: 2 mg/ kg/day q 12 hours Prophylaxis: 1 mg/ kg/day q 12 hours Adjust dose to achieve desired therapeutic level, usually antifactor Xa = 0.5 – 1.0 units/mL

Heparin, lowmolecular-weight heparin

low-molecularweight heparin that has antithrombotic properties

Nesiritide

Human B-type Natrecor natriuretic peptide (hBNP)

IV bolus of 2 µg/kg followed by a continuous infusion of 0.01 µg/kg/min

dizziness, chest pain, fast heart rate, feeling lightheaded, fainting

Protamine sulfate

heparin antidote Onset: 5 min Mode of action: Forms a stable salt with Heparin, thus neutralizing it’s effect

IV: Each 1-mg protamine neutralizes approx 100 U heparin given in preceding 3–4 hours Slow IV infusion at rate not exceeding 20 mg/min or 50 mg/10 min

Hypotension, Inj: 10 mg/mL bradycardia, 1 mg/ 100 U dyspnea, flushing, heparin coagulation problem

Sildenefil

Phosphodiesterase inhibitors act by increasing cGMP levels thereby causing pulmonary vasodilatation

0.5 to 1 mg/kg/ dose at 8 hourly intervals Max of 6 mg/kg/ day

Headaches, flush- Tab 25, 50, 100 ing, nasal conges- mg tion, gastritis, visual disturbances, seizures

Streptokinase

thrombolytic agent Streptase, Onset: Rapid Kabikinase Mode of action: Converts plasminogen to plasmin, thus promoting thrombolysis

For thrombolysis: Children: Bolus: 1000–4000 units/kg over 30 min Infusion: 1000– 1500 units/kg/h [Duration of infusion based on response but generally does not exceed 3 days] Obtain tests at baseline and 4 hours: APTT, TT, fibrinogen, PT, hematocrit, platelet count APTT and TT should be < 2 times control

Potential for allergic reaction with repeated use; premedicate with acetaminophen and antihistamine, and repeat q 4–6 hours Caution: Avoid IM injection Contraindication: Major surgery within 10 days, GI bleeding, recent trauma, severe hypertension, internal bleeding, CVA (within 2 months), intracranial or intraspinal surgery, brain carcinoma

Inj: 250,000, 600,000, 750,000, 1,500,000 U/6.5 mL vial

Urokinase

thrombolytic agent Abbokinase Onset: Rapid

IV -Occluded IV catheter:

Bleeding, allergic reactions, rash, fever and chills,

Inj: 5000 U/mL

Penagra, Caverta

100 mg/mL Concentration contains 10 mg enoxaparin sodium (approximate anti-Factor Xa activity of 1000 IU 150 mg/mL Concentration contains 15 mg enoxaparin sodium (approximate anti-Factor Xa activity of 1500 IU Enoxaparin sodium 40 mg/0.4 mL 1.5 mg vial white lyophilized powder for intravenous (IV) administration after reconstitution

Contd...

529

Drug Dosages Contd... Mode of action: Direct activation of plasminogen to plasmin, thus causing thrombolysis

5,000 U/mL conc. Instill a volume equal to that of the catheter in each lumen and leave for 1–4 hours, then aspirate catheter, do not flush. Infusion-DVT, pulmonary emboli: 4,400 U/kg over 10 min, then 4,400 U/kg/h for 12–72 hours Adults:

bronchospasm Caution: Avoid IM injection Contraindication: Bleeding, AV malformation, history of CVA or recent trauma, brain carcinoma, intracranial or intraspinal surgery

Vitamin K 1

Onset: PO 6–12 hours. IV 1–2 hours Mode of action: Cofactor in the synthesis of the clotting factors II, VII, IX and X

PO -2.5–5 mg/day IV, IM -1–2 mg/ dose 1 dose for correction of excessive PT from dicumarol or warfarin overdose

Side effects: Tab: 5 mg Flushing, hypoten- Inj: 2, 10 mg/mL sion, dizziness, GI upset, changes in taste, sweating, anaphylactoid-like reaction with IV administration Caution: IV administration should be restricted for emergencies only, since risk of severe adverse reaction could occur. Do not use in patients with prosthetic valves.

Warfarin

anticoagulant Onset: 36–72 hours Mode of action: Inhibits hepatic synthesis of vitamin K-dependent factors (I, VII, IX, X)

Children: PO-Loading: 0.2 mg/kg, max 15 mg Maintenance: 0.05–0.35 mg/kg, max = 10 mg Liver dysfunction-0.1 mg/kg/ day, max. 5 mg/ dose] Monitor INR after 5–7 days of new dosage. Keep INR at 2.5–3.5 for mechanical prosthetic valve; 2–3 for prophylaxis of DVT, pulmonary emboli. Heparin preferred initially for rapid anticoagulation; warfarin may be started concomitantly with heparin or may be delayed 3–6 days

Side effects: FeTab: 1, 2, 2.5, 3, ver, skin lesions, 4, 5, 6, 7.5, 10 mg anorexia, hemor- Inj: 5 mg rhage, hemoptysis Caution: Adjust to desired PT, INR, fever, skin lesions with necrosis, anorexia, hemorrhage, hemoptysis. Give 0.1 mg/ kg loading dose with impaired liver function. Drug interactions: Warfarin effect increases with ethacrynic acid, indomethacin, mefenamic acid, phenylbutazone, aspirin, Antidote: Vitamin K Contraindication: Bleeding, liver or renal failure, malignant hypertension

(Coumadin, Sofarin)

Index

A Abdominal examination 23 Accuracy of fetal echocardiography 368 Acromegaly and gigantism 356 Acute CHF 93 pericarditis 305 phase reactants 256 pulmonary edema 259 Acyanotic with a shunt (left-to-right) 163 without a shunt 163 Adenosine 486 Adrenal insufficiency 356 Adrenaline 383 Airway and respiratory support 380 Alagille syndrome 407 Amiodarone 486 Amplatzer device 426 Analgesic doses 458 Anaphylaxis 269 Aneurysm of the sinus of Valsalva 222 Angiotensin converting enzyme inhibitors 296 Anomalies of coronary arteries 449 Anomalous left coronary artery from pulmonary artery 137, 224, 475 Antiarrhythmic agents, used in children 488 Anticoagulation and aspirin 297 Antimicrobial drugs 322 Antistreptococcal antibodies 257 Aortic arch obstructions 211

early diastolic murmur 252 regurgitation 279, 280 stenosis 208, 277 valve dilatation 416 Aortopulmonary (AP) window 171, 439 septal defect 221 Apical four chamber view 369 mid-diastolic murmur 252 pansystolic murmur 252 Arrhythmias and heart blocks 480 classification of 142 in children 52, 142 Arterial complications 83 pressure monitoring 455 Arteriovenous fistula coronary 222 pulmonary 223 systemic 223 Asepsis 385 ASO natural history 258 values in SATH 258 Aspirin 340 Atrial fibrillation 481 flutter 149, 481 septal defect (ASD) 60, 70, 80, 169, 440, 422, 468, 502

532

Pediatric Cardiology

Atrial septostomy procedures 413 Atrioventricular septal defect (AVSD) 369, 441 Atrium 227 AV blocks 482 Axis detection 41

B Balloon atrial septostomy 413 pulmonary valvoplasty 415 valve dilatations 414 Becker muscular dystrophy 360 Benign adolescent chest pain 135 Beta-blockers and carvedilol 297 Bidirectional Glenn shunt 507 Blade and balloon dilatation atrial septostomy 414 atrial septostomy 414 Blalock-Taussig (BT) shunt 466, 505 Blood pressure measurement 10 Bradyarrhythmias 482 Breath holding spell 122 Broad QRS tachycardia 148 Bundle branch blocks 47 C Calcium channel blockade (CCB) 115 Cardiac arrhythmias 122 catheterization and angiography 80, 82, 217 complications of 83 causes 99, 120, 122 configuration 28 emergencies in the newborn 377 implications of changing lifestyle 388 interventions in complex congenital heart disease 426 manifestations in systemic illness 346 position related QRS changes 49 tamponade 309 Cardiopulmonary bypass (CPB) 434 Cardiovascular assessment 8 examination 378 surgery, general aspects of 434 Carditis, clinical picture of recurrence 251, 252, 256

Catheterization study 78 Cerebral protection strategies 489 Cervical aortic arch 225 Chamber identification 58 Chest deformity 22 examination 22 pain 5 causes of 133 in childhood 133 roentgenogram 347 with heart disease, clinical assessment of 1 Childhood pulmonary hypertension 111 Children on oral anticoagulation 508 Chorea 254, 256 Chromosomal disorders 403 Chronic carditis 253 rheumatic valvular disease 271 Circulatory support and inotropes 383 Closure of abnormal vascular communications 428 CNS dysfunction 486 effects 452 Coarctation of aorta 32, 64, 81, 211, 418, 439, 470, 504 Collagen synthesis, disorders of 361 vascular diseases 350 Colloid or crystalloids 383 Colloids 461 Common innocent heart murmurs 22 left-to-right shunts 169 medication 484 postoperative problems after pediatric cardiac surgery 476 Complete heart block 45 Congenital absence of the pericardium 304 Congenital anomalies of vena caval connection 227 Congenital heart diseases age at presentation of 153 age of onset of congestive failure aortic stenosis 155

Index

approach to cardiac catheterization 84 atrial septal defect 60, 155 cardiac malformations at birth 155 children 87 classification of mild 162 moderate 162 severe 162 coarctation of the aorta 155 complete transposition of the great arteries 155 complexity of 40 develop VT 146 dominant heart defects in males and females 157 drug exposure 158 benzodiazepines 158 carbamazepine 158 corticosteroids 158 diazepam 158 lithium 158 phenobarbital 158 phenothiazine 158 phenytoin sodium 158 thalidomide 158 valproate 158 echocardiogram for 60 epidemiology 153, 157 genetic syndromes 160 MRI in 66 newborns and infants 87 patent ducts arteriosus 155 persistent truncus arteriosus 155 prevalence of Indian scenario 155 selected congenital cardiovascular malformations 158 profile of congenital heart disease in India 156 pulmonic stenosis 155 risk factors 157 teratogens for alcohol 2 antimalignancy 2 carbamazepine 2 lithium 2 phenytoin 2

533

sodium valproate 2 trimethadione 2 viruses (especially rubella) 2 warfarin 2 Fallot 155 tricuspid atresia 155 ventricular septal defect 155 with higher prevalence of WPW syndrome 46 Congenital mitral insufficiency 226 stenosis 205, 226 valve lesions 449 pericardial defect 224 pulmonary vein stenosis 207 tricuspid stenosis 215 Connective tissue diseases 350 Conotruncal anomalies 371 Constrictive pericarditis 311 Continuous murmurs 19 Cor triatriatum 206, 225 Coronary angiogram 338 Coronary artery lesions classification according to diameter 337 in Kawasaki disease 336 Costochondritis 135 Critical aortic stenosis in the newborn 417 Critical pulmonary stenosis in the neonate 218, 415 Crystalloids 461 Cushing’s syndrome 356 Cyanosis with heart failure and decreased pulmonary blood flow 34 increased pulmonary blood flow 33 Cyanotic congenital heart defects 187, 180

D Dana point classification of pulmonary hypertension 110 Deep hypothermia and circulatory arrest 435, 453 Defects in diaphragmatic pericardium 305 Delayed after depolarization (DAD) 144 Derived hemodynamic variables 76 Diabetes mellitus 355

534

Pediatric Cardiology

Diagnostic cardiac catheterizations in children 75 tests for pediatric cardiomyopathy 288 Diastolic murmurs 19 Digoxin and diuretics 296 Dilated cardiomyopathy 52, 287 Dilation of systemic vein stenosis 421 Diseases atrial septal defects 80 cardiac 15 collagen vascular 350 complex cyanotic heart 162 congenital cardiac defects 205 cardiovascular 84, 290 heart 42, 50, 60, 153, 324 classification of 163 connective tissue 113, 350 coronary artery 342 cyanotic congenital heart 205 endocrine 346 glomerular 98 heart diseases in children 118 Kawasaki 304, 342 lifestyle related diseases 390, 396 lung 110 maternal autoimmune 367 myocardial 14, 92, 287 neuromuscular 359 noncommunicable 388 pediatric heart, X-ray chest for evaluation of 26 pericardial 139 polycystic kidney 98 pulmonary parenchymal 113 vascular obstructive 5 rheumatic fever 245 structural heart diseases 2, 54 thromboembolic 110 valvular 66 Dobutamine 383 Dominant heart defects in males and females 157 Dopamine 383 Double chamber right ventricle 81, 219, 228 orifice mitral valve 206 outlet right ventricle 194, 444

Drugs used in the treatment of cardiac failure in children 510 of childhood hypertension 106 hypertensive emergencies 102 D-transposition of great arteries 33, 197, 506 Duchenne’s muscular dystrophy 359

E Ebstein’s anomaly of tall P waves 51 tricuspid valve 46 ECG in acute rheumatic carditis 260 acute rheumatic fever 260 changes in acute pericarditis 307 evaluation 125 hypertrophic cardiomyopathy 139 patient with moderate pulmonary stenosis 217 parasternal long axis view showing vegetation on aortic valve 321 patient with moderate aortic stenosis 209 RF 261 monitoring 454 pericarditis 140 practical approach to the pediatric electrocardiogram 40 showing evidence of a large global pericardial effusion 308 viral myocarditis 139 Echo coronary artery lesions 336, 337 Echocardiography, basics of 54 Ectopia cordis 229 Ehlers-Danlos syndrome 362 Eisenmenger’s syndrome 38 Electrolyte management 462 Ellis-van Crevald (EVC) syndrome 407 Endocrine and metabolic conditions 355 Endomyocardial biopsy 295 Endothelin receptor antagonists 116 Epinephrine 484 Erythema marginatum 254 ESR 257 Estimated 22q11 deletion frequency in congenital heart disease4 405

F Factors contributing to raised PVR 479

Index Factors determining magnitude of left-to-right shunts 171 Factors influencing left-to-right shunt 172 Factors influencing procedural outcome 240 Failure to wean from ventilator 484 Femoral cannulation 78 Fetal cardiac hemodynamics 366 cardiology 365 circulation 366 congestive heart failure 373 echocardiography 365, 371 echocardiography, indications for 367 examinations 368 m-mode echocardiography showing ectopic atrial beats 372 Frank-Starling curves 89 Friedreich’s ataxia 360 Fungal endocarditis 322

G Gastrointestinal effects 453 Genetic heritable syndromes commonly associated with congenital heart disease 160 syndromes with CHD, genetic counseling in 160, 409 Gestational and natal history 1 Glycogen storage disorders 346 Graves’ disease 358

H Heart disease in the newborn, diagnosis and initial management of 376 Heart failure in children 86 age at presentation for various forms of 87 clinical features of 89 Heart murmur classification of 17 rate 477 size 28 sounds 14, 378 Hematological conditions 358 Hemitruncus arteriosus 229 Hemodynamic assessment 236 monitoring 454

535

Hemodynamics 173 Hemostasis 82 Hepatic dysfunction 491 Holter monitoring and event recorder 126 Holt-Oram syndrome 406 Hyperaldosteronism 356 Hyperoxia test 379 Hypertensive emergencies 102 urgency 104 Hyperthyroidism 357 Hypoparathyroidism 358 Hypoplastic seft heart syndrome 195 Hypothermia 489 Hypothyroidism 357

I Identification of organism 258 Idiopathic chest pain (ICP) 135 dilatation of the pulmonary artery 230 Illegal drugs and tobacco 159 Imaging pulmonary veins 59 the great vessels 58 Immuno-inflammatory effects 453 Implantable loop recorder (ILR) 126 Indolent carditis 253 Infection control 465 Infective endocarditis in children 317 complications of 323 diagnosis of 318 neonates 318 Infundibular pulmonary stenosis 219 Inhaled nitric ixide (INO) 115 Innocent murmurs of childhood 21 Inotropic agents in the acute care setting 93 Intermittent cerebral perfusion 490 Interrupted aortic arch (IAA) 214 Intrapericardial tumors 312 Intrauterine interventions 374 Intravascular stents in congenital heart disease 427 Intravenous inotropes and vasodilators 296 Ipsilateral lung 72 Isoproterenol 383, 485

536

Pediatric Cardiology

J Jugular venous distension 310 Junctional ectopic tachycardia (JET) 480 Juvenile idiopathic arthritis (JIA) 354 K Kawasaki disease diagnosis and management 328 other modalities of therapy 341 time sequence of principal findings 329

L Laboratory parameters 319 Leading causes of chest pain in children 135 Left atrial enlargement 44 sided obstructions, clinical features of 206 ventricular dysfunction in children, correctable causes of carnitine deficiency 290 critical aortic stenosis 290 ectopic atrial tachycardia 290 hypophosphatemia 290 infantile beriberi 290 selenium deficiency 290 Shoshin beriberi 290 Takayasu’s arteritis 290 tachyarrhythmias 290 Left ventricular hypertrophy 47, 48 Left-to-right shunts 168 Limitations of echocardiography 59 fetal echocardiography 367 Location of common murmurs 16 Low cardiac output causes of 477 clinical indicators of 476

M Magnetic resonance angiogram delineating discrete coarctation of aorta 213 resonance imaging and computed tomography of chest 213 Magnitude and definition of the problem 390 Management of acute pericarditis 308 fetal arrhythmias 371

fetal patient with cardiovascular disease 369 patients with left to right shunts 175 pulmonary hypertensive crisis 479 syncope 127 CNS injury 488 Marfan’s syndrome 361 Maternal alcohol 159 conditions 2 dactors 158 diabetes 158 Measurement of blood pressure 96 Mechanical ventilation 456 Metabolic and genetic work-up 294 Metabolic indicators of low cardiac output 476 Microdeletion syndrome and FISH 404 Mild mitral regurgitation 259, 263, 271, 279, 284 mitral stenosis 273, 278, 283 valve dilatation 419 involvement in carditis 262 Mixed lesions 283 Moderate mitral regurgitation 263 Modes of pain management 459 Modified Jones criteria 1992 251 Monitoring during catheterization 78 transport 385 Morphology of AML in carditis 261 PML in carditis 261 MRI in congenital heart disease 66 Mucopolysaccharidosis (MPS) 349 Muscle enzyme assays 295 relaxants 459 Myocardial disease 287

N Neonatal hypertension 107 lupus 352 Neurocardiogenic or reflex syncope 120 Neurologic symptoms 5 Neuromuscular diseases 359 Newborn during transport, care of 385 Nonpharmacological measures 128

Index Noonan syndrome 406 Norepinephrine 485 Normal or nearly normal ventricles 165

O Obstructed total anomalous pulmonary venous connection 35 Obstructive congenital heart diseases, classification of 205 lesions 31 Open vs closed heart surgery 434 Operations for TGA 474 requiring the use of conduits 507 Opioids 459 Orthostatic hypotension 121 Osteogenesis imperfecta 362 Oxygen consumption 79 saturation 378

P Palliative procedures 465 vs corrective surgery 435 Parachute mitral valve 206 Paralysis and pain management 458 Patent ductus arteriosus 62, 170, 425, 438, 469, 502 Pauciarticular 355 Pediatric cardiac postoperative intensive care 451 Percutaneous balloon angioplasty and stenting 213 Perforation of the heart 83 Pericardial cysts 305 disease 303 fluid analysis, characteristic features of 308 Perinatal changes in vascular resistances influencing left-to-right shunting 171 Persistent pulmonary hypertension of the newborn 110 Persistent truncus arteriosus 34 Pheochromocytoma 356 Phosphodiesterase inhibitors (PDE 5) 116 Polyarteritis nodosa (PAN) 352 Polyarthritis 253, 255 Polyarthritis/mild carditis 267

537

Polyarticular 355 Polycythemia and anemia 82 Pompe’s disease 51, 52, 346, 348 Postoperative pulmonary hypertension, diagnosis of 479 Potential environmental risk factors 157 PR segment, analysis of 45 Precatheterization assessment 77 Precordial examination 12 Predicting the natural history of congenital heart disease 235 Predictors of coronary artery lesion 338 Predisposing factors 490 Premature atrial complex (PAC) 144 ventricular contraction 481 Presentation of cardiac arrhythmias 144 problems 1 Pressure limited ventilation 457 Prevention of adult cardiovascular disease 388 syncope on long-term basis 128 Primary hypertension 101 Prostacyclin and its analogues 115 Prostaglandin infusion table 180 Pseudocoarctation of the aorta 231 Puffy eyelids and peripheral edema 4 Pulmonary hypertension in children 109 and airway complications 483 arterial blood flow 164 artery intact ventricular septum 82, 192 with intact intravascular stents (IVS) 426 with VSD 82 banding 438, 466, 507 pressure (PAP) monitoring 455 stenosis 230 auscultation 23 edema 483 effects 452 hypertension, Dana point classification of 110 stenosis 215 valve dilatation 414 disease 283

538

Pediatric Cardiology

valvular and RV function 69 vein dilation 422 Pulse characteristics 8 oximetry 456

Q Q waves in inferior leads 50 QRS complex, analysis of 47 QRS tachycardia 149 QRS vector 50 QT prolongation 42 Quincke’s sign 9, 280 R Radionuclide imaging in pediatric cardiology 73 Rationale for adequate analgesia and sedation in postoperative period 458 Rationale of drug therapy 276 Recording the effect of adenosine to diagnose tachyarrhythmia 150 Regimen of antibiotic prophylaxis recommended 325 Regional analgesia 460 Renal effects 452 failure 490 parenchymal disorders 98, 100 disease 99 Renovascular hypertension 101 Repair of partial or complete AV canal 472 pulmonary atresia 193 ToF/pulmonary atresia with MAPCAs 191 tricuspid atresia 185 Residual aortic arch obstruction 482 lesions 482 Respiratory assessment 11 infections 4 Retrograde left heart catheterization 79 Rheumatic diseases 245, 350 fever 248, 245 and the valves 250 carditis clinical picture 252, 258

clinical dilemmas in 255 in adults 256 major criteria SATH 249 pathogenesis of 249 treatment, algorithm for 268 Right and left atrial pressures 455 atrial enlargement 44 pulmonary artery 63 sided obstructions 215 ventricular hypertrophy 47, 48 factors and congenital heart defect 157 for neurological dysfunction 486 Role of cardiac MR in fetal cardiology 71 Rubella syndrome 231 Ruling out sepsis 387 RV to PA patent homograft 65

S Scimitar syndrome 232 Screening for hypertension 96 Seasonal variation of KD 331 Secondary hypertension 97, 98 prophylaxis 269 Sedation protocol 55 Senning operation 474 Sepsis in children 491 Severe coarctation of aorta 213 Ebstein’s anomaly of tricuspid valve 35 mitral regurgitation 263 pulmonary stenosis with tricuspid regurgitation 35 Short PR interval, causes of 46 Shunt at aortopulmonary level 164 atrial level 163 ventricular level 31, 163 more than one level 164 Sickle cell anemia 359 Signs of cardiac disease 3 cardiac tamponade 310 CHF 178 Chvostek 290

Index

congestive heart failure 173, 216, 221, 232 congestive heart failure and pulmonary overcirculation 184 constrictive pericarditis 311 corrigan 280 de Musset 280 de Quincke’s 280 Duroziez murmur 280 Ewart’s 306 heart failure 90 inadequate cardiac output 454 Kussmaul’s 312 left atrial enlargemen 207 ventricle and left atrial enlargement 361 ventricular dysfunction 12 ventricular volume and pressure overload 212 low cardiac output 311 Muller 280 multiple organ dysfunction 289 pulmonary arterial hypertension 206 hypertension 207, 226 right ventricular failure 218, 507 shock children 3 systemic venous congestion 4, 216 Trousseau 290 ventricular hypertrophy 360 Single gene disorders 406 ventricle physiology 82 Sinus bradycardia 482 Situs identification 57 Snow man appearance’ or ‘Figure of 8’ 35 Spinal muscular atrophy (SMA) 361 Spontaneous closure of defects 238 ST segment, analysis of 49 Standard transducer positions 55 Steroids 341 Strep throat, clinical diagnosis of 270 Subaortic stenosis 210 Subcutaneous modules 256 Supramitral stenosing ring 206 Supravalvar aortic stenosis 211 Supraventricular tachycardia (SVT) 480

539

Surgical management of single ventricle 447 options for the treatment of end-stage heart disease 298 therapy 268 treatment 273 Syndromes absent pulmonary valve 37 acute coronary 103 Alagille 160, 161 asplenia 27, 28 Bartter’s 363 brady-tachy 122 Brugada 49, 119, 122, 124, 125, 146 congenital rubella 231 Cri du chat 160 Cushing’s 98, 99 DiGeorge 160, 161, 200 Down’s 160, 161 Eisenmenger’s 38, 136 Ellis-Van Creveld 160 fetal alcohol 159 Friederich’s 136 Genetic heritable 160 Goldenhar 160, 161 Gordon 98, 99 heart-hand 160 hemolytic uremic 98 Holt-Oram 160, 161 hypoplastic left heart 64, 87, 50, 157, 158, 195 Kartagener’s 230 Liddle 98, 99 long QT 43, 120, 122, 138, 144 Lutembacher’s 163 Marfan 136, 153 maternal alcohol 159 mitral valve prolapse 134 neurocutaneous 98 Noonan’s 160, 161 Pierre-Robin 160 polysplenia 27, 28 precordial catch 133, 135 primary autonomic failure 120 pulmonary valve 161 respiratory distress 97 Scimitar 30, 232

540

Pediatric Cardiology



sick sinus 120, 122, 125 Smith-Lemli-Opitz 160, 161 thromobocytopenia absent radius (TAR) 160 Tietze 133, 135 Trisomy 13 160 Turner’s 99, 160, 161 velocardiofacial 160, 161 William’s 99, 136, 160, 161 Wolff Parkinson White 46, 51, 119, 120, 122, 134, 145, 146, 148, 153 Systemic artery to pulmonary artery 505 hypertension in children 95 lupus erythematosus 350 Systolic murmur 17

T T wave analysis of 49 inversion 53 Tachyarrhythmia after the initial event, drug treatment of 151 diagnosis and management of 146 Takayasu’s arteritis 352 Taussig-Bing anomaly 232 Tetralogy of Fallot (TOF) 36 62, 81 187, 442, 471, 505 TGA with VSD 446 Thalessemia major 358 Thyroid disorders 357 Tietze syndrome 135 TOF with pulmonary atresia 443 Torsades de pointes 123 Total anomalous pulmonary venous connection (TAPVC) 34, 442, 473 Total anomalous pulmonary venous return 181 Transcatheter closure of intracardiac shunts 422 replacement of other valves 429 pulmonary valve 429 Transducer positions in levocardia 55 Transportation of sick newborn infants with heart disease 384 Transposition of great arteries (TGA) 197, 444 Treatment of GAS infection 266

Treatment of persistent hypertension 104 rheumatic fever in adult 267 Tricuspid tresia classification of 184 with normally related great arteries with ASD and VSD 184 regurgitation 371 valve disease 282 Triggered activity 144 Truncus arteriosus 81, 200, 447, 475 Types of fluids 461 Types of interrupted aortic arch 214 Types of systolic murmurs 18

U Univentricle 202 Univentricular atrioventricular connection 202 Univentricular hearts 371 Upper airway complications 483 Urine output 456

V Valvar aortic stenosis 208, 504 involvement in echocardiography in carditis 260 pulmonary stenosis 215, 503 Valvular aortic stenosis (AS) 31, 32 regurgitation 482 Vasculitis and connective tissue diseases 304 Vasoactive agents 487 Vasodilators 273 Venous examination 10 Ventricular arrhythmias 481 fibrillation 481 septal defect 61, 81, 424, 440, 469, 503 Vital sign assessment 8 Volume limited ventilation 457

W Weaning 457 Weight gain 4 WHO criteria 2004 251

Index

X X-ray chest finding in tetralogy of Fallot with absent pulmonary valve syndrome 37 for evaluation of pediatric heart diseases 26 from patients with different degree of shunt at ductal level 31 in left-to-right (L to R) shunts 30 in patient with tetralogy of Fallot 36



541

of patient with critical PS with severe tricuspid regurgitation 32 PA view showing situs inversus 27 showing large midline liver with dextrocardia 28 signs of left atrial enlargement 207

Z Z score value 56