Challenging Cases in Pediatric Cardiology [1 ed.] 1581103182, 9781581103182

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Editor: W. Robert Morrow, MD, FAAP Written in a case-based format, this valuable resource is intended to familiarize primary care physicians with common and uncommon cardiac conditions that they may see in their practice so they can better care for their patients. Cases are grouped by treating location: office, nursery, emergency department, and pediatric intensive care unit. Following the case presentation, each chapter steps through a differential diagnosis, evaluation, treatment, and discussion. Key issues are reinforced as Practice Points, and high-quality images support and enhance in-depth understanding of critical concepts. Topics include

MORROW

Pediatric Cardiology in the Office • A Child With Stomach Pain • A New Murmur and Rash • An Athlete With a Murmur Pediatric Cardiology in the Nursery • Cyanosis in a Newborn • A Loud Murmur in a Neonate Without Symptoms • Tachypnea and Poor Pulses Pediatric Cardiology in the Emergency Department • Cardiac Arrest in an Adolescent • Recurrent Seizure and a Family History of Sudden Death • Fainting and Bradycardia Pediatric Cardiology in the Pediatric Intensive Care Unit • Wide QRS Tachycardia and Heart Failure • Failure to Thrive in a 6-Week-Old • Wheezing and Recurrent Pneumonia And more…

Challenging Cases inPediatric Cardiology

Challenging Cases in Pediatric Cardiology

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AAP

Challenging Cases in Pediatric Cardiology W. ROBERT MORROW, MD, FAAP EDITOR

Challenging Cases in Pediatric Cardiology W. ROBERT MORROW, MD, FAAP EDITOR

American Academy of Pediatrics Publishing Staff Mary Lou White, Chief Product and Services Officer/SVP, Membership, Marketing, and Publishing Mark Grimes, Vice President, Publishing Carrie Peters, Editor, Professional/Clinical Publishing Theresa Wiener, Production Manager, Clinical and Professional Publications Peg Mulcahy, Manager, Art Direction and Production Linda Smessaert, MSIMC, Senior Marketing Manager, Professional Resources Mary Louise Carr, MBA, Marketing Manager, Clinical Publications Published by the American Academy of Pediatrics 345 Park Blvd Itasca, IL 60143 Telephone: 630/626-6000 Facsimile: 847/434-8000 www.aap.org The American Academy of Pediatrics is an organization of 67,000 primary care pediatricians, pediatric medical subspecialists, and pediatric surgical specialists dedicated to the health, safety, and well-being of infants, children, adolescents, and young adults. The recommendations in this publication do not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. Statements and opinions expressed are those of the authors and not necessarily those of the American Academy of Pediatrics. Any websites, brand names, products, or manufacturers are mentioned for informational and identification purposes only and do not imply an endorsement by the American Academy of Pediatrics (AAP). The AAP is not responsible for the content of external resources. Information was current at the time of publication. The persons whose photographs are depicted in this publication are professional models. They have no relation to the issues discussed. Any characters they are portraying are fictional. The publishers have made every effort to trace the copyright holders for borrowed materials. If they have ­inadvertently overlooked any, they will be pleased to make the necessary arrangements at the first opportunity. This publication has been developed by the American Academy of Pediatrics. The contributors are expert authorities in the field of pediatrics. No commercial involvement of any kind has been solicited or accepted in development of the content of this publication. Every effort has been made to ensure that the drug selection and dosage set forth in this text are in a­ ccordance with the current recommendations and practice at the time of publication. It is the responsibility of the health care professional to check the package insert of each drug for any change in indications and dosage and for added warnings and precautions. Every effort is made to keep Challenging Cases in Pediatric Cardiology consistent with the most recent advice and information available from the American Academy of Pediatrics. Special discounts are available for bulk purchases of this publication. Email Special Sales at [email protected] for more information. Copyright © 2020 American Academy of Pediatrics All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means—electronic, mechanical, photocopying, recording, or otherwise—without prior permission from the publisher (locate title at http://ebooks.aappublications.org and click on © Get permissions; you may also fax the permissions editor at 847/434-8780 or email [email protected]). Printed in the United States of America 9-436/0420        1 2 3 4 5 6 7 8 9 10 MA0462 ISBN: 978-1-58110-318-2 eBook: 978-1-58110-485-1 Library of Congress Control Number: 2019944893

Contributors Jeffrey Anderson, MD, MPH, MBA, FAAP Professor of Pediatrics Cincinnati Children’s Hospital University of Cincinnati School of Medicine Cincinnati, OH Chapter 19: Tachycardia With Fetal Hydrops Joshua J. Blinder, MD, FAAP Staff Physician Division of Cardiac Critical Care University of Pennsylvania Perelman School of Medicine Philadelphia, PA Chapter 27: Syncope and Exercise Intolerance in an Adolescent Girl Joseph A. Camarda, MD Clinical Practice Director, Pediatric Cardiology Ann & Robert H. Lurie Children’s Hospital of Chicago Assistant Professor Northwestern University Feinberg School of Medicine Chicago, IL Chapter 12: An Athlete With a Murmur Waldemar F. Carlo, MD Associate Professor of Pediatrics University of Alabama at Birmingham Birmingham, AL Chapter 14: Sports Participation in a Child After Heart Surgery

Chesney Castleberry, MD Associate Professor of Pediatric Cardiology Dell Medical School at the University of Texas at Austin Medical Director, Pediatric Transplant Program Dell Children’s Medical Center Austin, TX Chapter 13: Syncope During a Basketball Game Jennifer Co-Vu, MD Assistant Professor Director, Fetal Cardiac Program UF Health Congenital Heart Center Gainesville, FL Chapter 6: Family History of Sudden Death Richard J. Czosek, MD Professor of Pediatrics The Heart Institute Cincinnati Children’s Hospital Cincinnati, OH Chapter 32: Wide QRS Tachycardia and Heart Failure Joshua Daily, MD, MEd Assistant Professor of Pediatrics Division of Pediatric Cardiology University of Arkansas for Medical Sciences Arkansas Children’s Hospital Little Rock, AR Chapter 34: Failure to Thrive in a 6-Week-Old

iv  Contributors Allison Divanovic, MD, FAAP Associate Professor of Pediatrics Associate Director, Fetal Heart Program The Heart Institute Cincinnati Children’s Hospital Cincinnati, OH Chapter 30: Hemiplegia in a 17-YearOld Athlete

Kenneth Knecht, MD Division of Pediatric Cardiology University of Arkansas for Medical Sciences Arkansas Children’s Hospital Little Rock, AR Chapter 2: Cyanosis Without a Murmur Chapter 35: Wheezing and Recurrent Pneumonia

Brian K. Eble, MD, FAAP Associate Professor of Pediatrics Division of Pediatric Cardiology University of Arkansas for Medical Sciences Little Rock, AR Chapter 9: Fainting in an Adolescent at School Chapter 11: Chest Pain With Exercise

Jarrod D. Knudson, MD, PhD, FACC Associate Professor of Pediatrics Chief, Pediatric Critical Care University of Mississippi Medical Center Jackson, MS Chapter 24: Recurrent Seizure and a Family History of Sudden Death

Erik G. Ellsworth, MD Director, Cardiac MRI Division of Pediatric Cardiology Phoenix Children’s Hospital Phoenix, AZ Chapter 26: Cardiac Failure and Abnormal Electrocardiogram in an Infant John Hambrook, MD Division of Pediatric Cardiology Aurora Health Milwaukee, WI Chapter 15: An Abnormal Electrocardiogram in an Athlete Steven J. Kindel, MD Medical Director, Advanced Heart Failure and Heart Transplantation Associate Professor of Pediatrics Children’s Hospital of Wisconsin Medical College of Wisconsin Milwaukee, WI Chapter 23: Syncope in an Adolescent Athlete

Joshua Kovach, MD Assistant Professor of Pediatrics Herma Heart Institute Children’s Wisconsin-Milwaukee Hospital Medical College of Wisconsin Milwaukee, WI Chapter 18: Cardiogenic Shock in a 2-Day-Old Elena N. Kwon, MD, FASE Director of Pediatric Echocardiography Assistant Professor of Pediatrics Division of Cardiology Cohen Children’s Medical Center New Hyde Park, NY Chapter 20: Small Heart With “White Out” on a Chest Radiograph Ryan A. Leahy, MD, MS Associate Professor of Pediatrics University of Colorado Children’s Hospital of Colorado Aurora, CO Chapter 10: A New Murmur and Rash

Contributors  v Aimee Liou, MD, FSCAI, FAAP Assistant Professor of Pediatrics Division of Pediatric Cardiology Baylor College of Medicine Texas Children’s Hospital Houston, TX Chapter 25: Increasing Shortness of Breath With Exercise Keila N. Lopez, MD, MPH, FAAP Assistant Professor of Pediatrics Director, Transition Medicine Division of Pediatric Cardiology Baylor College of Medicine Texas Children’s Hospital Houston, TX Chapter 7: Tachypnea in a 6-Week-Old Adam Lowry, MD Assistant Professor of Pediatrics University of Central Florida College of Medicine Nemours Cardiac Center Nemours Children’s Hospital Orlando, FL Chapter 17: A Loud Murmur in a Neonate Without Symptoms Scott L. Macicek, MD Division of Pediatric Cardiology Texas Children’s Hospital Houston, TX Chapter 4: Unexplained Tachycardia Peace Madueme, MD, MS Director, Advanced Non-Invasive Cardiac Imaging Nemours Children’s Hospital Orlando, FL Chapter 8: Cyanosis in a 4-Year-Old Boy

Shiraz A. Maskatia, MD Associate Director, Fetal Cardiology Associate Professor, Department of Pediatrics Division of Pediatric Cardiology Stanford University School of Medicine Stanford, CA Chapter 1: Refractory Supraventricular Tachycardia and Hypotension Shaine A. Morris, MD, MPH, FAHA, FAAP Associate Professor of Pediatrics Division of Pediatric Cardiology Medical Director of Cardiovascular Genetics Associate Director of Pediatric Cardiology Fellowship Program Baylor College of Medicine Texas Children’s Hospital Houston, TX Chapter 29: A Toddler With Failure to Thrive, Hypotonia, and a Heart Murmur W. Robert Morrow, MD, FAAP Professor of Pediatrics University of Arkansas for Medical Sciences Little Rock, AR Chapter 31: Recurrent Stridor in a 9-Year-Old Chapter 33: Acute Onset of Hemiplegia With Murmur Mary C. Niu, MD, FAAP Director, Exercise Physiology Service Division of Pediatric Cardiology University of Utah Salt Lake City, UT Chapter 21: Tachypnea and Poor Pulses

vi  Contributors Mark D. Norris, MD, MS Assistant Professor Division of Pediatric Cardiology University of Michigan Ann Arbor, MI Chapter 16: Cyanosis in a Newborn Fred H. Rodriguez III, MD, FAAP Assistant Professor of Pediatrics and Internal Medicine Divisions of Pediatric Cardiology and Adult Congenital Cardiology Emory University School of Medicine Atlanta, GA Chapter 5: A Child With Stomach Pain Anas Salkini, MD Pediatric Cardiologist The Children’s Hospital Oklahoma City, OK Chapter 22: Cardiac Arrest in an Adolescent

David Saudek, MD Associate Professor of Pediatric Cardiology Children’s Hospital of Wisconsin Medical College of Wisconsin Milwaukee, WI Chapter 28: Fainting and Bradycardia Pamela Sayger Cava, DO Department of Pediatrics Ascension Medical Group Racine, WI Chapter 3: Enlarged Cardiac Silhouette on Chest Radiography

Contents Preface............................................................................................................................ ix Part 1. Pediatric Cardiology in the Office Chapter 1. Refractory Supraventricular ­Tachycardia and Hypotension................3 Chapter 2. Cyanosis Without a Murmur................................................................... 11 Chapter 3. Enlarged Cardiac Silhouette on Chest Radiography............................19 Chapter 4. Unexplained Tachycardia........................................................................27 Chapter 5. A Child With Stomach Pain..................................................................... 33 Chapter 6. Family History of Sudden Death............................................................43 Chapter 7. Tachypnea in a 6-Week-Old .................................................................. 49 Chapter 8. Cyanosis in a 4-Year-Old Boy.................................................................. 55 Chapter 9. Fainting in an Adolescent at School.......................................................61 Chapter 10. A New Murmur and Rash..................................................................... 69 Chapter 11. Chest Pain With Exercise........................................................................77 Chapter 12. An Athlete With a Murmur....................................................................85 Chapter 13. Syncope During a Basketball Game......................................................91 Chapter 14. Sports Participation in a Child ­After Heart Surgery......................... 99 Chapter 15. An Abnormal Electrocardiogram in an ­Athlete................................107 Part 2. Pediatric Cardiology in the Nursery Chapter 16. Cyanosis in a Newborn......................................................................... 117 Chapter 17. A Loud Murmur in a Neonate ­Without Symptoms......................... 123 Chapter 18. Cardiogenic Shock in a 2-Day-Old.....................................................129 Chapter 19. Tachycardia With Fetal Hydrops.........................................................135 Chapter 20. Small Heart With “White Out” on a Chest Radiograph................. 141 Chapter 21. Tachypnea and Poor Pulses..................................................................149 Part 3. Pediatric Cardiology in the Emergency Department Chapter 22. Cardiac Arrest in an Adolescent.......................................................... 159 Chapter 23. Syncope in an Adolescent Athlete.......................................................167 Chapter 24. Recurrent Seizure and a Family ­History of Sudden Death............177 Chapter 25. Increasing Shortness of Breath With ­Exercise.................................. 185 Chapter 26. Cardiac Failure and Abnormal ­Electrocardiogram in an Infant.... 191 Chapter 27. Syncope and Exercise Intolerance in an Adolescent Girl................199

viii  Contents Chapter 28. Fainting and Bradycardia.................................................................... 207 Chapter 29. A Toddler With Failure to Thrive, ­Hypotonia, and a   Heart Murmur......................................................................................................... 215 Part 4. Pediatric Cardiology in the Pediatric Intensive Care Unit Chapter 30. Hemiplegia in a 17-Year-Old Athlete..................................................225 Chapter 31. Recurrent Stridor in a 9-Year-Old....................................................... 233 Chapter 32. Wide QRS Tachycardia and Heart ­Failure.........................................243 Chapter 33. Acute Onset of Hemiplegia With ­Murmur........................................ 251 Chapter 34. Failure to Thrive in a 6-Week-Old......................................................261 Chapter 35. Wheezing and Recurrent Pneumonia................................................271 Index............................................................................................................................ 279

Preface There are many textbooks of pediatric cardiology, most of which provide a comprehensive approach to the subject. This is not one of those books. Rather, our goal is to provide the pediatric health care professional with a representative sample of discussions of pediatric cardiac diagnoses presenting in a variety of pediatric care settings. The idea for this approach came in 2 ways. The initial inspiration for this book was a series of symposia given by me and others several years ago at the American Academy of Pediatrics (AAP) National Conference & Exhibition by using a case-based approach to diagnoses that were commonly encountered in pediatric practice or were less common but potentially lethal. The case-based approach to these “challenging cases” was so enthusiastically received that I was motivated to collect and provide more. Almost simultaneously, the AAP Section on Cardiology and Cardiac Surgery (SOCCS) Executive Committee was approached by AAP Publishing representatives with the opportunity to add to the Publishing Challenging Cases series. The executive committee decided to undertake the project and I was selected to lead the effort. In keeping with the SOCCS emphasis on encouraging the development of fellows and junior faculty in pediatric cardiology, we reached out to the faculty and fellows of 4 pediatric cardiology programs to contribute cases. The result is this collection of 35 cases in a format not unlike the presentations made at the AAP symposia. In each chapter a case is presented as the pediatric health care professional might encounter it, thought-provoking questions are asked, a differential diagnosis specific to the case is presented, and evaluation and treatment are described. A discussion focused on the issues raised by the case presentation follows, and emphasis is then placed on particular aspects to keep in mind and points to remember that are specific to pediatric practice. A concerted effort was made to be concise and to only provide content that was directly relevant to the practice of primary care pediatrics. Likewise, our goal was to provide information that is consistent with the current practice of pediatric cardiology and that conforms to AAP guidelines and policies. The information in these chapters is from multiple texts and scientific publications and the material has been compiled and arranged in what we hope is a useful format. In the interest of being concise, individual references for specific content have not been provided, although lists of additional resources are provided for pediatric health care professionals who wish to learn more. With any effort of this kind there are many to thank. First, I would like to thank all the contributors of cases, not only for their contribution but also for their patience and professionalism through the long gestation of this book. I would also like to thank Stuart Berger, MD; Steven Neish, MD; and Robert

x  Preface Spicer, MD, for their invaluable assistance in the initial collection of these cases. Daniel R. McMillan, PhD, is to be thanked for his assistance in transforming these chapters into their current format. I would like to express deep gratitude to the AAP for its ongoing commitment to the care of children and to educating those who provide that care. I am also very grateful to Carrie Peters, editor, professional/clinical publishing, and the AAP editorial and production team. Her artful management of the project, consistent leadership, and patience during the last 2 years have been instrumental in the successful publication of this book. Many thanks go to my colleagues in the division of pediatric cardiology, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, for the many ways they assisted with the collection of cases and illustrative material for this book. I would also like to thank the many members of the AAP SOCCS for their scientific review. Finally, I am very grateful to my wife, Susan J. Morrow, and my family for their patience and support despite my absence in mind or body while completing this text. Our hope is that this text, while not exhaustive, will be a useful day-to-day resource for pediatric health care professionals who may encounter difficult or challenging cases in pediatric cardiology. W. Robert Morrow, MD, FAAP

PART 1

Pediatric Cardiology in the Office

‹‹‹‹ CHAPTER 1 ››››

Refractory Supraventricular ­Tachycardia and Hypotension Presentation A 6-week-old white boy is seen in your office for being fussy and spitting up more than usual for approximately 2 days. The parents describe increasingly rapid and shallow breathing, which they term “panting.” At initial triage in your office, the infant’s heart rate is too rapid to count, and pulse oximetry immediately registers a heart rate of 280 beats/min (bpm) with an oxygen saturation of 96%. He is irritable but appears well perfused and looks well, although his blood pressure is hard to measure. He is afebrile, and his respiratory rate is 60 breaths per minute. His lungs are clear at auscultation, and his liver is not enlarged at examination. His neurological examination is essentially intact. In the office, you observe him to have occasional coughing followed by retching. Further history reveals that he has had no sick contacts, rash, recent trauma, change in bowel movements, or jitteriness. His parents indicate that his urine output has not changed appreciably. He was delivered vaginally at term. He has been taking cow’s milk formula, approximately 2 to 5 ounces every 3 hours, and has been feeding well until these recent changes. There is no family history of congenital heart disease, sudden death, or heart attacks at age younger than 50 years. There is no family history of other congenital defects, and he has no siblings. You immediately send the infant to the emergency department (ED) for further evaluation and treatment. ː Other than the heart rate of 280 bpm, are there any symptoms or signs suggesting clinically significant distress in this otherwise healthy infant? ː Are there any interventions that you could make in your office to evaluate or treat this infant’s tachycardia?

4  Challenging Cases in Pediatric Cardiology

Differential Diagnosis In an infant presenting with tachycardia and distress, the differential diagnosis should include the following: ː Sinus tachycardia © Fever © Thyrotoxicosis © Hypovolemia © Sepsis © Supraventricular tachycardia ː Atrial flutter ː Ventricular tachycardia

Evaluation The ED staff use a cardiorespiratory monitor, obtain a chest radiograph, obtain an electrocardiogram (ECG), and order a cardiology consultation. The chest radiograph demonstrates mild cardiomegaly. There are mildly increased pulmonary vascular markings bilaterally (Figure 1.1). His ECG demonstrates a narrow QRS complex, short R-P tachycardia (retrograde P waves), and a heart rate of 280 bpm (Figure 1.2).

Figure 1.1. Anteroposterior chest radiograph showing mild cardiomegaly.

Figure 1.2. Electrocardiogram showing narrow QRS complex tachycardia consistent with a diagnosis of supraventricular ­tachycardia. The heart rate is 280 beats/min. Because of the high ventricular rate, retrograde P waves are not visible.

Chapter 1. Refractory Supraventricular ­Tachycardia and Hypotension  5

Treatment The ED physicians quickly administer adenosine (0.1 mg/kg) via a peripheral intravenous (IV) line, followed by a physiologic (normal) saline solution flush, with no effect. Administration of adenosine (0.2 mg/kg) results in slowing of the ventricular rate to the 250s, without termination of the tachycardia. Increasing the adenosine dose (0.4 mg/kg) terminates the tachycardia and recovers sinus rhythm at a rate of approximately 130 bpm. The postcardio­ version ECG demonstrates ventricular preexcitation (Figure 1.3). His fussiness improves at termination of the tachycardia, with improved perfusion.

Figure 1.3. Electrocardiogram after conversion of tachycardia demonstrating preexcitation typical of Wolff-Parkinson-White syndrome. Preexcitation, indicated by the upward sloping of the QRS complex (arrows), is caused by the depolarization of the ventricle from the atrium via the accessory pathway before depolarization through the atrioventricular node.

A physiologic saline fluid bolus (20 mL/kg) is administered after the conversion of the patient’s rhythm, and an oral dose of propranolol (1 mg/kg) is adminis­ tered. Approxi­mately 15 minutes after administration of the propranolol and 1 hour after termination of the tachycardia, the nursing staff find that the patient is severely tachypneic, with a respiratory rate of 100 breaths/min. He then has a transient decrease in his heart rate to the 70s, with spontaneous recovery. At that time, his perfusion appears to be considerably worse, and his extremities are cool to the touch. He continues to experience transient bradycardia, until his heart rate decreases to the 40s. The nursing staff initiate cardiopulmonary resuscitation. The ED staff administer a code dose of 0.01 mg/kg epinephrine intravenously. His heart rate responds, but his perfusion continues to worsen. Cardiology staff obtain a bedside echocardiogram that demonstrates severely depressed left and right ventricular function. Venous blood gas measurement at the time demonstrates a pH of 6.8, a partial

6  Challenging Cases in Pediatric Cardiology pressure of venous carbon dioxide of 68, and a base deficit of 23. The ED staff then perform rapid sequence intubation, administer multiple doses of sodium bicarbonate, obtain central venous access, and start a dopamine infusion at 10 mcg/kg/min via a peripheral IV line. The follow-up chest radiograph after intubation demonstrates increased pulmonary edema and moderate right pleural effusion (Figure 1.4). The patient is transferred to the pediatric intensive care unit, where the team starts an epinephrine infusion. A follow-up echocardiogram demonstrates slightly improved ventricular function. The team performs a transfusion of 20 mL/kg of packed red blood cells, administers a stress dose of hydrocortisone 1 mg/kg and starts empiric broad-spectrum antibiotics (ampicillin and gentamicin). The patient’s acidosis begins to improve, and his hemodynamic status stabilizes. As his blood pressure stabilizes, milrinone is added as a continuous infusion of 0.4 mcg/kg/min.

Figure 1.4. Chest radiograph after ­cardiac deterioration and intubation showing increased cardiomegaly, ­pulmonary edema, and right p ­ leural effusion.

Over the course of the following 2 days, the patient is weaned from the epinephrine and dopamine; he then is weaned from the milrinone over the ensuing 2 days. The patient’s function normalizes on echocardiography, and he is extubated without incident. He then is transferred to the cardiac ward and oral sotalol at 100 mg/m2/d is initiated to prevent recurrence of the tachycardia.

Discussion Supraventricular tachycardia (SVT) occurs in 1 of 250 to 1,000 children and is the most common symptomatic tachyarrhythmia that requires medical intervention. In general, SVT is suspected when the pulse rate exceeds 180 bpm in children and adolescents and exceeds 220 bpm in infants. The term supraventricular tachycardia refers to any tachycardia that originates above the level of the ventricles: reentrant rhythms that include the ­atrioventricular (AV) node and AV reentry tachycardia, atrial flutter, atrial fibrillation, junctional tachycardia, atrial ectopic tachycardia, sinus tachycardia, and sinus node reentry tachycardia. In addition, the QRS complex may appear narrow in ventricular tachycardia in infants, particularly neonates, when compared with ventricular tachycardia in adolescents or adults, which makes the differentiation of SVT and ventricular tachycardia (VT) considerably more difficult. The most common mechanism for SVT in infants is AV node reentry (Figure 1.5).

Chapter 1. Refractory Supraventricular ­Tachycardia and Hypotension  7

MV TV

AVN HB

A

MV TV AP

AVN HB

B

Figure 1.5. Mechanisms of supraventricular tachycardia, including AVN reentry (A) and APs (B). A, In AVN reentry, the cycle of reentry occurs within the AVN and depolarization of the ventricles occurs via the HB. B, In Wolff-­Parkinson-White syndrome, the cycle of reentry tachycardia occurs with the depolarization traveling through the AVN and HB and ventricles and then retrograde to the atrium through the AP. This is referred to as orthodromic tachycardia. (AP, accessory pathway; AVN, atrioventricular node; HB, His bundle; MV, mitral valve; TV, tricuspid valve.)

In AV node reentry, the tachycardia circuit is within the AV node, resulting in conduction to the ventricle through the His bundle and a narrow QRS complex. In tachycardias mediated through accessory pathways (ie, WolffParkinson-White [WPW] syndrome), the tachycardia circuit usually involves conduction to the ventricles through the AV node, ­producing a narrow QRS complex, and then back to the atrium through the accessory pathway (orthodromic tachycardia). The accessory pathway may conduct in an anterograde (from atrium to ventricle) or a retrograde (from ventricle to atrium) direction during sinus rhythm. If conduction is anterograde, ventricular preexcitation occurs in sinus rhythm, resulting in the typical ECG seen in patients with WPW. In contrast to accessory pathway–mediated tachycardia, AV node reentry tachycardia is more common in adolescents and may occur via pathways at the AV node or within the AV node. The signs and symptoms associated with SVT vary significantly by age. Neonates and infants are much more likely to have nonspecific symptoms, such as irritability, difficulty feeding, and decreased level of activity. Infants in SVT for more than 48 hours are more likely to present with symptoms of heart failure. School-aged children may describe their palpitations as “chest pain” or as their heart “beeping.” Older children will recognize palpitations as an irregular heartbeat or light-headedness that may occur at rest or with activity. Incessant SVT is rare in older children compared with infants. Often tachycardia can be terminated in infants by using certain maneuvers, such as eliciting the diving reflex by placing an ice bag on the face or eliciting a vagal response through the gag reflex. Explaining these maneuvers before

8  Challenging Cases in Pediatric Cardiology performing them is very important so that the parents are reassured because these maneuvers may appear to be harmful to the infant. Vagal maneuvers, such as straining against a closed glottis, are useful in older children, who can learn to terminate tachycardia shortly after onset through these maneuvers. Although these maneuvers are useful in tachycardia of short duration (55%).

30  Challenging Cases in Pediatric Cardiology

Treatment On the patient’s arrival in the PICU, central access is obtained in preparation for continued IV treatment. The intensivist on call immediately starts dopamine and milrinone infusions for inotropic support and amiodarone to control tachycardia and consults pediatric cardiology. The patient’s rhythm stays predominantly in JET, although his heart rate is controlled to 100 to 130 bpm with amiodarone (Figure 4.4). The pediatric cardio­logist decides to continue oral amiodarone in the patient and considers ablation to terminate the tachycardia.

Discussion Tachycardia is a relatively common occurrence in the general pediatric population. Appropriately assessing tachycardia requires determining where it originated: the sinus node (sinus), above the ventricles (supraventricular), or within the ventricles (ventricular). The most common type is sinus tachycardia, which is relatively benign. Sinus tachycardia is the body’s physiological response to internal or external stressors. It usually is associated with other signs or symptoms, and only rarely is it the primary presenting sign. There are multiple causes of sinus tachycardia, and many are secondary to irritability, dehydration, pain, infection, and fever. It is important to understand the difference between sinus tachycardia and other, more pathological arrhythmias. In the pediatric population, a normal heart rate varies substantially with age. Likewise, the upper limits of sinus

Figure 4.4. Electrocardiogram demonstrating accelerated junctional rhythm after attempted rate control with adenosine. Arrows indicate P waves dissociated with QRS complexes.

Chapter 4. Unexplained Tachycardia  31 tachycardia vary. Generally, sinus tachycardia rarely exceeds 220 bpm in infants and preschool children. The most common tachyarrhythmia in infants and children is SVT, which can be difficult to distinguish from sinus tachycardia. In infants, SVT is typically in excess of 220 bpm (up to 280 bpm) and in older children and adolescents between 180 and 240 bpm. Most patients in sinus tachycardia with heart rates in the 200s are febrile, have sepsis, are dehydrated, or have some other underlying abnormality, whereas most patients with SVT tend to be in otherwise good health. There are several types of SVT, however. The 2 most common, AV reentrant tachycardia and AV nodal reentrant tachycardia, account for most cases. Typically, SVT has a narrow QRS with a one-to-one relationship between P waves and QRS. Reentry tachycardias characteristically are terminated by means of vagal maneuvers, adenosine, or cardioversion. Reentry SVT is usually well tolerated by infants and children and produces symptoms only after persisting for approximately 24 to 48 hours. A narrow QRS tachycardia that does not terminate with adenosine or cardioversion is likely to be ectopic in origin (atrial ectopic tachycardia or JET), as in this case. Automatic tachycardias (ectopic tachycardias) result from abnormal impulse generation in variable locations in the heart. Atrial ectopic tachycardia is seen most commonly in infants who have an indolent course with both a prolonged symptom-free period and ultimately the development of tachycardia-­ induced cardiomyopathy. JET is a rarer automatic tachycardia commonly seen immediately postoperatively after correction of congenital heart defects. The other major type of JET is congenital JET (as described in this case). The most common findings are a normal QRS tachycardia between 180 and 240 bpm with AV dissociation and more ventricular than atrial beats. With congenital JET, up to 370 bpm are recorded. Congenital JET also is associated with a tachycardia-­induced cardiomyopathy in a clinically significant number of patients. Automatic tachycardias, unlike reentry tachycardias, are difficult to terminate without invasive ablation procedures. Medications are used to control the heart rate while awaiting either spontaneous termination or achieving appropriate age, size, and weight to pursue ablation procedures.

Keep in Mind Abnormal tachycardia in infants and toddlers (1-3 years of age) often is unrecognized by parents until symptoms of cardiac insufficiency (heart failure) occur. In some cases, sporadic and sudden onset of irritability, fussiness, or tachypnea is the first indication of abnormal tachycardia. Toddlers who are verbal and young children may complain that their heart is “beeping.”

32  Challenging Cases in Pediatric Cardiology

Practice Points 1. Tachypnea and fussiness are common indications of abnormal tachycardia but often are attributed to other causes. 2. The most common abnormal tachycardia in infants and toddlers is SVT. The diagnosis is made by means of ECG where a narrow QRS tachycardia is seen with or without a one-to-one association with P waves. 3. The diagnosis of SVT is confirmed by termination via vagal maneuvers, IV administration of adenosine, or cardioversion. 4. Failure of a narrow QRS tachycardia to terminate with vagal maneuvers, with IV administration of adenosine, or with cardioversion is indicative of a tachycardia that does not involve reentry through the AV node and is suggestive of an automatic tachycardia (atrial ectopic tachycardia or JET). 5. JET may be difficult to eliminate with medication alone. An ablation may be necessary to restore normal heart rhythm if medication fails to do so. However, because of the proximity of the focus of the tachycardia to the AV node and the risk of damaging the AV node during ablation, the child may have to meet guidelines for age and size before the procedure can be performed safely.

Suggested Reading 1. Davignon A, Rautaharju P, Boisselle E, et al. Normal ECG standards for infants and children. Pediatr Cardiol. 1980;1(2):123–131 2. Collins KK, Van Hare GF, Kertesz NJ, et al. Pediatric nonpost-operative junctional ectopic tachycardia medical management and interventional therapies. J Am Coll Cardiol. 2009;53(8):690–697 3. Van Hare GF, Silva JNA. The normal electrocardiogram. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:547–564 4. Cannon BC, Snyder CS. Disorders of cardiac rhythm and conduction. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:623–653 5. Wackel PL. Palpitations and arrhythmia. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:147–159

‹‹‹ CHAPTER 5 ››››

A Child With Stomach Pain Presentation A 9-year-old white girl is seen in your office complaining of 5 weeks of abdo­ minal pain and increasing fatigue. The patient describes the pain as dull, achy, intermittent, and occasionally associated with chest tightness. She has had no recent illnesses or fevers. The patient’s mother cannot recall any trauma or viral type of illness during the previous several months. The patient has been referred to an allergist for chest tightness. The allergist prescribed prednisone and albuterol. She also has been referred to a gastroenterologist, who ordered abdominal ultrasonography for possible cholelithiasis. During your examination, the child appears anxious, with mild resting tachypnea. She prefers not to be supine, choosing to sit up during the examination. She has a heart rate of 100 beats/min and normal blood pressure. Her heart sounds are slightly muffled, with an S3 gallop. Her abdomen is mildly tender, particularly in the right upper quadrant and epigastrium. The liver edge is palpable, firm, and slightly tender. Her extremities are slightly cool, but there is no edema. There is no jugular venous distension. You decide to admit the patient to the hospital for further testing because of concern regarding a cardiac cause for the abdominal pain. ː What is the most concerning symptom that raises concern regarding a cardiac diagnosis? ː What sign at examination suggests a cardiac cause for abdominal pain? ː What critical studies should be performed to rule out a cardiac cause for this child’s discomfort?

34  Challenging Cases in Pediatric Cardiology

Differential Diagnosis Abdominal pain is a common symptom in children and has a broad differential diagnosis. Some important diagnoses to consider include the following: ː Gastroenterological © Gastroenteritis © Pancreatitis © Cholecystitis © Appendicitis © Peptic ulcer disease © Gastroesophageal reflux disease © Hiatal hernia © Hepatitis ː Gynecologic or urological © Ovarian torsion © Pelvic inflammatory disease © Ovarian cyst © Pyelonephritis or urinary tract infection ː Pulmonary © Reactive airway disease exacerbation © Pneumonia ː Cardiac © Dilated cardiomyopathy © Myocarditis © Structural heart disease with congestive heart failure

Evaluation After the patient’s admission, you begin the workup with chest radiography (Figure 5.1). The result shows severe cardiomegaly with left lower lobe atelectasis but no pulmonary edema. An ECG (­Figure 5.2) shows normal sinus rhythm and left ventricular enlargement (increased posterior voltage in the precordial leads). Results from laboratory analysis of electrolyte levels, renal function, and liver function are all normal. Ultrasonography ordered by the gastroenterology consultant confirms the presence of

Figure 5.1. Posteroanterior chest radiograph showing severe cardiomegaly with left lower lobe atelectasis. Left lower lobe atelectasis is commonly associated with severe cardio­ megaly because of compression of the left lower lobe bronchus by the left ventricle and left atrium.

Chapter 5. A Child With Stomach Pain  35

Figure 5.2. Electrocardiogram demonstrating markedly increased posterior and lateral voltage in the ­precordial leads and ST-T wave changes in the anterior precordial leads, which is diagnostic of left ventricular hypertrophy. The tracing also shows normal sinus rhythm.

hepatomegaly, and subsequent abdominal computed tomography (CT) reveals an enlarged liver that appears homogeneous without additional clinically significant hepatic findings. The CT also shows evidence of pericardial fluid. Because of the cardiomegaly and pericardial effusion, you ask for an echocardiogram and pediatric cardiology consultation. The echocardiogram shows a dilated left ventricle with severely depressed systolic function ejection fraction (20%) (­Figure 5.3). A small pericardial effusion is seen on the echocardiogram as well. There is no clinically significant valvular regurgitation. The pediatric cardiologist schedules cardiac catheterization to assess cardiac function and pulmonary arterial pressures and resistance.

Figure 5.3. Two-dimensional apical echocardiograms of diastole (A) and systole (B) showing severe LV dilatation and LA dilatation. There is little difference in LV size between diastole and systole and hence a very low ejection fraction. The measured ejection fraction is 20% (normal, ≥55%). (LA, left atrium; LV, left ventricle.)

36  Challenging Cases in Pediatric Cardiology

Treatment The pediatric cardiologist initiates treatment for heart failure with enalapril, furosemide, and spironolactone, with aspirin for anticoagulation. The patient has frequent premature ventricular contractions and a non-sustained 12-beat run of ventricular tachycardia on the ECG monitor (Figure 5.4). Amiodarone is administered orally for treatment of the ventricular tachycardia; after further monitoring, the child is discharged home. She is scheduled for follow-up treatment for congestive heart failure in the cardiology clinic.

Figure 5.4. Electrocardiogram showing non-sustained 12-beat run of ­ ventricular ­tachycardia with atrioventricular dissociation. V indicates ventricular depolarization.

Within days, the patient’s mother takes her to the emergency department for continued abdominal pain. Her physical examination again shows a gallop, a systolic ejection murmur, hepatomegaly with her liver margin 5 cm below the right costal margin, and clear breath sounds. She has diffuse bilateral upper quadrant tenderness but no rebound or guarding. Chest radiography is performed and shows cardiomegaly. Her initial brain natriuretic peptide level is 3,169 pg/mL (normal range, 1–100 pg/mL). The echocardiogram is repeated and shows worsening cardiac function. She has developed moderate right ­ventricular dysfunction, moderate to severe tricuspid regurgitation, and ­moderate mitral regurgitation. She is admitted to the pediatric intensive care unit and receives inotropic support (milrinone). After stabilization and improvement in symptoms, she is transitioned from intravenous inotropic support to oral carvedilol, and her other oral medications are continued. She is referred for evaluation for heart transplant.

Discussion Dilated cardiomyopathy (DCM), although relatively uncommon in general, is the most common type of cardiomyopathy seen in children. The incidence of pure DCM in childhood is 0.57 cases per 100,000 per year and is higher in

Chapter 5. A Child With Stomach Pain  37 boys than in girls, in blacks than in whites, and in infants (younger than 1 year) than in older children. It may be familial, with autosomal dominant, X-linked, and recessive forms; may occur after viral myocarditis; or may be associated with metabolic defects, including defects in mitochondrial respiratory chain enzymes. However, in many cases, the cause remains unknown. Unlike adults, children can tolerate substantial reductions of cardiac function without developing symptoms. Children rarely present with typical findings of congestive heart failure until near the end stage. It is not uncommon for the first presenting symptom to be abdominal pain or so-called abdominal angina. Assessing heart failure is particularly difficult in infants, but a classification developed by Ross et al is useful for grading the severity of congestive heart failure. The New York Heart Association grades heart failure on the basis of functional classifications from I to IV. This system relates symptoms to everyday activities and the patient’s quality of life. The American College of Cardiology and American Heart Association have developed a classification of heart failure on the basis of stages of the syndrome, graded from A to D. Guideline-based therapies are outlined for each of the stages. This classification system, however, is validated in adults and is not useful in young children. Historical findings may be helpful in diagnosing DCM in children. Children with heart failure have exertional fatigue and dyspnea that can be elicited with careful questioning. As noted, gastrointestinal symptoms may be the initial presenting symptoms of a child with heart failure, although the cause is not completely understood. Abdominal discomfort may be caused by decreased perfusion from a low cardiac output state. Venous congestion from impaired right-sided heart function also may play a role. A classification system for children has been developed using these symptoms and signs, as well as medical treatment, to predict severity (Table 5.1). Patients suspected of having cardiomyopathy should be evaluated for heart rate and rhythm, markers of systemic perfusion, and hepatomegaly. An ECG and echocardiogram also should be obtained when considering a ­diagnosis of heart failure. Arrhythmias of various types, including both atrial and v­ entricular dysrhythmias, can be seen in patients with DCM. As in this case, sinus tachycardia may be present. Left ventricular hypertrophy and ST-T wave changes also may occur. Varying degrees of heart blockage also may be seen. Highdegree heart blockage may require temporary pacing, and unstable arrhythmias should be treated emergently. If ventricular tachycardia is present or if there is a history of syncope, strong consideration should be given to placement of a pacing defibrillator, as well as long-term antiarrhythmic medication.

38  Challenging Cases in Pediatric Cardiology Table 5.1. The New York University Pediatric Heart Failure Index for Children Older Than 6 Months Score Signs and Symptoms +2

Abnormal ventricular function by echocardiogram or gallop

+2

Dependent edema of pleural effusion or ascites

+2

Failure to thrive or cachexia

+1

Marked cardiomegaly by radiograph or by physical examination

+1

Reported physical activity intolerance or prolonged feeding time

+2

Poor perfusion by physical examination

+1

Pulmonary edema by radiograph or auscultation

+2

Resting sinus tachycardia

+2

Retractions Hepatomegaly

+1

 4 cm below coastal margin Observed tachypnea or dyspnea

+1

 Mild to moderate

+2

 Moderate to severe

Medications +1

Digoxin Diuretics

+1

 Low to moderate dose

+2

 High dose or more than 1 diuretic

+1

ACE inhibitors or non-ACE inhibitor vasodilators or angiotensin receptor blockers

+1

β-blockers

+2

Anticoagulants not related to prosthetic value

+2

Anti-arrhythmic agents or ICD

Physiology +2

Single ventricle

Abbreviations: ACE, angiotensin-converting enzyme; ICD, implantable cardiac defibrillator. Heart failure severity is determined from signs and symptoms, medical regimen, and ventricular physiology. A total score is derived by adding scores attributed to each individual criterion. Scores can range from 0 (no heart failure) to 30 (severe heart failure). Reproduced with permission from Connolly D, Rutkowski M, Auslender M, Artman M. The New York University Pediatric Heart Failure Index: a new method of quantifying chronic heart failure severity in children. J Pediatr. 2001;138(5):644–648.

Chapter 5. A Child With Stomach Pain  39 Echocardiographic evaluation of heart function is the gold standard of diagnosis and should include quantitative analysis of both systolic and diastolic function. Measurement of left ventricular end-diastolic dimension, quantitative assessment of biventricular function, and Doppler interrogation for valvular regurgitation must be included. Cardiovascular magnetic resonance imaging may also be used to evaluate for the presence of inflammation (associated with myocarditis) or myocardial fibrosis (in cardiomyopathy). Cardiac catheterization, to assess pulmonary resistance and pulmonary vascular reactivity, is most useful as part of the evaluation for potential cardiac transplant. Laboratory tests that should be performed include assessing brain natriuretic peptide levels, complete chemistry panel, complete blood cell count, thyroid panel, and liver panel. If myocarditis is suspected, viral studies may be sent for analysis for potential culprits, including coxsackievirus, adenovirus, and parvovirus. Genetic testing for the detection of pathological mutations is also an important part of the complete evaluation of cardiomyopathy in children. Initial consideration of the symptoms and cause of DCM dictates initial treatment. Intravenous access should be obtained promptly. Dyspnea caused by pulmonary congestion should be treated without delay with intravenous loop diuretics. Diuretics help improve symptoms of acute heart failure by decreasing afterload. An initial dose of 1 mg/kg of furosemide is used in the acute setting, with escalation of the dose if needed. Patients who have low cardiac output with decreased perfusion and cool extremities may be candidates for milrinone therapy. A usual intravenous starting dose is 0.25 mcg/kg/ min, without a bolus dose. Milrinone is a vasodilator and is an inotropic and lusitropic agent, improving left ventricular relaxation. It should be used with caution when renal impairment is present because of potential toxicity. Other vasodilators, such as nitroglycerin, sodium nitroprusside, or nesiritide, also may be considered but are not commonly used in children. If suspicion is high for myocarditis, the patient may be considered for intravenous immunoglobulin treatment, although firm evidence of benefit is lacking. Long-term management of DCM with heart failure relies on treatment protocols that have, for the most part, been developed for adults with congestive heart failure, although there is some evidence of benefit in children. These protocols are based on the role of activation of the sympathoadrenal system in the pathological changes occurring in congestive heart failure. Elevated plasma renin, angiotensin, catecholamine, and natriuretic peptide levels lead to vasoconstriction, increased fluid retention, and increased cardiac mass. These changes can be reversed with early and aggressive treatment. Angiotensin-converting enzyme (ACE) inhibitors lower aortic pressure and systemic vascular resistance, do not affect pulmonary vascular resistance

40  Challenging Cases in Pediatric Cardiology clinically significantly, and lower left atrial and right atrial pressures in pediatric patients with heart failure. ACE inhibitors have shown a beneficial effect on prolonging the survival of infants and children with severe left ventricular dysfunction from DCM. The starting dose of enalapril is 0.05 mg/kg per dose twice daily, titrated slowly to a dose of 0.25 mg/kg per dose twice daily. Renal function and blood pressure must be monitored closely. Angiotensin-receptor blockers can be substituted for ACE inhibitors in patients with adverse effects. In adults, spironolactone is beneficial as an aldosterone inhibitor and may be used in children with congestive heart failure. β-blockers (metoprolol and carvedilol) are beneficial and improve outcomes before and during hospitalization in adults. Studies to date show some benefit in children with left-sided heart failure and cardiomyopathy. Patients who do not improve with medical therapy may be candidates for mechanical ventricular support and/or heart transplant. Outcomes for heart transplant are good, with 10-year survival rates better than 75%.

Keep in Mind Many pediatric patients with cardiomyopathy can be treated successfully with the combination of afterload reduction, diuresis, and β-blockade. It is common, though, for children with severely decreased function and enlarged hearts to deteriorate rapidly, even with heart failure management medication. Patients who are affected severely should be referred to a center capable of providing the full spectrum of treatment, including mechanical circulatory support and cardiac transplant.

Practice Points 1. Abdominal pain may be a symptom of heart failure in children and often is misdiagnosed. Likewise, hepatomegaly and growth failure may be signs of heart failure in infants and children when other symptoms or signs are ­absent. 2. Patients with abdominal pain and cardiomyopathy usually have severely reduced heart function and require urgent evaluation and treatment. 3. Symptom relief for heart failure can be obtained with diuresis; afterload reduction; and, when cardiac output is low, intravenous inotropic support. 4. Arrhythmia, particularly ventricular tachycardia, is a risk factor for sudden death in patients with cardiomyopathy and requires aggressive treatment.

Chapter 5. A Child With Stomach Pain  41

Suggested Reading 1. Lin KY, Rossano JW. Dilated cardiomyopathy. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:1283–1295 2. Ross RD, Bollinger RO, Pinsky WW. Grading the severity of congestive heart failure in infants. Pediatr Cardiol. 1992;13(2):72–75 3. Connolly D, Rutkowski M, Auslender M, Artman M. The New York University Pediatric Heart Failure Index: a new method of quantifying chronic heart failure severity in children. J Pediatr. 2001;138(5):644–648 4. Price JF. Congestive heart failure in children. Pediatr Rev. 2019;40(2):60–70 5. Lyon S, Sparks JD. Dilated cardiomyopathy. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:377–386 6. Towbin JA, Lowe AM, Colan SD, et al. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA. 2006;296(15):1867–1876

‹‹‹‹ CHAPTER 6 ››››

Family History of Sudden Death Presentation A 10-year-old girl is brought to your clinic because of a sudden death in the family and a history of syncope. The mother is very concerned and wants her daughter to be evaluated. The patient’s 25-year-old uncle collapsed while walking his dog 6 weeks earlier. He was pronounced dead by the time he reached the hospital. The autopsy reportedly showed that his heart was normal, but the exact cause of death was not identified. The patient is a healthy girl with no chronic illnesses, and she does not take medications. She had a syncopal episode, 2 years ago, while playing video games at home with her friends. She regained consciousness within a few ­minutes and resumed playing. She has no complaints of light-headedness, dyspnea, chest pain, or palpitations. The patient is cooperative and comfortable during the physical examination. She is afebrile, with a heart rate of 88 beats/min (bpm), respiratory rate of 18 breaths/min, and blood pressure of 92/60 mm Hg. Orthostatic blood pressures are normal. She is 100% saturated breathing room air. She has normal cardiac, respiratory, and neurological examinations. The rest of her physical examination is unremarkable. ː What aspects of the reported syncope in this patient raise concern? ː Is the sudden death of an uncle with no evidence of heart involvement ­reassuring? ː Is a normal cardiac examination also reassuring?

Differential Diagnosis Potential causes of syncope in children include the following: ː Neurocardiogenic syncope ː Vasovagal syncope

44  Challenging Cases in Pediatric Cardiology ː Orthostatic syncope (including postural orthostatic tachycardia syndrome) ː Arrhythmic syncope © Bradycardia or heart block © Tachycardia or ventricular fibrillation ƒ Long QT syndrome (other channelopathies) ː Syncope because of structural heart disease or cardiomyopathy (dilated, hypertrophic) ː Neurological loss of consciousness (seizure disorder, migraine)

Evaluation To evaluate the patient further for syncope and family history of sudden death, you order a 12-lead electro­cardiogram (ECG), which demonstrates normal sinus rhythm, a ventricular rate of 70 bpm, normal QRS axis, and a corrected QT interval (QTc) of 521 milliseconds (Figure 6.1). The prolonged QTc, a history of syncope, and sudden death in the family suggest a diagnosis of long QT syndrome (LQTS). You immediately refer the patient to a pediatric cardiologist and initiate plans to obtain ECGs in all her siblings, parents, and uncle’s children.

Figure 6.1. A 12-lead electrocardiogram demonstrating marked prolongation of the QT interval. The rate-corrected QT interval is 521 ms.

Treatment The pediatric cardiologist sends the patient for genomic testing, and she has LQTS type 1. β-blocker therapy (nadolol) is initiated as first-line treatment. In addition, the cardiologist restricts the child from activities known to precipitate torsades de pointes tachycardia and syncope or death and from

Chapter 6. Family History of Sudden Death  45 medications known to prolong the QT interval (https://crediblemeds.org/pdftemp/pdf/DrugsToAvoidList.pdf).

Discussion The clinical history should focus on circumstances surrounding suspicious events such as syncope, seizures, near drowning, and unexplained accidents. A comprehensive family history is essential to screen for unexplained sudden death before the age of 30 years, patterns of similar episodes of syncope, and congenital deafness. In this case, it is the history of sudden death in a relative that prompts the evaluation. The patient has been asymptomatic, and the only pertinent finding is her episode of syncope 2 years ago. Her syncopal episode could be of either cardiac or noncardiac origin. Cardiac syncope is caused by arrhythmias or structural heart disease. Noncardiac causes include reflex-mediated syncope (eg, neurocardiogenic syncope, vasovagal syncope), orthostatic hypotension, or neurological disease (eg, migraine headaches, seizures). Reflex-mediated syncope is the most common type of syncope in children, classically occurring with changes in posture from sitting to standing. Other precipitants for reflex-­mediated syncope include micturition, defecation, coughing, gagging, prolonged standing, and hair combing. The patient did not have a history suggestive of reflex-mediated syncope, with the single syncopal episode occurring while sitting and not associated with postural changes or other triggers. Malignant arrhythmias can manifest with palpitations, light-headedness, syncope, or sudden death. In this patient, with a history of syncope and a family history of sudden death, the suspicion for a malignant arrhythmia should be high in the differential diagnosis. Syncope caused by structural heart disease most often is seen during physical exertion. This patient’s normal physical examination and nonexertional syncope places structural heart disease lower in the differential diagnosis. An abnormal finding in the autopsy of her uncle (eg, hypertrophic cardiomyopathy) would have warranted stronger consideration for structural heart disease. An ECG should be obtained if LQTS is suspected, if syncope is associated with palpitations or chest pain, or if syncope occurs that does not fit the diagnosis of reflex-mediated syncope. The QT interval should be measured directly by the interpreting physician because computer-generated QT intervals are unreliable. The QT interval should be determined as a mean value derived from at least 3 to 5 cardiac cycles, measured from the onset of the QRS complex to the end of the T wave. The QT interval then should be adjusted for heart rate by using the Bazett formula by dividing the QT interval by the square root of

46  Challenging Cases in Pediatric Cardiology the R-R interval (in seconds) (Figure 6.2). This QTc is considered prolonged if greater than 460 milliseconds and borderline if it is 440 to 460 milliseconds. A patient with QTc prolongation and a history of syncope, by definition, has QTc = ⎯QT interval in seconds = QT LQTS. Acquired causes of QT prolon√ cardiac cycle in seconds √⎯ RR gation, usually caused by medications (eg, amiodarone, procainamide, clari- Figure 6.2. Method for heart rate correction of thromycin, amitriptyline), also should the QT interval by using the Bazett formula. ­be sought. Congenital LQTS is a rare cardiac condition with delayed repolarization after depolarization (excitation) of the heart associated with syncope and sudden death. The prevalence of LQTS is estimated to be from 1 in 2,500 to 1 in 7,000 people. Currently, there are at least 10 different genes in which mutations cause the LQTS phenotype. The LQTS genes encode proteins involved with sodium, potassium, or calcium ion channels. Most patients who are affected inherit the gene through a heterozygous mutation pattern, but patients who have the homozygous form of the disease present with greater clinical severity. Genetic testing for LQTS has become more accessible with the advancement of molecular genetics. Mutations causing LQTS type 1, 2, or 3 cause most genetically identifiable cases of LQTS. Thus, genetic testing may play an important role in screening family members for LQTS. However, a minority of patients with LQTS do not have an identifiable mutation despite clinical confirmation of the disease. Cardiac events, such as syncope and cardiac arrest, are due to a life-­threatening polymorphic arrhythmia (torsades de pointes tachycardia) (Figure 6.3). Deter­ mining a patient’s risk for a life-threatening cardiac event helps guide

Figure 6.3. Typical appearance of torsades de pointes (twisting of peaks) tachycardia, a ­variant of ventricular tachycardia characteristic of channelopathies.

Chapter 6. Family History of Sudden Death  47 appropriate, individualized therapy. On the basis of studies from the International Long QT Syndrome Registry, risk factors for cardiac events include sex, QTc duration, time-dependent syncope, and LQTS genotype (Figure 6.4). These risk factors have different weights for different age groups.

Figure 6.4. Different long QT syndrome genotypes are associated with different T-wave morphologies and impart different risk profiles. A, Long QT syndrome type 1 (as in this case) is more likely to result in sudden death during exercise. B, Type 2 is associated with higher risk as a result of sudden loud noises. C, Type 3 is more likely to be associated with sudden death during sleep.

A recent syncopal episode seems to be the most powerful predictor of subsequent life-threatening cardiac events. A QTc duration greater than 500 to 530 milliseconds (as in this case) also indicates a higher risk of sudden cardiac death. In children, boys have a 5-fold greater risk than do girls. In adults, the risk factor is reversed, and women have a 3-fold greater risk. β-blockers are the first-line therapy for LQTS because they decrease the risk of stress-induced arrhythmias by modulating adrenergic-mediated triggers. Use of β-blockers is associated with a marked reduction in the risk of lifethreatening cardiac events in patients with LQTS, but efficacy varies depending on the LQTS genotype. Implantable cardioverter defibrillators have shown efficacy in patients with LQTS who are at risk and may be effective in patients with LQTS who still experience life-threatening events despite β-blocker therapy. Placement of an implantable cardioverter defibrillator does not, however, obviate the need for medications that may decrease the number of shocks a patient receives. After LQTS is diagnosed, patients and families often need counseling because of the emotional effect of being at risk for sudden death. Patients and primary care physicians can find more information and support online at www.sads.org and www.nhlbi.nih.gov/health-topics/long-qt-syndrome.

48  Challenging Cases in Pediatric Cardiology

Keep in Mind Other measures to prevent cardiac events are of primary importance in certain LQTS genotypes; patients with LQTS type 1 should avoid strenuous physical activity, and patients with LQTS type 2 should avoid alarm clocks and other auditory triggers. Drugs that prolong the QT interval must be avoided. Once LQTS is diagnosed, ECGs should be obtained in all first-degree family members for screening purposes. If the proband has a genetically identifiable mutation, then genetic testing also can be used for screening family members.

Practice Points 1. Evaluation of a patient with a family history of early, sudden, or unexplained death should include a careful history of the circumstances of death; any symptoms of syncope, chest pain, or palpitations; and a thorough cardiac examination. 2. If arrhythmic syncope is suspected, an ECG should be obtained, and the ECG should be read with direct measurement of the QT interval. A computerized interpretation is unreliable in diagnosing an arrhythmia substrate. 3. Patients with a prolonged QT interval or other arrhythmic substrate on an ECG should undergo genetic testing to identify specific mutations. Family members should have ECGs obtained, at a minimum, and in some cases genetic testing as well.

Suggested Reading 1. Sivaswamy L, Gupta P. Syncope. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:133–146 2. Villafañe J. Long QT syndrome and other channelopathies. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:411–419 3. American Academy of Pediatrics Section on Cardiology and Cardiac Surgery. Pediatric sudden cardiac arrest. Pediatrics. 2012;129(4):e1094–e1102 4. Mauriello D. Electrocardiography. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:13–48 5. Tester DJ, Ackerman MJ. Cardiac channelopathies, syncope, and sudden death. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:565–578

‹‹‹‹ CHAPTER 7 ››››

Tachypnea in a 6-Week-Old Presentation A mother brings her 6-week-old Hispanic son to your clinic because of rapid breathing, decreased activity, and decreased urine output. The child had been seen 2 days earlier in the emergency department (ED) for coughing, emesis, and increased work of breathing. The patient’s mother indicated to the ED physicians that her son had symptoms of an upper respiratory tract infection, including congestion and fussiness, 3 days previously. She assumed he had caught a cold from another child in day care. The ED physicians diagnosed viral upper respiratory tract infection and discharged the patient home. Over the next 2 days, he began eating less and breathing faster, despite no fever or diarrhea. His urine output decreased, and he became less active, which precipitated her visit to your clinic. His mother insists that he had always seemed to breathe rapidly since birth, although he had a normal labor and delivery, which occurred in the home. During your examination, it is clear that the infant is tachypneic and cyanotic. His pulse oximetry is 85%, with a heart rate of 170 beats/min. His respiratory rate is 80 breaths/min. The infant appears well hydrated and has full pulses and normal capillary refill. At chest examination, he has mild to moderate subcostal retractions and coarse breath sounds with no wheezing or crackles. Cardiac examination reveals a narrowly split S2, with a 2/6 systolic ejection murmur loudest at the left lower sternal border and left upper sternal border, as well as a gallop. The liver edge is 1.5 cm below the right costal margin at abdominal examination. ː Which symptoms or signs exhibited by this patient suggest a cardiac issue? ː Does the history of birth and delivery suggest a potential diagnosis? ː What next steps should be performed in evaluating this patient?

50  Challenging Cases in Pediatric Cardiology

Differential Diagnosis Respiratory distress and cyanosis in infants may be caused by the following: ː Respiratory © Airway obstruction © Pneumonia © Pulmonary malformation ː Cardiac disease © Cyanotic (eg, total anomalous pulmonary venous return, Ebstein ­anomaly, tetralogy of Fallot) © Acyanotic ƒ Heart failure (eg, left-to-right shunts, cardiomyopathy) ƒ Infection (eg, myocarditis, pericarditis) ː Sepsis ː Other © Inborn errors of metabolism, severe anemia

Evaluation You have the infant transported to the local children’s hospital for further evaluation and treatment. Laboratory studies reveal a white blood cell count of 19,700/L, with 50% neutrophils and 34% lymphocytes. Urinalysis shows no evidence of infection. Given the infant’s degree of tachypnea, cultures for respiratory syncytial virus, influenza A and B, and adenovirus are sent, but results are negative. A chest radiograph shows no focal opacities but does show mild cardiomegaly and mild pulmonary interstitial edema with congested pulmonary vessels (Figure 7.1). Fullness of the superior mediastinum gives the so-called snowman appearance often associated with supracardiac total anomalous pulmonary venous return. An electrocardiogram (ECG) shows right-axis deviation, right atrial enlargement, and right ventricular hypertrophy (Figure 7.2). You obtain a pediatric cardiology consultation, and an echocardiogram is obtained, which shows a large secundum atrial septal defect (ASD) with unobstructed right-to-left flow (Figure 7.3). The pulmonary veins do not connect to the left atrium. A pulmonary venous confluence is seen posterior to the left atrium, draining the left-sided pulmo- Figure 7.1. Posteroanterior chest radio­ showing mild cardiomegaly, nary veins and the right upper pulmonary graph increased pulmonary interstitial m ­ arkings, vein, which then drain into a vertical vein and pulmonary vascular congestion.

Chapter 7. Tachypnea in a 6-Week-Old   51

Figure 7.2. Electrocardiogram showing right-axis deviation, right atrial enlargement, and right ventricular hypertrophy. Right ventricular hypertrophy is indicated by the qR pattern in V1 and V3R, high R-wave voltage in the anterior precordial leads, and deep S waves in V6 and V7.

that courses into the left innominate vein (Figure 7.4). All veins have nonobstructed low-velocity flow. Total anomalous pulmonary venous return (TAPVR) to the left innominate vein (type I) is diagnosed.

Treatment The patient is referred to the cardiac surgery service and is scheduled for immediate surgical connection of the pulmonary venous confluence to the left atrium.

Figure 7.3. Subcostal echocardio­gram showing a large ASD with unobstructed flow (blue) from the RA to the LA. The left pulmonary veins are not seen ­enter­ing the LA. (ASD, atrial septal defect; LA, left atrium; RA, right atrium.)

Figure 7.4. Suprasternal notch echocardiograms showing supracardiac total anomalous ­pulmonary venous return. In A, the PV CON is imaged posterior to the left atrium and flow (red) is away from the heart toward an ascending vein (Inn VEIN); in B, venous return occurs via an ascending vertical vein (Asc VEIN). (AO, aorta; Asc VEIN, ascending vein; Inn VEIN, innominate vein; PV CON, pulmonary venous confluence.)

52  Challenging Cases in Pediatric Cardiology

Discussion Total anomalous pulmonary venous return is a condition in which the pulmonary veins do not have a direct connection to the left atrium and instead drain into the right atrium or venous channel in communication with the right atrium. It is considered a cyanotic congenital heart defect. See Box 7.1 for the most common types of TAPVR (in order of frequency). To sustain life, oxygenated blood must reach the systemic circulation; therefore, nearly all patients with TAPVR require an ASD or patent foramen ovale for survival. Other features common to all patients with TAPVR include dilatation and hypertrophy of the right ventricle and right atrium because of increased venous return to the right side of the heart. In addition, there is often dilatation of the pulmonary artery. The left ventricle and left ventricular volume are typically normal. The left atrium is typically diminutive because it lacks pulmonary venous return. Cyanosis may not be readily apparent in the first week after birth because of the remarkable degree of pulmonary overcirculation in this defect. The exception is anomalous pulmonary venous return with obstruction, which manifests soon after birth. Given that the patient was born at home, neonatal screening for congenital heart disease was not performed. Parents often comment in retrospect that their infants have been breathing fast since birth. Infants who have nonobstructed TAPVR, as in this case, are initially tachypneic at rest and have baseline oxygen saturation between 87% and 95% but do not typically look cyanotic because of increased pulmonary blood flow. Over time, pulmonary overcirculation and pulmonary edema reduce lung compliance, resulting in worsening tachypnea, poor feeding, sweating with feeding, and failure to thrive. At physical examination, patients with TAPVR often have a Box 7.1. Types of Total Anomalous Pulmonary Venous Return Type I: Supracardiac Pulmonary veins that drain into venous structures superior to (above) the heart (~55%) Type II: Cardiac Pulmonary veins that drain into intracardiac structures, particularly the coronary sinus (~30%) Type III: Infracardiac Pulmonary veins that drain into venous structures below the diaphragm (~13%) Type IV: Mixed Connection at 2 or more of the type I, II, and III levels (~2%)

Chapter 7. Tachypnea in a 6-Week-Old   53 hyperdynamic precordium, pronounced S1 and S2 heart sounds, and a 2/6 systolic ejection murmur heartbeat at the left upper sternal border. Surgery to connect the pulmonary venous confluence to the left atrium is the definitive treatment and may be performed at any age. When obstruction is present, typically with infradiaphragmatic return, surgery is emergent. In addition, obstruction may be seen at the level of the ASD, and when this occurs surgery should be performed emergently or death may ensue.

Keep in Mind Infants with occult congenital heart disease may seem to have no symptoms, except for persistent tachypnea, which often is not recognized as cardiac in origin. Neonatal congenital heart disease screening is meant to detect cyanosis in infants who otherwise do not manifest symptoms or signs of congenital heart disease. This case antedated pulse oximetry screening in the newborn nursery and illustrates its potential benefit. Had screening been performed, this infant most likely would have received a diagnosis the first day after birth. It is important to remember, however, that even when screening is negative in the newborn period, cyanotic heart disease, and in particular acyanotic congenital heart disease, cannot be excluded completely.

Practice Points 1. In patients who are persistently tachypneic, congenital heart disease should be strongly considered. 2. Cyanosis may not be readily apparent at physical examination in patients with TAPVR but will be demonstrable on pulse oximetry. Infants who did not undergo neonatal screening for congenital heart disease should have documentation of oxygen saturation soon after birth at primary care ­follow-up. 3. Even in patients with unobstructed TAPVR, obstruction may develop at the atrial septum, resulting in the patient being in extremis or dying.

Suggested Reading 1. Ahmad H, Chowdhury D. Neonatal screening for heart disease. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:197–204 2. Brown DW, Geva T. Anomalies of the pulmonary veins. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:881–910

54  Challenging Cases in Pediatric Cardiology 3. Vanderlaan RD, Caldarone CA. Surgical approaches to total anomalous pulmonary venous connection. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2018;21:83–91

‹‹‹‹ CHAPTER 8 ››››

Cyanosis in a 4-Year-Old Boy Presentation A 4-year-old Nigerian boy is brought to your office by his adoptive American family. He arrived in the United States 2 months prior and seems to be adjusting well. He speaks English with an obvious accent and appears somewhat shy. He sits quietly during the evaluation and examination. His parents indicate that he is healthy with no obvious medical concerns and that his screening evaluation on entering the United States was noteworthy only for a heart murmur. He has a healthy appetite, now sleeps well after adjusting to new surroundings, and plays well without difficulty. The parents deny any respiratory difficulties, fatigue, or activity intolerance. His family history is unknown. The parents indicate that he habitually squats down during playful activities, although he resumes play after a short time. They think nothing of it, believing it might be a cultural practice. During your examination, the patient appears well, pleasant, and cooperative. His heart rate is 123 beats/min, and his respirations are normal. He is normotensive. His weight and height are below the 10th percentile. His cardiac examination shows increased precordial activity with 2/6 midfrequency systolic ejection murmur heard throughout but best at the left lower and midsternal border with radiation to the back. He has 2+ pulses in the upper and lower extremities. His extremities show mild cyanosis and subtle clubbing. A pulse oximetry probe is placed because of the findings of cyanosis and clubbing. His saturations are 75% to 80% in the office, despite changing out the device multiple times. ː What features of the patient’s history suggest possible cardiac disease? Which defect? ː What is the clinical significance of the history of adoption from a low-­ income country?

56  Challenging Cases in Pediatric Cardiology

Differential Diagnosis In a child this age with cyanosis and squatting, potential diagnoses include the following: ː Tetralogy of Fallot ː Double outlet right ventricle ː Ventricular septal defect with pulmonary stenosis ː Transposition of the great arteries with ventricular septal defect and pulmonary stenosis

Evaluation Because of the cyanosis and a ­murmur that does not sound like a functional murmur, you order a chest radiograph and an electrocardiogram (ECG). The radiograph shows mild cardiomegaly with diminished pulmonary blood flow and an upturned cardiac apex (Figure 8.1). The ECG shows right ventricular hypertrophy and rightaxis deviation (Figure 8.2). Right ventricular hypertrophy in this case is Figure 8.1. Posteroanterior chest radiograph indicated by the upright T wave showing abnormal cardiac contour with an in lead V1, as well as deep S waves in upturned cardiac apex. There are also diminished pulmonary vascular markings and mild V4 through V6. The T wave in lead V1 cardiomegaly. should be negative in a healthy child of this age. The patient is referred to a pediatric cardiologist because the abnormal findings on the chest radiograph and ECG indicate possible congenital heart disease. The pediatric cardiologist orders an echocardiogram (figures 8.3 and 8.4), which helps confirm the diagnosis of tetralogy of Fallot (TOF).

Treatment The patient is referred for elective repair of TOF. Surgery is uneventful and is accomplished with preservation of the pulmonary valve. He continues to be followed up annually.

Chapter 8. Cyanosis in a 4-Year-Old Boy  57

Figure 8.2. Electrocardiogram demonstrating right-axis d ­ eviation and right ventricular h ­ ypertrophy.

Figure 8.3. Apical 4-chamber view color flow Doppler echocardiogram showing a large-outlet ventricular septal defect (left panel; arrow) with bidirectional shunt (red and blue flow at the ventricular septal defect; right panel). (LV, left ventricle; RV, right ventricle.)

Discussion

Figure 8.4. Apical view swept anterior echocardiogram showing a narrowed right ventricular outflow tract and thickened pulmonary valve (left panel; arrow). Color flow Doppler shows signal aliasing indicative of obstruction beginning below the level of the valve (right panel). (PV, pulmonary valve; RVOT, right ventricular outflow tract.)

Tetralogy of Fallot is the most common cyanotic congenital cardiac lesion. It constitutes approximately 5% to 10% of all congenital cardiac lesions. The tetrad consists of right ventricular outflow tract (RVOT) obstruction, a ventricular septal defect (VSD), an overriding aorta, and right ventricular hypertrophy. The degree of RVOT obstruction is the most important and is the primary determinant of the presenting physiology and subsequent management. It is unusual in high-income countries for TOF to escape diagnosis in infancy. Typical TOF spells consist of paradoxical cyanosis associated with hyperpnea and tachycardia in infants. Because most children in high-income countries

58  Challenging Cases in Pediatric Cardiology have TOF diagnosed and undergo repair during infancy, children presenting with a history of squatting with exertion has become uncommon. It is helpful to understand the physiology of TOF to explain the occurrence of spells and squatting. Blood tends to follow the path of least resistance. Blood will cross the VSD from right to left, depending on the amount of downstream resistance within the pulmonary and systemic circuits. Right ventricular outflow tract obstruction will cause high resistance within the pulmonary circuit, thereby causing more blood to shunt from the right ventricle to the left ven­tricle. Pulmonary resistance is elevated for the first 2 to 3 weeks after birth, which also contributes to increased right-to-left shunt. In a similar fashion, cyanosis is lessened by increasing systemic vascular resistance or decreasing pulmonary vascular resistance, both of which lead to increased pulmonary blood flow and decreased right-to-left shunting at the VSD. The effect of resistance on shunt explains the occurrence of hypercyanotic spells (tet spells) in infants with unrepaired TOF. A change in the balance of systemic resistance (lower) and pulmonary resistance (increased because of pulmonary stenosis) leads to an acute increase in right-to-left shunt at the ventricular level, usually because of a change in the balance between pulmonary and systemic resistances. Deoxygenated blood, with no easy egress into the pulmonary vascular bed because of increased RVOT obstruction or increased resistance will cross the VSD to the left ventricle and aorta, which causes the oxygenated blood and desaturated blood to mix leading to clinical cyanosis and hyperpnea. Immediate treatment for a tet spell is aimed at increasing systemic vascular resistance to force more blood from the left to the right via the VSD and thus decrease the amount of cyanosis. This effect may be accomplished by the knee-to-chest maneuver or systemic vasoconstrictors such as ketamine or phenylephrine. Morphine is useful because it suppresses the respiratory drive, diminishes hyperpnea, and thus decreases the amount of venous return contributing to the right-to-left shunt. Historically, β-blockers also have been used because of their effects on inotropy and chronotropy, thus leading to less dynamic outflow tract obstruction within the right ventricle. Several lesions may simulate TOF physiology, including the following: ː Ventricular septal defect with pulmonary stenosis ː Double outlet right ventricle, VSD with pulmonary stenosis ː Transposition with VSD and pulmonary stenosis

Chapter 8. Cyanosis in a 4-Year-Old Boy  59

Keep in Mind Surgical correction is recommended at diagnosis, or as soon as possible thereafter, in patients with classic TOF with pulmonary stenosis. Precise timing depends on the degree of cyanosis, severity of pulmonary obstruction, and pulmonary artery anatomy. In neonatal patients with TOF with pulmonary atresia, systemic-to-pulmonary arterial shunts may be used in lieu of surgical correction. Interventional catheterization techniques may also be used to place endovascular stents in the ductus arteriosus to maintain ductal patency, in lieu of surgical shunts.

Practice Points 1. A high index of suspicion should be maintained for undiagnosed conditions, including congenital heart disease, in children from low-income countries. 2. Classic history and physical findings of TOF are observed infrequently in the current era because of early diagnosis and surgical repair. 3. Although β-blockers may be indicated as a temporizing measure, repair of TOF should be performed as soon as possible after diagnosis.

Suggested Reading 1. Madsen NL. Tetralogy of Fallot. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:329–333 2. Roche SL, Greenway SC, Redington AN. Tetralogy of Fallot with pulmonary stenosis, pulmonary atresia, and absent pulmonary valve. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:1029–1052 3. Karl TR, Stocker C. Tetralogy of Fallot and its variants. Pediatr Crit Care Med. 2016;17(8 suppl 1):S330–S336 4. Jacobs JP, Mayer JE Jr, Mavroudis C, et al. The Society of Thoracic Surgeons Congenital Heart Surgery Database: 2016 update on outcomes and quality. Ann Thorac Surg. 2016;101(3):850–862

‹‹‹‹ CHAPTER 9 ››››

Fainting in an Adolescent at School Presentation A 14-year-old white girl is brought to your office after she passed out at school. She complains of multiple syncopal episodes over the past year. The first episode was when she was ill with acute viral gastroenteritis while on a family ski trip. She had risen from bed and walked up stairs, became light-headed and weak, and collapsed at the top of the staircase. She was unresponsive for approximately 20 seconds and then quickly returned to her normal mental status. There were no further episodes until she had rare brief syncopal episodes several months ago, and, after 1 of these, she was seen in a local emergency department (ED). She had an additional episode in the ED during an attempted blood draw. The patient’s syncopal episodes have now become more frequent, occurring several times per week. They commonly occur after arising from bed or standing up from her desk at school, and a few have occurred after stepping out of the shower. She very frequently describes dizziness and light-­headedness after standing from a supine or sitting position, typically several times per day, although most of these episodes do not progress to loss of consciousness. When she does become truly syncopal, she is unresponsive for less than 1 minute. She has never injured herself during any of these falls. There is no history of tonic-clonic movements or incontinence of bowel or bladder during any of these episodes. She has had a single syncopal episode associated with exercise. However, she indicates it was during a track meet at school, and it was the longest event she had ever run. Immediately after completing the race, she felt weak, dizzy, and light-headed. Despite her coach’s suggestion to sit down, she walked over to get a drink and fell to the ground just before reaching the water cooler. She reports normal exercise tolerance and is active in her school’s athletic program. There is no history of chest pain or unusual shortness of breath. She

62  Challenging Cases in Pediatric Cardiology reports palpitations—specifically, her heart races “hard and fast” shortly after becoming dizzy during most of her episodes. She denies symptoms of subjective tachycardia at rest or irregular heartbeat. She drinks “a couple” glasses of tea or milk during a typical day but does not like to drink water. She never urinates at school because the school washrooms are “gross.” The patient’s medical history is otherwise unremarkable. Her mother has a history of mitral valve prolapse and infrequent episodes of syncope as an adolescent. She “grew out” of the syncope symptoms in her 20s. There is no other family history of congenital heart disease, long QT syndrome, cardiomyopathy, sudden death, early myocardial infarction, or unexplained death in young adults. During examination she is an athletic female adolescent who appears well. Her blood pressure is low normal at 95/60 mm Hg while supine and decreases slightly to 80/45 when standing. Her heart rate increases from 70 beats/ min (bpm) while supine to 90 bpm after standing. Her vital signs are other­ wise within normal limits for her age. A complete physical examination, including a detailed cardiac examination, is otherwise normal. The point of maximal impulse is located normally in the 5th intercostal space at the midclavicular line. S1 is normal, and S2 is physiologically split. There is a soft 1/6 smooth-sounding, medium-pitched, systolic ejection murmur along the left sternal border with the patient supine, but it completely disappears with a Valsalva maneuver or with the patient standing. Diastole is quiet, and there are no clicks, rubs, or gallops. Pulses are 2+ throughout, with no brachiofemoral delay. Her gross neurological examination results are normal, and she has a normal, ­pleasant affect. ː What is the most likely diagnosis on the basis of the history and examination? ː Is the history of palpitations of concern? ː Is additional evaluation needed to exclude other potential causes?

Differential Diagnosis Syncope, a common diagnosis in adolescents, may be caused by any of the following: ː Reflex-mediated syncope © Neurocardiogenic (including orthostatic and postural orthostatic ­tachycardia syndrome) © Vasovagal ː Structural heart disease © Severe left ventricular obstruction © Myocarditis © Cardiomyopathy

Chapter 9. Fainting in an Adolescent at School  63 © Coronary arterial anomaly or disease ː Arrhythmic syncope © Bradycardia or complete heart block © Tachycardia or ventricular fibrillation ƒ Long QT syndrome (other channelopathies, including Brugada ­syndrome) ƒ Wolff-Parkinson-White syndrome ː Neurological loss of consciousness (seizure disorder, migraine) ː Conversion disorder ː Drug or toxin ː Hypoglycemia ː Primary pulmonary hypertension

Evaluation The history of orthostatic changes or stress precipitating most syncopal ­episodes is consistent with a diagnosis of neurocardiogenic syncope. The diagnosis is supported by the patient’s examination and a lack of relevant family history. You order an electrocardiogram (ECG), primarily to rule out the unlikely possibility of long QT syndrome or hypertrophic cardiomyopathy. The ECG is normal for the patient’s age, and a manually calculated corrected QT interval is also normal at 0.42 seconds (Figure 9.1).

Figure 9.1. Normal electrocardiogram demonstrating a normal calculated corrected QT interval (QTc) (QTc = 0.42 s). Manual calculation is necessary because the computer-derived QTc is unreliable.

Treatment The patient and her parents are reassured that syncope is common among adolescents and is not a dangerous or life-threatening condition. The pathophysiology of neurocardiogenic syncope is reviewed with the family, and you suggest that the patient increase her salt and fluid intake. You counsel her to drink at least 12 glasses of noncaffeinated beverages per day and that if her urine is yellow then she needs to drink more until it is clear. You also provide a

64  Challenging Cases in Pediatric Cardiology school note requesting that the patient be allowed to carry a water bottle at all times and have unlimited washroom privileges. The patient returns for follow-up in 2 months. Her symptoms are improved, although she still experiences syncope on average once per week. She states that she has been compliant with the increased salt and fluid intake, that her urine is now almost always clear, and that she urinates at least 2 or 3 times during the school day. In consultation with your pediatric cardiologist, you initiate treatment with fludrocortisone 0.1 mg every morning. Her symptoms dramatically improve, with only occasional episodes of dizziness, typically when she forgets to take the fludrocortisone, and no further episodes of syncope. After 3 years, her symptoms have resolved completely, and the medication is discontinued.

Discussion Syncope is a sudden, brief loss of consciousness and postural tone with spontaneous recovery, typically secondary to inadequate cerebral blood flow and oxygen delivery. It is extremely common in children and adolescents, occurring in up to 35% of the population. The causes for syncope range from benign fainting to life-threatening cardiac causes. Neurocardiogenic syncope is the most common and likely constitutes 50% to 80% of syncope in adolescents. Typical triggers for neurocardiogenic episodes include upright posture, stress, pain, dehydration, cough, micturition, and hair brushing. Patients frequently report a prodrome that may include symptoms of weakness, pallor, heart pounding, dizziness, light-headedness, visual disturbances, or nausea. Loss of consciousness is typically less than 1 minute, although complete recovery may take as long as 30 minutes, with persistent fatigue and weakness. The pathophysiology of neurocardiogenic syncope is complex and incompletely understood, although it usually begins with upright posture and venous pooling in the lower extremities. Decreased cardiac stroke volume and blood pressure sensed by arterial baroreceptors result in increased sympathetic tone, which normally maintains cardiac output. However, in susceptible people, vigorous contractions of an underfilled heart lead to an abrupt sympathetic withdrawal (Bezold-Jarisch reflex), causing hypotension and bradycardia, and subsequent loss of consciousness. Although cardiac syncope is relatively rare in children and adolescents, a thorough evaluation is warranted to exclude potentially life-threatening disease. A detailed history is critical in evaluating the patient with syncope. Activity and circumstances during episodes, premonitory symptoms, duration of unconsciousness and time to full recovery, and other clinically significant illnesses and concurrent medications are crucial in understanding the nature

Chapter 9. Fainting in an Adolescent at School  65 of the syncopal episodes. Family history, especially of syncope, sudden death, or cardiomyopathy, is also very important. The physical examination should include supine and standing blood pressure, as well as a thorough cardiovascular examination. An ECG is indicated in all patients who have experienced true loss of consciousness, with particular attention to the corrected QT interval, possible preexcitation, presence or absence of heart block, and left ventricular hypertrophy. Long QT syndrome and other channelopathies (eg, Brugada syndrome), hypertrophic cardiomyopathy, and severe aortic stenosis (Figure 9.2) may cause syncope and sudden death and may be detected by characteristic findings on an ECG. Occasionally, cardiologists will use head-up tilt table testing (tilt test) in patients whose diagnosis is inconclusive after initial evaluation and history. Treatment for neurocardiogenic syncope begins with reassurance of the patient and family regarding its benign nature. Syncope may provoke extreme anxiety, especially with media coverage of rare sudden cardiac death events in adolescent athletes. Patients should be counseled to avoid dehydration, caffeine, or standing for prolonged periods. The importance of salt and fluid intake cannot be overemphasized, as well as encouraging consistent breakfast habits. Some patients may prefer swallowing salt tablets, rather than adding more table salt to their food. Loss of consciousness may be stopped by assuming a supine position at the onset of presyncopal symptoms. Pharmacological therapy may include fludrocortisone, a mineralocorticoid that increases renal sodium and fluid retention, increasing the circulating blood volume; midodrine, an α-agonist that increases peripheral vascular resistance; selective serotonin reuptake inhibitors; β-blockers; and clonidine.

Keep in Mind Syncope in adolescents is common and typically benign. Reassurance from the physician and relatively simple behavioral changes often substantially improve these patients’ quality of life, although proper evaluation and counseling take time. Consider referring patients to a pediatric cardiologist if they have the following: ː Syncope during exercise ː An abnormal physical examination or ECG suggesting underlying cardiac disease ː History suggestive of primary dysrhythmia ː Concerning family history (cardiomyopathy, long QT syndrome, sudden death) ː Persistent syncope despite initial therapy

66  Challenging Cases in Pediatric Cardiology

A

B

C

D

Figure 9.2. Examples of abnormal electrocardiograms that may be seen in patients with syncope: A, long QT interval; B, Brugada syndrome; C, septal hypertrophy in hypertrophic cardiomyopathy; and D, left ventricular hypertrophy in severe aortic stenosis.

Chapter 9. Fainting in an Adolescent at School  67

Practice Points 1. Neurocardiogenic syncope is common. Evaluation and diagnosis depend on a thorough detailed history. 2. A physical examination demonstrating orthostatic changes in heart rate or blood pressure may be helpful if positive, but the lack of these findings does not rule out neurocardiogenic syncope. 3. Tilt tests are of limited use in the diagnosis in most patients with neurocardiogenic syncope. However, they may be useful in some patients whose symptoms are severe or if the usual therapeutic measures fail to lead to improvement and the diagnosis is in question. 4. An ECG is useful in all patients with syncope to exclude long QT syndrome, Brugada syndrome, severe aortic stenosis, or hypertrophic cardiomyopathy. In some patients, however, the ECG may be normal even when these conditions are present. 5. Referral to a pediatric cardiologist is appropriate when symptoms are atypical for neurocardiogenic syncope or there is suspicion of a cardiac cause.

Suggested Reading 1. Sivaswamy L, Gupta P. Syncope. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:133–146 2. Harris JP. Cardiac arrhythmias. In: McInerny TK, Adam HM, Campbell DE, DeWitt TG, Foy JM, Kamat DM, eds. American Academy of Pediatrics Textbook of Pediatric Care. 2nd ed. Elk Grove Village, IL: American Academy of Pediatrics; 2017:1227–1235 3. Ramaswamy P. Syncope. In: McInerny TK, Adam HM, Campbell DE, DeWitt TG, Foy JM, Kamat DM, eds. American Academy of Pediatrics Textbook of Pediatric Care. 2nd ed. Elk Grove Village, IL: American Academy of Pediatrics; 2017:1636–1641 4. Stewart JM, Boris JR, Chelimsky G, et al; Pediatric Writing Group of the American Autonomic Society. Pediatric disorders of orthostatic intolerance. Pediatrics. 2018;141(1):e20171673

‹‹‹‹ CHAPTER 10 ››››

A New Murmur and Rash Presentation An 8-year-old Hispanic boy is seen in your office for a follow-up visit. He was previously seen 2 weeks ago for a presumed upper respiratory tract infection. During the initial visit, his lungs and heart were normal at auscultation. The patient has since developed clinically significant dyspnea, as well as a rash on his trunk, and bilateral knee pain. During the examination, the child’s temperature is 38.7°C, his heart rate is 165 beats/min, his respiratory rate is 40 breaths/min, his blood pressure is 96/40 mm Hg, and his pulse oximetry is 90%. He appears ill and in mild respiratory distress. He has an erythematous macular rash on his trunk that blanches with pressure but is not painful. Breath sounds are coarse bilaterally, with scattered crackles, but no wheezes. The cardiac examination reveals a prominent apical impulse; a regular rhythm; and a soft, high-frequency decrescendo diastolic murmur at the right upper sternal border. His joints are not swollen or tender, and he has full range of motion. A brief neurological examination is normal. His medical history is otherwise normal. There is no history of trauma, and he has no prior history of rash. The child has been in your care since his birth, and there is no record of him having had a murmur in the past and no history of congenital heart disease. He is taking no medications and has no known allergies to medications. ː What additional historical information would be useful in formulating a differential diagnosis? ː The murmur heard at examination is characteristic of what cardiac diagnosis?

70  Challenging Cases in Pediatric Cardiology

Differential Diagnosis The differential diagnosis of fever, knee pain, and a rash should include the following: ː Viral infection ː Septicemia ː Lyme disease ː Endocarditis ː Juvenile rheumatoid arthritis ː Systemic lupus erythematosus ː Rheumatic fever ː Drug reaction ː Leukemia

Evaluation Because of his clinically significant respiratory distress you send the patient to the emergency department for stabilization and laboratory evaluation, including complete blood count (CBC), blood cultures, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. The CBC reveals a white blood cell count of 12,000/mcL, hemoglobin level of 9.9 g/dL, hematocrit of 28.6%, and platelet count of 428,000/mcL. Blood cultures are pending. Both the ESR and CRP levels are elevated at 98 mm/h and 31 mg/L, respectively. A chest radiograph demonstrates mild cardiomegaly and increased pulmonary vascular markings. An electrocardiogram shows sinus rhythm with prolonged PR interval but no chamber enlargement or hyper­trophy (Figure 10.1). Because of the diastolic murmur at physical examination, you consult a pediatric cardiologist. An echocardiogram is obtained that shows a mildly dilated left ventricle with normal systolic function. The aortic and mitral valves have thickened valve leaflets (Figure 10.2). There is mild central aortic insufficiency with no aortic stenosis. There are no vegetations visible on the echocardiogram. In addition, there is mild mitral regurgitation and mild left ventricular dilatation.

Figure 10.1. A 12-lead electrocardiogram showing a prolonged PR interval measuring 200 ms (first-degree atrioventricular block), sinus rhythm, and no evidence of chamber enlargement or hypertrophy.

Chapter 10. A New Murmur and Rash  71

Figure 10.2. Two-dimensional and color flow Doppler echocardiograms in the long-axis view. Panel A demonstrates a mildly enlarged LV and aortic and MV leaflet thickening. In panel B, color flow shows mild AV insufficiency (arrow) during diastole. In systole (not shown), there is also mild MV insufficiency. (AO, aorta; AV, aortic valve; LA, left atrium; LV, left ventricle; MV, mitral valve.)

Because of the fever, rash, arthralgia, prolonged PR interval (first-degree heart block), and cardiac involvement, you suspect that rheumatic fever (RF) is the most likely diagnosis, and you order antideoxyribonuclease B and antistreptolysin O titers, a rapid strep test, and a throat culture. The rapid strep test is negative. The initial antistreptolysin O titer is elevated.

Treatment After fulfilling the Jones criteria (major criteria: carditis and erythema marginatum; minor criteria: fever, arthralgia, prolonged PR interval, and elevated acute phase reactant levels) (Box 10.1) and establishing a diagnosis of acute RF, Box 10.1. Summary of Jones Criteria Major Criteria

Minor Criteria

Carditis (clinical or subclinical)

Fever

Polyarthritis

Arthralgia

Chorea

Elevated acute phase reactant levels (erythrocyte sedimentation rate, C-reactive protein level)

Subcutaneous nodules

Prolonged PR interval on an electrocardiogram

Erythema marginatum Evidence of a preceding group A streptococcal infection • Positive throat culture or rapid strep test • Elevated or increasing antibody titer

72  Challenging Cases in Pediatric Cardiology in consultation with your pediatric cardiologist, you begin treating the patient with rest and anti-inflammatory medications. The patient has moderate carditis and receives 2 mg/kg/d of prednisone, in addition to 500 mg of penicillin V 3 times per day.

Discussion The presence of a new diastolic murmur is pathological and limits the ­diagnosis to RF, endocarditis, or systemic lupus erythematosus. There is no family history of rheumatologic conditions. Clinical findings suggest the patient has RF; however, his ill appearance and new murmur could indicate endocarditis. Carditis is present in approximately 30% to 70% of patients with RF and is associated with clinically significant long-term morbidity and mortality. In acute rheumatic carditis, most patients develop isolated mitral regurgitation. Approximately 25% of patients have aortic valve involvement in association with mitral regurgitation. Isolated aortic valvular regurgitation is uncommon. Valvular regurgitation can be caused by a combination of verrucous vegetations on the valve leaflets, valvular prolapse, annular dilatation, chordal elongation, and even flail leaflets. The vegetations associated with RF are often not visible at echocardiography, although the valve leaflets may appear thickened. Pericarditis also may develop in patients with acute RF. The advent of color flow Doppler echocardiography has made possible the diagnosis of subclinical degrees of valvular regurgitation. Recent changes in the Jones criteria now provide guidance on diagnosing subclinical carditis by means of echocardiography alone (without physical findings). Evidence of carditis on an echocardiogram is now sufficient to establish the diagnosis, in the absence of other clinical evidence. A recurrent episode of RF in a patient without chronic rheumatic heart disease also requires fulfillment of the Jones criteria. However, in patients with chronic rheumatic heart disease, only 2 minor criteria plus evidence of a preceding group A streptococcal (GAS) infection are needed to establish the diagnosis of RF recurrence. Also, the presence of chorea, without other symptoms, can establish the diagnosis of RF. Evaluating for a history of a recent GAS infection requires performing a rapid strep test, throat culture, and antibody testing. Elevated or increasing antibody titers are very reliable markers of a preceding GAS infection because the antibody response typically peaks at 3 to 4 weeks. Antistreptolysin O and antideoxyribonuclease B are the most commonly measured titers. More than 90% of patients with RF have a positive result in 1 titer when both are measured simultaneously. Anti-inflammatory medications are the mainstay for treating acute RF to provide symptom relief; however, there is limited and conflicting evidence of their

Chapter 10. A New Murmur and Rash  73 ability to prevent long-term cardiac abnormalities. In addition, many experts recommend steroids in patients with moderate to severe carditis despite limited evidence for their superiority over aspirin (Box 10.2). Afterload-reducing agents and diuretics may be needed to treat the acute symptoms of congestive heart failure in cases of severe carditis. In cases of intractable heart failure because of valvular insufficiency, surgical valve repair or replacement may be necessary. In addition to treating the carditis, treating the GAS infection is necessary to eradicate the organism. Oral penicillin V, 250 mg (≤27 kg) and 500 mg (≥27 kg and adults), 2 to 3 times per day for a total of 10 days is extremely effective. A single dose of 600,000 U (≤27 kg) or 1.2 million U (≥27 kg) penicillin G benzathine injected intramuscularly also can be used if patients prefer or if adherence is an issue. For patients allergic to penicillin, courses of clindamycin and azithromycin are also effective. All patients with acute RF, especially those with cardiac involvement, are at risk for subsequent attacks. Therefore, it is also important to begin secondary prophylaxis immediately after completion of the primary GAS treatment to prevent future recurrences. Monthly intramuscular injections of penicillin G benzathine (same dose as earlier) are the recommended regimen for secondary prophylaxis because recurrences are higher with oral regimens. Alternatively, 250 mg of penicillin V twice daily is acceptable, especially in patients with Box 10.2. Summary of Anti-inflammatory Treatment Strategy for P ­ atients With Carditis Mild Aspirin • Children: 80–100 mg/kg/d divided in 4 doses. • Adults: 50–70 mg/d divided in 4 doses. • Target salicylate levels: 20–30 mg/dL. • Treatment is continued for 2–3 wk,a then the dose is decreased to 40–60 mg/ kg/d for an additional 2–3 wk, and then it is tapered. • Total duration of therapy is approximately 12 wk. Moderate to Severe Steroids • Prednisone dosed 2 mg/kg/d for 2 wka and then tapered over 2 wk. • Begin aspirin 40–60 mg/kg/d divided in 4 doses 1 wk before stopping ­steroids to prevent rebound. • Total duration of therapy is approximately 12 wk. Alternatively, the patient can continue until the erythrocyte sedimentation rate or C-reactive protein level normalizes.

a

Adapted from Garekar S, Trivedi B. Acute rheumatic fever and rheumatic heart disease. In: Johnson JN, Kamat DM, eds. C ­ ommon Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:443–461.

74  Challenging Cases in Pediatric Cardiology lower risk of recurrence. For patients who are allergic to penicillin, once-daily sulfadiazine (0.5 g [≤27 kg] or 1 g [≥27 kg]) is recommended. Oral macrolides and azalides are recommended only in patients with both penicillin and sulfa allergies. The duration of therapy varies from 5 years to lifelong, depending on the severity of the carditis and associated conditions. Patients with mild carditis frequently show complete resolution when the acute inflammation subsides. Patients with moderate to severe carditis often develop chronic rheumatic heart disease, particularly if recurrent episodes of RF occur. Chronic mitral regurgitation is the most common form of chronic rheumatic heart disease in children and young adults. Chronic aortic valvular regurgitation also occurs. Evolution to mitral and aortic valve stenosis because of chronic rheumatic carditis more commonly occurs in the third to sixth decades. Given the clinically significant morbidity and mortality associated with rheumatic carditis, all patients require referral to a cardiologist during the acute stages and for long-term follow-up.

Keep in Mind Rheumatic fever is uncommon in high-income countries. Nonetheless, a number of outbreaks have occurred in various communities in the United States. Because RF is rare, it is possible to miss the early manifestations of this disease, which may result in very clinically significant long-term morbidity. In this case, the concern is the onset of a diastolic murmur, which should always trigger a high index of suspicion for endocarditis or RF.

Practice Points 1. A new diastolic murmur always requires complete evaluation, including echocardiography and cardiology consultation. 2. When a new finding of a murmur is associated with fever, then endocarditis and acute RF are likely diagnoses, and appropriate cultures and serological tests should be performed. 3. When a new murmur and fever are associated with symptoms of congestive heart failure, such as dyspnea, urgency is in order in establishing a diagnosis and treatment. 4. Acute RF is diagnosed by fulfilling the modified Jones criteria, which now include evidence of carditis established only by means of echocardiography. 5. With the diagnosis of acute RF, which requires evidence of preexisting GAS pharyngitis, treatment for the GAS infection is necessary. 6. Patients with a diagnosis of acute RF require long-term prophylaxis for the GAS infection to prevent subsequent episodes. Those with evidence of carditis require long-term follow-up by a cardiologist.

Chapter 10. A New Murmur and Rash  75

Suggested Reading 1. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation. 2009;119(11):1541–1551 2. Tani LY. Rheumatic fever and rheumatic heart disease. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:1373–1404 3. Gewitz MH, Baltimore RS, Tani LY, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young. Revision of the Jones Criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the American Heart Association. Circulation. 2015;131(20):1806–1818 4. Karthikeyan G, Guilherme L. Acute rheumatic fever. Lancet. 2018;392(10142): 161–174

‹‹‹‹ CHAPTER 11 ››››

Chest Pain With Exercise Presentation A 16-year-old black football player is seen in your office for clearance to return to play after experiencing chest pain during practice. The patient’s symptoms began several weeks prior during conditioning sprints and consisted of severe crushing, midsternal pain. This pain forced him to sit out the remainder of that practice. The pain was associated with subjective shortness of breath, but no coughing or wheezing, and there was no known trauma to the chest. He was already diaphoretic secondary to the exercise but had no increased ­diaphoresis during this episode. The pain resolved within approximately 30 minutes of resting. A few days before this office visit, he had a similar ­episode of chest pain with severe shortness of breath during a game. The symptoms forced him to stop playing, and he sat out the rest of the game. He denies other episodes of chest pain or shortness of breath. But, after you question him further, he reports a single syncopal episode last month, also during football practice. While running laps around the field, he felt dizzy and lightheaded and then fell forward on the track. He was unresponsive for several minutes and then returned to his normal mental status. The coach excused him from the remainder of that practice but allowed him to resume training the next day. There were no palpitations or chest pain associated with that episode, and there have been no further episodes of syncope.  His medical history is otherwise unremarkable. His family history is also ­negative, with no history of congenital heart disease, sudden death, cardio­ myopathy, or early myocardial infarction. At examination, he is a well-developed, athletic young man in no acute distress. His vital signs are normal. His complete physical examination is normal. His precordium is normally active, and the point of maximal impulse is normal. There is a regular normal S1 and physiologically split S2 without murmurs,

78  Challenging Cases in Pediatric Cardiology clicks, rubs, or gallops. His pulses are 2+ in both brachial and femoral arteries. His chest is well formed, with no chest wall deformities or tenderness at ­palpation. His lungs are clear at auscultation. ː What features of this patient’s history are of greatest concern? ː Knowing that most chest pain in children and adolescents is not cardiac in origin, are ­additional studies needed? ː On the basis of the patient’s history and physical examination, would you allow him to return to football practice?

Differential Diagnosis The differential diagnosis of chest pain in children and adolescents is as follows: ː Idiopathic, benign chest wall pain ː Musculoskeletal © Costochondritis © Tietze syndrome © Slipping rib syndrome © Trauma ː Precordial catch syndrome ː Asthma ː Other respiratory causes (pneumothorax, pulmonary embolus, pneumonia, pleural effusion) ː Gastrointestinal (gastroesophageal reflux, esophagitis, gastritis) ː Psychogenic (anxiety, hyperventilation) ː Sickle cell disease ː Substance abuse (cocaine) ː Cardiac © Coronary anomaly (congenital, acquired) © Aortic stenosis © Pericarditis or myocarditis © Severe outflow obstruction or hypertrophic cardiomyopathy © Aortic dissection (associated with Marfan syndrome) © Mitral valve prolapse © Tachyarrhythmia

Evaluation An electrocardiogram (ECG) (Figure 11.1) is obtained in the patient, and the results are normal, yet demonstrating pronounced lateral voltage and early repolarization. Given the severity of the pain and the association with exercising, you request a pediatric cardiology consultation for further evaluation

Chapter 11. Chest Pain With Exercise  79 before clearing him for sports. Because of the recurrent symptoms during exercise, the cardiologist repeats an ECG, which remains normal. A graded exercise stress test demonstrates a normal heart rate and blood pressure response to exercise, as well as normal aerobic capacity (suggesting normal oxygen delivery to exercising muscles). He is in sinus rhythm and has no ectopy throughout exercise, and there are no ST-segment changes suggestive of ischemia. Pulmonary function testing before and after exercise is also normal. Because of the exertional nature of the pain and the history of dyspnea and syncope, the cardiologist orders an echocardiogram (Figure 11.2). The result demonstrates normal cardiac anatomy and normal biventricular size and systolic function. However, the proximal coronary arteries are not well visualized on

Figure 11.1. Normal electrocardiogram demonstrating characteristic early repolarization and prominent lateral forces in the precordial leads that is typically seen in adolescents. These findings are often pronounced, particularly in black athletes, and sometimes are confused with left ventricular hypertrophy and ischemia.

Figure 11.2. Echocardiograms demonstrating normal LV size and ejection fraction. Apical images of the LV in diastole show normal LV size (A) and in systole (B) show normal ­ejection fraction. In this study, the coronary artery origins were not clearly delineated because of poor precordial windows. (LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.)

80  Challenging Cases in Pediatric Cardiology the transthoracic echocardiogram in this muscular patient. The ­cardiologist obtains a computed tomography angiogram (Figure 11.3), which demonstrates an anomalous origin of the left coronary artery from the right-facing sinus of Valsalva and coursing between the aorta and pulmonary artery, probably with an intramural course.

Treatment

Figure 11.3. Computed tomography angiogram demonstrating anomalous origin of the LCA arising anteriorly from the right-facing sinus of Valsalva and coursing between the aorta and pulmonary artery. (AO, aorta; LCA, left coronary artery; PA, pulmonary artery; RCA, right coronary artery.)

The patient is referred for surgical intervention and undergoes an unroofing procedure of the proximal left coronary artery. Intraoperative findings include a slitlike opening and an intramural course of the left coronary artery. His postoperative course is uncomplicated, and he returns to football the next ­season after a normal exercise stress test and nuclear perfusion study. He remains symptom free.

Discussion Chest pain in adolescents most commonly is caused by musculoskeletal pain from the chest wall. Proper evaluation necessitates a good understanding of both the benign and the potentially dangerous causes of chest pain in this patient population. Workup begins with a thorough history and physical examination and a family history that includes detailed questioning about early heart or lung disease. A benign cause may be apparent from the history and examination, and reassurance of the patient and family is appropriate. Benign chest wall pain of adolescence is typically a sharp or punching pain, lasting seconds to minutes, and occurs with or without exercise. The cause is incompletely understood but may include spasm of the intercostal muscles or pleuritic irritation. Treatment is thoughtful reassurance and encouragement to return to full activity participation. Pain that is reproducible with palpation suggests musculoskeletal origin. Tietze syndrome is a painful nonsuppurative swelling of the cartilaginous articulations of the chest wall, also of unclear cause. Nonsteroidal anti-inflammatory drugs, topical heat, and rest for a few weeks may help alleviate symptoms. Slipping rib syndrome involves pain and

Chapter 11. Chest Pain With Exercise  81 increased mobility of the 10th ribs anteriorly. Precordial catch syndrome is a benign stitch or sharp pain of the anterior part of the chest associated with bending over or deep inspiration. A burning pain associated with supine position or specific foods suggests gastroesophageal reflux. Pleural pain typically follows a history of upper respiratory tract infection and worsens with deep inspiration. Clinically significant fever and malaise associated with chest pain and dyspnea that is relieved by leaning forward may signify pericarditis. Patients with underlying sickle cell disease are at risk for both acute chest syndrome and sternal bone pain. Overall, 98% of children complaining of chest pain will have noncardiac pain. Chest pain secondary to cardiac ischemia is typically a crushing type of pain that is associated with exercise, when myocardial oxygen demands are greatest. The pain often builds to a peak and then gradually subsides. Light-headedness and presyncope also may be associated with exercise-induced angina. Special consideration should be made for patients who have undergone orthotopic heart transplant. Patients who have undergone heart transplant are at much higher risk of coronary insufficiency, and because the heart is denervated, the pain may be absent, atypical, or referred to the abdomen. Hypertrophic cardiomyopathy, myocarditis, and congenital coronary anomalies are among the most common causes of sudden death in young athletes. Sudden death may be the initial symptom in many of these patients. Some, however, may develop initial symptoms of exercise-induced pain (angina) or syncope. Because diagnosis may permit life-saving therapy or activity restriction, identification of adolescents who are at risk is critically important. History and examination remain key. An ECG may be useful in screening for ventricular hypertrophy or long QT syndrome. In patients with a history of typical angina or an abnormal cardiac examination, echocardiography is useful to evaluate cardiac structure and function. Exercise stress testing is indicated for patients with symptoms primarily during intense activity and may aid in the diagnosis of exercise-induced bronchospasm or coronary ischemia. Exercise testing also may be performed in athletes lacking additional features that suggest a cardiac cause for pain during exercise to provide reassurance to return to sports participation. In addition to abnormal findings at cardiac examination or an abnormal ECG, referral to a pediatric cardiologist is indicated for patients with the following: ː Chest pain with exertion ː Associated palpitations or syncope ː History of Kawasaki disease ː Previous cardiac surgery

82  Challenging Cases in Pediatric Cardiology ː Family history of early cardiac death ː Coronary disease ː Severe hypercholesterolemia Anomalous aortic origin of the left coronary artery from the right sinus of Valsalva (see Figure 11.3) likely produces ischemia secondary to proximal coronary ostial narrowing and compression of the left coronary artery between the aorta and pulmonary artery during exercise. Because the coronary insufficiency is episodic, patients with this anomaly may have completely normal ECGs both at rest and with exercise, so diagnosis depends on a high clinical index of suspicion. Specific treatment for chest pain in adolescents depends on the underlying cause, as detailed. Musculoskeletal pain often is alleviated with time, nonsteroidal anti-inflammatory medications, and reassurance that the pain is not dangerous or life-threatening. Frequently, relief of the anxiety associated with the pain improves both the patient’s tolerance of the symptoms and the pain itself. Chest pain secondary to coronary artery disease and myocardial ­ischemia may require surgical intervention.

Keep in Mind Although most chest pain in children and adolescents is benign and is not cardiac in origin, chest pain often provokes serious parental concern. Reassurance is appropriate if the history and physical examination are compatible with benign forms of chest pain. However, some families are reluctant to accept a limited evaluation, particularly when the patient is an athlete or when there is a family history of ischemic heart disease. Most pediatric patients with chest pain will not require cardiology evaluation, but, when parental or patient anxiety are overwhelming in a patient with benign noncardiac pain, cardiology evaluation with an ECG or exercise test may be indicated and often results in a resolution of symptoms.

Practice Points 1. Chest pain is common in children and is not cardiac in origin in more than 95% of children presenting to primary care settings. Usually, the history alone suffices to make the diagnosis of various forms of noncardiac pain. 2. Chest pain with exercise may be the only symptom of a potentially life-threatening cardiac condition in adolescents. 3. Exercise-associated chest pain that is severe, crushing, or squeezing and is associated with dyspnea, dizziness, palpitations, or syncope may be cardiac in origin and requires further evaluation.

Chapter 11. Chest Pain With Exercise  83 4. Although many patients with cardiac pain have an abnormal ECG or echocardiogram, some do not. Even exercise tests may be negative in patients with coronary anomalies or arrhythmic origin of chest pain. 5. Consultation with a pediatric cardiologist is necessary for patients in whom a cardiac diagnosis for chest pain is suspected.

Suggested Reading 1. Johnson JN, Driscoll DJ. Chest pain in children and adolescents. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:1627–1632 2. Nguyen T, Fundora MP, Welch E, et al. Application of the pediatric appropriate use criteria for chest pain. J Pediatr. 2017;185:124–128 3. Schroeder SA. Chest pain. In: McInerny TK, Adam HM, Campbell DE, DeWitt TG, Foy JM, Kamat DM, eds. American Academy of Pediatrics Textbook of Pediatric Care. 2nd ed. Elk Grove Village, IL: American Academy of Pediatrics; 2017:1235–1239 4. Son MB, Sundel RP. Musculoskeletal causes of pediatric chest pain. Pediatr Clin North Am. 2010;57(6):1385–1395 5. Bansal N, Aggarwal S. Chest pain. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:117–132 6. Prakash K, Sharma S. Interpretation of the electrocardiogram in athletes. Can J Cardiol. 2016;32(4):438–451

‹‹‹‹ CHAPTER 12 ››››

An Athlete With a Murmur Presentation A 15-year-old white boy is in your office for a routine physical examination after a 6-year absence from care. The patient states he is doing “great” and made this appointment to get a sports physical examination to participate on the track team. He has been running daily all summer as part of a personal training program with a goal of 8 to 10 miles per day. After further questioning, he admits that his training has not been going very well. He has not been able to run farther than 8 miles per day over the past few months and has noticed his average time has increased. He has attributed this to being “out of shape.” He denies chest pain, palpitations, dizziness, shortness of breath, syncope, or other symptoms. The patient appears to be in good physical condition, his body mass index is in the 21st percentile, and his resting heart rate is 52 beats/min. His other vital signs are normal, with a right upper extremity blood pressure of 102/66 mm Hg, a lower extremity blood pressure of 119/90 mm Hg, 100% oxygen saturation breathing room air, and height and weight in the 75th percentile. All aspects of the pulmonary, abdominal, musculoskeletal, and neurological examinations are normal. At cardiovascular examination, he has a dynamic, nondisplaced, bifid apical impulse at palpation of his precordium localized to the fourth intercostal space. Auscultation reveals a 3/6 harsh systolic ejection murmur that radiates to the carotid arteries and is loudest in the right upper sternal border preceded by a faint click best heard at the apex. His pulses are normal, without delay, in his arms and legs. The remainder of his preparticipation physical examination is normal. ː What are some potential causes for the new heart murmur heard at ­examination? ː Are there any features of the examination that suggest that the murmur is not a normal functional (physiologic) murmur?

86  Challenging Cases in Pediatric Cardiology ː Is his slowing of his pace while running of any concern?

Differential Diagnosis Heart murmurs are common in children of all ages and may be heard in patients with normal hearts or in those with cardiac anomalies. Some common potential causes of a systolic murmur in a teenager include the following: ː Still murmur ː Aortic or pulmonary normal flow murmur ː Atrial septal defect with pulmonary flow murmur ː Aortic valve stenosis ː Subaortic stenosis © Discrete subaortic ledge © Hypertrophic cardiomyopathy ː Pulmonary valve stenosis © Valvular pulmonary stenosis © Supravalvular pulmonary stenosis © Subpulmonary stenosis ː Ventricular septal defect

Evaluation Because of the systolic murmur associated with a click that is loudest in the aortic area and that radiates to the carotid arteries, you order an electrocardiogram (ECG) and a cardiology consultation. The ECG shows left ventricular hypertrophy with T-wave changes in the lateral precordial leads (Figure 12.1). The cardiology consultant confirms your physical findings and obtains an echocardiogram, which demonstrates left ventricular hypertrophy with normal function. The aortic valve is bicommissural (bicuspid), is thick, and domes during systole (Figure 12.2). The mean Doppler gradient across the aortic valve

Figure 12.1. Electrocardiogram demonstrating increased QRS voltage in the lateral precordial ­ ypertrophy. leads (V4 to V6) with associated T-wave changes typical of left ventricular h

Chapter 12. An Athlete With a Murmur  87 is 55 mm Hg, with a peak gradient of 104 mm Hg (Figure 12.3). There is no aortic insufficiency.

Treatment The cardiologist confirms the diagnosis of aortic stenosis and recommends restricting the patient from sports pending further evaluation. The presence of T-wave changes on an ECG and the echocardiographic findings are consistent with severe congenital aortic stenosis. Cardiac catheterization is planned, with likely balloon valvuloplasty of the aortic valve. If the aortic valve gradient is substantially reduced, consideration will be given to allowing this young athlete to return to sports participation. A graded exercise test will be performed before allowing him to return to sports.

Discussion

Figure 12.2. Echocardiogram in the long-axis view demonstrating both left ventricular hypertrophy (thickening of the interventricular septum and ­posterior wall of the left ventricle) and color flow ­evidence of turbulence at the thickened doming aortic valve. (AO, aorta; LA, left atrium; LVOT, left ventricular outflow tract.)

Figure 12.3. Continuous-wave Doppler echocardiogram

The athletic teenager with obtained at the right upper sternal border demonstrating increased peak and mean aortic velocity. The aortic a murmur is a common yet valve gradient calculated from the Doppler tracing is challenging clinical scenario a mean of 55 mm Hg, with a peak of 104 mm Hg, both encountered by the primary indicative of severe aortic stenosis. care physician. The main questions that must be answered are whether the murmur is benign and, if not, whether the patient should be referred to a cardiologist. Systolic ejection murmurs are commonly encountered throughout childhood, particularly in a young or thin child or an athletic adolescent. Heart murmurs in the structurally normal heart are caused by an increase in flow across a normal semilunar valve. These murmurs may be a direct result of the bradycardia and subsequent increased stroke volume caused by the increased physical fitness in the patient who is athletic. As the heart rate decreases, the diastolic filling time increases,

88  Challenging Cases in Pediatric Cardiology and the increased blood volume ejected across the aortic valve in systole results in an early systolic crescendo-decrescendo murmur. These functional murmurs (aortic flow murmur) are usually of low to medium pitch and can be associated with a physiological S3. A Still murmur, also normal, has a characteristic musical sound, the so-called twanging string, and is not associated with a click or radiation to the carotid arteries. A Still murmur has several potential mechanisms, one of which is tension in the aortic leaflets during systole, resulting in “trigonation” of the normal aortic valve. This patient has several concerning findings suggestive of cardiac disease. The history suggests progressive fatigability; however, he does not have chest pain, dyspnea during exertion, or syncope. These latter are the 3 most common presenting symptoms of severe aortic stenosis when the patient has symptoms. The history of decreased exercise tolerance suggests a relative limitation in cardiac output with exertion, which could be a worrying finding. Most patients with aortic stenosis have no symptoms. The patient has a negative family history for sudden death, which, while reassuring, does not exclude him from being at risk. A thorough physical examination has shown that he has a dynamic apical impulse and systolic ejection murmur in the aortic area, with an associated click heard best at the apex, which is consistent with aortic valve disease. A systolic click is always abnormal, and these physical findings in particular are consistent with a diagnosis of aortic stenosis. A thrill in the suprasternal notch is often present in patients with aortic stenosis, but it was not recognized in this patient. Both systolic clicks and thrill may be absent in patients with critical aortic stenosis. Patients with mild aortic stenosis have similar outcomes as do people without stenosis. However, because of the possibility of progression of stenosis, they require lifelong cardiology follow-up. Surveillance includes physical examination, along with periodic echocardiograms. The 2008 American College of Cardiology/American Heart Association guidelines recommend exercise stress testing of the patient without symptoms to determine the presence of any dynamic symptoms and abnormal blood pressure responses. Stress testing is not recommended for the patient with symptoms because of the high likelihood of complications. Medical therapy offers little help in the management of congenital aortic ­stenosis. Although the current recommendations on antibiotic prophylaxis state that nonrheumatic aortic stenosis does not require systemic bacterial endocarditis prophylaxis, it remains important to maintain good dental hygiene. To date, no medications have been shown to prevent or slow the progression of stenosis. Once symptoms develop, the risk of sudden death in

Chapter 12. An Athlete With a Murmur  89 aortic stenosis begins to increase, and treatment is recommended. Patients with severe stenosis, regardless of symptoms, should undergo treatment. Moderate stenosis also may be treated, particularly if there is clinically significant ventricular hypertrophy or an abnormal stress test. The goal of treatment is to reduce the degree of obstruction to the left ventricular outflow at the aortic valve. Therapies may include balloon valvuloplasty via cardiac catheterization or surgical interventions, such as aortic valvulotomy or valve replacement.

Keep in Mind The American Heart Association and American College of Cardiology 2015 eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities states that patients with mild aortic stenosis without symptoms do not require restriction from physical activity and should be allowed to participate in competitive athletics but should undergo reevaluation on a yearly basis. Patients with moderate stenosis can engage in low-level competitive sports, such as bowling and golf. Patients with moderate aortic stenosis without symptoms who have undergone exercise testing and who have normal exercise capacity can engage in low- to moderate-level competitive sports, such as baseball and tennis. Patients with severe stenosis or with moderate stenosis with symptoms should not be allowed to participate in dynamic or static competitive sports. Patients who undergo successful valvuloplasty should undergo stress testing to determine the safety of participation in sports.

Practice Points 1. Cardiac symptoms in trained athletes may be subtle, such as a reduction in previously established levels of performance without more obvious symptoms of cardiac limitation, such as chest pain, shortness of breath with exertion, or syncope. 2. Systolic clicks, thrills at palpation, and loud murmurs (grade 3/6 or greater) should be considered abnormal and require complete evaluation. 3. A potentially abnormal murmur at a preparticipation physical examination warrants thorough evaluation by a pediatric cardiologist. 4. Patients with severe aortic stenosis should be restricted from most sports until the stenosis is successfully treated. After treatment, an exercise stress test is useful in establishing parameters for sports participation. 5. Aortic stenosis often progresses during childhood and adolescence; therefore, patients require lifetime follow-up by a cardiologist.

90  Challenging Cases in Pediatric Cardiology

Suggested Reading 1. Kyle WB. Aortic valve problems, including bicuspid aortic valve and subaortic membranes. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:287–291 2. Friedland-Little JM, Zampi JD, Gajarski RJ. Aortic stenosis. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:1085–1106 3. Bonow RO, Nishimura RA, Thompson PD, Udelson JE; American Heart Association Electrocardiography and Arrhythmias Committee of Council on Clinical Cardiology, Council on Cardiovascular Disease in Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, and American College of Cardiology. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 5: valvular heart disease: a scientific statement from the American Heart Association and American College of Cardiology. Circulation. 2015;132(22):e292–e297 4. Mitchell JH, Haskell WL, Raven PB. Classification of sports. J Am Coll Cardiol. 1994;24(4):864–866

‹‹‹‹ CHAPTER 13 ››››

Syncope During a Basketball Game Presentation A 17-year-old white boy is seen in the clinic after he passed out during a basketball game. He remembers playing in the game and then waking up on the court with his coach and family standing over him. He recalls no warning and no symptoms before the event. First responders reported a weak pulse, tachycardia (120–150 beats/min [bpm]) spontaneous breathing, and no evidence of seizure activity. Within 2 minutes, the patient returned to full consciousness without intervention. He struck his head on the floor during the episode and sustained a large contusion above his right eye. He has no other clinically significant medical history. His mother and father are healthy; however, his family history includes an uncle who died at a young age of a heart attack. At examination, the patient is an athletic-appearing young man in no distress. His heart rate is 45 bpm, his respirations are 12 breaths/min, and his blood pressure is 110/70 mm Hg. His cardiac examination reveals an easily palpated apical cardiac impulse with normal S1 and S2. A systolic murmur (2/6) is heard at the left sternal border. The murmur diminishes with the patient squatting and becomes louder with him standing. His pulses are normal in his arms and legs. His neurological examination is normal, and he seems unconcerned about his syncopal episode. ː What features of the patient’s history are most concerning? ː Is the finding of a murmur at examination of any clinical significance in the presence of a history of syncope? ː What is the meaning of the changes in the murmur intensity with changes in body position?

92  Challenging Cases in Pediatric Cardiology

Differential Diagnosis The differential diagnosis in an adolescent athlete should include the following: ː Reflex-mediated syncope © Neurocardiogenic syncope (including orthostatic and postural ­orthostatic tachycardia syndrome) © Vasovagal syncope ː Structural heart disease © Severe left ventricular obstruction © Myocarditis © Cardiomyopathy © Coronary artery anomaly or disease ː Arrhythmic syncope (dysrhythmia) © Bradycardia or complete heart block © Tachycardia or ventricular fibrillation ƒ Long QT syndrome (other channelopathies, including Brugada ­syndrome) ƒ Wolff-Parkinson-White syndrome ː Neurological loss of consciousness (seizure disorder, migraine) ː Conversion disorder with motor symptom or deficit ː Drug or toxin ː Hypoglycemia ː Primary pulmonary hypertension

Evaluation Because of the patient’s history of syncope during exercise, you obtain an ­electrocardiogram (ECG), which demonstrates large septal Q waves in the inferior precordial leads and V6 and substantially increased voltage in the precordial leads (Figure 13.1). Because of the abnormal ECG and abnormal heart murmur, you then request a pediatric cardiology consultation and echocardiogram. The echocardiogram demonstrates severe ventricular hypertrophy affecting both the interventricular septum and the posterior wall. The septum is 3.1 cm in diameter (Figure 13.2). There is systolic anterior motion of the mitral valve producing left ventricular outflow tract (LVOT) obstruction and mild mitral insufficiency. The estimated LVOT gradient is 50 mm Hg on a Doppler echocardiogram.

Chapter 13. Syncope During a Basketball Game  93

Figure 13.1. Typical 12-lead electrocardiogram demonstrating large septal Q waves in leads II, III, and aVF and large R waves in V1 to V5 in hypertrophic cardiomyopathy.

Figure 13.2. A, Long-axis and B, short-axis 2-dimensional echocardiograms showing severe ventricular hypertrophy, affecting primarily the IVS and PW left ventricular hypertrophy. The interventricular septal thickness is 3.1 cm in the short-axis view. (IVS, intraventricular septum; PW, posterior wall.)

Treatment Given the severity of the ventricular hypertrophy and the occurrence of syncope (aborted sudden death) during exercise, the pediatric cardiologist refers the patient for evaluation for an implantable cardioverter defibrillator. Because the patient has no symptoms other than the single syncopal episode, surgical myomectomy of the interventricular septum is deferred pending further follow-up. The patient also is scheduled for a treadmill exercise test as part of risk stratification for hypertrophic cardiomyopathy. He is restricted from participation in basketball and all other sports except for low-intensity activities (eg, golf, bowling). Genetic studies of the patient are performed to genotype the variant of hypertrophic cardiomyopathy. Because of the genetic nature of hypertrophic cardiomyopathy, first-degree relatives are referred for evaluation.

94  Challenging Cases in Pediatric Cardiology

Discussion Syncope is a common symptom in the primary care clinic. It is estimated that as many as 15% of adolescents will experience at least 1 syncopal e­ pisode. Although syncope is common, previous studies have demonstrated that syncope is not a precursor or predictor of sudden cardiac death. The differential diagnosis for syncope is large, but important causes to be considered for syncope during exercise include the following: ː Hypertrophic cardiomyopathy ː Long QT syndrome ː Brugada syndrome ː Wolff-Parkinson-White syndrome ː Catecholaminergic polymorphic ventricular tachycardia ː Coronary arterial anomalies ː Pulmonary arterial hypertension Most cases of syncope in children and adolescents are not due to these serious causes but are likely secondary to an autonomic imbalance, sometimes known as vasovagal syncope, orthostatic syncope, neuro-inhibitory syncope, or neurocardiogenic syncope. The presence of true syncope during exercise (not after exercise), a family history of sudden cardiac death, and an abnormal physical examination distinguish this case from benign. Most practitioners would recommend only an ECG after an episode of syncope if the patient’s history is consistent with neurocardiogenic syncope, there is no family history of sudden death, and there is a normal physical examination. If the results of an ECG are negative, no further workup is necessary. This patient had syncope during exercise, an abnormal physical examination, and an abnormal ECG, all of which appropriately led to further evaluation by a pediatric cardiologist. Hypertrophic cardiomyopathy is a condition characterized by left ventricular hypertrophy in the absence of other cardiac disease or systemic illness. It occurs in 1 of every 500 people and is the most common cause of sudden cardiac death in adolescents and young adults. It is secondary to mutations in one of the many genes that encode the proteins of the cardiac sarcomere. The condition is termed nonobstructive hypertrophic cardiomyopathy if there is no LVOT obstruction. In obstructive hypertrophic cardiomyopathy, in addition to LVOT obstruction, often there is a coexisting systolic anterior motion of the mitral valve leaflets and their apparatus, resulting in mitral valve regurgitation. Hypertrophic cardiomyopathy is inherited in an autosomal dominant fashion; however, sporadic mutations occur. Most patients with hypertrophic ­cardiomyopathy have no symptoms and receive a diagnosis only after a murmur is noted or an ECG is obtained for

Chapter 13. Syncope During a Basketball Game  95 other reasons. It is the rare patient who receives a diagnosis during evaluation for syncope, chest pain, or palpitations. Many patients also receive a diagnosis during family screening after the index case for that family has been identified. Once a diagnosis is established, all first-degree relatives should be screened with an ECG and an echocardiogram. For those with a normal echocardiogram, repeat echocardiograms are recommended for life, given that findings can occur at any age. Screening typically begins after birth and is performed every 5 years. From ages 12 to 18, however, screening is recommended every 12 to 18 months. After age 18 years, screening should continue for life, but the frequency then is typically every 5 years. Genetic testing is available, but even with the most comprehensive testing a genetic cause is found in only approximately 70% to 75% of all cases (Table 13.1). The molecular substrate of hypertrophic cardiomyopathy is related to defects in the genetic makeup of contractile proteins and myocyte structural proteins. When a gene defect is identified in the index patient, genetic testing of family members for the gene defect can help identify others who are affected. Patients with symptoms typically complain of fatigue, shortness of breath, chest pain, and palpitations. Symptoms occur in some children but are rare before puberty. It is important to remember that there is a great deal of Table 13.1. Genetic and Molecular Substrate of Hypertrophic ­Cardiomyopathy Cardiac Protein

Affected Gene

Thick Filament β-myosin heavy chain

MYH7

Regulatory myosin light chain

MYL2

Essential myosin light chain

MYL3

Thin Filament Cardiac troponin T

TNNT2

Cardiac troponin I

TNNI3

Cardiac troponin C

TNNC1

α-tropomyosin

TPM1

α-cardiac actin

ACTC

Intermediate Filament Cardiac myosin-binding protein C

MYBPC3

Z-Disc α-actinin 2

ACTN2

Myozenin 2

MYOZ2

96  Challenging Cases in Pediatric Cardiology clinical variability, even among family members with the same mutation. Most patients remain stable for years, but some have progression. Overall, 25% of patients achieve a normal life expectancy, with a mean age of 75 years. Children and young adult patients with hypertrophic cardiomyopathy have more symptoms, greater septal hypertrophy, more rapid progression of disease, and increased risk for sudden cardiac death than do patients with hypertrophic cardiomyopathy diagnosed at a later age. Recent studies put the risk for sudden cardiac death in the setting of hypertrophic cardiomyopathy near 1% per year. Although sudden cardiac death occurs in only a few patients with hypertrophic cardiomyopathy each year, most cases occur in patients younger than 35 years. The risk for sudden cardiac death, however, is spread throughout life. In most cases, patients at high risk can be identified using risk factors including the following: ː Family history of sudden cardiac death ː Prior cardiac arrest ː Sustained or non-sustained ventricular tachycardia ː Unexplained syncope at rest or with exercise ː Hypotension with exercise ː Diagnosis in childhood ː Severe hypertrophy defined as a septal thickness greater than 30 mm ː Left ventricular outflow tract obstruction Approximately 90% to 95% of patients presenting with hypertrophic cardiomyopathy have an abnormal ECG. The most common ECG finding is left ventricular hypertrophy, including prominent R waves or deep S waves in the precordial leads or abnormal deep and narrow Q waves; ST-T wave changes and marked T-wave inversion in the inferior or lateral precordial leads also can occur. However, in the evaluation of a patient with hypertrophic cardio­ myopathy, a normal ECG does not rule out the diagnosis of the disease, especially in the screening of family members. The diagnosis is confirmed using echocardiography. The hallmark features are asymmetric left ventricular hypertrophy with septal thickening greater than the thickness of the free wall and systolic anterior motion of the mitral valve anterior leaflet and its chordal apparatus. Most of these patients also have abnormal diastolic filling. In patients with hypertrophic cardiomyopathy, treatment is directed at relieving symptoms and preventing sudden death. First-line therapy for symptoms of shortness of breath and exertional fatigue typically involves β-blockers. β-blockers decrease heart rate response and blunt the catecholamine response to exercise. Verapamil also has been used to improve cardiac symptoms and exercise capacity, but it is reserved primarily for adults. Overall, 60% to 80% of patients respond to medical therapy. Surgical therapy is reserved for patients

Chapter 13. Syncope During a Basketball Game  97 for whom therapy is unsuccessful and who have clinically significant LVOT obstruction. There is increasing evidence that elimination of the obstruction prolongs life and relieves symptoms. For patients with risk factors for sudden death, implantable ventricular defibrillator placement should be considered. Risk factors for sudden death include the following: ː Prior cardiac arrest or ventricular tachycardia ː Unexplained syncope ː Family history of early sudden death ː Severe left ventricular hypertrophy ː Hypotension during exercise Patients with hypertrophic cardiomyopathy should be restricted from participation in physical education and competitive athletics because of the risk of sudden death (see Suggested Reading for published guidelines for sports restrictions).

Keep in Mind Hypertrophic cardiomyopathy accounts for one-third of sudden cardiac death in adolescent and young adult competitive athletes and is the most common cause. However, although an ECG is abnormal in most patients with hyper­ trophic cardiomyopathy, screening using ECG alone for these patients is still controversial and has not been proven conclusively to prevent sudden death. This finding is in part because of the difficulty with false-positive and false-negative findings with ECGs and echocardiograms and the low prevalence of ECG-demonstrable diagnoses in the general population of athletes. Standardized screening of competitive athletes with medical history, family history, and ECGs has been shown to reduce the incidence of sudden cardiac death in Italy, but a formal screening process with ECGs is not used in the United States. Most athletes are required to have only a complete clinical history including family history and physical examination before clearance for sports participation, with further evaluation should risk factors be identified. Nonetheless, in a child with syncope, particularly during exercise, an ECG is essential and may be lifesaving.

Practice Points 1. Syncope in adolescents is usually benign and associated with typical history compatible with vasovagal, orthostatic, or neuro-inhibitory syncope. 2. Syncope, especially during exercise, requires thorough evaluation including medical history, detailed family history, physical examination, and an ECG. Further evaluation is dictated by the results of this evaluation.

98  Challenging Cases in Pediatric Cardiology 3. Sudden death is uncommon in patients with hypertrophic cardiomyo­ pathy, and most patients have no symptoms. Evaluation and treatment are ­directed at improving symptoms and preventing sudden death. 4. First-degree family members of patients with hypertrophic cardiomyopathy should be screened for the disease.

Suggested Reading 1. Sivaswamy L, Gupta P. Syncope. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:133–146 2. Friedman KG, Alexander ME. Chest pain and syncope in children: a practical approach to the diagnosis of cardiac disease. J Pediatr. 2013;163(3): 896–901.e1-3 3. Hogan W, Menon SC. Hypertrophic cardiomyopathy. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:361–375 4. Gersh BJ, Maron BJ, Bonow RO, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American Society of Echocardiography; American Society of Nuclear Cardiology; Heart Failure Society of America; Heart Rhythm Society; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124(24):e783–e831 5. Maron BJ. Hypertrophic cardiomyopathy. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:1263–1282 6. Maron BJ. Clinical course and management of hypertrophic cardiomyopathy. N Engl J Med. 2018;379(7):655–668 7. Maron BJ, Maron MS, Semsarian C. Genetics of hypertrophic cardiomyopathy after 20 years: clinical perspectives. J Am Coll Cardiol. 2012;60(8):705–715

‹‹‹‹ CHAPTER 14 ››››

Sports Participation in a Child ­After Heart Surgery Presentation You see a 16-year-old black girl as a new patient. She is seeking a preparticipation school physical examination and athletic clearance before the new school year. She felt well over the summer and denies any recent illnesses. She reports that she experienced a stabbing pain in the left side of her chest while running laps in school during the previous school year. The pain was exacerbated with each breath but resolved when she rested. She also reveals that she sometimes tires after only a few minutes of running around in her yard at home with her dog. Her medical history is highly clinically significant; tetralogy of Fallot (TOF) was diagnosed shortly after birth, and she underwent surgical repair at 1 month of age. She has not needed any subsequent cardiac interventions. Other than what she reports today, she has had no symptoms in the 5 years since her last pediatric cardiology follow-up. She specifically denies palpitations, tachycardia, dizziness, and syncope. She does not take any medications and denies use of any drugs, alcohol, stimulants, or over-the-counter remedies. She has never participated in competitive sports but would like to try out for the volleyball team this year. At physical examination, the patient appears healthy and well developed. Her resting heart rate is 70 beats/min, her blood pressure is 110/60 mm Hg in both the right arm and right leg, and her jugular venous pressure is not elevated. Her breathing is unlabored, and breath sounds are clear bilaterally. She has a well-healed sternal scar, with no tenderness at palpation. There is a very mild cardiac impulse felt at the left sternal border. S1 is normal, but there is a single S2 at the base of the heart. You hear a grade 2/6 low-pitched, midsystolic ejection murmur at the left upper sternal border followed by a fairly long

100  Challenging Cases in Pediatric Cardiology low-pitched, diastolic, decrescendo murmur. There is no gallop. Her distal pulses feel full and equal in the upper and lower extremities. Her abdomen is soft, nontender, nondistended, and without hepatosplenomegaly. She has no visible clubbing or cyanosis. ː Does the complaint of chest pain warrant further investigation? ː Under what circumstances would you recommend restricting the ­adolescent’s sports activities? ː When would you seek further input from your pediatric cardiology consultant?

Differential Diagnosis The differential diagnosis of chest pain in children and adolescents, including those with prior cardiac surgery, should include the following: ː Musculoskeletal © Costochondritis © Tietze syndrome © Post-traumatic (including prior surgery) © Precordial catch syndrome © Slipping rib syndrome © Benign chest wall pain ː Pulmonary © Asthma © Pneumothorax © Pneumonia © Pleurisy © Pulmonary thromboembolism ː Gastrointestinal © Gastroesophageal reflux disease © Peptic ulcer disease © Esophagitis or gastritis © Cholecystitis ː Cardiac © Ischemia ƒ Coronary arterial malformation or disease ƒ Outflow tract obstruction ƒ Mitral valve prolapse © Pericarditis or myocarditis © Arrhythmia (supraventricular tachycardia, ventricular tachycardia) © Pulmonary hypertension © Arterial dissection (Marfan syndrome) ː Idiopathic

Chapter 14. Sports Participation in a Child ­After Heart Surgery  101

Evaluation Before signing her school and athletic clearance forms, you decide to perform further testing. A chest radiograph demonstrates the presence of intact sternal wires and normal heart size and vascular markings, with a mild prominence of the main pulmonary arterial segment (Figure 14.1). The electrocardiogram (ECG) demonstrates normal sinus rhythm, with a right bundle branch block (Figure 14.2). Given her history of congenital heart disease and surgery, and the long interval since her last cardiology follow-up, you consult her pediatric cardiologist for further guidance.

Figure 14.1. Posteroanterior chest radiograph demonstrating normal heart size and pulmonary vascularity. The pulmonary knob is mildly prominent (arrow). Sternal wires are visible and are intact.

Figure 14.2. A 12-lead electrocardiogram showing the postoperative right bundle branch block characteristically seen in postoperative tetralogy of Fallot. The QRS duration is approximately 140 ms.

Her pediatric cardiologist obtains an echocardiogram and orders Holter monitor testing (ambulatory 24-hour electrocardiography). The echocardiogram demonstrates moderate pulmonary valve insufficiency with mild right ventricular dilatation (Figure 14.3). The Holter monitor demonstrates occasional uniform premature ventricular contraction. A graded cycle ergometer exercise test shows her exercise capacity is in the lower limits of normal, with normal maximal peak heart rate and oxygen consumption. There is no arrhythmia with exercise.

102  Challenging Cases in Pediatric Cardiology

Treatment You determine that the patient’s chest pain is musculoskeletal in origin and benign. Her exertional fatigue is mild and likely is caused by deconditioning. Because pulmonary insufficiency is known to progress after repair of TOF, she is scheduled for cardiology follow-up in 2 years. She is Figure 14.3. Echocardiogram demonstrating mild RV allowed to participate in sports ­enlargement due to moderate pulmonary valve insufficiency. The RV cavity is increased in diameter relative without restriction, provided to the LV cavity in this short-axis view. (IVS, intervenshe does not develop symptoms tricular septum; LV, left ventricle; RV, right ventricle.) of worsening fatigue with exertion, shortness of breath with exertion, prolonged and persistent chest pain, dizziness or syncope, persistent palpitations, or tachycardia.

Discussion Chest pain is a common finding in children who have undergone sternotomy or thoracotomy for congenital heart disease. It is also common in children who are healthy. Most chest pain is benign and attributed to pain in the chest wall, even when there is a history of repair of congenital heart defects. This pain may be associated with deep breathing with exercise, such as running, or may not be associated with activity. The pain is sharp (often described as “­stabbing”), fleeting, not associated with position, and not associated with tachycardia or syncope. It may be worsened with deep breaths but does not truly cause shortness of breath. Cardiac pain, however, is severe (sometimes described as “crushing”) persistent pain often brought on by exertion. The pain may be associated with tachycardia, dizziness, and shortness of breath. As with pericarditis, the pain is often associated with position. Any of these symptoms would be indication for further evaluation. Limitations in tolerance for exertion are common in children after heart surgery, as studies have shown. Children who have undergone heart surgery are often deconditioned because of lengthy restrictions from intense physical activities. After repair of TOF, there may be residual or progressive pulmonary valve insufficiency or stenosis. In addition, adolescent and adult patients may have varying degrees of impaired left ventricular function. Reduced heart rate with maximum exertion may require exercise studies to be discovered because it may not be apparent at rest. Restrictive pulmonary physiology also is seen

Chapter 14. Sports Participation in a Child ­After Heart Surgery  103 after thoracotomy or sternotomy and could lead to exertional fatigue and dyspnea. Exertional fatigue, when severe or limiting, can be quantified using graded exercise testing. The improved success of congenital heart surgery and perioperative care have resulted in a rapidly growing population of children and young adults with surgically corrected or palliated congenital heart disease. The patient’s family and primary care physicians must be aware that congenital heart disease is almost never truly repaired and that residual physiological or structural abnormalities are common. Although most children who have undergone surgical correction of congenital defects have minor or inconsequential residua, all patients live with some degree of heart abnormality that will be a lifelong, if not a life-­ limiting, condition. Even patients with a simple secundum atrial septal defect that is repaired may have limitations in exercise capacity many years later. In particular, patients with palliated complex congenital heart disease are at high risk of long-term sequelae, so they require the combined care of a cardiologist (pediatric or adult) and a primary care physician. Participation in sports has important psychosocial benefits in children and young adults with congenital heart disease. Furthermore, just as in the general population, regular exercise helps promote long-term cardiovascular health. Therefore, efforts have been made to develop guidelines for determining who among the heterogeneous group of patients with congenital heart disease may be permitted to participate in sports that require varying levels of static and dynamic physical activity. The 36th Bethesda Guidelines are a practical reference for cardiologists and general practitioners for evaluating patients with cardiac conditions before competition. These guidelines risk-stratify sports according to their static and dynamic requirements and make recommendations about participation on the basis of each unique heart disease and surgery. Every child and young adult requires a screening history that focuses on cardiovascular symptoms and family history, as well as a physical examination, before participation in competitive sports. This history should focus on exertional symptoms such as chest pain, palpitations, excessive dyspnea, and syncope or near-syncope. A family history of arrhythmias, long QT syndrome, cardiomyopathies, disability from a heart condition before age 30 years, and sudden cardiac death before age 50 years should be sought. The physical examination should include evaluating for heart murmur, blood pressure measurement, assessment of femoral pulses, and inspection for signs of Marfan syndrome. Patients with palliated congenital heart disease may require a more in-depth evaluation by a pediatric or adult cardiologist who specializes in congenital heart disease. In addition to the history and physical examination, this

104  Challenging Cases in Pediatric Cardiology evaluation may include 1 or more of the following: chest radiography, electrocardiography, echocardiography, computed tomography or magnetic resonance imaging, Holter monitor testing, and exercise stress testing. Delineating a patient’s hemodynamically significant residual lesions, electrophysiological abnormalities, and response to exercise should govern any restriction from competitive athletics. The 36th Bethesda Guidelines suggest that children who have had an “excellent” repair should not be restricted from participating in any sports. Characteristics of an excellent repair include the following ː Normal or near-normal right-sided heart pressure ː No or only mild right ventricular volume overload (ie, absence of marked residual pulmonary regurgitation) ː No evidence of a clinically significant residual ventricular shunt ː No atrial or ventricular tachyarrhythmia abnormality at ambulatory ECG monitoring or exercise testing Although not stated in the recommendations, normal right and left ventricular function, as well as absence of aortic root dilatation, is important to confirm. Patients who do not meet these parameters should be limited to low-intensity sports only (eg, golf, bowling). Finally, sports participation should not be permitted in any patient who is less than 3 to 6 months removed from cardiac surgery. Otherwise, patients with TOF who meet these parameters should not be restricted from competitive athletics postoperatively. After patients with TOF undergo surgery, like the adolescent in this case, they have an overall excellent long-term prognosis. Sudden cardiac death is the most common cause of long-term cardiac mortality and occurs with an incidence of less than 5% in patients who survive the immediate postoperative period. Multiple risk factors for sudden cardiac death in this patient population have been identified. These include the following: ː Operative characteristics (late age at surgical palliation, use of a transannular patch, transventricular repair) ː Patient characteristics (male sex) ː Hemodynamically significant residual lesions (clinically significant pulmonary or tricuspid regurgitation, right ventricular dilatation, right or left ventricular dysfunction, aortic root dilatation) ː Electrophysiological abnormalities (longer [>0.18 s] QRS duration, ventricular arrhythmias seen with a Holter monitor) A thorough evaluation by a cardiologist should seek to identify these risk factors.

Chapter 14. Sports Participation in a Child ­After Heart Surgery  105

Keep in Mind Sudden cardiac death in the young athlete is an extremely rare phenomenon that is often well publicized by the media and can, thus, have an inordinate effect on societal perceptions of the risk of sudden death among athletes. The American Heart Association has recommended screening guidelines in an effort to identify those who are potentially at risk before they participate in sports. Patients with palliated congenital heart disease constitute a population at risk for sudden cardiac death. The decision to allow children with palliated congenital heart disease to participate in competitive athletics is complex and must balance the risks of sudden cardiac death with the psychosocial and physical benefits. A reasonable preparticipation evaluation requires intimate knowledge of numerous congenital heart diseases and may involve specialized testing. The primary care physician must be familiar with the clearance process and work with the consulting cardiologist to ensure that these children and families receive appropriate counseling about sports participation. Although these patients should be followed up longitudinally and cleared for sports participation by pediatric cardiologists, the primary care physician must be familiar with the risks and benefits of, as well as the screening process associated with, sports participation.

Practice Points 1. Chest pain in children and adolescents, even those with repaired congenital heart disease, is most likely to be benign chest wall pain. A careful history is needed to elucidate the features of pain that are seen more commonly with cardiac pain, including severe crushing pain, tachycardia, dizziness, syncope, and clinically significant shortness of breath. 2. The evaluation of chest pain may include an ECG when features suggest a possible cardiac origin. 3. Graded exercise testing in patients with exertional pain may be helpful in eliciting symptoms to rule out evidence of ischemia. A negative test in patients with noncardiac pain can reassure parents about their children’s sports participation. 4. Most patients with prior congenital heart disease surgery can participate in physical activity without restrictions. Recommendations regarding appropriate levels of sports participation and exertion should be made in collaboration with the patient’s pediatric cardiology consultant.

106  Challenging Cases in Pediatric Cardiology

Suggested Reading 1. Bansal N, Aggarwal S. Chest pain. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:117–132 2. Maron BJ, Thompson PD, Ackerman MJ, et al; American Heart Association Council on Nutrition, Physical Activity, and Metabolism. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation. 2007;115(12):1643–1655 3. Maron BJ, Zipes DP. 36th Bethesda conference: Eligibility recommendations for competitive athletes with cardiovascular abnormalities. J Am Coll Cardiol. 2005;45(8):1312–1375 4. Molossi S, Grenier M. The management of athletes with congenital heart disease. Clin Sports Med. 2015;34(3):551–570

‹‹‹‹ CHAPTER 15 ››››

An Abnormal Electrocardiogram in an ­Athlete Presentation A 16-year-old white girl is seen in your office as a new patient because she was told she had an abnormal electrocardiogram (ECG) on a recent sports screening at her high school, where she plays competitive soccer. She has never been hospitalized or undergone surgery and takes no long-term medications. She denies any cardiac symptoms, including palpitations, tachycardia, dizziness, syncope, shortness of breath, or recent chest pain. Her multisystem review of systems is otherwise negative. There is no family history of sudden death or family members younger than 50 years with cardiac disease, pacemakers, defibrillators, or cardiomyopathy. Your physical examination reveals the patient is a well-nourished, fit-­appearing teen girl in no distress. Her pulse is 55 beats/min (bpm), and her blood p ­ ressure is 115/75 mm Hg in the right arm. Her cardiac examination reveals normal heart sounds without murmur or gallop. The rhythm is regular, and her peripheral pulses are normal. Her lungs are clear, her abdomen is benign, and her neurological examination results are normal. ː What are the concerns raised by a reportedly abnormal ECG obtained during sports screening? ː What evaluation is needed in addition to a careful history and physical examination?

108  Challenging Cases in Pediatric Cardiology

Differential Diagnosis Potential diagnoses associated with an abnormal ECG at sports screening examinations include the following: ː Cardiac channelopathies (long QT syndrome, others) ː Wolff-Parkinson-White (WPW) syndrome ː Atrioventricular (AV) block (second- and third-degree block) ː Ventricular hypertrophy ː False-positive or limited clinical significance © Sinus bradycardia © Early repolarization (J-point elevation) © Premature ventricular or atrial contractions © Inaccurate computerized QT interval measurement © High voltage in lateral precordial leads (in a fit athlete) © Nonspecific ST- and T-wave changes © First-degree AV and Wenckebach block

Evaluation You repeat the ECG because the previous ECG is not available for review. This ECG (Figure 15.1) demonstrates a short PR interval and ventricular preexcitation indicated by the slurring of the upstroke of the QRS complex (delta wave). After seeing this result, you consult a pediatric cardiologist and alert the cardiologist to the fact that the patient is a competitive athlete. The pediatric cardiologist repeats a detailed history and physical examination with specific reference to the fact that the patient is asymptomatic and has WPW syndrome.

Figure 15.1. A 12-lead electrocardiogram demonstrating preexcitation. This results in shortening of the PR interval and prolongation of the QRS c ­ omplex, which produces the typical slurring of the upstroke at onset of the QRS ­complex (arrows).

Chapter 15. An Abnormal Electrocardiogram in an ­Athlete  109 The cardiologist then proceeds with a treadmill exercise test, which demonstrates sudden resolution of preexcitation during exercise (loss of delta wave) in a single beat with normalization of the PR interval.

Treatment After seeing the result of the treadmill exercise test, the ­pediatric cardiolo­gist refers the patient to a pediatric electrophysiologist, who will discuss with the family the patient’s risk of developing supraventricular tachycardia (SVT) and the risk of sudden death due to the presence of preexcitation.

Discussion The evaluation and treatment of patients with ventricular preexcitation without symptoms is a controversial subject in pediatric cardiology. Caring for these patients has evolved over the past 10 to 20 years as catheter-based electrophysiology studies and ablation of accessory pathways have become much more common and are considered safe in pediatrics. During the cardiac cycle, normal depolarization of the myocardium progresses from the sinoatrial node across the atria, through the AV node, down the bundle of His, and to and through the right and left bundles (His-Purkinje system), and it activates the ventricular myocardium. The AV node and His-Purkinje system are generally the only means for an electrical impulse to travel from the atria to the ventricles. Normally, the tissue surrounding the tricuspid and mitral valves and the remainder of the tissue lining the junction of the atria and ventricles do not conduct electrical impulses, effectively providing a layer of insulation between the atria and ventricles. The upward, or positive, slurring of the QRS complex initiation (delta wave) that is present on ECGs in patients with ventricular preexcitation is caused by depolarization of the ­ventricular myocardium via conduction down an accessory pathway across the otherwise completely insulated AV tissue. This depolarization occurs before the normal ventricular depolarization via the normal AV node and His-Purkinje system (Figure 15.2), resulting in a short PR interval. Accessory pathways have been reported to be present in 0.15% to 0.25% of the general population. In a patient without symptoms, the clinical significance of ventricular preexcitation on an ECG and the accessory pathway is that it represents an electrophysiological substrate that enables the heart to produce multiple arrhythmias. First, it provides the substrate to allow SVT in the form of reentrant tachycardia (Figure 15.3). Thirty percent of patients with asymptomatic preexcitation

110  Challenging Cases in Pediatric Cardiology on ECGs will develop SVC arrhythmias during their lifetime, and LA RA SAN more than 95% of these arrhythmias MV will be simple SVT. Sudden death in TV AVN patients with WPW AP syndrome does not HB result from simple episodes of SVT. Second, the accessory pathway enables rapid conduction Figure 15.2. The normal cardiac impulse travels from the right from the atrium SAN (circle) through the right atrium to the LA and AVN where to the ventricle in it is delayed, resulting in the normal PR interval. It then travels to patients who develop the HB and the left and right bundle branches. This results in a narrow QRS. However, in patients with WPW syndrome, the atrial atrial fibrillation. In impulse travels first to the ventricle by way of the AP, resulting in atrial fibrillation, the depolarization of the ventricle before the normal impulse propathrough the AVN occurs. This results in a wide QRS and the accessory connection gation characteristic upward sloping of the QRS. (AP, accessory pathway; may allow the rapid AVN, atrioventricular node; HB, His bundle; LA, left atrium; MV, mitral valve; RA, right atrium; SAN, sinoatrial node; SVC, superior atrial impulses, up vena cava; TV, tricuspid valve; WPW, Wolff-Parkinson-White.) to 600 bpm, to be conducted directly to the ventricles without the usual rate protection, or decrement, provided by the AV node, which may result in the patient developing ventricular tachycardia or ventricular fibrillation. Episodes of ventricular fibrillation arrest in patients with WPW syndrome are thought to occur when these patients are participating in organized sports.

Figure 15.3. Typical reentrant supraventricular tachycardia (SVT) in a patient with Wolff-­ Parkinson-White (WPW) syndrome. There is the suggestion of retrograde P waves occurring early in the T waves (arrows) in this example of SVT. Retrograde P waves occur in approximately one-half of pediatric patients with WPW syndrome and SVT.

Chapter 15. An Abnormal Electrocardiogram in an ­Athlete  111 There is general agreement that patients with WPW syndrome should be assessed for any history of cardiac symptoms, such as palpitations, syncope, presyncope, or chest pain, and then be referred to a pediatric cardiologist. Further evaluation of patients with WPW syndrome with or without symptoms should be performed by a pediatric cardiologist or pediatric electrophysiologist. The goal of this evaluation is to determine whether the patient is at clinically significant risk for sudden death. The cardiologist or electrophysi­ ologist will repeat the history and physical examination from a specialist’s perspective. After WPW syndrome is established by means of an ECG, an ­echocardiogram generally should be obtained because of the higher incidence of coexisting structural heart disease than that in the general population. Further evaluation typically includes a treadmill exercise test. The goal of the exercise test is to increase the heart rate of patients in sinus rhythm and determine whether preexcitation resolves. Specifically, the ECG during a stress test will show sudden disappearance of the delta wave in a single beat as the heart rate increases, which portends a very low risk of sudden death. After the treadmill test, the pediatric cardiologist will refer the patient to an electrophysiologist if the cardiologist has not already done so. There are a number of ways of determining risk of sudden death; the approach varies among electrophysiologists. Generally, the electrophysiologist will discuss with the family the patient’s risk of developing SVT or sudden death. Through esophageal and invasive electrophysiological studies, the electrophysiologist is able to quantify more precisely the conduction properties of the accessory pathway by pacing the heart at incrementally faster rates and by assessing the inducibility of atrial fibrillation. In atrial fibrillation, risk stratification can be determined by measuring the shortest R-R interval (cycle length or heart rate) at which the preexcitation is visible on the ECG. An R-R interval of less than 250 milliseconds indicates a higher risk for developing ventricular tachycardia or fibrillation and for sudden death. Treatment of patients who are asymptomatic and have ventricular preexcitation on their ECGs is based on the results of their risk stratification. The electrophysiologist will counsel patients and families on the relative risks of intervention (radiofrequency ablation or cryoablation of the accessory pathway) versus observation and follow-up. In general, if patients undergo invasive or semi-invasive electrophysiological evaluation and their pathway is found to be low risk or unable to conduct at heart rates high enough to allow dangerous arrhythmias, observation without activity restriction is usually recommended. Catheter ablation may be recommended if the accessory pathway is found to be high risk but is balanced against the low risk of ablation. After successful catheter ablation of the accessory pathway, patients often can return to full physical activity without restriction. If those with a low-risk accessory pathway

112  Challenging Cases in Pediatric Cardiology develop tachyarrhythmia, they are still at low risk for acutely life-threatening arrhythmias. These patients may reasonably choose treatment with either medication or catheter ablation on the basis of the degree of the tachyarrhythmia. The initial care and follow-up of a patient with WPW syndrome should be managed by the patient’s pediatric cardiologist and electrophysiologist. Preparticipation ECG screenings for athletes are becoming more common, although the evidence supporting mass screening is lacking. One study in Italy showed that screening reduced the incidence of sudden death in athletes; however, other large population-based studies in Europe and the United States have failed to corroborate those findings, likely because conditions causing sudden death in athletes are rare. The American Academy of Pediatrics does not recommend obtaining an ECG as part of a standard preparticipation physical evaluation. The American Heart Association and American College of Cardiology also do not recommend preparticipation screening ECGs in children and adolescents who have negative history and examination results. However, an ECG should be part of a comprehensive evaluation if there is a positive family history of sudden death or early death; a history of heart disease in the patient; or an abnormal cardiac examination or cardiac symptoms, including syncope, dizziness, chest pain with exertion, palpitations, or sudden changes in heart rate (tachycardia or bradycardia).

Keep in Mind The possibility of SVT degrading into acutely life-threatening ventricular arrhythmias, although a rare event, is a real concern in patients with accessory pathways. The true incidence of sudden cardiac death in children with ventricular preexcitation without symptoms is unknown; however, in adults with accessory pathways (WPW syndrome) and a history of SVT, the incidence of sudden cardiac death is estimated at 0.15% to 0.39% over 10 years of follow-up.

Practice Points 1. Electrocardiographic screening before sports participation is currently not supported by the medical evidence and is not recommended by the American Academy of Pediatrics, American Heart Association, or American College of Cardiology. 2. An ECG should be part of a comprehensive evaluation if there is a positive family history of sudden death or early death; a history of heart disease in the patient; or an abnormal cardiac examination or cardiac symptoms, ­including syncope, dizziness, chest pain with exertion, palpitations, or sudden changes in heart rate, or any finding related to the cardiac system or physical examination.

Chapter 15. An Abnormal Electrocardiogram in an ­Athlete  113 3. Evidence on an ECG of WPW syndrome may be seen in patients without symptoms or in patients with SVT or other arrhythmias. 4. Patients with WPW syndrome should be under the care of a pediatric cardiologist and may benefit from evaluation by a pediatric electrophysiologist for risk stratification.

Suggested Reading 1. Cannon B. Cardiac screening for athletic participation. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:603–612 2. Wackel PL. Palpitations and arrhythmia. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:147–159 3. Chandra N, Bastiaenen R, Papadakis M, Sharma S. Sudden cardiac death in young athletes: practical challenges and diagnostic dilemmas. J Am Coll Cardiol. 2013;61(10):1027–1040 4. Maron BJ, Haas TS, Ahluwalia A, Murphy CJ, Garberich RF. Demographics and epidemiology of sudden deaths in young competitive athletes: from the United States National Registry. Am J Med. 2016;129(11):1170–1177 5. Cannon BC, Snyder CS. Disorders of cardiac rhythm and conduction. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:623–653 6. Cohen MI, Triedman JK, Cannon BC, et al; Pediatric and Congenital Electrophysiology Society (PACES); Heart Rhythm Society (HRS); American College of Cardiology Foundation (ACCF); American Heart Association (AHA); American Academy of Pediatrics (AAP); Canadian Heart Rhythm Society (CHRS). PACES/HRS expert consensus statement on the management of the asymptomatic young patient with a Wolff-ParkinsonWhite (WPW, ventricular preexcitation) electrocardiographic pattern. Heart Rhythm. 2012;9(6):1006–1024 7. Maron BJ, Friedman RA, Kligfield P, et al; American Heart Association Council on Clinical Cardiology, Advocacy Coordinating Committee, Council on Cardiovascular Disease in the Young, et al; American College of Cardiology. Assessment of the 12-lead electrocardiogram as a screening test for detection of cardiovascular disease in healthy general populations of young people (12-25 years of age). J Am Coll Cardiol. 2014;64(14):1479–1514

PART 2

Pediatric Cardiology in the Nursery

‹‹‹‹ CHAPTER 16 ››››

Cyanosis in a Newborn Presentation You are called to evaluate an 18-hour-old white male in the newborn nursery whose skin has a bluish discoloration, most notably in the lips, face, and extremities. The neonate was born at 39 weeks’ gestation to a 24-year-old woman who received routine prenatal care, including normal screening laboratory tests. Screening ultrasonography at 20 weeks’ gestation (4-chamber view) is reported to be normal. Delivery of the 3.5-kg neonate was uncomplicated, and he required no resuscitation. He breastfed vigorously after delivery. At examination, the neonate is cyanotic and tachypneic but appears comfortable and calm. He is afebrile, with a respiratory rate of 80 breaths/min and a heart rate of 160 beats/min. His blood pressure is 95/50 mm Hg in the right upper extremity and 91/52 mm Hg in the left lower extremity. Pulse oximetry of upper and lower extremities is symmetrical, with oxygen saturations of 65%. The neonate’s face, chest, hands, and feet show no signs of defect. Cyanosis is visible on his oral mucosa, as well as extending over his trunk. His chest is clear at auscultation, with excellent chest excursion and without retraction. You do not hear a murmur. The S2 is loud at the second left intercostal space. Brachial and femoral pulses are strong with no delay. ː On the basis of the history so far, which findings favor a cardiac diagnosis and which do not? ː Does the reportedly normal screening ultrasonography at 20 weeks’ gestation rule out heart defects? ː What are the implications of the neonate appearing comfortable and calm while tachypneic?

118  Challenging Cases in Pediatric Cardiology

Differential Diagnosis Potential causes of cyanosis in newborns include the following: ː Pulmonary © Hyaline membrane disease © Meconium aspiration syndrome © Pneumonia © Pneumothorax © Pulmonary malformation © Persistent pulmonary hypertension of the newborn ː Cardiac © Cyanotic congenital heart disease ƒ Transposition of the great arteries, tetralogy of Fallot, tricuspid ­atresia, pulmonary atresia, critical pulmonary stenosis, Ebstein anomaly, ­hypoplastic left heart syndrome, truncus arteriosus © Heart failure, cardiogenic shock ː Other © Sepsis © Methemoglobinemia © Hypoglycemia © Polycythemia

Evaluation You order an electrocardiogram (ECG) and chest radiography, in addition to blood work to assess glucose level, differential blood cell count, and C-reactive protein level and to collect cultures before the empiric initiation of antibiotics. The results of the laboratory tests are normal. Pulse oximetry is repeated at pre- and postductal locations. The ECG is normal and consistent with neonatal age (Figure 16.1). The chest radiograph (Figure 16.2) shows cardiomegaly, a narrow superior mediastinum, and increased vascular markings consistent with pulmonary overcirculation. No findings of respiratory distress syndrome or clinically significant noncardiac congenital anomalies are demonstrated. You decide to order a hyperoxia test. The neonate receives 100% oxygen, but after 10 minutes his partial pressure of arterial oxygen (Pao2) remains low at 40 mm Hg in both pre- and postductal samples. Your suspicion of possible transposition of the great arteries (TGA) is high. You decide to transport the neonate to an advanced cardiac care center for diagnosis by means of echocardiography and cardiology consultation.

Chapter 16. Cyanosis in a Newborn  119

Figure 16.1. Normal electrocardiogram findings showing normal axis and precordial voltage. Upright T waves in lead V1 are normal in newborns, but after 7 days of age and before 6 years of age, they are suggestive of right ventricular hypertrophy.

Treatment Prostaglandin E1 (PGE1) is instituted at 0.1 mcg/kg/min via an umbilical venous catheter, and the neonate is intubated before transport. An echocardiogram (Figure 16.3) at the referral center demonstrates TGA without a ventricular septal defect or pulmonary stenosis (so-called simple transposition). The coronary arterial pattern is the most common variant, with the right and left coronary arteries arising from the right- and left-­ Figure 16.2. Anteroposterior chest radiograph facing sinuses, respectively. There is demonstrating cardiomegaly, increased pulmoa large patent ductus arteriosus and nary vascular markings, and a narrow mediastinum. The narrow mediastinum is due to a small patent foramen ovale. The the anteroposterior position of the aorta and neonate is scheduled for an arterial pulmonary artery and strongly suggests transposition of the great arteries. There are no signs switch procedure the following of pulmonary ­parenchymal disease or decreased pulmonary blood flow. week. He develops metabolic acidosis associated with decreasing arterial saturation, so balloon atrial septostomy is performed. This procedure leads to improvement in saturation and resolution of the metabolic acidosis. The arterial switch procedure is performed as planned.

120  Challenging Cases in Pediatric Cardiology

Discussion Cyanosis as a result of hypoxemia is an alarming manifestation that requires rapid evaluation and intervention. Although pulmonary causes of oxygen desaturation and cyanosis are common, the affected neonates often have chest retractions and auscultatory signs of ­pulmonary parenchymal disease, Figure 16.3. Typical echocardiogram findings in transposition of the great arteries. The aorta such as the rales in hyaline memarises in a transposed fashion from the RV brane disease. Newborns with sep- ­anterior to the PA, which is connected to the sis or pneumonia often have known LV. (AO, aorta; LV, left ventricle; PA, pulmonary artery; RV, right ventricle.) risk factors. Other causes of cyanosis, such as polycythemia, hypoglycemia, and methemoglobinemia, are easily ruled out. Although cyanosis from congenital heart disease may be associated with a murmur or other physical findings, that is not always the case, particularly when there is no obstruction of the pulmonary or aortic outflow tracts, atrioventricular valve insufficiency, or ventricular septal defect. Transposition of the great arteries is the classic example of cyanotic heart disease without murmur or other findings suggestive of a cardiac defect. Characteristically, the S2 is loud and single because of the anterior position of the aortic valve beneath the sternum, but this sound may not be obvious in a neonate. Newborns with TGA are typically tachypneic but not in distress, as in this case. Transposition of the great arteries causes severe cyanosis because systemic venous return to the right ventricle is recirculated to the transposed aorta, while systemic circulation and oxygenated pulmonary venous return recirculate through the left ventricle to the transposed pulmonary artery. This situation results in rapid depletion of oxygen in the systemic arterial circulation. Survival is possible only to the extent that oxygenated blood can pass from the left atrium to the right atrium via a patent foramen ovale or from the pulmonary artery to the aorta via a patent ductus arteriosus. Consequently, PGE1 administration is lifesaving and should be initiated as soon as possible once the diagnosis of critical congenital heart disease is suspected. After central venous access (umbilical venous in most cases) is established, PGE1 is administered at 0.05 to 0.1 mcg/kg/min. Prostaglandins cause hypoventilation and apnea, so, immediately after initiating PGE1 treatment, care should be taken to monitor sufficiency of ventilation, and preparation should be made to intubate and ventilate the patient mechanically. Other short-term adverse effects of PGE1 include fever, tachycardia, and flushing.

Chapter 16. Cyanosis in a Newborn  121 The definitive surgical treatment for TGA is the arterial switch procedure. Excellent outcomes should be expected, with hospital survival in excess of 95%. Balloon atrial septostomy is not performed routinely in some centers where neonates with TGA undergo surgery within days of diagnosis. However, in other centers, balloon atrial septostomy is performed routinely or reserved for patients whose saturations remain low with use of PGE1. Newborns with TGA usually present with severe cyanosis shortly after birth, often within minutes to hours of birth, but other cyanotic congenital defects may not produce obvious clinical indications. Screening for critical congenital heart disease by using pulse oximetry was designed to identify 7 conditions (tricuspid atresia, pulmonary atresia, tetralogy of Fallot, TGA, hypoplastic left heart syndrome, truncus arteriosus, and total anomalous pulmonary venous return [TAPVR]), but pulse oximetry screening must be accompanied by a complete cardiac examination, including blood pressures in both arms and 1 leg to maximize detection of congenital heart defects, particularly those that do not produce cyanosis.

Keep in Mind Differentiation between pulmonary and cardiac causes of cyanosis may be aided by the hyperoxia test, which assesses the increase in Pao2 in response to the increased fraction of inspired oxygen. The test involves obtaining baseline arterial blood samples in pre- and postductal locations and then repeating them after administration of 100% oxygen for at least 10 minutes. The normal physiological response to an increase in the fraction of inspired oxygen to 100% is an increase in Pao2 to greater than 300 mm Hg. In cyanotic heart disease, the Pao2 will not increase, whereas with pulmonary disease a clinically significant increase is observed. A Pao2 of less than 50 mm Hg with use of 100% oxygen is very likely to indicate congenital heart disease, whereas a Pao2 greater than 150 mm Hg is unlikely to indicate congenital heart disease. There are exceptions, however. In cyanotic heart defects with high pulmonary blood flow and clinically significant intracardiac mixing of arterial and venous blood, an increase in Pao2 of 50 to 150 mm Hg may be observed (such as in unobstructed TAPVR). Conversely, with very severe pulmonary parenchymal disease, there may be no clinically significant increase in Pao2. Also, differential pre- and postductal changes may give a clue to the nature of the congenital defect. There is very little risk to performing the hyperoxia test, including no risk of inducing closure of the ductus arteriosus by administering 100% oxygen.

122  Challenging Cases in Pediatric Cardiology

Practice Points 1. Newborns with cyanotic congenital heart disease may not have physical examination findings other than cyanosis to suggest a heart defect. 2. Suspicion for cyanotic heart disease, with or without an abnormal examination or chest radiograph, should suggest immediate referral of the patient to a tertiary care center capable of making an echocardiographic diagnosis. 3. If cyanotic heart disease is likely, PGE1 administration should be initiated quickly and not delayed because ductal closure may lead to deterioration and death. Initiation of PGE1 before transport, if at all possible, is essential. 4. Prostaglandin E1 may cause hypoventilation and apnea, so careful monitoring of the newborn’s airway and ventilation is essential after administration. 5. Rapid access to a center whose staff can perform a catheter balloon atrial septo­stomy may be lifesaving because in some infants, a patent ductus ­arteriosus is not adequate to sustain life. 6. The arterial switch procedure is lifesaving for neonates with TGA, with surgical survival better than 95%.

Suggested Reading 1. Haxel C, Glickstein J. Evaluation of the neonate with congenital heart disease. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:171–184 2. Ahmad H, Chowdhury D. Neonatal screening for heart disease. In: Johnson JN, Kamat DM, eds. Common Cardiac Issues in Pediatrics. Itasca, IL: American Academy of Pediatrics; 2018:197–204 3. Qureshi AM, Justino H, Heinle JS. Transposition of the great arteries. In: Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F, eds. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2016:1163–1186 4. Moe TG, Bardo DME. Long-term outcomes of the arterial switch operation for d-transposition of the great arteries. Prog Cardiovasc Dis. 2018;61(3-4): 360–364

‹‹‹‹ CHAPTER 17 ››››

A Loud Murmur in a Neonate ­Without  Symptoms Presentation You are asked to perform a routine newborn examination in an 18-hour-old black male before he is discharged. The pregnancy, delivery, and immediate transition period were unremarkable. The neonate has passed meconium and has had 3 wet diapers since delivery. He has no visible cyanosis or tachypnea and appears to be comfortable and appropriately alert. At birth, his weight was 3.1 kg (50th percentile), his length was 45.5 cm (10th percentile), and his frontooccipital circumference was 31 cm (