The Cleveland Clinic Cardiology Board Review, 3e (Dec 24, 2021)_(1496399188)_(LWW).pdf 9781496399182, 9781496399199

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The Cleveland Clinic

Cardiology Board Review THIRD EDITION

THE CLEVELAND CLINIC CARDIOLOGY BOARD REVIEW

THE CLEVELAND CLINIC CARDIOLOGY BOARD REVIEW THIRD EDITION EDITORS Brian P. Griffin, MD, FACC John and Rosemary Brown Chair in Cardiovascular Medicine Section Head, Cardiovascular Imaging Department of Cardiovascular Medicine Heart, Thoracic and Vascular Institute Cleveland Clinic Cleveland, Ohio

Samir R. Kapadia, MD, FACC Professor of Medicine Chairman, Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Venu Menon, MD, FACC, FAHA, FESC Mehdi Razavi MD, Education Endowed Chair Director of Cardiac Intensive Care Unit Director, Cardiovascular Fellowship Associate Director C5 Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Cleveland Clinic Cleveland, Ohio

...._....~ Wolters

Kluwer

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Senior Acquisitions Editor: Keith Donnellan Senior Development Editor: Ashley Fischer Editorial Coordinator: Christopher Rodgers Marketing Manager: Kirsten Wartrud Production Project Manager: Bridgett Dougherty Manager, Graphic Arts & Design: Stephen Druding Senior Manufacturing Coordinator: Beth Welsh Prepress Vendor: Straive Third Edition Copyright © 2022 Wolters Kluwer Copyright © 2013 by LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER business. First Edition © 2007 by LIPPINCOTT WILLIAMS & WILKINS. All rights reserved. This book is protected by copyright. No part of this book may be reproduced or transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. government employees are not covered by the abovementioned copyright. To request permission, please contact Wolters Kluwer at Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103, via email at [email protected], or via our website at shop.lww.com (products and services). 987654321 Printed in China Library of Congress Cataloging-in-Publication Data Names: Griffin, Brian P., 1956-editor. | Kapadia, Samir R., editor. | Menon, Venu, editor. Title: The Cleveland Clinic cardiology board review / editors, Brian P. Griffin, Samir R. Kapadia, Venu Menon.Other titles: Cardiology board review Description: Third edition. | Philadelphia : Wolters Kluwer, [2022] | Includes bibliographical references and index. | Summary: “Providing a comprehensive, state-of-the-art review of every area of contemporary cardiovascular medicine, The Cleveland Clinic Cardiology Review is an excellent tool for learning and reviewing key concepts in major areas of cardiology. The ThirdEdition contains fully revised content, review questions used on the board exam. A new, easy-to-follow chapter template facilitates quick review and retention of the material. Emphasizes board-relevant clinical material and accurate, real-world clinical decision making.Covers every major topic you’ll encounter on certification and recertification exams, including congenital heart disease, electrophysiology, valvular heart disease, vascular disease, and pharmacology, and more. Presents review questions with each chapter for thorough exam preparation and self-assessment. Uses a new, consistent format for most chapters: introduction, clinical presentation, diagnosis, algorithm, treatment, suggested readings, and questions/answers.Written by distinguished clinicians from the Cleveland Clinic Foundation’s Department of Cardiovascular Medicine and based on the Cleveland Clinic Foundation’s popular annual Intensive Review of Cardiology course. Enrich Your eBook Reading ExperienceRead directly on your preferred device(s), such as computer, tablet, or smartphone. Easily convert to audiobook, powering your content with natural language text-to-speech”—Provided by publisher.

Identifiers: LCCN 2021041912 (print) | LCCN 2021041913 (ebook) | ISBN 9781496399182 (casebound) | ISBN 9781496399199 (epub) Subjects: MESH: Cardiovascular Diseases | Examination Questions | Outline | BISAC: MEDICAL / Cardiology | MEDICAL / Education & Training Classification: LCC RC667 (print) | LCC RC667 (ebook) | NLM WG 18.2 | DDC 616.10076—dc23 LC record available at https://lccn.loc.gov/2021041912 LC ebook record available at https://lccn.loc.gov/2021041913 This work is provided “as is,” and the publisher disclaims any and all warranties, express or implied, including any warranties as to accuracy, comprehensiveness, or currency of the content of this work. This work is no substitute for individual patient assessment based upon healthcare professionals’ examination of each patient and consideration of, among other things, age, weight, gender, current or prior medical conditions, medication history, laboratory data and other factors unique to the patient. The publisher does not provide medical advice or guidance and this work is merely a reference tool. Healthcare professionals, and not the publisher, are solely responsible for the use of this work including all medical judgments and for any resulting diagnosis and treatments. Given continuous, rapid advances in medical science and health information, independent professional verification of medical diagnoses, indications, appropriate pharmaceutical selections and dosages, and treatment options should be made and healthcare professionals should consult a variety of sources. When prescribing medication, healthcare professionals are advised to consult the product information sheet (the manufacturer’s package insert) accompanying each drug to verify, among other things, conditions of use, warnings and side effects and identify any changes in dosage schedule or contraindications, particularly if the medication to be administered is new, infrequently used or has a narrow therapeutic range. To the maximum extent permitted under applicable law, no responsibility is assumed by the publisher for any injury and/or damage to persons or property, as a matter of products liability, negligence law or otherwise, or from any reference to or use by any person of this work. shop.lww.com

To our families

CONTRIBUTING AUTHORS Philip Aagaard, MD Cardiovascular Medicine Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Haitham Ahmed, MD Cardiovascular Medicine Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Chonyang L. Albert, MD, FACC Assistant Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Staff, Advanced Heart Failure and Transplant Cardiology Cleveland Clinic Cleveland, Ohio

Craig R. Asher, MD, FACC, FASE Department of Cardiology Cleveland Clinic Florida Weston, Florida

Ajay Bhargava, MD Section of Clinical Cardiology Department of Cardiovascular Medicine

Cleveland Clinic Cleveland, Ohio

Mandeep Bhargava, MD Staff Physician Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Pavan Bhat, MD, FACC Advanced Heart Failure and Transplantation Staff Section of Heart Failure and Transplantation Medicine Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Sanjeeb Bhattacharya, MD, FACC Section of Heart Failure and Cardiac Transplant Medicine Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Ashley Bock, MD Advanced Heart Failure Cardiologist TriStar Centennial Heart and Vascular Center TriStar Centennial Medical Center Nashville, Tennessee

Michael A. Bolen, MD Associate Professor of Radiology Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Staff Radiologist Cardiovascular and Thoracic Sections Imaging Institute

Cleveland Clinic Cleveland, Ohio

Nyal E. Borges, MD Chief Fellow, Intervention Cardiology Cleveland Clinic Cleveland, Ohio

Thomas D. Callahan IV, MD, FACC, FHRS Director of Inpatient Services Section of Electrophysiology and Pacing Department of Cardiovascular Medicine Family Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Joseph D. Campbell, MD Staff Physician Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Daniel J. Cantillon, MD Associate Section Head of Cardiac Electrophysiology and Pacing Medical Director Central Monitoring Unit Heart, Thoracic and Vascular Institute Cleveland Clinic Cleveland, Ohio

Michael Chetrit, MD, FRCPC, FACC Assistant Professor of Medicine McGill University Cardiologist McGill University Health Centre

Co-Director McGill Amyloidosis Project Montreal, Quebec, Canada

Leslie Cho, MD, FACC, FSCAI, FESC Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Section Head, Preventive Cardiology and Rehabilitation Director, Women's Cardiovascular Center Cleveland, Ohio

Patrick Collier, MD, PhD, FASE, FESC, FACC Staff, Cardiovascular Medicine Co-Director of Cardio-Oncology Center Deputy Director Echo Lab Associate Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Cleveland Clinic Cleveland, Ohio

Paul C. Cremer Associate Director Cardiovascular Training Program and Cardiac Intensive Care Unit Cleveland Clinic Cleveland, Ohio

Thomas M. Das, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Kara Denby, MD

Fellow Department of Cardiovascular Medicine Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Milind Y. Desai, MD, MBA, FACC, FAHA, FESC Haslam Family Endowed Chair in Cardiovascular Medicine Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Director, Clinical Operations Director, HCM Center Medical Director, Aorta Center Department of Cardiovascular Medicine Heart, Thoracic and Vascular Institute Cleveland Clinic Cleveland, Ohio

Eoin Donnellan, MD Fellow in Cardiac Electrophysiology Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Stephen G. Ellis, MD Director, Interventional Cardiology Cleveland Clinic Cleveland, Ohio

Jerry D. Estep, MD, FACC, FASE Section Head of Heart, Failure and Transplantation Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Michael D. Faulx, MD, FACC Associate Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Staff Cardiologist Section of Clinical Cardiology Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

J. Emanuel Finet, MD, FACC, FHFSA Clinical Assistant Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Staff, Section of Heart Failure and Transplantation Medicine Medical Director, Metabolic Exercise Testing Center Department of Cardiovascular Medicine Heart, Vascular and Thoracic Institute Cleveland Clinic

James L. Gentry III, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Foundation Cleveland, Ohio

Joanna Ghobrial, MD, MSc Director of Adult Congenital Heart Disease Department of Cardiovascular Medicine Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Marcelo Gomes, MD, FSVM, RPVI

Co-Associate Section Head—Vascular Medicine Department of Cardiovascular Medicine Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Matthew Gonzalez, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, OH

Steven M. Gordon, MD Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Chairman, Department of Infectious Diseases Respiratory Institute Cleveland Clinic Foundation Cleveland, Ohio

Brian P. Griffin, MD, FACC John and Rosemary Brown Chair in Cardiovascular Medicine Section Head, Cardiovascular Imaging Department of Cardiovascular Medicine Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Adam Grimaldi, MD Department of Cardiovascular Medicine Heart and Vascular Institute Cleveland Clinic Cleveland, Ohio

Jonathan D. Hansen, MD, MPH

Fellow, Interventional Cardiovascular Medicine Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Serge C. Harb, MD, FACC Assistant Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Staff, Section of Cardiovascular Imaging Department of Cardiovascular Medicine Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Jeffrey S. Hedley, MD, MSc Fellow, Clinical Cardiac Electrophysiology Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Grant Henderson, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Andrew R. Higgins, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Eileen Hsich, MD

Medical Director for Heart Transplant at Cleveland Clinic Department of Cardiology Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Cleveland, Ohio

Peter T. Hu, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Chetan P. Huded, MD, MSc, FACC, FSCAI Cardiovascular Consultant Interventional and Structural Cardiology Saint Luke's Mid America Heart Institute University of Missouri–Kansas City School of Medicine Kansas City, Missouri

Muzna Hussain, MD Research Fellow Department of Cardiovascular Medicine, Imaging Section Cleveland Clinic Cleveland, Ohio

Ayman A. Hussein, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Erika Hutt-Centeno, MD Fellow Department of Cardiovascular Medicine

Cleveland Clinic Cleveland, Ohio

Zachary J. Il'Giovine, MD Fellow Department of Cardiovascular Medicine Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Wael A. Jaber, MD, FACC, FESC Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Fuad Jubran Endowed Chair in Cardiovascular Medicine Heart, Thoracic and Vascular Institute Cleveland Clinic Cleveland, Ohio

Miriam Jacob Staff Physician, Program Director Cardiovascular Medicine Section of Advances Heart Failure and Transplantation Cleveland Clinic Cleveland, Ohio

Christine Jellis, MD, PhD, FACC, FASE Associate Professor of Medicine Staff Cardiologist Department of Cardiovascular Medicine Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Vidyasagar Kalahasti, MD, FACC

Staff, Department of Cardiovascular Imaging Assistant Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Associate Director Clinical Endpoints Committee Heart, Thoracic and Vascular Institute Cleveland Clinic Cleveland, Ohio

Mohamed Kanj, MD Co-Director, Electrophysiology Laboratories Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Samir R. Kapadia, MD, FACC Professor of Medicine Chairman, Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Deborah Kerrigan, MD, MA Assistant Professor of Medicine Department of Neurology Vanderbilt University School of Medicine Vanderbilt University Medical Center Nashville, Tennessee

Jimmy Kerrigan, MD, FACC, FSCAI Assistant Professor of Medicine Division of Cardiology University of Tennessee College of Medicine Interventional Cardiologist Ascension Saint Thomas Heart

Co-Director, Advanced Coronary Therapeutics Program Ascension Saint Thomas West Hospital Co-Director, Pulmonary Embolism Response Team Ascension Saint Thomas West Hospital Chair, Ascension Chronic Total Occlusion Interventional Cardiology Affinity Group University of Tennessee Health Science Center Ascension St. Thomas West Hospital Nashville, Tennessee

Allan L. Klein, MD, FRCP(C), FACC, FAHA, FASE, FESC Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Director, Center for the Diagnosis and Treatment of Pericardial Diseases Section of Cardiovascular Imaging Department of Cardiovascular Medicine Heart, Vascular and Thoracic Institute Past-President, American Society of Echocardiography Cleveland Clinic Cleveland, Ohio

Robert A. Koeth, MD, PhD Clinical Assistant Professor of Molecular Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Fellow, Cardiac Electrophysiology Department of Cardiovascular Medicine, Section of Cardiac Pacing and Electrophysiology Heart, Thoracic and Vascular Institute Cleveland Clinic Cleveland, Ohio

Amar Krishnaswamy, MD Section Head, Interventional Cardiology Director, Sones Cardiac Catheterization Laboratories

Program Director, Interventional Cardiology Fellowship Cleveland Clinic Cleveland, Ohio

Anirudh Kumar, MD, MSc Fellow, Interventional Cardiology Heart, Thoracic and Vascular Institute Cleveland Clinic Cleveland, Ohio

Luke J. Laffin, MD, FACC Co-Director, Center for Blood Pressure Disorders Medical Director of Cardiac Rehabilitation Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Cameron T. Lambert, MD Fellow, Cardiac Electrophysiology Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Harry M. Lever, MD Staff Physician Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

A. Michael Lincoff, MD Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Vice Chairman for Research Department of Cardiovascular Medicine

Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Kyle Mandsager, MD, FACC Cardiac Electrophysiologist Centennial Heart Centennial Hospital Nashville, Tennessee

Preethi Mani, MD, MPH Fellow, Advanced Cardiac Imaging Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Kenneth A. Mayuga, MD, FHRS, FACC, FACP Staff Physician in Cardiac Electrophysiology Director of the Syncope Center Cleveland Clinic Assistant Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Cleveland, Ohio

Venu Menon, MD, FACC, FAHA, FESC Mehdi Razavi MD, Education Endowed Chair Director of Cardiac Intensive Care Unit Director, Cardiovascular Fellowship Associate Director C5 Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Cleveland Clinic Cleveland, Ohio

Richard D. Meredith, MD Cleveland Clinic Foundation Cleveland, Ohio

Michael A. Militello, PharmD, BCPS Pharmacotherapy Residency Program Director Department of Pharmacy Cleveland Clinic Cleveland, Ohio

Maria M. Mountis, DO Staff Cardiologist Section of Heart Failure and Transplant Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Vinayak Nagaraja, MBBS, MS, MMed (Clin Epi), FRACP Department of Cardiovascular Medicine Cleveland Clinic Foundation Cleveland, Ohio

Shady Nakhla, MD Fellow, Department of Cardiovascular Medicine Clinical Instructor of Medicine Cleveland Clinic Cleveland, Ohio

David M. Nemer, MD Fellow Cleveland Clinic Cleveland, Ohio

Andrew E. Noll, MD

Section of Electrophysiology Department of Cardiovascular Medicine Cleveland Clinic Foundation Cleveland, Ohio

Divyang Patel, MD Fellow, Department of Cardiovascular Medicine Cleveland Clinic Foundation Cleveland, Ohio

Dermot Phelan, MD, PhD, FASE, FACC Medical Director, Cardiovascular Imaging Director, Sports Cardiology Program Co-Director, Hypertrophic Cardiomyopathy Program Sanger Heart & Vascular Institute Atrium Health Charlotte, North Carolina

Varinder Kaur Randhawa, MD, PhD Research Fellow Section of Heart Failure and Transplantation Medicine Department of Cardiovascular Medicine Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Claire E. Raphael, MBBS MA. PhD Interventional Cardiologist Heart, Vascular and Thoracic Institute Cleveland Clinic Main Campus

Russell E. Raymond, DO Interventional Cardiology Cleveland Clinic Cleveland, Ohio

Grant W. Reed, MD, MSc, FACC, FSCAI Associate Program Director Cardiovascular Medicine Fellowship Director, STEMI Program Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

John Rickard, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Christina Rigelsky, MS, CGC Lead Cardiovascular Genetic Counselor Center for Personalized Genetic Healthcare Cleveland Clinic Cleveland, Ohio

L. Leonardo Rodriguez, MD, FACC, FASE, FESC Program Director of Advanced Cardiovascular Imaging Fellowship Associated Director of Echocardiography Laboratory Department of Cardiovascular Medicine Heart, Thoracic and Vascular Institute Cleveland Clinic Cleveland, Ohio

Jeffrey E. Rossi, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Joshua Saef, MD

Fellow, Adult Congenital Heart Disease Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania

Walid Saliba, MD Director, Atrial Fibrillation Center Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Aldo L. Schenone, MD Chief Non-Invasive Cardiovascular Imaging Fellow Brigham and Women's Hospital Harvard Medical School Boston, Massachusetts

Nishant P. Shah, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Zarina M. Sharalaya, MD Fellow, Interventional Cardiology Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Abhinav Sharma, MD Assistant Professor Department of Cardiovascular Medicine Medical College of Wisconsin Wauwatosa, Wisconsin

Calvin Chen Sheng, MD Fellow Department of Cardiovascular Medicine Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Conrad C. Simpfendorfer, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Nikolaos Spilias, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Khaldoun G. Tarakji, MD, MPH Associate Section Head, Cardiac Electrophysiology Associate Professor Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Patrick J. Tchou, MD Section of Cardiac Electrophysiology and Pacing Department Cardiovascular Medicine Heart, Thoracic and Vascular Institute Cleveland Clinic Cleveland, Ohio

Kartik S. Telukuntla, MD Fellow, Advanced Heart Failure and Transplant Cardiology Heart, Vascular and Thoracic Institute Cleveland Clinic Cleveland, Ohio

Albree Tower-Rader, MD, FACC Division of Cardiology Department of Medicine Harvard Medical School Massachusetts General Hospital Boston, Massachusetts

Kevin M. Trulock, MD Fellow Department of Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Rayji S. Tsutsui, MD, ChB, MPH Structural Interventional Cardiologist Department of Cardiology Straub Medical Centre Hawaii Pacific Health Honolulu, Hawaii

Sneha Vakamudi, MD Ascension Seton Heart & Vascular Assistant Professor Dell Medical School The University of Texas at Austin Austin, Texas

Oussama Wazni, MD

Section Head, Cardiology Department of Cardiovascular Medicine Cardiology Cleveland Clinic Cleveland, Ohio

Bruce L. Wilkoff, MD Cardiovascular Medicine Fellow Department of Cardiovascular Medicine Cleveland Clinic Foundation Cleveland, Ohio

Bo Xu, MD Imaging Cardiologist Section of Cardiovascular Imaging Department of Cardiovascular Medicine Heart, Vascular and Thoracic Institute Cleveland, Ohio

Laura Young, MD Fellow, Interventional Cardiology Department of Cardiovascular Medicine Clinical Instructor Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Cleveland, Ohio

Kenneth G. Zahka, MD, FACC, FAAP, FAHA Professor of Pediatrics Cleveland Clinic Lerner College of Medicine Case Western Reserve University School of Medicine Department of Pediatric Cardiology Adult Congenital Heart Disease Center Cleveland Clinic Cleveland, Ohio

PREFACE The aim of this edition of the book is unchanged in its essence and is to provide a comprehensive topical overview of cardiovascular medicine in a concise and readable format. The needs of those seeking to revise the practice of cardiology broadly with a view to undertaking certification and recertification examinations were very much to the fore as we revised the book and led to the inclusion of new material and questions. We hope that this book will be useful not only to exam takers but also to cardiology fellows, cardiologists, and other providers seeking a targeted review of the current scope of cardiovascular medicine. We wish to acknowledge the support and assistance of both faculty and fellows in cardiovascular medicine and related disciplines at Cleveland Clinic who wrote the individual chapters and questions. We particularly want to dedicate this book to our colleagues and fellows and of course to our families. We hope you find this updated edition easy to use and helpful. Brian P. Griffin Samir R. Kapadia Venu Menon

CONTENTS Contributing Authors Preface

I FUNDAMENTALS 1 How to Pass the Cardiovascular Disease Board Examination

John Rickard and Grant W. Reed

2 Cardiac Physical Examination Craig R. Asher

3 Cardiac Anatomy

Samir R. Kapadia and Nishant P. Shah

4 Cardiovascular Physiology: Flow–Volume Loops Richard D. Meredith and Michael D. Faulx

5 Basic Cardiac Electrophysiology Patrick J. Tchou

6 Cardiac Biochemistry

Robert A. Koeth and Venu Menon

7 Clinical Epidemiology and Biostatistics Sneha Vakamudi and Paul C. Cremer

II CARDIOVASCULAR IMAGING AND STRESS TESTING 8 Chest Radiography for the Cardiovascular Medicine Boards

Albree Tower-Rader and Michael A. Bolen

9 Doppler Echocardiography Bo Xu and Christine Jellis

10

Electrocardiographic Stress Testing

11

Stress Echocardiography

12

Nuclear Cardiac Imaging: A Primer

13

Cardiac MRI and CT

Philip Aagaard and Haitham Ahmed

Abhinav Sharma and L. Leonardo Rodriguez

Aldo L. Schenone, Paul C. Cremer, and Wael A. Jaber

James L. Gentry III and Milind Y. Desai

III CONGESTIVE HEART CARDIOMYOPATHY

FAILURE

14

Pathophysiology of Heart Failure

15

Medical Treatment of Heart Failure

Varinder Kaur Randhawa, Ashley Bock, and J. Emanuel Finet

AND

Chonyang L. Albert and Jerry D. Estep

16

Heart Transplantation

17

Devices for Heart Failure

18

Myocarditis and Dilated Cardiomyopathy

19

Pulmonary Hypertension

20

Heart Failure with Preserved Ejection Fraction

21

Hypertrophic Cardiomyopathy

Kartik S. Telukuntla, Matthew Gonzalez, and Eileen Hsich

Pavan Bhat and Maria M. Mountis

Zachary J. Il’Giovine and Sanjeeb Bhattacharya

Kartik S. Telukuntla and Miriam Jacob

Albree Tower-Rader and Allan L. Klein

Sneha Vakamudi and Harry M. Lever

IV CONGENITAL HEART DISEASE 22

Congenital Heart Disease in the Adult

23

Echocardiography in Congenital Heart Disease

Joshua Saef and Joanna Ghobrial

Serge C. Harb and Christine Jellis

V CARDIAC ELECTROPHYSIOLOGY

24

Twelve-Lead Electrocardiography

25

Electrophysiologic Testing, Including His Bundle and Other Intracardiac Electrograms

Peter T. Hu and Ajay Bhargava

Kevin M. Trulock and Thomas D. Callahan IV

26

Sudden Cardiac Death and Ventricular Tachycardia

27

Atrial Fibrillation and Flutter

28

Supraventricular Tachycardias

29

Wide Complex Tachycardia: Ventricular Tachycardia versus Supraventricular Tachycardia

Cameron T. Lambert, Daniel J. Cantillon, and Oussama Wazni

Ayman A. Hussein and Mohamed Kanj

Andrew E. Noll and Mandeep Bhargava

Adam Grimaldi and Walid Saliba

30

Pacemakers and Defibrillators

31

Syncope

Divyang Patel, Bruce L. Wilkoff, and Khaldoun G. Tarakji

Erika Hutt-Centeno, Jeffrey S. Hedley, and Kenneth A. Mayuga

VI VALVULAR HEART DISEASE 32

Aortic and Pulmonary Valve Disease Richard D. Meredith, Amar Krishnaswamy, and Brian P. Griffin

33

Mitral Valve and Tricuspid Valve Disease

34

Infective Endocarditis

35

Prosthetic Valve Disease

Bo Xu and Serge C. Harb

Andrew R. Higgins and Steven M. Gordon

Preethi Mani and Paul C. Cremer

VII CORONARY ARTERY DISEASE CARDIAC CATHETERIZATION

AND

36

Evaluation of Chest Discomfort

37

Coronary Artery Disease: Epidemiology

38

Stable Angina: Diagnosis, Risk Stratification, Medical Therapy, and Revascularization Strategies

David M. Nemer and Wael A. Jaber

Calvin Chen Sheng and Leslie Cho

Chetan P. Huded and Conrad C. Simpfendorfer

39

Unstable Coronary Syndrome

40

Acute Myocardial Infarction

41

Complications of Myocardial Infarction

Jonathan D. Hansen and A. Michael Lincoff

Venu Menon and Chetan P. Huded

Thomas M. Das and Venu Menon

42

Risk Stratification and Post–Myocardial Infarction Therapy Nyal E. Borges and Samir R. Kapadia

43

Radiation Safety Laboratory

in

the

Cardiac

Catheterization

Rayji S. Tsutsui and Samir R. Kapadia

44

Hemodynamic Measurements

45

Catheterization Laboratory Imaging and Functional Assessment

Jeffrey E. Rossi and Amar Krishnaswamy

Anirudh Kumar and Samir R. Kapadia

46

Percutaneous Coronary Intervention Claire E. Raphael and Stephen G. Ellis

VIII AORTA/PERIPHERAL DISEASE 47

Diseases of the Aorta

48

Venous Thromboembolism

49

Peripheral Artery Disease

VASCULAR

Grant Henderson and Vidyasagar Kalahasti

Erika Hutt-Centeno and Marcelo Gomes

Nikolaos Spilias and Joseph D. Campbell

HEART

50

Carotid Disease Jimmy Kerrigan, Deborah Kerrigan, and Joseph D. Campbell

IX CLINICAL CARDIOLOGY

AND

PREVENTATIVE

51

Hallmarks of Primary and Secondary Hypertension

52

The Dyslipidemias

53

Preoperative Evaluation Noncardiac Surgery

Luke J. Laffin and Leslie Cho

Nishant P. Shah and Leslie Cho

of

Cardiac

Patients

for

Laura Young and Ajay Bhargava

54

Pregnancy and Heart Disease

55

Women and Heart Disease

56

Pericardial Diseases

57

Effects of Systemic Diseases on the Cardiovascular System

Zarina M. Sharalaya and Russell E. Raymond

Ashley Bock and Leslie Cho

Michael Chetrit and Allan L. Klein

Jeffrey S. Hedley and Michael D. Faulx

58

Cardiac Neoplasms Eoin Donnellan and Brian P. Griffin

Heart and

X PHARMACOLOGY 59

Cardiovascular Drug Interactions

60

XI MISCELLANEOUS901Patent Foramen Ovale and Atrial Septal Defect Closure

Aldo L. Schenone and Michael A. Militello

Kara Denby, Anirudh Kumar, and Joanna Ghobrial

61

Transcatheter Aortic Valve Replacement

62

Percutaneous Mitral Interventions

63

Genetics and Heart Disease

64

Summary of Important Guidelines

65

Sports Cardiology

66

Cardio-oncology

Grant W. Reed, Samir R. Kapadia, and Amar Krishnaswamy

Vinayak Nagaraja and Samir R. Kapadia

Kartik S. Telukuntla, Christina Rigelsky, and Kenneth G. Zahka

Vinayak Nagaraja and Samir R. Kapadia

Kyle Mandsager and Dermot Phelan

Eoin Donnellan, Muzna Hussain, and Patrick Collier

Appendix (Common Formulae) Shady Nakhla and Venu Menon Index

I FUNDAMENTALS

CHAPTER 1

How to Pass the Cardiovascular Disease Board Examination JOHN RICKARD AND GRANT W. REED

GENERAL INFORMATION Board certification in Cardiovascular Disease is an attainable goal made possible with careful planning and preparation. Each year, the American Board of Internal Medicine (ABIM) Certifying Examination is offered in the fall, typically in October. The initial certification exam is given over 1.5 days. The first day consists of multiple choice questions, and the second half day includes an ECG examination and an imaging studies section comprising echocardiograms and coronary angiograms, focused on proper coding of studies. Registration dates are specified by the ABIM. In general, registration for the standard examination occurs from December 1 of the prior year through June 15 of the examination year, and late registration dates are typically June 16 through June 28. However, there may be exceptions, as in 2020 when late fees were waved in light of the COVID-19 pandemic. Applications with a disability may be eligible for the Special Accommodation Examination, which has the same registration periods but is usually offered a few weeks after the standard examination. The initial certification examination fee for 2020 was $2,480. In addition, a nonrefundable fee of $400 is added for late registration, and a $500 fee is added for international testing centers. A 70% refund will be given if the examination is cancelled at least 48 hours prior to the examination, and a 55% refund given for cancellation within 48 hours. As

registration test centers often fill up rapidly, early registration is key to assure the ability to take the examination at a nearby test center. Applicants can register for the examination at the official ABIM Web site: www.abim.org/certification/exam-information/. All applicants should become familiar with the ABIM Web site, which provides detailed policies, information about the examination, and a practice test using the same software used on the day of the examination. Test results are typically first available on the ABIM Web site approximately 3 months after the examination. After initial certification, for certification to be considered current, one must be active in the ABIM Maintenance of Certification (MOC) program. In 2020, the MOC program requirements were as follows: 1. Participate in at least 1 activity every 2 years to earn “MOC Points”. The activity can be of any point value. 2. Earn at least 200 MOC points every 5 years. 3. Pass a separate MOC Assessment (detailed below). As of 2020, the options for the MOC Assessment are to 1. Take a recertification examination every 10 years. 2. Take a “Knowledge Check-In (KCI)” assessment every 2 years instead of a 10-year examination. 3. Participate in the “Collaborative Maintenance Pathway (CMP),” which consists of shorter annual performance assessments administered through the ACC Adult Clinical Cardiology SelfAssessment Program (ACCSAP). There have been several recent changes to the recertification process in Cardiovascular Diseases, and as such applicants should visit the ABIM Web site for full up-to-date details: https://www.abim.org/maintenance-ofcertification/assessment-information/assessment-options.aspx In addition, examinees are now permitted to use UpToDate as a reference during the examination. Examinees are encouraged to visit the UpToDate User Academy for ABIM Exam preparation to learn how to make the most of this resource: https://www.uptodate.com/home/uptodate-user-academyabim-exam.

FORMAT As of 2020, the Cardiovascular Diseases Board examination is taken over the course of 1.5 days for first-time takers and 1 day for those taking it to recertify and opting for the 10-year examination option (those recertifying are exempt from the ECG and imaging sections). The first day is a full day lasting up to 10 hours. Day 1 consists of four 2-hour blocks consisting up to 60 multiple choice questions each. Break time between sessions is limited to 100 minutes total but can be divided between breaks however the examinee chooses. The second day is a half-day consisting of an ECG section of 35 to 40 tracings lasting 2 hours 15 minutes and an imaging section lasting 2 hours consisting of 35 to 40 video images that include echocardiograms, ventriculograms, aortograms, and angiograms. Table 1.1 delineates the weighted subject content for the examination. Many cardiology trainees do not have sufficient exposure to peripheral vascular disease, pharmacology, and congenital heart disease during their training and must overcome this deficiency during their preparation for the examination. For the ECG section, a brief one- or two-line clinical vignette is provided with each ECG tracing. The test taker then must code relevant findings using a coding sheet, available in advance for review at the ABIM Web site. Similarly, for the imaging section, coding sheets are provided to capture the various findings. Test takers must make sure they review the coding sheet prior to the test. Sample cases and practice coding sheets could be found on the ABIM Web site.

Table 1.1 Breakdown in Content of the Cardiology Board Examination

Examination questions in the content areas above may also address topics in preventative and rehabilitative cardiology, cardiovascular disease in women, geriatric cardiovascular disease, preoperative assessment of noncardiac surgery, postoperative cardiac care, critical care medicine, cardiovascular surgery, and general internal medicine as encountered in the practice of cardiology.

HOW YOU ARE SCORED For first-time test takers, the multiple choice components and the ECG and imaging sections are scored separately. The ECG and imaging sections are combined for scoring purposes. For a passing score, both the multiple choice and the ECG and imaging components must be passed. While the imaging section can be challenging, due to the combination of scoring with the ECG section, a poor performance on the imaging section can be balanced out by a stronger score on the ECG section (or vice versa). While there is no penalty for guessing on the multiple choice section, overcoding on the ECG and imaging sections leads to point deductions. The strategy we advocate is to code the 2 to 3 main diagnoses per ECG or image and any obvious minor diagnoses and omit any borderline or uncertain codes. For first-time takers, pass rates for the examination from 2004 to 2019 are listed in Table 1.2. The ultimate pass rate within 3 subsequent years from 2009 to 2019 was 97%.

Table 1.2 First-Time Taker Pass Rates

TIPS A 3-month study period prior to the test is a reasonable amount of time to prepare for the examination. Reviewing information in a scheduled way over this time period is important. The examination encompasses a large quantity of information making a last-minute approach ill advised. Fellows who are enrolled in busy advanced fellowship programs such as electrophysiology and intervention must be realistic about the need to study for the examination. Too often, these trainees do not allow themselves sufficient time to prepare. They may consider signing up for a dedicated course, which would force them to focus on the material covered on the examination. The multiple choice section of the boards is structured such that a clinical vignette is presented and typically five answer choices are provided. While the clinical vignettes are often long, each block of 60 questions is allotted 2 hours of time (2 minutes/question). Very few questions on the boards simply ask a question on a medical fact. The large majority of questions make the test taker read through a patient scenario complete with a past medical history, current symptomatology, in-depth physical examination findings, and imaging and laboratory data prior to asking how to proceed with the patient’s management. In addition, the examination will often challenge the test taker to determine the most likely condition from the physical examination and then determine the treatment options based on other information given. Therefore, knowing the physical examination findings of common cardiovascular conditions is imperative. A good strategy is to make sure each question is answered to avoid missing easy questions by getting hung up by long ones, and then returning to tougher questions to check one’s work after. The board examination will not ask questions on any areas that are controversial or not supported by evidence. The majority of questions will focus on information obtained from guidelines—most notably class I and III recommendations. In preparing, it is important to focus on common therapeutic and diagnostic conditions rather than rare conditions. Anticipate questions regarding common conditions structured in complex ways. In addition, the results of major, practice-changing clinical trials are favorite board topics. Examinees are encouraged to remember that clinical trials or major guideline changes published within 1 to 2 years are typically not

included and thus should answer questions accordingly. Some board questions may strike the test taker as strange or potentially even unfair. It is important not to get stressed out by such questions as the board pilots new questions every year. These new questions will not be included in the final score. Lastly, the imaging section of the boards can be difficult due to variable image quality. One should ensure not to waste time overcoding but simply code the major findings that are clearly identifiable, as above. It is also critical to make sure that all the available images have been viewed. It is vitally important not to underestimate the ECG section. The majority of test takers who failed the boards in the past have done so by failing this section. Knowing the coding sheet cold prior to sitting for the test is vital (the coding sheet is available online from the ABIM). Many test takers run into time issues with this section. Searching for the correct codes on the sheet can waste a significant amount of time and may cause some examinees not to finish. Secondly, the board examination commonly tests clinical syndromes on the ECG section. The test taker should be very familiar with the clinical syndromes on the code sheet and be able to identify such conditions rapidly. While electronic calipers are provided, they are rarely required to obtain the correct answer. Overuse of calipers can waste valuable time. It is also important not to overcode the ECG portion of the test. The board examiners want to ensure that the examinee can identify the major findings on each tracing. Taking time to code small, somewhat questionable ECG findings will waste time and possibly cause point deductions. Examinees are encouraged to start preparing early, and obtain several books or online resources containing practice multiple choice questions. One should then focus one’s study on completing the resources that emphasize one’s weaknesses. Examinees are also encouraged to practice ECG and image coding with one of several books or online services available. Lastly, it is important to get a good night sleep prior to the examination as the test is lengthy and can be fatiguing, especially toward the end of the examination session. Taking the examination at the first opportunity after completion of your fellowship is strongly advised as the material learned in training will be the freshest at that time. Use in-service scores to identify areas you need to work on the most. The examination typically rewards tests takers who are well rounded without major deficiencies in knowledge rather than individuals who are experts in a few areas and deficient in others.

Finally, and as mentioned previously, early registration is important to secure a nearby test location. Having to travel large distances or staying in a hotel prior to the test will only cause unneeded stress and distraction.

TEN PITFALLS TO AVOID 1. Underestimating the ECG and imaging sections 2. Not being familiar with the coding sheets for the ECG and imaging sections prior to the test 3. Not being able to identify common cardiovascular conditions based on physical examination findings 4. Overcoding the ECG and imaging sections 5. Spending a disproportionate time on one or two questions at the expense of other easier questions 6. Getting upset by what appears to be very strange, “out of left field”– type questions that are probably pilot questions that are not factored into the final score 7. Wasting too much time with the electronic calipers on the ECG section 8. Cramming for the test at the last minute 9. Registering late forcing the test to be administered a distance away from home 10. Not reviewing the tutorial on the ABIM Web site

CHAPTER 2

Cardiac Physical Examination CRAIG R. ASHER

INTRODUCTION EXAMINATION

TO

PHYSICAL

Over the years, the bedside skills of the cardiologist have diminished, due in part to the readily available access to echocardiography. However, the Cardiology Board examination expects a high level of understanding of physical diagnosis. Most of the testing of physical diagnosis is indirect. Many of the questions are structured with a brief history and physical examination that provide clues about the diagnosis or answer. Often these are subtle hints that will not be appreciated by the unprepared. This chapter provides many of the pearls of physical diagnosis that are important for taking the boards.

INSPECTION Basic principles (these descriptors may correlate with a specific diagnosis): General appearance: Distress, diaphoresis, tachypnea, cyanosis, pallor Posture: Orthopnea, platypnea/orthodeoxia (dyspnea and O2 desaturation in the upright position such as seen in patients with patent foramen ovale [PFO] and atrial septal defect [ASD] with R-to-L shunt), trepopnea (dyspnea lying on one side but not the other such as with

large pleural effusions), bendopnea (dyspnea with bending as seen with congestive heart failure) Stature: Tall (Marfan syndrome, acromegaly), short (Turner and Noonan syndromes, Down syndrome), dwarfism (Ellis–van Creveld syndrome associated with ASD) Nutritional status: Obese (sleep apnea, metabolic syndrome), cachexia (end-stage systolic heart failure, chronic disease, malignancy), athletic or muscular (anabolic steroid use) Abnormal movements: Chorea (Sydenham chorea as seen with rheumatic fever), ataxia (Friedreich ataxia associated with hypertrophic cardiomyopathy [HCM] or tertiary syphilis associated with aortic aneurysms), head bobbing (aortic regurgitation [AR] or tricuspid regurgitation [TR]), Cheyne–Stokes respirations See Table 2.1 for additional associated conditions and specific diseases found with various skin, head and neck, eye, chest and abdomen, extremity findings.

Table 2.1 Physical Examination Findings with Associated Conditions and Disease States

ARTERIAL PULSE Basic Principles Described by upstroke, magnitude, and contour Central aortic or carotid pulse composed of percussion (ejection, early portion) and tidal waves (reflected wave from periphery, mid to later portion) Graded 0 to 4. Grade 0 is absent; grade 1 is barely palpable; grade 2 is normal; grade 3 is increased; and grade 4 is bounding. Normal pulse pressure approximately 30 to 40 mm Hg (systolic minus diastolic blood pressure) Anacrotic notch is present at the systolic upstroke in the arterial pulse (ascending limb). Dicrotic notch is present in the diastolic downstroke in the arterial pulse (descending limb) at aortic valve closure.

Disease States See Figure 2.1.

FIGURE 2.1 Carotid pulse findings in normal and disease states. A:The normal carotid pulse. There is a rapid ascending and descending limb. The descending limb is slower than the ascending limb and has a dicrotic notch that occurs during aortic valve closure. The dicrotic notch is generally not palpable on examination. B:Hyperdynamic pulse. There is a rapid, highvolume ascending and descending limb. C:Parvus/tardus pulse with anacrotic notch refers to a small-amplitude pulse with a delayed systolic peak associated with AS. The anacrotic notch on the ascending limb may be appreciated on examination. D:Pulsus alternans is the beat-to-beat variation in the arterial pulse amplitude that is seen with left ventricular dysfunction and low

stroke volume. E:Pulsus bisferiens is characterized by two systolic peaks during systole. The amplitude of the pulse is high. The initial peak is due to the ejection or percussion wave, and the second peak is due to a reflected or tidal wave in the periphery. This type of pulse is most often seen with isolated AR or combined AR and stenosis. F:Dicrotic pulse is another form of double-peaked pulse where the dicrotic notch is present in diastole just after S2. The dicrotic pulse usually occurs in patients with hypotension due to low CO or low SVR. G:Spike and dome pulse is another form of double-peaked pulse that occurs with HOCM. There is an initial rapid systolic peak followed by a lower-amplitude systolic peak.

Pulsus Alternans Alternating beat to beat pulse amplitude with strong and weak pulsations in sinus rhythm Most often reflects left ventricular myocardial failure due to alterations in preload, afterload, and contractility with each beat Also described with HCM with obstruction

Pulsus Paradoxus Exaggeration of normal inspiratory fall of systolic blood pressure (SBP) > 10 mm Hg Causes include cardiac tamponade, chronic lung disease/acute asthma, pulmonary embolism (PE), right ventricular infarction, congestive heart failure, tension pneumothorax, pregnancy, obesity, and rarely constrictive pericarditis (only effusive form) Major mechanisms include (a) ↑ venous return to the right heart during inspiration with shift of the septum to the left resulting in ↓ left ventricle (LV) stroke volume and therefore ↓ SBP (reverse Bernheim effect) and (b) ↑ pulmonary venous reservoir with inspiration resulting in ↓ leftsided filling (lower pulmonary vein to left ventricular gradient). Cardiac tamponade may occur without pulsus paradoxus due to loss of interventricular dependence with high LV end-diastolic pressure (AR or

LV dysfunction), ASD (volume of shunted blood exceeds change in volume of blood between inspiration and expiration), or right ventricular hypertrophy (RVH) and pulmonary hypertension (PH). The paradox is that heart sounds can be heard during inspiration, while the pulse weakens and may not be palpable. Reversed pulsus paradoxus may occur with HCM or in mechanically ventilated patients.

Double-Peaked Pulse ↑ amplitude pulse with two systolic peaks and midsystolic dip Results from accentuated percussion wave and tidal wave Most common cause is severe AR (bisferiens) with or without aortic stenosis (AS), but may also occur with hypertrophic obstructive cardiomyopathy (HOCM, bifid or “spike and dome”) and hyperdynamic states (patent ductus arteriosus [PDA], arteriovenous malformations)

Pulsus Tardus and Parvus Carotid pulse with tardus (delayed peak and slower upstroke) and parvus (low amplitude) Caused by AS, though may be absent even in the setting of severe AS in elderly with noncompliant carotid vessels Associated with an anacrotic pulse and carotid shudder (thrill)

Anacrotic Pulse Notch on the upstroke of the carotid pulse (anacrotic notch) may be palpable Two distinct waves can be seen (slow initial upstroke and delayed peak, which is close to S2). Present in AS

Dicrotic Pulse

Accentuated upstroke with second peak, the dicrotic notch in diastole (after S2) Second peak in diastole differentiates the dicrotic pulse from a bisferiens pulse. Occurs in patients with low cardiac output (CO) and high systemic vascular resistance (SVR) or high CO and low SVR (in both cases the SBP is low) Other miscellaneous signs/findings related to arterial pulse include the following:

Osler Sign or Maneuver Obliteration of brachial pulse by BP cuff with sustained palpable and rigid radial artery Invasive BP measurements are lower than the cuff pressures (pseudohypertension). Due to atherosclerotic, stiffened, calcified blood vessels

Pulse Deficit Difference in the heart rate by direct cardiac auscultation and by palpation of the peripheral arterial pulse rate when in atrial fibrillation (AF) Due to short diastoles (short RR interval), ventricular contraction may not be strong enough to generate enough stroke volume to the periphery and thus the peripheral pulse may underestimate the heart rate.

Radial-to-Femoral Delay Generally radial and femoral pulses occur at nearly the same time (femoral slightly earlier ~5 ms). Due to obstruction of arterial flow in coarctation, the femoral pulse is delayed.

Confirmed by (>20 mm Hg) in upper-extremity pressure compared to lower-extremity pressure in the supine position

Pressure/Pulse Difference in Two Arms (>10 mm Hg Systolic) Due to obstruction involving the aorta, innominate and subclavian arteries due to the following etiologies: congenital, arteriosclerosis, embolism, arteritis, dissection, postsurgical (subclavian flap repair for coarctation) or external obstruction (thoracic outlet syndrome)

Asymmetric Right Greater Than Left Pulses and Pressures Supravalvular AS: The blood flow is directed toward the right side of the aorta in greater proportion to the left side (due to the Coanda effect) resulting in a disparity with ↑ right-sided pulse amplitude and pressures, including inequality of carotid pulses. Historical signs of severe AR due to high stroke volume detected by pulse abnormalities include the following:

Hill Sign Extreme augmentation of systolic BP in the popliteal artery compared with the brachial artery (>40 mm Hg with severe AR) Results from a summation of reflected pressure waves traveling distally in the aorta

Mayne Sign ↓ in diastolic BP with arm elevation of >15 mm Hg compared to standard arm position Seen with severe AR

Traube Sign “Pistol Shot”

Loud systolic sound heard over the femoral artery

Corrigan Pulse: “Water-Hammer” Pulse Large-amplitude, rapid upstroke followed by rapid collapse of the peripheral pulse Due to high left ventricular stroke volume and low SVR Most commonly seen with chronic severe aortic regurgitation

Duroziez Sign Systolic and diastolic bruit heard over the femoral artery with gentle compression with the bell of the stethoscope

JUGULAR VENOUS PULSE Basic Principles Pressure and waveforms should be evaluated Adjust level of head/torso until pulsations optimally visualized, generally around 45 degrees Internal jugular vein preferable to external jugular vein and right internal jugular vein preferable to left internal jugular vein Jugular venous pulse (JVP) ↓ with inspiration in normal patients

Jugular Venous Pressure Measure the vertical height above the sternal angle or angle of Louis (junction of manubrium and sternum), which is considered to be 5 cm above the mid–right atrium (RA) in all positions. However, this distance may not be constant for all patients and may vary in some patients (especially based on size) and with different positions.

5 cm + height of jugular venous pressure above the sternal angle = right atrial pressure Above 9 cm H2O is considered elevated. Conversion: 1.36 cm H2O = 1 mm Hg (or 1 cm H2O = 0.74 mm Hg) Abdominojugular reflux (previously referred to as the hepatojugular) can be performed to confirm or determine elevated venous pressure. Application of pressure >10 to 30 seconds over the right upper quadrant (RUQ) results in sustained elevation of jugular pressure 4 cm above the sternal angle for >10 seconds following release of pressure. Straining (Valsalva maneuver) must be avoided since it will cause a false reading.

Jugular Venous Waveforms See Figure 2.2.

FIGURE 2.2 Internal jugular pulsations in normal individuals and during AF. The physiology attributed to each wave is noted. Typically, there are two positive waves (“a” and “v” waves) and two negative waves (“x” and “y” descents) in normal individuals.

The “a” wave is lost with AF. The “c” wave is not appreciable on physical examination. RA, right atrium; RV, right ventricle.

Disease States See Figure 2.3.

FIGURE 2.3 Internal jugular pulsations during various disease states. A:Large “v” or “cv” wave characteristic of TR along with a rapid “y” descent. B:Large “a” wave as seen with obstruction to right ventricular filling with TS. The “y” descent is slow when TS is present. A large “a” wave without a blunted “y” descent may occur with RVH or PH. C:Cannon “a” waves are present with AV dissociation and describe the presence of intermittent prominent “a” waves that occur during contraction against a closed AV valve during ventricular systole. It should not be confused with a prominent “v” wave. D:Loss or blunting of the “y” descent is an important feature of cardiac tamponade that corresponds with impairment of diastolic filling. E:A prominent “x” and “y” descent is present with constrictive pericarditis. The rapid “y” descent is a marker of early rapid filling due to an abnormality of compliance. F: With restrictive cardiomyopathy a blunted “x” descent is present with a rapid “y” descent. AF: loss of “a” wave resulting in just one major positive and prominent “v” wave Complete heart block, atrioventricular (AV) dissociation/ventricular tachycardia—cannon “a” wave due to contraction against a closed tricuspid valve

Tricuspid stenosis (TS), RVH, PH, severe left ventricular hypertrophy (LVH) with hypertrophied septum (Bernheim effect)—large or giant “a” waves Severe TR: large “v” wave and rapid “y” descent ASD: prominent and equal “a” and “v” waves Constrictive pericarditis: prominent “y” descent (predominant filling during early diastole) and prominent “x” descent giving “w” shape waveform along with elevated jugular venous pressure and Kussmaul sign Restrictive cardiomyopathy: Blunted “x” descent and prominent “y” descent with elevated jugular venous pressure and Kussmaul sign. Cardiac tamponade: prominent “x” wave and loss of the “y” descent representing loss of filling in diastole along with elevated jugular venous pressure Superior vena cava (SVC) obstruction— elevated but nonpulsatile JVP

Other Miscellaneous Signs/Findings Kussmaul sign: paradoxical rise in JVP during inspiration due to increased resistance of RA filling during inspiration. The opposite of the normal fall in JVP with inspiration due to negative intrathoracic pressure Due to right ventricular increased volume and reduced compliance, and restricted flow from SVC Classical finding in constrictive pericarditis. May also occur with RV infarct, severe TR or TS, PE, and restrictive cardiomyopathy, but is absent with cardiac tamponade except for the effusive constrictive form

PRECORDIAL MOTION Basic Principles

The normal left ventricular apex moves toward the chest wall during isovolumic contraction/as the heart rotates counterclockwise. The normal LV impulse is best palpated in the fourth or the fifth left intercostal space just medial to the midclavicular line in the left lateral decubitus position. It is about 1 to 3 cm in size and lasts less than one-third of systole. The apical pulsation is not always the point of maximal impulse (PMI) (e.g., in rheumatic mitral stenosis [MS], the PMI may be produced by the right ventricle or pulmonary artery).

Hypertrophy LVH results in an apical impulse that is sustained and not diffuse. RVH or PH results in a left parasternal heave or lift that is sustained and not diffuse.

Dilation LV enlargement results in a diffuse, laterally displaced apical impulse. RV enlargement results in a diffuse impulse occurring in the parasternal region.

Disease States LV aneurysms may produce diffuse outward bulging and a rocking effect. Constrictive pericarditis may be characterized by systolic (inward) retraction of the chest instead of outward motion (Broadbent sign) with absent palpable apical impulse. Hyperactive precordium occurs in volume overload (severe aortic and mitral regurgitation [MR], large left-to-right shunt). HCM causes a double systolic outward motion. This is due to a palpable “a” wave (increased atrial filling wave) and a sustained outward movement of the apex. In some patients, there are two systolic

motions as well as the motion during atrial systole resulting in a triple apical impulse (triple ripple).

FIRST HEART SOUND Basic Principles Ventricular systole begins with closure of the mitral (first) and tricuspid (second) valves. S1 is best heard with the diaphragm of the stethoscope at the apex for the mitral and the left sternal border for the tricuspid valve. Opening sounds of the mitral and tricuspid valves are pathologic sounds.

Intensity Mitral closure is generally louder than tricuspid closure. S1 is generally louder than S2 at the apex and the left sternal border and softer than S2 at the left and the right second interspaces. S1 (particularly M1) is ↑ with Short PR interval (due to wide separation of leaflets at onset of ventricular systole) or preexcitation syndromes MS with mobile leaflets Hyperdynamic LV function or ↑ transvalvular flow due to shunts (↑ force of leaflet closure) TS or ASD (T1 ↑) S1 is ↓ with Long PR interval (leaflets close together at onset of ventricular systole) MS with immobile or calcified leaflets

Severe AR (due to mitral preclosure from the jet hitting the mitral valve and high left ventricular end diastolic pressure [LVEDP]) MR due to prolapse or flail (poor coaptation of leaflets) Severe LV dysfunction with poor CO (↓ force of leaflet closure) S1 is variable with Atrial fibrillation Complete heart block and AV dissociation

Splitting Split S1 must be differentiated from an S4 gallop heard best at the apex with the bell of the stethoscope and an ejection sound (ES) (pulmonic or aortic) heard at the base of the heart.

Persistent Splitting Late T1 closure due to severe TS, ASD or right bundle branch block (RBBB) Late T1 closure due to Ebstein anomaly (S2 also split) with associated multiple systolic and diastolic clicks “sail-like sounds” Early M1 closure due to LV preexcitation

Reverse Splitting (Rare) Late M1 closure due to severe MS (usually associated with TR), left bundle branch block (LBBB), RV pacing

SECOND HEART SOUND Basic Principles

Ventricular systole ends at the dicrotic notch with closure of the aortic (first) and pulmonic (second) valves S2 closure sounds are heard best with the diaphragm of the stethoscope

Intensity Aortic closure heard best at the second right intercostal space adjacent to the sternum is generally louder than pulmonic closure heard best at the second left intercostal space adjacent to the sternum. S2 (A2) is ↑ with hypertension (HTN) or a dilated, anteriorly positioned or aneurysmal aorta (may have tambour quality) S2 (A2) is ↓ with AS, AR, and hypotension. S2 (P2) is ↑ with pulmonary HTN, dilated pulmonary artery (PA) or ASD. S2 (P2) is ↓ with pulmonary stenosis (PS) either valvular or subvalvular or pulmonary regurgitation (PR).

Single S2 A2 is absent with severe AS or AR. P2 is absent with chronic obstructive pulmonary disease (COPD) and obesity (inaudible sound due respiratory noise) or PS, pulmonary atresia, right ventricular outflow tract (RVOT) obstruction, and tetralogy of Fallot. A2-P2 occur together with aging due to decreased inspiratory delay of P2.

Splitting Normally A2 and P2 separate during inspiration and come together during expiration (physiologic splitting) (Fig. 2.4). This occurs due to ↓ pulmonary vascular impedance and a relatively longer RV ejection period relative to LV ejection period

FIGURE 2.4 Illustration of normal S2 (physiologic) splitting and pathologic S2 splitting (persistent, fixed, paradoxical) with the changes that occur as a result of the respiratory cycle. With normal physiologic splitting, P2 closure occurs later than does A2 closure during inspiration with associated increased preload and a longer right ventricular ejection period. During expiration, a single S2 sound is heard. With persistent splitting, A2 and P2 are heard throughout the respiratory cycle but separated by a wider distance during inspiration. This is due either to a delay in the closure of P2 or an early closure of A2. Fixed splitting may occur with hemodynamically significant ASDs and describes the equal and persistent separation of A2 and P2 during the respiratory cycle. Paradoxical splitting is the opposite of normal splitting (P2 precedes A2) during expiration, and a single sound is heard during inspiration. This is due to either a delay in A2 closure or an early P2 closure.

Splitting of the S2 may be physiologic or pathologic.

Pathologic Splitting Fixed splitting: wide and persistent splitting that remains unchanged throughout the respiratory cycle (defined as ≤20 ms of variation) Mechanism: With ASD and left-to-right shunt, this occurs due to prolonged RV ejection due to increased stroke volume that delays P2 during inspiration. During expiration there is decreased caval inflow and so increased left to right shunt. Therefore, the total preload stays the same during inspiration and expiration and S2 split is fixed. Conditions: ASD (~70% secundum ASD when hemodynamically significant), RV failure (most common cause in adults) Persistent splitting: Splitting occurs with both inspiration and expiration but is not fixed with a further widening occurring with inspiration. Mechanism: This type of splitting occurs when there is an electromechanical delay in P2 closure or early A2 closure. Conditions: P2 delayed—RBBB, pulmonary HTN, RV dysfunction, PS, dilated PA A2 early—severe MR, VSD, Wolff–Parkinson–White (WPW) (LV preexcitation) Paradoxical splitting: The normal sequence of A2 followed by P2 closure is reversed so that with expiration P2 precedes A2 and with inspiration the sounds come together. Mechanism: This type of splitting occurs either when there is an electromechanical delay in A2 closure or if P2 closure occurs early. Conditions: A2 delayed—LBBB or RV pacing, AS or AR, LV dysfunction, HCM, dilated aorta, or myocardial ischemia P2 early—WPW (RV preexcitation)

THIRD HEART SOUND Basic Principles Physiologic diastolic sound in young adults though may disappear with standing. Almost all adults lose S3 after 40 years of age. It is normal during the third trimester of pregnancy. Best heard with light pressure of the bell of stethoscope (low frequency) in the left lateral decubitus position at the apex Right-sided S3 can be heard at left sternal border and may ↑ with inspiration. Most commonly heard in conditions of high flow across an AV valves S3 follows an opening snap (OS) and pericardial knock (PK) in timing. S3 corresponds with the “y” descent of the central venous or atrial waveform or the Doppler e wave on an echocardiogram. An S3 is not expected with severe MS.

FOURTH HEART SOUND Basic Principles S4 is usually pathologic (atrial gallop). S4 is heard best with the bell of the stethoscope and occurs just before S1, after the P wave on the EKG and is equivalent to the Doppler a wave on an echocardiogram. A left-sided S4 is heard best in the left lateral decubitus position at the apex during expiration, and a right-sided S4 is heard at the left sternal border to midsternum best with inspiration. Common pathologic states associated with a left-sided S4 include AS, HTN, HCM, and ischemic heart disease. A right-sided S4 is heard with

PH and PS. S4 gallop is not heard with AF. When S3 and S4 are heard simultaneously such as may occur with tachycardia and prolonged PR intervals, a loud “summation gallop” (SG) is present. A quadruple rhythm with a distinct S3 and S4 may be heard with tachycardia.

EXTRA HEART SOUNDS Diastole See Figure 2.5.

FIGURE 2.5 The relative timing of heart sounds heard during diastole is shown. The earliest sound audible is an OS. A pericardial knock (PK) present with constrictive pericarditis occurs later than an OS but slightly earlier than an S3 gallop. The PK can be distinguished from an S3 since it is louder and higher pitched. An S4 occurs before the onset of ventricular systole. Sometimes with rapid heart rates, there is a fusion of S3 and S4 to create a summation gallop (SG).

Opening Snap Pathologic sound generated by abrupt movement of the body of the mitral leaflets in early diastole due to MS or tricuspid stenosis (TS) OS is a high-pitched sound best heard medial to the apex with the diaphragm of the stethoscope. If the valve is calcified and not mobile or MR is present, an OS may not occur. A S2 to OS interval of 3 WU, and an elevated pulmonary capillary wedge pressure. In some instances, an LVAD will be placed as DT, since the elevated PVR precludes listing for transplant. With medical therapy and unloading of the ventricle with the LVAD, there may be improvement in PVR and allow listing for transplant.

Right Ventricular Function The evaluation of RV function deserves special attention in patients being considered for LVAD, especially in patients implanted with a secondgeneration CF device. RV failure following LVAD implant is an important cause of morbidity and mortality for patients who often require prolonged inotropic therapy or ultimately placement of a RVAD. There have been a number of risk scores devised in an attempt to better predict which patients

may develop RV failure after LVAD implantation, to allow for better medical optimization prior to the LVAD implant or for planned simultaneous biventricular support. Fitzpatrick et al. performed a retrospective analysis from 266 patients who underwent LVAD implantation at a single center from 1995 to 2007 and found that the multivariate risk factors predicting the need for biventricular mechanical support were cardiac index ≤2.2 L/min/m2, RV stroke work index ≤0.25 mm Hg × L/m2, severe preoperative RV dysfunction, preoperative creatinine ≥1.9 mg/dL, previous cardiac surgery, and systolic blood pressure ≤96 mm Hg.23 Multiple types of LVADs, the majority of which were pulsatile devices, were reviewed in that study. A recent review of patients implanted with a CF LVAD enrolled in the HM II LVAD BTT clinical trial showed that multivariate independent predictors of RV failure following LVAD implant included a central venous pressure/pulmonary capillary wedge pressure ratio >0.63, need for preoperative ventilator support, and blood urea nitrogen level >39 mg/dL.24 The difficulty in consistently predicting RV failure lies, in part, on the unmasking of native RV dysfunction in the presence of restored cardiac output and increased venous return following LVAD implantation. It is estimated that approximately 20% to 25% of patients undergoing LVAD implant develop RV failure.25 This continues to be an area of active investigation.

Anatomic Considerations Perhaps one of the most important anatomic considerations prior to LVAD implantation is the competency of the aortic valve. Following LVAD implantation, the LV is unloaded and pressure rises in the aortic root with output from the device. Pathologic specimens either at time of transplant or autopsy may show commissural fusion of aortic leaflets leading to a central jet of aortic insufficiency. Mild to moderate aortic regurgitation prior to implant may progress to more severe grades of aortic regurgitation and worsening heart failure. This situation is best avoided by preemptively repairing at least moderate grades of aortic insufficiency at the time of LVAD implantation. Other important considerations include repairing severe mitral and tricuspid insufficiency and converting mechanical aortic and mitral valves to bioprosthetic valves at the time of VAD implant. There is increased risk of thrombosis of the mitral valve due to a lower INR goal and in the

aortic valve that may remain in the closed position due to VAD speed and lack of native contractility. Interatrial septal abnormalities such as a patent foramen ovale and atrial septal defect are generally closed at the time of surgery. Complex congenital heart anatomy and hypertrophic cardiomyopathy may present surgical challenges that preclude LVAD implantation.

Nutritional Status Cardiac cachexia (BMI < 21 kg/m2 in males and 1.1, use of vasodilator therapy, mean pulmonary artery pressure ≤25 mm Hg, aspartate aminotransferase >45 U/mL, hematocrit ≤34%, blood urea nitrogen >51 U/dL, and lack of intravenous inotrope use were all multivariate risk factors for 90-day in-hospital mortality following LVAD implantation. It should be noted that these studies evaluated patients implanted with the pulsatile LVADs, although their applicabilities to those patients considered for CF LVAD implantation are likely to be similar and studies are currently under way to investigate this question.

OUTCOMES AFTER CIRCULATORY SUPPORT IMPLANTATION Infection and bleeding were two of the most common adverse events seen post VAD implant in the 2005 Registry from the International Society for Heart and Lung Transplantation Mechanical Circulatory Support Device (ISHLT-MCSD).12 Table 17.6 summarizes the postimplantation patientrelated events. Infection was seen in approximately one-third of patients with almost 30% having significant bleeding episodes. Neurologic dysfunction was observed in 14% of the registry patients.

Table 17.6 ISHLT MCSD 2005 Registry Analysis (N = 655): Postimplantation Patient-Related Events

In 655 patients analyzed in the ISHLT-MCSD Registry (entered between January 2002 and December 2004), 1-month survival was 83% and 12month survival was 50%, censoring patients at the time of transplantation. Age played a significant factor in outcomes, with an individual 40 years of age having a predicted 6-month mortality of about 5% versus a 70-year-old patient with a predicted mortality of almost 20% after an LVAD alone was implanted. With the combination of an LVAD and RVAD during the same operation, for a 50-year-old individual, the mortality approaches 20%, compared to a little more 5% for an LVAD alone. In individuals under the age of 30 years receiving MCS as a bridge to transplant, 51% were transplanted at the 6-month mark, with 33% alive and still waiting transplantation and 10% dying before transplant. This should be compared to those individuals >50 years of age who, at the 6-month mark, say only 39% transplanted, with a 33% pretransplant mortality and 27% of patients still waiting for transplant. Interestingly, though recovery sometimes occurs and MCS devices can be explanted, this is a rare event in patients >50 years of age, with only a 0.4% recovery–explantation rate noted over a 12-month period of time, compared to a 6-month explanted–recovery rate observed in patients 95%) blood when a sample is drown from the distal port 3. Stagnation of injected dye in the pulmonary artery

When in doubt, the threshold to perform a left heart catheterization (for direct measurement of LVEDP) should be low. These pressures can then be used to calculate TPG and PVR. In addition, volume challenge during RHC can be useful if resting hemodynamic data are inconclusive to make a diagnosis of PAH. 500 cc of normal saline is infused over 5 to 10 minutes if the resting right atrial pressure is 50% of the variables (noted above) are abnormal. This algorithm is usually applied to a fairly normal group of patients. In patients likely to have diastolic dysfunction (myocardial pathology), recommendations are to estimate LV filling pressures and grade diastolic function into grades I, II, and III (Fig. 20.3). If grade II cannot be assessed due to missing variables, then this will be called indeterminate diastolic function. If the patient has shortness of breath, and there is grade I diastolic function, a diastology stress test is recommended.

FIGURE 20.2 An algorithm for assessment of diastolic dysfunction in patients with normal left ventricular function. LV, left ventricular; EF, ejection fraction; TR, tricuspid regurgitation; LA, left atrial. (From Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29:277314, with permission from Elsevier.)

FIGURE 20.3 Algorithm for estimation of LV filling pressures and grading LV diastolic function in patients with depressed LVEFs and patients with myocardial disease and normal LVEF after consideration of clinical and other 2-D data. TR, tricuspid regurgitation; LA, left atrial; Vol, volume; LAP, left atrial pressure; CAD, coronary artery disease. (From Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29:277-314, with permission from Elsevier.) This algorithm should not be applied to special populations, and different criteria should be used (Table 20.2).

Table 20.2 Assessment of LV Filling Pressures in Special Populations

Conclusions should not be made on single measurements, and estimation of PASP utilizing peak velocity of the TR jet (>2.8 m/s) and LA volume index (>34 mL/m2) should also be incorporated to predict filling pressures >15 mm Hg. The role of LA volume index is limited in mitral valve disease, atrial fibrillation, and athletes. Though this newer algorithm was intended to simplify grading of diastolic dysfunction and estimation of left atrial pressure, previously utilized parameters may be considered ancillary and may be found within the guidelines for assessment of diastolic dysfunction for specific populations. These include (a) pulmonary vein flow velocities, (b) isovolumic relaxation time, (c) E velocity deceleration time, (d) color M mode propagation velocity, (e) Tei index, and (f) B bump on mitral valve M mode echocardiography. Recently, there is an emphasis incorporating global longitudinal strain of the LV (GLS) and left atrial reservoir strain (LARS) especially in patients with indeterminate diastolic function.

PROGNOSIS Despite earlier studies that suggested better outcomes among HFpEF patients compared with HFrEF patients, more recent data suggest similar prognosis with both entities. Additionally, diastolic dysfunction, particularly of a moderate or severe degree, has now been shown to be a powerful predictor of increased morbidity and mortality (Fig. 20.4). It has been observed that 22% to 29% of patients with HFpEF die within 1 year of hospital discharge and 65% die within 5 years.

FIGURE 20.4 Kaplan–Meier survival curves for patients with heart failure and preserved or reduced ejection fraction. (Reprinted from Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355: 251-259, with permission from the Massachusetts Medical Society.)

TREATMENT OF DIASTOLIC HEART FAILURE Despite evidence of a clear mortality benefit in patients with HFrEF, multiple medications have failed to show a similar benefit in patients with HFpEF. Previously conducted studies which have failed to demonstrate a mortality benefit include CHARM (candesartan), PRESERVE (irbesartan), and TOPCAT (spironolactone). Additionally, the use of nitrates (NEAT-

HFpEF) and sildenafil (RELAX) have not been shown to improve functional capacity. Thus, current treatment consists of reducing elevated filling pressures, maintaining atrial contraction, decreasing heart rate, preventing ischemia, improving relaxation, and implementing strategies to regress LV hypertrophy. Treatment is generally geared toward the management of the underlying pathologic condition in addition to the following: 1. Diuresis as needed to decrease central venous pressure 2. Beta-blockers to improve ventricular relaxation and enhance filling 3. Angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers, calcium channel blockers, and other antihypertensives to decrease blood pressure and for afterload reduction 4. Restoration of normal sinus rhythm (NSR) in patients with atrial fibrillation and atrial flutter

RESTRICTIVE CARDIOMYOPATHIES Restrictive cardiomyopathy is defined as a disease of the myocardium, which is characterized by “restrictive filling and reduced diastolic volume of either or both ventricles with normal or near-normal systolic function.” Systolic function may be normal in the early stage of the disease, whereas wall thickness may be normal or increased depending on the etiology. The disease may be “idiopathic” or associated with other disease. Restrictive cardiomyopathies are recognized as primary and secondary, in which the secondary forms include the specific heart muscle diseases in which the heart is affected as part of a multisystem disorder—for example, infiltrative, storage, and noninfiltrative diseases. A “working classification” of restrictive cardiomyopathy is shown in Figure 20.5. Infiltrative cardiomyopathies can be further divided into interstitial and storage disorders. In interstitial diseases, the infiltrates localize to the interstitium (between myocardial cells), as with cardiac amyloidosis and sarcoidosis. In storage disorders, the deposits are within cells, as with hemochromatosis and glycogen storage diseases. These secondary forms of restrictive

cardiomyopathies are probably more common than the primary form and display the classic restrictive hemodynamics only in their advanced form.

FIGURE 20.5 Working classification of restrictive cardiomyopathy. (From Leung DY, Klein AL. Restrictive cardiomyopathy; diagnosis and prognostic implications. In: Otto CM, ed. Practice of Clinical Echocardiography. WB Saunders; 1997:474-493, with permission from Elsevier.)

Primary Restrictive Cardiomyopathies Idiopathic restrictive cardiomyopathy is associated with familial transmission and skeletal myopathies. There is no specific pathology on endomyocardial biopsies. The atria are disproportionately large, with normal LV function. Histologic examination shows nonspecific degenerative changes seen in other cardiomyopathies, including interstitial fibrosis that may also occur in the sinoatrial and the atrioventricular nodes, causing possible heart block. Most small series show a protracted clinical course in adults, with a mean survival from time of diagnosis of 9 years (range 4 to 14 years). Loeffler endocarditis is associated with idiopathic hypereosinophilia. There are three described stages which may overlap and include an acute

necrotic stage, an intermediate stage with thrombus formation along the endocardium, and a fibrotic stage with endocardial thickening, obliteration of the LV apex, and potential entrapment of the subvalvular apparatus leading to mitral and/or tricuspid regurgitation. Steroids and hydroxyurea may be helpful in management. Endomyocardial fibrosis is endemic to tropical Africa and has a similar appearance to the fibrotic stage of Loeffler endocarditis with obliteration of the left and right ventricular apices and involvement of the subvalvular apparatus. Thromboembolism is common. Treatment is mainly palliative, although surgical debulking has been attempted, with increased surgical mortality.

Secondary Restrictive Cardiomyopathies Cardiac amyloidosis is caused by extracellular deposition of insoluble proteins in the heart and is classified by the type of protein deposited. The two most common types are AL (primary or light chain) amyloidosis, and ATTR (transthyretin, familial, or senile) amyloidosis. Patients with cardiac amyloidosis present with HFpEF, atrial fibrillation, or progressive biventricular heart failure, depending on the stage of disease, as shown by two-dimensional and Doppler echocardiography (Fig. 20.6). Low voltage may be present on ECG, though normal voltage is present in 25% to 50% of patients with cardiac amyloidosis depending on the etiology. Beta-blockers should be avoided as patients have a low, fixed stroke volume.

FIGURE 20.6 Parasternal long (A) and short-axis (B) and apical long-axis (C) views show typical echocardiographic features of advanced cardiac amyloidosis. Note that LV size is normal with markedly thickened ventricular walls (ventricular septum = 22 mm, posterior wall = 18 mm, and right ventricular free wall = 15 mm) and its characteristic granular sparkling appearance. Small pericardial effusion (PE) and left pleural effusion (PLEFf) are also present. AO, aorta; AV, aortic valve; LA, left atrium; LV, left ventricle; PM, papillary muscle; RA, right atrium; RV, right ventricle; VS, ventricular septum. (From Klein AL, Oh JK, Miller FA, et al. Two-dimensional and Doppler echocardiographic assessment of infiltrative cardiomyopathy. J Am Soc Echocardiogr. 1988;1:48-59, with permission.) AL amyloid is the most common etiology of cardiac amyloidosis composing 85% of cases. It is due to extracellular deposition of fibrils composed of κor λ-immunoglobulin light chains and often associated with multiple myeloma. The identification of a monoclonal paraprotein in the setting of typical imaging and clinical features of cardiac amyloidosis is highly suggestive of AL amyloid, though definitive diagnosis may be made by a

positive biopsy of a noncardiac site, or rarely endomyocardial biopsy. Associated clinical features include macroglossia, periorbital purpura, and nephrotic syndrome. Treatment consists of autologous hematopoietic stem cell transplantation following conditioning with dose-intensive melphalan, or combination chemotherapy (currently with a bortezomib- based regimen) for those ineligible for transplantation. ATTR amyloid is due to deposition of transthyretin, previously known as prealbumin. In the senile type, wild-type, or nonmutated, transthyretin deposits with a typical age at the time of diagnosis >70 years. In the familial type, a mutated transthyretin deposits with age of onset varying from 30 to 70 depending on the mutation. Associated mutations may present with cardiomyopathy, neuropathy, or nephropathy. Carpal tunnel syndrome or spinal stenosis may present 10 to 15 years prior to the diagnosis of cardiac amyloidosis. The most common mutation is the Val122Ile mutation, which is present in 3% to 4% of African Americans with typical age of onset >50 years. Diagnosis may be made with a nuclear scintigraphy utilizing either technetium-99 pyrophosphate (PYP) or technetium-99 diphosphonate (DPD) in Europe. Newer treatments targeting the amyloid fibrils, including Tafamidis which is now FDA approved, appear to be promising. Liver transplantation is sometimes considered in this patient population. Hemochromatosis can be primary, due to an autosomal recessive disorder due to a mutation in HFE (C282Y or H63D), or secondary, due to iron overload (e.g., from blood transfusions, typically >15 units of packed RBCs). Iron overload should be suspected with elevated ferritin and transferrin saturation (>45% in men and >40% in women). Cardiac MRI utilizing a T2* sequence can be useful for identifying both liver and cardiac iron overload. Phlebotomy or chelation therapy may be used to treat iron overload and can improve cardiac symptoms. Storage disorders may be caused by a number of enzymatic defects that lead to accumulation of lipids or polysaccharides in the myocardium with typical symptom onset in adolescence or early adulthood. Fabry disease, Pompe disease, Danon disease, cardiac oxalosis, and mucopolysaccharidoses may all be categorized as storage disorders (Table 20.3).

Table 20.3 Characteristics of Cardiac Storage Disorders

Sarcoidosis is a multisystem disease characterized histologically by the formation of granulomas in many tissues. Autopsy series of patients with pulmonary sarcoidosis have shown the presence of noncaseating granulomas in the myocardium in up to 25% of patients; though most were asymptomatic from a cardiac perspective. Patients may present with heart failure, atrioventricular block, ventricular arrhythmias, and sudden death. Nuclear imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and cardiac MRI may both be useful for diagnosis, though endomyocardial biopsy may be necessary for diagnosis. Steroid treatment is used for patients with conduction block or arrhythmias.

ACKNOWLEDGMENT The authors wish to thank Andrew O. Zurick III and Oussama Wazni, MD, for their work on the previous versions of this chapter.

SUGGESTED READINGS Dorbala S, Cuddy S, Falk RH. How to image cardiac amyloidosis. J Am Coll Cardiol. 2020;13:13681383. Klein AL, Asher CR. Diseases of the pericardium, restrictive cardiomyopathy and diastolic dysfunction. In: Topol EJ, ed. Textbook of Cardiovascular Medicine. 2nd ed. Lippincott Williams & Wilkins; 2002:595-646. Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29:277314. Paulus WJ, Tschope C, Sanderson JE, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007;28: 2539-2550. Yamada H, Klein AL. Diastology 2010: clinical approach to diastolic heart failure. J Echocardiogr. 2010;8:65-79.

Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: part 1, diagnosis, prognosis and measurements of diastolic function. Circulation. 2002;105:1387-1393. Zile MR, Brutasert DL. New concepts in diastolic dysfunction and diastolic heart failure: part II: causal mechanisms and treatment. Circulation. 2002;105:1503-1508.

Chapter 20 Review Questions and Answers QUESTIONS

D. .

A 63-year-old male engineer undergoes echocardiography 2 months following a large posterolateral myocardial infarction due to acute stent thrombosis in his proximal left circumflex coronary artery. Which of the following is associated with a better prognosis? Ejection fraction (EF) of 29% E/e′ of 23 Presence of moderate-to-severe mitral regurgitation (MR) with ERO = 0.3 cm2 Lateral wall e′ of 6 cm/s Deceleration time of 133 ms

A. . C. D. .

The best two-dimensional (2-D) and Doppler echocardiographic finding to differentiate restrictive cardiomyopathy from constrictive pericarditis would be to evaluate Pulmonary venous flow pattern Atrial size Early diastolic mitral annular velocity Mitral inflow pattern Inferior vena cava dilatation

1.

A. . C.

2.

Which parameters are relatively preload independent? A. Mitral inflow E wave . Tissue Doppler echo annular E′ wave C. Color M-mode flow propagation velocity D. Tissue Doppler echo annular E′ wave and color M-mode flow propagation velocity

3.

Which of the following is the most common symptom associated with HFpEF? Chest pain Paroxysmal nocturnal dyspnea Exertional dyspnea Dyspnea at rest

4.

A. . C. D.

A 67-year-old obese woman is experiencing increasing dyspnea, fatigue, leg swelling, and peripheral neuropathy that have developed over the past 9 months. Physical examination reveals a mildly distressed patient with visible dyspnea and 3+ bilateral leg edema. Auscultation is difficult and only distant heart sounds can be discerned. Electrocardiogram shows low voltage and a pseudoinfarct pattern. At this time, which is the best diagnostic study? Echocardiogram with respirometry and longitudinal strain Angiography Cardiac CT scan Cardiac MRI

5.

A. . C. D.

ANSWERS 1.

Correct Answer: D. Regional ischemic injury will decrease the longitudinal systolic and diastolic excursion of the affected wall. Therefore, a lower value of e′ in the lateral wall of this patient is not an entirely unexpected finding (lateral e′ should normally be ≥10 cm/s). It is now recommended to acquire and measure tissue Doppler signals at least at the septal and lateral sides of the mitral annulus and calculate their average to measure E/e′. The other possible answers each have been shown to carry important prognostic information in patients with a history (recent or not) of myocardial infarction.

2.

Correct Answer: C. Differentiating restrictive from constrictive pericarditis by echocardiography can be particularly challenging. Mitral inflow, pulmonary venous flow, or tricuspid inflow does not always exhibit the typical respiratory changes displayed in textbooks. The inferior vena cava (IVC) is commonly dilated in patients with constriction; however, this can also be seen in patients with advanced restrictive cardiomyopathy. Atrial size will usually be increased in patients with restrictive cardiomyopathy, but constrictive pericarditis will also eventually result in (particularly right-sided) atrial enlargement. In patients with restrictive cardiomyopathy, myocardial relaxation (e′) will be severely impaired; whereas in patients with constriction, annular vertical excursion will usually be preserved. A septal e′ velocity ≥7 cm/s has been shown to be highly accurate in

differentiating patients with constrictive pericarditis from those with restrictive cardiomyopathy.

3.

Correct Answer: D. Both tissue Doppler echocardiography annular E′ wave and color M-mode flow propagation are measures of relaxation and are relatively preload independent. Mitral inflow E wave is dependent on preload.

4.

Correct Answer: C. Exertional dyspnea. With exertion, diastolic filling worsens and left ventricular (LV) filling pressure increases, resulting in dyspnea.

5.

Correct Answer: A. Echocardiogram with respirometry and longitudinal strain. Echocardiography is the modality of choice for the initial assessment of cardiac amyloidosis. Often there may be a characteristic apical sparing pattern with a “cherry on top” appearance noted on strain imaging.

CHAPTER 21

Hypertrophic Cardiomyopathy SNEHA VAKAMUDI AND HARRY M. LEVER

PREVALENCE AND DEFINITION Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease. The prevalence in the general adult population for people with phenotypic evidence of HCM is estimated at 1 per 500. HCM has traditionally been defined as myocardial hypertrophy of ≥1.5 cm in the setting of a nondilated left ventricle (LV) without an alternative identifiable cause (Figs. 21.1 and 21.2). Other etiologies of hypertrophy must be excluded before diagnosing HCM (Table 21.1). While there are multiple synonyms for HCM, including muscular subaortic stenosis (MSS), hypertrophic obstructive cardiomyopathy (HOCM), and idiopathic hypertrophic subaortic stenosis (IHSS), the World Health Organization (WHO) recommends that HCM be used as the term for the disease.

FIGURE 21.1 Transthoracic echocardiogram of HCM in the young —diffuse hypertrophy. Parasternal long-axis view depicts a markedly thickened interventricular septum. The thickening is diffuse, extending from base to beyond the midventricle. LV, left ventricle; RV, right ventricle; LA, left atrium; IVS, interventricular septum.

FIGURE 21.2 Transthoracic echocardiogram of HCM in the elderly—proximal septal hypertrophy. Apical three-chamber view depicts focal thickening of the interventricular septum at its base. The midventricle appears to be uninvolved. LV, left ventricle; LA, left atrium.

Table 21.1 Alternative Causes of LV Wall Thickening

CLASSIFICATION HCM can be classified as obstructive or nonobstructive, depending on the presence of a left ventricular outflow tract (LVOT) gradient—either at rest or with provocative maneuvers. Seventy percent of subjects with HCM have LVOT gradients ≥30 mm Hg at rest or with exercise. Obstruction is usually caused by systolic anterior motion (SAM) of the anterior mitral valve leaflet resulting in septal contact. Anatomic variants of HCM exist, and these can be categorized based on the location of the hypertrophy (e.g., proximal septal, apical, or diffuse). Apical hypertrophy is also known as Yamaguchi disease (Fig. 21.3). In a smaller subset of HCM patients, anomalous papillary muscle insertion can cause midcavitary muscular obstruction in the absence of SAM.

FIGURE 21.3 Transthoracic echocardiogram of apical variant of HCM (Yamaguchi). Apical four-chamber view depicts ventricular thickening of the apex. LV, left ventricle; LA, left atrium; RV, right ventricle; RA, right atrium.

PATHOPHYSIOLOGY AND HISTOLOGY LVOT obstruction is the pathophysiologic change in obstructive HCM (Figs. 21.4 and 21.5). When SAM occurs, the mitral valve leaflets are pulled or dragged anteriorly toward the ventricular septum, producing LVOT obstruction. The left ventricle (LV) thus must generate higher pressures to overcome the obstruction and pump blood. Premature closure of the aortic valve frequently occurs due to the drop in pressure distal to the outflow tract obstruction.

FIGURE 21.4 Transthoracic echocardiogram of SAM of mitral valve. Apical three-chamber view illustrates SAM of the mitral valve, resulting in obstruction of the LVOT. LV, left ventricle; LA, left atrium; MV, mitral valve; LVOT, left ventricular outflow tract.

FIGURE 21.5 Transthoracic echocardiogram of mitral regurgitation in HCM. Apical three-chamber view illustrates the classic posterolaterally directed mitral regurgitation jet in HCM. The jet direction occurs secondary to SAM of the mitral valve. LV, left ventricle; LA, left atrium; MR, mitral regurgitation jet. Obstruction with HCM is dynamic whereas obstruction with aortic stenosis and subvalvular aortic membranes is fixed in nature. In dynamic obstruction, the degree of obstruction depends primarily on cardiac contractility and loading conditions. This is contrasted to fixed obstruction, where cardiac contractility and preload have less impact on the degree of obstruction. In HCM, an underfilled LV results in greater obstruction because there is less separation between the hypertrophied interventricular septum and the mitral valve. As the LV cavity gets smaller and the flow stream is directed against the mitral valve, SAM of the mitral valve occurs. Augmenting cardiac contractility also worsens LVOT obstruction, because more vigorous contraction is more likely to cause the obstructing components to come into contact. As the mitral leaflet comes closer to the septum, the outflow tract is decreased in size, which further increases the pressure differential. This

feedback loop is represented on continuous-wave Doppler imaging as a dagger-shaped contour (see Fig. 21.10). Histologically, HCM manifests as hypertrophied, disorganized cardiac myocytes present throughout the myocardium. The abnormal cells may take on bizarre shapes, and the connections among cells are often in disarray. Myocardial scarring and growth of the collagen matrix also occur.

SYMPTOMS AND CLINICAL COURSE While the most common symptom of HCM is dyspnea on exertion, the majority of patients with HCM are asymptomatic. Importantly, symptoms are not always concordant with severity of LV outflow tract obstruction and may be more closely related to diastolic dysfunction. With diastolic dysfunction, the increased chamber thickness in HCM results in increased left ventricular stiffness, impaired filling, and relaxation. These diastolic abnormalities result in elevated left atrial, LV end-diastolic, and pulmonary pressures. Symptoms may also be caused by mitral regurgitation from SAM of the mitral valve, LVOT obstruction, arrhythmias such as atrial fibrillation, and myocardial ischemia. Patients may also complain of chest pain with exertion, syncope or near syncope, or palpitations. The clinical course of HCM is variable. Most individuals with the disease experience a normal life expectancy. Other patients may have a more complicated course resulting in premature death. Annual mortality rate from HCM is approximately 1%. Congestive heart failure and atrial fibrillation may be part of the natural progression of HCM. SCD is a catastrophic initial presentation of the disease. HCM is the most common etiology for sudden cardiac death (SCD) in young adults. SCD may occur during heavy exertion, during light exertion, or even at rest.

PHYSICAL EXAMINATION

The physical examination may provide several clues that suggest obstructive HCM. With dynamic LVOT obstruction, a harsh systolic murmur exists at the upper sternal border. It is important that this murmur be differentiated from that of fixed LVOT obstruction (i.e., aortic stenosis) as well as that of mitral regurgitation, which can also be present in HCM secondary to SAM of the mitral valve. The classic auscultatory finding of HCM is a crescendo–decrescendo systolic murmur along the left sternal border that increases with the Valsalva maneuver. The Valsalva maneuver decreases preload, which results in decreased filling of the LV. An underfilled LV results in increased obstruction. Of note, in aortic stenosis Valsalva decreases murmur intensity. The response in HCM to various physiologic and pharmacologic maneuvers is illustrated in Tables 21.2A and 21.2B.

Table 21.2A The Response in HCM to Various Physiologic and Pharmacologic Maneuvers

LVOT, left ventricular outflow tract.

Table 21.2B Differentiating the Murmur of HCM from Aortic Stenosis

Palpation of the carotid pulse also aids in distinguishing HCM from aortic stenosis or the presence of a subaortic membrane. With HCM, little difficulty exists during early systole in ejecting blood through the LVOT into the aorta; therefore, the carotid upstroke is brisk. As systole progresses, LVOT obstruction occurs, resulting in collapse of the pulse and then a secondary rise as LV pressure increases to overcome the obstruction. This sign is known as a bisferiens, or spike-and-dome, pulse. In contrast, because the fixed obstruction of aortic stenosis or a subaortic membrane is present during the entire cardiac cycle, the carotid upstroke in these entities is the classic parvus et tardus pulse—a carotid pulse with delayed amplitude and upstroke. Therefore, any patient carrying a diagnosis of HCM in the presence of decreased carotid pulses should prompt thoughts of a mistaken diagnosis and further investigation into fixed obstruction of the LVOT.

Unless congestive heart failure has developed, the lungs are clear and the jugular venous pressure is normal. The point of maximal impulse is often forceful and sustained, and a palpable S4 gallop may be present. Occasionally, a bifid apical impulse may be palpated; the first impulse represents forceful atrial contraction and the second impulse represents sustained ventricular contraction. During the cardiac examination, it is also imperative to listen carefully for a mitral regurgitation murmur as SAM of the mitral valve frequently causes mitral regurgitation. The remainder of the physical examination is generally unremarkable in HCM.

DIAGNOSTIC TESTING Initial testing in a HCM patient should include at minimum an electrocardiogram (ECG), echocardiogram with provocative LVOT gradient testing if the resting gradient is 55 mm. Left atrial enlargement often occurs with HCM secondary to long-standing mitral regurgitation from SAM of the mitral valve and/or diastolic dysfunction, whereas in an athlete’s heart, the left atrial size should be normal. Finally, diastolic dysfunction often exists in HCM as a result of the increased ventricular thickness and stiffness, whereas diastolic function should be normal in athletes. If it is still not certain whether a patient has HCM or athlete’s heart, the athlete should stop training; after 3 to 6 months, ventricular hypertrophy will persist with HCM, whereas with athlete’s heart, hypertrophy should regress.

Cardiac Magnetic Resonance Cardiac magnetic resonance (CMR) has emerged as an increasingly useful tool in the diagnosis of HCM. It provides a comprehensive evaluation of myocardial anatomy, and is especially useful in detecting those patients with atypical forms of HCM and papillary muscle abnormalities. CMR can also assist with identification of alternative diagnoses such as of Fabry disease and cardiac amyloidosis. CMR can also provide a more accurate assessment of LV function and volumes. It is recommended for use in those patients in whom HCM is suspected and echocardiogram is suboptimal or inconclusive. Additionally, the use of gadolinium-based contrast agents during CMR can identify the presence and distribution of myocardial fibrosis. Several recent studies have examined the relationship between scar burden as assessed in CMR and the incidence of SCD. Interestingly, in HCM patients traditionally considered low or intermediate risk, there is an association between the percentage of late gadolinium enhancement (LGE) and the incidence of SCD. Thus, CMR holds the potential to further refine current risk stratification algorithms by incorporating the percentage LGE.

Cardiac Catheterization While the use of cardiac catheterization has become less relevant in the era of echocardiography and CMR, it is still useful as an adjunctive test in cases where there are discordant data from Doppler echocardiography and the physical exam. LVOT gradients can be assessed by positioning a diagnostic catheter near the LV apex and recording ventricular pressures during slow catheter pullback. Patients with HCM often have no obstructive coronary artery disease. However, they may have thickened vessels and small-vessel disease from increased collagen deposition in the intima and media. The mismatch between myocardial oxygen supply and demand, driven primarily by the increased myocardial mass, may then cause microvascular myocardial ischemia. Microvascular dysfunction if present in HCM patients is associated with worse clinical outcomes. Hemodynamic demonstration of HCM physiology can be observed during catheterization in the setting of what is termed the Brockenbrough response (Fig. 21.11). In the beat following a PVC, there is increased filling of the LV from the compensatory pause. The augmented preload results in augmented contractility. In patients with HCM, the increased contractility results in subsequent worsening of the LVOT obstruction. Thus, during the beat after the PVC, there is an increase in LV systolic pressure with an associated decrease in aortic systolic pressure—thus increasing the gradient between LV and aorta. In contrast, in normal subjects, the increased contractility associated with the post-PVC beat results in an increase in both LV systolic and aortic systolic pressure, with no gradient between the LV and aorta.

FIGURE 21.11 The Brockenbrough response to a PVC. In normal subjects, a PVC results in a compensatory pause, increased ventricular filling, and subsequent increased cardiac contractility. There is no LV–aortic gradient, either at rest or in the beat postPVC. The aortic pulse pressure in the beat post-PVC usually increases because of the increased contractility. In contrast, as illustrated in the figure, the Brockenbrough response in the postPVC beat (fourth beat) suggests HCM. In HCM, the increased contractility occurring with the post-PVC beat results in increased LVOT obstruction and a subsequent increase in the LV–aorta gradient (shaded) as well as decreased aortic pulse pressure during the post-PVC beat.

GENETICS OF HCM Being the most common form of genetic heart disease, the link between genetic mutations and the phenotypic expression of HCM has been extensively studied. Thousands of mutations involving at least 11 HCM susceptibility genes have thus far been identified and continue to increase. The mutations associated with HCM are inherited in an autosomal dominant pattern and primarily involve the myosin, actin, or troponin components of

the cardiac sarcomere. The most common mutations that cause HCM involve the b-myosin heavy chain (chromosome 14), myosin-binding protein C (chromosome 11), and cardiac troponin-T (chromosome 1). However, having the HCM genotype does not necessarily imply that subjects will have the phenotypic traits of HCM. Variable penetrance exists, and environmental factors as well as modifier genes affect whether a particular subject will manifest HCM phenotypically. With time, genetic testing has become less expensive and readily available. It is recommended that all patients clinically diagnosed with HCM be referred to a genetic counselor and offered genetic testing.

SCREENING OF FAMILY MEMBERS It is recommended that first-degree relatives of HCM patients be screened on a 12- to 18-month basis, beginning at age 12 years, with a 12-lead ECG and TTE. The recommended screening interval reflects the fact that latent HCM may be unmasked by growth spurts and subsequent worsening of hypertrophy during adolescence. Evidence of late-onset ventricular hypertrophy occurring well into adulthood has spurred a push toward continuing serial echocardiograms past adolescence and into middle age for HCM relatives. It is now recommended that adult relatives of HCM patients undergo screening transthoracic echocardiograms at a minimum of every 5 years. Again, MRI should be pursued if echocardiogram is suboptimal or inconclusive. Genetic testing has also been incorporated into the screening process. If the patient has an HCM-causing mutation identified, then first-degree relatives can be screened for the presence of that mutation as well. If a relative is mutation positive, then surveillance should be done in a close manner with an annual clinical and echocardiographic exam. If a relative is mutation negative, then casual or no further routine surveillance can be elected provided the TTE is negative and the relative is asymptomatic. Family members should not have genetic testing performed if no pathogenic gene is identified in the index patient.

THERAPY Treatment options for HCM include pharmacologic therapy, surgical septal myectomy, percutaneous alcohol septal ablation, and heart transplantation.

Medical Therapy Treatment with beta-blockers is considered first-line therapy as these drugs improve symptoms and exercise intolerance. Beta-blockers decrease the outflow gradient during exercise and decrease oxygen demand by decreasing contractile force. Beta-blockers also slow heart rate thus lengthening diastolic filling time and improving any component of myocardial ischemia. Our practice is to start patients on metoprolol, 50 mg twice a day, or extended-release metoprolol, 50 mg daily. If the patient continues to be symptomatic, the dose of short acting or extended-release metoprolol can be increased further by 25-mg increments every few weeks to reach a goal heart rate approximately 60 beats per minute. Alternative beta-blocker choices include propranolol, nadolol, and atenolol. Second-line therapy includes the non-dihydropyridine calcium channel blocker verapamil and the Class IA antiarrhythmic agent disopyramide. Both verapamil and disopyramide exert a negative inotropic effect and improve ventricular relaxation. Verapamil can be used in addition to beta-blocker therapy or as a standalone treatment for those intolerant of beta-blockers. The extended-release formulation of verapamil can be started at 240 mg daily and increased by 60 mg every few weeks up to 480 mg daily. Verapamil should not be used in patients with severe resting LVOT obstruction, advanced heart failure, or severe pulmonary hypertension. Patients with severe pulmonary hypertension who are given verapamil may develop excessive vasodilation that worsens LVOT obstruction and cardiac output, resulting in pulmonary edema or even death. Diltiazem has been used in HCM patients, but there are limited data on its effectiveness. Disopyramide improves diastolic function and lowers the LVOT gradient. The extended-release formulation of disopyramide may be started at 150 mg twice a day. Concomitant therapy with beta-blockers is recommended because disopyramide may cause accelerated A–V nodal

conduction, which may be deleterious, especially during episodes of atrial fibrillation. Anticholinergic side effects may occur with disopyramide. Certain pharmacologic agents should be avoided or used with caution in HCM. Dihydropyridine calcium channel blockers, such as nifedipine and amlodipine, should be avoided because they cause peripheral vasodilation, which may result in decreased LV filling and worsening of outflow tract obstruction. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which also cause peripheral vasodilation, should be avoided. Diuretics, if deemed necessary, should be used cautiously, because subjects with HCM often have stiff ventricles that require high filling pressures. Digoxin is not favored in HCM because its positive inotropic effect may worsen LVOT obstruction. Finally, drugs such as dopamine, dobutamine, and norepinephrine can have deleterious effects in the treatment of acute hypotension due to their positive inotropic effects and should not be used. For cases of refractory hypotension that do not respond to IV fluid administration, phenylephrine, an alpha agonist that causes pure vasoconstriction, is recommended.

Septal Myectomy Septal myectomy is considered the definitive treatment for patients with medically refractory, symptomatic, obstructive (resting or latent gradient of 50 mm Hg or more) HCM. Septal myectomy involves resecting part of the proximal septum through an aortotomy so that the outflow tract obstruction is lessened (Fig. 21.12). Sometimes myectomy may be combined with other cardiac surgery such as coronary artery bypass surgery, mitral valve repair, or mitral valve replacement.

FIGURE 21.12 Septal myectomy. Septal myectomy involves resecting a portion of the proximal septum. Septal myectomy is not recommended in subjects with gradients >50 mm Hg but absent or mild symptoms. One exception is young patients with marked LVOT obstruction (gradient ≥75 mm Hg), who should be considered for

septal myectomy even in the absence of significant symptoms. In assessing risk and benefit of septal myectomy, the young age of this subgroup decreases the operative risk. Surgery has traditionally not been advocated in midcavitary or apical obstruction; however, in one study, patients with apical hypertrophy complicated by progressive, drug-refractory diastolic heart failure with severely limiting symptoms experienced improved functional status following apical myectomy. In our practice, we have also had success reducing LVOT obstruction by performing surgical papillary muscle reorientation although the long-term outcomes still need to be assessed. Operative mortality for isolated myectomy is low, approximately 0.38% at our institution. Increasing age and concomitant cardiac procedures may increase the surgical risk. Septal myectomy is associated with high success rates in decreasing LVOT gradients as well as the degree of mitral regurgitation. In doing so, it improves symptoms, and increases exercise capacity. Results postmyectomy are durable. Rarely is reoperation needed secondary to recurrence of LVOT obstruction. Retrospective, nonrandomized data suggest that long-term survival for HCM subjects undergoing myectomy does not differ significantly when compared to the age- and sex-matched general population. Furthermore, myectomy patients had higher survival rates than did obstructive HCM patients who did not undergo surgery. Thus, myectomy patients appear to fare no worse long term than the general population. Because the left bundle of the conduction system lies within the LV septum, left bundle branch block is common after surgical myectomy. Thus, conduction abnormalities that exist prior to surgery influence the likelihood of needing permanent pacing postmyectomy. Patients with preexisting right bundle branch block are at highest risk for requiring a permanent pacemaker postmyectomy. In subjects with normal conduction systems on ECG, there was a 2% rate of permanent pacemaker implantation postmyectomy.

Percutaneous Alcohol Septal Ablation For patients with medically refractory HCM and resting or provocative gradients ≥50 mm Hg who are poor surgical candidates or for those who choose not to undergo open heart surgery, alcohol septal ablation is another option (Fig. 21.13). During alcohol septal ablation, the first major septal

branch of the left anterior descending artery is identified and cannulated. Then, 2 to 5 mL of pure alcohol is slowly injected into the septal artery thus destroying a portion of the hypertrophied LV septum.

FIGURE 21.13 Alcohol septal ablation. In alcohol septal ablation, a balloon is inflated in the proximal septal perforator and alcohol is injected into the septal artery through the distal port of the balloon. The goal is to create a controlled myocardial infarction of

the proximal septum, resulting in shrinkage of the septum and lessening of the LVOT obstruction. Review of the patient’s cardiac anatomy is critical in selecting subjects for alcohol ablation. In order for alcohol ablation to succeed, LVOT obstruction needs to be secondary to contact of the mitral valve with the proximal septum. If the LVOT obstruction actually occurs in the mid-distal LV cavity, then alcohol ablation will not be of benefit. Alcohol ablation does result in decreased LVOT gradients and improvement of symptoms, but has not been shown to improve survival. At the Cleveland Clinic, most alcohol ablations have been performed on elderly, suboptimal surgical candidates. We generally prefer that the septum be between 1.8 and 2.5 cm, to provide a safety margin; if the septum is too thick, favorable ablation results may be difficult to attain, whereas if it is too thin, the patient is at higher risk for development of a ventricular septal defect. A septum 30 mm, prolonged or repetitive episodes of nonsustained ventricular tachycardia on Holter monitor, family history of SCD, no change or a decrease in blood pressure with exercise, and syncope or near syncope.

Table 21.4 Major Risk Factors for SCD

In a multicenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM, there was a 3.6% rate per year of appropriate ICD therapy for primary prevention of SCD. Of the patients that

had an ICD placed for primary prevention and experienced appropriate therapy for ventricular tachycardia, 35% had only one risk factor. This suggests that one or more major risk factors for SCD may be enough to warrant implantation of an ICD in select patients with HCM. There are several patient features that are not considered major criteria, but have been shown to be markers of increased SCD risk including a higher percentage of LGE on MRI, young age at diagnosis, and LVOT gradient ≥30 mm Hg. In cases where patients meet no major risk criteria but demonstrate several of these modifiers of increased risk, the decision to implant a primary prevention ICD should be made as part of a multidisciplinary team including the primary cardiologist as well as electrophysiologist. Holter monitors are recommended as a means of risk stratification for primary prevention of SCD to better define the presence and burden of nonsustained ventricular tachycardia. Electrophysiologic testing has not been shown to be predictive of SCD in HCM, and presently not recommended to aid risk stratification in HCM.

HCM AND ATHLETICS Patients with HCM should be restricted from competitive athletics or strenuous athletic activity because of the risk for SCD. Low-level exercise and participation in informal recreational activities, such as bowling and golf, are generally acceptable but should be considered on an individual basis. ICDs should not be implanted to permit participation in competitive athletics.

ATRIAL FIBRILLATION AND HCM Atrial fibrillation, which occurs in 20% of HCM subjects, is the most prevalent sustained arrhythmia in HCM. HCM subjects with atrial fibrillation have lower long-term survival rates compared to those in sinus rhythm. Lower survival rates are attributed to an excess of heart failure– related deaths as opposed to SCD.

Atrial fibrillation is a significant cause of morbidity in HCM. Strokes occur in 6% of subjects with HCM, nearly all of whom have atrial fibrillation. Medical treatment of persistent atrial fibrillation in HCM includes anticoagulation and rate control, preferably with beta-blockers. Anticoagulation is recommended in all patients with HCM and atrial fibrillation regardless of CHA2DS2-VASc score due to elevated stroke risk in this population. HCM patients who develop atrial fibrillation may present with acute clinical deterioration. The hypertrophied ventricle is stiff and may require atrial contraction for optimal filling. Losing the atrial contribution to ventricular filling may result in decreased cardiac output and potentially pulmonary edema. The substantial morbidity and increased mortality associated with atrial fibrillation in the setting of HCM justifies an aggressive approach to attempting to maintain sinus rhythm. Given that HCM patients often tolerate atrial fibrillation poorly, expeditious TEE followed by electrical cardioversion is generally preferred. Amiodarone or sotalol is the preferred therapy for pharmacologic conversion to sinus rhythm or maintenance of sinus rhythm in HCM patients. Digoxin should be avoided in HCM patients, particularly in those with resting or latent obstruction, because of its positive inotropic effect. Atrial fibrillation ablation or the maze procedure may be considered for those with refractory, highly symptomatic atrial fibrillation. In a small number of patients with severe HCM and refractory atrial fibrillation, we have performed combined maze–myectomy procedures.

HCM AND PREGNANCY Although pregnant women with HCM are at slightly higher risk for maternal or fetal complications than the average pregnant woman, the absolute morbidity and mortality rate for asymptomatic pregnant women with HCM is low. However, patients with resting or provocable LVOT obstruction should be referred to a high-risk obstetrician for care in collaboration with a cardiologist. Generally, such women do not need to undergo cesarean section and can deliver vaginally. Adequate fluid intake during pregnancy should be emphasized in pregnant women with HCM to ensure that the LV does not

become underfilled. Certain beta-blocking drugs, such as extended-release metoprolol, can be continued during pregnancy but require increased monitoring for fetal bradycardia.

NONOBSTRUCTIVE HCM Nonobstructive HCM is diagnosed when there is ventricular thickness of >15 mm in the absence of other etiologies, and when no significant LVOT obstruction exists (i.e., LVOT gradient 50 mm Hg) that is refractory to medical therapy, with alcohol septal ablation only performed in patients deemed poor operative candidates The available therapeutic options for HCM are associated with high success rates in improving symptoms and decreasing LVOT gradients in combination with low mortality rates.

ACKNOWLEDGMENTS The authors would like to acknowledge the contributions of Dr. Anthony J. Hart to previous versions of this chapter.

SUGGESTED READINGS Al-Khatib SM, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2018;72(14):e91-e220.

Ommen SR, Mital et al.2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Circulation. 2020;142(25)e558-e631. Maron BJ, Maron MS. Hypertrophic cardiomyopathy. Lancet. 2013;381:242-255. Maron B, et al. Hypertrophic cardiomyopathy. In: Mann D, Zipes D, Libby P, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. Vol. 2. Elsevier Health Sciences; 2014:15741588.

Chapter 21 Review Questions and Answers QUESTIONS A 15-year-old male comes to you for an initial evaluation. His father was diagnosed with hypertrophic cardiomyopathy last year. Genetic testing performed on the father did not reveal any pathogenic mutations. Which of the following should be used in the initial screening of the 15-year-old patient? Echocardiogram only Echocardiogram, ECG, and genetic testing Echocardiogram and ECG Cardiac MRI

1.

A. . C. D.

All of the following are true of the Brockenbrough response except: A. There is increased filling of the left ventricle (LV) with the compensatory pause. . The premature beat causes a decrease in contractility in HCM but not in normal individuals. C. There is an increase in ventricular pressure in both normal individuals and in patients with HCM. D. There is a decrease in aortic pressure in HCM.

2.

You are examining a patient in your office. Her chief complaint is shortness of breath on exertion. On cardiac auscultation you note a systolic murmur. The murmur decreases with handgrip maneuver and increases with squatting. Your preliminary diagnosis is: Hypertrophic cardiomyopathy Aortic stenosis Mitral regurgitation Aortic regurgitation

3.

A. . C. D.

Which of the following is not considered a major risk factor for sudden cardiac death in HCM? A. Septal thickness >30 mm . Prolonged or repetitive episodes of nonsustained ventricular tachycardia C. Family history of sudden death

4.

D. Increase in blood pressure with exercise What is the mechanism of action for disopyramide in its use as therapy for HCM? Decreased inotropy Decreased chronotropy Decreased lusitropy Decreased cellular calcium uptake

5.

A. . C. D.

ANSWERS 1.

Correct Answer: C. Echocardiogram and ECG It is recommended that first degree relatives of patients diagnosed with HCM be screened with both ECG and echocardiogram annually from ages 12 to 18 years. Because the patient’s father tested negative for a pathogenic mutation, genetic testing should not be used as a screening tool. Cardiac MRI, while useful if echo is inconclusive or nondiagnostic, should not be used as a first-line test for screening.

2.

Correct Answer: B. The premature beat causes a decrease in contractility in HCM but not in normal individuals. The Brockenbrough maneuver causes the contractility to increase in both normal individuals and in patients with HCM. All of the other statements are true.

3.

Correct Answer: B. Aortic stenosis The key to this question is understanding how different cardiac murmurs vary with certain maneuvers. Handgrip will increase afterload, which will decrease the murmur of both HCM and aortic stenosis but increase the murmur of mitral regurgitation. Squatting will increase preload—this will decrease the murmur in HCM but increase the murmur of fixed aortic stenosis. The murmur of aortic regurgitation is diastolic.

4.

Correct Answer: D. All of the answer choices are considered established major risk factors for sudden cardiac death in HCM except for increase in blood pressure with exercise.

5.

Correct Answer: A. Decreased inotropy Disopyramide is a class Ia antiarrhythmic and thus blocks sodium channels to inhibit conduction. It does not have any negative chronotropic effects but is a potent negative inotrope. In fact, because disopyramide may accelerate conduction through the AV node it is recommended to be given with a beta-blocker. Lusitropy refers to the rate of cardiac relaxation—disopyramide has no effect on lusitropy and decreased relaxation of the cardiac muscle would have a negative impact on the physiology of HCM.

IV CONGENITAL DISEASE

HEART

CHAPTER 22

Congenital Heart Disease in the Adult JOSHUA SAEF AND JOANNA GHOBRIAL Adults with congenital heart disease (CHD) are a rapidly growing population of patients owing to advances in the diagnosis and treatment of children with CHD. Most children with CHD are now expected to survive to adulthood with (or in some cases without) surgical correction or palliation. According to recent estimates, there are now nearly a million adults with CHD, and these numbers will continue to rise with further advancements in diagnosis and treatment. Although ideally served by cardiologists with advanced training in adult CHD, most patients predominantly receive care from primary care physicians and general cardiologists. Few cardiology training programs have a formalized adult CHD curriculum. Being aware of the unique anatomy and pathophysiologic consequences of CHD is vital to facilitating appropriate medical care to this unique patient population including percutaneous, electrophysiologic, and surgical care.

TYPES OF CONGENITAL LESIONS Congenital heart lesions can be divided into three general categories (by descending incidence): simple shunt lesions, obstructive lesions, and complex lesions. The most frequently encountered pathologies within these categories are mentioned below.

Shunt Lesions

Intracardiac shunts are the most common congenital heart lesions and are frequently diagnosed in otherwise healthy adults. They are associated with increased pulmonary blood flow, which can lead to heart chamber enlargement, either right or left depending on shunt location, and arrhythmias, as well as pulmonary hypertension. Surgical correction of many of these lesions is safe and efficacious. More recently, percutaneous closure devices have been increasingly utilized to avoid open heart surgery. There are three main types of shunt lesions to be aware of: atrial septal defects (ASDs), ventricular septal defects (VSDs), and patent ductus arteriosus (PDA). These lesions are conduits for left-to-right shunting under normal physiologic conditions.

Atrial Septal Defect ASDs account for up to 15% of all adult CHD. They result from the failure of proper embryologic development of the atrial septum. Almost one-third of patients with ASD will have associated additional malformations such as pulmonary stenosis, VSD, mitral valve prolapse, subaortic stenosis, aortic coarctation, Ebstein anomaly, and anomalous pulmonary venous drainage.1 There are multiple types of ASDs, the most common of which is the secundum ASD (Fig. 22.1). These result from a defect in the septum primum, leaving a defect in the middle of the atrial septum. The secundum ASD is often mistaken for other abnormalities or overlooked because the symptoms associated with it (typically fatigue, palpitations, and breathlessness) can be subtle and nonspecific.2 Secundum ASDs can be familial or syndromic such as in the case of Holt–Oram syndrome, which is also associated with dysplasia of the bones of the arms and hands and is autosomal dominant.

FIGURE 22.1 Secundum ASD. A:Transthoracic echocardiogram image demonstrating a secundum ASD with right heart enlargement and color Doppler with left to right flow. B:Transesophageal image demonstrating a secundum ASD with color Doppler with left to right flow. Less common variations of ASD include the sinus venosus ASD, the primum ASD, and the coronary sinus (CS) septal defect (or unroofed coronary sinus) (Fig. 22.2). The sinus venosus ASD results from abnormal fusion of the vena cava (superior or inferior) to the left atrium. This defect is commonly associated with partial anomalous return of the pulmonary veins (right pulmonary veins draining into the SVC or IVC).3 Because of its location, this defect can be missed on transthoracic echocardiography and usually requires either focused transesophageal echo, cardiac magnetic resonance (MRI), or cardiac computed tomography (CT) to make the diagnosis. The primum ASD involves the endocardial cushion at the crux of the heart in the lower portion of the interatrial septum and typically affects the ventricular septum as well (the so-called atrioventricular septal defect or AV canal defect). Both atrioventricular (AV) valves are structurally abnormal, have the same septal insertion point, and the mitral valve is often cleft. This defect is commonly seen in patients with trisomy 21 (Down syndrome).4 The least common ASD, the CS septal defect, is an unroofing of the CS within the left atrium. The CS septal defect is often associated with a persistent left SVC or an abnormal pulmonary venous drainage.5 Important differences in the clinical findings among the various types of ASD are listed in Table 22.1.

FIGURE 22.2 A:Partial anomalous pulmonary venous return with right upper pulmonary vein and superior sinus venosus ASD noted on transesophageal echocardiogram. B:Pulmonary angiogram on levophase demonstrating right-sided pulmonary venous return via scimitar vein into the inferior vena cava. C:Atrioventricular septal defect with primum ASD and membranous VSD. D:Partially unroofed coronary sinus.

Table 22.1 Unique Features of the ASDs

ASD should be suspected whenever right heart enlargement is present without an alternative explanation. Physical examination findings, such as a fixed-split second heart sound (due to loss of differential effects on right- and left-sided filling pressures from a drop in intrathoracic pressure that normally occurs during inspiration) and a pulmonic outflow murmur (the result of increased pulmonary blood volume from shunting), can easily be overlooked. Blood flow across the defect (shunt) is determined by the size of the defect and the compliance of the atria. Occasionally, patients can present late in life with ASD-related symptoms when the left atrial pressure rises because of a stiff left ventricle and diastolic dysfunction (usually the result of long-standing hypertension or coronary artery disease) leading to an increase in the shunt flow. On electrocardiography, an incomplete right bundle branch block, rightaxis deviation in secundum ASD, and right atrial enlargement are commonly seen. Due to anatomic position of the conduction bundles, a superior left axis is usually noted in primum ASD. On chest x-ray prominent pulmonary arteries, right atrial and ventricular enlargement and pulmonary plethora can be seen.6 The larger the left-to-right shunt in patients with ASD, the greater is the risk for long-term complications such as atrial flutter or atrial fibrillation (typically occurring in the fifth decade) and pulmonary hypertension. The latter condition affects up to 5% to 10% of adults with ASD, and if left uncorrected can result in Eisenmenger syndrome. In Eisenmenger syndrome, the pulmonary vascular resistance increases to the point that shunting is reversed (becoming right to left) and systemic oxygenation decreases. Patients with this complication will not improve their oxygen saturation when oxygen is administered to them (the telltale sign of a right-to-left shunt). Multiple complications eventually ensue, and until recently, this condition was considered irreversible.7 Another condition associated with ASD is stroke, which presumably results from paradoxical embolization (blood clots forming in the extremities and reaching the cerebral circulation by passing through the ASD).8 The guideline-based indication to repair an ASD is right heart enlargement from volume overload resulting from the associated shunting. Closure should be considered for patients with hemodynamically significant net left-to-right shunts (Qp/Qs > 1.5) provided that systolic PA pressure is

⅔ systemic, and/or a net right-to-left shunt given potential for hemodynamic decompensation with increased RV afterload. Repair of an ASD may also be reasonable in the context of paradoxical embolism or documented platypnea–orthodeoxia.9 Closure after before the age of 40 is associated with a decreased incidence of arrhythmias (i.e., atrial fibrillation) compared with closure after age 40. Epidemiologic evidence also suggests that long-term survival is worse with unrepaired defects, but the difference is lost as the patient is older at the time of repair and outcomes may be worsened with repair after irreversible pulmonary vascular remodeling with pulmonary hypertension has become well established.10

Ventricular Septal Defect VSD is the most commonly encountered congenital heart defect in children. They can develop in the ventricular inlet, outflow tract, the membranous septum, and anywhere within the muscular septum. The perimembranous VSD (Fig. 22.3) is the most common (80% of the cases), occurring in the membranous septum and adjacent to the septal tricuspid valve leaflet. Small, muscular VSDs often close spontaneously during childhood. VSDs are most often isolated lesions but are also commonly present in complex abnormalities such as TOF and transposition of the great vessels.11

FIGURE 22.3 Ventricular septal defect: transesophageal image demonstrating a perimembranous VSD with color Doppler flow across it. Clinical presentation in adulthood depends on the defect size and the pulmonary vascular resistance. Left-to-right shunting across the defect can lead to left ventricular volume overload and pulmonary hypertension. Large defects are more likely to present in childhood with symptoms of heart failure. VSD is also the most frequent cause of Eisenmenger syndrome, with shunt reversal to right to left. The unrepaired adult may present with symptoms of exercise intolerance, infective endocarditis (IE), pulmonary hypertension, heart failure, paradoxical emboli, cyanosis, or arrhythmias.12 On exam, small VSDs produce a very loud systolic murmur and frequently a palpable thrill at the left sternal border. Patients with small defects are asymptomatic and require regular follow-up without a need for intervention. Larger defects have less conspicuous murmurs. The perimembranous or outlet VSD can lead to prolapse of the right aortic valve cusp into the defect.

This can result in the development of progressive aortic regurgitation, which may be detected on exam with a diastolic murmur. On electrocardiography, patients with large VSD and significant pulmonary hypertension will have isolated right ventricular or biventricular hypertrophy. The chest x-ray typically is normal in patients with small VSD; however, in those with large left-to-right shunt, left atrial and left ventricular enlargement as well as increased pulmonary vascular markings may be noted. Cardiac catheterization is helpful in assessing the operability of an adult patient with VSD and pulmonary hypertension, including quantification of shunting and assessment of pulmonary pressures, pulmonary vascular resistance, and pulmonary vasoreactivity.13 VSD closure is indicated with evidence of left ventricular volume overload, large pulmonary-to-systemic flow (Չp/Չs > 1.5), or in patients with history of IE provided that PA systolic pressure is ⅔ systemic, and/or a net rightto-left shunt. VSD closure is usually accomplished surgically, although the role of percutaneous intervention is expanding.9

Patent Ductus Arteriosus PDA is a persistent communication between the descending aorta and the left PA at the level of the left subclavian artery. PDA is most often present as an isolated lesion in adults, unlike in children where it is frequently seen with more complex heart defects and/or premature birth. It has classically been associated with in utero exposure to rubella.14 Like in VSD, patients with a large, uncorrected PDA can present with dyspnea and easy fatigability as well as Eisenmenger physiology with differential cyanosis and clubbing. Patients with PDA have a continuous murmur that is often described as a “machinery murmur,” heard best under the left clavicle and accompanied by a widened pulse pressure.

The ECG of adults with PDA may be normal or show left atrial enlargement, left ventricular enlargement, or right ventricular hypertrophy (the latter in setting of pulmonary hypertension). The chest x-ray may show cardiomegaly and increased pulmonary venous markings depending on the size of the shunt. The need for closure of a PDA in adults is uncommon. Defects can be ligated surgically or closed percutaneously (device closure or coils) depending on size.15

Stenotic Lesions Pulmonary Stenosis Congenital pulmonic stenosis (PS) is a common entity within CHD with an incidence of 0.5 per 1,000 live births. Though most often found in isolation, valvular PS is frequently associated with comorbid CHD such as tetralogy of Fallot (TOF), transposition of the great vessels, and double-outlet right ventricle. Valvular dysplastic PS is associated with the genetic Noonan syndrome. Valvular PS is the most common form of RVOT obstruction (Fig. 22.4), though infundibular, supravalvular, and peripheral pulmonary arterial pathologies are well established.16

FIGURE 22.4 Congenital pulmonary valve stenosis: cardiac MRI image with RV outflow tract demonstrating doming pulmonary

valve leaflets and stenosis. Valvular PS presentations vary from right ventricular failure and cyanosis to incidental discovery without symptoms depending on the severity of pathology. Patients with pulmonary valvular gradients 3 to 4 m/s, PG 36 to 64 mm Hg) and symptoms such as heart failure, cyanosis from a concomitant shunt, or exercise intolerance. Intervention may be warranted in those with severe stenosis regardless of symptoms. Interventions on PS mainly involve percutaneous balloon valvuloplasty, with surgery reserved if percutaneous route is not feasible or not successful.9

Coarctation of the Aorta Aortic coarctation (CoA) is a common congenital heart defect, accounting for 4% to 8% of all congenital defects. It is postulated to result from extraneous ductal tissue that contracts following birth. It is associated with Turner syndrome. Anatomically it can occur proximal, at, or distal to the ductus

arteriosus. Associated cardiac defects include bicuspid aortic valve (present in up to 85% of cases), subaortic stenosis, VSD, mitral valve abnormalities, aortic aneurysms, as well as cerebral aneurysms in the circle of Willis (seen in up to 10% of patients and which can lead to CNS bleeding).19 The most common presentation in adults is fortuitous discovery during secondary workup for systemic hypertension. Lower extremity and renal hypoperfusion leads to a hyperrenin state that may not abate even after coarctation repair. In most patients, there is upper extremity hypertension and the development of collateral vessels around the coarctation to the lower extremities.20 Accordingly, adults with CoA may present with hypertension and discrepant upper and lower extremity pulses, if the coarctation is preductal, before the take-off of the left subclavian artery, the right and left upper extremity pressure will also be discrepant, lower in the left. They may complain of claudication, leg fatigue, or exertional headaches. Accelerated coronary artery disease, left ventricular hypertrophy and dysfunction, with congestive heart failure, stroke, and aortic dilation and dissection are common complications in the unoperated patient or those intervened on in childhood with recurrence.21 On examination, collateral channels result in a continuous murmur heard over the back, there is a systolic ejection murmur, best heard in the back, left ventricular apical displacement can occur. Extensive collateral vessels may mask the severity of the obstruction by reducing the gradient across the coarctation. Hypertension is present in the right arm relative to the lower extremities. A radial–femoral pulse delay may be noted. There may be an ejection click with a systolic murmur in the setting of a bicuspid aortic valve. Electrocardiographic findings in aortic coarctation may include left ventricular hypertrophy with associated repolarization abnormalities. On chest x-ray, rib notching due to collateral vessels may be noted as well as dilation of the proximal aorta and a “3 sign” due to indentation at the coarctation site. Involvement of the intercostal arteries leads to the familiar rib notching noted on chest x-rays. Echocardiography with a focus on the descending aorta is an excellent noninvasive test to diagnose CoA in patients with suspicious clinical findings. Cardiac MRI and CT scanning can identify the precise location and anatomy of the coarctation and assess the entire aorta and the collateral vessels.22 Cardiac catheterization is indicated to assess for concomitant

coronary artery disease when surgery is planned as well as when catheterbased interventions are contemplated. Repair of coarctation of the aorta may be accomplished via percutaneous catheter intervention or surgically. The main indication for intervention of CoA is a peak-to-peak coarctation gradient >20 mm Hg invasively, a mean gradient be echocardiography of 20 mm Hg, or a right upper extremity to lower extremity systolic gradient of 20 mm Hg. Intervention may also be sought with lower gradients (of >10 mm Hg) in the setting of collateral flow, or with significant aortic narrowing on anatomic imaging, or aortic regurgitation.9 Surgery was previously the mainstay in the approach to native CoA, with available options including resection and end-to-end anastomosis, other techniques include subclavian flap repair, prosthetic patch aortoplasty, and interposition (tube bypass) grafting. Notably, Dacron patch aortoplasty has fell out of favor due to high occurrence of aneurysmal dilation at the site of repair. Angioplasty and stenting is now considered the procedure of choice in adult patients with coarctation or re-coarctation following surgery, with uncovered and covered stents mainly used, given high risk of recurrence with only angioplasty techniques. The covered stents also offer a reduction in pseudoaneurysm formation. They are performed in experiences centers with adult CHD expertise.

Complex Lesions Transposition of the Great Arteries Transposition of the great arteries (TGA) is defined by departure from the traditional ventriculo–arterial relationship, with the aorta emanating from the morphologic RV and the PA coming off of the morphologic left ventricle. There are two varieties, -TGA (rightward) and -TGA (leftward), with the Latin prefix referencing embryologic ventricular rotation. The postrotational position of the ventricle determines its input (i.e., systemic vs. pulmonary venous return) and the consequent physiology. The defects are the result of abnormal rotation structures within the primitive cardiac tube.23 In -TGA, the right ventricle sits in its traditional position, receiving systemic venous return and advancing into the aorta without involvement of

the pulmonary circulation, while the left ventricle receives pulmonary venous return and advancing into the pulmonary artery and the lungs. This creates two separate parallel circulation not amenable to life. As such surgical intervention is required during infancy and childhood. Maintaining ductal patency and percutaneous atrial septostomy may be indicated to provide palliative shunting between the parallel circulations. More durable correction is accomplished surgically, via atrial or arterial switch procedures. The atrial switch method (Senning and Mustard procedures) involves baffling the vena cavae to the left atrium and the pulmonary veins to the right atrium. The primary long-term concern in these patients is that the RV is ill prepared to serve as a systemic ventricle. It can weaken and fail over time (usually when the patient enters their 40s), and these patients typically also develop significant systemic atrioventricular valve (SAVV) (tricuspid valve) regurgitation. Other common complications include baffle obstruction, baffle leak, pulmonary venous obstruction, and conduction disturbances such as bradyarrhythmias and tachyarrhythmias. In the late 1980s, patients with -TGA have been surgically corrected with an arterial switch (Jatene procedure), where the ascending aorta and the main PA are transected and reattached to the opposite root with translocation of the coronary arteries into the “neo-aorta.”24 Long-term concerns after this operation include coronary stenosis at the anastomotic sites, ventricular dysfunction and arrhythmias, and aortic and pulmonary arterial dilatation and valvular regurgitation.25 The ECG may be normal in -TGA (postarterial switch) or may reveal right-axis deviation and right ventricular hypertrophy (postatrial switch). On chest radiography, because of the parallel relationship of the great vessels, a narrow mediastinal shadow is common. Ventricular size and pulmonary markings vary depending on the patient’s clinical status. -TGA is the so-called congenitally corrected lesion and consists of both atrioventricular and ventriculoarterial discordance. This positions the right ventricle to the left of the morphologic left ventricle, receiving pulmonary venous return and advancing into the aorta. This variation results in systemic venous return moving from vena cavae to RA to morphologic left ventricle to PA to pulmonary veins to left atrium to morphologic RV to aorta. Associated anomalies are common in -TGA and include VSD, PS, abnormalities of the

SAVV, and conduction abnormalities, with complete heart block occurring at a rate of approximately 2% per year. Many patients with -TGA may be asymptomatic and escape diagnosis until adulthood. Patients with -TGA may present with heart failure due to significant SAVV regurgitation or systemic right ventricular dysfunction, arrhythmias, or complete heart block.26 On electrocardiography, PR prolongation may be noted and there may be complete heart block. Because of the inversion of the left and right bundle branches, a pattern of inferior infarction may be seen. On chest radiography, the vascular pedicle may be abnormal or narrow and the ventricular silhouette has a “humped” appearance. Cardiomegaly may be noted as well as dextrocardia, which also occurs with -TGA. In -TGA as well as -TGA with atrial switch, the long-term morbidity is the systemic RV and systemic AVV. Surgical repair for important SAVV regurgitation should be undertaken before the systemic ventricular function deteriorates.27 Patients with systemic ventricular dysfunction may benefit from therapy with beta-blockers and afterload reducers such as ACE inhibitors or angiotensin II receptor blockers, though data demonstrating any mortality benefit are lacking due to small numbers of patients studied, with only some symptomatic benefit or improvement in functional status noted. Cardiac transplantation is often considered in the patients with severe systemic ventricular dysfunction refractory to medical therapy.

Tetralogy of Fallot Tetralogy of Fallot refers to the classic constellation of four findings: right ventricular outflow obstruction, a large subaortic VSD, an aorta that overrides the ventricular septum, and hypertrophy of the RV. Embryologically, this anatomy is caused by the anterior displacement of the aortic–pulmonary arterial (or spiral) septum. The frequent coexistence of an ASD can make for a “pentalogy.” Other associations with TOF include a right aortic arch and presence of an anomalous left anterior descending coronary artery arising from the right coronary artery passing anterior to the right ventricular outflow tract.28 Occasionally, unrepaired patients with TOF can present in adulthood owing to a remarkable balance between the pulmonic obstruction and the VSD, which limits cyanosis, the so-called “pink tet.”

Early palliation with a systemic to arterial shunt (i.e., the Blalock– Taussig–Thomas shunt connecting the subclavian artery and the PA) facilitates growth of the pulmonary arteries and is a precursor to definitive surgical repair in the young child in the era where complete surgical repair wasn’t feasible in infancy. Definitive repair comprises of closure of the VSD, as well as relief of the right ventricular outflow tract obstruction, which may include simple resection of infundibular stenosis, patch augmentation of the right ventricular outflow tract that may disrupt the pulmonary valve, or pulmonary valvotomy resulting in significant pulmonic regurgitation. Those with pulmonary atresia will require a right ventricular to pulmonary arterial conduit, often a valved homograft, which can be prone to either stenosis or regurgitation with time and often requires re-interventions, surgical or percutaneous. Though pulmonary regurgitation or mixed PR/PR in the case of conduits can be tolerated for many years, patients commonly experience consequences in adulthood. Additionally, adult patients with TOF experience increased risk of arrhythmias and sudden cardiac death.29 Findings on physical examination of the unoperated patient may include cyanosis, clubbing, a right ventricular lift, a thrill at the left sternal border due to severe pulmonary obstruction, or a loud continuous murmur over the thorax as a result of aortopulmonary collaterals in the setting of severe right ventricular outflow tract obstruction. After surgical repair, a diminished or an absent radial pulse (postclassic Blalock–Taussig–Thomas shunt), a soft ejection murmur across the right ventricular outflow tract, a low-pitched diastolic murmur from pulmonary regurgitation, or an absent P2 may be noted. On the ECG of a patient with repaired TOF, a complete right bundle branch block is typically present. Chest radiography may be normal postTOF repair; however, cardiomegaly may be seen in the setting of significant pulmonic and/or tricuspid valve regurgitation. A right aortic arch is often seen. After repair of TOF, cardiomegaly as well as development of atrial or ventricular arrhythmia should prompt search for an underlying hemodynamic abnormality, commonly pulmonary regurgitation. Cardiac MRI is the modality of choice for surveillance of RV size, function, and overall hemodynamics in these patients.30 Guidelines advocate for intervention on the pulmonary valve, surgically or percutaneously, in TOF patients with symptomatic moderate to severe

pulmonary regurgitation, and the asymptomatic with evidence of (a) mild or greater RV or LV dysfunction; (b) severe RV dilation on cardiac MRI (RV end-diastolic volume index ≥160 mL/m2, RV end-systolic volume index ≥80 mL/m2); (c) RV end-diastolic volume ≥2 times the LV end-diastolic volume; (d) RV systolic pressure ⅔ or higher systemic pressure; and (e) progressive objective reduction in exercise capacity.9 Adults with TOF are at increased risk of arrhythmia, both atrial and ventricular, especially after age 45. While pulmonic regurgitation and consequent RV remodeling are associated with an increased likelihood of VT, valve replacement does not appear to eliminate risk. Accepted risk factors for sudden cardiac death include LV systolic or diastolic dysfunction, nonsustained VT, QRS duration ≥180 ms, and extensive RV fibrosis on cardiac MRI. There should be a low threshold to proceed to electrophysiologic study if there is reasonable suspicion based on history. ICD implantation should be considered in patients with multiple risk factors for sudden cardiac death, documented history of sustained VT, sustained VT during electrophysiologic study, and in those who meet standard qualifying criteria by LVEF refractory to medical management.31

Ebstein Anomaly Ebstein anomaly is the result of failed delamination of the septal and/or posterior tricuspid leaflet, and rarely the anterior leaflet, causing an “atrialization” of the RV and tricuspid regurgitation. As a result, the RV is small and often hypocontractile. The posterior and septal leaflets of the tricuspid valve are often small and inadequate, while the anterior leaflet is often large and redundant, resembling a “sail” (Fig. 22.5). The latter feature results in the characteristic “sail sound,” which occurs during closure of the tricuspid valve, followed by the tricuspid regurgitation murmur (if present).32

FIGURE 22.5 Ebstein anomaly. A, B:Transthoracic echocardiogram in the apical view demonstrating the apically displaced septal leaflet of the tricuspid valve, with color Doppler demonstrating severe tricuspid regurgitation with a dilated right heart. The age at presentation depends on the degree of tricuspid leaflet regurgitation, right ventricular substrate, and comorbid CHD. Fetal, neonatal, and infant patients are more likely to have additional CHD diagnoses and suffer dire manifestations. Children, adolescents, and adults can present with progressive right ventricular failure causing dyspnea, fatigue, ascites, edema, or exertional intolerance. A large portion comes to attention with atrial arrhythmias. Over 50% of patients have a comorbid ASD or patent foramen ovale (PFO) and consequently right-to-left shunting with exertional cyanosis. About 25% of the patients have an accessory conduction pathway (Wolf– Parkinson–White syndrome). The age at presentation depends on the degree of anatomic and hemodynamic derangements.33 Physical examination may be notable for a characteristic tricuspid regurgitation murmur during systole at the lower left sternal border with a possible added mid-diastolic rumble caused by turbulent blood flow across the dysmorphic tricuspid annulus. Jugular venous pressure may be elevated, though V-waves will be blunted due to the increased compliance of the right atrium and atrialized RV. S1 and S2 are often widely split and accompanied by an S3 and/or S4 in what is termed a “triple” or “quadruple” rhythm. ECGs of affected patients can show very tall (Himalayan) P waves, which are a characteristic finding. Pre-excitation may be noted as well as QRS prolongation with a “splintered” right bundle branch block pattern.

Chest radiography may reveal marked cardiomegaly with clear lung fields. The cardiac contour tends to be “globular” due to right atrial enlargement.33 The diagnosis is typically confirmed using echocardiography. There is also an increasing role for cardiac MRI for clearer delineation of cardiac structure and function. Surgery involves complex repair or replacement of the tricuspid valve in addition to closure of the atrial communication and should be limited to centers with extensive experience in this area.34 Indications for surgery include significant symptoms or worsening exercise capacity, progressive RV dysfunction, systemic desaturation, or paradoxical emboli from the severe TR across a PFO or ASD.9

Single Ventricle Circulations Among those suffering with CHD, those with single ventricle physiology are particularly complex. The designation applies to patients born with one effective pumping chamber who have undergone a series of surgical palliations to organize the pulmonic and systemic circulations in series and bypass the dysplastic or nonfunctional ventricle. Patients invariably manifest with hypoxia and circulatory compromise in their infancy and often present to adult cardiologists with complex surgical and medical histories. Several CHDs are considered for surgical conversion to a single ventricular circulation, including hypoplastic left heart syndrome, tricuspid atresia, and double-inlet left ventricle. At birth, these patients have complete mixing of pulmonary and systemic venous blood, leading to cyanosis as well as the hazards inherent to chronic left to right shunting.35 Though there are many surgical sequences, the endpoint is commonly the Fontan circuit where the vena cavae are directly connected to the pulmonary arterial circulation, leaving the single ventricle acting as the systemic ventricle, separating systemic and pulmonary venous blood. This provides passive pulmonary blood flow, minimizing intracardiac shunting and allowing for ventricular function to more efficiently provide antegrade flow of oxygenated blood. Although this group of procedures dramatically improves prognosis, it leaves patients with a fundamentally disordered physiology. Fontan-palliated patients are unable to augment their cardiac output normally as they lack the contractile support of a subpulmonic

ventricle. As a result of passive pulmonary perfusion, these patients also experience substantially elevated central venous pressures. Over the course of years, these patients develop end-organ damage due to chronic venous congestion and limited cardiac output.36 Traditional Fontan circulations are not cyanotic. If physical exam indicates cyanosis during initial evaluation or as an interval development, prompt referral to CHD specialty care to evaluate for fenestration or development of systemic venous collaterals is warranted. Edema or ascites should raise concern for Fontan obstruction, cardiac dysfunction, proteinlosing enteropathy, or hepatic congestion and/or cirrhosis. Findings of venous stasis and thromboembolism are common.37 There is also an increased risk of hepatocellular carcinoma and regular hepatic surveillance is warranted. Given these patients’ reliance on passive pulmonary flow, even mild elevations in pulmonary vascular resistance can lead to both significant increases in central venous pressure and decreased ventricular preload. Current guidelines suggest consideration toward pulmonary vasodilators (i.e., endothelin antagonists or phosphodiesterase inhibitors) and/or anticoagulation to improve flow through the pulmonary circuit.9 It is reasonable to obtain serial imaging and laboratory evaluation to assess for renal dysfunction and hepatic fibrosis, cirrhosis, and/or hepatocellular carcinoma as these are red flags for deterioration. Decreased serum protein and albumin levels may indicate onset of protein losing enteropathy. Atrial arrhythmias are poorly tolerated, and their discovery should prompt evaluation at a specialized center. As patients with single ventricle circulations are among the most complex in CHD, it is imperative to coordinate care with a center with specialized expertise in CHD.

Eisenmenger Syndrome Eisenmenger physiology refers to the condition where an intracardiac shunt (of any kind) has resulted in extensive pulmonary vascular remodeling and pulmonary hypertension that is so severe, systemic or suprasystemic, that the shunt has reversed. Patients may present with dyspnea on exertion, palpitations, progressive cyanosis, hemoptysis, syncope, or volume overload. Rapid deterioration can be seen during atrial or ventricular arrhythmias or with complications such

as pulmonary embolism or infection, or conditions that result in transient hypotension such as induction with anesthesia. The physical exam of these patients is notable for cyanosis (which often worsens during exercise) and clubbing. If differential clubbing is seen (usually clubbing of the feet and not the arms), then the clinical diagnosis is Eisenmenger physiology in the context of PDA. Jugular venous pressure is typically elevated with a prominent “a” wave. There may also be a right ventricular heave, a palpable P2, an audible P2 in the LV apex, and a diastolic murmur due to pulmonary regurgitation. Because pulmonary and systemic pressures only slightly differ, a systolic murmur across the shunt lesion is often not heard. In general, patients with Eisenmenger syndrome may have better longterm survival than comparable patients with idiopathic (primary) pulmonary hypertension, but their functional limitation is considerable.38 There are a number of complications that result from long-standing hypoxia, including significant secondary erythrocytosis (elevated red blood cell count). Symptoms of hyperviscosity (changes in mental status, fatigue, and headache) are quite rare, and phlebotomy should only be performed to relieve these symptoms (typically in the presence of a hematocrit >65%) in the absence of dehydration. If phlebotomy is attempted, it should be accompanied by at least equal fluid replacement. Repeated phlebotomy can result in iron deficiency and actually increases the risk of hyperviscosity. Iron should be repleted in these patients if deficiency is present. Patients with Eisenmenger syndrome often develop proteinuria and a decreased glomerular filtration rate (GFR). The low GFR and the high turnover of red blood cells lead to elevated uric acid levels, which can result in acute renal failure. Patients are particularly susceptible after administration of contrast dye if not adequately hydrated. Patients with Eisenmenger physiology are at risk of both thrombosis and hemorrhage, hemoptysis that may be life threatening, cerebral abscesses, stroke, scoliosis, and arthropathy as well as pigment gallstones. Given coagulopathy, they can be quite difficult to manage if anticoagulation is indicated such as when they develop in situ thrombosis in the pulmonary arterial tree, and risk and benefit needs to be weighed carefully. Rarely, they may present with cardiac ischemia in the setting of coronary artery compression by a dilated PA or from right ventricular ischemia.39

It is imperative that patients with Eisenmenger physiology avoid dehydration, moderate-to-severe strenuous exercise, exposure to excessive heat, chronic high altitude, and pregnancy.40 If catheterization or noncardiac surgery is required, they should be hospitalized in centers with adult CHD expertise and experienced cardiac anesthesia. All intravenous lines should be filtered to exclude air bubbles. Improved quality of life has been noted with the use of pulmonary vasodilators in patients with Eisenmenger physiology and survival may be positively impacted. Lung transplantation with repair of CHD or combined heart–lung transplantation may be considered in those with severe disease.41

DIAGNOSTIC EVALUATION Adult general cardiologists may encounter CHD at variable time points, from a patient with a de novo diagnosis of mild CHD to patients with complex CHD that have had poor follow-up. Coordination with a CHD-specialized center should be pursued in most cases as patients generally have better outcomes. However, it is important that general cardiologists serve as an access point for CHD patients and act to collaborate with subspecialists. As with any cardiac patient, a detailed history and physical exam are of the utmost importance. Particular focus should be placed on the patient’s initial CHD diagnosis or diagnoses, prior surgical and procedural history, current imaging findings, and access to a CHD-specialized center. There should be a low threshold to evaluate for the presence of arrhythmias, as these are not uncommon in adults with CHD and often originate near the myocardial scars of previous surgeries. Many lesions also cause dynamic obstruction, and syncope or presyncope is cause for concern. As outlined below, multimodality imaging and cardiac catheterization play important roles in clinical decision-making regarding medical and surgical management of these patients.

DIAGNOSTIC IMAGING

Diagnostic imaging is a critical adjunct, and less invasive modalities such as echocardiography are an important first step. Subsequent computerized tomography (CT) scanning or magnetic resonance imaging (MRI) may add substantially to understanding the specifics of a patient’s condition. Given the anatomic complexity in many CHD patients, a systematic approach is helpful in providing orientation. Morphologic aspects of cardiac structures (e.g., IVC connection with the RA or the presence of a moderator band in the RV) are recognized and used to provide orientation. One of the more common methods to maintain orientation is a segmental approach, in which a patient’s cardiac anatomy is divided into three segments: (a) the atria and viscera, (b) the ventricular loop, and (c) the great vessels. This approach discerns the rotation of embryologic structures in forming the heart from the primitive cardiac tube. The position of structures is often described as a three-letter, Latin-derived acronym in the study report (e.g., S,D,S representing situs solitus of the atria and viscera, dextrorotation of the ventricular loop, and situs solitus of the great vessels—the common anatomy encountered by the general cardiologist). While echocardiography holds a crucial role in CHD diagnostics and management, cardiac MRI has emerged as a favored modality in CHD patients given its ability to provide reproducible, dynamic cardiac assessment unencumbered by restrictive windows, or hazardous radiation exposure. It is the guideline-recommended surveillance modality in CHD patients who have or who are at risk of developing RV enlargement and dysfunction, such as those with TOF or a systemic RV. It also frequently elucidates extracardiac components of CHD such as coarctation of the aorta, peripheral pulmonary stenosis, or arteriovenous malformations.42 Cardiac CT imaging continues to have a role in care for CHD patients given its superior spatial resolution, though its use is often deferred in young women given ionizing radiation exposure. It is a reasonable modality to exclude coronary artery disease in CHD patients with low to intermediate pretest probability and to elucidate structures needing further characterization on echocardiography or MRI.43 Important differences in imaging modalities used for CHD patients are listed in Table 22.2.

Table 22.2 Imaging Modalities in Evaluation of Congenital Heart Disease

*** indicates widely available, ** available at most centers, * available at specialized centers. $$ more expensive, $ less expensive. ++ provides detailed assessment, + provides assessment, +/− possible utility. CCT, cardiac computed tomography; CMR, cardiac magnetic resonance.

CARDIAC CATHETERIZATION Diagnostic cardiac catheterization, though generally performed later in the diagnostic workup of CHD patients, remains the gold standard for pressure measurement, cardiac output calculation, and vascular resistance determination. The relative size of shunt lesions can be assessed using oximetry, and the hemodynamic consequences of additional blood flow can be assessed. Most importantly, cardiac catheterization affords the opportunity to intervene and palliate or repair anatomic defects or to clarify the suitability of further surgical intervention. Anatomic shunting can be quantified in the catheterization laboratory by examining the blood oxygen saturations in the respective chambers. The mixed venous (MV) saturation is the saturation of blood returning to the right atrium (RA) with contributions from the inferior vena cava (IVC), superior vena cava (SVC), and coronary sinus (CS). IVC saturation is normally higher than the SVC due to high renal blood flow and less oxygen extraction by the kidney. The CS saturation is very low, but its volume of contribution is negligible and usually ignored.44 Because so much mixing of blood with differing saturations occurs in the RA, an 11% increase in oxygen step-up (saturation increase from a chamber

to its successive chamber) is required to diagnose a shunt lesion between the SVC and the RA. A 7% increase is necessary to detect a shunt between the RA and the RV and a 5% increase to detect a shunt between the RV and the pulmonary artery (PA). A quick and simple measure of the overall size of a left-to-right shunt ratio can be obtained by using the formula (the PV saturation can be assumed to be 97% if not directly measured): (Aortic saturation – MV saturation)/ (PV saturation – PA saturation) In general, a “significant shunt” is present when the shunt ratio is ≥1.5:1.0. This simplified definition may not apply to older adults. As pulmonary hypertension develops and RV compliance falls, a left-to-right shunt that was 3:1 for 30 years may become 7 Wood units or a ratio of the pulmonary-to-systemic vascular resistance of >0.5) have been associated with considerably higher

perioperative mortality.45 In addition, assessment of pulmonary vascular reactivity with endothelium-dependent vasodilators, such as inhaled nitric oxide or intravenous adenosine, may provide additional prognostic information in these patients by confirming whether any of the observed pulmonary hypertension has a vasoconstrictor component. In patients with shunt lesions and pulmonary arterial hypertension (mean PA pressure ≥20 mm Hg and mean pulmonary capillary wedge pressure ≤15 mm Hg), growing evidence supports the use of selective pulmonary vasodilator therapy (such as endothelin blockers and phosphodiesterase-5 inhibitors) to improve exercise capacity and reduce symptoms.46 No patients with CHD should be started on these medications, however, without first undergoing thorough hemodynamic assessment in the catheterization laboratory.

GENERAL STRATEGIES

MANAGEMENT

Although adult patients with CHD can be intimidating at first presentation, sticking to basic concepts can be helpful in choosing appropriate management strategies. Patients with intracardiac shunts should be counseled to avoid high-risk activities and have filtering devices placed on all intravenous lines whenever hospitalized to prevent the risk of paradoxical embolization. Noncardiac surgery should be considered after the risks and benefits have been carefully considered, particularly in the patient with Eisenmenger syndrome. Most adults with CHD will require lifelong follow-up and should be referred to specialized centers with expertise in their care. Approximately 18% of congenital heart defects are associated with a congenital syndrome, including coexisting cognitive and neurologic deficits or chromosomal abnormalities (Down syndrome with trisomy 21 and TOF with 22q11.2 deletion).47 This is why patients should undergo genetic testing if a syndrome is suspected. Those with a congenital syndrome should be appropriately screened for coexisting noncardiac conditions affecting them including sleep apnea, endocrinopathies, renal disease, and psychiatric issues with appropriate referrals provided.

Some patients with CHD are at increased risk of developing IE and should be educated on the recommendations for prophylaxis. According to the most recent guidelines, antibiotic prophylaxis before dental procedures is recommended to the “high-risk” group of patients with CHD including (a) those with prior IE; (b) those with prosthetic heart valves; (c) those with palliated or unrepaired cyanotic CHD, including surgically constructed palliative conduits and shunts; (d) those with repaired CHD with prosthetic material or device, whether placed percutaneously or surgically, during the first 6 months postprocedure; and (e) those with repaired CHD with residual defects at the site or adjacent to the site of a prosthetic device or patch that prevents endothelialization.48 Fertility, pregnancy, and contraception are common considerations in the young CHD patient. Menarche may onset later in women with complex CHD, and prevalence of primary amenorrhea may be as high as 40%. Women with CHD also have higher rates of miscarriage than the general population. Regarding contraception, estrogen-containing therapies should be avoided in women with CHD prone to thromboembolism. Prior to pregnancy, women should receive individualized counseling from a cardiologist with advanced training CHD as well as maternal–fetal medicine subspecialty obstetricians. While the hemodynamic effects of pregnancy are variable with different CHDs, patients with severe pulmonary hypertension, left-sided obstructive lesions, LV dysfunction, or Fontan palliation have historically handled them poorly and should be counseled on the substantial risk of maternal morbidity and mortality.49

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25. Schwartz ML, Gauvreau K, del Nido P, Mayer JE, Colan SD. Long-term predictors of aortic root dilation and aortic regurgitation after arterial switch operation. Circulation. 2004;110(11 Suppl 1):II128-II132. 26. Warnes CA. Transposition of the great arteries. Circulation. 2006;114(24):2699-2709. 27. Kollars CAK, Kral Kollars CA, Gelehrter S, Bove EL, Ensing G. Effects of morphologic left ventricular pressure on right ventricular geometry and tricuspid valve regurgitation in patients with congenitally corrected transposition of the great arteries. Am J Cardiol. 2010;105:735-739. doi:10.1016/j.amjcard.2009.10.066 28. Dabizzi RP, Caprioli G, Aiazzi L, et al. Distribution and anomalies of coronary arteries in tetralogy of Fallot. Circulation. 1980;61:95-102. doi:10.1161/01.cir.61.1.95 29. Bakhtiary F, Dähnert I, Leontyev S, et al. Outcome and incidence of re-intervention after surgical repair of tetralogy of Fallot. J Card Surg. 2013;28(1):59-63. 30. Oosterhof T, Mulder BJM, Vliegen HW, de Roos A. Cardiovascular magnetic resonance in the follow-up of patients with corrected tetralogy of Fallot: a review. Am Heart J. 2006;151:265272. doi:10.1016/j.ahj.2005.03.058 31. Khairy P, Harris L, Landzberg MJ, et al. Implantable cardioverter-defibrillators in tetralogy of Fallot. Circulation. 2008;117(3):363-370. 32. Attenhofer Jost CH, Connolly HM, Dearani JA, Edwards WD, Danielson GK. Ebstein’s anomaly. Circulation. 2007;115(2): 277-285. 33. Celermajer DS, Bull C, Till JA, et al. Ebstein’s anomaly: presentation and outcome from fetus to adult. J Am Coll Cardiol. 1994;23(1):170-176. 34. da Silva JP, Baumgratz JF, da Fonseca L, et al. The cone reconstruction of the tricuspid valve in Ebstein’s anomaly. The operation: early and midterm results. J Thorac Cardiovasc Surg. 2007;133(1):215-223. 35. Rychik J, Atz AM, Celermajer DS, et al. Evaluation and management of the child and adult with Fontan circulation: a scientific statement from the American Heart Association. Circulation. 2019:CIR0000000000000696. 36. Mori M, Aguirre AJ, Elder RW, et al. Beyond a broken heart: circulatory dysfunction in the failing Fontan. Pediatr Cardiol. 2014;35(4):569-579. 37. Tsang W, Johansson B, Salehian O, et al. Intracardiac thrombus in adults with the Fontan circulation. Cardiol Young. 2007;17(6):646-651. 38. Vongpatanasin W, Brickner ME, Hillis LD, Lange RA. The Eisenmenger syndrome in adults. Ann Intern Med. 1998;128(9):745-755. 39. Kochav J. Pulmonary hypertension and Eisenmenger physiology. In: DeFaria Yeh D, Bhatt A, eds. Adult Congenital Heart Disease in Clinical Practice. Springer International Publishing; 2018:117-141. 40. Müller J, Hess J, Hager A. Exercise performance and quality of life is more impaired in Eisenmenger syndrome than in complex cyanotic congenital heart disease with pulmonary stenosis. Int J Cardiol. 2011;150(2):177-181. 41. Hjortshøj CS, Gilljam T, Dellgren G, et al. Outcome after heart–lung or lung transplantation in patients with Eisenmenger syndrome. Heart. 2020;106(2):127-132. 42. Partington SL, Valente AM. Cardiac magnetic resonance in adults with congenital heart disease. Methodist Debakey Cardiovasc J. 2013;9(3):156-162. 43. Goo HW, Park I-S, Ko JK, Kim YH, Seo D-M, Park J-J. Computed tomography for the diagnosis of congenital heart disease in pediatric and adult patients. Int J Cardiovasc Imaging. 2005;21:347-365. doi:10.1007/s10554-004-4015-0 44. Sommer RJ, Hijazi ZM, Rhodes JF Jr. Pathophysiology of congenital heart disease in the adult: part I: shunt lesions. Circulation. 2008;117(8):1090-1099.

45. Pilkington M, Craig Egan J. Noncardiac surgery in the congenital heart patient. Semin Pediatr Surg. 2019;28:11-17. doi:10.1053/j.sempedsurg.2019.01.003 46. Arnott C, Strange G, Bullock A, et al. Pulmonary vasodilator therapy is associated with greater survival in Eisenmenger syndrome. Heart. 2017;heartjnl-2017-311876. doi:10.1136/heartjnl-2017311876 47. Ko JM. Genetic Syndromes associated with Congenital Heart Disease. Korean Circ J. 2015;45(5):357-361. 48. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135:e1159-e1195. doi:10.1161/cir.0000000000000503 49. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Outcome of pregnancy in women with congenital heart disease: a literature review. J Am Coll Cardiol. 2007;49(24):2303-2311.

SUGGESTED READINGS Attenhofer Jost CH, Connolly HM, Dearani JA, Edwards WD, Danielson GK. Ebstein’s anomaly. Circulation. 2007;115(2): 277-285. Babu-Narayan SV, et al. Imaging of congenital heart disease in adults. Eur Heart J. 2016;37(15):11821195. Bashore TM. Adult congenital heart disease: right ventricular outflow tract lesions. Circulation. 2007;115:1933-1947. Diller GP, Gatzoulis MA. Pulmonary vascular disease in adults with congenital heart disease. Circulation. 2007;115: 1039-1050. Mouhammad F, Krasuski RA. Pulmonic valve disease: review of pathology and current treatment options. Curr Cardiol Rep. 2017;19(11):108. Perloff J. Perloff ’s Clinical Recognition of Congenital Heart Disease Textbook. 6th ed. 2012. Rhodes JF, Hijazi ZM, Sommer RJ. Pathophysiology of congenital heart disease in the adult, part II Simple obstructive lesions. Circulation. 2008;117:1228-1237. Rychik J, et al. Evaluation and management of the child and adult with Fontan circulation: a scientific statement from the American Heart Association. Circulation. 2019;140(6):e234-e284. Sommer RJ, Hijazi ZM, Rhodes JF Jr. Pathophysiology of congenital heart disease in the adult: part I: shunt lesions. Circulation. 2008;117:1090-1099. Sommer RJ, Hijazi ZM, Rhodes JF. Pathophysiology of congenital heart disease in the adult: part III: complex congenital heart disease. Circulation. 2008;117:1340-1350. Stout KK, et al. 2018 AHA/ACC guideline for the management of adults with congenital heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(14):e637-e697.

Chapter 22 Review Questions and Answers QUESTIONS You are seeing a 27-year-old female postal employee in outpatient clinic. She has a history of asthma treated with inhalers, though her pulmonary function tests and methacholine challenge were recently normal. She has noted progressive fatigue over the past months and finds that getting up large hills on her mail route gets her out of breath. On examination, she has a fixed split second heart sound and soft systolic ejection murmur over the left upper sternal border. Her lungs are clear and all her extremity pulses are equal and of normal intensity. All the following would be expected to be present on her diagnostic studies except: Unexplained right heart enlargement on echocardiography An RSR’ (incomplete bundle branch block) pattern on electrocardiogram (ECG) Unexplained mild pulmonary hypertension Right-to-left shunt by bubble study on echocardiography Decreased pulmonary vascularity on chest x-ray

1.

A. . C. D. .

2.

You are evaluating a 35-year-old female librarian with a history of complex congenital heart disease (CHD). She tells you that she has a “hole in the heart” but was told about 10 years ago that it was “too late to operate.” Her health has recently been stable and she denies worsening dyspnea, headaches, chest pain, or other symptoms. She is currently able to walk from her home to her mail box (~300 feet) before she has to stop and rest. On exam, she appears cyanotic but is breathing comfortably. She has a loud pulmonic closure sound and a II/VI holosystolic murmur at the right lower sternal border. There are no surgical scars over her back or chest and her pulses are equal in all four extremities. Her blood work demonstrates: White blood cell count = 8,000 Hemoglobin = 22.4 Platelets = 295,000 Urea nitrogen = 1

Creatinine = 0.9

A. . C. D. .

Reasonable therapeutic considerations in this patient include all of the following except: Endocarditis prophylaxis with dental procedures Supplemental oxygen to wear at night or with exertion Phlebotomy of 2 units with equal volume repletion Invasive assessment of cardiac hemodynamics followed by initiation of bosentan Avoiding studies that administer intravenous contrast dye All of the following statements about anomalous pulmonary venous return are correct except: Anomalous pulmonary venous return can lead to right heart enlargement and elevations in pulmonary arterial pressures. Sinus venosus atrial septal defects (ASDs) are often associated with anomalous pulmonary veins. Cardiac computed tomography, magnetic resonance imaging (MRI), and transesophageal echocardiography are all reasonable modalities to assess for anomalous pulmonary veins. A bubble study during transthoracic echocardiography can help detect an anomalous pulmonary vein.

3.

A. . C. D.

You are seeing a 35-year-old flight attendant with a history of coarctation of the aorta. At age 10, the patient underwent a coarctation resection and end-to-end anastomosis. She has noted no limitations since that time but notes that in general she has had slightly “less stamina” than her friends and colleagues over the past several years. On exam, she has equal blood pressures in all four extremities and a soft systolic ejection murmur. All of the following statements are true concerning this patient except: It is likely that the patient has a bicuspid aortic valve. There is a 10% chance that the patient has a berry aneurysm in the brain. The type of surgery that the patient underwent makes the possibility of aneurysmal dilatation at the surgical site very likely. The patient is at a higher risk of developing hypertension than the general population. All of the choices are true.

4.

A. . C. D. .

The lesions that constitute tetralogy of Fallot (TOF) include all of the following except: A ventricular septal defect (VSD) An overriding aorta An ASD Right ventricular outflow obstruction Right ventricular hypertrophy

5.

A. . C. D. .

D. .

A 21-year-old college student presents for a routine medical checkup. He has never seen an adult cardiologist and last saw a pediatric cardiologist while in high school. He has been told he has congenitally corrected transposition with an intact ventricular septum and no known valvular dysfunction. All of the following concerns about this young man are valid except: His systemic right ventricle (RV) is at risk for dilatation and failure. He has a 10% lifetime risk of develop Eisenmenger syndrome. His systemic tricuspid valve is at risk for developing significant regurgitation. He has a 32% lifetime probability of developing complete heart block. All of the choices are correct.

A. . C. D. .

All of the following syndromes and cardiac anomalies are associated except: Trisomy 21 and atrioventricular canal defects Noonan syndrome and pulmonic stenosis (PS) Holt–Oram syndrome and ASDs Marfan syndrome and mitral valve prolapse Williams syndrome and VSDs

6.

A. . C.

7.

Which of the following statements regarding Ebstein anomaly is not correct? An ASD or a PFO is present in up to 80% of patients. The cardinal feature is an apically displaced tricuspid valve resulting in atrialization of ventricular tissue. Wolf–Parkinson–White syndrome is common in these patients and multiple tracts can exist. A bicuspid aortic valve is commonly present.

8.

A. . C. D.

. A “sail sound” is a common finding on physical examination. You are seeing a 34-year-old gentleman in clinic. He has a history of TOF and underwent a palliative Blalock–Taussig–Thomas shunt at 10 months followed by a complete repair at age 3. He has been reasonably active for several years but recently has been “slowing down” a little bit. His physical examination demonstrates scars over his left scapulae and midsternum. He has a III out of VI systolic ejection murmur and a II out of IV diastolic murmur over the left upper sternum. He has clear lungs and equal pulses in all four extremities and no peripheral edema. An echocardiogram is somewhat limited in quality due to the fact he is a rather large individual, but you are able to see evidence that the right heart appears enlarged and there is some pulmonic regurgitation present. The ECG shows some widening of the QRS complex with right bundle branch block morphology. The most reasonable next step in the diagnostic evaluation of this patient would be: A repeat echocardiogram with an agitated saline (bubble) study An electrophysiologic study to look for ventricular arrhythmias A cardiac catheterization to formally examine the hemodynamics A cardiac MRI study The initiation of diuretics and digitalis

9.

A. . C. D. .

10. You have been asked to see a 45-year-old woman with a VSD. She

A. . C. D. .

has been in excellent health for many years and voices no particular complaints. She had been taking antibiotic prophylaxis with dental procedures but discontinued this as a result of the recent guideline changes. On examination, she has a III/VI pansystolic murmur and normal intensity first and second heart sounds. Her lungs are clear and she has no jugular venous distention. All of the following characteristic would argue for a benign clinical course in this patient except: A loud murmur Normal intensity heart sounds A supracristal (or subaortic) morphology The absence of right or left heart enlargement All of the choices are benign characteristics.

11. A 28-year-old woman is referred to you for evaluation of a heart

A. . C. D. .

murmur. She states that she is a long-distance runner and has not noted any significant symptoms. On examination, you note very brisk pulses and her blood pressure is 100/40 mm Hg. Her murmur extends from systole into diastole, and there is a near “machinery”-type quality to it. The remainder of her physical examination is essentially unremarkable, as is her blood work. The most likely cardiac anomaly in this case is: An ASD Coarctation of the aorta A patent ductus arteriosus (PDA) Congenitally corrected transposition with a VSD and pulmonic valve stenosis VSD

12. A 19-year-old basketball player is brought to the emergency

A. . C. D. .

department after he collapsed on the court. He received bystander cardiopulmonary resuscitation and was apparently defibrillated using an automatic external defibrillator (AED). All of the following abnormalities should be part of the differential diagnosis for this young man with the exception of: Anomalous origin of the coronary arteries (from opposite cusps) Hypertrophic cardiomyopathy Congenitally prolonged QT syndrome ASD Arrhythmogenic right ventricular dysplasia

ANSWERS 1.

Correct Answer: E. Decreased pulmonary vascularity on chest xray The lung x-ray in this case would be expected to demonstrate increased lung vascularity. The patient describe in this case has an ASD. The telltale physical examination findings are the pulmonic outflow murmur resulting from increased pulmonary blood flow due to left-to-right shunting and the fixed split second heart sound. ASDs, if sufficiently large, lead to right heart enlargement and an incomplete right bundle branch block pattern on electrocardiography. Pulmonary

hypertension can result from increased blood flow and up to 10% may develop Eisenmenger physiology if uncorrected. As with any atrial flow communication, a bubble study on echocardiography would be expected to be positive providing the right atrial pressure can be made to exceed the left atrial pressure (such as following a Valsalva maneuver).

2.

Correct Answer: C. Phlebotomy of 2 units with equal volume repletion Phlebotomy should not be performed in patients with Eisenmenger physiology unless they demonstrate evidence suggesting active sludging due to polycythemia. Suggestive symptoms include headaches and visual changes. Unnecessary phlebotomy can provoke iron deficiency, which can further increase the risk of sludging and its consequences. If phlebotomy is necessary, equal volume replacement with saline is essential. Iron levels should be checked in these patients and repleted as necessary. As with all cyanotic heart disease, endocarditis prophylaxis for dental procedures is recommended. The use of oxygen has not been well studied in this population but is reasonable if it affords the patient symptomatic improvement. An oral endothelin blockade, bosentan, has been demonstrated in a randomized, placebo-controlled study to improve functional capacity and reduce symptoms compared to placebo for patients with class III symptoms. Since our patient seems fairly limited, this may be a very reasonable therapeutic option for her. Any procedures requiring the use of anesthesia or contrast dye should be approached very carefully in patients with Eisenmenger syndrome due to the risk for adverse consequences.

3.

Correct Answer: D. A bubble study during transthoracic echocardiography can help detect an anomalous pulmonary vein. A bubble study would not be expected to be abnormal in the presence of an anomalous pulmonary vein unless a concurrent ASD was present. Normally, all four pulmonary veins drain back to the left atrium. Rarely one or multiple pulmonary veins can drain back to the RA and result in a left-to-right shunt. This can result in right heart

enlargement and even pulmonary hypertension. Anomalous pulmonary veins are present in most sinus venosus ASDs and in up to 10% of secundum ASDs. Though transthoracic echocardiography is generally unable to image an anomalous pulmonary vein, CT, MRI, and transesophageal echocardiography are all helpful in its detection.

4.

Correct Answer: C. The type of surgery that the patient underwent makes the possibility of aneurysmal dilatation at the surgical site very likely. End-to-end resection of an aortic coarctation is most likely to be complicated by eventual recoarctation, which can often be approached percutaneously. Another procedure that was previously popularized for coarctation repair, the so-called patch aortoplasty, can lead to aneurysmal dilatation, and these patients require very close monitoring. Coarctation of the aorta is believed to result from the migration of ductus arteriosus tissue into the aorta proper. As a result, constriction of the aorta occurs and leads to upper extremity hypertension and lower extremity hypoperfusion. In the adult, this lesion is most commonly diagnosed during evaluation for secondary causes of hypertension. A bicuspid aortic valve is present in 50% to 85% of patients and ascending aortic enlargement can also be seen. There is also a 10% chance of having a concurrent berry aneurysm. Despite surgical or percutaneous repair, patients are at increased risk of developing hypertension, even in the absence of an appreciable residual gradient.

5.

Correct Answer: C. An ASD The lesions of TOF include a VSD, an overriding aorta, the presence of right ventricular outflow obstruction (valvular or subvalvular), and right ventricular hypertrophy. The concurrence of an ASD has been referred to a “pentalogy” but is not part of the primary lesion complex.

6.

Correct Answer: B. He has a 10% lifetime risk of develop Eisenmenger syndrome. In the absence of any significant shunt lesions, there is no risk to this patient of developing Eisenmenger

syndrome. Congenitally corrected transposition of the great vessels implies that the patient has both atrioventricular and ventriculoarterial discordances. In other words, his venous draining enters the RA, which is connected to a left ventricle and then is taken to the lungs via the pulmonary artery (PA). Pulmonary venous return then enters the left atrium and enters the RV, which then pumps blood to the body through the aorta. Although this reproduces a near-normal circulation, the RV has not been adequately designed to withstand the workload of being a systemic ventricle. As a result, it begins to fail. Also, the tricuspid valve (the systemic AV valve—valves always follow their respective ventricles) begins to leak. Patients with congenitally corrected transposition have conduction issues and are prone to developing heart block.

7.

Correct Answer: E. Williams syndrome and VSDs The characteristic cardiovascular lesion of Williams syndrome is supravalvular aortic stenosis, though coarctation of the aorta and peripheral PA stenosis has also been described. The characteristic lesion of trisomy 21 (Down syndrome) is an atrioventricular canal defect (also known as a primum ASD/VSD), though ASD, VSD, and PDA are also common. Noonan syndrome has most classically been associated with dysplastic or stenotic pulmonic valves. Holt–Oram syndrome is an autosomal-dominant disorder in which ASDs and VSDs are most common. Marfan syndrome’s most worrisome cardiovascular involvement is of the aorta, which can lead to dissection and even death. Many of these patients have concurrent mitral valve prolapse, though it is less likely a cause of morbidity or mortality.

8.

Correct Answer: D. A bicuspid aortic valve is commonly present. A bicuspid aortic valve does not appear to be a common finding in most patients with Ebstein anomaly. Ebstein anomaly is characterized by apical displacement of the septal and the posterior tricuspid valve leaflets, leading to atrialization of the RV. An atrial flow communication (ASD or PFO) exists in up to 80% of patients. The ECG often demonstrates very large or “Himalayan” P waves. Wolf–

Parkinson–White syndrome is present in up to 30% of patients with half of these having multiple accessory tracts. The loud snapping sound of the ballooning leaflets has been compared to that of a sail flapping in the wind and can be a very characteristic examination finding.

9.

Correct Answer: D. A cardiac MRI study Primary repair of TOF entails not only closing the VSD but also resecting the right ventricular outflow obstruction and often placing a patch over the resected tissue. Because the valve is often dysplastic, significant regurgitation of the pulmonic valve results. This patient demonstrates the typical examination of patient with prior repair complicated by significant pulmonic valve regurgitation. These patients do remarkably well for many years but then develop progressive right heart dilatation, heart failure, and arrhythmias. Widening of the QRS complex has been well described as a precursor to adverse clinical outcomes. The timing of reoperation to implant a pulmonic valve is very challenging, and the status of the RV appears to be the most important determining factor. A bubble study would only clarify whether an atrial level or a pulmonary shunt was present, which is unlikely to be a pathophysiologic contributor to this case. Though arrhythmias are a complication of right heart dilatation, the role of electrophysiologic testing in this population of patients is far from clear, and in this patient without a history of syncope would not be indicated. It is also unlikely that invasive hemodynamics would provide crucial diagnostic information. Finally, without evidence for significant volume overload, the initiation of diuretics and digoxin would not be recommended at this time.

10. Correct Answer: C. A supracristal (or subaortic) morphology Of

the various types of VSDs, supracristal (subaortic) defects should be monitored closely because of their predilection for spontaneous closure by aortic leaflet tissue resulting in significant aortic regurgitation. The patient in this case has a small, restrictive, and asymptomatic VSD. Flow in such cases is determined by the size of the shunt and the compliance of the ventricles. Smaller lesions in

general will have increased turbulence and thus louder murmurs. Thus, a louder murmur isolated to systole is reassuring in this case as is the presence of normal intensity heart sounds. In the presence of pulmonary hypertension, the pulmonic component of the second heart sound is often accentuated. Cardiac chamber enlargement results from volume overload and its absence in this case again suggests a more benign lesion.

11. Correct Answer: C. A patent ductus arteriosus (PDA) PDA is the

persistence of an in utero communication between the aorta and the left PA, which is again designed to bypass blood away from the collapse lungs. It is the third most common congenital heart defect found in adults and is generally found in isolation in the adult. Most adult patients with patent ductus are asymptomatic, though this depends on the size of the left-to-right shunt and the size of the ductus. Frequently, this lesion is discovered by the unusual quality of a continuous murmur at the left upper sternal border that can often sound like an innocent venous hum. Because a patent ductus is an aortopulmonary runoff, however, the pulse pressure frequently is widened, and the pulses are brisk to bounding. Because of the risk of endocarditis, some advocate repair, even if the shunt is not significant. Fortunately, most ductus lesions can now be closed in the catheterization laboratory without the need for surgery.

12. Correct Answer: D. ASD Though an ASD does increase the risk of

developing atrial fibrillation later in life and unrepaired may shorten lifespan, there has been no link between ASD and sudden death. The most common lesions to exclude in a young person who suffers a sudden death include hypertrophic cardiomyopathy, an autosomaldominant disorder that results in abnormal myocardial architecture and increases arrhythmogenic risk. Abnormal coronary artery origins appear to be a risk for sudden death as well, though the mechanism remains poorly understood and controversial. It may be due to compression between the great vessels or an abnormal slit-like orifice at the take-off of the vessel from the aortic cusp. Congenital QT-prolongation can result in sudden death and can occasionally be

diagnosed from an ECG. Arrhythmogenic RV dysplasia and Brugada syndrome are other abnormalities that disturb the normal electrophysiologic milieu and increase the risk for sudden death.

CHAPTER 23

Echocardiography in Congenital Heart Disease SERGE C. HARB AND CHRISTINE JELLIS Congenital heart disease is by definition an abnormality in cardiac structure that is present at birth, even if it is not diagnosed until later in life. These defects are usually the result of altered embryonic development of a normal structure or failure of development. Four categories of etiologic agents may be responsible for this abnormal development. They include hereditary and chromosomal defects (Table 23.1), viruses (rubella with patent ductus arteriosus [PDA]), chemicals (thalidomide with truncus arteriosus or tetralogy of Fallot), and radiation (ventricular septal defects [VSDs]). Although these agents are associated with certain known defects, most defects have no specific cause and the etiology may in fact be multifactorial. The incidence of congenital heart disease (excluding bicuspid aortic valve and myxomatous mitral valve (MV) disease with mitral valve prolapse [MVP]) is approximately 0.5% to 0.8% of live births. Congenital cardiac malformations are much more common in stillbirths than in live births. Some congenital lesions have a high rate of survival without surgery and may be seen in the unoperated adult with different relative frequencies (Table 23.2). Other lesions, with worse prognosis, are usually not seen in adults due to childhood mortality. However, as both diagnosis and treatment (both medical and surgical) improve, more of these patients are surviving into adulthood and are more likely to be seen in a cardiology office as adults. Thus, all cardiologists should be familiar with the lesions discussed in this chapter.

Table 23.1 Chromosomal Anomalies and Their Congenital Syndromes Associated with Heart Defects

VSD, ventricular septal defect; PDA, patent ductus arteriosus; PS, pulmonic stenosis; AV, atrioventricular; AS, aortic stenosis; ASD, atrial septal defect.

Table 23.2 Congenital Heart Defects in the Unoperated Adult

ATRIAL SEPTAL DEFECTS Atrial septal defect (ASD) accounts for 22% of adult congenital defects. Excluding bicuspid aortic valves and MVP, ASDs are the most common form

of adult congenital heart disease. They make up 10% of all congenital heart defects and demonstrate a female-to-male preponderance of 3:2. Diagnosis of ASD is aided by the following features: On auscultation, a wide fixed split S2 with a pulmonary flow murmur is heard. On electrocardiogram (ECG), ostium primum (OP) ASD shows marked left axis or right bundle branch block (RBBB) with signs of right ventricular (RV) enlargement. There may be first-degree atrioventricular (AV) block. Ostium secundum (OS) ASD is marked by RSR or rSR in V1, QRS < 0.11 seconds, right axis deviation, right ventricular hypertrophy (RVH), and possibly first-degree AV block and right atrial enlargement (RAE). Shunt can be visualized by echocardiography (transthoracic [TTE] and transesophageal [TEE]) with color Doppler and agitated saline contrast. Direction and severity of the shunt can also be calculated (Qp:Qs). Cardiac magnetic resonance (CMR) provides further evaluation of shunt size, location, and hemodynamic severity (Qp:Qs), while also accurately measuring biventricular size and function. Assessment for other associated congenital abnormalities is important. Shunt at the atrial level is a potential source of paradoxical embolus. The locations of types of ASD are shown in Figure 23.1. The four types of ASD are as follows:

FIGURE 23.1 Location of types of ASD. SV, sinus venosus ASD; OP, ostium primum ASD; OS, ostium secundum ASD; CS, coronary sinus ASD. Primum ASD Secundum ASD Sinus venosus (SV) Unroofed coronary sinus (CS)

Primum Atrial Septal Defect Primum ASD accounts for 20% of cases of ASD (Fig. 23.2A–C) and is part of an AV canal defect in which embryonic endocardial cushions fail to fuse normally and partition the heart (Figs. 23.3 and 23.4).

FIGURE 23.2 A:Apical four-chamber view of a patient with AV canal defect. Note the primum ASD (arrow) and the dilated right side. B:Magnified apical four-chamber view with color Doppler demonstrating the left-to-right flow (arrow) across the primum ASD. C:3D TEE view of the mitral valve from the left atrial aspect (“surgeon’s view”) showed a cleft in the mid anterior leaflet (arrow).

FIGURE 23.3 Apical four-chamber view of partial AV canal defect (left) and complete AV canal defect (right). The partial AV canal defect has a primum ASD, cleft MV, and widened anteroseptal tricuspid commissure. The complete AV canal defect has all of these and a VSD.

FIGURE 23.4 Parasternal short-axis view showing complete AV canal defect (right) compared to a normal heart (left). Note the cleft anterior mitral leaflet and VSD in the complete AV canal defect. A complete AV canal defect consists of four components: Inlet VSD Primum ASD Cleft MV Widened anteroseptal tricuspid commissure A partial AV canal defect is as above without the VSD.

Secundum Atrial Septal Defect Secundum ASD is an ASD at the fossa ovalis (Fig. 23.5A–E). It is the most common form of ASD (75% of cases). The following features distinguish a secundum ASD:

FIGURE 23.5 A:Four-chamber mid-esophageal TEE view of a large secundum ASD demonstrated on biplane imaging (arrow). B:TEE with color Doppler demonstrating bidirectional flow across the secundum ASD. C:3D zoom “en face” view of the secundum ASD from the LA. D:TEE with agitated saline contrast demonstrating the intermittent right-to-left shunting across the secundum ASD. E:TEE with agitated saline contrast demonstrating the intermittent left-to-right shunting across the secundum ASD (arrow) and the unopacified blood from the left side of the heart (specifically the left atrium [LA]) displacing the contrast within the RA. The combination of this image and the prior image demonstrates the bidirectional shunting across this ASD. Usually a left-to-right shunt, because the thin-walled right ventricle (RV) has low filling pressures relative to the left ventricle (LV) (due to lower pulmonary vascular resistance compared with higher systemic vascular resistance). Shunt reversal (right to left) is seen in the context of pulmonary hypertension and Eisenmenger physiology. Increased pulmonary blood flow, of often two to four times normal

Dilated right heart due to right atrial (RA) and RV volume overload The pulmonary artery (PA) is often dilated.

Sinus Venosus Atrial Septal Defect Sinus venosus ASD accounts for 5% of ASD (Fig. 23.6). The following are typical features:

FIGURE 23.6 Bicaval TEE view with color Doppler demonstrating a sinus venosus ASD with left-to-right shunting. This ASD is located near the connection between the SVC and the RA. Defect near the junction of the superior vena cava (SVC) or the inferior vena cava (IVC) with the RA (posterior to fossa ovalis) Often difficult to detect (typically requires TEE or cardiac computed tomography (CT)/CMR)

If unexplained right-sided dilatation is seen on echocardiography, further imaging with agitated saline contrast injection to look for a right to left shunt should be performed. TEE may be also needed. Superior sinus venosus ASD is almost always associated with partial anomalous pulmonary venous (PV) return: typically right PV to either SVC or high RA.

Coronary Sinus Atrial Septal Defect Coronary sinus ASD is very rare. A distinguishing feature is that the roof of the CS is absent or has multiple fenestrations, enabling a shunt directly from the left atrium into the CS (Fig. 23.7).

FIGURE 23.7 Cardiac computed tomography scan showing a coronary sinus ASD: The red arrow points to the coronary sinus entry into the RA. The blue double arrow shows the completely unroofed coronary sinus.

VENTRICULAR SEPTAL DEFECT VSD is the most common form of congenital abnormality at birth but accounts for only 10% cases of congenital heart disease in adults as 50% to 80% will close spontaneously during childhood (Fig. 23.8).

FIGURE 23.8 Locations of types of VSD: perimembranous, muscular (may be multiple), supracristal (“subpulmonic”), or AV canal (“inlet”) defects.

Types of VSDs include the following: Perimembranous VSD: most common form of congenital VSD accounting for 80% of cases, has the highest rate of spontaneous closure and is often associated with a ventricular septal aneurysm formed by the septal leaflet of the tricuspid valve (TV) partially closing the defect (the defect may be larger than it appears) (Fig. 23.9A,B) Muscular VSD: accounts for 10% of VSD and may be multiple (Fig. 23.10) Supracristal (“sub-pulmonic”) VSD: accounts for 5% of VSD (Fig. 23.11A,B), involves left ventricular outflow track (LVOT)/right ventricular outflow track (RVOT), and carries a high incidence of aortic insufficiency (AI) due to prolapse of right coronary cusp (RCC) or left coronary cusp (LCC) into the VSD AV canal defect (inlet VSD): discussed in relation to ASD

FIGURE 23.9 A:Inverted apical four-chamber view (pediatric convention) demonstrating a perimembranous VSD with a ventricular septal aneurysm formed as the septal leaflet of the TV attempts to close the defect. The big arrow denotes the VSD and the region enclosed by the smaller arrows demonstrates the extent of the ventricular septal aneurysm. B:Parasternal short-axis views (two-dimensional [2-D] images on the left and color Doppler images on the right) demonstrate a perimembranous VSD (arrow) with a 2-D defect noted near the RV inflow region near the TV, with left-to-right shunting seen in that location. Other important considerations include the following: VSD carries a risk of endocarditis. Restrictive VSDs have high-velocity jets with a large pressure difference between the right and left ventricles (larger defects are associated with a low-velocity jet). Recall the modified Bernoulli equation: △P = 4V2.

Like ASDs, CMR is valuable in demonstrating the defect size and location, determining its hemodynamic severity (Qp:Qs), accurately measuring biventricular size and function, along with evaluating for other associated congenital abnormalities.

FIGURE 23.10 Zoomed apical four-chamber view demonstrating a large muscular VSD (arrow) in the mid interventricular septum on 2D gray scale imaging (left) and with left to right shunt on color Doppler imaging (right).

FIGURE 23.11 A:Parasternal short-axis view demonstrating the 2-D defect of a supracristal VSD (arrow) located near the RVOT. B:Parasternal short-axis view with color Doppler demonstrating a fine jet of left-to-right flow through the supracristal VSD.

BICUSPID AORTIC VALVE Bicuspid aortic valve occurs in 1% to 2% of the general population. Most cases are familial, with a prevalence of approximately 9% in first-degree relatives. The most common form is a fusion of the RCC and the LCC. Congenital abnormalities of aortic cusp anatomy are shown in Figure 23.12A–E. Characteristics of bicuspid aortic valve include the following:

FIGURE 23.12 A:Parasternal short axis view showing a bicuspid aortic valve with a vertical opening.B:Parasternal short axis view showing a unicuspid aortic valve. C:Gross pathologic specimen of a unicuspid aortic valve. D:Magnified midesophageal short axis view of the aortic valve demonstrating a quadricuspid valve in diastole. E:Magnified midesophageal short axis view of the aortic valve demonstrating a quadricuspid valve in systole. Note the presence of four separate cusps. The mechanism of AI is typically prolapse of the less supported conjoined cusp. The long-axis view on echocardiography shows asymmetric closure of the AV with doming of leaflets. May be associated with coarctation of the aorta. At least 50% of patients with coarctation have bicuspid AV; although only 6% with bicuspid valves have coarctation. Early affected individuals (typically ages 30s to 40s) present with with AI. RCC and LCC fusion produces a posteriorly directed jet. In the

absence of concurrent degenerative stenosis, these valves may be amenable to surgical repair. Later presentation (typically, ages 50s to 60s) is usually characterized by a process of accelerated degeneration resulting in aortic stenosis (AS). Patients with bicuspid aortic valves commonly have an associated aortopathy, which may manifest as aneurysmal dilation of the aortic root or ascending thoracic aorta, with increased risk of dissection. The ascending aorta may be incompletely visualized by echocardiogram and cardiac CT/MR may be required for evaluation of associated aortopathy (in addition to coarctation). CMR can be additionally employed to assess for valve morphology, quantification of aortic regurgitant fraction, and evaluation of LV size and function. Typically indication for aortic surgery is based upon a maximal aortic dimension of ≥5.0 cm, although rapid growth (>5 mm/y) and crosssectional area-to-height ratio may be better predictors of aortic dissection than aortic diameter. For patients having bicuspid aortic valve surgery, concurrent aortic surgery is usually recommended at dimensions of ≥4.5 cm. Helpful hint: To identify and name cusps, look for the interatrial septum. The leaflet closest to the interatrial septum is the noncoronary cusp (NCC). The RCC is the most anterior cusp.

SUBAORTIC AORTIC STENOSIS Subaortic stenosis usually results from a hemispheric or circumferential subaortic membrane occurring in the LVOT usually 1 to a few millimeters below the AV (Fig. 23.13).

FIGURE 23.13 TEE long axis view showing the subaortic membrane (arrow in A) with flow acceleration on color Doppler (B). The membrane may be associated with a perimembranous VSD, coarctation of the aorta, or valvular AS. Eccentric turbulent flow through the AV often causes premature aortic valve degeneration, leading to development of AI. Patients are at risk for endocarditis; however, antibiotic prophylaxis is no longer routinely recommended. Patients can develop left ventricular hypertrophy (LVH) in response to LVOT obstruction and increased LV afterload. A small percentage of membranes grow back post-surgical resection. Surgical excision is appropriate for patients with symptoms, LVH with strain, or significant outflow tract gradients. Prophylactic resection may be appropriate for valve preservation in patients who are asymptomatic with low gradient but are developing progressive AI.

PATENT DUCTUS ARTERIOSUS In the fetus, the ductus arteriosus diverts blood flow from the nonfunctioning pulmonary circuit into the aorta and back to the placenta. It normally closes within 24 to 48 hours of birth. PDA is found in 2% of adults with congenital heart disease (Figs. 23.14A,B and 23.15A,B). It is distinguished by the following:

FIGURE 23.14 A:Suprasternal aortic arch view demonstrating the opening of a PDA into the PA (arrow). B:Suprasternal aortic arch view with color Doppler demonstrating flow from the descending aorta into the PA (arrow).

FIGURE 23.15 A:Diagram of PDA. Aortic arch view with great vessels arising superiorly off the aorta, with the patent ductus arising from the aorta across from the origin of the subclavian

artery, with flow into the PA. B:Continuous wave Doppler pattern of flow in PDA. It is usually isolated, but it can occur with complex lesions, coarctations, or VSD. When the ductus arteriosis remains patent after birth, there is left-toright shunting through an abnormal persistent fetal connection between the left PA and the descending aorta. Auscultation reveals a machinery-type murmur. Applying a modified Bernoulli equation, the peak systolic velocity of the PDA jet can be used to determine the systolic gradient between the aorta and the PA. If a PDA is left untreated, patients may develop congestive heart failure (CHF) from chronic left heart volume overload. Rarely, they can develop endocarditis, so antibiotic prophylaxis is routinely recommended and is typically continued for 6 months after surgical or percutaneous closure.

COARCTATION OF THE AORTA Coarctation of the aorta in adults involves a discrete ridge or focal narrowing of the proximal descending aorta at the ligamentum arteriosus of the ductus arteriosus (Fig. 23.16A). Characteristics of this condition include the following:

FIGURE 23.16 A:Diagram of coarctation of the aorta. Aortic arch view showing narrowing immediately distal to the takeoff of the subclavian artery. B:Continuous wave Doppler in the proximal descending aorta across the coarctation, with classic “sawtooth” flow pattern.

Clinical presentation includes hypertension, LVH, and reduced femoral pulses. Fifty percent of adults with coarctation have bicuspid aortic valves as noted above. Continuous-wave Doppler through the proximal descending aorta displays high peak velocity flow in systole and a gradient that persists into diastole (Fig. 23.16B). Chest radiography shows rib notching due to development of collaterals (intercostal arteries) (Fig. 23.17). Cardiac tomographic imaging (cardiac CT/MR) is excellent in depicting the aortic anatomy, determining the severity of coarctation, and assessing for the presence of collaterals.

FIGURE 23.17 Chest radiograph demonstrating rib notching (arrow) that is characteristic of coarctation of the aorta, resulting from the markedly increased blood flow through the intercostal arteries. Coarctation of the aorta is further illustrated in Figure 23.18A–D.

FIGURE 23.18 A:TEE long axis view of the proximal descending aorta demonstrating the coarctation narrowing. B:TEE long axis view of the proximal descending aorta with color Doppler demonstrating flow acceleration across the coarctation narrowing. C:Aortography demonstrating aortic coarctation narrowing in the descending aorta. D:Volume-rendered cardiac magnetic resonance

angiography depicting the narrowed site of coarctation in the proximal descending thoracic aorta (red arrow).

PULMONIC STENOSIS Pulmonic stenosis (PS) can be valvular, subvalvular (infundibular), or supravalvular (Fig. 23.19A–C). The following features distinguish PS:

FIGURE 23.19 A:Parasternal short-axis view demonstrating doming (arrows) of the stenotic pulmonic valve. B:Parasternal

short axis view with color Doppler demonstrating flow acceleration across the stenotic pulmonic valve. There is a relatively large proximal flow convergence zone proximal to the pulmonic valve, due to the high transvalvular gradient. C:Continuous wave Doppler across the pulmonic valve. ECG findings may be normal in mild cases. Right axis deviation and RVH are seen on ECG in moderate cases. The degree of RVH correlates with the severity of the PS. On chest radiograph, the heart size is usually normal, but the main PA is prominent due to post-stenotic dilation. Pulmonary vascular marking are usually normal but may be decreased in severe cases. Balloon valvuloplasty is often recommended if RV pressure ≥50 mm Hg. Surgery is usually reserved for cases of failed percutaneous intervention. Although patients are at increased risk for endocarditis, subacute bacterial endocarditis (SBE) prophylaxis is no longer routinely recommended.

TETRALOGY OF FALLOT The four elements of tetralogy of Fallot are as follows: 1. VSD (large and nonrestrictive) 2. Overriding aorta 3. Infundibular PS 4. RVH Abnormalities comprising in this condition result from abnormal conotruncal septation (anterior deviation of the infundibular septum). About 15% of patients also have an ASD, making the condition “pentalogy” of Fallot. Other associated defects may include valvular PS (50% to 60%), right aortic arch (25%), muscular VSD (2%), and coronary anomalies (5%).

Cardiac magnetic resonance is a valuable tool in determining the combined anatomic defects, assessing the hemodynamic impact of the VSD (Qp:Qs), and measuring biventricular size and function. Early in life, mild PS may be present with no significant shunting, known as “pink tetralogy.” As subvalvular PS increases with time, pulmonary blood flow decreases and patients develop significant right-to-left shunting, causing cyanosis, or “blue tetralogy.” Tetralogy of Fallot is illustrated in Figure 23.20A–D.

FIGURE 23.20 A:Parasternal short-axis view demonstrating a nonrestrictive perimembranous VSD (thick arrow) and infundibular PS (thin arrows) with hypertrophy of the RVOT. B:Parasternal short axis view with color Doppler showing a leftto-right shunt across the VSD (thick arrow) and color acceleration/high-velocity flow associated with the sub-pulmonic PS (long thin arrow). C:Parasternal long axis view demonstrating the perimembranous VSD (arrow) and an overriding aorta. D:Continuous wave Doppler through the RVOT/pulmonic valve demonstrating the high pressure gradients of the infundibular PS. The peak gradient across the stenosis is 76 mm Hg.

EBSTEIN ANOMALY TRICUSPID VALVE

OF

THE

Ebstein anomaly of the TV is characterized by apical displacement of the TV into the RV (Fig. 23.21). The following features distinguish this condition:

FIGURE 23.21 Apical four-chamber view (pediatric view) demonstrating apical displacement of the TV with apical tethering of the leaflets (arrows) causing severe tricuspid regurgitation (TR). Note the severe RA dilatation. TV tissue is dysplastic, with often a large, redundant “sail-like” anterior leaflet and portions of the septal and inferior cusps adherent to the RV away from the AV junction due to failed delamination from the myocardium. Clinical manifestations are variable, depending on associated manifestations. Patent foramen ovale (PFO) or secundum ASD is present in >50% cases. A common important associated defect is PS or pulmonic valve atresia. Other associations include primum ASD and VSD or congenitally corrected transposition. Wolf–Parkinson–White syndrome (WPW) is found in 10% to 15% of patients with Ebstein anomaly.

ECG commonly shows RBBB or WPW. Most common is giant P waves and prolonged P–R interval with variable degrees of RBBB. The presence of WPW increases the risk of paroxysmal supraventricular tachycardia. Chest radiography shows a large RA and small RV with decreased pulmonary vascularity if a large right-to-left shunt is present.

TRANSPOSITION ARTERIES

OF

THE

GREAT

Transposition of the great arteries (TGA) is defined as “ventriculoarterial discordance,” with the aorta connected to the RV and the PA connected to the left ventricle (Fig. 23.22A,B). It is caused by abnormal conotruncal septation in development.

FIGURE 23.22 A:Apical four-chamber view with baffles (arrows) at the atrial level directing blood from the pulmonary veins to the RA and caval flow directed to the LA. Note that the pacemaker wire is within the LA (a clue to the presence of d transposition). B:Parasternal short axis view of both the aortic and pulmonic valves showing the parallel course of the great vessels in d-TGA. In d transposition, the aorta (with the left coronary artery marked by arrows) is located anterior and to the right of the PA. In “d-transposition” (d-TGA), the direction of septal rotation is in a dextro, or rightward, direction (Fig. 23.23).

FIGURE 23.23 Diagram of d transposition both with and without VSD. In d-TGA, there must be mixing of venous and systemic blood at some level for survival (ASD, VSD, or PDA). Otherwise, the pulmonic circulation and the systemic circulation would be two separate and parallel circuits, which is not compatible with life. Common associated defects include ASD, perimembranous VSD, coarctation of the aorta, PS, and PDA. Further features of this condition include the following: The aorta is anterior and to the right of the PA, because the aorta arises from the RV. The two great arteries run parallel (Fig. 23.24). There is fibrous continuity between the anterior mitral leaflet and the pulmonic valve compared to the normal relationship of continuity between the anterior mitral leaflet and the aortic valve.

FIGURE 23.24 Relative position of great arteries in TGA. Normal position of great arteries (center): the PA wraps anteriorly around the aorta. d transposition (left): great arteries run parallel, with the aorta anterior and to the right of the PA. l transposition (right): great arteries run parallel with the aorta anterior and to the left of the PA. In contrast, in “l-transposition” (l-TGA) there is levotransposition, with the great arteries being transposed, along with inversion of both ventricles as well (Fig. 23.25). This congenitally corrected TGA or “double switch” is less morbid as it allows a physiologically appropriate flow of blood. Atria are in the normal position and are connected to the “opposite ventricle.” Systemic venous return is pumped to the lungs by the morphologic left ventricle and returns via the pulmonary veins to the morphologic RV, which pumps blood via the aorta to the systemic circulation (Fig. 23.26A,B).

FIGURE 23.25 Normal blood flow versus blood flow and anatomy in congenitally corrected transposition. In congenitally corrected transposition (right), systemic venous return → RA → LV → PA → lungs. Pulmonary venous return → LA → RV → Aorta → body.right = right figure RA = right atrium LV = left ventricle PA = pulmonary artery LA = left atrium RV = right ventricle

FIGURE 23.26 Cardiac magnetic resonance imaging L-TGA. A:Relationship of cardiac chambers and outflow tracts: In L-TGA, the venous return → RA → morphologic pulmonic LV → PA and the pulmonary venous return → LA → morphologic systemic RV → aorta. B:In L-TGA: the aorta is anterior and to the left of the PA. IVC, inferior vena cava; RA, right atrium; LV, left ventricle; PA, pulmonary artery; RV, right ventricle; Ao, aorta. The TV is the apically displaced AV valve with respect to the MV. The morphologic RV is identified by the presence of a moderator band and the presence of trabeculations. Recall that AV valves always feed the appropriate ventricle (i.e., TV always feeds the RV). The sub-pulmonic ventricle (morphologic LV) is identified by its smooth walls, absence of moderator band, and continuity between the AV and semilunar valves. There is discontinuity between the left-sided AV valve and the semilunar valve (aortic). The PA and aorta run parallel (as opposed to normal orthogonal position). The aorta lies anterior and to the left of the PA. Several associated lesions can be found in patients with l-TGA. Abnormalities of left-sided TV occur in 90% of patients. Ebstein-type abnormality is the most common of these, with apical displacement of the valve and the septal leaflet typically being most deformed. VSD occurs in

70% of patients and are most commonly perimembranous. Pulmonic outflow obstruction (i.e., obstruction of the morphologic LVOT) occurs in 40% of patients, sometimes in conjunction with VSD. On chest radiograph, because the aorta is anterior and to the left, the left heart border is straightened and the left PA is not well defined. If there is PS, there may be decreased lung markings; and if there is a VSD, there may be increased lung markings. ECG, typically demonstrates left axis deviation. A variety of AV node conduction abnormalities may be seen due to displacement of the AV node. Over time this can progress to complete heart block. In addition to echocardiography, cardiac tomographic imaging (cardiac CT/MR) is valuable in defining the AV and ventriculoarterial connections, and determining the associated defects in both forms of TGA.

OPERATIONS FOR HEART DISEASE

CONGENITAL

Surgical techniques to treat congenital heart disease have evolved over the last 50 years. Early techniques were predominantly palliative, providing temporary relief of symptoms or of a clinical condition. Over time, with improvement in diagnostic as well as surgical capabilities, corrective techniques were developed. Corrective operations can achieve “normal anatomy,” “normal hemodynamics,” and/or normal physiology. Some surgical approaches may require staged procedures. The trend has been toward performing corrective procedures earlier, with fewer palliative procedures being performed. Many acronyms are used to describe the various surgical techniques (Table 23.3). As more of these surgical techniques are performed, more of these patients will survive into adulthood and will transition to the care of specialists in adult cardiology. Having a basic knowledge of simple congenital heart disease as well as of classic postoperative conditions will be useful for all cardiologists.

Table 23.3 Palliative and Corrective Operations for Congenital Heart Lesions

LV, left ventricle; RV, right ventricle; PA, pulmonary artery; SVC, superior vena cava; MV, mitral valve.

Chapter 23 Review Questions and Answers QUESTIONS A cleft mitral valve (MV) is associated with which of the following conditions? Secundum atrial septal defect (ASD) Primum ASD Coarctation of the aorta Sinus venosus (SV) ASD Tetralogy of Fallot

1.

A. . C. D. .

All of the following regarding bicuspid aortic valves are true except: A. May be associated with coarctation of the aorta . Often associated with posteriorly directed jets of aortic insufficiency (AI) C. Commonly seen with congenitally corrected transposition of the great vessels D. May be amenable to aortic valve repair . Most common type involves fusion of the right coronary cusp (RCC) and left coronary cusp (LCC)

2.

A sinus venosus ASD is most often associated with which of the following? Coarctation of the aorta Marfan syndrome Partial anomalous pulmonary venous (PV) drainage Tetralogy of Fallot

3.

A. . C. D.

All of the following regarding Ebstein anomaly are true except: A. A portion of the right ventricular (RV) is atrialized. . Tricuspid valve (TV) leaflets are dysplastic and adherent to the RV. C. Common important associated defects include pulmonic stenosis (PS) or atresia. D. A patent foramen ovale (PFO) or secundum ASD is associated in >50% of cases. . A common associated defect is coarctation of the aorta.

4.

A. . C. D.

Complications associated with a subaortic membrane include all of the following except Aortic insufficiency (AI) Left ventricular hypertrophy (LVH) Atrial arrhythmias May recur post resection

A. . C. D. .

Which of the following lesions are associated with an aortopathy that may increase a patient’s risk for developing an aortic dissection? Hypertrophic obstructive cardiomyopathy (HOCM) Bicuspid aortic valve Pulmonic stenosis (PS) Sinus venosus ASD Mitral valve prolapse (MVP)

5.

6.

The most common form of ASD seen in adults is A. Secundum ASD . Primum ASD C. Unroofed coronary sinus (CS) D. Sinus venosus ASD . Supracristal ASD

7.

All of the following are features of tetralogy of Fallot except: A. Right ventricular hypertrophy (RVH) . Ventricular septal defect (VSD) C. ASD (primum) D. Infundibular PS . Overriding aorta

8.

Which statement is true regarding patients with coarctation of the aorta? Fifty percent of patients with bicuspid aortic valves have coarctation of the aorta. Patients typically have asymmetric septal hypertrophy. PW Doppler in the descending aorta demonstrates pan diastolic flow reversal. CW Doppler through the proximal descending aorta displays a high peak velocity in systole and a gradient that persists into diastole.

9.

A. . C. D.

10. All of the following may be true for a patient with PS except

. C. D. .

A. Balloon valvuloplasty is often the procedure of choice for treatment (for RV pressures >50 mm Hg). EKG may show right axis deviation and RVH. Pulmonary artery may be dilated on chest x-ray (CXR). Pulmonary vascular markings may be increased in severe cases. The degree of RVH correlates with the severity of PS.

ANSWERS 1.

Correct Answer: B. Primum ASD. A cleft MV is part of an atrioventricular (AV) canal defect, which is due to failure of the embryonic endocardial cushions to meet and partition the heart normally. A complete endocardial cushion defect has four components: primum ASD, cleft MV, inlet VSD, and a widened anteroseptal tricuspid commissure. A partial AV canal defect does not have the VSD.

2.

Correct Answer: C. Commonly seen with congenitally corrected transposition of the great vessels. The most common form is fusion of the RCC and LCC, and the mechanism of AI in those patients is prolapse of the conjoined cusp. The conjoined cusp in the case of RCC and LCC fusion is anterior, and thus, the AI is directed posteriorly. At least 50% of patients with coarctation of the aorta have a bicuspid valve. A bicuspid aortic valve with severe AI can often be surgically repaired, depending on the expertise of the surgical center.

3.

Correct Answer: C. Partial anomalous pulmonary venous (PV) drainage. A sinus venosus ASD is a defect located near the junction of the inferior vena cava (IVC) or superior vena cava (SVC) and the right atrial (RA). It is typically difficult to see by surface echocardiogram, often requiring a transesophageal echocardiography (TEE) for

diagnosis. It is usually associated with drainage of the right pulmonary veins to the RA.

4.

Correct Answer: E. A common associated defect is coarctation of the aorta. Ebstein anomaly of the TV is characterized by apical displacement of the TV into the RV. As a result, a portion of the RV becomes atrialized. TV tissue is dysplastic, with portions of the septal and inferior leaflets becoming adherent to the RV. Clinical manifestations depend on associated conditions. An important associated defect is PS or atresia. Other associations include primum ASD and VSD, and congenitally corrected transposition of the great vessels.

5.

Correct Answer: C. Atrial arrhythmias. The turbulent, high-velocity jets produced by the membrane damage the aortic valve over time, and patients often develop AI that requires surgery. The subaortic membrane is a fixed obstruction, which requires the left ventricle to develop high intracavitary pressures for ejection. As the left ventricular (LV) pumps against the fixed obstruction, LVH develops (similar to what is seen with valvular AS). Subaortic membranes are known to recur occasionally postresection, although the frequency with which this occurs is unknown.

6.

Correct Answer: B. Bicuspid aortic valve. Patients with a bicuspid aortic valve have an aortopathy involving cystic medial necrosis and decreased expression of fibrillin-1 with a tendency toward aneurysm formation and an increased risk for aortic dissection. The guidelines used for timing of aortic surgery for a dilated aorta in a patient with a bicuspid aortic valve are the same as those used in Marfan’s patients.

7.

Correct Answer: A. Secundum ASD.

Secundum ASDs are the most common form of ASD at 75% with primum ASD representing 20%, sinus venosus ASDs in 5%, and unroofed coronary sinus ASDs being rare. Supracristal is a type of VSD, not ASD.

8.

Correct Answer: C. ASD (primum). A primum ASD is part of either a partial or complete AV canal defect. The other features of a complete AV canal defect include inlet VSD, cleft MV, and Widened anteroseptal tricuspid commissure. The features of tetralogy of Fallot include VSD, RVH, infundibular PS, and overriding aorta.

9.

Correct Answer: D. CW Doppler through the proximal descending aorta displays a high peak velocity in systole and a gradient that persists into diastole. Fifty percent of patients with coarctation of the aorta have a bicuspid AV; however, the percentage of patients with bicuspid AVs who have a coarct is much smaller. CW Doppler through the proximal descending aorta in a patient with a coarctation of the aorta does show a high peak gradient as well as a gradient that persists into diastole. Pan diastolic flow reversal in the descending aorta by PW Doppler is characteristic of severe AI, not a coarctation of the aorta.

10. Correct Answer: D. Pulmonary vascular markings may be

increased in severe cases. All of the above are true in a patient with PS except answer D. In fact pulmonary vascular markings may be decreased in patients with severe PS due to decreased flow to the lungs due to the severe obstruction to flow at the level of the pulmonic valve. There is not an increase in lung markings in these patients.

V CARDIAC ELECTROPHYSIOLOGY

CHAPTER 24

Twelve-Lead Electrocardiography PETER T. HU AND AJAY BHARGAVA The electrocardiogram (ECG) is an essential diagnostic test. In many ways, it is an ideal diagnostic modality because it is noninvasive, is readily performed without discomfort or potential patient injury, is inexpensive, and its results are immediately available. Most important, it provides a diagnostic window of cardiovascular surveillance for a multitude of cardiac pathophysiologic problems, including valvular, myocardial, pericardial, and ischemic heart disease. The ECG’s diagnostic utility is critically dependent on its accurate interpretation. This chapter addresses the diagnostic possibilities encountered in routine ECG interpretation, including a broad collection of clinical examples. A clinical history, detailed interpretation, and diagnostic summary are included for each tracing. A detailed review of this chapter will provide comprehensive preparation for the Cardiovascular Medicine Subspecialty Board Examination.

BOARD PREPARATION To receive a passing score on the Cardiovascular Medicine Subspecialty Board Examination, the examinee must also receive a passing score on the ECG subsection. To best prepare for the ECG section, familiarization with the scoring sheet is essential. The scoring sheet is sent to each examinee before the test date, with diagnoses grouped systematically for easy reference. It is also available on the American Board of Internal Medicine Web site. In preparation, understanding and being able to recognize each diagnosis is a “foolproof” preemptive approach.

A RECOMMENDED APPROACH TO ELECTROCARDIOGRAM INTERPRETATION To ensure accurate and consistent ECG interpretation, a systematic approach is required. ECG interpretation is not an exercise in pattern recognition. To the contrary, employing a methodical strategy based on a thorough knowledge of the cardiac conduction sequence, cardiac anatomy, cardiac physiology, and cardiac pathophysiology can be applied to all ECGs, regardless of the findings. One systematic approach to each ECG is to ascertain the following in this recommended order: 1. Assess the standardization and identify the recorded leads accurately. 2. Determine the atrial and ventricular rates and rhythms. 3. Determine the P-wave and QRS-complex axes. 4. Measure all cardiac intervals. 5. Determine if cardiac chamber enlargement or hypertrophy is present. 6. Assess the P-wave, QRS-complex, and T-wave morphologies. 7. Draw conclusions and correlate clinically. Cardiac pathology is manifest differently on the surface ECG, depending on which lead is interrogated. Each lead provides an “electrical window of opportunity” and, by this virtue, offers a unique electrical perspective. The experienced electrocardiographer amalgamates these different windows into a mental three-dimensional electrical assessment, drawing accurate conclusions pertaining to conduction system and structural heart disease. For example, precordial lead V1 predominantly overlies the right ventricle, explaining why right ventricular cardiac electrical events are best observed in this lead. Likewise, precordial lead V6 overlies the left ventricle. This lead optimally represents left ventricular cardiac electrical events.

Assess the Standardization and Identify the Recorded Leads Accurately

Standard ECG graph paper consists of 1-mm × 1-mm boxes divided by narrow lines, which are separated by bold lines into larger, 5-mm × 5-mm boxes. At standard speed (25 mm/s), each small box in the horizontal axis represents 0.040 second (40 ms) of time and each large box represents 0.200 second (200 ms). At standard calibration (1 mV/10 mm), each vertical small box represents 0.1 mV and each vertical large box represents 0.5 mV. One must be very careful to inspect the standardization square wave (1 mV in amplitude) at the left of each ECG to determine the calibration of the ECG. ECGs with particularly high or low voltages are often recorded at half standard or twice standard, respectively. In these cases, the 1-mV square wave possesses an amplitude of either 5 or 20 mm. This distinction is important because it will affect the interpretation of all other voltage criteria. All further references to amplitude in this chapter are under the assumption of the default or preset standardization (1 mV/10 mm).

Determine the Atrial and Ventricular Rates and Rhythms The first step in determining the rate and rhythm is to identify atrial activity. If P waves are present, it is important to measure the P wave to P wave interval (P–P interval). This determines the rate of atrial depolarization. To estimate quickly either an atrial or ventricular rate on a standard 12-lead ECG, one can count the number of 5-mm boxes in an interval and divide 300 by that number. For example, if there are four boxes between P waves, the rate is 300 divided by 4, or 75 complexes per minute. Once the atrial activity and rate are identified, the P-wave frontal plane axis should be ascertained. A normal P-wave axis (i.e., −0 to 75 degrees) typically reflects a sinus node P-wave origin. A simple way of determining a normal P-wave axis is to confirm a positive P-wave vector in leads I, II, III, and aVF. An abnormal P-wave axis supports an ectopic or non–sinus node Pwave origin. Several possible atrial and junctional rhythms are listed below. They are grouped by cardiac rhythm origin and subsequently subcategorized by atrial rate. Distinguishing features are italicized for emphasis.

Rhythms of Sinus Nodal and Atrial Origin

Normal Sinus Rhythm. A normal sinus rhythm (NSR) is defined as a regular atrial depolarization rate between 60 and 100 per minute of sinus node origin, as demonstrated by a positive P-wave vector in leads I, II, III, and aVF.

Sinus Bradycardia. Sinus bradycardia is characterized by a regular atrial depolarization rate 160 ms or >10% variation between the longest and shortest P-P interval.)

Sinus Arrest or Pause. Sinus arrest or pause is characterized by a pause of >2.0 seconds without identifiable atrial activity. This may be caused by frank sinus arrest or may be simply a sinus pause secondary to Nonconducted premature atrial contraction (PAC), in which case, a P wave can be seen deforming the preceding T wave Sinoatrial block (SA block), which, like atrioventricular (AV) nodal block, has several forms

First-degree SA block involves a fixed delay between the depolarizing SA node and the depolarization exiting the node and propagating as a P wave. Because the delay is fixed, this delay cannot be detected on the surface ECG. Second-degree SA block has two varieties. In Type I (Wenckebach) SA block, there is a progressive delay between SA nodal depolarization and exit of the impulse to the atrium. This is manifest as a progressive shortening of the P–P interval until there is a pause, reflecting an SA node impulse that was blocked from exiting the node. In Type II SA block, there is a constant P–P interval with intermittent pauses. These pauses also represent an SA node impulse that was blocked from exiting the node. However, in this case, the duration of the pause is a multiple of the basic P–P interval. Third-degree SA block demonstrates no P-wave activity, as no impulses exit the sinus node. On the surface ECG, this is indistinguishable from sinus arrest, in which there is no sinus node activity.

Sinus Node Reentrant Rhythm. Sinus node reentrant rhythm is characterized by a reentrant circuit involving the sinus node and perisinus nodal tissues. Given the sinus origin, the Pwave morphology and axis are normal and indistinguishable from a normal sinus P wave. The rate is regular at a rate of 60 to 100 per minute. (This is very similar to NSR, except characterized by abrupt onset and termination.)

Sinus Node Reentrant Tachycardia. Sinus node reentrant tachycardia is characterized by a reentrant circuit involving the sinus node and perisinus nodal tissues. Given the sinus origin, the P-wave morphology and axis are normal and indistinguishable from a normal sinus P wave. The rate is regular at a rate of ≥100 per minute. (This is very similar to sinus tachycardia, except characterized by abrupt onset and termination.)

Ectopic Atrial Rhythm. Ectopic atrial rhythm is characterized by a regular atrial depolarization at a rate of 60 to 100 per minute from a single nonsinus origin, as reflected by an abnormal P-wave axis. The PR interval may be shortened, particularly in the presence of a low ectopic atrial origin, closer to the AV node with a

reduced intra-atrial conduction time. In the presence of slowed atrial conduction, the PR interval may be normal or even prolonged.

Ectopic Atrial Bradycardia. Ectopic atrial bradycardia is characterized by a regular atrial depolarization at a rate of ≤60 per minute from a single nonsinus origin, as reflected by an abnormal P-wave axis. (This is similar to an ectopic atrial rhythm, except slower.)

Atrial Tachycardia. Atrial tachycardia is characterized by a regular, automatic tachycardia from a single, ectopic atrial focus typically with an atrial rate of 180 to 240 per minute. The ventricular rate may be regular or irregular, depending on the AV conduction ratio. The P-wave axis is abnormal, given the ectopic atrial focus. (This is similar to an ectopic atrial rhythm, except faster.)

Wandering Atrial Pacemaker. A wandering atrial pacemaker (WAP) has a rate of 60 to 100 per minute from multiple ectopic atrial foci, as evidenced by at least three different Pwave morphologies on the 12-lead ECG, possessing variable P–P, PR, and R–R intervals. Be careful not to confuse this dysrhythmia with atrial fibrillation (AF). Unlike AF, discrete P waves are identifiable.

Multifocal Atrial Tachycardia. Multifocal atrial tachycardia (MAT) is characterized by a rate of >100 per minute with a P wave preceding each QRS complex from multiple atrial ectopic foci, as evidenced by at least three different P-wave morphologies on the 12-lead ECG possessing variable P–P, PR, and R–R intervals. The ventricular response is irregularly irregular, given the unpredictable timing of the atrial depolarization and variable AV conduction. Nonconducted atrial complexes during the ventricular absolute refractory period are also often present. Be careful not to confuse this dysrhythmia with AF. Unlike AF, discrete P waves are identifiable. (This is similar to WAP, but the atrial rate is faster.)

Atrial Fibrillation.

AF is characterized by a rapid, irregular, and disorganized atrial depolarization rate of 400 to 600 per minute devoid of identifiable discrete P waves, instead characterized by fibrillatory waves. In the absence of fixed AV block, the ventricular response to AF is irregularly irregular. Be careful not to confuse this dysrhythmia with WAP or MAT. The key is the lack of identifiable P waves.

Atrial Flutter. Atrial flutter (AFl) is characterized by a rapid, regular atrial depolarization rate of 250 to 350 per minute, representing an intra-atrial reentrant circuit. The atrial waves are termed “flutter waves” and often demonstrate a “sawtoothed” appearance, best seen in leads V1, II, III, and aVF. Although the atrial rate is regular, the ventricular response rate may be either regular or irregular, depending on the presence of fixed versus variable AV conduction. Common AV conduction ratios are 2:1 and 4:1.

Rhythms of Atrioventricular Nodal and Junctional Origin Atrioventricular Nodal Reentrant Tachycardia. Atrioventricular nodal reentrant tachycardia (AVNRT) is a micro-reentrant dysrhythmia that depends on the presence of two separate AV nodal pathways. Slowed conduction is present in one pathway and unidirectional conduction block is present in the second pathway. This is a regular rhythm with a typical ventricular rate of 140 to 200 per minute, with abrupt onset and termination. Its onset is often initiated by premature atrial complexes (PACs). Atrial activity typically consists of inverted or retrograde P waves occurring before, during, or after the QRS complex, best identified in lead V1. The QRS complex may be conducted normally or aberrantly.

Atrioventricular Reentrant Tachycardia. Atrioventricular reentrant tachycardia (AVRT) is a macro-reentrant circuit that consists of an AV nodal pathway and an accessory pathway. This dysrhythmia may conduct antegrade down the AV nodal pathway with

retrograde conduction through the accessory pathway (orthodromic AVRT), or antegrade down the accessory pathway with retrograde conduction up the AV nodal pathway (antidromic AVRT). As opposed to AVNRT, the P wave is always present after the QRS complex. With antidromic AVRT, the QRS complex, by definition, is aberrantly conducted (wide).

Junctional Premature Complexes. Junctional premature complexes are premature QRS complexes of AV nodal origin that may have resultant retrograde P waves (a negative P-wave vector in leads II, III, and aVF) occurring immediately before (with a short PR interval), during, or after the QRS complex.

AV Junctional Bradycardia. AV junctional bradycardia is characterized by QRS complexes of AV nodal origin that occur at a regular rate of 100 ms) at a rate of 200 ms), and each P wave is followed by a QRS complex. Typically the PR interval is constant.

Second-Degree AV Block, Mobitz Type I (Wenckebach). Second-degree AV block, Mobitz Type I (Wenckebach) is characterized by progressive prolongation of the PR interval, terminating with a P wave followed by a nonconducted QRS complex. Normal antegrade conduction resumes with a repetitive progressive prolongation of the PR interval with each cardiac depolarization, resuming the cycle. This results in a “grouped beating” pattern. In its most common form, the R–R interval shortens from beat to beat (not including the interval in which a P wave is not conducted). This typically represents conduction block within the AV node, superior to the bundle of His.

Second-Degree AV Block, Mobitz Type II. Second-degree AV block, Mobitz Type II is characterized by regular P waves followed by intermittent nonconducted QRS complexes in the absence of atrial premature complexes. The resulting R–R interval spanning the nonconducted complex is exactly double the conducted R–R intervals. This typically represents AV conduction block below the bundle of His and has a high propensity to progress to more advanced forms of AV block. Note that when there is AV block with a ratio of 2:1, one cannot definitively distinguish between Mobitz Type I and Type II. Longer rhythm strips, maneuvers, and intracardiac recordings may be necessary. A widened QRS complex supports Mobitz Type II but lacks certainty.

Third-Degree AV Block (Complete Heart Block). Third-degree AV block (complete heart block) is characterized by independent atrial and ventricular activity with an atrial rate that is faster than the ventricular rate. PR intervals vary with dissociation of the P waves from the QRS complexes. Typically the ventricular rhythm is either a junctional (narrow complex) or ventricular (wide complex) rhythm. (Note this should be distinguished from AV dissociation, which is also characterized by independent atrial and ventricular activity, but the ventricular rate is faster than the atrial rate.)

QRS Complex Interval The QRS complex interval is best measured in the limb leads from the onset of the R wave (or Q wave if present) to the offset of the S wave. A normal QRS duration is 100 ms Indeterminate morphology not satisfying the criteria for either RBBB or LBBB

QT Interval The QT interval demonstrates heart rate interdependence. The QT interval is directly proportional to the R–R interval. The QT interval shortens as heart rate increases. To account for this variability with heart rate, the corrected QT interval (QTc) is calculated, in which the QT interval is divided by the square root of the R–R interval. Normative tables for heart rate and gender are available. A normal QTc is typically 50% of the R–R interval, this supports QT-interval prolongation. In this circumstance, calculating a QTc interval is appropriate. Differential diagnosis of a prolonged QT interval includes the following: Congenital (idiopathic, Jervell–Lange–Nielsen syndrome, Romano– Ward syndrome) Medications (psychotropics, antiarrhythmics, antimicrobials, etc.) Metabolic disorders (hypocalcemia, hypokalemia, hypothyroidism, hypomagnesemia, etc.) The morphology of QT-interval prolongation in hypocalcemia deserves special mention. Typically, hypocalcemia produces prolongation and straightening of the QT interval as a result of prolongation of the ST segment, without frank widening of the T wave. Neurogenic, such as an intracranial hemorrhage Ischemia

Determine if Cardiac Chamber Enlargement or Hypertrophy Is Present If a patient is in sinus rhythm, the atria can be evaluated by analyzing the Pwave morphology in leads II, V1, and V2. Given the superior right atrial location of the sinus node, right atrial depolarization precedes left atrial

depolarization. Therefore, right atrial depolarization is best represented in the first half of the surface ECG P wave. In lead II, if a bimodal P wave is present, the first peak represents right atrial depolarization and the second peak represents left atrial depolarization. In leads V1 and V2, the P wave is typically biphasic. The early portion is upright, representing right atrial depolarization toward leads V1 and V2, with the negative latter half representing left atrial depolarization, away from these leads.

Right Atrial Abnormality Delayed activation of the right atrium due to hypertrophy, dilation, or intrinsically slowed conduction can result in the summation of right and left atrial depolarization. This typically produces a tall peaked P wave (≥2.5 mm) in lead II or >1.5 mm in lead V1 on the initial upward deflection of the P wave.

Left Atrial Abnormality Delayed activation of the left atrium due to hypertrophy, dilation, or intrinsically slowed conduction can result in a broadening (>110 ms) and notching of the P wave in lead II, or a deeper inverted phase of the P wave in leads V1 and V2: Negative terminal phase of P wave in lead V1 or V2 ≥ 40 ms in duration and ≥1 mm in amplitude, or Biphasic P wave in lead II with peak-to-peak interval of ≥40 ms (This is not very sensitive, but is quite specific.)

Right Ventricular Hypertrophy In RVH, there is a dominance of the right ventricular forces, which produce prominent R waves in the right precordial leads and deeper S waves in the left precordial leads. RVH is suggested by one or more of the following: Right-axis QRS-complex deviation (>+90 degrees) R:S ratio in lead V1 > 1 R wave in V1 ≥ 7 mm R:S ratio in V6 < 1

ST–T-wave “strain” pattern in right precordial leads supported by asymmetric T-wave inversion Right atrial abnormality in the absence of: Posterior wall myocardial infarction Wolff–Parkinson–White (WPW) syndrome Counterclockwise rotation Dextrocardia RBBB

Left Ventricular Hypertrophy Several criteria have been described and validated for the diagnosis of left ventricular hypertrophy (LVH) by electrocardiography. 1. Sokolow and Lyon: Amplitude of the S wave in lead V1 + amplitude of the R wave in V5 or V6 (whichever is the tallest) ≥35 mm 2. Cornell: Amplitude of the R wave in aVL + amplitude of the S wave in V3 > 28 mm for men, or >20 mm for women 3. Peguero-Lo Presti Criteria: Largest S + S in V4 > 22 mm in women or >27 mm in men. 4. Romhilt–Estes: This is a scoring system in which a total score of 4 indicates “likely LVH,” and a score of ≥5 indicates “definite LVH.” Voltage criteria = 3 points: Amplitude of limb lead R wave or S wave ≥20 mm or Amplitude of S wave in V1 or V2 ≥ 30 mm or Amplitude of R wave in V5 or V6 ≥ 30 mm ST–T-wave changes typical of strain (in which the ST segment and Twave vector is shifted in a direction opposite to that of the QRS complex vector) = 3 points (only 1 point if the patient is taking digitalis) Left atrial abnormality = 3 points: Terminal portion of P wave in V1 ≥ 40 ms in duration and ≥1 mm in amplitude Left-axis deviation = 2 points: Axis ≥ −30 degrees

QRS duration = 1 point: Duration ≥90 ms Intrinsicoid deflection = 1 point: Duration of interval from the beginning of the QRS complex to the peak of the R wave in V5 or V6 ≥ 50 ms

Combined or Biventricular Hypertrophy Combined ventricular hypertrophy is suggested by any of the following: ECG meets criteria for isolated RVH and LVH. This is the most reliable criterion. Precordial leads demonstrate LVH by voltage, but there is right-axis deviation (>+90 degrees) in the frontal plane. Precordial leads demonstrate LVH, with limb leads demonstrating right atrial abnormality. Katz-Wachtel phenomenon. Large amplitude equiphasic complexes (R = S) in the mid precordial leads

Assess the P-Wave, QRS-Complex, and T-Wave Morphologies Once the cardiac rate, rhythm, axes, intervals, and chambers have been assessed, one should proceed with the identification of various morphologies that suggest pathologic states. There have been virtually innumerable descriptions of various morphologic criteria for a broad spectrum of pathologic states, but here we discuss those that are most common and/or most important.

ECG Abnormalities and Corresponding Differential Diagnoses Incorrect Lead Placement or Lead Fracture. Incorrect lead placement or lead fracture is most commonly identified in the limb leads, with a negative P-wave vector in leads I and aVL and normal precordial R-wave progression.

Low Voltage.

Low voltage in limb leads is defined as a QRS-complex amplitude of 60 per minute. The PR interval is prolonged to 220 ms, representing first-degree AV block. Left atrial abnormality is seen, as the Pwave morphology is terminally negative in lead V1 and bifid in lead II. Diffuse nonspecific ST–T changes are present. Most important, each lead demonstrates a prominent prolonged QT interval. Both the QT-interval prolongation and ST segment scooping are secondary to the concomitant quinidine effect and digitalis effect.

Commentary QT-interval prolongation in the setting of quinidine administration may represent quinidine toxicity and near-future proarrhythmia. Comparison with prior ECGs is important to confirm whether this is a new or preexisting finding.

Keyword Diagnoses NSR First-degree AV block Left atrial abnormality Prolonged QT interval Nonspecific ST–T changes Digitalis effect

Quinidine effect

ELECTROCARDIOGRAM #27

FIGURE 24.27

Clinical History A 77-year-old woman status post an acute left middle cerebral artery occlusion and urokinase administration is now experiencing recurrent atrial arrhythmias. Medications at the time of this ECG included diltiazem, topical nitroglycerin, and isosorbide mononitrate. An echocardiogram performed during this hospitalization demonstrated moderate left atrial enlargement and normal left ventricular systolic function without evidence of a prior myocardial infarction.

Electrocardiogram Interpretation This ECG demonstrates two P waves for each QRS complex, best seen in lead aVF. The second P wave occurs on the downslope of the S wave at the

beginning of the ST segment. This represents ectopic atrial tachycardia with 2:1 AV conduction. There are small narrow inferior Q waves that are not of diagnostic significance.

Commentary When interpreting ECGs that show arrhythmias, it is important to survey each lead, which may yield a subtle and different clue. For this tracing, regular atrial activity is seen best in the inferior leads. Other leads such as lead V1 demonstrate nearly isoelectric atrial activity and suggest a junctional tachycardia. When a tachycardia is present, it is important to ascertain the shortest P–P interval and compare it to the R–R interval. Without this approach, 2:1 AV conduction may be overlooked.

Keyword Diagnoses Ectopic atrial tachycardia 2:1 AV conduction

ELECTROCARDIOGRAM #28

FIGURE 24.28

Clinical History A 66-year-old man status post recent coronary artery bypass graft surgery, paroxysmal AF, and a cerebrovascular accident has returned for a follow-up evaluation after his bypass surgery. Other comorbidities include hypertension, non–insulin-requiring diabetes mellitus, and hyperlipidemia.

Electrocardiogram Interpretation NSR is present. The 9th P wave is premature, reflecting a premature atrial complex with a similar QRS-complex morphology. The QRS-complex duration is prolonged but 3 mm, consistent with right atrial abnormality. Prominent precordial QRScomplex voltage is present, with asymmetric ST–T changes indicative of LVH with secondary ST–T changes. Negative U waves are seen in the lateral precordial leads, supporting the presence of LVH.

Commentary

This ECG satisfies many criteria for LVH. In addition to the prominent QRScomplex voltage and asymmetric T-wave inversion indicative of a strain pattern, a slightly prolonged QRS complex and prominent left atrial abnormality are also present. Negative U waves are readily seen. The differential diagnosis of negative U waves includes coronary artery disease and LVH. With the associated ECG findings, the negative U waves are secondary to LVH.

Keyword Diagnoses NSR Left atrial abnormality Right atrial abnormality LVH with secondary ST–T changes Negative U waves

ELECTROCARDIOGRAM #31

FIGURE 24.31

Clinical History A 47-year-old man with a history of aortic stenosis status post prior aortic valve replacement re-presents with perivalvular moderately severe aortic insufficiency and congestive heart failure. Comorbid conditions include insulin-requiring diabetes mellitus and a recently repaired rectal fistula. His medications included insulin, potassium, metolazone, metoprolol, captopril, and digoxin.

Electrocardiogram Interpretation The ECG baseline demonstrates an absence of organized atrial activity. The ventricular response is irregularly irregular, representing AF. An intermittent complete RBBB pattern is seen at shorter R–R intervals. Note that the initiation of the complete RBBB occurs at a shorter R–R interval than does sustaining the complete RBBB. This is a typical finding in accelerationdependent complete RBBB. With QRS-cycle length slowing, the complete RBBB transiently disappears. There is no evidence of a prior myocardial infarction. High lateral nonspecific ST–T changes are present.

Commentary Acceleration-dependent complete RBBB is a common ECG finding. The right bundle branch has a longer refractory period than the left bundle branch, and therefore, rate dependent right bundle branch conduction delay is a more common entity. This may precede permanent complete RBBB.

Keyword Diagnoses AF Acceleration-dependent complete RBBB Nonspecific ST–T changes

ELECTROCARDIOGRAM #32

FIGURE 24.32

Clinical History A 72-year-old woman with advanced AV block necessitating prior permanent pacemaker placement returns for pacemaker follow-up. Comorbid conditions include coronary artery disease, hypertension, and hyperlipidemia. Medications at the time of this ECG included metoprolol, aspirin, digoxin, and simvastatin.

Electrocardiogram Interpretation The ECG baseline is devoid of discrete atrial activity. This represents AF. The QRS complexes occur at regular R–R intervals at a ventricular rate slightly >60 per minute. This is an unexpected finding in the presence of AF. This represents an accelerated junctional rhythm and AV dissociation. Presumed ventricular pacemaker deflections occur at regular intervals throughout the ECG with no relationship to the QRS complexes. This represents both pacemaker sensing failure and pacemaker capture failure. Lateral and high lateral nonspecific ST–T changes are demonstrated. The scooping of the ST segments supports the presence of digitalis effect.

Commentary This ECG demonstrates abnormal pacemaker function, necessitating further evaluation. This may represent pacemaker lead dislodgement. In the presence of AF, it is important to evaluate the ECG for a second independent cardiac rhythm. The important clue on this tracing is the constant R–R interval. AV dissociation and an accelerated junctional rhythm both support the possible presence of digitalis toxicity, warranting further clinical investigation.

Keyword Diagnoses AF Accelerated junctional rhythm AV dissociation Ventricular pacemaker Pacemaker sensing failure Pacemaker capture failure Nonspecific ST–T changes Digitalis effect

ELECTROCARDIOGRAM #33

FIGURE 24.33

Clinical History A 34-year-old woman with a history of an AV canal and ostium primum ASD status post surgical repair is readmitted for a cardiac evaluation. She is experiencing paroxysmal atria dysrhythmias and is on no current medications.

Electrocardiogram Interpretation This patient is known to have ostium primum ASD. This ECG demonstrates a group of findings consistent with this diagnosis. The atrial rhythm is NSR. The PR interval is prolonged at 240 ms, representing first-degree AV block. The P wave is terminally negative in lead V1 and broadened in lead II, suggesting left atrial abnormality. The QRS-complex axis is deviated leftward, satisfying the criteria for left-axis deviation, as the QRS-complex frontal-plane vector is positive in lead I and deeply negative in leads II, III, and aVF. An rsR′ QRS complex is seen in lead V1 with a normal QRS complex duration, supporting incomplete RBBB.

Commentary

A narrow rsR′ QRS complex morphology in the presence of left axis deviation and left atrial abnormality are a group of findings consistent with the diagnosis of an ostium primum ASD.

Keyword Diagnoses NSR First-degree AV block Incomplete RBBB Left atrial abnormality Left-axis deviation Ostium primum ASD

ELECTROCARDIOGRAM #34

FIGURE 24.34

Clinical History

A 38-year-old man presented with severe dyspnea of 1 week’s duration. An echocardiogram demonstrated a large pericardial effusion with evidence supporting cardiac tamponade. The patient underwent urgent surgical pericardial drainage.

Electrocardiogram Interpretation The cardiac rhythm is sinus tachycardia, as the P waves are of normal axis and precede each QRS complex at an atrial rate slightly >100 per minute. The frontal-plane QRS complex axis demonstrates right-axis deviation, as the QRS complex vector is negative in lead I and positive in leads II, III, and aVF. There are diffuse low-voltage QRS complexes. Nonspecific ST–T changes are also seen. Alternation of the QRS-complex voltage, best seen in rhythm strip lead V1, is apparent. This alternation occurs with every other QRS complex and is termed electrical alternans. Electrical alternans is an ECG marker of a large pericardial effusion.

Commentary The ECG findings of diffuse low-voltage QRS complexes and electrical alternans suggest the presence of a significant pericardial effusion and cardiac tamponade. The electrical alternans is secondary to the beat-to-beat variability of cardiac position. This is sometimes referred to as a “swinging heart.”

Keyword Diagnoses Sinus tachycardia Right-axis deviation Nonspecific ST–T changes Low-voltage QRS Electrical alternans Pericardial effusion Cardiac tamponade

ELECTROCARDIOGRAM #35

FIGURE 24.35

Clinical History A 69-year-old woman with a history of severe subaortic stenosis presented to the hospital with a several-day history of dyspnea consistent with congestive heart failure. A cardiac catheterization demonstrated a 100-mm Hg pressure gradient between the left ventricular outflow tract and the left ventricle. Her medications at the time of this ECG included diltiazem, furosemide, and doxazosin.

Electrocardiogram Interpretation A P wave of normal axis precedes each QRS complex at a regular rate of approximately 110 per minute, reflecting sinus tachycardia. An rSR′ QRS complex is present in lead V1 with a QRS-complex duration of 140 ms, consistent with complete RBBB. The P wave in lead V1 demonstrates a terminal negativity and is bifid in lead II, supporting left atrial abnormality.

Down-sloping 3- to 4-mm ST segment depression is present in leads V4 to V6, I, and II, consistent with myocardial ischemia and possibly an NSTEMI.

Commentary Most often, myocardial ischemia is a bedside diagnosis and requires clinical correlation. In this case, the down-sloping ST segment depression in the setting of a congestive heart failure exacerbation and subaortic stenosis most likely does represent myocardial ischemia. To confirm this suspicion, a follow-up tracing should be obtained after treatment, to demonstrate interval improvement and ST–T-change resolution.

Keyword Diagnoses Sinus tachycardia Complete RBBB Left atrial abnormality Myocardial ischemia

ELECTROCARDIOGRAM #36

FIGURE 24.36

Clinical History A 29-year-old woman who was 37 weeks pregnant was admitted to the hospital for close observation of pregnancy-induced hypertension. She has known complete heart block without cardiovascular symptoms requiring no specific treatment or evaluation other than periodic Holter monitoring.

Electrocardiogram Interpretation On this tracing, the cardiac rhythm is best discerned in rhythm strip lead V1. P waves occur at regular intervals at an atrial rate of approximately 85 per minute. The P-wave axis as ascertained in leads I, II, and aVF is upright and normal. This suggests NSR. The PR interval varies and suggests a lack of association between the P waves and the QRS complexes. The QRS complexes are of normal duration and occur regularly at a rate of approximately 45 per minute. These findings collectively support NSR, junctional bradycardia, and complete heart block.

Commentary

The ECG criteria for complete heart block include two independent cardiac rhythms, lack of AV association, and a noncompeting ventricular rhythm that is slower than the atrial rhythm.

Keyword Diagnoses NSR Junctional bradycardia Complete heart block

ELECTROCARDIOGRAM #37

FIGURE 24.37

Clinical History A 72-year-old man was admitted to the hospital for further evaluation of an erythematous and bullous eruptive rash. His past medical history includes hypertension and chronic obstructive pulmonary disease, for which he takes prednisone and numerous inhalers.

Electrocardiogram Interpretation The ventricular rate is rapid, irregular, and >100 per minute, representing a tachycardia. Each QRS complex is preceded by a P wave of differing morphology and PR-interval duration. This represents MAT. Nonspecific ST–T changes are present in the lateral leads.

Commentary MAT is a common dysrhythmia in patients with advanced chronic obstructive pulmonary disease. This dysrhythmia commonly demonstrates resistance to pharmacologic therapy and is best addressed by treating the underlying condition, in this case the chronic obstructive pulmonary disease.

Keyword Diagnoses MAT Nonspecific ST–T changes

ELECTROCARDIOGRAM #38

FIGURE 24.38

Clinical History A 53-year-old man with diffuse coronary artery disease status post inferior and anterior myocardial infarctions 15 years prior to this ECG returns for routine cardiology follow-up. Subsequent to the myocardial infarctions, the patient underwent ventricular aneurysmectomy. He continued with symptoms of stable angina pectoris in the setting of mild mitral insufficiency and moderate left ventricular systolic dysfunction. His medications include digoxin, furosemide, and captopril.

Electrocardiogram Interpretation On this tracing, with many findings, a systematic approach is necessary. Sinus bradycardia is present. The PR interval is prolonged, indicating firstdegree AV block. The QRS complex axis is deviated leftward secondary to diagnostic Q-wave formation in leads II, III, and aVF, supporting an ageindeterminate inferior myocardial infarction. Additional Q waves are noted in leads V2 to V4, representing an age-indeterminate anterior myocardial infarction. Premature complexes differing from the native QRS complex morphology are seen without a preceding P wave. These are premature ventricular complexes (PVCs). The PR interval immediately following each PVC is prolonged and reflects retrograde concealed conduction of the PVC into the conduction system slowing antegrade conduction to the ventricle. Unlike most PVCs, there is no compensatory pause and therefore these are classified as interpolated PVCs.

Commentary Frequently, ECGs demonstrate a myocardial infarction in two separate myocardial territories, as demonstrated on this tracing. The PVCs are of complete RBBB morphology and therefore are left ventricular in origin. They demonstrate prominent inferior and anterolateral Q waves, supporting the presence of both prior myocardial infarctions.

Keyword Diagnoses Sinus bradycardia First-degree AV block Inferior myocardial infarction, age indeterminate Anterior myocardial infarction, age indeterminate Interpolated PVC Concealed conduction

ELECTROCARDIOGRAM #39

FIGURE 24.39

Clinical History A 57-year-old woman with a history of adenocarcinoma of the rectum and a pulmonary embolism presented to the hospital urgently, secondary to severe shortness of breath and respiratory failure. Pulmonary angiography demonstrated evidence of both acute and subacute pulmonary emboli and severe pulmonary hypertension. The patient expired shortly after this ECG.

Electrocardiogram Interpretation NSR is present. Frontal-plane QRS-complex right-axis deviation is noted, given the positive QRS-complex vector in leads II, III, and aVF and a negative QRS-complex vector in lead I. Incomplete RBBB is best seen in lead V1 with an rsR′ QRS-complex pattern. Also notable in lead V1 is a terminally negative P-wave vector suggesting left atrial abnormality. In lead II, the P wave is peaked and 3 mm in amplitude, supporting right atrial abnormality. Nonspecific ST–T changes are noted throughout the tracing. Given the incomplete RBBB, right atrial abnormality, and right-axis deviation, RVH with secondary ST–T changes merits consideration.

Commentary This ECG is consistent with an acute pulmonary embolism. It demonstrates a dominant S wave in lead I and a Q wave with T-wave inversion in lead III. This is the so-called S1, Q3, T3 QRS-complex pattern described in the setting of an acute pulmonary embolism.

Keyword Diagnoses NSR Right-axis deviation Incomplete RBBB Left atrial abnormality Right atrial abnormality Nonspecific ST–T changes Pulmonary embolism

ELECTROCARDIOGRAM #40

FIGURE 24.40

Clinical History A 41-year-old man with a history of intravenous substance use, endocarditis, and prior mitral and tricuspid valve replacement re-presents with symptoms and signs of congestive heart failure. He has also noted recent-onset palpitations.

Electrocardiogram Interpretation This ECG demonstrates a regular narrow QRS-complex tachycardia. P waves are possibly seen within the nadir of the ST segment in lead III. Determination of the exact cardiac rhythm is difficult and would require further testing in the form of an electrophysiology study. Therefore, this is best categorized as a supraventricular tachycardia. The QRS-complex frontal-plane axis demonstrates right-axis deviation, as the QRS-complex vector is negative in lead I, isoelectric in lead II, and positive in leads III and aVF. A prominent rsR′ QRS complex of normal duration is seen in lead V1. In the presence of QRS-complex frontal-plane right-axis deviation, this represents RVH. Diffuse nonspecific ST–T changes are also present.

Commentary This patient was known to have advanced tricuspid valvular heart disease, prosthetic valve mitral stenosis, pulmonary hypertension, and RVH. The atrial arrhythmias may be secondary to the cardiac valvular abnormality.

Keyword Diagnoses Supraventricular tachycardia Right-axis deviation RVH Nonspecific ST–T changes

ELECTROCARDIOGRAM #41

FIGURE 24.41

Clinical History

A 94-year-old woman was admitted to the hospital with acute-onset diarrhea and dehydration. She was noted to have lower-extremity swelling, and venous Doppler studies demonstrated an acute deep venous thrombosis. A subsequent ventilation perfusion scan was interpreted as high probability for an acute pulmonary embolism.

Electrocardiogram Interpretation In the lead V1 rhythm strip, a P wave is seen preceding each QRS complex. A P wave is also noted immediately following each T wave. This demonstrates a regular P–P interval at an atrial rate of approximately 70 per minute, denoting NSR. The QRS complex is broadened, with an RSR′ QRScomplex pattern in lead V1, suggesting complete RBBB. The T wave is upright in lead V1, supporting primary T-wave changes. The QRS-complex frontal-plane axis is deviated leftward, with a positive QRS-complex vector in lead I and negative QRS complex vectors in leads II, III, and aVF, consistent with left anterior hemiblock. Given the bifascicular block, the 2:1 AV block most likely represents second-degree Mobitz Type II AV block. Diffuse nonspecific ST–T wave changes are seen. Sinus arrhythmia is also documented. The P–P interval encompassing the QRS complexes is shorter than the P–P interval between the QRS complexes. This is more precisely termed ventriculophasic sinus arrhythmia. This has no known clinical significance.

Commentary Given the bifascicular block and 2:1 AV block, this patient has advanced conduction system disease. It is not known if these findings were new in the setting of her suspected acute pulmonary embolism.

Keyword Diagnoses NSR 2:1 AV block Complete RBBB Left anterior hemiblock Nonspecific ST–T changes

Sinus arrhythmia

ELECTROCARDIOGRAM #42

FIGURE 24.42

Clinical History A 61-year-old man was seen in cardiology outpatient follow-up after an acute inferior myocardial infarction 3 years prior to this ECG. This was followed by urgent right coronary artery percutaneous transluminal coronary angioplasty. He feels well, with infrequent episodes of angina pectoris. His medications include metoprolol, aspirin, nicotinic acid, simvastatin, and vitamins.

Electrocardiogram Interpretation The atrial rhythm is most easily identified in the lead V1 rhythm strip and lead aVF. In these leads, P waves are seen to precede each QRS complex at a rate of approximately 85 per minute, representing NSR. The 2nd, 3rd, 8th,

9th, 10th, and 11th QRS complexes are wide, with a complete left bundle branch configuration. This represents an AIVR. The native QRS complex is abnormal, with a wide Q wave present in leads III and aVF indicating an age-indeterminate inferior myocardial infarction. The first QRS complex is intermediate between the native QRS complex and the AIVR complex and represents a ventricular fusion complex. P-wave activity is seen during the AIVR as a downward deflection within the proximal ST segment of the third QRS complex noted best in leads II, III, and V1. This supports simultaneous atrial activity and AV dissociation.

Commentary This patient also had a history of syncope following his myocardial infarction. An electrophysiology study demonstrated readily inducible sustained monomorphic VT, and he underwent subsequent defibrillator placement.

Keyword Diagnoses NSR AIVR Fusion complex Inferior myocardial infarction, age indeterminate AV dissociation

ELECTROCARDIOGRAM #43

FIGURE 24.43

Clinical History A 72-year-old man with recently diagnosed myasthenia gravis was admitted for rehabilitation. His past medical history includes diabetes mellitus, chronic obstructive pulmonary disease, recurrent AF, and coronary artery disease.

Electrocardiogram Interpretation On this ECG, the atrial rhythm is best discerned in lead aVL. This demonstrates a P wave preceding and immediately following a diminutive QRS complex. This represents AFL with 2:1 AV conduction. Another possibility is a rapid ectopic atrial tachycardia. Diffuse nonspecific ST–T changes are present, as are frequent PVCs. The frequent PVCs occur at a constant interectopic interval with a differing coupling interval to the immediately preceding QRS complex. There is evidence of ventricular fusion complexes between the native QRS complex and a PVC. These features together confirm the presence of ventricular parasystole.

Commentary This is an unusual tracing, as the atrial rhythm is best discerned in lead aVL. This underscores the importance of a systematic evaluation of each ECG lead, particularly in the setting of an atrial dysrhythmia. The P wave immediately following the QRS complex is best seen in lead aVL and allows for the accurate diagnosis of this atrial dysrhythmia. When frequent PVCs are present, it is also important to evaluate for the presence of ventricular parasystole. Ventricular parasystole is an independent automatic dysrhythmia that discharges at a constant rate from the same ventricular focus.

Keyword Diagnoses AFL 2:1 AV conduction PVC Nonspecific ST–T changes Ventricular parasystole Fusion complex

ELECTROCARDIOGRAM #44

FIGURE 24.44

Clinical History A 49-year-old man with recurrent idiopathic left VT was referred for radiofrequency ablation. A recent echocardiogram demonstrated normal left ventricular systolic function without evidence of a prior myocardial infarction. His medications include verapamil, sotalol, simvastatin, and aspirin.

Electrocardiogram Interpretation This ECG demonstrates a regular wide QRS-complex tachycardia at a rate of approximately 175 per minute. This tachycardia demonstrates a complete RBBB morphology with a qR QRS-complex pattern in lead V1 and terminal S-wave slowing in leads V1 and V6. The QRS-complex frontal-plane axis is deviated far leftward, is prolonged, and has a qR QRS complex pattern in lead V1, suggestive of VT. In the center of the tracing, best seen in leads V1 and aVF, a more narrow QRS complex occurs. This is a sinus capture complex and lends greater support to the diagnosis of VT. In lead aVF, within the sinus capture QRS complex, a prominent Q wave is seen with ST segment elevation, suggestive of an acute inferior myocardial infarction. Periodic P waves are seen throughout the tracing, suggesting an independent

atrial rhythm and AV dissociation. The precise atrial rhythm diagnosis is not discernible on this tracing. Wandering baseline artifact is also seen.

Commentary This ECG contains important features supporting the presence of VT. When assessing a wide complex tachycardia, each of these features should be specifically sought. They include AV dissociation in the presence of an independent atrial rhythm and sinus capture complexes. Not seen on this ECG but often present in the setting of VT are ventricular fusion complexes. The apparent Q wave occurring in lead aVF remains unexplained, given the patient’s normal heart function and normal regional wall motion on echocardiography.

Keyword Diagnoses VT Sinus capture complex AV dissociation Inferior myocardial infarction, acute Baseline artifact

ELECTROCARDIOGRAM #45

FIGURE 24.45

Clinical History A 48-year-old woman presented with severe hypertrophic cardiomyopathy and pronounced symptoms of exertional dyspnea and presyncope immediately status post–percutaneous alcohol ablation of her first septal perforator branch of the left anterior descending coronary artery. The patient was resting comfortably in the intensive care unit.

Electrocardiogram Interpretation The cardiac rhythm is NSR, as the P-wave vector is upright in leads I, II, III, and aVF. The atrial rate is regular and slightly >60 per minute. Approximately 2 mm of ST segment elevation is seen in lead V1, and 1 mm of ST segment elevation is present in lead V2. Reciprocal ST segment depression is seen inferiorly and laterally. This represents an acute septal myocardial infarction and acute myocardial injury.

Commentary The ST segment elevation in leads V1 and V2 reflects the proximal septal iatrogenic myocardial infarction created by the alcohol injection. This is a

pure proximal septal myocardial injury pattern reflected electrocardiographically. The purpose of this procedure is to infarct the proximal interventricular septum and therefore reduce the degree of left ventricular outflow tract obstruction, avoiding otherwise necessary cardiac surgery.

Keyword Diagnoses NSR Septal myocardial infarction, acute Acute myocardial injury

ELECTROCARDIOGRAM #46

FIGURE 24.46

Clinical History A 51-year-old woman with metastatic breast carcinoma is undergoing bone marrow transplantation. Her serum potassium level at the time of this ECG

was 2.9 mEq/L.

Electrocardiogram Interpretation The extreme left-hand portion of this ECG demonstrates upright P waves in leads I, II, and III, suggesting NSR. A prolonged QT interval is present, with nonspecific ST–T changes. The first QRS complex is reflective of NSR and a native QRS complex. This is followed by a PVC, and a disorganized wide QRS-complex tachycardia ensues. The wide QRS-complex tachycardia has a changing or rotating axis consistent with torsades de pointes. A fine baseline artifact is present.

Commentary Torsades de pointes is a potentially fatal ventricular arrhythmia, in this instance triggered by extreme hypokalemia. It is also seen in the presence of antiarrhythmic therapy initiation. It is characterized as a wide QRS-complex VT with a varying QRS-complex axis as depicted on this ECG. Prompt correction of any underlying metabolic disturbance and withdrawal of potentially contributing medications is essential.

Keyword Diagnoses NSR Prolonged QT interval Torsades de pointes Baseline artifact Nonspecific ST–T changes Hypokalemia

ELECTROCARDIOGRAM #47

FIGURE 24.47

Clinical History A 42-year-old man was found unconscious under a bridge and brought to the Emergency Department by ambulance.

Electrocardiogram Interpretation Sinus bradycardia is present, as the atrial rate is regular at approximately 50 beats per minute. Baseline artifact, especially in leads I and II, is noted. The QRS complex is significantly widened, with a terminal QRS-complex delay, evident in all leads. Diffuse nonspecific ST–T changes denoting abnormal repolarization are also seen. This is an example of profound hypothermia and Osborne waves. The Osborne or “J” waves represent the terminal QRScomplex conduction delay.

Commentary Hypothermia is a medical emergency. This ECG is a classic example. The etiology of the Osborne wave is not completely clear but is related to slow cardiac conduction. Atrial arrhythmias and PR interval prolongation are

often identified. Osborne waves are named for the person who first identified them and their relationship to hypothermia.

Keyword Diagnoses Sinus bradycardia Baseline artifact Osborne wave Hypothermia

ELECTROCARDIOGRAM #48

FIGURE 24.48

Clinical History A 59-year-old female presents to the Emergency Department with palpitations and dizziness.

Electrocardiogram Interpretation Sinus rhythm is present. There is characteristic prominent coved ST segment elevation (>2 mm) noted in leads V1 and V2, less prominently in V3. This is followed by a negative T-wave with little isoelectric separation. These findings are consistent with a Type 1 Brugada pattern. This should not be confused with a right bundle branch block.

Commentary There are mainly two distinct patterns described on a 12-lead ECG in Brugada syndrome. This ECG demonstrates a type I pattern with coved ST segment elevation of 2 mm or more in at least 2 leads from V1 to V3. The ST segment elevation in leads to an inverted T wave. In type 2, the ST segment has a “saddle back” shape. The elevated ST segment descends, then rises again to an upright or biphasic T wave. The characteristic ECG pattern can be provoked/unmasked by fever, and sodium channel blockers such as flecainide and procainamide. Patients with Brugada pattern on ECG who have experienced syncope, VT, VF or sudden cardiac death have Brugada Syndrome. This syndrome has been linked to mutations in SCN5A, the gene which codes for the alpha subunit of the sodium channel.

Keyword Diagnoses Brugada syndrome Brugada pattern ST segment elevation

ELECTROCARDIOGRAM #49

FIGURE 24.49

Clinical History A 78-year-old female presents to the Emergency Department with a 2 week history of intermittent chest discomfort. She was asymptomatic at the time of ECG acquisition. Troponins negative.

Electrocardiogram Interpretation Sinus bradycardia is present. There are deep symmetrical T wave inversions across the precordial leads, most prominent in leads V2 to V4 In the correct clinical context, these findings should raise concern for a severe proximal stenosis in the left anterior descending artery.

Commentary Left heart catheterization demonstrated a severe stenosis in the proximal left anterior descending artery. This pattern was described by De Zwaan, Wellens and colleagues in 1982. The Wellen’s pattern refers to progressive symmetrical T wave inversions in the precordial leads, most commonly in V2 and V3. There may or may not be ST segment elevation. Often there is no significant loss of R-wave progression. These are primary T waves.

Keyword Diagnoses Wellen’s pattern T wave inversion Left anterior descending artery stenosis

ELECTROCARDIOGRAM #50

FIGURE 24.50

Clinical History A 52-year-old woman presented to the Emergency Department with chest discomfort and nausea.

Electrocardiogram Interpretation Sinus rhythm is present. There is a wide QRS complex >120 ms with broad and notched R waves in I, aVL, V5 and V6 and absent septal Q waves in I, V5 and V6 which are consistent with left bundle branch block. There is

discordant ST segment elevation in leads V5 and V6. In the presence of a left bundle branch block, one would normally expect secondary ST segment depression and T-wave inversion in these leads. In leads V1 to V3, there is the expected (in the presence of a left bundle branch block) ST segment elevation, but it does appear that the ST segment elevation may be more prominent than expected (discordant/disproportionate ST segment elevation). These findings in the presence of a LBBB and in the appropriate clinical context should raise concern for associated myocardial injury.

Commentary In patients with underlying left bundle branch block who present with symptoms concerning for ongoing myocardial ischemia, the Sgarbossa Criteria can be used to assess likelihood of associated myocardial infarction: ST segment elevation ≥1 mm concordant with the QRS complex in any lead (5 points), ST segment depression ≥1 mm in leads V1, V2, or V3 (3 points) and ST segment elevation ≥5 mm discordant with QRS complex in any lead (2 points). A total score ≥3 has a specificity of >95% with a sensitivity of 20%. Substituting an ST/S ratio >25% improves sensitivity to >90%.

Keyword Diagnoses Sinus rhythm Sgarbossa Criteria Left bundle branch block ST segment elevation myocardial infarction

ELECTROCARDIOGRAM #51

FIGURE 24.51

Clinical History A 69-year-old male presents with persistent chest pain, nausea, and diaphoresis.

Electrocardiogram Interpretation Sinus rhythm is present. There is significant 3 mm ST elevation in lead aVR and lead V1. The ST elevation is greater in lead aVR than lead V1. There are diffuse ST depressions in the anterior precordial leads and inferior and lateral limb leads.

Commentary This ECG pattern should raise concern for severe left main trunk stenosis or multivessel coronary artery disease. ST segment depression in 8 or more leads plus ST segment elevation in aVR and V1 in the correct clinical context has a 75% predictive accuracy for left main trunk/multivessel coronary artery stenosis. Higher ST segment elevation in aVR is associated with a worse prognosis. Coronary angiography in this patient demonstrated severe left main trunk stenosis.

Keyword Diagnoses Sinus rhythm ST segment elevation Left main coronary artery ischemia

CHAPTER 25

Electrophysiologic Testing, Including His Bundle and Other Intracardiac Electrograms KEVIN M. TRULOCK AND THOMAS D. CALLAHAN IV This chapter aims to summarize the components of a comprehensive electrophysiology (EP) study. However, the components of a diagnostic EP study are usually selected based upon the indications for the study. Readers who are primarily aiming for a board certification examination should principally direct their attention to components listed in the summary to this chapter and to the review questions.

INDICATIONS FOR ELECTROPHYSIOLOGIC TESTING Indications for performance of an EP study have evolved somewhat in recent years with the indications for implantable cardioverter–defibrillators (ICDs) expanding to defined populations without the need for a “positive” EP study. Thus, the use of EP studies for risk stratification of patients at possible high risk for sudden cardiac death has become more limited. Based on recent multicenter trials, ICDs are currently indicated for primary prevention of sudden cardiac death in patients with:

Prior myocardial infarction (MI), at least 40 days before and left ventricular ejection fraction (LVEF) ≤ 35% with New York Heart Association (NYHA) functional class II or III, or LVEF < 30% with NYHA functional class I Nonischemic cardiomyopathy, LVEF ≤ 35%, and NYHA functional class II or III These patients do not require EP studies to qualify for ICD implantation. However, ICD implantation is also indicated in patients who have LVEF < 40%, prior MI, nonsustained ventricular tachycardia (NSVT), and inducible sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) at EP study. Thus, EP studies can be indicated to risk stratify patients with an LVEF less than 35%. These patients include patients with coronary artery disease (CAD), prior MI, LVEF ≤ 40%, and NSVT. Clinical guidelines regarding the use of EP studies in the risk stratification of patients prior to device implantation may be obtained from the American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) 2008 guidelines for device implantation (1). An EP study is also helpful in the diagnosis of patients presenting with syncope of undetermined etiology and in the diagnosis of wide complex tachycardia. EP studies may also be used to assess for bradyarrhythmias, including sinus node or atrioventricular (AV) conduction system disease, particularly in patients with possible infra-Hisian conduction system disease. The most common application for EP studies, however, is for the diagnosis and mapping of tachyarrhythmias as part of a catheter mapping and ablation procedure. The diagnosis of supraventricular tachycardia (SVT) type and localization of ablatable supraventricular and ventricular substrates are integral parts of ablation procedures (see ACC/AHA/ESC guidelines for management of patients with supraventricular arrhythmias) (2). Clinical competency guidelines are reported in the ACC/AHA clinical competence statement on invasive EP studies, catheter ablation, and cardioversion (3).

THE BASICS ELECTROPHYSIOLOGY STUDIES

OF

During an EP study, multipolar catheters are positioned, typically in the right ventricular apex (RVA) and/or right ventricular outflow tract, the His bundle, the coronary sinus (CS), and/or the right atrium (RA) (Fig. 25.1). Programmed electrical stimulation (PES) is performed via bipolar electrodes by pacing at various rates and by introduction of premature extrastimuli. Typical baseline recordings include the surface electrocardiograms (ECGs), particularly leads I, AVF, V1, and V6, as well as intracardiac electrograms (EGMs) from the high right atrium (HRA), His bundle (His, or HBE), RVA, and CS. The electrodes are by convention numbered consecutively with the most distal electrode being number 1.

FIGURE 25.1 Typical catheter positions and recordings during EP studies. RA, right atrium; LA, left atrium; LV, left ventricle, RV, right ventricle.

Intracardiac Electrograms When approaching the interpretation of intracardiac EGMs, it is useful to understand the differences between the surface ECG and intracardiac EGMs. The surface ECG is recorded on the body surface and reflects the electrical activity of the whole heart. The intracardiac EGM is recorded within the heart and is usually filtered differently from surface ECGs to remove highfrequency noise and low-frequency interference (e.g., from respiration). The intracardiac EGM reflects local electrical activity of the myocardium near the recording electrodes. The display or paper speed is generally faster than the conventional 25 mm/s surface 12-lead ECG speed. Time markers are generally present at the top or bottom of EGM tracings. When interpreting intracardiac EGMs, the reader should first orient themselves to the tracings, using the labels, which are usually displayed along the left margin. The atrial and ventricular activity can be identified by correlation with the surface ECG recordings. EGMs reflect local depolarization. EGMs from atrial or ventricular catheters show local atrial or ventricular depolarization, respectively. EGMs recorded at either the mitral or tricuspid annulus show both atrial and ventricular depolarization. Thus, EGMs from the CS show both atrial and ventricular EGMs. In the CS, the atrial EGMs are typically large in amplitude and the ventricular EGMs smaller, unless the catheter is advanced into a ventricular branch. His bundle EGMs are recorded at the tricuspid annulus and will typically display atrial, His, and ventricular EGMs with the size of the atrial or ventricular component dependent on whether the recording electrodes are situated more proximally in the atrium or distally in the ventricle.

Cycle Lengths versus Rates During an EP study, intervals are more commonly measured than rates. The “cycle length” of pacing drives or rhythms is measured. The conversion between cycle length and rates is as follows: cycle length (milliseconds) = 60,000 per rate (bpm). Conversely, rate (bpm) = 60,000 per cycle length (milliseconds). Thus, a rate of 60 bpm corresponds to a cycle length of 1,000 ms, 100 bpm corresponds to 600 ms, 120 bpm corresponds to 500 ms, 150 bpm to 400 ms, and 200 bpm to 300 ms.

Baseline Intervals Typical baseline intervals reported in EP studies include the sinus cycle length (SCL), defined as the interval between sinus atrial EGMs (A–A interval or P–P interval), the surface PR, QRS, and QT intervals. The AH and HV intervals are the most commonly measured intervals (Fig. 25.2). The AH interval is measured on the His bundle catheter (HBE) as the time interval from the first major deflection at its baseline crossing to the onset of the His bundle EGM. The AH interval estimates conduction time across the AV node (AVN). The AH interval is highly variable and dependent upon vagal tone, medications, and preceding atrial rates, but typically ranges from 50 to 130 ms. The HV interval is also measured on the HBE. The HV interval is the interval from the onset of the His deflection to the earliest onset of ventricular activation on any surface lead or intracardiac EGM. The normal HV interval ranges from 35 to 55 ms. Other baseline intervals are less commonly measured unless markedly abnormal. These include the PA interval, defined as the earliest onset of surface P wave to the earliest intracardiac atrial EGM (normal 20 to 60 ms). The His width from the beginning to end of the His deflection generally ranges from 10 to 25 ms. The RB–V interval measures the interval from the onset of the right bundle potential to the earliest ventricular activation on any surface lead or intracardiac EGM.

FIGURE 25.2 AH and HV intervals.

Normal Activation Sequences Anterograde Atrial and Ventricular Activation Sequence. Normal atrial activation during sinus rhythm is from the HRA to low RA and then concentrically from proximally to distally along the CS. This reflects initial activation from the sinus node, which spreads downward and leftward

across the atria. Normal ventricular activation is from the RV apex and concentrically from proximal to distal along the CS (Fig. 25.3, left panel).

FIGURE 25.3 Normal activation patterns: anterograde and retrograde activation. Retrograde Atrial Activation Sequence. The sequence of atrial activation during ventricular pacing is from the septum proximally to distally along the CS and from low RA in the midline to high RA (Fig. 25.3, right panel). Programmed Extrastimuli (PES). During an EP study, pacing at various cycle lengths (or rates) or various intracardiac sites is performed. The length of this pacing train can be programmed. Common paced cycle lengths (PCLs) are at 600 ms (100 bpm), 500 ms (120 bpm), and 400 ms (150 bpm). The

stimuli during the fixed drive train are termed S1. Premature extrastimuli may be introduced in intrinsic rhythm or after a fixed paced drive train (Fig. 25.4). The first extrastimulus is termed S2. The second extrastimulus, when introducing double extrastimuli, is termed S3. The third extrastimulus, when introducing triple extrastimuli, is termed S4, and so on. The common terminology of the paced stimuli, their subsequent intracardiac EGMs and intervals, is summarized below.

FIGURE 25.4 Programmed ventricular stimulation.

Pacing Drive Trains and Extrastimuli S1 = drive train pacing stimulus Continuous overdrive burst, or During programmed extrastimuli, typically eight pacing stimuli at a fixed PCL PCL = paced cycle length (e.g., PCL 600 ms = S1S1 interval, pacing rate 100 bpm)

S2 = first extrastimulus (S1–S2 = coupling interval between S2 and S1) S3 = second extrastimulus (S2–S3 = coupling interval between S2 and S3) S4 = third extrastimulus (S3–S4 = coupling interval between S3 and S4) A1 = atrial EGM associated with S1 drive or spontaneous atrial rhythm A2 = atrial EGM associated with S2 or the first spontaneous atrial EGM after A1 A3 = atrial EGM associated with S3 or the second spontaneous atrial EGM after A1 H1 = His bundle EGM associated with S1 drive or spontaneous rhythm H2 = His bundle EGM associated with S2 or after second spontaneous depolarization V1 = ventricular EGM associated with S1 drive or spontaneous ventricular rhythm V2 = ventricular EGM associated with S2 or the first spontaneous ventricular EGM after A1 V3 = ventricular EGM associated with S3 or the second spontaneous ventricular EGM after A1

Refractory Periods The effective refractory period (ERP) is defined as the longest interval after onset of depolarization that fails to propagate. The ERP is usually determined during PES with the delivery of single extrastimuli after paced drive trains. With each successive drive train, the coupling interval is progressively shortened, until the extrastimulus fails to capture the stimulated tissue. This coupling interval identifies the ERP (Fig. 25.5). This interval represents the longest coupling interval that fails to capture the conduction system or myocardium distal to the stimulus (e.g., in the ventricle, S1–S2 interval that produces a V1 but no V2) The relative refractory period (RRP)

is the longest S1–S2 interval resulting in conduction delay distal to the stimulus, for example, when the output interval (V1–V2) is longer than the S1– S2 interval (e.g., when “latency” of ventricular activation is observed). The functional refractory period (FRP) is the minimum interval between two consecutively conducted impulses, that is, the shortest output possible (e.g., the shortest V1–V2 interval). A summary and the normal ranges of ERPs are as follows:

FIGURE 25.5 VERP. A:PCL 400 ms, CI 280 ms. B:S1-S1 400 ms, S1-S2 260 ms (VERP).

ERP—longest interval (e.g., S1–S2 interval) that fails to propagate S1 – S2 = V1 — no V2 (input measurement) RRP—longest S1–S2 interval resulting in conduction delay S1 – S2 ≠ V1 – V2 (input ≠ output) FRP—minimum interval between two consecutively conducted impulses. Shortest V1–V2 (shortest output possible)

Normal Effective Refractory Periods

BRADYARRHYTHMIA BY EPS

EVALUATION

EP study to assess bradyarrhythmias is not indicated if symptomatic bradycardia has already been documented or if patients already have a clear indication for a permanent pacemaker. However, EP study may be helpful in patients with sinus node or AV conduction disease and symptoms but for whom noninvasive monitoring has failed to document correlation of the bradyarrhythmia with symptoms; patients in whom symptoms might also be due to another arrhythmia (e.g., atrial, supraventricular, VT); or patients with a permanent pacemaker who continue to have symptoms.

SINUS NODE FUNCTION

The sinus cycle length (SCL) is defined as the A–A interval during sinus rhythm. Assessment of sinus node function may include assessment of the sinus node recovery times (SNRTs) and/or the sinoatrial conduction time (SACT). SNRT. Atrial overdrive pacing is performed at a rate faster than the sinus rate for approximately 30 seconds, usually at multiple PCLs (e.g., PCL 700, 600, 500, 400 ms). The SNRT is the interval from the last paced atrial EGM to the return sinus atrial EGM (Fig. 25.6). SNRT usually lengthens as PCL shortens until retrograde sinus node entrance block occurs at which point the sinus node is no longer being overdriven as quickly. Then, as PCL shortens further, SNRT typically shortens. Maximal SNRT is the longest SNRT measured after pacing at different PCLs and is reported with the PCL that produces the longest SNRT.

FIGURE 25.6 Determination of SNRT. Corrected Sinus Node Recovery Time (CSNRT). The CSNRT is the difference between the maximal SNRT and the SCL. Normal CSNRT is 50 ms after a decrease in A1A2 coupling interval of 10 ms) suggests the presence of two conduction pathways (typically a fast-conducting AV nodal pathway with a longer refractory period than a slow-conducting AV nodal pathway that has a shorter refractory period) (Fig. 25.15). Dual AVN physiology is confirmed by the occurrence of an AV nodal echo beat, in which anterograde conduction down the slow AVN pathway is followed by retrograde conduction to the atria via the slow pathway (Fig. 25.15). This typical echo beat occurs with atrial activation occurring within 70 ms of the onset of ventricular activation; on intracardiac EGMs, atrial and ventricular activation occurs near simultaneously.

FIGURE 25.14 Normal AVN conduction curve.

FIGURE 25.15 AH jump and AVN echo beat. A:Single atrial premature extrastimuli are delivered after eight-beat paced drive cycles. The AH interval is 140 ms with a coupling interval of 290 ms. After a coupling interval of 280 ms, the AH interval “jumps” to 470 ms, indicating the presence of dual AVN pathway physiology. The atrial EGMs evident in the CS leads (arrows) indicate the AVN echo beat with retrograde conduction to the atria. B:AVN conduction curve demonstrating an AH jump at the fast pathway ERP of 420 ms and induction of echo beats and AVNRT. AV Nodal Refractory Periods. The AV Nodal Effective Refractory Period (AVN ERP) is the longest A1A2 interval that fails to conduct through the AVN (Fig. 25.16). Prolongation may occur with high vagal tone or concomitant medications. Other refractory periods that can be measured include the AV nodal relative refractory period (AVN RRP), which represents the longest A1A2, which results in an H1H2 > A1A2 during atrial extrastimulus testing. The AV nodal functional refractory period (AVN FRP) is the shortest H1H2 interval (AVN output) observed during extrastimulus testing.

FIGURE 25.16 AV node effective refractory period (AVN ERP).

INCREMENTAL PACING

VENTRICULAR

While not a component of EP testing that directly assesses anterograde AV conduction, incremental ventricular pacing (pacing in the ventricle at faster and faster cycle lengths) can help determine whether retrograde conduction occurs via the AVN (Fig. 25.17) or an accessory pathway (Fig. 25.18). Atrial activation occurring with a midline activation pattern that decrements with more rapid pacing rates or a shorter premature extrastimulus coupling interval suggests conduction via the His–Purkinje–AVN system. In this pattern, concentric activation is seen in the CS leads with earliest atrial activation occurring at the AVN, septal region, and later activation occurring

at more lateral atrial sites (Fig. 25.17). In contrast, retrograde conduction via a left lateral free wall accessory pathway (Fig. 25.18) would cause an eccentric activation pattern with earliest ventricular activation occurring near the accessory pathway in the lateral CS leads and earliest retrograde atrial activation in the distal CS as well.

FIGURE 25.17 Normal anterograde and retrograde activation.

FIGURE 25.18 Abnormal anterograde and retrograde activation: left-sided accessory pathway. PCL of VA Block. The longest ventricular PCL associated with failure of retrograde VA conduction is determined by decremental ventricular pacing. Pacing is performed at shorter and shorter cycle lengths. During retrograde AV nodal conduction, VA intervals gradually increase as pacing cycle length shortens. PCL is shortened until VA block occurs (e.g., retrograde Wenckebach or 2:1 VA block). In the presence of a typical accessory pathway, a constant VA interval is usually observed, and VA block occurs when the accessory pathway refractory period is reached. This usually occurs with a 2:1 VA block pattern, rather than in a retrograde Wenckebach pattern.

Ventricular Extrastimulus Testing. Analogous to atrial extrastimulus testing, single premature ventricular extrastimuli (V2) are delivered after eight-beat trains of ventricular pacing (V1) at several ventricular PCLs (e.g., PCL 600, 500, 400 ms). The coupling interval of the extrastimulus (V1V2) is shortened by 10 to 20 ms with each succeeding drive train. In this manner, retrograde VA conduction can be assessed. Decremental retrograde conduction suggests that conduction is occurring via the His–Purkinje–AVN system. Retrograde conduction via a typical accessory pathway is generally nondecremental, unless the accessory pathway is an atypical, decremental pathway. In addition, retrograde atrial activation patterns are examined to determine if atrial activation occurs with a typical AV nodal midline activation pattern (Fig. 25.17).

TACHYARRHYTHMIA EVALUATION BY EPS Ventricular Tachycardia Most patients undergoing EP study for assessment of ventricular arrhythmias have CAD or dilated cardiomyopathy and reduced left ventricular function. In selected patients, EP study may be useful for assessment of risk and need for ICD implantation, drug testing, assessment of device/antitachycardia pacing function, or mapping for ablation. EP testing has limited sensitivity and specificity in the prediction of arrhythmic events in nonischemic disease. EP studies have been more useful in risk stratification of patients with CAD after MI. Based on data from Multicenter Unsustained Tachycardia Trial (MUSTT) (4) and Multicenter Automatic Defibrillator Implantation Trial (MADIT) (5), survival is improved with ICD implantation in patients with CAD, prior MI, nonsustained VT, and LVEF ≤ 40%, and inducible sustained VT or reproducibly inducible VF with double ventricular extrastimuli that is not suppressible with an antiarrhythmic drug (MADIT) (5). These studies provide a rationale for performing EP studies for risk stratification in these patient groups. MADIT II (6) demonstrated the value of prophylactic ICD

implantation without EP testing in patients with CAD and LVEF ≤ 30%. DEFiNITE (7) and SCDHeFT (8) studied the value of prophylactic ICD implantation and included patients with nonischemic cardiomyopathy. SCDHeFT demonstrated survival benefits for ICD implantation in ischemic or nonischemic cardiomyopathy patients with heart failure and LVEF ≤ 35% without the need for EP testing. EP testing is generally not necessary in patients who have criteria that already meet approved ICD indications. Patients with normal LV function and VT usually have special types of ventricular arrhythmias that may be studied by EP testing, particularly in conjunction with mapping and ablation.

Ventricular Programmed Stimulation Protocols Several stimulation protocols have been of utility in stratifying risk for sustained ventricular arrhythmias. Some of the most common are summarized below:

Ventricular overdrive burst pacing.

Ventricular Effective Refractory Period (VERP). Single ventricular premature extrastimuli are delivered with shortening coupling intervals until the stimulus fails to capture the ventricle (Fig. 25.19). The VERP is the longest ventricular extrastimulus V1V2 that fails to capture the ventricle during ventricular extrastimulus testing. It is measured from pacing stimulus to pacing stimulus and is recorded at different sites (e.g., right ventricular apical [RVA], right ventricular outflow tract [RVOT]) and PCLs (e.g., 600, 400 until S2 is refractory).

FIGURE 25.19 Determination of VERP by ventricular extrastimulus delivery. Single ventricular premature extrastimuli are introduced with shortening coupling intervals until the stimulus fails to capture the ventricle. In this example, at PCL 400 ms, a ventricular premature extrastimulus captures the ventricle at a coupling interval of 280 ms but fails to capture the ventricle at 260 ms. The VERP is 260 ms at PCL 400 ms. Ventricular Functional Refractory Period (VFRP). The VFRP is the shortest ventricular coupling interval produced with premature ventricular

stimulation. The VFRP is measured from EGM to EGM and recorded at different sites (e.g., RVA, RVOT) and PCLs (e.g., 600, 400 until S2 is refractory). Induced Arrhythmias. Definitions of ventricular arrhythmias that can be induced with programmed ventricular stimulation include the following: Repetitive ventricular responses—1 to 3 PVCs NSVT—three or more ventricular complexes lasting 30 seconds or requiring earlier termination due to hemodynamic compromise Sustained monomorphic VT—sustained VT of uniform morphology Sustained polymorphic VT—sustained VT of multiform morphology Pleomorphic VT—multiple morphologies of monomorphic VT Ventricular flutter—rapid VT < 220 or 240 ms CL with no isoelectric baseline and a sine wave appearance VF—disorganized chaotic ventricular complexes with loss of organized ventricular contraction. Morphology. Morphology of VT can be described by bundle-branch block morphology and axis using surface ECG leads I, aVF, and V1:

VA Relationship During VT. VA dissociation can be readily recognized using intracardiac atrial and ventricular EGMs (Fig. 25.20), helping to confirm the diagnosis of VT.

FIGURE 25.20 Ventricular stimulation and induction of sustained monomorphic VT with VA dissociation, LB/LSA morphology. VA dissociation is evident during the induction pacing sequence as well as during VT. A, atrial activation.

Supraventricular Tachycardia During EP studies performed for the diagnosis and mapping of SVT, multipolar catheters are generally placed in the HRA or CS, at the His bundle (HBE), and in the right ventricle (RVA or RVOT). SVT mechanisms include atrial arrhythmias (including ectopic atrial tachycardia, macroreentrant atrial tachycardia, atrial flutter, and atrial fibrillation), AV node reentrant tachycardia (AVNRT), and atrioventricular reciprocating tachycardia (AVRT) mediated by an accessory pathway. Stimulation Protocols. Programmed atrial and ventricular stimulation protocols are used in the determination of SVT mechanism and are summarized as follows: Ventricular Pacing. Incremental ventricular pacing at constant rates, but delivered at progressively faster PCLs, is used for assessment of VA conduction. In particular, retrograde atrial activation pattern (via AVN vs.

accessory pathway) is examined to determine the earliest atrial activation site from atrial EGMs recorded on catheters at various atrial sites (Figs. 25.17 and 25.18). The shortest cycle length at which 1:1 VA conduction occurs is recorded and the pattern of VA block at shorter cycle lengths examined. A decremental VA conduction pattern (longer VA times with faster pacing rates) that is concentric (earliest atrial activation in septal leads and later activation in lateral free wall electrodes) suggests retrograde conduction is occurring via the AVN. Retrograde conduction using an accessory pathway may cause an eccentric atrial activation pattern in the CS (earliest atrial activation in the posterior or lateral CS in left-sided accessory pathways, Fig. 25.18) or early activation away from the septum in the RA. In addition, typical accessory pathways do not display significant decremental conduction, so VA conduction times generally are constant. Exceptions occur for septal accessory pathways in which earliest activation will be at septal leads and also for decremental accessory pathways in which VA conduction times may be longer at faster pacing rates. Programmed Ventricular Stimulation. Premature ventricular extrastimuli. Single premature ventricular beats are delivered at one or more drive cycle lengths (e.g., 600, 400 ms) to assess retrograde refractory periods, pattern and change in retrograde atrial activation patterns, site of retrograde VA block, and the presence of dual retrograde AVN pathway physiology. Atrial Pacing. Assessment of anterograde conduction is performed with atrial pacing and programmed atrial stimulation. Baseline AH and HV intervals are assessed, and evidence for decremental AVN conduction is sought. Anterograde conduction via the AVN is characterized by increasing AH intervals with faster atrial pacing rates. The shortest PCL at which 1:1 AV conduction occurs and the pattern of anterograde activation and block at PCL shorter than this are noted. A Wenckebach AV block pattern and a narrow QRS supports conduction occurring anterogradely through the AVN. Anterograde ventricular preexcitation by an accessory pathway may become more manifest by atrial pacing, as faster pacing rates will cause decremental, or slower, conduction through the AVN. Thus, at faster atrial pacing rates, the AVN will conduct slower, leading to later ventricular activation from the AVN–HPS. Since conduction through a typical accessory pathway does not significantly decrement with more rapid pacing rates and ventricular

activation times via the accessory pathway will remain relatively constant, there is less contribution of ventricular activation that occurs via the AVN and more via the accessory pathway (Fig. 25.21). Another potential important function of burst atrial pacing is the induction of SVT for mapping and ablation.

FIGURE 25.21 Left free wall accessory pathway. In sinus rhythm (left panel), there is fusion of ventricular activation occurring via the atrial node and accessory pathway. During atrial pacing and introduction of premature atrial extrastimuli (right panel), preexcitation becomes more manifest as activation via the AVN decrements and becomes later, leaving a larger component of ventricular activation to occur via the accessory pathway. Programmed Atrial Stimulation. Delivery of single or double atrial extrastimuli may serve to study AVN physiology, to determine the presence of an accessory pathway and its refractory period, and to induce SVT. Single premature beats are delivered after fixed drive cycles (e.g., typically after

eight-beat 600, 500, and/or 400 ms PCL atrial drive trains). Normal AVN physiology is characterized by decremental conduction: the faster the stimulation (shorter A1A2 coupling intervals or faster PCLs), the slower the AVN conducts and the longer the AH interval becomes (Fig. 25.22 APD1 and APD2). The following are typical SVT substrates that may be demonstrated:

FIGURE 25.22 Single atrial extrastimuli. Dual AVN physiology and induction of single typical AVN echo beat. Single APD1 and single APD2: decremental AVN conduction with longer AH interval after shorter A1–A2 coupling interval. Decremental AVN conduction is demonstrated with AH 140 and 160 ms with shortening of APD coupling interval (APD1 to APD2). Single APD3: AH jump (>50-ms increase in AH interval for a 10-ms decrease in A1–A2 coupling interval) with single typical AV nodal echo (note atrial activation seen in the CS with a short VA interval). APD, atrial premature depolarization.

AH (jump >50 ms over a decrement of 10 ms in A1S2) ⇒ dual AVN physiology (Fig. 25.22 APD2 and APD3) Induction of AV nodal echo beats or AVNRT by occurrence of block typically in the fast pathway and conduction delay in the slow pathway allowing recovery for retrograde fast pathway conduction and activation of retrograde atrial depolarization (Fig. 25.22, APD3 and Fig. 25.23) Induction of orthodromic AVRT by causing antegrade block in the AP so it is excitable when the impulse returns to conduct retrograde to the atrium

FIGURE 25.23 Initiation of AVNRT single APDs CS 400/250 AH jump, initiation of AVNRT. Refractory Periods. As in the ventricle, refractory periods of the components of the anterograde conduction system can be determined and are defined as follows:

Atrial Effective Refractory Period—Longest atrial coupling interval (A1A2) that fails to capture the atrium, measured from pacing stimulus to pacing stimulus Atrial Functional Refractory Period (AFRP)—Shortest atrial coupling interval during premature atrial stimulation (A1A2), measured from EGM to EGM Fast AVN Pathway ERP—Longest atrial coupling interval that produces an AH jump to conduction via the slow pathway, measured from EGM to EGM during atrial extrastimulus testing Slow AVN Pathway ERP—Longest atrial coupling interval that produces a block in slow pathway conduction (if only two pathways are present and the fast pathway has already blocked, slow AVN pathway ERP = AVN ERP), measured from EGM to EGM during atrial extrastimulus testing Accessory Pathway Anterograde ERP—Longest atrial coupling interval that produces a block in accessory pathway conduction, measured from EGM to EGM during atrial extrastimulus testing Accessory Pathway Retrograde ERP—Longest ventricular coupling interval that produces a block in retrograde accessory pathway conduction, measured from EGM to EGM during ventricular extrastimulus testing Shortest Preexcited R–R during Atrial Fibrillation. Short R–R intervals suggest a short AP ERP and potential increased risk. Activation Patterns. As discussed above, the pattern of atrial and ventricular activation is examined. The anterograde ventricular activation sequence is the sequence of ventricular activation during sinus rhythm, atrial pacing, atrial extrastimuli, or SVT. Eccentric activation of the CS suggests a left-sided accessory pathway (Fig. 25.18, left panel). The atrial activation sequence is the sequence of atrial activation during ventricular pacing, ventricular extrastimuli, or SVT. Eccentric retrograde activation of the CS suggests a left-sided accessory pathway (Figs. 25.18, right panel and 25.24).

FIGURE 25.24 Left-sided accessory pathway. Retrograde atrial activation during ventricular pacing—earliest retrograde atrial activation at CS 3 (arrows). Inducible Supraventricular Tachyarrhythmias. Types of SVTs that may be induced include the following: AV node reentrant tachycardia—AVNRT is usually associated with dual AV nodal pathway physiology (discontinuous AVN conduction curves; an AH “jump”) (Figs. 25.15 and 25.22). In typical AVNRT, antegrade conduction occurs via the slow AVN pathway (long AH) and retrograde conduction via the fast AVN pathway with near-simultaneous atrial and ventricular activation (Figs. 25.22 and 25.23). In a typical AVNRT, antegrade conduction occurs via the fast AVN pathway (with a short PR) and retrograde conduction via the slow AVN pathway (long R–P interval). Atrioventricular reentrant tachycardia—AVRT refers to accessory pathway-mediated reentrant tachycardia. In AVRT, there is 1:1 AV association, as the atria and the ventricles are integral components of the reentrant circuit. In orthodromic AVRT, antegrade conduction occurs via the AVN (with a narrow QRS in the

absence of bundle-branch block/aberration) and retrograde conduction occurs via the accessory pathway (Figs. 25.25 and 25.26). In antidromic AVRT, antegrade conduction occurs via the accessory pathway (with wide QRS) and retrograde conduction via the AVN or another accessory pathway. Atrial flutter—In type I (typical) atrial flutter, right atrial activation proceeds in a counterclockwise activation pattern through the posterior isthmus between the inferior vena cava and tricuspid annulus. There may also be clockwise activation utilizing the isthmus. Type II (atypical) atrial flutter refers to atrial flutter using non–isthmus-dependent flutter circuits. Atrial tachycardia—Atrial tachycardias may be macroreentrant in mechanism, including most incisional or scar-related atrial tachycardias, or due to ectopic (to the sinus node) foci and/or automatic mechanisms. Atrial fibrillation—This most common sustained clinical arrhythmia typically initiates from pulmonary vein ostial or other focal triggering sites or microreentrant circuits. It may sustain with multiple wandering reentrant circuits. Sinus node reentrant tachycardia—This tachycardia is characterized by a similar P-wave morphology to sinus rhythm and may be induced and terminated with premature extrastimuli. Inappropriate sinus tachycardia—Inappropriate sinus tachycardia (IST) is characterized by an inappropriately high resting sinus rate and enhanced sensitivity to adrenergic stimulation.

FIGURE 25.25 Left-sided accessory pathway mediating orthodromic AVRT—earliest retrograde atrial activation occurs via an accessory pathway at CS 2–3 (VA interval 95 ms). Evaluation during tachycardia. Once a tachycardia is induced, various observations and maneuvers can be performed to help determine the SVT mechanism. These include the following: Morphology: Narrow complex, RBBB or LBBB aberrant conduction, or preexcited Atrial activation sequence Ventricular activation sequence HA or VA interval—Short HA interval (100 ms) suggests orthodromic AVRT mediated by an accessory pathway Single ventricular premature extrastimuli during SVT (Fig. 25.27)—If single ventricular premature extrastimuli delivered during His refractoriness advances retrograde atrial activation, then a retrogradely conducting or concealed accessory pathway is present. However, this only demonstrates the presence of an accessory pathway. It does not

prove that the pathway is an integral part of the circuit, as it could be a bystander pathway. Bundle-branch block aberration in SVT (Figs. 25.28 to 25.30)—VA interval prolongation during aberration in SVT indicates a retrogradely conducting accessory pathway ipsilateral to the bundle-branch block. On a surface ECG recording, this may be manifest by a longer cycle length (slower rate) during the wide complex tachycardia/aberration than during narrow complex conduction (Fig. 25.28). The prolongation of the cycle length occurs due to a prolongation of VA conduction times. Bundle-branch block aberration ipsilateral to the accessory pathway results in longer retrograde (VA) activation times due to additional time required for transseptal myocardial conduction (Figs. 25.28 to 25.30). Demonstration of such a change in VA time with aberration demonstrates the presence of the accessory pathway ipsilateral to the bundle-branch blocked and also indicates that the accessory pathway is a component of the reentrant circuit.

FIGURE 25.26 Left free wall accessory pathway mediating orthodromic AVRT—earliest atrial activation occurs in the distal CS at CS 1–2 (arrows).

FIGURE 25.27 Orthodromic AVRT with single VPD introduced during His refractoriness. The single ventricular extrastimulus delivered during His bundle refractoriness advances retrograde atrial activation, suggesting the presence of a retrogradely conducting accessory pathway, in this case located in the right posteroseptal region.

FIGURE 25.28 A:Conversion of wide complex to narrow complex tachycardia with longer RR interval during wide complex tachycardia. This is diagnostic for AVRT with an accessory pathway ipsilateral to the bundle-branch block. B:Orthodromic AVRT with ipsilateral BBB. BBB aberration ipsilateral to the accessory pathway results in longer retrograde (VA) activation times as a result of additional time required for transseptal myocardial conduction.

FIGURE 25.29 Initiation of orthodromic AVRT with initial LBBB aberration. Retrograde VA activation times are longer during LBBB aberration, indicating participation of a left-sided accessory pathway. Local VA time measured nearest the accessory pathway (CS distal 55 ms) is similar, but earliest ventricular to atrial activation is longer with LBBB aberration.

FIGURE 25.30 RBBB aberration during AVRT utilizing a right posteroseptal accessory pathway. Retrograde VA activation times are longer during RBBB aberration, confirming the presence of a right-sided accessory pathway.

MAPPING DURING ABLATION A diagnostic EP study is critical to confirmation and definition of arrhythmia substrate prior to ablation of most SVTs and VTs. Currently, various mapping techniques based on determination of earliest activation sites include the utilization of electrophysiologic recordings and various electroanatomic, contact catheter and noncontact mapping systems that can graphically tag and record activation times in three-dimensional space with computer generation of a display of activation or voltage maps. Although ablation of some arrhythmias is based on anatomic locations (e.g., slow pathway region for AVNRT or pulmonary vein antral isolation for atrial fibrillation ablation), successful ablation of other tachycardias often requires determination of the earliest site of activation, which helps to determine the location of the targeted arrhythmia substrate. An example is shown in Figure 25.31, which demonstrates the fusion of atrial and ventricular EGMs on the ablation catheter at the site of an accessory pathway. Ablation here using radiofrequency energy resulted in prompt ablation of the pathway, loss of ventricular preexcitation, and restoration of normal AV conduction.

FIGURE 25.31 Left-sided accessory pathway. A:Successful ablation site. B:Radiofrequency ablation.

SUMMARY This chapter aims to summarize the components of a comprehensive diagnostic EP study. For users of this book aiming for cardiovascular board

examination review, focus should be paid to the following: Recognition of the His bundle EGM and determination of the sites of AV block (AV nodal vs. infranodal block) Recognition of VA dissociation during wide complex tachycardia using intracardiac EGMs, indicating that the rhythm is most likely VT Recognition of the initiation of AVNRT with demonstration of an “AH jump” and induction of an SVT with near-simultaneous atrial and ventricular activation Recognition of a left free wall accessory pathway with abnormal, eccentric early activation via a more distal CS location (e.g., rather than the normal earliest activation at the septum and later activation in the lateral CS/left atrial or ventricular free wall) Recognition that bundle-branch block that manifests during SVT with a longer cycle length or longer VA time indicates the presence of an accessory pathway ipsilateral to the bundle-branch block

SUGGESTED READINGS Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005;352:225-237. Blomstrom-Lundqvist C, Scheinman MM, Aliot EM, et al. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias—executive summary: a report of the American college of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (writing committee to develop guidelines for the management of patients with supraventricular arrhythmias) developed in collaboration with NASPE-Heart Rhythm Society. J Am Coll Cardiol. 2003;42:1493-1531. Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med. 1999;341:1882-1890. Epstein AE, DiMarco JP, Ellenborgen KA, et al. ACC/AHA/HRS 2008 Guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) Developed in Collaboration With the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;51:e1-e62; originally published online May 15, 2008. Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004;350:2151-2158.

Knight BP, Ebinger M, Oral H, et al. Diagnostic value of tachycardia features and pacing maneuvers during paroxysmal supraventricular tachycardia. J Am Coll Cardiol. 2000;36:574-582. Knight BP, Zivin A, Souza J, et al. A technique for the rapid diagnosis of atrial tachycardia in the electrophysiology laboratory. J Am Coll Cardiol. 1999;33:775-781. Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med. 1996;335:1933-1940. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346:877-883. Tracy CM, Akhtar M, DiMarco JP, et al. American College of Cardiology/American Heart Association clinical competence statement on invasive electrophysiology studies, catheter ablation, and cardioversion. A report of the American College of Cardiology/American Heart Association/American College of Physicians—American Society of Internal Medicine Task Force on clinical competence. J Am Coll Cardiol. 2006;114:1654-1668. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Europace. 2006;8:746-837.

Chapter 25 Review Questions and Answers QUESTIONS 1.

Where is the site of block in Figure 25.32?

FIGURE 25.32 A. . C. D.

AV node (AVN) Infra-His Intra-His AVN and Infra-His

2.

Where is the site of block in Figure 25.33?

FIGURE 25.33 A. . C. D.

AVN Infra-His Intra-His AVN and Infra-His

3.

Where is the site of block in Figure 25.34?

FIGURE 25.34

A. . C. D.

AVN Infra-His Intra-His AVN and Infra-His

4.

What is the diagnosis based on Figure 25.35?

FIGURE 25.35 A. . C. D.

Orthodromic AVRT Left-sided accessory pathway Atrial tachycardia AVN reentrant tachycardia

5.

What is the diagnosis based on Figure 25.36?

FIGURE 25.36 A. . C. D.

Left-sided accessory pathway Right-sided accessory pathway AVN reentrant tachycardia Sinus tachycardia

ANSWERS 1.

Correct Answer: B. Infra-His The tracing (Fig. 25.32) shows atrial pacing with right bundle-branch block (RBBB) and second-degree AV block without prolongation of the PR or AH intervals prior to the blocked beat (third paced beat). On this third paced beat, the His electrode shows an atrial EGM followed by a His deflection but not following ventricular EGM or QRS. Thus, the block occurs below the bundle of His (infra-Hisian block).

2.

Correct Answer: A. AVN

The tracing (Fig. 25.33) shows atrial pacing (S1 drive) with 2:1 AV block. Inspection of the His bundle EGM tracings demonstrates S1 atrial pacing stimuli followed by atrial EGMs. After the first paced beat, there is a His bundle EGM followed by a ventricular EGM and QRS on the surface electrocardiogram (ECG). After the second paced beat, no His bundle EGM follows the atrial EGM. The next paced beats repeat this pattern. The block is at the level of the AVN, because conduction is blocked prior to arrival to the His bundle.

3.

Correct Answer: D. AVN and Infra-His This tracing (Fig. 25.34) shows second-degree AV block during atrial pacing. The His bundle EGM demonstrates the atrial pacing stimuli followed by atrial EGMs. After the first atrial paced beat, there is a long AH interval followed by a His EGM but no ventricular EGM or QRS. This beat blocks below the His bundle. After the second paced beat, there is a slightly longer AH interval followed by a ventricular EGM on the RVA tracing and a corresponding surface QRS. After the third paced beat, the AH is longer still, but there is no conduction after the His EGM to the ventricles. This beat again shows infraHisian block. After the fourth paced beat, there is no His electrogram. This beat blocks in the AVN, and the series shows AVN Wenckebach occurring (gradually prolonging AH interval followed by block in the AVN). The fifth paced beat shows conduction after the block with a shorter AH interval followed by conduction to the ventricles. The sixth paced beat shows a small His deflection with slightly longer AH but infra-Hisian block (no ventricular activation). The seventh paced beat shows a slightly longer AH interval with conduction to the ventricles. Thus, the tracing demonstrates two levels of block—in the AVN (Mobitz I Wenckebach pattern) and infra-Hisian block.

4.

Correct Answer: D. AVN reentrant tachycardia The tracing (Fig. 25.35) shows a narrow QRS complex tachycardia with a cycle length of 350 ms. The coronary sinus (CS) atrial EGMs show a concentric atrial activation pattern (earliest at CS 7 to 8 at the septum and later at more distal CS electrodes) with near-simultaneous

activation of the atrium and ventricle. The earliest atrial activation is likely the small deflection at the onset of the QRS on the HBE tracing, which actually slightly precedes the ventricular activation. This pattern is consistent with AVN reentrant tachycardia.

5.

Correct Answer: A. Left-sided accessory pathway This tracing (Fig. 25.36) shows a narrow complex tachycardia with cycle length of 370 ms. The anterograde activation occurs via the AVN and HPS (AH seen in HBE 1 to 3 with narrow QRS). The earliest atrial activation occurs in the distal CS at CS 1 to 2. This eccentric activation pattern indicates retrograde activation via a left lateral accessory pathway. The tachycardia is consistent with orthodromic AVRT using a retrogradely conducting left-sided accessory pathway.

CHAPTER 26

Sudden Cardiac Death and Ventricular Tachycardia CAMERON T. LAMBERT, DANIEL J. CANTILLON, AND OUSSAMA WAZNI

DEFINITION OF SUDDEN CARDIAC DEATH Sudden cardiac death (SCD) is defined by the 2017 American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) guidelines as the sudden and unexpected death occurring within 1 hour of the onset of symptoms or within 24 hours of a patient being asymptomatic. The definition excludes noncardiac conditions such as pulmonary embolism, intracranial hemorrhage, or airway obstruction. However, it does not exclude nonarrhythmic deaths, as the terminal rhythm is often unknown.

EPIDEMIOLOGY OF SUDDEN CARDIAC DEATH The incidence of SCD is estimated to be 230,000 to 350,000 per year in the United States with some estimates exceeding >450,000 depending on measurement methods. Ninety-seven percent of these deaths are observed in patients over the age of 18. The mortality rate is high, with an overall survival rate of 10%. Of those patients who reach the hospital, 50% die

before discharge. Among those who survive to hospital discharge, the 5 year survival approaches 80%. There is a high recurrence rate of 35% to 50%. More than 75% to 85% of SCDs are associated with ventricular arrhythmias. The most common arrhythmias are ventricular tachycardia (VT) (62%), torsades de pointes (TdP) (13%), primary ventricular fibrillation (VF) (8%), followed by bradycardia (7%). SCD is the first presentation of cardiac disease in 25% of patients. The incidence increases with age at an absolute incidence of 0.1% to 0.2% per year. Men are more commonly affected (3:1) although this discrepancy may be lessening. SCD in patients 35 years old, SCD is most commonly associated with coronary artery disease. Determinants of survival are rapid external defibrillation and bystander cardiopulmonary resuscitation.

RISK FACTORS PATHOPHYSIOLOGY

AND

Risk factors include the following: Prior cardiac arrest: high recurrence rate, up to 35% to 50% at 2 years Syncope in the presence of coexisting cardiac diseases Reduced left ventricular (LV) function and congestive heart failure (CHF) Ventricular premature contractions and nonsustained ventricular tachycardia (NSVT) post myocardial infarction Myocardial ischemia and/or documented scar Conduction system disease The pathophysiology of these arrhythmias requires an underlying substrate conducive to maintaining an arrhythmia and trigger factors that can incite the abnormal rhythm. Examples of these SCD mechanisms include the following: Anatomical reentry around scarred myocardium

Functional reentry using a diseased His–Purkinje system, or areas of nonhomogeneous (anisotropic) conduction Ischemia, electrolyte imbalance, ion channel abnormalities, surges in neurosympathetic tone, pro-arrhythmic effect from antiarrhythmic drugs Rapid and irregular ventricular activation (i.e., atrial fibrillation [AF] with rapid ventricular response in Wolff–Parkinson–White [WPW]) Bradycardic SCD is overall uncommon; however, it remains an important consideration in specific situations (i.e., cardiac transplant recipients).

SUDDEN CARDIAC DEATH CORONARY ARTERY DISEASE

AND

Coronary artery disease is present in 80% of those with SCD. Approximately 75% have a history of prior myocardial infarction (MI). Sudden death can be the first clinical manifestation in up to 25% of patients with coronary artery disease. Approximately 65% have three-vessel obstructive coronary disease at the time of diagnosis. Given this correlation, the most updated SCD guidelines recommend coronary evaluation (CTA or angiography) for patients who were successfully resuscitated from SCD. Risk factors for coronary artery disease–related SCD include depressed LV systolic function and frequent premature ventricular contractions (PVCs). Despite PVCs being a risk factor for SCD, the Cardiac Arrhythmia Suppression Trial (CAST) study demonstrated that suppression with class IC medications resulted in higher mortality. Data from large clinical trials have identified groups of patients with coronary artery disease, depressed LV systolic function, and nonsustained ventricular arrhythmias at increased risk for SCD, as discussed later in this chapter.

NONISCHEMIC CARDIOMYOPATHY Patients with impaired LV systolic function in the absence of coronary artery disease are also at increased risk for ventricular tachyarrhythmias and SCD,

particularly those with symptomatic heart failure. In the heart failure population, total mortality is approximately 25% at 2.5 years, with SCD accounting for 25% to 50% of these deaths. Mortality due to SCD is much higher in New York Heart Association (NYHA) classes II and III than in class IV patients, who have excess mortality due to pump failure. Recent studies have attempted to clarify which patients with NICM may suffer SCD. Noninvasive imaging modalities such as cardiac MRI have demonstrated myocardial late gadolinium enhancement (LGE) to be a reliable marker for heightened risk.

Dilated Cardiomyopathy Fifty percent of deaths in this patient subgroup are arrhythmic. Left ventricular ejection fraction (LVEF) is predictive of sudden death, due to either circulatory failure or fatal arrhythmia. While ventricular ectopy is very common in patients with dilated cardiomyopathy (DCM), it is less predictive of SCD compared to patients with coronary artery disease. Up to 80% of patients may have NSVT on Holter monitor. Inducibility for ventricular tachyarrhythmias at the time of electrophysiologic (EP) study is also less predictive when compared to patients with coronary disease and has almost no role in risk stratification. While some modalities such as abnormal Twave alternans and heart rate variability have been associated with increased risk in this population, only LVEF ≤ 35% and the presence of symptomatic heart failure are recommended by practice guidelines for the purposes of risk stratification, particularly regarding selecting candidates for implantable cardioverter–defibrillator (ICD) implantation.

Hypertrophic Cardiomyopathy HCM is an autosomal dominant disease with incomplete penetrance associated with an increasingly recognized number of genetic mutations. The overall incidence of SCD is 2% to 4% in adults and up to 6% in children. It is the most common cause of SCD in young athletes. Identification of patients at increased risk for SCD is important and requires specific criteria as most of these patients maintain normal left ventricular EF and thus will not meet the traditional indications for ICD therapy. Maron et al. identified factors associated with increased risk

including the presence of NSVT, hypotension with exercise, unexplained syncope, septal thickness >3 cm, and a family history of sudden death in a first-degree relative younger than 50 years old. Among patients with HCM and primary prevention ICDs, appropriate therapy was uncommon among patients with none of the above listed risk factors. Appropriate ICD therapies were delivered in 14% of patients with one risk factor, 11% of patients with two risk factors, and 17% of patients with three or more risk factors. Cardiac magnetic resonance imaging (MRI) has been increasingly utilized for risk stratification in HCM patients (>15% myocardium showing LGE associated with VT). This enhancement is histopathologically associated with scarring and fibrosis and is typically located in the basal septal wall. To help guide clinicians’ decision regarding ICD therapy in HCM, the American Heart Association and European Society of Cardiology provide guidelines to help predict risk for SCD. The AHA guidelines support ICD implant for patients with HCM and additional risk factors for SCD, which include left ventricular outflow tract (LVOT) obstruction (resting gradient ≥ 30 mm Hg), LGE on cardiac MRI, LV apical aneurysm, or high-risk genetic mutations (LAMP2). The 2015 European recommendations add a risk score (HCM Risk-SCD score), which integrates the patient’s age, LV wall thickness, left atrial size, LVOT gradient, family history of SCD, presence of NSVT, and history of unexplained syncope to provide a 5-year SCD risk output.

Arrhythmogenic Right Ventricular Cardiomyopathy Progressive fibrofatty right ventricular tissue replacement is the histopathologic hallmark of arrhythmogenic right ventricular cardiomyopathy (ARVC), although this disease process can affect both ventricles and less commonly even the left ventricle only This pathologic replacement of normal myocardium with fibrofatty tissue is a nidus for ventricular arrhythmia and SCD, although variants of this condition involve only fibrosis without fatty replacement. Given a strong familial inheritance pattern, the 2017 ACC/AHA/HRS guidelines recommend referral for genetic counseling. Globally, it is thought that up to 20% of SCD may be due to ARVC (3% in the United States). MRI is the most useful imaging modality to make the diagnosis. Characteristic epsilon waves may be present on the electrocardiogram (ECG), as shown in Figure 26.1. The frequency and the

severity of ventricular arrhythmias in this disease increase with time making the timing of ICD implantation important. According to the guidelines, a primary prevention ICD should be considered for a patient with ARVC with a marker for increased SCD risk. These risk factors include previous aborted SCD, documented sustained VT, and reduced ventricular function (either RV or LV EF ≤ 35%). Beyond device-based therapy, these patients should avoid intensive exercise and beta-blockers should be prescribed to patients with a history of ventricular arrhythmia.

Figure 26.1 ECG reading in ARVD.

Cardiac Sarcoidosis An increasingly recognized cause of SCD is cardiac sarcoidosis. This condition, pathologically identified by noncaseating granulomas, presents most commonly during the third, fourth, or fifth decades of life. While it traditionally is associated with inducing AV conduction abnormalities sometimes requiring pacemaker implantation, the inflammatory changes to the myocardium can induce ventricular arrhythmias. Common diagnostic modalities include PET scan imaging with FDG avidity present in among granulomas, as well as diagnostic criteria involving cardiac MRI. There is a paucity of epidemiologic data regarding SCD in patients with cardiac sarcoidosis. Inducible ventricular arrhythmias during EP study, unexplained syncope, and poor LV function may be markers of elevated SCD risk. A 2014 consensus statement from the Heart Rhythm Society can assist in the decision-making process relating to ICD therapy in patients with cardiac sarcoidosis.

Myocarditis Myocarditis, or inflammatory changes of the myocardium, often seen in various infections may impact the conduction system leading to abnormal conduction or arrhythmias ranging from AF to more sinister ventricular arrhythmias. Causes include influenza, coxsackie B virus, Chagas disease, HIV, and systemic lupus erythematous. It is imperative that these patients be managed in a hospital equipped to provide mechanical hemodynamic support given these arrhythmias often occurring alongside cardiogenic shock. There should be a high index of suspicion for myocarditis (specifically giant cell myocarditis)-related arrhythmia in a young patient who has suffered SCD. Patients who suffer aborted SCD due to myocarditis can be managed with antiarrhythmics until recovery or mechanical circulatory support can be established (LVAD, transplant).

Noncompaction of the Left Ventricle In this rare congenital condition, there are prominent trabeculations within the LV cavity without other significant structural abnormalities. Diagnosis can be achieved with echocardiography, cardiac CT, or MRI. Ventricular arrhythmias are common and can affect up to 40% of children, although

predictors for SCD are not well established. Specific data regarding the incidence of SCD are not available but given the observed increased rates of SCD, placement of a primary prevention ICD among select patients is considered reasonable.

Catecholaminergic Tachycardia

Polymorphic

Ventricular

SCD in the setting of emotional or physical stress without baseline ECG abnormalities is the hallmark of catecholaminergic polymorphic VT (CPVT). Arrhythmias are typically inducible with exercise stress testing and may display characteristic bidirectional morphology. This is an inherited condition with both autosomal dominant and recessive forms described that can present at any age. Once identified, exercise restriction and beta-blocker therapy are commonly prescribed. An ICD is considered reasonable for selected patients on maximally tolerated beta-blocker therapy with documented VF, hemodynamically intolerant VT, or unexplained syncope. Left-sided cardiac sympathetic denervation is also an option for these patients. Genetic testing plays a prominent role in the diagnosis of this condition.

INHERITED AND CHANNELOPATHIES

ACQUIRED

Long-QT Syndrome Long-QT syndrome consists of the inherited abnormalities that prolong cardiac repolarization as measured by the corrected QT (QTc) interval on surface ECG, which confer an increased risk of SCD by polymorphic ventricular tachycardia (PMVT) or TdP. There are numerous identified mutations involving mostly sodium and potassium ion channels (Table 26.1). Abnormal QTc cutoff values are >470 ms in symptomatic patients and >480 ms in asymptomatic patients, although actual cardiac events occur on a skewed curve and are highest among patients with QTc > 500 ms. The most

common symptoms associated with long QT syndrome are palpitations and unexplained syncope, although associations also exist with seizure disorders. Characteristic clinical triggers for arrhythmia events have been described by genotype including exercise or swimming (LQT1), auditory stimuli, or during the postpartum period (LQT2) and during sleep (LQT3). Features associated with higher risk for SCD include the Jervel and Lange-Nielsen syndrome (congenital deafness), syncope or ventricular arrhythmias while on betablocker therapy, QTc > 500 ms with an LQT1 or LQT2 genotype, female gender, and family history of SCD. Treatment usually includes beta-blocker therapy, except for in the case of LQT3, where a gain-of-function mutation in SCN5A results in voltage-gated sodium channels remaining open that is sometimes treated with mexiletine, a class IB drug. The 5-year sudden death risk in patients on beta-blocker therapy (Long QT Registry) is 30 seconds in duration or requires abortive therapy (i.e., shocks) to return to normal rhythm. This includes patients with acute MI with events occurring beyond 48 hours and not related to immediately reversible causes (i.e., overinjection of contrast dye during angiography of the right coronary artery).

For primary prevention, ICD therapy is recommended in patients 40 days after a medically managed MI (no revascularization performed) with LVEF ≤ 35% on optimal medical therapy and with life expectancy >1 year. For those patients who received successful revascularization, ICD therapy is recommended in patients 90 days after the MI who have LVEF ≤ 35%. Key trials in formulating these primary prevention indications include the MADIT-2 trial (ICD benefit for patients post-MI with LVEF < 30% and NYHA class I symptoms) and SCD-HeFT (ICD benefit for LVEF ≤ 35% and NYHA class II symptoms). In addition, patients may be considered for a primary prevention ICD with prior MI, LVEF < 40%, NSVT detected by ambulatory Holter or telemetry, and inducible VT with programmed stimulation at the time of EP study, largely on the basis of the MADIT-1 trial (LVEF ≤ 35% with NSVT) and MUSST registry (LVEF ≤ 40% with NSVT). Current ICD therapy can terminate up to 90% of all spontaneous VT with antitachycardia pacing (ATP). However, up to one-third of patients will still require antiarrhythmic medications to suppress VT and to minimize shocks and ATP. Catheter ablation of reentrant circuits is indicated for patients with VT that is refractory to medications and requiring multiple ICD shocks.

Dilated Cardiomyopathy More than a quarter of patients with DCM have NSVT on Holter monitoring during a 24-hour period. ICD implantation is recommended for secondary prevention in patients with DCM and prior sustained VT/VF and also as primary prevention for patients with LVEF ≤ 35% with NYHA class II symptoms based on the SCD-HeFT trial. Studies have shown more robust increases in longevity in patients with DCM and appropriate ICD indications when compared to patients with ischemic cardiomyopathy and indications for ICD. The 2012 device therapy guidelines also allow a primary prevention ICD to be offered to patients with DCM, LVEF ≤ 35%, and NYHA class I symptoms, although this is based on weaker evidence. In addition to scar-related VT, patients with DCM are particularly susceptible to bundle branch reentry VT. This is a VT most commonly occurring with left bundle branch bundle (LBBB) morphology. EP testing reveals abnormal conduction in the His–Purkinje system as measured by a

prolonged HV interval in sinus rhythm. Most frequently, the right bundle is used as the antegrade limb and the left bundle as the retrograde limb of the tachycardia, and the right bundle is typically targeted for catheter ablation.

Ventricular Tachycardia and the Structurally Normal Heart Outflow Tract Ventricular Tachycardia VT occurring in patients without structural heart disease most commonly originates from discrete foci in the right and the left ventricular outflow tracts (LVOTs). These arrhythmias are thought to be secondary to enhanced automaticity related to delayed after depolarization (DAD)–mediated triggered activity resulting from increases in intracellular calcium (during phase 4 of the action potential). DAD–mediated outflow tract VT is frequently inducible during an EP study using pacing maneuvers, in addition to provocation by an isoproterenol infusion (typically in the “wash-out” phase of infusion). The right ventricular outflow tract (RVOT) is more common than the LVOT by a ratio of 9:1. However, data by Iwai et al. suggest that these tachycardias share identical EP mechanisms and clinical behavior due to embryologic origin in the maturation of the outflow tract. Outflow tract tachycardias can occur as sustained monomorphic VT, frequent salvos of NSVT, or frequent symptomatic VPDs. The classic ECG pattern for RVOT VT is a LBBB with precordial Rwave transition in V2–V3, and an inferior limb lead axis, with tall R waves in II, III, and aVF. LVOT VT can occur with a RBBB morphology, inferior axis, or a LBBB morphology, inferior axis with earlier precordial R-wave transition by V2 (Fig. 26.3). In the EP lab, outflow tract tachycardia may be induced with programmed stimulation and has a characteristic pharmacologic response of adenosine sensitivity in most cases. Mapping and ablation of the site of earliest origin is highly successful. Left-sided foci are also commonly ablated from left and right coronary cusps either just above or immediately beneath the aortic valve. Outflow tract VTs are not associated with SCD, and catheter ablation is curative. Therefore, ICD therapy is not indicated (class III recommendation by 2012 guidelines).

Figure 26.3 ECG reading in RVOT VT.

Idiopathic Left Ventricular Tachycardia This is a paroxysmal VT that occurs predominantly in men between 15 and 40 years of age. It is also called “fascicular VT” because of the circuit’s typical involvement of the LV anterior and posterior fascicles. It accounts for 10% to 20% of all idiopathic VTs and is characterized by the following triad: (a) inducibility by atrial pacing or premature complexes, (b) RBBB morphology most commonly with left anterior hemiblock pattern, and (c) absence of structural heart disease. This type of VT is highly sensitive to calcium channel blockers like verapamil. Ventricular activation at the earliest site is usually preceded by high-frequency potentials termed Purkinje potentials. Ablation at these sites is highly successful in terminating this arrhythmia (70% success rate). In the absence of concomitant structural heart disease, true fascicular VT is not associated with SCD and thus not recommended for ICD implantation according to the 2012 guidelines.

Papillary Muscle Ventricular Tachycardia Ventricular arrhythmias originating from the papillary muscles (LV more often than RV) have become more recognized over the past 10 years and account for a small fraction of the structurally normal heart ventricular arrhythmias (5% to 12%). They typically affect men and women in their 50s and 60s and are frequently exercise induced. Patients may present with frequent PVCs, NSVT, or SCD (often VT triggered by a PVC). Treatment consists of beta blockade and catheter ablation albeit with a lower success rate (60%) than with other forms of ventricular tachycardia ablation.

ACKNOWLEDGMENTS The authors wish to acknowledge the contributions of J. David Burkhart, MD, to an earlier version of this chapter.

SUGGESTED READINGS Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. ACC/AHA/HRS 2017 guideline for management of patients with ventricular arrhythmias and prevention of sudden cardiac death. J Am Coll Cardiol. 2018;72:e91-e220. Birnie DH, Sauer WH, Bogun F, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm. 2014;11:13041323. Dukkipati SR, Choudry S, Koruth JS, et al. Catheter ablation of ventricular tachycardia in structurally normal hearts. J Am Coll Cardiol. 2017;70:2909-2923. Elliot PM, Anastasakis A, Borger MA, et al. 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy. Eur Heart J. 2014;35:2733-2779. Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities. J Am Coll Cardiol. 2008;51:E1-E62. Epstein AE, DiMarco JP, Ellenbogen KA, et al. 2012 ACC/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities. J Am Coll Cardiol. 2008;61:e6-e75. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy. Circulation. 2011;124:e783-e831. Haïssaguerre M, Derval N, Sacher F, et al. Sudden cardiac death associated with early repolarization. N Eng J Med. 2008;358(19):2016-2023. Iwai S, Cantillon DJ, Kim RJ, et al. Right and left ventricular outflow tract tachycardias: evidence for a common electrophysiologic mechanism. J Cardiovasc Electrophysiol. 2006;17(10):1052-1058. Nogami A. Idiopathic left ventricular tachycardia: assessment and treatment. Cardiac Electrophysiol Rev. 2002;6:448-457. Samie FH, Jalife J. Mechanisms underlying ventricular tachycardia and its transition to ventricular fibrillation in the structurally normal heart. Cardiovasc Res. 2001;50:242-250. Trivedi A, Knight BP. ICD therapy for primary prevention in hypertrophic cardiomyopathy. Arrhythm Electrophysiol Rev. 2016;5:188-196. Wever EFD, Robles de Medina EO. Sudden death in patients without structural heart disease. J Am Coll Cardiol. 2004;43(7):1137-1144.

Chapter 26 Review Questions and Answers QUESTIONS A 57-year-old male presents to your clinic to discuss primary prevention ICD implant after an ST elevation myocardial infarction 6 weeks prior managed with a single drug eluting stent to the left anterior descending coronary artery. His vital signs include a heart rate of 52 bpm, BP 126/64 mm Hg, respiratory rate of 12, and a pulse oximetry of 99%. He reports dyspnea with moderate exertion. His ECG shows sinus rhythm with QRS duration 100 ms without Q waves. His ejection fraction on the day of the office visit is 30%. Medications include aspirin, ticagrelor, and metoprolol. He has no drug allergies, and lab work reveals normal electrolytes and renal function. What is the most appropriate next course of action? Schedule for single chamber ICD implant Schedule for dual chamber ICD implant Schedule for biventricular ICD implant (CRT-D) Add angiotensin-converting enzyme inhibitor and schedule follow-up appointment

1.

A. . C. D.

A primary prevention implantable cardioverter–defibrillator (ICD) is most strongly indicated in which of following patients? Male patient with syncope, QTc 440 ms, and LQT1 genotype not previously treated with beta-blockers Young patient with syncope, NSVT, and diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC), including cardiac magnetic resonance imaging (MRI) Asymptomatic patient with newly diagnosed nonischemic dilated cardiomyopathy (DCM), left ventricular ejection fraction (LVEF) 35% Young patient without structural heart disease and monomorphic ventricular tachycardia (VT) (left bundle branch block [LBBB] morphology, right inferior axis, precordial R-wave transition in V3)

2.

A. . C. D.

Which of the following patients with Wolff–Parkinson–White syndrome should be taken for electrophysiology study and ablation? Asymptomatic 18-year-old male with preexcitation and shortest preexcited R–R interval during induced atrial fibrillation of 350 msec Asymptomatic 24-year-old male with resting intermittent preexcitation that reliably resolves with any level of exertion A 28-year-old male with recurrent lightheadedness episodes and presyncope associated with preexcited tachycardia A and C

3.

A. . C. D.

Bundle branch reentry VT is most commonly associated with A. Enhanced automaticity in the right bundle . Enhanced automaticity in the left bundle C. Supranormal conduction in the His bundle D. Abnormally slow conduction in the His–Purkinje system

4.

5.

The ECG shown in Figure 26.4 is consistent with

Figure 26.4 A. . C. D.

Acute anteroseptal MI Abnormal SCN5A channel Abnormal KCQN1 channel Old anteroseptal MI with an aneurysm

ANSWERS 1.

Correct Answer: D. Add angiotensin-converting enzyme inhibitor and schedule follow-up appointment

The patient is not on guidelines-directed medical therapy and does not have a contraindication to adding an angiotensin-converting enzyme inhibitor to his medical regimen (normotensive, no drug allergies, normal renal function). If the patient returns after 90 days of appropriate guideline-directed medical therapy after a successful revascularization procedure and continues to have a decreased ejection fraction (300 to 400 beats/min (bpm) Mechanical effects: Loss of coordinated atrial contraction

Irregular electrical inputs to the AV node and His–Purkinje system leading to irregular ventricular contraction Surface electrocardiogram: No discrete P waves Irregular fibrillatory waves Irregularly, irregular ventricular response

Atrial Flutter Reentrant Mechanism Cavotricuspid Isthmus–Dependent Atrial Flutter Cavotricuspid isthmus (CTI)-dependent flutters refer to circuits, which involve the isthmus of tissue in the right atrium between the tricuspid annulus and inferior vena cava (IVC) (Fig. 27.1). The circuit can propagate around the isthmus in a clockwise or counterclockwise direction. Counterclockwise atrial flutter is characterized by dominant negative flutter waves in the inferior leads and positive flutter deflection in lead V1. Clockwise atrial flutter is characterized by positive flutter waves in inferior leads and negative flutter waves in lead V1. In contrast to coarse AF, the flutter waves on an ECG will usually have the same morphology, amplitude, and cycle length. Ablation of the CTI is curative.

FIGURE 27.1 Type I counterclockwise right atrial flutter.

Noncavotricuspid Isthmus–Dependent Atrial Flutter Noncavotricuspid isthmus (NCTI)-dependent flutters do not use the CTI. NCTI flutters are often related to atrial scar, which creates a conduction block and a central obstacle that allows for reentry. NCTI can be found in patients with prior cardiac surgery involving the atrium, such as repair of congenital heart disease, mitral valve surgery, or MAZE procedure as well as in patients post pulmonary vein isolation procedures. NCTI-dependent flutters are less common than CTI flutters.

Treatment

Atrial flutter may be difficult to treat medically (it is notoriously difficult to rate control) and may develop with organization of AF reentrant flutter circuits during treatment with antiarrhythmic therapy. Successful ablation is dependent on identifying a critical portion of the reentry circuit where it can be interrupted with catheter ablation.

ATRIAL FIBRILLATION DEFINITIONS Lone: Patients under the age of 60 years with absence of cardiopulmonary or other conditions predisposing to AF New onset: First episode of AF Recurrent: Has two or more paroxysmal or persistent episodes Paroxysmal: Self-terminating or with an intervention (medical or cardioversion) within 7 days Persistent: Sustaining for more than 7 days but less than a year Long-standing persistent: Sustaining for more than a year Permanent: Decision made to rate control only with no further attempts to restore SR

EVALUATION History Precipitating factors and conditions Alcohol, caffeine, sympathomimetics, herbal supplements, or other drug use Duration and frequency of episodes Degree of associated symptoms Manner of AF initiation Prior therapies for AF (past antiarrhythmic drugs that may have failed or past ablation attempts)

Documentation of Atrial Fibrillation and Initiation ECGs, rhythm strips Transtelephonic (remote) event monitoring Evaluation for precipitating bradycardia, paroxysmal supraventricular tachycardia (PSVT), atrial flutter, atrial ectopy, atrial tachycardia

Diagnostic Testing Lab studies—thyroid function, renal, and hepatic tests Echocardiogram—evaluate LV function, valves, atrial size. Functional stress testing or cardiac catheterization—evaluate for CAD in patients with risk factors and evaluate candidacy for 1C agents.

MANAGEMENT FIBRILLATION

OF

ATRIAL

Treatment Strategies Ventricular rate control AV nodal–blocking drugs Atrioventricular node (AVN) modification/ablation and pacing Achievement and maintenance of SR Antiarrhythmic drugs Cardioversions Nonpharmacologic therapies Ablation Surgery—MAZE procedure Anticoagulation

Atrial Fibrillation Follow-Up Investigation of Rhythm Management

The Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study was a multicenter trial of rate versus rhythm control strategies (Table 27.1). It tested the hypothesis that in patients with AF, total mortality with primary therapy intended to maintain SR is equal to that with primary therapy intended to control heart rate. The study randomized 4,060 patients (>65 years old or with risk factors for stroke), with a primary endpoint of total mortality. No significant difference in total mortality was found among strategies. The study also showed that continued anticoagulation is important even in the rhythm control arm, so this may be the best strategy in relatively asymptomatic older patients with good rate control.

Table 27.1 Rate Control versus Rhythm Control

Control of Ventricular Rate Rapid ventricular rates can cause symptoms and/or ventricular dysfunction. The goal of treatment, a heart rate of 70 to 100 bpm at rest, can be achieved pharmacologically with agents that slow AV nodal conduction, such as digoxin, beta-adrenergic blockers, and calcium channel blockers (Table

27.2). These agents, however, should not be used in patients with ventricular preexcitation due to the risk of very rapid antidromic conduction during AF over the pathway. In patients who are hemodynamically stable with evidence of preexcited AF, amiodarone, ibutilide, procainamide, and disopyramide are acceptable choices.

Table 27.2 Pharmacologic Rate Control for Atrial Arrhythmias

The RACE II trial compared strict rate control (resting heart rate S in V1 (Fig. 28.7). APs on the right free wall will typically have a positive delta wave in leads I and/or aVL (as the wavefront travels from the right toward the leftsided leads), as well as a positive delta wave and R < S in V1, with a precordial R/S transition occurring in V3 or later (Fig. 28.8). Septal APs typically have a negative delta wave in V1.

FIGURE 28.6 Milstein algorithm for localization of APs. LL, left lateral; PS, posteroseptal; RAS, right anteroseptal; RL, right lateral. *LBBB, +QRS LL, rS V1 and V2. (Reprinted from Milstein S, Sharma AD, Guiraudon GM, et al. An algorithm for the electrocardiographic localization of accessory pathways in the Wolff–Parkinson–White syndrome. Pacing Clin Electrophysiol. 1987;10(3 pt 1):555-563, with permission from John Wiley and Sons.)

FIGURE 28.7 ECG showing left free wall accessory pathway.

FIGURE 28.8 ECG showing right free wall accessory pathway.

Mechanism AVRT is a reentrant arrhythmia in which one limb of the reentrant circuit is the AV node/His–Purkinje system and the other limb is the AP. The conduction properties of the AP (speed of conduction and recovery)

determine the likelihood of developing a reentrant circuit arrhythmia. The direction of the circuit differentiates the two types of AVRT: orthodromic and antidromic. Orthodromic reciprocating tachycardia comprises the majority of the reciprocating tachycardias and is diagnosed when the antegrade limb of the reentrant circuit is the AV node and the retrograde limb is the AP. Because the ventricle is activated via the AV node, the QRS complex is narrow. Antidromic reciprocating tachycardia (ART) is less common and uses the AP as the antegrade limb and the AV node as the retrograde limb. Because the ventricle is activated via the AP, the QRS complex is wide (maximal preexcitation).

Electrophysiologic Characteristics and Diagnostic Maneuvers ORT is typically characterized by a short RP and a long PR interval as the circuit is conducting up the AP and down the AV node. Because conduction from the atria to the ventricles is via the AV node, the QRS morphology during tachycardia should be similar (in the absence of aberration) to the QRS morphology during normal sinus rhythm. An interesting and potentially useful phenomenon may be observed if a functional bundle-branch block develops during ORT. As demonstrated in Figure 28.9, if a bundle-branch block ipsilateral to a free wall bypass tract develops during tachycardia, then the retrograde reentrant wavefront is compelled to traverse a greater distance from the His–Purkinje fibers to the AP and the atrium. As a result, the VA conduction time during the tachycardia must increase (usually by at least 35 ms). The tachycardia cycle length may also increase such that the rate of the tachycardia becomes slower. In contrast, if the bundle-branch block is contralateral to a free wall bypass tract, there is no change in the distance the retrograde reentrant wavefront must travel to reach the atrium. Thus, there is no effect on the VA conduction time or tachycardia cycle length. Therefore, an SVT that slows with the development of bundle-branch block should raise suspicion for ORT using an AP located on the free wall ipsilateral to the side of bundle-branch block.

FIGURE 28.9 A:A narrow complex tachycardia utilizing the ipsilateral bundle (left bundle) antegrade and accessory pathway retrograde. Note the cycle length of the tachycardia and compare to (B) where the tachycardia now utilizes the contralateral bundle as the left bundle is blocked. This may result in prolongation of the cycle length of the tachycardia and is diagnostic of the location of the pathway.

Exceptions and Rare Forms of AVRT Occasionally, patients present with an incessant ORT involving retrograde conduction up a decrementally conducting posteroseptal AP; this is called permanent junctional reciprocating tachycardia (PJRT). The slow, decremental conduction of this AP prolongs the time between the R and P, often leading to a “long RP” tachycardia. Because of the incessant nature of

this arrhythmia, it has been associated with tachycardia-induced cardiomyopathy. Antidromic tachycardia is the least common arrhythmia associated with WPW syndrome, occurring in only 5% to 10% of patients. This tachycardia is characterized by a wide QRS complex that is fully preexcited with a regular R–R interval. If the diagnosis of WPW is not recognized, this tachycardia may be mistaken for ventricular tachycardia. Uncommonly, patients may have more than one AP, therefore allowing for multiple potential reentrant arrhythmia circuits. Of such patients, 33% to 60% will present with antidromic tachycardia. Even less common is a tachycardia involving one AP as the antegrade limb and another AP as the retrograde limb of the circuit, without any involvement of the AV node. In these very rare cases, the tachycardia does not terminate with AV node blockade. In patients with more than one pathway, the more likely scenario is ORT or ART involving only one pathway in the circuit, while the other pathways remain as “bystanders.” Occasionally, the presence of multiple APs will become apparent only after the dominant pathway has been ablated. Ebstein anomaly is a congenital heart defect, which is associated multiple right-sided APs; WPW syndrome occurs in 6% to 26% of such patients.

Treatment Treatment of a patient with WPW syndrome may include both drug therapy and catheter ablation. In the acute setting, patients with ORT (conduction down the AV node and thus a narrow QRS complex) can be treated with AV nodal–blocking agents such as adenosine and vagal maneuvers. If adenosine is given for ORT in a patient with a known AP, defibrillation pads should be in place on the patient, as adenosine may trigger AF that, in the setting of adenosine-induced AV block, may conduct rapidly down the AP leading to VF arrest. Chronic treatment may be directed at any essential component of the circuit. Administration of calcium channel antagonists or beta-adrenergic blockers affects the AV node, whereas antiarrhythmic drugs including flecainide, propafenone, quinidine, procainamide, and amiodarone may be chosen to target the AP. Catheter ablation is a class I recommendation for patients with AVRT. With newer electroanatomic mapping technologies, the success rate is >93% with a 250 beats per minute) to the ventricles in a 1:1 manner, inducing a VF arrest (Fig. 28.10). Preexcited AF or AFL should be treated with intravenous procainamide or ibutilide; beta-blockers, calcium channel blockers, and amiodarone are contraindicated. Of course, if the arrhythmia is hemodynamic unstable or refractory to pharmacologic therapy, then electrical cardioversion is the treatment of choice.

FIGURE 28.10 Preexcited atrial fibrillation; note the varying degrees of ventricular preexcitation.

Asymptomatic Accessory Pathways and Sudden Cardiac Death Sudden cardiac death (SCD) has been reported to occur rarely in patients with ventricular preexcitation on ECG, with an incidence of VF of 0.15% in one population-based study. SCD in this circumstance has been associated with a history of symptomatic arrhythmias, multiple APs, and APs with rapid antegrade conduction (shortest preexcited R–R interval 250 ms indicates an AP that is incapable of dangerously rapid antegrade conduction. Finding a shortest preexcited R–R interval 100 beats/min (bpm) and a QRS duration >120 ms on a 12-lead electrocardiogram (ECG). Utilizing the ECG, the correct mechanistic diagnosis of a WCT rhythm is often difficult. Besides being an intellectual exercise, it is very important to establish the correct diagnosis in order to deliver appropriate acute therapy and to plan subsequent long-term patient management. Several criteria and algorithms have been developed to help distinguish among different causes of WCT. When used individually, none of these criteria reaches 100% specificity; however, when properly applied together and in conjunction with the clinical history and presentation, the algorithms serve as a guide to the correct diagnosis in the majority of the cases. WCT can result from either a ventricular or a supraventricular mechanism. Ventricular tachycardia (VT) originates below the level of the His bundle. Supraventricular tachycardia (SVT) originates in or involves structures above the His bundle. SVT may involve atrial tachycardia, atrial fibrillation, atrial flutter, atrioventricular (AV) node reentrant tachycardia (Fig. 29.1), or AV reentrant tachycardia. AV reentrant tachycardia may be either orthodromic reentrant tachycardia or antidromic reentrant tachycardia (Fig. 29.2). Orthodromic reentrant tachycardia occurs when antegrade ventricular conduction occurs via the AV node and retrograde conduction to the atrium is via the accessory pathway. Antidromic reentrant tachycardia

occurs when ventricular antegrade conduction occurs over the accessory pathway and retrograde conduction occurs via the AV node.

FIGURE 29.1 Supraventricular tachycardia.

FIGURE 29.2 AV reentrant tachycardia.

DIFFERENTIAL DIAGNOSIS WCT can occur by three different mechanisms: 1. VT is the most common cause of WCT in the general population, accounting for >80% of all cases. It is even more common in patients with structural heart disease, and it may occur in 98% of patients with a prior history of a myocardial infarction. VT may be either monomorphic or polymorphic. Monomorphic VT occurs when the QRS morphology is stable and uniform, whereas polymorphic VT occurs when the QRS complexes vary in morphology. 2. The second mechanism of WCT occurs when the tachycardia originates above the ventricle and has abnormal ventricular activation, also known as SVT with aberrancy. It accounts for 15% to 20% of all cases of WCT and includes a variety of disorders. The first example is SVT with bundle branch block aberration, which may be either a right bundle branch block (RBBB) or a left bundle branch block (LBBB) morphology (Fig. 29.3). Activation of the

ventricle through the His–Purkinje system (His bundle and both bundle branches) results in a narrow QRS complex. Activation of the ventricle unilaterally via one bundle branch results in a wide QRS complex, because activation of the remainder of the ventricular myocardium is dependent on slow myocardial conduction. Aberration occurs when there are abnormalities of intraventricular conduction in response to changing heart rate, and when the conduction over the His–Purkinje conduction system is delayed or blocked in either the right or left bundle branch. RBBB is more common, occurring in 80% of cases. The aberration may be fixed, occurring in normal sinus rhythm at a slow heart rate, or it may be functional and present only during tachycardia. SVT with antegrade conduction via an accessory pathway, such as in Wolff–Parkinson–White syndrome, accounts for 1% to 5% of all WCT. The accessory pathway is an anomalous AV connection that inserts directly into ventricular myocardium at the base of the ventricle along the mitral or tricuspid valve annulus. Ventricular activation is initiated at this insertion point and is termed ventricular preexcitation. Preexcited tachycardia can occur with SVT with antegrade conduction via the accessory pathway. The accessory pathway is not part of the tachycardia circuit and is not essential for its perpetuation. The other form of preexcited tachycardia can occur with antidromic reciprocating tachycardia, in which the accessory pathway is part of the tachycardia circuit (Fig. 29.4). Another form of WCT is SVT with an intraventricular conduction delay. This can occur in patients with cardiomyopathy, corrected congenital heart disease such as tetralogy of Fallot, or Ebstein anomaly, in which myocardial conduction is further impaired. The conduction abnormality is usually apparent during normal sinus rhythm. Some medications are capable of producing nonspecific widening of the QRS complex during SVT. These include Na+ channel blockers, especially Class IC agents (flecainide, encainide), less so Class IA antiarrhythmics (quinidine, procainamide, disopyramide), and amiodarone. The most common example is a patient with atrial flutter being treated with flecainide. Flecainide can induce flutter rate slowing to permit 1:1 AV nodal conduction and a secondary increase

in the ventricular rate with a wide QRS complex. This is as a result of the slow ventricular conduction in response to the Na+ channel blockade. This can be easily and erroneously interpreted as VT (Fig. 29.5). Electrolyte abnormalities such as hyperkalemia can cause widening of the QRS complex and can be mistakenly interpreted as VT. The morphology is typically LBBB. 3. Ventricular paced rhythms can also mimic WCT (Fig. 29.6). Most pacemakers are dual chamber, with a lead in the right atrium and one in the right ventricle. Pacing of the right ventricle causes an LBBB QRS morphology. The surface ECG representation of the pacing stimulus is less apparent with the use of bipolar pacing modes and a resultant decrease in the energy requirement for reliable ventricular pacing. Therefore, the pacing spike may be overlooked or even absent from ECG tracings. A wide QRS tachycardia can occur in any SVT with atrial tracking, in which the ventricle is paced in response to atrial sensing. In these cases, it is essential to obtain an adequate history and to analyze a previous ECG to evaluate the baseline morphology of the QRS complex. 4. Pacemaker-mediated tachycardia can also produce a WCT. The pacemaker is itself responsible for the tachycardia when ventricular pacing results in retrograde conduction to the atrium. The pacemaker senses the atrial conduction, resulting in ventricular pacing, which in turn is followed by retrograde conduction to the atrium, resulting in “endless loop tachycardia” (Fig. 29.7). 5. Lastly, artifacts from recording equipment problems (such as fastsweep speed recording) or from external repetitive motion (such as brushing teeth) can present as “WCT” (Fig. 29.8).

FIGURE 29.3 SVT with bundle branch block.

FIGURE 29.4 SVT with preexcitation.

FIGURE 29.5 Atrial flutter with 1:1 conduction.

FIGURE 29.6 Ventricular paced tachycardia.

FIGURE 29.7 Ventricular paced tachycardia. A: Atrial tracking. B: Pacemaker-mediated tachycardia.

FIGURE 29.8 Artifact mimicking WCT.

DIAGNOSIS Clinical Presentation

In order to diagnose the etiology of the WCT, it is important to evaluate the clinical presentation. As mentioned before, obtaining an accurate patient history is crucial in formulating an accurate rhythm diagnosis. A prior history of heart disease, myocardial infarction, or congestive heart failure makes the diagnosis of VT highly suggestive as the cause of the WCT. Akhtar et al. have reported that the positive predictive value of a WCT representing VT in a patient with a prior history of myocardial infarction is 98%. Tchou reported that of patients who had a prior myocardial infarction and a first episode of tachycardia occurring after the infarction, 28 of 29 patients presented with VT and were diagnosed correctly. The older the patient is, the more likely that the tachycardia is ventricular; however, there is a significant overlap with SVT patients. It is also helpful to know if there is any presence of congenital heart disease, or if the patient has a pacemaker or defibrillator. Knowing that the patient has an implantable cardioverter–defibrillator (ICD) raises a concern for pacemaker-associated tachycardia, but more important, the presence of the device suggests that the patient has risk factors for VT. A history of a prior similar episode may also be useful. The first occurrence of the arrhythmia after a myocardial infarction is highly suggestive of VT, whereas SVT may be more likely if there is recurrence of the arrhythmia over several years. The presence of other medical conditions can point to a diagnosis of WCT. For example, in a patient with renal failure, the WCT may be attributable to hyperkalemia. In a patient with known peripheral vascular disease, the WCT may be indicative of VT, because such patients are likely to have underlying coronary artery disease. Knowing what medications the patient is taking, especially cardiac medications, is vital when evaluating WCT. It is important to identify medications that prolong the QT interval, such as dofetilide, sotalol, quinidine, and erythromycin, which can all cause torsade de pointes, a form of polymorphic VT. Electrolyte abnormalities caused by certain medications such as diuretics (hypokalemia and hypomagnesemia) or angiotensinconverting enzyme (ACE) inhibitors (hyperkalemia) may predispose to VT. Patients who are on digoxin are more susceptible to an arrhythmia when hypokalemia is present. The most common arrhythmias are monomorphic VT, bidirectional tachycardia, and junctional tachycardia and typically occur when the plasma digoxin concentration is >2.0 ng/mL. As stated earlier, Class IC agents can cause rate-related aberrant conduction during SVT.

Symptoms such as palpitations, lightheadedness, or chest pain are generally not useful in evaluating the etiology of the WCT. One of the priorities in evaluating a patient with WCT is determining if the patient is hemodynamically stable or unstable. The patient’s blood pressure and heart rate are required. In a patient who is unstable, emergency cardioversion is required and the mechanism of the arrhythmia may not necessarily be known. VT can be present when the patient is hemodynamically stable and should not be mistaken for SVT, lest the patient be given inappropriate medical therapy (such as adenosine or verapamil) that can lead to hemodynamic compromise with VT. When the patient is hemodynamically stable, a more detailed physical examination can be performed. Inspection of the chest can point to underlying cardiovascular disease when there is a sternal incision, a pacemaker, or defibrillator. AV dissociation occurs in 60% to 75% of patients with VT and is a result of the atria and ventricles depolarizing independently. It almost never occurs in SVT. This finding is usually identifiable on the surface ECG. However, it is also possible to make this diagnosis on physical examination by assessing the jugular venous pulsation. Cannon A waves are irregular pulsations that are of greater amplitude than the normal jugular venous waves, and occur intermittently when the atrium and ventricle contract simultaneously. When the tachycardia rate is slower, there can be variable intensity of the first heart sound. However, evaluating this may not be practical in an acute situation. Laboratory tests should be performed for patients with WCT to determine potassium and magnesium levels. If the patient is on digoxin, it is also important to obtain the serum digoxin level. If a chest x-ray is available, one can readily identify the presence of a pacemaker, defibrillator, or sternal wires that might point to underlying structural heart disease.

Provocative Maneuvers Certain bedside maneuvers can be performed to distinguish VT from SVT. The Valsalva maneuver or carotid sinus massage enhances vagal tone, which depresses sinus nodal and AV nodal activity. These maneuvers will slow the heart rate during sinus tachycardia, but once they are completed, the heart rate will increase again. If the patient is in SVT, these maneuvers may terminate the rhythm. If the patient is in an atrial tachycardia or flutter, the

rhythm will persist though the ventricular rate may be slower, thus uncovering the background atrial activity. These maneuvers can also elicit VA conduction block, which can induce AV dissociation during VT. Certain medications can be used to diagnose the tachyarrhythmias. For example, adenosine, given in 6- to 12-mg boluses intravenously during WCT, can result in one of the following scenarios: 1. The tachycardia terminates, making it more likely to be supraventricular in etiology, invoking AV node participation. Some atrial tachycardias may also terminate with adenosine. 2. AV block occurs, uncovering the background atrial activity such as atrial tachycardia, flutter, or fibrillation, thus allowing the diagnosis of an atrial tachyarrhythmia. 3. If 1:1 AV association is present and evident during WCT, adenosineinduced AV block results in AV dissociation, thus making the diagnosis VT. Adenosine has a short half-life of about 10 seconds. However, it has to be used with caution, because it may cause hemodynamic compromise in a patient with VT. Some paroxysmal VT in structurally normal hearts may terminate with adenosine. Termination of the rhythm with lidocaine suggests VT as the mechanism. Amiodarone and procainamide, however, will not diagnose the rhythm if the WCT is terminated. Beta-blockers may be given as well. They can terminate SVT or uncover AV dissociation during VT in a manner similar to adenosine. It is important that verapamil not be given if the diagnosis is in question, because it can lead to significant hemodynamic compromise in VT and induce ventricular fibrillation and cardiac arrest.

ECG Criteria The most reliable way to differentiate VT from SVT is by evaluating the ECG. A 12-lead ECG is more helpful than a rhythm strip. A rhythm strip may be additive as a result of analyzing the beginning and termination of the tachycardia. A previous ECG during a normal rhythm will help to identify the baseline QRS morphology and the presence of Q waves that might suggest a

prior myocardial infarction. Ventricular preexcitation may be suggested if there is the presence of delta waves. There are several ECG criteria and different algorithms that may be used to differentiate VT from SVT in WCT: 1. The tachycardia rate has no diagnostic value in determining the mechanism of the WCT. 2. Regularity of the RR intervals is also not a useful criterion, because VT can be irregular in patients on antiarrhythmic medications. 3. QRS complex duration can be useful in differentiating VT from SVT. The WCT is more suggestive of VT when the QRS duration is >140 ms with an RBBB morphology and >160 ms with an LBBB morphology. A study by Wellens showed that all of 70 patients with WCT due to SVT had QRS complex durations 140 ms. Another study, by Akhtar, showed that 15% of patients with VT had QRS complex duration 140 ms with RBBB pattern or >160 ms with LBBB pattern correlates with VT. Wide QRS complex duration can still be seen with preexcitation, ventricular pacing, use of antiarrhythmic drugs, and marked baseline intraventricular conduction delays. VT in structurally normal hearts may have a relatively narrow QRS complex in a case with idiopathic left ventricular VT. 4. The QRS complex axis may also be helpful in diagnosing WCT. A right superior QRS complex axis in the frontal plane is more suggestive of VT. Presence of LBBB and right axis deviation is also almost always due to VT. Presence of Q waves that are also present in normal sinus rhythm suggests prior myocardial infarction, which makes the diagnosis of VT more likely. Pseudo-Q waves can be seen in SVT, which represents retrograde atrial activation. 5. QRS complex concordance in the precordial leads is highly predictive of VT, with a specificity as high as 90% or greater. The sensitivity is low because it is only present in 160 ms RBBB with monophasic R in V1 LBBB with monophasic R in V6

5.

ANSWERS 1.

Correct Answer: D. rSR′ in V1 Options A through C are all part of the Brugada algorithm. The last step of the Brugada algorithm when options A through C are not met is to refer to the morphologic criteria in V1 and V6. A RBBB pattern with an rSR′ is more suggestive of SVT.

2.

Correct Answer: B. Capture; VT

The third beat is a capture beat which is highly suggestive of VT. The second beat is actually a fusion beat which would also be indicative of VT.

3.

Correct Answer: C. Digoxin This strip (Fig. 29.21) shows bidirectional VT and can be caused by digoxin.

4.

Correct Answer: A. VT The rhythm strip (Fig. 29.22) clearly demonstrates AV dissociation which is indicative of VT.

5.

Correct Answer: D. LBBB with monophasic R in V6 The presence of a LBBB pattern throughout the precordial leads with a monophasic R (no q waves) supports the diagnosis of SVT instead.

SUGGESTED READINGS Akhtar M, Shenasa M, Jazayeri M, et al. Wide QRS complex tachycardia: reappraisal of a common clinical problem. Ann Intern Med. 1988;109:905-912. Baerman JM, Morady F, DiCarlo LA, et al. Differentiation of ventricular tachycardia from supraventricular tachycardia with aberration: value of the clinical history. Ann Emerg Med. 1987;16:40-43. Belhassen B, Rotmensch HH, Laniado S. Response of recurrent sustained ventricular tachycardia to verapamil. Br Heart J. 1981;46:679-682. Brugada P, Brugada J, Mont L, et al. A new approach to the differential diagnosis of a regular tachycardia with a wide QRS complex. Circulation. 1991;83:1649-1659. Buxton AE, Marchlinski FE, Doherty JU, et al. Hazards of intravenous verapamil for sustained ventricular tachycardia. Am J Cardiol. 1987;59:1107-1110. Coumel P, Leclercq JF, Attuel P, et al. The QRS morphology in post-myocardial infarction ventricular tachycardia: a study of 100 tracings compared with 70 cases of idiopathic ventricular tachycardia. Eur Heart J. 1984;5:792-805. Curione M, Fuoco U, Borgia C, et al. An electrocardiographic criterion to detect AV dissociation in wide QRS tachyarrhythmias. Clin Cardiol. 1988;11:250-252.

Gelband H, Waldo AL, Kaiser GA, et al. Etiology of right bundle branch block in patients undergoing total repair of tetralogy of Fallot. Circulation. 1971;44:1022-1033. Kindwall KE, Brown J, Josephson ME. Electrocardiographic criteria for ventricular tachycardia in wide complex left bundle branch block morphology tachycardias. Am J Cardiol. 1988;61: 12791283. Miller JM. The many manifestations of ventricular tachycardia. J Cardiovasc Electrophysiol. 1992;3:88-107. Miller JM. Ventricular tachycardia: ECG manifestations. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology: From Cell to Bedside. 2nd ed. WB Saunders; 1995:990-1008. Miller JM, Marchlinski FE, Buxton AE, et al. Relationship between the 12-lead electrocardiogram during ventricular tachycardia and endocardial site of origin in patients with coronary artery disease. Circulation. 1988;77:759-766. Morady F, Baerman JM, DiCarlo LA, et al. A prevalent misconception regarding wide-complex tachycardias. JAMA. 1985;254:2790-2792. Nathan AW, Hellestrand KJ, Bexton RS, et al. Proarrhythmic effects of the new antiarrhythmic agent flecainide acetate. Am Heart J. 1984;107:222-228. Pick A, Langendorf R. Differentiation of supraventricular and ventricular tachycardias. Prog Cardiovasc Dis. 1960;2: 391-407. Rankin AC, Oldroyd KG, Chong E. Value and limitations of adenosine in the diagnosis and treatment of narrow and broad complex tachycardias. Br Heart J. 1989;62:195-203. Reddy GV, Leghari RU. Standard limb lead QRS concordance during wide QRS tachycardia: a new surface ECG sign of ventricular tachycardia. Chest. 1987;92:763-765. Steinman RT, Herrera C, Schuger CD, et al. Wide QRS tachycardia in the conscious adult: ventricular tachycardia is the most frequent cause. JAMA. 1989;261:1013-1016. Vereckei A, Duray G, Szenasi G, et al. New algorithm using only lead aVR for differential diagnosis of wide QRS complex tachycardia. Heart Rhythm. 2008;5:89-98. Wellens HJJ, Bar FWHM, Lie K. The value of the electrocardiogram in the differential diagnosis of a tachycardia with a widened QRS complex. Am J Med. 1978;64:27-33. Wellens HJJ, Brugada P. Diagnosis of ventricular tachycardia from the 12 lead electrocardiogram. In: Barold SS, ed. 12-Lead Electrocardiography. Cardiology Clinics. Vol. 5, no 3. WB Saunders; 1987:511-525.

Wide Complex Tachycardia: Ventricular Tachycardia (VT) versus supraventricular tachycardia (SVT) Worksheet 1. QRS Complex Duration VT: QRS > 140 ms for right bundle branch block (RBBB), QRS > 160 ms for left bundle branch block (LBBB) 2. QRS Complex Axis VT: right superior

3. Capture and Fusion Complexes 4. QRS Precordial Concordance 5. WCT: Brugada’s Criteria I Step 1.Absence of an RS complex in all precordial leads? Step 2.R-to-S interval >100 ms in one precordial lead? Step 3.AV dissociation? Step 4.Morphology criteria for VT present in both V1 to V2 and V6? RBBB morphology

6. WCT: Brugada’s Criteria II Step 1.Predominantly negative QRS complex in precordial leads V4 to V6? Step 2.Presence of a QR complex in one or more of leads V2 to V6? Step 3.Atrioventricular dissociation? 7. Diagnosis: ECG Criteria Miscellaneous Conditions 1. QRS complex during WCT narrower than during NSR: suggests VT. 2. Contralateral BBB in NSR and WCT: suggests VT. 3. Rapid irregular WCT + beat-to-beat QRS-to-QRS interval variation: atrial fibrillation with WPW. 8. Special Cases 1. Misclassification of SVT for VT: Preexcited tachycardia, paced ventricular rhythm. 2. Misclassification of VT for SVT: BBR-VT (without evidence of AV dissociation). 3. Narrow QRS VT: ILV-VT

CHAPTER 30

Pacemakers and Defibrillators DIVYANG PATEL, BRUCE L. WILKOFF AND KHALDOUN G. TARAKJI

CARDIAC PACING Cardiac pacing is the only definitive therapy for symptomatic bradycardia. Whether iatrogenic, ischemic, or intrinsic conduction system disease is present, cardiac pacing can be a temporary bridge to recovery, a backup safety therapy, or a permanent therapy, depending on the clinical scenario. What follows is a review of major topics and advances in the field of cardiac pacing.

Indications Indications for cardiac pacing vary with the clinical scenario. The major determinant of need for permanent pacing is the anticipated duration of the pacing indication. For example, symptomatic bradycardia associated with a toxic ingestion of a nodal blocking drug (e.g., digitalis, toluene) or infection (e.g., Lyme carditis) can be anticipated to resolve as the drug/toxin is cleared and/or treated. Temporary pacing may be indicated in the short term, but a permanent device is usually not needed. Alternatively, a transient neurocardiogenic (cardioinhibitory) bradycardic episode may resolve spontaneously, and temporary pacing should not be needed. However, if episodes recur on medical therapy to the point of causing recurrent syncope, a permanent pacemaker is indicated to protect the patient from subsequent syncopal episodes.

Temporary Pacing

In the emergency department setting, transcutaneous pacing can be used as a bridge to a transvenous temporary pacing system in the setting of symptomatic bradycardia of any etiology with hemodynamic compromise. In the critical care setting, temporary pacing can be a life-saving bridge to recovery or, further, to a definitive therapy for the underlying cause of bradycardia. The indications can roughly be divided into those related to ischemia, and all other categories. Acute myocardial infarction can be associated with bradycardia due to either sinus bradycardia, which does not require therapy unless it is causing hemodynamic compromise, or due to AV block or intraventricular block. AV block can be (a) intranodal, which is usually associated with inferoposterior infarcts (right coronary artery [RCA] 90%, left circumflex artery [LCX] 10%), manifests as first degree or Mobitz I pattern, is usually transient with benign prognosis, and rarely requires temporary pacing and almost never requires permanent pacing, or (b) infranodal, which is usually associated with anteroseptal infarcts (left anterior descending artery [LAD]), manifests as Mobitz II or third-degree block, is usually transient but may persist, and carries a poor prognosis as it signifies extensive infarction; it often requires temporary pacing and if it persists permanent pacing. In general, “high-degree” heart block such as Mobitz type II seconddegree heart block and third-degree heart block warrant temporary pacing during the acute phase of anterior (LAD territory) infarcts or inferior (RCA territory) infarcts. Further, new bifascicular block or alternating bundle branch block reflects ischemia within the interventricular septum and warrants temporary pacing as a backup in case of progression to complete heart block. Refractory bradycardia in the setting of an infarct in any territory necessitates temporary pacing. In the absence of an acute myocardial infarction, symptomatic bradycardia with or without AV dissociation and third-degree AV block with ventricular escape warrant temporary pacing. Backup pacing indications include temporary ventricular pacing during right heart catheterization in the setting of preexisting left bundle branch block (LBBB), new bundle branch block or AV block in the setting of endocarditis, and essential pharmacologic therapies that may induce or exacerbate bradycardia. In contrast to patients with ischemia, certain patients with endocarditis, electrolyte/drug abnormalities, or infection may require prolonged temporary pacing until

recovery of intrinsic conduction system and therefore may benefit from an active fixation lead over a passive pacing lead. Temporary pacing systems with temporary epicardial atrial and ventricular wires are routinely used in the setting of open heart surgery. These systems are used to optimize cardiac output coming off cardiopulmonary bypass, and subsequently as a backup system in case AV nodal conduction block occurs postoperatively, especially in the setting of valvular heart surgery.

Permanent Pacing The indications for permanent pacing are listed in detail in the 2018 ACC/AHA/HRS guidelines on the evaluation and management of patients with bradycardia and cardiac conduction delay: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. This document is summarized in Table 30.1.

Table 30.1 Indications for Permanent Pacemakers

AV, atrioventricular; MI, myocardial infarction; SND, sinus node dysfunction; VT, ventricular tachycardia; LV, left ventricular; EPS, electrophysiology study; CRT, cardiac resynchronization therapy; NYHA, New York Heart Association; HV, Histo ventricular conduction time; DCM, dilated cardiomyopathy; LVEF, left ventricular ejection fraction; HOCM, hypertrophic obstructive cardiomyopathy. Derived from Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS guidelines on the evaluation and management of patients with bradycardia and cardiac conduction delay: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. Circulation. 2019;140:e382-e482.

Device Features Single-chamber devices that only pace the ventricle or atrium have fallen by the wayside in favor of more sophisticated dual chamber atrioventricular pacing devices that have the ability to track the sinus node rate when appropriate and pace the ventricle after a set delay or pace in the atrium if the intrinsic sinus rate falls below a set lower rate limit. Further, cardiac resynchronization therapy (CRT) with biventricular pacing has a significant beneficial role in patients with symptomatic heart failure (New York Heart Association [NYHA] Class III and ambulatory Class IV) and evidence of left ventricular dysynchrony (EF ≤ 35% and wide QRS duration ≥120 ms). Recent advances in pacing have led to an increased interest of implanting a His pacing lead in the His bundle region to allow for more physiologic

pacing than that produced by right ventricular pacing. Early data suggest that it may be a better alternative than RV pacing and an alternative option for CRT nonresponders or when the implantation of coronary sinus lead fails, though more data are needed on its long-term outcomes and the patient population that would derive the most benefit given its difficult learning curve for implantation. Patients who may not need atrioventricular pacing, biventricular pacing, or patients with difficult transvenous/surgical anatomy or infection history may be candidates for a leadless pacemaker. This is a device the size of a capsule that is implanted into the RV via the femoral vein and paces the patient in VVI mode. Figure 30.1 shows a schematic of pacemaker timing cycles.

FIGURE 30.1 Schematic of important device timing cycles and impulses. PVARP: Post-ventricular atrial refractory period

Rate-Adaptive Pacing A variety of methods have been employed to allow for implantable pacemakers to increase their pacing rate in the setting of metabolic demand for increased cardiac output. The most commonly employed methods include activity sensors (vibration, acceleration), or minute ventilation sensors. Other sensors include peak endocardial oxygen sensors and right ventricle

(RV) impedance-based sensors, which have the advantages of responding to nonexertional stimuli (emotions). These techniques utilize vibration, acceleration, minute ventilation, or other measurements as a surrogate for increased metabolic demand for oxygen delivery. In patients with chronotropic incompetence, or the inability to increase cardiac output in response to exercise, rate-adaptive devices can utilize these surrogates to increase the pacing rate and therefore increase cardiac output. There are advantages and disadvantages to each type of sensor system. Vibration sensors and accelerometers provide an almost immediate rise in rate and therefore cardiac output when they detect activity. However, they can be “fooled” by stimuli external to the patient that mimics patient activity (i.e., turbulence during flight, etc.). The accelerometer tends to respond more specifically to patient activity than does the motion sensor. The advantage of the minute ventilation sensor is that it responds specifically to the patient’s respiratory rate—a parameter that is controlled by the brainstem. Although this parameter perhaps more reliably reflects the degree of patient exertion, it tends to lag behind the initiation of strenuous activity. Dual-sensor systems that utilize data collected from more than one sensor modality may actually be best suited for effective rate-adaptive pacing.

Mode Switching Another feature of dual-chamber cardiac pacemakers that allows the devices to respond to changes in the physiology of the patient is mode switching. Mode switching is the ability of the device to revert to a separate, backup pacing mode in the event that the primary pacing mode no longer best serves the patient’s pacing need. For example, in a patient with AV nodal block, a dual-chamber device may be programmed to sense or track the patient’s intrinsic sinoatrial rate and to pace the ventricle after a set delay within the range of 60 to 120 beats/min (bpm). If the atria begin to fibrillate, the sensed atrial rate would exceed the rate parameter and the device would switch modes to a backup ventricular-only mode with a set rate sufficient to prevent hemodynamic compromise. If the patient reverts to sinus rhythm subsequently, the device would recognize the atrial rate back within the set parameter range and switch back to the primary mode, tracking the atrium and pacing the ventricle. Mode switching allows for the maximum responsiveness to the patient’s intrinsic rhythm. These devices are most

commonly programmed DDDR and revert to DDI, DDIR, or VVIR during periods of high atrial rates.

Other Programmable Features Modern pacemakers now include a myriad of programmable features to better match the patient’s physiologic status. They can be programmed to pace at a lower “sleep” rate during typical sleeping hours, with absence of strenuous activity confirmed by the devices metabolic sensing system. Programmable pulse width and output allow the programmer to optimize the impulse specifications to ensure capture while preserving battery power. Diagnostic information and event data including mode-switching data can be stored and retrieved later to assess for the presence and prevalence of atrial arrhythmias and other events. Atrial and ventricular electrograms can be obtained and stored. Device status data can also be retrieved, including battery usage and projected battery life given current settings.

Leads The pacing leads conduct the electrical pacing impulse to the myocardium and conduct the intrinsic electrical activity of the myocardium to the sense amplifiers within the device. Unipolar leads, which have a single electrode at their tip, exhibited a large pacing artifact on ECG and direct current from their tip to the can of the device through the patient’s tissues, or vice versa. For this reason, problems such as pectoral, intercostal, or diaphragmatic stimulation are more likely to occur, particularly in implants requiring higher outputs to capture the ventricle. Bipolar leads have two electrodes with close proximity at their tip and direct current proximal to distal or distal to proximal over much smaller distances. These leads can achieve capture of the myocardium with lower output energies and thus are more efficient. They are capable of unipolar function as well, but with the same limitations as standard unipolar leads. Furthermore, they are less likely to sense noncardiac signals than unipolar leads. Of note, bipolar leads are by necessity larger and stiffer than unipolar leads and have been historically more prone to mechanical failures than unipolar leads. Coronary sinus leads are small, highly flexible unipolar or bipolar leads. They can be directed from the right atrium via the coronary sinus into a branch cardiac vein for the purpose of pacing the left ventricle in synchrony

with the RV in patients with ventricular dysfunction and delayed intraventricular conduction, usually manifest as a LBBB. Epicardial leads can be placed surgically using minimally invasive techniques or during open heart surgery for another indication such as valve surgery for endocarditis and subsequently utilized instead of transvenous leads for standard pacing or more commonly for CRT (biventricular pacing) in patients without a suitable coronary sinus anatomy. Often two leads are placed at the time of surgery and one of the two is subsequently utilized for biventricular pacing, depending on the thresholds and pacing characteristics of each at the time of device implant. A variety of fixation techniques are utilized to maintain the contact of the lead tip with the myocardium. Active fixation leads employ a fixed extended or retractable screw to engage the myocardium. These systems allow for better localization of the lead tip at the desired site of implantation during deployment of the fixation helix. Passive fixation systems utilize plastic projections near the distal electrode that entrap in the trabeculations of the right ventricle or the right atrial appendage to maintain the position of the lead. As lead implants “mature” over time, pacing thresholds tend first to rise due to inflammation and then improve as healing continues and the inflammation resolves. Most leads have a small amount of steroid impregnated at the lead tip that reduces the size of the fibrotic tissue capsule and reduces the chronic thresholds.

Basic Concepts of Impulses and Timing Following is a review of some basic concepts in pacemaker theory that are central to an understanding of the clinical application of pacing technology. Stimulation threshold: The minimum amount of electrical energy that consistently produces a cardiac depolarization. The energy is a combination of voltage and pulse duration. It can be expressed in terms of amplitude (milliamperes or volts), pulse duration (milliseconds), charge (microcoulombs), or energy (microjoules). Voltage output: The amount of voltage being delivered to the heart every time the pacemaker emits a stimulus. It is expressed in volts (V).

Impedance (R): Resistance of flow of current across the lead. Used to measure lead integrity over time. High or low values can indicate lead fracture. Pulse width (or pulse duration): The length in milliseconds the voltage is delivered to the heart. Strength–duration curve: The hyperbolic relationship between the voltage output and the pulse width that defines the stimulation threshold (Fig. 30.2). Sensing: Sensing occurs when the electrical wave front through the myocardium passes directly underneath the electrode. Atrial sensitivity: A programmed parameter that defines the largest signal that will be ignored by the device and thus determines which signals are detected by the pacemaker or implantable cardioverter/defibrillator (ICD) in the atrial channel. Atrial sensing in the dual-chamber pacing mode, DDD, will inhibit the atrial stimulus which would occur at the end of the atrial escape interval (V-to-A interval), initiate the AV interval, and trigger the ventricular output at the end of the AV interval. Ventricular sensitivity: A programmed parameter that defines the largest signal that will be ignored by the device and thus determines which signals are detected by the pacemaker or ICD in the ventricular channel. Ventricular sensing in the dual-chamber pacing mode, DDD, will inhibit both atrial and ventricular stimuli that were scheduled to be output at the end of the atrial escape interval (atrial) or AV interval (ventricle) and initiate a new atrial escape interval (V-to-A interval). Atrial oversensing: Sensing on the atrial channel that occurs due to signals on the atrial lead either related to signals originating outside the atrium, such as far-field ventricular signals, myopotentials from the pectoralis major muscle or diaphragm, or from noise originating from a dysfunctional lead (insulation or conductor fractures or a loose set screw). Depending on the mode of pacing, atrial oversensing will either inhibit or trigger atrial and/or ventricular stimuli. Ventricular oversensing: Sensing on the ventricular channel that occurs due to signals on the ventricular lead either relating to signals originating outside the ventricle, such as myopotentials from

the pectoralis major muscle in a unipolar lead system or from lead dysfunction secondary to insulation or conductor fracture or loose set screws. Sometimes the ventricular channel will oversense the atrial paced output and inhibit the ventricular output. This is called crosstalk inhibition and is usually prevented by a blanking of the ventricular sensing amplifier during the atrial paced outputs. Chronotropic competence: The ability to match cardiac output to the metabolic needs of the body by appropriate modification of the heart rate. Minimum rate: Also called the escape rate, this is the slowest rate at which the pacemaker will allow the heart to beat. The minimum paced rate is calculated by the ventricular paced or sensed event to atrial paced output interval plus the programmed A–V delay measured in milliseconds and converted to rate by dividing 60,000 by that sum. V–A interval: Also called the atrial escape interval, this is calculated by subtracting the paced AV interval from the minimum rate interval. It is initiated by a paced or sensed ventricular event and concludes with a paced atrial event or is interrupted by either an atrial or ventricular sensed event. A–V delay: This programmed interval is initiated by an atrial sensed or paced event and is terminated with a ventricular paced stimulus unless interrupted by a ventricular sensed event (either a conducted beat through the AV node or a premature ventricular beat). Often AV delays initiated by sensed atrial events are programmed to be shorter than AV delays initiated by atrial paced events. Upper rate limit: The fastest rate at which the ventricular channel can track intrinsic P waves or, in the case of rate-adaptive pacing on the basis of a sensor, the fastest rate at which the ventricular channel can track the sensor rate algorithm. The atrial tracking or upper rate limit is constrained by dividing 60,000 by the sum of the sensed AV delay and the postventricular atrial refractory period (PVARP). PVARP: This is the Post-Ventricular Atrial Refractory Period. The PVARP is the timeframe during which the atrial channel is refractory after either a paced or sensed (R wave) ventricular event.

Its purpose is to prevent atrial sensing and tracking of any V–A (retrograde) conduction of ventricular events to the atrium that would trigger a pacemaker-mediated tachycardia (see later).

FIGURE 30.2 The strength–duration curve.

Programming Device programming has become more complex as dual-chamber pacing systems have become ubiquitous and biventricular pacing is becoming common place. It is important to note that the basic parameters discussed above can usually be derived with caliper measurements of the intervals observed on a 12-lead electrocardiogram (ECG) or rhythm strip. Following is a concise review of programming codes and timing cycles that provide the underpinnings of device programming.

Codes A standard coding system has been adopted to delineate the basic settings of the device as follows: The first designation is the chamber paced, the second designation is the chamber sensed, the third designation is the device

response to a sensed event, and the final designation reflects the rateadaptive status of the device. There is a fifth position in the code that was originally used to indicate the antitachycardia response that the device will provide during a tachycardia, but now indicates whether multisite pacing is present or not. Table 30.2 reviews the mode codes in detail.

Table 30.2 Mode Codes for Cardiac Pacemakers

As an example, a DDIR pacemaker can pace in both the atrium and the ventricle, and sense activity in both the atrium and the ventricle. Further, it will inhibit upon sensing intrinsic activity, and it has rate-adaptive functionality as well. A VOO device will pace the ventricle asynchronously, without sensing intrinsic activity.

Timing Cycles When a dual-chamber device paces the atrium, the ventricular channel is blanked for a period of 20 to 40 ms as a safety feature to prevent inhibition of the ventricular channel by far-field (ventricular) sensing of the atrial paced output. The blanking period prevents “crosstalk inhibition,” which could cause, in patients with complete lack of AV conduction, a string of atrial paced events and ventricular asystole. After the blanking period, the ventricular channel is open to sensed events. Typically, the first 100 ms is the safety alert period. If, during this alert period a sensed event occurs, then the AV interval is abbreviated, usually to 120 ms. This abbreviated AV delay is designed to prevent pacing during the vulnerable period of the ventricle, for instance, when the sensed event is caused by a premature ventricular depolarization. During the remainder of the AV delay (after the blanking and safety alert period), any sensed ventricular event will cause the ventricular

output to be inhibited and reinitiate the atrial escape interval. If by the end of the programmed AV interval no event has been sensed, the device will pace the ventricle. After every paced or sensed ventricular event, a PVARP is initiated. During this period, the atrial channel is refractory to detecting atrial activity. The purpose of the PVARP is to prevent detection of atrial activity produced by retrograde conduction through the AV node. Without making the atrium refractory to retrograde atrial events (V-to-A conducted beats), an endless loop cycle can be set up that continues until the retrograde conduction fails. This endless loop tachycardia is one of several types of pacemaker-mediated tachycardia (see Fig. 30.1 for a schematic of pacemaker timing cycles in comparison to the surface ECG).

Diagnostics Modern pacing devices are capable of storing tremendous amounts of data and reporting data in a variety of usable formats. Following is a brief review of device diagnostics and their applications. Histograms: Histograms are a statistical report of a parameter describing the relative frequency of an event relative to time, heart rate, or another parameter. Histograms do not correlate symptoms to specific events, and from them one can only infer cause and effect (Fig. 30.3). Trends: Trends evaluate the progression of a parameter over time. They are not a statistical representation but instead describe the correlation of an activity over time with symptoms. Trends can document concurrence of patient and rhythm events if interrogated quickly after the event occurs. Trends require extrapolation to connect patient and rhythm events (see Fig. 30.3). Event monitoring: Event monitoring captures an exact record of an event as characterized by electrograms, marker channel, and intervals. These monitored records are not statistical reflections of data but the actual recordings. Therefore, they can capture the relationship of symptoms and objective data. They require neither inference nor extrapolation (see Fig. 30.3).

FIGURE 30.3 Histogram: ventricular hysteresis.

Troubleshooting and Complications While pacemaker implantation is a low-risk procedure, proper device follow-up and troubleshooting must be done to ensure pacemaker integrity. Device troubleshooting most often involves interrogation of the device and adjustment of the pacing mode or timing cycles in order to optimize device function. Further, device interrogation using a programmer can reveal diagnostic information about the integrity of the leads, status of the battery, and performance of the device’s algorithms, including the behavior of the rate-adaptive sensor function. A review of some specific device troubleshooting issues follows. Pacemaker Mediated Tachycardia Endless loop tachycardia is a type of pacemaker-mediated tachycardia specific to dual-chamber devices programmed to the VDD or DDD mode. Endless loop tachycardia is triggered by the atrial channel sensing retrograde conduction of a paced ventricular impulse. In response to the sensed event, the ventricle is paced again after the set AV interval, and retrograde conduction to the atrium recurs. As the atrium senses the retrograde V–A signal, the cycle begins again. The phenomenon is terminated by either applying a magnet to the

device, thus reverting the device to nominal asynchronous pacing, or by reprogramming the device to lengthen the PVARP so that the atrial channel is refractory during the retrograde (V–A) conduction.

Pacemaker Syndrome The so-called pacemaker syndrome is a constellation of physical symptoms and signs associated with loss of AV synchrony, most commonly associated with VVI pacing. Affected patients suffer weakness, dizziness, lightheadedness, dyspnea on exertion, and sometimes even orthopnea and dyspnea at rest, independent of their underlying ventricular function. The symptoms result from ventricular pacing, typically with retrograde atrial conduction, which produces atrial contraction against a closed AV valve. The decrease in efficiency associated with loss of atrial kick as well as the increased back pressure within the pulmonary circuit both contribute to the symptomatology. Similar symptoms and physiology can result from atrial pacing with delayed AV conduction. The result is also related to atrial contraction against a closed AV valve. The treatment for pacemaker syndrome is device upgrade to a dual-chamber device. An atrial tracking ventricular pacemaker eliminates the physiologic underpinnings of pacemaker syndrome and typically alleviates the symptoms.

Pacing-Induced Cardiomyopathy A certain subset of patients who are being paced the majority of time with a single ventricular lead may develop pacing-induced cardiomyopathy, which is likely secondary to deleterious neurohormonal remodeling from RV pacing. Therefore, devices are set to minimize RV pacing. Nevertheless, patients with pacemakers should be interrogated about their heart failure symptoms and echoes should be considered in follow-up in patients with pacemakers who there is a strong suspicion for pacing-induced cardiomyopathy. Patients who have developed pacing-induced cardiomyopathy should be considered for upgrade to a CRT device given that the majority will see an improvement in their LVEF and symptoms. In patients with reduced LVEF who have an indication for pacing and high likelihood for having a significant pacing burden, it is reasonable to consider implanting a BiV device instead of a single ventricular lead pacemaker.

Lead Fracture/Failure Lead fracture is the term used to describe failures in the integrity of the lead wires, insulation, and/or coil. Fractures often occur at the ingress of the lead into the thorax within the subclavian vein as it passes between the clavicle and the first rib, particularly at the suture sleeve, due to tight ligatures or a sharp angulation of the lead in the pacemaker pocket. Crush injuries and chronic abrasion at this site are common etiologies of lead fracture. Disruption of the insulation causes a significant reduction of the pacing impedance and is often manifest by intermittent oversensing and either failure to produce a paced output or failure to capture the heart. Disruption of the lead conductor causes an increase in the pacing impedance and can also be manifest by intermittent oversensing and failure either to produce a paced output or to capture the heart. After the ECG, the chest x-ray is often the first diagnostic modality to reveal a lead fracture. Device interrogation typically suggests the diagnosis (abnormally high or low lead impedance, as noted in the previous section).

Infection/Erosion Device infection occurs most commonly from bacterial contamination at the time of device implantation. Most infections do not present within the first month after implantation but are manifest within the first 2 years after implantation. Some infections can be indolent and persist for years before becoming apparent. The most commonly responsible organisms are Staphylococcus species, with gram-negative organisms occurring predominantly in diabetic patients or those otherwise immunocompromised. Physical findings associated with device infection may range from normal pocket appearance to mildly erythematous overlying tissue, to a swollen, boggy pocket and incision line. Occasionally a device will erode through the skin in the setting of a chronic device infection. When the pocket appears normal, the infection is typically endovascular and is unmasked by the presence of fevers and positive blood cultures along with supportive findings from transesophageal echo or chest CT scan. Less commonly, device infection can occur secondary to bacterial endocarditis or other bloodstream infection. Vegetations can sometimes be observed on the leads, most commonly utilizing transesophageal echocardiography.

The treatment for device infection with or without endocarditis is with antibiotics and device and lead extraction. The replacement device cannot be reimplanted at the time of device and lead extraction but should be delayed for few days or longer until it is deemed appropriate from the infectious disease stand point. Not all patients require immediate reimplant after extraction and the indication should be reinvestigated prior to reimplant. The reimplant is usually performed on the contralateral side.

Extraction The most compelling reason for lead extraction is device–related infection, either localized to the pocket or endovascular with associated bacteremia or endocarditis. Other reasons for extraction may include lead migration, untreatable thrombosis or embolism of the lead or lead fragment, or, compromise of venous flow from multiple leads, risking subclavian or superior vena cava (SVC) occlusion with symptoms, or prevent the addition of leads for upgrade to an ICD or BiV system. Lead extraction can range from simply applying traction to a recently implanted lead, to the use of mechanical, electrosurgical, or excimer laser extraction sheaths to facilitate the removal of fibrosed leads from the endovascular surface. Lead extraction using these devices can be complicated by serious bleeding complications leading to tamponade and even death and are thus best relegated to experienced operators in large volume centers.

IMPLANTABLE DEFIBRILLATORS

CARDIOVERTER–

ICDs initiated a new era in the treatment of ventricular tachyarrhythmias. In contrast to modern devices, the early ICD systems were implanted via thoracotomy with epicardial placement of defibrillating patches and sensing electrodes and abdominal implantation of the device can. The devices themselves had no programmability, no significant diagnostics, and an abbreviated battery life of about 1 year. Patients requiring permanent pacing had to have a separate pacing device implanted. Over time, ICD components have reduced in size, allowing for prepectoral implantation with transvenous

leads, possess bradycardia and antitachycardia pacing (ATP), and hundreds of programmable parameters, diagnostics, and event storage, all while device longevity has expanded to 5 to 7 years. The devices now have full pacing and resynchronization capabilities as well.

Indications Indications for implantation of ICDs have expanded greatly over the past decade, based on data collected from the major ICD trials and are summarized in Table 30.3. It is very important to note that all these indications require a reasonable expectation of survival with an acceptable functional status for at least 1 year. ICDs are not indicated for patients with incessant ventricular tachycardia (VT) or ventricular fibrillation (VF), NYHA Class IV patients with drug refractory heart failure who are not transplant candidates or candidates for a CRT device, patients with significant psychiatric illnesses, when VF or VT is amenable to surgical or catheter ablation (e.g., atrial arrhythmias associated with Wolf–Parkinson– White [WPW] syndrome, right ventricular outflow tract [RVOT] or left ventricular outflow tract [LVOT], idiopathic VT in the absence of structural heart disease), or patients with ventricular arrhythmias due to a completely reversible disorder in the absence of structural heart disease.

Table 30.3 Indications for ICDs

VF, ventricular fibrillation; VT, ventricular tachycardia; EPS, electrophysiology study; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NYHA, New York Heart Association; HCM, hypertrophic cardiomyopathy; SCD, sudden cardiac death; DCM, dilated cardiomyopathy.

The Center for Medicare and Medicaid Services (CMS) published updated guidelines in 2005 for reimbursement for ICD implantation, recognizing the data from the primary and secondary prevention trials of ICDs with and without capacity for cardiac resynchronization. The practical (reimbursed) indications for ICD implantation are listed in Table 30.4.

Table 30.4 CMS-Approved (Reimbursed) Indications for ICD Therapy

VF, ventricular fibrillation; VT, ventricular tachycardia; EPS, electrophysiology study; MI, myocardial infarction; HCM, hypertrophic cardiomyopathy; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; DCM, dilated cardiomyopathy. Providers must be able to justify the medical necessity of devices other than single-lead devices.

Devices The current generation of ICDs includes single-chamber VVI devices, dualchamber devices with fully programmable pacing capabilities, and CRT devices capable of biventricular pacing and antitachycardia therapies. As technology has progressed, these devices have become smaller, with better longevity and greater programmability. The diagnostics available allow for extensive troubleshooting and event monitoring.

Lead Systems Typically, single-chamber ICD systems are implanted using active- or passive-fixation multipolar leads with shocking coils that lie in the RV apposed to the endocardium as well as the SVC. With this configuration, the device can deliver energy from the RV (+) coil to the SVC (−) coil or vice versa, or from either coil (+) to the ICD can (−) itself or vice versa. Various investigations have demonstrated that defibrillation thresholds (DFTs) can be reduced using optimal polarity and an “active can” configuration. ICDs can be attached to epicardial leads or patches implanted during surgery. These leads are typically placed using minimally invasive techniques for patients with high DFTs or during open heart surgery performed for other indications. Subcutaneous arrays and even azygous vein leads can be placed. Virtually all ICDs are implanted with transvenous in lieu of surgically placed leads. Dual-chamber devices possess an atrial lead in addition to the ventricular shocking coil lead. The atrial lead is typically a standard bipolar pacing lead without a shocking coil and plays no role in defibrillation. Newer subcutaneous ICDs deliver shocks via left lateral generator and a subcutaneous left parasternal lead. These devices are MRI compatible and preferred in patients who do not need pacing therapy, younger, and/or have had previous transvenous device infections.

Implantation The most common site for device implantation is the left prepectoral space. This site gives access to the left subclavian vein for transvenous lead placement. Especially in “active can” configurations, this site of implantation allows for lower DFTs as the path for energy transmission from can to coil or vice versa traverses the LV myocardium. In the case of prior device infection, scarring, subclavian stenosis, or mastectomy on the left side, the right prepectoral space may be used. Lead implantation technique is much like that used for standard pacing lead implantation; however, there is an impetus to implant the lead tip at the RV apex so that the RV shocking coil rests completely within the right ventricle. The subcutaneous ICD is placed in the 4th to 5th intercostal space in the left axillary region with a subcutaneous parasternal lead tunneled across the rib in a position located just left of the patient’s sternum.

Device Function Detection ICDs have a variety of programmed routines designed to aid in the detection and verification of VT and VF, and to minimize the number of inappropriately delivered therapies. The device must be able to sense low-amplitude highrate signals in VF, while not oversensing far-field atrial activity or ventricular repolarization. Appropriate sensing thresholds must be achieved at the time of implantation, or the device cannot be relied on to appropriately detect and treat malignant ventricular arrhythmias. Detection algorithms utilize counters, and detection criteria are based on signal counts registered faster than the tachycardia threshold criterion programmed into the device. For example, if an ICD is programmed to detect VT at cycle lengths of 30 Gy of radiation and generally presents 15 to 20 years after exposure. There is a greater tendency toward aortic valve disease, followed by mitral and then tricuspid valve disease. Usually, radiation-associated aortic disease is mixed stenosis and regurgitation. Subvalvular AS is a rare form of AS and may be due to a tunnel of muscular tissue or a discrete band or membrane. Subvalvular stenosis should be suspected in any patient who has symptoms of AS or high LV outflow velocities on echocardiography but whose aortic valve is structurally normal. Subvalvular stenosis also presents as a component of the Shone complex: multiple left-sided heart obstructions, including supravalvular mitral stenosis, parachute mitral valve, subvalvular AS, BAV, and aortic coarctation. Additionally, subaortic stenosis may be associated with a patent ductus and ventricular septal defects (VSDs). Over time, the jet from subvalvular stenosis will damage the native aortic valve and will lead to AI. For this reason, early surgical repair of asymptomatic subvalvular stenosis is often recommended. Supravalvular AS is a rare variant of AS that is classically associated with Williams syndrome (child-like facies, peripheral pulmonary stenosis, hypercalcemia) and familial dyslipidemias. A mutation in the gene for elastin has been linked to Williams syndrome. Other cardiovascular associations of supravalvular stenosis include coarctation of the thoracic or abdominal aorta and renal artery stenosis.

Clinical Findings in Aortic Stenosis The history of patients with AS varies with the etiology of the stenosis. Patients with rheumatic heart disease or BAV are more likely to present with symptomatic disease at a younger age. In contrast, patients with degenerative AS are usually older in their seventh or eighth decade, and may present with symptoms without prior knowledge of aortic valve pathology. The symptoms of AS are most frequently the direct result of the heart’s compensatory changes. Initially, patients develop diastolic heart dysfunction, which often manifests as exertional dyspnea. With stress, patients with AS may become significantly symptomatic because their cardiac output cannot augment adequately and left ventricular end-diastolic pressure (LVEDP) markedly increases. Dyspnea and early fatigability result. As the AS progresses, the classic symptoms of angina, syncope, and heart failure develop. This triad of symptoms has been well studied and allows a rough estimate of disease severity and prognosis: if untreated, survival in patients with angina approximates 5 years, with syncope is 3 years, and with heart failure is 1.5 cm2, peak gradient 35 mm Hg. Echocardiography monitoring is recommended every 36 to 60, 24, and 12 months for mild, moderate, and severe PS, respectively.

Treatment of Pulmonic Stenosis For patients with symptoms or elevated gradients, balloon valvotomy is preferred over replacement in patients with favorable valve anatomy and less than moderate pulmonic regurgitation. Indications for intervention

include symptoms with a peak gradient >50 mm Hg or a mean gradient >30 mm Hg, or an asymptomatic patient with a peak gradient >60 mm Hg or a mean gradient >40 mm Hg.

Pulmonary Insufficiency The main etiologies of significant pulmonary insufficiency (PI) are annular dilation due to pulmonary hypertension, dilation of the PA (which may be idiopathic or secondary to Marfan syndrome), a late complication of tetralogy of Fallot repair, or a primary valve disorder, caused by carcinoid, rheumatic disease, or endocarditis. Mild PI is quite common in normal hearts, and even moderately severe PI is hemodynamically well tolerated. Over long periods of time, however, severe PI may create a volume and pressure overload on the RV, which leads eventually to RV dilation and failure.

Physical Findings Pulmonic insufficiency is frequently very difficult to appreciate on physical exam, particularly if the pulmonary pressures are normal. On chest palpation, one may appreciate a hyperdynamic RV. On auscultation, PI may be heard as a low-pitched diastolic murmur along the LSB, which accentuates with respiration. In the setting of pulmonary hypertension, PI results in a Graham–Steel murmur, a high-pitched, decrescendo murmur heard best along the LSB. It immediately follows an accentuated P2. With respiration, this murmur also increases in intensity.

Diagnostic Studies The CXR may variably show RV enlargement. Key data to be obtained from transthoracic echocardiography include RV size and function, PA size and pressures, and the degree of PI. Characteristics of severe PI include RV dilation, color Doppler whose regurgitant jet fills a majority of the RVOT, and a dense regurgitant Doppler signal with a steep deceleration (representing a rapid equalization of pressure between the RV and PA). Stress echocardiography may be used to

assess RV function and reserve. Severe PI may be difficult to evaluate quantitatively with Doppler echocardiography, and cardiac MRI is the imaging technique of choice in quantification of regurgitation and the effect on RV volume and function in this condition. MRI is indicated if there is any doubt as to the severity of PI especially in patients with prior surgery for congenital heart disease such as Fallot tetralogy.

Treatment for Pulmonary Insufficiency Pulmonary insufficiency usually requires valve surgery only if there is progressive evidence of RV dilatation or decrease in exercise capacity. Biologic prostheses or homografts are favored because of lower associated thrombotic risk as compared to mechanical prostheses at this position. Increasingly catheter-based placement of valves is possible at the pulmonary position.

SUGGESTED READINGS Bonow RO, Greenland P. Population-wide trends in aortic stenosis incidence and outcomes. Circulation. 2016;131:969-971. Clavel MA, Magne J, Pibarot P. Low-gradient aortic stenosis. Eur Heart J. 2016;37(34):2645-2657. Fathallah M, Krasuski RA. Pulmonic valve disease: review of pathology and current treatment options. Curr Cardiol Rep. 2017;19(11):108. Genereux P, Stone GW, O’Gara PT, et al. Natural history, diagnostic approaches, and therapeutic strategies for patients with asymptomatic severe aortic stenosis. J Am Coll Cardiol. 2016;67(19):2263-2288. Lindman BR, Clavel MA, Mathieu P. Calcific aortic stenosis. Nat Rev Dis Primers. 2016;3(2). Makkar RR, Thourani VH, Mack MJ, et al. Five-year outcomes for transcatheter or surgical aortic valve replacement. N Engl J Med. 2020;382:799-809. Masri A, Svensson LG, Griffin BP, Desai MY. Contemporary natural history of bicuspid aortic valve disease: a systematic review. Heart. 2017;103(17):1323-1330. Popovic ZB, Desai MY, Griffin BP. Decision making with imaging in asymptomatic aortic regurgitation. JACC Cardiovasc Imaging. 2018;11(10):1499-1513.

Chapter 32 Review Questions and Answers QUESTIONS A 71-year-old otherwise healthy female has been referred to you for evaluation of a murmur. She denies having any symptoms but endorses she is not particularly active. On exam, she has a III/VI systolic murmur best heard at the right upper sternal border, radiating to the apex. Resting transthoracic echocardiogram shows a heavily calcified aortic valve with a peak gradient of 68 mm Hg, mean gradient of 42 mm Hg, and a calculated aortic valve area of 0.9 cm2. The ejection fraction is 65%. What is the most appropriate best next step in her management? Repeat resting echocardiogram in 12 to 24 months Referral for aortic valve replacement Referral for exercise stress echocardiogram Referral for cardiac CT to quantify aortic valve calcification

1.

A. . C. D.

2.

A 75-year-old man with prior bypass surgery is referred to you for shortness of breath and heart failure symptoms. He has a past history of hypertension and chronic obstructive pulmonary disease (COPD). His FEV1 is 1.6 L. He also complains of occasional exertional angina. A recent regadenoson stress, technetium-99m perfusion study revealed a fixed defect in the inferior wall, but no reversible defects. On gated images, the ejection fraction was 25%. On physical exam, his heart rate is 80 bpm and his blood pressure is 110/80. He appears fatigued and somewhat frail. His JVP is elevated to 10 cm. He has bibasilar rales on pulmonary exam. Cardiac exam shows a normal S1 and a paradoxically split S2. There is a harsh III/VI systolic ejection murmur at the LSB, which peaks very late in systole and radiates to the carotids. A II/VI holosystolic murmur is appreciated at the apex that radiates to the axilla. Carotid pulsations are delayed. You order an echocardiogram that confirms the severe LV systolic dysfunction. His LV is mildly dilated. The entire inferior and basal posterior walls are akinetic and thinned. The LAD and LCx territory

A. . C. D.

is hypokinetic. The aortic valve is heavily calcified and has poor leaflet excursion. Peak and mean gradients across the aortic valve are 27 and 17 mm Hg, respectively. By continuity, the aortic valve area (AVA) is 0.8 cm2. There is 2+ mitral regurgitation (MR) due to posterior leaflet restriction. What is your next step in this patient’s management? Suggest left heart catheterization to pursue percutaneous balloon valvuloplasty. Refer for cardiac surgery for aortic valve replacement (AVR) and MV repair. Refer for transcatheter aortic valve replacement. Order dobutamine stress echocardiography. A 37-year-old woman with an active history of IV drug abuse presents to the emergency department with abrupt-onset shortness of breath. She is tachycardic to 110 bpm and has a systolic blood pressure of 95 mm Hg. Her boyfriend reports that over the past 7 days she has been febrile and anorectic. He also adds that the patient was “born with an abnormal” aortic valve. Which of the following findings is inconsistent with acute aortic insufficiency (AI)? Diminished S1 on auscultation Diastolic MR on echocardiography A holodiastolic murmur heard at the LSB Premature closure of the mitral valve on two-dimensional (2-D) echocardiography

3.

A. . C. D.

A 21-year-old male with a past medical history of an unclear murmur presents to you for further evaluation. He reports progressive fatigue. On exam, there is a widely split S2, and a crescendo–decrescendo systolic murmur at the left upper sternal border, that decreases in intensity with inspiration. An echocardiogram shows pulmonic stenosis with a peak gradient of 52 mm Hg and a mean gradient of 32 mm Hg, with an anatomy suitable for percutaneous balloon intervention. What is the next best step in management? A. Referral for percutaneous pulmonic valve balloon valvotomy . Referral for cardiac MRI C. Repeat echocardiogram in 36 months

4.

D. Treadmill stress test

A. . C. D.

A 42-year old female with no past medical history presents to you for evaluation of a murmur. She denies any symptoms. On exam, there is a II/VI systolic ejection murmur heard best in the right upper sternal border. There is also a II/VI decrescendo, blowing, holodiastolic murmur, appreciated best at end-expiration with the patient leaning forward. Echocardiogram reveals a bicuspid aortic valve. Which of the following is least likely to be found in this patient? Dilation of the ascending aorta Coarctation of the Aorta Family history of aortic valve disease Fusion of the left- and noncoronary cusps

A. . C. D.

A 48-year-old female with a past medical history of hypertension presents for evaluation of a murmur. She endorses mild shortness of breath with moderate, but nothing life limiting. On exam, there is a III/VI systolic ejection murmur at the mid-sternum. There is a II/VI decrescendo, blowing, holodiastolic murmur best heard at the left sternal border. Subsequent transthoracic and transesophageal echocardiograms confirm a subaortic membrane with a peak flow acceleration of 52 mm Hg. There is moderate aortic valve insufficiency. There is normal left ventricular size and function. What is the best next step in management? Dobutamine stress echocardiogram Cardiac surgery referral for membrane resection Start metoprolol succinate 25 mg daily Cardiac MRI

5.

6.

7.

A 33-year-old man presents to you to re-establish cardiac care. He has a history of Tetralogy of Fallot s/p Blalock–Thomas–Taussig shunt at 6 months. At 7 years old, he had a surgical RVOT repair and VSD closure. He has been doing well since and has not seen a physician since graduating from college. He denies any symptoms. He denies any history of arrhythmia or syncope. Physical exam reveals a low-pitched diastolic murmur along the left sternal border. An echocardiogram shows at least moderate pulmonary insufficiency.

A. . C. D.

The right ventricle is poorly visualized. The left ventricle has normal function. What is the next best step in management? Repeat echocardiogram in 2 to 3 years Referral for ICD Cardiac MRI Referral for pulmonic valve replacement

A. . C. D.

You see a 48-year-old man in follow-up. He has a history of moderate aortic valve insufficiency due to bicuspid aortic valve. Echocardiogram today shows severe aortic insufficiency. Which of the following would be indications for aortic valve surgery? Ascending aorta stable at 4.0 cm Left ventricular ejection fraction of 58% Left ventricular end-systolic dimension of 5.2 cm Left ventricular end-diastolic dimension of 6.3 cm

A. . C. D.

You are seeing a patient with aortic stenosis. You obtain the following aortic valve measurements on echocardiogram. LVOT diameter = 2.0 cm, VTILVOT = 0.22 m, and VTIAV = 1.0 m. What is the calculated aortic valve area? 0.69 cm2 1.38 cm2 2.76 cm2 0.44 cm2

8.

9.

10. A 50-year-old female presents for follow-up of a dysfunctional aortic

valve. She hasn’t been seen in several years. Over the past 6 months, she has noticed becoming easily fatigued with exertion. On exam, there is a II/VI crescendo–decrescendo systolic murmur at the right upper sternal border, with an associated ejection click. There is a III/VI blowing diastolic murmur at the left sternal border with an associated low-pitched mid-diastolic rumble at the apex. The PMI is displaced laterally. Her echocardiogram shows a bicuspid aortic valve. Which of the following findings would be most suggestive of severe aortic insufficiency? A. A pressure half time of 350 ms . Vena contracta of 0.5 cm

C. Diastolic flow reversal in the aortic sinus D. Mitral regurgitation seen during diastole

ANSWERS 1.

Correct Answer: C. Referral for exercise stress echocardiogram Referral for exercise stress echocardiogram. On exam, this patient has a murmur known as the Gallavardin phenomenon, occasionally auscultated in AS. Echocardiogram confirms severe range aortic stenosis. The patient appears asymptomatic; however, given her sedentary nature, it is difficult to assess symptoms and functional status by history alone. In these situations, exercise stress echo is the diagnostic test of choice to assess functional capacity to help guide timing of interventional therapies. Given this patient has severe-range aortic stenosis, it is recommended she undergo echocardiogram monitoring every 6 to 12 months. Generally, asymptomatic aortic stenosis in this range is managed conservatively until symptoms, decline in functional status, or objective measures of cardiac dysfunction are found. Aortic valve calcium quantification is most useful in cases where the severity of aortic stenosis in uncertain.

2.

Correct Answer: D. Order dobutamine stress echocardiography. This patient has low-gradient AS with moderately severe LV dysfunction. His chief complaint is consistent with AS but could be secondary to CHF or COPD. His physical exam, with narrow pulse pressure, paradoxically split S2, and SEM radiating to the carotids, all suggest AS. Loss of A2 is also consistent with severe AS. The nuclear stress test argues against ischemia. A relatively small fixed defect on nuclear study and preserved wall thickness in the left coronary territory both suggest that the LV dysfunction may be out of proportion to coronary artery disease (CAD) and may be secondary to valvular disease. For patients with low-gradient AS, dobutamine echo can be very helpful in assessing true stenosis versus pseudostenosis. In this patient, we would expect dobutamine to result in an increased EF (contractile reserve), increased gradients across the valve, and a valve area that remained severe. If he has

pseudostenosis and a cardiomyopathy unrelated to the valve disease, dobutamine will increase cardiac output but will not result in significant increases in the transaortic gradient or AVA. Patients with LV dysfunction who have contractile reserve and severe AS should undergo AVR. This patient has no contraindications to valve replacement, and thus valvuloplasty should not be considered definitive treatment.

3.

Correct Answer: C. A holodiastolic murmur heard at the LSB Acute AI typically has a brief, early diastolic murmur. Rapid equilibration of aortic and LVED pressures causes termination of the murmur by mid-diastole. All of the remaining answers are typical of acute AI. A diminished S1 may be seen in acute or chronic AI.

4.

Correct Answer: A. Referral for percutaneous pulmonic valve balloon valvotomy Referral for percutaneous pulmonic valve balloon valvotomy. This patient presents with symptomatic pulmonary stenosis. The indication for intervention in pulmonic stenosis for a symptomatic individual is a peak gradient >50 mm Hg or a mean gradient >30 mm Hg, or an asymptomatic patient with a peak gradient >60 mm Hg or a mean gradient >40 mm Hg. Cardiac MRI can sometimes be useful to assess right ventricle function, or pulmonary insufficiency. However, given symptoms in this case, and valve suitability for percutaneous intervention, a cardiac MRI is not the best next step as it will not significantly alter management. Repeat echocardiogram in 36 months would be appropriate in an asymptomatic individual with mild pulmonic stenosis. As symptoms attributable to PS were found on history, functional stress testing is not needed.

5.

Correct Answer: D. Fusion of the left- and noncoronary cusps Fusion of the left- and noncoronary cusps. Bicuspid aortic valve is the most common congenital heart disease, being found in up to 2% of the population. These valves are associated with early stenosis and

insufficiency. Aortopathy is common in patients with bicuspid aortic valve. Depending on age, follow-up, and definition of aorta dilation, aortopathy is found in 30% to 80% of patients with bicuspid aortic valve. Approximately 20% of people with a bicuspid aortic valve have other congenital abnormalities. Up to 80% of coarctation patients have a bicuspid aortic valve as well. In patients with bicuspid aortic valve, approximately 10% of first-degree relatives will also have bicuspid aortic valve. The most common anatomic cause of bicuspid aortic valve is fusion of the right- and left-coronary cusps (80% of cases), while fusion of the left- and noncoronary cusp is rare (3% of cases).

6.

Correct Answer: B. Cardiac surgery referral for membrane resection Cardiac surgery referral for membrane resection. There are classically four variants of subaortic membrane: a thin discrete membrane, a fibromuscular ridge, a fibromuscular “tunnel-like” narrowing of the LVOT, and accessory mitral valve tissue. In this question, our patient has the most common form of subaortic stenosis —a thin discrete membrane. As this membrane obstructs LVOT flow, a high-velocity systolic flow is generated that can damage the aortic valve and cause subsequent aortic insufficiency. There is a IIb surgical resection indication in asymptomatic subaortic membrane patients to prevent progression of aortic insufficiency (AI) when the peak gradient is ≥50 mm Hg, and there is at least mild AI. While additional imaging may be helpful in cases of diagnostic uncertainty, in this example, the diagnosis has been made clear. Beta blockers have a role in dynamic LVOT obstruction due to conditions like hypertrophic obstructive cardiomyopathy, but limited role in fixed LVOT obstructions, such as this one.

7.

Correct Answer: C. Cardiac MRI Cardiac MRI. Tetralogy of Fallot (TOF) is a congenital heart disease characterized by pulmonic stenosis (usually due to RVOT narrowing), VSD, over-riding aorta, and RV hypertrophy. In modern practice,

these are generally repaired in childhood with surgical repair of the RVOT and closure of the VSD. Long-term complications of this repair are generally pulmonary insufficiency and sudden cardiac death (SCD). When following adults with repaired TOF, it is important to follow RV and pulmonic valve (PV) function, in addition to monitoring SCD risk factors. In our patient he was seemingly asymptomatic, but it is critical to accurately assess RV function in these patients. Cardiac MRI is an elegant test in TOF patients because it allows precise assessment of both RV and PV function. Furthermore, cardiac MRI allows assessment of RV scar, used in SCD risk stratification. The indications for pulmonary valve replacement in TOF patients include moderate-or-greater pulmonic insufficiency with symptoms of heart failure or asymptomatic patients with mild or greater RV dysfunction. Primary prevention with ICDs are sometimes needed in TOF patients who have multiple risk factors, which include LV systolic or diastolic dysfunction, history of nonsustained ventricular tachycardia, QRS ≥ 180 ms, extensive RV scar, and inducible sustained ventricular tachycardia with EP study. In our example, the patient does not yet have any indications for either valve replacement or ICD.

8.

Correct Answer: C. Left ventricular end-systolic dimension of 5.2 cm Left ventricular end-systolic dimension of 5.2 cm. In asymptomatic patients with severe aortic insufficiency, the indications for aortic valve surgery include LVEF < 55%, LVESD > 5.0 cm, LVEDD > 6.5 cm, or undergoing other cardiac surgery. In this question, the only answer that meets a guideline indicated surgical threshold is the LVESD of 5.2 cm.

9.

Correct Answer: A. 0.69 cm2 .69 cm2. In this example, use the radius to calculate the area of the LVOT, and subsequently use the continuity equation to calculate the

aortic valve area:

10. Correct Answer: D. Mitral regurgitation seen during diastole Mitral regurgitation seen during diastole. Generally during diastole, the pressure in the left ventricle is low, allowing passive filling from the left atrium to ventricle. In the cases of severe aortic insufficiency, left ventricular pressure rises rapidly, prematurely closing the mitral valve, and potentially causing diastolic mitral regurgitation. In this example, the patient has a bicuspid aortic valve with auscultation being notable for an ejection click and Austin-flint murmur. Other features of severe aortic insufficiency include dilation of the LV, a vena contracta >0.6 cm, a regurgitant jet >65% of the LVOT, a pressure half time 5 mm is considered “classic” MVP, whereas prolapse with thinner valve leaflets is considered “nonclassic prolapse.”

FIGURE 33.1 M-mode echocardiography showing late-systolic prolapse (arrow) of the mitral valve. Accepted indications for performing echocardiographic study in mitral prolapse include establishing the diagnosis, determining the severity of MR, evaluating leaflet morphology, and defining LV size and systolic function.1,2 An estimate of the right ventricular systolic pressure should also be made, to assess for potential associated pulmonary hypertension. Echocardiography should be used when it can add information to findings available from history and the physical examination. Indications for echocardiography may also include exclusion of MVP in patients diagnosed with MVP when there is no clinical evidence to support the diagnosis. Most patients with mitral prolapse, even if there is a murmur, or if the echocardiogram shows significant MR, do not need antibiotic prophylaxis for endocarditis. The current American Heart Association (AHA)/American College of Cardiology (ACC) guidelines do not recommend routine antibiotic prophylaxis prior to dental procedures for native valve disease. The current recommendations for antibiotic prophylaxis prior to dental procedures include patients with prosthetic cardiac valve, or prosthetic material used in valve repair, and prior episodes of infective endocarditis.3 Prophylaxis during procedures likely to cause bacteremia (including teeth cleaning) is recommended if the patient has had previous endocarditis or if a prosthetic valve has been implanted (Table 33.1).

Table 33.1 Recommendations for Infective Endocarditis Prophylaxis in Valvular Heart Disease

Derived from Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007;116:1736-1754.

The natural history of MVP is frequently benign. Follow-up studies in large population samples show that most patients with MVP do quite well, and most do not develop any significant congestive heart failure, atrial fibrillation (AF), stroke, or syncope. After a prolonged asymptomatic

interval, a small percentage of patients with MVP develop more severe MR, ruptured mitral valve chordae (flail), left atrial and ventricular enlargement, or AF.4 In addition, with gradual progression of MR, LV dilatation and dysfunction may occur, leading to congestive heart failure. A substantial negative effect on survival has been seen in patients who develop LV dysfunction, AF, left atrial enlargement, age >50 years, and flail mitral leaflet. Recently, reduced LV global longitudinal strain has been found to be prognostic in asymptomatic patients with severe primary MR.5 The development of infective endocarditis in patients with MVP is another mechanism of worsening MR severity. Predictors of infective endocarditis in patients with MVP include male gender, age >45 years, the presence of MR, and leaflet thickening and redundancy. Patients with MVP with significant MR also have a small but significantly increased risk of sudden death, most likely secondary to ventricular tachyarrhythmias, which may be related to the so-called mitral annulus disjunction (MAD) syndrome.6 MVP has been associated with a pattern of multiple nonspecific symptoms such as palpitations, atypical chest pain, syncope, and anxiety, and this constellation has been frequently termed the “mitral valve prolapse syndrome.” No such associations have been found in multiple studies, but a small group of patients may have a complex set of symptoms associated with MVP. For example, a few studies have shown a pattern of autonomic dysfunction, with increased catecholamines and decreased vagal tone, in patients with MVP. The mainstay of medical management of patients with MVP is reassurance. Beta-blockers are the treatment of choice for patients with increased adrenergic symptoms such as palpitations, chest pain, or anxiety. In patients with AF, there should be a low threshold for instituting anticoagulation, individualized for the patient’s risks of stroke versus bleeding using the CHA2DS2-VASc and HAS-BLED scores. Surgery for MVP is only a consideration in patients with significant, and usually symptomatic MR, similar to other forms of nonischemic MR, which is discussed later.

ACUTE MITRAL REGURGITATION

Acute MR is a relatively uncommon medical condition, requiring urgent medical and often surgical intervention. Acute MR may result from disruption of mitral valve leaflets, chordae tendineae, or papillary muscles associated with infective endocarditis, acute myocardial infarction, trauma, or rheumatic fever. The most common cause may be acute myocardial ischemia leading to acute severe MR, and acute pulmonary edema. High left atrial pressure and reduced left atrial compliance secondary to severe acute MR are the mechanisms of pulmonary edema. A less common complication of severe acute MR is reduced forward flow resulting in cardiogenic shock. Acute MR usually presents as sudden and marked increase in congestive heart failure symptoms, with weakness, fatigue, dyspnea, and sometimes respiratory failure and shock. Peripheral vasoconstriction, pallor, and diaphoresis are usually associated presenting signs. In some patients, a loud systolic murmur and a diastolic rumble or third heart sound are heard. In others, a very soft murmur or no murmur is heard, because the severity of MR and the lack of atrial compliance may lead to mid systolic equalization of pressures between the left atrium and ventricle. Echocardiography is the diagnostic procedure of choice. In acute coronary syndromes, emergency catheterization and cardiac surgery are lifesaving. There is little need for contrast LV angiography, except in cases where there is discrepancy in clinical and noninvasive findings. In some cases, hemodynamic measurements and monitoring may also be helpful in management. Acute MR after myocardial infarction is discussed in detail in another chapter of this book. It is the cause of about 7% of cases of cardiogenic shock after myocardial infarction. The onset of MR is most commonly between days 2 and 7 after myocardial infarction. Focal infarction most commonly involves the posteromedial papillary muscle, because it derives its blood supply solely from one artery, the right coronary artery. In contrast, the anterolateral papillary muscle has a dual blood supply, often derived partly from the circumflex and partly from left anterior descending artery. Despite the devastating effects of acute severe MR, the infarct size is not always large, and acute severe MR may be associated with smaller infarctions (0.4 cm2 is indicative of severe regurgitation, whereas 0.6 cm2

3.

A. . C. D. .

What is the most common etiology of tricuspid regurgitation (TR)? A. Rheumatic disease . Prolapse or flail C. Trauma D. Carcinoid . Left-sided heart failure

4.

5.

A 55-year-old man has posterior mitral valve prolapse (MVP) that was detected on a recent physical examination. His MR is anteriorly directed, and his ROA measures 0.5 cm2 on proximal convergence

A. . C. D. .

method. He has an LVEF of 50%, has normal pulmonary artery pressures, and can run 3 miles every other day without difficulty. He has never experienced AF to his knowledge. His left ventricular (LV) end systolic dimension is 4.2 cm, and his LV end diastolic dimension is 6 cm. His left atrial diameter is 4.5 cm. What do you recommend now? Watchful waiting with repeat echocardiogram in a year Mitral valve replacement (MVR) with a bioprosthesis given his age MVR with a mechanical valve given his age Mitral valve repair within the next few months Afterload reduction with an angiotensin-converting enzyme (ACE) inhibitor and careful monitoring of his LV function A 70-year-old woman with long-standing mitral stenosis (MS) comes to see you. She claims that she is perfectly fine and can do all her activities of daily living. Her family who accompany her suggest that she has gradually reduced her activities and is now house bound. The valve is heavily calcified and her mean transmitral gradient is 6 mm Hg by echocardiography. There is 2+ MR. The pulmonary artery systolic pressure is 50 mm Hg. Her other valves are thickened but not stenotic. She has 3+ TR. She has long-standing AF that is rate controlled. She is taking warfarin, digoxin, and a beta-blocker. The next step in her evaluation is Start furosemide to reduce her filling pressures. Do a stress echocardiogram to assess her functional capacity and change in valve gradients, regurgitation, and pulmonary pressures with stress. Recommend cardiac catheterization to measure her intracardiac pressures invasively. Perform transesophageal echocardiography (TEE) to better assess her MS. Recommend balloon valvuloplasty now to improve her valve gradients.

6.

A. . C. D. .

7.

A 45-year-old woman presents with increasing weight gain and abdominal fullness for a number of months. She sustained a motor vehicle accident about 6 months ago and had a major injury to her chest. She had made a reasonable recovery but is now limited. On examination, she is in normal sinus rhythm. Her venous pressure wave is prominent and elevated. She has a Grade 3/6 systolic murmur at the

A. . C. D. .

right sternal border. She has abdominal distention with hepatomegaly. She has 3+ pitting edema bilaterally. The most likely cause of her problems is Carcinoid syndrome with resultant severe TR Right heart failure from respiratory insufficiency following her traumatic injury to the chest Constrictive pericarditis consequent on her chest injury Ischemic injury to the right coronary artery and ruptured papillary muscle to the tricuspid valve Traumatic chordal rupture of tricuspid valve leaflet with severe TR

The following is true about tricuspid stenosis: A. It often occurs as an isolated lesion independent of other valve involvement. . Balloon valvuloplasty is the treatment of choice in most situations. C. If mitral valve disease is present, tricuspid stenosis is usually evident before mitral valve disease is manifest. D. It is often accompanied by severe TR. . Often an audible opening snap (OS) is present over the tricuspid valve.

8.

A 55-year-old woman has severe symptomatic MS and has a valve area of 0.8 cm2. She has 2+ MR, moderate aortic regurgitation (AR), and a splitability score of 11. She had an open commissurotomy in the past. Which of the following statements is most likely to be correct? She should not undergo mitral balloon valvuloplasty as the degree of MR and splitability score are absolute contraindications to the procedure. You tell her that balloon mitral valvuloplasty is unlikely to be successful because of her prior commissurotomy. You tell her that balloon mitral valvuloplasty may be attempted but she is unlikely to have an optimal result based on her splitability score and her prior commissurotomy but may provide symptomatic relief. You recommend watchful waiting as she will likely improve with an exercise program. You tell her that her only option is MVR and that this will be a low-risk procedure with estimated mortality of 0.4 cm2 The following cutoff points have been established for severe MR when using proximal isovelocity surface area (PISA) to calculate instantaneous ROA:

0.4 cm2 is severe.

4.

Correct Answer: E. Left-sided heart failure The most common etiology of TR is left-sided heart disease.

5.

Correct Answer: D. Mitral valve repair within the next few months He has severe MR with ROA > 0.5 cm2. He now has LV dysfunction as his LVEF is 50%. LV systolic function in a patient with severe MR is a Class I indication for surgical intervention. Mitral valve repair is favored over MVR in the treatment of MR when feasible as long-term outcomes are generally better and LV systolic function is more likely to be preserved postoperatively with repair. Waiting further in this man may only cause his contractile function to deteriorate further. There is no evidence that afterload reduction or any other medical therapy will alter the natural history of MR. Either a mechanical or bioprosthetic valve might be a reasonable choice in this individual if repair were not feasible.

6.

Correct Answer: B. Do a stress echocardiogram to assess her functional capacity and change in valve gradients, regurgitation, and pulmonary pressures with stress. This lady has mixed MS and regurgitation and significant pulmonary hypertension. She has a heavily calcified mitral valve with moderate mitral gradients. The first thing to establish with her is how severely limited she is and whether the mitral valve is contributing to this. A stress echocardiogram will allow her functional capacity and her hemodynamic changes on exercise to be determined. In some patients with mixed mitral valve disease, the MR may worsen on exercise and lead to a significant increase in the pulmonary artery pressures. TEE

is useful in evaluating MR, but planimetry of the mitral valve is often difficult with TEE. Cardiac catheterization is very useful in evaluating the hemodynamics of mitral valve disease but will not give an assessment as to how limited the patient is. This is crucial for decision making as to the best options for her.

7.

Correct Answer: E. Traumatic chordal rupture of tricuspid valve leaflet with severe TR Traumatic injury to the tricuspid valve may occur following a motor vehicle accident and can present insidiously with severe TR and right heart failure. Surgical repair is usually feasible and curative.

8.

Correct Answer: D. It is often accompanied by severe TR. Tricuspid stenosis is relatively uncommon and is almost always seen in the setting of significant rheumatic mitral valve disease. It usually manifests late often with accompanying significant TR. Balloon valvuloplasty is feasible in some instances but is rarely considered because of concomitant severe TR.

9.

Correct Answer: C. You tell her that balloon mitral valvuloplasty may be attempted but she is unlikely to have an optimal result based on her splitability score and her prior commissurotomy but may provide symptomatic relief. Balloon valvuloplasty is not contraindicated based on either the splitability score or a history of prior commissurotomy or 2+ MR. The results are less likely to be optimal in this situation but may afford symptomatic relief. It is unlikely that her symptoms will improve with exercise as she has critical MS. MVR will have a >1% risk given her prior surgical procedure.

10. Correct Answer: C. Men are more likely to have significant complications including surgery on the mitral valve than are women.

MVP is equally prevalent in men and women, but men are more likely to have complications such as endocarditis and significant MR. In most patients, mitral prolapse is a benign condition and does not require surgery. Mitral valve thickening of >5 mm—classic mitral prolapse—is more likely to have a complicated course. Mitral prolapse is best detected and diagnosed on the parasternal long-axis view and not the apical four-chamber echocardiographic view because the saddle shape of the mitral annulus may lead to apparent but factitious prolapse on the apical four-chamber view.

CHAPTER 34

Infective Endocarditis ANDREW R. HIGGINS AND STEVEN M. GORDON The incidence of infective endocarditis (IE) in the United States has remained relatively constant over the past 15 years at approximately 8 cases per 100,000 people or 30,000 cases per year.1 There have been changes in the distribution of pathogens causing IE as well as a dramatic surge in cases of IE in persons who inject drugs (PWID) associated with the opioid use disorder (OUD) epidemic. Additionally, although rheumatic heart disease remains a key risk factor in developing countries where antibiotic use is less widespread, in industrialized countries, age-associated degenerative valve lesions have superseded rheumatic heart disease as the most common structural risk factors for IE. Concomitantly, invasive medical interventions including intravascular catheters, hemodialysis, cardiac implantable electronic devices (CIED), and prosthetic valves have led to the emergence of health care associated endocarditis. This has led to the average IE patient being older, more frail, and more comorbid than their counterpart of several decades ago. These shifts in patients at risk for IE in the United States have been reflected in the microbiology of endocarditis, with Staphylococcus aureus surpassing the viridans Streptococcal group as the most common pathogen, particularly among cases of device-associated IE and in PWID. The latter patients tend to be younger and present more acutely with fever and sepsis syndromes rather than with the classic Oslerian subacute and chronic presentation of fever of unknown origin with regurgitant valvulitis, splinter hemorrhages (Fig. 34.1), Osler nodes (Fig. 34.2), Janeway lesions (Fig. 34.3), or Roth spots.2

FIGURE 34.1 Splinter hemorrhages.

FIGURE 34.2 Osler nodes.

FIGURE 34.3 Janeway lesions.

DEFINITIONS IE is defined as a microbial infection of the endocardium. Acute and subacute IE are further subdivisions based on the tempo and severity of the

infection with subacute presentation usually defined as having weeks of symptoms before diagnosis. Early prosthetic valve endocarditis (PVE) may be defined as occurring within 12 months after valve surgery and is often caused by drug-resistant nosocomial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). Infections that are acquired after this period, presumably after endothelialization of the valve prosthesis, are defined as late. With the exception of coagulase-negative Staphylococci (CoNS), most pathogens causing late PVE reflect those same pathogens that cause NVE, such as oral viridans Streptococci, Enterococcal species, and the HACEK group (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species). Health care–associated IE has been defined as either IE with onset of symptoms >72 hours after hospitalization or IE occurring from 4 to 8 weeks after discharge from the hospital if an invasive procedure was performed during hospitalization.3

EPIDEMIOLOGY There are approximately 30 to 40,000 cases of IE annually in the United States (incidence of 8 per 100,000) of which 2/3 are native valve IE. The associated mortality has also remained unchanged (between 10% and 30%) over the same period.1 The incidence of prosthetic valve and CIED IE have increased over the past 15 years, reflecting more patients at risk. Left-sided IE (aortic and/or mitral valve) is more frequent than right-sided IE (tricuspid and pulmonic valve), accounting for over two-thirds of NVE.2 Contemporary data shows that after an initial higher-risk period within the first year, the annualized risk for PVE decreases significantly and suggests a higher risk with mechanical than bioprosthetic valves.4 Right-sided IE commonly occurs in the setting of IDU, indwelling central venous catheter, CIED, congenital heart disease (CHD), and immunosuppression. Although its prognosis is generally better than that of left-sided IE, in patients with advanced underlying immunodeficiency, mortality remains high. Hospital-acquired IE has increased in frequency in recent years owing to greater use of invasive procedures. MRSA, CoNS, and gram-negative bacilli

tend to predominate as causative agents, with mortality rates as high as 40% to 60%.5

RISK FACTORS Important risk factors for IE include the following: Prosthetic heart valves or rings Injection drug use/people who inject drugs Prior history of IE Rheumatic heart disease Unrepaired significant CHD or recently repaired CHD ( Pa > Pc throughout this zone. There is minimal to no blood flow in this zone because the pressure exerted on the pulmonary artery by the alveoli prevents blood flow to the capillaries. Zone 2 (middle elevation): This region of the lung lies between where the pulmonary artery pressure equals the alveolar pressure and where the alveolar pressure equals the pulmonary capillary pressure; such that Pa > PA > Pc. Zone 3 (lowest in elevation): This is the region of the lung that lies below the level where the alveolar pressure equals the pulmonary capillary pressure, such that Pa > Pc > PA. If the pulmonary catheter is in an area where the alveolar pressure is greater than the pulmonary capillary pressure, then the PCW waveform will be falsely elevated. Thus, the PCW pressure accurately reflects left atrial pressure only when the catheter is in zone 3 of the lung. In the catheterization laboratory, a newly placed pulmonary artery catheter selectively advances to zone 3, thereby assuring valid PCW measurement. However, when in the intensive care unit, the patient can be repositioned or significant fluid changes can occur thereby changing the intrapulmonary hemodynamics. Thus, it is often necessary to verify that the location of the catheter tip still exhibits zone 3 physiology. Marked respiratory variation in the pulmonary artery wedge pressure (PAWP) tracing and a loss of the normal atrial pressure waveform suggest that the catheter is in a zone other than zone 3. When using a balloon-tipped pulmonary artery catheter, withdrawing the catheter back to the right ventricle (RV) and then readvancing the catheter with the balloon tip inflated will usually reposition the catheter into zone 3. Accurate PCW pressures may be difficult to obtain in patients with near systemic levels of pulmonary hypertension. Characteristically, the PCW pressures may appear falsely elevated, which may lead to a false impression of postcapillary pulmonary hypertension. In these cases, direct left ventricular and/or left atrial pressure measurement may be required to determine if the left heart pressures are truly elevated.

Pressure Wave Artifacts In addition to the artifacts that may be produced by low-frequency response and overshoot, catheter structure or placement may introduce artifacts in pressure recordings. End-hole artifacts may occur when the tip of an end-hole catheter becomes occluded during contraction of an atrial or ventricular wall. If this occurs during atrial systole with a catheter in the atrium, the A wave will appear greatly magnified (Fig. 44.4). If end-hole occlusion occurs with a catheter in a pulmonary artery, the PCWP will appear falsely low and flat.

Figure 44.4 Falsely elevated A wave recorded from an end-hole catheter in the right atrium. Simultaneous recording of ventricular and aortic pressures may occur when the tip of a pigtail catheter is located in the ventricle and the side port in the aorta. This may produce a bizarre-looking pressure wave with an apparently elevated diastolic left ventricular pressure (Fig. 44.5).

Figure 44.5 A:Pressure recording from pigtail catheter with end hole in the left ventricle and side holes in the aorta revealing a falsely elevated LVEDP. B:Pressure recording in the same patient with pigtail catheter completely in left ventricle demonstrating the accurate LVEDP. Catheter-whip artifact is a high-frequency oscillation that results from rapid movement of the catheter by blood flow. This is particularly likely to occur in the pulmonary artery and above a stenotic aortic valve.

Cardiac Output Measurement The fundamental function of the heart is to deliver enough blood to the systemic circulation to meet the oxygen demands of tissues. The normal cardiac output (CO) increases with body size and exercise and decreases with age. Numerous other factors may affect resting CO. In order to account for body size, the CO is normalized to body surface area (BSA) in square meters (m2), and the result is the cardiac index. BSA may be obtained from a nomogram or calculated by the following formula:

The normal resting cardiac index falls from about 4.5 L/min/m2 at age 7 years to 3 L/min/m2 in middle age, and to 2.5 L/min/m2 at age 70. The two major methods for measurement of CO in the cardiac catheterization lab are the Fick oxygen technique and the indicator dilution technique.

The Fick Technique The Fick principle states that the total uptake or release of any substance (such as oxygen) by an organ (such as the lungs) is the product of blood flow to the organ and the arteriovenous (A-V) concentration difference of the substance. If pulmonary blood flow equals systemic blood flow, then

Oxygen consumption can be estimated by measuring the oxygen uptake from room air by use of a Douglas bag or metabolic hood. In order to conserve time and expense, many laboratories use an assumed oxygen consumption based on the formula 125 mL/min/m2 for younger patients (110 mL/min/m2 for older patients) or 3 mL/min/kg. However, assumed oxygen consumption values may produce discrepancies of ±10% to 25% in about half of patients. A-V oxygen difference is obtained by subtracting the oxygen content of pulmonary venous (or systemic arterial) from pulmonary arterial (or “mixed venous”) blood. Oxygen content may be calculated using the formula

where Hb is hemoglobin. The final formula for calculation of CO then becomes

Estimation of pulmonary arterial oxygen content by using “mixed venous” blood from the venae cavae is less accurate. Mixed venous blood oxygen saturation is an estimation of what the pulmonary artery blood oxygen saturation would be if no shunt were present. This can be approximated by the following formula:

and

where superior vena cava (SVC) and inferior vena cava (IVC) are the respective O2 saturations. Use of arterial blood to estimate pulmonary venous blood oxygen content is acceptable, because, in the absence of shunts, only a small amount of venous blood enters the arterial circuit within the heart via the thebesian veins. Narrow A-V oxygen differences (as seen with high CO) are more

likely to introduce error than wide differences (as seen with low CO). Thus, the Fick method is most accurate in patients with low CO. Assume that a patient has the following measured values: Oxygen consumption = 250 mL/min Femoral artery oxygen saturation = 97% SVC oxygen saturation = 70% IVC oxygen saturation = 78% Hb concentration = 14.0 g% The mixed venous blood saturation will be

In this case, the CO can be calculated as

Indicator Dilution Methods The most commonly used indicator dilution method today is the thermodilution technique. This method utilizes a bolus injection of saline, followed by continuous measurement of the temperature of the blood by a thermistor in the pulmonary artery. The resulting curve is analyzed by computer to derive the CO using the basic indicator dilution equation. With this method, the temperature of the injectate (measured in the injectate fluid container before injection) is assumed to increase by a predictable amount during injection.

Accurate measurement of both blood and injectate temperatures immediately before injection is important for measuring thermodilution COs. According to the formula for calculating thermodilution CO, the temperature difference between blood and injectate (typically 16°C when roomtemperature injectate is used) is directly proportional to CO. Small errors in either of these measurements can produce errors in calculated CO. Thermodilution CO will be overestimated if the injectate temperature is inappropriately increased by permitting the injectate to remain in the syringe or by holding the syringe in the hand before and during injection. Use of cooled injectate, as opposed to room-temperature injectate, may produce an even greater mean error, probably because warming of the cooled injectate in the tubing and syringe produces an even greater increase in temperature than does use of room-temperature injectate. Even though there is a theoretical advantage to iced injectate because of its greater signal-to-noise ratio, most studies have shown no advantage to iced over room-temperature injectate. A dual-thermistor catheter appears to minimize these problems with injectate temperature, resulting in more consistent and accurate CO measurements, but at increased expense. The thermodilution technique will overestimate CO in low-flow states because of warming of blood by the cardiac chambers. The thermodilution method is most accurate in high-flow states. It is unreliable in the presence of significant tricuspid regurgitation because the injectate is warmed during its prolonged stay within the RA and RV. Overall, the thermodilution method should have an error of no more than 5% to 10% when performed correctly.

Shunt Calculation An intracardiac shunt is an abnormal communication between the left and right heart chambers. A left-to-right intracardiac shunt increases pulmonary blood flow in relation to systemic flow, and a right-to-left shunt does the opposite. Oximetry is the most common method for calculating intracardiac shunts in the catheterization laboratory, although dye dilution curves and angiography may also be used. Oximetry is not as sensitive as dye dilution curves for detecting small shunts, but it should be capable of detecting any shunt that is large enough to merit surgical correction. Detailed oximetric

analysis requires sampling in the RA (three sites), SVC (high and low), IVC (at renal artery level and below the diaphragm), RV (three sites), pulmonary artery, and aorta. When a left-to-right shunt exists at the atrial level, it is necessary to use the SVC and IVC oxygen saturations to calculate the mixed venous blood saturation, as described above. The same principle applies when a left-toright shunt exists at the right ventricular level, especially when tricuspid regurgitation is present. A significant increase in oxygen saturation in the right side of the heart is considered to exist when there is >7% increase from the SVC/IVC to the RA, >5% from the RA to the RV, and >5% from the RV to the PA. Left-to-right shunts are commonly expressed as Qp/Qs. Qp, or pulmonary flow, and Qs, or systemic flow, are calculated using the formula given above for calculating CO. The A-V O2 difference for Qp requires pulmonary arterial and pulmonary venous samples (or assumption of a pulmonary venous saturation of 95%). The A-V O2 difference for Qs requires arterial and mixed venous samples. A Qp/Qs < 1.5 signifies a small left-to-right shunt, 1.5 to 2.0 an intermediate size, and >2.0 a large shunt. A Qp/Qs < 1.0 indicates a net right-to-left shunt. When Qp/Qs is calculated, all the components of the CO formula factor out, leaving only the oxygen saturations. Therefore, Qp/Qs can be calculated by the following formula:

Assume that a patient with an ostium secundum interatrial septal defect has the following measured values: LV oxygen saturation = 96% SVC oxygen saturation = 67.5% IVC oxygen saturation = 73% PA oxygen saturation = 80% The mixed venous blood saturation is

In this case, Qp/Qs is calculated as follows:

Vascular Resistance Vascular resistance is defined by the ratio of pressure gradient across a vascular circuit divided by the flow. In a rigid tube with steady laminar flow of a homogeneous fluid, the relationship between pressure and flow is described by Poiseuille law, which states that the pressure drop across a circuit with fluid flowing at a constant rate (and therefore its resistance) is directly proportional to the length of the tube and the viscosity of the fluid and indirectly proportional to the fourth power of the radius of the tube. Within the bloodstream, Poiseuille law is inaccurate because blood flow is pulsatile and nonlaminar, blood is not homogeneous, and blood vessels are nonlinear and elastic. However, the basic principles of this law still apply in clinical measurements of resistance. For clinical purposes, two important vascular resistance concepts are commonly derived from pressure and flow data:

where

is the mean systemic arterial pressure,

right atrial pressure,

the mean

the mean pulmonary arterial pressure,

the mean left atrial pressure, Qs the systemic blood flow, and Qp the pulmonary blood flow. The mean PCW pressure is often used as an approximation of the left atrial pressure. These calculations yield vascular resistance in Wood units, named after Dr. Paul Wood. To convert to metric resistance units, expressed in dynessec-cm−5, multiply vascular resistance by 80. Vascular resistance index (VRI) is obtained by multiplying vascular resistance by BSA. Normal values for vascular resistance (in dynes-sec-cm−5) are SVR: 1,150 ± 300 SVRI: 2,100 ± 500 PVR: 70 ± 40 PVRI: 125 ± 70 Clinically, SVR calculations are commonly used to diagnose and treat patients with hypotension or heart failure, and PVR to evaluate pulmonary arterial hypertension and the suitability of patients with congenital heart disease for cardiac surgery. PVR calculations are also frequently used to determine the severity of PVR in patients with end-stage heart failure being evaluated for heart transplantation and in patients with end-stage liver failure being evaluated for liver transplantation. Because the length of the vascular

bed is likely to be constant in any adult patient, changes in SVR and PVR reflect either altered viscosity of blood or a change in the cross-sectional area of the vascular bed. Severe chronic anemia lowers the values for measured vascular resistance. If the hematocrit remains stable, changes in SVR are produced primarily by altered arteriolar tone. Thus, measurement of SVR becomes the basis for hemodynamic evaluation of shock. Vasodilatory shock, such as in sepsis or adrenal insufficiency, is associated with markedly decreased SVR and normal or increased CO. Cardiogenic and hypovolemic shock usually produce a decreased CO and markedly increased SVR due to intense peripheral vasoconstriction. In congenital heart disease, the ratio of PVR to SVR is commonly used as a criterion for operability. Normal is 100 mm Hg, and a low diastolic pressure, often 0.5 to 0.75 cm/year) or symptom development has also been advocated as indications for surgery. The decision for operative repair must of course take into account the patient’s medical comorbidities, and a risk/benefit ratio must be individualized for each patient. Patients who are otherwise at low medical risk may be considered for intervention at smaller aortic sizes at aortic centers of excellence with low surgical morbidity and mortality. Thoracic endovascular aortic repair (TEVAR) was FDA approved in 2005 as a management strategy for descending TAA and has increasingly been used in practice as an alternative to open surgical aortic repair. Retrospective analysis of Medicare data suggests a reduced risk of early postoperative mortality and superior mean survival with TEVAR as compared to open repair.

Abdominal Aortic Aneurysm The incidence of abdominal aortic aneurysm (AAA) is estimated at 36.5 per 100,000 person years. AAA represents the most common form of arterial aneurysm. The majority of AAAs are infrarenal in location (75%).

Atherosclerosis is the dominant risk factor in the development of an AAA. Additional risk factors associated with AAAs are male gender (AAA is four to five times more common in men), increasing age, smoking, and hypertension. There is a clear familial predisposition to AAA, with relatives of affected patients having up to 25% increased risk for the development of an AAA. Asymptomatic AAA is often diagnosed on physical examination by abdominal palpation. The most common symptom is pain and is usually steady. The pain may be localized abdominal pain or may radiate to the back, flank, or groin. Sudden onset of severe abdominal and back pain suggests rupture, representing a surgical emergency. Up to only a third of patients with rupture will present with the classic triad of pain, pulsatile abdominal mass, and hypotension. Atheroemboli may be the first manifestation of an AAA.

Noninvasive Imaging Ultrasonography, CT scanning, aortography, and MRA have all been used in the initial diagnosis, sizing, and monitoring of AAA. Ultrasonography represents the most practical method of screening and serial monitoring, while CT scanning and MRA remain superior in accurately detailing the morphology and extent of the AAA. At initial diagnosis, the rate of dilatation cannot be determined and thus the next serial study should be performed in 6 months. In general, for AAAs < 4.0 cm, yearly surveillance imaging is recommended; for AAAs 4.0 to 5.0 cm, imaging every 6 to 12 months; and for AAAs > 5.0 cm, imaging every 3 to 6 months. Baseline AAA size is the best predictor of rate of dilatation. Larger aneurysms expand at higher rates than smaller ones.

Medical Treatment Beta-adrenergic blockade with careful control of hypertension appears to have impact on delaying the rate of AAA expansion. Smoking should be discontinued, as rupture risk is greater among active smokers.

Indications for Surgical Treatment Mortality from an AAA is primarily related to rupture. As with thoracic aneurysms, increasing size is the harbinger of rupture risk. Aneurysms 5 cm in size have a 22% risk of rupture over 2 years, with those >6 cm showing the sharpest rise in risk. As such, an aortic diameter of 5.0 to 5.5 cm is recommended as an indication for prophylactic surgery in asymptomatic AAA patients. Although AAAs are less common in women, when they are present, they are at greater risk of rupture and at smaller aortic diameters than in men. Thus, it is recommended that women undergo prophylactic AAA repair at 4.5 to 5.0 cm. Aneurysms that expand rapidly (>0.5 to 1.0 cm/year) are also associated with an increased risk of rupture and are thus considered for elective surgical repair. Inflammatory AAA is present in up to 10% of cases. There appears to be a familial tendency for these, and they often occur in the context of smoking. Patients will present with constitutional symptoms and have an elevated sedimentation rate in addition to the classic symptoms of pain. CT scanning or MRA can identify the inflammatory component. Treatment is aortic surgery.

Endovascular Stent Graft Repair Percutaneous placement of an endovascular stent graft is often used to treat AAA. The endovascular stent graft is placed within the aneurysmal segment of the aorta, bridging the normal segments and excluding the aneurysm. Data suggest that endovascular repair of AAA, as compared to open surgical repair, is associated with a substantial early survival advantage that gradually decreases over time.

ATHEROMATOUS AORTIC DISEASE Atherosclerotic plaques in the aorta can give rise to cerebral and peripheral embolic events (Fig. 47.8).

TEE and CTA have been a valuable imaging modalities in assessing the presence, composition, and extent of these plaques. Plaques >4 mm in thickness, or those with mobile or ulcerated components, appear to be strongly associated with subsequent embolic events.

FIGURE 47.8 TEE in a short-axis view identifying a protruding thick (>4-mm) atheroma in the descending thoracic aorta. Treatment strategies for patients with such plaques have not been evaluated in sufficient numbers in a prospective randomized fashion. However, there is evidence that lipid-lowering therapy with a statin is a reasonable treatment option, and anticoagulation with warfarin or antiplatelet therapy may benefit some patients. Earlier reports of a potential association between warfarin and the cholesterol embolization syndrome have produced some reluctance to use

such anticoagulant therapy in these patients, and further study is thus needed. The potential role of aortic replacement or removal of atheroma remains to be defined. In addition, endovascular stent placement to cover the atheromatous aorta is gaining prominence. It has become increasingly common for cardiac surgeons to assess the aorta before the institution of cardiopulmonary bypass. The presence of significant plaque may alter the cross-clamp site or may even lead to endarterectomy or aortic replacement at the time of surgery.

Cholesterol Embolization Syndrome The cholesterol embolization syndrome can be seen in patients undergoing diagnostic angiography but can also occur spontaneously. There is a reported association between warfarin anticoagulation and these events. The syndrome represents a showering of emboli, typically from the descending aorta. Patients most often present with the skin findings of livedo reticularis and blue toes, in the presence of palpable pulses. Renal insufficiency may occur and may not be reversible. Transient eosinophilia is often present, and treatment is supportive. If the atheroma arose from an AAA, then surgical intervention can help prevent future events.

INFLAMMATORY AORTITIS Giant Cell Arteritis Giant cell arteritis is an inflammatory disease that affects the temporal arteries, producing local tenderness and headaches. Patients affected are typically over the age of 55 years, and women are affected twice as frequently as men. The most devastating consequence is blindness. Although temporal arteritis is the hallmark of this disorder, there may be involvement of the thoracic aorta and the great vessels. This can lead to branch vessel occlusion, aneurysm formation, or even dissection.

Corticosteroid treatment is the mainstay of therapy. With the development of advanced aortic involvement, surgical treatment may be required for ascending segments and endovascular stent placement in descending aorta.

Takayasu Arteritis Takayasu arteritis is an inflammatory disorder of the aorta that typically affects women under age 40 years. Its prevalence is greater in Asian and African populations than in those of European or North American descent. A subacute inflammatory illness phase is manifested by constitutional symptoms. Later, there is occlusive inflammation of the aorta and branch vessels, with segmental narrowing apparent. Symptoms of arterial insufficiency will be present, depending on the vessels involved. Acquired coarctation can occur, leading to hypertension, as an aneurysm formation. Treatment is corticosteroids. For occlusive lesions that do not respond to steroids, surgical bypass may be warranted.

Syphilitic Aortitis Syphilitic aortitis represents a manifestation of tertiary syphilis, which may occur 10 to 30 years after the initial infection. This inflammation results in a weakening of the vessel wall and can lead to aneurysm formation, usually saccular. Syphilitic aortitis most commonly affects the ascending aorta and hence can result in aortic insufficiency. The arch may also be affected. Involvement of the descending aorta occurs less often.

Other Inflammatory Aortitis Aortitis can also be seen in other systemic inflammatory diseases such as reactive arthritis, ankylosing spondylitis, rheumatoid arthritis, Wegener granulomatosis, and enteropathic arthropathies. A common genetic underpinning of these conditions is the HLA-B27 genotype, which should be considered in cases of lone aortic regurgitation, ascending aortic dilatation, and conduction system disease.

Treatment involves addressing the underlying disorder, with surgery as needed for aneurysmal or aortic valvular complications.

Mycotic Aneurysms Bacteremia (from endocarditis, trauma, intravenous drug abuse) can result in infection within the weakened aneurysmal arterial wall. Persistent fevers after treatment of the inciting event should raise concern for an infected aneurysm. Mycotic aneurysms more commonly involve the abdominal aorta. Atheromatous plaques can also become infected (bacterial aortitis), serving as a nidus for infection requiring prolonged antibiotic therapy.

ESSENTIAL FACTS Aortic Dissection The hallmark of aortic dissection is an intimal flap. Increasing aortic size and aneurysm formation is a harbinger of aortic dissection. Proximal (ascending) aortic dissections are treated with surgery. In cases of cardiac tamponade, evacuation of hematoma should be performed in the operating room under cardiopulmonary bypass support. Distal (descending) aortic dissections are treated medically, with surgery guided by a complication-specific approach. Marfan syndrome, congenital bicuspid aortic valve, familial aortic aneurysm/dissection syndrome, Loeys–Dietz syndrome, prior aortic surgery, and the peripartum period represent risk factors for aortic dissection in the young. A negative surface echocardiogram, absence of pulse deficits, or a normal mediastinum on chest x-ray does not exclude the presence of aortic dissection.

CTA is the imaging modality of choice in the initial diagnosis as well as for long-term follow-up after surgery or medical treatment to assess for interval change. Anti-impulse medical therapy with intravenous beta-blockade followed by sodium nitroprusside is the mainstay of medical treatment.

Intramural Hematoma and Penetrating Aortic Ulcer Penetrating aortic ulcers arise more commonly in areas of atheromatous disease such as the thoracoabdominal aorta. Penetrating aortic ulcers that involve the ascending aorta are treated surgically. Intramural hematomas that involve the ascending aorta are generally treated surgically, although recent publications have raised some controversy and suggest that medical management may be an option in some populations. Neither of the aortic dissection variants involves an intimal dissection flap.

Aortic Aneurysm Indications for surgery: Symptoms Inflammatory or infectious Rapidly expanding 0.5 cm/year, even if asymptomatic >5.0 to 5.5 cm diameter for ascending thoracic >6.0 to 6.5 cm diameter for descending thoracic >5.0 to 5.5 cm diameter for abdominal Aortic cross-sectional area index may be used in surgical decision-making (threshold value of >10 cm2/m). Earlier surgical intervention (>4.5 to 5.0 cm) is recommended in Marfan syndrome, Loeys–Dietz syndrome, and bicuspid aortic valve patients. Beta-adrenergic blockade may slow the progression of aortic dilatation.

Atheromatous Aortic Disease Mobile, ulcerated, or thick atheromatous plaques (>4 mm) identified by TEE are associated with embolic events.

SUGGESTED READINGS Chiu P, Goldstone AB, Schaffer JM, et al. Endovascular versus open repair of intact descending thoracic aortic aneurysms. J Am Coll Cardiol. 2019;73(6):643-651. doi:10.1016/j.jacc.2018.10.086 Creager MA, Sundt TM, Albert NM, et al. Surgery for aortic dilatation in patients with bicuspid aortic valves. Circulation. 2015;133(7):680-686. doi:10.1161/cir.0000000000000331 Curran T, Schermerhorn ML, McCallum JC, et al. Long-term outcomes of abdominal aortic aneurysm in the medicare population. N Engl J Med. 2015;373(4):328-338. doi:10.1056/nejmoa1405778 Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the diagnosis and management of patients with thoracic aortic disease: executive summary. J Am Coll Cardiol. 2010;55(14):1509-1544. doi:10.1016/j.jacc.2010.02.010 Mokashi SA, Svensson LG. Guidelines for the management of thoracic aortic disease in 2017. Gen Thorac Cardiovasc Surg. 2019;67(1):59-65. doi:10.1007/s11747-017-0831-8

Chapter 47 Review Questions and Answers QUESTIONS A 70-year-old man presents with the sudden onset of tearing chest pain. On presentation, he has a heart rate of 130 beats/min (bpm) with a systolic blood pressure of 80 mm Hg. A CTA done showed the presence of a proximal aortic dissection, and bedside echocardiography demonstrates the pericardial effusion with partial diastolic collapse of the right ventricle. Significant respiratory variation is noted across mitral and tricuspid Doppler inflows. Appropriate treatment is: Immediate percutaneous pericardiocentesis to relieve the tamponade, followed by surgery to replace the ascending aorta To proceed immediately to the operating room Emergency angiography to define coronary anatomy, followed by surgery Intra-aortic balloon pump to stabilize the hemodynamics, followed by surgery

1.

A. . C. D.

A 60-year-old hypertensive man presents with tearing back pain. CTA confirms the presence of a descending thoracic dissection originating beyond the left subclavian artery. Appropriate initial treatment includes which of the following? Immediate surgery to replace the descending aorta Intravenous nitroprusside followed by immediate surgery Intravenous nitroprusside alone; surgery for persistent pain, or for involvement of renal or mesenteric arteries Intravenous beta-blockade and nitroprusside; endovascular treatment for persistent pain or for involvement of renal or mesenteric arteries

2.

A. . C. D.

A 56-year-old man presents for screening physical examination. He is asymptomatic. Vital signs reveal a heart rate of 80 bpm with a blood pressure of 160/90 mm Hg. His examination is remarkable only for a pulsatile mass in the abdomen. Ultrasound reveals the presence of a 3.9-cm abdominal aortic aneurysm (AAA). Appropriate management includes which of the following? A. Immediate referral for surgery

3.

. Start a beta-blocker and repeat ultrasound in 6 months. C. Refer for stenting of the AAA. D. None of the above

C. D.

A 76-year-old woman with hypertension presents with severe chest pain. Her blood pressure is 200/110 mm Hg. Electrocardiogram reveals nonspecific ST–T changes. Chest x-ray is unremarkable. CT scan demonstrates the presence of a penetrating ulcer in the ascending aorta. No dissection flap is seen. Appropriate management includes which of the following? Start intravenous beta-blocker and nitroprusside while plans are being made for surgery. Intravenous beta-blocker and nitroprusside, with surgery only if complications develop Intravenous nitroprusside alone, with surgery only if complications develop All of the above

A. . C. D.

A 23-year-old patient with Marfan syndrome presents for routine evaluation. He is asymptomatic. Workup includes a CT scan that reveals the presence of a 4.2-cm ascending aorta. Appropriate management includes which of the following? Refer for surgery. Start on beta-blocker and reimage in 6 to 12 months. Reimage in 6 to 12 months. None of the above

A. . C. D.

The same patient returns for follow-up in 12 months. The aorta now measures 5.0 cm in size. He remains asymptomatic. Appropriate management includes which of the following? Refer for surgery. Continue beta-blocker, reassess in 6 months. Reassess in 3 months. None of the above

4.

A. .

5.

6.

Which of the following disorders is associated with involvement of the aorta? A. Marfan syndrome . Giant cell arteritis

7.

C. Ankylosing spondylitis D. All of these disorders can have aortic involvement. Which of the following statements regarding transesophageal findings of aortic atheroma is not true? Plaques >2 mm in the ascending aorta are associated with increased risk of stroke. Plaques >4 mm in the ascending aorta are associated with increased risk of stroke. Mobile components are associated with an increased risk of stroke. Limited data suggest that these patients may benefit from anticoagulation therapy with warfarin.

8.

A. . C. D.

ANSWERS 1.

Correct Answer: B. To proceed immediately to the operating room This patient should be taken to the operating room immediately. Percutaneous drainage has been associated with increased mortality in this setting. Given the hemodynamic status, there is no time to proceed with angiography first. Balloon pumps are contraindicated with aortic dissection.

2.

Correct Answer: D. Intravenous beta-blockade and nitroprusside; endovascular treatment for persistent pain or for involvement of renal or mesenteric arteries Initial therapy for descending aortic dissection is medical, with surgery reserved for special circumstances. The goal of treatment is reduction in blood pressure, as well as reduction in dp/dt. Both betablockade, started immediately, and nitroprusside should be used.

3.

Correct Answer: B. Intravenous beta-blocker and nitroprusside, with surgery only if complications develop Asymptomatic aneurysms of 3.9 cm have a very small risk of rupture. The patient should be followed by serial examination to assess size

and rate of expansion. Control of his hypertension with beta-blockers may delay the growth of the aneurysm. There are no data as of yet that endovascular stent grafts will lower the threshold for intervention for these aneurysms.

4.

Correct Answer: A. Start intravenous beta-blocker and nitroprusside while plans are being made for surgery. Penetrating aortic ulcers involving the ascending aorta are generally treated like dissections, with prompt referral for surgery.

5.

Correct Answer: B. Start on beta-blocker and reimage in 6 to 12 months. The patient’s aorta has not yet reached a size that would be considered for surgery in the absence of symptoms. There are data that beta-blockers can slow the rate of expansion of these aneurysms and improve survival.

6.

Correct Answer A. Refer for surgery. There has been rapid growth in the size of the aneurysm (0.8 cm in 1 year). The patient should be referred for surgery.

7.

Correct Answer: D. All of these disorders can have aortic involvement. All of the disorders listed can include involvement of the aorta.

8.

Correct Answer: A. Plaques >2 mm in the ascending aorta are associated with increased risk of stroke. Plaques >4 mm have been associated with cerebral embolic events. The role of anticoagulation needs to be more clearly defined, but there are some data to support its use.

CHAPTER 48

Venous Thromboembolism ERIKA HUTT-CENTENO AND MARCELO GOMES Venous thromboembolism (VTE), including acute deep vein thrombosis (DVT) and pulmonary embolism (PE), is a multifactorial disease with an annual incidence ranging from 0.75 to 2.69 per 1,000 individuals.1 Overall annual VTE incidence is similar to that reported for ischemic stroke.2 The number of annual VTE-related deaths has been estimated to be approximately 300,000 and 500,000 in the United States and Europe, respectively, but the death burden from VTE is likely underestimated.1

ESSENTIAL FACTS ABOUT VTE Venous thromboembolic events can be defined as “provoked” or “unprovoked” based on the presence or absence of an identifiable risk factor.3 The risk of recurrent VTE following unprovoked events is significantly higher than the risk of recurrence after provoked events.3–6 After discontinuation of anticoagulation, the overall cumulative incidence of recurrence of VTE has been reported as 15% to 20% after 3 years, 30% after 5 to 10 years, and 44% after 20 years.5,7–10 The risk of recurrent VTE is 3 to 4 times higher in men than that in women.11 A high-probability ventilation/perfusion scan (suggestive of acute PE) is seen in 35% to 40% of patients with proximal (i.e., above the

popliteal vein) acute lower extremity DVT (LE-DVT) who have no chest symptoms suspicious for acute PE.12,13 Postthrombotic syndrome (PTS)—characterized by chronic, intermittent leg pain and edema—is the most common long-term complication of LE-DVT, occurring in 20% to 79% of patients following LE-DVT.8,14–16 The incidence of PTS is highest after iliofemoral DVT and after recurrent ipsilateral DVT.17,18 Most cases of PTS develop within 2 years after the DVT event.19 Severe PTS, which is associated with chronic nonhealing venous stasis ulcers, occurs in 5% to 10% of patients after proximal LE-DVT.8,15,16 Acute PE is the third most common cause of hospital-related death and is the most common preventable cause of hospital death.3,4 Acute PE is a frequently unrecognized cause of death; most cases of fatal PE are not diagnosed until postmortem.20–22 The mortality rate associated with acute PE without treatment is approximately 30%.21,22 The presence of right ventricular (RV) systolic dysfunction by echocardiography, RV enlargement by chest computed tomographic angiography (CTA), as well as elevated plasma levels of markers of myocardial injury (troponin I or T) and RV dysfunction (N-terminal Btype natriuretic peptide—NT-proBNP) have all been associated with increased short-term mortality in patients with acute PE.23 Chronic thromboembolic pulmonary hypertension (CTEPH) has been reported in as few as 0.4% and as many as 9.1% of patients within the first 2 years following an episode of symptomatic PE.23 In patients with CTEPH, pulmonary hypertension is caused by incomplete resolution and fibrotic transformation of thromboemboli within the pulmonary arteries, leading to chronic obstruction of flow and microvascular remodeling with progressive increase in pulmonary vascular resistance.24,25 In patients with operable disease, the treatment of choice for CTEPH is surgical pulmonary thromboendarterectomy (PTE). In patients with inoperable disease, riociguat (a soluble guanylate cyclase stimulator) and/or balloon pulmonary angioplasty may be considered in selected cases.26,27

RISK FACTORS FOR THROMBOEMBOLISM

VENOUS

In any given patient, the risk of developing acute DVT and/or PE increases with the number of predisposing risk factors present.28 Risk factors for VTE can be classified as inherited or acquired (Table 48.1).

Table 48.1 Risk Factors for VTE

Heterozygous factor V Leiden and prothrombin gene G20210A mutation are the two most common inherited predispositions to VTE. As many as 20% of patients presenting with an unprovoked VTE may have heterozygous factor V Leiden mutation, while 6% may have heterozygous prothrombin G20210A mutation.29

D-DIMER TESTING FOR THROMBOEMBOLISM

VENOUS

-Dimer is a specific fragment resulting from the degradation of cross-linked fibrin. High-sensitivity -dimer assays can be used in emergency department and outpatient settings to rule out VTE because of their high sensitivity and negative predictive value (NPV).30 However, an elevated -dimer is not specific for VTE and can be caused by many conditions (Table 48.2).

Table 48.2 Causes of an Elevated -Dimer

The diagnostic performance varies among different quantitative and qualitative -dimer assays: quantitative enzyme-linked immunosorbent assay (ELISA)-derived assays have higher sensitivity than quantitative latexderived and whole-blood agglutination assays.16,31 Thus, it is important for clinicians to know what -dimer assay is available in their centers of practice. Acute VTE (DVT or PE) can be excluded—and anticoagulation withheld —in outpatients with low/moderate pretest probability of VTE and a negative ELISA -dimer, with a 3-month VTE risk 20 mm Hg indicates prosthetic valve dysfunction. An AV gradient of >20 mm Hg measured invasively immediately following TAVR may indicate patent prosthesis mismatch and should be a clue to further dilate the THV at time of procedure. This sometimes is more evident at follow-up given hemodynamic conditions at time of TAVR, typically in patients with large body surface area. Pannus formation may be seen and may be an explanation for gradually rising AV gradients over the first year after TAVR and can be diagnosed with gated cardiac CT. The most common cause of a rise in AV gradients within the first month after TAVR is subacute leaflet thrombosis. This is diagnosed with a gated cardiac CT and treated with anticoagulation over a 3-month period, and typically resolves. There are not clear guidelines on the long-term management of subacute leaflet thrombosis, though most providers will continue anticoagulation for as long as tolerated if there is low bleeding risk, and if stopped follow the patient with echocardiogram every 3 to 6 months to assess valve function.

5.

Correct Answer: A. Surgical AVR + Mitral valve repair + Single vessel CABG with LIMA to LAD + MAZE and LAA ligation This patient has a class I indication for AVR given his severe, symptomatic aortic stenosis. Though his preference may be to wait for as long as possible, the physician should counsel the patient that this is not advisable, as morbidity and mortality of untreated, symptomatic aortic stenosis is high. Given his concomitant need for coronary revascularization and mitral valve repair, surgical AVR + MV repair

+ CABG + MAZE/LAA ligation would be most appropriate in this circumstance and is most supported by current guidelines.

CHAPTER 62

Percutaneous Mitral Interventions VINAYAK NAGARAJA AND SAMIR R. KAPADIA The mitral valve is a complex structure consisting of six scallops and subvalvular apparatus. The mitral annulus is a saddle-shaped structure that is extremely dynamic during the cardiac cycle. Several pathophysiologic states affect the mitral valve, and this ranges from rheumatic mitral stenosis (MS) to mitral annular calcification (MAC) resulting in mixed mitral valve disease. The complexity of the disease and varying pathophysiologic states offers new challenges for percutaneous interventions. This chapter provides an overview of different mitral valve interventions that are currently prevalent in clinical practice.

PERCUTANEOUS TRANSVENOUS MITRAL VALVULOPLASTY Rheumatic MS continues to be the most common valvular heart disease in the 12

developing world and the prevalence rate ranges between 0.6% and 14%. , Percutaneous transvenous mitral valvuloplasty (PTMV) was first described 3

in 1984 by Inoue et al. and was designed to open fused commissures. It is essential to select right patient for PTMV. Transthoracic/transesophageal echocardiography are powerful tools to assess patients with MS. This provides valuable information regarding mitral valve area (MVA), transmitral gradient, mitral regurgitation, pulmonary pressures, and right ventricular function. It is also important to identify subvalvular calcification, leaflet thickening/calcification/pliability, and commissural fusion. The main

advantage of PTMV is that it avoids the need for multiple mitral surgeries and the demerits associated with a mitral prosthesis (anticoagulation, infective endocarditis, mechanical mitral valve) especially in young individuals. The Class I indication for PTMV is severe MS, a MVA of 30 mL/beat) and the COAPT 23 26

trial (Grades 3+ to 4+). – The MITRA-FR trial included patients who had a left ventricular endsystolic dimension of more than 70 mm, whereas the COAPT trial did not. The COAPT trial included patients who were well established on maximal guideline-directed medical treatment, and MITRA-FR trial

allowed for escalation of guideline-directed medical treatment before enrolment; however, the optimization was not monitored during followup. MITRA-FR’s procedural success rate was inferior and associated with higher peri-procedural complications compared to the COAPT trial. The follow-up duration was longer, and sample size was twice as large in the COAPT trial compared to the MITRA-FR trial providing adequate statistical power and assessing the impact of plication long term.

TRANSCATHETER REPLACEMENT

MITRAL

VALVE

Not every patient is suitable for transcatheter mitral valve repair. Patients with MR jet across the entire coaptation line, multiple prolapsing segments, or with a large coaptation gap, a MVA < 3.5 cm2, short (4, respectively. Prior studies of healthy athletes have shown aortic root sizes

>40 mm in males and 36 mm in females to be exceedingly rare (45 mm should be restricted from all sports.

REFERENCES 1. Mitchell JH, Haskell W, Snell P, Van Camp SP. Task Force 8: Classification of sports. J Am Coll Cardiol. 2005;45:1364-1367. 2. Harmon KG, Drezner JA, Maleszewski JJ, et al. Pathogeneses of sudden cardiac death in National Collegiate Athletic Association Athletes. Circ Arrhythm Electrophysiol. 2014;7:198204. 3. Drezner JA, Sharma S, Baggish A, et al. International criteria for electrocardiographic interpretation in athletes: consensus statement. Br J Sports Med. 2017;51:704-731. 4. Johnson JN, Ackerman MJ. Competitive sports participation in athletes with congenital long QT syndrome. JAMA. 2012;308:764-765. 5. Lampert R, Olshansky B, Heidbuchel H, et al. Safety of sports for athletes with implantable cardioverter-defibrillators. Circulation. 2017;135:2310-2312.

Chapter 65 Review Questions and Answers QUESTIONS A 19-year-old male collegiate soccer player is referred for further cardiac evaluation after an abnormal preparticipation ECG. His ECG demonstrates T-wave inversions in leads V1 and V2 with a sharp, positive deflection at the terminal end of the QRS in these leads. His transthoracic echo reveals moderately severe right ventricular enlargement with regional areas of akinesia. He undergoes cardiac MRI, which confirms his TTE findings and further demonstrates areas of fatty infiltration of the right ventricle. He discusses with you his desire to return to competitive sports, and his ambitions of becoming a professional soccer player. The most appropriate recommendation for this athlete is: Continued competitive sports participation with repeat cardiac MRI every 6 to 12 months Prophylactic implantation of an ICD and subsequent clearance to resume competitive sports Disqualification from all competitive sports and restriction from vigorous exercise Initiation of beta-blocker therapy and restriction from all competitive sports Exercise stress testing and resumption of competitive sports in the absence of exercise-induced arrhythmias

1.

A. . C. D. .

2.

A 52-year-old female avid runner is admitted following cardiac arrest at mile 25 of a local marathon. She received bystander CPR and was successfully defibrillated by race personnel with a single shock with an available AED. She has no prior medical history and takes no medications. She has no recollection of the event and has no current complaints other than mild chest tenderness, which she attributes to chest compressions. Her vital signs are within normal limits. Physical examination is unremarkable and cardiac examination reveals a normal rhythm without murmurs. ECG reveals sinus bradycardia with a heart rate of 52 beats per minute but is otherwise

A. . C. D. .

unremarkable. The most likely contributor to sudden cardiac death in this patient is: Myocarditis Coronary artery disease Hypertrophic cardiomyopathy Arrhythmogenic right ventricular cardiomyopathy Catecholaminergic polymorphic ventricular tachycardia

3.

An 18-year-old African American male basketball player presents for a preparticipation assessment and ECG (Fig. 65.4). He has no known underlying health issues. He denies episodes of chest pain, dyspnea, or syncope. He is adopted and does not know the medical history of his biological parents. Based on his ECG, the most appropriate next step in his evaluation is:

FIGURE 65.4 A. . C. D. .

Transthoracic echocardiogram Exercise ECG testing Cardiac MRI Genetic testing for inherited cardiomyopathies No further testing

A 16-year-old female volleyball player is referred for further evaluation of a murmur heard by her primary care physician. She has generally felt well and is a star player on her high school team. She describes several episodes of near syncope, typically at the end of practice, which she has attributed to dehydration. She denies syncope, chest pain, or dyspnea. Her family history is unremarkable for cardiac disease. On examination, you hear a faint systolic murmur at the left sternal border, which is increased with Valsalva maneuver and decreased by hand grip. An ECG reveals sinus bradycardia, increased precordial voltages with T-wave inversions across the precordium as well as in leads I and aVL. A transthoracic echocardiogram demonstrates a septal wall thickness of 1.6 cm, small LV cavity size, and mild systolic anterior motion of the mitral valve with mild mitral regurgitation. Regarding ongoing sports participation, the 2015 AHA/ACC recommendations are: Restriction from competitive sports (except class IA) Resumption of competition after initiation of beta-blocker therapy Prophylactic implantation of ICD with resumption of competition Resumption of competition if no arrhythmias on exercise testing or 24-hour Holter monitor and no evidence of myocardial fibrosis on cardiac MRI Continued participation in all competitive sports

4.

A. . C. D. .

5.

A 23-year-old male collegiate swimmer is referred for evaluation for exertional chest pain. He describes episodes of dull, substernal chest pain, which started several month ago and occur on a weekly basis. Episodes always occur during exercise and are associated with shortness of breath out of proportion to his level of exertion. They last 5 to 10 minutes in duration and resolve with rest. He denies any episodes at rest. There is no association with upright or supine positioning or with deep inspiration. He has otherwise felt well without recent illness. He denies syncope or any cardiac history. An ECG demonstrates sinus arrhythmia with a heart rate of 48 beats per minute and LVH by voltage criteria. Baseline echocardiography reveals mild biventricular dilation, mild left atrial enlargement, and septal wall thickness of 1.2 cm. The origin of the right coronary artery is visualized from the right sinus of Valsalva, but the origin of the left main coronary artery is not seen. Stress echocardiography is negative

A. . C. D. .

for evidence of ischemia or exercise-induced arrhythmias. CT angiography reveals an anomalous left main coronary artery arising from the right sinus of Valsalva with an interarterial course and ostial narrowing. The patient strongly wishes to continue participation in competitive athletics. The most appropriate recommendation for this athlete is: Return to competition with repeat exercise stress testing in 1 year Surgical referral with lifelong restriction from competitive athletes Restriction from competitive athletics (except class IA sports) Surgical referral with return to competitive athletics 3 months postoperatively if asymptomatic and negative repeat stress testing Referral for percutaneous coronary intervention with return to competitive athletics in 3 months if asymptomatic and negative repeat stress testing

ANSWERS 1.

Correct Answer: C. Disqualification from all competitive sports and restriction from vigorous exercise This athlete fulfills criteria for ARVC. Vigorous exercise has been demonstrated to result in more aggressive progression of disease with an increased risk of malignant ventricular arrhythmias and death. Such athletes should be counseled to discontinue all vigorous exercise.

2.

Correct Answer: B. Coronary artery disease CAD is the most common cause of SCD in masters athletes (>35 years). Her normal examination and lack of changes on her ECG make it most likely that this event was related to a fixed coronary stenosis.

3.

Correct Answer: E. No further testing This pattern is a normal variant in African American athletes.

4.

Correct Answer: A. Restriction from competitive sports (except class IA) According to the 2015 ACA/AHA recommendations this athlete should be restricted from all competitive sports except class 1A.

However, the 2020 guidelines do permit participation in more intense exercise after appropriate risk stratification and a shared-decision making process. This should do done by a HCM expert/sports cardiology.

5.

Correct Answer: D. Surgical referral with return to competitive athletics 3 months postoperatively if asymptomatic and negative repeat stress testing An anomalous left main from right sinus with an interarterial/intramural course should be referred for surgical correction irrespective of symptoms. Stress testing is not necessary.

CHAPTER 66

Cardio-oncology EOIN DONNELLAN, MUZNA HUSSAIN, AND PATRICK COLLIER Cardio-oncology refers to the newly organized subspecialty that covers the broad intersection between heart disease and cancer. With focus on cancer survivors who get cardiovascular disease, and cardiovascular disease survivors who gets cancer, this subspecialty has emerged because of increased survivorship in both cohorts and a recognition of an expanding epidemiology. Annual cancer statistics released by the American Cancer Society estimate that there are currently over 20 million cancer survivors in the United States, and this is a growing cohort. Many of these cancer survivors have established cardiovascular disease or preexisting cardiovascular risk factors that impact their long-term outcomes. Among children that survive cancer, cardiac mortality is 7-fold higher with a 15-fold higher lifetime risk of developing heart failure compared to an age-matched population. Contributing to this growth are our aging population (both disease groups are much more prevalent with age) and shared risk factors (such as obesity, physical inactivity, smoking, diabetes, genetic predispositions). Recognizing that this overlap cohort is big and growing and includes some patients with complex and unmet needs, there has been a rapid growth in dedicated cardiooncology clinics. Patients are typically referred as a consult service from oncology or as subspecialist referrals from other cardiologists with a subset of patients directly referred or via pediatric survivorship clinics with a wide range of potential diagnoses (typically focused on specific cancer therapy–related problems, but some centers may also triage patients with cardiac masses, amyloidosis, and cancer-related thrombosis, etc.).

Although most patients tolerate cancer therapy without deleterious cardiovascular effects, an important minority will experience cardiovascular complications. Heart failure with reduced left ventricular systolic dysfunction induced by anthracycline chemotherapy has been the most published complication. However, increasing use of a broader range of chemotherapeutic agents has led to recognition of a spectrum of potential cardiovascular complications including rhythm disorders including atrial fibrillation, coronary artery disease including myocardial infarction, hypertension, and stroke. Mediastinal radiation therapy has been associated with toxic effects on all cardiac tissues (myocardium, pericardium, valves, conduction system, and coronary arteries), typically with a latency period of several decades.

CANCER THERAPEUTICS–RELATED CARDIAC DYSFUNCTION As discussed above, we now recognize many forms of cancer therapeutics– related cardiac dysfunction (CTRCD).1 From a purely echocardiographic perspective, this term has been narrowly defined by the American Society of Echocardiography as a decrease in left ventricular ejection fraction (LVEF) >10% points to a value less than the normal reference value lower limit (2. C is correct due to Qp/Qs of 2.35. A is a correct statement; however, it is not an indication for repair independently. B is a false statement; PVR is not elevated.

2.

Correct Answer: A. Proceed with a surgical referral for aortic valve replacement The patient has severe symptomatic aortic valve stenosis and is overall a low-risk patient based on the information available; hence, surgical replacement is indicated. There is no role for further surveillance at this time.

3.

Correct Answer: C. PAPi The PAPi in this setting is 1.5, which is low and suggestive of possible RV failure after LVAD implantation.

INDEX Page numbers followed by t indicate table, those followed by f indicate figure.

A AAA. See Abdominal aortic aneurysm (AAA) Abciximab (Reopro), 585, 700 Abdominal aortic aneurysm (AAA), 719 Abdominojugular reflex, 8 Ablation, 384–385 atrial flutter, 413 atrioventricular junction, 405 catheter, 413 Absolute risk reduction (ARR), 65 Accelerated AV junctional rhythm, 306 Accelerated idioventricular rhythm (AIVR), 306 ACE. See Angiotensin-converting enzyme Acromegaly, 872 ACS. See Acute coronary syndrome Action to Control Cardiovascular Risk in Diabetes (ACCORD), 790t, 791 ACTION trial, 563 Active fixation leads, 449 Active myocardial relaxation, 240 Acute chest pain, nuclear-based cardiac imaging in, 126 Acute coronary syndrome (ACS), 534, 538, 960. See also Non-ST-elevation acute coronary syndrome (NSTE-ACS) ACC/AHA classification for, 576, 577t angiotensin-converting enzyme inhibitors (ACE-I), 588–589 clinical presentation for, 576–577 discharge planning and noninvasive stress testing, 589

epidemiology and prognosis, 576 management of anti-ischemic agents, 587 antiplatelet agents, 583–586, 584f antithrombin therapy, 587 aspirin for, 583–584, 584f DTIs, 586 glycoprotein IIb/IIa inhibitors for, 578 heparins low molecular weight, 586 unfractionated, 586, 586 initial approach, 581 invasive therapy, 581–583 miscellaneous agents, 588–589 thienopyridines, 584–585 pathophysiology, 577–579 risk stratification biomarkers as, 577 ECG and, 577 TIMI risk score, 580, 581f summary on, 585 terminology and overview, 576 Acute corpulmonale, 312 Acute limb ischemia, 745 Acute mitral regurgitation, 489–490. See also Mitral regurgitation diagnosis for, 619, 619f symptoms and signs of, 618–619 treatment for, 619–620 Acute myocardial infarction (AMI), 20, 849–850 dobutamine for, 624 dopamine for, 615 norepinephrine for, 615 phenylephrine for, 625 Acute pericarditis, 311, 857–860. See also Pericarditis

acute episode, beyond, 860–861 etiology of, 857–858, 859t major and minor predictors for, 859t presentation and diagnosis, 857, 858t, 858f treatment for, 858–859, 860t Acute right to left interatrial shunting (ARLIAS), 901 Acute VTE (DVT/PE), 726 Adalat. See Nifedipine Adenosine pharmacologic stress echocardiography, 107 stress protocols, nuclear perfusion imaging, 117 ADMIRAL trial, 604 Adrenal carcinomas, 784 Adrenal insufficiency, 872–873 Adult congenital heart disease, guidelines for, 947 AFCAPS/TexCAPS. See Air Force/Texas Coronary Atherosclerosis Prevention Study AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management), 403, 403t African-American Study of Kidney Disease and Hypertension (AASK), 790t, 791–792 AFRP. See Atrial Functional Refractory Period Afterload, 37–38 AHA. See American Heart Association Air Force/Texas Coronary Atherosclerosis Prevention Study, 810t AIVR. See Accelerated idioventricular rhythm Alagille syndrome, 936t Alcohol septal ablation (ASA), 928 Aldomet. See Methyldopa Aldosterone, 50 antagonists, 168 Aldosterone blockade, 640 ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), 641–642, 790t, 791

Alpha-adrenergic agonist, midodrine, 468 Alström syndrome, 937t AltaValve device, 930t American Board of Internal Medicine (ABIM) Certifying Examination, 1 assessment, 1 first-time taker pass rates, 2t initial certification examination fee, 1 late fees and COVID-19 pandemic, 1 Maintenance of Certification (MOC) program, 1 registration dates, 1 score, 2 American Heart Association (AHA), 518–519 AMI. See Acute myocardial infarction Aminoglycosides, 517–518 Aminophylline, stress protocols, nuclear perfusion imaging, 118 Amiodarone, 406t, 408, 840t, 892t–897t Amlodipine, 169, 563t Ampicillin, 516t–517t Amplatzer PFO Occluder, 903, 905f Amplatzer Septal Occluder, 908f Amyl nitrite, 20 Anacrotic pulse, 7 Anemia, 875–876 Angina, 475 classifications, 579 medical treatment antiplatelet therapy, 560–561 lipid-lowering therapy, 561 renin–angiotensin–aldosterone system blockade, 561 pathophysiology of, 555 refractory, 571–572 revascularization in ACC/AHA recommendations, 565t coronary artery bypass grafting versus medical therapy, 566–568

PCI versus CABG for Patients with Diabetes Mellitus, 571 PCI versus CABG for Patients with Left Main Trunk Stenosis, 570–571 PCI versus CABG in Multivessel CAD, 569–570 PCI versus CABG in Single-Vessel CAD, 569 percutaneous coronary intervention versus medical therapy, 568– 569 stable CAD, 559t coronary angiography, 557–558 echocardiography, 556 electrocardiography, 555 exercise ECG testing, 555–556 stress testing with nuclear/echocardiographic imaging, 556–557, 557t symptomatic medical therapies, antianginals beta-blockers, 562–563, 562t calcium channel blockers, 563, 563t combination therapy, 564 nitroglycerin and nitrates, 563–564, 564t ranolazine, 564–565 unstable, 579–580 Angiography, 759 pulmonary, 730 Angiotensin II, 50 Angiotensin-converting enzyme (ACE) for stable angina, 561 for STEMI, 606 Angiotensin-converting enzyme inhibitor (ACEi), 58, 166, 760–761 Angiotensin-II (Ang-II), heart failure, 159 Angiotensin receptor blockers (ARBs), 166–167 for hypertension, 788, 792 in post-MI patients, 640 Angiotensin receptor neprilysin inhibitor (ARNI), 167–168

Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOTLLA), 810t–811t Ankle-Brachial Index, 745, 746t, 746f Annuloplasty, TR, 502–504 Anthracyclines, 959 limiting dose, 961 liposomal formulation of, 962 Antianginals, stable angina beta-blockers, 562–563, 562t calcium channel blockers, 563, 563t combination therapy, 564 nitroglycerin and nitrates, 563–564, 564t ranolazine, 564–565 Antiarrhythmic drugs, AF, 403, 892t–893t CHA2DS2-VASC, 410–411 class IA, 406t, 407 class IB, 407 class IC, 407 class III, 406t, 407–408 inpatient vs. outpatient initiation, 410 proarrhyrhmia risks associated with, 409–410 selection, 409–410 Antibiotics, 478 Anticholinergic agents, 468 Anticoagulants, 892t–893t during pregnancy, 839–841, 841t therapy, 760 for valves, 524–528, 525t Anticoagulation, 411, 526, 639 recommendations for, 411 Anti-CTLA-4 blocker ipilimumab, 959–960 Antihyperlipidemic therapy, 761 Antihypertensive therapy, 477, 760–761 Anti-ischemic agents, 587, 606

for ACS, 586 Antiplatelet agents, 747–748 for ACS aspirin, 583–584 glycoprotein IIb/IIIa inhibitors, 578 thienopyridines and ADP inhibitors, 584–585 for STEMI, 603–604 Antiplatelet therapies, 637–639, 699–700, 760, 903 Antiproliferative agents, 190 Antitachycardia pacing (ATP), 457 Antithrombin therapies, 587, 700 Antithrombotic agents, for STEMI, 604–606 Antithrombotic Trialists Collaboration, 560 Aorta, 31, 31f. See also Coarctation of aorta anatomy of, 711 diseases of, pathologic processes for, 711–712 Aortic aneurysm, 137, 717–719, 721 abdominal, 719 thoracic, 717–719, 717f Aortic coarctation (CoA), 269–270 Aortic disease, 141 cardiac MRI aortic aneurysm, 137 aortic dissection, 137 intramural hematoma, 137 Aortic dissection, 137, 480, 712–715, 712f, 721 chronic, 715 classifications of, 712, 713t, 713f clinical presentations of, 712–714 diagnostic testing, 714, 714t iatrogenic, 715, 715f management of, 714–715 type A, 21 in young, 715

Aortic insufficiency anorectic drugs, 480 chest X-ray for, 480 clinical findings on, 480 ECG for, 480 echocardiography for, 480–481 etiology of, 479–480 pathophysiology of, 479 physical exam, 480 radiation heart disease, 480 secondary causes, 480 subaortic stenosis, 480 treatment for, 481–482 valvular causes, 479–480 vasodilators for, 481 Aortic regurgitation (AR), 666 diastolic murmurs, 18 pregnancy and, 833 Aortic root dilatation, 480 Aortic sclerosis, systolic murmurs, 15 Aortic stenosis (AS), 666–667, 836 cardiomediastinal silhouette patterns, 76, 76f classifications of, 477 clinical findings in, 475–477, 476f ECG for, 475 estimation, 476–477 etiologies of, 473–475, 474f invasive assessment of, 477, 477f pathophysiology of, 473 pseudostenosis vs. low gradient, 479 stress echo, 111 subvalvular, 474 supravalvular, 474–475 treatment of, 477–478, 478t

TTE for, 475–477 vasodilators for, 477 Aortic valve(s), 30, 30f anatomy, 473, 474f morphology of, 476 resistance, 664 Aortic valve area (AVA), 476 Aortic valve morphology, 476 Aortic valve replacement, AS, 478–479, 478t Aortic valvular stenosis, systolic murmurs, 14–15, 14f–15f Aortography, 680–683, 682f, 684f Aortopathies, 956 Apixaban, 412 Apresoline. See Hydralazine AR. See Aortic regurgitation ARBS. See Angiotensin-receptor blockers Arixtra. See Fondaparinux ARR. See Absolute risk reduction Arrhythmias, 413, 426–427, 463, 953–955, 960 heart failure (HF) and, 212 Arrhythmic complications bradyarrhythmias, 626, 627t tachyarrhythmias, 626–627 Arrhythmogenic right ventricular cardiomyopathy (ARVC), 221, 953 cardiac MRI, 136, 136t Arrhythmogenic right ventricular dysplasia (ARVD), 392f, 938t Arterial pulse(s). See also Pulse(s) anacrotic pulse, 7 Corrigan, 8 dicrotic pulse, 7 disease states, 4, 5t–6t, 6f double-peaked pulse, 7 Duroziez sign, 8 Hill sign, 7

loud systolic sound, 8 Mayen sign, 8 normal, 6f osler sign, 7 pressure/pulse difference in two arms, 7 principles, 4 pulse deficit, 7 pulsus alternans, 4 pulsus paradoxus, 6–7 pulsus tardus and parvus, 7 radial-to-femoral delay, 7 supravalvular AS and, 7 Traube sign and, 8 water-hammer pulse, 8 ARVC. See Arrhythmogenic right ventricular cardiomyopathy ARVD. See Arrhythmogenic right ventricular dysplasia AS. See Aortic stenosis ASCOT-LLA. See Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm ASD. See Atrial septal defect Aspiration thrombectomy, 602 Aspirin, 411–412, 635, 699–700, 760, 903 for ACS, 583–584 for PCI, 700 for stable angina, 560 for STEMI, 608 ASSENT (Assessment of Safety and Efficacy of a New Thrombolytic) and ASSENT-PLUS studies, 633 ASSENT-3 trial, 605–606 Asymptomatic carotid artery stenosis (ACAS), 757 Asymptomatic Carotid Surgery Trial (ACST), 761–762 Asymptomatic patients, AS, 477 Atheromatous aortic disease, 720–721, 720f Atherosclerosis, 712

Athlete's heart, 948–949 Atorvastatin for NSTEMI, 588 for STEMI, 607 Atrial arrhythmias, 908 ablation of maze procedure, 414 pacemaker therapy, 414 pulmonary vein isolation, 413–414 catheter ablation of, 413 Atrial bradycardia, ectopic, 305 Atrial extrastimulus testing, 375 Atrial fibrillation (AF), 10, 261, 305, 902 antiarrhythmic drugs for class IA, 406t, 407 class IB, 407 class IC, 407 class III, 406t, 407–408 inpatient vs. outpatient initiation of, 410 proarrhythmia risks associated with, 409–410 selection of, 409–410 AV node ablation, 413 catheter ablation, 413 definitions, 402 epidemiology, 400 evaluation, 402–403 factors predisposing, 400 management, 403–404, 403t–404t morbidity and mortality, 400–401 nonpharmacologic rate control, 405 onset of, 489 pathogenesis, 401–402 pharmacologic conversion, 405–406, 406t sinus rhythm

maintenance of, 406, 406t restoration of, 405–406, 406t Atrial flutter, 305 clinical presentation and diagnosis, 426 mechanism, 426–427 nonpharmacologic management, 412–413 reentrant mechanism, 401–402 cavotricuspid isthmus–dependent atrial flutter, 401, 402f noncavotricuspid isthmus-dependent atrial flutter, 401 treatment, 427 Atrial Functional Refractory Period (AFRP), 381 Atrial natriuretic peptide (ANP), 58–59 Atrial oversensing, 449 Atrial pacing EP and, 379–380, 380f incremental, 372 Atrial rhythm, ectopic, 305 Atrial sensitivity, 449 Atrial septal aneurysm/large interatrial shunt, 902–903 Atrial septal defect (ASD), 21, 265–267, 266f, 267t, 833 coronary sinus ASD, 287 primum, 283, 284t, 285f, 312 secundum ASD, 283, 286f, 312 sinus venosus ASD, 283, 287f types of, 283–287, 284f Atrial septal defect closure, 903–908 diagnosis, 906 follow-up, 908 management of, 906–908, 907t outcomes, 908 pathophysiology of, 906 presentation, 906 Atrial systole phase, 240 Atrial tachycardia, 305

clinical presentation and diagnosis, 426 mechanisms, 426 treatment, 426 Atrial-dependent arrhythmias, 426–427, 427f Atrial Flitter, 426–427 atrial tachycardia, 426 Atrioventricular block (AVB) first degree, 307 second degree Mobitz Type I (Wenckebach), 307 Mobitz Type II, 307 third degree (complete heart block), 307 Atrioventricular (AV) dissociation/ventricular tachycardia, 8 Atrioventricular junction ablation, 405 Atrioventricular junctional bradycardia, 306 Atrioventricular junctional rhythm, accelerated, 306 Atrioventricular junctional tachycardia, 306 Atrioventricular nodal reentrant tachycardia (AVNR), 305, 954 Atrioventricular (AV) node, 33, 33f Atrioventricular reentrant tachycardia (AVRT), 305, 954 differential diagnosis, 430–432, 431f Atropine, pharmacologic stress echocardiography, 107 Attributable risk, 65 Atypical antipsychotics, 897t Auscultation, dynamic, 19–20 hemodynamic maneuvers, 19–20 pharmacologic agents, 20 respiration, 19 valsalva, 19, 20f Autonomic dysfunction, primary and secondary causes of, 462t Autonomic nervous system dysfunction, heart failure, 159 Autosomal dominant long QT syndrome (LQTS), genes with mutations definitively associated with, 938t Autosomal/mitochondrial genetic disorders, 936t

A–V delay, 450 AV junctional bradycardia, 306 AV junctional tachycardia, 306 AV nodal reentrant tachycardia (AVNRT), 954 AV nodal refractory periods, 375–376, 376f AV node ablation, 413 AV node-dependent tachycardias (AVNRT) clinical presentation and diagnosis, 420 mechanism, 420–421, 421f treatment, 421 AV reciprocating tachycardia (AVRT).See also Wolff–Parkinson–White (WPW) syndrome accessory pathways, 422, 422f–423f antidromic tachycardia, 423–424 clinical presentation and diagnosis, 421–422 electrophysiologic characteristics and diagnostic maneuvers, 423 mechanism, 422–423 treatment, 424–425 Wolff-Parkinson-White syndrome and sudden cardiac death, 425 AVNRT. See Atrioventricular nodal reentrant tachycardia Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension trial (ACCOMPLISH), 790t, 791 AVRT. See Atrioventricular reentrant tachycardia Azathioprine (Imuran), 190 Azole antifungals, 894t–896t

B β-Adrenergic signaling, 56–57 of cardiac myocyte, 57f subtypes, 56–57 Ball-in-cage valve, 13, 523f–524f Balloon aortic valvuloplasty (BAV), 479 Balloon valvotomy, 505 Balloon valvuloplasty, 479 β-Arrestins, 56–57

Baseline intervals, 366–367, 367f Basiliximab (Simulect), 188 Bayes theorem, 66 BBB. See Bundle branch block Bcr-Abl inhibitors, 959–960 Beam-width artifacts, 92 Behçet disease, 875 Bernoulli principle, 93 Beta-adrenergic blockers, 404 Beta-blockers, 562–563, 562t, 587–588, 606, 749, 840t, 962 for MI, 640–641 for syncope, 468 Beta-receptor blockade (beta-blockers), 640–641 Bevacizumab, 959–960, 960t Bias in biostatistics, 67 observation, 67 recall, 67 selection, 67 verification, 67 Bicuspid aortic valve, 288–289, 290f Bileaflet mechanical valve, 523f–524f Biologic valves, 478 Biomarkers, 581, 635, 961 Biostatistics bias in, 67 causality and validity in, 67 confounding and interaction in, 66–67, 67f data presentation/outcomes reporting in, 65–66, 66f, 67f diagnostic test, 66, 66f exposures, 63 outcomes, 63 statistical tests for, 64 types of clinical studies in

case reports as, 63 case series as, 63 case–control study as, 63, 64f cohort study as, 63, 64f meta-analysis, 64 prospective vs. retrospective, 63 randomized controlled trials as, 63–64 Biphasic waveforms, 455 Bipolar leads, pacing leads, 448 Bivalirudin, 605, 700 Blood cultures, 513 microbiology, 511 Blood flow definition, 93 principles of flow, 93 turbulent flow, 93 velocity of, 93 Blood pressure control, 748–749, 749f BMD. See Bone mineral density BMI. See Body mass index Board certification, 1–2. See also American Board of Internal Medicine (ABIM) Certifying Examination Body mass index (BMI), 198 Bone mineral density (BMD), 194 Bortezomib, 959–960, 960t Bradyarrhythmias, 369, 626, 627t, 840 Brain natriuretic peptide (BNP), 58–59, 580, 635 Braunwald classification of unstable angina, 579–580 BRAVE-2 trial, 601 Brockenbrough response, 256, 257f Brucella, 513, 517–518 Brugada syndrome, 394, 394f, 938t Bruton tyrosine kinase inhibitors, 959–960

Bundle branch block (BBB), 626 Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI-2D) trial, 571

C CABG. See Coronary artery bypass graft CAD. See Coronary artery disease Cadaveric homografts, 478 CADILLAC trial, 604 Calan. See Verapamil Calcification patterns calcific constrictive pericarditis, 79, 79f calcified post-MI left ventricular true aneurysm, 80, 80f cardiac, 79 coronary artery calcification, 81, 81f left atrial wall calcification, 79, 79f mitral annular calcification, 80, 80f paracardiac, 79 Calcineurin inhibitors, 188–190, 189t Calcium blockers, dihydropyridine, 791 elemental, 194 Calcium channel blockers (CCBs), 403, 563, 563t, 840t for HF, 169 for syncope, 468 Calcium-dependent AP versus tissues with sodium channels, 51, 51f Canadian Cardiovascular Society (CCS), 554, 555t Canadian Cardiovascular Society Angina Pectoris Scale, 693t Cancer, 962–963 and venous thromboembolic disease (VTE), 962–963 prevention of, 962–963 risk assessment, 962 risk factors, 962 treatment and secondary prevention, 964 Cancer therapeutics–related cardiac dysfunction (CTRCD), 959–961

cardiotoxic effects and active cardiac surveillance, 962 clinical presentations of, 960–961 limiting anthracycline dose, 961 patient selection, 961–962 prevention of, 961–962 referral to cardio-oncology programs, 962 type 1, 959 type II, 959 type III–IX, 959–960, 960t Candida, 192 Cangrelor, 604 CAPRICORN (Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction) trial, 640–641 Captopril, 787, 787t, 892t–893t CAR. See Coxsackie-adenovirus receptor (CAR) Carbamazepine, 896t Carcinoid heart disease, 888 Carcinomas, 887–888 Cardene. See Nicardipine Cardiac allograft vasculopathy (CAV), 183 Cardiac amyloidosis, 245 cardiac MRI, 135 SPECT imaging in, 127 Cardiac anatomy. See also Heart cardiac chambers left atrium, 28, 28f left ventricle, 28–29, 28f right atrium, 27, 27f right ventricle, 28, 28f cardiac valves aortic valve, 30, 30f mitral valve, 29–30, 30f pulmonic valve, 29, 29f tricuspid valve, 29, 29f

conducting system, 33–34, 33f great vessels aorta, 31, 31f cardiac lymphatic system, 33 cardiac veins, 32–33, 33f coronary arteries, 31–32, 31f–32f pulmonary arteries, 30–31 pulmonary veins, 31 vena cavae, 30 location, 26 pericardium, 26–27, 27f position, 26, 27f shape, 26 size, 26 Cardiac arrhythmias, genetic variants of, 938t Cardiac biochemistry, cardiac contractility and calcium homeostasis, 56 Cardiac calcification patterns, 79. See also Calcification patterns Cardiac catheterization, 256, 257f, 646–657, 647f, 649t, 650f, 651f, 652t– 655t, 652f Cardiac chambers enlargement, 308–309 left atrium, 28, 28f left ventricle, 28–29, 28f right atrium, 27, 27f right ventricle, 28, 28f Cardiac computed tomography angiography, 851 cardiac masses evaluation, 142–143, 143t clinical applications, 139–141 CT physics, 137–139 indications, 137 limitations, 141–142 contrast exposure, 142 image quality, 141, 141t radiation exposure, 141–142, 142t

technical considerations, 137–139 Cardiac diseases, 390. See also specific types Cardiac electrophysiology conduction system anatomy and physiology, 51–53 electrical coupling cells (gap junction), 51 fundamental aspects, 49 membrane action potential calcium-dependent AP versus tissues with sodium channels, 51, 51f Na+ channel activity regulation, 50–51 sodium-dependent cells, 49 Cardiac free wall rupture diagnosis of, 620, 621f signs and symptoms of, 620 treatment for, 620 Cardiac hemangiomas, 886 Cardiac imaging guidelines for, 946–947 cardiovascular computed tomography, 946 echocardiography, 946–947 Cardiac intervals, measurement of, 307 Cardiac lipomas, 884 Cardiac lymphatic system, 33 Cardiac magnetic resonance imaging (CMR) 961 aortic disease aortic aneurysm, 137 aortic dissection, 137 intramural hematoma, 137 basic imaging sequences, 132–134 cardiac masses evaluation, 142–143, 143t clinical applications arrhythmogenic right ventricular cardiomyopathy (ARVC), 136, 136t cardiac amyloidosis, 135

cardiac sarcoidosis, 135–136 coronary artery disease, 134 dilated cardiomyopathy, 134 heart failure, 134 hemochromatosis, 136 hypertrophic cardiomyopathy, 135 myocardial disease, 134 myocardial fibrosis, 135 myocarditis, 135–136 restrictive cardiomyopathy, 135 viability assessment, 134 contraindications, 138t delayed hyperenhancement short-axis image, 133f flow curve, 133f gadolinium-based contrast media agents, 134 indications, 133t limitations of, 137 MRI physics, 132 pulse sequences, 132 Cardiac myocyte, 56 Cardiac output (CO), 660 heart failure, 153–156 measurement, 660–661 Cardiac pacing. See also Implantable cardioverter defibrillators basic concepts of impulses and timing, 449–450 device features, 446–449 indications, 445 permanent pacing, 446, 446t–447t programming, 450–451 summary on, 458 temporary pacing, 445–446 troubleshooting and complications, 451–452 Cardiac papillary fibroelastoma, 883t, 884, 884f Cardiac physical examination

arterial pulse anacrotic pulse, 7 Corrigan, 8 dicrotic pulse, 7 disease states, 4, 5t–6t, 6f double-peaked pulse, 7 Duroziez sign, 8 Hill sign, 7 loud systolic sound, 8 Mayen sign, 8 normal, 6f osler sign, 7 pressure/pulse difference in two arms, 7 principles, 4 pulse deficit, 7 pulsus alternans, 4 pulsus paradoxus, 6–7 pulsus tardus and parvus, 7 radial-to-femoral delay, 7 supravalvular AS and, 7 Traube sign and, 8 water-hammer pulse, 8 dynamic auscultation, 19–20 extra heart sound diastole, 12, 12f opening snap, 12 pacemaker sounds, 13 prosthetic heart sounds, 13 systole, 12–13 findings, 5t–6t first heart sound intensity, 10 principles, 10 splitting, 10

fourth heart sound, 11–12 heart murmurs, 13–14 inspection, 4 jugular venous pulse disease states, 8–9 pressure, 8 principles, 8 waveforms, 8 precordial motion dilation, 9 disease states, 9–10 hypertrophy, 9 principles, 9 principles, 4 second heart sound intensity, 10 principles, 10 single S2, 10 splitting, 10–11, 11f third heart sound, 11 Cardiac power output (CPO), 671 Cardiac radioactive tracers nitrogen-13 ammonia, 114–115 oyxgen-15 water, 115 PET tracers, myocardial metabolism, 115 PET tracers, myocardial perfusion, 114 rubidium-82, 114 SPECT perfusion agents, 114 technetium pyrophosphate (PYP-Tc99m), 115 technetium-99m-labeled agents, 114 thallium-201 chloride, 114 transthyretin (ATTR) amyloid cardiomyopathy, 115 Cardiac resynchronization therapy (CRT) with biventricular pacing, 446–447 Cardiac rhabdomyomas, 883t, 884–885

Cardiac sarcoidosis, 392 cardiac MRI, 135–136 PET imaging, 127–128 Cardiac SPECT imaging, 116–117 Cardiac syncope, 463 Cardiac tamponade, 9, 21, 860–862 Cardiac tumors benign, 882–886, 883t, 883f, 884f, 885f malignant, 886–887, 886t, 887f secondary, 887–888, 887f Cardiac valves aortic valve, 30, 30f mitral valve, 29–30, 30f pulmonic valve, 29, 29f tricuspid valve, 29, 29f Cardiac veins, 32–33, 33f Cardiogenic shock, 607, 632, 690 Cardiomediastinal silhouette patterns aortic stenosis, 76, 76f coarctation, 77, 77f mitral regurgitation, 78, 78f mitral stenosis, 78, 78f normal cardiac silhouette, 74, 74f normal landmarks, 74 pectus excavatum, 75, 75f pericardial cyst, 75, 75f pseudocoarctation, 76, 76f size, 74 valvar pulmonic stenosis, 77, 77f Cardiomyopathies, 836, 952–953. See also Dilated cardiomyopathy; Hypertrophic cardiomyopathy arrhythmogenic right ventricular, 221 classification, 215f, 220t dilated, 219–220

forms of, 220t genetic variants of, 937t idiopathic dilated See (Idiopathic dilated cardiomyopathy (IDCM)) inflammatory, 218t inherited, 59, 60t metabolic, 220 mitochondrial, 221 and pressure–volume loop, 41, 41f primary, 215f Cardio-oncology baseline cardiovascular assessment and monitoring, 961 cancer and venous thromboembolic disease (VTE), 962–963 prevention of, 962–963 risk assessment, 962 risk factors, 962 treatment and secondary prevention, 964 cancer therapeutics–related cardiac dysfunction (CTRCD)., 959–961 cardiotoxic effects and active cardiac surveillance, 962 clinical presentations of, 960–961 limiting anthracycline dose, 961 patient selection, 961–962 prevention of, 961–962 referral to cardio-oncology programs, 962 type 1, 959 type II, 959 type III–IX, 959–960, 960t cardioprotective medical therapy, 962 definition of, 959 radiation-associated cardiac disease (RACD), 963–964 screening guidelines and multimodality imaging in, 964, 964t Cardioprotective medical therapy, 962 CardioValve device, 930t Cardiovascular computed tomography, 946 Cardiovascular diseases (CVDs), 72–73

after pregnancy, 836–839, 838t board exam, 2 breakdown in content of, 2t first-time taker pass rates, 2, 2t format, 2, 2t general information, 2t pitfalls, 3b tips, 2–3 management of athletes with, 951–956, 952t aortopathies, 956 arrhythmias, 953–955 cardiomyopathies, 952–953 coronary anomalies, 955–956 Marfan syndrome, 956 pericarditis, 956 valvular disease, 955 risk factors nonconventional, 551 traditional modifiable, 549–551 diabetes mellitus, 550 hypertension, 550 lipids, 549–550 obesity and metabolic syndrome, 550–551 tobacco, 549–550 in United States age and gender variation of, 545–546, 545f, 546f cost and health care resources utilization, 548–549, 549t prognosis and risks associated with SCD, 547–548 racial and socioeconomic disparities of, 545t, 546–547, 547f silent myocardial ischemia/infarction, 544–545, 545f–546f temporal trends of, 543 unrecognized myocardial ischemia/infarction, 544–545, 545f–546f young people and, 547 Cardiovascular drug interactions

food and natural products drug interactions, 897–898 mechanism of action for, 58t pharmacodynamic drug–drug interactions, 897, 897t pharmacokinetic drug–drug interactions, 891–897, 892t–896t Cardiovascular magnetic resonance imaging, 852 Cardioversion, 457 Cardizem. See Diltiazem CARDS. See Collaborative Atorvastatin Diabetes Study CARE. See Cholesterol and Recurrent Events Carfilzomib, 959–960 Carney complex, 882, 883t Carotid aortic arch anatomy, 757–758, 758f artery stenting, 762–763 clinical presentation, 758, 759t diagnostic testing, 758–759 angiography, 759 carotid intima–media thickness, 758 carotid ultrasound, 758, 759t computed tomography angiography, 759 Doppler criteria, 759t magnetic resonance angiography, 759 endarterectomy, 761–762, 762t–763t, 762f epidemiology, 757 medical treatment, 759–761 anticoagulant therapy, 760 antihyperlipidemic therapy, 761 antihypertensive therapy, 760–761 antiplatelet therapy, 760 pathophysiology of, 757 recommendation, 760 Carotid artery stenting, 762–763 Carotid endarterectomy, 761–762, 762t–763t, 762f Carotid intima–media thickness, 758

Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), 762–763 Carotid sinus hypersensitivity (CSH), 465 Carotid sinus massage (CSM), 465 Carotid sinus syncope, 462 Carotid stenosis, 762t Carotid ultrasound, 758, 759t Carvedilol, 640–641 CASS (Coronary Artery Surgery Study), 566 Catapres. See Clonidine Catecholaminergic polymorphic ventricular tachycardia (CPVT), 393, 938t, 948, 954 Catheter(s), 702–703 ablation of AF, 413 maze, 414 Causality, 67 CAV. See Cardiac allograft vasculopathy CBC. See Complete blood count CCBs. See Calcium channel blockers Cellcept. See Mycophenolate mofetil Center for Medicare and Medicaid Services (CMS), 453 Cephea device, 930t CETP. See Cholesteryl ester transfer protein Chagas heart disease, 219 Channelopathies, 953–954 CHARGE (Coloboma, heart defects, atresia choanae, growth retardation, genital and ear abnormalities) syndromes, 936t CHD. See Congenital heart disease; Coronary heart disease Checkpoint inhibitors, 959–960 Chemotherapy, 876–877 Chest discomfort anomalous coronary artery, 540 atypical syndrome, 534 cardiac biomarkers, 536–537

cardiac magnetic resonance (CMR) imaging, 539 causes of, 537t chest x-ray, 538 computed tomography coronary angiography, 539 coronary angiography, 539 diagnostic testing and triage, 535–539 differential diagnosis, 533, 534t electrocardiogram, 535 family/social/medication history and, 535 history of, 533–535 location of, 533 medical history, 534–535 myocardial infarction with nonobstructive coronary arteries, 539–540 physical examination, 535 plaintive and palliative factors, 533 quality of, 533 radiation of, 533 repeat testing, 540 risk scores, 537–538, 538t severity of, 533–534 special populations, 539–540 stress testing, 538–539 syncope, 540 timing of, 533 transthoracic echocardiogram, 538 typical syndrome, 534 in women, 539–540 Chest radiography (CXR) approach and projections, 71 calcification patterns calcific constrictive pericarditis, 79, 79f calcified post-MI left ventricular true aneurysm, 80, 80f cardiac, 79 coronary artery calcification, 81, 81f

left atrial wall calcification, 79, 79f mitral annular calcification, 80, 80f paracardiac, 79 cardiomediastinal silhouette patterns aortic stenosis, 76, 76f coarctation, 77, 77f mitral regurgitation, 78, 78f mitral stenosis, 78, 78f normal cardiac silhouette, 74, 74f normal landmarks, 74 pectus excavatum, 75, 75f pericardial cyst, 75, 75f pseudocoarctation, 76, 76f size, 74 valvar pulmonic stenosis, 77, 77f pulmonary vascular patterns cardiovascular disease states, 72–73 pulmonary edema patterns, 74 Chest x-ray (CXR), 475, 538 Cholesterol absorption inhibitors for dyslipidemias, 807, 808t embolization syndrome, 720 Cholesterol and Recurrent Events (CARE), 810t Cholesteryl ester transfer protein (CETP), 798–799 Cholestyramine, 808t–809t Chromosomal abnormalities, 936t Chronic kidney disease (CKD), 786, 792 Chronic mitral regurgitation, 490–491, 490f, 491f Chronic renal dysfunction, 193 Chronotropic competence, 450 Churg–Strauss syndrome, 875 Chylomicrons, 798, 799f, 803t, 805 CI. See Confidence interval Cilostazol, 750

Cimetidine, 189t, 894t–896t CIN. See Contrast induced nephropathy Ciprofibrate, 808t Circle of Willis, 269 Circulatory-assist devices, 615–616 CK. See Creatine kinase Clarithromycin, 894t–896t CLARITY-TIMI 28 trial, 604 Classic OH, 463 Clevidipine, 793t Clofibrate, 808t–809t Clonidine (Catapres), 786, 793t, 840t Clopidogrel (Plavix), 584, 603, 760, 903 Closing click (CC), 13 CM. See Cardiomyopathy CO. See Cardiac output COA. See Coarctation of aorta Coagulopathies, 603–604 Coarctation, cardiomediastinal silhouette patterns, 77, 77f Coarctation of aorta (CoA), 269–270, 292, 292f, 294f, 834 hypertension, 789 pregnancy and, 834 Coding system, cardiac pacemakers, 450, 450t Colchicine, 858–859 COlchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) trial, 858–859 Colesevelam, 808t Colestipol, 808t Collaborative Atorvastatin Diabetes Study (CARDS), 811t Color Doppler vs. continuous wave and pulsed wave Doppler, 90t COMET (Carvedilol or Metoprolol European Trial), 640–641 Complete blood count (CBC), 579 Complete heart block, 8 Complex cyanotic congenital heart disease, 835

Complex lesions Ebstein anomaly, 271–272, 272f Eisenmenger Syndrome, 273–274 Single Ventricle Circulations, 272–273 Tetralogy of Fallot, 271 Transposition of the great arteries (TGA), 270–271 Compliance, pressure–volume loop, 40 Computed tomography angiography, 759 Computed tomography pulmonary angiography (CTPA), 730 Computer tomography (CT), cardiac cardiac masses evaluation, 142–143, 143t clinical applications, 139–141 CT physics, 137–139 indications, 137 limitations, 141–142 contrast exposure, 142 image quality, 141, 141t radiation exposure, 141–142, 142t technical considerations, 137–139 Conduction system, 33–34, 33f anatomy and physiology, 51–53 disease, 964 Confidence interval (CI), 64 Confounding factor, 66, 67f altering study design, 67 Congenital heart disease (CHD) in adult cardiac catheterization, 274–275 complex lesions (acyanotic), 270–274 concepts, 265 diagnostic evaluation, 274 diagnostic imaging, 274, 274t general management strategies, 275–276 shunt lesions, 265–268, 267t

stenotic lesions, 268–270 hereditary and chromosomal defects, 283, 284t operations for, 296–298, 299t Congenital valve disease, 474 Congenitally corrected D-TGA, 293, 295, 298f Conn syndrome, 872 Connective tissue disorders, 873–875 Constrictive pericarditis, 8–9, 21, 668–669, 669f, 861t, 862–865, 863f– 865f, 863f, 864f, 865f, 866t differential clinical characteristics, 861t differential imaging characteristics, 861t, 866t presentation and diagnosis, 862–865 Constrictive physiology, 667–670, 668f, 669f, 670f Continuous wave Doppler low-velocity flow on, 91f vs. pulsed wave and color, 90t Contractility myocardial performance, determinants of, 38 pressure–volume loop, 40 Contrast induced nephropathy (CIN), 700 Contrast materials, 703 Convective acceleration, 93 Corlopam. See Fenoldopam Corneal Arcus, 801f–802f Coronary angiography, 557–558, 824 Coronary anomalies, 955–956 Coronary arteries, 31–32, 31f–32f Coronary artery bypass graft (CABG), 757, 824 PCI vs. for diabetes mellitus patients, 571 for left main trunk stenosis, 570–571 in multivessel CAD, 569–570 in single-vessel CAD, 569 PCI/post, 689

Coronary Artery Bypass Graft Surgery, 603 Coronary artery calcification, 81, 81f Coronary artery disease (CAD), 139–140, 395, 837–838, 849–850 cardiac MRI, 134 in catheterization laboratory, 675 global burden of, 543, 544t risk factors nonconventional, 551 traditional modifiable, 549–551 diabetes mellitus, 550 hypertension, 550 lipids, 549–550 obesity and metabolic syndrome, 550–551 tobacco, 549–550 in United States age and gender variation of, 545–546, 545f, 546f cost and health care resources utilization, 548–549, 549t prognosis and risks associated with SCD, 547–548 racial and socioeconomic disparities of, 545t, 546–547, 547f silent myocardial ischemia/infarction, 544–545, 545f–546f temporal trends of, 543 unrecognized myocardial ischemia/infarction, 544–545, 545f–546f young people and, 547 Coronary calcium scoring, 140–141 Coronary CT angiography (CTA), 139 Coronary heart disease (CHD) morbidity/mortality and, 798 prevention of early lipid-regulating trials for, 809t primary, landmark statin trials, 810t secondary, landmark statin trials, 810t subsequent statin trials for, 811t Coronary intravascular imaging intravascular ultrasound

applications of, 679, 679f atherosclerosis, characterization of, 678 normal coronary artery anatomy, 678, 678f optical coherence tomography, 679–680, 680f Coronary sinus defect, 905, 905f Coronary sinus leads, 449 Coronary stents, 602 Corrigan pulse, 8 Corticosteroids, 191, 859 Counterregulatory systems (natriuretic peptides), heart failure, 160 COURAGE study (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation), 693–694 CoveValve Extreme Risk Study high–surgical-risk patients, 913–914, 913t inoperable patients, 912–913, 912t Coxiella burnetii, 511, 517–518 Coxsackie-adenovirus receptor (CAR), 214 Creatine kinase (CK), 633 CREDO (Clopidogrel for the Reduction of Events during Observation), 637– 639, 699 CREST syndrome, 874 Critical limb ischemia, 745 Cryptogenic stroke, 902t CsA. See Cyclosporine CTPA. See Computed tomography pulmonary angiography C-type natriuretic peptide (CNP), 58–59 CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) study, 584, 637–639 CURRENT-OASIS 7 trial, 583 Cushing syndrome, 785, 872 CVDs. See Cardiovascular diseases CXR. See Chest x-ray Cyclophosphamide, 960t Cyclosporine (CsA), 188

Cystic medial degeneration, 711

D Dabigatran, 412 Daclizumab (Zenapax), 188 Dallas criteria, 212 DCM. See Dilated cardiomyopathy D-Dimer test, 726 Deep vein thrombosis (DVT) clinical presentation and diagnosis, 726–727, 727f D-Dimer, 726 diagnostic testing, 728 duplex ultrasonography, 727–728 venography, 728 Defibrillation, 457 DEFINITE trials, 377 Degenerative mitral regurgitation, 923, 925–927 Delayed/progressive OH, 463 Device infection/erosion, 452 Device programming, 450–451 Dexrazoxane, 962 Dextrocardia, 312 Diabetes mellitus (DM), 845–846 CAD and, 550 occurrence, 534–535 Diastasis (slow filling) phase, 240 Diastole, 12, 12f Diastole, phase of atrial systole phase, 240 diastasis (slow filling) phase, 240 isovolumic relaxation phase, 239 rapid filling phase, 239–240 Diastolic function, 476 Diastolic murmurs, 14, 17f aortic regurgitation, 18

mitral stenosis, 17–18 pulmonic regurgitation, 18 tricuspid stenosis, 18 Dicrotic pulse, 7 Digitalis, 58 effect of, 311 toxicity, 311 Digitalis Investigation Group (DIG) trial, 170 Digoxin (Lanoxin), 403, 840t, 892t–896t Dihydropyridines, calcium blockers, 791 Dilacor. See Diltiazem Dilated cardiomyopathy (DCM), 20, 219–220, 391, 823, 953 cardiac MRI, 134 inherited forms, 220–221 SCD and, 391 VT and, 396 Diltiazem, 257–258, 563t, 786, 892t–896t Dimensionless index (DI), 476 definition, 525 DINAMIT trials, 608 Dipyridamole (DP), 760 pharmacologic stress echocardiography, 107 stress protocols, nuclear perfusion imaging, 117 Direct thrombin inhibitors (DTIs), 586–587, 732 Disability-adjusted life year (DALY), 543 Disopyramide, 406t, 407, 897t Diuretics, 619–620, 892t–893t DM. See Diabetes mellitus Dobutamine, pharmacologic stress echocardiography, 106 Dofetilide, 406t, 408, 840t, 892t–897t Dopamine (Inotropic) for AMI, 615 physiologic effects of, 607 Doppler echocardiography, 89–91

Dose modulation, 142 Double-peaked pulse, 7 Down syndrome, 905, 936t Doxorubicin, 960t Dressler syndrome, 608 Dronedarone, 406t, 408, 892t–897t Droperidol, 897t Drug(s). See also specific drugs antiarrhythmic drugs, AF, 403 class IA, 406t, 407 class IB, 407 class IC, 407 class III, 406t, 407–408 inpatient vs. outpatient initiation, 410 selection, 409–410 cardiovascular pharmacodynamic interactions of, 897, 897t pharmacokinetic interactions of, 891–897, 892t–896t DTIs. See Direct Thrombin Inhibitors Dual antiplatelet therapy (DAT), 760 Duke criteria, 512–513 Duke Treadmill Scores, 555–556, 556t Duplex ultrasonography, 727–728 Duroziez sign, 8 Dutch Lipid Network, 802 DVT. See Deep vein thrombosis Dynamic auscultation hemodynamic maneuvers, 19–20 pharmacologic agents, 20 respiration, 19 valsalva, 19, 20f Dynamic LVOT obstruction, 624–626 diagnosis for, 625 signs/symptoms of, 624–625

treatments for, 625 Dyslipidemias apheresis therapies for, 813–814 classification of, 801–802, 802f diabetes and lipid management, 814 diagnosis of, 800–801, 801f–802f fibrates, 805, 808t, 811 future directions for, 813t, 814–815 lipid lipoproteins and, 798–800, 799f, 800t other, 812t metabolic syndrome (metS), 805, 805t metS and, 805t niacin, 807, 811 pharmacologic therapies for, 807–813, 807t–808t primary, 802–804, 803t, 804f secondary, 804–805 TLC for, 806–807, 806t treatments for, 806–807, 806t, 807f Dystrophin (DMD), 937t

E Early menopause, 848 EBCT. See Electron-beam CT Ebstein anomaly, 271–272, 272f, 293, 296f ECG. See Electrocardiogram ECG interpretation in athletes, 951, 951f Echocardiography, 253–256, 254f, 255f, 556, 946–947, 961.See also Stress Echocardiography; Transthoracic echocardiography monitoring prosthetic valves with, 525–528, 525f stress, 851 valve prostheses, dysfunction and complications, 526–528, 527f ECSS. See European Coronary Surgery Study Ectopic atrial bradycardia, 305 Ectopic atrial rhythm, 305

Edwards-Sapien 3 (S3) valve, 523f–524f, 911 EECP. See Enhanced external counterpulsation Effective refractory period (ERP), 367–369 accessory pathway anterograde/retrograde AVN, 371 fast/slow AVN, 381 Effusive–constrictive pericarditis, 865–867 Ehlers–Danlos syndrome, 870 Eisenmenger syndrome, 273–274, 833–835 Ejection murmurs, 14 Ejection systolic murmurs, 14 Ejection type systolic murmurs, 14–16 Elastance, pressure–volume loop, 40 Electrical coupling cells (gap junction), 51 Electrocardiogram (ECG), 632–633, 632f for AS, 475 for ACSs, 579 board preparation, 303 case history, 314–364, 314f–364f interpretation of assessment of standardization/recorded leads and, 304 atrial/ventricular rates/rhythms in, 304–308 measurement of cardiac intervals in, 307 P-wave/QRS-complex axes in, 306–307 P-wave/QRS-complex/T-wave morphologies in, 310–312 twelve-lead, 303 intracardiac, 366 Electrocardiography, 555, 632–633, 632f Electromagnetic interference (EMI), 457–458 Electron-beam CT (EBCT), 139 Electrophysiology (EP) assessment of atrioventricular nodes and, 375–376, 375f, 376f atrioventricular block and, 372–375, 373f–374f atrioventricular conduction, 371–372 basis of, 365–369, 366f, 367f, 368f, 369f

bradyarrhythmia evaluation by, 369 guidelines for, 945–946 indications for, 365 sinus node function and, 369–371, 370f, 371f summary, 385–386 tachyarrhythmia evaluation by, 377–383, 383f–385f testing, syncope, 467, 467t Elevated cholesterol, 846 ELISA. See Enzyme-linked immunosorbent assay ELITE 1. See Evaluation of Losartan in the Elderly study Embolic protection devices, 757 Embolic stroke, 902t Embryology, 901 Emergency cardiac surgery with concomitant CABG, 617 Enalapril, 873 Enalaprilat, 793t Endless loop tachycardia, 450–451 Endocarditis, 527 Loeffler, 244 prophylaxis, 477 Endomyocardial fibrosis, 245 Endothelin-1 (ET-1), 228 antagonist, 892t–893t Enhanced external counterpulsation (EECP), 572 Enzyme-linked immunosorbent assay (ELISA), 729 Eosinophilic endomyocardial disease, 219 EP. See Electrophysiology EPHESUS trial (Eplerenone Postacute Myocardial Infarction Heart failure Efficacy and Survival Study), 640 Epicardial leads, 449 Epidemiology, clinical bias, 67 causality and validity, 67 data presentation/outcomes reporting, 65–66, 66f, 67f

exposures, 63 outcomes, 63 statistical tests, 64 types of clinical studies in case reports as, 63 case series as, 63 case–control study as, 63, 64f cohort study as, 63, 64f meta-analysis, 64 prospective vs. retrospective, 63 randomized controlled trials as, 63–64 Eptifibatide (Integrilin), 585 ERP. See Effective refractory period Erythromycin, 894t–897t Esmolol, 404t Estrogen Replacement and Atherosclerosis (ERA) trial, 848 Estrogen therapy, 848 European Coronary Surgery Study (ECSS), 566 Evaluation of Losartan in the Elderly study (ELITE), 167 Event monitoring, 451, 451f Everolimus (Certican), 189t, 191 Evolut low-risk trial, 915, 915t Evolut-PRO valve, 911–912, 911f Evolut-R valve (Medtronic), 911–912, 911f EVOQUE device, 930t Exercise electrocardiographic (ECG) stress test, 850–851 advantages of, 98 age and gender estimated functional capacity, 101t beta-blockers, 101 contraindications, 98–100, 100t diagnostic interpretation, 101 essential evidence/current guidelines, 98 indications, 98–100, 99t metabolic gas-exchange analyses, 102

methods of testing, 100, 100t placement of electrodes, 100 primary goal of, 98 prognostic interpretation, 101, 101t safety of, 98 in women, 102 Exercise stress test, 636–637, 637t Exercise-induced syncope, 467 Extended VTE prophylaxis, 736 External validity, 67 External-beam radiation therapy (XRT), 876 Extrastimulus, 367 Ezetimibe, 807, 808t, 809–813

F FA. See Fatty acids Fabry disease, 935t Fallot, tetralogy of, 293, 296f Familial combined hyperlipidemia (FCH), 803t Familial Defective Apolipoprotein B100, 802 Familial hypercholesterolemia (FH), 802, 803t Fatty acids (FAs), 798 FC. See Free cholesterol FCH. See Familial combined hyperlipidemia FDA. See U.S. Food and Drug Administration Felodipine, 563t, 892t–893t Fenofibrate, 808t, 812t Fenoldopam, 793t FFR. See Fractional flow reserve FH. See Familial hypercholesterolemia Fibrates, 805, 808t, 811 Fibrinolysis, 598t, 691–692 Fibrinolytics, 690–692 therapy, for STEMI, 601 Fibrin-specific agents, 601

Fibroelastomas, 884, 884f Fibromas, 883t, 885–886, 885f Fibromuscular dysplasia (FMD), 787, 874 Fick technique, 661–662 Fiedler myocarditis, 219 First heart sound intensity, 10 principles, 10 splitting, 10 First-pass radionuclide angiography (FPRNA), 128 Fixation techniques, 449 Flecainide, 406t, 407, 840t Florinef, 472 Flow, basic principles of jets, 93–94 Fludrocortisone, 468 Fluoroscopy, 680–683, 681f, 682f, 683f, 684f 5-Fluorouracil, 960, 960t and its metabolites, 959–960 Fluvastatin, 807t–808t FMD. See Fibromuscular dysplasia Fondaparinux (Arixtra), 605, 732 Foot care, and ulcer prevention, 747 Force–frequency response, heart failure, 159 Force–tension curves, 39, 39f Fractional flow reserve (FFR), 675–676, 677f Fragile X syndrome, 936t Framingham risk score (FRS), 743–744 Frank–Starling Curves, 39, 39f Free cholesterol (FC), 798 Frequency (f), 85 Friedrich ataxia, 871 FRISC II (Fast Revascularization during Instability in Coronary Artery Disease), 636 Functional mitral regurgitation, 927

diagnosis for, 619, 619f symptoms and signs of, 618–619 treatment for, 619–620 Furosemide, 840t

G Gadolinium-based contrast media agents, cardiac MRI, 134 Gap junction, 51 GBS. See Guillain–Barré syndrome (GBS) Gemfibrozil, 808t, 812t General cardiology, guidelines for, 943–944 Genetics and heart disease autosomal dominant long QT syndrome, genes with mutations definitively associated with, 938t autosomal/mitochondrial genetic disorders with, 936t cardiac arrhythmias, variants of, 938t cardiomyopathy, variants of, 937t chromosomal abnormalities, 936t genotype and genetic compositions, 935t HCM, genes with mutations definitively associated with, 937t hereditary thoracic aortic diseases, 937t principles, 934 storage disorders, 935t Gentamicin, 512, 516t German Epidemiological Trial on Ankle-Brachial Index (GET ABI), 743– 744 Gestational diabetes, 847 Gestational hypertension, 847 Giant cell arteritis, 720 Giant cell myocarditis, 219 GISSI. See Italian Group for the Study of Streptokinase in Myocardial Infarction Global registry of acute coronary events (GRACE) score, 580, 636 Glucocorticoids, 194 Glucose, regulation of, 839

Glycemic control, in diabetic patients with PAD, 749–750, 749t Glycoprotein IIb/IIIa inhibitors for ACS, 578 for PCI, 700 for STEMI, 604 Glycosylation, 50 Gore Helex Septal Occluder, 908f Gore Septal Cardioform Occluder, 903, 905f Gorlin formula, 664 GRACE Score, 598–599 Granulomatous myocarditis, 219 Great vessels aorta, 31, 31f cardiac lymphatic system, 33 cardiac veins, 32–33, 33f coronary arteries, 31–32, 31f–32f pulmonary arteries, 30–31 pulmonary veins, 31 vena cavae, 30 Growth hormones, 872 Guidelines for adult congenital heart disease, 947 cardiac imaging, 946–947 cardiovascular computed tomography, 946 echocardiography, 946–947 for electrophysiology, 945–946 general cardiology, 943–944 for heart disease prevention in women, 848–849, 849f for interventional cardiology, 944–945 Guillain–Barré syndrome (GBS), 871–872 GUSTO (Global Utilization of Streptokinase and TPA for Occluded Arteries) I trial, 601, 631 GUSTO (Global Utilization of Streptokinase and TPA for Occluded Arteries) IIb trial, 579

H HAART. See Highly active antiretroviral therapy HACEK organisms, 516t–517t Hakki formula, 664 Haloperidol, 897t Hamman sign, 13 Harmonic imaging, 107 Hazard ratio, 65 HBE. See His bundle catheter HCM. See Hypertrophic cardiomyopathy HCTZ. See Hydrochlorothiazide HDL. See High-density lipoproteins HDL cholesterol (HDL-C), 798–799, 804 Heart blocks, 307, 372–373 cardiac chambers left atrium, 28, 28f left ventricle, 28–29, 28f right atrium, 27, 27f right ventricle, 28, 28f cardiac valves aortic valve, 30, 30f mitral valve, 29–30, 30f pulmonic valve, 29, 29f tricuspid valve, 29, 29f conducting system, 33–34, 33f diseases carcinoid, 888 radiation, 474 rheumatic, 473–474, 479, 496–497, 504 structural, 409 great vessels aorta, 31, 31f cardiac lymphatic system, 33

cardiac veins, 32–33, 33f coronary arteries, 31–32, 31f–32f pulmonary arteries, 30–31 pulmonary veins, 31 vena cavae, 30 location, 26 murmurs, 13–14 characteristics, 14 diastolic, 14–17 ejection, 14 ejection systolic, 14 intensity of, 13 regurgitant systolic, 14 systolic, 14–17 pericardium, 26–27, 27f position, 26, 27f rate, 403 shape, 26 size, 26 sound continuous, 18–19 extra, 12–13 diastole, 12f, 12 pacemaker sounds, 13 prosthetic heart sounds, 13 systole, 12–13 first intensity, 10 principles, 10 splitting, 10 fourth, 11–12 pacemaker, 13 prosthetic, 13 second

intensity, 10 pathologic splitting, 11f principles, 10 single S2, 10 splitting, 11f, 10–11 third, 11 transplantation complications post, 192–194 donor, 180–181 immunosuppresant agents, 187–188 organ allocation, 180 recipient, 181–182, 181t, 182f, 183t–184t rejection, 182–186, 184t survival after, 194 Heart failure (HF), 960 abnormal cellular/molecular mechanisms, 159–160 ACE for, 165–168 acute medical therapy admission to hospital, 170–171 agents, 173 decongestion, 171–172 inotropes, 172–173 invasive hemodynamic monitoring, 171 nerohormonal blockage, 169–170 vasodilators, 172 adaptive mechanisms, 157–161 angiotensin-II (Ang-II), 159 and arrhythmia development, 212 autonomic nervous system dysfunction, 159 beta-blockers, 165 cardiac MRI, 134 cardiac output, 153–156 chronic medical therapy digitalis glycosides, 169–170

investigational agents, 170 neurohormonal blockade, 165–168, 165t related conditions, treatment of, 170 vasodilators, 169 classification, 154t–155t counterregulatory systems (natriuretic peptides), 160 definition and classification, 153 development of, 212–213 devices for circulatory support implantation, 206 clinical trials, 206–207, 206t components and configurations, 200–201, 200f, 201t–202t, 201f considerations regarding, 198–199, 199t operative risk, assessment of, 205–206 patient selection, 201–205, 202t types of, 199–200 diastolic clinical presentation of, 240 function, 240, 240f heart failure, 243 laboratory examination for, 241–243, 241t, 242f, 243t phases of, 239–240 physiology of, 239 prognosis for, 243, 244f treatment, 243 digitalis for, 169–170 force–frequency response, 159 hemodynamics, 153–156 inflammation and oxidative stress, 160–161 lifestyle measures excerise, 164 fluid restriction, 164 sodium restriction, 164 maladaptive compensatory mechanisms, 155f

medications antiarrhythmic, 173–174 calcium channel blockers, 173 chemotherapy agents, 174 NSAIDs, 173 oral hypoglycemics, 174 monitoring and follow-up, 174 pathophysiologic mechanisms, 153–157, 155f, 156t peripheral vascular and skeletal muscle adaptations, 161 preserved LVEF, 173–174 pressure–volume loop analysis in, 156–157, 157f, 158f prevalence, 153 renin–angiotensin–aldosterone system dysfunction, 159 salt and water, renal retention, 161 ventricular remodeling and reverse remodeling, 160 women and, 852–853 survival, 852–853 treatment, 845 Heart failure with preserved ejection fraction (HFpEF) clinical presentation, 240 diastole, phases of, 239–240 diastole, physiology of, 239 diastolic function, 240, 240f diastolic heart failure, 243 laboratory examination, 241–243, 241t, 242f, 243t physical examination, 241 prognosis, 243, 244f restrictive cardiomyopathies, 244–246, 245f, 246f Heart rate, 38–39, 240 Heart transplantation donor, 180–181 organ allocation, 180 posttransplant complications chronic renal dysfunction, 193

fungal infections, 192 hyperlipidemia, 193–194 hypertension, 193 infection, 192 malignancies, 192–193 osteoporosis, 194 protozoal infections, 192 tricuspid regurgitation, 194 viral infections, 192 posttransplant management issues antiproliferative agents, 189t, 190 calcineurin inhibitors, 188–190, 189t combination regimen, 191 corticosteroids, 191 immunosuppressive strategies, 186–187 individual immunosuppresant agents, 187–188 rejection, 182–186, 184t TOR inhibitors, 190–191 recipient, 181–182, 181t, 182f, 183t–184t survival, 194 HeartMate II, 200 Heberden, William, 554 HeFH. See Heterozygous FH Hemangiomas, cardiac, 883t, 886 Hematologic disorders, 875–877 Hematomas, intramural, 716, 716f, 721 Hemochromatosis, 245–246 cardiac MRI, 136 Hemodynamic criteria, 669–670, 670f, 671f heart failure, 153–156 Hemodynamic maneuvers, 19–20 Heparin. See also Low molecular weight heparin agents, 700 intravenous, 601

low molecular weight, 586 subcutaneous, 524 unfractionated, 586 Hepatic lipase (HL), 798 Hereditary hemochromatosis, 935t Hereditary thoracic aortic diseases, 937t HER-2/neu inhibitors, 959 Hertz (Hz), 85 Heterozygous FH (HeFH), 802 Hibernation, 126 myocardial perfusion images, 119 High defibrillation thresholds, 457–458 High-density lipoproteins (HDL), 798–799 High-sensitivity C-reactive protein (hs-CRP), 551, 580 High-sensitivity cTn (hs-cTn), 537 HighLife device, 930t Highly active antiretroviral therapy (HAART), 800, 804 Hill sign, 7 His bundle, 33–34, 52–53 His bundle catheter (HBE), 366–367 His-Purkinje system (HPS), 371 Histone deacetylase inhibitors, 959–960 HIV (human immunodefi ciency virus), 877 HL. See Hepatic lipase HLAs. See Human leukocyte antigens HOCM. See Hypertrophic Obstructive Cardiomyopathy Hodgkin lymphoma, 964f HoFH. See Homozygous FH Holosystolic and holodiastolic murmur, 18 Holt–Oram syndrome, 936t Homografts, 478 Homozygous FH (HoFH), 802 HOPE (Heart Outcomes Prevention Evaluation) trial, 639–640, 786 Hormone replacement therapy (HRT), 848

Hospitalization, 636–637 HPS. See His-Purkinje system hs-CRP. See High- sensitivity C-reactive protein HTN. See Hypertension Human leukocyte antigens (HLAs), 181 Hunter syndrome (type 2 mucopolysaccharidosis), 935t Hurler syndrome (type 1 mucopolysaccharidosis), 935t Hydralazine (Apresoline), 169, 793t, 840t Hydrochlorothiazide (HCTZ), 777, 840t, 892t–896t 11-β-hydroxysteroid dehydrogenase deficiency (11-β-OHSD), 783–784 Hyperactive precordium, 9 Hyperaldosteronism/Conn syndrome, 872 Hypercalcemia, 312 Hyperkalemia, 311 Hyperlipidemia, 193–194, 544–545, 549 Hypersensitive/eosinophilic myocarditis, 219 Hypertension (HTN), 823, 846, 846f angiotensin II receptor blockers for, 788, 792 CAD and, 550 clinical approaches, 789–792, 790t coarctation of aorta, 789 diastolic/ systolic, pulse pressure and, 778 emergencies, 792–794, 793t evaluation of, 778–780, 779f, 780t genetics of, 777–778 isolated systolic, 778 pathogenesis of, 777 prevalence, 153 refractory, 780, 781t, 781f resistant, 780–782, 781t, 781f secondary, 782–789, 782t in women, 788 Hypertension management post-MI, 641–642 Hypertensive emergency, 961

Hyperthyroidism, 50, 872 Hypertriglyceridemia, 805 Hypertrophic cardiomyopathy (HCM), 312, 391–392, 834, 937t, 952–953 and athletics, 261 atrial fibrillation, 261 cardiac MRI, 135 centers, 261–262 classification, 250, 251f diagnostic testing cardiac catheterization, 256, 257f cardiac magnetic resonance, 256 echocardiography, 253–256, 254f, 255f labs, chest X-ray, and electrocardiogram, 253, 253f–254f genetics, 257 infective endocarditis prophylaxis, 260 medical therapy, 257–258 nonobstructive HCM, 261 pathophysiology and histology, 250, 252f percutaneous alcohol septal ablation, 259, 259f permanent pacemaker implantation, 259 physical examination, 251–252, 252t and pregnancy, 261 prevalence and definition, 250, 251t, 251f screening of family members, 257 septal myectomy, 258–259, 258f vs. alcohol ablation, 259, 259f stress echo, 112 sudden cardiac death, 260, 260t symptoms and clinical course, 251 systolic murmurs, 15–16 Hypertrophic obstructive cardiomyopathy (HOCM), 250, 667, 667f, 668f, 823 Hypertrophy, 308–309 Hypocalcemia, 312

Hypokalemia, 312 Hypotension, 872–873 Hypothermia, 312 Hypothyroidism, 872–873 HYVET study, 790t Hz. See Hertz

I IABP. See Intra-aortic balloon pump Ibrutinib, 959–960, 960t Ibutilide, 405, 897t ICDs. See Implantable cardioverter defibrillators ICE. See Intracardiac echocardiography Idiopathic dilated cardiomyopathy (IDCM) cardiotropic viral infections, 214 etiologies, 212–213 hereditary hemochromatosis (HFE) gene, 221 immune related adverse events (IRAE), 215 pathophysiology, 212–213 prevalence, 212 Idiopathic hypertrophic subaortic stenosis (IHSS), 250 Idiopathic interstitial myocarditis, 219 Idiopathic pericarditis, 858 Idiopathic restrictive cardiomyopathy, 244 Idioventricular rhythm, 306 IDL. See Intermediate-density lipo-proteins IE. See Infective endocarditis IHSS. See Idiopathic hypertrophic subaortic stenosis Imaging. See also specific types of imaging radionuclide, 851–852 Imaging artifacts, 92 range ambiguity, 92 Imatinib, 959–960, 960t Impedance (R), 449 Implantable cardioverter defibrillators (ICDs), 631, 948

cause of failure, ventricular arrhythmias, 458 detection algorithms, 454 detection criteria, 455–457, 456f devices, 453 function of, 454–455, 455f implantation, 454 indications, 453, 453t lead systems, 454 management, surgical procedures and MRI, 458 patient care, 458 polarity, 455 programming, 455 shock evaluation, 457–458 shock waveform, VT and VF, 455 summary on, 458 therapies, 457 troubleshooting, 457–458 VF therapy, 454–455 VT therapy, 454–455 Indicator dilution methods, 662–663 Indomethacin, 858–859 Infarct-related artery (IRA), 601 Infection fungal, 192 protozoa, 192 viral, 192 Infective endocarditis (IE) antibiotic therapy, 516–518, 516t–517t blood cultures/microbiology, 511 cardiac complications, 514–515 CIEDs, infections in patients, 518 clinical features, 511–512 complications with, 514–516 definitions of, 509

diagnosis for, 512–514, 513f early detection, 518–519 echocardiography, 513–514 epidemiology of, 509–510 health care–associated, 509 imaging techniques, 514 incidence, 509 invasive medical interventions, 509 medical therapy, 516–518, 516t–517t neurologic complications, 515 pathogenesis of, 510–511 PET imaging, 128 prophylaxis, 518, 519t risk factors for, 510 surgery indications for, 518 systemic embolization, 515–516 treatment for, 515, 516t TTE for, 513–514 uncommon causes, 517–518 Infective endocarditis prophylaxis in valvular heart disease, 489t Inferior vena cava interruption (IVC Filters), 735–736 Infiltrative cardiomyopathies, 244 Inflammation, heart failure, 160–161 Inflammatory aortitis, 720–721 Inflammatory cardiomyopathy, 218t clinical trials of, 218t Inflammatory disorders, 712 Inherited cardiomyopathies, biochemistry of, 59, 60t Inherited and acquired channelopathies Brugada syndrome, 394, 394f idiopathic ventricular fibrillation, 394 long-QT syndrome, 393–394, 393t short-QT syndrome, 394 Inherited disorders, 870–871

Injection drug use, 510 Innocent murmur, systolic murmurs in children (still murmur), 16 in children to young adults (pulmonary ejection murmur), 16 Inotropic. See Dopamine Inoue technique, 922 In-stent restenosis (ISR), 703 Insulin, 329, 341, 344 Insulin resistance syndrome. See Metabolic syndrome Intentional Percutaneous Laceration of the Anterior Mitral Leaflet to Prevent Outflow Obstruction (LAMPOON), 928 Interatrial septum, embryologic formation of, 902f INTERHEART study, 549 Intermediate-density lipo-proteins (IDL), 798 Internal carotid arteries (ICAs), 758 Internal validity, 67 International Society for Heart and Lung Transplantation (ISHLT), 180–181, 183–184, 184t, 185b, 186b, 188b, 190–191, 191b, 194, 203, 206, 206t Interstitial disorder, 244 Interventional cardiology, guidelines for, 944–945 Intra-aortic balloon pump (IABP), 198, 588, 615–616, 619–620 counterpulsation, 607 Intracardiac echocardiography (ICE), 683–684 Intracardiac pressures, pressure–volume loop, 40 Intracardiac waveforms, 658–664, 659t, 659f Intramural hematoma (IMH) , 137, 716, 716f, 721 Intravascular ultrasound (IVUS) applications of, 679, 679f atherosclerosis, characterization of, 678 normal coronary artery anatomy, 678, 678f Intraventricular conduction delay (IVCD), 626 Intrepid device, 930t Ipilimumab, 960t IRA. See Infarct-related artery

Irbesartan Diabetic Nephropathy Trial (IDNT) study, 790t, 792 Iron overload, 875 ISAR trial, 604 ISAR-COOL trial, 636 ISAR-REACT 2 trial, 585–586 2019 ISAR REACT 5 trial, 604 ISHLT. See International Society for Heart and Lung Transplantation Isoptin. See Verapamil Isosorbide dinitrate, 169 Isotretinoin, 800, 804 Isovolumic relaxation phase, 239 ISR. See In-stent restenosis Isradipine (Dynacirc), 563t Italian Group for the Study of Streptokinase in Myocardial Infarction (GISSI), 615, 850 Itraconazole, 894t–897t Ivabradine, 165 and IF current, 57–58 IVC filters. See Inferior Vena Cava Interruption IVCD. See Intraventricular conduction delay IVUS. See Intravascular ultrasound

J Jacobsen syndrome, 936t Janeway lesions, 509, 510f Jet velocity, 476 Jugular venous pulse disease states, 8–9 pressure, 8 principles, 8 waveforms, 8 Junctional premature complexes, 305–306 JVP. See Jugular venous pulse

K

Kaplan–Meier estimates, 641, 641f KE. See Kinetic energy Kearns–Sayre syndrome, 871 Ketoconazole, 894t–897t Khorana Score, 963t Killip classification, 598–599, 599t, 614, 615t Kinetic energy (KE), 93 Klippel–Feil syndrome, 936t Kussmaul sign, 9

L Labetalol, 785, 788, 793–794, 793t LAFB. See Left anterior fascicular block Lamin A/C, 937t Late gadolinium enhancement (LGE), 953 LBBB. See left bundle branch block LDL-C management, 811t Lead extraction, 452 Lead fracture/failure, 452 Left anterior descending artery calcification, 122f Left anterior fascicular block (LAFB), 307 Left atrial abnormality, 309 Left atrial wall calcification, 79, 79f Left atrium, 28, 28f Left bundle branch block (LBBB), 308, 601 Left posterior fascicular block (LPFB), 308 Left ventricle, 28–29, 28f Left ventricular aneurysm diagnosis for, 623 signs and symptoms of, 623 treatment for, 623 Left ventricular dysfunction, 614–615, 615t Left ventricular ejection fraction (LVEF), 164, 365 Left ventricular end diastolic pressure (LVEDP), 10 Left ventricular function, 633

Left ventricular hypertrophy (LVH), 309 Left ventricular outflow tract (LVOT), 624–626 diagnosis for, 625 obstruction murmur, 15, 15t signs/symptoms of, 624–625 treatments for, 625 Legionella IE, 513, 517–518 Levophed. See Norepinephrine Lidocaine, 435, 840t Likelihood ratio (LR), 66 LIPID. See Long-term Intervention with Pravastatin in Ischemic Disease Lipid(s), 798–800. See also Dyslipidemias lipoproteins and, 798–800, 799f, 800t other, 812t Lipid management, 641 Lipid-lowering therapy, 748 Lipoma, 883t, 884 Lipoprotein lipase (LPL), 798 Lipoproteins, 798–800, 799f. See also specific types of lipoproteins Liposomal formulation of anthracyclines, 962 LMWH. See Low Molecular Weight Heparin Loeffler endocarditis, 244 Loeys–Dietz syndrome/TGF-beta–related aneurysm conditions, 937t Loffler endomyocardial fibrosis, 219 Long-QT syndrome (LQTS), 393–394, 393t, 938t, 948, 953–954 Long-term Intervention with Pravastatin in Ischemic Disease (LIPID), 810t Losartan intervention for endpoint (LIFE), 792 Lotus Edge, 911f, 912 Loud systolic sound, 8 Lovastatin, 807t–808t, 892t–893t, 896–898 Low-gradient aortic stenosis versus pseudostenosis, 479 Low high-density lipoprotein, 805 Low molecular weight heparin (LMWH), 524–525, 605–606, 732 for acs, 586

during pregnancy, 839–841, 841t LPFB. See Left posterior fascicular block LPL. See Lipoprotein lipase LQTS. See Long-QT Syndrome (LQTS) LR. See Likelihood ratio LV noncompaction cardiomyopathy, 937t LVEF. See Left ventricular ejection fraction LVH. See Left ventricular hypertrophy LVOT. See Left ventricular outflow tract LVOT obstruction, 928 Lysosomal storage disease, 59, 60t

M MACE. See Major adverse cardiovascular events Magnesium, 190, 426, 435 Magnetic resonance angiography (MRA), 759, 787 Magnetic resonance direct thrombus imaging (MRDTI), 728 Magnetic resonance imaging (MRI), cardiac aortic disease aortic aneurysm, 137 aortic dissection, 137 intramural hematoma, 137 basic imaging sequences, 132–134 clinical applications arrhythmogenic right ventricular cardiomyopathy (ARVC), 136, 136t cardiac amyloidosis, 135 cardiac sarcoidosis, 135–136 coronary artery disease, 134 dilated cardiomyopathy, 134 heart failure, 134 hemochromatosis, 136 hypertrophic cardiomyopathy, 135 myocardial disease, 134 myocardial fibrosis, 135

myocarditis, 135–136 restrictive cardiomyopathy, 135 viability assessment, 134 contraindications, 138t delayed hyperenhancement short-axis image, 133f flow curve, 133f gadolinium-based contrast media agents, 134 indications, 133t limitations of, 137 MRI physics, 132 prosthetic valves, 525 pulse sequences, 132 Magnetic resonance venography (MRV), 728 Major adverse cardiovascular events (MACE), 561, 762 Make Early Diagnosis and Prevent Early Death (MEDPED) criteria, 802 Malignant tumors, 886–887, 886t, 887f Mammary souffle, 18–19 Mapping, 384–385 Marfan syndrome, 718, 833–834, 870, 937t, 956 MAs. See Mycotic aneurysms MASS. See Medicine, Angioplasty or Surgery Study MAT. See Multifocal atrial tachycardia Mayen sign, 8 Maze procedure, 414 MDCT. See Multidetector Computed Tomography MDPIT trial, 169 Means–Lerman scratch, 13 Mechanical prostheses, 478 Mechanical ventilation, 203, 205 Mediastinal crunch, 13 Mediastinal radiation therapy, 959 Medical Research Council/British Heart Foundation (MRC/ BHF), 810t Medicare, 548–549 Medicine, Angioplasty or Surgery Study (MASS), 569

Medtronic CoreValve, 523f–524f Medtronic Open Pivot valve, 522 MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) syndrome, 221, 936t MERIT-HF (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure), 640–641 Metabolic cardiomyopathy, 220 Metabolic syndrome (MetS), 805, 805t Methyldopa (Aldomet), 785–786, 788, 793–794, 840t Metoprolol, 640–641 MetS. See Metabolic syndrome Midodrine, 468 Minimum rate, 450 Mitochondrial cardiomyopathy, 221 MitraClip system, 923, 925–927, 926f, 927t Mitral annular calcification (MAC), 80, 80f, 922 Mitral closure, 10 Mitral regurgitation (MR), 607–608, 665, 665f, 833 acute, 489–490, 617–620 cardiomediastinal silhouette patterns, 78, 78f chronic, 490–491, 490f, 491f functional, 617–620, 619f mechanisms, 492–493, 492f–494f medical management, 495 quantitation of, 494–496, 496f stress echo, 111 systolic murmurs, 16, 16f Mitral stenosis (MS), 665–666, 665f, 835–836 cardiomediastinal silhouette patterns, 78, 78f diastolic murmurs, 17–18 features and history of, 496–501, 498f–499f management of, 500 stress echo, 111–112 Mitral valve(s), 10, 29–30, 30f

anatomy, 488 Mitral valve prolapse (MVP), 12, 833 diagnosis of, 488–489, 489t, 489f signs and symptoms of, 488 Mitral valve repair, 495 Mitral valve replacement (MVR), 495, 497f MMF. See Mycophenolate mofetil Mode codes, cardiac pacemakers, 450, 450t Monophasic waveforms, 455 Morganroth hypothesis, 948–949 Morquio (mucopolysaccharidosis type IV), 935t MPA. See Mycophenolic acid MR. See Mitral regurgitation MRA. See Magnetic resonance angiography MRV. See Magnetic resonance venography MS. See Mitral stenosis MSS. See Muscular subaortic stenosis Multidetector computed tomography (MDCT), 137, 139, 684–685 Multifocal atrial tachycardia (MAT), 305 Multigated acquisition (MUGA) imaging, 961 Multiplanar reformation (MPR) image, 140f Multiple endocrine neoplasia (MEN) syndrome, 785 Muscular dystrophies, 59, 60t, 871 Muscular subaortic stenosis (MSS), 250 MUSTT Trial, 377 MVP. See Mitral valve prolapse Myasthenia gravis, 871 Mycophenolate mofetil (MMF), 188, 189t, 190 Mycophenolic acid (MPA), 190 Mycotic aneurysms (MAs), 721 Myocardial blood flow quantification, PET imaging, 124 Myocardial disease, 963 cardiac MRI, 134 Myocardial fibrosis, cardiac MRI, 135

Myocardial flow reserve (MFR), 124 Myocardial infarction (MI). See also Acute myocardial infarction antiplatelet therapies for, 631, 637–639 beta-blockers, 640–641 calcified post left ventricular aneurysm, 622–623 left ventricular pseudo-aneurysm, 620, 622 complications additional, 624–626 arrhythmic, 626–627, 627t of left ventricular dysfunction, 614–615, 615t mechanical, 616–623, 617f, 618f, 619f, 621f, 622f medical therapies, 619–620 revascularization and, 620, 624 post conclusions on, 642 therapies for, 637–642 risk factor management, 641–642 risks for, 538 statins for, 640 stress test predictors of cardiac death and, 636–637, 638t Myocardial injury after noncardiac surgery (MINS), 825–826 Myocardial injury and infarction, 311 Myocardial metabolism, PET imaging, 115 Myocardial performance components of, 41 determinants of, 39 afterload, 37–38 contractility, 38 heart rate, 38–39 mechanisms of action, 38t preload, 37 graphic illustration of force–tension curves, 39, 39f

pressure–volume loops, 39–40, 40f Starling Law and Frank–Starling Curves, 39, 39f Myocardial perfusion imaging, 821–822 clinical use of, 121–124, 122f interpretation of, 118–121 myocardial scar/myocardial hibernation, 119 PET imaging, 114 reversible defect, 121f segmental perfusion, 119 tomographic reconstruction, 119 Myocardial relaxation, 91 Myocardial viability, PET imaging, 124–126 Myocarditis, 392, 953 acute phase, 212–213 with cardiac dysfunction, 212 cardiac MRI diagnostic criteria, 135–136, 216t causes of, 212–213, 214t chronic phase, 214 classification, 212 clinical presentation, 215 clinical trials of, 218t clinicopathologic classification, 213t coxsackie A9, 214 coxsackie B3, 214 coxsackie-adenovirus receptor (CAR), 214 cytokine expression, 213 Dallas criteria, 212 endothelium injury, 213 evaluation, 216–217 giant cell, 219 human herpesvirus-6, 212–213 hypersensitive/eosinophilic, 219 immune checkpoint inhibitors (ICI), 214–215 incidence, 212

infectious and noninfectious agents, 212–213 inflammatory response, 213, 215f parvovirus B19 (PVB19), 212–213 prevalence, 212 protein decay-accelerating factor, 214 SARS-CoV-2 (coronavirus), 212–213 subacute phase, 213 treatment and prognosis, 217–219 viral, 212–214 World Heart Foundation Marburg Criteria, 212 Myocardium, 124, 126 Myofibril, 56 Myotonic dystrophy, 871 Myxedema, 312 Myxomas, 882–884, 883t, 883f

N Na+. See Sodium Na+ channel activity regulation, 50–51 N-acetyl procainamide (NAPA), 405 Nafcillin, 516t–517t Na+/K+ ATPase, 58 NAME syndrome (nevi, Atrial myxoma, myxoid neurofibromata, and ephelides), 882 NAPA. See N-acetyl procainamide Narula method, 370, 370f National Cholesterol Education Program (NCEP), 641 National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP III), 805 National Institutes of Health (NIH), 680 National Surgical Quality Improvement Program (NSQIP), 822 Natriuretic peptide system, 58–59 heart failure, 160 Naxos disease, 221

NCEP. See National Cholesterol Education Program NCEP ATP III. See National Cholesterol Education Program's Adult Treatment Panel III Negative predictive value (NPV), 66 Neoplastic disease, 876 Neo-Synephrine. See Phenylephrine Neprilysin inhibitors, 892t–893t Nesiritide, 172 Neurocardiogenic syncope, 461–462 Neurofibromatosis 1, 936t Neurohormonal blockade, 639–641 Neuromuscular disorders, 871–872 New York Heart Association (NYHA), 500, 640 NFAT. See Nuclear factor of activated T cells Niacin, 807, 811 Nicardipine (Cardene), 563t, 793t Nicotinic acid, 808t Nifedipine, 786 Nifedipine (Procardia, Adalat), 563, 563t Nitrates, 840t for ACS, 580 for stable angina, 563–564, 564t Nitric oxide (NO), 59, 229, 230f production of, 229 Nitric oxide synthases (NOS), 229 Nitrogen-13 ammonia, 114–115 Nitroglycerin, 172, 325, 340, 490, 534, 563–564, 564t, 587, 606, 793t Nitroprusside (Nipride), 617, 793t sodium, 619–620 Nivolumab, 959–960, 960t NO. See Nitric oxide Nocardia, 192 Noncardiac surgery, 819 controversy and further research, 826

evaluation of patients undergoing, 822–823, 822f management of other cardiovascular conditions and, 823 myocardial infarction and myocardial injury after, 825–826 myocardial perfusion imaging and, 821–822 perioperative coronary revascularization, 824–825, 825f perioperative medical therapy and, 823–824 preoperative cardiac risk assessment, 820–822, 821t, 821f Noncompaction of left ventricle, 392 Nonculprit CAD, 602–603 Non-high-density lipoprotein cholesterol (non-HDL-C), 798. See also Nonhigh-density lipoprotein cholesterol Nonischemic cardiomyopathy arrhythmogenic right ventricular cardiomyopathy, 392, 392f cardiac sarcoidosis, 392 catecholaminergic polymorphic ventricular tachycardia, 393 dilated cardiomyopathy, 391 hypertrophic cardiomyopathy, 391–392 myocarditis, 392 noncompaction of the left ventricle, 392 Non-ST-elevation acute coronary syndrome (NSTE-ACS), 692 risk stratification, 635 Non-ST-elevation myocardial infarction (NSTEMI), 587, 624–625 clinical presentation, 576–577 epidemiology and prognosis, 576 fibrinolytic therapy for, 581 management of ACE-I for, 588–589 anti-ischemic agents, 587 antiplatelet agents, 583–586 antithrombin therapy, 587 aspirin for, 583–584, 584f atorvastatin for, 588 beta-blockers, 587 glycoprotein IIb/IIa inhibitors for, 585–586

initial approach, 581 invasive therapy, 581–583 mechanical devices for, 588 miscellaneous agents for, 588–589 PCI for, 590 predischarge risk stratification for, 579–581, 589 risk stratification, 579–581, 635–636 summary on, 585, 590 thienopyridines for, 584–585 Nonsteroidal anti- inflammatory drugs (NSAIDs), 858–860 Nonsustained VT (NSVT), 955 Noonan syndrome, 871, 936t Norepinephrine, for AMI, 615 Normal sinus rhythm (NSR), 304 NOS. See Nitric oxide synthases NPV. See Negative predictive value NSR. See Normal sinus rhythm NSTE-ACS. See Non-ST-elevation acute coronary syndrome (NSTE-ACS) NSTEMI. See Non-ST-elevation myocardial infarction Nuclear factor of activated T cells (NFAT), 189 Nuclear-based cardiac imaging in acute chest pain, 126 cardiac radioactive tracers nitrogen-13 ammonia, 114–115 oyxgen-15 water, 115 PET tracers, myocardial metabolism, 115 PET tracers, myocardial perfusion, 114 rubidium-82, 114 SPECT perfusion agents, 114 technetium pyrophosphate (PYP-Tc99m), 115 technetium-99m-labeled agents, 114 thallium-201 chloride, 114 transthyretin (ATTR) amyloid cardiomyopathy, 115 cardiac SPECT imaging, 116–117

gamma camera, 115f in heart failure, 127–128 onventional SPECT myocardial perfusion imaging (MPI) study, 115 overview of, 115–116 perfusion studies, 123 PET imaging, 116f, 117 post-MI and postrevascularization, 126–127 stress protocols, nuclear perfusion imaging, 117–118 Number needed to treat (NNT), 65 Nutritional status, 4

O Obesity CAD and, 642 sedentary lifestyle and, 847 Observation bias, 67 OCP. See Oral contraceptives OCT. See Optical coherence tomography Odds ratio, 65 Ohm's law, 228 OHSD. See 11-β-hydroxysteroid dehydrogenase deficiency Omega-3 FAs, 808t Oncologic disorders, 875–877 Ondansetron, 897t ONTARGET study, 790t On-X valve, 522, 524 Opening click (OC), 13 Opening snap (OS), 12, 497 OPO. See Organ procurement organizations Optical coherence tomography (OCT), 679–680, 680f OPTIMAAL study, 167 OPTIME-HF trial, 173 OPUS-TIMI 16 (Oral Glycoprotein IIb/IIIa Inhibition with Orbofi ban in Patients with Unstable Coronary Syndromes), 635 Oral contraceptives (OCPs), 804

Organ procurement organizations (OPOs), 180 Orthostatic challenge, 466 Orthostatic hypotension (OH), 461–463 Osler nodes, 509, 510f Osler sign, 7 Osler–Weber–Rendu syndrome, 871, 936t Osteoporosis, 194 Ovarian diseases, 546 Oxacillin, 516t–517t Oxidative stress, heart failure, 160–161 Oximetry, 663 Oyxgen-15 water, 115

P PA. See Plasma aldosterone Pacemaker(s) device timing cycles and impulses, 446–447, 448f, 450–451 event monitoring, 451 histogram, ventricular hysteresis, 451, 451f implantation, 468 mode switching, 448 pacing leads, 448–449 permanent, 446, 446t–447t strength–duration curve, 449f temporary, 445–446 therapy, 414 trends, 451 Pacemaker Mediated Tachycardia Endless loop tachycardia, 451 Pacemaker sounds, 13 Pacemaker syndrome, 451–452 Pacing-induced cardiomyopathy, 452 PAD. See Peripheral artery disease PAN. See Polyarteritis nodosa Papillary fibroelastoma, 883t, 884, 884f Papillary muscle ventricular tachycardia, 397

Paracardiac calcification patterns, 79 Parathyroid disorders, 788–789 Paravalvular regurgitation, 526, 527f PARTNER 1A trial, 913, 913t PARTNER 1B trial, 912, 912t PARTNER 2A study, 914, 914t PARTNER 2 S3i (P2 S3i) study, 914, 914t PARTNER 3 trial, 915, 915t Passive fixation systems, 449 Passive pressure–volume relationships, 240, 240f Patent ductus arteriosus (PDA), 19, 268, 284t, 291–292, 291f–292f, 833 Patent foramen ovale diagnosis, 902 follow-up, 903 management of, 902–903, 903f, 904t outcomes, 903 pathophysiology, 901, 902f percutaneous closure, 903, 905f postprocedural care, 903 presentation, 901, 902t PATHWAY-2 trial, 781–782, 790t PCI. See Percutaneous coronary intervention PCSK9 inhibitors, 808t, 813 PCW. See Pulmonary capillary wedge PD-1 inhibitors, 959–960 PDA. See Patent Ductus Arteriosus PDIs. See Phosphodiesterase inhibitors PE. See Pulmonary embolism PEACE. See Prevention of Events with Angiotensin Converting Enzyme inhibition Peak aortic valve jet velocity, 476 Peak transaortic valve gradients, 476 Pectus excavatum, cardiomediastinal silhouette patterns, 75, 75f Pembrolizumab, 959–960, 960t

Penetrating aortic ulcer (PAU), 716, 717f, 721 clinical presentations of, 716 intramural hematoma, 716–717, 717f management of, 716–717 Penicillin, 478, 516t, 517–518 Pentoxifyline, 750 Percutaneous alcohol septal ablation, 259, 259f Percutaneous coronary intervention (PCI), 127 adjunct therapy for, 699–700 antithrombin therapies for, 700 bleeding, 701–702, 701t complications following, 700–702, 701t indications for, 689–699, 690t in NSTE-ACS, 693t periprocedural myocardial infarction, 702 post-CABG, 698–699 for STEMI, 586, 601–603 technical aspects of, 702–703 Percutaneous left ventricular assist device, 607 Percutaneous mitral interventions percutaneous transvenous mitral valvuloplasty, 922–923, 924t–925t, 924f, 926f advantage of, 922 Class I indication for, 922 echocardiographic scoring systems for, 924t–925t Inoue technique for, 922 transcatheter mitral valve repair, 923–927 degenerative MR, 925–927 functional MR, 927 transcatheter mitral valve replacement (TMVR), 928, 929f devices for, 928, 930t LVOT obstruction, 928 valve in MAC (ViMAC), 928 valve in ring (ViR), 928

valve in valve (ViV) TMVR, 928 Percutaneous mitral valve repair, 923 Percutaneous revascularization, 692–693 Percutaneous transluminal coronary angioplasty (PTCA), 568, 689–690 Percutaneous transluminal renal angioplasty (PTRA), 787 Percutaneous transvenous mitral valvuloplasty, 922–923, 924t–925t, 924f, 926f advantage of, 922 Class I indication for, 922 echocardiographic scoring systems for, 924t–925t Inoue technique for, 922 Pericardial cyst, cardiomediastinal silhouette patterns, 75, 75f Pericardial disease, 961, 963 Pericardial effusion, 311, 860–862, 861f, 862t Pericardial knock (PK), 12 Pericardial rubs friction, 13 mimic, 13 Pericardial tamponade, 667–668, 668f, 669f Pericarditis, 956. See also Acute pericarditis diagnosis for, 625–626, 625t STEMI and, 608 symptoms and signs of, 625 treatment for, 626 Pericardium, 26–27, 27f Peripartum cardiomyopathy (PPCM), 831, 836–837 Peripheral artery disease (PAD) Ankle-Brachial Index, 745, 746t, 746f definition, 743 diagnostic testing, 745–747 epidemiology and risk factors, 743, 744t foot care and ulcer prevention, 747 imaging studies for, 745–747, 746t marker of cardiovascular risk, 743–744

natural history, 744 physical examination findings in, 745 prevention of cardiovascular events, 747–750 antiplatelet agents, 747–748 beta-blockers and, 749 blood pressure control, 748–749, 749f cilostazol, 750 education about, 751 glycemic control in diabetic patients with, 749–750, 749t lipid-lowering therapy, 748 pentoxifyline, 750 pharmacotherapy for, 750 rehabilitation for, 750 revascularization of, 750, 751f rivaroxaban, 748 smoking cessation, 747 supervised exercise rehabilitation, 750 warfarin, 748 symptoms and signs of, 744–745, 744f therapies to improve function and quality of life, 750 Peripheral vascular disease (PVD), 800 Peripheral vascular muscle adaptations, heart failure, 161 Peripheral vasculature, 534–535 Pernicious myocarditis, 219 PES. See Programmed electrical stimulation PH. See Pulmonary hypertension Pharmacologic lipid management after MI, 641 Phenobarbital, 894t–896t Phenothiazine antipsychotics, 897t Phentolamine, 793t Phenylephrine, for AMI, 625 Phenytoin, 894t–896t Pheochromocytoma, 785–786 Phosphodiesterase inhibitors (PDIs), 58

Phospholamban, 56 Phosphorylation/dephosphorylation, 50 PIOPED trial, 730 Pistol shot, 8 Plasma aldosterone (PA), 782–783 Platelet P2Y12 receptor inhibitor, 603 PLATO trial, 604 Plavix. See Clopidogrel Pletal. See Cilostazol Pleural rubs, 13 Point of maximum pulsation, 465 Polyarteritis nodosa (PAN), 874–875 Polycystic ovarian disease, 546 Polycystic ovary syndrome (PCOS), 847–848 Polycythemia, 876 Polygenic hypercholesterolemia, 802 Polymerase chain reaction (PCR), 513 Polymorphic ventricular tachycardia, 306 Polymyositis, 874 Pompe disease, 935t Positron emission tomography (PET) imaging cardiac sarcoidosis, 127–128 infective endocarditis, 128 metabolic imaging, myocardial viability, 124–126 myocardial blood flow quantification, 124 scanning, 634 tracers myocardial metabolism, 115 myocardial perfusion, 114 Post thrombotic syndrome (PTS), 725, 734 Post-MI, smoking cessation, 642 Post–myocardial infarction therapy, 637–642 Posttransplant lymphoproliferative disease (PTLD), 187 Postural/OH, 462

Postural orthostatic tachycardia syndrome (POTS), 463 Posture, 4 Post-Ventricular Atrial Refractory Period (PVARP), 450 POTS. See Postural orthostatic tachycardia PPCM. See Peripartum cardiomyopathy PR. See Pulmonic regurgitation PRAISE, 169 PRAMI trial, 602–603 Prasugrel, 603–604 Pravastatin, 807t–808t Precordial motion dilation, 9 disease states, 9–10 hypertrophy, 9 principles, 9 Preeclampsia, 847 Pregnancy anticoagulation during, 839–841, 841t AR and, 833 arrhythmias, 838–839 COA and, 834 coronary artery disease and, 837–838 CVDs after, 836–839 expected “normal” findings during, 21–22 HCM and, 261 hypertension, 837 LMWH during, 839–841, 841t and Marfan syndrome, 718, 870 medications during, 840t physiologic changes during, 829–831, 830t planning for optimal maternal and fetal outcomes, 833–836 pre-existing cardiac diseases and, 831–836, 832t unfractionated hepuin during, 839–840, 841t women and, 524–525

Preload, 37 Pressure measurements, 658, 659f wave artifacts, 660, 661f Pressure/pulse, difference in two arms, 7 Pressure–volume loop analysis, 39–40, 40f cardiomyopathy and, 41, 41f compliance, 40 contractility, 40 elastance, 40 in heart failure, 156–157, 157f, 158f intracardiac pressures, 40 stroke work, 41 valvular heart disease, 41t valvular heart disease and, 41, 41f ventricular volumes, 40 Presyncope, 461 Prevention of Events with Angiotensin Converting Enzyme inhibition (PEACE), 561 Primary aldosteronism, 782–785, 783t, 785t Primary cardiomyopathy, 215f Primary CHD prevention, trials for, 810t Primum ASDs, 905, 905f Proarrhythmia, 406t, 407 Procainamide, 406t, 407, 840t, 897t Prochlorperazine, 894t–896t Programmed electrical stimulation (PES), 367, 368f Propafenone, 406t, 407, 840t Propranolol, 371 Prostacyclin, 229, 232–233 Prosthetic heart sounds, 13 Prosthetic valve endocarditis (PVE), 526–527 Proteasome inhibitors, 959–960 PROVED, 170

PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy), 641 PS. See Pulmonic stenosis Pseudoaneurysm diagnosis for, 622, 623f signs/symptoms of, 622 treatment for, 622 Pseudocoarctation, cardiomediastinal silhouette patterns, 76, 76f Pseudomonas aeruginosa, 517–518 Pseudostenosis versus low-gradient aortic stenosis, 479 PTCA. See Percutaneous transluminal coronary angioplasty PTLD. See Posttransplant lymphoproliferative disease PTRA. See Percutaneous transluminal renal angioplasty PTS. See Post thrombotic syndrome Pulmonary angiography, 680, 683f, 730 Pulmonary arterial hypertension, 225–227 Pulmonary arteries, 30–31 Pulmonary artery pulsatility index (PAPi), 670 Pulmonary capillary wedge (PCW), 659–660, 659f Pulmonary edema patterns, 74 Pulmonary embolism (PE) clinical presentation and diagnosis, 728–729, 729f CTPA, 730 echocardiography, 729–730 laboratory biomarkers, 730–731 MRA, 730 objective testing, 729–731 pulmonary angiography, 730 transthoracic echocardiogram, 729–730 ventilation/perfusion scintigraphy, 730 Pulmonary hypertension (PH), 21 chronic thromboembolic pulmonary hypertension, 228 combination therapy, 234 definition and classification, 225–228, 226t

diagnosis and evaluation, 229–232 clinical evaluation, 229–230 echocardiography, 230–231 hemodynamic evaluation, 231–232 left heart disease, 227 lung diseases and/or hypoxia, 228 pathophysiology, 229f endothelin-1 (ET-1), 228 hemodynamic consequences, 229 nitric oxide, 229 prostacyclin and thromboxane A2, 228 serotonin (5-hydroxytryptamine), 229 prognosis, 226t, 232, 232f pulmonary arterial hypertension, 225–227 randomized clinical trials, 234 surgical therapies, 234 treatment endothelin pathway, 233 general measures, 232 nitric oxide pathway, 233 prostacyclin pathway, 232–233 pulmonary vasodilators, 232, 233f with unclear multifactorial mechanisms, 228 Pulmonary insufficiency (PI), 482–483 Pulmonary stenosis (PS), 833 Pulmonary vascular patterns cardiovascular disease states, 72–73 pulmonary edema patterns, 74 Pulmonary vascular resistance (PVR), 204, 231 Pulmonary vasculature, 227 Pulmonary vein assessment, 141 Pulmonary vein flow profiles, 494–495, 496f Pulmonary veins, 31, 265–267, 297f, 680 Pulmonic regurgitation, diastolic murmurs, 18

Pulmonic stenosis, 482 systolic murmurs, 16 Pulmonic stenosis (PS), 268–269, 269f, 293, 295f Pulmonic valve, 29, 29f Pulmonic valve disease, 482–483 Pulse(s). See also Arterial pulse(s) deficit, 7 Pulse width (or pulse duration), 449 Pulsed wave vs. color and continuous wave Doppler, 90t Pulsus alternans, 4 Pulsus paradoxus, 6–7 Pulsus tardus and parvus, 7 Purkinje fibers, 33–34, 33f, 52–53 PURSUIT risk score, 636–637, 637f PVD. See Peripheral vascular disease PVE. See Prosthetic valve endocarditis PVR. See Pulmonary vascular resistance P waves, 304–305

Q QRS complex axes, 306–307 interval, 307 morphologies, 306 QT interval, 308, 894t–897t, 897 QT syndrome, 463. See also Long-QT syndrome long, 393–394, 393t short, 394 Quinidine, 406t, 407, 840t, 892t–893t, 897t Quinolone, 897t Q-waves, 310

R RA. See Rheumatoid arthritis RAD. See Renal artery disease

Radial-to-femoral delay, 7 RADIANCE study, 170 Radiation heart disease, 474 Radiation safety, 655 dose estimation and displays, 648–650, 649t, 650f, 651f ionizing radiation and radiation effects deterministic/nonstochastic risk, 650–651, 652t, 652f stochastic risk, 651–652, 652t management collimation, 654 dose and frame rate settings, 653 fluoroscopy time and number of acquisitions, 653 grid use, 654 magnification modes, 654 minimizing patient radiation exposure, 653, 653t operator radiation management, 654, 654t patient radiation, 653 source and distance, 653 x-ray beam, path length and approach, 653 production, 647f generator, 647 image receptor, 647 operating console, 648 x-ray tube, 646–647 regulatory recommendations, 654–655, 655t Radiation-associated cardiac disease (RACD), 963–964 screening guidelines and multimodality imaging in, 964, 964t Radionuclide imaging, 851–852, 961 Radionuclide ventriculography, 128–129 RALES trial (Randomized Aldactone Evaluation Study), 168t, 640 Rapamycin (Sirolimus), 190–191 Rapid filling phase, 239–240 RAPPORT trials, 604 Rate-adaptive pacing, 447

RBBB. See Right bundle branch block RCT. See Reverse cholesterol transport Recall bias, 67 Receiver operating characteristic (ROC) curve, 66, 67f Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, 790t, 792 Reflex syncope (neurally mediated), 461–462 atypical forms of, 462 Refractory angina ACC/AHA recommendations, 572 enhanced external counterpulsation (EECP), 572 spinal cord stimulation (SCS), 572 Regent valve, 522 Regurgitant systolic murmurs, 14 Regurgitant type, systolic murmurs, 16–17 Relapsing polychondritis, 875 Relative risk, 65 Relative risk reduction (RRR), 65 Remote telemetry, 466 Renal artery disease (RAD), 787 Renal cell carcinoma, 887–888 Renal failure, 700–701, 877 Renal parenchymal disease, 786–787 Renal retention, salt and water, 161 Renin–angiotensin system (RAS), 58–59, 59f Renin–angiotensin–aldosterone system (RAAS), 639–640 dysfunction, heart failure, 159 inhibitors, 962 Renovascular disease, 787–788, 787t Reopro. See Abciximab Reperfusion therapy, 600 REPLACE-2 trial, 586–587 REPRISE III trial, 913–914 RER. See Respiratory exchange ratio

Resin, 803t, 807, 808t Respiratory exchange ratio (RER), 181–182 Restrictive cardiomyopathy, 9, 21, 866t cardiac MRI, 135 definition, 244 primary restrictive cardiomyopathies, 244–245 secondary restrictive cardiomyopathies, 245–246, 247t working classification, 244, 245f Reteplase, r-PA (Retavase), 601 Revascularization MI complications and, 620 stable angina and ACC/AHA recommendations, 565t coronary artery bypass grafting versus medical therapy, 566–568 PCI versus CABG for diabetes mellitus patients, 571 PCI versus CABG for left main trunk stenosis, 570–571 PCI versus CABG in multivessel CAD, 569–570 PCI versus CABG in single-Vessel CAD, 569 percutaneous coronary intervention versus medical therapy, 568– 569 Reverberation artifacts, 92 Reverse cholesterol transport (RCT), 798–799 Reverse remodeling, heart failure, 160 Revised cardiac risk index (RCRI), 822 Revised Geneva Score for Pretest Probability of Acute PE, 729t Rhabdomyomas, 883t, 884–885 Rheumatic fever, AS, 477–478, 478t Rheumatic heart disease, 473–474, 479, 496–497, 504 Rheumatic mitral stenosis (MS), 922 stages of, 923f Rheumatoid arthritis (RA), 873 Rhythms of ventricular origin, 306 Rifampin, 189t, 517–518, 894t–896t Right atrial abnormality, 309

Right atrium, 27, 27f Right bundle branch block (RBBB), 308 Right ventricle, 28, 28f Right ventricular function, 204 Right ventricular hypertrophy (RVH), 283, 309 Right ventricular infarction diagnosis for, 624 symptoms and signs of, 624 treatment for, 624 Right ventricular pacing, 607 Risk ratio (RR), 65 Ritonavir, 896t Rivaroxaban, 412, 748 Ross procedure, 478–479 Rosuvastatin, 807t–808t r-PA. See Reteplase, r-PA (Retavase) RR. See Risk ratio RRR. See Relative risk reduction Rubidium-82, 114 RV infarction, 20 RVH. See Right ventricular hypertrophy

S SA. See Sinoatrial node SA block. See Sinoatrial block SACT. See Sinoatrial conduction time St. Jude's Masters valve, 522 Salt and water, heart failure and renal retention, 161 Sapien M3 device, 930t Sarcoidosis, 246, 875 Sarcomere, anatomy, 57f Sarcoplasmic reticulum (SR), 56 SAVE. See Survival and Ventricular Enlargement SBP. See Systolic blood pressure Scandinavian Simvastatin Survival Study, 810t

SCD. See Sudden cardiac death SCD-HeFT trials, 471 Scleroderma, 874 SCN5A, 937t SCS. See Spinal cord stimulation sdLDL. See Small dense low-density lipoprotein Secondary cardiac tumors, 887–888, 887f Secondary CHD prevention, trials for, 810t Secundum ASDs, 903, 905f, 906f Selection bias, 67 Sensing, 449 Septal myectomy, 258–259, 258f Seronegative spondyloarthropathies, 873 SHOCK (Should We Emergently Revascularize Occluded Coronary Arteries for Cardiogenic Shock) Trial Registry, 618–619, 633 Short-QT syndrome, 394 Short-term circulatory-assist devices, 615–616 Shunt calculations, 663 left-to-right, 663 lesions atrial septal defect, 265–267, 266f, 267t patent ductus arteriosus, 268 ventricular septal defect, 268, 268f operations for, 296–298, 299t Sick sinus syndrome, 312 Sildenafil, 587–588 SIMA (Stenting v. Internal Mammary Artery study), 566 Simvastatin, 892t–896t, 896–898 Single photon emission computed tomography (SPECT) imaging, 852 in cardiac amyloidosis, 127 perfusion agents, 114 Single ventricle circulations, 272–273 Single-chamber devices, 446–447

Sinoatrial block (SA block), 304 Sinoatrial conduction time (SACT), 370, 370f Sinoatrial (SA) node, 33, 33f Sinus arrest/pause, 304–305 Sinus arrhythmia, 304 Sinus bradycardia, 304 Sinus node dependent, 417, 418f, 419f functions, EP and, 369–371, 370f, 371f recovery time, 370 reentrant rhythm, 305 reentrant tachycardia, 305 refractory period, 367–369 Sinus rhythm, 405–406, 406t. See also Normal sinus rhythm Sinus tachycardia, 304 Sinus venosus ASDs, 905, 907f Sinus-dependent arrhythmias, 427–428 Sirolimus. See Rapamycin Situational syncope, 462 Skeletal muscle adaptations, heart failure, 161 SLE. See Systemic lupus erythematosus Small dense low-density lipoprotein (sdLDL), 798, 805 Small molecule tyrosine kinase inhibitors, 959–960 Smoking, 637, 642 CAD and, 549–550 pregnancy and, 846–847 Smooth muscle dysfunction genes, 937t Sodium (NA+), nitroprusside, 619–620 Sodium glucose co-transporter inhibitors (SGLT2 inhibitors), 168–169 Sodium–calcium exchange (NCX1) pump, 58 Sodium-dependent cells, 49 SOLVD. See Studies of Left Ventricular Dysfunction Sorafenib, 959–960, 960t Sorin Carbomedics valve, 522

Sotalol, 406t, 408, 840t, 897t Sound waves, 85 Speckle tracking techniques, 91 SPECT imaging in cardiac amyloidosis, 127 perfusion agents, 114 Spinal cord stimulation (SCS), 572 Splinter hemorrhages, 509, 510f Splitting first heart sound, 10 fixed, 11 paradoxical, 11 pathologic, 11 persistent, 10–11 reverse, 10 S2 (physiologic), 11f second heart sound, 10–11, 11f Sports cardiology, 948 athlete's heart, 948–949 ECG interpretation in athletes, 951, 951f management of athletes with cardiovascular disease, 951–956, 952t aortopathies, 956 arrhythmias, 953–955 cardiomyopathies, 952–953 coronary anomalies, 955–956 Marfan syndrome, 956 pericarditis, 956 valvular disease, 955 preparticipation screening, 950–951 sports, classification of, 949f sudden cardiac death in athletes, 949–950, 950f Stable angina, 692–698 CCS classification of, 554, 555t definition of, 554

diagnostic testing/risk stratification CAD, 559t coronary angiography, 557–558 echocardiography, 556 electrocardiography, 555 exercise ECG testing, 555–556 stress testing with nuclear/echocardiographic imaging, 556–557, 557t medical treatment antiplatelet therapy, 560–561 lipid-lowering therapy, 561 renin–angiotensin–aldosterone system blockade, 561 pathophysiology of, 555 refractory angina, 571–572 revascularization in ACC/AHA recommendations, 565t coronary artery bypass grafting versus medical therapy, 566–568 PCI versus CABG for Patients with Diabetes Mellitus, 571 PCI versus CABG for Patients with Left Main Trunk Stenosis, 570–571 PCI versus CABG in Multivessel CAD, 569–570 PCI versus CABG in Single-Vessel CAD, 569 percutaneous coronary intervention versus medical therapy, 568– 569 symptomatic medical therapies, antianginals beta-blockers, 562–563, 562t calcium channel blockers, 563, 563t combination therapy, 564 nitroglycerin and nitrates, 563–564, 564t ranolazine, 564–565 STAMINA-HF trial, 170 Staphylococcus aureus, 511–512, 518 bacteremia, 518 prosthetic valve endocarditis, 527

Starling Law, 39f Statin(s), 753, 761, 962 for dyslipidernias, 807, 807t high- risk primary prevention, 810t Intolerance, 813 LDL-C management, 809–811 for MI, 640 primary prevention, 810t secondary prevention, 810t trials for, 810t–811t Statistical tests, 64 confidence interval, 64 error analysis type I errors, 64, 64f type II errors, 64, 64f hypothesis testing, 64 Stature, 4 ST-elevation myocardial infarction (STEMI), 586, 614, 626, 689–692 assessment for risk of sudden cardiac death, 634–635 biomarker assessment, 633 clinical and demographic factors, 631–632 clinical presentations of, 595 diagnosis for, 595–597, 596f–597f electrocardiogram, 632–633 free wall rupture, 608 history and physical examination, 597 during hospitalization, 633–635 imaging, 633 implantable cardioverter–defibrillator implantation, 608–609 inferior ST-elevation AMI, 597f left ventricular aneurysm, 608 LV function assessment, 634 management of anti-ischemic agents for, 606

antiplatelet agents, 603–604 antithrombotic agents for, 604–606 aspirin for, 608 atorvastatin for, 607 fibrinolytic therapy, 601 glycoprotein IIb/IIa inhibitors for, 604 mechanical complications, 607–608 PCI for, 601–603 predischarge risk stratification for, 609 regional systems of care, 599 reperfusion therapy for, 600 secondary prevention, 606–607 mitral regurgitation, 607–608 pericarditis for, 608 physical examination, 632 predischarge assessment, 634 predischarge management, 635 risk stratification, 598–599, 631–637, 632t, 635t, 636f, 637t stress testing, 634 thienopyridines for, 603–604 ventricular septal rupture, 608 STEMI. See ST-elevation myocardial infarction Stenotic lesions, 268–270 aortic coarctation, 269–270 pulmonic stenosis (PS), 268–269, 269f Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial, 762 Stenting, coronary, 560–561 Stents, 699, 703 Stickler syndrome, 936t Stimulation threshold, 449 Storage disorders, 244, 246, 247t and associated cardiac manifestations, 935t Strain imaging, 91

Strauss method, 370, 371f Strength–duration curve, 449 Streptokinase, 601 Streptomycin, 517–518 Stress echocardiography (SE), 851 class I indications, 106 diastolic function assessment, 111 DSE role to assess viability, 111 false-positive and false-negative, 110t forms of, 106–107 exercise echocardiography, 106 pharmacologic, 106–107 imaging technique, 107 interpretation of, 108, 109t, 112f diagnosis of CAD, 109–110 ischemic cascade, 107f in nonischemic cardiac conditions, 111–112 prognostic role, 110–111 prognostic significance, 106 responses, 109t uses for, 108–112 Stress imaging technique, 821–822 Stress testing, 465 chest discomfort, 538–539 exercise electrocardiographic (ECG). See electrocardiographic (ECG) stress test Stroke Prevention in Reversible Ischemia Trial (SPIRIT), 760 Stroke work, pressure–volume loop, 41 Strokes, 401 Structural cardiac interventions fluoroscopy, 680–683, 681f, 682f, 683f, 684f intracardiac echocardiography, 683–684 multidetector computed tomography, 684–685 transesophageal echocardiography, 683

Exercise

Structural heart disease, 463 ST-segment depression, 310–311 elevation, 310 Studies of Left Ventricular Dysfunction (SOLVD), 166t Subaortic aortic stenosis, 289–290, 291f Subaortic stenosis, 478 Subclinical hemolysis, 526–527 Subvalvular AS, 474 Sudden cardiac death (SCD), 260, 260t, 948 arrhythmogenic right ventricular cardiomyopathy, 392, 392f assessment for, 634–635 in athletes, 949–950, 950f Brugada syndrome, 394, 394f and coronary artery disease, 391 DCM and, 391 definition, 390 epidemiology, 390 evaluation and management of, 395 HCM and, 391–392 idiopathic ventricular fibrillation, 394 long-QT syndrome, 393–394, 393t nonischemic cardiomyopathy, 391–393 risk factors and pathophysiology, 390–391 short-QT syndrome, 394 survivors of, 395 valvular heart disease, 394–395 Wolff–Parkinson–White syndrome, 394 Sunitinib, 959–960, 960t Superior vena cava (SVC) obstruction, 9 Supervised exercise rehabilitation, 750 Supracristal VSDs, 480 Supravalvular AS, 7, 474–475 Supraventricular tachycardia (SVT), 954–955, 960

algorithm, 418f approach, 417–419, 419f–420f atrial-dependent arrhythmias, 426–427, 427f AV node-dependent, 420–425, 422f–423f sinus-dependent arrhythmias, 427–428 wide-complex tachycardia bundle branch block, 430–431, 432f–434f differential diagnosis, 430–432, 431f with pre-excitation, 431, 432f SURTAVI trial, 914–915, 914t Survival and ventricular enlargement (SAVE), 166t SVC. See Superior vena cava SVT. See Supraventricular tachycardia Swedish Angina Pectoris Aspirin Trial, 560 Syncope acute episodes management, 467 alarming features, 464 beta-blockers, 468 CCBs for, 468 clinical features, 465t clinical history, 464, 464t conservative/nonpharmacologic therapy, 467–468 definition, 461 diagnosis, 463–467 diagnostic workup, 464–467 due to orthostatic hypotension, 462–463 ECG monitoring, 465–466 echocardiography, 467 electrophysiology testing, 467, 467t etiology, 461 follow-up, 468–469 incidence of, 461 neurally mediated, 462 pathophysiology, 461

patient morbidity, 468 pharmacologic treatment, 468 physical examination, 463 prevalence of, 461 prognosis, 468–469 stress testing, 467 treatment for, 467–468 types, 461 vasovagal, 462–463 Syphilitic aortitis, 720 Systemic lupus erythematosus (SLE), 873 Systole ejection murmurs, 15f ejection sounds, 12 aortic, 12 pulmonic, 12 nonejection clicks, 12–13 pericardial friction rubs, 13 Systolic blood pressure (SBP), 6 Systolic Blood Pressure Intervention Trial (SPRINT), 790t, 791 Systolic function, 476 Systolic murmurs aortic sclerosis, 15 aortic valvular stenosis, 14–15, 14f–15f ejection type, 14–16 hypertrophic cardiomyopathy, 15–16 innocent murmur in children (still murmur), 16 in children to young adults (pulmonary ejection murmur), 16 mitral regurgitation, 16, 16f pulmonic stenosis, 16 regurgitant type, 16–17 tricuspid regurgitation, 16–17 ventricular septal defect, 17

T Tachyarrhythmias, 626–627 evaluation of, 377–383– 378f, 386f Tachycardia-induced cardiomyopathy, 401 Tacrolimus (Tac), 190 TACTICS (Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy) TIMI 18 trial, 635 Takayasu arteritis, 720, 874 Takotsubo cardiomyopathy, 961 Tansthoracic echocardiogram (TTE), 525 Target lesion revascularization, 699, 703 Task Force for the Diagnostic Management Syncope of the European Society of Cardiology, 461 T-cell receptor (TCR), 189 Technetium pyrophosphate (PYP-Tc99m), 115 Technetium-99m-labeled agents, 114 TEE. See Transesophageal echocardiography Temporary right ventricular pacing, 607 Tendyne device, 930t Tenecteplase, weight-based dosing, 601, 601t Tetralogy of Fallot (TOF), 271, 293 TGA. See Transposition of the great arteries TGRLs. See Triglyceride-rich lipoproteins Thallium-201 chloride, 114 Theophylline, stress protocols, nuclear perfusion imaging, 118 Therapeutic lifestyle changes (TLC), 806–807, 806t Thienopyridines, 637–639, 699–700 for NSTEMI, 584 for STEMI, 603–604 Thoracic aortic aneurysm (TAA), 717–719 ascending, 717, 717f descending, 717 familial screening, 718 incidence, 717

Marfan syndrome and pregnancy, 718 medical treatment, 718 noninvasive imaging, 718 surgical treatment, 718–719 Thoracic endovascular aortic repair (TEVAR), 719 Thoratec device, 203 Three-dimensional echocardiography, 89 Thromboembolism, 401, 410 Thrombolytics, 850 Thromboprophylaxis, 736 Thyroid disorders, 788–789 Thyroid-stimulating hormone (TSH), 779, 789 Tiara device, 930t Tilt table test, 466 abnormal hemodynamic patterns, 466, 466t relative contraindications, 466 TIMI risk score, 598–599, 599f TIMI (Thrombolysis in Myocardial Infarction ) study 16, 635 18, 636 22, 641, 641f risk score, 636f–637f Tip-to-base technique, 928 Tissue Doppler techniques, 91 Tissue-type plasminogen activator (t-PA), 742 TLC. See Therapeutic lifestyle changes TMP-SMX. See Trimethoprim-sulfamethoxazole TNT. See Treating to New Targets Tobacco, 549–550 Toxoplasma, 192 t-PA. See Tissue-type plasminogen activator TR. See Tricuspid regurgitation Transaortic valve gradients, 476 Transcatheter aortic valve implantation (TAVI), 479

Transcatheter aortic valve replacement (TAVR), 523 access routes for, 915–916 for aortic regurgitation, 916 approved devices in United States, 911–912, 911f for bicuspid AS, 916 cerebral embolic protection, 917 clinical trials, 910 complications, 917 DAPT duration, 918 EARLY TAVR trial, 917 evidence supporting for, 912–916 high–surgical-risk patients, 913–914, 913t inoperable patients, 912–913, 912t intermediate surgical risk, 914–915, 914t low surgical risk, 915, 915t future directions for, 918 hypoattenuation and leaflet thickening after, 918 indications for, 910–911, 911f outcomes in extreme-risk patients, 912t SBE prophylaxis, 918 UNLOAD trial, 917 valve durability, 917–918 valve-in-valve, 916 Transcatheter heart valves (THVs), 911 Transcatheter mitral valve repair, 923–927 degenerative MR, 925–927 functional MR, 927 Transcatheter mitral valve replacement (TMVR), 928, 929f devices for, 928, 930t LVOT obstruction, 928 valve in MAC (ViMAC), 928 valve in ring (ViR), 928 valve in valve (ViV) TMVR, 928 Transducers, 86–87, 86t

Transesophageal echocardiography (TEE), 683 Transient ischemic attack (TIA), 758 Transposition of the great arteries (TGA), 270–271, 294–296, 297f Transthoracic echocardiography (TTE), 475–477, 624 of HCM, 251f, 253, 256 for MR, 491 Transthyretin (ATTR) amyloid cardiomyopathy, 115 Trastuzumab, 959, 960t Traube sign, 8 Trauma, aortic injury, 712 Treadmill, 555 Treating to New Targets (TNT), 811t Triamterene, 894t–896t Tricuspid regurgitation (TR), 194 etiology of, 501 signs/symptoms of, 501–504, 502f, 503f systolic murmurs, 16–17 treatments for, 502–504 Tricuspid stenosis (TS), 8 diastolic murmurs, 18 Tricuspid valves, 10, 29, 29f Tricuspid valve stenosis (TS), signs/symptoms of, 504–505 Tricyclic antidepressants, 393, 897t Triglyceride-rich lipoproteins (TGRLs), 798, 799f Trimethoprim, 894t–896t Trimethoprim-sulfamethoxazole (TMP-SMX), 192 Triple apical impulse, 9–10 Trisomy 21, 936t TS. See Tricuspid valve stenosis Tuberous sclerosis, 936t Tumor plop (TP), 12 Tumors, cardiac benign, 882–886, 883t, 883f, 884f, 885f malignant, 886–887, 886t, 887f

Turner syndrome, 936t T waves, 311

U U waves, 311 Ulcer and foot care prevention, 747 Ultrafiltration, 172 Ultrasound harmonic imaging, 88–89 imaging modalities, 87–88 principles of, 85 with tissue, interaction of, 85 transducers, 86–87, 86t velocity of sound through different media, 86t Unfractionated heparin (UFH), 525 Unipolar leads, pacing leads, 448 United Network for Organ Sharing (UNOS), 180, 184t United States (U.S), CVDs in, 543–549 age and gender variation of, 545–546, 545f, 546f cost and health care resources utilization, 548–549, 549t prognosis and risks associated with SCD, 547–548 racial and socioeconomic disparities of, 545t, 546–547, 547f silent myocardial ischemia/infarction, 544–545, 545f–546f temporal trends of, 543 unrecognized myocardial ischemia/infarction, 544–545, 545f–546f young people and, 547 United States Preventive Services Task Force (USPSTF), 758 Unroofed coronary sinus, 905, 905f Upper rate limit, 450 U.S. Food and Drug Administration (FDA), 564, 733, 794

V V–A interval, 450 VALIANT trial (Valsartan in Acute Myocardial Infarction), 640 Validity, 67

Valsalva maneuvers, 19, 20f, 252, 435 Valvar pulmonic stenosis, 77, 77f Valve(s) anticoagulation, 524–528, 525t biologic, 478 bioprosthetic, 522, 523f–524f gradients, 476 mechanical, 522, 523f–524f Medtronic Open Pivot, 522 monitoring prosthetic with echocardiography, 525–528, 525f, 527f On-X, 522 replacement options, 478–479 Sorin Carbomedic, 522 St. Jude's Masters, 522 types, selection of, 522–523 Valve in MAC (ViMAC), 928 Valve in ring (ViR), 928 Valve in valve (ViV) TMVR, 928 Valve-in-valve TAVR, 916 Valve orifice area (VOA), 664 Valvular disease, 955, 963–964 Valvular heart disease, 823 and pressure–volume loop, 41, 41t, 41f Valvular pulmonic stenosis, 293, 295f Vancomycin, 516, 516t VANQWISH, 692 Vascular access, PCI, 602 Vascular disease, 964 Vascular Ehlers–Danlos syndrome, 937t Vascular endothelial growth factor (VEGF) inhibitors, 959–960 Vascular resistance, 663–664 Vasoactive intestinal peptide, 229 Vasoconstriction, 228 Vasodilators, 614, 617

for AS, 481 pharmacologic stress echocardiography, 107 Vasopressin, antagonists, 172 Vasopressors, 615 Vasovagal syncope, 462 Velocity time integral (VTI), 476 Vena cavae, 30 Vena contracta, 93 Venography, 728 Venous hum, 18 Venous thromboembolism (VTE) and cancer, 962–963 prevention of, 962–963 risk assessment, 962 risk factors, 962 treatment and secondary prevention, 964 diagnosis of, 728–729 DVT clinical presentation and diagnosis, 726–727, 727f D-Dimer testing, 726 diagnostic testing, 728 duplex ultrasonography, 727–728 venography, 728 essential facts about, 725 risk factors, 726, 726t treatment of anticoagulants, 733, 734t DOACs, 733, 733t DTI, 732 fondaparinux, 732 LMWH, 732 mechanical/pharmacologic, 736 pulmonary embolism clinical presentation and diagnosis, 729f, 728–729

CTPA, 730 echocardiography, 729–730 laboratory biomarkers, 730–731 MRA, 730 objective testing, 729–731 pulmonary angiography, 730 transthoracic echocardiogram, 729–730 ventilation/perfusion scintigraphy, 730 thrombolytic therapy for, 734 thromboprophylaxis, 736 unfractionated heparin, 732 VKA, 732–733 Ventilation/perfusion scans (V/Q), 730 Ventricular activation, 367, 372 Ventricular arrhythmias, 955 Ventricular contraction, 91 Ventricular extrastimulus testing, 376–377 Ventricular fibrillation (VF), 306 Ventricular function, 204 Ventricular oversensing, 449–450 Ventricular pacing, 376–377, 376f–377f, 379, 381 Ventricular parasystole, 306 Ventricular rate, 304–308, 403–404, 404t Ventricular remodeling and reverse remodeling heart failure, 160 Ventricular sensitivity, 449 Ventricular septal defect (VSD), 21, 268, 268f, 287–288, 287f, 616–617, 833 diagnosis for, 616–617, 617f membranous, 268, 287 muscular, 287, 288f–289f signs/symptoms of, 616 supracristal, 287, 289f systolic murmurs, 17

treatment for, 617 types of, 287, 287f Ventricular systole, 10 Ventricular tachycardia (VT), 306. See also Supraventricular tachycardia; Wide-complex tachycardia coronary artery disease, 395 dilated cardiomyopathy, 396 idiopathic left ventricular tachycardia, 396–397 morphology of, 379 outflow tract, 396, 396f papillary muscle, 397 short-QT syndrome, 394 structurally normal heart and, 396–397 Ventricular volumes, pressure–volume loop, 40 Verapamil, 169, 257–258, 404t, 563t, 786, 894t–896t Verification bias, 67 Very low-density lipoprotein (VLDL), 798 Veterans Administration Cooperative Study (VA Study), 566 Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT), 812t Veterans Affairs Cooperative Study (VACS), 757 V-HeFT II, 169 Viability assessment, cardiac MRI, 134 Viral pericarditis, 858 Vitamin D, 194 Vitamin K antagonists (VKA), 731 VKA. See Vitamin K Antagonists VLDL. See Very low-density lipoprotein VMAC, 172 VOA. See Valve orifice area Voltage output, 449 Vorinostat, 959–960, 960t V/Q. See Ventilation/perfusion scans VSD. See Ventricular Septal Defect

VT. See Ventricular tachycardia VTE. See Venous thromboembolism VTI. See Velocity time integral

W Wandering atrial pacemaker (WAP), 305 WAP. See Wandering atrial pacemaker Warfarin, 411, 524–525, 639, 732–733, 748, 839, 841, 892t–896t Warfarin-Aspirin Symptomatic Intracranial Disease (WASID), 760 Water-hammer pulse, 8 Waveforms, 455, 456f intracardiac, 658–664, 659t, 659f Wavelength (λ), 85 Wegener granulomatosis, 875 West of Scotland Coronary Prevention Study (WOSCOPS), 810t Wide-complex tachycardia (WCT) algorithms, 437–438, 438f, 439f, 440f conclusions on, 439–440 diagnosis clinical presentation, 434–435 ECG criteria, 435–437, 436f–437f provocative maneuvers, 435 differential diagnosis, 430–432, 432f–434f special cases, 438–439, 441f Williams syndrome, 474–475, 871, 936t Wolff–Parkinson–White (WPW) syndrome, 394, 954 and sudden cardiac death, 425 Women AHA/ACC guidelines for, 845, 848 cardiac computed tomography angiography, 851 cardiovascular magnetic resonance imaging, 852 chest discomfort in, 539–540 coronary artery disease, 849–850 epidemiology/problem of, 845, 846f exercise electrocardiograms, 850–851

guidelines for heart disease prevention in, 848–849, 849f heart failure and, 852–853 survival, 852–853 treatment, 845 noninvasive evaluation of, 850 pregnancy, 524–525 prevention of, estrogen therapy for, 848 radionuclide imaging, 851–852 risk factors associated with, 847–848 for coronary artery disease, 845–847 stress echocardiography (ECHO), 851 Women's Health Initiative Observational Study (WHI-OS), 788 World Health Organization (WHO), global burden of disease, 543 WOSCOPS. See West of Scotland Coronary Prevention Study

X Xanthomas, 801f X-ray imaging system, 647f generator, 647 image receptor, 647 operating console, 648 x-ray tube, 646–647 XRT. See External-beam radiation therapy

Z Ziprasidone, 897t Z-scores, 956