NETTER’S CARDIOLOGY EDITED BY ILLUSTRATIONS BY George A. Stouffer, MD Frank H. Netter, MD Ernest and Hazel Craige Distinguished Professor of Medicine Chief, Division of Cardiology Physician in Chief, UNC Heart and Vascular Service Line CONTRIBUTING ILLUSTRATORS University of North Carolina at Chapel Hill Chapel Hill, North Carolina Carlos A.G. Machado, MD Marschall S. Runge, MD, Ph@ John A. Craig, MD Professor of Internal Medicine Dean, University of Michigan Medical Schoo\ David J. Mascaro, MS Executive Vice President for Medical Affairs Enid Hatton Chief Executive Officer, Michigan Medicine Ann Arbor, Michigan Steven Moon, MA Cam Patterson, MD, MBA Chancellor Kip Carter, MS, CMI University of Arkansas for Medical Sciences Little Rock, Arkansas Tiffany S. Davanzo, MA, CMI Joseph S. Rossi, MD Associate Professor of Medicine Director, Cardiac Catheterization Laboratory University of North Carolina at Chapel Hill Chapel Hill, North Carolina ELSEVIER 1600 John F. Kennedy Blvd. Ste 1600 Philadelphia, PA 19103-2899 NETTER’S CARDIOLOGY, THIRD EDITION ISBN: 978-0-323-54726-0 Copyright © 2019 by Elsevier, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted 2010 and 2004. Library of Congress Cataloging-in-Publication Data Names: Stouffer, George A., editor. | Runge, Marschall Stevens, 1954- editor. | Patterson, Cam, editor. | Rossi, Joseph S., editor. | Netter, Frank H. (Frank Henry), 1906-1991, illustrator. Title: Netter’s cardiology / edited by George A. Stouffer, Marschall S. Runge, Cam Patterson, Joseph S. Rossi ; illustrations by Frank H. Netter ; contributing illustrations, Carlos A. G. Machado [and 6 others]. Other titles: Cardiology Description: 3rd edition. | Philadelphia, PA : Elsevier, [2019] | Includes bibliographical references and index. Identifiers: LCCN 2018013552 | ISBN 9780323547260 (hardcover : alk. paper) Subjects: | MESH: Cardiovascular Diseases | Diagnostic Techniques, Cardiovascular Classification: LCC RC667 | NLM WG 120 | DDC 616.1/2—dc23 LC record available at https://lccn.loc. gov/2018013552 Content Strategist: Marybeth Thiel Publishing Services Manager: Catherine Albright Jackson Senior Project Manager: Claire Kramer Design Direction: Patrick Ferguson Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1 ABOUT THE EDITORS George A. Stouffer, MD, was born in Indiana, Pennsylvania, and Cam Patterson, MD, MBA, was born in Mobile, Alabama. He was graduated from Bucknell University and the University of was a Harold Sterling Vanderbilt Scholar and studied psychology Maryland, School of Medicine. He completed his internal medicine and English at Vanderbilt University, graduating summa cum laude. residency, cardiology fellowship, and interventional cardiology fel- Dr. Patterson attended Emory University School of Medicine, lowship at the University of Virginia. During his cardiology fel- graduating with induction in the Alpha Omega Alpha Honor Society, lowship, he completed a 2-year National Institutes of Health research and completed a residency in Internal Medicine at Emory University fellowship in the laboratory of Gary Owens at the University of Hospitals and Chief Residency at Grady Memorial Hospital. He Virginia. He was on the faculty at the University of Texas Medical completed 3 years of research fellowship under the guidance of Branch from 1995 to 2000, where he became an associate professor Edgar Haber at the Harvard School of Public Health, developing and served as Co-Director of Clinical Trials in the Cardiology an independent research program in vascular biology and angio- Division and as Associate Director of the Cardiac Catheterization genesis that was supported by a National Institutes of Health fel- Laboratory. He joined the faculty at the University of North Caro- lowship. He did a cardiology fellowship and was on the faculty at lina in 2000 and currently serves as the Henry A. Foscue Distin- the University of Texas Medical Branch from 1996 to 2000. Dr. guished Professor of Medicine and Chief of Cardiology. Dr. Stouffer’s Patterson was at the University of North Carolina at Chapel Hill main focus is clinical cardiology with an emphasis on interventional from 2000 to 2014 where he served as founding director of the cardiology, but he is also involved in clinical and basic science UNC McAllister Heart Institute, Chief of Cardiology, and the research. His basic science research is in the areas of regulation of Ernest and Hazel Craige Distinguished Professor of Cardiovascular smooth muscle cell growth, the role of the smooth muscle cyto- Medicine. He received his MBA from the UNC Kenan-Flagler skeleton in regulating signaling pathways, thrombin generation, School of Business in 2008. He is an elected member of the American and renal artery stenosis. Society of Clinical Investigation and the Association of University Cardiologists. Until recently he was Senior Vice President and Marschall S. Runge, MD, PhD, was born in Austin, Texas, and Chief Operating Officer at New York Presbyterian–Weill Cornell was graduated from Vanderbilt University with a BA in general Medical Center and currently serves as Chancellor of the University biology and a PhD in molecular biology. He received his medical of Arkansas for Medical Sciences. degree from the Johns Hopkins School of Medicine and trained in internal medicine at Johns Hopkins Hospital. He was a cardiology Joseph S. Rossi, MD, was born in Hopedale, Illinois. He completed fellow and junior faculty member at Massachusetts General Hospital. his undergraduate studies at the University of Illinois and then Dr. Runge’s next position was at Emory University, where he directed completed his medical education at the University of Illinois–Chicago, the Cardiology Fellowship Training Program. He then moved to graduating with induction into the Alpha Omega Alpha Honor the University of Texas Medical Branch in Galveston, where he Society. He completed residency and fellowships in internal medi- was Chief of Cardiology and Director of the Sealy Center for cine, cardiovascular disease, and interventional cardiology at North- Molecular Cardiology. He was at the University of North Carolina western University, where he also obtained a master’s degree in from 2000 to 2015, where he served as Charles Addison and Eliza- clinical investigation. Dr. Rossi is currently the Director of the beth Ann Sanders Distinguished Professor of Medicine, Chair of Cardiac Catheterization Lab at the University of North Carolina. the Department of Medicine, President of UNC Physicians, and He is actively involved in multiple clinical trials and has received Vice Dean for Clinical Affairs. He is currently Dean of the Medical research grants to support his interest in the pharmacogenomics School at the University of Michigan, Executive Vice President for of dual antiplatelet therapy and complex coronary artery revascu- Medical Affairs, and Chief Executive Officer of Michigan Medicine. larization among Medicare beneficiaries. Dr. Rossi is particularly Dr. Runge is board-certified in internal medicine and cardiovascular interested in pairing clinical and administrative data to enhance diseases and has spoken and published widely on topics in clinical our knowledge of trends and resource utilization for patients with cardiology and vascular medicine. advanced vascular disease. v PREFACE Our goal for the third edition of Netter’s Cardiology was to provide chapters. The result is a text that is truly clinically useful and less a concise and practical overview of cardiovascular medicine that has of a compendium than is commonly the case in many medical texts. been updated to include new information and important clinical We believe that the changes we have made in the third edition areas that were not well covered in the previous editions or in other substantially improve Netter’s Cardiology and ensure that it will con- cardiology texts. To accomplish this expansion while maintaining a tinue to be a highly useful resource for all physicians, both generalists focused text that could be used as a ready reference, we again avoided and subspecialists, who need to remain current in cardiology—from exhaustive treatment of topics. We also have made every effort to trainees to experienced practitioners. Whether we have succeeded present the essential information in a reader-friendly format that will obviously be determined by our readers. We welcome the com- increases the reader’s ability to learn the key facts without getting ments, suggestions, and criticisms of readers that will help us improve lost in details that can obfuscate the learning process. future editions of this work. The first two editions of Netter’s Cardiology were an effort to present in a concise and highly visual format the ever-increasing George A. Stouffer, MD amount of medical information on cardiovascular disease. The Ernest and Hazel Craige Distinguished Professor of Medicine challenge that clinicians face in “keeping up” with the medical Chief, Division of Cardiology literature has continued to grow in the 14 years since the first Physician in Chief, UNC Heart and Vascular Service Line edition of Netter’s Cardiology. This need to process the ever-expanding University of North Carolina at Chapel Hill medical information base and apply new findings to the optimal Chapel Hill, North Carolina care of patients is acute in all areas of medicine, but perhaps it is most challenging in disciplines that require practitioners to Marschall S. Runge, MD, PhD understand a broad spectrum of evidence-based medicine, such Professor of Internal Medicine as the field of cardiovascular diseases. The explosion of medical Dean, University of Michigan Medical School knowledge is also a real educational challenge for learners at all Executive Vice President for Medical Affairs levels—students, residents, and practicing physicians—who must Chief Executive Officer, Michigan Medicine rapidly determine what is and is not important, organize the key Ann Arbor, Michigan information, and then apply these principles effectively in clinical settings. Cam Patterson, MD, MBA The third edition includes substantial changes. All the chapters Chancellor have been updated, there is a new section on Structural Heart University of Arkansas for Medical Sciences Disease, and new chapters have been added on Basic Anatomy and Little Rock, Arkansas Embryology of the Heart, Stem Cell Therapies for Cardiovascular Disease, Diabetes and Cardiovascular Events, Coronary Hemody- Joseph S. Rossi, MD namics and Fractional Flow Reserve, Epidemiology of Heart Failure: Associate Professor of Medicine Heart Failure with Preserved Ejection Fraction and Heart Failure Director, Cardiac Catheterization Laboratory with Reduced Ejection Fraction, Management of Acute Heart Failure, University of North Carolina at Chapel Hill Cardiac Transplantation and Mechanical Circulatory Support Chapel Hill, North Carolina Devices, Cardiovascular Manifestations of Rheumatic Fever, Clinical Presentation of Adults with Congenital Heart Disease, Transcatheter Aortic Valve Replacement, Transcatheter Mitral Valve Repair, Tri- cuspid and Pulmonic Valve Disease, Deep Vein Thrombosis and Pulmonary Embolism, Cardiac Tumors and Cardio-oncology, and Cardiovascular Disease in the Elderly. As in the first two editions, the contributing authors have taken advantage of the genius of Frank Netter by carefully selecting the best of his artwork to illustrate the most important clinical concepts covered in each chapter. When Netter artwork was unavailable or difficult to apply to illustrate modern clinical concepts, we again used the great artistic talents of Carlos A. G. Machado, MD, to create new artwork or to skillfully edit and update some of Frank Netter’s drawings. The combination of Dr. Machado’s outstanding skills as a medical artist and his knowledge of the medical concepts being illustrated was an invaluable asset. As in the first two editions, we chose to use authors from the University of North Carolina School of Medicine at Chapel Hill or those with close ties to the university. This allowed us to select authors who are clinical authorities, many of whom are also well known for their national and international contributions. All have active clinical practices that require daily use of the information covered in their chapters, and all are well aware of the approach to patient management used by their peers at other institutions and in other practice settings. Many of the contributing authors for this edition also contributed to prior editions of this textbook. Each author, whether a previous contributor or not, was given clearly defined guidelines that emphasized the need to distill the large amount of complex information in his or her field and to present it concisely in a carefully prescribed format maintained across all vi Preface vii Algorithms have been color coded for quick reference. Algorithm for Evaluating Patients in Whom Renal Artery Stenosis Is Suspected Clinical findings associated with renal artery stenosis Present Absent Noninvasive evaluation Follow clinically (duplex ultrasonography of renal Treat risk factors arteries, magnetic resonance Orange (cid:31) test angiography, or computed tomographic angiography) Renal artery stenosis present Renal artery stenosis absent Blue (cid:31) all other Nuclear imaging Follow clinically to estimate fractional Treat risk factors flow to each kidney Unilateral renal artery Unilateral renal artery Bilateral renal artery stenosis and asymmetric stenosis and symmetric stenosis present perfusion present perfusion present Follow clinically Green (cid:31) treatment options Treat risk factors Consider revascularization ABOUT THE ARTISTS Frank H. Netter, MD Carlos A. G. Machado, MD Frank H. Netter was born in 1906 in New York City. He studied Carlos Machado was chosen by Novartis to be Dr. Netter’s suc- art at the Art Student’s League and the National Academy of Design cessor. He continues to be the main artist who contributes to the before entering medical school at New York University, where he Netter collection of medical illustrations. received his medical degree in 1931. During his student years, Dr. Self-taught in medical illustration, cardiologist Carlos Machado Netter’s notebook sketches attracted the attention of the medical has contributed meticulous updates to some of Dr. Netter’s original faculty and other physicians, allowing him to augment his income plates and has created many paintings of his own in the style of by illustrating articles and textbooks. He continued illustrating as Netter as an extension of the Netter collection. Dr. Machado’s a sideline after establishing a surgical practice in 1933, but he ulti- photorealistic expertise and his keen insight into the physician/ mately opted to give up his practice in favor of a full-time com- patient relationship inform his vivid and unforgettable visual style. mitment to art. After service in the United States Army during His dedication to researching each topic and subject he paints places World War II, Dr. Netter began his long collaboration with the him among the premier medical illustrators at work today. CIBA Pharmaceutical Company (now Novartis Pharmaceuticals). Learn more about his background and see more of his art at This 45-year partnership resulted in the production of the extraor- https://www.netterimages.com/artist-carlos-a-g-machado.html. dinary collection of medical art so familiar to physicians and other medical professionals worldwide. In 2005, Elsevier, Inc., purchased the Netter Collection and all publications from Icon Learning Systems. There are now more than 50 publications featuring the art of Dr. Netter available through Elsevier, Inc. (www.elsevierhealth.com). Dr. Netter’s works are among the finest examples of the use of illustration in the teaching of medical concepts. The 13-book Netter Collection of Medical Illustrations, which includes the greater part of the more than 20,000 paintings created by Dr. Netter, became and remains one of the most famous medical works ever published. The Netter Atlas of Human Anatomy, first published in 1989, presents the anatomic paintings from the Netter Collection. Now translated into 16 languages, it is the anatomy atlas of choice among medical and health professions students the world over. The Netter illustrations are appreciated not only for their aes- thetic qualities, but also, more important, for their intellectual content. As Dr. Netter wrote in 1949, “. . . clarification of a subject is the aim and goal of illustration. No matter how beautifully painted, how delicately and subtly rendered a subject may be, it is of little value as a medical illustration if it does not serve to make clear some medical point.” Dr. Netter’s planning, conception, point of view, and approach are what inform his paintings and what makes them so intellectually valuable. Frank H. Netter, MD, physician and artist, died in 1991. Learn more about the physician-artist whose work has inspired the Netter Reference collection at https://www.netterimages.com/ artist-frank-h-netter.html. viii ACKNOWLEDGMENTS This third edition of Netter’s Cardiology benefited enormously from the hard work and talent of many dedicated individuals. First, we thank the contributing authors. All are current or former faculty members at the University of North Carolina School of Medicine, Chapel Hill, or have close ties to the institution. Without their intellect, dedication, and drive for excellence, Netter’s Cardiol- ogy, third edition, could not have been published. We had a solid foundation on which to build the third edition, thanks to the hard work of the contributing authors of the second edition, many of whom we were fortunate to have continue on to this edition. We are also grateful for the invaluable editorial contribution that Dr. E. Magnus Ohman made to the first edition. Special recognition goes to John A. Craig, MD, and Carlos A. G. Machado, MD. They are uniquely talented physician-artists who, through their work, brought to life important concepts in medicine in the new and updated figures included in this text. Marybeth Thiel at Elsevier was invaluable in bringing the third edition to fruition. We would especially like to acknowledge our families: our wives— Susan Runge, Meg Stouffer, Emma Rossi, and Kristine Patterson— whose constant support, encouragement, and understanding made completion of this text possible; our children—Thomas, Elizabeth, William, John, and Mason Runge; Mark, Jeanie, Joy, and Anna Stouffer; Paul, Samuel, and James Rossi; and Celia, Anna Alyse, and Graham Patterson—who inspire us and remind us that there is life beyond the computer; and, finally, our parents—whose per- sistence, commitment, and work ethic got us started on this road many, many years ago. ix CONTRIBUTORS EDITORS Sharon Ben-Or, MD Assistant Professor Cam Patterson, MD, MBA Department of Surgery Chancellor University of South Carolina at Greenville University of Arkansas for Medical Sciences Greenville, South Carolina Little Rock, Arkansas Hannah Bensimhon, MD Joseph S. Rossi, MD Cardiology Fellow Associate Professor of Medicine Department of Medicine Director, Cardiac Catheterization Laboratory University of North Carolina at Chapel Hill University of North Carolina at Chapel Hill School of Medicine Chapel Hill, North Carolina Chapel Hill, North Carolina Marschall S. Runge, MD, PhD Christoph Bode, MD, PhD Professor of Internal Medicine Chairman of Internal Medicine Dean, University of Michigan Medical School Medical Director, Department of Cardiology and Angiology Executive Vice President for Medical Affairs Albert-Ludwigs-Universität Freiburg Chief Executive Officer, Michigan Medicine Freiburg, Germany Ann Arbor, Michigan Michael Bode, MD George A. Stouffer, MD Cardiovascular Disease Fellow Ernest and Hazel Craige Distinguished Professor of Medicine Department of Medicine Chief, Division of Cardiology Division of Cardiology Physician in Chief, UNC Heart and Vascular Service Line University of North Carolina at Chapel Hill University of North Carolina at Chapel Hill Chapel Hill, North Carolina Chapel Hill, North Carolina Weeranun D. Bode, MD Assistant Professor AUTHORS Department of Medicine Division of Cardiology Basil Abu-el-Haija, MD University of North Carolina at Chapel Hill Clinical Cardiac Electrophysiology Chapel Hill, North Carolina Staff Physician, Kaweah Delta Hospital Visalia, California Mark E. Boulware, MD Interventional Cardiologist Tiffanie Aiken, BS University of Colorado Health Heart and Vascular Center MD Candidate 2019 Colorado Springs, Colorado University of South Carolina School of Medicine Greenville Greenville, South Carolina Michael E. Bowdish, MD Director, Mechanical Circulatory Support Sameer Arora, MD Assistant Professor of Surgery Cardiovascular Disease Fellow Keck School of Medicine of University of Southern California University of North Carolina at Chapel Hill Los Angeles, California Chapel Hill, North Carolina Timothy Brand, MD Matthew S. Baker, MD Cardiothoraic Surgery Resident Assistant Professor of Medicine University of North Carolina Hospitals Division of Cardiology Chapel Hill, North Carolina University of North Carolina School of Medicine Chapel Hill, North Carolina Bruce R. Brodie, MD, FACC Past President, LeBauer Cardiovascular Research Foundation Charles Baggett, MD Cone Health Heart and Vascular Center Cardiologist Greensboro, North Carolina The Harbin Clinic Rome, Georgia Adam W. Caldwell, MD Cardiovascular Disease Fellow Thomas M. Bashore, MD Division of Cardiology Professor of Medicine University of North Carolina School of Medicine Senior Vice Chief, Division of Cardiology Chapel Hill, North Carolina Duke University Medical Center Durham, North Carolina Eric P. Cantey, MD Department of Medicine Feinberg School of Medicine at Northwestern University Chicago, Illinois x