Netter’s Cardiology 2nd edition EditEd by MARSCHALL S. RUNGE, Md, Phd GEORGE A. StOUFFER, Md CAM PAttERSON, Md, MbA Illustrations by Frank H. Netter, MD CONTRIBUTING ILLUSTRATORS Carlos A. G. Machado, MD John A. Craig, MD David J. Mascaro, MS Enid Hatton Steven Moon, MA Kip Carter, MS, CMI Tiffany S. DaVanzo, MA, CMI 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899 NETTER ’ S CARDIOLOGY, SECOND EDITION I SBN: 978-1-4377-0637-6 ISBN (online): 978-1-4377-0638-3 Copyright © 2010 by Saunders, an imprint of 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. 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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 identifi ed, 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 edition copyrighted 2004 Library of Congress Cataloging-in-Publication Data Netter ’ s cardiology / edited by Marschall S. Runge, George A. Stouffer, Cam Patterson ; illustrations by Frank H. Netter ; contributing illustrator, Carlos A. G. Machado.— 2nd ed. p. ; cm. Other title: Cardiology Includes bibliographical references and index. ISBN 978-1-4377-0637-6 1. Cardiology. 2. Cardiovascular system — Diseases. I. Runge, Marschall S. II. Stouffer, George A. III. Patterson, Cam. IV. Netter, Frank H. (Frank Henry), 1906-1991. V. Title: Cardiology. [DNLM: 1. Cardiovascular Diseases. 2. Diagnostic Techniques, Cardiovascular. WG 120 N474 2011] RC667.N47 2011 616.1 ′ 2 — dc22 2010005892 N etter Director: Anne Lenehan Editor: Elyse O ’ Grady Editorial Assistant : Julie Goolsby Project Manager: David Saltzberg Design Manager: Steven Stave Working together to grow Illustrations Manager : Karen Giacomucci Marketing Manager: Jason Oberacker libraries in developing countries Printed in China www.elsevier.com | www.bookaid.org | www.sabre.org Last digit is the print number: 9 8 7 6 5 4 3 2 1 About the Editors Marschall S. Runge, MD, PhD, was born in Austin, Texas, clinical and basic science research. His basic science research is and was graduated from Vanderbilt University with a BA in in the areas of regulation of smooth muscle cell growth, the role General Biology and a PhD in Molecular Biology. He received of the smooth muscle cytoskeleton in regulating signaling path- his medical degree from the Johns Hopkins School of Medicine ways, thrombin generation, and renal artery stenosis. and trained in internal medicine at Johns Hopkins Hospital. He Cam Patterson, MD, MBA, was born in Mobile, Alabama. was a cardiology fellow and junior faculty member at Massachu- He was a Harold Sterling Vanderbilt Scholar and studied Psy- setts General Hospital. Dr. Runge’s next position was at Emory chology and English at Vanderbilt University, graduating University, where he directed the Cardiology Fellowship Train- summa cum laude. He participated in the Honors Research ing Program. He then moved to the University of Texas Medical Program at Vanderbilt and conducted research in behavioral Branch in Galveston, where he was Chief of Cardiology and pharmacology during that time. Dr. Patterson attended Emory Director of the Sealy Center for Molecular Cardiology. He University School of Medicine, graduating with induction in the came to the University of North Carolina (UNC) in 2000 as Alpha Omega Alpha Honor Society, and completed his resi- Chair of the Department of Medicine. He is currently the dency in Internal Medicine at Emory University Hospitals. He Charles Addison and Elizabeth Ann Sanders Distinguished Pro- became the youngest-ever Chief Resident at Grady Memorial fessor of Medicine and Chair of the Department of Medicine. Hospital at Emory University in 1992, supervising over 200 In addition, in 2004, Dr. Runge was appointed President of house officers in four hospitals. He completed 3 years of research UNC Physicians and Vice Dean for Clinical Affairs. Dr. Runge fellowship under the guidance of Edgar Haber at the Harvard is board-certified in internal medicine and cardiovascular dis- School of Public Health, developing an independent research eases and has spoken and published widely on topics in clinical program in vascular biology and angiogenesis that was sup- cardiology and vascular medicine. He maintains an active clini- ported by a National Institutes of Health fellowship. In 1996, cal practice in cardiovascular diseases and medicine in addition he accepted his first faculty position at the University of Texas to his teaching and administrative activities in the Department Medical Branch, and in 2000, Dr. Patterson was recruited to the of Medicine and the UNC School of Medicine. University of North Carolina at Chapel Hill to become the George A. Stouffer, MD, was born in Indiana, Pennsylva- founding director of the UNC McAllister Heart Institute. In nia, and was graduated from Bucknell University and the Uni- 2005, he also became Chief of the Division of Cardiology at versity of Maryland School of Medicine. He completed his UNC. Dr. Patterson is the Ernest and Hazel Craige Distin- internal medicine residency, cardiology fellowship, and inter- guished Professor of Cardiovascular Medicine, and he has been ventional cardiology fellowship at the University of Virginia. recognized at UNC with the Ruth and Phillip Hettleman Prize During his cardiology fellowship, he completed a 2-year National for Artistic and Scholarly Achievement. He is an Established Institutes of Health research fellowship in the laboratory of Gary Investigator of the American Heart Association and a Burroughs Owens at the University of Virginia. He was on the faculty at the Wellcome Fund Clinical Scientist in Translational Research. University of Texas Medical Branch from 1995 to 2000, where He is a member of several editorial boards, including Circulation he became an associate professor and served as Co-Director of and Journal of Clinical Investigation, and is an elected member of Clinical Trials in the Cardiology Division and as Associate the American Society of Clinical Investigation and the Associa- Director of the Cardiac Catheterization Laboratory. He joined tion of University Cardiologists. Dr. Patterson maintains active the faculty at the University of North Carolina in 2000 and cur- research programs in the areas of angiogenesis and vascular rently serves as the Henry A. Foscue Distinguished Professor of development, cardiac hypertrophy, protein quality control, and Medicine and Director of the Cardiac Catheterization Labora- translational genomics and metabolomics. He is also the direc- tory. Dr. Stouffer’s main focus is clinical cardiology with an tor of the Cardiac Genetics Clinic. He received his MBA from emphasis on interventional cardiology, but he is also involved in the UNC Kenan-Flagler School of Business in 2008. Preface The first edition of Netter’s Cardiology was an effort to present lead to patient harm. We also added boxes and algorithms that to clinicians the ever-increasing amount of medical information provide in an easy-to-read format quick overviews of critical on cardiovascular diseases in a concise and highly visual format. diagnostic and therapeutic information covered in the text. (See The challenge that clinicians face in “keeping up” with the the sample algorithm on the following page.) References are medical literature has continued to grow in the 5 years since the annotated in the second edition of Netter’s Cardiology to guide the first edition of Netter’s Cardiology. This need to process the ever- reader to a more in-depth review, if considered necessary. As in expanding medical information base and apply new findings to the first edition, the contributing authors have taken advantage the optimal care of patients is acute in all areas of medicine, but of the genius of Frank Netter by carefully selecting the best of perhaps it is most challenging in disciplines that require practi- his artwork to illustrate the most important clinical concepts tioners to understand a broad spectrum of evidence-based medi- covered in each chapter. When Netter artwork was unavailable cine, such as the field of cardiovascular diseases. The explosion or difficult to apply to illustrate modern clinical concepts, we of medical knowledge is also a very real educational issue for again utilized the great artistic talents of Carlos A. G. Machado, learners at all levels—students, residents, practicing physicians— MD, to create new artwork or to skillfully edit and update some who must rapidly determine what is and is not important, orga- of Frank Netter’s drawings. The combination of Dr. Machado’s nize the key information, and then apply these principles outstanding skills as a medical artist and his knowledge of the effectively in clinical settings. medical concepts being illustrated was an invaluable asset. For the second edition of Netter’s Cardiology, our goal was As in the first edition, we chose to use authors from the to produce an improved text that keeps these issues in clear University of North Carolina School of Medicine at Chapel focus and also addresses important clinical areas that were Hill or those with close ties to the university. This allowed us not well covered in the first edition or in many other cardiol- to select authors who are clinical authorities, many of whom ogy texts. To accomplish this expansion while maintaining a are also well known for their national and international contri- concise text that could be used as a ready reference, we again butions. All have active clinical practices that require daily use avoided exhaustive treatment of topics. We also have made of the information covered in their chapters, and all are well every effort to present the essential information in a reader- aware of the approach to patient management utilized by their friendly format that increases the reader’s ability to learn the peers at other institutions and in other practice settings. Many key facts without getting lost in details that can obfuscate the of the contributing authors of the first edition have continued learning process. on as second-edition authors and have provided updates. Each After a careful review of reader comments about the first author, whether a previous contributor or not, was given edition, we made some substantial changes to achieve our clearly defined guidelines that emphasized the need to distill educational goals. Chapters were added and topics expanded to the large amount of complex information in his or her field and address reader concerns about the lack of coverage of a number to present it concisely in a carefully prescribed format main- of important topics commonly encountered in clinical practice. tained across all chapters. The result is a text that is truly clini- Examples include these new chapters: Chest Radiography, cally useful and less of a compendium than is commonly the Echocardiography, Stress Testing and Nuclear Imaging, Car- case in many medical texts. diac Computed Tomography and Magnetic Resonance Imaging, We believe that the changes we have made in the second Left and Right Heart Catheterization, Identifying the Patient at edition substantially improve Netter’s Cardiology and ensure that High Risk for Acute Coronary Syndrome: Plaque Rupture and it will continue to be a highly useful resource for all physicians, “Immediate Risk,” Cardiogenic Shock after Myocardial Infarc- both generalists and subspecialists, who need to remain current tion, Stress-Induced Cardiomyopathy, Supraventricular Tachy- in cardiology—from trainees to experienced practitioners. cardia, Sleep Disorders and the Cardiovascular System, Whether we have succeeded will obviously be determined by Cardiovascular Toxicity of Noncardiac Medications, and Sudden our readers. Based on our experience with the revision of Cardiac Death in Athletes. The chapter subheadings of “Opti- the first edition, we welcome the comments, suggestions, and mum Treatment” and “Avoiding Treatment Errors” are new criticisms of readers that will help us improve future editions of additions that address concerns about therapeutic errors that can this work. vi  Preface 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 Marschall S. Runge, MD, PhD Cam Patterson, MD, MBA Charles Addison and Elizabeth Ann Sanders Ernest and Hazel Craige Distinguished Professor of Medicine Distinguished Professor of Medicine Professor of Medicine, Pharmacology, and Cell Professor and Chair, Department of Medicine and Developmental Biology The University of North Carolina School of Medicine Chief, Division of Cardiology Chapel Hill, North Carolina Director, UNC McAllister Heart Institute Associate Chair for Research, Department of Medicine George A. Stouffer, MD The University of North Carolina School of Medicine Henry A. Foscue Distinguished Professor of Medicine Chapel Hill, North Carolina Chief of Clinical Cardiology Director, C.V. Richardson Cardiac Catheterization Laboratory Director, Interventional Cardiology Division of Cardiology The University of North Carolina School of Medicine Chapel Hill, North Carolina About the Artists Frank H. Netter, MD of choice among medical and health professions students the Frank H. Netter was born in 1906 in New York City. He world over. studied art at the Art Student’s League and the National The Netter illustrations are appreciated not only for their Academy of Design before entering medical school at New York aesthetic qualities but, more importantly, for their intellectual University, where he received his MD degree in 1931. During content. As Dr. Netter wrote in 1949, “clarification of a subject his student years, Dr. Netter’s notebook sketches attracted the is the aim and goal of illustration. No matter how beautifully attention of the medical faculty and other physicians, allowing painted, how delicately and subtly rendered a subject may be, it him to augment his income by illustrating articles and text- is of little value as a medical illustration if it does not serve to books. He continued illustrating as a sideline after establishing make clear some medical point.” Dr. Netter’s planning, concep- a surgical practice in 1933, but he ultimately opted to give up tion, point of view, and approach are what inform his paintings his practice in favor of a full-time commitment to art. After and what makes them so intellectually valuable. service in the United States Army during World War II, Dr. Frank H. Netter, MD, physician and artist, died in 1991. Netter began his long collaboration with the CIBA Pharmaceu- Learn more about the physician–artist whose work has tical Company (now Novartis Pharmaceuticals). This 45-year inspired the Netter Reference Collection: www.netterimages. partnership resulted in the production of the extraordinary col- com/artist/netter.htm. lection of medical art so familiar to physicians and other medical professionals worldwide. Carlos A. G. Machado, MD In 2005, Elsevier Inc. purchased the Netter Collection Carlos A. G. Machado was chosen by Novartis to be Dr. Net- and all publications from Icon Learning Systems. Now ter’s successor. He continues to be the main artist who contrib- over 50 publications featuring the art of Dr. Netter are avail- utes to the Netter Collection of Medical Illustrations. able through Elsevier Inc. (in the United States: www. Self-taught in medical illustration, cardiologist Carlos A. G. us.elsevierhealth.com/Netter; outside the United States: www. Machado has contributed meticulous updates to some of Dr. elsevierhealth.com). Netter’s original plates and has created many paintings of his Dr. Netter’s works are among the finest examples of the use own in the style of Netter as an extension of the Netter Collec- of illustration in the teaching of medical concepts. The 13-book tion. Dr. Machado’s photorealistic expertise and his keen insight Netter Collection of Medical Illustrations, which includes the into the physician–patient relationship inform his vivid and greater part of the more than 20,000 paintings created by Dr. unforgettable visual style. His dedication to researching each Netter, has become one of the most famous medical works ever topic and subject he paints places him among the premier published. The Netter Atlas of Human Anatomy, first published medical illustrators at work today. in 1989, presents the anatomic paintings from the Netter Col- Learn more about his background and see more of his art at: lection. Now translated into 16 languages, it is the anatomy atlas www.netterimages.com/artist/machado.htm. Acknowledgments This second edition of Netter’s Cardiology benefited enormously Julie Goolsby at Elsevier were instrumental in helping us make from the hard work and talent of many dedicated individuals. a very good first edition more comprehensive and more focused First, we thank the contributing authors. All are current or in its second edition. former faculty members at the University of North Carolina We are also indebted to Ms. Angela Clotfelter-Rego, whose School of Medicine, Chapel Hill, or have close ties to the insti- superb organizational skills helped make this text a reality. tution. Without their intellect, dedication, and drive for excel- Special thanks go to Carolyn Kruse for excellent editing and Dr. lence, Netter’s Cardiology, 2nd edition, could not have been Deborah Montague for invaluable reviewing and updating of published. We had a solid foundation on which to build the the pharmacologic information. second edition, thanks to the hard work of the first-edition We would especially like to acknowledge our families: our contributing authors, many of whom we were fortunate to have wives—Susan Runge, Meg Stouffer, and Kristine Patterson— continue on to this edition. We are also grateful for the invalu- whose constant support, encouragement, and understanding able editorial contribution that Dr. E. Magnus Ohman made to made completion of this text possible; our children—Thomas, the first edition. Elizabeth, William, John, and Mason Runge; Mark, Jeanie, Special recognition goes to John A. Craig, MD, and Carlos Joy, and Anna Stouffer; and Celia, Anna Alyse, and Graham A. G. Machado, MD. They are uniquely talented physician– Patterson—who inspire us and remind us that there is life artists who, through their work, brought to life important con- beyond the computer; and, finally, our parents—whose persis- cepts in medicine in the new and updated figures included in tence, commitment, and work ethic got us started on this road this text. Anne Lenehan, Elyse O’Grady, Marybeth Thiel, and many, many years ago.