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2 E DI T ION DIASTOLOGY Clinical Approach to Heart Failure with Preserved Ejection Fraction ALLAN L. KLEIN, MD, FRCP (C), FACC, FAHA, FASE, FESC Professor of Medicine Cleveland Clinic Lerner College of Medicine of Case Western University Director, Center for the Diagnosis and Treatment of Pericardial Diseases Department of Cardiovascular Medicine Heart, Vascular, and Thoracic Institute Past-President of the American Society of Echocardiography Cleveland Clinic Cleveland, Ohio MARIO J. GARCIA, MD Professor of Medicine and Radiology Albert Einstein College of Medicine Chief, Division of Cardiology Co-Director, Montefiore-Einstein Center for Heart and Vascular Care Bronx, New York 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899 DIASTOLOGY: CLINICAL APPROACH TO HEART FAILURE WITH PRESERVED EJECTION FRACTION, SECOND EDITION ISBN: 978-0-323-64067-1 Copyright © 2021 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). Notice Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. 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Sticker Here For technical assistance: email [email protected] call 1-800-401-9962 (inside the US) call +1-314-447-8200 (outside the US) Use of the current edition of the electronic version of this book (eBook) is subject to the terms of the nontransferable, limited license granted on expertconsult.inkling.com. Access to the eBook is limited to the first individual who redeems the PIN, located on the inside cover of this book, at expertconsult.inkling.com and may not be transferred to another party by resale, lending, or other means. 2015v1.0 L I S T O F C O N T R I B U TO R S Øyvind Senstad Andersen, MD Christopher Michael Bianco, DO Patrick Collier, MD, PhD, FASE, FESC, Cardiology Assistant Professor of Medicine FACC Oslo University Hospital West Virginia University School of Medicine Associate Professor of Medicine Cardiologic Department and Institute of Department of Cardiology Cleveland Clinic Lerner College of Medicine Surgical Research Heart and Vascular Institute of Case Western Reserve University Oslo, Norway Morgantown, West Virginia Co-Director Cardio-oncology Center Associate Director Echo Lab Bonita A. Anderson, DMU (Cardiac), Barry A. Borlaug, MD Department of Cardiovascular Medicine MAppSc (Med Ultrasound), ACS, Professor of Medicine Heart, Vascular, and Thoracic Institute FASE, FASA Director of Circulatory Failure Research Cleveland Clinic Clinical Fellow Department of Cardiovascular Medicine, Cleveland, Ohio Faculty of Health Mayo Clinic School of Clinical Sciences Rochester, Minnesota Kristine Y. DeLeon-Pennell, PhD Queensland University of Technology Assistant Professor Advanced Cardiac Scientist Amy D. Bradshaw, PhD Division of Cardiology Cardiac Sciences Unit Professor Department of Medicine The Prince Charles Hospital Medicine Division of Cardiology Medical University of South Carolina Brisbane, Queensland, Australia Division of Cardiology Charleston, South Carolina Medical University of South Carolina Christopher P. Appleton, MD, FACC, FASE Charleston, South Carolina Hisham Dokainish, MD, FRCPC, Professor of Medicine FACC, FASE Mayo Clinic School of Medicine Darryl J. Burstow, MBBS, FRACP, Director, Cardiology and Echocardiography Department of Cardiovascular Diseases FCSANZ, FASE Laboratory Mayo Clinic Arizona Associate Professor Circulate Cardiac and Vascular Centre Phoenix, Arizona Department of Medicine, University of Burlington, Ontario, Canada Queensland Craig R. Asher, MD, FACC, FASE Eminent Cardiologist Department of Cardiology Frank A. Flachskampf, MD, FESC, Department of Cardiology Medical Director Hypertrophic FACC The Prince Charles Hospital Cardiomyopathy Clinic Senior Cardiology Consultant Brisbane, Queensland, Australia Cleveland Clinic Florida Department of Medical Sciences Weston, Florida Uppsala University and Uppsala University Shemy Carasso, MD, FESC, FASE Clinic Gerard P. Aurigemma, MD Clinical Associate Professor of Medicine Uppsala, Sweden Division of Cardiovascular Medicine The Azrieli Faculty of Medicine in the Department of Medicine Galilee, Zefat, Israel Mark K. Friedberg, MD University of Massachusetts Medical School Head, Non-invasive Cardiac Imaging Unit Professor of Pediatrics Worcester, Massachusetts Cardiovascular Division Labatt Family Heart Centre B Padeh Medical Center, Poriya, Israel Department of Pediatrics, The Hospital for Catalin F. Baicu, PhD Sick Children and University of Toronto Research Associate Professor of Medicine Manuel D. Cerqueira, MD, FACC, Toronto, Ontario, Canada Division of Cardiology MASNC Department of Medicine Professor of Medicine and Radiology Andrea C. Furlani, MD Medical University of South Carolina Cleveland Clinic Lerner College of Medicine Diagnostic Radiology Resident Charleston, South Carolina of Case Western Reserve University Department of Radiology Chairman of Nuclear Medicine Depart Ruxandra Beyer, MD, PhD Imaging Institute Montefiore Medical Center Department of Cardiology Staff Cardiologist Albert Einstein College of Medicine Heart Institute Department of Cardiovascular Medicine Bronx, New York University of Cluj-Napoca Heart, Vascular, and Thoracic Institute Cluj-Napoca, Romania Cleveland Clinic Mario J. Garcia, MD Cleveland, Ohio Professor of Medicine and Radiology Pavan Bhat, MD, FACC Albert Einstein College of Medicine Staff Physician Michael Chetrit, MD Chief, Division of Cardiology Section of Heart Failure and Transplantation Assistant Professor of Medicine, McGill Co-Director, Montefiore-Einstein Center for Medicine University Heart and Vascular Care Department of Cardiovascular Medicine Cardiologist, McGill University Health Centre Bronx, New York Heart, Vascular, and Thoracic Institute Co-Director, McGill Amyloidosis Project Cleveland Clinic Monteral, Quebec, Canada Cleveland, Ohio v vi LIST OF CONTRIBUTORS Eiran Z. Gorodeski, MD, MPH, FACC, Cesar J. Herrera, MD, FACC, CEDIMAT Garvan C. Kane, MD, PhD, FAHA, FHFSA Director, Clinical Associate Professor of FASE Associate Professor of Medicine Medicine (Adjunct) Professor of Medicine Case Western Reserve University School of Department of Cardiology Mayo Clinic College of Medicine Medicine CEDIMAT Cardiovascular Center Director, Echocardiography Laboratory Department of Medicine Albert Einstein College of Medicine- & Chair, Division of Cardiovascular Harrington Heart and Vascular Institute Montefiore Center for Heart and Vascular Ultrasound University Hospitals Cleveland Medical Care Department of Cardiovascular Medicine Center Santo Domingo, Dominican Republic Mayo Clinic Cleveland, Ohio Albert Einstein College of Medicine Rochester, Minnesota Montefiore Center for Heart and Vascular Care Allan L. Klein, MD, FRCP (C), FACC, Stephen H. Gregory, MD Bronx, New York FAHA, FASE, FESC Assistant Professor of Anesthesiology Professor of Medicine Washington University in St. Louis Brian D. Hoit, MD Cleveland Clinic Lerner College of Medicine Department of Anesthesiology Professor of Medicine and Physiology and of Case Western University St. Louis, Missouri Biophysics Director, Center for the Diagnosis and Case Western Reserve University Treatment of Pericardial Diseases Richard A. Grimm, DO, FACC, FASE Department of Medicine Department of Cardiovascular Medicine Charles and Loraine Moore Endowed Chair Division of Cardiology Heart, Vascular, and Thoracic Institute in Cardiovascular Imaging University Hospitals Cleveland Medical Past-President of the American Society of Chief Medical Information Officer Center Echocardiography Director, Echocardiography Laboratory Harrington Heart and Vascular Center Cleveland Clinic Department of Cardiovascular Medicine Cleveland, Ohio Cleveland, Ohio Heart, Vascular, and Thoracic Institute Cleveland Clinic Massimo Imazio, MD, FESC Lara C. Kovell, MD Cleveland, Ohio Professor of Cardiology Assistant Professor of Medicine Referral Senior Consultant for Division of Cardiovascular Medicine Jong-Won Ha, MD, PhD, FESC Myopericardial Diseases and Department of Medicine General Director Cardiovascular Multimodality Imaging University of Massachusetts Medical School Severance Hospital University Cardiology, Cardiovascular and Worcester, Massachusetts Professor of Medicine Thoracic Department Department of Cardiology AOU Citta’della Salute e della Scienza di Torino Deborah H. Kwon, MD, FACC, FSCMR, Yonsei University College of Medicine Torino, Italy FASE Seoul, Korea Associate Professor of Medicine Katsuji Inoue, MD, PhD Cleveland Clinic Lerner College of Medicine Associate Professor of Case Western Reserve University Manhal Habib, MD, PhD Department of Cardiology, Pulmonology, Director of Cardiac MRI Cardiology Department Hypertension, and Nephrology Co-Director, Center for the Diagnosis & Peter Munk Cardiac Center Ehime University Graduate School Treatment of Pericardial Diseases Toronto General Hospital of Medicine Department of Cardiovascular, Medicine Toronto, Ontario, Canada Toon, Japan and Radiology Heart, Vascular, and Thoracic Institute Serge C. Harb, MD, FACC Wael A. Jaber, MD, FACC, FESC, FASE Cleveland Clinic Assistant Professor of Medicine Professor of Medicine Cleveland, Ohio Cleveland Clinic Lerner College of Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve University of Case Western Reserve University Cameron T. Lambert, MD Staff, Section of Cardiovascular Imaging Director, Nuclear Cardiology and Imaging Fellow Department of Cardiovascular Medicine CoreLab Cardiac Electrophysiology and Pacing Heart, Vascular, and Thoracic Institute Department of Cardiovascular Medicine Department of Cardiovascular Medicine Cleveland Clinic Heart, Vascular, and Thoracic Institute Heart, Vascular, and Thoracic Institute Cleveland, Ohio Cleveland Clinic Cleveland Clinic Cleveland, Ohio Cleveland, Ohio LIST OF CONTRIBUTORS vviiii Benjamin D. Levine, MD, FACC, FAHA, William R. Miranda, MD Ileana Piña, MD, MPH, FAHA, FACC, FACSM Assistant Professor of Medicine Department FHFSA Professor of Medicine and Cardiology of Cardiovascular Diseases Professor of Medicine Distinguished Professorship in Exercise Science Mayo Clinic Senior Staff Fellow, Medical Officer The University of Texas Southwestern Rochester, Minnesota Department of Medicine Medical Center Wayne State University Director, Institute for Exercise and Sandhya Murthy, MD Detroit, Michigan Environmental Medicine Assistant Professor of Medicine S. Finley Ewing Jr. Chair for Wellness at Montefiore Medical Center Zoran B. Popovic´, MD, PhD Texas Health Presbyterian Dallas Albert Einstein College of Medicine Associate Professor of Medicine Harry S. Moss Heart Chair for Department of Medicine Cleveland Clinic Lerner College of Medicine Cardiovascular Research The Center for Heart and Vascular Care of Case Western Reserve University Dallas, Texas Director, Pulmonary Hypertension Center Staff Department of Cardiovascular Medicine Bronx, New York Heart, Vascular, and Thoracic Institute Martin M. LeWinter, MD Cleveland Clinic Professor of Medicine and Molecular Sherif F. Nagueh, MD, FACC, FASE, FAHA Cleveland, Ohio Physiology and Biophysics Emeritus Professor of Medicine Department of Medicine Weill Cornell Medical College Miguel A. Quinones, MD, MACC, FASE Larner College of Medicine at the University Medical Director Echocardiography Winters Family Distinguished Centennial of Vermont Laboratory Chair In Cardiovascular Education Attending in Cardiology Houston Methodist DeBakey Heart and Professor of Medicine University of Vermont Medical Center Vascular Center Weil Cornell Medicine Burlington, Vermont Houston, Texas Department of Cardiology Houston Methodist Hospital James P. MacNamara, MD Satoshi Nakatani, MD, PhD, FACC, FESC, Houston, Texas FASE (hon) Division of Cardiology Professor Emeritus, Osaka University Harry Rakowski, MD, FACC, FASE, ED University of Texas Southwestern Director of Saiseikai Senri Hospital Professor of Medicine Institute of Exercise and Environmental Saiseikai Senri Hospital Department of Medicine Medicine Suita, Osaka, Japan University of Toronto Dallas, Texas Douglas Wigle Research Chair in Lakshmi Nambiar, MD Hypertrophic Cardiomyopathy Mohammed Makkiya, MD Fellow Development Director, Peter Munk Cardiac General Cardiology and Advance Imaging Weill Cornell Medicine Imaging Centre Fellow Department of Cardiology Division of Cardiology Department of Cardiology and Hospital New York-Presbyterian Hospital/Weill Department of Medicine Medicine Cornell Medical Center Toronto General Hospital, University Health Albert Einstein College of Medicine New York City, Network Bronx, New York New York Toronto, Ontario, Canada Dimitrios Maragiannis, MD, FESC, FASE, Kazuaki Negishi, MD, PhD Yogesh NV Reddy, MBBS, MSc FACC, FAHA Professor of Medicine Assistant Professor of Medicine Department of Cardiology Head of Discipline of Medicine Department of Cardiovascular Diseases 401 General Army Hospital Nepean Clinical School Mayo Clinic Athens, Greece Cardiologist Rochester, Minnesota Department of Medicine and Health Vojtech Melenovsky, MD, PhD University of Sydney Leonardo Rodriguez, MD Associate Professor of Medicine New South Wales, Australia Program Director Advanced Imaging Department of Cardiology Fellowship Institute for Clinical and Experimental Masaru Obokata, MD, PhD Associated Director, Transesophageal Medicine – IKEM Department of Cardiovascular Medicine Echocardiography Laboratory Charles University, Prague, Czech Republic Mayo Clinic Department of Cardiovascular Medicine Rochester, Minnesota Heart, Vascular, and Thoracic Institute Donald R. Menick, PhD, FAHA Cleveland Clinic Professor of Medicine Jae K. Oh, MD, FACC, FAHA, FESC, FASE Cleveland, Ohio Director of the Gazes Cardiac Research Samsung Professor of Cardiovascular Diseases Satyam Sarma, MD Institute Director, Echo Core Lab Research Health Scientist Director, Pericardial Diseases Clinic Assistant Professor of Medicine Ralph H. Johnson VA Medical Center President, Asian Pacific Association of Department of Internal Medicine, Division Department of Medicine/Division of Echocardiography of Cardiology Cardiology Department of Cardiovascular Medicine University of Texas Southwestern Medical Medical University of South Carolina Mayo Clinic Dallas, Texas Charleston, South Carolina Rochester, Minnesota viii LIST OF CONTRIBUTORS Aldo L. Schenone, MD Madhav Swaminathan, MD, MMCi, Lynne Williams, MBBCh, FRCP, PhD Chief Non-invasive Cardiovascular Imaging FASE, FAHA Consultant Cardiologist Fellow Professor Department of Cardiology Non-invasive Cardiovascular Imaging Vice chair, Faculty Development Royal Papworth Hospital NHS Foundation Department Department of Anesthesiology Trust Brigham and Women’s Hospital/Harvard Duke University Cambridge, United Kingdom Medical School Durham, North Carolina Boston, Massachusetts Dmitry M. Yaranov, MD Edlira Tam, DO, MS Advanced Heart Failure Failure and Partho Sengupta, MD Division of Cardiology Transplant Cardiologist Professor of Medicine Montefiore-Einstein Heart Center Advanced Heart Failure, Heart Transplant, J.W. Ruby Memorial Hospital Bronx, New York Mechanical Circulatory Support Chief, Division of Cardiology Baptist Memorial Hospital Director, Cardiovascular Imaging W.H. Wilson Tang, MD FACC, FAHA, Memphis, Tennessee J.W. Ruby Memorial Hospital FHFSA WVU Heart and Vascular Institute Professor of Medicine Laura Young, MD Morgantown, West Virginia Cleveland Clinic Lerner College of Medicine Clinical Instructor of Medicine of Case Western Reserve University Cleveland Clinic Lerner College of Otto A. Smiseth, MD, PhD, FESC, FACC, Research Director Medicine of Case Western Reserve FASE Section of Heart Failure and Cardiac University Professor of Medicine Transplantation Medicine Interventional Cardiology Fellow Division Head Department of Cardiovascular Medicine Department of Cardiovascular Medicine Division of Cardiovascular and Pulmonary Heart, Vascular, and Thoracic Institute Heart, Vascular, and Thoracic Institute Diseases Cleveland Clinic Cleveland Clinic Oslo University Hospital Cleveland, Ohio Cleveland, Ohio Oslo, Norway Randall C. Starling, MD, MPH, FACC, Harsh V. Thakkar, MBBS Michael R. Zile, MD FAHA, FESC, FHFSA Clinical Lecturer Charles Ezra Daniel Professor of Medicine Professor of Medicine School of Medicine Distinguished University Professor Cleveland Clinic Lerner College of Medicine University of Tasmania Medical University of South Carolina of Case Western Reserve University Department of Cardiology Chief, Division of Cardiology Department of Cardiovascular Medicine The Royal Hobart Hospital RHJ Department of Veterans Affairs Medical Heart, Vascular, and Thoracic Institute Hobart CBD, Tasmania, Australia Center Cleveland Clinic Charleston, South Carolina James D. Thomas, MD, FACC, FASE Cleveland, Ohio Professor of Medicine Marie Stugaard, MD, PhD, FESC Feinberg School of Medicine Doctor of Medicine Northwestern University Department of Health Sciences Director, Center for Heart Valve Disease Osaka University Graduate School of and Co-director Medicine Center for Artificial Intelligence in Suita, Osaka, Japan Cardiovascular Disease Division of Cardiology in the Bluhm Cardiovascular Institute Northwestern Medicine Chicago, Illinois F O R E WO R D Diastolic dysfunction and its clinical cousin, heart failure with pre- chapter addresses the ASE/EACVI Diastolic Guidelines (of which there served ejection fraction (HFpEF), are among the most baffling of topics have been two since the first edition), examining the strengths and in clinical cardiology. Is it primarily a cardiac condition? Related to limitations of these important formulations. comorbidities? A manifestation of poor peripheral muscular oxygen On a personal note, I congratulate dear friends Allan and Mario on extraction? Maybe a bit of each. And so many cardiac parameters to this great achievement. I have known Allan for over 30 years and well consider: E wave, A wave, tissue Doppler, LA size, torsion, RV pressure, recall planning the first conference on diastolic function in 1992, diastolic strain rate, just to name a few! How to put them together in a where we coined for the first time (I think) the word diastology. Soon unified way is nearly impossible. It is rare to find a resource that ad- thereafter, Mario joined us at the Cleveland Clinic, and together the dresses all the myriad manifestations of diastolic function: basic prin- three of us and our colleagues produced some of the landmark re- ciples from cellular physiology to the physics of intracardiac blood flow, search and education in diastolic function. With this book, Allan and multimodality assessment and diagnosis, as well as standard and evolv- Mario continue their masterful scholarship into the science of diastolic ing therapies for this challenging syndrome. In 2008, Drs. Allan Klein function. It is thus with great enthusiasm that I commend the second and Mario Garcia brought forth their landmark book Diastology, which edition of Diastology to you. for the first time brought all aspects of diastolic function, especially the James D. Thomas, MD, FASE, FACC, FESC diagnostic aspects, under one cover. It’s hard to believe it’s been 12 years Professor of Medicine since that initial publication, but the science of diastology has pro- Feinberg School of Medicine gressed rapidly in that time. Building on the great achievement of the Northwestern University first edition of Diastology, Allan and Mario now bring us their second Director, Center for Heart Valve Disease and edition, completely updated with the latest basic and clinical informa- Co-director, Center for Artificial Intelligence in Cardiovascular Disease tion. In addition to updating all the chapters from the first edition, they Division of Cardiology in the Bluhm Cardiovascular Institute bring out four new chapters. These include the diastolic function stress Northwestern Medicine test, the perioperative assessment of diastolic function, and the impor- Chicago, Illinois tant entity of pulmonary hypertension in HFpEF. An important new ix F O R E WO R D I am pleased to say a few words about the 2nd Edition of Diastology restrictive, infiltrative and storage cardiomyopathies are also now well edited by Allan Klein and Mario Garcia. I have known both editors for recognized as etiologies of diastolic dysfunction leading to the devel- more than 20 years and have followed their careers with great pride. The opment of heart failure. Valvular heart disease and pericardial disor- first edition of this book in 2008 was a magnificent achievement. Dia- ders are still with us and may also lead to diastolic dysfunction and stolic heart failure at that time had evolved substantially to a point where heart failure. we were beginning to better understand how to define it and manage its Each of these entities are discussed in great detail by expert contrib- various phenotypes. New and improved imaging techniques, including uting authors in the new edition of Diastology. Clinical and laboratory magnetic resonance imaging and use of echo to image strain rate were diagnoses are also featured in great detail and treatment options are quickly evolving. The book very much captured our attention regarding carefully discussed. Each of the contributing authors brings substantial the diagnosis and management of this very important clinical syndrome experience to bear in describing the subtleties of diastolic dysfunction. as it emerged from a somewhat obscure clinical entity in the 1970s to a The book is richly endowed with many tables and figures. major diagnostic entity with multiple etiologies by 2008. This very comprehensive book is the best we have in the field of Now it is 2020, and the clinical syndrome of diastolic heart failure Diastology. Doctors Klein, Garcia and their contributing authors are to is one of the more common diagnoses in cardiology. Heart failure with be congratulated for their magnificent contribution. It will be most preserved ejection fraction (HFpEF) is now similar in prevalence to useful for clinicians, but others will find it to be the definitive text in heart failure with reduced ejection fraction (HFrEF) in terms of hos- this complex but important field of cardiac relaxation and filling. pitalization for heart failure in the United States. Hospitalization for Trainees, internists, cardiologists and sonographers will benefit from HFrEF has steadily declined between 2002 and 2013, while increases in this wholly updated and outstanding text. heart failure hospitalizations are now being driven by more cases of Gary S. Francis, M.D. HFpEF. Of course, other conditions such as amyloidosis, hypertrophic Professor of Medicine cardiomyopathy, left ventricular hypertrophy due to long-standing University of Minnesota hypertension, chronic renal disease, coronary disease as well as primary Minneapolis, Minnesota x

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