Table Of Content2
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
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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
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