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G. Jagadeesh, P. Balakumar, K. Maung-U(Eds.)
Pathophysiology and Pharmacotherapy of CardiovascularDisease
Covers basic principles of cardiovascular physiology,
pathophysiology and advanced pharmacology
Provides particular emphasis on cellular mechanisms of drug action
Fills gaps in understanding and optimally treating cardiovascular
disease
The present book covers the basic principles of cardiovascular physiology,
pathophysiology and advanced pharmacology with particular emphasis on cellular
mechanisms of drug action. It provides an update on the progress made in several
aspects of cardiovascular diseasesso that it might kindle scientists and clinicians alike
in furthering basic and translational research. In addition, the book is expected to fillimperative gaps in understanding and optimally treating cardiovascular disease.
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Pathophysiology and Pharmacotherapyof Cardiovascular Disease
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Gowraganahalli Jagadeesh Pitchai BalakumarKhin Maung-U
Editors
Pathophysiology
and Pharmacotherapyof Cardiovascular Disease
Adis
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ISBN 978-3-319-15960-7 ISBN 978-3-319-15961-4 (eBook)DOI 10.1007/978-3-319-15961-4
Library of Congress Control Number: 2015937615
Springer Cham Heidelberg New York Dordrecht London Springer International Publishing Switzerland 2015This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part ofthe material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,broadcasting, reproduction on microfilms or in any other physical way, and transmission or information
storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodologynow known or hereafter developed.The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoes not imply, even in the absence of a specific statement, that such names are exempt from the relevantprotective laws and regulations and therefore free for general use.The opinions expressed are those of the respective chapter authors and do not necessarily represent thoseof their employers or the editors and their employers. The editors, publisher or any other party involvedin the preparation of this work are not responsible for any inaccurate or incomplete information providedin this book. Readers should confirm the accuracy of the information contained in the book from othercurrently available sources considering the fact that the drug related information might change over thetime. The editors and publisher of this book do not undertake any liability for any inconvenience arisingfrom use of this book, either print or electronic media.
Printed on acid-free paper
Adis is a brand of SpringerSpringer International Publishing AG Switzerland is part of Springer Science+Business Media(www.springer.com)
EditorsGowraganahalli JagadeeshCenter for Drug Evaluation and ResearchDivision of Cardiovascular
and Renal ProductsUS Food and Drug AdministrationSilver Spring, MDUSA
Pitchai BalakumarPharmacology UnitAIMST UniversityBedongMalaysia
Khin Maung-UCenter for Drug Evaluation and ResearchDivision of Cardiovascular
and Renal ProductsUS Food and Drug AdministrationSilver Spring, MDUSA
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v
Preface
With the advance of modern civilization, the historical causes of death in human
populations such as war, drought, famine and the spread of microbes have been
replaced by a new wave of global killers: non-communicable diseases (NCDs).
According to the World Health Organization report, NCDs kill 38 million people
each year, with cardiovascular diseases (CVDs) accounting for most NCD deaths
(17.5 million deaths, or 46.2 % of NCD deaths). Urbanization, industrialization,
globalization and a larger ageing population have amplified the role of NCDs in
global mortality and morbidity. NCDs affect both men and women, devastating both
rich and poor nations alike, although more people in poor nations are more likely todie as they lack access to lifesaving medicines. In the past, we tussled against nature
to combat communicable diseases; now, it is a battle against the lifestyles, dietary
habits and indulgences of human nature to combat these NCDs, of which one
important battlefront is to prevent, delay and effectively treat CVDs and promote
global cardiovascular health.
While we are acquainted with a lot of information about CVDs and relevant
treatment strategies, we still need to know more about current advances in CVD
patterns, pathophysiology, diagnosis and pharmacotherapy. In addition, there is a
constant stream of newly approved medicines entering the pharmaceutical drugmarket necessitating periodical updates in drug information to meet the rational use
of drugs. We have attempted to collate here the knowledge of experts in different
aspects of CVDs. This effort has been an innovative collaboration of global clini-
cians and scientists with the goal of advancing our thinking and testing new
approaches to combat CVDs. Keeping these principles in mind, our authors have
narrated the basic understanding of physiology and pathophysiology of the cardio-
vascular system, its regulation, and its excessive indulgence or over-activation caus-
ing an imbalance in the neural and hormonal systems to release harmful factors/
chemicals changing the integrity of the cells, tissues and organs to precipitatedisease(s). Applying the findings from these studies, treatment algorithms were
generated by the authors, giving detailed descriptions of complex cellular mecha-
nisms of drug action for the CVDs described in each chapter.
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The book has eight major sections comprising 62 chapters. The emphasis is
clinical, covering all key areas such as heart failure, cardiac hypertrophy and
cardiomyopathy, coronary heart disease, atherosclerosis and hyperlipidemia,
hypertension, cardiac arrhythmias, valvular heart diseases and cardiovascular
conditions of childhood and pregnancy. Emerging areas of cardiovascular therapies
such as cell and gene therapy, microRNA therapeutics, biomarkers, devices and
mechanical approaches to control diseases are presented in addition to classic
pharmacologic and therapeutic approaches. The editors are greatly indebted to all
authors and co-authors for the expert write-up of their respective chapters in a field
that is dynamic and ever growing.
Our objective is to provide meaningful guidance in understanding and treating
CVDs. This book is not just a database of therapeutics for CVDs. This book is
particularly intended for pharmaceutical, biomedical and health science
professionals. We have tried our level best to make the subject contents interestingand thought provoking. This book offers an opportunity for readers to keep
abreast of recent advances in the practice of cardiovascular medicine. We sincerely
welcome comments and suggestions from readers.
We are grateful to Dr. Amitabh Prakash, Editor of Clinical Pharmacokinetics
and theAmerican Journal of Cardiovascular Drugsfor having initiated the project
and for his timely advice in the preparation of the book. We are also pleased to
acknowledge the indispensable role played by Ms. Lorna Venter-Lewis, Ms. Ursula
Gramm, Mr. Gurunadham Prasad and Mr. PremLal Prejith of Springer in the prepa-
ration of this book.The opinions expressed in the book are those of the respective chapter authors
and do not necessarily represent those of the editors and their employers.
Silver Spring, MD, USA Gowraganahalli Jagadeesh
Bedong, Malaysia Pitchai Balakumar
Silver Spring, MD, USA Khin Maung-U
Preface
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Contents
Part I Heart Failure
1 Heart Failure, Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Tina Shah, Nicholas Palaskas, and Biykem Bozkurt
2 Cardiac Prevention Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
John W. McEvoy, Roger S. Blumenthal, and Erin D. Michos
3 Pathophysiology of Heart Failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Leany Capote, Ruth Nyakundi, Brandon Martinez,and Anastasios Lymperopoulos
4 Calcium Signaling in Cardiovascular Physiology
and Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Nadjib Hammoudi and Djamel Lebeche
5 Sympathetic Nervous System Signaling in Heart Failure
and Cardiac Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Gaetano Santulli
6 The Parasympathetic Nervous System and Heart Failure:
Pathophysiology and Potential Therapeutic Modalities
for Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Brian Olshansky, Renee M. Sullivan, Wilson S. Colucci,
and Hani N. Sabbah
7 Risk for Sudden Cardiac Death in Heart Failure:
Underlying Mechanisms and Therapeutic Modalities. . . . . . . . . . . . 129
Philip B. Adamson, Emilio Vanoli, and Eduardo Gronda
8 Pharmacological Management of Heart Failureand Device Therapy in Heart Failure. . . . . . . . . . . . . . . . . . . . . . . . . . 151
Jens Jakob Thune and Finn Gustafsson
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9 Exercise in Heart Failure: Effectiveness Versus Safety . . . . . . . . . . . 165
Stuart D. Russell
10 Cardiac Muscle and the Troponins . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Elizabeth A. Hausner
11 Circulating Cardiac Troponins as Specific Biomarkers
of Myocardial Damage: Clinical Considerations . . . . . . . . . . . . . . . . 193
Karen A. Hicks
12 Natriuretic Peptides and Biomarkers in the Diagnosis
of Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
Nicholas Phreaner, Kevin Shah, and Alan Maisel
13 MicroRNAs in Cardiovascular Disease: From Pathogenesis
to Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231Ioana Barb, Britta Vogel, Hugo A. Katus, and Benjamin Meder
14 MicroRNA Therapeutics in Cardiovascular Disease. . . . . . . . . . . . . 253
Antoine Bril
15 Gene Therapy in Cardiovascular Disease. . . . . . . . . . . . . . . . . . . . . . 265
Michael G. Katz, Anthony S. Fargnoli, Andrew P. Kendle,
and Charles R. Bridges
Part II Cardiac Hypertrophy and Cardiomyopathy
16 Cardiac Hypertrophy and Hypertrophic Cardiomyopathy:
Introduction and Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
Roy Beigel, Robert J. Siegel, and Florian Rader
17 Myocardial Metabolic Abnormalities and Cardiac Dysfunction . . . 325
Petra C. Kienesberger
18 Molecular Targets in the Treatment
of Cardiac Hypertrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343Christian Kuhn, Susanne Hille, and Norbert Frey
Part III Coronary Heart Disease
19 Acute Coronary Syndromes: Introduction and Pathophysiologic
Classification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375
Kjell Nikus and Yochai Birnbaum
20 Pathophysiology and Management of Myocardial Infarction . . . . . . 397
Mahmoud H. Abdou, Niels Engberding, and Nanette K. Wenger
21 Pathophysiology and Lifetime Risk Factors for Atherosclerosis
and Coronary Artery Disease in Women and in the Elderly . . . . . . . 425
Stacy Westerman, Niels Engberding, and Nanette K. Wenger
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22 Medical Management of Chronic Stable Angina . . . . . . . . . . . . . . . . 443
John D. Parker
23 Therapy for Acute Coronary Syndrome and Unstable Angina . . . . . 467
Daniel M. Shivapour and A. Michael Lincoff
24 Drug-Eluting Stents and Coronary Artery Disease . . . . . . . . . . . . . . 495
Eliano Pio Navarese, Mariusz Kowalewski,
and Michalina Koodziejczak
Part IV Atherosclerosis and Hyperlipidemia
25 Atherosclerosis, Introduction and Pathophysiology . . . . . . . . . . . . . . 527
Kazuyuki Yahagi, Harry R. Davis, Michael Joner, and Renu Virmani
26 Vascular Endothelial Dysfunction and Atherosclerosis:
Role of Nitric Oxide System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 547
Estelle R. Simo Cheyou and Ashok K. Srivastava
27 Cardioprotective Role of Omega-3 Polyunsaturated Fatty
Acids Through the Regulation of Lipid Metabolism . . . . . . . . . . . . . 563
Kayode A. Balogun and Sukhinder K. Cheema
28 Prevention and Treatment of Atherosclerotic Vascular Disease:
Hypolipidemic Agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589
Antonio M. Gotto Jr. and Henry J. Pownall
29 Prevention of Cardiovascular Disease: The Polypill Concept . . . . . . 613
Prem Pais, Deepak Y. Kamath, Alben Sigamani, and Denis Xavier
Part V Hypertension
30 Hypertension: Introduction, Types, Causes, and Complications. . . . 635
Yoshihiro Kokubo, Yoshio Iwashima, and Kei Kamide
31 Pathophysiology of Hypertension. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 655
Michel Burnier and Grgoire Wuerzner
32 Blood Pressure Genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 685
Georg B. Ehret
33 Hypertension and Vascular Endothelial Growth Factors . . . . . . . . . 695
Marcelo Rizzatti Luizon and Valeria Cristina Sandrim
34 Role of Gi Proteins in Hypertension. . . . . . . . . . . . . . . . . . . . . . . . . . . 709
Yuan Li and Madhu B. Anand-Srivastava
35 Sympathetic and ReninAngiotensin Activity
in the Pathophysiology of Hypertension . . . . . . . . . . . . . . . . . . . . . . . 723
Adrian Covic and Liviu Segall
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36 Drugs Targeting RAAS in the Treatment of Hypertension
and Other Cardiovascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . 751
Pitchai Balakumar and Gowraganahalli Jagadeesh
37 Calcium Channel Blockers in the Treatment of Hypertension . . . . . 807Yoshihiko Kanno, Yoichi Ohno, and Tsuneo Takenaka
38 Diuretics for the Treatment of Hypertension . . . . . . . . . . . . . . . . . . . 823
Domenic A. Sica
39 Centrally Acting Antihypertensive Agents in the Treatment
of Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 853
Domenic A. Sica
40 Vasodilators and Management of Hypertensive Emergencies . . . . . . 869
Jaya Mallidi, C. Gabriela Macas, and Amir S. Lotfi
41 Combination Therapy for the Clinical Management
of Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 887
Giuliano Tocci and Massimo Volpe
42 Resistant Hypertension: Definition, Prevalence,
and Therapeutic Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 903
Anthony J. Viera
43 Drug Adherence in Hypertension. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 919
Michel Burnier
44 The Glycemic Consequences of Antihypertensive Medications . . . . 935
Joshua I. Barzilay, Paul K. Whelton, and Barry R. Davis
45 Pathophysiology and Treatment of Pulmonary
Arterial Hypertension. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 949
Nina Rol, Christophe Guignabert, and Harm Jan Bogaard
Part VI Cardiac Arrhythmias
46 Cardiac Arrhythmias: Introduction, Electrophysiology
of the Heart, Action Potential and Membrane Currents . . . . . . . . . . 977
Norbert Jost, Danina M. Muntean, and Torsten Christ
47 Pathophysiology of Cardiac Arrhythmias:
Arrhythmogenesis and Types of Arrhythmias . . . . . . . . . . . . . . . . . . 1003
Peter P. Karpawich
48 Proarrhythmic Effects of Antiarrhythmic
and Non-antiarrhythmic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1015
J. William Schleifer and Komandoor Srivathsan
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49 Drug-Induced Prolongation of the QT Interval:
Present and Future Challenges for Drug Discovery . . . . . . . . . . . . . . 1039
Gary Gintant and Jean-Pierre Valentin
50 Treatment of Atrial Fibrillation and Atrial Flutter . . . . . . . . . . . . . . 1059Torsten Christ, Simon Pecha, and Norbert Jost
51 Use of Mechanical Devices to Reduce Stroke
in Atrial Fibrillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1081
Peter Pollak and David Holmes
52 Antiarrhythmic Drugs and Management
of Ventricular Arrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1101
J. William Schleifer and Komandoor Srivathsan
53 Cardiac Arrest and Cardiopulmonary Resuscitation:Recent Advances in Management Approach
for Cardiopulmonary Resuscitation. . . . . . . . . . . . . . . . . . . . . . . . . . . 1135
Allan R. Mottram and Karen Serrano
Part VII Valvular Heart Disease
54 Valvular Heart Disease: Introduction,
Clinical Pathogenesis, and Management . . . . . . . . . . . . . . . . . . . . . . . 1151
Siri Kunchakarra, Jyothy Puthumana, and Kameswari Maganti
55 Mitral Regurgitation in Heart Failure: Mechanisms
and Therapeutic Options. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1187
Michael Huntgeburth and Volker Rudolph
56 Pathophysiology and Management of Functional Tricuspid
Regurgitation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1201
Jason H. Rogers and Steven F. Bolling
57 Aortic Valve Stenosis and Aortic Regurgitation:
Pathophysiology and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1221
Wilbert S. Aronow
58 Induction of Valvular Heart Disease by Pharmacological
Interventions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1247
Steven Droogmans and Bernard Cosyns
Part VIII Cardiovascular Conditions of Childhood and Pregnancy
59 Pathophysiology and Pharmacotherapy of AdultCongenital Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1269
Anushree Agarwal, Saurabh Aggarwal, and Ian S. Harris
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60 Cardiac Disease in Pregnancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1293
Henry Boardman and Lucy Mackillop
61 Placental Insufficiency: The Impact on Cardiovascular Health
in the Mother and Her Offspring Across the Lifespan. . . . . . . . . . . . 1315John Henry Dasinger, Suttira Intapad, and Barbara T. Alexander
62 miRNAs in Cardiovascular Development . . . . . . . . . . . . . . . . . . . . . . 1331
Katharina K. Wystub and Thomas Boettger
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Contributors
Mahmoud H. Abdou, MD Cardiology Fellow, Division of Cardiology,
Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
Philip B. Adamson, MD, FACC Director, Heart Failure Institute, Oklahoma
Heart Hospital, Oklahoma City, OK, USA
Adjunct Associate Professor, Department of Physiology, University of Oklahoma
Health Sciences Center, Oklahoma City, OK, USA
Anushree Agarwal, MD Advanced Fellow in Adult Congenital Cardiology,
Division of Cardiology, University of California School of Medicine,
San Francisco, CA, USA
Saurabh Aggarwal, MD Cardiology Fellow, Division of Cardiology, Creighton
University School of Medicine, Omaha, NE, USA
Barbara T. Alexander, PhD Professor, Department of Physiology and
Biophysics, Director, Basic Research Center for Developmental Disorders
Research, Center for Cardiovascular and Renal Research, Womens Health
Research Center, University of Mississippi Medical Center, Jackson, MS, USA
Madhu B. Anand-Srivastava, PhD Professor, Department of Molecular and
Integrative Physiology, Faculty of Medicine, University of Montreal, Montreal,
QC, Canada
Wilbert S. Aronow, MD, FACC, FAHA Professor, Divisions of Cardiology,
Geriatrics, and Pulmonary/Critical Care, Department of Medicine, New York
Medical College, Valhalla, NY, USA
Pitchai Balakumar, PhD Associate Professor and Head, Pharmacology Unit,
Faculty of Pharmacy, AIMST University, Bedong, Kedah Darul Aman, Malaysia
Kayode A. Balogun, PhD Department of Biochemistry, Memorial University,
St. Johns, NL, Canada
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Ioana Barb, MD Department of Internal Medicine III, University of Heidelberg,
University Hospital of Heidelberg, Heidelberg, Germany
Joshua I. Barzilay, MD Kaiser Permanente of Georgia and Emory University
School of Medicine, Duluth, GA, USA
Roy Beigel, MD Division of Cardiology, Department of Medicine,
The Heart Institute Cedars Sinai Medical Center, Los Angeles, CA, USA
The Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Israel
The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Yochai Birnbaum, MD, FACC, FAHA Professor of Medicine, John S. Dunn
Chair in Cardiology Research and Education, Section of Cardiology, Department
of Medicine, Baylor College of Medicine, Houston, TX, USARoger S. Blumenthal, MD Director, Division of Cardiology, Johns Hopkins
Ciccarone Center for the Prevention of Heart Disease, Professor of Medicine,
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Henry Boardman, MBBS, BSc Cardiovascular Clinical Research Facility,
Department of Cardiovascular Medicine, University of Oxford,
John Radcliffe Hospital, Headley Way, Oxford, UK
Thomas Boettger, PD Dr. rer. nat. Max-Planck-Institut fuer Herz- und
Lungenforschung, Department of Cardiac Development and Remodelling,Bad Nauheim, Germany
Harm Jan Bogaard, MD Associate Professor, Department of Pulmonary
Medicine, VU University Medical Center, Amsterdam, The Netherlands
Steven F. Bolling, MD Professor of Cardiac Surgery, University of Michigan
Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA
Biykem Bozkurt, MD, PhD, FACC, FAHA Professor of Medicine, Cardiology
Section, Department of Medicine, Michael E. DeBakey Veterans Affairs Medical
Center, Winters Center for Heart Failure Research, Cardiovascular ResearchInstitute, Baylor College of Medicine, Houston, TX, USA
Charles R. Bridges, MD, ScD, FACC, FACS Professor and Chairman,
Department of Cardiovascular Surgery, Sanger Heart and Vascular Institute,
Carolinas HealthCare System, Charlotte, NC, USA
Antoine Bril, PharmD, PhD Scientific Director Research and Partnerships,
Institut de Recherches Internationales Servier, Suresnes Cedex, France
Michel Burnier, MD Professor, Service of Nephrology and Hypertension,
Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV),
Lausanne, Switzerland
Leany Capote Laboratory for the Study of Neurohormonal Control of the
Circulation, Department of Pharmaceutical Sciences, Nova Southeastern
University College of Pharmacy, Ft. Lauderdale, FL, USA
Contributors
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Sukhinder K. Cheema, PhD Professor & Deputy Head (Graduate Studies),
Department of Biochemistry, Memorial University, St. Johns, NL, Canada
Estelle R. Simo Cheyou, PhD Laboratory of Cell Signaling, Research Center of
the University of Montreal Hospital, Center Department of Nutrition, Montreal,QC, Canada
Department of Nutrition, University of Montreal, Montreal, QC, Canada
Torsten Christ, MD Associate professor, Department of Experimental
Pharmacology and Toxicology, University Medical Center, Hamburg-Eppendorf,
Hamburg, Germany
Wilson S. Colucci, MD Professor, Department of Medicine, Boston University,
Boston, MA, USA
Bernard Cosyns, MD, PhD Professor, In Vivo Cellular and Molecular Imaging
Laboratory (ICMI), Department of Cardiology, Vrije Universiteit Brussel, Jette,
Belgium
Adrian Covic, MD, PhD, FRCP (London), FERA Nephrology Clinic, Parhon
University Hospital, Gr. T. Popa University of Medicine and Pharmacy, Iasi, Romania
John Henry Dasinger, PhD Department of Physiology and Biophysics,
Center for Cardiovascular and Renal Research, Womens Health Research Center,
University of Mississippi Medical Center, Jackson, MS, USABarry R. Davis, MD, PhD Guy S. Parcel Chair in Public Health, University of
Texas School of Public Health, Houston, TX, USA
Harry R. Davis, PhD CVPath Institute, Inc., Gaithersburg, MD, USA
Steven Droogmans, MD, PhD Department of Cardiology, UZ Brussel, Jette,
Belgium
In Vivo Cellular and Molecular Imaging Laboratory (ICMI), Department of
Cardiology, Vrije Universiteit Brussel, Jette, BelgiumGeorg B. Ehret, MD Department of Cardiology, Geneva University Hospitals,
Rue Gabrielle-Perret-Gentil, Geneva, Switzerland
Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic
Medicine Johns Hopkins University School of Medicine, Baltimore, MD, USA
Niels Engberding, MD, FACC, FESC Assistant Professor, Division of
Cardiology, Department of Medicine, Emory University School of Medicine,
Atlanta, GA, USA
Anthony S. Fargnoli, PhD Department of Cardiovascular Surgery, Sanger Heart
and Vascular Institute, Carolinas HealthCare System, Charlotte, NC, USA
Norbert Frey, MD Professor and Chair, Department of Internal Medicine III
Cardiology and Angiology, University Medical Center of Schleswig-Holstein, Kiel,
Germany
Contributors
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Gary Gintant, PhD Department of Integrative Pharmacology, Integrated Science
and Technology, North Chicago, IL, USA
Antonio M. Gotto Jr., MD, DPhil Dean Emeritus and Co-Chair of the Board of
Overseers, Lewis Thomas University Professor, Houston Methodist ResearchInstitute, Weill Cornell Medical College, New York, NY, USA
Vice President and Provost for Medical Affairs Emeritus, Department of Medicine,
Cornell University, New York, NY, USA
Eduardo Gronda, MD Department of Cardiovascular Medicine, IRCCS,
MultiMedica, Sesto San Giovanni, Italy
Christophe Guignabert, PhD INSERM U999, Universit Paris Sud,
Le Plessis-Robinson, France
Finn Gustafsson, MD, PhD, DMSci Consultant cardiologist, Medical director
cardiac transplantation and MCS, Department of Cardiology B2142, Copenhagen
University Hospital, Rigshospitalet, Copenhagen, Denmark
Nadjib Hammoudi, MD Institut de Cardiologie, Groupe Hospitalier Piti-
Salptrire, Assistance Publique-Hpitaux de Paris, Paris, France
Ian S. Harris, MD, FACP, FACC Associate Professor of Medicine, Director,
Adult Congenital Cardiology Program, Division of Cardiology, University of
California School of Medicine, San Francisco, CA, USAElizabeth A. Hausner, DVM, DABT, DABVT Senior Pharmacologist, Division
of Cardiovascular and Renal Products, Center for Drug Evaluation and Research
(CDER), US Food and Drug Administration, Silver Spring, MD, USA
Karen A. Hicks, MD Medical Officer, Division of Cardiovascular and Renal
Products, Center for Drug Evaluation and Research (CDER), US Food and Drug
Administration, Silver Spring, MD, USA
Susanne Hille Department of Internal Medicine III Cardiology and Angiology,
University Medical Center of Schleswig-Holstein, Kiel, Germany
David Holmes, MD Division of Cardiology, Mayo Clinic, Rochester, MN, USA
Michael Huntgeburth, MD Department of Cardiology, Clinic III for Internal
Medicine, Heart Center, University of Cologne, Cologne, Germany
Suttira Intapad, PhD Department of Physiology and Biophysics, Center for
Cardiovascular and Renal Research, Womens Health Research Center, University
of Mississippi Medical Center, Jackson, MS, USA
Yoshio Iwashima, MD, PhD, FAHA Divisions of Hypertension and Nephrology,National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Gowraganahalli Jagadeesh, PhD Senior Expert Pharmacologist, Division of
Cardiovascular and Renal Products, Center for Drug Evaluation and Research, US
Food and Drug Administration (FDA), Silver Spring, MD, USA
Contributors
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Michael Joner, MD CVPath Institute, Inc., Gaithersburg, MD, USA
Norbert Jost, PhD Associate professor, Division of Cardiovascular Pharmacology,
Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged,
Hungary
Department of Pharmacology, Victor Babes University of Medicine and
Pharmacy, Timisoara, Romania
Deepak Y. Kamath, MD Division of Clinical Research and Training,
Department of Medicine, St. Johns Research Institute and Medical College,
Bengaluru, India
Kei Kamide, MD, PhD, FAHA Division of Health Science, Osaka University
Graduate School of Medicine, Suita, Osaka, Japan
Yoshihiko Kanno, MD Department of Nephrology, Tokyo Medical University,
Shinjuku, Tokyo, Japan
Peter P. Karpawich, MSc, MD, FACC, FAHA, FHRS Section of Cardiology,
Department of Pediatrics, The Childrens Hospital of Michigan, Wayne State
University School of Medicine, Detroit, MI, USA
Hugo A. Katus, MD Department of Internal Medicine III, University of
Heidelberg, University Hospital of Heidelberg, Heidelberg, Germany
DZHK (German Centre for Cardiovascular Research), Heidelberg, Germany
Klaus Tschira Institute for Computational Cardiology, University of Heidelberg,
Heidelberg, Germany
Michael G. Katz, MD, PhD Senior Scientist, Department of Cardiovascular
Surgery, Sanger Heart and Vascular Institute, Carolinas HealthCare System,
Charlotte, NC, USA
Andrew P. Kendle, BS Department of Cardiovascular Surgery, Sanger Heart and
Vascular Institute, Carolinas HealthCare System, Charlotte, NC, USA
Petra C. Kienesberger, PhD Professor, Department of Biochemistry and
Molecular Biology, Dalhousie University, Dalhousie Medicine New Brunswick,
Saint John, New Brunswick, Canada
Yoshihiro Kokubo, MD, PhD, FAHA, FACC, FESC, FESO Chief Doctor,
Department of Preventive Cardiology, National Cerebral and Cardiovascular
Center, Suita, Osaka, Japan
Michalina Koodziejczak, MD Division of Cardiology, Pulmonology
and Vascular Medicine, Department of Internal Medicine,Heinrich-Heine-University, Dsseldorf, Germany
Systematic Investigation and Research on Interventions and Outcomes (SIRIO)
MEDICINE Research Network, Dsseldorf, Germany
Contributors
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Mariusz Kowalewski, MD Division of Cardiology, Pulmonology and Vascular
Medicine, Department of Internal Medicine, Heinrich-Heine-University,
Dsseldorf, Germany
Systematic Investigation and Research on Interventions and Outcomes (SIRIO)MEDICINE Research Network, Dsseldorf, Germany
Christian Kuhn, MD Department of Internal Medicine III Cardiology and
Angiology, University Medical Center of Schleswig-Holstein, Kiel, Germany
Siri Kunchakarra, MD Division of Cardiology, Department of Medicine,
Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Djamel Lebeche, PhD Professor, Department of Medicine, Cardiovascular
Research Institute, Graduate School of Biological Sciences, Icahn School of
Medicine at Mount Sinai, New York, NY, USA
Yuan Li, MD Department of Molecular and Integrative Physiology, Faculty of
Medicine, University of Montreal, Montreal, QC, Canada
A. Michael Lincoff, MD Vice Chairman, Department of Cardiovascular
Medicine, Director, Cleveland Clinic Coordinating Center for Clinical Research
(C5Research), Cleveland Clinic, Cleveland, OH, USA
Amir S. Lotfi, MD Vice Chair, Cardiology, Director, Heart and Vascular
Inpatient, Director, Regional MI program, Division of Cardiology, BaystateMedical Center, Tufts University, Springfield, MA, USA
Marcelo Rizzatti Luizon, PhD Department of Pharmacology, Institute of
Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, SP, Brazil
Anastasios Lymperopoulos, BPharm, MSc, PhD, FAHA Assistant Professor of
Pharmacology, Laboratory for the Study of Neurohormonal Control of the
Circulation, Department of Pharmaceutical Sciences, Nova Southeastern
University College of Pharmacy, Ft. Lauderdale, FL, USA
C. Gabriela Macas, PharmD, BCPS Heart and Vascular Clinical PharmacySpecialist, Baystate Medical Center, Acute Care Pharmacy Services, Springfield,
MA, USA
Lucy Mackillop, MA, FRCP Consultant Obstetric Physician, Department of
Obstetric Medicine, University of Oxford, Womens Centre, Oxford University
Hospitals NHS Trust, John Radcliffe Hospital, Headley Way, Oxford, UK
Kameswari Maganti, MD Director of Cardiac Rehabilitation, Associate
Professor of Medicine, Division of Cardiology, Department of Medicine,
Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Alan Maisel, MD, FACC Professor, Division of Cardiovascular Medicine,
Department of Medicine, San Diego Veterans Affairs Healthcare System, San
Diego, CA, USA
Contributors
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Jaya Mallidi, MD, MHS Cardiology Fellow, Division of Cardiology, Baystate
Medical Center, Tufts University, Springfield, MA, USA
Brandon Martinez Laboratory for the Study of Neurohormonal Control of the
Circulation, Department of Pharmaceutical Sciences, Nova SoutheasternUniversity College of Pharmacy, Ft. Lauderdale, FL, USA
John W. McEvoy, MB BCh, BAO, MRCPI Chief Fellow, Division of
Cardiology, Johns Hopkins Ciccarone Center for the Prevention of Heart Disease,
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Benjamin Meder, MD Professor, Department of Internal Medicine III,
University of Heidelberg, University Hospital of Heidelberg, Heidelberg, Germany
DZHK (German Centre for Cardiovascular Research), Heidelberg, Germany
Klaus Tschira Institute for Computational Cardiology, University of Heidelberg,
Heidelberg, Germany
Erin D. Michos, MD Division of Cardiology, Johns Hopkins Ciccarone Center
for the Prevention of Heart Disease, Johns Hopkins University School of
Medicine, Baltimore, MD, USA
Allan R. Mottram, MD Professor, Emergency Department, William S. Middleton
Memorial Veterans Hospital, Madison, University of Wisconsin, Madison, WI, USA
Danina M. Muntean, MD Professor, Department of Pathophysiology,
Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
Eliano Pio Navarese, MD, PhD, FESC Professor, Division of Cardiology,
Pulmonology and Vascular Medicine, Department of Internal Medicine, Heinrich-
Heine-University, Dsseldorf, Germany
Systematic Investigation and Research on Interventions and Outcomes (SIRIO)
MEDICINE Research Network, Dsseldorf, Germany
Kjell Nikus, MD, PhD Department of Cardiology, Tampere University Hospitaland University of Tampere, Medical School, Tampere, Finland
Ruth Nyakundi, PhD Laboratory for the Study of Neurohormonal Control of the
Circulation, Department of Pharmaceutical Sciences, Nova Southeastern
University College of Pharmacy, Ft. Lauderdale, FL, USA
Yoichi Ohno, MD Department of Nephrology, Saitama Medical University,
Iruma, Saitama, Japan
Brian Olshansky, MD Professor Emeritus, Division of Cardiology, University of
Iowa Hospitals, Iowa City, IA, USA
Prem Pais, MD Professor of Medicine, Former Dean, St Johns Medical College,
Head, Division of Clinical Research and Training, St Johns Medical College and
Research Institute, Bangalore, India
Contributors
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Nicolas Palaskas, MD Cardiology Section 3C-332E, Michael E. DeBakey
Veterans Affairs Medical Center, Winters Center for HF Research, Baylor College
of Medicine, Houston, TX, USA
John D. Parker, MD, FRCP (C) Professor of Medicine and Pharmacology,Department of Medicine, Mount Sinai and University Health Network
Hospitals, University of Toronto, Toronto, ON, Canada
Simon Pecha, MD Department of Cardiovascular Surgery, University Heart
Center Hamburg, University Medical Center, Hamburg-Eppendorf, Hamburg,
Germany
Nicholas Phreaner, MD Internal Medicine, Division of Cardiovascular
Medicine, Department of Medicine, San Diego Veterans Affairs Healthcare
System, San Diego, CA, USA
Peter Pollak, MD Director of Structural Heart Disease, Division of Cardiology,
Mayo Clinic Florida, Jacksonville, FL, USA
Henry J. Pownall, PhD Director, Atherosclerosis and Lipoprotein Research, Houston
Methodist Research Institute, Department of Cardiology, Weill Cornell Medical
College, Houston, TX, USA
Jyothy Puthumana, MD Division of Cardiology, Department of Medicine,
Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Florian Rader, MD, MSc Cardiac Non-Invasive Lab, Division of
Cardiology, Department of Medicine, Hypertension Center of Excellence,
The Heart Institute Cedars Sinai Medical Center, Los Angeles, CA, USA
Jason H. Rogers, MD, FACC, FSCAI Director, Interventional Cardiology,
Division of Cardiovascular Medicine, University of California, Davis Medical
Center, Sacramento, CA, USA
Nina Rol, MD Department of Pulmonary Medicine, VU University Medical
Center, Amsterdam, The Netherlands
Volker Rudolph, MD Department of Cardiology, Clinic III for Internal
Medicine, Heart Center, University of Cologne, Cologne, Germany
Stuart D. Russell, MD Associate Professor of Medicine, Department of
Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Hani N. Sabbah, PhD Department of Medicine, Henry Ford Hospital,
Detroit, MI, USA
Valeria Cristina Sandrim, PhD Department of Pharmacology,
Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu,
SP, Brazil
Contributors
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Gaetano Santulli, MD, PhD Department of Advanced Biomedical Sciences,
Federico II University, Naples, Italy
College of Physicians and Surgeons, Columbia University Medical Center,
New York, NY, USA
Liviu Segall, MD Nephrology Clinic, Parhon University Hospital, Gr. T. Popa
University of Medicine and Pharmacy, Iasi, Romania
Karen Serrano, MD Department of Emergency Medicine, University of
Wisconsin, Madison, WI, USA
Kevin Shah, MD Assistant Professor, Division of Cardiovascular Medicine,
Department of Medicine, San Diego Veterans Affairs Healthcare System, San
Diego, CA, USA
Tina Shah, MD Assistant Professor, Cardiology Section 3C-332E, Michael
E. DeBakey Veterans Affairs Medical Center, Winters Center for HF Research,
Baylor College of Medicine, Houston, TX, USA
Daniel M. Shivapour, MD Clinical and Research Fellow, Department of
Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA
Domenic A. Sica, MD President, American Society of Hypertension,
Professor of Medicine and Pharmacology, Chairman, Clinical Pharmacology
and Hypertension, Section of Clinical Pharmacology and Hypertension,Division of Nephrology, Virginia Commonwealth University Health System,
Richmond, VA, USA
Robert J. Siegel, MD, FACC Director, Cardiac Noninvasive Laboratory,
Division of Cardiology, Department of Medicine, The Heart Institute Cedars Sinai
Medical Center, Los Angeles, CA, USA
Alben Sigamani, MD, MSc (Clin. trials) Associate Professor, Department of
Pharmacology, St. Johns Medical College and Research Institute, St. Johns
National Academy of Health Sciences, Bengaluru, India
Ashok K. Srivastava, PhD Professor, Laboratory of Cell Signaling, Research
Center of the University of Montreal Hospital Center, Montreal, QC, Canada
Department of Nutrition and Medicine, University of Montreal,
Montreal, QC, Canada
Komandoor Srivathsan, MD Assistant Professor of Medicine, Division of
Cardiovascular Diseases, Mayo Clinic Arizona, Phoenix, AZ, USA
Renee M. Sullivan, MD Covance, Princeton, NJ, USA
Tsuneo Takenaka, MD, PhD Professor, Department of Medicine,
International University of Health and Welfare, Clinical Research Center,
Minato Tokyo, Japan
Contributors
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Jens Jakob Thune, MD, PhD Department of Cardiology B2142, Copenhagen
University Hospital, Rigshospitalet, Copenhagen, Denmark
Giuliano Tocci, MD, PhD Assistant Professor in Cardiology, Hypertension Unit,
Division of Cardiology, Department of Clinical and Molecular Medicine,University of Rome Sapienza, SantAndrea Hospital, Rome, Italy
Jean-Pierre Valentin, PhD Senior Director, Investigative Toxicology, UCB
Biopharma SPRL, Braine-lAlleud, Belgium
Emilio Vanoli, MD Department of Physiology, University of Oklahoma Health
Sciences Center, Oklahoma City, OK, USA
Department of Molecular Medicine, University of Pavia, Sesto San Giovanni, Italy
Department of Cardiovascular Medicine, IRCCS, MultiMedica, Sesto SanGiovanni, Italy
Anthony J. Viera, MD, MPH, FAHA Department of Family Medicine,
Hypertension Research Program, University of North Carolina at Chapel Hill
School of Medicine, Chapel Hill, NC, USA
Renu Virmani, MD Director, CVPath Institute, Inc., Gaithersburg, MD, USA
Britta Vogel, MD Department of Internal Medicine III, University of Heidelberg,
University Hospital of Heidelberg, Heidelberg, Germany
Massimo Volpe, MD, FAHA, FESC Professor and .Chair, Division of Cardiology,
Department of Clinical and Molecular Medicine, Faculty of Medicine and
Psychology, University of Rome Sapienza, SantAndrea Hospital, Rome, Italy
IRCCS Neuromed, Pozzilli, Italy
Nanette K. Wenger, MD, MACC, MACP, FAHA Professor Emeritus, Division
of Cardiology, Department of Medicine, Emory University School of Medicine,
Atlanta, GA, USA
Emory Heart and Vascular Center, Lawrenceville, GA, USA
Stacy Westerman, MD, MPH Fellow, Cardiovascular Disease, Division of
Cardiology, Department of Medicine, Emory University School of Medicine,
Atlanta, GA, USA
Paul K. Whelton, MB, MD, MSc Show Chwan Professor of Global Public
Health, Tulane University School of Public Health and Tropical Medicine,
New Orleans, LA, USA
J. William Schleifer, MD Division of Cardiovascular Diseases,
Mayo Clinic Arizona, Phoenix, AZ, USA
Grgoire Wuerzner, MD Service of Nephrology and Hypertension,
Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV),
Lausanne, Switzerland
Contributors
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Katharina K. Wystub, PD Dr. rer. nat. Department of Cardiac Development
and Remodelling, Max-Planck-Institute of Heart and Lung Research, Bad
Nauheim, Germany
Denis Xavier, MD, MSc (Clin Epi) Professor and Head, Department ofPharmacology, St. Johns Medical College, Bangalore, India
Division of Clinical Research and Training, St. Johns Research Institute and
Medical College, St. Johns National Academy of Health Sciences, Bangalore, India
Kazuyuki Yahagi, MD Cardiovascular Research Fellow, CVPath Institute, Inc.,
Gaithersburg, MD, USA
Contributors