CVD Book TOC Contributors Springer GJ 5 2015

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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
http://www.springer.com/http://www.springer.com/


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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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vi

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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vii

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

Contents


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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

Contents


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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

Contents


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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

Contents


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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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xvi

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



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,


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



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,


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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xxi

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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xxii

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

Documents

CVD Book TOC Contributors Springer GJ 5 2015