Electrophysiological Foundations of Cardiac Arrhythmias: A Bridge Between Basic Mechanisms and Clinical Electrophysiology

by Andrew L. Wit, PhD; Hein J. Wellens, MD, PhD;
and Mark E. Josephson, MD

Published May 2017
Format: Hardcover and eBook set; eBook
ISBN: 9780979016455

Trim size: 7 x 10 inches
672 pages

Print book includes a free digital edition.

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This book teaches the fundamental concepts of cardiac cellular electrophysiology with an emphasis on the relationship of basic mechanisms to clinical cardiac arrhythmias. Understanding this relationship and the underlying mechanisms of arrhythmogenesis will be valuable to medical students in general and physicians entering the fields of cardiology and clinical electrophysiology, as well as those scientists and clinicians already working in this field.

The foundations of electrophysiology are explained in a way that will enable the student/reader to go on to more advanced texts such as Josephson’s Clinical Cardiac Electrophysiology by Mark E. Josephson (Wolters Kluwer), who is one of the authors of this book.

The book is divided into three parts that cover the major mechanisms of arrhythmogenesis: Part I – Automaticity, Part II – Afterdepolarizations and Triggered Activity, and Part III – Abnormal Impulse Conduction and Reentry. Each part starts with a chapter that describes the basic science principles related to that particular mechanism. Topics include: impulse initiation and rate control, membrane currents, conduction, and the effects of programmed electrical stimulation and pharmacologic agents. Subsequent chapters in each part are organized around examples of clinical arrhythmias and then focus on the relevant EP mechanisms and the characteristic responses to interventions. The characteristics of the three different mechanisms are compared and contrasted throughout the text.

Each example works through these three key questions:

  1. What are the ECG characteristics of the arrhythmia?
  2. What is the underlying electrophysiological mechanism?
  3. What are the characteristic properties of the arrhythmia that point to its mechanism?

Throughout the book, the aspects of basic EP mechanisms and examples from EP studies and pharmacologic interventions are paired with clinical examples. The end result is enhanced understanding of how EP mechanisms and testing relate to arrhythmogenesis in a way that can be applied broadly to a variety of situations in a clinical setting.

This definitive book also includes:

  • More than 300 figures, including ECGs and original diagrams that illustrate essential electrophysiology concepts.
  • Case studies of clinical arrhythmias with explanations of how ECG characteristics and the responses to electrical stimulation denote arrhythmogenic mechanisms.


Electrophysiological Foundations of Cardiac Arrhythmias by Wit, Josephson, and Wellens is a long overdue text bridging basic science and clinical medicine, thus providing basic scientists, clinical investigators and practicing physicians, unique insights into the mechanisms underlying cardiac arrhythmias. The complex mechanisms responsible for the development of clinical arrhythmias are discussed in detail, but with clarity and appreciation of continuing gaps in our knowledge.
- Charles Antzelevitch, PhD, FACC, FAHA, FHRS; Lankenau Institute for Medical Research; Philadelphia, Pennsylvania

I read Electrophysiological Foundations of Cardiac Arrhythmias, written by three icons of cardiac electrophysiology with great joy. This is an amazingly comprehensive text, written so that students of all ability level can understand the basic mechanisms of cardiac electrophysiology. My friend Mark Josephson often complained that contemporary electrophysiology had become “electrotechnology.” Physicians had become so concerned with doing things (implanting ICDs, performing ablations) that the underlying understanding of what they were doing was often missed. This text provides a powerful antidote to electrotechnology, appropriate for all true students of electrophysiology.
- David J. Callans, MD; University of Pennsylvania Health System Philadelphia, Pennsylvania

It is fair to say that this textbook is a gem, and one every electrophysiologist should want to have. It is one of the last masterpieces that Mark Josephson contributed to with his friends and life-long colleagues, Hein J. Wellens and Andrew L. Wit. It reflects their unique perspective on the integration of basic science into an understanding of human clinical electrophysiology. We are talking about “bench to bedside,” and this fine volume includes some of the best basic and clinical science I have read anywhere. The book is an essential addition to every electrophysiologist’s library.
- Kenneth A. Ellenbogen, MD; VCU School of Medicine Richmond, Virginia

The electrophysiologist as the name implies has traditionally been a “physiologist.” Advances in our discipline, be they pharmacological, ablative, or other, have been made on a foundation of better understanding of the mechanism of arrhythmia coupled with technical advances to allow this knowledge to become clinically useful and practical. It seems obvious to conclude that continued progress will be laid on a foundation of more knowledge. Unfortunately, the traditional emphasis on understanding the basic physiology in our specialty has been challenged by clinical exigencies and pressure of time in busy clinical units.

It is thus very timely that we now have available a concise and very readable text providing the fundamentals of the physiology underlying clinical EP. Unique is the emphasis of directly linking the underlying physiology to our understanding of clinical arrhythmias. This link is provided masterfully and clearly by arguably the most influential leaders of our time in the basic arena, Dr. Wit, and in the clinical arena, the tandem of Drs. Wellens and Josephson. I highly recommend this volume to any current trainee as a cornerstone of their chosen career, especially since it is unlikely to be taught to them so clearly and systematically in their current program. Of course, it goes without saying that such a text will enhance the depth of understanding of our craft regardless of the particular path we have taken. I am sure that many of us will join me in expressing their enthusiasm and gratitude to the authors for producing this unique contribution.
- George Klein, MD; Western University, London, Ontario, Canada

This is a uniquely authoritative and lucid contribution that seamlessly weaves an understanding of cellular cardiac electrophysiology to inform a deep appreciation of clinical arrhythmias and their ECG recognition. Written by three of the leading pioneers of cellular and clinical electrophysiology for nearly the last half-century, this scholarly yet practical tour de force should prove an invaluable guide to trainees and experienced electrophysiologists alike.
- Bruce B. Lerman, MD; Cornell University Medical Center, New York Presbyterian Hospital, New York, New York

Three of the most gifted teachers in the field of cardiac electrophysiology, Wit, Wellens and Josephson, have successfully built the bridge from cellular electrophysiology to the bedside ECG and clinical arrhythmias. This book is a must-read for bench researchers in cardiology regardless of their focus, students looking to understand the clinical application of basic electrophysiologic principles and, of course, the curious clinician who, like me, learns best not from pattern recognition but rather from building on a solid framework of understanding cardiac cellular mechanisms.  The organization of the effort is well thought out and the delivery uniquely clinically relevant. This is a more than a delicious meal; it is a feast of electrophysiology knowledge that will sustain the reader for years to come.
- Francis Marchlinski, MD; University of Pennsylvania Health System Philadelphia, Pennsylvania

It is my great pleasure to enthusiastically endorse this incredibly informative book by the giants in the discipline of cardiac electrophysiology. Although this text has experienced a long gestational period, it was well worth the wait.The authors have chosen a unique route namely centering the text on the exposition of basic precepts of cardiac electrophysiology and linking the physiology to clinical arrhythmias. I cannot think of an author set more appropriate for this rather novel and intriguing undertaking. The product is an exciting, informative, well written and well-illustrated text.The book was put together an author set extremely well versed in both basic as well as clinical electrocardiography and electrophysiology and who are acknowledged great teachers and clinicians (Wellens and Josephson) who have a deep appreciation for the links between physiology and clinical arrhythmology. This text is truly unique and will no doubt take its place with iconic texts of our discipline like those of Pick and Langendorff as well as prior books by Josephson and Wellens.

This book is a real treat for the arrhythmia community, and we are very fortunate to have an up-to-date, refreshing, new “bible” for our community of arrhythmia experts. I would recommend this book for both physician in training as well as the more seasoned colleagues. I learned a great deal from these masters over the years and am so excited and pleased that they codified their great knowledge into a formal text. There is no doubt that the reader will share my enthusiasm and excitement when perusing this book.
- Melvin Scheinman, MD; University of California, San Francisco, San Francisco, California

Table of Contents:

Part I – Automaticity
Chapter 1.  Basic Principles of Normal Automaticity
Chapter 2. Sinus Node Normal Automaticity and Automatic Arrhythmias
Chapter 3. Atrial, A-V Junctional, and Ventricular Normal Automaticity and Automatic Arrhythmias
Chapter 4. Abnormal Automaticity: Basic Principles and Arrhythmias

Part II – Afterdepolarizations and Triggered Activity
Chapter 5. Basic Principles of Delayed Afterdepolarizations and Triggered Action Potentials
Chapter 6. Delayed Afterdepolarization: Triggered Arrhythmias
Chapter 7. Basic Principles of Early Afterdepolarization and Triggered Action Potentials
Chapter 8. Early Afterdepolarization: Triggered Arrhythmias

Part III - Altered (Abnormal) Impulse Conduction and Reentry
Chapter 9. Basic Principles of Reentry: Altered Conduction and Reentrant Excitation   
Chapter 10. Atrial Reentrant Arrhythmias
Chapter 11. Atrioventricular (A-V) Junctional Reentrant Arrhythmias
Chapter 12. Ventricular Reentrant Arrhythmias


Andrew L. Wit, PhD, FACC
Emeritus Professor of Pharmacology, Department of Pharmacology
College of Physicians and Surgeons of Columbia University
New York, New York

Hein J. Wellens, MD, PhD, FACC, FAHA, FESC
Emeritus Professor of Cardiology, University of Maastricht
Maastricht, The Netherlands

Mark E. Josephson, MD, FACC, FHRS, FAHA
Director, Harvard-Thorndike Electrophysiology Institute and Arrhythmia Service
Chief Emeritus, Division of Cardiovascular Medicine
Beth Israel Deaconess Medical Center
Herman C. Dana Professor of Medicine
Harvard Medical School
Boston, Massachusetts