CARDIAC BIOELECTRIC THERAPY mechanisms and practical implications.

421 Pages·2021·37.061 MB·English

Igor R. Efi mov
Fu Siong Ng
Jacob I. Laughner
Editors
Cardiac
Bioelectric Therapy
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123
Cardiac Bioelectric Therapy
Igor R. Efimov • Fu Siong Ng • Jacob I. Laughner
Editors
Cardiac Bioelectric Therapy
Mechanisms and Practical Implications
Second Edition
Editors
Igor R. Efimov Fu Siong Ng
Department of Biomedical Engineering National Heart & Lung Institute
The George Washington University Imperial College London
Washington, DC London
USA UK
Jacob I. Laughner
Philips EPD Solutions
Cambridge, MA
USA
Cover illustration by Jessica A. Vasserman
ISBN 978-3-030-63354-7 ISBN 978-3-030-63355-4 (eBook)
https://doi.org/10.1007/978-3-030-63355-4
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Foreword
It is a rare privilege to contribute a foreword to the second edition of this remarkable book by
Drs. Igor Efimov, Fu Siong Ng, and Jacob Laughner. Cardiac electrophysiology is a magical
field that connects the most fundamental basic science to the fascinating technologies to study
electrical phenomena in the heart and most of all to treat patients with heart disease. Cardiac
disease is responsible for 34 deaths per minute in the world today (17 million deaths/year), and
by some estimates, a staggering 12 million deaths (22 deaths/minute) are related to sudden
cardiac death (due to serious ventricular arrhythmias). This is the challenge faced by scientists
and clinicians focused on the study of cardiac bioelectrical phenomena and their modulation.
The second edition of this book has been eagerly awaited and lives up to its promise, beauti-
fully building on the first edition. The readers of this remarkable book will be enthralled to read
about the history of how pioneers studied the electrical phenomena of the heart and how this
work has helped inform therapeutics. Almost every therapy we offer to patients in 2020 for
cardiac care involves bioelectronics (from diagnosis using ECGs to therapy with catheter abla-
tion and implanted electronic device); indeed the highest level of evidence for preventing sud-
den deaths is the implanted defibrillator. The continued importance and success of the field is
evidenced by the remarkable explosion of technologies for scientific investigation, which have
also opened up powerful bioelectronic therapeutic approaches to heart disease and arrhyth-
mias. Specific new areas such as microelectronics and advanced computing in devices are
highlighted in this edition. Professor Efimov, a pioneer and scholar of the field, and his
esteemed colleagues have been able to collate a treasure and I am certain that the book will
continue to inspire the readers, some of whom are surely contemplating an area of specializa-
tion, and it is hoped they will choose this field and help our patients!
September 2020 Kalyanam Shivkumar, MD, PhD
University of California, Los Angele s
Los Angeles, CA, USA
v
Preface
Cardiovascular science and technology provided the foundation for an unprecedented increase
in life expectancy, which was sustained for nearly half a century, starting from 1970. The pri-
mary cause of lifespan increase by a decade is improved diagnostics and therapy of heart dis-
ease leading to the declining cardiovascular mortality. Cardiac bioelectric therapy was among
the major contributors to the reduction of cardiovascular mortality. Classical examples of such
lifesaving technologies are cardiac pacemaker, implantable cardioverter defibrillators, and
ablation of arrhythmias. However, regrettably, there is now an evidence of the reversal of this
trend during the last decade, which necessitated doubling our efforts in developing a new gen-
eration of the diagnostic and therapeutic approaches to treat heart disease.
Reductionist Approach to Arrhythmia
A dramatic increase in understanding of the molecular mechanisms of normal and pathological
cellular electrophysiology led to the development of new theories of arrhythmia. A number of
these theories have been supported by a convincing empirical evidence “from cell to bedside.”
And, as a result, the field has been driven by promises of elegant “silver bullet” pharmacologi-
cal solutions to treat lethal cardiac arrhythmias. Nearly every generation of electrophysiolo-
gists has come up with a target for their own silver bullet: sodium channel, calcium channel,
potassium channel, gap junction, and so forth. Visions of several generations of electrophysi-
ologists have crystallized into a theory of channelopathies.
There is a proverb: nearly every new thought is a long forgotten one. The state of arrhythmia
research is reminiscent in some sense to an earlier history of the elementary particle physics.
It appeared to most physicists at the time that the foundation of laws of matter can be elo-
quently explained by interactions of few elementary particles and a handful of fundamental
laws governing these interactions. Yet, as more and more new particles and/or novel peculiar
properties of the existing particles were uncovered, the increasingly more sophisticated theo-
ries were produced, making the elegance and eloquence of the earlier theories irrelevant.
Cardiac electrophysiology went along a very similar path in search of arrhythmia therapy.
A giant of the field, Carl J. Wiggers, drafted a roadmap in 1940: “As to the fundamental mecha-
nisms of fibrillation we have plenty of theories, but none is universally accepted … they all
center around two ideas, viz. (a) that the impulses arise from centers, or pacemakers, or (b) that
the condition is caused by the re-entry of impulses and the formation of circles of excitation.”1
The old ion-channel-based theory seemed to have done a pretty good job explaining both
focal and reentrant theories of arrhythmia. These early theories of arrhythmia, with their four
classes of antiarrhythmic drugs, were almost Aristotelian. But they fell under the pressure of the
empirical evidence:2 ever multiplying channel isoforms and subunits, alternative splicing vari-
ants, mutations in genes encoding ion channels and related proteins, the involvement of numer-
1 Wiggers CJ. The mechanism and nature of ventricular fibrillation. Am Heart J. 1940;20:399–412
2 Are implantable cardioverter-defibrillators or drugs more effective in prolonging life? The Antiarrhythmics
Versus Implantable Defibrillators (AVID) Trial Executive Committee. Am J Cardiol. 1997;79:661–663
vii
viii Preface
ous increasingly complex signaling pathways, epigenetic regulation of transcription, cell
memory, circadian variability, gene-gene interaction, and chromatin landscape. These important
players had been unknown in the past and will present new opportunities in the future, if gene
editing, epigenetic control, and novel approaches will become a clinical reality one day.
Can a cardiac arrhythmia with broad clinical impact be explained within a framework based
on a single channel biophysics, or a signaling pathway, or even a single cell mechanism? And,
most importantly, can a therapy be developed for arrhythmia based on such a mechanism?
Despite the explosion in the numbers of filed patents aimed at offering such answers, it is
becoming more and more apparent that these questions will not be so easy to answer within the
reductionist paradigm. Integrative approaches are needed to synthesize the wealth of knowl-
edge accumulated by a century of the reductionist science.
Integrative Approach
Integrative physiologists looked at the problem of arrhythmia from an entirely different angle:
How can we restore normal heart rhythm when sinoatrial or atrioventricular nodes fail with the
technology at hand? How can one terminate lethal ventricular fibrillation using cardiovascular
engineering approaches, when the pharmacological approach failed? Electrotherapy, both
device and ablation, has emerged as the only effective therapy to treat arrhythmia, often with-
out precise knowledge of the mechanisms of arrhythmia it treats. History of cardiac bioelectric
therapy is a long and fascinating one, spanning several centuries and many countries. Ideas of
using electricity for treating cardiac disorders have been born in the minds of the Italian,
French, and British physiologists and physicians as evident from the numerous eighteenth-
century publications in these languages. The nineteenth-century cardiac physiology framed
recognition of arrhythmia as a direct cause of death and provided a compelling evidence for the
ability of electric stimulation to restore normal rhythm. The twentieth-century cardiovascular
physiology finally brought to fruition three centuries of research and developed an array of
bioelectric therapies that save lives of millions of patients worldwide.
But the twenty-first century has a truly transformative beginning in the field of cardiac bio-
electric therapy. Novel implantable and wearable devices are becoming truly widespread
among hundreds of millions of patients and healthy individuals, who are concerned with their
cardiovascular health and take a proactive approach. Machine learning is an excellent example
of an emerging breakthrough approach to decipher electrophysiological information collected
by myriads of sensors, which are becoming more and more ubiquitous. An advent of organ
conformal flexible and stretchable bioelectronics will usher in a new era of integration of
cybernetics with our biology, powered by rapidly evolving machine learning and artificial
intelligence. These advances create conditions for population-wide surveillance of cardiovas-
cular health becoming a reality. However, it also opens a Pandora box of safety concerns due
to security vulnerability of digital technologies.
And finally, we are about to enter an era of synthesis of integrative and reductionist
approaches. A growing wealth of information from OMICS technologies is merging with func-
tional high-fidelity multidimensional physiological data.
Washington, DC, USA Igor R. Efimov, PhD
London, UK Fu Siong Ng, MRCP, PhD
Cambridge, MA, USA Jacob I. Laughner, PhD
Contents
Part I History of Electrotherapy
1 History of Cardiac Pacing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Srijoy Mahapatra
2 History of Defibrillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Hana Akselrod, Mark W. Kroll, and Michael V. Orlov
3 The History of Mapping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Ivan Cakulev, Andrew L. Wit, and Albert L. Waldo
4 History of Optical Mapping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Sharon A. George
Part II Theory of Electric Stimulation and Defibrillation
5 The Bidomain Theory of Stimulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Deborah L. Janks and Bradley J. Roth
6 Bidomain Model of Defibrillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Natalia Trayanova and Gernot Plank
7 The Generalized Activating Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Leslie Tung
Part III E lectrode Mapping and Defibrillation
8 Extracellular Mapping of Arrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Richard B. Schuessler
9 The Upper Limit of Vulnerability and Critical Points for Defibrillation . . . . . . . .107
Derek J. Dosdall and Raymond E. Ideker
10 His-Purkinje Involvement in Arrhythmias and Defibrillation . . . . . . . . . . . . . . . .121
Matthias Lange and Derek J. Dosdall
Part IV O ptical Mapping of Stimulation and Defibrillation
11 The Role of Microscopic Tissue Structure in Defibrillation . . . . . . . . . . . . . . . . . .135
Andre G. Kleber and Anne M. Gillis
12 Virtual Electrode Theory of Pacing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .147
Bradley J. Roth, Veniamin Y. Sidorov, and John P. Wikswo
13 The Virtual Electrode Hypothesis of Defibrillation . . . . . . . . . . . . . . . . . . . . . . . . .181
Crystal M. Ripplinger and Igor R. Efimov
ix
x Contents
14 Advanced Three-Dimensional Optical Mapping . . . . . . . . . . . . . . . . . . . . . . . . . . .199
Olivier Bernus and Richard D. Walton
Part V M ethodology
15 The Bidomain Model of Cardiac Tissue: From Microscale to Macroscale . . . . . .211
Craig S. Henriquez and Wenjun Ying
16 Newer Models of Cardiac Tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .225
Zexu Lin and Sharon A. George
17 The Role of Electroporation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .233
Vladimir P. Nikolski and Igor R. Efimov
18 Frequency and Phase Domains Methods for Mechanisms of Fibrillation . . . . . . .243
David Calvo and Omer Berenfeld
19 Lessons Learned from Implantable Cardioverter-Defibrillator Recordings . . . .259
Jeff Gillberg, Troy Jackson, and Paul Ziegler
20 Radiofrequency Versus Cryoablation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .287
Matthew S. Sulkin and Jason Meyers
Part VI N ovel and Future Cardiac Electrotherapies
21 Multistage Defibrillation Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .297
Balvinder S. Handa and Fu Siong Ng
22 Leadless Pacing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .311
Paul R. Roberts
23 His Purkinje Conduction System Pacing: Methods, Mechanisms,
and Best Practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .327
Parikshit S. Sharma and Pugazhendhi Vijayaraman
24 State of the Art in Artificial Intelligence and Machine Learning
Techniques for Improving Patient Outcomes Pertaining
to the Cardiovascular and Respiratory Systems . . . . . . . . . . . . . . . . . . . . . . . . . . .335
Wan-Tai M. Au-Yeung, Rahul Kumar Sevakula, Jagmeet P. Singh,
E. Kevin Heist, Eric M. Isselbacher, and Antonis A. Armoundas
25 State of the Art on Wearable and Implantable Devices
for Cardiac and Respiratory Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .353
Antonis A. Armoundas, Jagmeet P. Singh, E. Kevin Heist, and
Eric M. Isselbacher
26 Optogenetic Control of Arrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .363
Balázs Ördög, Antoine A. F. de Vries, and Daniël A. Pijnappels
27 Conformal Electronics Therapy for Defibrillation . . . . . . . . . . . . . . . . . . . . . . . . .381
Kedar Aras, John A. Rogers, and Igor R. Efimov
28 The Future of the Implantable Cardioverter-Defibrillator . . . . . . . . . . . . . . . . . . .391
Charles D. Swerdlow and Michael R. Gold
29 Cybersecurity of Cardiac Implantable Electronic Devices . . . . . . . . . . . . . . . . . . .411
David Slotwiner, Arnab Ray, Kevin Fu, and Bruce L. Wilkoff
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .425
Contributors
Hana Akselrod, MS Freelance Writer, Boston, MA, USA
Kedar Aras, PhD Department of Biomedical Engineering, Cardiovascular Engineering
Laboratory, The George Washington University, Washington, DC, USA
Antonis  A.  Armoundas, PhD Cardiovascular Research Center, Massachusetts General
Hospital, Boston, MA, USA
Institute for Medical Engineering and Science, Massachusetts Institute of Technology,
Cambridge, MA, USA
Wan-Tai  M.  Au-Yeung, PhD Cardiovascular Research Center, Massachusetts General
Hospital, Boston, MA, USA
Omer Berenfeld, PhD Center for Arrhythmia Research, University of Michigan, Ann Arbor,
MI, USA
Olivier  Bernus, PhD Université de Bordeaux, Electrophysiology and Heart Modeling
Institute Liryc, CRCTB U1045, Avenue du Haut-Lévèque – Xavier Arnozan, Pessac, France
Ivan  Cakulev, MD Case Western Reserve University School of Medicine, University
Hospitals of Cleveland, Cleveland, OH, USA
David Calvo, MD, PhD Arrhythmia Unit, Cardiology Department, Hospital Universitario
Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo,
Spain
Derek J. Dosdall, PhD Division of Cardiothoracic Surgery, Department of Surgery and The
Nora Eccles Harrison Cardiovascular Research Training Institute, University of Utah, Salt
Lake City, UT, USA
Igor R. Efimov, PhD Department of Biomedical Engineering, The George Washington
University, Washington, DC, USA
Kevin Fu, PhD University of Michigan, Ann Arbor, MI, USA
Sharon A. George, PhD Department of Biomedical Engineering, Science and Engineering
Hall, The George Washington University, Washington, DC, USA
Jeff Gillberg, MS Medtronic plc., Mounds View, MN, USA
Anne M. Gillis, MD, FRCPC Department of Cardiac Sciences, University of Calgary, Libin
Cardiovascular Institute, Calgary, AB, Canada
Michael R. Gold, MD, PhD Division of Cardiology, Medical University of South Carolina,
Charleston, SC, USA
Balvinder S. Handa, BSc, MRCP National Heart & Lung Institute, Imperial College London,
London, UK
xi