Clinical arrhythmology and electrophysiology : a companion to Braunwald's heart disease

734 Pages·2012·100.53 MB·English

by  Issa

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CLINICAL ARRHYTHMOLOGY AND ELECTROPHYSIOLOGY ISBN: 978-1-4557-1274-8
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Library of Congress Cataloging-in-Publication Data
Issa, Ziad F.
Clinical arrhythmology and electrophysiology: a companion to Braunwald’s heart disease / Ziad F. Issa,
John M. Miller, Douglas P. Zipes.— 2nd ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4557-1274-8 (hardcover : alk. paper)
I. Miller, John M. (John Michael), 1954- II. Zipes, Douglas P. III. Braunwald’s heart disease. IV. Title.
[DNLM: 1. Arrhythmias, Cardiac—diagnosis. 2. Arrhythmias, Cardiac—physiopathology.
3. Electrophysiologic Techniques, Cardiac. WG 330]
616.1′28—dc23 2012012441
Content Strategist: Dolores Meloni
Content Developmental Specialist: Andrea Vosburgh
Publishing Services Manager: Patricia Tannian
Project Manager: Linda Van Pelt
Design Direction: Steve Stave
Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
PREFACE
Readers’ responses to the first edition of this textbook have been and educate in a comprehensive, cohesive fashion while avoid-
extremely gratifying, so much so that we were encouraged to update ing redundancies and contradictions.” Having lived through the
and revise the text relatively early after its initial publication in 2009. changes of the past several years, we have been able to extract and
As all who work in this field know, however, the knowledge base is write about those advances that we think are important and use-
changing very rapidly at virtually all levels, from basic understand- ful to the readers. This is similar to a travel guidebook written by
ing of mechanisms to new ablation techniques, mapping, imaging someone who has actually stayed in that unique hotel or eaten
advances, and development of new ablation energy sources. In in that special restaurant. We have experienced the progress first-
addition, we are learning about new clinical states that have been hand and are able to pass on our experiences to you. In addition,
“right under our noses” for a long time, such as the short QT and J as before—but expanded even further—readers have the option
wave syndromes. We have therefore added new chapters on those to delve deeper into basic mechanisms or invasive procedures…
topics as well as on molecular mechanisms and ion channels, or not, depending on the level of interest. We have tried to keep
advanced mapping and navigation, and arrhythmias in congenital the appeal for all levels of learners, from the beginner to the expe-
heart disease. For clarity, we have divided the idiopathic ventricular rienced electrophysiologist, so that you can stop reading with the
tachycardias (VTs) into adenosine- and verapamil-sensitive types fascinating array of ECGs or dig deeper into the mechanism of cal-
and have written new chapters on both epicardial VTs and VTs in cium handling—your call. We hope you enjoy learning from this
the different cardiomyopathies. The “old” chapters are no longer second edition.
old; all have been totally revised and expanded with updated infor-
mation. Additionally, we have included 27 new videos that vividly Ziad F. Issa
exemplify a variety of techniques and mapping observations. John M. Miller
As with the first edition, this book has been written by just the Douglas P. Zipes
three of us, so that once again we can “explain, integrate, coordinate
ix
We would like to thank our families for their support during the writing of this book, since it
meant time away from them.
My wife Dana and my sons Tariq and Amr
Ziad F. Issa
My wife Jeanne and my children Rebekah, Jordan, and Jacob
John M. Miller
My wife Joan and my children Debbie, Jeff, and David
Douglas P. Zipes
We would also like to thank Julie Shelby, Leslie Ardebili, and Ralph Chambers for their help
in preparing this manuscript.
FOREWORD
Disturbances in cardiac rhythm occur in a large proportion of the The first seven chapters, on Molecular Mechanisms of Cardiac
population. Arrhythmias can have sequelae that range from incon- Electrical Activity, Cardiac Ion Channels, Electrophysiological
sequential to life-shortening. Sudden cardiac deaths and chronic Mechanisms of Cardiac Arrhythmias, Electrophysiological Test-
disability are among the most frequent serious complications ing, Conventional Intracardiac Mapping Techniques, Advanced
resulting from arrhythmias. Mapping and Navigation Modalities, and Ablation Energy Sources,
Braunwald’s Heart Disease: A Textbook of Cardiovascular Medi- provide a superb introduction to the field. This is followed by 24
cine includes an excellent section on rhythm disturbances edited chapters on individual arrhythmias, each following a similar out-
and largely written by Douglas Zipes, the most accomplished and line. Here, the authors lead us from a basic understanding of the
respected investigator and clinician in this field. However, there arrhythmia to its clinical recognition, natural history, and manage-
are many subjects that simply cannot be discussed in sufficient ment. The latter is moving rapidly from being largely drug-based
detail, even in a 2000-page, densely packed book. For this reason, to device-based, although many patients receive combination
the current editors and I decided to commission a series of com- device-drug therapy. These options, as well as ablation therapy, are
panions to the parent title. We were extremely fortunate to enlist clearly spelled out as they apply to each arrhythmia. The final chap-
Dr. Zipes’ help in editing and writing Clinical Arrhythmology and ter discusses the complications of catheter ablation of cardiac
Electrophysiology. Dr. Zipes, in turn, enlisted two talented collabora- arrhythmias.
tors, Drs. Ziad F. Issa and John M. Miller, to work with him to pro- We are proud to include Clinical Arrhythmology and Electrophysi-
duce this excellent volume. ology as a Companion to Braunwald’s Heart Disease, and we are
This second edition is superbly illustrated, with the number of fully confident that it will prove to be valuable to cardiologists,
figures and tables increasing by almost half from its predecessor. internists, investigators, and trainees.
What has not changed, however, is the very high quality of the
content, which is accurate, authoritative, and clear; second, it is as Eugene Braunwald, MD
up-to-date as last month’s journals; and third, the writing style and Peter Libby, MD
illustrations are consistent throughout with little, if any, duplication. Robert Bonow, MD
As this important branch of cardiology has grown, so has this book. Douglas Mann, MD
vii
Clinical Arrhythmology
and Electrophysiology
A Companion to Braunwald’s Heart Disease
SECOND EDITION
Ziad F. Issa, MD
Clinical Assistant Professor
Internal Medicine
Southern Illinois University School of Medicine
Cardiac Electrophysiology
Prairie Cardiovascular Consultants
Prairie Heart Institute
St. John’s Hospital
Springfield, Illinois
John M. Miller, MD
Professor of Medicine
Krannert Institute of Cardiology
Indiana University School of Medicine
Director
Clinical Cardiac Electrophysiology
Indiana University Health
Indianapolis, Indiana
Douglas P. Zipes, MD
Distinguished Professor
Professor Emeritus of Medicine, Pharmacology, and Toxicology
Director Emeritus
Division of Cardiology and the Krannert Institute of Cardiology
Indiana University School of Medicine
Indianapolis, Indiana
Look for These Other Titles in the
Braunwald’s Heart Disease
Family
Braunwald’s Heart Disease Companions
PIERRE THÉROUX
Acute Coronary Syndromes
ELLIOTT M. ANTMAN & MARC S. SABATINE
Cardiovascular Therapeutics
CHRISTIE M. BALLANTYNE
Clinical Lipidology
DOUGLAS L. MANN
Heart Failure
HENRY R. BLACK & WILLIAM J. ELLIOTT
Hypertension
ROBERT L. KORMOS & LESLIE W. MILLER
Mechanical Circulatory Support
ROGER BLUMENTHAL, JOANNE FOODY, & NATHAN WONG
Preventive Cardiology
CATHERINE M. OTTO & ROBERT O. BONOW
Valvular Heart Disease
MARC A. CREAGER, JOSHUA A. BECKMAN, & JOSEPH LOSCALZO
Vascular Disease
Braunwald’s Heart Disease Imaging Companions
ALLEN J. TAYLOR
Atlas of Cardiac Computed Tomography
CHRISTOPHER M. KRAMER & W. GREGORY HUNDLEY
Atlas of Cardiovascular Magnetic Resonance Imaging
AMI E. ISKANDRIAN & ERNEST V. GARCIA
Atlas of Nuclear Imaging
JAMES D. THOMAS
Atlas of Echocardiography
Look for These Other Titles in the
Braunwald’s Heart Disease
Family
Braunwald’s Heart Disease Companions
PIERRE THÉROUX
Acute Coronary Syndromes
ELLIOTT M. ANTMAN & MARC S. SABATINE
Cardiovascular Therapeutics
CHRISTIE M. BALLANTYNE
Clinical Lipidology
DOUGLAS L. MANN
Heart Failure
HENRY R. BLACK & WILLIAM J. ELLIOTT
Hypertension
ROBERT L. KORMOS & LESLIE W. MILLER
Mechanical Circulatory Support
ROGER BLUMENTHAL, JOANNE FOODY, & NATHAN WONG
Preventive Cardiology
CATHERINE M. OTTO & ROBERT O. BONOW
Valvular Heart Disease
MARC A. CREAGER, JOSHUA A. BECKMAN, & JOSEPH LOSCALZO
Vascular Disease
Braunwald’s Heart Disease Imaging Companions
ALLEN J. TAYLOR
Atlas of Cardiac Computed Tomography
CHRISTOPHER M. KRAMER & W. GREGORY HUNDLEY
Atlas of Cardiovascular Magnetic Resonance Imaging
AMI E. ISKANDRIAN & ERNEST V. GARCIA
Atlas of Nuclear Imaging
JAMES D. THOMAS
Atlas of Echocardiography
1 Molecular Mechanisms of Cardiac
C H A P T E R
Electrical Activity
IONIC EQUILIBRIUM, 1 EXCITABILITY, 7 REFERENCES, 9
TRANSMEMBRANE POTENTIALS, 1 REFRACTORINESS, 7
THE CARDIAC ACTION POTENTIAL, 2 CONDUCTION, 7
The Fast Response Action Potential, 3
EXCITATION-CONTRACTION COUPLING, 8
The Slow Response Action Potential, 6
Ionic Equilibrium excess of negative ions on the inside of the membrane, resulting in
a difference in the electrical charge (i.e., voltage difference) across
The lipid bilayer of the cell membrane is hydrophobic and imper- the cell membrane, called the membrane potential (E ). A mem-
m
meable to water-soluble substances such as ions. Hence, for the brane that exhibits an E is said to be polarized.2
m
hydrophilic ions to be able to cross the membrane, they need In nonexcitable cells, and in excitable cells in their baseline
hydrophilic paths that span the membrane (i.e., pores), which are states (i.e., not conducting electrical signals), the E is held at a
m
provided by transmembrane proteins called ion channels. Once a relatively stable value, called the resting potential. All cells have
hydrophilic pore is available, ions move passively across the mem- a negative resting E (i.e., the cytoplasm is electrically negative
m
brane driven by two forces: the electrical gradient (voltage differ- relative to the extracellular fluid), which arises from the interac-
ence) and the chemical gradient (concentration difference). The tion of ion channels and ion pumps embedded in the membrane
chemical gradient forces the ions to move from a compartment of that maintain different ion concentrations on the intracellular and
a higher concentration to one of lower concentration. The electri- extracellular sides of the membrane.2
cal gradient forces ions to move in the direction of their inverse When an ion channel opens, it allows ion flux across the mem-
sign (i.e., cations [positively charged ions] move toward a nega- brane that generates an electrical current (I). This current affects
tively charged compartment, whereas anions [negatively charged the E , depending on the membrane resistance (R), which refers
m
ions] move toward a positively charged compartment). Because to the ratio between the E and electrical current, as shown
m
the chemical and electrical gradients can oppose each other, the in Ohm’s law: E = I × R or R = E/I. Resistance arises from the fact
direction of net ion movement will depend on the relative con- that the membrane impedes the movement of charges across it;
tributions of chemical gradient and electrical potential (i.e., the hence, the cell membrane functions as a resistor. Conductance
net electrochemical gradient), so that ions tend to move spontane- describes the ability of a membrane to allow the flux of charged
ously from a higher to a lower electrochemical potential.1-3 ions in one direction across the membrane. The more permeable
The movement of an ion down its chemical gradient in one direc- the membrane is to a particular ion, the greater is the conductance
tion across the cell membrane results in build-up of excess charge of the membrane to that ion. Membrane conductance (g) is the
carried by the ion on one side of the membrane, which generates reciprocal of R: g = 1/R.1
an electrical gradient that impedes continuing ionic movement in Because the lipid bilayer of the cell membrane is very thin, accu-
the same direction. When the driving force of the electrical gradient mulation of charged ions on one side gives rise to an electrical
across the membrane becomes equal and opposite to the force gen- force (potential) that pulls oppositely charged particles toward
erated by the chemical gradient, the ion is said to be in electrochemi- the other side. Hence, the cell membrane functions as a capaci-
cal equilibrium, and the net transmembrane flux (or current) of that tor. Although the absolute potential differences across the cell
particular ion is zero. In this setting, the electrical potential is called the membrane are small, they give rise to enormous electrical poten-
equilibrium potential (E ) (reversal potential or Nernst potential) of tial gradients because they occur across a very thin surface. As a
ion
that individual ion. The E for a given ion depends on its concentra- consequence, apparently small changes in E can produce large
ion m
tion on either side of the membrane and the temperature, and it mea- changes in potential gradient and powerful forces that are able to
sures the voltage that the ion concentration gradient generates when induce molecular rearrangement in membrane proteins, such as
it acts as a battery. At membrane voltages more positive to the rever- those required for opening and closing ion channels embedded in
sal potential of the ion, passive ion movement is outward, whereas it the cell membrane. The capacitance of the membrane is generally
is inward at a membrane potential (also known as transmembrane fixed and unaffected by the molecules that are embedded in it. In
potential; E ) more negative to the Nernst potential of that channel.1,3 contrast, membrane resistance is highly variable and depends on
m
When multiple ions across a membrane are removed from their the conductance of ion channels embedded in the membrane.2,3
electrochemical equilibrium, each ion will tend to force the E The sodium (Na+), potassium (K+), calcium (Ca2+), and chlo-
m
toward its own E . The contribution of each ion type to the overall ride (Cl−) ions are the major charge carriers, and their movement
ion
E at any given moment is determined by the instantaneous per- across the cell membrane creates a flow of current that generates
m
meability of the plasma membrane to that ion. The larger the mem- excitation and signals in cardiac myocytes. The electrical current
brane conductance to a particular ion, the greater is the ability of generated by the flux of an ion across the membrane is deter-
that ion to bring the E toward its own E . Hence, the E is the aver- mined by the membrane conductance to that ion (g ) and the
m ion m ion
age of the E of all the ions to which the membrane is permeable, potential (voltage) difference across the membrane. The potential
ion
weighed according to the membrane conductance of each individ- difference represents the potential at which there is no net ion flux
ual ion relative to the total ionic conductance of the membrane.1,2 (i.e., the E ) and the actual E : current = g × (E − E ).1,4
ion m ion m ion
By convention, an inward current increases the electroposi-
Transmembrane Potentials tivity within the cell (i.e., causes depolarization of the E [to be
m
less negative]) and can result from either the movement of posi-
All living cells, including cardiomyocytes, maintain a difference in tively charged ions (most commonly Na+ or Ca2+) into the cell or
the concentration of ions across their membranes. There is a slight the efflux of negatively charged ions (e.g., Cl−) out of the cell. An
excess of positive ions on the outside of the membrane and a slight outward current increases the electronegativity within the cell
1
2
(i.e., causes hyperpolarization of the E [to become more nega- R
m
tive]) and can result from either the movement of anions into the
cell or the efflux of cations (most commonly K+) out of the cell.3
Opening and closing of ion channels can induce a departure
T wave
from the relatively static resting E , called a depolarization if the
m P wave
CH interior voltage rises (becomes less negative) or a hyperpolariza-
1 tion if the interior voltage becomes more negative. The most impor- ECG
tant ion fluxes that depolarize or repolarize the membrane are
Q
passive (i.e., the ions move down their electrochemical gradient S
without requiring the expenditure of energy), occurring through
transmembrane ion channels. In excitable cells, a sufficiently large
depolarization can evoke a short-lasting all-or-none event called an
action potential, in which the E very rapidly undergoes specific
m
and large dynamic voltage changes.1
Both resting E and dynamic voltage changes such as the action
m Ventricular
potential are caused by specific changes in membrane permeabili- A AP waveform
ties for Na+, K+, Ca2+, and Cl−, which, in turn, result from concerted Putative protein/
changes in functional activity of various ion channels, ion trans- Gene ionic current
porters, and exchangers.3 SCN5A Nav1.5/INa
CACNA1C Cav1.2 / L-type ICa
The Cardiac Action Potential CACNA1G? Cav3.1 / T-type ICa ?
CACNA1H? Cav3.2 / T-type ICa ?
NCX1 Na/Ca exchanger
Dfuunrcintigo np ohfy stiimoleo.g Tichael ceulrercetnritc flaol waicntgiv itthy,r othueg hE tmh ei sc eal l cmoenmtinburaonues KCND2/KCND3 Kv4.2/Kv4.3 +KMCiRHPIP1 ??/ Ito,1
is, at each instant, provided by multiple channels and transporters ? -- / Ito, 2
KCNQ1 KvLQT1 / IKs
carrying charge in opposite directions because of their different
KCNH2 hERG / IKr
ion selectivity. The algebraic summation of these contributions is
referred to as net transmembrane current.1 KCCFTNRA,5 CLC2/3 ?, KICvI1.5 / IKur or IKq
The cardiac action potential reflects a balance between inward CLCA1 ?, KCNK2 TREK-1 / Iss ?
and outward currents. When a depolarizing stimulus (typically KCNJ2/KCNJ12 Kir2.1 / Kir2.2 / IK1
KCNJ3/KCNJ5 Kir3.1 / Kir3.4 / IKACh
from an electric current from an adjacent cell) abruptly changes KCNJ11 Kir6.2 / IKATP
the Em of a resting cardiomyocyte to a critical value (the threshold B HCN1,2,4 If
level), the properties of the cell membrane and ion conductances
change dramatically, precipitating a sequence of events involving FIGURE 1-1 A, Depiction of a standard ECG tracing with respect to its under-
the influx and efflux of multiple ions that together produce the lying ventricular action potential (AP). B, The different ionic currents (see text) 
action potential of the cell. In this fashion, an electrical stimulus that contribute to action potential generation and the putative encoding genes 
are shown. Depolarizing currents are shown in yellow, repolarizing currents in 
is conducted from one cell to all the cells that are adjacent to it.2
blue. (Modified with permission from Saenena JB, Vrints CJ: Molecular aspects of the
Unlike skeletal muscle, cardiac muscle is electrically coupled
congenital and acquired long QT syndrome: clinical implications. J Mol Cell Cardiol
so that the wave of depolarization propagates from one cell to
44:633-646, 2007.)
the next, independent of neuronal input. The heart is activated
by capacitive currents generated when a wave of depolarization
approaches a region of the heart that is at its resting potential. value, regenerative action potential results, whereby intracellular
Unlike ionic currents, which are generated by the flux of charged movement of Na+ depolarizes the membrane more, a process that
ions across the cell membrane, capacitive currents are generated increases conductance to Na+ more, which allows more Na+ to
by the movement of electrons toward and away from the surfaces enter, and so on. In this fashion, the extent of subsequent depolar-
of the membrane.2,3 The resulting decrease in positive charge at the ization becomes independent of the initial depolarizing stimulus,
outer side of the cell membrane reduces the negative charge on the and more intense stimuli do not produce larger action potential
intracellular surface of the membrane. These charge movements, responses; rather, an all-or-none response results.2
which are carried by electrons, generate a capacitive current. When Electrical changes in the action potential follow a relatively fixed
an excitatory stimulus causes the E to become less negative and time and voltage relationship that differs according to specific
m
beyond a threshold level (approximately −65 mV for working atrial cell types. Whereas the entire action potential takes several milli-
and ventricular cardiomyocytes), Na+ channels activate (open) seconds in nerve cells, the cardiac action potential lasts several
and permit an inward Na+ current (I ), resulting in a rapid shift of hundred milliseconds. The course of the action potential can be
Na
the E to a positive voltage range. This event triggers a series of suc- divided into five phases (numbered 0 to 4). Phase 4 is the resting
m
cessive opening and closure of selectively permeable ion channels. E , and it describes the E when the cell is not being stimulated.
m m
The direction and magnitude of passive ion movement (and the During the action potential, membrane voltages fluctuate in the
resulting current) at any given transmembrane voltage are deter- range of −94 to +30 mV (Fig. 1-1). With physiological external K+, the
mined by the ratio of the intracellular and extracellular concentra- reversal potential of K+ (E ) is approximately −94 mV, and passive
K
tions and the reversal potential of that ion, with the net flux being K+ movement during an action potential is out of the cell. On the
larger when ions move from the more concentrated side.3 other hand, because the calculated reversal potential of a cardiac
The threshold is the lowest E at which opening of enough Na+ Ca2+ channel (E ) is +64 mV, passive Ca2+ flux is into the cell.5
m Ca
channels (or Ca2+ channels in the setting of nodal cells) is able In normal atrial and ventricular myocytes and in His-Purkinje
to initiate the sequence of channel openings needed to generate fibers, action potentials have very rapid upstrokes, mediated by the
a propagated action potential. Small (subthreshold) depolarizing fast inward I . These potentials are called fast response potentials.
Na
stimuli depolarize the membrane in proportion to the strength In contrast, action potentials in the normal sinus and atrioventricu-
of the stimulus and cause only local responses because they do lar (AV) nodal cells and many types of diseased tissues have very
not open enough Na+ channels to generate depolarizing currents slow upstrokes, mediated by a slow inward, predominantly L-type
large enough to activate nearby resting cells (i.e., insufficient to voltage-gated Ca2+ current (I ), rather than by the fast inward
CaL
initiate a regenerative action potential). On the other hand, when I (Fig. 1-2). These potentials have been termed slow response
Na
the stimulus is sufficiently intense to reduce the E to a threshold potentials.2,5
m