Clinical Arrhythmology and Electrophysiology: A Companion to Braunwald's Heart Disease

509 Pages·2009·30.41 MB·English

by  Ziad Issa MD

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CLINICAL ARRHYTHMOLOGY AND ELECTROPHYSIOLOGY:
A COMPANION TO BRAUNWALD’S HEART DISEASE ISBN: 978-1-4160-5998-1
Copyright © 2009 by Saunders, an imprint of Elsevier Inc.
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The Publisher
Library of Congress Cataloging-in-Publication Data
Issa, Ziad.
Clinical arrhythmology and electrophysiology : a companion to Braunwald’s heart disease /
Ziad Issa, John M. Miller, Douglas P. Zipes.—1st ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4160-5998-1
1. Arrhythmia. 2. Heart–Electric properties. I. Miller, John M. (John
Michael). 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 I86c 2009]
RC685.A65I87 2009
616.1′28–dc22 2008027014
ISBN: 978-1-4160-5998-1
Acquisitions Editor: Natasha Andjelkovic
Developmental Editor: Robin Bonner
Publishing Services Manager: Frank Polizzano
Senior Project Manager: Robin Hayward
Design Direction: Steven Stave
Working together to grow
libraries in developing countries
Printed in China. www.elsevier.com | www.bookaid.org | www.sabre.org
Last digit is the print number: 9 8 7 6 5 4 3 2
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 Reed, Donna Hillyer,
Leslie Ardebili, Alice Towers, and Ralph Chambers for their
help in preparing this manuscript.
Foreword
Disturbances in cardiac rhythm occur in a large proportion Mechanisms of Cardiac Arrhythmias, Electrophysiological
of the population. Arrhythmias can have sequelae that range Testing, Mapping and Navigation Modalities, and Ablation
from inconsequential to life-shortening. Sudden cardiac Energy Sources provide a superb introduction to the field.
deaths and chronic disability are among the most frequent This is followed by eighteen chapters on individual arrhyth-
serious complications resulting from arrhythmias. mias, each following a similar outline. Here, the authors
Braunwald’s Heart Disease: A Textbook of Cardiovascular lead us from a basic understanding of the arrhythmia to its
Medicine includes an excellent section on rhythm distur- clinical recognition, natural history, and management. The
bances edited and largely written by Douglas Zipes, the latter is moving rapidly from being largely drug-based to
most accomplished and respected investigator and clinician device-based, although many patients receive combination
in this field. However, there are many subjects that simply device-drug therapy. These options, as well as ablation
cannot be discussed in sufficient detail, even in a 2000-page therapy, are clearly spelled out as they apply to each
densely packed book. For this reason, the current editors arrhythmia.
and I decided to commission a series of companions to the We are proud to include Clinical Arrhythmology and
parent title. We were extremely fortunate to enlist Dr. Zipes’ Electrophysiology as a Companion to Braunwald’s Heart
help in editing and writing Clinical Arrhythmology and Disease, and we are fully confident that it will prove to be
Electrophysiology. Dr. Zipes, in turn, enlisted two talented valuable to cardiologists, internists, investigators, and
collaborators, Drs. Ziad F. Issa and John M. Miller, to work trainees.
with him to produce this excellent volume.
Eugene Braunwald, MD
This book is unique in several respects. First and
foremost is the very high quality of the content, which Peter Libby, MD
is accurate, authoritative, and clear; second, it is as up-to-
date as last month’s journals; third, the writing style and Robert O. Bonow, MD
illustrations are consistent throughout with little, if any, Douglas L. Mann, MD
duplication. The first four chapters on Electrophysiological
M
vii
Preface
Many books have been written about cardiac arrhythmias explanatory. In addition, our practical experience allowed
and cardiac electrophysiology, and many chapters in general us to detail the actual application of the diagnostic and
cardiology textbooks discuss the same subjects. However, therapeutic concepts, from interpreting the scalar ECG
they often focus on individual topics, such as a specific to understanding intracavitary electrograms, from drug
arrhythmia, rather than integrate, as they should, the choices to implantable devices or placement of a catheter to
electrophysiologic processes that underlie the clinical shock, record, or ablate. In all chapters the readers can
events. decide how much detail they want, from straightforward
In the chapters published in the parent title to this book, electrocardiography to practical electrophysiology to
Braunwald’s Heart Disease: A Textbook of Cardiovascular reading about mechanisms of arrhythmias. Other books in
Medicine, 8th Edition, we presented a synthesis of clinical this field give abundant information on mechanisms but are
arrhythmias with underlying electrophysiology. Size limi- of limited practical use, while others have a very pragmatic
tations, however, prevented us from discussing these topics focus without much emphasis on the mechanistic under-
in great detail. Thus, we present this companion volume not pinnings of therapy. We believe that this book provides a
only to provide more depth to these topics but also to present balanced, comprehensive perspective on the expanding
them in a format suitable for trainees, internists, and general field of diagnosis and treatment of clinical arrhythmias by
cardiologists who specialize or are interested in arrhyth- featuring consistently organized chapters and juxtaposing
mias and electrophysiology, as well as for electrophysiolo- theory and practical aspects of arrhythmia management, all
gists who need an up-to-date resource. enhanced by detailed full-color figures and useful refer-
Unlike many other clinical texts that feature chapters ences. We think that this book will find its place in the
contributed by dozens of respected authors in the field, this libraries of physicians and trainees and we hope readers
text was written by the three of us. By using this approach will enjoy and learn from it.
we could explain, integrate, coordinate, and educate in a
Ziad F. Issa
comprehensive, cohesive fashion while avoiding redundan-
cies and contradictions. We were able to choose our illustra- John M. Miller
tions in a way that is certain to be understandable and
Douglas P. Zipes
M
ix
BRAUNWALD’S HEART DISEASE COMPANIONS
Upcoming Titles
2009
Theroux: Acute Coronary Syndromes, 2nd Ed.
Otto & Bonow: Valvular Heart Disease, 3rd Ed.
Mann: Heart Failure, 2nd Ed.
Taylor: Atlas of Cardiac CT (Imaging Companion with DVD)
Kramer & Hundley: Atlas of Cardiovascular MR (Imaging Companion with DVD)
Cerqueira: Atlas of Nuclear Cardiology (Imaging Companion with DVD)
Thomas: Atlas of Echocardiography (Imaging Companion with DVD)
2010
Kormos: Mechanical Circulatory Support and Artificial Hearts
Blumenthal: Prevention of Cardiovascular Disease
Published Titles
Ballantyne: Clinical Lipidology (2008, ISBN 9781416054696)
Antman: Cardiovascular Therapeutics, 3rd Ed. (2007, ISBN 9781416033585)
Black & Elliott: Hypertension (2007, ISBN 9781416030539)
Creager, Dzau & Loscalzo: Vascular Medicine (2006, ISBN 9780721602844)
Chien: Molecular Basis of Cardiovascular Disease, 2nd Ed. (2004, ISBN 9780721694283)
Manson: Clinical Trials in Heart Disease, 2nd Ed. (2004, ISBN 9780721604084)
St. John-Sutton & Rutherford: Clinical Cardiovascular Imaging (2004, ISBN 9780721690681)
M
1
C H A P T E R
Automaticity,  Electrophysiological Mechanisms
Enhanced Normal Automaticity, 1
Abnormal Automaticity, 4 of Cardiac Arrhythmias
Overdrive Suppression of Automatic
Rhythms, 4
Arrhythmias Caused by
Automaticity, 5
Triggered Activity, 6
Delayed Afterdepolarizations and The mechanisms responsible for cardiac is found in the primary pacemaker of the
Triggered Activity, 7 arrhythmias are generally divided into cat- heart, the sinus node, as well as in certain
Early Afterdepolarizations and egories of disorders of impulse formation subsidiary or latent pacemakers that can
Triggered Activity, 9 (automaticity and triggered activity), disor- become the functional pacemaker under
ders of impulse conduction (reentry), or certain conditions. Impulse initiation is
Reentry, 0
combinations of both. The term impulse a normal property of these latent
Basic Principles of Reentry, 10
initiation is used to indicate that an electri- pacemakers.
Requisites for Reentry, 10
cal impulse can arise in a single cell or a Abnormal automaticity occurs in
Types of Reentrant Circuits, 12
group of closely coupled cells through cardiac cells only when there are major
Excitable Gaps in Reentrant
depolarization of the cell membrane and, abnormalities in their transmembrane
Circuits, 15
once initiated, can spread through the rest potentials, in particular in steady-state
Resetting Reentrant Tachycardias, 16
of the heart. There are two major causes for depolarization of the membrane potential.
Entrainment of Reentrant
the impulse initiation that can result in This property of abnormal automaticity is
Tachycardias, 19
arrhythmias, automaticity and triggered not confined to any specific latent pace-
Mechanism of Slow Conduction in
activity. Each has its own unique cellular maker cell type but can occur almost
the Reentrant Circuit, 21
mechanism that results in membrane depo- anywhere in the heart.
Anisotropy and Reentry, 22
larization. Reentry is the likely mechanism The discharge rate of normal or abnor-
Mechanism of Unidirectional Block in
of most recurrent clinical arrhythmias. mal pacemakers can be accelerated by
the Reentrant Circuit, 24
Diagnosis of the underlying mechanism drugs, various forms of cardiac disease,
References, 25 of an arrhythmia can be of great impor- reduction in extracellular potassium, or
tance in guiding appropriate treatment alterations of autonomic nervous system
strategies. Spontaneous behavior of the tone.
arrhythmia, mode of initiation and termi-
nation, and response to premature stimu-
Enhanced Normal
lation and overdrive pacing are the most
commonly used tools to distinguish among Automaticity
the different mechanisms responsible for
Pacemaker Mechanisms
cardiac arrhythmias. Our present diagnos-
tic tools, however, do not always permit Normal automaticity involves a spontane-
unequivocal determination of the electro- ous, slow, progressive decline in the
physiological mechanisms responsible for transmembrane potential during diastole
many clinical arrhythmias or their ionic (spontaneous diastolic depolarization or
bases. In particular, it can be difficult to phase 4 depolarization). Once this sponta-
distinguish among several mechanisms neous depolarization reaches threshold
that appear to have a focal origin with cen- (about −40 mV), a new action potential is
trifugal spread of activation (automaticity, generated.2
triggered activity, reentry). This is further The ionic mechanisms responsible for
complicated by the fact that some arrhyth- normal pacemaker activity in the sinus
mias can be started by one mechanism and node are still controversial. The fall in
perpetuated by another. membrane potential during phase 4 seems
to arise from a changing balance between
positive inward currents, which favor
AUTOMATICITY depolarization, and positive outward cur-
rents, with a net gain in intracellular posi-
Automaticity, or spontaneous impulse ini- tive charges during diastole (i.e., inward
tiation, is the property of cardiac cells to depolarizing current; Fig. 1-1).1,3-7
undergo spontaneous diastolic depolariza- There is evidence that diastolic depo-
tion (phase 4 depolarization) and initiate larization results from activation of an
an electrical impulse in the absence of inward current, called the pacemaker
external electrical stimulation. Altered current, I, which is carried largely by Na+
f
automaticity can be caused by enhanced but is relatively nonselective for monova-
normal automaticity or abnormal automa- lent cations. The I channels are deacti-
f
ticity.1 vated during the action potential upstroke
Enhanced normal automaticity refers to and the initial plateau phase of repolariza-
the accelerated generation of an action tion but begin to activate as repolarization
M
potential by normal pacemaker tissue and brings the membrane potential to levels

2 Normal automaticity Sinus node is a normal property, the automaticity generated by these
1 2 • Ca�� influx cells is classified as normal.
0
• Na� independent There is also a natural hierarchy of intrinsic rates of
0 3
subsidiary pacemakers that have normal automaticity, with
�40
mV 4 atrial pacemakers having faster intrinsic rates than AV junc-
�80 tional pacemakers, and AV junctional pacemakers having
1 1 2 faster rates than ventricular pacemakers.
0 HPS
• Na� influx Subsidiary Pacemakers
�40 0 3 • Cinad�e�pendent Subsidiary Atrial Pacemakers. Subsidiary atrial
mV
pacemakers have been identified in the atrial myocardium,
�80 4
especially in the crista terminalis, at the junction of the
100 ms inferior right atrium (RA) and inferior vena cava (IVC), near
or on the eustachian ridge, near the coronary sinus ostium
FIGURE 1–1 Normal cardiac automaticity. Action potentials from typical sinus
(CS os), in the atrial muscle that extends into the tricuspid
nodal and His-Purkine cells are shown with the voltage scale on the vertical axes;
dashed lines are threshold potential and numbers on figure refer to phases of the and mitral valves, and in the muscle sleeves that extend into
action potential. Note the qualitative differences between the two types of cells, as the cardiac veins (venae cavae and pulmonary veins).12
well as different rates of spontaneous depolarization. Latent atrial pacemakers can be expected to contribute
to impulse initiation in the atrium if the discharge rate of
the sinus node is reduced temporarily or permanently. In
contrast to the normal sinus node, these latent or ectopic
more negative than about −60 mV; however, because the pacemakers usually generate a fast action potential (refer-
maximum diastolic potential is about −60 mV, the role of I ring to the rate of upstroke of the action potential, dV/dT)
f
current in normal pacemaker activity has been mediated by sodium ion fluxes. However, when severely
challenged.6-9 damaged, the atrial tissue may not be able to generate a fast
Important roles for other membrane currents, including action potential (which is energy-dependent) but rather gen-
the K+ current, I , and the T- and L-type Ca2+ currents in erates a slow, calcium ion–mediated action potential (which
K
causing spontaneous diastolic depolarization, also have is energy-independent). Automaticity of subsidiary atrial
been proposed. One hypothesis is that the first third of dia- pacemakers can also be enhanced by coronary disease and
stolic depolarization results from an inward leak of Na+ ischemia, chronic pulmonary disease, or drugs such as
coupled with a time-dependent decay in the outward K+ digitalis and alcohol, possibly overriding normal sinus
current that is activated during the action potential. During activity.13,14
the latter two thirds of diastolic depolarization, a slow Subsidiary Atrioventricular Junctional Pace­
inward movement of Ca2+ occurs (T-type Ca2+ channels). makers. Some data suggest that the AVN itself has pace-
This process moves the membrane potential to the threshold maker cells, but that is controversial. However, it is clear
potential, at which time there is a more rapid inward Ca2+ that the AV junction, which is an area that includes atrial
current (L-type Ca2+ channels), generating a slow action tissue, the AVN, and His-Purkinje tissue, does have pace-
potential.2,10 Therefore, there can be no single pacemaker maker cells and is capable of exhibiting automaticity.
current in the sinus node; rather, a number of currents can Subsidiary Ventricular Pacemakers. In the ventri-
contribute to the occurrence of automaticity.4-6 cles, latent pacemakers are found in the His-Purkinje system
Automaticity in subsidiary pacemakers appears to arise (HPS), where Purkinje fibers have the property of spontane-
via a mechanism similar to that occuring in the sinus node. ous diastolic depolarization. Isolated cells of the HPS dis-
Diastolic depolarization is likely the result of an increase charge spontaneously at rates of 15 to 60 beats/min, whereas
in an inward current, I, and a decrease in outward currents ventricular myocardial cells usually do not normally exhibit
f
(I and I ).1,11 spontaneous diastolic depolarization or automaticity. The
K1 K
relatively slow spontaneous discharge rate of the HPS pace-
Hierarchy of Pacemaker Function
makers, which further decreases from the His bundle (HB)
Automaticity is an intrinsic property of all myocardial cells. to the distal Purkinje branches, ensures that pacemaker
In addition to the sinus node, cells with pacemaking capa- activity in the HPS will be suppressed on a beat-to-beat
bility in the normal heart are located in some parts of the basis by the more rapid discharge rate of the sinus node and
atria and ventricles. However, the occurrence of spontane- atrial and AV junctional pacemakers. However, enhanced
ous activity is prevented by the natural hierarchy of pace- Purkinje fiber automaticity can be induced by certain situ-
maker function, causing these sites to be latent or subsidiary ations, such as myocardial infarction (MI). In this setting,
pacemakers.1,3 The spontaneous discharge rate of the sinus some Purkinje fibers that survive the infarction develop
node normally exceeds that of all other subsidiary pacemak- moderately reduced maximum diastolic membrane poten-
ers (see Fig. 1-1). Therefore, the impulse initiated by the tials and therefore accelerated spontaneous discharge
sinus node depolarizes and keeps the activity of subsidiary rates.
pacemaker sites depressed before they can spontaneously
Autonomic and Other Influences
reach threshold. However, slowly depolarizing and previ-
ously suppressed pacemakers in the atrium, atrioventricu- The intrinsic rate at which the sinus node pacemaker cells
lar node (AVN), or ventricle can become active and assume generate impulses is determined by the interplay of three
pacemaker control of the cardiac rhythm if the sinus node factors—the maximum diastolic potential, the threshold
pacemaker becomes slow or unable to generate an impulse potential at which the action potential is initiated, and the
(e.g., secondary to depressed sinus node automaticity) or if rate or slope of phase 4 depolarization (Fig. 1-2). A change
impulses generated by the sinus node are unable to activate in any one of these factors will alter the time required for
the subsidiary pacemaker sites (e.g., sinoatrial exit block, or phase 4 depolarization to carry the membrane potential
AV block). The emergence of subsidiary or latent pacemak- from its maximum diastolic level to threshold and thus alter
ers under such circumstances is an appropriate fail-safe the rate of impulse initiation.1,7,15
mechanism, which ensures that ventricular activation is The sinus node is innervated by the parasympathetic and
M
maintained. Because spontaneous diastolic depolarization sympathetic nervous systems, and the balance between
A kinase A system; the increment in inward Ca2+ current 
0
increases the slope of diastolic depolarization and enhances
pacemaker activity (see Fig. 1-2). The redistribution of Ca2+
�40
can also increase the completeness and the rate of I deac-
mV K
tivation; the ensuing decline in the opposing outward
�80
current can result in a further net increase in inward
current. Catecholamines can also enhance the inward I 1
B f
current by shifting the voltage dependence of I to more
0 f
positive potentials, thus augmenting the slope of phase 4 E
le
�40 5 1 2 3 4 and increasing the rate of sinus node firing. ct
mV Sympathetic stimulation explains the normal response ro
p
�80 of the sinus node to stress such as exercise, fever, and hyper- h
y
thyroidism. In addition to altering ionic conductance, s
io
C 0 cohf athneg essin iuns a nuotodneo bmy isch tiofntien cg atnh ep prordimucaer yc hpaancegmesa ikne rt hree griaotne logic
within the pacemaker complex. Mapping of activation indi- a
�40 cates that at faster rates, the sinus node impulse originates l M
mV in the superior portion of the sinus node, whereas at slower ec
h
�80 200 ms rates it arises from a more inferior portion of the sinus node. an
The sinus node can be insulated from the surrounding atrial is
m
FIGURE 1–2 Abnormalities of automaticity. A, Normal His-Purkinje action myocytes, except at a limited number of preferential exit s
potential. B, Modulation of rate of depolarization from baseline (1) by slowing rate sites. Shifting pacemaker sites can select different exit path- o
of phase 4 depolarization (2), increasing threshold potential (3), starting from a ways to the atria. As a result, autonomically mediated shifts f C
more negative resting membrane potential (4), all of which slow discharge rate, or of pacemaker regions can be accompanied by changes in the ar
d
by increasing rate of phase 4 depolarization (5), yielding a faster discharge rate. sinus rate. Vagal fibers are denser in the cranial portion of ia
C, Abnormal automaticity with change in action potential contour (resembling c
sminousst snooddiaulm c eclhl)a wnnheelns. resting membrane potential is less negative, inactivating tnheer vsoiunsu ssy snteomde s hainfdts tshtiem puaclaetmioank eorf c etnhtee rp taor aa smyomrep actahuedtaicl Arrh
region of the sinus node complex, resulting in slowing of y
t
the heart rate, whereas stimulation of the sympathetic hm
these systems importantly controls the pacemaker rate. The nervous system or withdrawal of vagal stimulation shifts ia
s
classic concept has been that of a reciprocal relationship the pacemaker center cranially, resulting in an increase in
between sympathetic and parasympathetic inputs. More heart rate.16
recent investigations, however, stress dynamic, demand- Atrial, AV junctional, and HPS subsidiary pacemakers
oriented interactions, and the anatomical distribution of are also under similar autonomic control, with the sympa-
fibers that allows both autonomic systems to act quite selec- thetics enhancing pacemaker activity through beta-
1
tively. Muscarinic cholinergic and beta-adrenergic recep- adrenergic stimulation and the parasympathetics
1
tors are nonuniformly distributed in the sinus node and inhibiting pacemaker activity through muscarinic receptor
they modulate both the rate of depolarization and impulse stimulation.1
propagation.1,16 Adenosine (Ado) binds to A receptors, activating
1
Parasympathetic Activity. Parasympathetic tone I , a subtype of I identical to I , increasing outward
K/Ado K K/Ach
reduces the spontaneous discharge rate of the sinus node, K+ current in a manner similar to that of marked para-
whereas its withdrawal accelerates sinus node automaticity. sympathetic stimulus. It also has similar effects on I
f
Acetylcholine, the principal neurotransmitter of the para- channels.7,15
sympathetic nervous system, inhibits spontaneous impulse Digitalis exerts two effects on the sinus rate. It has a
generation in the sinus node by increasing K+ conductance. direct positive chronotropic effect on the sinus node, result-
Acetylcholine acts through M muscarinic receptors to acti- ing from depolarization of the membrane potential caused
2
vate the G protein, which subsequently results in activation by inhibition of the Na+-K+ exchange pump. The reduction
i
of I (an acetylcholine-activated subtype of inward rec- in the maximum diastolic membrane potential decreases
K/Ach
tifying current) in tissues of the sinus node and AVN as well the time required for the membrane to depolarize to thresh-
as of the atria, Purkinje fibers, and ventricles. The increased old, thereby accelerating the spontaneous discharge rate.14
outward repolarizing K+ current leads to membrane hyper- However, it also enhances vagal tone, which decreases spon-
polarization (i.e., the resting potential and the maximum taneous sinus discharge. The latter effect can dominate
diastolic potential become more negative). The resulting when sympathetic activity has been enhanced, such as
hyperpolarization of the membrane potential lengthens the during heart failure.5
time required for the membrane potential to depolarize to Enhanced subsidiary pacemaker activity may not require
threshold, thereby decreasing the automaticity of the sinus sympathetic stimulation. Normal automaticity can be
node (see Fig. 1-2). In addition, activation of G protein affected by a number of other factors associated with heart
i
results in inhibition of beta receptor–stimulated adenylate disease.8 Inhibition of the electrogenic Na+-K+ exchange
cyclase activity, reducing cyclic adenosine monophosphate pump results in a net increase in inward current during
(cAMP) and inhibiting protein kinase A, with subsequent diastole because of the decrease in outward current nor-
inhibition of the inward Ca2+ current, I . This results in mally generated by the pump, and therefore can increase
Ca
reduction of the rate of diastolic depolarization because of automaticity in subsidiary pacemakers sufficiently to cause
less calcium entry and subsequent slowing of the pacemaker arrhythmias. This can occur when adenosine triphosphate
activity. Inhibition of beta receptor–stimulated adenylate (ATP) is depleted during prolonged hypoxia or ischemia, or
cyclase activity can also inhibit the inward I current.15,16 in the presence of toxic amounts of digitalis. Hypokalemia
f
Sympathetic Activity. Increased sympathetic nerve can reduce the activity of the Na+-K+ exchange pump, thereby
traffic as well as the adrenomedullary release of catechol- reducing the background repolarizing current and enhanc-
amines increases the sinus rate. Stimulation of beta recep- ing phase 4 diastolic depolarization. The end result would
1
tors by catecholamines enhances the L-type of inward Ca2+ be an increase in the discharge rate of pacemaking cells.
M
current by increasing cAMP and activating the protein Additionally, the flow of current between partially depolar-
 ized myocardium and normally polarized latent pacemaker automaticity in the AVN—for example, where the mem-
cells can enhance automaticity. This mechanism has been brane potential is normally low—is not classified as abnor-
proposed to be a cause of some of the ectopic complexes that mal automaticity.
arise at the borders of ischemic areas in the ventricle. Several different mechanisms probably cause abnormal
Slightly increased extracellular K+ can render the maximum pacemaker activity at low membrane potentials, including
diastolic potential more positive (i.e., reduced or less nega- activation and deactivation of delayed rectifier K+ currents,
1 tive), thereby also increasing the discharge rate of pacemak- intracellular Ca2+ release from the sarcoplasmic reticulum,
ing cells. A greater increase in extracellular K+, however, causing activation of inward Ca2+ currents and inward Na+
renders the heart inexcitable by depolarizing the membrane current (through Na+-Ca2+ exchange), and potential contri-
potential and inactivating the Na+ current.15 bution by the pacemaker current I.5,20 It has not been deter-
f
Evidence indicates that active and passive changes in the mined which of these mechanisms are operative in the
mechanical environment of the heart provide feedback to different pathological conditions in which abnormal auto-
modify cardiac rate and rhythm, and are capable of influ- maticity can occur.1
encing both the initiation and spread of cardiac excitation. The upstroke of the spontaneously occurring action
This direction of the crosstalk between cardiac electrical potentials generated by abnormal automaticity can be caused
and mechanical activity is referred to as mechanoelectric by Na+ or Ca2+ inward currents or possibly a combination of
feedback, and is thought to be involved in the adjustment the two.1 In the range of diastolic potentials between approx-
of heart rate to changes in mechanical load, which would imately −70 and −50 mV, repetitive activity is dependent on
help explain the precise beat-to-beat regulation of cardiac extracellular Na+ concentration and can be decreased or
performance. Acute mechanical stretch enhances automa- abolished by Na+ channel blockers. In a diastolic potential
ticity, reversibly depolarizes the cell membrane, and short- range of approximately −50 to −30 mV, Na+ channels are
ens the action potential duration. Feedback from cardiac predominantly inactivated; repetitive activity depends on
mechanics to electrical activity involves mechanosensitive extracellular Ca2+ concentration and is reduced by L-type
ion channels, among them K+-selective, chloride-selective, Ca2+ channel blockers.
nonselective, and ATP-sensitive K+ channels. In addition, The intrinsic rate of a focus with abnormal automaticity
Na+ and Ca2+ entering the cells via nonselective ion channels is a function of the membrane potential. The more positive
are thought to contribute to the genesis of stretch-induced the membrane potential, the faster the automatic rate (see
arrhythmia.15,17-19 Fig. 1-2). Abnormal automaticity is less vulnerable to sup-
pression by overdrive pacing (see later). Therefore, even
occasional slowing of the sinus node rate can allow an
Abnormal Automaticity
ectopic focus with abnormal automaticity to fire without a
In the normal heart, automaticity is confined to the sinus preceding long period of quiescence.5
node and other specialized conducting tissues. Working The decrease in the membrane potential of cardiac cells
atrial and ventricular myocardial cells do not normally required for abnormal automaticity to occur can be induced
have spontaneous diastolic depolarization and do not initi- by a variety of factors related to cardiac disease, such as
ate spontaneous impulses, even when they are not excited ischemia and infarction. The circumstance under which
for long periods of time by propagating impulses.8 Although membrane depolarization occurs, however, can influence
these cells do have a pacemaker current, I, the range of the development of abnormal automaticity. For example, an
f
activation of this current in these cells is much more nega- increase in extracellular K+ concentration, as occurs in
tive (−120 to −170 mV) than in Purkinje fibers or in the sinus acutely ischemic myocardium, can reduce membrane poten-
node. As a result, during physiological resting membrane tial; however, normal or abnormal automaticity in working
potentials (−85 to −95 mV), the pacemaker current is not atrial, ventricular, and Purkinje fibers usually does not
activated and ventricular cells do not depolarize spontane- occur because of the increase in K+ conductance (and hence
ously.1 When the resting potentials of these cells are depo- net outward current) that results from an increase in extra-
larized sufficiently, to about −70 to −30 mV, however, cellular K+ concentration.8 Catecholamines also increase
spontaneous diastolic depolarization can occur and cause the rate of discharge caused by abnormal automaticity
repetitive impulse initiation, a phenomenon called depolar- and therefore can contribute to a shift in the pacemaker
ization-induced automaticity or abnormal automaticity (see site, from the sinus node to a region with abnormal
Fig. 1-2). Similarly, cells in the Purkinje system, which are automaticity.
normally automatic at high levels of membrane potential,
show abnormal automaticity when the membrane potential
Overdrive Suppression of
is reduced to around −60 mV or less, which can occur in
ischemic regions of the heart. When the steady-state mem- Automatic Rhythms
brane potential of Purkinje fibers is reduced to around
Suppression of Normal and Abnormal
−60 mV or less, the I channels that participate in normal
f Automatic Subsidiary Pacemakers
pacemaker activity in Purkinje fibers are closed and non-
functional and automaticity is, therefore, not caused by The sinus node likely maintains its dominance over subsid-
the normal pacemaker mechanism. It can, however, be iary pacemakers in the AVN and the Purkinje fibers by
caused by an “abnormal” mechanism. In contrast, enhanced several mechanisms. During sinus rhythm in a normal
automaticity of the sinus node, subsidiary atrial pacemak- heart, the intrinsic automatic rate of the sinus node is faster
ers, or the AVN caused by a mechanism other than accelera- than that of the other potentially automatic cells. Conse-
tion of normal automaticity has not been demonstrated quently, the latent pacemakers are excited by propagated
clinically.5 impulses from the sinus node before they have a chance to
A low level of membrane potential is not the only crite- depolarize spontaneously to threshold potential. The higher
rion for defining abnormal automaticity. If this were so, the frequency of sinus node discharge also suppresses the auto-
automaticity of the sinus node would have to be considered maticity of other pacemaker sites by a mechanism called
abnormal. Therefore, an important distinction between overdrive suppression. The diastolic (phase 4) depolariza-
abnormal and normal automaticity is that the membrane tion of the latent pacemaker cells with the property of
potentials of fibers showing the abnormal type of activity normal automaticity is actually inhibited because they are
M
are reduced from their own normal level. For this reason, repeatedly depolarized by the impulses from the sinus