ContentsPreface to the Fourth Edition, viiAcknowledgements, viiiPart I: Disorders of the Heart Rhythm: Basic Principles, 1 1 The Cardiac Electrical System, 3 2 Abnormal Heart Rhythms, 12 3 Treatment of Arrhythmias, 22Part II: The Electrophysiology Study in the Evaluation andTherapy of Cardiac Arrhythmias, 33 4 Principles of the Electrophysiology Study, 35 5 The Electrophysiology Study in the Evaluation of the SA Node, AV Node and His-Purkinje System, 58 6 The Electrophysiology Study in the Evaluation of Supraventricular Tachyarrhythmias, 103 7 The Electrophysiology Study in the Evaluation and Treatment of Ventricular Arrhythmias, 158 8 Transcatheter Ablation: Therapeutic Electrophysiology, 211 9 Cardiac Resynchronization: Pacing Therapy for Heart Failure, 25310 The Evaluation of Syncope, 26611 Electrophysiologic Testing in Perspective: The Evaluation and Treatment of Cardiac Arrhythmias, 278Index, 288 v
Preface to the Fourth EditionIt is gratifying to me that Electrophysiologic Testing has continued togenerate an audience through three editions, and especially gratifyingthat that audience has remained the one I originally intended. Whenthis book was ﬁrst written, there were no other books available thatattempted to explain and de-mystify the arcane world of the electro-physiologist to students, residents, cardiology fellows, primary carephysicians, cardiologists, nurses, and technicians. Now that there are afew others that do so, I am very pleased that readers continue to ﬁnd thisone useful. I have made extensive revisions to this fourth edition. Chapters 5 and7 have been completely rewritten, Chapters 6 and 8 have been substan-tially revised, Chapter 9 is entirely new, and smaller changes have beenmade throughout. Despite making these many changes, I have attempteddiligently to adhere to my original intent — to provide a quick and rela-tively painless introduction to the ﬁeld of cardiac electrophysiology.This latest edition continues to emphasize the basic principles of elec-trophysiology, and to show how those principles underlie the testing(and the therapy) that take place in the electrophysiology laboratory, aswell as the clinical decisions made by electrophysiologists, whether ornot those decisions involve invasive testing. I would like to thank once again the many readers who took the timeto let me know that this volume has made a difference in their profes-sional lives. It is that, above everything else, which has motivated me tocontinue working hard to keep this project relevant and useful. Richard N. Fogoros, MD vii
AcknowledgementsI would like to acknowledge the suggestions made to me by severalreaders as to how I could improve this book. I hope at least a few of youﬁnd evidence herein that your advice was listened to. I would especially like to thank Liz Bush, Principal Systems Engineerat St Jude Medical, who suggested to me a few years ago (after listening tome lecture on matters electrophysiologic for a day and a half), that mybook would be much better if only I would ﬁx numerous typos and othersmall errors. When I explained that I had ﬁxed all the errors I knewabout, she rolled her eyes and said she would make a list. I had forgottenthe exchange entirely until last year, when I was about to begin work onthis present edition. Out of the blue I received an e-mail from Liz — herlist was ready. It was a much longer list than I had thought possible, butevery item on it accurately identiﬁed something that required my atten-tion. Liz, I have tried diligently to ﬁx every problem you identiﬁed (and,if only to spare you any more work, have also tried diligently not to intro-duce any new ones). I deeply appreciate all the time you spent on this,and I am truly gratiﬁed that a busy professional such as yourself caredenough about this project to extend such an effort. Finally, I would like to thank my wife Anne and my children Emilyand Joe, who, once again, lovingly accepted the periods of moodinessand inattentiveness that seem to accompany my working on new edi-tions of Electrophysiologic Testing. Without their love and support,neither this book nor anything else I might have accomplished in lifewould seem the least bit worthwhile.viii
PA R T IDisorders of the Heart Rhythm:Basic Principles
CHAPTER 1The Cardiac Electrical SystemThe heart spontaneously generates electrical impulses, and these elec-trical impulses are vital to all cardiac functions. On a basic level, by con-trolling the ﬂux of calcium ions across the cardiac cell membrane, theseelectrical impulses trigger cardiac muscle contraction. On a higher level,the heart’s electrical impulses organize the sequence of muscle contrac-tion during each heartbeat, important for optimizing the cardiac strokevolume. Finally, the pattern and timing of these impulses determine theheart rhythm. Derangements in this rhythm often impair the heart’sability to pump enough blood to meet the body’s demands. Thus, the heart’s electrical system is fundamental to cardiac func-tion. The study of the electrical system of the heart is called cardiac elec-trophysiology, and the main concern of the ﬁeld of electrophysiology iswith the mechanisms and therapy of cardiac arrhythmias. The electro-physiology study is the most deﬁnitive method of evaluating the cardiacelectrical system; it is the subject of this book. As an introduction to the ﬁeld of electrophysiology and to the electro-physiology study, this chapter reviews the anatomy of the cardiac elec-trical system and describes how the vital electrical impulse is normallygenerated and propagated.The anatomy of the heart’s electrical systemThe heart’s electrical impulse originates in the sinoatrial (SA) node,located high in the right atrium near the superior vena cava. The impulseleaves the SA node and spreads radially across both atria. When theimpulse reaches the atrioventricular (AV) groove, it encounters the“skeleton of the heart,” the ﬁbrous structure to which the valve rings areattached, and that separates the atria from the ventricles. This ﬁbrousstructure is electrically inert and acts as an insulator — the electrical 3
4 I Disorders of the Heart Rhythm: Basic Principlesimpulse cannot cross this structure. Thus, the electrical impulse wouldbe prevented from crossing over to the ventricular side of the AV grooveif not for the specialized AV conducting tissues: the AV node and thebundle of His (Figure 1.1). As the electrical impulse enters the AV node, its conduction is slowedbecause of the electrophysiologic properties of the AV nodal tissue. Thisslowing is reﬂected in the PR interval on the surface electrocardiogram(ECG). Leaving the AV node, the electrical impulse enters the Hisbundle, the most proximal part of the rapidly conducting His-Purkinjesystem. The His bundle penetrates the ﬁbrous skeleton and delivers theimpulse to the ventricular side of the AV groove. Once on the ventricular side, the electrical impulse follows the Hisbundle as it branches into the right and left bundle branches. Branchingof the Purkinje ﬁbers continues distally to the furthermost reaches ofthe ventricular myocardium. The electrical impulse is thus rapidly dis-tributed throughout the ventricles.Fig. 1.1 Anatomy of the electrical system of the heart.
1 The Cardiac Electrical System 5 Hence, the heart’s electrical system is designed to organize thesequence of myocardial contraction with each heartbeat. As the electri-cal impulse spreads over the atria toward the AV groove, the atria con-tract. The delay provided by the AV node allows for complete atrialemptying before the electrical impulse reaches the ventricles. Once theimpulse leaves the AV node, it is distributed rapidly throughout the ven-tricular muscle by the Purkinje ﬁbers, providing for brisk and orderlyventricular contraction. We next consider the character of the electrical impulse, its genera-tion, and propagation.The cardiac action potentialThe cardiac action potential is one of the most despised and misunder-stood topics in cardiology. The fact that electrophysiologists claim tounderstand it is also a leading cause of the mystique that surrounds themand their favorite test, the electrophysiology study. Because the purposeof this book is to debunk the mystery of electrophysiology studies, wemust confront the action potential and learn to understand it. Fortu-nately, this is far easier than legend would have it. Although most of us would like to think of cardiac arrhythmias as anirritation or “itch” of the heart (and of antiarrhythmic drugs as a balmor a salve that soothes the itch), this conceptualization of arrhythmias iswrong and leads to the faulty management of patients with arrhythmias.In fact, the behavior of the heart’s electrical impulse and of the cardiacrhythm is largely determined by the shape of the action potential; theeffect of antiarrhythmic drugs is determined by how they change thatshape. The inside of the cardiac cell, like all living cells, has a negative electri-cal charge compared to the outside of the cell. The resulting voltage dif-ference across the cell membrane is called the transmembrane potential.The resting transmembrane potential (which is −80 to −90 mV in cardiacmuscle) is the result of an accumulation of negatively charged molecules(called ions) within the cell. Most cells are happy with this arrangementand live out their lives without considering any other possibilities. Cardiac cells, however, are excitable cells. When excitable cells arestimulated appropriately, tiny pores or channels in the cell membraneopen and close sequentially in a stereotyped fashion. The opening ofthese channels allows ions to travel back and forth across the cellmembrane (again in a stereotyped fashion), leading to patternedchanges in the transmembrane potential. When these stereotypicvoltage changes are graphed against time, the result is the cardiac action
6 I Disorders of the Heart Rhythm: Basic PrinciplesFig. 1.2 The cardiac action potential.potential (Figure 1.2). The action potential is thus a reﬂection of theelectrical activity of a single cardiac cell. As can be seen in Figure 1.2, the action potential is classically dividedinto ﬁve phases. However, it is most helpful to consider the action poten-tial in terms of three general phases: depolarization, repolarization, andthe resting phase.DepolarizationThe depolarization phase (phase 0) is where the action of the actionpotential is. Depolarization occurs when the rapid sodium channels inthe cell membrane are stimulated to open. When this happens, posi-tively charged sodium ions rush into the cell, causing a rapid, positivelydirected change in the transmembrane potential. The resultant voltagespike is called depolarization. When we speak of the heart’s electricalimpulse, we are speaking of this depolarization. Depolarization of one cell tends to cause adjacent cardiac cells todepolarize, because the voltage spike of a cell’s depolarization causes thesodium channels in the nearby cells to open. Thus, once a cardiac cell isstimulated to depolarize, the wave of depolarization (the electricalimpulse) is propagated across the heart, cell by cell. Further, the speed of depolarization of a cell (reﬂected by the slope ofphase 0 of the action potential) determines how soon the next cell will
1 The Cardiac Electrical System 7depolarize, and thus determines the speed at which the electrical impulseis propagated across the heart. If we do something to change the speed atwhich sodium ions enter the cell (and thus change the slope of phase 0),we therefore change the speed of conduction (the conduction velocity)of cardiac tissue.RepolarizationOnce a cell is depolarized, it cannot be depolarized again until the ionicﬂuxes that occur during depolarization are reversed. The process ofgetting the ions back to where they started is called repolarization. Therepolarization of the cardiac cell roughly corresponds to phases 1through 3 (i.e., the width) of the action potential. Because a seconddepolarization cannot take place until repolarization occurs, the timefrom the end of phase 0 to late in phase 3 is called the refractory period ofcardiac tissue. Repolarization of the cardiac cells is complex and poorly understood.Fortunately, the main ideas behind repolarization are simple: 1) repo-larization returns the cardiac action potential to the resting transmem-brane potential; 2) it takes time to do this; 3) the time that it takes to dothis, roughly corresponding to the width of the action potential, is therefractory period of cardiac tissue. There is an additional point of interest regarding repolarization of thecardiac action potential. Phase 2 of the action potential, the so-calledplateau phase, can be viewed as interrupting and prolonging the repo-larization that begins in phase 1. This plateau phase, which is unique tocardiac cells (e.g., it is not seen in nerve cells), gives duration to thecardiac potential. It is mediated by the slow calcium channels, whichallow positively charged calcium ions to slowly enter the cell, thus inter-rupting repolarization and prolonging the refractory period. Thecalcium channels have other important effects in electrophysiology, aswe will see.The resting phaseFor most cardiac cells, the resting phase (the period of time betweenaction potentials, corresponding to phase 4) is quiescent, and there is nonet movement of ions across the cell membrane. For some cells, however, the so-called resting phase is not quiescent.In these cells, there is leakage of ions back and forth across the cellmembrane during phase 4 in such a way as to cause a gradual increasein transmembrane potential (Figure 1.3). When the transmembranepotential is high enough (i.e., when it reaches the threshold voltage), theappropriate channels are activated to cause the cell to depolarize.
8 I Disorders of the Heart Rhythm: Basic PrinciplesFig. 1.3 Automaticity. In some cardiac cells, there is a leakage of ions across the cellmembrane during phase 4 in such a way as to cause a gradual, positively directedchange in transmembrane voltage. When the transmembrane voltage becomessufﬁciently positive, the appropriate channels are activated to automatically generateanother action potential. This spontaneous generation of action potentials due tophase 4 activity is called automaticity.Because this depolarization, like any depolarization, can stimulatenearby cells to depolarize in turn, the spontaneously generated electri-cal impulse can be propagated across the heart. This phase 4 activity,which leads to spontaneous depolarization, is called automaticity. Automaticity is the mechanism by which the normal heart rhythm isgenerated. Cells in the SA node (the pacemaker of the heart) normallyhave the fastest phase 4 activity within the heart. The spontaneouslyoccurring action potentials in the SA node are propagated as describedearlier, resulting in normal sinus rhythm. If, for any reason, the automa-ticity of the sinus node should fail, there are usually secondary pace-maker cells (often located in the AV junction) that take over thepacemaker function of the heart, but at a slower rate. Thus, the shape of the action potential determines the conductionvelocity, refractory period, and automaticity of cardiac tissue. Later weshall see how these three electrophysiologic characteristics directlyaffect the mechanisms of cardiac rhythms, both normal and abnormal.To a large extent, the purpose of the electrophysiology study is to assessthe conduction velocities, refractory periods, and automaticity ofvarious portions of the heart’s electrical system.Localized variations in the heart’selectrical systemIn understanding cardiac arrhythmias, it is important to consider twoissues involving localized differences in the heart’s electrical system:variations in the action potential and variations in autonomicinnervation.
1 The Cardiac Electrical System 9Localized differences in the action potentialThe cardiac action potential does not have the same shape in every cellof the heart’s electrical system. The action potential we have been usingas a model (see Figure 1.2) is a typical Purkinje ﬁber action potential.Figure 1.4 shows representative action potentials from several key loca-tions of the heart — note the differences in shape. The action potentials that differ most radically from the Purkinjeﬁber model are found in the SA node and AV node. Note that the actionpotentials from these tissues have slow instead of rapid depolarizationphases (phase 0). This slow depolarization occurs because SA nodal andAV nodal tissues lack the rapid sodium channels responsible for therapid depolarization phase (phase 0) seen in other cardiac tissues. Infact, the SA and AV nodes are thought to be dependent entirely on theslow calcium channel for depolarization. Because the speed of depolar-ization determines conduction velocity, the SA and AV nodes conductelectrical impulses slowly. The slow conduction in the AV node isreﬂected in the PR interval on the surface ECG (see Figure 1.5).Localized differences in autonomic innervationIn general, an increase in sympathetic tone causes enhanced automatic-ity (pacemaker cells ﬁre more rapidly), increased conduction velocity(electrical impulses are propagated more rapidly), and decreased actionpotential duration and thus decreased refractory periods (cells are readyfor repeated depolarizations more quickly). Parasympathetic tone hasFig. 1.4 Localized differences in the cardiac action potential. Cardiac action potentialsfrom different locations within the heart have different shapes. These differencesaccount for the differences seen in electrophysiologic properties in various tissueswithin the heart.
10 I Disorders of the Heart Rhythm: Basic PrinciplesFig. 1.5 Relationship between the ventricular action potential (top) and the surfaceECG (bottom). The rapid depolarization phase (phase 0) of the action potential isreﬂected in the QRS complex on the surface ECG. Because phase 0 is almostinstantaneous, the QRS complex yields directional information on ventriculardepolarization. In contrast, the repolarization portion of the action potential hassigniﬁcant duration (phases 2 and 3). Consequently, the portion of the surface ECG thatreﬂects repolarization (the ST segment and the T wave) yields little directionalinformation. PR interval, beginning of P to beginning of QRS; ST segment, end of QRSto beginning of T; QT interval, beginning of QRS to end of T.the opposite effect (i.e., depressed automaticity, decreased conductionvelocity, and increased refractory periods). Sympathetic and parasympathetic ﬁbers richly innervate both the SAnode and the AV node. In the remainder of the heart’s electrical system,while sympathetic innervation is abundant, parasympathetic innerva-tion is relatively sparse. Thus, changes in parasympathetic tone have arelatively greater effect on the SA nodal and AV nodal tissues than onother tissues of the heart. This fact has implications for the diagnosisand treatment of some heart rhythm disturbances.
1 The Cardiac Electrical System 11Relationship between action potential andsurface ECGThe cardiac action potential represents the electrical activity of a singlecardiac cell. The surface ECG reﬂects the electrical activity of the entireheart — essentially, it represents the sum of all the action potentials of allcardiac cells. Consequently, the information one can glean from thesurface ECG derives from the characteristics of the action potential(Figure 1.5). For most cardiac cells, the depolarization phase of the action poten-tial is essentially instantaneous (occurring in 1 to 3 msec) and occurssequentially, from cell to cell. Thus, the instantaneous wave of depolar-ization can be followed across the heart by studying the ECG. The Pwave represents the depolarization front as it traverses the atria, and theQRS complex tracks the wave of depolarization as it spreads across theventricles. Changes in the spread of the electrical impulse, such as occurin bundle branch block or in transmural myocardial infarction, can bereadily diagnosed. Because the depolarization phase of the action poten-tial is relatively instantaneous, the P wave and the QRS complex canyield speciﬁc directional information (i.e., information on the sequenceof depolarization of cardiac muscle). In contrast, the repolarization phase of the action potential is notinstantaneous — indeed, repolarization has signiﬁcant duration. Thus,while depolarization occurs from cell to cell sequentially, repolarizationoccurs in many cardiac cells simultaneously. For this reason, the STsegment and T wave (the portions of the surface ECG that reﬂect ven-tricular repolarization) give little directional information, and abnor-malities in the ST segments and T waves are most often (and quiteproperly) interpreted as being nonspeciﬁc. The QT interval representsthe time of repolarization of the ventricular myocardium and reﬂectsthe average action potential duration of ventricular muscle.
CHAPTER 2Abnormal Heart RhythmsAbnormalities in the electrical system of the heart result in two generaltypes of cardiac arrhythmias: heart rhythms that are too slow (brady-arrhythmias) and heart rhythms that are too fast (tachyarrhythmias).To understand the use of the electrophysiology study in evaluatingcardiac arrhythmias, one needs a basic understanding of the mecha-nisms of these arrhythmias.BradyarrhythmiasThere are two broad categories of abnormally slow heart rhythms — thefailure of pacemaker cells to generate appropriate electrical impulses(disorders of automaticity) and the failure to propagate electricalimpulses appropriately (heart block).Failure of impulse generationFailure of SA nodal automaticity, resulting in an insufﬁcient number ofelectrical impulses emanating from the SA node (i.e., sinus bradycardia[Figure 2.1]), is the most common cause of bradyarrhythmias. If theslowed heart rate is insufﬁcient to meet the body’s demands, symptomsresult. Symptomatic sinus bradycardia is called sick sinus syndrome. Ifsinus slowing is profound, subsidiary pacemakers located near the AVjunction can take over the pacemaker function of the heart. The electro-physiology study, as we will see in Chapter 5, can be useful in assessingSA nodal automaticity.Failure of impulse propagationThe second major cause of bradyarrhythmias is the failure of the electri-cal impulses generated by the SA node (or by subsidiary atrial pacemak-ers) to conduct normally to the ventricles. This condition, known as12
2 Abnormal Heart Rhythms 13Fig. 2.1 Sinus bradycardia.heart block or AV block, implies an abnormality of conduction velocityand/or refractoriness in the conducting system. Because conduction ofthe electrical impulse to the ventricles depends on the function of theAV node and the His-Purkinje system, heart block is virtually alwaysdue to AV nodal or His-Purkinje disease. Heart block is classiﬁed into three categories based on severity (Figure2.2). First-degree AV block means that, while all atrial impulses aretransmitted to the ventricles, intraatrial conduction, conductionthrough the AV node, and/or conduction through the His bundle is slow(manifested on the ECG by a prolonged PR interval). Second-degree AVblock means that conduction to the ventricles is intermittent; that is,some impulses are conducted and some are blocked. Third-degree AVblock means that block is complete and no atrial impulses are conductedto the ventricles. If third-degree AV block is present, then sustaining life depends onthe function of subsidiary pacemakers distal to the site of block. Thecompetence of these subsidiary pacemakers, and therefore the patient’sprognosis, depends largely on the site of block (Figure 2.3). When blockis within the AV node, subsidiary pacemakers at the AV junction usuallytake over the pacemaker function of the heart, resulting in a relativelystable, non–life-threatening heart rhythm, with a rate often in excess of50 beats/min. On the other hand, if block is distal to the AV node, thesubsidiary pacemakers tend to produce a profoundly slow (usually lessthan 40 beats/min) and unstable heart rhythm. If heart block is less than complete (i.e., ﬁrst- or second-degree), it isstill important to pinpoint the site of block to either the AV node or theHis-Purkinje system. First- or second-degree block in the AV node isbenign and tends to be nonprogressive. Thus, implanting a permanentpacemaker is rarely required. First- and especially second-degree blockdistal to the AV node, on the other hand, tends to progress to a higherdegree of block; prophylactic pacing is often indicated. Differentiating the site of heart block requires careful evaluation.This evaluation can usually be made noninvasively by studying thesurface ECG and taking advantage of the AV node having rich autonomicinnervation which the His-Purkinje system does not have. Sometimes,
14 I Disorders of the Heart Rhythm: Basic PrinciplesFig. 2.2 Three categories of heart block. In ﬁrst-degree block (top tracing), all atrialimpulses are conducted to the ventricles, but conduction is slow (the PR interval isprolonged). In second-degree block (middle tracing), some atrial impulses areconducted and some are not. In third-degree block (bottom tracing), none of the atrialimpulses are conducted to the ventricles.Fig. 2.3 Examples of escape pacemakers. When block is localized to the AV node (toptracing), junctional escape pacemakers (JE) are usually stable enough to preventhemodynamic collapse. When block is located in the distal conducting tissues (bottomtracing), escape pacemakers are usually located in the ventricles (VE) and are slowerand much less stable.however, the electrophysiology study is useful in locating the site ofblock. Chapter 5 considers this in detail.TachyarrhythmiasCardiac tachyarrhythmias can cause signiﬁcant mortality and mor-bidity. It is the ability of the electrophysiology study to address the
2 Abnormal Heart Rhythms 15evaluation and treatment of tachyarrhythmias that has brought thisprocedure into widespread use. We will discuss three mechanismsfor tachyarrhythmias — automaticity, reentry, and triggered activity.AutomaticityAutomaticity has been discussed as a normal pacemaker function of theheart. When abnormal acceleration of phase 4 activity occurs in somelocation of the heart, an automatic tachyarrhythmia is said to occur(Figure 2.4). Such an abnormal automatic focus can appear in the atria,the AV junction, or the ventricles (thus leading to automatic atrial, junc-tional, or ventricular tachycardia). Automaticity is not a common cause of tachyarrhythmias, probablyaccounting for less than 10% of all abnormal tachyarrhythmias. Auto-matic tachyarrhythmias are usually recognizable by their characteris-tics and the settings in which they occur. In gaining an understanding of the automatic tachyarrhythmias, it ishelpful to consider the characteristics of sinus tachycardia, which is anormal automatic tachycardia. Sinus tachycardia usually occurs as aresult of appropriately increased sympathetic tone (for instance, inresponse to increased metabolic needs during exercise). When sinustachycardia develops, the heart rate gradually increases from the basic(resting) sinus rate; when sinus tachycardia subsides, the rate likewisedecreases gradually. Similarly, automatic tachyarrhythmias often display a warm-up andwarm-down in rate when the arrhythmia begins and ends. Analogous tosinus tachycardia, automatic tachyarrhythmias also often have meta-bolic causes, such as acute cardiac ischemia, hypoxemia, hypokalemia,hypomagnesemia, acid–base disorders, high sympathetic tone, and theuse of sympathomimetic agents. Therefore, automatic arrhythmias areoften seen in acutely ill patients, often in the intensive care setting, withall the attendant metabolic abnormalities. For example, acute pulmo-nary disease can lead to multifocal atrial tachycardia, the most commontype of automatic atrial tachycardia. Induction of, and recovery from,general anesthesia can cause surges in sympathetic tone and automaticarrhythmias (both atrial and ventricular) can result. In addition, acutemyocardial infarction is often accompanied by early ventriculararrhythmias which are most likely automatic in mechanism. Of all tachyarrhythmias, automatic arrhythmias resemble an “itch ofthe heart” the most closely, and it is tempting to apply the salve of antiar-rhythmic drugs. Antiarrhythmic drugs can sometimes decrease auto-maticity; automatic arrhythmia, however, should be treated primarilyby identifying and reversing the underlying metabolic cause.
16 I Disorders of the Heart Rhythm: Basic PrinciplesFig. 2.4 Abnormal automaticity causes the rapid generation of action potentials andthus inappropriate tachycardia. Automatic tachyarrhythmias cannot be induced by programmedpacing techniques, so these arrhythmias are generally not amenable toprovocative study in the electrophysiology laboratory.ReentryReentry is the most common mechanism for tachyarrhythmias; it is alsothe most important, because reentrant arrhythmias cause the deaths ofhundreds of thousands of people every year. Fortunately, reentrantarrhythmias lend themselves nicely to study in the electrophysiologylaboratory. It was the recognition that most tachyarrhythmias are reen-trant in mechanism and that the electrophysiology study can help sig-niﬁcantly in assessing reentrant arrhythmias that led to widespreadproliferation of electrophysiology laboratories since the early 1980s. Unfortunately, the mechanism of reentry is not simple to explain or tounderstand, and the prerequisites for reentry seem on the surface to beunlikely at best. The failure to understand (and possibly to believe in)reentry has helped keep the electrophysiology study an enigma to mostpeople in the medical profession. The following explanation of reentrytherefore errs on the side of simplicity and might offend some electro-physiologists. If the reader can keep an open mind and accept this expla-nation for now, we hope to show later (in Chapters 6 and 7) that reentryis a compelling explanation for most cardiac tachyarrhythmias. Reentry requires that the following criteria be met (Figure 2.5). First,two roughly parallel conducting pathways (shown as pathways A and B)must be connected proximally and distally by conducting tissue, thusforming a potential electrical circuit. Second, one of the pathways(pathway B in our example) must have a refractory period that is sub-stantially longer than the refractory period of the other pathway. Third,the pathway with the shorter refractory period (pathway A) mustconduct electrical impulses more slowly than the other pathway.
2 Abnormal Heart Rhythms 17Fig. 2.5 Prerequisites for reentry. An anatomic circuit must be present in which twoportions of the circuit (pathways A and B in the ﬁgure) have electrophysiologicproperties that differ from one another in a critical way. In this example, pathway Aconducts electrical impulses more slowly than pathway B; pathway B has a longerrefractory period than pathway A. If all these seemingly implausible prerequisites are met, reentry canbe initiated when an appropriately timed premature impulse is intro-duced to the circuit (Figure 2.6). The premature impulse must enter thecircuit at a time when pathway B (the one with the long refractory period)is still refractory from the previous depolarization and at a time whenpathway A (the one with the shorter refractory period) has alreadyrecovered and is able to accept the premature impulse. While pathway Aslowly conducts the premature impulse, pathway B has a chance torecover. By the time the impulse reaches pathway B from the oppositedirection, pathway B is no longer refractory and is able to conduct thebeat in the retrograde direction (upward in the ﬁgure). If this retrogradeimpulse reenters pathway A and is conducted antegradely (as it is likelyto do, given the short refractory period of pathway A), a continuouslycirculating impulse is established, spinning around and around thereentrant loop. All that remains in order for this reentrant impulse tousurp the rhythm of the heart is for the impulse to exit from the circuit atsome point during each lap and thereby to depolarize the myocardiumoutside of the loop.
18 I Disorders of the Heart Rhythm: Basic PrinciplesFig. 2.6 Initiation of reentry. If the prerequisites in Fig. 2.5 are present, then anappropriately timed premature impulse can block in pathway B (which has a relativelylong refractory period) while conducting down pathway A. Because conduction downpathway A is slow, pathway B has time to recover, allowing the impulse to conductretrogradely up pathway B. The impulse can then reenter pathway A. A continuouslycirculating impulse is thus established. Just as reentry can be initiated by premature beats, it can be termi-nated by premature beats (Figure 2.7). An appropriately timed impulsecan enter the circuit during reentry and collide with the reentrantimpulse, thus abolishing the reentrant arrhythmia. Because reentry depends on critical differences in conduction veloci-ties and refractory periods in the various pathways of the reentrantcircuit, and because conduction velocity and refractory periods aredetermined by the shape of the action potential, it should be obviousthat the action potentials in pathway A and pathway B are different fromone another. This means furthermore that drugs that change the shapeof the action potential might be useful in the treatment of reentrantarrhythmias. Reentrant circuits occur with some frequency in the human heart.Some reentrant circuits are present at birth, especially those causingsupraventricular tachycardias (e.g., reentry associated with AV bypass
2 Abnormal Heart Rhythms 19Fig. 2.7 Termination of reentry. An appropriately timed premature impulse can enterthe circuit during a reentrant tachycardia, collide with the reentrant impulse as shown,and terminate reentry.tracts or with dual SA nodal and AV nodal tracts). More malignantforms of reentrant circuits, however, are usually not congenital but areacquired as cardiac disease develops during life. In reentrant ventriculartachyarrhythmias, the reentrant circuits arise in areas where normalcardiac tissue is interspersed with patches of scar tissue, forming manypotential anatomic circuits. Thus, ventricular reentrant circuits usuallyoccur only when scar tissue develops in the ventricles (such as during amyocardial infarction or with cardiomyopathic diseases). Theoretically, if all the anatomic and electrophysiologic criteria forreentry are present, any impulse that enters the circuit at the appropriatetime will induce a reentrant tachycardia. The time from the end of therefractory period of pathway A to the end of the refractory period ofpathway B, during which reentry can be induced, is called the tachycar-dia zone. Treating reentrant arrhythmias sometimes involves trying tonarrow or abolish the tachycardia zone (by increasing the refractoryperiod of pathway A or decreasing the refractory period of pathway B). Because reentrant arrhythmias can be reproducibly induced and ter-minated with appropriately timed impulses, reentrant arrhythmias areideal for study in the electrophysiology laboratory. In fact, it is mainly
20 I Disorders of the Heart Rhythm: Basic Principlesthe inducibility of reentrant arrhythmias that distinguishes them fromautomatic arrhythmias in the electrophysiology lab. By inducing reen-trant arrhythmias in a controlled setting, the location of the anatomiccircuit can be mapped and the effect of various therapies assessed.Triggered activityElectrophysiologists try to divide the universe of tachyarrhythmias intotwo parts— automatic arrhythmias (which cannot be induced in thelaboratory) and reentrant arrhythmias (which can be induced). This is auseful and practical way of thinking about tachyarrhythmias. Simpleand convenient classiﬁcation systems are usually wrong, however, andthis classiﬁcation system is no exception. There are other mechanisms for tachyarrhythmias, no doubt includ-ing some that have not yet been identiﬁed. While most of these othermechanisms can safely be ignored, at least one appears commonly in theclinical setting — triggered activity. Triggered activity has some features of both automaticity and reentryand can be difﬁcult to distinguish in the electrophysiology laboratory.Like automaticity, triggered activity involves the leakage of positive ionsinto the cardiac cell, leading to a bump on the action potential (Figure2.8A) in late phase 3 or early phase 4. This bump is called an afterdepolar-ization. If these afterdepolarizations are of sufﬁcient magnitude toengage the rapid sodium channels (i.e., if they reach the thresholdvoltage), another action potential can be generated (Figure 2.8B). Thus,triggered activity resembles automaticity in that new action potentialscan be generated by leakage of positive ions into the cell. Many electro-physiologists classify triggered activity as a subgroup of automaticity. Unlike automaticity (and like reentry), however, triggered activity isnot always spontaneous (and therefore not truly automatic). Triggeredactivity can be provoked by premature beats. Thus, triggered activity,like reentry, can be induced with programmed pacing techniques. Theoretically, because it can be induced during electrophysiologictesting, triggered activity poses a potential threat to the use of the induc-ibility of an arrhythmia as the major criterion for diagnosing a reentrantmechanism. If an arrhythmia is induced, the following have been pro-posed as methods of differentiating between reentry and triggeredautomaticity: triggered activity resembles automaticity in displayingwarm-up and warm-down; triggered activity is felt to depend on calciumchannels and thus may respond to calcium channel blockers; in distinc-tion to most reentrant arrhythmias, inducing arrhythmias due totriggered activity may require introducing a pause into the sequenceof paced beats used for induction (such arrhythmias, called “pause-
2 Abnormal Heart Rhythms 21Fig. 2.8 Triggered activity. (A) In some circumstances, premature cardiac actionpotentials will display a late bump (called an afterdepolarization). (B) If theafterdepolarization is of sufﬁcient magnitude, the rapid sodium channels are engagedand a second action potential is generated.dependent” arrthythmias, will be discussed in Chapter 7); reentry is themore likely mechanism in the presence of underlying structural cardiacdisease. The clinical signiﬁcance of triggered activity has become more clearover the past decade. Triggered activity is most likely the mechanism fordigitalis-toxic supraventricular and ventricular arrhythmias, as well asfor some of the rare cases of ventricular tachycardia that respond tocalcium-blocking agents. More importantly, triggered activity is nowthought to be the mechanism of torsades de pointes — the polymorphic,pause-dependent ventricular arrhythmias often associated with the useof certain antiarrhythmic drugs. Triggered activity as a cause of ventricular arrhythmias will bediscussed more fully in Chapter 7.
CHAPTER 3Treatment of ArrhythmiasPharmacologic therapyAntiarrhythmic drugs are not arrhythmia suppressants in the same waythat menthol is a cough suppressant. They do not work by soothingirritable areas. In fact, most antiarrhythmic drugs work merely bychanging the shape of the cardiac action potential. By changing theaction potential, these drugs alter the conductivity and refractoriness ofcardiac tissue. Thus, it is hoped, the drugs will change the critical elec-trophysiologic characteristics of reentrant circuits to make reentry lesslikely to occur.Channels and gatesAntiarrhythmic drugs are thought to affect the shape of the actionpotential by altering the channels that control ionic ﬂuxes across thecardiac cell membrane. The class I antiarrhythmic drugs, which affectthe rapid sodium channel, provide the clearest example (Figure 3.1). The rapid sodium channel is controlled by two gates: the m gateand the h gate. In the resting state (A), the m gate is closed and the hgate is open. When an appropriate stimulus occurs, the m gate opens (B)and positively charged sodium ions rush into the cell rapidly, causingthe cell to depolarize (phase 0 of the action potential). After a few milli-seconds, the h gate slams shut (C), closing the sodium channel andending phase 0. Class I antiarrhythmic drugs work by binding to the h gate, making itbehave as if it is partially closed (D). In this case, when the m gate is sti-mulated to open, the opening through which sodium ions enter the cellis narrower (E). Consequently, it takes longer to depolarize the cell (i.e.,the slope of phase 0 is decreased). Because the speed of depolarizationdetermines how quickly adjacent cells will depolarize (and therefore the22
3 Treatment of Arrhythmias 23Fig. 3.1 The effect of class I drugs on the rapid sodium channel. (A) through (C) displaythe baseline (drug-free) state. In (A), the resting state, the m gate is closed and the hgate is open. The cell is stimulated in (B), causing the m gate to open, thus allowingpositively charged sodium ions to enter the cell rapidly (large arrow). In (C), the h gateshuts and sodium transport stops (i.e., phase 0 ends). (D) through (E) display the effectof adding a class I antiarrhythmic drug (open circles). (D) shows the class I drug bindingto the h gate, making it behave as if it is partially closed. When the cell is stimulated in(E), the m gate still opens normally, but the channel through which sodium ions enterthe cell is narrower and sodium transport is slower. It subsequently takes longer toreach the end of phase 0 (F), and the slope of phase 0 is decreased.speed of impulse propagation), class I drugs as a group tend to decreasethe conduction velocity of cardiac tissue. Although their precise sites of action have not all been worked out,most antiarrhythmic drugs act in a similar fashion, that is, by alteringthe function of the various channels that control transport of ions acrosscardiac cell membranes. The resultant changes in the cardiac actionpotential (Figure 3.2) cause changes in the conduction velocity, refrac-toriness, and automaticity of cardiac tissue, and also provide the basisfor the classiﬁcation of antiarrhythmic drugs.
24 I Disorders of the Heart Rhythm: Basic PrinciplesFig. 3.2 The effect of antiarrhythmic drugs on the cardiac action potential. The solidlines represent the baseline action potential and the dotted lines represent the changesthat result in the action potential when various classes of antiarrhythmic drugs aregiven. The Purkinje ﬁber action potential is represented except in the case of class IVdrugs, for which the AV nodal action potential is depicted.Classiﬁcation of antiarrhythmic drugsTable 3.1 lists the most frequently used classiﬁcation system for antiar-rhythmic drugs. Class I is reserved for drugs that block the rapid sodium channel(as shown in Figure 3.1). Because drugs assigned to class I block thesodium channel in varying degrees and also have varying effects onaction potential duration, class I is currently broken down into threesubgroups (Table 3.2). Class Ia drugs (quinidine, procainamide, anddisopyramide) slow conduction velocity and increase refractoryperiods. Class Ib drugs (lidocaine, tocainide, mexiletine, and pheny-toin) actually have little effect on depolarization when used in systemic
3 Treatment of Arrhythmias 25Table 3.1 Classiﬁcation of Antiarrhythmic Drugs.Class I Bind to sodium channel, decrease speed of depolarizationClass II β-blocking drugs, decrease sympathetic tone atenolol nadolol bisoprolol carvedilol labetolol propranolol metoprolol timolol Affect mainly SA and AV nodes (indirectly by blocking β receptors)Class III Increase action potential duration amiodarone N-acetylprocainamide bretylium sotalol ibutilide dofetilideClass IV Calcium channel blockers diltiazem verapamil Affect mainly SA and AV nodes (direct membrane effect, see Fig. 3.2)Class V Digitalis agents digitoxin digoxin Affect mainly SA and AV nodes (indirectly by increasing vagal tone)Table 3.2 Subclassiﬁcation of Class I Antiarrhythmic Agents. Class Ia Quinidine, procainamide, disopyramide slow upstroke of action potential + + prolong duration of action potential + + decrease conductivity, increase refractoriness Class Ib Lidocaine, phenytoin, tocainide, mexiletine minimal effect on upstroke of action potential shorten duration of action potential decrease refractoriness Class Ic Flecainide, encainide, propafenone, moricizine* marked slowing of upstroke of action potential + + + + minimal effect on action potential duration + marked decrease in conductivity, little effect on refractoriness*The classiﬁcation of moricizine is controversial, and some place it in class Ib. It is placedin class Ic here to emphasize its class Ic–like proarrhythmic potential.
26 I Disorders of the Heart Rhythm: Basic Principlesdoses (although in high concentrations these drugs, too, can blocksodium transport — this is why lidocaine is an excellent local anestheticagent). In systemic doses, class Ib drugs decrease action potential dura-tion and shorten refractory periods but have little effect on conductionvelocity. Class Ic drugs (ﬂecainide, encainide, and propafenone) have apronounced depressant effect on conduction velocity, with relativelylittle effect on refractory periods. β-Blocking agents are assigned to class II. These drugs have littledirect effect on the action potential and work mainly by decreasing thesympathetic tone. Class III drugs (amiodarone, bretylium, dofetilide, ibutilide, N-acetylprocainamide, and sotalol) increase the action potential durationand therefore refractory periods, and have relatively little effect on theconduction velocity. Class IV includes the calcium channel blockers. They mainly affectthe SA and AV nodes, because these structures are almost exclusivelydepolarized by the slow calcium channels. Class V includes digitalis agents, whose antiarrhythmic effects arerelated to the increase in parasympathetic activity caused by thesedrugs.Effect of antiarrhythmic drugsMost antiarrhythmic drugs are felt to ameliorate automatic tachyar-rhythmias to some extent, although it must again be stressed that theprimary treatment for automatic arrhythmias is to remove the underly-ing cause. Many antiarrhythmic drugs slow the phase 4 ionic ﬂuxes,which are responsible for automaticity. Figure 3.3 shows two examples of how antiarrhythmic drugs mayaffect reentrant circuits. Figure 3.3A shows a reentrant circuit with thesame characteristics as described in Chapter 2. Figure 3.3B illustratesthe changes that may occur if a class Ia drug is administered. Thesedrugs increase refractory periods. By further lengthening the alreadylong refractory period of pathway B, the class Ia drugs can convert uni-directional block to bidirectional block, thus chemically amputatingone pathway of the reentrant circuit. Figure 3.3C shows what happens ifa class Ib drug is given. These drugs shorten the duration of the actionpotential, thus decreasing the refractory period. In this example a classIb drug shortens the refractory period of pathway B, thus rendering therefractory periods in pathway A and pathway B relatively equal. (In otherwords, the tachycardia zone is signiﬁcantly narrowed.) Without a differ-ence in refractory periods between the two pathways of the anatomiccircuit, reentry cannot be initiated.
3 Treatment of Arrhythmias 27 The drug effects illustrated in Figure 3.3 should not be taken literally.The key point in understanding how drugs affect reentry is this: becausereentry requires a critical relationship between the refractory periodsand the conduction velocities of the two pathways of the reentrantcircuit, and because antiarrhythmic drugs alter the refractory periodsand conduction velocities, these drugs can make reentry less likely tooccur.ProarrhythmiaUnfortunately, there is another side to that coin. Consider the followingscenario: A patient with a previous myocardial infarction and complexventricular ectopy (but no sustained tachyarrhythmias) has an ana-tomic circuit whose electrophysiologic characteristics are like thoseshown in Figure 3.3B. In other words, while the anatomic circuitis present, the electrophysiologic characteristics necessary to activatethe circuit are not present. If this patient is placed on a class Ib drug,it is possible to selectively decrease the refractory period of pathway B,giving this circuit the characteristics shown in Figure 3.3A. In otherwords, the antiarrhythmic drug may make a sustained tachycardiamore likely to occur. A similar scenario may develop if a class Ia drug isused in a patient with a circuit resembling the one shown in Figure 3.3C.By increasing the refractory period of pathway B, the benign circuit maybe converted to a potentially malignant one. To say it another way, whenwe administer an antiarrhythmic drug we may be just as likely toincrease, as we are to decrease, the tachycardia zone within a potentialreentrant circuit — and thus make a sustained arrhythmia more likelyinstead of less likely. The phenomenon just described is proarrhythmia, or arrhythmiaexacerbation. Although proarrhythmia is a common occurrence, it wasuntil recently only poorly recognized by many physicians who use anti-arrhythmic drugs. Failing to recognize that drug therapy is actuallyworsening arrhythmias, frequently leads to inappropriate therapy (suchas increasing or adding to the offending drug) and sometimes leads todeath. Herein lies the problem with considering antiarrhythmic drugsto be simply arrhythmia suppressants. Proarrhythmia is an inherentproperty of antiarrhythmic drugs; the mechanism that controlsreentrant arrhythmias is the same mechanism that can worsenarrhythmias. Unfortunately, whether a drug will improve or worsen an arrhythmiais difﬁcult to predict before actually administering the drug. Proar-rhythmia, therefore, is a possibility for which one must be vigilantwhenever using antiarrhythmic drug therapy.
28 I Disorders of the Heart Rhythm: Basic Principles
3 Treatment of Arrhythmias 29Drug toxicityProarrhythmia is probably the most important, and is certainly themost universal, type of toxicity seen with antiarrhythmic drugs. Theform of proarrhythmia just mentioned, i.e., the worsening of reentrantarrhythmias, can be seen with any class of antiarrhythmic drugs. In addition, certain antiarrhythmic drugs can produce a second typeof proarrhythmia called torsade de pointes. Torsade de pointes (whichis discussed in more detail in Chapter 7), is a polymorphic, pause-dependent ventricular tachycardia that is associated with prolongationof the QT interval and the subsequent development of triggered activity.(Triggered activity was described brieﬂy in Chapter 2.) Torsade com-monly causes syncope and can cause sudden death. It is seen in asubset of otherwise normal individuals — probably 3% to 4% of thepopulation at large — who are prone to develop triggered activity when-ever something acts to prolong their cardiac action potentials. Thus,antiarrhythmic drugs in class Ia and class III tend to cause torsade insuch individuals. Table 3.3 lists the relative risk of drug-induced proar-rhythmia of both types for the various antiarrhythmic drugs. Even aside from proarrhythmia, antiarrhythmic drugs as a group arerelatively toxic and poorly tolerated. Table 3.4 lists some of the commonside effects of antiarrhythmic drugs. Amiodarone, a class III drug, deserves special recognition as a drugthat is uniquely toxic not only among antiarrhythmic drugs but alsoamong all drugs used legally in the United States. Amiodarone has a sin-gular spectrum of toxicities that can be subtle in onset and difﬁcult torecognize and to treat: it can affect virtually every organ system, is accu-mulated slowly in many organs (toxicity may be related to cumulativelifetime dose), and its half-life may be as long as 100 days. The onlyreason amiodarone is used, given this toxic potential, is that it is the mostefﬁcacious drug yet developed for the treatment of serious cardiacarrhythmias. In carefully selected patients, the use of amiodarone isappropriate and quite helpful.Fig. 3.3 Effect of antiarrhythmic drugs on a reentrant circuit. (A) A prototype reentrantcircuit (same as described in Figs. 2.5 and 2.6). (B) Changes that may occur withadministration of a class la drug. The refractory period of pathway B may be sufﬁcientlyprolonged by the drug to prevent reentry from occurring. (C) Changes that may occurwith administration of class lb drug. The refractory period of pathway B may beshortened, so that the refractory periods of pathways A and B are now nearly equal. Apremature impulse would now be more likely to either conduct or block down bothpathways, thus preventing the initiation of reentry.
30 I Disorders of the Heart Rhythm: Basic Principles Table 3.3 Relative Risk of Drug-Induced Proarrhythmia. Risk of Exacerbation Risk of Torsade Drug of Reentry de Pointes Class Ia Quinidine ++ ++ Procainamide ++ ++ Disopyramide ++ ++ Class Ib Lidocaine + 0 Mexiletine + 0 Phenytoin + 0 Class Ic Flecainide +++ 0 Propafenone +++ 0 Moricizine +++ + Class III Amiodarone + + Bretylium + + Sotalol + +++ Ibutilide + +++ Dofetilide + +++ Because of the problems associated with the use of antiarrhythmicdrugs, as a general rule these drugs should be used only when arrhyth-mias are signiﬁcantly symptomatic or life-threatening.Nonpharmacologic therapyReversing the underlying cause for arrhythmiasThe treatment of cardiac arrhythmias should always begin with anattempt to identify and treat reversible etiologies for the arrhythmias.To those etiologies already listed (including electrolyte and acid–basedisturbances, ischemia, and pulmonary disorders), we must now addantiarrhythmic drugs. A patient with recurrent arrhythmias who is onantiarrhythmic drug therapy should be regarded in the same way as apatient with fever of unknown origin who is on antibiotic therapy —strong consideration should be given to stopping the drug and reassess-ing the baseline state. Stopping antiarrhythmic drugs will often improvethe frequently recurring arrhythmias.
3 Treatment of Arrhythmias 31Table 3.4 Common Side Effects of Antiarrhythmic Drugs.Hypotension Negative inotropy BradycardiaIV procainamide β blockers β blockersIV quinidine ﬂecainide calcium blockersIV phenytoin disopyramide amiodaroneIV bretyliumCNS effects GI effects Hepatic effectsall class Ib all drugs, amiodaroneamiodarone especially quinidine, phenytoinβ blockers procainamide,ﬂecainide & class IbPneumonitis Blood dyscrasias Autonomic effectsamiodarone quinidine disopyramidetocainide tocainide quinidine phenytoin β blockers digitalis sotalolOther notable toxicitiesprocainamide — drug-induced lupusamiodarone — peripheral neuropathy, proximal myopathy, skin discoloration, skin photosensitivity, hypothyroidism, hyperthyroidismdisopyramide — urinary hesitancyCNS, central nervous system; GI, gastrointestinal.Surgical and ablation therapySurgical procedures are frequently helpful in the treatment of arrhy-thmias. Arrhythmias due to cardiac ischemia often respond to coronaryartery bypass surgery. The location of reentrant circuits can be mapped(especially those due to AV bypass tracts and to ventricular tachycardiasassociated with a discrete ventricular aneurysm), and the reentrantcircuit can be disrupted surgically. Transcatheter ablation in theelectrophysiology laboratory has largely supplanted most types ofarrhythmia surgery and is extremely useful in the management of supra-ventricular tachyarrhythmias. (Transcatheter ablation will be discussedin detail in Chapter 8.) All these procedures carry at least some risk ofcomplications.Device therapyPermanent artiﬁcial pacemakers are the mainstay of treatment forbradyarrhythmias. Permanent pacemakers consist of a source of electri-cal current that is attached to cardiac muscle (usually to ventricular
32 I Disorders of the Heart Rhythm: Basic Principlesmuscle) by a wire (lead) and is under the control of an integrated circuit(a small computer). If the heart is not generating intrinsic electricalimpulses often enough, the pacemaker sends an electrical current downthe lead to stimulate the heart. The current depolarizes the cardiac cellsat the tip of the lead (i.e., an action potential is generated), and that depo-larization propagates across the myocardium in the normal fashion. Pacemakers today are increasingly sophisticated and complex. Manyfeatures are now programmable, such as the rate of pacing and the energyused with each impulse. Pacemakers are available that guarantee thenormal sequence of AV contraction with each heartbeat. Other pace-makers can use some physiologic variable (such as the patient’s level ofexercise) to judge the optimal heart rate from moment to moment andvary the rate of pacing accordingly. Selecting the appropriate pacemakerfor a patient requires extensive knowledge of the technology available. Devices are also useful for patients with tachyarrhythmias. Manypatients with malignant ventricular tachyarrhythmias are now beingoffered the automatic implantable cardioverter–deﬁbrillator (ICD).This device monitors the heart rhythm constantly and, if a potentiallylethal tachyarrhythmia occurs, will automatically deliver a large deﬁ-brillating current (shock) to the heart to terminate the arrhythmia. Theimplantable deﬁbrillator has prevented sudden death in thousands ofpatients who have lethal ventricular arrhythmias. The use of thesedevices, however, can be difﬁcult and patient selection less straightfor-ward than it might be. (This is discussed in detail in Chapter 7.)
PA R T IIThe Electrophysiology Study inthe Evaluation and Therapy ofCardiac Arrhythmias
CHAPTER 4Principles of the Electrophysiology StudyThe electrophysiology study can be helpful in evaluating a broad spec-trum of cardiac arrhythmias. It can help with assessing the function ofthe SA node, the AV node, and the His-Purkinje system; with determin-ing the characteristics of reentrant arrhythmias; with mapping the loca-tion of arrhythmogenic foci for potential ablation; and with evaluatingthe efﬁcacy of antiarrhythmic drugs and devices. One might expect a test that can accomplish all this to be extraordi-narily complex. On the contrary (although electrophysiologists may notlike to admit it), the electrophysiology study is performed by doing twosimple things: Recording the heart’s electrical signals, and pacing fromlocalized areas within the heart. Using the information obtained fromthese relatively simple tasks and keeping in mind the concepts outlinedin Part I, one can assess and decide on treatment for a wide array of heartrhythm disturbances. In this chapter, we introduce the principles used in performing theelectrophysiology study.Recording and pacingTo discuss intracardiac recording and pacing, we need to introduce twoterms that are used by electrophysiologists relating to time measure-ments. Time measurements are reported in milliseconds (msec, onethousandth of a second), the basic unit of time in electrophysiology.Cycle lengthWhen electrophysiologists talk about heart rate, they typically speak interms of cycle length — the length of time between each heartbeat (Figure4.1A). Thus, the faster the heart rate, the shorter the cycle length: Anarrhythmia with a rate of 100 beats/min has a cycle length of 600 msec, 35
36 II Electrophysiology Testing for Cardiac Arrhythmiaswhile an arrhythmia with a rate of 300 beats/min has a cycle lengthof 200 msec. Nonelectrophysiologists must pay close attention whendiscussing heart rate with electrophysiologists, to avoid some amusingmiscommunications.Coupling intervalWhen using a pacemaker to introduce a premature impulse, the cou-pling interval is the time between the last normal impulse and the pre-mature impulse (Figure 4.1B). With earlier premature impulses, thecoupling interval is shorter; with later premature impulses, the couplinginterval is longer.The electrode catheterThe electrophysiology study is performed by inserting electrode cathe-ters into blood vessels and positioning these catheters in strategic loca-tions within the heart. Once in position, the catheters can be used toperform the two essential tasks of the electrophysiology study: Record-ing the heart’s electrical signals and pacing.Fig. 4.1 Time measurements in the electrophysiology laboratory. This ﬁgure depictspacing from the right ventricular apex. (A) Cycle length is the interval of time betweenheartbeats during either incremental pacing (as in this ﬁgure) or a spontaneous rhythm.The cycle length of the incrementally paced beats in (A) is 600 msec. (B) Couplinginterval is the interval of time between the last normal beat and a premature impulse.In this ﬁgure, the normal beats are represented by eight incrementally paced beats at acycle length of 600 msec. Following the last incrementally paced beat, a singlepremature stimulus is delivered with a coupling interval of 250 msec.
4 Principles of the Electrophysiology Study 37 Electrode catheters consist of insulated wires; at the distal tip of thecatheter (the end inserted into the heart [Figure 4.2]), each wire isattached to an electrode, which is exposed to the intracardiac surface. Atthe proximal end of the catheter (the part not inserted into the body[Figure 4.3]), each wire is attached to a plug, which can be connected toan external device (such as a recording device or an external pacemaker).With the exception that they usually have more than two electrodes,these catheters are similar to many temporary pacemaker catheters usedin emergency rooms and coronary care units. The catheter shown inFigures 4.2 and 4.3 is a quadripolar electrode catheter, the type mostcommonly used in electrophysiology studies.Recording intracardiac electrogramsThe recording made of the cardiac electrical activity from an electrodecatheter placed in the heart is called an intracardiac electrogram. Theintracardiac electrogram is essentially an ECG recorded from withinthe heart. The major difference between a body surface ECG and anintracardiac electrogram is that the surface ECG gives a summation ofFig. 4.2 The tip of a quadripolar electrode catheter. The electrodes are numbered 1through 4, the distal (tip) electrode being number 1. The spacing between electrodesis 1 cm.Fig. 4.3 The proximal end of a quadripolar electrode catheter. The number on eachplug corresponds to the appropriate electrode at the tip of the catheter.
38 II Electrophysiology Testing for Cardiac Arrhythmiasthe electrical activity of the entire heart, whereas the intracardiac elec-trogram records only the electrical activity of a localized area of theheart — the cardiac tissue located near the electrodes of the electrodecatheter. In general, the intracardiac electrogram records the electricalactivity between two of the electrodes (i.e., an electrode pair) at the tip ofthe catheter. This is called a bipolar recording conﬁguration. The intracardiac electrogram is ﬁltered electronically, so that ingeneral only the rapid depolarization phase of the cardiac tissue (corre-sponding to phase 0 of the action potential) is recorded. Figure 4.4 showsan intracardiac electrogram recorded from a catheter in the right atriumduring normal sinus rhythm. As the wave of depolarization spreadingoutward from the SA node passes by the catheter, a discrete high-frequency, high-amplitude signal is recorded. This signal indicates theprecise moment at which myocardial depolarization occurs at the elec-trode pair which is being used for recording. By having catheters posi-tioned in several different intracardiac locations, one can accuratelymeasure the conduction time from one location to another. Further,if enough catheter positions are used, one can map the sequence ofmyocardial depolarization as an electrical impulse traverses theheart. In summary, the deﬂection recorded from the electrode catheterrepresents depolarization of the cardiac tissue in the immediate vicinityFig. 4.4 Surface ECG and intracardiac electrogram recorded from the high right atrium(RA) during sinus rhythm. The deﬂection recorded on the RA electrogram reﬂects theprecise moment at which the portion of the right atrium at the tip of the electrodecatheter is being depolarized.
4 Principles of the Electrophysiology Study 39of the catheter’s electrodes. Thus, the intracardiac electrogram givesprecise, localized data on the heart’s electrical impulse.PacingThe electrode catheter is also used for pacing. To pace, a pulse of electri-cal current is carried by the electrode catheter from an external pace-maker to the intracardiac surface, where it causes cardiac cells near thecatheter’s electrodes to depolarize. The depolarization of these cardiaccells is then propagated across the heart, just as an electrical impulsearising in the SA node is propagated. Thus, to pace is to artiﬁcially gener-ate a cardiac impulse. By careful positioning of the electrode catheter,one can initiate electrical impulses from almost any desired intracar-diac location. During the electrophysiology study, pacing is used to introducepremature electrical impulses, delivered in predetermined patternsand at precisely timed intervals. Such pacing is called programmedstimulation. There are several reasons for performing programmed stimulation.Precisely timed premature impulses allow us to measure the refractoryperiods of cardiac tissue. By introducing premature impulses in onelocation and recording electrograms in other locations, one can assessthe conduction properties of the intervening cardiac tissue and thepattern of myocardial activation. Programmed stimulation can alsohelp to assess the automaticity of an automatic focus and to study thepresence and characteristics of reentrant circuits. Programmed stimulation consists of two general types of pacing:Incremental and extrastimulus pacing (Figure 4.5). Incremental pacing (or burst pacing) consists of introducing a train ofpaced impulses at a ﬁxed cycle length. The incremental train may last fora few beats or for several minutes. The extrastimulus technique consists of introducing one or more pre-mature impulses (called extrastimuli), each at its own speciﬁc couplinginterval. The ﬁrst extrastimulus is introduced at a coupling intervaltimed either from an intrinsic cardiac impulse or from the last of a shorttrain of incrementally paced impulses. (This train is usually eight beatsin duration, owing to tradition rather than to scientiﬁc reasons.) Thegenerally accepted nomenclature for the extrastimulus technique isillustrated in Figure 4.5. The term S1 (stimulus 1) is used for the incre-mentally paced impulses or the intrinsic beat from which the ﬁrst extra-stimulus is timed; S2 is used for the ﬁrst programmed extrastimulus;S3 stands for the second programmed extrastimulus, and so on. Thisnomenclature (in which, e.g., the number 2 is attached to the ﬁrst extra-stimulus) causes a lot of confusion among the uninitiated.
40 II Electrophysiology Testing for Cardiac ArrhythmiasFig. 4.5 Extrastimulus and incremental pacing. Right ventricular pacing is depicted.(A) Extrastimulus pacing consists of introducing one or more extrastimuli either duringthe patient’s spontaneous rhythm or (as depicted here) following a train of impulsesdelivered at a ﬁxed cycle length. This panel shows a single extrastimulus. The ﬁxed-cycle-length impulses from which the extrastimuli are timed are referred to as the S1beats. The ﬁrst extrasimulus is labeled S2. (B) Same as in (A), except that a secondextrastimulus is delivered (labeled S3). (C) Same as in (A) and (B), except that a thirdextrastimulus is delivered (labeled S4). (D) Incremental pacing consists of a train ofpaced impulses at a ﬁxed cycle length. The S1 beats in (A) through (C) are incrementallypaced impulses.Performance of the electrophysiology studyThe physical setup of the electrophysiology laboratoryThe electrophysiology study is a type of heart catheterization, and muchof the equipment necessary for electrophysiologic testing can be foundin a general cardiac catheterization laboratory. This includes a ﬂuoro-scopic unit, a radiographic table, a physiologic recorder, oscilloscopes,instrumentation for gaining vascular access, and emergency equip-ment. Equipment required speciﬁcally for electrophysiologic testingincludes a programmable stimulator, a multichannel lead switching box(a junction box), and electrode catheters. An arrangement for a typicalelectrophysiology laboratory is shown in Figure 4.6. The programmable stimulator is a specialized pacing unit built espe-cially for electrophysiology studies. It has the capability of introducingcomplex sequences of paced beats with an accuracy of within 1 msec. Itcan also synchronize pacing to the intrinsic heart rhythm and can pacemultiple intracardiac sites simultaneously.
4 Principles of the Electrophysiology Study 41Fig. 4.6 Schematic for the layout of a typical electrophysiology laboratory. The junction box allows the laboratory personnel to control the con-nections from the electrode catheters to the various recording andpacing devices. With a series of switches, multiple electrode pairs frommultiple catheters can be sorted out for recording and pacing. The physiologic recorder should have enough channels to processthree or four surface ECG leads and multiple intracardiac leads (oftenup to 12). Most electrophysiology laboratories today are equipped withspecialized physiologic recorders designed speciﬁcally for electrophysi-ology studies. Such recorders are computer-based and provide featuressuch as color-coded intracardiac leads, electronic calipers for precisemeasurements, and hard-disk storage of the entire study. Equipment to deal with cardiac emergencies is essential especiallybecause many electrophysiology studies include the intentional induc-tion of arrhythmias that can cause hemodynamic collapse. Thisincludes a deﬁbrillator, a full complement of cardiac medications, and
42 II Electrophysiology Testing for Cardiac Arrhythmiasequipment for maintaining airway support. Likewise, enough trainedpersonnel should always be present to deal with any cardiac emergency.As a minimum, this should include the electrophysiologist, two cardiacnurses who are trained in electrophysiologic procedures (or one nurseand a second physician), and a technician.Preparation of the patientAlthough preparation of the patient will vary somewhat dependingon the nature of the study to be performed, all patients having electro-physiology studies should be given a clear understanding of the purposeand nature of the procedure and the potential beneﬁts and risks. As withany procedure in medicine, the patient should sign a statement ofinformed consent prior to the study. Ideally, the electrophysiologic evaluation should be performed whilethe patient is in a baseline state — nonessential drugs should be with-drawn (especially antiarrhythmic agents), any cardiac ischemia or heartfailure maximally treated, electrolytes controlled, and every effort madeto prevent excessive anxiety — which can cause excessive sympathetictone. Anxiety is most easily kept to an acceptable level by adequatelypreparing the patient for what to expect in the electrophysiologylaboratory. Any cardiac catheterization procedure can cause potentially danger-ous arrhythmias, but patients having electrophysiology studies espe-cially need to be aware of this possibility. In particular, patients who arehaving studies for known or suspected ventricular tachyarrhythmiasshould be psychologically prepared for the possibility that induction ofan arrhythmia may produce loss of consciousness and require deﬁbril-lation. Fortunately, the efﬁcacy of electrophysiologic testing and theremarkable safety record achieved in most laboratories go a long waytoward allaying the fears of most patients and their families. Detaileddiscussions with the patient serve not only to guarantee truly informedconsent but also to alleviate the patient’s anxiety and build his or herconﬁdence in the electrophysiologist.Insertion and positioning of electrode cathetersThe patient is brought to the catheterization laboratory in the fastingstate, and the catheterization sites are prepared and draped. The major-ity of electrophysiology studies can be performed from the venous sideof the vascular system, thus precluding the necessity of catheterizingthe arterial tree. Under sterile conditions and after local anesthesia isgiven, catheters are inserted in most instances percutaneously by themodiﬁed Seldinger technique (a needle-stick technique that does not
4 Principles of the Electrophysiology Study 43require a cutdown). Only extremely rarely do patients need to beplaced under general anesthesia to perform an electrophysiology study;however, premedication with a benzodiazepine is sometimes used inpatients who are extremely anxious. Most often, catheters are insertedinto the femoral veins (two catheters can safely be inserted into the samefemoral vein). Catheters are inserted from the upper extremities eitherfor more complicated studies, which require multiple catheters; whenthere is a contraindication to the use of the femoral veins; when a cathe-ter will be left in place at the end of the procedure; or when positioning ofthe catheter is easier from the upper extremities (such as in coronarysinus catheterization). In these cases, the internal or external jugularveins, the subclavian veins, or the brachial veins may be used. In thoseinstances where access to the left ventricle is required, the femoral arte-rial approach is used most often. In many laboratories, a small catheteris routinely inserted into an artery for continuous monitoring of bloodpressure. Under ﬂuoroscopic guidance, the catheters are placed into the properintracardiac positions. For a simple diagnostic study, generally one cath-eter is positioned in the high right atrium and the second catheter isplaced in the His position (described later). One of these catheters canlater be moved to the right ventricle if ventricular pacing is required.For studies of supraventricular tachycardias, additional catheters arecommonly placed in the right ventricle and the coronary sinus (thusallowing recordings from all four major cardiac chambers and from theHis position). In the right atrium, catheters are most commonly positioned in thehigh lateral wall, near the junction of the superior vena cava. This posi-tion approximates the location of the SA node and is the region of theatrium that is depolarized earliest during normal sinus rhythm. Pacingfrom this area results in P wave conﬁgurations that are similar to normalsinus beats. Pacing and recording from the left atrium are usually accomplishedby inserting an electrode catheter into the coronary sinus (Figure 4.7).The os of the coronary sinus lies posterior and slightly inferior to the tri-cuspid valve and is most easily entered from a superior approach (i.e.,from the upper extremities). The coronary sinus itself lies in the AVgroove — that is, between the left atrium and the left ventricle. Thus,deﬂections from both the left atrium and the left ventricle are easilyrecorded from a catheter positioned in the coronary sinus. Pacing theleft atrium from the coronary sinus is accomplished routinely — onlyrarely can the left ventricle be paced from this position. Although apatent foramen ovale will sometimes allow direct entry into the left
44 II Electrophysiology Testing for Cardiac ArrhythmiasFig. 4.7 A catheter positioned in the coronary sinus can record left atrial and leftventricular electrograms because the coronary sinus lies in the AV groove betweenthe left atrium and the left ventricle. AVN, AV node; CS, coronary sinus; EC, electrodecatheter; FS, ﬁbrous skeleton of the heart; HIS, His bundle; IVC, inferior vena cava;MV, mitral valve; OS, os of the coronary sinus; RA, right atrium; RV, right ventricle; SVC,superior vena cava; TV, tricuspid valve.atrium, we prefer to use the coronary sinus to avoid the slight possibilityof causing an embolus in the systemic circulation. Electrode catheters in the right ventricle are usually positioned in theapex for recording and the apex or the outﬂow tract for pacing. Placing electrode catheters in the left ventricle is not part of the stan-dard electrophysiology study. When it is necessary to do so (e.g., when
4 Principles of the Electrophysiology Study 45ablation procedures require access to the left ventricle or left atrium),vascular access is usually gained through one of the femoral arteries;although some electrophysiologists have become adept at entering theleft side of the heart transseptally from the right atrium. The His bundle electrogram is the recording that gives the most infor-mation about AV conduction. To record the His bundle electrogram, anelectrode catheter is passed across the posterior aspect of the tricuspidvalve (near the penetration of the His bundle into the ﬁbrous skeleton[Figure 4.8]). The catheter is maneuvered while continuously recordingelectrograms from several electrode pairs (so that the best pair forrecording can be selected), until an electrogram similar to the one shownin Figure 4.8 is seen. The electrode pair that records the His electrogramis thus placed in a strategic location. It straddles the important struc-tures of the AV conduction system and allows one to record the electricalactivity of the low right atrium, the AV node, the His bundle, and aportion of the right ventricle — all from one electrode pair. Once the catheters are in position, the various electrode pairs are setup for recording and pacing. The leads recorded include various surfaceECG leads and intracardiac electrograms from each electrode catheter.Figure 4.9 shows a typical baseline recording for a typical baseline elec-trophysiology study, displaying surface ECG leads I, II, and V1 (thus pro-viding a lateral, an inferior, and an anterior lead from which to assess theQRS axis) as well as leads from two intracardiac catheters (high rightatrium and His positions). For ventricular recording and pacing, theright atrial catheter is moved to the right ventricle after atrial pacing iscompleted.The basic electrophysiology protocolThe protocol used in electrophysiology studies varies according to thespeciﬁc type of procedure being performed; but most electrophysiologicprocedures follow the same general outline:1 Measurement of baseline conduction intervals2 Atrial pacing a. Assessment of SA nodal automaticity and conductivity b. Assessment of AV nodal conductivity and refractoriness c. Assessment of His-Purkinje system conductivity and refractoriness d. Induction of atrial arrhythmias3 Ventricular pacing a. Assessment of retrograde conduction b. Induction of ventricular arrhythmias4 Drug testing
46 II Electrophysiology Testing for Cardiac ArrhythmiasFig. 4.8 Positioning of the His bundle catheter. The His bundle electrogram is recordedfrom a catheter that lies across the posterior aspect of the tricuspid valve. Abbreviationsare the same as in Figure 4.7. See p. 49 for a description of “A”, “H” and “V” spikes onthe His electrogram.Chapters 5, 6, and 7 discuss the individual steps of the electrophysiologystudy in detail. Before proceeding to speciﬁcs, however, we need toreview the principles of how one can evaluate the electrophysiologicproperties of the heart and assess and treat reentrant arrhythmias fromthe simple expediency of recording and pacing from intracardiacelectrodes.
4 Principles of the Electrophysiology Study 47Fig. 4.9 Typical baseline recording of intracardiac electrograms. In this ﬁgure, onesurface ECG lead is shown, as well as intracardiac electrograms from the high rightatrium (RA), His bundle, coronary sinus, and right ventricular apex. Conductionintervals are as follows: BCL (basic cycle length) is the interval between successiveA waves (measured from the RA catheter); PR interval is the time from the beginning ofthe P wave to the beginning of the QRS complex (measured from the surface ECG); QRSduration is the width of the QRS complex on the surface ECG; IACT (intraatrialconduction time) is the interval from the SA node to the AV node and is measured fromthe beginning of the P wave on the surface ECG to the A deﬂection on the His bundleelectrogram. The AH and HV intervals are discussed in detail in the text (see p. 49).Evaluation of the electrophysiologic propertiesof the heartBy recording and pacing from electrode catheters, one can evaluate thefundamental electrophysiologic properties of the heart — namely, auto-maticity, conduction velocity, and refractory periods.AutomaticityThe electrophysiology study can be used to assess the normal automatic-ity of the SA node, thanks to the phenomenon known as overdrive sup-pression. An automatic focus such as the SA node can be overdriven by a
48 II Electrophysiology Testing for Cardiac Arrhythmiasmore rapidly ﬁring pacemaker. This means that the more rapid pace-maker depolarizes the SA node faster than it can be depolarized by itsintrinsic automaticity. When the overdriving pacemaker stops, there isoften a relatively long pause before the SA node recovers and beginsdepolarizing spontaneously again. The pause induced in an automaticfocus by a temporarily overdriving pacemaker is called overdrivesuppression. Overdrive suppression of the SA node is accomplished in the electro-physiology laboratory by pacing the atrium rapidly (thus overdrivingthe SA node), then suddenly turning off the pacemaker, and measuringhow long it takes for the SA node to recover. A diseased SA node tendsto have a grossly prolonged recovery time after overdrive pacing. Theevaluation of SA nodal dysfunction is covered in detail in Chapter 5. Overdrive suppression of automatic foci is also clinically relevantwhen patients are dependent on subsidiary escape pacemakers tosustain life (e.g., patients with complete heart block and ventricularescape rhythms). These subsidiary pacemakers are automatic foci likethe SA node and are thus subject to overdrive suppression. If such apatient receives a temporary pacemaker and after a time the temporarypacemaker suddenly loses capture (as temporary pacemakers some-times do), the patient may be left with a prolonged, possibly fatal asys-tolic episode due to overdrive suppression of the escape pacemaker. Insuch patients, careful positioning of the temporary pacemaker to guar-antee excellent pacing thresholds in a very stable location is essential,and every precaution must be taken to keep the temporary lead stable(such as enforced bed rest) until a permanent pacemaker can beinserted. Tachyarrhythmias due to abnormal automaticity (such as automaticventricular tachycardia due to ischemia) do not lend themselves well tostudy in the electrophysiology laboratory. Overdrive suppression ofsuch abnormal automatic foci is not a prominent feature and usuallycannot be demonstrated. Also, as we have already discussed, automaticarrhythmias cannot be induced during electrophysiologic testing. Thus,the evaluation of automatic tachyarrhythmias is not an indication for anelectrophysiology study.Conduction velocityConduction velocity refers to the speed of conduction of an electricalimpulse across the heart and, as we have noted, is related to the rate ofrise (i.e., the slope) of the depolarization phase (phase 0) of the actionpotential. By measuring the time it takes for an electrical impulse totravel from one intracardiac location to another (referred to as a conduc-
4 Principles of the Electrophysiology Study 49tion interval), one can use electrode catheters to assess the conductionvelocities of various portions of the cardiac electrical system. The best example of measuring conduction velocity from intracar-diac electrograms is given by the His bundle electrogram. As noted pre-viously, this electrogram contains signals from all the critical structuresof the AV conducting system. Figure 4.8 represents the His bundle elec-trogram from a patient in normal sinus rhythm. As shown, the Hiselectrogram contains three major deﬂections. The ﬁrst deﬂection is theA spike. This deﬂection represents depolarization of the tissue in thelow right atrium, just as the electrical impulse enters the AV node. Oncein the AV node, the impulse encounters tissue that depolarizes slowly.(As discussed in Chapter 1, the slow depolarization of the AV nodaltissue is a result of the lack of rapid sodium channels in AV nodal cells).Because the depolarization of the AV node is slow, no high-frequencysignal is generated, and the passage of the impulse through the AV nodedoes not produce a deﬂection on the His bundle electrogram. When theimpulse exits the AV node and zips down the His bundle (again encoun-tering rapidly depolarizing cells), the His bundle deﬂection (i.e., the Hspike) is produced on the electrogram. As the impulse passes distallythrough the bundle branches and on to the farther reaches of the Pur-kinje system, it moves away from the recording electrode pair. Becauseof their distance from the recording electrodes, the Purkinje ﬁber depo-larizations are not recorded on the His electrogram (although the rightbundle branch depolarization is sometimes seen). Finally, as the impulseis spread to the ventricular myocardium, the depolarization of theventricular muscle near the His catheter produces the V deﬂection onthe His electrogram. By analyzing the deﬂections on the His bundle electrogram, the con-duction properties of the major structures of the AV conduction systemcan be deduced. The conduction interval from the beginning ofthe A deﬂection to the beginning of the H deﬂection (the AH interval)represents the conduction time through the AV node (normally 50 to120 msec). The interval from the beginning of the H deﬂection to thebeginning of the V deﬂection (the HV interval) represents the conduc-tion time through the His-Purkinje system (normally 35 to 55 msec).Disease in the AV node will often produce a prolongation in the AHinterval, whereas disease in the distal conducting system produces aprolongation in the HV interval. The AH and HV intervals are two of the basic conduction intervalsmeasured at the beginning of the electrophysiology study. Other basicconduction intervals (shown in Figure 4.9) include the basic cardiaccycle length, the QRS duration, the PR interval, and the intraatrial
50 II Electrophysiology Testing for Cardiac Arrhythmiasconduction interval. The basic cycle length is the interval between suc-cessive atrial impulses as measured in the right atrial catheter (in orderto approximate the basic rate of depolarization of the SA node). The PRinterval is measured from the surface ECG leads and is deﬁned as theinterval from the beginning of the P wave to the beginning of the QRScomplex. The QRS duration, the interval from the beginning of the QRScomplex to the end of the QRS complex, is also measured from thesurface ECG leads. The intraatrial conduction interval approximatesthe conduction time from the sinus node to the AV node and is measuredfrom the beginning of the P wave on the surface ECG to the beginningof the A spike on the His bundle electrogram. Note that the intraatrialconduction interval, the AH interval, and the HV interval, are the threebasic components of the PR interval. Depending on the type of electrophysiology study being performedand the type of information needed, other conduction intervals may bemeasured, such as retrograde conduction intervals (from the ventricleto the atrium).Refractory periodsThus far, we have deﬁned the refractory period as the period of time afterdepolarization during which a cell cannot be depolarized again, and wehave related the refractory period of a cell to the duration of the actionpotential. Because we cannot measure a cell’s action potential durationin the electrophysiology laboratory, the refractory period must be rede-ﬁned in such a way as to make it meaningful in the laboratory setting.Thus, the refractory period of cardiac tissue is deﬁned in terms of the tis-sue’s response to premature paced impulses. Here, electrophysiologistshave outdone themselves by deﬁning three different kinds of refractoryperiods: The effective refractory period, the relative refractory period,and the functional refractory period. The effective refractory period (ERP; Figure 4.10) is the deﬁnition thatmost closely coincides with our original deﬁnition of the refractoryperiod. When introducing a premature impulse, that impulse will fail topropagate through tissue that is refractory. The ERP of a tissue is thelongest coupling interval for which a premature impulse fails to propa-gate through that tissue. In other words, the ERP refers to the latest earlyimpulse that is blocked — if the premature impulse were any later, thetissue would be recovered and would propagate the impulse. In general,the end of ERP occurs sometime during the last third of phase 3 of theaction potential. The relative refractory period (RRP; Figure 4.10) requires the intro-duction of a new concept. Recovery from refractoriness turns out to be a