- Email: [email protected]
Electrophysiologic approach to therapy of recurrent sustained ventricular tachycardia
REVIEWS
Electrophysiologic Approach to Therapy of Recurrent Sustained Ventricular Tachycardia
MARK E. JOSEPHSON, MD, FACC’ LEONARD N. HOROWITZ, MD, FACC’ Philadelphia,
Pennsylvania
From the Electrophysiology Laboratory, Hospital of the University of Pennsylvania, Cardiovascular Section, Department of Medicin’e, University of Pennsylvania School of Medicin,e, Philadelphia, Pennsylvania. This work was supported in part by grants from the American tieart Association, Southeastern Pennsylvania Chapter, and National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. Manuscript received July 18, 1978; revis+ manuscript received September 26, 1978, accepted September 27, 1978. * Recipient of a Research Career Development Award, Grant 1 KO 4 HL00361-0 1National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. t Recipient of a Career Development Investigatorship, American Heart Association, Southeastern Pennsylvania Chapter. Address for reprints: Mark E. ,Josephson. MD, Electrophysiology Laboratpry, 666 White Building, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104.
The refinement of the techniques of programmed stimulation and intracardiac recording has led to understanding of the mechanism of ventricular tachycardia and these techniques can be applied clinically to the development of therapeutic regimens. The efficacy of drug therapy can be assessed in sequential studies evaluating the ability of drugs to prevent initiation of the arrhythmia by electrical stimulation. The efficacy of pacemaker therapy can be evaluated by assessing the effects of stimulation during the tachycardia. The recent development of endocardial mapping provides the surgeon with a tool to guide therapeutic surgical ablation of the site of origin of the tachycardia. Such an electrophysiologic approach to recurrent ventricular tachycardia can lead to the rapid development of successful therapy under controlled conditions.
The treatment of recurrent. sustained ventricular tachycardia remains difficult and often frustrating. The choice of pharmacologic, pacemaking or surgical therapy, alone or in combination, has heretofore been empirically based without objective measures to predict efficacy. In most patients with recurrent sustained ventricular tachycardia, particularly those with coronary artery disease and ventricular aneurysm, the arrhythmia can be reproducibly initiated and terminated with programmed electrical stimulation and the origin localized with endocardial mapping. This observation providks the basis for an organized electrophysiologic approach to the therapy of this arrhythmia.‘-” The ability to initiate the tachycardia reproducibly with programmed stimulation permits rapid and accurate assessment of pharmacologic therapy, whereas termination of the arrhythmia with programmed stimulation provides the data on which the choice of pacing therapy can be based. Finally, localization of the site of origin of the arrhythmia can guide the surgical approach to ablation of ventricular tachycardia if drug therapy and pacing prove unsuccessful. Similar electrophysiologic approaches have led to the development of therapeutic regimens for the treatment of arrhythmias that complicate the Wolff-Parkinson-White syndrome7-l4 and recurrent supraventricular tachycardias not associated with preexcitation. 15-lx The present review will describe in detail our electrophysiologic approach to recurrent sustained ventricular tachycardia in 34 patients. Patient Population Forty patients with recurrent sustained ventricular tachycardia were studied after giving informed consent. The patients ranged in age from 8 to 73 years. The majority (25) of the patients had coronary artery disease, and 21 had a left ventricular aneurysm or healed myocardial infarction. The remaining patients had cardiomyopathy (four patients), valvular heart disease (four patients) or no structural heart disease (seven patients). Each patient had had at least four spontaneous episodes of ventricular tachycardia although most had had many more (18 f 6 episodes [mean f standard deviation]). In none of these patients
March 1979
The American Journal of CARDIOLOGY
Volume 43
631
ELECTROPHYSIOLOGIC
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
ventricular tachycardia related to transient clinical states such as drug toxicity or congestive heart failure. Thirty-two patients were referred for study because they had recurrent arrhythmias despite empiric therapy with at least one antiarrhythmic agent, usually procainamide or quinidine.
AND HOROWITZ
Assessment of Pharmacologic Therapy
was
In our experience recurrent sustained ventricular tachycardia, particularly that due to coronary artery disease and the idiopathic variety, can be reproducibly
FIGURE 1. Initiation of ventricular tachycardia with programmed stimulation. Panels A through C are arranged from top to bottom as follows: electrocardiographic leads II (2) and VI; electrograms from the coronary sinus (CS). His bundle recording site (HBE). right ventricular apex (WA), the border of a left ventricular aneurysm (LV-An, border) and in the aneurysm (LV-AN) and time lines (T) at 10 inset intervals. The lefl ventricular electrograms were recorded from a quadripolar catheter with the distal pair of electrodes in the left ventricular aneurysm and the proximal pair at its border. The ventricles and atria were paced at a basic cycle length of 700 msec (S, A, - A, and V, - V,), and after every eighth paced complex progressively premature ventricular extrastimuli were delivered from the right ventricular apex (S and V,). In A and B ventricular extrastimuli delivered at 310 and 300 msec, respectively, produced fractionation of the electrogram in the aneurysm (arrows). At a critical coupling interval of 290 msec (C) fractionation of the electrogram in the aneurysm spanned diastole, and ventricular tachycardia ensued.
632
March 1979
The American
Journal of CARDIOLOGY
Volume 43
ELECTROPHYSIOLOGICAPPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON AND HOROWITZ
initiated in the vast majority of patients (34 of 40; 85 percent) with programmed electrical stimulation that includes the introduction of progressively premature single or double ventricular extrastimuli and rapid ventricular pacing to cycle lengths of 250 msec (Fig. 1). The details of the stimuiation protocol have previously been reported.4 The effect of a variety of antiarrhythmic agents, alone or in combination, on the ability to initiate the tachycardia can be assessed with programmed stimulation over a period of several days. However, programmed stimulation can be used to assess drug therapy only in those patients in whom the tachycardia can be reproducibly initiated. Thirty-four of the 40 patients studied met this criterion and form the basis for the present review. The use of an electrophysiologic protocol for drug selection is based on two assumptions: (1) The tachy-
cardia initiated in the laboratory with programmed stimulation is identical to the clinical tachycardia, and (2) the response to antiarrhythmic agents in the laboratory predicts the clinical response. The first of these assumptions appears to be well established; our own experience and that of several other centers employing this approach support the second assumption.5J~1517.19-22
’
Prevention of initiation of sustained tachycardia: A drug is considered successful only if it prevents the initiation of sustained tachycardia. Although some investigators use the width of the “tachycardia zone” to judge drug efficacy,‘lg we believe that this end point is not definitive for determining chronic drug therapy. The acutely administered drugs in our protocol include procainamide (1 to 2 g intravenously), quinidine (800 mg intramuscularly), disopyramide (200 to 300 mg orally), lidocaine (225 mg intravenously) and diphenylhydan-
Control “1
FIGURE 2. Serial electrophysiologic study to establish pharmacologic therapy for ventricular tachycardia. Each panel shows electrocardiographic lead V, and a right ventricular (RV) electrogram. Stimuli during ventricular pacing (S,) and programmed extrastimuli (S2 and Ss) are indicated. The coupling intervals of the extrastimuli are shown at left between S, and S2 and S2 and Ss. The cycle length of the tachycardia is indicated on the right. A, in the control study, ventricular tachycardia initiated by two extrastimuli had a (cycle length of 270 msec. B, after the intravenous administration of 1,500 mg of procainamide (plasma level 18.7 fig/ml). ventricular tachycardia was still inducible at slightly longer coupling intervals; however, the cycle length of the tachycardia was greatly prolonged. The QRS complex was also widened to 215 msec (control value 165 msec). C, after the oral administration of 2,000 mg of quinidine (plasma level 3.4 pug/ml), ventricular tachycardia was inducible at the control coupling intervals and the cycle length was not significantly different from the control value. D, after the intravenous administration of 175 mg of lidoc.aine, nonsustained ventricular tachycardia (one complex) was induced. E, after the intravenous administration of 1,000 mg of diphenylhydantoin (plasma level 9.75 pg/ml), two ventricular extrastimuli failed to induce ventricular tachycardia. No other coupling intervals or stimulation protocol produced ventricular tachycardia after the administration of diphenylhydantoin. Identical results were obtained 3 days later during long-term oral administration of diphenylhydantoin (plasma level 10.5 Fg/ml). (From Horowitz et al.,2’ with permission of the American Heart Association, Inc.)
Procainamide
B
Quinidine
Lidocaine
D yy$~$. Diphenylhydantoin
E
V’--
March 1979
The American Journal of CARDIOLOGY
Volume 43
633
ELECTROPiiYSlOi_OGiCAPmoAch
TO VENTRICULAR TACHYCAR~IA-JOSEPHSON AND HOROWITZ
FIGURE 3. Prevention of initiation of sustained ventricular tachycardia with drug therapy. A and B are organized from top to bottom as electrocardiographic leads aVF and V, and a left ventricular (LV) electrogram. Time lines (T) at the bottom of B are at 10 msec intervals. During the control study (A), sustained ventricular tachycardia at a cycle length of 250 msec was initiated by two ventricular extrastimuli (S? and Sg) delivered from the left ventricle. After the administration of 1 g of intravenous procainamide produced a plasma level of 10.2 mg/liter, the initiation of sustained ventricular tachycardia was prevented although a short run of four complexes is seen. Long-term oral therapy with procainamide producing trough plasma levels of 10.5 to 11.0 mg/liter has prevented the recurrence of spontaneous ventricular tachycardia.
Control A
B
Rocainamide
toin (1 g intravenously). Propranolol (0.1 mg/kg) was used only if no contraindications (heart failure, for example) were present. Examples of the use of this method to select a drug regimen are shown in Figures 2 and 3. In Figure 2 both lidocaine and diphenylhydantoin prevent the initiation of ventricular tachycardia with programmed stimulation, and diphenylhydantoin was selected for long-term therapy. In Figure 3 procainamide at a plasma level of 10.2 mg/liter prevents the initiation of sustained tachycardia although a short run of four complexes of the arrhythmia is seen. In neither case has sustained ventricular tachycardia occurred in the follow-up period. Isoproterenol as an additional stress test: In three patients with exercise-induced ventricular tachycardia in whom ventricular stimulation alone failed to initiate the tachycardia, an infusion of isoproterenol to increase the sinus rate to 125 to 150 beats/min was used. This resulted in spontaneous ventricular tachycardia or allowed programmed stimulation to induce a tachycardia that was not inducible before the infusion of isoproterenol. Isoproterenol therefore serves as a stress test for either exercise- or ischemia-induced arrhythmias in these cases. In such instances propranolol has been uniformly successful in prevention of tachycardia, both acutely and on a long-term basis (Fig. 4). Selection of suitable plasma drug level: Acute pharmacologic testing also allows one to select an approximate plasma level that should be maintained during long-term oral therapy in order to prevent the arrhythmia (Fig. 5).“l Although a close correlation appears to exist between the short and long-term blood levels required for arrhythmia prophylaxis for group 1A agent9 (procainamide and quinidine, for example) and diphenylhydantoin, this is not the case with propran0101. The efficacy of beta adrenergic blocking drugs depends on the relation between the prevailing sym-
634
March 1979
The American Journal of CARDIOLOGY
pathetic tone and concentration of the drug. Therefore, the demonstration that acutely administered propranolol is effective suggests that long-term administration of the drug will be successful but that the appropriate dose may vary depending on sympathetic tone. Correlation of failure to prevent initiation of tachycardia and the occurrence of spontaneous episodes: We also found that the failure of a drug to prevent the initiation of ventricular tachycardia correlates closely with the spontaneous development of this arrhythmia. In our series, in all 10 patients in whom each acutely administered drug failed to prevent the initiation of ventricular tachycardia, spontaneous episodes of ventricular tachycardia occurred within 30 days during therapy, even with the agent that made the tachycardia most difficult to induce.” In addition to demonstrating failure of the various antiarrhythmic agents to prevent initiation of arrhythmia, serial drug testing can demonstrate occasional paradoxic acceleration of the rate of tachycardia (Fig. 6). We noted such paradoxic acceleration in five patients after the administration of lidocaine and in one patient after the administration of diphenylhydantoin.” In these cases the long-term use of an oral lidocaine derivative (tocainide, for example) or diphenylhydantoin would be contraindicated. Although an increase in the rate of tachycardia has not been observed after the administration of group 1A drugs, as increasing doses of group 1A agents are administered, the tachycardia frequently becomes easier to induce or even incessant (Fig. 5 and 6). This phenomenon can be explained by a greater slowing of conduction in the reentrant circuit than prolongation of the refractory period of the components of the reentrant circuit. Thus the circulating wave front will never encounter a refractory “tail” of the preceding circulating
Volume 43
ELECTROPHYSIOLOGIC
A
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
AND HOROWITZ
control
:s-“I:
C
propranolol
FIGURE 4. Initiation of ventricukr tachycardia after administration of isoproterenol and its abolition with propranolol. A through C are arranged from top to bottom as electrocardiographic leads I (1). Ii (2) and VI and intracardiac electrograms from the coronary sinus (CS). His bundle recording site (HBE), right ventricular apex (RVA), right ventricular outflow tract (NOT) and time lines (T) at 10 msec intervals. In A, pacing from the right ventricular apex at a cycle length of 300 msec (S. arrows) failed to induce an arrhythmia. In B. after infusion of isoproterenol at 4 pg/min increased the sinus rate to 125 beats/mirl, identical stimulation produced polymorphic ventricular tachycardia. Intravenously administered propranolol (5 mg at 1 mg/min) during the isoproterenol infusion abolished the tachycardia and prevented its reinitiation by rapid pacing (C).
March 1979
The American Journal of CARDIOLOGY
Volume 43
635
ELECTROPHYSlOLOGlC
RV
*
Yb 51
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
AND HOROWITZ
FIGURE 5. Evaluation of dose-responsiveness for procainamide. Each panel shows electrocardiographic lead VI and a right ventricular (RV) electrogram. Stimuli are introduced as in Figure 1. A, in the control study, ventricular tachycardia with a cycle length of 400 msec was initiated by two ventricular extrastimuli (S2 and S3). B, after 1,000 mg of procainamide was administered intravenously (plasma level 12.5 mg/ml), the tachycardia could still be induced but had a longer cycle length (490 msec). C, after an additional infusion of 250 mg of procainamide (plasma level 15.0 mg/ml), the tachycardia could be induced more easily by a single ventricular extrastimulus during sinus rhythm. However, the cycle length was further prolonged (540 msec). After another 250 mg of procainamide (plasma level 17.5 mg/ml) the tachycardia was no longer inducible.
600
’
Procainamide
FIGURE 6. Failure of antiarrhythmic agents to prevent initiation of ventricular tachycardia. Each panel shows electrocardiographic lead VI and a ventricular (LV or RV) electrogram. Abbreviations, coupling intervals and cycle lengths are as indicated in the previous figures. A, during the control study, ventricular tachycardia was induced by a single extrastimulus during ventricular pacing. B, after intravenous administration of 1,250 mg of procainamide (plasma level 1 f .3 ~glml), ventricular tachycardia was induced by a single extrastimulus during sinus rhythm and the cycle length was longer than the control value. The difference in QRS configuration in B was primarily due to a change in gain and QRS prolongation. C, after oral administration of 2,000 mg of quinidine (plasma level 3.4 fig/ml), ventricular tachycardia was initiated by a single extrastimulus during ventricular pacing, and the cycle length was 730 msec. D, after oral administration of disopyramide (200 mg loading dose and 400 mg in 24 hours), ventricular tachycardia (cycle length 560 msec) was induced by a single extrastimulus during ventricular pacing. E, after intravenous administration of 150 mg of lidocaine, ventricular tachycardia was more difficult to induce, requiring two extrastimuli; however, the cycle length of the tachycardia was shortened to 320 msec from a control value of 470 msec. No antiarrhythmic agent. at tolerated plasma concentrations prevented the initiation of ventricular tachycardia. (From Horowitz et al.*’ with permission of the American Heart Association, Inc.)
Quinidine
Disopyramide
636
March 1979
The American Journal of CARDIOLOGY
Volume 43
ELECTROPHYSIOLOGIC
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
AND HOROWITZ
A PACING BCL= 400
FIGURE 7. Role of pacing site in the termination of ventricular tachycardia. During ventricular tachycardia (VT) at a cycle length of 500 msec atrial (A) pacing at a basic cycle length (ECL) of 400 msec captured the ventricle but failed to terminate ventricular tachycardia (top). However, ventricular (V) pacing at the same basic cycle length terminated the tachycardia. Thus, the optimal pacing site and resultant wave front of depolarization should be ascertained before a permanent pacemaker is implanted. NSR = normal sinus rhythm.
v
PACING BCL=400
NSR 1
impulse. We have found that a further increase in the dose of that agent usually results in termination of the arrhythmia and in the inability to reinitiate the arrhythmia (Fig. 5). One must therefore assume that increasing the dosage either prolongs refractoriness more than conduction or produces bidirectional block in the reentrant circuit; in eith,er case the tachycardia can no longer be initiated or sustained.
ventricular extrastimuli failed to terminate the arrhythmia, bursts of rapid ventricular pacing for 3 to 10 beats at cycle lengths from the tachycardia cycle length to 200 msec were employed. In the 27 patients, 10 episodes of tachycardia could be terminated with a single ventricular extrastimulus, 11 could be terminated with double ventricular extrastimuli, and 6 required bursts of rapid ventricular pacing.
Long-term results of the testing method: In this series, a successful pharmacologic regimen was devised in 20 of 34 patients (59 percent). No episode of ventricular tachycardia has occurred in an average followup period of 18 f 8 months. The most effective single agent has been procainamide (successful in 11 patients whose tachycardia was eventually controlled with drugs), but doses commonly considered “toxic” have been required.‘4 The short and long-term plasma levels required for successful therapy range from 9.3 to 19.3 mg/liter. In the other nine patients a different drug was effective. However, no clinical or electrophysiologic criteria allowed prediction of either the agent (or agents) or the dose eventually f’ound successful without systematic evaluation with programmed stimulation. The success of experimental antiarrhythmic agents can also be tested with this method.
Right versus left ventricular stimulation: Factors affecting the ability of programmed stimulation to terminate the tachycardia included the site of stimulation, the electrophysiologic properties of the intervening tissue, the size of the reentrant circuit and the rate of the tachycardia. As found by Wellens et al.,” stimulation could more easily or was more likely to terminate an arrhythmia at some sites than at others (Fig. 7). Because all 27 episodes of tachycardia could be terminated with right ventricular stimulation, stimulation from the left ventricle was not performed in all patients. However, in the 14 patients in whom it was performed, the tachycardia could be terminated with a single ventricular extrastimulus in 7 patients and with double ventricular extrastimuli in the remaining 7 patients; nevertheless, the tachycardia in these 14 patients tended to be more rapid than in the group as a whole. The effects of right or left ventricular stimulation may have important implications when one is choosing between endocardial and epicardial pacemakers. The ability of atria1 pacing to terminate the arrhythmia was also assessed in 12 patients, and the technique was unsuccessful in 11.
Evaluation
of F’acemaker
Therapy
Stimulation protocol: In 27 of 34 patients(79 percent) in whom ventricular tachycardia could be reproducibly initiated, the hemodynamic status during ventricular tachycardia allowed evaluation of modes of pacemaker termination of the tachycardia. In seven patients cardioversion u’as required because of hemodynamic deterioration or development of angina pectoris, or both. In the remaining 27 patients programmed ventricular stimulation similar to that used to initiate the tachycardia was utilized.4 The stimulation protocol included the introduction of single ventricular premature depolarizations scanning diastole until ventricular refractoriness was reached. If refractoriness was encountered before termination of the tachycardia, a second ventricular extrastimulus was introduced. The coupling intervals of both the first and second extrastimuli were varied until both were refractory. If double
Choosing types of long-term pacing therapy: When applying the results of programmed stimulation to the choice of types of long-term pacing therapy, the most obvious generalization apparent in our patients was that slow tachycardias were more likely to be terminated with single ventricular extrastimuli, especially when they arose ipsilateral to the pacing site, whereas more rapid tachycardias (rate greater than 175 beats/ min) uniformly required double ventricular extrastimuli or bursts of rapid pacing.4 ‘l’he group with a slow tachycardia in whom single ventricular extrastimuli could terminate the arrhythmia could successfully utilize a patient-initiated pacemaker (radiofrequency
March 1979
The American Journal of CARDIOLOGY
Volume 43
637
ELECTROPHYSIOLOGIC
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
B
...L + . .., .._
A
FIGURE 6. Underdrive pacemaker therapy for ventricular tachycardia. During the electrophysiologic study (A), a single, appropriately timed ventricular extrastimulus (S, arrow) reproducibly terminated ventricular tachycardia. HBE = His bundle electrogram; HRA = high right atrial electrogram; 1 = electrocardiographic lead I; RV = right ventricular electrogram; T = time lines. B. a ventricular demand pacemaker was triggered by the same patient to interrupt spontaneous ventricular tachycardia as a random stimulus fell at the appropriate interval shown in A
.,
Y
_~_
AND HOROWITZ
_ :
....
‘1
FIGURE 9. Termination of ventricular tachycardia with a burst of rapid ventricular pacing. During the electrophysiologic study (A), ventricular tachycardia (cycle length 300 msec) with a left ventricular origin required a burst of rapid ventricular pacing (cycle length 200 msec) for termination, AVJ = atrioventricular junction; WA = right ventricular apex; RVOT = right ventricular outflow: tract: V-sep = ventricular septum. In B, bursts of rapid pacing from the right ventricle triggered by the physician in the emergency room terminated clinical ventricular tachycardia.
B"1
or demand) to terminate arrhythmia. This was accomplished in two patients (Fig. 8). In patients with rapid rates who require double ventricular extrastimuli or rapid pacing.for termination of the arrhythmia, the only currently available pacing modality is a burst of rapid right ventricular pacing.ss We utilized this form of therapy in only one patient (Fig. 9). Because acceleration of the tachycardia is not uncommon with these techniques, we believe that the pacemaker should be triggered only by a physician with defibrillator equipment available in such patients. As noted by Wellens et al.,2O drugs that can slow the tachycardia (that is, group 1A agents) can change a tachycardia requiring double ventricular extrastimuli for termination to one in which a single random ventricular extrastimulus can terminate the arrhythmia. In such a patient a combination of drugs plus random “underdrive” pacing can be an ac-
636
March 1979
The American Journal of CARDIOLOGY
ceptable form of therapy. One patient in our series (Fig. 6) was treated with a combination of quinidine and a pacemaker. Therefore, successful pacemaker therapy for long-term termination of ventricular tachycardia was used in four patients in whom long-term. pharmacologic regimens could not be devised to prevent recurrences. Patients who require cardioversion because their clinical status has deteriorated or they cannot comprehend methods of pacemaker termination are not candidates for long-term pacemaker therapy. With this group of patients, if drug therapy does not work, surgery should be considered. Evaluation
of Surgical Therapy
The surgical approach to the therapy of medically resistant ventricular tachycardia has evolved consid-
Volume 43
ELECTROPHYSIOLOGIC
erably over the past 10 years. The interventions most commonly used include ventricular aneurysmectomy and coronary bypass grafting, both of which have met with variable success, and in many instances have been accompanied by high surgical mortality rates.2s-“5 A major reason for this lack of success has been the failure to localize the site of origin of the arrhythmia preoperatively to either the aneurysm to be resected or to the area of the myocardium to which the coronary bypass graft is to be placed. Although intraoperative epicardial mapping has recently been used as a surgical guide to localize more accurately the site of origin of the arrhythmia, limitations of’ this technique have recently been reported.:j” Studies both in human being@ and in animal@ have shown that the site of origin of the tachycardia may be distant from the site of epicardial breakthrough. To circumvent these complicating factors we use ventricular endocardial mapping preoperatively. This procedure can establish a rational basis for surgery as well as identify particularly difficult surgical candidates, such as patients whose ventricular tachycardia either arises from within the interventricular septum or uses the interventricu lar septum as a route of myocardial excitation. Methodology of endocardial mapping: Multiple standard electrode catheters (1 cm interelectrode distance) are introduced either percutaneously or by cutdown and positioned in the atrioventricular junction at the point where the His bundle electrogram is recorded, in the right ventricular apex and in the coronary sinus. In addition, catheters are positioned in the right and left ventricles for mapping. Once the tachycardia is initiated with programmed stimulation, the mapping catheters in both ventricles are used as exploring electrodes to map their respective chambers. The catheters at the atrioventricular junction, right ventricular apex, and coronary sinus are not moved and are utilized as reference sites for measurement. The sites that are mapped are listed in Table I. If an aneurysm is present we attempt to map one to three sites within that aneurysm. The positions are verified with fluoroscopy in multiple
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
TABLE
AND HOROWITZ
I
Endocardial
Mapping
Sites
Right Ventricle
Left Ventricle
A-V junction Apex Mid septum Outflow tract Lateral inflow tract Anterior wall
Apex Low septum Mid septum High septum Anterior wall High lateral wall Low lateral wall Posterobasal (CS) Inferior
A-V = atrioventricular; CS = coronary sinus.
planes. Although such mapping cannot localize the site of origin to a discrete point, it can localize the site of origin of the tachycardia to a segment of the heart that has relevance to the operation being contemplated, that is, the origin of the tachycardia can be localized within an aneurysm or to within an area supplied by a coronary artery that is to be grafted. The site of origin is determined by locating the earliest recorded discrete or fragmented ventricular electrogram. The presence of diastolic fragmented ac-
tivity strongly suggests that a part of the reentrant circuit is being recorded.:j’ However, it is not always possible to record diastolic activity because this depends on the spatial arrangement of the catheter and the reentrant circuit. Although continuous electrical activity throughout the cardiac cycle can occasionally be recorded, more often only part of the reentrant circuit can be recorded and nonholodiastolic activity is noted. The ability of catheter mapping to localize the tachycardia to a left ventricular aneurysm was verified in seven patients in whom intraoperative epicardial and endocardial mapping confirmed the site of origin to be within the aneurysm. Relation ventricular
of site of origin to QRS configuration of tachycardia: We analyzed the site of or-
igin of 39 morphologically distinct episodes of ventricular tachycardia in 25 patients including 14 patients
FIGURE 10. Localization of the site of origin by demonstration of continuous activity. The panel is arranged from top to bottom as electrocardiographic leads I (1). aVF .and VI and intracardiac electrogra,ms from the coronary sinus (CS), atrioventricular junction (AVJ), right ventricular apex (WA) and a left ventricular apical aneurysm (LVAn). T = time lines at intervals of 100 msec. Fragmented low amplitude continuous activity (arrows) present in the aneurysm is consistent with recording of an area of reentry-that is. the origin of the tachycardia. The vertkal line marks the onset of the QRS complex, .and the activation times at the coronary sinus, atrioventricular junction and right ventricular apex are listed.
March 1979
The American Journal of CARDIOLOGY
Volume 43
939
ELECTROPHYSIOLOGIC
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
AND HOROWITZ
V
V
AVJ --+
V h *-
:V
>-
\-
V
V
Y-
RVA
LVA
V FIGURE 11. Ventricular tachycardia with a left bundle branch block configuration arising in a left ventricular aneurysm. The panel is arranged from top to bottom as electrocardiographic leads II and VI and electrograms from the high right atrium (HRA), atrioventricular junction (AVJ), right ventricular (RV) septum and inferior left ventricular aneurysm (LV-An). T = time lines. Despite the left bundle branch block pattern of the ventricular tachycardia, the site of origin was in the left ventricular aneurysm. Ventricular activation at the right ventricular septum and atrioventricular junction occurred, respectively, 32 and 50 msec later than in the aneurysm (dotted vertical line).
640
March 1979
The American Journal of CARDIOLOGY
:V
V
V
V
AVJ I. v
RVA + A
V
V
1. Y i A
Y
V
Y
iv
cs
LVA T
who had patterns of both right and left bundle branch block during the tachycardia. There were 20 episodes of ventricular tachycardia with a right bundle branch block pattern and 19 with a left bundle branch block pattern. Seventeen episodes of tachycardia with a right bundle branch block pattern originated within the left ventricle including 14 that were localized to a left ventricular aneurysm. In 5 of these 14, continuous fragmented activity was recorded from within the aneurysm during the tachycardia (Fig. 10) thus supporting a reentrant mechanism. In 8 of the remaining 12 episodes of ventricular tachycardias with a right bundle branch block configuration (including 6 localized to an aneunonholodiastolic activity was observed, rysm), suggesting that a part of the reentrant circuit was being recorded. In three patients with ventricular tachycardia and a right bundle branch block pattern the tachycardia originated in the interventricular septum. Fourteen episodes of ventricular tachycardia with a left bundle branch block configuration, all in patients with a ventricular aneurysm involving the septum, had sites of origin within a left ventricular aneurysm (Fig. 11). Of the remaining episodes of tachycardia with a left bundle branch block configuration, two arose from the septum, and three, all in patients without heart disease, arose from the right ventricle.” In the patients with multiple patterns associated with tachycardia we observed spontaneous or stimulationinduced changes from one to the other. In all patients with ventricular tachycardia with both right and left bundle branch block patterns and ventricular aneu-
V
,.,,,’,,,,,,I,,,,,,,,,,,,’,... :,,
”
FIGURE 12. Pleomorphic ventricular tachycardia originating from a left ventricular aneurysm. Panels A and B demonstrate ventricular tachycardia with a left (panel A) and right (panel B) bundle branch block pattern in the same patient. Both panels are arranged from top to bottom as electrocardiographic lead VI and electrograms from the atrioventricular junction (AVJ), right ventricular apex (WA), coronary sinus (CS) and left ventricular apical aneurysm (LVA). Both morphologic forms arose from the aneurysm and had identical cycle lengths of 250 msec.
rysm, both morphologic forms had their origin in the left ventricular aneurysm (Fig. 12). Although the rate of each morphologic type could differ, slight movement of the catheter always recorded an early diastolic site within the aneurysm. Intraoperative epicardial and endocardial mapping confirmed the site of origin of multiform ventricular tachycardia to be within the aneurysm in seven patients who underwent aneurysmectomy. Surgical implications: The ability to localize a ventricular tachycardia to a left ventricular aneurysm provides the rationale for aneurysmectomy. Pleomorphism (ventricular tachycardia with right and left bundle branch configurations) suggests that the aneurysm involves the septum, which funct.ions as a route of exit of the tachycardia to the epicardial surface of both ventricles. Thus the presence of such pleomorphism necessitates the removal of part of the septum in order to extirpate successfully an exit site or integral component of the reentrant circuit, or both. Finally, the localization of a tachycardia to the interventricular septum makes surgical cure of the arrhythmia extremely
Volume 43
ELECTROPHYSIOLOGIC
difficult. Special surgical techniques, including endocardial excision or encircling ventriculotomy, have been developed to manage this problem.:s8 In our series of 34 patients, 10 could not be treated successfully with pharmacologic or pacemaker techniques. All subsequent:iy underwent left ventricular aneurysmectomy with endocardial excision of the site of origin of the tachycardia as determined from intraoperative epicardial and endocardial mapping. Eight patients survived and underwent electrophysiologic study before discharge. Xn no patient could ventricular tachycardia be induced. No patient subsequently had a recurrence of sustained ventricular tachycardia. Complications
and Limitations
The most frequent complication of our study protocol was local minor vascular problems, such as superficial phlebitis. Arterial complications requiring reexploration and secondary repair c’ccurred in three patients. In seven patients ventricular tachycardia could not be terminated with programmed stimulation and cardioversion was required. No cardiovascular or neurologic complications occurred as a result of frequent induction of ventricular tachycardia during the serial drug studies. No embolic complications were noted despite left ventricular catheterization in 25 patients including 16 with a ventricular aneurysm. This protocol is applicable only to patients in whom ventricular tachycardia can be initiated and terminated with electrical stimulation or isoproterenol infusion. If ventricular tachycardia cannot be reproducibly initiated
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
AND HOROWITZ
and terminated, the choice of therapy must be empiric, based on results in spontaneous episodes. It must be emphasized that this electrophysiologic approach requires the use of sophisticated equipment and highly specialized personnel. It should therefore be performed only at specialized referral centers. Perspective The selection of an antiarrhythmic agent for the therapy of recurrent sustained ventricular tachycardia has heretofore been based on trial and error. Although the majority (32) of our patients were referred for study when ventricular tachycardia recurred after empiric trials of one to six drugs, we believe there is a place for an empiric trial in some patients. If the rate of ventricular tachycardia is relatively slow (less than 175/min), well tolerated by the patient without angina, cerebral symptoms or other incapacitating symptoms, and the arrhythmia is stable for several hours, an empiric trial of one drug could be attempted because failure would not have dire consequences. On the other hand, when the tachycardia poses significant risks (such as rapid degeneration to ventricular fibrillation or unconsciousness), we believe that this electrophysiologic approach should be instituted initially. Acknowledgment We are grateful to John A. Kastor, MD, chief of the Cardiovascular Section, Hospital of the University of Pennsylvania, for continued support and encouragement. We also thank Marie Coscia for preparing the manuscript.
References 1. Wellens HJJ, Schuilenburg RM, Durrer D: Electrical stimulation of the heart in patients with ventricular tachycardia. Circulation 46:216-226, 1972 2. Wellens HJJ, Lie KI, Durrer D: Further observations on ventricular tachycardia as studied by electrical stimulationof the heart. Chronic recurrent ventricular tachycardia and ventricular tachycardia during acute myocardial infarction. Circulation 49:647-653, 1974 3. Wellens HJJ, Duren DR, Lie KI: Observations on mechanisms of ventricular tachycardia in man. Circulation 54:237-244, 1976 4. Josephson ME, Horowitz LN, Farshidi A, Kastor JA: Recurrent sustained ventricular tachycardia I. Mechanisms. Circulation 571431-440, 1978 5. Fisher JD, Cohen HL, Mehra R, Furman S: Cardiac pacing and pacemakers. II. Serial electrophysiologic-pharmacologic testing for control of recurrent tachyarrhythmias. Am Heart J 93:658-668, 1977 6. Josephson ME, Horowitz LN, Farshidi A, Spear JF, Kastor JA, Moore EN: Recurrent sustained ventricular tachycardia Il. Endocardial mapping. Circulation 57:440-447, 1978 7. Wellens HJJ, Durrer D: Effect of digitalis on atrioventricular conduction and circus movement tachycardia in patients with WolffParkinson-White syndrome. Circulation 47:1229-1233, 1973 8. Mandel WJ, Laks MM, Obayasi K, Hayakawa H, Daloy W: The Wolff-Parkinson-White syndrome. pharmacologic effect of procaine amide. Am Heart J 90:744-754, 1975 9. Wellens HJJ, Durrer D: Eifect of procaine amide, quinidine and ajmaline on the Wolff-Parkinson-White syndrome. Circulation 50:114-120, 1974 10. Spurrell RAJ, Krikler DM, Sowton E: Effects of verapamil on electrophysiological properties of anomalous atrioventricular connexion in Wolff-Parkinson-White syndrome. Br Heart J 36: 256-264, 1974
11. Spurrell RAJ, Thorburn CW, Camm J, Sowton E, Deuchar DC: Effects of disopyramide on electrophysiological properties of specialized conduction system in man and on accessory atrioventricular pathway in the Wolff-Parkinson-White syndrome. Br Heart J 37:861-867, 1975 12. Wellens HJJ, Lie KI, Bar FW, Wesdorp JC, Dohmen HJ, Duren DR, Durrer D: Effect of amiodarone in the Wolff-Parkinson-White syndrome. Am J Cardiol 38:189-194. 1976 13. Sellers TD Jr, Campbell RWF, Bashore TM, Gallagher JJ: Effects of procainamide and quinidine sulfate in the Wolff-Parkinson-White syndrome. Circulation 55: 15-22, 1977 14. Zipes DP, Gaum WE, Foster PR, Rosen KM, Wu D, Amat-y-Leon F, Noble RJ: Aprindine for treatment of supraventricular tachycardias with particular application to Wolff-Parkinson-White syndrome. Am J Cardiol 40: 586-596, 1977 15. Wu D, Denes P, Dhingra R, Khan A, Rosen KM: The effects of propranolol on induction of A-V nodal re-entrant paroxysmal tachycardia. Circulation 50:665-677, 1974 16. Wu D, Wyndham C, Amat-y-Leon F, Denes P, Dhingra RC, Rosen KM: The effects of ouabain on induction of A-V nodal re-entrant paroxysmal supraventricular tachycardia. Circulation 52:201-207, 1975 17 Wellens HJJ, Duren DR, Liem KL, Lie KI: Effect of digitalis in patients with paroxysmal atrioventricular nodal tachycardia. Circulation 52:779-788, 1975 18. Wellens HJJ, Tan SL, Bar FW, [)uren DR, Lie KI, Dohmen H: Effect of verapamil studied by programmed electrical stimulation of the heart in patients with paroxysmal re-entrant supraventricular tachycardia. Br Heart J 39:1058-1066, 1977 19. Denes P, Wu D, Dhingra RC, Amat-y-Leon F, Wyndham C, Mautrer RK, Rosen KM: Electrophysiological studies in patients with chronic recurrent ventricular tachycardia. Circulation 54:
March 1979
The American Journal of CARDIOLOGY
Volume 43
641
ELECTROPHYSIOLOGIC
APPROACH TO VENTRICULAR TACHYCAROIA-JOSEPHSON
229-236, 1976 20. Wellens HJJ, Bar FWHM, Lie KI, Duren DR, Dohmen HJ: Effect of procainamide, propranolol and verapamil on mechanism of tachycardia in patients with chronic recurrent ventricular tachycardia. Am J Cardjol 40:579-585, 1977 2 1. Horowitz LN, Josephson ME, Farshidi A, Spielman S, Michelson EL, Greenspan AM: Recurrent sustained ventricular tachycardia. 3. Role of electrophysiologic study in selection of antiarrhythmic regimes. Circulation 58:986-987, 1978 22. Wu D, Wyndham CR, Denes P, Amat-y-Leon F, Miller RH, Dinghra RC, Rosen KM: Chronic electrophysiological study in patients with recurrent paroxysmal tachycardia: a new method for developing successful oral antiarrhythmic therapy. In, Reentrant Arrhythmias (Kulbertus H. edl. Baltimore, University Park Press, 1976, p i94-311 23. Singh BN, Hanswirlh 0: Comparative mechanisms of action of antiarrhvthmic druos. Am Heart J 87:367-382, 1974 24. Koch-Weser J, Kieen SW: Procainamide dosage schedules, plasma concentrations, and clinical effects. JAMA 215: 1454-1460, 1971 25. Fisher JD, Mehra R, Furman S: Termination of ventricular tachycardia with bursts of rapid ventricular pacing. Am J Cardiol 41: 94-102, 1978 26. Graham AF, Miller DC, Stinson EB, Daily PO, Fogarty TJ, Harrison DC: Surgical treatment of refractory life-threatening ventricular tachycardia. Am J Cardiol 32:909-912, 1973 27. Magdison 0: Resection of post-myocardial infarction ventricular aneurysm for cardiac arrhythmia. Chest 56:211-218, 1969 28. Thind GS, Blakemore WS, Zinsser HF: Ventricular aneurysmectomy for the treatment of recurrent ventricular tachycardia. Am J Cardiol 27:690-694, 197 1
642
March 1979
The American Journal of CARDIOLOGY
AN0 HOROWITZ
29. Bryson AL, Parisi AF, Schechter E, Wolfson S: Life threatening ventricular arrhythmias induced by exercise: cessation after coronary bypass surgery. Am J Cardiol 32:995-999, 1973 30. Ecker RR, Mullins CB, Grammer JC, Rea WJ, Atkins JM: Control of intractable ventricular tachycardia by coronary revascularization. Circulation 44:666-670, 197 1 31. Tilkian AG, Pfeifer JF, Barry WH, Lipton MJ, Hultgren HN: The effect of coronary bypass surgery on exercise-induced ventricular arrhythmias. Am Heart J 92:707-714, 1976 32. Nordstrom LA, Cillehei JP, Adicoff A, Sako Y, Gobel FL: Coronary artery surgery for recurrent ventricular arrhythmias in patients with variant angina. Am Heart J 89:236-241, 1975 33. Lown B, Graboys TB: Management of patients with malignant ventricular arrhythmias. Am J Cardiol 39:910-918. 1977 34. McIntosh HD, Garcia JA: The first decade of aortocoronaty bypass grafting. Circulation 57:405-431, 1978 35 Wittig JH, Boineau JP: Surgical treatment of ventricular arrhythmias using epicardial, transmural, and endocardial mapptng Ann Thorac Surg 20:117-126, 1975 36. Spielman SR, Michelson EL, Horowitz LN, Spear JF, Moore EN: The limitations of epicardial mapping as a guide to the surgical therapy of ventricular tachycardia. Circulation 57:666-670, 1978 37. Josephson ME, Horowitz LbJ, Farshidi A: Continuous electrical activity: a mechanism of ventricular tachycardia. Circulation 57: 659-665, 1978 38. Guirqudon G, Fontaine G, Frank R, Escande 0, Etievent P: Encircling endocardial ventriculotomy. A new surgical treatment for life-threatening ventricular tachycardias resistant to medical treatment following myocardial infarction. Ann Thorac Surg 26: 438-444, 1978
Volume 43
Electrophysiologic Approach to Therapy of Recurrent Sustained Ventricular Tachycardia
MARK E. JOSEPHSON, MD, FACC’ LEONARD N. HOROWITZ, MD, FACC’ Philadelphia,
Pennsylvania
From the Electrophysiology Laboratory, Hospital of the University of Pennsylvania, Cardiovascular Section, Department of Medicin’e, University of Pennsylvania School of Medicin,e, Philadelphia, Pennsylvania. This work was supported in part by grants from the American tieart Association, Southeastern Pennsylvania Chapter, and National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. Manuscript received July 18, 1978; revis+ manuscript received September 26, 1978, accepted September 27, 1978. * Recipient of a Research Career Development Award, Grant 1 KO 4 HL00361-0 1National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. t Recipient of a Career Development Investigatorship, American Heart Association, Southeastern Pennsylvania Chapter. Address for reprints: Mark E. ,Josephson. MD, Electrophysiology Laboratpry, 666 White Building, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104.
The refinement of the techniques of programmed stimulation and intracardiac recording has led to understanding of the mechanism of ventricular tachycardia and these techniques can be applied clinically to the development of therapeutic regimens. The efficacy of drug therapy can be assessed in sequential studies evaluating the ability of drugs to prevent initiation of the arrhythmia by electrical stimulation. The efficacy of pacemaker therapy can be evaluated by assessing the effects of stimulation during the tachycardia. The recent development of endocardial mapping provides the surgeon with a tool to guide therapeutic surgical ablation of the site of origin of the tachycardia. Such an electrophysiologic approach to recurrent ventricular tachycardia can lead to the rapid development of successful therapy under controlled conditions.
The treatment of recurrent. sustained ventricular tachycardia remains difficult and often frustrating. The choice of pharmacologic, pacemaking or surgical therapy, alone or in combination, has heretofore been empirically based without objective measures to predict efficacy. In most patients with recurrent sustained ventricular tachycardia, particularly those with coronary artery disease and ventricular aneurysm, the arrhythmia can be reproducibly initiated and terminated with programmed electrical stimulation and the origin localized with endocardial mapping. This observation providks the basis for an organized electrophysiologic approach to the therapy of this arrhythmia.‘-” The ability to initiate the tachycardia reproducibly with programmed stimulation permits rapid and accurate assessment of pharmacologic therapy, whereas termination of the arrhythmia with programmed stimulation provides the data on which the choice of pacing therapy can be based. Finally, localization of the site of origin of the arrhythmia can guide the surgical approach to ablation of ventricular tachycardia if drug therapy and pacing prove unsuccessful. Similar electrophysiologic approaches have led to the development of therapeutic regimens for the treatment of arrhythmias that complicate the Wolff-Parkinson-White syndrome7-l4 and recurrent supraventricular tachycardias not associated with preexcitation. 15-lx The present review will describe in detail our electrophysiologic approach to recurrent sustained ventricular tachycardia in 34 patients. Patient Population Forty patients with recurrent sustained ventricular tachycardia were studied after giving informed consent. The patients ranged in age from 8 to 73 years. The majority (25) of the patients had coronary artery disease, and 21 had a left ventricular aneurysm or healed myocardial infarction. The remaining patients had cardiomyopathy (four patients), valvular heart disease (four patients) or no structural heart disease (seven patients). Each patient had had at least four spontaneous episodes of ventricular tachycardia although most had had many more (18 f 6 episodes [mean f standard deviation]). In none of these patients
March 1979
The American Journal of CARDIOLOGY
Volume 43
631
ELECTROPHYSIOLOGIC
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
ventricular tachycardia related to transient clinical states such as drug toxicity or congestive heart failure. Thirty-two patients were referred for study because they had recurrent arrhythmias despite empiric therapy with at least one antiarrhythmic agent, usually procainamide or quinidine.
AND HOROWITZ
Assessment of Pharmacologic Therapy
was
In our experience recurrent sustained ventricular tachycardia, particularly that due to coronary artery disease and the idiopathic variety, can be reproducibly
FIGURE 1. Initiation of ventricular tachycardia with programmed stimulation. Panels A through C are arranged from top to bottom as follows: electrocardiographic leads II (2) and VI; electrograms from the coronary sinus (CS). His bundle recording site (HBE). right ventricular apex (WA), the border of a left ventricular aneurysm (LV-An, border) and in the aneurysm (LV-AN) and time lines (T) at 10 inset intervals. The lefl ventricular electrograms were recorded from a quadripolar catheter with the distal pair of electrodes in the left ventricular aneurysm and the proximal pair at its border. The ventricles and atria were paced at a basic cycle length of 700 msec (S, A, - A, and V, - V,), and after every eighth paced complex progressively premature ventricular extrastimuli were delivered from the right ventricular apex (S and V,). In A and B ventricular extrastimuli delivered at 310 and 300 msec, respectively, produced fractionation of the electrogram in the aneurysm (arrows). At a critical coupling interval of 290 msec (C) fractionation of the electrogram in the aneurysm spanned diastole, and ventricular tachycardia ensued.
632
March 1979
The American
Journal of CARDIOLOGY
Volume 43
ELECTROPHYSIOLOGICAPPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON AND HOROWITZ
initiated in the vast majority of patients (34 of 40; 85 percent) with programmed electrical stimulation that includes the introduction of progressively premature single or double ventricular extrastimuli and rapid ventricular pacing to cycle lengths of 250 msec (Fig. 1). The details of the stimuiation protocol have previously been reported.4 The effect of a variety of antiarrhythmic agents, alone or in combination, on the ability to initiate the tachycardia can be assessed with programmed stimulation over a period of several days. However, programmed stimulation can be used to assess drug therapy only in those patients in whom the tachycardia can be reproducibly initiated. Thirty-four of the 40 patients studied met this criterion and form the basis for the present review. The use of an electrophysiologic protocol for drug selection is based on two assumptions: (1) The tachy-
cardia initiated in the laboratory with programmed stimulation is identical to the clinical tachycardia, and (2) the response to antiarrhythmic agents in the laboratory predicts the clinical response. The first of these assumptions appears to be well established; our own experience and that of several other centers employing this approach support the second assumption.5J~1517.19-22
’
Prevention of initiation of sustained tachycardia: A drug is considered successful only if it prevents the initiation of sustained tachycardia. Although some investigators use the width of the “tachycardia zone” to judge drug efficacy,‘lg we believe that this end point is not definitive for determining chronic drug therapy. The acutely administered drugs in our protocol include procainamide (1 to 2 g intravenously), quinidine (800 mg intramuscularly), disopyramide (200 to 300 mg orally), lidocaine (225 mg intravenously) and diphenylhydan-
Control “1
FIGURE 2. Serial electrophysiologic study to establish pharmacologic therapy for ventricular tachycardia. Each panel shows electrocardiographic lead V, and a right ventricular (RV) electrogram. Stimuli during ventricular pacing (S,) and programmed extrastimuli (S2 and Ss) are indicated. The coupling intervals of the extrastimuli are shown at left between S, and S2 and S2 and Ss. The cycle length of the tachycardia is indicated on the right. A, in the control study, ventricular tachycardia initiated by two extrastimuli had a (cycle length of 270 msec. B, after the intravenous administration of 1,500 mg of procainamide (plasma level 18.7 fig/ml). ventricular tachycardia was still inducible at slightly longer coupling intervals; however, the cycle length of the tachycardia was greatly prolonged. The QRS complex was also widened to 215 msec (control value 165 msec). C, after the oral administration of 2,000 mg of quinidine (plasma level 3.4 pug/ml), ventricular tachycardia was inducible at the control coupling intervals and the cycle length was not significantly different from the control value. D, after the intravenous administration of 175 mg of lidoc.aine, nonsustained ventricular tachycardia (one complex) was induced. E, after the intravenous administration of 1,000 mg of diphenylhydantoin (plasma level 9.75 pg/ml), two ventricular extrastimuli failed to induce ventricular tachycardia. No other coupling intervals or stimulation protocol produced ventricular tachycardia after the administration of diphenylhydantoin. Identical results were obtained 3 days later during long-term oral administration of diphenylhydantoin (plasma level 10.5 Fg/ml). (From Horowitz et al.,2’ with permission of the American Heart Association, Inc.)
Procainamide
B
Quinidine
Lidocaine
D yy$~$. Diphenylhydantoin
E
V’--
March 1979
The American Journal of CARDIOLOGY
Volume 43
633
ELECTROPiiYSlOi_OGiCAPmoAch
TO VENTRICULAR TACHYCAR~IA-JOSEPHSON AND HOROWITZ
FIGURE 3. Prevention of initiation of sustained ventricular tachycardia with drug therapy. A and B are organized from top to bottom as electrocardiographic leads aVF and V, and a left ventricular (LV) electrogram. Time lines (T) at the bottom of B are at 10 msec intervals. During the control study (A), sustained ventricular tachycardia at a cycle length of 250 msec was initiated by two ventricular extrastimuli (S? and Sg) delivered from the left ventricle. After the administration of 1 g of intravenous procainamide produced a plasma level of 10.2 mg/liter, the initiation of sustained ventricular tachycardia was prevented although a short run of four complexes is seen. Long-term oral therapy with procainamide producing trough plasma levels of 10.5 to 11.0 mg/liter has prevented the recurrence of spontaneous ventricular tachycardia.
Control A
B
Rocainamide
toin (1 g intravenously). Propranolol (0.1 mg/kg) was used only if no contraindications (heart failure, for example) were present. Examples of the use of this method to select a drug regimen are shown in Figures 2 and 3. In Figure 2 both lidocaine and diphenylhydantoin prevent the initiation of ventricular tachycardia with programmed stimulation, and diphenylhydantoin was selected for long-term therapy. In Figure 3 procainamide at a plasma level of 10.2 mg/liter prevents the initiation of sustained tachycardia although a short run of four complexes of the arrhythmia is seen. In neither case has sustained ventricular tachycardia occurred in the follow-up period. Isoproterenol as an additional stress test: In three patients with exercise-induced ventricular tachycardia in whom ventricular stimulation alone failed to initiate the tachycardia, an infusion of isoproterenol to increase the sinus rate to 125 to 150 beats/min was used. This resulted in spontaneous ventricular tachycardia or allowed programmed stimulation to induce a tachycardia that was not inducible before the infusion of isoproterenol. Isoproterenol therefore serves as a stress test for either exercise- or ischemia-induced arrhythmias in these cases. In such instances propranolol has been uniformly successful in prevention of tachycardia, both acutely and on a long-term basis (Fig. 4). Selection of suitable plasma drug level: Acute pharmacologic testing also allows one to select an approximate plasma level that should be maintained during long-term oral therapy in order to prevent the arrhythmia (Fig. 5).“l Although a close correlation appears to exist between the short and long-term blood levels required for arrhythmia prophylaxis for group 1A agent9 (procainamide and quinidine, for example) and diphenylhydantoin, this is not the case with propran0101. The efficacy of beta adrenergic blocking drugs depends on the relation between the prevailing sym-
634
March 1979
The American Journal of CARDIOLOGY
pathetic tone and concentration of the drug. Therefore, the demonstration that acutely administered propranolol is effective suggests that long-term administration of the drug will be successful but that the appropriate dose may vary depending on sympathetic tone. Correlation of failure to prevent initiation of tachycardia and the occurrence of spontaneous episodes: We also found that the failure of a drug to prevent the initiation of ventricular tachycardia correlates closely with the spontaneous development of this arrhythmia. In our series, in all 10 patients in whom each acutely administered drug failed to prevent the initiation of ventricular tachycardia, spontaneous episodes of ventricular tachycardia occurred within 30 days during therapy, even with the agent that made the tachycardia most difficult to induce.” In addition to demonstrating failure of the various antiarrhythmic agents to prevent initiation of arrhythmia, serial drug testing can demonstrate occasional paradoxic acceleration of the rate of tachycardia (Fig. 6). We noted such paradoxic acceleration in five patients after the administration of lidocaine and in one patient after the administration of diphenylhydantoin.” In these cases the long-term use of an oral lidocaine derivative (tocainide, for example) or diphenylhydantoin would be contraindicated. Although an increase in the rate of tachycardia has not been observed after the administration of group 1A drugs, as increasing doses of group 1A agents are administered, the tachycardia frequently becomes easier to induce or even incessant (Fig. 5 and 6). This phenomenon can be explained by a greater slowing of conduction in the reentrant circuit than prolongation of the refractory period of the components of the reentrant circuit. Thus the circulating wave front will never encounter a refractory “tail” of the preceding circulating
Volume 43
ELECTROPHYSIOLOGIC
A
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
AND HOROWITZ
control
:s-“I:
C
propranolol
FIGURE 4. Initiation of ventricukr tachycardia after administration of isoproterenol and its abolition with propranolol. A through C are arranged from top to bottom as electrocardiographic leads I (1). Ii (2) and VI and intracardiac electrograms from the coronary sinus (CS). His bundle recording site (HBE), right ventricular apex (RVA), right ventricular outflow tract (NOT) and time lines (T) at 10 msec intervals. In A, pacing from the right ventricular apex at a cycle length of 300 msec (S. arrows) failed to induce an arrhythmia. In B. after infusion of isoproterenol at 4 pg/min increased the sinus rate to 125 beats/mirl, identical stimulation produced polymorphic ventricular tachycardia. Intravenously administered propranolol (5 mg at 1 mg/min) during the isoproterenol infusion abolished the tachycardia and prevented its reinitiation by rapid pacing (C).
March 1979
The American Journal of CARDIOLOGY
Volume 43
635
ELECTROPHYSlOLOGlC
RV
*
Yb 51
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
AND HOROWITZ
FIGURE 5. Evaluation of dose-responsiveness for procainamide. Each panel shows electrocardiographic lead VI and a right ventricular (RV) electrogram. Stimuli are introduced as in Figure 1. A, in the control study, ventricular tachycardia with a cycle length of 400 msec was initiated by two ventricular extrastimuli (S2 and S3). B, after 1,000 mg of procainamide was administered intravenously (plasma level 12.5 mg/ml), the tachycardia could still be induced but had a longer cycle length (490 msec). C, after an additional infusion of 250 mg of procainamide (plasma level 15.0 mg/ml), the tachycardia could be induced more easily by a single ventricular extrastimulus during sinus rhythm. However, the cycle length was further prolonged (540 msec). After another 250 mg of procainamide (plasma level 17.5 mg/ml) the tachycardia was no longer inducible.
600
’
Procainamide
FIGURE 6. Failure of antiarrhythmic agents to prevent initiation of ventricular tachycardia. Each panel shows electrocardiographic lead VI and a ventricular (LV or RV) electrogram. Abbreviations, coupling intervals and cycle lengths are as indicated in the previous figures. A, during the control study, ventricular tachycardia was induced by a single extrastimulus during ventricular pacing. B, after intravenous administration of 1,250 mg of procainamide (plasma level 1 f .3 ~glml), ventricular tachycardia was induced by a single extrastimulus during sinus rhythm and the cycle length was longer than the control value. The difference in QRS configuration in B was primarily due to a change in gain and QRS prolongation. C, after oral administration of 2,000 mg of quinidine (plasma level 3.4 fig/ml), ventricular tachycardia was initiated by a single extrastimulus during ventricular pacing, and the cycle length was 730 msec. D, after oral administration of disopyramide (200 mg loading dose and 400 mg in 24 hours), ventricular tachycardia (cycle length 560 msec) was induced by a single extrastimulus during ventricular pacing. E, after intravenous administration of 150 mg of lidocaine, ventricular tachycardia was more difficult to induce, requiring two extrastimuli; however, the cycle length of the tachycardia was shortened to 320 msec from a control value of 470 msec. No antiarrhythmic agent. at tolerated plasma concentrations prevented the initiation of ventricular tachycardia. (From Horowitz et al.*’ with permission of the American Heart Association, Inc.)
Quinidine
Disopyramide
636
March 1979
The American Journal of CARDIOLOGY
Volume 43
ELECTROPHYSIOLOGIC
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
AND HOROWITZ
A PACING BCL= 400
FIGURE 7. Role of pacing site in the termination of ventricular tachycardia. During ventricular tachycardia (VT) at a cycle length of 500 msec atrial (A) pacing at a basic cycle length (ECL) of 400 msec captured the ventricle but failed to terminate ventricular tachycardia (top). However, ventricular (V) pacing at the same basic cycle length terminated the tachycardia. Thus, the optimal pacing site and resultant wave front of depolarization should be ascertained before a permanent pacemaker is implanted. NSR = normal sinus rhythm.
v
PACING BCL=400
NSR 1
impulse. We have found that a further increase in the dose of that agent usually results in termination of the arrhythmia and in the inability to reinitiate the arrhythmia (Fig. 5). One must therefore assume that increasing the dosage either prolongs refractoriness more than conduction or produces bidirectional block in the reentrant circuit; in eith,er case the tachycardia can no longer be initiated or sustained.
ventricular extrastimuli failed to terminate the arrhythmia, bursts of rapid ventricular pacing for 3 to 10 beats at cycle lengths from the tachycardia cycle length to 200 msec were employed. In the 27 patients, 10 episodes of tachycardia could be terminated with a single ventricular extrastimulus, 11 could be terminated with double ventricular extrastimuli, and 6 required bursts of rapid ventricular pacing.
Long-term results of the testing method: In this series, a successful pharmacologic regimen was devised in 20 of 34 patients (59 percent). No episode of ventricular tachycardia has occurred in an average followup period of 18 f 8 months. The most effective single agent has been procainamide (successful in 11 patients whose tachycardia was eventually controlled with drugs), but doses commonly considered “toxic” have been required.‘4 The short and long-term plasma levels required for successful therapy range from 9.3 to 19.3 mg/liter. In the other nine patients a different drug was effective. However, no clinical or electrophysiologic criteria allowed prediction of either the agent (or agents) or the dose eventually f’ound successful without systematic evaluation with programmed stimulation. The success of experimental antiarrhythmic agents can also be tested with this method.
Right versus left ventricular stimulation: Factors affecting the ability of programmed stimulation to terminate the tachycardia included the site of stimulation, the electrophysiologic properties of the intervening tissue, the size of the reentrant circuit and the rate of the tachycardia. As found by Wellens et al.,” stimulation could more easily or was more likely to terminate an arrhythmia at some sites than at others (Fig. 7). Because all 27 episodes of tachycardia could be terminated with right ventricular stimulation, stimulation from the left ventricle was not performed in all patients. However, in the 14 patients in whom it was performed, the tachycardia could be terminated with a single ventricular extrastimulus in 7 patients and with double ventricular extrastimuli in the remaining 7 patients; nevertheless, the tachycardia in these 14 patients tended to be more rapid than in the group as a whole. The effects of right or left ventricular stimulation may have important implications when one is choosing between endocardial and epicardial pacemakers. The ability of atria1 pacing to terminate the arrhythmia was also assessed in 12 patients, and the technique was unsuccessful in 11.
Evaluation
of F’acemaker
Therapy
Stimulation protocol: In 27 of 34 patients(79 percent) in whom ventricular tachycardia could be reproducibly initiated, the hemodynamic status during ventricular tachycardia allowed evaluation of modes of pacemaker termination of the tachycardia. In seven patients cardioversion u’as required because of hemodynamic deterioration or development of angina pectoris, or both. In the remaining 27 patients programmed ventricular stimulation similar to that used to initiate the tachycardia was utilized.4 The stimulation protocol included the introduction of single ventricular premature depolarizations scanning diastole until ventricular refractoriness was reached. If refractoriness was encountered before termination of the tachycardia, a second ventricular extrastimulus was introduced. The coupling intervals of both the first and second extrastimuli were varied until both were refractory. If double
Choosing types of long-term pacing therapy: When applying the results of programmed stimulation to the choice of types of long-term pacing therapy, the most obvious generalization apparent in our patients was that slow tachycardias were more likely to be terminated with single ventricular extrastimuli, especially when they arose ipsilateral to the pacing site, whereas more rapid tachycardias (rate greater than 175 beats/ min) uniformly required double ventricular extrastimuli or bursts of rapid pacing.4 ‘l’he group with a slow tachycardia in whom single ventricular extrastimuli could terminate the arrhythmia could successfully utilize a patient-initiated pacemaker (radiofrequency
March 1979
The American Journal of CARDIOLOGY
Volume 43
637
ELECTROPHYSIOLOGIC
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
B
...L + . .., .._
A
FIGURE 6. Underdrive pacemaker therapy for ventricular tachycardia. During the electrophysiologic study (A), a single, appropriately timed ventricular extrastimulus (S, arrow) reproducibly terminated ventricular tachycardia. HBE = His bundle electrogram; HRA = high right atrial electrogram; 1 = electrocardiographic lead I; RV = right ventricular electrogram; T = time lines. B. a ventricular demand pacemaker was triggered by the same patient to interrupt spontaneous ventricular tachycardia as a random stimulus fell at the appropriate interval shown in A
.,
Y
_~_
AND HOROWITZ
_ :
....
‘1
FIGURE 9. Termination of ventricular tachycardia with a burst of rapid ventricular pacing. During the electrophysiologic study (A), ventricular tachycardia (cycle length 300 msec) with a left ventricular origin required a burst of rapid ventricular pacing (cycle length 200 msec) for termination, AVJ = atrioventricular junction; WA = right ventricular apex; RVOT = right ventricular outflow: tract: V-sep = ventricular septum. In B, bursts of rapid pacing from the right ventricle triggered by the physician in the emergency room terminated clinical ventricular tachycardia.
B"1
or demand) to terminate arrhythmia. This was accomplished in two patients (Fig. 8). In patients with rapid rates who require double ventricular extrastimuli or rapid pacing.for termination of the arrhythmia, the only currently available pacing modality is a burst of rapid right ventricular pacing.ss We utilized this form of therapy in only one patient (Fig. 9). Because acceleration of the tachycardia is not uncommon with these techniques, we believe that the pacemaker should be triggered only by a physician with defibrillator equipment available in such patients. As noted by Wellens et al.,2O drugs that can slow the tachycardia (that is, group 1A agents) can change a tachycardia requiring double ventricular extrastimuli for termination to one in which a single random ventricular extrastimulus can terminate the arrhythmia. In such a patient a combination of drugs plus random “underdrive” pacing can be an ac-
636
March 1979
The American Journal of CARDIOLOGY
ceptable form of therapy. One patient in our series (Fig. 6) was treated with a combination of quinidine and a pacemaker. Therefore, successful pacemaker therapy for long-term termination of ventricular tachycardia was used in four patients in whom long-term. pharmacologic regimens could not be devised to prevent recurrences. Patients who require cardioversion because their clinical status has deteriorated or they cannot comprehend methods of pacemaker termination are not candidates for long-term pacemaker therapy. With this group of patients, if drug therapy does not work, surgery should be considered. Evaluation
of Surgical Therapy
The surgical approach to the therapy of medically resistant ventricular tachycardia has evolved consid-
Volume 43
ELECTROPHYSIOLOGIC
erably over the past 10 years. The interventions most commonly used include ventricular aneurysmectomy and coronary bypass grafting, both of which have met with variable success, and in many instances have been accompanied by high surgical mortality rates.2s-“5 A major reason for this lack of success has been the failure to localize the site of origin of the arrhythmia preoperatively to either the aneurysm to be resected or to the area of the myocardium to which the coronary bypass graft is to be placed. Although intraoperative epicardial mapping has recently been used as a surgical guide to localize more accurately the site of origin of the arrhythmia, limitations of’ this technique have recently been reported.:j” Studies both in human being@ and in animal@ have shown that the site of origin of the tachycardia may be distant from the site of epicardial breakthrough. To circumvent these complicating factors we use ventricular endocardial mapping preoperatively. This procedure can establish a rational basis for surgery as well as identify particularly difficult surgical candidates, such as patients whose ventricular tachycardia either arises from within the interventricular septum or uses the interventricu lar septum as a route of myocardial excitation. Methodology of endocardial mapping: Multiple standard electrode catheters (1 cm interelectrode distance) are introduced either percutaneously or by cutdown and positioned in the atrioventricular junction at the point where the His bundle electrogram is recorded, in the right ventricular apex and in the coronary sinus. In addition, catheters are positioned in the right and left ventricles for mapping. Once the tachycardia is initiated with programmed stimulation, the mapping catheters in both ventricles are used as exploring electrodes to map their respective chambers. The catheters at the atrioventricular junction, right ventricular apex, and coronary sinus are not moved and are utilized as reference sites for measurement. The sites that are mapped are listed in Table I. If an aneurysm is present we attempt to map one to three sites within that aneurysm. The positions are verified with fluoroscopy in multiple
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
TABLE
AND HOROWITZ
I
Endocardial
Mapping
Sites
Right Ventricle
Left Ventricle
A-V junction Apex Mid septum Outflow tract Lateral inflow tract Anterior wall
Apex Low septum Mid septum High septum Anterior wall High lateral wall Low lateral wall Posterobasal (CS) Inferior
A-V = atrioventricular; CS = coronary sinus.
planes. Although such mapping cannot localize the site of origin to a discrete point, it can localize the site of origin of the tachycardia to a segment of the heart that has relevance to the operation being contemplated, that is, the origin of the tachycardia can be localized within an aneurysm or to within an area supplied by a coronary artery that is to be grafted. The site of origin is determined by locating the earliest recorded discrete or fragmented ventricular electrogram. The presence of diastolic fragmented ac-
tivity strongly suggests that a part of the reentrant circuit is being recorded.:j’ However, it is not always possible to record diastolic activity because this depends on the spatial arrangement of the catheter and the reentrant circuit. Although continuous electrical activity throughout the cardiac cycle can occasionally be recorded, more often only part of the reentrant circuit can be recorded and nonholodiastolic activity is noted. The ability of catheter mapping to localize the tachycardia to a left ventricular aneurysm was verified in seven patients in whom intraoperative epicardial and endocardial mapping confirmed the site of origin to be within the aneurysm. Relation ventricular
of site of origin to QRS configuration of tachycardia: We analyzed the site of or-
igin of 39 morphologically distinct episodes of ventricular tachycardia in 25 patients including 14 patients
FIGURE 10. Localization of the site of origin by demonstration of continuous activity. The panel is arranged from top to bottom as electrocardiographic leads I (1). aVF .and VI and intracardiac electrogra,ms from the coronary sinus (CS), atrioventricular junction (AVJ), right ventricular apex (WA) and a left ventricular apical aneurysm (LVAn). T = time lines at intervals of 100 msec. Fragmented low amplitude continuous activity (arrows) present in the aneurysm is consistent with recording of an area of reentry-that is. the origin of the tachycardia. The vertkal line marks the onset of the QRS complex, .and the activation times at the coronary sinus, atrioventricular junction and right ventricular apex are listed.
March 1979
The American Journal of CARDIOLOGY
Volume 43
939
ELECTROPHYSIOLOGIC
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
AND HOROWITZ
V
V
AVJ --+
V h *-
:V
>-
\-
V
V
Y-
RVA
LVA
V FIGURE 11. Ventricular tachycardia with a left bundle branch block configuration arising in a left ventricular aneurysm. The panel is arranged from top to bottom as electrocardiographic leads II and VI and electrograms from the high right atrium (HRA), atrioventricular junction (AVJ), right ventricular (RV) septum and inferior left ventricular aneurysm (LV-An). T = time lines. Despite the left bundle branch block pattern of the ventricular tachycardia, the site of origin was in the left ventricular aneurysm. Ventricular activation at the right ventricular septum and atrioventricular junction occurred, respectively, 32 and 50 msec later than in the aneurysm (dotted vertical line).
640
March 1979
The American Journal of CARDIOLOGY
:V
V
V
V
AVJ I. v
RVA + A
V
V
1. Y i A
Y
V
Y
iv
cs
LVA T
who had patterns of both right and left bundle branch block during the tachycardia. There were 20 episodes of ventricular tachycardia with a right bundle branch block pattern and 19 with a left bundle branch block pattern. Seventeen episodes of tachycardia with a right bundle branch block pattern originated within the left ventricle including 14 that were localized to a left ventricular aneurysm. In 5 of these 14, continuous fragmented activity was recorded from within the aneurysm during the tachycardia (Fig. 10) thus supporting a reentrant mechanism. In 8 of the remaining 12 episodes of ventricular tachycardias with a right bundle branch block configuration (including 6 localized to an aneunonholodiastolic activity was observed, rysm), suggesting that a part of the reentrant circuit was being recorded. In three patients with ventricular tachycardia and a right bundle branch block pattern the tachycardia originated in the interventricular septum. Fourteen episodes of ventricular tachycardia with a left bundle branch block configuration, all in patients with a ventricular aneurysm involving the septum, had sites of origin within a left ventricular aneurysm (Fig. 11). Of the remaining episodes of tachycardia with a left bundle branch block configuration, two arose from the septum, and three, all in patients without heart disease, arose from the right ventricle.” In the patients with multiple patterns associated with tachycardia we observed spontaneous or stimulationinduced changes from one to the other. In all patients with ventricular tachycardia with both right and left bundle branch block patterns and ventricular aneu-
V
,.,,,’,,,,,,I,,,,,,,,,,,,’,... :,,
”
FIGURE 12. Pleomorphic ventricular tachycardia originating from a left ventricular aneurysm. Panels A and B demonstrate ventricular tachycardia with a left (panel A) and right (panel B) bundle branch block pattern in the same patient. Both panels are arranged from top to bottom as electrocardiographic lead VI and electrograms from the atrioventricular junction (AVJ), right ventricular apex (WA), coronary sinus (CS) and left ventricular apical aneurysm (LVA). Both morphologic forms arose from the aneurysm and had identical cycle lengths of 250 msec.
rysm, both morphologic forms had their origin in the left ventricular aneurysm (Fig. 12). Although the rate of each morphologic type could differ, slight movement of the catheter always recorded an early diastolic site within the aneurysm. Intraoperative epicardial and endocardial mapping confirmed the site of origin of multiform ventricular tachycardia to be within the aneurysm in seven patients who underwent aneurysmectomy. Surgical implications: The ability to localize a ventricular tachycardia to a left ventricular aneurysm provides the rationale for aneurysmectomy. Pleomorphism (ventricular tachycardia with right and left bundle branch configurations) suggests that the aneurysm involves the septum, which funct.ions as a route of exit of the tachycardia to the epicardial surface of both ventricles. Thus the presence of such pleomorphism necessitates the removal of part of the septum in order to extirpate successfully an exit site or integral component of the reentrant circuit, or both. Finally, the localization of a tachycardia to the interventricular septum makes surgical cure of the arrhythmia extremely
Volume 43
ELECTROPHYSIOLOGIC
difficult. Special surgical techniques, including endocardial excision or encircling ventriculotomy, have been developed to manage this problem.:s8 In our series of 34 patients, 10 could not be treated successfully with pharmacologic or pacemaker techniques. All subsequent:iy underwent left ventricular aneurysmectomy with endocardial excision of the site of origin of the tachycardia as determined from intraoperative epicardial and endocardial mapping. Eight patients survived and underwent electrophysiologic study before discharge. Xn no patient could ventricular tachycardia be induced. No patient subsequently had a recurrence of sustained ventricular tachycardia. Complications
and Limitations
The most frequent complication of our study protocol was local minor vascular problems, such as superficial phlebitis. Arterial complications requiring reexploration and secondary repair c’ccurred in three patients. In seven patients ventricular tachycardia could not be terminated with programmed stimulation and cardioversion was required. No cardiovascular or neurologic complications occurred as a result of frequent induction of ventricular tachycardia during the serial drug studies. No embolic complications were noted despite left ventricular catheterization in 25 patients including 16 with a ventricular aneurysm. This protocol is applicable only to patients in whom ventricular tachycardia can be initiated and terminated with electrical stimulation or isoproterenol infusion. If ventricular tachycardia cannot be reproducibly initiated
APPROACH TO VENTRICULAR TACHYCARDIA-JOSEPHSON
AND HOROWITZ
and terminated, the choice of therapy must be empiric, based on results in spontaneous episodes. It must be emphasized that this electrophysiologic approach requires the use of sophisticated equipment and highly specialized personnel. It should therefore be performed only at specialized referral centers. Perspective The selection of an antiarrhythmic agent for the therapy of recurrent sustained ventricular tachycardia has heretofore been based on trial and error. Although the majority (32) of our patients were referred for study when ventricular tachycardia recurred after empiric trials of one to six drugs, we believe there is a place for an empiric trial in some patients. If the rate of ventricular tachycardia is relatively slow (less than 175/min), well tolerated by the patient without angina, cerebral symptoms or other incapacitating symptoms, and the arrhythmia is stable for several hours, an empiric trial of one drug could be attempted because failure would not have dire consequences. On the other hand, when the tachycardia poses significant risks (such as rapid degeneration to ventricular fibrillation or unconsciousness), we believe that this electrophysiologic approach should be instituted initially. Acknowledgment We are grateful to John A. Kastor, MD, chief of the Cardiovascular Section, Hospital of the University of Pennsylvania, for continued support and encouragement. We also thank Marie Coscia for preparing the manuscript.
References 1. Wellens HJJ, Schuilenburg RM, Durrer D: Electrical stimulation of the heart in patients with ventricular tachycardia. Circulation 46:216-226, 1972 2. Wellens HJJ, Lie KI, Durrer D: Further observations on ventricular tachycardia as studied by electrical stimulationof the heart. Chronic recurrent ventricular tachycardia and ventricular tachycardia during acute myocardial infarction. Circulation 49:647-653, 1974 3. Wellens HJJ, Duren DR, Lie KI: Observations on mechanisms of ventricular tachycardia in man. Circulation 54:237-244, 1976 4. Josephson ME, Horowitz LN, Farshidi A, Kastor JA: Recurrent sustained ventricular tachycardia I. Mechanisms. Circulation 571431-440, 1978 5. Fisher JD, Cohen HL, Mehra R, Furman S: Cardiac pacing and pacemakers. II. Serial electrophysiologic-pharmacologic testing for control of recurrent tachyarrhythmias. Am Heart J 93:658-668, 1977 6. Josephson ME, Horowitz LN, Farshidi A, Spear JF, Kastor JA, Moore EN: Recurrent sustained ventricular tachycardia Il. Endocardial mapping. Circulation 57:440-447, 1978 7. Wellens HJJ, Durrer D: Effect of digitalis on atrioventricular conduction and circus movement tachycardia in patients with WolffParkinson-White syndrome. Circulation 47:1229-1233, 1973 8. Mandel WJ, Laks MM, Obayasi K, Hayakawa H, Daloy W: The Wolff-Parkinson-White syndrome. pharmacologic effect of procaine amide. Am Heart J 90:744-754, 1975 9. Wellens HJJ, Durrer D: Eifect of procaine amide, quinidine and ajmaline on the Wolff-Parkinson-White syndrome. Circulation 50:114-120, 1974 10. Spurrell RAJ, Krikler DM, Sowton E: Effects of verapamil on electrophysiological properties of anomalous atrioventricular connexion in Wolff-Parkinson-White syndrome. Br Heart J 36: 256-264, 1974
11. Spurrell RAJ, Thorburn CW, Camm J, Sowton E, Deuchar DC: Effects of disopyramide on electrophysiological properties of specialized conduction system in man and on accessory atrioventricular pathway in the Wolff-Parkinson-White syndrome. Br Heart J 37:861-867, 1975 12. Wellens HJJ, Lie KI, Bar FW, Wesdorp JC, Dohmen HJ, Duren DR, Durrer D: Effect of amiodarone in the Wolff-Parkinson-White syndrome. Am J Cardiol 38:189-194. 1976 13. Sellers TD Jr, Campbell RWF, Bashore TM, Gallagher JJ: Effects of procainamide and quinidine sulfate in the Wolff-Parkinson-White syndrome. Circulation 55: 15-22, 1977 14. Zipes DP, Gaum WE, Foster PR, Rosen KM, Wu D, Amat-y-Leon F, Noble RJ: Aprindine for treatment of supraventricular tachycardias with particular application to Wolff-Parkinson-White syndrome. Am J Cardiol 40: 586-596, 1977 15. Wu D, Denes P, Dhingra R, Khan A, Rosen KM: The effects of propranolol on induction of A-V nodal re-entrant paroxysmal tachycardia. Circulation 50:665-677, 1974 16. Wu D, Wyndham C, Amat-y-Leon F, Denes P, Dhingra RC, Rosen KM: The effects of ouabain on induction of A-V nodal re-entrant paroxysmal supraventricular tachycardia. Circulation 52:201-207, 1975 17 Wellens HJJ, Duren DR, Liem KL, Lie KI: Effect of digitalis in patients with paroxysmal atrioventricular nodal tachycardia. Circulation 52:779-788, 1975 18. Wellens HJJ, Tan SL, Bar FW, [)uren DR, Lie KI, Dohmen H: Effect of verapamil studied by programmed electrical stimulation of the heart in patients with paroxysmal re-entrant supraventricular tachycardia. Br Heart J 39:1058-1066, 1977 19. Denes P, Wu D, Dhingra RC, Amat-y-Leon F, Wyndham C, Mautrer RK, Rosen KM: Electrophysiological studies in patients with chronic recurrent ventricular tachycardia. Circulation 54:
March 1979
The American Journal of CARDIOLOGY
Volume 43
641
ELECTROPHYSIOLOGIC
APPROACH TO VENTRICULAR TACHYCAROIA-JOSEPHSON
229-236, 1976 20. Wellens HJJ, Bar FWHM, Lie KI, Duren DR, Dohmen HJ: Effect of procainamide, propranolol and verapamil on mechanism of tachycardia in patients with chronic recurrent ventricular tachycardia. Am J Cardjol 40:579-585, 1977 2 1. Horowitz LN, Josephson ME, Farshidi A, Spielman S, Michelson EL, Greenspan AM: Recurrent sustained ventricular tachycardia. 3. Role of electrophysiologic study in selection of antiarrhythmic regimes. Circulation 58:986-987, 1978 22. Wu D, Wyndham CR, Denes P, Amat-y-Leon F, Miller RH, Dinghra RC, Rosen KM: Chronic electrophysiological study in patients with recurrent paroxysmal tachycardia: a new method for developing successful oral antiarrhythmic therapy. In, Reentrant Arrhythmias (Kulbertus H. edl. Baltimore, University Park Press, 1976, p i94-311 23. Singh BN, Hanswirlh 0: Comparative mechanisms of action of antiarrhvthmic druos. Am Heart J 87:367-382, 1974 24. Koch-Weser J, Kieen SW: Procainamide dosage schedules, plasma concentrations, and clinical effects. JAMA 215: 1454-1460, 1971 25. Fisher JD, Mehra R, Furman S: Termination of ventricular tachycardia with bursts of rapid ventricular pacing. Am J Cardiol 41: 94-102, 1978 26. Graham AF, Miller DC, Stinson EB, Daily PO, Fogarty TJ, Harrison DC: Surgical treatment of refractory life-threatening ventricular tachycardia. Am J Cardiol 32:909-912, 1973 27. Magdison 0: Resection of post-myocardial infarction ventricular aneurysm for cardiac arrhythmia. Chest 56:211-218, 1969 28. Thind GS, Blakemore WS, Zinsser HF: Ventricular aneurysmectomy for the treatment of recurrent ventricular tachycardia. Am J Cardiol 27:690-694, 197 1
642
March 1979
The American Journal of CARDIOLOGY
AN0 HOROWITZ
29. Bryson AL, Parisi AF, Schechter E, Wolfson S: Life threatening ventricular arrhythmias induced by exercise: cessation after coronary bypass surgery. Am J Cardiol 32:995-999, 1973 30. Ecker RR, Mullins CB, Grammer JC, Rea WJ, Atkins JM: Control of intractable ventricular tachycardia by coronary revascularization. Circulation 44:666-670, 197 1 31. Tilkian AG, Pfeifer JF, Barry WH, Lipton MJ, Hultgren HN: The effect of coronary bypass surgery on exercise-induced ventricular arrhythmias. Am Heart J 92:707-714, 1976 32. Nordstrom LA, Cillehei JP, Adicoff A, Sako Y, Gobel FL: Coronary artery surgery for recurrent ventricular arrhythmias in patients with variant angina. Am Heart J 89:236-241, 1975 33. Lown B, Graboys TB: Management of patients with malignant ventricular arrhythmias. Am J Cardiol 39:910-918. 1977 34. McIntosh HD, Garcia JA: The first decade of aortocoronaty bypass grafting. Circulation 57:405-431, 1978 35 Wittig JH, Boineau JP: Surgical treatment of ventricular arrhythmias using epicardial, transmural, and endocardial mapptng Ann Thorac Surg 20:117-126, 1975 36. Spielman SR, Michelson EL, Horowitz LN, Spear JF, Moore EN: The limitations of epicardial mapping as a guide to the surgical therapy of ventricular tachycardia. Circulation 57:666-670, 1978 37. Josephson ME, Horowitz LbJ, Farshidi A: Continuous electrical activity: a mechanism of ventricular tachycardia. Circulation 57: 659-665, 1978 38. Guirqudon G, Fontaine G, Frank R, Escande 0, Etievent P: Encircling endocardial ventriculotomy. A new surgical treatment for life-threatening ventricular tachycardias resistant to medical treatment following myocardial infarction. Ann Thorac Surg 26: 438-444, 1978
Volume 43