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Incidence and clinical significance of induced ventricular tachycardia
APRIL 1980
The American
Journal
of CARDIOLOGY” VOLUME 45 NUMBER 4
CLINICAL STUDIES
Incidence and Clinical Significance of Induced Ventricular Tachycardia
CHRISTINE J. VANDEPOL, MD ARDESHIR FARSHIDI, MD, FACC’ SCOTT R. SPIELMAN, MD+ ALLAN M. GREENSPAN, MD* LEONARD N. HOROWITZ:, MD, MARK
E. JOSEPHSON,
Philadelphia,
MD,
FACC*
FACCll
Pennsylvania
From the Electrophysiology Laboratory, Hospital of the University of Pennsylvania, Cardiovascular Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. This study was supported in part by grants from the American Iieart Association, Southeastern Pennsylvania Chapter, Philadelphia, Pennsylvania, and the National Heart, Lung, and Blood Institute, Bethesda, Malryland. Manuscript received October 2, 1979; revised manuscript received November 14.1979, accepted November 14, 1979. Division of Cardiology, Yale University, New Haven, Connecticut. + Recipient of Institutional Training Grant 1 T32 HL0734601 from the National Institutes of Health, Bethesda, Maryland. + Recipient of Grant 1 F32 HL05816-01 from the National Institutes of Health, Bethesda, Maryland. 5 Recipient of a Career Development Investigatorship, American Heart Association, Southeastern Pennsylvania Chapter, Philadelphia, Pennsylvania, and Young Investigator Award 1 R23 HL21292-01 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. 11 Recipient of a Research C.sreer Development Award, Grant 1 K04 HL00361-01, from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. Address for reprints: Mark I~. Josephson, MD, Electrophysiology Laboratory, 666 White Building, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. l
Five hundred twenty-nine patients were studied with programmed ventricular stimulation for evaluation of supraventricular and ventricular tachyarrhythmias. Eighty-six patients had clinical ventricular tachycardia. Sustained ventricular tachycardia was induced in 52 (91 percent) of the 57 patients with a sustained form of the arrftythmla clinically. Nonsustained ventricular tachycardia was induced in 18 (82 percent) of 29 patients wfth a symptomatic nonsustained form clinically, in 2 (4 percent) of 57 patients with a sustained form and in 3 (0.7 percent) of the 443 patients with no documented spontaneous ventricular tachycardia. Ventricular tachycardia (sustained or nonsustained) was induced by double right or left ventricular extrastimult in 47 patients (83 percent) and by single right ventricular extrastimuli in 23 (31 percent); in 5 (7 percent), it was inducible only by rapid ventricular pacing and in 9 (12 percent) only by left ventricular stimulation. All 52 patients with induced sustained ventricular tachycardia had the sustained form clinically. Of the 23 patients with induced nonsustained ventricular tachycardia, 18 (78 percent) had the nonsustalned form clinically. Four hundred fifty-four patients had no induced ventricular tachycardia; only 14 (3 percent) of these had the arrhythmia spontaneously. The morphologic features, axis and cycle length of 54 of 82 episodes of induced ventricular tachycardia in 43 patients were similar to those of the clinically observed arrhythmia. It is concluded that ventricular tachycardia resembling the cllnical variety can be induced in the laboratory in almost all patients with sustained ventricular tachycardia clinically, in the majortty of those with symptomatic nonsustained ventricular tachycardia clinically, and only rarely in patients with no previously documented ventricular tachycardia. Conversely, induction of ventricular tachycardia implies the likelihood of spontaneous episodes of this arrhythmia.
Programmed electrical stimulation is used in the electrophysiologic study of patients with a wide variety of supraventricular and more recently ventricular arrhythmias.‘-l3 In patients with spontaneous ventricular tachycardia, reproducible initiation of the arrhythmia in the catheter-
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ization laboratory has made it possible to evaluate pharmacologic and pacemaker therapy of the arrhythmia and to perform endocardial mapping during ventricular tachycardia as a guide to surgical interventions.7sJ0J1J4 These modes of evaluation and therapy are based on the assumption that the ventricular arrhythmia induced in the laboratory is clinically significant in that it reproduces the clinical effects, electrocardiographic characteristics and response to therapy of the patient’s spontaneous ventricular tachycardia. Although most workers in the field consider this a valid assumption, few studies are available to support this hypothesis. The purpose of this study is to evaluate the incidence and clinical significance of ventricular tachycardia induced by programmed electrical stimulation and to relate these findings to spontaneous arrhythmias. Methods Patients:Five hundred
twenty-nine adult patients ranging in age from 18 to 85 years underwent electrophysiologic studies either for evaluation of documented or suspected tachyarrhythmias or bradyarrhythmias or as part of research protocols from July 1974 to April 1979. There were 398 patients with organic heart disease, including 301 with atherosclerotic heart disease. One hundred thirty-one patients had no organic heart disease. All available electrocardiograms, Holter monitor recordings and rhythm strips were used to determine the presence or absence of spontaneous ventricular tachycardia as defined with standard electrocardiographic criteria.‘5 Patients with sustained or nonsustained ventricular tachycardia, spontaneous or laboratory-induced, or both, form the basis of this report. Whenever possible, complete data on the morphologic features, QRS axis and cycle length of the spontaneous ventricular tachycardia were obtained. If the only available records showing ventricular tachycardia were obtained while the patient was receiving antiarrhythmic drug therapy, the arrhythmia was compared with induced ventricular tachycardia recorded while the patient was (1) on a similar drug regimen, and (2) on no therapy. Definitions: The following definitions were used: Sustained ventricular tachycardia-lasting longer than 1 minute or requiring termination by programmed ventricular stimulation or cardioversion before that time. Nonsustained ventricular tachycardia-ventricular tachycardia that terminated spontaneously in less than 60 seconds (usually 3 to 10 complexes, but no less than 3 complexes). Noninducible-two or fewer responses to any stimulation techniques to be described. Inducible-reproducible initiation (at least three times) of ventricular tachycardia by a specific technique of programmed electrical stimulation. Torsade de pointes-paroxysms of ventricular tachycardia, usually rapid (more than 2OO/min), irregular and nonsustained in which the QRS complex undergoes continual changes in configuration, duration, amplitude and axis. This arrhythmia is classically associated with a long Q-T interval (spontaneous or drug- or metabolism-related).16-1s Electrophysiologic studies: Studies were performed in the non-sedated postabsorptive state after informed consent was obtained. Three to six multipolar electrode catheters were introduced percutaneously or by cutdown procedure and positioned in the heart with fluoroscopic guidance. Quadru-
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polar electrode catheters were used when both stimulation and recording from a site were required. Recording sites usually included the right atrium, the atrioventricular junction at the His bundle site and the right ventricular apex, interventricular septum and the inflow or outflow tract, or both. Left ventricular recording was performed in patients who had sustained ventricular tachycardia (spontaneous or induced) during the study. Stimulation was performed with a specially designed programmable stimulator and an optically isolated constant current source (Bloom Associates, Ltd., Narberth, Pennsylvania). The stimuli were rectangular impulses, 1 ms in duration, that were delivered at twice diastolic threshold. Intracardiac electrograms were filtered at 40 to 500 hertz and simultaneously displayed with two to three electrocardiographic leads, usually leads I, aVF and Vi, on a multichannel oscilloscope (Electronics for Medicine, DR 16), stored on an analog tape (Honeywell model 5600) and later retrieved on photographic paper at speeds of 100 to 200 mm/s. Programmed ventricular stimulation (Table I) was performed as follows: Single premature ventricular extrastimuli (Ss) were introduced in late diastole during normal sinus rhythm and at varying paced cycle lengths (Si-Si intervals of 400 to 1000 ms, usually 500 or 600 ms) and moved earlier until ventricular refractoriness was reached. Double premature ventricular extrastimuli (Sz and Ss) were introduced beginning at an Si-Sz interval of 50 to 100 ms longer than the ventricular refractory period and an Sz-Ss interval equal to the Si-Sz interval. The Sz-Ss interval was progressively shortened until Ss did not depolarize the ventricles. The Si-Sz interval was then shortened until Ss again captured the ventricles. This process was continued until Ss and Ss reached ventricular refractoriness or ventricular tachycardia was initiated. Rapid right ventricular or left ventricular pacing with sudden cessation of stimulation after 15 to 60 seconds was performed at incremental rates with cycle lengths ranging from 400 to 250 ms and with introduction of the initial stimulus in late diastole during normal sinus rhythm. Both rapid ventricular pacing and introduction of premature ventricular extrastimuli were performed at multiple sites in the right or left ventricle, or both, if ventricular tachycardia was not inducible at the initial site. All 529patients were studied with rapid right ventricular pacing and administration of single right ventricular premature extrastimuli. One hundred ninety-two patients, including 135 with documented or suspected clinical ventricular tachyarrhythmias, received double right ventricular extrastimuli. Left ventricular stimulation was performed in 66 patients with documented or suspected ventricular tachyarrhythmias, including all patients in this group in whom right ventricular stimulation failed to initiate the tachycardia. All 66 received single and 50 received double left ventricular extrastimuli. Results Patients with clinical ventricular tachycardia: Eighty-six patients had symptomatic ventricular tachycardia clinically; in 57 of these, the tachycardia was recurrent (three or more episodes) and sustained, and in 29 it was nonsustained. The 57 patients with sustained arrhythmia included 48 men and 9 women aged 18 to 73 years; 52 of them (91 percent) had organic heart disease, including 47 patients (83 percent) with coronary artery disease and 38 (67 percent) with left ventricular aneurysm. The 29 patients with nonsustained ventric-
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ET AL.
TABLE I
TABLE II
Programmed Stimulation Techniques in 529 Patients
Method of Induction of Tachycardla In Patients With Clinical Ventricular Tachycardla
Site of Stimulation
Stimulation Techniques Method of Stimulation Ventricular extrastimuli Single Double Rapid ventricular pacing
Right Ventricle 529 192 500
Lefl Ventricle 66 ;“2
ular tachycardia included 21 men and 8 women aged 21 to 72 years; 20 (69 percent) had organic heart disease, including 13 (45 percent) with coronary artery disease. Nine patients had no clinical evidence or catheterization findings (five patients) of organic heart disease. The group with nonsustained ventricular tachycardia was heterogenous and comprised three types:
The largest subgroup included 11 patients with nonexercise-related tachycardia of uniform morphologic features lasting less than 1 minute. A second group comprised 10 patients whose tachycardia was historically related to exercise; in 6 of these the tachycardia was replicated during a standard exercise test. The third group included eight patients with paroxysmal ventricular tachycardia meeting the criteria for torsade de pointes. Their cardiac diagnoses were heterogenous and included cardiomyopakhy (two patients), rheumatic heart disease (two patients), coronary artery disease (two patients), long Q-T interval syndrome (one patient) and coronary arterial spasm (one patient). Only in the one patient with the long Q-T interval syndrome was the arrhythmia temporally related to the administration of drugs (procainamide). In no other patients were metabolic factors or drugs related to the arrhythmia. Sensitivity of programmed stimulation in patients with sustained ventricular tachycardia (Table II): Ventricular tachycardia was induced in 54 (95 percent) of the 57 patients with sustained ventricular tachycardia clinically (Fig. 1); in 52 of the 54 the induced tachycardia was sustained. The method of induction of the arrhythmia in the laboratory varied. In all but four instances it was induced by the introduction of one or two ventricular extrastimuli. In 23 (43 percent) of the 54 the tachycardia was initiated by two right ventricular extrastimuli, whereas in 19 (35 percent) it was initiated by a single right ventricular extrastimulus. In 12 patients it was initiated by rapid ventricular pacing at cycle lengths of 400 to 250 ms; in 4 of the 12 this was the only met.hod of induction. Ventricular tachycardia was initiated by left ventricular stimulation in 22 patients in whom the latter was attempted-in 16 by double and in 6 by single left ventricular extrastimuli. In six patients (11 percent) the only method of induction was by double left ventricular stimuli. In two patients with sustained ventricular tachycardia clinically, nonsustained tachycardia was induced by double right ventricular extrastimuli.
Induced Ventricular Tachycardia
Ventricular Extrastimuli Single
Double
RVP
RVP (only)
LVS (only)
19
29
12
4
6
4
15
5
1
3
Sustained (52 patients) Nonsustained (20 patients)*
Includes two patients with sustained ventricular tachycardia clinically. LVS = left ventricular stimulation; RVP = rapid ventricular pacing. l
Sensitivity of programmed stimulation in patients with nonsustained ventricular tachycardia (Table II): Nonsustained ventricular tachycardia was initiated in 18 of the 29 patients who were clinically symptomatic with this arrhythmia (Fig. 1). The tachycardia was induced with right ventricular double extrastimuli in 10 patients (34 percent), by right ventricular single extrastimuli in 4 (14 percent), by rapid right ventricular pacing in 5 (17 percent) and by double left ventricular stimuli alone in 3 (10 percent). Within the subgroups of patients with nonsustained ventricular tachycardia the arrhythmia was induced (1) in 7 of 11 patients with nonexercise-related ventricular tachycardia of uniform configuration, (2) in 6 of 10 patients with exercise-related ventricular tachycardia (induced in 5 of these only after isoproterenol infusion), and (3) in 5 of 8 patients with clinical episodes of torsade de pointes. Of the 14 patients with clinical ventricular tachycardia (3 with the sustained and 11 with the nonsus-
_.’ 3 S”STAINE0
0.57
NON-
NONE
.9us1uNEo
Il.29
CLINICAL
“. 443
VT
FIGURE 1. Incidence of ventricular tachycardia (VT) induced by programmed stimulation in patients with this arrhythmia clinically.
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INDUCED VENTRICULAR TACHYCARDIA-VANDEPOL
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mined form) in whom the arrhythmia was not inducible in the laboratory, 8 were studied with left ventricular stimulation, 3 with isoproterenol and 3 with both isoproterenol and left ventricular stimulation, In each, routine stimulation with single and double right ventricular extrastimuli and rapid right ventricular pacing had failed to induce tachycardia. Patients without clinical ventricular tachycardia: Ventricular tachycardia could be induced in only 3 (0.7 percent) of 443 patients with no clinically documented ventricular tachycardia (Fig. 2). In all three the arrhythmia was nonsustained and was induced by double right ventricular extrastimuli. In two of the three, both with a history of unexplained syncope, the induced arrhythmia was classified as torsade de pointes. In the remaining 440 patients no ventricular tachycardia was inducible. All of the remaining 440 patients were studied with right ventricular pacing and single right ventricular extrastimuli. One hundred twenty-six patients were also tested with double right ventricular extrastimuli, including 20 who were also tested with single and double left ventricular extrastimuli. Specificity of laboratory-induced ventricular tachycardia: Ventricular tachycardia was induced by programmed stimulation in 75 patients (Fig. 2), and in 52 of these the arrhythmia was sustained. Forty-seven (90 percent) of the 52 had organic heart disease, primarily coronary artery disease. All 52 patients with induced sustained ventricular tachycardia had the sustained form clinically. Nonsustained ventricular tachycardia was induced by programmed stimulation in a total of 23 patients. Organic heart disease was present in 18 (78 percent) of these, including 13 who had coronary artery disease; however, only 5 had ventricular aneurysm, and 7 had no heart disease. Eighteen of these 23 patients also had symptomatic nonsustained ventricular tachycardia
TO-
20fO-
\ SUSTAINED ” * 52
r
*ONSUSTUNED
NONL II=454
Il.23
INDUCED
/II 41-‘3
q
j+\\
VT
FIGURE 2. Incidence of clinical ventricular tachycardia (VT) in patients in whom this arrhythmia was induced by programmed stimulation.
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clinically (Fig. 2); 2 of the 23 had the sustained form clinically, and the remaining 3 had no documented ventricular tachycardia before the study. Two of these three were being evaluated for unexplained syncopal episodes; in both patients the nonsustained ventricular tachycardia induced in the laboratory was of the torsade de pointes variety and reproduced their symptoms. In 7 of the 23 patients the induced nonsustained ventricular tachycardia was of the torsade de pointes type that had been documented clinically in 5 of the patients. Four hundred fifty-four of the 529 patients had no inducible uentricular tachycardia in the laboratory (Fig. 2). Fourteen (3 percent) of the 454 had the arrhythmia clinically, and in 3 of these the tachycardia was sustained. Each of these three had spontaneous ventricular tachycardia in the laboratory, and the responses to overdrive pacing and programmed stimulation suggested an automatic mechanism. The remaining 11 had spontaneous nonsustained ventricular tachycardia in the laboratory. Two of these, one patient with a long Q-T interval and one with mitral valve prolapse, had a torsade de pointes rhythm clinically. Three had exercise-induced nonsustained ventricular tachycardia and two had no evidence of heart disease. Eight of these 14 patients in whom ventricular tachycardia was not inducible by programmed stimulation despite its clinical occurrence had one or two intraventricular reentrant complexes that were similar in configuration to the clinical ventricular tachycardia. Comparison of morphologic features of clinical and induced ventricular tachycardia: The QRS configuration, axis and cycle length of both the clinical and induced ventricular tachycardia were available for comparison in 43 patients. Comparisons and morphologic data were limited by the number of electrocardiographic leads recorded in the laboratory which were either leads I, II or aVF, and VI or I, II, III and VI. In 12 patients, however, a 12 lead electrocardiogram of the induced tachycardia was recorded in the laboratory and compared with the prestudy 12 lead electrocardiogram of the arrhythmia. In the remaining patients documentation of their arrthymia was by modified precordial or limb leads, or both, during Holter monitoring or telemetry and thus adequate comparisons of morphologic features could not be made. The 43 patients in whom comparisons were made included 54 percent of the patients with sustained ventricular tachycardia clinically and 43 percent of those with nonsustained tachycardia clinically. There were no significant differences in frequency or type of heart disease between these 43 patients and the patients who did not have complete documentation of their clinical arrhythmia. Sixty-two distinct patterns of ventricular tachycardia (sustained and nonsustained) were induced in these 43 patients in the laboratory. Fifty-four patterns (87 percent) were documented to occur spontaneously and had the same configuration (right or left bundle branch block) and axis as those of the induced ventricular tachycardias (Fig. 3). The difference in cycle lengths between clinical and induced ventricular tachycardias
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INDUCED VENTRICULARTACHYCARDIA-VANDEPDL ET AL.
was less than 10 ms in 22 of 54 episodes and ranged from 10 to 80 ms (37 f 22) in the remaining 32. Each of the eight patients in whom a configuration of ventricular tachycardia was induced that was not seen clinically had two different configurations of ventricular tachycardia induced in the laborat.ory. In each case the electrocardiographic characteristics of one of the configurations were similar to the clinical ventricular tachycardia. Complications of programmed stimulation: The programmed stimulation in these 529 patients was not accompanied by any mortality. Ventricular fibrillation was induced in 12 patients including 10 who had clinical episodes of ventricular fibrillation and have previously been described.lg In two cases the ventricular fibrillation was drug-related. In four cases a stable ventricular tachycardia had degenerated into ventricular fibrillation analogous to clinical cardiac arrest experienced by these patients before thLestudy. In each of these patients who didnot have spontaneous conversion, sinus rhythm was restored by direct shock using 200 to 320 watt seconds (seven patients). There were no cardiac or neurologic sequelae in these patients or in the 10 patients whose ventricular tachycardia required cardioversion. Discussion Significance of Laboratory-Induced Tachycardias
Laboratory inducticln of supraventricular and ventricular arrhythmias b,y programmed electrical stimuNSR
’
lation has become an increasingly important technique in evaluating antiarrhythmic drug regimens and in defining patients at risk for arrhythmias.1-12 These clinical applications of electrophysiologic studies require confidence in the ability of programmed electrical stimulation to duplicate the patient’s spontaneous arrhythmias. The clinical significance of laboratory-induced supraventricular tachycardia in patients with the WolffParkinson-White syndrome was reported by Denes et al 2o who concluded that laboratory induction of tazhycardia in patients with a preexcitation syndrome implied the likelihood of spontaneous supraventricular tachycardia. Goldreyer and Damatol suggested the use of programmed stimulation as a diagnostic test for atrioventricular nodal reentrant supraventricular tachycardia as a result of their observations that patients with this arrhythmia induced in the laboratory were clinically symptomatic and had spontaneous supraventricular tachycardia, unlike patients who did not have the arrhythmia with programmed stimulation. We and others4-6rgJ2 have previously noted that laboratory-induced tachycardias were similar in configuration to the patients’ clinical tachycardias. In a preliminary report, Wellens et a1.21demonstrated that tachycardias induced in their laboratory were identical in configuration to those noted clinically. Their study included 56 patients with ventricular tachycardias and 289 patients with supraventricular tachycardias. In the present study we also observed that induced ventricular
*
VT
FIGURE 3. Initiation of sustained ventricular tachycardia (VT) morphologically similar to that occurring spontaneously. Left, sustained ventricular tachycardia with a right bundle branch block configuration and superior axis (rate 140 beats/min; cycle length 430 ms) induced (at arrow) by right ventricular pacing at a cycle length of 400 ms. Leads I, aVL and VI are shown with electrograms from the high right atrium (HRA), coronary sinus (CS), His bundle region (HSE), and right ventricular apex (RVA). T = time lines. Rfght, same patient. Standard electrocardiogram revealing spontaneous sustained ventricular tachycardia with the same morphologic features and axis as those of the induced tachycardia (rate 170 beats/min).
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tachycardias were similar to the patients’ spontaneous ventricular tachycardias. Our data, however, are limited by the use of only three or four surface electrocardiographic leads. Although our lead selection usually included leads from three planes, it is conceivable that subtle differences might have been observed had a 12 lead electrocardiogram been obtained in the laboratory. In 12 instances this was done using a standard electrocardiograph and the configuration of the induced ventricular tachycardia was observed to be comparable with that of the spontaneous arrhythmia. Differences in cycle lengths of clinical and laboratory ventricular tachycardias were not significant, and when they occurred were often due to the effects of antiarrhythmic agents. This report demonstrates that patients in whom ventricular tachycardia (sustained or nonsustained) is induced in the laboratory are overwhelmingly those who experience spontaneous attacks of ventricular tachycardia. This is particularly true of patients in whom sustained ventricukn tachycardia is induced. One hundred percent of these patients had documented sustained ventricular tachycardia clinically. It is equally significant that only 3 percent (14) of 454 patients in whom ventricular tachycardia was not inducible had spontaneous ventricular tachycardia. Correlation of Clinical Ventricular Tachycardia With lnducibility
Patients with recurrent sustained ventricular tachycardia have been studied in detail by many investigators.4-12 A large incidence of coronary artery disease has been previously noted.5*7,g Similarly, coronary artery disease was diagnosed with coronary angiography in 82 percent of our 57 patients with clinical sustained ventricular tachycardia. Previous myocardial infarction was documented in all but one patient with coronary artery disease, and left ventricular aneurysm was present in 67 percent of the 57 patients. We9 have previously reported an 85 percent success rate of inducing sustained ventricular tachycardia in patients with clinical episodes of sustained ventricular tachycardia. In the present report, which includes only adult patients, our success rate was 91 percent (52 of 57 patients). Fisher et a1.7described induction of ventricular tachycardia in 95 percent of 19 patients with ventricular tachycardia, 68 percent of whom had coronary artery disease and 16 percent a ventricular aneurysm. The clinical and laboratory duration of ventricular tachycardia (that is, sustained versus nonsustained) was not presented. In contrast, other investigators have reported a much lower success rate of ihduction of ventricular tachycardia in patients with sustained ventricular tachycardia clinically. Wellens et al.5 induced ventricular tachycardia in only 29 of 50 patients with sustained ventricular tachycardia. However, ventricular tachycardia was induced in 86 percent (18) of the 21 patients with a history of chronic coronary artery disease. Denes et a1.6 were able to induce ventricular tachycardia reproducibly in only 2 of 11 patients with
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clinical ventricular tachycardia, neither of whom had a primary diagnosis of arteriosclerotic heart disease. The differences in results from these laboratories probably reflect differences in patient population and stimulation techniques. The incidence of chronic coronary artery disease and, in particular, of left ventricular aneurysm is large in our patients. We believe that a broad spectrum of
techniques of programmed ventricular stimulation, including ventricular extrastimuli delivered during multiple paced cycle lengths and stimulation at multiple sites in the left as well as the right ventricle, is essential before one can state that ventricular tachycardia is truly noninducible. In 6 (11.5 percent) of our 52 patients with induced sustained ventricular tachycardia, the tachycardia was reproducibly initiated only from the left ventricle. Patients with spontaneous nonsustained ventricular tachycardia constitute a more heterogeneous group than those with sustained ventricular tachycardia.
Fewer patients have prior myocardial infarction and aneurysm, despite a 45 percent incidence rate of coronary artery disease. Thirty-one percent of these patients had no known heart disease. The mechanisms of ventricular tachycardia in this group of patients are probably varied but have not been well studied, in part because laboratory duplication of ventricular tachycardia has been less successful in this group. Denes et a1.6were unable to induce ventricular tachycardia in any of their 16 patients with nonsustained ventricular tachycardia. Our ability to induce ventricular tachycardia in 62 percent of our 29 patients with clinical nonsustained ventricular tachycardia may have been due to differences in stimulating techniques. Our patients with clinical nonsustained ventricular tachycardia represent a selected population generally referred or monitored because of palpitations or syncope, or both. The actual incidence and clinical signif-
icance of nonsustained ventricular tachycardia in the general population is unknown. In patients with cardiac disease, nonsustained ventricular tachycardia documented during Holter monitoring is usually asymptomatic.22s23 Whether electrophysiologic studies or antiarrhythmic therapy, or both, is useful in asymptomatic patients remains controversial, because the need for treating these arrhythmias is not established. Some patients with clinical nonsustained ventricular tachycardia could be classified into three subgroups. In some patients, presumably those whose
ventricular tachycardia is ischemia-related or catecholamine-dependent, or both, exercise testing may reveal the presence of ventricular arrhythmias not observed during long-term ambulatory monitoring.24 In general, however, 24-hour Holter monitoring is considered more sensitive in detecting ventricular arrhythmias.25 The electrophysiologic laboratory may be useful in further delineating mechanisms and therapy in patients who do manifest ventricular tachycardia during exercise testing and may be able to simulate
INDUCED VENTRICULAR TACHYCARDIA-VANDEPOL
some of the physiologic conditions of exercise testing in patients unable to undergo such testing because of physical limitations. With regard to our observations of torsade de pointes, we suggest that laboratory induction of this arrhythmia is clinically significant and may portend vulnerability of the patient to life-threatening arrhythmias; welg and others26 have noted a tendency of torsade de pointes to degenerate into ventricular fibrillation. The ability to induce this arrhythmia in patients in whom it has been documented clinically26 makes it possible to consider use of programmed ventricular stimulation in evaluating antiarrhythmic therapy in these patients. Therapeutic implications: Electrophysiologic testing appears to be a sensitive and specific method of initiating sustained ventricular tachycardia and as a result has been used to develop pharmacologic, pacing
ET AL.
and surgical therapy in this arrhythmia. Although the clinical significance of nonsustained ventricular tachycardia is unknown, electrophysiologic testing may provide useful data upon which to base therapy in certain symptomatic patients, particularly those with torsade de pointes or exercise-induced ventricular tachycardia who have a reasonable chance of having the arrhythmia reproduced in the laboratory. Prospective studies are necessary to demonstrate the utility of this technique toward this end. Acknowledgment We thank Marie Coscia and Frances Laird for assistance in preparing the manuscript; the technicians in the Cardiac Electrophysiology Laboratory; and John A. Kastor, MD, Chief of the Cardiovascular Section, for his continued support and encouragement.
References 1. Goldreyer BN, Damato AN. The essential role of atrioventricular conduction delay in the Initiation of paroxysmal supraventricular tachycardia. Circulation 1971; 43:679-87. 2. Josephson ME, Kastor JA. Supraventricular tachycardia: mechanisms and management. Ann Intern Med 1977; 87:346-58. 3. Wu D, Denes P, Amat-y-Leon F, Dhingra R, et al. Clinical, electrocardiographic and electrophysiologic observations in patients with paroxysmal supraventricular tachycardia. Am J Cardiol 1978; 41:1045-51. 4. Wellens HJJ, Lie KI, Durrer D. Further observations on ventricular tachycardia as studied by electrical stimulation of the heart. Chronic recurrent ventricular tachycardia and ventricular tachycardia during acute myocardial infarction. Circulation 1974; 49:647-53. 5. Wellens HJJ, Duren DR, Lie Ki. Observations on mechanisms of ventricular tachycardia in man. Circulation 1976; 54:237-44. 6. Denes P, Wu D, Dhingral RC, et al. Electrophysiologic studies in patients with chronic recurrent ventricular tachycardia. Circulation 1976; 54:229-36. 7. Fisher JD, Cohen HL, Mehra R, Altschuler H, Escher DJW, Furman S. Cardiac pacing and pacemakers. II. Serial electrophysiologic-pharmacologic testing for control of recurrent tachyarrhythmias. Am Heart J 1077; 93:658-68. 8. Hartzier GO, Maloney JC). Programmed ventricular stimulation in management of recurrent ventricular tachycardia. Mayo Clin Proc 1977; 52~731-41. 9. Josephson ME, Horowitz LN, Farshidl A, Kastor JA. Recurrent sustained ventricular tachycardia. 1. Mechanisms. Circulation 1978; 57:431-40. 10. Horowitz LN, Josephson ME, Farshidl A, Spielman SR, Michelson EL, Greenspan AM. Recurrent sustained ventricular tachycardia. 3. Role of the electrophysllologicstudy in selection of antiarrhythmic regimens. Circulation 1978: 58:986-97. 11. Ruskin JN, Garan H. Chronic electrophysiologic testing in patients with recurrent sustained ventricular tachycardia (abstr). Am J Cardiol 1979; 43:400. 12. Josephson ME, Horowitz LN, Farshidl A, Splelman SR, Mlcheison EL, Greenspan AM. Recurrent sustained ventricular tachycardia. 4. Pleomorphism. Circulation 1979; 59:459-68.
13. Wellens HJJ. Value and limitations of programmed electrical stimulation of the heart in the study and treatment of tachycardias. Circulation 1978; 57:845-53. 14. Josephson ME, Horowitz LN, Farshidi A, Spear JF, Kastor JA, Moore EN. Recurrent sustained ventricular tachycardia. 2. Endocardial mapping. Circulation 1978; 57:440-47. 15. Bellet S. Clinical Disorders of the Heart Beat. 3rd ed. Philadelphia: Lea 8 Febiger, 1971: 528. 16. Dessertenne F. La tachycardie ventriculaire B deux foyers oppods variables. Arch Mal Coeur 1966; 59:263-72. 17. Krlkler DM. A fresh look at cardiac arrhythmias. Pathogenesis and presentation. Lancet 1974; 1:913-8. 18. Krikler DM, Curry PVL. Torsade de pointes, an atypical ventricular tachycardia. Br Heart J 1976; 38:117-20. 19. Sptelman SR, Farshidl A, Horowttz LN, Josephson ME. Ventricular fibrillation during programmed ventricular stimulation: incidence and clinical implications. Am J Cardiol 1978; 42:913-8. 20. Denes P, Wu D, Amat-y-Leon F, et al. Paroxysmal supraventricular tachycardia induction in patients with Wolff-Parkinson-White syndrome. Ann Intern Med‘1979; 90: 153-7. 21. Wellens HJJ. Bar FW. Wiener I. FarrC J. Ross DL. Kersemakers J. Clinical relevance df tachycakdias indhced during programmed cardiac stimulation (abstr). Am J Cardiol 1979; 43:400. 22. Winkle RA, Derrington DC, Schroeder JS. Characteristics of ventricular tachycardia in ambulatory patients. Am J Cardiol 1977; 39:487-92. 23. Jelinek MV, Lohrbauer L, Lown B. Antiarrhythmic drug therapy for sporadic ventricular ectopic arrhythmia. Circulation 1974; 49:659-66. 24. Kosowsky BD, Lown B, Whiting R, Guiney T. Occurrence of ventricular arrhythmias with exercise as compared to monitoring. Circulation 1971; 44:826-32. 25. Lown B, Calvert AF, Armington R, Ryan M. Monitoring for serious arrhythmias and high risk of sudden death. Circulation 1975; 52: Suppl lll:lll-189-98. 26. Evans TR, Curry PVL, Fltchett DH, Krlkler DM. Torsade de pointes initiated by electrical stimulation. J Electrocardiol 1976; 9:22558.
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The American
Journal
of CARDIOLOGY” VOLUME 45 NUMBER 4
CLINICAL STUDIES
Incidence and Clinical Significance of Induced Ventricular Tachycardia
CHRISTINE J. VANDEPOL, MD ARDESHIR FARSHIDI, MD, FACC’ SCOTT R. SPIELMAN, MD+ ALLAN M. GREENSPAN, MD* LEONARD N. HOROWITZ:, MD, MARK
E. JOSEPHSON,
Philadelphia,
MD,
FACC*
FACCll
Pennsylvania
From the Electrophysiology Laboratory, Hospital of the University of Pennsylvania, Cardiovascular Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. This study was supported in part by grants from the American Iieart Association, Southeastern Pennsylvania Chapter, Philadelphia, Pennsylvania, and the National Heart, Lung, and Blood Institute, Bethesda, Malryland. Manuscript received October 2, 1979; revised manuscript received November 14.1979, accepted November 14, 1979. Division of Cardiology, Yale University, New Haven, Connecticut. + Recipient of Institutional Training Grant 1 T32 HL0734601 from the National Institutes of Health, Bethesda, Maryland. + Recipient of Grant 1 F32 HL05816-01 from the National Institutes of Health, Bethesda, Maryland. 5 Recipient of a Career Development Investigatorship, American Heart Association, Southeastern Pennsylvania Chapter, Philadelphia, Pennsylvania, and Young Investigator Award 1 R23 HL21292-01 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. 11 Recipient of a Research C.sreer Development Award, Grant 1 K04 HL00361-01, from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. Address for reprints: Mark I~. Josephson, MD, Electrophysiology Laboratory, 666 White Building, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. l
Five hundred twenty-nine patients were studied with programmed ventricular stimulation for evaluation of supraventricular and ventricular tachyarrhythmias. Eighty-six patients had clinical ventricular tachycardia. Sustained ventricular tachycardia was induced in 52 (91 percent) of the 57 patients with a sustained form of the arrftythmla clinically. Nonsustained ventricular tachycardia was induced in 18 (82 percent) of 29 patients wfth a symptomatic nonsustained form clinically, in 2 (4 percent) of 57 patients with a sustained form and in 3 (0.7 percent) of the 443 patients with no documented spontaneous ventricular tachycardia. Ventricular tachycardia (sustained or nonsustained) was induced by double right or left ventricular extrastimult in 47 patients (83 percent) and by single right ventricular extrastimuli in 23 (31 percent); in 5 (7 percent), it was inducible only by rapid ventricular pacing and in 9 (12 percent) only by left ventricular stimulation. All 52 patients with induced sustained ventricular tachycardia had the sustained form clinically. Of the 23 patients with induced nonsustained ventricular tachycardia, 18 (78 percent) had the nonsustalned form clinically. Four hundred fifty-four patients had no induced ventricular tachycardia; only 14 (3 percent) of these had the arrhythmia spontaneously. The morphologic features, axis and cycle length of 54 of 82 episodes of induced ventricular tachycardia in 43 patients were similar to those of the clinically observed arrhythmia. It is concluded that ventricular tachycardia resembling the cllnical variety can be induced in the laboratory in almost all patients with sustained ventricular tachycardia clinically, in the majortty of those with symptomatic nonsustained ventricular tachycardia clinically, and only rarely in patients with no previously documented ventricular tachycardia. Conversely, induction of ventricular tachycardia implies the likelihood of spontaneous episodes of this arrhythmia.
Programmed electrical stimulation is used in the electrophysiologic study of patients with a wide variety of supraventricular and more recently ventricular arrhythmias.‘-l3 In patients with spontaneous ventricular tachycardia, reproducible initiation of the arrhythmia in the catheter-
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ization laboratory has made it possible to evaluate pharmacologic and pacemaker therapy of the arrhythmia and to perform endocardial mapping during ventricular tachycardia as a guide to surgical interventions.7sJ0J1J4 These modes of evaluation and therapy are based on the assumption that the ventricular arrhythmia induced in the laboratory is clinically significant in that it reproduces the clinical effects, electrocardiographic characteristics and response to therapy of the patient’s spontaneous ventricular tachycardia. Although most workers in the field consider this a valid assumption, few studies are available to support this hypothesis. The purpose of this study is to evaluate the incidence and clinical significance of ventricular tachycardia induced by programmed electrical stimulation and to relate these findings to spontaneous arrhythmias. Methods Patients:Five hundred
twenty-nine adult patients ranging in age from 18 to 85 years underwent electrophysiologic studies either for evaluation of documented or suspected tachyarrhythmias or bradyarrhythmias or as part of research protocols from July 1974 to April 1979. There were 398 patients with organic heart disease, including 301 with atherosclerotic heart disease. One hundred thirty-one patients had no organic heart disease. All available electrocardiograms, Holter monitor recordings and rhythm strips were used to determine the presence or absence of spontaneous ventricular tachycardia as defined with standard electrocardiographic criteria.‘5 Patients with sustained or nonsustained ventricular tachycardia, spontaneous or laboratory-induced, or both, form the basis of this report. Whenever possible, complete data on the morphologic features, QRS axis and cycle length of the spontaneous ventricular tachycardia were obtained. If the only available records showing ventricular tachycardia were obtained while the patient was receiving antiarrhythmic drug therapy, the arrhythmia was compared with induced ventricular tachycardia recorded while the patient was (1) on a similar drug regimen, and (2) on no therapy. Definitions: The following definitions were used: Sustained ventricular tachycardia-lasting longer than 1 minute or requiring termination by programmed ventricular stimulation or cardioversion before that time. Nonsustained ventricular tachycardia-ventricular tachycardia that terminated spontaneously in less than 60 seconds (usually 3 to 10 complexes, but no less than 3 complexes). Noninducible-two or fewer responses to any stimulation techniques to be described. Inducible-reproducible initiation (at least three times) of ventricular tachycardia by a specific technique of programmed electrical stimulation. Torsade de pointes-paroxysms of ventricular tachycardia, usually rapid (more than 2OO/min), irregular and nonsustained in which the QRS complex undergoes continual changes in configuration, duration, amplitude and axis. This arrhythmia is classically associated with a long Q-T interval (spontaneous or drug- or metabolism-related).16-1s Electrophysiologic studies: Studies were performed in the non-sedated postabsorptive state after informed consent was obtained. Three to six multipolar electrode catheters were introduced percutaneously or by cutdown procedure and positioned in the heart with fluoroscopic guidance. Quadru-
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polar electrode catheters were used when both stimulation and recording from a site were required. Recording sites usually included the right atrium, the atrioventricular junction at the His bundle site and the right ventricular apex, interventricular septum and the inflow or outflow tract, or both. Left ventricular recording was performed in patients who had sustained ventricular tachycardia (spontaneous or induced) during the study. Stimulation was performed with a specially designed programmable stimulator and an optically isolated constant current source (Bloom Associates, Ltd., Narberth, Pennsylvania). The stimuli were rectangular impulses, 1 ms in duration, that were delivered at twice diastolic threshold. Intracardiac electrograms were filtered at 40 to 500 hertz and simultaneously displayed with two to three electrocardiographic leads, usually leads I, aVF and Vi, on a multichannel oscilloscope (Electronics for Medicine, DR 16), stored on an analog tape (Honeywell model 5600) and later retrieved on photographic paper at speeds of 100 to 200 mm/s. Programmed ventricular stimulation (Table I) was performed as follows: Single premature ventricular extrastimuli (Ss) were introduced in late diastole during normal sinus rhythm and at varying paced cycle lengths (Si-Si intervals of 400 to 1000 ms, usually 500 or 600 ms) and moved earlier until ventricular refractoriness was reached. Double premature ventricular extrastimuli (Sz and Ss) were introduced beginning at an Si-Sz interval of 50 to 100 ms longer than the ventricular refractory period and an Sz-Ss interval equal to the Si-Sz interval. The Sz-Ss interval was progressively shortened until Ss did not depolarize the ventricles. The Si-Sz interval was then shortened until Ss again captured the ventricles. This process was continued until Ss and Ss reached ventricular refractoriness or ventricular tachycardia was initiated. Rapid right ventricular or left ventricular pacing with sudden cessation of stimulation after 15 to 60 seconds was performed at incremental rates with cycle lengths ranging from 400 to 250 ms and with introduction of the initial stimulus in late diastole during normal sinus rhythm. Both rapid ventricular pacing and introduction of premature ventricular extrastimuli were performed at multiple sites in the right or left ventricle, or both, if ventricular tachycardia was not inducible at the initial site. All 529patients were studied with rapid right ventricular pacing and administration of single right ventricular premature extrastimuli. One hundred ninety-two patients, including 135 with documented or suspected clinical ventricular tachyarrhythmias, received double right ventricular extrastimuli. Left ventricular stimulation was performed in 66 patients with documented or suspected ventricular tachyarrhythmias, including all patients in this group in whom right ventricular stimulation failed to initiate the tachycardia. All 66 received single and 50 received double left ventricular extrastimuli. Results Patients with clinical ventricular tachycardia: Eighty-six patients had symptomatic ventricular tachycardia clinically; in 57 of these, the tachycardia was recurrent (three or more episodes) and sustained, and in 29 it was nonsustained. The 57 patients with sustained arrhythmia included 48 men and 9 women aged 18 to 73 years; 52 of them (91 percent) had organic heart disease, including 47 patients (83 percent) with coronary artery disease and 38 (67 percent) with left ventricular aneurysm. The 29 patients with nonsustained ventric-
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TABLE I
TABLE II
Programmed Stimulation Techniques in 529 Patients
Method of Induction of Tachycardla In Patients With Clinical Ventricular Tachycardla
Site of Stimulation
Stimulation Techniques Method of Stimulation Ventricular extrastimuli Single Double Rapid ventricular pacing
Right Ventricle 529 192 500
Lefl Ventricle 66 ;“2
ular tachycardia included 21 men and 8 women aged 21 to 72 years; 20 (69 percent) had organic heart disease, including 13 (45 percent) with coronary artery disease. Nine patients had no clinical evidence or catheterization findings (five patients) of organic heart disease. The group with nonsustained ventricular tachycardia was heterogenous and comprised three types:
The largest subgroup included 11 patients with nonexercise-related tachycardia of uniform morphologic features lasting less than 1 minute. A second group comprised 10 patients whose tachycardia was historically related to exercise; in 6 of these the tachycardia was replicated during a standard exercise test. The third group included eight patients with paroxysmal ventricular tachycardia meeting the criteria for torsade de pointes. Their cardiac diagnoses were heterogenous and included cardiomyopakhy (two patients), rheumatic heart disease (two patients), coronary artery disease (two patients), long Q-T interval syndrome (one patient) and coronary arterial spasm (one patient). Only in the one patient with the long Q-T interval syndrome was the arrhythmia temporally related to the administration of drugs (procainamide). In no other patients were metabolic factors or drugs related to the arrhythmia. Sensitivity of programmed stimulation in patients with sustained ventricular tachycardia (Table II): Ventricular tachycardia was induced in 54 (95 percent) of the 57 patients with sustained ventricular tachycardia clinically (Fig. 1); in 52 of the 54 the induced tachycardia was sustained. The method of induction of the arrhythmia in the laboratory varied. In all but four instances it was induced by the introduction of one or two ventricular extrastimuli. In 23 (43 percent) of the 54 the tachycardia was initiated by two right ventricular extrastimuli, whereas in 19 (35 percent) it was initiated by a single right ventricular extrastimulus. In 12 patients it was initiated by rapid ventricular pacing at cycle lengths of 400 to 250 ms; in 4 of the 12 this was the only met.hod of induction. Ventricular tachycardia was initiated by left ventricular stimulation in 22 patients in whom the latter was attempted-in 16 by double and in 6 by single left ventricular extrastimuli. In six patients (11 percent) the only method of induction was by double left ventricular stimuli. In two patients with sustained ventricular tachycardia clinically, nonsustained tachycardia was induced by double right ventricular extrastimuli.
Induced Ventricular Tachycardia
Ventricular Extrastimuli Single
Double
RVP
RVP (only)
LVS (only)
19
29
12
4
6
4
15
5
1
3
Sustained (52 patients) Nonsustained (20 patients)*
Includes two patients with sustained ventricular tachycardia clinically. LVS = left ventricular stimulation; RVP = rapid ventricular pacing. l
Sensitivity of programmed stimulation in patients with nonsustained ventricular tachycardia (Table II): Nonsustained ventricular tachycardia was initiated in 18 of the 29 patients who were clinically symptomatic with this arrhythmia (Fig. 1). The tachycardia was induced with right ventricular double extrastimuli in 10 patients (34 percent), by right ventricular single extrastimuli in 4 (14 percent), by rapid right ventricular pacing in 5 (17 percent) and by double left ventricular stimuli alone in 3 (10 percent). Within the subgroups of patients with nonsustained ventricular tachycardia the arrhythmia was induced (1) in 7 of 11 patients with nonexercise-related ventricular tachycardia of uniform configuration, (2) in 6 of 10 patients with exercise-related ventricular tachycardia (induced in 5 of these only after isoproterenol infusion), and (3) in 5 of 8 patients with clinical episodes of torsade de pointes. Of the 14 patients with clinical ventricular tachycardia (3 with the sustained and 11 with the nonsus-
_.’ 3 S”STAINE0
0.57
NON-
NONE
.9us1uNEo
Il.29
CLINICAL
“. 443
VT
FIGURE 1. Incidence of ventricular tachycardia (VT) induced by programmed stimulation in patients with this arrhythmia clinically.
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mined form) in whom the arrhythmia was not inducible in the laboratory, 8 were studied with left ventricular stimulation, 3 with isoproterenol and 3 with both isoproterenol and left ventricular stimulation, In each, routine stimulation with single and double right ventricular extrastimuli and rapid right ventricular pacing had failed to induce tachycardia. Patients without clinical ventricular tachycardia: Ventricular tachycardia could be induced in only 3 (0.7 percent) of 443 patients with no clinically documented ventricular tachycardia (Fig. 2). In all three the arrhythmia was nonsustained and was induced by double right ventricular extrastimuli. In two of the three, both with a history of unexplained syncope, the induced arrhythmia was classified as torsade de pointes. In the remaining 440 patients no ventricular tachycardia was inducible. All of the remaining 440 patients were studied with right ventricular pacing and single right ventricular extrastimuli. One hundred twenty-six patients were also tested with double right ventricular extrastimuli, including 20 who were also tested with single and double left ventricular extrastimuli. Specificity of laboratory-induced ventricular tachycardia: Ventricular tachycardia was induced by programmed stimulation in 75 patients (Fig. 2), and in 52 of these the arrhythmia was sustained. Forty-seven (90 percent) of the 52 had organic heart disease, primarily coronary artery disease. All 52 patients with induced sustained ventricular tachycardia had the sustained form clinically. Nonsustained ventricular tachycardia was induced by programmed stimulation in a total of 23 patients. Organic heart disease was present in 18 (78 percent) of these, including 13 who had coronary artery disease; however, only 5 had ventricular aneurysm, and 7 had no heart disease. Eighteen of these 23 patients also had symptomatic nonsustained ventricular tachycardia
TO-
20fO-
\ SUSTAINED ” * 52
r
*ONSUSTUNED
NONL II=454
Il.23
INDUCED
/II 41-‘3
q
j+\\
VT
FIGURE 2. Incidence of clinical ventricular tachycardia (VT) in patients in whom this arrhythmia was induced by programmed stimulation.
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clinically (Fig. 2); 2 of the 23 had the sustained form clinically, and the remaining 3 had no documented ventricular tachycardia before the study. Two of these three were being evaluated for unexplained syncopal episodes; in both patients the nonsustained ventricular tachycardia induced in the laboratory was of the torsade de pointes variety and reproduced their symptoms. In 7 of the 23 patients the induced nonsustained ventricular tachycardia was of the torsade de pointes type that had been documented clinically in 5 of the patients. Four hundred fifty-four of the 529 patients had no inducible uentricular tachycardia in the laboratory (Fig. 2). Fourteen (3 percent) of the 454 had the arrhythmia clinically, and in 3 of these the tachycardia was sustained. Each of these three had spontaneous ventricular tachycardia in the laboratory, and the responses to overdrive pacing and programmed stimulation suggested an automatic mechanism. The remaining 11 had spontaneous nonsustained ventricular tachycardia in the laboratory. Two of these, one patient with a long Q-T interval and one with mitral valve prolapse, had a torsade de pointes rhythm clinically. Three had exercise-induced nonsustained ventricular tachycardia and two had no evidence of heart disease. Eight of these 14 patients in whom ventricular tachycardia was not inducible by programmed stimulation despite its clinical occurrence had one or two intraventricular reentrant complexes that were similar in configuration to the clinical ventricular tachycardia. Comparison of morphologic features of clinical and induced ventricular tachycardia: The QRS configuration, axis and cycle length of both the clinical and induced ventricular tachycardia were available for comparison in 43 patients. Comparisons and morphologic data were limited by the number of electrocardiographic leads recorded in the laboratory which were either leads I, II or aVF, and VI or I, II, III and VI. In 12 patients, however, a 12 lead electrocardiogram of the induced tachycardia was recorded in the laboratory and compared with the prestudy 12 lead electrocardiogram of the arrhythmia. In the remaining patients documentation of their arrthymia was by modified precordial or limb leads, or both, during Holter monitoring or telemetry and thus adequate comparisons of morphologic features could not be made. The 43 patients in whom comparisons were made included 54 percent of the patients with sustained ventricular tachycardia clinically and 43 percent of those with nonsustained tachycardia clinically. There were no significant differences in frequency or type of heart disease between these 43 patients and the patients who did not have complete documentation of their clinical arrhythmia. Sixty-two distinct patterns of ventricular tachycardia (sustained and nonsustained) were induced in these 43 patients in the laboratory. Fifty-four patterns (87 percent) were documented to occur spontaneously and had the same configuration (right or left bundle branch block) and axis as those of the induced ventricular tachycardias (Fig. 3). The difference in cycle lengths between clinical and induced ventricular tachycardias
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was less than 10 ms in 22 of 54 episodes and ranged from 10 to 80 ms (37 f 22) in the remaining 32. Each of the eight patients in whom a configuration of ventricular tachycardia was induced that was not seen clinically had two different configurations of ventricular tachycardia induced in the laborat.ory. In each case the electrocardiographic characteristics of one of the configurations were similar to the clinical ventricular tachycardia. Complications of programmed stimulation: The programmed stimulation in these 529 patients was not accompanied by any mortality. Ventricular fibrillation was induced in 12 patients including 10 who had clinical episodes of ventricular fibrillation and have previously been described.lg In two cases the ventricular fibrillation was drug-related. In four cases a stable ventricular tachycardia had degenerated into ventricular fibrillation analogous to clinical cardiac arrest experienced by these patients before thLestudy. In each of these patients who didnot have spontaneous conversion, sinus rhythm was restored by direct shock using 200 to 320 watt seconds (seven patients). There were no cardiac or neurologic sequelae in these patients or in the 10 patients whose ventricular tachycardia required cardioversion. Discussion Significance of Laboratory-Induced Tachycardias
Laboratory inducticln of supraventricular and ventricular arrhythmias b,y programmed electrical stimuNSR
’
lation has become an increasingly important technique in evaluating antiarrhythmic drug regimens and in defining patients at risk for arrhythmias.1-12 These clinical applications of electrophysiologic studies require confidence in the ability of programmed electrical stimulation to duplicate the patient’s spontaneous arrhythmias. The clinical significance of laboratory-induced supraventricular tachycardia in patients with the WolffParkinson-White syndrome was reported by Denes et al 2o who concluded that laboratory induction of tazhycardia in patients with a preexcitation syndrome implied the likelihood of spontaneous supraventricular tachycardia. Goldreyer and Damatol suggested the use of programmed stimulation as a diagnostic test for atrioventricular nodal reentrant supraventricular tachycardia as a result of their observations that patients with this arrhythmia induced in the laboratory were clinically symptomatic and had spontaneous supraventricular tachycardia, unlike patients who did not have the arrhythmia with programmed stimulation. We and others4-6rgJ2 have previously noted that laboratory-induced tachycardias were similar in configuration to the patients’ clinical tachycardias. In a preliminary report, Wellens et a1.21demonstrated that tachycardias induced in their laboratory were identical in configuration to those noted clinically. Their study included 56 patients with ventricular tachycardias and 289 patients with supraventricular tachycardias. In the present study we also observed that induced ventricular
*
VT
FIGURE 3. Initiation of sustained ventricular tachycardia (VT) morphologically similar to that occurring spontaneously. Left, sustained ventricular tachycardia with a right bundle branch block configuration and superior axis (rate 140 beats/min; cycle length 430 ms) induced (at arrow) by right ventricular pacing at a cycle length of 400 ms. Leads I, aVL and VI are shown with electrograms from the high right atrium (HRA), coronary sinus (CS), His bundle region (HSE), and right ventricular apex (RVA). T = time lines. Rfght, same patient. Standard electrocardiogram revealing spontaneous sustained ventricular tachycardia with the same morphologic features and axis as those of the induced tachycardia (rate 170 beats/min).
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tachycardias were similar to the patients’ spontaneous ventricular tachycardias. Our data, however, are limited by the use of only three or four surface electrocardiographic leads. Although our lead selection usually included leads from three planes, it is conceivable that subtle differences might have been observed had a 12 lead electrocardiogram been obtained in the laboratory. In 12 instances this was done using a standard electrocardiograph and the configuration of the induced ventricular tachycardia was observed to be comparable with that of the spontaneous arrhythmia. Differences in cycle lengths of clinical and laboratory ventricular tachycardias were not significant, and when they occurred were often due to the effects of antiarrhythmic agents. This report demonstrates that patients in whom ventricular tachycardia (sustained or nonsustained) is induced in the laboratory are overwhelmingly those who experience spontaneous attacks of ventricular tachycardia. This is particularly true of patients in whom sustained ventricukn tachycardia is induced. One hundred percent of these patients had documented sustained ventricular tachycardia clinically. It is equally significant that only 3 percent (14) of 454 patients in whom ventricular tachycardia was not inducible had spontaneous ventricular tachycardia. Correlation of Clinical Ventricular Tachycardia With lnducibility
Patients with recurrent sustained ventricular tachycardia have been studied in detail by many investigators.4-12 A large incidence of coronary artery disease has been previously noted.5*7,g Similarly, coronary artery disease was diagnosed with coronary angiography in 82 percent of our 57 patients with clinical sustained ventricular tachycardia. Previous myocardial infarction was documented in all but one patient with coronary artery disease, and left ventricular aneurysm was present in 67 percent of the 57 patients. We9 have previously reported an 85 percent success rate of inducing sustained ventricular tachycardia in patients with clinical episodes of sustained ventricular tachycardia. In the present report, which includes only adult patients, our success rate was 91 percent (52 of 57 patients). Fisher et a1.7described induction of ventricular tachycardia in 95 percent of 19 patients with ventricular tachycardia, 68 percent of whom had coronary artery disease and 16 percent a ventricular aneurysm. The clinical and laboratory duration of ventricular tachycardia (that is, sustained versus nonsustained) was not presented. In contrast, other investigators have reported a much lower success rate of ihduction of ventricular tachycardia in patients with sustained ventricular tachycardia clinically. Wellens et al.5 induced ventricular tachycardia in only 29 of 50 patients with sustained ventricular tachycardia. However, ventricular tachycardia was induced in 86 percent (18) of the 21 patients with a history of chronic coronary artery disease. Denes et a1.6 were able to induce ventricular tachycardia reproducibly in only 2 of 11 patients with
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clinical ventricular tachycardia, neither of whom had a primary diagnosis of arteriosclerotic heart disease. The differences in results from these laboratories probably reflect differences in patient population and stimulation techniques. The incidence of chronic coronary artery disease and, in particular, of left ventricular aneurysm is large in our patients. We believe that a broad spectrum of
techniques of programmed ventricular stimulation, including ventricular extrastimuli delivered during multiple paced cycle lengths and stimulation at multiple sites in the left as well as the right ventricle, is essential before one can state that ventricular tachycardia is truly noninducible. In 6 (11.5 percent) of our 52 patients with induced sustained ventricular tachycardia, the tachycardia was reproducibly initiated only from the left ventricle. Patients with spontaneous nonsustained ventricular tachycardia constitute a more heterogeneous group than those with sustained ventricular tachycardia.
Fewer patients have prior myocardial infarction and aneurysm, despite a 45 percent incidence rate of coronary artery disease. Thirty-one percent of these patients had no known heart disease. The mechanisms of ventricular tachycardia in this group of patients are probably varied but have not been well studied, in part because laboratory duplication of ventricular tachycardia has been less successful in this group. Denes et a1.6were unable to induce ventricular tachycardia in any of their 16 patients with nonsustained ventricular tachycardia. Our ability to induce ventricular tachycardia in 62 percent of our 29 patients with clinical nonsustained ventricular tachycardia may have been due to differences in stimulating techniques. Our patients with clinical nonsustained ventricular tachycardia represent a selected population generally referred or monitored because of palpitations or syncope, or both. The actual incidence and clinical signif-
icance of nonsustained ventricular tachycardia in the general population is unknown. In patients with cardiac disease, nonsustained ventricular tachycardia documented during Holter monitoring is usually asymptomatic.22s23 Whether electrophysiologic studies or antiarrhythmic therapy, or both, is useful in asymptomatic patients remains controversial, because the need for treating these arrhythmias is not established. Some patients with clinical nonsustained ventricular tachycardia could be classified into three subgroups. In some patients, presumably those whose
ventricular tachycardia is ischemia-related or catecholamine-dependent, or both, exercise testing may reveal the presence of ventricular arrhythmias not observed during long-term ambulatory monitoring.24 In general, however, 24-hour Holter monitoring is considered more sensitive in detecting ventricular arrhythmias.25 The electrophysiologic laboratory may be useful in further delineating mechanisms and therapy in patients who do manifest ventricular tachycardia during exercise testing and may be able to simulate
INDUCED VENTRICULAR TACHYCARDIA-VANDEPOL
some of the physiologic conditions of exercise testing in patients unable to undergo such testing because of physical limitations. With regard to our observations of torsade de pointes, we suggest that laboratory induction of this arrhythmia is clinically significant and may portend vulnerability of the patient to life-threatening arrhythmias; welg and others26 have noted a tendency of torsade de pointes to degenerate into ventricular fibrillation. The ability to induce this arrhythmia in patients in whom it has been documented clinically26 makes it possible to consider use of programmed ventricular stimulation in evaluating antiarrhythmic therapy in these patients. Therapeutic implications: Electrophysiologic testing appears to be a sensitive and specific method of initiating sustained ventricular tachycardia and as a result has been used to develop pharmacologic, pacing
ET AL.
and surgical therapy in this arrhythmia. Although the clinical significance of nonsustained ventricular tachycardia is unknown, electrophysiologic testing may provide useful data upon which to base therapy in certain symptomatic patients, particularly those with torsade de pointes or exercise-induced ventricular tachycardia who have a reasonable chance of having the arrhythmia reproduced in the laboratory. Prospective studies are necessary to demonstrate the utility of this technique toward this end. Acknowledgment We thank Marie Coscia and Frances Laird for assistance in preparing the manuscript; the technicians in the Cardiac Electrophysiology Laboratory; and John A. Kastor, MD, Chief of the Cardiovascular Section, for his continued support and encouragement.
References 1. Goldreyer BN, Damato AN. The essential role of atrioventricular conduction delay in the Initiation of paroxysmal supraventricular tachycardia. Circulation 1971; 43:679-87. 2. Josephson ME, Kastor JA. Supraventricular tachycardia: mechanisms and management. Ann Intern Med 1977; 87:346-58. 3. Wu D, Denes P, Amat-y-Leon F, Dhingra R, et al. Clinical, electrocardiographic and electrophysiologic observations in patients with paroxysmal supraventricular tachycardia. Am J Cardiol 1978; 41:1045-51. 4. Wellens HJJ, Lie KI, Durrer D. Further observations on ventricular tachycardia as studied by electrical stimulation of the heart. Chronic recurrent ventricular tachycardia and ventricular tachycardia during acute myocardial infarction. Circulation 1974; 49:647-53. 5. Wellens HJJ, Duren DR, Lie Ki. Observations on mechanisms of ventricular tachycardia in man. Circulation 1976; 54:237-44. 6. Denes P, Wu D, Dhingral RC, et al. Electrophysiologic studies in patients with chronic recurrent ventricular tachycardia. Circulation 1976; 54:229-36. 7. Fisher JD, Cohen HL, Mehra R, Altschuler H, Escher DJW, Furman S. Cardiac pacing and pacemakers. II. Serial electrophysiologic-pharmacologic testing for control of recurrent tachyarrhythmias. Am Heart J 1077; 93:658-68. 8. Hartzier GO, Maloney JC). Programmed ventricular stimulation in management of recurrent ventricular tachycardia. Mayo Clin Proc 1977; 52~731-41. 9. Josephson ME, Horowitz LN, Farshidl A, Kastor JA. Recurrent sustained ventricular tachycardia. 1. Mechanisms. Circulation 1978; 57:431-40. 10. Horowitz LN, Josephson ME, Farshidl A, Spielman SR, Michelson EL, Greenspan AM. Recurrent sustained ventricular tachycardia. 3. Role of the electrophysllologicstudy in selection of antiarrhythmic regimens. Circulation 1978: 58:986-97. 11. Ruskin JN, Garan H. Chronic electrophysiologic testing in patients with recurrent sustained ventricular tachycardia (abstr). Am J Cardiol 1979; 43:400. 12. Josephson ME, Horowitz LN, Farshidl A, Splelman SR, Mlcheison EL, Greenspan AM. Recurrent sustained ventricular tachycardia. 4. Pleomorphism. Circulation 1979; 59:459-68.
13. Wellens HJJ. Value and limitations of programmed electrical stimulation of the heart in the study and treatment of tachycardias. Circulation 1978; 57:845-53. 14. Josephson ME, Horowitz LN, Farshidi A, Spear JF, Kastor JA, Moore EN. Recurrent sustained ventricular tachycardia. 2. Endocardial mapping. Circulation 1978; 57:440-47. 15. Bellet S. Clinical Disorders of the Heart Beat. 3rd ed. Philadelphia: Lea 8 Febiger, 1971: 528. 16. Dessertenne F. La tachycardie ventriculaire B deux foyers oppods variables. Arch Mal Coeur 1966; 59:263-72. 17. Krlkler DM. A fresh look at cardiac arrhythmias. Pathogenesis and presentation. Lancet 1974; 1:913-8. 18. Krikler DM, Curry PVL. Torsade de pointes, an atypical ventricular tachycardia. Br Heart J 1976; 38:117-20. 19. Sptelman SR, Farshidl A, Horowttz LN, Josephson ME. Ventricular fibrillation during programmed ventricular stimulation: incidence and clinical implications. Am J Cardiol 1978; 42:913-8. 20. Denes P, Wu D, Amat-y-Leon F, et al. Paroxysmal supraventricular tachycardia induction in patients with Wolff-Parkinson-White syndrome. Ann Intern Med‘1979; 90: 153-7. 21. Wellens HJJ. Bar FW. Wiener I. FarrC J. Ross DL. Kersemakers J. Clinical relevance df tachycakdias indhced during programmed cardiac stimulation (abstr). Am J Cardiol 1979; 43:400. 22. Winkle RA, Derrington DC, Schroeder JS. Characteristics of ventricular tachycardia in ambulatory patients. Am J Cardiol 1977; 39:487-92. 23. Jelinek MV, Lohrbauer L, Lown B. Antiarrhythmic drug therapy for sporadic ventricular ectopic arrhythmia. Circulation 1974; 49:659-66. 24. Kosowsky BD, Lown B, Whiting R, Guiney T. Occurrence of ventricular arrhythmias with exercise as compared to monitoring. Circulation 1971; 44:826-32. 25. Lown B, Calvert AF, Armington R, Ryan M. Monitoring for serious arrhythmias and high risk of sudden death. Circulation 1975; 52: Suppl lll:lll-189-98. 26. Evans TR, Curry PVL, Fltchett DH, Krlkler DM. Torsade de pointes initiated by electrical stimulation. J Electrocardiol 1976; 9:22558.
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