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Mode of stimulation versus response: Validation of a protocol for induction of ventricular tachycardia
Mode of stimulation versus response: Validation of a protocol for induction of ventricular tachycardia Daniel 5. Oseran, M.D., Eli S. Gang, M.D., Angas W. Hamer, M.D., Carol A. Zaher, M.D., Mark E. Rosenthal, M.D., William J. Mandel, Thomas Peter, M.D. Los Angeles, Calif.
Programmed electrical stimulation has become a widely used tool in the evaluation and management of patients with ventricular tachyarrhythmias. The indications for intracardiac electrophysiologic studies are in a state of evolution. The last several years have witnessed the use of this technique in an increasing number of patient subgroups. Initial studies in patients with sustained ventricular tachycardia1m3 have led to investigations in patients with nonsustained ventricular tachycardia,4 survivors of sudden cardiac death:” patients with recurrent unexplained syncope,7F* and finally in patients with recent myocardial infarction as a means for prognostication.ga lo The evaluation of medical and surgical interventions in these groups of patients continues to be an area of active clinical investigation. Meaningful comparisons between the results of studies from different institutions have been hampered by the lack of a uniform stimulation protocol. Protocols often differ in the number of extrastimuli, the sites of stimulation in the right and left ventricle, and the current strength used for stimulation. The effect that each of these variables has on the ability to induce ventricular tachyarrhythmias in the susceptible patient is not clear. In an effort to answer this question, we prospectively evaluated a stepwise stimulation protocol which incorporated these parameters in consecutive patients with recurrent sustained ventricular tachycardia and in survivors of sudden cardiac death. From Sinai
the Division of Cardiology and Department of Medicine, Medical Center and the UCLA School of Medicine.
Supported Received Reprint Medical
646
in part
by the ECHO
for publication requests: Center,
March
Fund
of Cedars-Sinai
19, 1985;
accepted
Medical Apr.
CedarsCenter.
2, 1985.
Thomas Peter, M.D., Dept. of Cardiology, 8700 Beverly Blvd., Los Angeles, CA 90048.
Cedars-Sinai
Table
I. Clinical
M.D., and
characteristics Cardiac
Group Sustained VT (n = 52) Sudden cardiac death (n = 39)
Age*
(yr)
62 (25-82) 59 (20-80)
CAD
CM
43 28
5 5
disease Mix
3 3
NHD
1 3
CAD = coronary artery disease; CM = cardiomyopathy; Mist = miscellaneous heart disease; NHD = no recognizable heart disease; VT = ventricular tacbycardia. *Mean age and range.
METHODOLOGY Patients. We studied 91 consecutive patients referred for evaluation of ventricular arrhythmias between July 1, 1982, and May 1, 1984. Fifty-two patients were studied following one or more episodes of sustained ventricular tachycardia. Thirty-nine patients were studied following one or more episodes of sudden cardiac death. Patients undergoing electrophysiologic evaluation for nonsustained ventricular tachycardia or unexplained syncope were excluded from this analysis. Similarly, patients were excluded if their arrhythmias occurred in the setting of electrolyte imbalances, overt drug toxicity, or acute myocardial ischemia. Twelve-lead ECGs during tachycardia were available for review in 38 of the 52 patients in the group with sustained ventricular tachycardia. In the remaining patients only monitor strips were available. The clinical characteristics of the two patient groups are described in Table I. There were 65 men and 26 women. The patients ranged in age from 20 to 82 years, with a mean age of 62 years in the sustained ventricular tachycardia group and 59 years in the sudden cardiac death group. The major-
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tachycardirr
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647
II. Results of programmed stimulation Gwp Sustained VT in = 52) Sudden cardiac death (n = 39)
Sustained
VT
41 (79”l ) 21 (54°C )
ity of patients (75 % ) had underlying coronary artery disease. Other cardiac diseases included congestive cardiomyopathy, hypertrophic cardiomyopathy, mitral valve prolapse, sarcoidosis (one), and scleroderma (one). Four patients had no recognizable structural heart disease. Definitions. Sustained ventricular tachycardia: Ventricular tachycardia of more than 30 seconds’ duration or requiring termination because of hemodynamic compromise. Nonsustained ventricular tachycardia: Ventricular tachycardia of greater than six beats that terminated spontaneously within 30 seconds. Inducible ventricular tachycardia: Ventricular tachycardia initiated at least twice during programmed electrical stimulation. Electrophysiologic study protocol. Studies were performed in the postabsorptive state after obtaining informed consent. All antiarrhythmic drugs had been stopped for at least 5 half-lives prior to testing. Electrode catheters were inserted percutaneously or by cutdown, and were positioned under fluoroscopic control in the right atrium, right ventricular apex, and in the His bundle position. Intracardiac recordings were filtered at 30 to 500 Hz and were displayed simultaneously with three surface ECG leads (I,aV,,V,) on a multichannel oscilloscope (Electronics for Medicine, VR-12). Stimulation was performed using a programmable stimulator (Bloom Associates) that delivered rectangular impulses of 2 msec duration at two and five times late diastolic threshold. Diastolic threshold was always less than 1 mA. The following stimulation protocol was used in all patients. Step 1 = Atria1 pacing for 30 seconds at cycle lengths of 600 msec to 300 msec in 50 msec increments, or until the development of atrioventricular block; Step 2 = “Burst” ventricular pacing from the right ventricular apex for 8 to 10 beats at cycle lengths of 600 msec to 250 msec in 50 msec increments.
Step 3 = Premature ventricular stimuli during ventricular pacing at cycle lengths of 550 msec and 400 msec. Ventricular extrastimuli were introduced at increasing prematurity beginning in late diastole and at progressively shorter coupling intervals until
Nonsustained 7 ( 13 “’ ) 7 (17“, I
VT 1 I?‘, 1 (3’,
) 1
:1 cl;‘, 1 IO (“6’. J
reaching ventricular refractoriness. The coupling interval of the first premature stimulus was then set at 10 msec longer than the effective refractory period. In this manner single, double, and triple ventricular extrastimuli were introduced at twice diastolic threshold. Step 4 = Ventricular stimulation with single, double, and triple extrastimuli was repeated at a paced cycle length of 400 msec at five times diastolic threshold; Step 5 = Ventricular stimulation with single, double, and triple extrastimuli was then performed from the right ventricular outflow tract at a paced cycle length of 400 msec at five times diastolic threshold. The end point of the stimulation protocol was the induction of sustained ventricular arrhythmias or ventricular refractoriness. Left ventricular stimulation and isoproterenol infusion, although used in selected patients, were not evaluated as part of this study. Statistical comparisons were performed with chi square analysis, Fisher’s exact test, and Student’s t test. OBSERVATIONS Results of programmed stimulation. The results of programmed stimulation in the two patient groups are summarized in Table II. In patients referred with a history of sustained ventricular tachycardia, programmed stimulation induced sustained ventricular tachycardia in 41 of 52 cases (79% ) and nonsustained ventricular tachycardia in seven patients (13%). In patients with a history of sudden cardiac death, programmed stimulation induced sustained ventricular tachycardia in 21 of 39 cases (54%) and nonsustained ventricular tachycardia in seven patients (17%). One patient in each group had ventricular fibrillation induced at the time of electrophysiologic study. There were three patients (6 % ) in the sustained ventricular tachycardia group who had no inducible ventricular tachyarrhythmias, as compared to 10 patients (26% ) in the sudden cardiac death group without inducible ventricular arrhythmias (p < 0.02). Overall, ventricular tachycardia was induced in 4% of 52 patients (92% )
648
Oseran
Table
111.Mode
September, 1985 American Heart Journal
et al.
of ventricular
tachycardia
Group
AP
Sustained VT (n = 48) Sudden cardiac death (n = 28)
2 0
AP = atria1 ventricular
Table dia
induction v Burst 5 4
pacing: 5XDT = five times diastolic threshold; RVOT extrastimuli; S,SS,S, = triple ventricular extrastimuli:
IV. Characteristics
of induced
ventricular
No. of patient.s Cycle length
Group Sustained VT (n = 48) Sudden cardiac death (n = 28) VT = ventricular
Monomorphic VT
s,s,s,
sss,s4
5XDT
3 0
11
19 10
7
1
6
4
4
= right ventricular outflow tract: S,S, = single ventricular V Burst = ventricular burst pacing; VT = ventricular
tachycarwith
Polymorphic VT
59
44
4
267 + 56
19
9
311+
ss2
tachycardia.
referred with a history of sustained ventricular tachycardia versus 28 of 39 patients (72%) with a history of sudden cardiac death (p < 0.02). Mode of VT induction. The mode of ventricular tachycardia induction is summarized in Table III. In patients with a history of sustained ventricular tachycardia, atria1 pacing induced ventricular tachycardia in two patients and burst ventricular pacing induced ventricular tachycardia in five patients. Single ventricular extrastimuli induced ventricular tachycardia in three patients, while double extrastimuli were required in 11 patients and triple extrastimuli were required in 19 patients. Seven patients required triple extrastimuli at five times diastolic threshold for ventricular tachycardia induction. One patient was only inducible with stimulation from the right ventricular outflow tract with triple extrastimuli at five times diastolic threshold. Ventricular fibrillation was induced in one patient by triple ventricular extrastimuli at twice diastolic threshold from the right ventricular apex. In the sudden cardiac death group, there were no patients inducible with atria1 pacing. Four patients had inducible ventricular tachycardia with burst ventricular pacing. No patients had inducible ventricular tachycardia with single extrastimuli, while double extrastimuli induced ventricular tachycardia in four patients and triple extrastimuli induced ventricular tachycardia in 10 patients. Six patients were inducible with triple extrastimuli at five times diastolic threshold, and four patients were inducible only from the right ventricular outflow tract with triple extrastimuli at five times diastolic threshold.
extrastimuli; tachycardia.
R VOT
S,SS:
= double
Ventricular fibrillation was induced in one patient with triple extrastimuli at twice diastolic threshold from the right ventricular apex. The cumulative yield of inducible ventricular tachycardia as a function of the mode of stimulation is shown in Figs. 1 and 2. Using this stepwise protocol, 40% of patients with sustained ventricular tachycardia were inducible with a maximum of two ventricular extrastimuli. The addition of a third extrastimulus increased the yield of ventricular tachycardia to 77%. The last two steps of the protocol (i.e., five times diastolic threshold and stimulation of the right ventricular outflow tract) added a 15% increment in the overall yield. In patients presenting with sudden cardiac death, the addition of a third extrastimulus increased the yield of inducible ventricular tachycardia from 21% to 46%. Stimulating at five times diastolic threshold and stimulating from the outflow tract increased the yield an additional 26%. Characteristics of induced VT. The characteristics of the induced tachycardias in the two groups of patients is shown in Table IV. Forty-eight patients in the sustained ventricular tachycardia group had inducible ventricular tachycardia. The mean cycle length of the tachycardias was 311 -t 59 msec. This was significantly longer than the cycle length of the tachycardias in the 28 patients in the sudden cardiac death group, who had inducible ventricular tachycardia (267 k 56 msec, p < 0.02). Forty-four of the 48 inducible patients in the sustained ventricular tachycardia group had inducible monomorphic ventricular tachycardia as compared to 19 of 28 patients in the sudden cardiac death group 0, < 0.02). Four patients in the sustained ventricular tachycardia group had inducible polymorphic ventricular tachycardia. In three of these four cases, conversion to a monomorphic ventricular tachycardia was obtained after the administration of a type I antiarrhythmia drug. Rapid polymorphic ventricular tachycardia was induced in nine patients in the sudden cardiac death group. In the sustained ventricular tachycardia group, 38 patients had 12-lead ECGs obtained during their spontaneous arrhythmia which were available for review. In 35 of these 38 cases, pro-
Volume
110
Number
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Ventricular
tachvcardia
induction
649
100
100 PATIENTS
WITH
SUSTAINED
VT
PATIENTS
WITH
(N-52)
SUDDEN
CARDIAC
DEATH
(N= 39)
75
75
P d5
50
ae
25
25
0
1 (2) AP
r-r 1 (5)
1 (3)
V burst
S,S2
(1)
(11) StS2S3
S,S,S.$,
SXDT
0
RVOT
(0)
(4)
(0)
AP
V burst
SlS2
1. Relation betweenmode of stimulation and cumu-
lative yield of inducible ventricular tachycardia in patients with a history of sustained ventricular tachycardia. AP = atria1 pacing; 5XDT = five times diastolic threshold; RVOT = right ventricular outflow tract; S,S, = single ventricular extrastimuli; S,S,S, = double ventricular extrastimuli; S,S,S,S, = triple ventricular extrastimuli; V burst = ventricular burst pacing; VT = ventricular tachycardia. Numbers in parentheses refer to the total number of patients inducible with each mode of stimulation. grammed stimulation induced the clinical ventricular tachycardia. COMMENTS
The lack of a uniform stimulation protocol among laboratories engaged in clinical electrophysiologic testing in part reflects uncertainties regarding the optimal method for maximizing sensitivity and specificity with respect to induction of ventricular tachycardia. In an effort to increase the yield of inducible arrhythmias in susceptible patients as well as to avoid the need for left ventricular stimulation, more aggressive protocols have been developed over the
last several years. These protocols involve the use of three and four ventricular extrastimuli as well as multiple stimulation sites.“-I4 Another variable which has not been systematically studied but has been suggested as potentially influencing the yield of inducible arrhythmias, is the stimulating current
(10)
(6)
(4)
SW3S4
5x1~7
RVOT
MODE OF INDUCTION
MODE OF INDUCTION Fig.
(4) +A
Fig.
2. Relation between mode of stimulation
and cumu-
lative yield of inducible ventricular tachycardia in patients with a history of suddencardiac death. AP = atrial pacing; 5XDT = five times diastolic threshold; RVOT = right ventricular outflow tract; S,S, = single ventricular extrastimuli; S,S,S, = double ventricular extra-
stimuli:
S,&S,S, = triple
ventricular
burst = ventricular burst pacing. Numbers
extrastimuli;
V
in parentheses
refer to the total number of patients inducible with each mode of stimulation.
strength. The goal of this study was to evaluate the yield of inducible arrhythmia, using a protocol which incorporated several of these variables. This study demonstrated that using the described stimulation protocol, ventricular tachycardia was inducible in 92% of patients with a history of sustained ventricular tachycardia and in 72% of patients with a history of sudden cardiac death. These yields for ventricular tachycardia induction are comparable to those of previously published studies and confirm the finding of somewhat lower yield of inducible arrhythmias in sudden death survivors.5.6’ *I, I22l6 This level of inducible arrhythmias was achieved without the use of left ventricular stimulation. Third extrastimulus. The protocol used in this study allows only for the determination of the cumulative yield of ventricular tachycardia induction, rather than the absolute yield of ventricular tachycardia at
650
Oseran
et al.
each step in the protocol. Nonetheless, several trends are suggested by the results. The largest increase in yield in both groups was observed with the addition of a third extrastimulus, increasing the yield by 37% in patients with a history of sustained ventricular tachycardia and 25% in patients with a history of sudden cardiac death. Other studies have noted a similar substantial increase in yield with the addition of a third extrastimulus. Buxton et a1.12 found that a third extrastimulus was required for ventricular tachycardia induction in 23 % of patients with a history of sustained ventricular tachycardia and in 63% of patients with a history of sudden cardiac death. Stimulation at five times diastolic threshold. In addition to the number of extrastimuli introduced, the other steps in the protocol which were evaluated included stimulation at five times diastolic threshold and stimulation from the right ventricular outflow tract. With respect to the stimulating current strength, most reported studies in the field have used protocols in which stimulation is performed at twice diastolic threshold. In this study, careful calculation of late diastolic threshold was performed and was always less than 1 mA. Stimulation was then performed at exactly two times and five times threshold. In this study, stimulating at five times threshold increased the yield of inducible ventricular tachycardia by 13% in the sustained ventricular tachycardia group and by 16% in the sudden death group. Studies by Hamer et all7 on normal canine myocardium found that stimulation at five times threshold was unlikely to produce spurious ventricular fibrillation, whereas stimulation at higher levels of current produced a significantly greater incidence of ventricular fibrillation. Our data suggest that stimulation at five times diastolic threshold increased the yield of inducible arrhythmias without producing ventricular fibrillation. RV outflow tract stimulation. The stimulating catheter was positioned in the right ventricular outflow tract only after stimulation had been performed at five times threshold from the right ventricular apex. Using this stepwise approach, stimulation from the right ventricular outflow tract induced ventricular tachycardia in one additional patient in the sustained ventricular tachycardia group and in four patients in the sudden death group. Thus the vast majority of inducible ventricular tachycardia in both groups was produced by stimulation from the right ventricular apex. A somewhat greater increment in yield with stimulation from the outflow tract has been reported by Doherty et a1.14In our protocol the use of triple extrastimuli and higher current at the
September, American
1985
Heart Journal
right ventricular apex substantially reduced the need for stimulation from the outflow tract. Incidence of artifactual arrhythmias. There has been concern among investigators that the use of aggressive stimulation protocols involving three and four extrastimuli may produce a high incidence of nonclinical arrhythmias. 13,15It should be noted, however, that the reproduction of the patient’s “clinical” arrhythmia at the time of programmed stimulation may be hampered by several factors. First, adequate documentation of the morphology of the spontaneously occurring arrhythmia may not be available. Second, many patients are on antiarrhythmic agents at the time of the “clinical” ventricular tachycardia, thus potentially affecting the morphology and rate of the spontaneous arrhythmia. And third, the individual patient may well have several morphologies of spontaneous ventricular tachycardia even though not all morphologies have been documented. Given these pitfalls, it is perhaps more useful to examine the results of programmed stimulation in terms of whether or not the induced arrhythmia is likely to have been an artifact. As demonstrated by Brugada et a1.,15 the induction of nonsustained polymorphic ventricular tachycardia or ventricular fibrillation by aggressive stimulation may well be artifactual. Conversely, the induction of monomorphic ventricular tachycardia is unlikely to be an artifact and should be viewed as clinically relevant in the patient with a history of ventricular tachycardia. In this study, monomorphic ventricular tachycardia was induced in 44 patients with a history of sustained ventricular tachycardia. There were four instances of induction of polymorphic ventricular tachycardia in this group. In three cases the ventricular tachycardia became monomorphic after the administration of type I antiarrhythmic agents. In patients with a history of sudden death, polymorphic ventricular tachycardia was induced in nine cases. This higher rate of induction of polymorphic ventricular tachycardia may reflect differences in the two patient groups and may account for their different clinical presentations. Thus this stimulation protocol appears to produce a low incidence of artifactual arrhythmias in patients with a history of sustained ventricular tachycardia. The significance of inducible polymorphic ventricular tachycardia in survivors of sudden cardiac death is uncertain. In conclusion, this study prospectively evaluated a protocol with a hierarchy of stimulation intensity for the induction of ventricular tachycardia in patients with a history of sustained ventricular tachycardia or sudden death. The importance of a third extrastimulus in enhancing the yield of induc-
"Ol"me
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ible ventricular tachycardia in these two groups is emphasized. Moreover, stimulation at five times diastolic threshold appears to increase further the yield of inducible arrhythmias. Using such a stimulation protocol, left ventricular stimulation can be avoided in the majority of cases. Finally, this protocol appears to have produced a low incidence of artifactual or nonclinical arrhythmias in cases where the clinical arrhythmias had been documented. SUMMARY
Electrophysiologic studies were prospectively performed in 91 consecutive patients referred for evaluation of sustained ventricular tachycardia or sudden cardiac death. Fifty-two patients had a history of sustained ventricular tachycardia and 39 patients had a history of sudden cardiac death. The identical stimulation protocol was used in all patients. The stepwise protocol involved atria1 pacing, burst ventricular pacing, single, double, and triple extrastimuli during ventricular pacing. Stimulation was performed at the right ventricular apex at two and five times diastolic threshold. Using this protocol, ventricular tachycardia was inducible in 48 (92 % ) of the 52 patients with a history of sustained ventricular tachycardia and in 28 (72% ) of 39 patients with a history of sudden cardiac death (p < 0.02). The use of a third extrastimulus increased the yield of inducible ventricular tachycardia by 37% in patients with a history of sustained ventricular tachycardia and by 25 % in patients with a history of sudden cardiac death. Stimulation at five times diastolic threshold and stimulation from the right ventricular outflow tract added a 15% increment in overall yield of inducible ventricular tachycardia in patients with a history of sustained ventricular tachycardia, and a 26% increment in yield in patients with a history of sudden cardiac death. Forty-four (92%) of the 48 inducible patients in the sustained ventricular tachycardia group had inducible monomorphic ventricular tachycardia as compared to 19 (68% ) of 28 patients in the sudden cardiac death group (p < 0.02). The use of such a stimulation protocol with a hierarchy of intensity, which includes triple extrastimuli and stimulation at five times diastolic threshold, obviates the need for left ventricular stimulation in the majority of patients with previously documented sustained ventricular arrhythmias. This protocol appears to produce a low incidence of artifactual arrhythmias in patients with previously documented sustained ventricular tachycardia. The significance of inducible polymorphic ventricular tachycardia in sudden death survivors is uncertain.
Ventricular
tachycardin
induction
651
REFERENCES
1. Wellens H,JJ, Schuilenburg RM, Durrer 1): Electrical stimulation of the heart in patients with ventricular t,achycardia. Circulation 46:216, 1972. LN, Josephson ME, Farshidl A. Spielman SK. 2. Horowitz Michelson EL. Greenspan AM: Recurrent sustained ventricular tachycardia. 3. Role of the electrophysiologic study in the selection of antiarrhythmic regimens. t ‘irculat ion 58:9X, 1978. JW, Winkle RA: Elect.rode c;itheter arrhyt,hmia 3. Mason induction in the selection and assessment of’ antiarrhythmic drug therapy for recurrent ventricular tachycardia. Cirrulation 58:971. 1978. 4. Buxton AE, Waxman HL, Marchilinaki FE. .Josephson ME: Electrophgsiologic studies in nonsustained ventricular tachycardia. Am .J Cardiol 52:985, 198:?. 5. Ruskin JN. DiMarco .JP. Garan H: 0111 ol hosoital cardiac arrest: Electrophysiologic observations in selec;ion of longterm antiarrhythmic therapy. N Engl J Med 3033607. 19X0. 6. Morady F, Scheinman MM, Hess DS, Sung R-7, Shen E, Shapiro W: Electrophysiologic test.ing in the management of survivors of out-of-hospital cardiac arrest. Am cJ Cardiol 51935. 1983. 7. DiMarco JP, Garan H, Harthorne .JW, Huskin .JN: Intracardiac electrophysiologic techniques in recurrent syncope of unknown cause. Ann Intern Med 95.742. 1982. 8. Hess DS, Morady F, Scheinman MM: Electrophysiologic testing in the evaluation of patients with ;yncope of undetermined origin. Am ,J Cardiol 50:1:X)9, 198% of sudtlen 9. Hamer A, Vohra J, Hunt D, Sloman G: Prediction death by electrophysiologic studies in high risk patients surviving acute myocardial infarction. A,n ,J Cardiol 50:22X. 1982. 10. Richards DA, Cody DV, Denniss AR. Russel PA, Young AA, Uther JB: Ventricular electrical instability: A predictor of death after myocardial infarction. An. .I Cnrdiol 51:‘;s. 1983. 11. Morady F, DiCarlo L, Winston S, Davis .JC. Scheinman MM: A prospective comparison of triple extrastimuli and left ventricular stimulation in studies of ventricular tachycardia induction. Circulation 70:52, 1984. 12. Buxton AE, Waxman HI,, Marehlinski FE, Untereker WJ, Waspe LE, Josephson ME: Role of triple extrastimuli during electrophysiologic study of patients with documented sustained ventricular tachqarrhvthmias. “irculation 69:X12, 1984. DE, Luck .JC, Griffin JC, et al: Induction of clinical 13. Mann ventricular tachycardia using programmed stimulation: Value of third and fourth ext.rastimuli. An: .I Cardiol 52:X)1, 1983. 14. Doherty JV, Kienzle MG, Buxton AK. et al: Discordant results of programmed ventricular stimulation at different right ventricular sites in patients with anll without spontaneous sustained ventricular tachycardia: A prospective study of 56 patients. Am J Cardiol 54:336. 1984. 15. Brugada P, Green M, Abdullah H, Wellens HJJ: Significance of ventricular arrhythmias initiated by programmed ventricular stimulation: The importance of the type of ventricular arrhythmia induced and the number 01‘ premature stimuli required. Circulation 69:87, 1984. 16. Vandepol CJ. Farshidi A, Spielman SK, Greenspan AM, Horowitz LN, Josephson ME: Incidence and clinical signiticame of induced ventricular tachycardm Am .I Cardiol 45:725, 1980. AW’, Karagueuzian HS, Sugi K, Zaher CA, Mandel 17. Hamer W.J, Peter T: Factors related to the induction of ventricular hhrillation in the normal canine heart bv programmed electrical stimulation. .I Am Co11 Cardiol 3:7:51. 1984.
Programmed electrical stimulation has become a widely used tool in the evaluation and management of patients with ventricular tachyarrhythmias. The indications for intracardiac electrophysiologic studies are in a state of evolution. The last several years have witnessed the use of this technique in an increasing number of patient subgroups. Initial studies in patients with sustained ventricular tachycardia1m3 have led to investigations in patients with nonsustained ventricular tachycardia,4 survivors of sudden cardiac death:” patients with recurrent unexplained syncope,7F* and finally in patients with recent myocardial infarction as a means for prognostication.ga lo The evaluation of medical and surgical interventions in these groups of patients continues to be an area of active clinical investigation. Meaningful comparisons between the results of studies from different institutions have been hampered by the lack of a uniform stimulation protocol. Protocols often differ in the number of extrastimuli, the sites of stimulation in the right and left ventricle, and the current strength used for stimulation. The effect that each of these variables has on the ability to induce ventricular tachyarrhythmias in the susceptible patient is not clear. In an effort to answer this question, we prospectively evaluated a stepwise stimulation protocol which incorporated these parameters in consecutive patients with recurrent sustained ventricular tachycardia and in survivors of sudden cardiac death. From Sinai
the Division of Cardiology and Department of Medicine, Medical Center and the UCLA School of Medicine.
Supported Received Reprint Medical
646
in part
by the ECHO
for publication requests: Center,
March
Fund
of Cedars-Sinai
19, 1985;
accepted
Medical Apr.
CedarsCenter.
2, 1985.
Thomas Peter, M.D., Dept. of Cardiology, 8700 Beverly Blvd., Los Angeles, CA 90048.
Cedars-Sinai
Table
I. Clinical
M.D., and
characteristics Cardiac
Group Sustained VT (n = 52) Sudden cardiac death (n = 39)
Age*
(yr)
62 (25-82) 59 (20-80)
CAD
CM
43 28
5 5
disease Mix
3 3
NHD
1 3
CAD = coronary artery disease; CM = cardiomyopathy; Mist = miscellaneous heart disease; NHD = no recognizable heart disease; VT = ventricular tacbycardia. *Mean age and range.
METHODOLOGY Patients. We studied 91 consecutive patients referred for evaluation of ventricular arrhythmias between July 1, 1982, and May 1, 1984. Fifty-two patients were studied following one or more episodes of sustained ventricular tachycardia. Thirty-nine patients were studied following one or more episodes of sudden cardiac death. Patients undergoing electrophysiologic evaluation for nonsustained ventricular tachycardia or unexplained syncope were excluded from this analysis. Similarly, patients were excluded if their arrhythmias occurred in the setting of electrolyte imbalances, overt drug toxicity, or acute myocardial ischemia. Twelve-lead ECGs during tachycardia were available for review in 38 of the 52 patients in the group with sustained ventricular tachycardia. In the remaining patients only monitor strips were available. The clinical characteristics of the two patient groups are described in Table I. There were 65 men and 26 women. The patients ranged in age from 20 to 82 years, with a mean age of 62 years in the sustained ventricular tachycardia group and 59 years in the sudden cardiac death group. The major-
“Ol”me
110
Number
3
Table
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Ventricular
tachycardirr
induction.
647
II. Results of programmed stimulation Gwp Sustained VT in = 52) Sudden cardiac death (n = 39)
Sustained
VT
41 (79”l ) 21 (54°C )
ity of patients (75 % ) had underlying coronary artery disease. Other cardiac diseases included congestive cardiomyopathy, hypertrophic cardiomyopathy, mitral valve prolapse, sarcoidosis (one), and scleroderma (one). Four patients had no recognizable structural heart disease. Definitions. Sustained ventricular tachycardia: Ventricular tachycardia of more than 30 seconds’ duration or requiring termination because of hemodynamic compromise. Nonsustained ventricular tachycardia: Ventricular tachycardia of greater than six beats that terminated spontaneously within 30 seconds. Inducible ventricular tachycardia: Ventricular tachycardia initiated at least twice during programmed electrical stimulation. Electrophysiologic study protocol. Studies were performed in the postabsorptive state after obtaining informed consent. All antiarrhythmic drugs had been stopped for at least 5 half-lives prior to testing. Electrode catheters were inserted percutaneously or by cutdown, and were positioned under fluoroscopic control in the right atrium, right ventricular apex, and in the His bundle position. Intracardiac recordings were filtered at 30 to 500 Hz and were displayed simultaneously with three surface ECG leads (I,aV,,V,) on a multichannel oscilloscope (Electronics for Medicine, VR-12). Stimulation was performed using a programmable stimulator (Bloom Associates) that delivered rectangular impulses of 2 msec duration at two and five times late diastolic threshold. Diastolic threshold was always less than 1 mA. The following stimulation protocol was used in all patients. Step 1 = Atria1 pacing for 30 seconds at cycle lengths of 600 msec to 300 msec in 50 msec increments, or until the development of atrioventricular block; Step 2 = “Burst” ventricular pacing from the right ventricular apex for 8 to 10 beats at cycle lengths of 600 msec to 250 msec in 50 msec increments.
Step 3 = Premature ventricular stimuli during ventricular pacing at cycle lengths of 550 msec and 400 msec. Ventricular extrastimuli were introduced at increasing prematurity beginning in late diastole and at progressively shorter coupling intervals until
Nonsustained 7 ( 13 “’ ) 7 (17“, I
VT 1 I?‘, 1 (3’,
) 1
:1 cl;‘, 1 IO (“6’. J
reaching ventricular refractoriness. The coupling interval of the first premature stimulus was then set at 10 msec longer than the effective refractory period. In this manner single, double, and triple ventricular extrastimuli were introduced at twice diastolic threshold. Step 4 = Ventricular stimulation with single, double, and triple extrastimuli was repeated at a paced cycle length of 400 msec at five times diastolic threshold; Step 5 = Ventricular stimulation with single, double, and triple extrastimuli was then performed from the right ventricular outflow tract at a paced cycle length of 400 msec at five times diastolic threshold. The end point of the stimulation protocol was the induction of sustained ventricular arrhythmias or ventricular refractoriness. Left ventricular stimulation and isoproterenol infusion, although used in selected patients, were not evaluated as part of this study. Statistical comparisons were performed with chi square analysis, Fisher’s exact test, and Student’s t test. OBSERVATIONS Results of programmed stimulation. The results of programmed stimulation in the two patient groups are summarized in Table II. In patients referred with a history of sustained ventricular tachycardia, programmed stimulation induced sustained ventricular tachycardia in 41 of 52 cases (79% ) and nonsustained ventricular tachycardia in seven patients (13%). In patients with a history of sudden cardiac death, programmed stimulation induced sustained ventricular tachycardia in 21 of 39 cases (54%) and nonsustained ventricular tachycardia in seven patients (17%). One patient in each group had ventricular fibrillation induced at the time of electrophysiologic study. There were three patients (6 % ) in the sustained ventricular tachycardia group who had no inducible ventricular tachyarrhythmias, as compared to 10 patients (26% ) in the sudden cardiac death group without inducible ventricular arrhythmias (p < 0.02). Overall, ventricular tachycardia was induced in 4% of 52 patients (92% )
648
Oseran
Table
111.Mode
September, 1985 American Heart Journal
et al.
of ventricular
tachycardia
Group
AP
Sustained VT (n = 48) Sudden cardiac death (n = 28)
2 0
AP = atria1 ventricular
Table dia
induction v Burst 5 4
pacing: 5XDT = five times diastolic threshold; RVOT extrastimuli; S,SS,S, = triple ventricular extrastimuli:
IV. Characteristics
of induced
ventricular
No. of patient.s Cycle length
Group Sustained VT (n = 48) Sudden cardiac death (n = 28) VT = ventricular
Monomorphic VT
s,s,s,
sss,s4
5XDT
3 0
11
19 10
7
1
6
4
4
= right ventricular outflow tract: S,S, = single ventricular V Burst = ventricular burst pacing; VT = ventricular
tachycarwith
Polymorphic VT
59
44
4
267 + 56
19
9
311+
ss2
tachycardia.
referred with a history of sustained ventricular tachycardia versus 28 of 39 patients (72%) with a history of sudden cardiac death (p < 0.02). Mode of VT induction. The mode of ventricular tachycardia induction is summarized in Table III. In patients with a history of sustained ventricular tachycardia, atria1 pacing induced ventricular tachycardia in two patients and burst ventricular pacing induced ventricular tachycardia in five patients. Single ventricular extrastimuli induced ventricular tachycardia in three patients, while double extrastimuli were required in 11 patients and triple extrastimuli were required in 19 patients. Seven patients required triple extrastimuli at five times diastolic threshold for ventricular tachycardia induction. One patient was only inducible with stimulation from the right ventricular outflow tract with triple extrastimuli at five times diastolic threshold. Ventricular fibrillation was induced in one patient by triple ventricular extrastimuli at twice diastolic threshold from the right ventricular apex. In the sudden cardiac death group, there were no patients inducible with atria1 pacing. Four patients had inducible ventricular tachycardia with burst ventricular pacing. No patients had inducible ventricular tachycardia with single extrastimuli, while double extrastimuli induced ventricular tachycardia in four patients and triple extrastimuli induced ventricular tachycardia in 10 patients. Six patients were inducible with triple extrastimuli at five times diastolic threshold, and four patients were inducible only from the right ventricular outflow tract with triple extrastimuli at five times diastolic threshold.
extrastimuli; tachycardia.
R VOT
S,SS:
= double
Ventricular fibrillation was induced in one patient with triple extrastimuli at twice diastolic threshold from the right ventricular apex. The cumulative yield of inducible ventricular tachycardia as a function of the mode of stimulation is shown in Figs. 1 and 2. Using this stepwise protocol, 40% of patients with sustained ventricular tachycardia were inducible with a maximum of two ventricular extrastimuli. The addition of a third extrastimulus increased the yield of ventricular tachycardia to 77%. The last two steps of the protocol (i.e., five times diastolic threshold and stimulation of the right ventricular outflow tract) added a 15% increment in the overall yield. In patients presenting with sudden cardiac death, the addition of a third extrastimulus increased the yield of inducible ventricular tachycardia from 21% to 46%. Stimulating at five times diastolic threshold and stimulating from the outflow tract increased the yield an additional 26%. Characteristics of induced VT. The characteristics of the induced tachycardias in the two groups of patients is shown in Table IV. Forty-eight patients in the sustained ventricular tachycardia group had inducible ventricular tachycardia. The mean cycle length of the tachycardias was 311 -t 59 msec. This was significantly longer than the cycle length of the tachycardias in the 28 patients in the sudden cardiac death group, who had inducible ventricular tachycardia (267 k 56 msec, p < 0.02). Forty-four of the 48 inducible patients in the sustained ventricular tachycardia group had inducible monomorphic ventricular tachycardia as compared to 19 of 28 patients in the sudden cardiac death group 0, < 0.02). Four patients in the sustained ventricular tachycardia group had inducible polymorphic ventricular tachycardia. In three of these four cases, conversion to a monomorphic ventricular tachycardia was obtained after the administration of a type I antiarrhythmia drug. Rapid polymorphic ventricular tachycardia was induced in nine patients in the sudden cardiac death group. In the sustained ventricular tachycardia group, 38 patients had 12-lead ECGs obtained during their spontaneous arrhythmia which were available for review. In 35 of these 38 cases, pro-
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Ventricular
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100
100 PATIENTS
WITH
SUSTAINED
VT
PATIENTS
WITH
(N-52)
SUDDEN
CARDIAC
DEATH
(N= 39)
75
75
P d5
50
ae
25
25
0
1 (2) AP
r-r 1 (5)
1 (3)
V burst
S,S2
(1)
(11) StS2S3
S,S,S.$,
SXDT
0
RVOT
(0)
(4)
(0)
AP
V burst
SlS2
1. Relation betweenmode of stimulation and cumu-
lative yield of inducible ventricular tachycardia in patients with a history of sustained ventricular tachycardia. AP = atria1 pacing; 5XDT = five times diastolic threshold; RVOT = right ventricular outflow tract; S,S, = single ventricular extrastimuli; S,S,S, = double ventricular extrastimuli; S,S,S,S, = triple ventricular extrastimuli; V burst = ventricular burst pacing; VT = ventricular tachycardia. Numbers in parentheses refer to the total number of patients inducible with each mode of stimulation. grammed stimulation induced the clinical ventricular tachycardia. COMMENTS
The lack of a uniform stimulation protocol among laboratories engaged in clinical electrophysiologic testing in part reflects uncertainties regarding the optimal method for maximizing sensitivity and specificity with respect to induction of ventricular tachycardia. In an effort to increase the yield of inducible arrhythmias in susceptible patients as well as to avoid the need for left ventricular stimulation, more aggressive protocols have been developed over the
last several years. These protocols involve the use of three and four ventricular extrastimuli as well as multiple stimulation sites.“-I4 Another variable which has not been systematically studied but has been suggested as potentially influencing the yield of inducible arrhythmias, is the stimulating current
(10)
(6)
(4)
SW3S4
5x1~7
RVOT
MODE OF INDUCTION
MODE OF INDUCTION Fig.
(4) +A
Fig.
2. Relation between mode of stimulation
and cumu-
lative yield of inducible ventricular tachycardia in patients with a history of suddencardiac death. AP = atrial pacing; 5XDT = five times diastolic threshold; RVOT = right ventricular outflow tract; S,S, = single ventricular extrastimuli; S,S,S, = double ventricular extra-
stimuli:
S,&S,S, = triple
ventricular
burst = ventricular burst pacing. Numbers
extrastimuli;
V
in parentheses
refer to the total number of patients inducible with each mode of stimulation.
strength. The goal of this study was to evaluate the yield of inducible arrhythmia, using a protocol which incorporated several of these variables. This study demonstrated that using the described stimulation protocol, ventricular tachycardia was inducible in 92% of patients with a history of sustained ventricular tachycardia and in 72% of patients with a history of sudden cardiac death. These yields for ventricular tachycardia induction are comparable to those of previously published studies and confirm the finding of somewhat lower yield of inducible arrhythmias in sudden death survivors.5.6’ *I, I22l6 This level of inducible arrhythmias was achieved without the use of left ventricular stimulation. Third extrastimulus. The protocol used in this study allows only for the determination of the cumulative yield of ventricular tachycardia induction, rather than the absolute yield of ventricular tachycardia at
650
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et al.
each step in the protocol. Nonetheless, several trends are suggested by the results. The largest increase in yield in both groups was observed with the addition of a third extrastimulus, increasing the yield by 37% in patients with a history of sustained ventricular tachycardia and 25% in patients with a history of sudden cardiac death. Other studies have noted a similar substantial increase in yield with the addition of a third extrastimulus. Buxton et a1.12 found that a third extrastimulus was required for ventricular tachycardia induction in 23 % of patients with a history of sustained ventricular tachycardia and in 63% of patients with a history of sudden cardiac death. Stimulation at five times diastolic threshold. In addition to the number of extrastimuli introduced, the other steps in the protocol which were evaluated included stimulation at five times diastolic threshold and stimulation from the right ventricular outflow tract. With respect to the stimulating current strength, most reported studies in the field have used protocols in which stimulation is performed at twice diastolic threshold. In this study, careful calculation of late diastolic threshold was performed and was always less than 1 mA. Stimulation was then performed at exactly two times and five times threshold. In this study, stimulating at five times threshold increased the yield of inducible ventricular tachycardia by 13% in the sustained ventricular tachycardia group and by 16% in the sudden death group. Studies by Hamer et all7 on normal canine myocardium found that stimulation at five times threshold was unlikely to produce spurious ventricular fibrillation, whereas stimulation at higher levels of current produced a significantly greater incidence of ventricular fibrillation. Our data suggest that stimulation at five times diastolic threshold increased the yield of inducible arrhythmias without producing ventricular fibrillation. RV outflow tract stimulation. The stimulating catheter was positioned in the right ventricular outflow tract only after stimulation had been performed at five times threshold from the right ventricular apex. Using this stepwise approach, stimulation from the right ventricular outflow tract induced ventricular tachycardia in one additional patient in the sustained ventricular tachycardia group and in four patients in the sudden death group. Thus the vast majority of inducible ventricular tachycardia in both groups was produced by stimulation from the right ventricular apex. A somewhat greater increment in yield with stimulation from the outflow tract has been reported by Doherty et a1.14In our protocol the use of triple extrastimuli and higher current at the
September, American
1985
Heart Journal
right ventricular apex substantially reduced the need for stimulation from the outflow tract. Incidence of artifactual arrhythmias. There has been concern among investigators that the use of aggressive stimulation protocols involving three and four extrastimuli may produce a high incidence of nonclinical arrhythmias. 13,15It should be noted, however, that the reproduction of the patient’s “clinical” arrhythmia at the time of programmed stimulation may be hampered by several factors. First, adequate documentation of the morphology of the spontaneously occurring arrhythmia may not be available. Second, many patients are on antiarrhythmic agents at the time of the “clinical” ventricular tachycardia, thus potentially affecting the morphology and rate of the spontaneous arrhythmia. And third, the individual patient may well have several morphologies of spontaneous ventricular tachycardia even though not all morphologies have been documented. Given these pitfalls, it is perhaps more useful to examine the results of programmed stimulation in terms of whether or not the induced arrhythmia is likely to have been an artifact. As demonstrated by Brugada et a1.,15 the induction of nonsustained polymorphic ventricular tachycardia or ventricular fibrillation by aggressive stimulation may well be artifactual. Conversely, the induction of monomorphic ventricular tachycardia is unlikely to be an artifact and should be viewed as clinically relevant in the patient with a history of ventricular tachycardia. In this study, monomorphic ventricular tachycardia was induced in 44 patients with a history of sustained ventricular tachycardia. There were four instances of induction of polymorphic ventricular tachycardia in this group. In three cases the ventricular tachycardia became monomorphic after the administration of type I antiarrhythmic agents. In patients with a history of sudden death, polymorphic ventricular tachycardia was induced in nine cases. This higher rate of induction of polymorphic ventricular tachycardia may reflect differences in the two patient groups and may account for their different clinical presentations. Thus this stimulation protocol appears to produce a low incidence of artifactual arrhythmias in patients with a history of sustained ventricular tachycardia. The significance of inducible polymorphic ventricular tachycardia in survivors of sudden cardiac death is uncertain. In conclusion, this study prospectively evaluated a protocol with a hierarchy of stimulation intensity for the induction of ventricular tachycardia in patients with a history of sustained ventricular tachycardia or sudden death. The importance of a third extrastimulus in enhancing the yield of induc-
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ible ventricular tachycardia in these two groups is emphasized. Moreover, stimulation at five times diastolic threshold appears to increase further the yield of inducible arrhythmias. Using such a stimulation protocol, left ventricular stimulation can be avoided in the majority of cases. Finally, this protocol appears to have produced a low incidence of artifactual or nonclinical arrhythmias in cases where the clinical arrhythmias had been documented. SUMMARY
Electrophysiologic studies were prospectively performed in 91 consecutive patients referred for evaluation of sustained ventricular tachycardia or sudden cardiac death. Fifty-two patients had a history of sustained ventricular tachycardia and 39 patients had a history of sudden cardiac death. The identical stimulation protocol was used in all patients. The stepwise protocol involved atria1 pacing, burst ventricular pacing, single, double, and triple extrastimuli during ventricular pacing. Stimulation was performed at the right ventricular apex at two and five times diastolic threshold. Using this protocol, ventricular tachycardia was inducible in 48 (92 % ) of the 52 patients with a history of sustained ventricular tachycardia and in 28 (72% ) of 39 patients with a history of sudden cardiac death (p < 0.02). The use of a third extrastimulus increased the yield of inducible ventricular tachycardia by 37% in patients with a history of sustained ventricular tachycardia and by 25 % in patients with a history of sudden cardiac death. Stimulation at five times diastolic threshold and stimulation from the right ventricular outflow tract added a 15% increment in overall yield of inducible ventricular tachycardia in patients with a history of sustained ventricular tachycardia, and a 26% increment in yield in patients with a history of sudden cardiac death. Forty-four (92%) of the 48 inducible patients in the sustained ventricular tachycardia group had inducible monomorphic ventricular tachycardia as compared to 19 (68% ) of 28 patients in the sudden cardiac death group (p < 0.02). The use of such a stimulation protocol with a hierarchy of intensity, which includes triple extrastimuli and stimulation at five times diastolic threshold, obviates the need for left ventricular stimulation in the majority of patients with previously documented sustained ventricular arrhythmias. This protocol appears to produce a low incidence of artifactual arrhythmias in patients with previously documented sustained ventricular tachycardia. The significance of inducible polymorphic ventricular tachycardia in sudden death survivors is uncertain.
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tachycardin
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651
REFERENCES
1. Wellens H,JJ, Schuilenburg RM, Durrer 1): Electrical stimulation of the heart in patients with ventricular t,achycardia. Circulation 46:216, 1972. LN, Josephson ME, Farshidl A. Spielman SK. 2. Horowitz Michelson EL. Greenspan AM: Recurrent sustained ventricular tachycardia. 3. Role of the electrophysiologic study in the selection of antiarrhythmic regimens. t ‘irculat ion 58:9X, 1978. JW, Winkle RA: Elect.rode c;itheter arrhyt,hmia 3. Mason induction in the selection and assessment of’ antiarrhythmic drug therapy for recurrent ventricular tachycardia. Cirrulation 58:971. 1978. 4. Buxton AE, Waxman HL, Marchilinaki FE. .Josephson ME: Electrophgsiologic studies in nonsustained ventricular tachycardia. Am .J Cardiol 52:985, 198:?. 5. Ruskin JN. DiMarco .JP. Garan H: 0111 ol hosoital cardiac arrest: Electrophysiologic observations in selec;ion of longterm antiarrhythmic therapy. N Engl J Med 3033607. 19X0. 6. Morady F, Scheinman MM, Hess DS, Sung R-7, Shen E, Shapiro W: Electrophysiologic test.ing in the management of survivors of out-of-hospital cardiac arrest. Am cJ Cardiol 51935. 1983. 7. DiMarco JP, Garan H, Harthorne .JW, Huskin .JN: Intracardiac electrophysiologic techniques in recurrent syncope of unknown cause. Ann Intern Med 95.742. 1982. 8. Hess DS, Morady F, Scheinman MM: Electrophysiologic testing in the evaluation of patients with ;yncope of undetermined origin. Am ,J Cardiol 50:1:X)9, 198% of sudtlen 9. Hamer A, Vohra J, Hunt D, Sloman G: Prediction death by electrophysiologic studies in high risk patients surviving acute myocardial infarction. A,n ,J Cardiol 50:22X. 1982. 10. Richards DA, Cody DV, Denniss AR. Russel PA, Young AA, Uther JB: Ventricular electrical instability: A predictor of death after myocardial infarction. An. .I Cnrdiol 51:‘;s. 1983. 11. Morady F, DiCarlo L, Winston S, Davis .JC. Scheinman MM: A prospective comparison of triple extrastimuli and left ventricular stimulation in studies of ventricular tachycardia induction. Circulation 70:52, 1984. 12. Buxton AE, Waxman HI,, Marehlinski FE, Untereker WJ, Waspe LE, Josephson ME: Role of triple extrastimuli during electrophysiologic study of patients with documented sustained ventricular tachqarrhvthmias. “irculation 69:X12, 1984. DE, Luck .JC, Griffin JC, et al: Induction of clinical 13. Mann ventricular tachycardia using programmed stimulation: Value of third and fourth ext.rastimuli. An: .I Cardiol 52:X)1, 1983. 14. Doherty JV, Kienzle MG, Buxton AK. et al: Discordant results of programmed ventricular stimulation at different right ventricular sites in patients with anll without spontaneous sustained ventricular tachycardia: A prospective study of 56 patients. Am J Cardiol 54:336. 1984. 15. Brugada P, Green M, Abdullah H, Wellens HJJ: Significance of ventricular arrhythmias initiated by programmed ventricular stimulation: The importance of the type of ventricular arrhythmia induced and the number 01‘ premature stimuli required. Circulation 69:87, 1984. 16. Vandepol CJ. Farshidi A, Spielman SK, Greenspan AM, Horowitz LN, Josephson ME: Incidence and clinical signiticame of induced ventricular tachycardm Am .I Cardiol 45:725, 1980. AW’, Karagueuzian HS, Sugi K, Zaher CA, Mandel 17. Hamer W.J, Peter T: Factors related to the induction of ventricular hhrillation in the normal canine heart bv programmed electrical stimulation. .I Am Co11 Cardiol 3:7:51. 1984.