Limited value of programmed electrical stimulation from multiple right ventricular pacing sites in clinically sustained ventricular fibrillation or ventricular tachycardia associated with coronary artery disease

ARRHYTHMIAS

AND CONDUCTION DISTURBANCES

limitedValueof Programmed ElectricalStimulation fromMultipleRightVentricular PacingSites in Clinically Sustained Ventricular Fibrillation or Ventricular Tachycardia Associated withCoronary ArteryDisease PETER J. KUDENCHUK, MD, JACK KRON, MD, CHARLES WALANCE, BS, and JOHN H. MCANULTY, MD

One-hundred and ftfty patients with coronary artery disease and a documented history of sustained ventricular tachyanhythmias were studied to determine if programmed electrical stimulation (PES) from a second right ventricular (RV) pacing site optimizes the kductkn of such sustained arrhythmias. The first PES test was performed from 2 RV pacing sftes (apex and outflow tract or septum) using the apex first in each patient. All patients underwent a second PES within 6 to 24 hours of the first; both studies used up to 4 ventricular extrastimuli, in the absence of antiarrhythmic treatment. The second PES was performed from a skgte RV apical site using a pacing catheter retained from the first study. During the first day’s study, 74 pattents (49%) had sustained ventricular tachycardia induced from the RV

apex. Only 11 of the remaining 76 patients (7% of the total group) were inducible exclusively from a second RV pa&g location during the first day’s testing. Seven of these 11 patients, as well as 15 additional patients who did not have ventrkular tachycardia induced from either site on the first day’s study, were inducible from the RV- apex during the,second drug-free study. Among patients with sustained ventricular tachyarrhythmias, limitfng PES to a single RV site, with the optii of performing a second study in those who are initially nonkduciMe is more effective in inducing sustained vehtrtailar tachyarrhythmias than is PES performed from 2 RV pacing sites. (Am J Cardiol 1966;61:303-306)

I

ntracardiac electrophysiologic testing is widely used to evaluate and direct the treatment of cardiac arrhyth-

From the Division of Cardiology, Department of Medicine, Oregon Health Sciences University, Portland, Oregon. This study was supported in part by funds from the Oregon Chapter of the American Heart Association. Manuscript received May 11, 1987; revised manuscript received and accepted October 13, 1987. Address for reprints: Peter J. Kudenchuk, MD, Division of Cardiology (ZA-35).Harborview Medical Center, 325 Ninth Avenue, Seattle, Washington 98104.

mias. Induction of ventricular arrhythmias during programmed electrical stimulation (PES) studies has identified patients at risk for spontaneous ventricular arrhythmias and sudden death.1 To facilitate the induction of arrhythmias among such patients, most stimulation protocols have used 2,3 or up to 4 ventricular extrastimuli from at least 2 ventricular pacing sites, usually the right ventricular (RV) apex and outflow tract or septum. Although stimulation from a second RV site is widely used, few studies have examined whether it adds measurably to the induction rates achieved by pacing with 3 or up to 4 extrastimuli from the RV apex alone. We examined whether PES from

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TABLE I

LIMITED VALUE OF MULTIPLE PACING SITES

Arrhythmia Point Score

1 2 3 4 5 6 7

a

Scoring System Arrhythmia No induced arrhythmia 1 to3RVR 4 to 6 beats of NSVT >7 beats of NSVT VT at rate 100 to 160 VT at rate 161 to 200 VT at rate 201 to 300 VT at rate >300 BPM

BPM BPM BPM (or VF)

From reference 2. BPM = beatslmin; NSVT = nonsustained ventricular tachycardia; RVR = repetitive ventricular response; VT = sustained ventricular tachycardia.

the RV outflow tract or RV aspect of the ventricular septum enhances the yield of electrophysiologic studies among patients with clinical sustained ventricular tachyarrhythmias.

Methods Patients: We studied 150 consecutive patients with coronary artery disease and a documented history of sustained ventricular tachyarrhythmias (78 with ventricular fibrillation and 72 with ventricular tachycardia) not associated with an acute myocardial infarction. Patients with undocumented arrhythmias or with nonsustained clinical arrhythmias were not included. Studied patients included 128 men and 22 women whose mean age was 62 f 10 years (range 33 to 83). Coronary artery disease was defined as a 150% narrowing of at least 1 major epicardial vessel on coronary angiography (141 patients] or as clinical and electrocardiographic findings consistent with a remote myocardial infarction. Protocol: This study was approved by the Committee on Human Research at the Oregon Health Sciences University, and all participating patients gave informed consent. Our stimulation protocol has been previously reported in detail.2 All patients underwent 2 baseline PES studies, 6 to 24 hours apart, in the absence of antiarrhythmic medications. All previously administered antiarrhythmic agents were discontinued for at least 4 half-lives before PES evaluation. During the initial baseline study, catheters were placed in the RV apex, at the bundle of His and in the coronary sinus. The optimal current intensity for the induction of ventricular arrhythmias during electrophysiologic stimulation has not been defined, and a variety of current strengths have been used in previous studies.3-6All of our patients were studied at a stimulation current strength of 5 mA using a digital stimulator that delivered rectangular pulses of 2-ms duration. Stimulation thresholds were recorded before the study from the RV apex, outflow tract or septum, and in no instance exceeded 1 mA. The average stimulation threshold from the RV apex was 0.6 mA during the first study and 0.7 mA during the second study (difference not significant). The initial PES study included measurement of baseline conduction intervals and testing for supraventricular arrhythmias. Testing for ventricular ar-

rhythmias began with rapid RV pacing at rates of 140 to 240 beats/min using 16 beats at each level. Based on recent experimental data, which questions the value of random rapid ventricular burst pacing,7s8and corroborated by our own clinical observations, this portion of our protocol was subsequently discontinued; thus only 46 of 150 patients underwent rapid pacing during PES testing. Extrastimulus techniques followed and were performed in all 150 patients. One to 4 ventricular extrastimuli were delivered during spontaneous rhythm and during ventricular pacing for 6 beats at 2 fixed cycle lengths (usually 600 and 400 ms). The study endpoint in each patient was induction of a sustained ventricular tachyarrhythmia. If stimulation from the RV apex did not produce a sustained ventricular tachyarrhythmia, the His bundle pacing catheter was advanced and redirected toward the RV outflow tract or septum and an identical stimulation sequence repeated from this region. The catheter placed in the RV apex was not moved from its original location. At the completion of the first PES study, all pacing catheters were removed, except the one placed in the RV apex, which was secured at its subclavian vein entry site. The following criteria were used to define the second RV pacing site: a fluoroscopic change in catheter position to the region of the outflow tract or RV septum, and a distinct change of paced QRS morphology on the surface electrocardiogram. Six to 24 hours after the initial electrophysiologic study, patients underwent repeat testing while not receiving any antiarrhythmic agent using the pacing catheter placed in the RV apex during the initial study. The stability of this site was confirmed on follow-up studies by a radiographic position and a paced QRS morphology comparable to that observed upon insertion Patients underwent a ventricular pacing and extrastimulus sequence from the RV apex identical to that performed during the first study. Pacing from a second site (RV outflow tract or septum), however, was not repeated during the second study. Definitions: Rhythms: Repetitive ventricular response equalled 1 to 3 ventricular beats following capture of the last ventricular pacing stimulus. Nonsustained ventricular tachycardia equalled L4 ventricular beats (lasting 130 seconds] after capture of the last pacing stimulus, not requiring therapeutic intervention. Sustained ventricular tachycardia equalled ventricular tachycardia lasting >30 seconds or requiring intervention. Ventricular fibrillation equalled a completely disorganized cardiac electrical activity necessitating therapeutic intervention. Inducibility equalled provocation of sustained ventricular tachycardia or fibrillation. Rhythm evaluation: Rhythm morphology could not be consistently analyzed in this study because tracings of patients’ clinical rhythms from referral sources were frequently recorded in, at most, 1 lead. Rhythms were therefore analyzed and compared using a previously described 8-point scoring system that characterized rhythms by rate and duration2 (Table I).

February I,1968

Statistical analysis: Statistical analysis was performed using a Mailed chi square test and Fisher’s exact test. A p value of 10.05 was defined as significant.

Results Pacing from two right ventricular sites: One-hundred and fifty patients underwent PES from the RV apex, 74 of whom (49%) had a sustained ventricular tachyarrhythmia induced from that site on the first day of study (Figure I]. Seventy-six patients (51%) did not have a sustained ventricular arrhythmia induced from an apical site on the first day of testing and were therefore immediately also studied from the RV outflow tract or septum. Eleven of these 76 patients (14%), or 7% of the total of 150 patients studied, developed a sustained ventricular tachyarrhythmia when stimulated from this second RV site (Table II). Five of these 11 patients (45%) who were inducible from a second RV location had a clinical history of sustained ventricular tachycardia, and 6 patients (55%) had a history of ventricular fibrillation. In 7 of these 11 patients (64%), sustained ventricular rhythms were also induced from the RV apex during their second drug-free study. In these 7 patients, rhythm scores achieved from the RV outflow tract stimulation on the first day and apical stimulation on the second day were virtually identical. There were no significant differences in the number of extrastimuli required to provoke sustained ventricular tachycardia (Table II). Sequential programmed electrical stimulation from the right ventricular apex: Fifteen of 65 patients (23%), or 10% of the total of 150 patients studied, who initially did not have ventricular tachycardia provoked from either the RV apex or from a second RV pacing site on the first day’s study, were inducible from the RV apex during the second drug-free study (Figure 1). In addition, 7 patients induced exclusively from a second RV pacing site on the first day of study had inducible sustained ventricular arrhythmias from the RV apex on the second day of study. Thus, overall, 96 of 150 patients (64%) had a sustained ventricular tachyarrhythmia induced solely from an apical site on either the first or second drug-free PES study. In contrast, 85 of 150 patients (57%) were induced during the first study (p = 0.11) using 2 RV sites. When results from all stimulation sites on both days of study were combined, a total of 100 patients (67% of the group of 150 patients) were induced to sustained ventricular tachyarrhythmias during PES. Sustained ventricular tachyarrhythmias were induced during PES in 62 of 72 patients (86%) with a clinical history of sustained ventricular tachycardia and in 38 of 78 patients (49%) with clinical sustained ventricular fibrillation (p = 0.000003).Had a second PES study not been performed, 15 patients (15% of the group of 100 patients) with inducible sustained ventricular tachyarrhythmias would have remained undetected by stimulation from 2 RV sites alone. In contrast, had a second ventricular site of stimulation not been used during PES, only 4 patients (4% of the group of 100 patients) with inducible sustained ventricular tachyarrhythmias

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TABLE II Programmed Electrlcal Stimulation Results Among Patients Induced to Sustalned Ventricular Arrhythmias During Stlmulatlon from a Second Right Ventricular (RV) Locatlon Patient’s Clinical Rhythm

Rhythm Score Second RV Site

Extrastimuli (n)

Rhythm Score Second Study (RV Apex)

VT VF VF VT VT VT VF VT VF VF VF

6 a 6 7 5 7 7 6 7 6 8

Double Triple Quadruple Double Quadruple Double Quadruple Double Quadruple Double Triple

6 0 7 8 5 7 4 2 7 2 4

Extrastimuli (n)

Quadruple Double Quadruple Quadruple Double Quadruple Double Double Triple

VF = ventricular fibrillation; VT = ventricular tachycardia; extrastimuli refers to the number of programmed extrastimuli.

number

of

would have remained undetected at the completion of 2 PES studies from the RV apex (p <0.007). That is, performing a second PES study from the RV apex identified nearly 4 times the number of patients with inducible sustained arrhythmias than recognized by a single study from 2 RV locations. In 76 patients, PES from the RV apex initially failed to provoke a sustained ventricular tachyarrhythmia. Figure 2 compares the cumulative percentage of sustained ventricular arrhythmias induced by each added extrastimulus among these patients during additional stimulation from either a second RV site or a second PES study from the RV apex. Of note, stimulating strictly from the second RV site (outflow tract or septum] made a relatively small contribution to the overall frequency of sustained ventricular arrhythmias induced, compared with a successive day’s stimulation from the previous apical site (p = 0.02) Eight of 74 patients (ll%), or 5% of the total of 150 patients studied, who were initially inducible from the RV apex, could not be reinduced from the identical site during their second study. No ostensible factors (such as a change in stimulation threshold, number of

74 PATIENTS INDUCED FROM RV APEX

76 PATIENTS NOT INDUCED FROM RV APEX

/\

I\

11 PATIENTS INDUCED SITE 2

66 PATIENTS INDUCED STUDY 2 RV APEX

6 PATIENTS NOT INDUCED STUDY 2 RV APEX

7 PATIENTS INDUCED STUDY 2 RV APEX

65 PATIENTS NOT INDUCED SITE 2

15 PATIENTS INDUCED STUDY 2 RV APEX

50 PATIENTS NOT INDUCED STUDY 2 RV APEX

FIGURE 1. The outcome of electrophyslologlc stlmulatlon. Results from successive days of testing are compared with results from multiple right ventricular (RV) sites In 150 patients wlth coronary artery dlsease and cllnlcal sustained ventricular tachycardla or flbrlllatlon.

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LIMITED VALUE OF MULTIPLE PACING SITES

extrastimuli used to induce sustained ventricular tachycardia, metabolic alterations or clinical characteristics] were identified that could explain this apparent change in electrical instability in patients who either became inducible or noninducible between their first and second PES tests. Variability in induced arrhythmias: Using the 8point scoring system, rhythms induced from 2 different RV pacing sites during the first PES study were individually scored and compared. Rhythms induced from a single apical site on 2 sequential studies were also similarly compared. The difference in scores of rhythms induced from 2 separate studies at the RV apex was consistently either equal to or greater than the difference in scores of rhythms induced from 2 RV pacing sites during the first PES study. That is, the apparent day-to-day variability in induced arrhythmias from the same apical site was always of either equal or greater magnitude than the variability attributed to a major change in stimulation site. Complications: No deaths, myocardial infarctions or cerebrovascular events occurred among the group of patients studied. Three patients developed pneumothoraces as a complication of subclavian catheter placement. All 3 received chest tubes and recovered without sequelae. No patients developed fever or evidence of catheter-related infection within the first 24 hours of line placement. There were no instances of venous thrombosis, myocardial perforation or pericardial tamponade.

9 q

p=.o* 2ND RV SITE

n

- ‘UPIDP*c4No SlNGLE

0wBLE

TRlPLE

OUAORUPLE

EXTRASTIYULI

FIGURE 2. The cumulative frequency of sustained ventricular tachyarrhylhmlas induced during additional programmed stimulatlon among 76 patlents in whom lnltial study from the right ventricular (RV) apex failed lo provoke sustained ventricular tachycardla or fibrillation. Comparison is made between programmed electrical stimulation from a second RV stimulation site, and a second programmed electrical stimulation study from an RV aplcal location. The numerator of each fraction represents the cumulative number of patients In whom a sustained ventricular tachyarrhythmla was induced by that point in the stimulation protocol. The denomlnator represents the cumulative number of patients evaluated up to that point in lhe protocol. For example, patients who had reached an endpoint with rapid pacing, single, double or triple protocols contributed to the quadruple stimulation protocol results. Single = rapid pacing with the addition of a single programmed extrastimulus; double = rapid pacing with up to 2 programmed extrasllmull; triple = rapid pacing with up to 3 programmed extrastlmuli; quadruple = rapld pacing with up to 4 programmed extrastimuli.

Discussion Initiation of ventricular tachycardia during electrophysiologic studies has been said to be influenced not only by basic pacing rate and the number of extrastimuli, but also by the site of stimulation.9 Studies in an animal model have suggested that the distance from an area of abnormal impulse generation is a potentially important determinant of arrhythmia provocation by premature stimuli. lo Extrastimuli introduced in closer proximity to a potential reentry circuit may be more capable of penetrating the circuit to provoke ventricular tachycardia. l* There is, however, conflicting data when relating such information to PES in humans. Studies performing PES from the right ventricle of clinical ventricular tachycardia survivors, in the absence of antiarrhythmic drugs, have reported induction of sustained ventricular tachyarrhythmias in 65 to 90% of patients. 2~12-16 The added yield of ventricular tachyarrhythmias induced by using a second right or left ventricular pacing site and up to 3 extrastimuli has been reported to be marginal (2aj00).~~ Doherty et all* evaluated 37 patients with documented clinical sustained ventricular tachyarrhythmias, by stimulating all patients from both the RV apex and the RV outflow tract. They found that the difference in sensitivity between these RV pacing sites was not statistically significant. Oseran et al6 reported that among patients with clinical sustained ventricular tachycardias, the vast majority of such arrhythmias were induced by stimulation at 5 times the diastolic threshold from the RV apex. Such data question the need for stimulation from additional locations during drug-free PES studies. The present study demonstrates that PES from a second RV site among patients with clinical sustained ventricular tachyarrhythmias facilitates the induction of sustained ventricular arrhythmias in only 7% of such patients. Moreover, provocation of sustained ventricular tachycardia from a second RV pacing location (usually the RV outflow tract or septum] is not necessarily a phenomenon unique to the site of stimulation. When a second PES study is performed among such patients, even from an apical location, a nearly identical ventricular tachycardia can frequently be reproduced. This study also demonstrates that among patients with a history of sustained ventricular tachyarrhythmias, a negative baseline PES test, even from 2 ventricular stimulation sites, does not preclude either the presence of a provokable rhythm disorder or the potential need for antiarrhythmic treatment. Performing a second drug-free electrophysiologic study by means of an indwelling catheter in such patients enhanced the yield of induced ventricular tachycardias by 1570, and identified 15 new patients with inducible sustained ventricular tachyarrhythmias not seen on initial study from 2 RV pacing sites. This finding is at variance with the recent report by Duff et al,lg who found that there is a loss of ability to induce ventricular tachycardia if an electrode catheter is left in situ during serial PES testing. The latter study, however, only repeated PES testing among patients who were initially inducible and did not, as we did, reexamine all

February 1, 1968

patients, both those who were inducible and those who were not inducible to sustained ventricular tachyarrhythmias during initial PES evaluation. We identified an equal or greater likelihood of patients becoming inducible as becoming noninducible, upon restudy with a chronic, indwelling catheter. Our study suggeststhat the day-to-day variability in PES results may play a greater role in the overall ability to induce ventricular tachyarrhythmias than does the specific site or sites of programmed stimulation. The day-to-day variability in induced arrhythmias at the same apical site was consistently equal to or greater than the variation attributed to a major stimulation site change (RV apex to outflow tract or septum) carried out during the first baseline PES test. That is, even a major site change from apex to outflow tract or septum failed to evoke more than the degree of variability observed during day-to-day apical site testing. Further, the ability to provoke sustained ventricular tachyarrhythmias during PES did not assure the persistence of such inducibility during subsequent studies. Whether induced from an RV apical site, the outflow tract, the interventricular septum or not at all, a proportion of sustained ventricular tachyarrhythmias was observed to appear unpredictably (in 23% of 65 previously noninducible patients] and abate (in 11% of 74 previously inducible patients) upon restudy. Such results raise concern over whether the variability in PES results obtained by stimulation from multiple separate ventricular sites is so much the result of site disparity or simply a result of repeated stimulation from any ventricular site (PES reproducibility).2 Limitations: The findings of this report are limited to patients with coronary artery disease and a history of sustained ventricular tachyarrhythmias, and only addresses PES tests repeated from the RV apex in the drug-free state. It is not known if patients who were not inducible from the RV apex during their second study may have become inducible had their second study also been performed from another RV site. Although possible, extrapolation of our own data would suggest that only a minority (7%) of the patients falling into this group would demonstrate inducible sustained arrhythmias when restudied from another RV location. That is, if conditions holding true for the first PES study are applicable to the second study, at most, 3 patients from the combined group of 50 patients not found to be inducible from the RV apex on the second PES study might be inducible from another site. Finally, although this study cannot address the value of pacing from the left ventricle, other reports have found only a marginal benefit in ventricular tachycardia induction from such a location, except in the specific setting of drug-testing.20 The use of 3 or 4 extrastimuli during PES is controversial. Many authorities have voiced concern over the induction of nonclinical arrhythmias by excessive stimulation, particularly in patients without documented or suspected rhythm disturbances.21 However, among patients with clinical sustained ventricular tachyarrhythmias, “nonclinical arrhythmias” become more ambiguous and difficult to discriminate from

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clinical rhythms that perhaps have not been previously documented or rhythms having a different exit site from the same reentrant circuit.22 Moreover, among such patients, more aggressive induction protocols using up to 4 extrastimuli may even be preferable. Mann et all5 reported that use of 3 and 4 extrastimuli increased the percentage of patients in whom clinical sustained ventricular tachyarrhythmias were induced from 37 to 65%) compared with using 1 or 2 extrastimuli alone. Thus, while the use of up to 4 extrastimuli may be viewed as a limitation to the present study, such a protocol is not necessarily inappropriate for patients with clinical sustained ventricular tachyarrhythmias. Of note, if data obtained from the use of 4 extrastimuli in this study were ignored and only results from the use of lesser numbers of extrastimuli evaluated (Figure 21, the trend supporting the low yield of stimulation from a second RV site would persist and the relative contribution of stimulation strictly from a second RV site would be even smaller (<7%). The necessity for and the prognostic importance of performing at least 2 drug-free PES studies in all patients with clinical sustained ventricular tachyarrhythmias remain unknown. Many questions also remain regarding the optimal current strength, the optimal number of extrastimuli, whether a single drug-free PES study is sufficient for rhythm diagnosis (particularly when it is “negative”) and how discordant PES results, whether from separate sites or separate days of study, ought to reconciled. Certainly, the ability to provoke sustained ventricular tachyarrhythmias upon restudy in 23% of patients who were initially not inducible, even from multiple RV sites [i.e., in 15% of all patients undergoing PES), raises important concerns over how such “negative” PES studies ought to be interpreted. Acknowledgment: The authors recognize the thoughtful care of the cardiac catheterization technicians and the coronary care nurses at the Oregon Health Sciences University without whose assistance this work would not have been possible. We also appreciate the patient support provided by Karen Griffith, RN, ANP, and the work of Marie Watkins in preparing this manuscript.

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7. El-Sherif N. Mehra R, Gough WB, Zeiler RH. Reentrant ventricular arrhythmias in the late myocardial infarction period. Burst pacing versus multipJe premature stimulation in the induction of reentry. lACC 1984;4:295-304. 6. Akhtar M. Clinical application of rapid ventricular burst pacing versus extrastimulation for induction of ventricular tachycardia. lACC 1984;4:365307. 9. Wellens HJJ,Duren DR, Lie KI. Observations on mechanisms of ventricular tachycardia in man. Circulation 1976;54:237-244. 10. Michelson EL, Spear JF, Moore EN. Initiation of sustained ventricular tachyarrhythmias in a canine model of chronic myocardial infarction: importance of the site of stimulation. Circulation 1982;63:776-784. 11. Wellens HJJ. Value and limitations of programmed electrical stimulation of the heart in the study and treatment of tachycardias. Circulation 1978; 57:845-851. 12. Benditt DG, Benson DW, Klein GJ, Pritzker MR, Kriett JM, Anderson RW. Prevention of recurrent sudden cardiac arrest: role of provocative electropharmacologic testing. lACC 1983;2:418-425. 13. Brugada P, Green M. Abdollah H, Wellens HJJ. Significance of ventricufar arrhythmias initiated by programmed ventricular stimulation: the importance of the type of ventricular arrhythmia induced and the number of premature stimuli required. Circulation 1984;69:87-92. 14. Buxton AE, Waxman HL. Marchlinski FE, Untereker WJ. Waspe LE, Josephson ME. Role of triple extrastimuli during electrophysiologic study of patients with documented sustained ventricular tachyarrhythmias. Circulation 1984;69:532-540. 15. Mann DE, Luck JC. Griffin JC, Herre JM, Limacher MC, Magro SA, Robertson NW, Wyndham CRC. Induction of clinical ventricular tachycardia

using programmed stimulation: value of third and fourth extrastimuli. Am 1 CardioJ 1983;52:501-506, 16. Vandepol C]. Farshidi A, Spielman SR. Greenspan AM, Horowitz LN. Josephson ME. Incidence and clinical significance of induced ventricular tachycardia. Am l Cardiol I989;45:725-731. 17. 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 I984;76:52-57. 16. Doherty JU, Kienzle MG, Buxton AE, Marchlinski FE, Waxman HL, Josephson ME. Discordant results of programmed ventricular stimulation at different right ventricular sites in patients with and without spontaneous sustained ventricular tachycardia: a prospective study of 56 patients. Am l Cardiol 1984;54:336-342. 19. Duff HJ, Mitchell LB, Whyse DG. Programmed electrical stimulation studies for ventricular tachycardia induction in humans. II. Comparison of indwelling electrode catheter and daily catheter replacement. [ACC 1986; 8:576-581. 20. Morady F, Hess D, Scheinman MM. Electrophysiologic drug testing in patients with malignant ventricular arrhythmias: importance ofstimulationat more than one ventricular site. Am l CardioJ 1982;50:1055-1060. 21. Brugada P, Abdollah H, Heddle B. Wellens HJJ. Results of a ventricular stimulation protocol using a maximum of 4 premature stimuli in patients without documented or suspected ventricular arrhythmias. Am l CardioJ 1983;52:1214-1218. 22. Josephson ME, Horowitz LN, Spielman SR, Waxman HL, Greenspan A. Role of catheter mapping in the preoperative evaluation of ventricular tachycardia. Am 1 Cardiol 1982;49:201-220.