Sustained Polymorphic Arrhythmias Induced by Programmed Ventricular Stimulation have Prognostic Value in Patients Receiving Defibrillators

Sustained Polymorphic Arrhythmias Induced by Programmed Ventricular Stimulation have Prognostic Value in Patients Receiving Defibrillators SCOTT L. GREENBERG, M.D., J. MAURICIO SÁNCHEZ, M.D., JONAS A. COOPER, M.D., MICHAEL E. CAIN, M.D., JANE CHEN, M.D., MARYE J. GLEVA, M.D., BRUCE D. LINDSAY, M.D., TIMOTHY W. SMITH, D.PHIL, M.D., and MITCHELL N. FADDIS, M.D., PH.D. From the Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri Background: Patients with ischemic cardiomyopathy (ICM) who have monomorphic ventricular tachycardia (VT) induced by programmed ventricular stimulation (PVS) are at increased risk of sudden cardiac death (SCD). Among a primary prevention population, the prognostic significance of induced polymorphic ventricular arrhythmias is unknown. Methods: A total of 105 consecutive patients who received an implantable cardioverter-defibrillator (ICD) for primary prevention of SCD in the setting of ICM and non-sustained VT were retrospectively evaluated. Seventy-five patients (group I) had induction of monomorphic VT and 30 patients (group II) had a sustained ventricular arrhythmia other than monomorphic VT (ventricular flutter, ventricular fibrillation, and polymorphic VT) induced during PVS. Results: Baseline characteristics were similar between group I and group II except for ejection fraction (25% vs. 31%, P = 0.0001) and QRS duration (123 milliseconds vs. 109 milliseconds, P = 0.04). Sixteen of 75 (21.3%) patients in group I and 6 of 30 (20%) patients in group II received appropriate ICD therapy (P = 0.88). Survival free from ICD therapy was similar between groups (P = 0.54). There was a trend toward increased all-cause mortality among patients in group I by Kaplan-Meier analysis (P = 0.08). However, when adjusted for age, EF, and QRS duration mortality was similar (P = 0.45). Conclusions: There is no difference in rates of appropriate ICD discharge or mortality between patients dichotomized by type of rhythm induced during PVS. These results suggest that patients in this population who have inducible VF or sustained polymorphic VT have similar rates of subsequent clinical ventricular tachyarrhythmias as those with inducible monomorphic VT. (PACE 2007; 30:1067–1075) sudden cardiac death, programmed ventricular stimulation, implantable cardioverter-defibrillator, ventricular fibrillation, primary prevention Introduction Programmed ventricular stimulation (PVS) has been utilized to identify a patient population at high risk of sudden cardiac death (SCD).1–3 An abnormal response to PVS, defined as the induction of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF), was a requirement for subject entry into both MUSTT4 and MADIT,5 both of which demonstrated significant benefit of the implantable cardioverter-defibrillator (ICD) in patients without prior sustained ventricular tachyarrhythmic events (a primary prevention population). As a direct result of the mortality reduction shown in these trials, recent (2002) ACC/AHA/NASPE guidelines6 incorporated both Address for reprints: Scott L. Greenberg, M.D., 660 S. Euclid Ave., Campus Box 8086, St. Louis, MO 63110. Fax: 314-4548250; e-mail: scottgre@hotmail.com Received April 16, 2006; revised February 25, 2007; accepted June 4, 2007. the induction of sustained VT and VF into accepted indications for ICD implantation in patients with non-sustained ventricular tachycardia (NSVT), coronary artery disease (CAD), prior myocardial infarction (MI), and left ventricular (LV) dysfunction. However, in these randomized studies demonstrating mortality benefit, only a small fraction (∼10%) of the total number of subjects had a non-monomorphic ventricular tachyarrhythmia induced by PVS. The relative value of induced polymorphic VT/VF in identifying a population at high risk of SCD among patients without prior spontaneous arrhythmic events remains unknown. The majority of published reports in other patient populations suggest differences in long-term outcome based on the type of induced7–9 or spontaneous (presenting)10–12 ventricular arrhythmia. Specifically, the induction of monomorphic VT (versus VF) portends a worse prognosis, with higher arrhythmic event and cardiac arrest rates during followup. We sought to compare patients with induced  C 2007, The Authors. Journal compilation  C 2007, Blackwell Publishing, Inc. PACE, Vol. 30 September 2007 1067 GREENBERG, ET AL. polymorphic VT and VF to those who have induced monomorphic VT to determine the relative frequency of spontaneous cardiac arrhythmia occurrences in a primary prevention population at high risk of SCD. Methods Patient Population After obtaining approval from our institutional review board, we retrospectively analyzed 105 consecutive patients who underwent both PVS and subsequent ICD implantation for primary prevention of SCD between January 1999 and December 2003 at Barnes-Jewish Hospital (Washington University, St. Louis, MO). During that time, we routinely performed PVS for risk stratification in all patients referred for consideration of ICD implantation for primary prevention of SCD.4,5 A total of 123 potential subjects were identified by searching operative and billing databases and 18 were excluded from further analysis as a result of no (n = 12) or inadequate (n = 6) follow-up at our institution. Patient information was extracted from records maintained by the electrophysiology department. All patients had prior MI, a cardiomyopathy of ischemic origin, and NSVT unrelated to an acute coronary syndrome. Ejection fraction (EF) was objectively measured by 2-D echocardiogram, nuclear imaging, or ventriculography at the time of cardiac catheterization. PVS was performed and either sustained VT or VF was induced in each patient prior to ICD implant. Patients were excluded from this study if they had a history of documented (1) resuscitated cardiac arrest; (2) sustained spontaneous VT (regardless of hemodynamic stability); (3) wide complex tachycardia presumed to be ventricular in origin; (4) syncope or near-syncope (of any etiology); (5) terminal medical illness precluding ICD implantation; or (6) inadequate follow-up at our institution. Patients were divided into two groups based on the results of baseline PVS. Group I patients had induction of a monomorphic VT. Group II patients had induction of polymorphic VT, ventricular flutter, and VF (defined below). PVS The precise PVS protocol was at the discretion of the individual electrophysiologist performing the procedure and was not prespecified. Universally, however, PVS was executed in the postabsorbtive state and with a benzodiazepine for sedation. In general, PVS was accomplished at twice diastolic threshold utilizing two drive cycle lengths (usually 600 and 400 milliseconds) and up to three extrastimuli (>99% of patients) at both the right ventricular (RV) apex and outflow tract (if re- 1068 quired). In all but five patients, the coupling interval of the final extrastimulus utilized for induction of the qualifying arrhythmia was ≥200 milliseconds. RV burst pacing (with rates determined by the individual electrophysiologist) was employed in those patients not inducible with ventricular extrastimuli as described. The endpoint of PVS was successful induction of VF or sustained VT as defined below (achieved in all patients).The induced rhythm terminated with overdrive pacing, electrical cardioversion/defibrillation, or spontaneously (after 30 seconds). Reproducible induction of the rhythm was not required. ICD Implantation ICD implantation was generally performed immediately following PVS. All patients received a Food & Drug Administration (FDA) approved multiprogrammable, tiered-therapy pulse generator capable of intracardiac electrogram storage from one of two manufacturers. All leads were implanted by a nonthoracotomy (transvenous) approach with the generator in the subpectoral region. The specific pulse generator and lead(s) utilized were at the discretion of the implanting physician as was the decision to use a single or dual chamber system. Defibrillation threshold testing was performed in each patient to ensure an adequate defibrillation safety margin. Initial programming of ICD therapy (e.g. number of tiers) was at the discretion of the implanting physician. Follow-Up All follow-up was performed at Washington University (Barnes-Jewish Hospital) at intervals of 3 to 6 months. Distinction of appropriate vs. inappropriate therapy, and further classification of all stored ICD therapies, was made by two physicians, the treating electrophysiologist (JC, MF, MG, BL, or TS) as documented in the medical chart and one of the authors (SG) after independent analysis of all available stored electrograms. The Social Security Death Index, current through July 31, 2004, provided information on vital status and date of death, if applicable. Outcomes Patient outcomes were followed with a primary end point of survival free of appropriate ICD discharge therapy. Secondary end-points included total number of ICD discharge therapies and mortality. Definitions Ischemic Cardiomyopathy (ICM) was defined as angiographic evidence of 75% or greater luminal occlusion of at least one of the major epicardial coronary arteries resulting in left ventricular September 2007 PACE, Vol. 30 SUSTAINED POLYMORPHIC ARRHYTHMIAS systolic dysfunction.13 Classification of the rhythm induced at PVS into one of four types of sustained tachyarrhythmias (monomorphic VT, polymorphic VT, VF, or Ventricular Flutter) was determined by the electrophysiologist (JC, MF, MG, BL, or TS) performing the procedure. However, generally accepted and applied definitions of these induced arrhythmia subtypes can be found in the MADIT and MUSTT design and clinical protocol publications.14,15 Duration of follow-up for the primary endpoint was defined as the time between the implant date and the date of the most recent interrogation. Statistical Analysis Baseline characteristics were compared between groups dichotomized by the type of rhythm induced at PVS. We compared categorical variables using the chi-square test (or Fisher’s exact test for expected counts <5) and the (nonpaired) Student’s t-test for continuous variables. Kaplan-Meier survival curves16 for time to first ICD discharge were compared by the log-rank test. Covariate-adjusted analyses of outcomes were performed using a Cox proportional-hazards model.17 Predictor variables were entered into multivariate Cox proportional hazards model. For all analyses, a P value of <0.05 was considered statistically significant. All tests of significance were two-tailed. Power analysis based on sample size included in the study suggested that there was 90% probability of detecting a ≥20% difference in events between groups [α = 0.05 (two-tailed); β = 0.10]. Analyses were performed using the SPSS for Windows statistical software package, version 10.0.5 (SPSS, Chicago, IL, USA). Results Baseline Characteristics One hundred five patients in whom VT or VF was induced by PVS underwent ICD implantation during a 5-year period and met criteria for study inclusion. Seventy-five of these 105 patients (71.4%) had a monomorphic VT induced at PVS (group I). Group II consisted of 30 patients with induced polymorphic VT (n = 21), VF (n = 7), and ventricular flutter (n = 2). Baseline characteristics with respect to age, sex, race, and past medical history were similar between groups (Table I). Patients in group I had a lower EF (25% vs. 31%; P = 0.0001) and a longer QRS duration (123 vs. 109 milliseconds; P = 0.04). Though patients in group I were more likely to be prescribed digoxin, other medical therapy was similar, including use of betablocker and antiarrhythmic drug (AAD) therapy. Only eight patients were taking an AAD (amio- PACE, Vol. 30 darone, n = 7) within the month preceding ICD implantation (for atrial tachyarrhythmias). PVS Information regarding the method utilized to induce tachycardia was available in 102 of the 105 patients. One hundred patients had their qualifying rhythm induced by the ventricular extrastimulus method (98% of patients with two or three extrastimuli) and two by burst ventricular pacing. The mean cycle length of the induced ventricular tachyarrhythmia was 253 ± 44 milliseconds in group I and 201 ± 27 milliseconds in group II (P = 0.001). Group I patients had mVT induced by 1 (n = 1), 2 (n = 21), 3 (n = 47), or 4 (n = 1) extrastimuli. Group 2 patients had ventricular arrhythmias induced with 2 (n = 11) or 3 (n = 19) extrastimuli. There was no difference between groups in the number of extrastimuli utilized to induce the respective rhythms (P = 0.95). Significantly more patients in Group 2 required cardioversion/defibrillation at the time of PVS for hemodynamic instability of the induced rhythm (83% vs. 51%; P = 0.008). ICD Implantation At the time of ICD implantation, eight patients had a permanent transvenous pacemaker upgraded to an ICD. Almost equivalent numbers of patients received single and dual chamber devices (n = 47 and n = 49 respectively). The remaining nine patients underwent implantation of a left ventricular lead via the coronary sinus as part of cardiac resynchronization therapy (CRT). The initial ICD programming protocol was single tier (shock) in 89% of the patients and two-tiered in 10% [antitachycardia pacing (ATP) shock]. There were no significant differences in these parameters between groups. Appropriate ICD Discharge Therapy Sixteen of 75 (21.3%) patients in Group I and 6 of 30 (20%) patients in Group II had at least one appropriate ICD therapy (P = 0.88) over a mean follow-up of 21.8 ± 13.7 months (Table II). Survival free from ICD discharge therapy was also similar (P = 0.54) between groups (Kaplan-Meier Curve, Fig. 1). Initial therapy for the first arrhythmia occurrence was deemed successful in 88% of patients in Group I and 100% of patients in Group II (P = 0.66). Nineteen of the 22 initial ICD therapies were administered as shocks; all successfully resulted in restoration of sinus rhythm. Of the three patients in group I receiving initial ATP therapy, one was successful, one required additional ATP therapy, and one resulted in acceleration of the rhythm and required subsequent shock therapy. September 2007 1069 GREENBERG, ET AL. Table I. Baseline Characteristics Among Patients Dichotomized by Type of Induced Rhythm Characteristics Age (years) Male Caucasian Current/former smoker Diabetes mellitus PCI CABG Hypertension MI < 6 months Medical Therapy: β-Blocker Calcium channel blocker Antiarrhythmic drug ACE-I/ARB Statin Digoxin Aspirin/warfarin/clopidogrel Ejection fraction (%) QRS duration (msec) QT interval (msec) Programmed ventricular stimulation: Double extrastimuli Triple extrastimuli Induced CL (msec) Shock required for termination Single chamber ICD Initial ICD programming: shock only Group I (mVT) n = 75 (%) Group II n = 30 (%) 67 ± 10 67 (89) 66 (88) 52 (69) 24 (32) 28 (37) 46 (61) 47 (63) 9 (12) 65 ± 9 26 (87) 24 (80) 16 (60) 12 (40) 13 (43) 18 (60) 22 (73) 4 (13) 63 (84) 12 (16) 7 (9) 70 (93) 53 (71) 32 (43) 74 (99) 25 ± 7 123 ± 33 415 ± 44 0.95 21 (28) 47 (63) 253 ± 44 38 (51) 40 (53) 73 (97) 26 (87) 5 (17) 1 (3) 28 (93) 20 (67) 6 (20) 30 (100) 31 ± 7 109 ± 28 416 ± 46 1.0 1.0 .43 1.0 .82 .04 1.0 .0001 .04 .94 11 (37) 19 (63) 201 ± 27 25 (83) 12 (41) 25 (84) .0001 .008 .26 .36 P Value .23 .74 .35 .66 .50 .66 1.0 .51 .93 PCI = percutaneous intervention; CABG = coronary artery bypass grafting; MI = myocardial infarction; ACE-I = angiotensin coverting enzyme inhibitor; ARB = angiotensin receptor blocker; ICD = implantable cardioverter-defibrillator; CL = cycle length. The type of induced rhythm did not predict the subsequent type of first spontaneous ventricular arrhythmia (P = 0.54). However, VT was the first rhythm identified in 75% of group I patients and in 50% of group II patients receiving an appropriate ICD therapy. Overall, patients in the two groups had equivalent mean numbers of spontaneous arrhythmias resulting in ICD therapy (1.4 ± 4.2 vs. 1.1 ± 4.4; P = 0.80). Among those patients receiving at least one appropriate ICD therapy, there was also no difference between groups in mean total number of ICD therapies administered during the follow up period (6.4 ± 7.3 vs. 5.5 ± 9.1; P = 0.82). Inappropriate ICD Discharge Therapy Similar numbers of patients in group I (n = 4) and group II (n = 3) received inappropriate ICD discharge therapy (P = 0.41) for the following reasons: atrial fibrillation with rapid ventricular re- 1070 sponse (n = 3), sinus tachycardia (n = 2), T-wave oversensing (n = 1), and lead fracture (n = 1). Five of these seven (71.4%) patients had a dual chamber device. Two (28.6%) of these patients also had appropriate ICD discharge during the follow-up period. Mortality Fourteen of 75 (18.7%) patients in group I and two of 30 (6.7%) patients in group II expired for any cause during a mean follow-up of 27.8 ± 14.1 months. Figure 2A shows a trend toward increased all-cause mortality among patients in group I by Kaplan-Meier analysis (P = 0.08 by log rank). However, as illustrated in figure 2B, when adjusted for age, EF, and QRS duration, there was no difference in all-cause mortality between groups (P = 0.45). Four of 16 patients (25%) who expired had at least one documented appropriate ICD therapy administered prior to their date of death. These September 2007 PACE, Vol. 30 SUSTAINED POLYMORPHIC ARRHYTHMIAS Table II. Implantable Cardioverter-Defibrillator Discharge Therapy Dichotomized by Type of Induced Rhythm Outcome Appropriate ICD Therapy Initial Spontaneous Rhythm = VT Successful Initial Therapy Mean Number of Therapies* Mean Number of Therapies** Inappropriate Therapy Group I (mVT) Group II (pVT/VF/VFL) P Value 16/75 (21) 12/16 (75) 14/16 (88) 6.4 ± 7.3 1.4 ± 4.2 4/75 (5) 6/30 (20) 3/6 (50) 6/6 (100) 5.5 ± 9.1 1.1 ± 4.4 3/30 (10) .88 .54 .66 .82 .80 .41 ICD = Implantable cardioverter-defibrillator; VT = ventricular tachycardia. *of patients in each group receiving at least one appropriate ICD therapy (n = 22) **of all patients in each group, including those without any therapy (n = 105) four patients were evenly split between group I and group II. Aggressiveness of Stimulation Protocol The minimum number of ventricular extrastimuli required to induce the qualifying tachyarrhythmia was available for all (n = 100) patients known to be induced by this technique. For the population as a whole, the number of extrastimuli required to induce tachyarrhythmia did not predict the subsequent requirement for ICD therapy (P = 0.31) or mortality (P = 0.98). Nineteen of the 30 patients in group II required triple ventricular extrastimuli for arrhythmia induction. In these patients, double extrastimuli failed to induce VT or VF. Five of these 19 patients subsequently received appropriate ICD discharge therapy during follow-up. Figure 1. Kaplan-Meier curves of freedom from appropriate ICD therapy stratified by type of induced ventricular arrhythmia. There is no difference (P = 0.54) between group I (mVT) and group II (pVT/VF/VFL) in event free survival. mVT = monomorphic ventricular tachycardia; pVT = polymorphic ventricular tachycardia; VF/VFL = ventricular fibrillation/flutter. PACE, Vol. 30 September 2007 1071 GREENBERG, ET AL. Figure 2. Kaplan-Meier curves of freedom from all-cause death stratified by type of induced ventricular arrhythmia. Figure 2A shows a trend toward increased all-cause mortality among patients with induced monomorphic VT (P = 0.08). However, as illustrated by the survival curves in figure 2B, when adjusted for age, ejection fraction, and QRS duration, there was no difference in all-cause mortality between groups (P = 0.45). mVT = monomorphic ventricular tachycardia; pVT = polymorphic ventricular tachycardia; VF/VFL = ventricular fibrillation/flutter. 1072 September 2007 PACE, Vol. 30 SUSTAINED POLYMORPHIC ARRHYTHMIAS the induced CL demonstrated a trend toward predicting subsequent spontaneous (clinical) ventricular tachyarrhythmia cycle length (R2 = 0.22; P = 0.058). Figure 3 shows the relationship between the induced and spontaneous CL for each patient. Figure 3. Comparison of the cycle length (CL) of the induced tachycardia to the CL of the tachycardia resulting in the first appropriate ICD therapy. Overall, the mean CL of the induced and spontaneous tachycardias was similar (240 ± 40 vs. 256 ± 47 milliseconds; P = 0.17). Each line represents an individual patient. The induced CL demonstrated a trend toward predicting subsequent spontaneous (clinical) ventricular tachyarrhythmia cycle length (R2 = 0.22; P = 0.058). Induced Tachyarrhythmia Cycle Length and Outcome The cycle length (CL) of the induced tachyarrhythmia was known for 94 of the 105 patients (72 patients in group I and 22 patients in group II). The induced CL was similar between patients who received an appropriate device discharge (n = 19) compared to those that did not (247 ± 44 milliseconds vs. 240 ± 47 milliseconds; P = 0.55). However, patients with an induced CL > 230 milliseconds trended toward increased mortality (P = 0.07) compared to those with an induced CL ≤ 230 milliseconds. When adjusted for age, EF, and QRS duration in a Cox regression model, induced CL > 230 milliseconds was not a predictor of mortality (hazard ratio 0.63; 95% confidence interval 0.15 to 2.64; P = 0.52). Among the 19 patients receiving appropriate ICD therapy in this cohort, the cycle length of the first spontaneous tachyarrhythmia was available in all but two patients. For these 17 patients, PACE, Vol. 30 Discussion The results of this investigation suggest that patients with induced, sustained polymorphic arrhythmias receiving an ICD for primary prevention of SCD suffer spontaneous arrhythmic events at rates similar to their peers with induced monomorphic VT at baseline. This study provides evidence that the induction of VF and polymorphic VT in this patient population are clinically meaningful and support the current guidelines recommending ICD implantation in this population with ischemic cardiomyopathy and NSVT.6 In contrast, previously published studies suggest that induction of polymorphic arrhythmias by PVS in other patient populations is unlikely to be significant. For example, patients who have suffered a recent MI (<1 month) in the absence of prior clinical arrhythmias are more likely to experience a sustained spontaneous arrhythmic event (VT/VF or sudden death) during follow-up if monomorphic VT is inducible at baseline PVS (as compared to both VF and no inducible rhythm).7,8 In these studies, patients with inducible VF had similar long-term outcomes to patients who were noninducible at baseline PVS. Similarly, patients who have experienced a prior clinical arrhythmic event are more likely to have at least one recurrent tachyarrhythmic event as well as more frequent numbers of recurrences if monomorphic VT (compared to VF) is inducible.9 More recently, Meyborg18 assessed the prognostic significance of induced VF in a mixed population of patients at high risk of SCD. In the subgroup of patients (n = 56) who received an ICD for primary prevention of SCD, significantly fewer patients with induced VF, polymorphic VT, and ventricular flutter (compared with monomorphic VT) had subsequent clinical arrhythmias resulting in ICD discharge therapy (17% vs. 50%). In addition, the total number of administered ICD therapies was significantly lower in the former group. This published evidence7–9,18 suggests that in the above patient populations, those with induced monomorphic VT are more likely to suffer a subsequent clinical arrhythmic event when compared to patients with induced VF. The findings in our study differ markedly from these earlier reports. This may be secondary to the specific baseline characteristics required of our patients, including reduced ejection fraction due to CAD and NSVT. September 2007 1073 GREENBERG, ET AL. In addition, we specifically excluded patient populations assessed in these other studies (e.g. recent MI, prior spontaneous arrhythmic events, cardiomyopathy of non-ischemic origin). Also, there are significant differences in baseline medical therapies (e.g. beta-blocker) utilized in our patients and those reported in the earlier publications. The presence of an ICD in our patients may have permitted recognition of arrhythmias not clinically apparent in some of the other studies. Lastly, the stimulation protocol employed in our study appears to be less aggressive than in each of these studies, perhaps resulting in fewer non-specific responses. Protocols for performing PVS are institutional dependent and may even differ among electrophysiologists at a given center. The sensitivity and specificity of PVS vary with the number of extrastimuli as well as the shortest extrastimuli coupling interval employed in a given protocol. Among subjects who were excluded from randomization, but included in the MUSTT registry, the rate of cardiac arrest or death from arrhythmia was similar in those patients with polymorphic VT/VF compared to patients who were non-inducible.19 In our study, however, those patients requiring triple extrastimuli for the induction of polymorphic VT or VF (excluded from randomization in MADIT I and MUSTT)4,5 still had a high rate of spontaneous arrhythmic events resulting in appropriate ICD discharge. The incidence of inappropriate ICD therapy in our patient population is much lower (6.7%) than previously published cohorts.20–22 The reasons for this are unclear; 45% of patients received a single chamber device and only 7.6% of patients were using an antiarrhythmic drug at the time of ICD implant. The low incidence of inappropriate therapy may be related to the initial ICD programming of single tier therapy in the majority of patients. Though the incidence of appropriate ICD discharge was similar between groups, patients with induced monomorphic VT trended toward increased mortality by Kaplan-Meier analysis. After controlling for ejection fraction and QRS duration, there was no mortality difference between groups. Our results demonstrate a trend in the value of the cycle length of the induced tachycardia in predicting the cycle length of the spontaneous rhythm in a primary prevention population. Previously published data on this subject has yielded conflicting results.23–25 The utility, if any, of this parameter in the programming of ATP therapy in not clear given the high success rate of empiric ATP programming.9,26 In a recent ICD coverage decision,27 the Center for Medicare and Medicaid Services (CMS) has eliminated the requirement for physicians to 1074 demonstrate that VT or VF is inducible prior to ICD implantation in several patient groups. This has resulted in a reduction in the utilization of PVS by clinicians. This procedure, however, may still be useful as an additional risk stratification measure in the setting of CAD and a moderately reduced ejection fraction greater than 30%.17,28 Our study population includes these patients, though not exclusively. One limitation of our study was that patients who were noninducible at baseline PVS were not compared to the two groups of inducible patients. Noninducible patients did not receive ICD implantation nor continued follow-up in our electrophysiology clinic. However, previous studies1–3 have consistently documented a worse outcome for patients who have inducible monomorphic VT compared with those who are noninducible at baseline. A recent substudy of the MADIT II patients29 provides further evidence that induced monomorphic VT identifies patients with EF ≤ 30% at higher risk of future VT. However, in that study, the risk of subsequent VF was higher in non-inducible patients and a population at low risk of SCD was not identified by PVS. Another limitation of this study stems from its retrospective nature. PVS was performed by five electrophysiologists whose precise protocol and classification of the induced rhythm may have differed. However, for purposes of this investigation, these differences were likely minimized by combining those subjects with induced VF, polymorphic VT, and ventricular flutter into a single group (group II). Prior studies have demonstrated the ability to induce multiple ventricular tachyarrhythmias in an individual patient. This was not evaluated in the current study as there were no routine attempts made to reinduce the initial qualifying rhythm. Though not all patients received an ICD from the same manufacturer, all devices were FDA approved with the capacity to store intracardiac electrograms. While it is possible that the primary protocol for ICD therapy (single tier) resulted in a reduction in the number of both appropriate and inappropriate ICD therapies administered, there was no difference in programming between groups. The initial use of AAD in this study, known to affect both the recurrence of tachycardia and its cycle length, was low (n = 8) and only 15 additional patients were started on AAD during the entire follow-up period (mostly for ventricular arrhythmias, n = 11). Conclusion Patients with CAD, prior MI, LV dysfunction, and NSVT who have VF or polymorphic VT induced during PVS have similar rates of subsequent clinical ventricular tachyarrhythmias as September 2007 PACE, Vol. 30 SUSTAINED POLYMORPHIC ARRHYTHMIAS those patients with inducible monomorphic VT. These spontaneous ventricular arrhythmias are appropriately treated by ICD therapy. Acknowledgment: This investigation was supported by National Institutes of Health, National Research Service Award 5-T32-HL07081–29, from the National Heart, Lung, and Blood Institute. Financial Disclosures: Scott L. Greenberg, M.D. None; José Mauricio Sánchez, M.D. None; Jonas A. Cooper, M.D. None; Michael E. 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