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TREATMENT OF SUDDEN CARDIAC DEATH SURVIVORS: Patients who survive an episode of sustained defined as 100% suppression of VT runs> IS beats, ventricular trachycardia (VT) or out-of-hospital 80% suppression of pairs, and 70% suppression of ventricular fibrillation (VF) are known to have a high PVCs. Electrophysiologic study efficacy was defined recurrence rate of 10% to 20% at 2 years.' Until the as suppression of the VT inducibility (no VT induced early 1990s, the preferred therapy for this high-risk > IS beats in duration). The primary endpoint was population remained unclear. A variety of therapies recurrence of arrhythmia in a patient receiving a drug have been proposed, including serial drug testing predicted to be effective by serial testing. Secondary guided by Holter monitor or eletrophysiologic study, endpoints included death trom any cause, death trom empiric amiodarone, direct surgical ablation, cardiac cause, and death from arrhythmia. Of 242 electrophysiology-guided amiodarone therapy, and electrophysiologic study limb patients, 108 (45%) implantable cardioverter defibrillator (lCD).2-7 achieved efficacy, whereas 187 (77%) of 244 Holter Despite its proven efficacy in preventing recurrent monitoring patients achieved efficacy. There was no sudden cardiac death (SCD), the ICD was not statistical difference (P = 0.69) between the two subjected to a prospective randomi.zed trial against techniques in predicting arrhythmia recurrence (58% other effective therapies until recently. Many recurrence rate at 2 years).9 Compared with other electrophysiologists thought that such a trial would drugs tested, sotalol had a statistically lower be unethical because it would withhold obviously recurrence rate of arrhythmia (P < 0.001), death trom effective therapy from high-risk patients. But the any cause (P < 0.004), death trom cardiac cause (P < continued miniaturization and case of implantation of 0.02), and death trom arrhythmia (P = 0.04).10 the lCD, coupled with its high price and the widening The main finding of ESVEM was that Holter infl~ence of managed case which resisted this costly monitoring was equally predictive of arrhythmia therapy, made such trials inevitable. It became clear recurrence, when compared with serial in the early 1990s that detailed definition of the electrophysiologic testing. In the author's perspective, efficacy and relative cost of the ICD was necessary the high 2-year arrhythmia recurrence rates utilizing to justify both its expanding implantation and its both techniques, suggest that serial testing, using cost. Very recently, a few important clinical trials either method has limited value in this patient have provided information about the management of population. The higher efficacy of sotalol may be patients who survived an episodes of SCD. The debate as to whether anti-arrhythmic therapy combination of its beta-blocker and Class III was best guided by Holter monitoring or invasive antiarrhythmic effects. Recent data from ESVEM II electrophysiologic study (EPS) led to the demonstrated that arrhythmia recurrence of Class I Electrophysiologic Study Versus patients plus a beta-blocker was similar to sotalol, Electrocardiographic Monitoring (ESVEM) trial. 8.9 and both were better that Class I agents without a In this trial, 486 patients who had been resuscitated betablocker. Although sotalol appeared more trom sudden cardiac death or effective than the other drugs in this study, the lack of electrocardiographically documented VT or a placebo group limits this interpretation. The results unmonitored syncope, were randomized Holter- ofESVEM are limited by the fact that patients were versus EPS-guided treatment, with imipramin, required to have both frequent PVCs and inducible mexiletine, procainamide, quinidine, sotalol, VT. Previous studies have shown that these findings pirmenol or propafenone. In the Holter limb, drug are relevant to < 35% of the sustained VTNF population. efficacy was Journal of the Saudi Heart Association, Vol. II, No.1, 1999 The Cardiac Arrest Study in Seattle: Conventional amiodarone, metoprolol, and ICD limbs. Enrollment versus Amiodarone Drug Evaluation (CASCADE)13 in this trial has recently been completed (n = 349), evaluated antiarrhythmia drug treatment of 228 and findings suggest that the final results are survivors of out-of-hospital VF not associated with a consistent with the interim analyses, except that total Q wave MI. Patients qualified if they had ~ 10 PVCs/ mortality was statistically lower (P = 0.047) in the h on Holter, and had inducible sustained VT or VF. ICD group, compared with the combined metoprolol Patients were randomized to empiric treatment with plus amiodarone-treated groups. The results of CASH amiodarone (n = 113) or electrophysiologic study- suggest that Class I therapy is not as effective as ICD guided treatment (n = 115), using conventional therapy in survivors of cardiac arrest. ICD therapy antiarrhythmic therapy (Class I antiarrhythmics). The appears to have a better sudden death and overall primary endpoint was cardiac survival. The mean EF survival compared with the antiarrhythmic drug-of randomized patients was 35%::!:: 10%. Of note, treated limbs of the study. The potential benefit of a 46% of patients received ICDs. Patients treated with beta-blocker in this study is consistent with beneficial amiodarone had better "cardiac survival" (defined as effects noted in other retrospective studies.ls.16 cardiac mortality, syncope/ICS shock, resuscitated The primary objective of the Antiarrhythmics cardiac arrest) than the conventional treated group) (P versus Implantable Defibrillator (AVID) Tria(l7.ls = 0.007). In addition, the amiodarone patients had was to determine whether "best" antiarrhythmic greater survival free of sustained arrhythmias (P = therapy (empiric amiodarone or guided sotalol) or 0.00 \). There were no significant differences in ICD therapy is superior in reducing total mortality in outcomes between conventionally treated patients patients with a history of sustained VT/VF. Secondary whose inducible arrhythmias were or were not objectives included quality-of-life assessment and suppressed. Amiodarone was associated with a \ 0% costeffectiveness of the two study sections. Of the 1,0 3-year pulmonary toxicity rate. Although amiodarone \6 patients (22.2% of the registered group) who were appeared superior to guided therapy with randomized (50% to CD and 50% to antiarrhythmic conventional agents, only 4\ % of the amiodarone section), only 2.8% of the drug section was groups had no cardiac death or sustained arrhythmia discharged on sotalol; the remaining were treated with by 6-year followup. Therefore, ICD therapy may be a amiodarone. Enrollment was stopped prematurely better alternative to either of the pharmacologic (April 7, \977) because of a significant survival approaches. Given the high recurrence rate in the advantage in the ICD group. In the ICD group, 89.3%, empiric amiodarone group, 81.6%, and 75.4% survived \,2, and 3 years, serial guided therapy, using amiodarone may provide respectively, compared with a more predictive approach when drugs are used 82.3%,74.7%, and 64.1% in the drug group (P < 0.02). Thus, \-, 2-, and 3-year mortality was reduced To compare the efficacy of antiarrhythmia by 39%, 27%, and 3\%, respectively, with the therapy against an ICD in survivors of sudden majority ofICD cardiac death unrelated to MI, the Cardiac Arrest benefits occurring in the first 9 months. The ICD only Study, Hamburg (CASH) tria(l4 was initiated. Total extended survival by 2.8 months, although the premature termination of this trial may cause some primary endpoint, with secondary endpoints of underestimation of the ICD benefit, and have hemodynamically unstable VT and incidence of drug detrimental effects in any cost-benefit analysis. ICD withdrawal. Patients were randomized to empiric benefit was most prominent amiodarone, metoprolol, propafenone, or an ICD in patients with EF < 35%, with no statistical benefit within 3 months of their cardiac arrest. Published data of the ICD noted in patients with EF > 35%. Patient from the first 287 patients have shown that the total characteristics were similar in the two treatment mortality, although lowest in the ICD section, was groups, except that the ICD group had a lower similar (about incidence of prior atrial fibrillation/flutter and Class 14%) in the lCD, amiodarone, and metoprolol III CHF patients, and a higher number of patients sections of the study. When compared with the lCD, discharged on a beta-blocker. However, multivariate the propafenone section was associated with analysis showed that the beneficial effects of ICD significantly higher incidence of total mortality and therapy persisted after adjustment of other cardiac arrest recurrence. For that reason the safety factors.19.2o monitoring board recommended the deletion of the The Canadian Implantable Defibrillator Study propafenone treatment limb, and this study is now (CIDS)21 was randomized, multicenter trial being continued with comparing the efficacy of ICD therapy (n = 328) to Journal of the Saudi Heart Association, Vol. II, No.1, 1999 The Cardiac Arrest Study in Seattle: Conventional amiodarone, metoprolol, and ICD limbs. Enrollment versus Amiodarone Drug Evaluation (CASCADE)13 in this trial has recently been completed (n = 349), evaluated antiarrhythmia drug treatment of 228 and findings suggest that the final results are survivors of out-of-hospital VF not associated with a consistent with the interim analyses, except that total Q wave MI. Patients qualified if they had ~ 10 PVCs/ mortality was statistically lower (P = 0.047) in the h on Holter, and had inducible sustained VT or VE ICD group, compared with the combined metoprolol Patients were randomized to empiric treatment with plus amiodarone-treated groups. The results of CASH amiodarone (n = 113) or electrophysiologic study- suggest that Class I therapy is not as effective as ICD guided treatment (n = 115), using conventional therapy in survivors of cardiac arrest. ICD therapy antiarrhythmic therapy (Class I antiarrhythmics). The appears to have a better sudden death and overall primary endpoint was cardiac survival. The mean EF survival compared with the antiarrhythmic drug-of randomized patients was 35%:1: 10%. Of note, treated limbs of the study. The potential benefit of a 46% of patients received ICDs. Patients treated with beta-blocker in this study is consistent with beneficial amiodarone had better "cardiac survival" (defined as effects noted in other retrospective studies.\5.\6 cardiac mortality, syncope/ICS shock, resuscitated The primary objective of the Antiarrhythmics cardiac arrest) than the conventional treated group) (P versus Implantable Defibrillator (AVID) TrialJ7,'8 = 0.007). In addition, the amiodarone patients had was to determine whether "best" antiarrhythmic greater survival tree of sustained arrhythmias (P = therapy (empiric amiodarone or guided sotalol) or 0.001). There were no significant differences in ICD therapy is superior in reducing total mortality in outcomes between conventionally treated patients patients with a history of sustained VT/VF. Secondary whose inducible arrhythmias were or were not objectives included quality-of-life assessment and suppressed. Amiodarone was associated with a 10% costeffectiveness of the two study sections. Of the 3-year pulmonary toxicity rate. Although amiodarone 1,016 patients (22.2% of the registered group) who appeared superior to guided therapy with were randomized (50% to CD and 50% to conventional agents, only 41 % of the amiodarone antiarrhythmic section), only 2.8% of the drug section groups had no cardiac death or sustained arrhythmia was discharged on sotalol; the remaining were treated by 6-year followup. Therefore, ICD therapy may be a with amiodarone. Enrollment was stopped better alternative to either of the pharmacologic prematurely (April 7, 1977) because of a significant approaches. Given the high recurrence rate in the survival advantage in the ICD empiric amiodarone group, serial guided therapy, group. In the ICD group, 89.3%, 81.6%, and 75.4% using amiodarone may provide survived 1,2, and 3 years, respectively, compared with a more predictive approach when drugs are used 82.3%,74.7%, and 64.1% in the drug group (P < without ICDs. 0.02). Thus, 1-, 2-, and 3-year mortality was reduced To compare the efficacy of anti arrhythmia by 39%, 27%, and 31 %, respectively, with the therapy against an ICD in survivors of sudden cardiac majority of ICD benefits occurring in the first 9 death unrelated to MI, the Cardiac Arrest Study, months. The ICD only extended survival by 2.8 Hamburg (CASH) triap4 was initiated. Total months, although the premature termination of this mortality was the trial may cause some underestimation of the ICD primary endpoint, with secondary endpoints of benefit, and have detrimental effects in any cost-hemodynamically unstable VT and incidence of drug benefit analysis. ICD benefit was most prominent withdrawal. Patients were randomized to empiric in patients with EF < 35%, with no statistical benefit amiodarone, metoprolol, propafenone, or an ICD of the ICD noted in patients with EF > 35%. Patient within 3 months of their cardiac arrest. Published data characteristics were similar in the two treatment from the first 287 patients have shown that the total groups, except that the ICD group had a lower mortality, although lowest in the ICD section, was incidence of prior atrial fibrillation/flutter and Class similar (about III CHF patients, and a higher number of patients 14%) in the lCD, amiodarone, and metoprolol discharged on a beta-blocker. However, multivariate sections of the study. When compared with the lCD, analysis showed that the beneficial effects of ICD the propafenone section was associated with therapy persisted after adjustment of other significantly higher incidence of total mortality and factors.'9,2o cardiac arrest recurrence. For that reason the safety The Canadian Implantable Defibrillator Study monitoring board recommended the deletion of the (CIDS)2\ propafenone treatment limb, and this study is now comparing the efficacy of ICD therapy (n = 328) to being continued with Journal of the Saudi Heart Association, Vol. II, No.1, 1999 (n = 331) in 659 patients with prior cardiac of electrophysiological testing with Holter monitoring to predict arrest or hemodynamically unstable VT. The antiarrhythmic-drug efficacy for ventricular tachyarrhythmias. N Eng J enrollment criteria included documented VF, out-of- 5. Winkle RA, Mead RH, Rudes MA, Gaudiani VA, et al. Longterm hospital cardiac arrest requiring defibrillation, outcome with the automatic implantable cardioverter documented sustained VT ~ 150 beats/min causing defibrillator. JAm CardioI1989;13:1353-61. presyncope or angina in a patient with an EF::;:; 6. Kelly PA, Can nom DS, Garan H, et al. The automati, implantable 35%, or syncope with documented spontaneous VT ~ cardioverter defibrillator: efficacy, complication! and survival in patients with malignant ventriculal arrhythmias. J Am Coli 10 seconds or induced sustained VT. The primary endpoint was to compare these two therapies in 7. Powell AC, Fuchs TE, Finkelstein DM, et al. Influence 01 reducing arrhythmic death. Secondary endpoints implantable cardioverter defibrillators on the long-term prognosis of included quality-of-life assessment and cost efficacy survivors of out-of-hospital cardiac arrest. Circulation 1993;88: I 083- analyses, all-cause mortality, nonfatal recurrence of 8. The ESVEM Investigators. The ESVEM trial: electrophysiologic study VF, sustained VT causing syncope, or cardiac arrest versus electrocardiographic monitoring for selection of antiarrhythmic requiring external cardioversion or defibrillation. therapy of ventricular tachyarrhythmias. Circulation 1989;79: 1354-60. Preliminary results suggest that the ICD trended 9. Mason JW, for the ESVEM investigators. A comparison of toward overall improvement in survival (P = 0.07), electrophysiologic testing with Holter monitoring to predict producing a 20% reduction in mortality compared antiarrhythmic efficacy for ventricular tachyarrhythmia. N Engl J Med with amiodarone. Many of the ICD patients took 10. Mason JW, for the ESVEM investigators. A comparison of seven beta-blockers, sotalol, and had amiodarone added. antiarrhythmic drugs in patients with ventricular tachyarrhythmias. N The results of CASH, AVID and CIDS support using the ICD as first-line therapy to prolong total II. Reiffel JA, Hahn E, Hartz V, et ai, for the ES VEM investigators. Sotalol and! or sudden death survival in patients at high-risk for ventricular tachyarrhythmias: Beta-blocking and Class III contributions, and relative efficacy versus Class I drugs after prior drug for sudden death. Future cost efficacy and quality-of- life analysis will help clinicians in prescribing the 12. Skale BT, Mils WM, Heger JJ, et al. Survivors of cardiac arrest: most effective therapy. The results from these studies prevention of recurrence by drug therapy as predicted by have helped clarify the ICD versus antiarrhythmic electrophysiologic testing or electrocardiographic monitoring. Am J drug controversy.22.23 Whether amiodarone would 13. The CASCADE investigators. Randomized antiarrhythmic drug therapy have compared better with the ICD if serial in survivors of cardiac arrest (the CASCADE study). Am J electrophysiologic testing and other predictors of outcome 24 had been used, is not known at this time. 14. Siebels J, Cappato R, Ruppel R, et ai, and the CASH investigators. Preliminary results ofthe Cardiac Arrest Study, Hamburg (CASH). Am J 15. Hallstrom AP, Cobb LA, Yu BH, et al. An antiarrhythmic drug Division of Electrophysiology and Pacing experience in 941 patients resuscitated from an initial cardiac arrest between 1970 and 1985. Am J Cardiol 1991 ;68: 1025-31. 16. Steinbeck G, Andresen D, Bach P, et al. A comparison of electrophysiologically guided antiarrhythmic drug therapy with beta-blocker therapy in patients with symptomatic, sustained ventricular tachycardia. N Engl J Med 17. The AVID investigators. Antiarrhythmics versus Implantable Defibrillators (AVID): rationale, design and methods. Am J I. Mitchell LB. Clinical trials of antiarrhythmic drugs in 18. The Antiarrhythmics versus Implantable Defibrillators (AVID) patients with sustained ventricular tachyarrhythmias.Curr investigators. A comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from near fatal 2. Wilber DJ, Garan H, Finkelstein D, et al. Out-of-hospital xentricular arrhythmias. N Engl J Med 1997;337: 1576-83. cardiac arrest: use of electrophysiologic testing in the 19. Curtis AB, Hollstrom AF, Klein RC, et al. Influence of patient prediction of long-term outcome. N Engl J Med 1988;318: 19- characteristics in the selection of patients for defibrillator implantation (the AVID registry). Am J Cardiol 1997;79: 1885-9. 3. Horowitz LN, Josephson ME, Farshidi A, et al. Role of the electrophysiologic study in selection of anfifirrhythmic agents. 4. Mason JW, for the electrophysiologic study versus electrocardIOgraphic monitoring investigators. A comparison Journal of the Saudi Heart Association, Vol. II, No.1, 1999 20. Kim SG, Hallstom A, Love JC, et ai, for the AVID 22. Zipes DP. Are the implantable cardioverter defibrillators better investigators. Comparison of clinical characteristics and than conventional antiarrhythmic drugs for survivors of frequency of implantable defibrillator use between cardiac arrest? Circulation 1995;9:2115-7. randomized patients in the Antiarrhythmics versus 23. Connolly SJ. An AVID dissent: commentary. PACE Implantable Detibrillators (AVID) trial and nonrandomized registry patients. Am J Cardiol 1997;80:454-7. 24. Naccarelli GV, Fineberg NS, Zipes DP, et al. Amiodarone: risk 21. Connolly S, Gent M, Roberts R, et al. Canadian Implantable factors for recurrence of symptomatic ventricular tachycardia Defibrillator Study (CIDS): study design and organization. identified at electrophysiologic study. J Am Coli Cardiol Journal of the Saudi Heart Association, Vol. 11, No.1, 1999

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