Hafley, Gail E.

Background. ICD implantation for primary prevention of sudden death in patients with ischemic cardiomyopathy and left ventricular dysfunction is well established. However debate exists between the relationship between ischemia and the proarrhythmic state. Persistent ischemia may counter antiarrhythmic (AA) drug and/or device efficacy. Furthermore, the extent to which revascularization mitigates this influence of ischemia on efficacy is unknown. Methods . 704 patients enrolled in the MUSTT trial were studied. Ischemia was determined by the presence of angina within 6 weeks of enrollment and ≥ 2 reversible thallium defects. Revascularization was characterized as CABG or PTCA within 1 year of enrollment or the use of thrombolytics with the sentinal myocardial infarction (MI). We compared groups who were randomized to background medical treatment (BG Rx) verses those who were randomized to AA drug therapy in addition to EP testing (EP AARx). Results . 507 (81%) patients had ≤2 vessel CAD, whereas the remaining 19% had 3 vessel disease. 268 patients reported angina within 6 weeks of study enrollment. Thallium imaging revealed 0–1 defects in 458 (65%) and ≥2 in another 246 (35%). Those with ≥ 2 defects on Thallium and angina within 6 weeks of device implant had a significantly lower 5-year freedom from mortality in the EP AARx and BG Rx cohorts (Table ). Patients with EP AARx had an 8% lower mortality than those with BG Rx therapy alone if they received thrombolytics. However, if they did not receive thrombolytics, their mortality rate was 5% higher than the BG Rx group. Conclusion . Outcomes are worse in patients on antiarrhythmic therapy with ischemic factors compared to those on background therapy alone, particularly in the setting of recent angina. A proarrhythmic effect from antiarrhythmic drug therapy in patients with ischemia may underlie the higher mortality. ICD therapy mitigates the negative long-term effect of ischemia on mortality in those treated with AA therapy. Five Year Freedom from Mortality

Background — The Multicenter Unsustained Tachycardia Trial (MUSTT) was designed to evaluate an antiarrhythmic treatment strategy, including drugs and implantable defibrillators (ICDs), guided by electrophysiological (EP) testing. We performed several statistical analyses to assess the contribution of defibrillators to the observed treatment benefit. Methods and Results — First, the effects of defibrillators were indirectly examined by comparing the randomized treatment arms (EP-guided therapy versus no antiarrhythmic therapy) within subgroups that varied according to ICD usage. Use of ICDs increased during the trial; hence, the randomized treatments were compared according to date of enrollment. There were also site-specific differences in ICD use; hence, the randomized arms were compared within groups of sites defined by level of ICD use. There was a distinct “dose response” in relation to ICD use. Where ICD use was high, EP-guided therapy produced significant reductions in arrhythmic death or cardiac arrest ( P <0.004). Where ICD use was low, there was no benefit of EP-guided therapy. Finally, outcomes of EP-guided therapy patients who received an ICD were directly compared with outcomes of other patients using the Cox proportional hazards model with receipt of an ICD as a time-dependent covariate. Adjusted for other prognostic factors, patients who received an ICD had risk reductions of >70% in arrhythmic death or cardiac arrest and >50% in total mortality ( P <0.001 for both end points). Conclusions — The benefit of EP-guided antiarrhythmic therapy observed in MUSTT was due to improved outcomes among patients who received an ICD but not among patients who received antiarrhythmic drugs.