Buxton, Alfred 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

Catheter ablation has brought major advances in the management of patients with atrial fibrillation (AF). As evidenced by multiple randomized trials, AF catheter ablation can reduce the risk of recurrent AF and improve quality of life. In some studies, AF ablation significantly reduced cardiovascular hospitalizations. Despite the existing data on AF catheter ablation, numerous knowledge gaps remain concerning this intervention. This report is based on a recent virtual workshop convened by the National Heart, Lung, and Blood Institute to identify key research opportunities in AF ablation. We outline knowledge gaps related to emerging technologies, the relationship between cardiac structure and function and the success of AF ablation in patient subgroups in whom clinical benefit from ablation varies, and potential platforms to advance clinical research in this area. This report also considers the potential value and challenges of a sham ablation randomized trial. Prioritized research opportunities are identified and highlighted to empower relevant stakeholders to collaborate in designing and conducting effective, cost-efficient, and transformative research to optimize the use and outcomes of AF ablation.

AbstractBackgroundRecipients of implantable cardioverter defibrillator (ICD) generator replacement with multiple medical comorbidities may be at higher risk of adverse outcomes that attenuate the benefit of ICD replacement. The aim of this investigation was to study the association between the Charlson comorbidity index (CCI) and outcomes after ICD generator replacement.MethodsAll patients undergoing first ICD generator replacement at Mayo Clinic, Rochester and Beth Israel Deaconess Medical Center, Boston between 2001 and 2011 were identified. Outcomes included: (a) all‐cause mortality, (b) appropriate ICD therapy, and (c) death prior to appropriate therapy. Multivariable Cox regression analysis was performed to assess association between CCI and outcomes.ResultsWe identified 1421 patients with mean age of 69.6 ± 12.1 years, 81% male and median (range) CCI of 3 (0‐18). During a mean follow‐up of 3.9 ± 3 years, 52% of patients died, 30.6% experienced an appropriate therapy, and 23.6% died without experiencing an appropriate therapy. In multivariable analysis, higher CCI score was associated with increased all‐cause mortality (Hazard ratio, HR 1.10 [1.06‐1.13] per 1 point increase in CCI, P < .001), death without prior appropriate therapy (HR 1.11 [1.07‐1.15], P < .0001), but not associated with appropriate therapy (HR 1.01 [0.97‐1.05], P = .53). Patients with CCI ≥5 had an annual risk of death of 12.2% compared to 8.7% annual rate of appropriate therapy.ConclusionsCCI is predictive of mortality following ICD generator replacement. The benefit of ICD replacement in patients with CCI score ≥5 should be investigated in prospective studies.

Background— The effectiveness of implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden death in patients with an ejection fraction (EF) ≤35% and clinical heart failure is well established. However, outcomes after replacement of the ICD generator in patients with recovery of EF to >35% and no previous therapies are not well characterized. Methods and Results— Between 2001 and 2011, generator replacement was performed at 2 tertiary medical centers in 253 patients (mean age, 68.3±12.7 years; 82% men) who had previously undergone ICD placement for primary prevention but subsequently never received appropriate ICD therapy. EF had recovered to >35% in 72 of 253 (28%) patients at generator replacement. During median (quartiles) follow-up of 3.3 (1.8–5.3) years after generator replacement, 68 of 253 (27%) experienced appropriate ICD therapy. Patients with EF ≤35% were more likely to experience ICD therapy compared with those with EF >35% (12% versus 5% per year; hazard ratio, 3.57; P =0.001). On multivariable analysis, low EF predicted appropriate ICD therapy after generator replacement (hazard ratio, 1.96 [1.35–2.87] per 10% decrement; P =0.001). Death occurred in 25% of patients 5 years after generator replacement. Mortality was similar in patients with EF ≤35% and >35% (7% versus 5% per year; hazard ratio, 1.10; P =0.68). Atrial fibrillation (3.24 [1.63–6.43]; P <0.001) and higher blood urea nitrogen (1.28 [1.14–1.45] per increase of 10 mg/dL; P <0.001) were associated with mortality. Conclusions— Although approximately one fourth of patients with a primary prevention ICD and no previous therapy have EF >35% at the time of generator replacement, these patients continue to be at significant risk for appropriate ICD therapy (5% per year). These data may inform decisions on ICD replacement.

Background The decision to initially implant an implantable cardioverter-defibrillator (ICD) is informed by robust randomized controlled trials, but no such data exist to guide the decision to replace an ICD generator. In this study, we aimed to determine outcomes after ICD generator replacement. Methods All patients with ischemic or nonischemic cardiomyopathy who underwent ICD generator replacement from 2001 to 2011 at Mayo Clinic, MN, or Beth Israel Deaconess Medical Center, MA, were included. Outcomes included (1) appropriate therapy after generator replacement and (2) death before appropriate therapy after generator replacement. Cox proportional hazards modeling was used to determine the associations between patient characteristics and outcomes. Results In 1421 patients undergoing ICD generator replacement (mean±SD age 69.6±12.1 years, 81% male), appropriate therapy occurred after replacement in 435 patients (30.6%) over a mean follow-up of 2.7±2.6 years. Associated factors included lower left ventricular ejection fraction and history of appropriate therapy before generator replacement. Death before appropriate ICD therapy occurred in 336 (23.7%) patients. Older age, lower left ventricular ejection fraction, and noncardiac comorbidities, including diabetes mellitus, chronic lung disease, peripheral vascular disease, lower hemoglobin, and lower glomerular filtration rate, were associated with greater risk of death before appropriate therapy. A progressive increase in mortality was observed with aggregation of these noncardiac comorbidities. Conclusions The decision to replace the ICD should take into consideration not only left ventricular ejection fraction and history of ventricular arrhythmias, but also comorbid illnesses that may impact the duration and the quality of life.

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.