Association between implanted cardioverter-defibrillator and mortality for patients with left ventricular ejection fraction near 35%

Abstract

Abstract Background Consensus guidelines support the use of implanted cardioverter-defibrillators (ICD) for primary prevention of sudden cardiac death in patients with either non-ischemic or ischemic cardiomyopathy with left ventricular ejection fraction ≤ 35%. Despite that class 1 recommendation, evidence from trials for efficacy specifically for patients with left ventricular ejection fraction (LVEF) near 35% is weak. Past trials are underpowered for this population and future trials are unlikely to be performed. As such, we aimed to use a large longitudinal echocardiography database linked to mortality to assess the comparative effectiveness of ICD therapy near the conventional primary prevention LVEF threshold. Methods Patients with lowest LVEF between 33-38% without an ICD prior to the lowest-LVEF echo (defined as "time zero") were identified by querying echocardiography data from November 28, 2001 until July 9, 2020 at large general hospital-based echocardiography registry linked to ICD treatment status. These data were then linked to mortality and comorbidity data. After inclusion and exclusion criteria were applied, 6,144 patients remained for the analytic cohort. Given evidence of covariate imbalance around the LVEF = 35% threshold, fuzzy regression discontinuity methods were considered but not used. Instead, to assess the association between ICD and mortality, multiple propensity score methods including matching and inverse probability of treatment weighting (IPTW) were used to create synthetic reference groups. Survival was then assessed with Cox proportional hazards models considering treatment status as a time-dependent covariate. Results In bivariate unadjusted comparisons, patients who received ICDs were substantially more often male (85.6% vs. 64.9%, p < 0.0001), more often white (87.3% vs. 82.9%, p < 0.048), and more often had a history of ventricular tachycardia (41.1% vs. 12.1%, p < 0.0001) and myocardial infarction (42.1% vs. 34.7%, p = 0.008). In the propensity matched sample, after accounting for time-dependence, there was no association between ICD and mortality (HR 1.09, 95% CI 0.86-1.39, p = 0.474). In the IPTW analysis, there also was no association between ICD and mortality (HR 1.09, 95% CI 0.91-1.30, p = 0.3672). Conclusions ICD therapy was not associated with reduced mortality near the conventional LVEF threshold of 35%. Although this treatment design cannot definitively demonstrate lack of efficacy, our results are concordant with available prior trial data. A definitive, well-powered trial is needed to answer the common and important clinical question of primary prevention ICD efficacy near the threshold of LVEF = 35%.