Differing effects of cardiac resynchronization therapy on long-term mortality in patient subgroups of MADIT-CRT defined by baseline conduction and 1-year post-treatment left ventricular remodeling

Background: Long-term mortality data after cardiac resynchronization therapy with implanted defibrillator (CRT-D) in minimally symptomatic patients are limited. Objective: To clarify influences on long-term mortality after CRT-D, we assessed MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy) patient outcomes by baseline conduction abnormality and 1-year posttreatment remodeling. Methods: MADIT-CRT followed 1820 patients assigned to CRT-D or implanted cardioverter-defibrillator (ICD) only. Using Cox proportional hazards regression analysis, treatment effects (CRT-D vs ICD only) on mortality were evaluated in patients with left bundle branch block (LBBB) and non-LBBB. Among 1196 patients with echocardiography repeated at 1 year, effect of CRT-D on later mortality (landmark analysis) was analyzed by baseline conduction and 1-year change in left ventricular end-systolic volume (LVESV). Results: Overall mortality was not reduced by CRT-D (hazard ratio [HR] for CRT-D/ICD only 0.94; P =.72). Among 761 patients with LBBB and CRT-D, mortality trended lower (HR 0.71; P =.10) after adjustment for clinical covariates. The effect of CRT-D on mortality was further evaluated in patients who did (responders) and did not (hypo-responders) have reduction in LVESV by≥30%. LBBB responders (n = 323) had significantly reduced mortality with CRT-D (HR 0.36; P =.027), and LBBB hypo-responders (n = 182) did not (HR 0.99). By contrast, non-LBBB responders (n = 89) trended toward more deaths with CRT-D (HR 2.11; P =.22). Non-LBBB hypo-responders (n = 118) had significantly worsened mortality (HR 3.72; P =.011). Conclusions: In MADIT-CRT, late mortality with CRT-D varied markedly with baseline conduction defect and remodeling response. Patients with both LBBB and substantially reduced LVESV had improved mortality. Those with non-LBBB or with LBBB and less-reduced LVESV had unchanged or worsened mortality after CRT-D.