Long-term Outcomes of Cardiac Resynchronization Therapy by Left Ventricular Ejection Fraction

AIMS: Despite our prior report suggesting heart failure (HF) risk reduction from cardiac resynchronization therapy with defibrillator (CRT-D) in mild HF patients with higher left ventricular ejection fraction (LVEF > 30%), data on mortality benefit in this cohort are lacking. We aimed to assess long-term mortality benefit from CRT-D in mild HF patients by LVEF > 30%. METHODS AND RESULTS: Among 1274 patients with mild HF and left bundle branch block enrolled in MADIT-CRT, we analysed long-term effects of CRT-D vs. implantable cardioverter defibrillator (ICD) therapy only, and reverse remodelling to CRT-D (left ventricular end-systolic volume percent change ≥ median at 1 year), on all-cause mortality and HF for the LVEF ≤ 30% and LVEF > 30 subgroups using Kaplan-Meier and Cox analyses. During long-term follow-up, CRT-D vs. ICD was associated with reduction in all-cause mortality in both patients with LVEF > 30% and LVEF ≤ 30% [hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.25-0.85, P = 0.036 vs. HR 0.69, 95% CI 0.49-0.98, P = 0.013, interaction P = 0.261]. The efficacy of CRT-D vs. ICD only to reduce HF was similar in those with LVEF above and below 30% (HR 0.36, 95% CI 0.35-0.61, P < 0.001 vs. HR 0.46, 95% CI 0.35-0.61, P < 0.001; interaction P = 0.342). Patients with CRT-D-induced reverse remodelling had significant mortality reduction when compared to ICD, with either LVEF > 30% or LVEF ≤ 30% (HR 0.17 and 0.39), but no mortality benefit was seen in patients with less reverse remodelling. HF events, however, were reduced in both CRT-D-induced high and low reverse remodelling vs. ICD only, in both LVEF subgroups. CONCLUSIONS: In MADIT-CRT, left bundle branch block patients with higher LVEF (> 30%) derive long-term mortality benefit from CRT-D when exhibiting significant reverse remodelling. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID NCT00180271, NCT01294449, and NCT02060110.