Clinical Implications of Complete Left-Sided Reverse Remodeling With Cardiac Resynchronization Therapy: A MADIT-CRT Substudy

Background: Clinical implications of complete left-sided reverse remodeling due to cardiac resynchronization therapy with a defibrillator (CRT-D), defined as reduction in both left ventricular end-systolic volume (LVESV) and left atrial volume (LAV), are unknown.

Objectives: This study aimed to evaluate the rate and predictive value of complete left-sided reverse remodeling on heart failure (HF) and death events in CRT-D patients with left bundle branch block (LBBB) enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy).

Methods: The study population comprised 533 CRT-D patients with LBBB, 212 (40%) with complete left-sided reverse remodeling (above-median change in both LAV and LVESV), 115 (22%) with discordant reverse remodeling (above-median change in only LAV or LVESV), and 206 (38%) with lesser reverse remodeling (below-median LAV and LVESV change). The primary endpoint was HF or death; secondary endpoints included HF alone and death alone during long-term follow-up.

Results: Patients with complete left-sided reverse remodeling had a significantly lower rate of HF or death than those with discordant reverse remodeling or lesser reverse remodeling (p < 0.001). Multivariate Cox proportional hazard models consistently showed a decreased risk for HF and death in patients with complete reverse remodeling compared with discordant reverse remodeling or lesser reverse remodeling (hazard ratio: 0.66 per each group; 95% CI: 0.50 to 0.85; p = 0.002). This finding was similar for HF alone and death alone.

Conclusions: In MADIT-CRT, >20% of CRT-D patients exhibited discordant reverse remodeling in the left ventricle and the left atrium. CRT-D patients with LBBB and complete left-sided reverse remodeling had a significantly lower risk of HF and death, HF alone, and death alone during long-term follow-up than patients with discordant or lesser reverse remodeling. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271).