Dissociation between structural reverse remodeling and clinical outcomes in ischemic cardiomyopathy undergoing cardiac resynchronization therapy: a real-world analysis

Patients with non-ischemic cardiomyopathy (NICM) generally exhibit better responses to cardiac resynchronization therapy (CRT) due to more pronounced reverse remodeling compared to ischemic cardiomyopathy (ICM) patients. However, the prognostic impact of CRT in ICM patients remains uncertain. This study aimed to evaluate the impact of heart failure (HF) etiology on reverse remodeling, clinical outcomes, and survival following CRT in a real-world population. We conducted a retrospective observational study including patients who underwent CRT-P (pacing)/CRT-D (defibrillator) implantation. Patients were stratified according to HF etiology (ICM vs. NICM). The primary composite endpoint was the occurrence of all-cause mortality and HF hospitalization. Secondary outcomes focused on echocardiographic measures of left ventricular reverse remodeling. Survival analysis was performed using Kaplan-Meier curves and Cox regression models. Of the 95 patients initially screened, 83 were included in the final analysis, of whom 38 (45.8%) had ICM. The mean age was 69.5±10.4 years, and 75.8% were male. Both groups received similar medical therapy. NICM patients demonstrated a significant improvement in reverse remodeling after CRT [left ventricular ejection fraction (LVEF): 32.3±11.5% to 44.0±13.2%, p=0.001); end-diastolic volume (LVEDV): 189.6±74.3 mL to 143.9±48.9 mL, p=0.010] with post-CRT LVEF being higher than in ICM patients (44.0±13.2% vs. 35.5±13.5%, p=0.003). NICM patients were more likely to be super-responders (58.1% vs. 25.0%, p=0.014). No significant differences were observed between groups in the primary composite endpoint (27.3% vs. 42.1%, p=0.171) or overall survival over a mean follow-up of 35 months (log-rank p=0.733). Although ICM patients showed less pronounced reverse remodeling following CRT, long-term clinical outcomes and survival were comparable to those observed in NICM. These findings reinforce the role of CRT as a disease-modifying therapy that prevents disease progression irrespective of HF etiology and support its systematic use in all eligible patients.