BACKGROUND: Cardiac resynchronization therapy (CRT) improves cardiac function in patients with heart failure (HF) and dyssynchrony. However, a subset of responders develops a delayed decline in left ventricular (LV) systolic function, referred to as "delayed negative reverse remodeling (DNRR)." OBJECTIVE: This study aimed to investigate the characteristics and prognosis of DNRR in CRT responders. METHODS: A total of 203 patients undergoing CRT device implantation were analyzed. Among them, 100 responders were identified on the basis of a ≥5% absolute LV ejection fraction (LVEF) increase and a ≥15% relative LV end-systolic volume reduction at 6 months post-CRT. DNRR was defined as a ≥5% absolute decrease in LVEF at 1 year after treatment response determination. RESULTS: Of the responders, 22 (22.0%) exhibited DNRR, while 78 (78.0%) were classified as non-DNRR. The DNRR group showed a decline in LVEF from 41.2%±8.3% to 32.7%±9.6% (P<
.001), while the non-DNRR group showed improvement from 42.8%±9.5% to 46.2%±10.5% (P<
.001). Multivariate analysis identified LV end-systolic volume ≥ 100 mL (odds ratio [OR] 3.575
P=.041), paced QRS duration ≥ 150 ms (OR 4.427
P=.023), synchronized LV pacing <
85% (OR 5.753
P=.043) at 6 months post-CRT, and intraventricular conduction disturbance (OR 5.593
P=.018) as independent predictors of DNRR. The DNRR group had significantly worse outcomes, including cardiac death and HF-related hospitalization, than did the non-DNRR group. CONCLUSION: Despite an initial response to CRT, a subset of patients with HF developed DNRR, which correlated with worse clinical outcomes. Identifying risk factors associated with DNRR may help optimize CRT management and improve long-term patient care.