Association of Angiotensin Receptor Neprilysin Inhibitors Duration with Latent Remodeling Following Implantable Cardioverter Defibrillator Implantation.

BACKGROUND: The optimal duration of angiotensin receptor neprilysin inhibitors (ARNI) exposure prior to implantable cardioverter defibrillator (ICD) implantation remains undefined. In nonischemic dilated cardiomyopathy (NIDCM), reverse remodeling may continue beyond device implantation. However, predictors of post-implant latent left ventricular reverse remodeling (LVRR) remain unclear. OBJECTIVE: This study investigated the association between duration of pre-ICD ARNI therapy and latent LVRR in patients with NIDCM. METHODS: Seventy-five NIDCM patients (69.3% male, mean age 61 years) with LVEF of ≤35% and prior ARNI treatment before primary prevention ICD implantation were retrospectively analyzed. Latent LVRR was defined as an absolute ≥ 10% increase in LVEF with a final LVEF ≥40% at 1-year post-implant. Multivariable logistic regression identified the predictors of latent LVRR. RESULTS: At 1 year, 22 patients (29.3%) exhibited latent LVRR. Shorter duration from heart failure diagnosis (4.8 vs. 30.1 months, OR 0.88, P=0.007), and ARNI initiation (2.3 vs. 7.2 months, OR 0.90, P=0.029) to ICD implant were independently associated with latent LVRR. Cardiac magnetic resonance imaging analysis showed uniformly elevated fibrosis markers across groups, with no difference observed in native T1, T2, extracellular volume, or late gadolinium enhancement (LGE). Conventional variables including age, sex, QRS duration, heart rate, and LGE burden were not predictive. Over a median follow-up of 33.8 months, ventricular arrhythmia incidence was comparable (9.1% vs. 7.5%). CONCLUSIONS: Shorter ARNI exposure before ICD implantation was independently associated with latent LVRR, highlighting the need for sufficient GDMT to optimize reverse remodeling while residual arrhythmic risk warrants continued ICD protection.