Cardiac Resynchronization as an Enabler of ARNI Efficacy: Insights From a Real‐World Cohort

ABSTRACT Background Sacubitril/valsartan (ARNI) improves outcomes in heart failure with reduced ejection fraction (HFrEF). In patients undergoing cardiac resynchronization therapy (CRT), the potential synergy between device‐based and pharmacological strategies remains underexplored. Methods The aim of this study was to assess the effect of ARNI therapy on reverse remodeling, clinical response, and cardiovascular events at 1 year in CRT recipients, in order to clarify the potential synergistic role of pharmacological and device‐based strategies. A retrospective cohort of 194 consecutive CRT patients was analyzed, of whom 65 (33.5%) received ARNI. Echocardiographic response was defined as an increase in LVEF > 5% or ≥ 15% reduction in LV end‐systolic volume at 12 months; clinical response as an improvement of at least one NYHA class. The primary endpoint was echocardiographic response. Device‐detected remote monitoring heart failure (RM‐HF) events were pre‐specified as the key time‐to‐event endpoint, while mortality and HF hospitalization were exploratory. Results Baseline characteristics were comparable, although systolic blood pressure was higher in ARNI recipients. At 12 months, ARNI therapy was associated with greater reverse remodeling (ΔLVEF 14.4% ± 10.2% vs. 10.8% ± 11.0%, p = 0.04). Rates of echocardiographic (68% vs. 67%) and clinical response (68% vs. 74%) were similar. Mortality and HF hospitalization did not differ significantly. In contrast, ARNI recipients showed fewer RM‐HF events, with higher event‐free survival among echocardiographic responders (95.7% vs. 82.6%; log‐rank p = 0.021, q = 0.042) and clinical responders (93.4% vs. 85.3%; p = 0.040, q = 0.040). Conclusions In this real‐world CRT cohort, ARNI therapy enhanced reverse remodeling and reduced subclinical congestion events detected by remote monitoring. These findings support a synergistic interaction between CRT and ARNI, where resynchronization provides the substrate for pharmacological efficacy.