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

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%, 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.