Impact of Sacubitril/Valsartan on Cardiac Autonomic Function Assessed Using Physiological Data from Implantable Cardioverter-Defibrillators

<b>Background/Objectives</b>: Sacubitril/Valsartan is a cornerstone therapy to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate the effect of Sacubitril/Valsartan on cardiac autonomic balance using physiological sensor data obtained from implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds). <b>Methods</b>: This observational study involved 54 ICD and CRT-D patients who initiated Sacubitril/Valsartan therapy to treat HFrEF. The evaluated key parameters included heart rate variability (HRV), 24 h mean heart rate (24 h-HR), and nocturnal heart rate (nHR). Device electrical parameters and ventricular arrhythmias were also assessed. The data were collected by remote monitoring and averaged over a 7-day window at baseline (before treatment) and at 3 and 12 months after treatment initiation. <b>Results</b>: Sacubitril/Valsartan significantly improved HRV at 3 months (from 78.6 ms [interquartile range: 54.2-104.6] to 80.8 ms [60.8-108.0]; <i>p</i> = 0.041), reduced 24 h-HR (from 73.2 bpm [67.3-77.7] to 69.9 bpm [64.2-75.7]; <i>p</i> = 0.016), and reduced nHR (from 63.0 bpm [58.1-70.0] to 60.4 bpm [56.0-68.6]; <i>p</i> = 0.028). No significant changes in HRV, 24 h-HR, and nHR were observed between 3- and 12-month follow-up. The device electrical parameters were not influenced by the treatment. While the overall ventricular arrhythmia burden did not change post-treatment, patients with pre-treatment arrhythmias experienced a significant reduction in episodes from 2.97 (pre-treatment) to 0.82 (post-treatment) events per 100 patient years (<i>p</i> = 0.008). <b>Conclusions</b>: Sacubitril/Valsartan therapy in HFrEF patients was associated with statistically significant changes in cardiac autonomic indices, including a small increase in HRV and a slight reduction in heart rate, mainly during the first three months of treatment.