Cardiac autonomic modulation with sacubitril/valsartan in HfrEF

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Created On: 01/04/2026

Heart failure with reduced ejection fraction

Sacubitril/valsartan is a guideline-directed therapy widely used to ameliorate clinical outcomes in heart failure with reduced ejection fraction (HFrEF).

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Key take away

In heart failure with reduced ejection fraction patients, sacubitril/valsartan enhances heart rate variability and reduces both daytime and nocturnal heart rate within 3 months.

Background

Sacubitril/valsartan is a guideline-directed therapy widely used to ameliorate clinical outcomes in heart failure with reduced ejection fraction (HFrEF). This study evaluated its effect on cardiac autonomic regulation using real-world physiological data derived from implantable cardiac devices, including implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-Ds).

Method

In this observational study, 54 HfrEF-affected people receiving ICD or CRT-D therapy were initiated on sacubitril/valsartan. Key autonomic and cardiac parameters assessed were heart rate variability (HRV), nocturnal heart rate (nHR), and 24-hour mean heart rate (24 h-HR). Additional endpoints included device electrical performance and ventricular arrhythmia burden. Data were collected via remote monitoring and averaged over 7-day intervals at baseline, 3 months, and 12 months following therapy initiation.

Result

Sacubitril/valsartan therapy illustrated remarkable improvement in cardiac autonomic markers within the first 3 months. HRV elevated from 78.6 milliseconds (interquartile range [IQR]: 54.2–104.6) to 80.8 milliseconds (60.8–108.0; p = 0.041), indicating enhanced autonomic balance. Concurrently, 24 h-HR dropped from 73.2 beats per minute (bpm, 67.3–77.7) to 69.9 bpm (64.2–75.7), and nHR declined from 63.0 bpm (58.1–70.0) to 60.4 bpm (56.0–68.6). These improvements remained stable, with no further vital changes noted between 3 and 12 months.

Device electrical parameters remained unaffected by treatment. While the overall ventricular arrhythmia burden did not considerably alter across the cohort, those with pre-existing arrhythmias experienced a marked reduction in episode frequency, dropping from 2.97 to 0.82 events per 100 patient-years.

Conclusion

Sacubitril/valsartan therapy in HFrEF patients was linked with early and sustained improvements in cardiac autonomic function, reflected by increased HRV and reduced heart rate. These findings, derived from ICD and CRT-D remote monitoring data, highlight its potential role in optimizing autonomic balance and minimizing arrhythmic risk in selected patients.