Precision therapeutics in heart failure: continuous cardiac device data detect early response to sacubitril/valsartan

Background Traditional clinical assessments in heart failure with reduced ejection fraction (HFrEF) occur at fixed intervals (3-6 months) and may miss early physiologic changes that precede symptom improvement.1,2 Continuous physiologic data from implantable cardioverter-defibrillators (ICDs) can potentially enable earlier recognition of therapeutic benefit. Purpose To assess changes in individual ICD parameters and the HeartLogic index, a multi-sensor composite predictive of HF decompensation, following sacubitril/valsartan initiation. We also sought to identify when physiologic transitions occur and determine impact on HeartLogic alert burden. Methods This retrospective study of HFrEF patients with Boston Scientific ICDs capable of HeartLogic monitoring who initiated sacubitril/valsartan (2017–2023). Patient-level 7-day rolling means for ICD parameters (heart rate, heart rate variability, S1, S3, thoracic impedance, respiration rate, nighttime heart rate, activity) and composite HeartLogic score were compared at 30, 90, and 180 days post-initiation to baseline (30-day pre-initiation mean) using inverse probability-weighted paired t-tests. Change point analysis identified timing of physiologic transitions. HeartLogic alert burden (frequency and duration) was evaluated using interrupted time series regression. Results Among 148 patients included in the study (mean age 64.8 years, 28% female), 27% were in hospitalized or in HeartLogic alert at the time of sacubitril/valsartan initiation. By 6 months, sacubitril/valsartan was associated with decreased weighted mean S3 (-0.06 ± 0.21 mG, p=0.01), S1 (-0.11 ± 0.49 mG, p=0.04), nighttime heart rate (-1.71 ± 6.26 bpm, p=0.01), respiratory rate (-0.43 ± 1.36 respirations per minute, p<0.01), and mean heart rate (-2.25 ± 6.62 bpm, p=0.01). Initial increases in physical activity [30 days (+6.12 ± 24.5 minutes per day, p=0.02); 90 days (+4.57 ± 24.8, p=0.10)] were not sustained [180 days (-0.23 ± 23.51; p=0.90)] (Figure). Heart rate variability and thoracic impedance did not change significantly. Change point analysis detected increased heart rate variability and physical activity by days 13 and 16 respectively, decreased HeartLogic score by day 49, decreased mean heart rate by day 64, and decreased nighttime heart rate by day 69. While HeartLogic alert frequency remained stable from baseline to end of follow up, time in alert decreased by 37% (OR 0.54, 95% CI 0.40–0.74, p<0.001). Conclusion Sacubitril/valsartan produced detectable physiologic improvements within 13 days, well before traditional clinical reassessment, with sustained benefits through 6 months. Continuous device monitoring provides objective, precision assessment of therapeutic response and may inform HF medication optimization.