Abstract 11025: Markers of Heart Rate Variability Represent Strong and Independent Predictors of All-Cause Death in Heart Failure - Results from the Myovasc Study

Abstract

Introduction: Although different measures of heart rate variability (HRV) have been proposed as markers of autonomic dysfunction (AD) in heart failure (HF), evidence on their clinical relevance is limited. Methods: Data from the MyoVasc study (NCT04064450; N=3,289), a prospective cohort study on chronic HF, were analyzed. Study participants received a highly standardized, 5-hour examination including 24-hour Holter ECG recording. RR intervals were extracted to evaluate HRV markers from time and frequency domain analyses, and non-linear markers derived via phase space reconstruction, phase-rectified signal averaging, and entropy analyses. HRV markers of interest were selected using a systematic literature screen, and a random survival forest model predicting cardiac death. Reference values were determined in a healthy subsample. To evaluate clinical relevance, HRV markers were investigated in multivariable Cox regression analyses for their relationship to all-cause death considering potential confounders and mediators. Results: Holter ECG recordings were available for analysis in 1,001 study participants (mean age 64.5±10.5 years; female sex: 35.4%). While the top 10 most frequently reported HRV markers in literature screen were from the time and frequency domains, the data-driven approach revealed predominantly non-linear HRV measures. Values outside reference ranges for SDANN, rMSSD, frequency bands (i.e., ULF, VLF, LF, total power, ULF MED wavelet ), acceleration capacity (AC), deceleration capacity (DC), and time lag, were strong predictors of all-cause death in Cox regression analysis (median follow-up time: 6.1 [IQR 4.7/7.1] years) adjusted for age, sex, clinical profile and medication. In linear Cox regression analyses of the total sample, LF/HF (hazard ratio per SD (HR SD ) 0.78 [95% confidence interval (CI) 0.62, 0.98], p=0.034), time lag (HR SD 1.23 [95%CI 1.05, 1.44], p=0.0095), AC (HR SD : 1.57 [95%CI 1.24, 1.99], p=0.0002), and DC (HR SD 0.67 [95%CI 0.53, 0.85], p=0.0012) were strong predictors for all-cause mortality independent of age, sex, clinical profile and medication. Conclusions: HRV markers reflecting AD are strong predictors of all-cause death in HF, suggesting clinical relevance and potential for intervention.