Abstract
Background: Reduced heart rate recovery (HRR) has been associated with cardiac autonomic dysfunction, particularly the parasympathetic nervous system, and all-cause mortality in patients with heart failure (HF). Methods: In the present study, data of the MyoVasc study (NCT04064450; N=3,289), a prospective cohort study on chronic HF, were analyzed. Participants received a comprehensive 5-hour examination in a dedicated study center including cardiopulmonary exercise testing (CPET) using modified WHO protocols. HRR 60 was defined as the decrease in heart rate in beats per minute one minute after cessation of CPET peak strain. Information on clinical outcome (i.e. all-cause mortality, worsening of HF (wHF)) was derived from structured follow-up with subsequent validation and independent adjudication of endpoints. Results: The analysis sample comprised N=1,179 individuals (mean age: 65.0±10.4 years; 28.2% females) with data on HRR 60 . In a multivariable linear regression analysis, age (β-estimate -0.171 ([95% confidence interval -0.226; -0.116]; P<0.0001), sex (β -0.189 [-0.311;-0.0678]; P=0.0023), diabetes mellitus (β -0.300 [-0.424; -0.175]; P<0.0001), smoking (β -0.236 [-0.361; -0.111]; P= 0.00021), obesity (β: -0.266 [-0.380; -0.151]; P <0.0001), peripheral artery disease (β -0.432 [-0.640; -0.224]; P<0.0001), chronic obstructive pulmonary disease (β -0.179 [-0.304;-0.0542]; P=0.0050) and chronic kidney disease (β -0.322 [-0.474; -0.170]; P<0.0001) were identified as clinical determinants of HRR 60 . In Cox regression analysis, HRR 60 ≤15 bpm (1 st tertile vs. 2 nd /3 rd tertile of HRR 60 ) demonstrated an increased risk for all-cause death (hazard ratio (HR) 1.90 [1.29; 2.79]; P=0.0011). HRR 60 was also a strong predictor of w HF (HR T1vsT2-3 1.58 [1.17; 2.13]; P=0.0031) independent of clinical determinants and medication. The results remained robust for all-cause mortality (HR T1vsT2-3 1.61 [1.10; 2.38]; P =0.016) and wHF (HR T1vsT2-3 1.36 [1.01; 1.84]; P= 0.045) after additional adjustment for NT-proBNP. Conclusion: HRR 60 - a measure associated with cardiac autonomic function - was identified as a strong predictor of clinical outcome of HF patients independent of NT-proBNP, suggesting a potential to advance risk stratification in HF.
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