Abstract 12486: Predictive Value of Chronotropic Incompetence for Clinical Outcomes in Heart Failure: Findings From the MyoVasc Study

Abstract

Introduction: Chronotropic incompetence (CI), an important aspect of exercise intolerance, is related to adverse clinical outcomes in heart failure (HF). However, the lack of standardized evaluation of CI results in inconsistent evidence. Aim: To evaluate CI with regard to clinical and medical determinants and relationship to clinical outcomes in HF. Methods: Data from the MyoVasc study (NCT04064450), a prospective cohort on HF, were analyzed. Subjects underwent deep clinical phenotyping, including cardiopulmonary exercise testing on a cycle ergometer. Measures of CI were evaluated, with continuous predicted heart rate reserve (pHRR) emerging as the most clinically relevant definition for operationalizing CI. Clinical and medical determinants of CI were assessed in multivariable linear regression models and outcomes in Cox regression models. Results: The analysis sample included 886 subjects (median age 63 years [interquartile range (IQR) 55; 72]; 29.9% women) who achieved maximal exertion (respiratory exchange ratio>1.0). Symptomatic HF stage C/D was present in 42.8% (379) of the subjects. Sixteen drug groups were identified as CI modulators including β-blockers (β-estimate per SD -0.83 [95% confidence interval -0.95;-0.70], p<0.0001) and antiarrhythmics (β SD -0.93 [-1.30;-0.56], p<0.0001). New York Heart Association functional class, smoking, fatty liver index (FLI), and diabetes mellitus (DM) were the strongest determinants of CI in all subjects independently of sex, age, and previously identified medication. Determinants differed according to left ventricular ejection fraction [LVEF] (≥50 vs <50%), being strongly associated with markers of HF (NT-proBNP) and lung function (FEV1) in HF with reduced EF and more linked to DM or the FLI in HF with preserved EF. In Cox regression analysis adjusted for clinical profile, pHRR independently predicted all-cause death (HR SD 1.86 [1.41;2.45], p<0.0001) and worsening of HF (HR SD 1.37 [1.04;1.81], p=0.025). Conclusions: CI strongly predicted clinical outcomes and revealed relevant differences between HF with preserved and reduced EF. This highlights the relevance of impaired response to exercise in the clinical course of HF with implication for risk stratification and intervention.