Chronotropic response in heart failure: clinical, structural, and metabolic predictors and long-term mortality

Area of Science:

• Cardiology and Exercise Physiology
• Heart Failure Research
• Metabolic Syndrome and Cardiovascular Disease

Background:

• Chronotropic incompetence (CI) is common in heart failure (HF) but lacks precise definition.
• Understanding CI determinants and its impact on clinical outcomes is crucial for risk stratification in HF patients.

Purpose of the Study:

• To refine the definition of chronotropic incompetence (CI) in heart failure (HF).
• To identify clinical determinants associated with CI.
• To evaluate the relationship between CI and adverse clinical outcomes in HF.

Main Methods:

• Analysis of data from the MyoVasc study (NCT04064450) including deep clinical phenotyping and cardiopulmonary exercise testing (CPET).
• Exclusion of subjects with a respiratory exchange ratio < 1.0.
• Operationalization of CI using continuous predicted heart rate reserve (pHRR) and derivation of a new reference range from a healthy subsample; assessment of determinants and outcomes using stepwise regression and Cox regressions, respectively.

Main Results:

• The study included 880 subjects, with 64.7% identified as CI using the traditional 80% threshold.
• A new definition of CI was established as pHRR < 56.4%, with determinants including peak oxygen uptake (VO2), beta-blockers, age, sex, smoking, CPET protocol, HF severity, C-peptide, and fatty liver.
• CI independently predicted all-cause death (HR 1.77), cardiac death (HR 1.74), and worsening of HF (HR 1.39).

Conclusions:

• Chronotropic incompetence (CI) is a significant independent predictor of mortality and morbidity in heart failure (HF).
• The association of CI with metabolic factors like hyperinsulinemia and abnormal liver function suggests a link between metabolism and exercise response.
• These findings underscore the clinical relevance of impaired exercise response in HF and its utility in risk stratification.