Cardiopulmonary exercise capacity markers and their link to symptom burden in patients at risk for heart failure with non-reduced ejection fraction

Abstract The American Heart Association (AHA) guidelines assess heart failure (HF) via comorbidities, laboratory markers, and echocardiography, while the New York Heart Association (NYHA) classification evaluates functional capacity. The primary objective of this study was to investigate the correlation between objectified HF-related symptoms and cardiac and muscular exercise capacity in Stage B HF patients with non-reduced ejection fraction. As secondary endpoints, we stratified this analysis for subgroups of NYHA classes to evaluate the primary endpoint for different levels of impairment and for sex to address for differences between men and women. Sixty-two Stage B HF patients with non-reduced EF were screened from an HF-risk cohort. Assessments included medical history, HF-related symptoms (Kansas City Cardiomyopathy Questionnaire, KCCQ), physical examination, laboratory tests, echocardiography, and cardiopulmonary exercise testing (CPET) with cardiac output monitoring. Correlations were analyzed between KCCQ score and exercise capacity markers: maximal oxygen uptake (VO 2 max), arterio-venous oxygen difference (avDO 2 ), cardiac power output (CPO), mean arterial pressure (MAP), and respiratory efficiency (Ve/VO 2 ). Subgroup analyses were performed by sex and NYHA class determined by VO 2 max or KCCQ functional scores. Our HF patient cohort showed reduced KCCQ scores (78.3) and VO₂max (22.9 ml/kg/min), and a progressed reduction in avDO₂. In the total cohort, KCCQ scores showed moderate correlations with Ve/VO₂ ( r = -0.39) and MAP ( r = 0.27). NYHA stratification by VO₂max revealed differences in avDO₂ and cardiac output but not KCCQ scores, while KCCQ-functional stratification only showed differences in Ve/VO₂. Sex-specific analysis showed KCCQ scores correlated with CPO in men ( r = 0.65) and Ve/VO 2 in women ( r = -0.68). Our identified Stage B HFpEF cohort showed already alterations in total, cardiac and muscular exercise limitation. The HF symptom severity was weakly associated to the higher blood pressure and ventilatory inefficiency and, but moderately to strongly correlated CPO in men and Ve/VO 2 in women in sex-specific analyses.