Determinants of exercise capacity in heart failure with preserved ejection fraction: central hemodynamics, ventilatory efficiency, and peripheral muscle oxygen utilization and function

Background Exercise intolerance, reflected by reduced peak oxygen uptake (V˙O 2 peak), is a hallmark feature of heart failure with preserved ejection fraction (HFpEF). Impairments along the oxygen cascade, including central hemodynamics, ventilatory efficiency, and peripheral factors, have been described, but their relative contributions remain incompletely defined. Methods This cross-sectional analysis included baseline data from the HIT-HF trial. V˙O 2 peak and ventilatory efficiency were assessed by cardiopulmonary exercise testing. Stroke volume was measured using impedance cardiography, heart rate via electrocardiography, total hemoglobin mass (tHbmass) by carbon monoxide rebreathing, muscle oxygen saturation (SmO 2 ) by near-infrared spectroscopy, and leg power by countermovement jump testing. Associations with relative and absolute V˙O 2 peak were examined using multivariable linear regression adjusted for age, sex, and body fat mass. Missing data were handled by multiple imputations. Results Of 46 patients, 43 were included in the final analysis [mean age: 73 (10) years, BMI: 25.6 (4.3) kg/m 2 , 65% female]. In multivariable models, leg power showed the strongest positive association with relative V˙O 2 peak ( β = 0.35, 95% CI: −0.20 to 0.89), whereas leg fat-free mass showed the strongest association with absolute V˙O 2 peak ( β = 0.57, 95% CI: 0.21–0.92). Stroke volume and heart rate showed smaller associations, whereas SmO 2 , tHbmass, and ventilatory efficiency showed trivial associations ( β between −0.1 and 0.1). Conclusion In HFpEF, peripheral muscle function was more strongly associated with exercise capacity than central hemodynamics or ventilatory efficiency.