Determinants of exercise capacity in heart failure with preserved ejection fraction: central hemodynamics,...

Exercise intolerance, reflected by reduced peak oxygen uptake (V˙O₂peak), 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.

This cross-sectional analysis included baseline data from the HIT-HF trial. V˙O₂peak 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 (SmO₂) by near-infrared spectroscopy, and leg power by countermovement jump testing. Associations with relative and absolute V˙O₂peak were examined using multivariable linear regression adjusted for age, sex, and body fat mass. Missing data were handled by multiple imputations.

Of 46 patients, 43 were included in the final analysis [mean age: 73 (10) years, BMI: 25.6 (4.3) kg/m², 65% female]. In multivariable models, leg power showed the strongest positive association with relative V˙O₂peak (β = 0.35, 95% CI: -0.20 to 0.89), whereas leg fat-free mass showed the strongest association with absolute V˙O₂peak (β = 0.57, 95% CI: 0.21-0.92). Stroke volume and heart rate showed smaller associations, whereas SmO₂, tHbmass, and ventilatory efficiency showed trivial associations (β between -0.1 and 0.1).

In HFpEF, peripheral muscle function was more strongly associated with exercise capacity than central hemodynamics or ventilatory efficiency.