Skeletal Muscle Oxidative Capacity and Tissue Composition in Heart Failure with Preserved Ejection Fraction

Increasing evidence suggests that exercise intolerance in heart failure with preserved ejection fraction (HFpEF) is related to peripheral abnormalities; however, the roles of muscle oxidative capacity and muscle steatosis remain incompletely understood. To address this knowledge gap, 38 HFpEF patients (mean age 69.8±6.1 years, BMI 37.6±6.9 kg/m²) and 17 healthy older adults (HOAs, mean age: 67.6±5.4 years, BMI 27.3±4.8 kg/m²) performed a graded exercise test on a cycle ergometer to assess exercise tolerance (peak Watts) and whole-body aerobic capacity (VO_2peak). In vivo quadriceps oxidative capacity (τPCr) and thigh tissue composition (i.e., lean thigh mass - LTM; intermuscular fat-% - IMF%) were measured separately via ³¹P-MRS and T₂-weighted MRI, respectively. LTM was similar between HFpEF patients and HOAs (p=0.854), but IMF% was significantly greater in HFpEF (p≤0.001). Peak Watts and VO_2peak normalized to LTM were lower, and quadriceps τPCr were slower in HFpEF patients compared to HOAs (p<0.03, all). Although IMF% was associated with peak Watts normalized to LTM (R²=0.148) and whole-body VO_2peak normalized to body mass (R²=0.347), it was not associated with VO_2peak normalized to LTM (R²<0.001) or τPCr (R²=0.020). In contrast, VO_2peak normalized to LTM and quadriceps τPCr () were both associated with peak Watts (R²=0.509 and 0.252, respectively) and with each other (R²=0.298). Taken together, these data suggest that exercise intolerance in HFpEF is associated with increased muscle steatosis and impaired whole-body and quadricep muscles oxidative capacity. However, the lack of association between IMF% and measures of oxidative capacity suggest they affect exercise tolerance via different physiological mechanisms.