Key result
Females with HFpEF have ~40% lower muscle oxygen diffusive conductance during peak exercise than males.
Why the study?
HFpEF disproportionately affects females, but the influence of sex on peripheral contributors to exercise intolerance remains poorly understood.
Does female sex affect peripheral determinants of oxygen transport and utilization during exercise in patients with HFpEF?
Observational (n=43)
Does female sex affect peripheral determinants of oxygen transport and utilization during exercise in patients with HFpEF?
Absolute Event Rate: 3.6% vs 6.4%
p-value: p=<0.0001
Females with HFpEF have significantly lower muscle oxygen diffusive conductance during peak exercise compared to males, highlighting a sex-specific peripheral limitation to exercise capacity.
May indicate sex-specific peripheral limitations to exercise in female HFpEF; leaves open causal and therapeutic implications.
Background: Heart failure with preserved ejection fraction (HFpEF) disproportionately affects females, however the influence of sex on peripheral contributors to exercise intolerance remains poorly understood. Methods: 43 patients with HFpEF (71±7 years, 28 females; 38.3±6.7 kg/m 2 ) performed incremental single leg knee extension (SLKE) exercise to determine peak leg blood flow (BF; duplex Doppler ultrasound), a-vO 2 difference (femoral venous catheter), leg VO 2 , and muscle oxygen diffusive conductance (DMO 2 ). Whole body and thigh adiposity and lean mass (TLM) were determined by DXA, and myosteatosis (TLM/fat ratio) by MRI. Results: After adjusting for differences in TLM, females had ~30% lower peak exercise leg VO 2 /TLM (p<0.001) and ~15% lower BF/TLM compared to males (p=0.024). However, when normalized to VO 2 , the leg BF/leg VO 2 slope was higher in females (9.5±2.3 vs. 8.1±2.1, p=0.017) and was associated with markedly lower a-vO 2 difference (p<0.001) and ~40% lower DMO 2 (3.6±1.6 vs 6.4±1.7, p<0.0001). Metrics of muscle adiposity were not correlated with peak leg VO 2 or its determinants (p>0.150 for all). Conclusion: Females with HFpEF have lower muscle oxygen diffusive conductance during peak SLKE compared to males. However, peripheral determinants of aerobic capacity were not differentially related to adiposity in males and females with HFpEF. Interventions to improve muscle quality and diffusive capacity are of particular importance for improving peripheral limitations to exercise in females with obesity and HFpEF.
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Jr. et al. (2026) conducted an observational in Heart failure with preserved ejection fraction (HFpEF) (n=43). Female sex vs. Male sex was evaluated on Muscle oxygen diffusive conductance (DMO2) (p=<0.0001). Females with HFpEF had ~40% lower muscle oxygen diffusive conductance during peak exercise compared to males (3.6 vs 6.4, p<0.0001).
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