Sex-based differences in peak oxygen uptake among individuals with heart failure: systematic review and meta-analysis

Heart failure (HF) studies examining peak oxygen uptake (V̇o₂) have largely focused on males, leaving a significant gap in the understanding of the magnitude and the mechanisms underpinning the impairment in females with HF. The objective of this systematic review and meta-analysis is to examine sex differences in peak V̇o₂ in HF. Studies were found through Medline, EMBASE, Scopus, CINAHL, and SPORTDiscus and included if they compared peak V̇o₂ in males and females with HF. Data extraction and methodological quality assessment were completed by two independent coders. Main outcomes and measures included peak V̇o₂ (mL/kg/min, primary outcome) and its Fick determinants (secondary outcome). The weighted mean difference (WMD) was calculated for each outcome between females and males. After screening 1,579 articles, 33 studies were included. Peak V̇o₂ was lower in females versus males (n = 20,115, WMD: -2.1 mL/kg/min, 95% CI: -2.4 to -1.8 mL/kg/min). In studies reporting the Fick determinants, peak exercise cardiac output (n = 1,219, WMD: -1.3 L/min, 95% CI: -1.7 to -1.0 L/min), stroke volume (n = 1,151, WMD: -15.2 mL, 95% CI: -18.8 to -11.7 mL), and arterial-venous oxygen difference (n = 1,131, WMD: -1.4 mL/dL, 95% CI: -2.3 to -0.5 mL/dL) were lower, whereas peak heart rate was higher compared with males (n = 10,103, WMD: 2.4 beats/min, 95% CI: 0.1-4.7 beats/min). The greater peak V̇o₂ impairment among females with HF is likely due to lower peak exercise cardiac output and arterial-venous oxygen difference. Future research should prioritize interventions aimed at addressing these physiological constraints in females with HF.NEW & NOTEWORTHY This meta-analysis revealed that peak exercise oxygen uptake is 2.1 mL/kg/min lower in females with heart failure compared with males, which may be due to having a lower peak cardiac output and arterial-venous O2 content difference. These findings highlight the importance of developing sex-specific therapeutic approaches to better address the added physiological challenges faced by females with heart failure to improve cardiovascular and skeletal muscle health outcomes.