Females and Exercise Capacity Impairment in Heart Failure: A Sex-Focused Analysis

Heart failure (HF) is becoming increasingly common, especially in older females, and displays marked sex-related differences in pathophysiology, treatment, and outcomes. Submaximal exercise capacity (SEC), frequently measured by the six-minute walk test (6MWT), is an important marker of aerobic function, prognosis, and quality of life in HF. However, evidence regarding sex differences in SEC remains limited and inconsistent. This single-centre, prospective cohort study included 1069 patients with chronic HF enrolled between 2004 and 2014. SEC was assessed using the 6MWT, and extensive clinical and psychosocial data were collected. Multivariate models evaluated the independent association between sex and SEC. Results showed that females had significantly shorter 6MWT distances (155 ± 149 m) than males (265 ± 164 m; p < 0.001). Female sex was an independent predictor of impaired SEC in both unadjusted and adjusted analyses (odds ratios 2.226-3.609; p < 0.001). Additional determinants of reduced SEC included advanced age, higher NYHA class, elevated heart rate, diabetes, iron deficiency, dependence in activities of daily living, cognitive impairment, and depressive symptoms. These findings demonstrate that female sex is a strong, independent predictor of reduced functional capacity in chronic HF and emphasize the need for sex-specific strategies addressing both clinical and psychosocial factors to improve outcomes.