Sex differences in clinical characteristics and outcomes in heart failure with mildly reduced and preserved ejection fraction

Heart failure with mildly reduced and preserved ejection fraction (HFmrEF and HFpEF) exhibits significant sex-based differences in clinical presentation, management, and outcomes. This study aimed to evaluate these differences using data from the Swedish Heart Failure Registry (SwedeHF). We analyzed 64,046 patients with HFmrEF or HFpEF (EF ≥40%) from the SwedeHF registry. Baseline characteristics, treatment patterns, and outcomes were compared between females and males. Multivariable logistic regression was used to evaluate predictors of guideline-directed medical therapy (GDMT) use as odds ratios (OR). Cox proportional hazards models were used to assess the risk of cardiovascular mortality and heart failure (HF) hospitalization as hazard ratios (HR), adjusting for demographic and clinical variables. Females (42.5%) were older than males (median age 79 years vs 75 years), had a higher prevalence of hypertension (73.8% vs 70.0%), and were more likely to present with severe symptoms (NYHA class III-IV: 36.8% vs 28.8%). Males had a higher prevalence of ischemic heart disease (52.3% vs 42.9%) and diabetes (27.4% vs 23.8%). Females were significantly less likely to receive SGLT2 inhibitors (OR 1.24, 95% confidence interval [CI] 1.13-1.36), while males were less likely to receive beta-blockers, digoxin, nitrates, and loop diuretics. During a median follow-up of 2.3 years, males had a higher adjusted risk of the composite outcome of cardiovascular mortality or HF hospitalization (HR 1.16, 95% CI 1.13-1.19), as well as higher risks for cardiovascular mortality (HR 1.28, 95% CI 1.23-1.32) and HF hospitalization (HR 1.12, 95% CI 1.08-1.15). Females with HFmrEF and HFpEF in the SwedeHF registry had a distinct clinical profile, were less likely to receive certain GDMTs, yet exhibited a lower risk of cardiovascular mortality compared to males. These findings underscore the importance of targeted strategies to optimize HF care for females.