Abstract 4367194: Sex-Specific Outcomes in Heart Failure with Mildly Reduced Ejection Fraction: A Real-World Analysis

Background: Heart failure with mildly reduced ejection fraction (HFmrEF), defined by a left ventricular ejection fraction (LVEF) of 41–49%, is a growing clinical entity. However, limited real-world data exist regarding sex-specific outcomes in this subgroup. This study aimed to evaluate differences in cardiovascular outcomes between male and female patients with HFmrEF. Methods: We conducted a retrospective cohort study using de-identified electronic health records from the TriNetX US Collaborative Network, comprising data from 68 healthcare organizations. Adults aged 18–90 years with a diagnosis of heart failure (ICD-10-CM: I50) and a documented left ventricular ejection fraction (LVEF) between 41–49% were included. Patients with prior heart transplant, mechanical circulatory support, artificial heart, end-stage renal disease, or neoplasms were excluded. Female (n=15,169) and male (n=26,658) cohorts were identified and matched 1:1 using propensity scores, yielding 12,783 patients per group. Matching was based on demographics, comorbidities, and cardiovascular medication use. The index event was defined as the first recorded HF diagnosis with LVEF 41–49%, and outcomes were assessed starting one day after the index date until final follow-up. Primary outcomes included all-cause mortality, cardiac arrest, acute myocardial infarction (MI), cerebral infarction, and acute kidney injury (AKI), analyzed using Kaplan-Meier survival analysis and risk-based comparisons. Natriuretic peptide B (NPB) levels were also compared between groups. Results: After matching, females had a higher hazard for overall mortality (HR 1.051, 95% CI: 0.994–1.111, p =0.048) with lower survival probability (44.2% vs. 22.3%). Females also had a higher risk and hazard of acute MI (HR 1.092, 95% CI: 1.022–1.165, p =0.008). No significant differences were observed for cardiac arrest (HR 0.917, p =0.604), cerebral infarction (HR 1.020, p =0.665), or AKI (HR 1.020, p =0.476). NPB levels were slightly higher in females (mean: 1533.5 vs. 1355.6 pg/mL), but the difference was not statistically significant ( p =0.192). Conclusion: In this large, real-world analysis, female patients with HFmrEF had a significantly higher hazard of mortality and acute MI compared to males, despite matching for baseline characteristics. These findings highlight the need for sex-specific risk stratification and tailored management strategies in HFmrEF.