Sex-Related Differences in Long-term Outcomes across the Spectrum of Ejection Fraction in Heart Failure Patients

BackgroundRecently, patients with supra-normal left ventricular ejection fraction (snLVEF) are reported to have high risk of adverse outcomes, especially in women. We sought to evaluate sex-related differences in the association between LVEF and long-term outcomes in heart failure (HF) patients. MethodsThe multicenter WET-HF Registry enrolled all patients hospitalized for acute decompensated HF (ADHF). We analyzed 3,943 patients (age 77 years; 59.8% male) registered from 2006 to 2017. According to LVEF the patients were divided into the 3 groups: HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF) and preserved EF (HFpEF). The primary endpoint was defined as the composite of cardiac death and ADHF rehospitalization after discharge. ResultsImplementation of guideline-directed medical therapy (GDMT) such as renin-angiotensin-system inhibitor (RASi), {beta}-blocker and their combination at discharge was significantly lower in women than men in HFmrEF. Lower prescription of RASi + {beta}-blocker combination in female HFmrEF was noted even after adjustment for covariates (p=0.007). There were no such sex-related differences in HFrEF. Female sex was associated with higher incidence of the primary endpoint and ADHF rehospitalization after adjustment for covariates exclusively in HFmrEF. Restricted cubic spline analysis demonstrated a U-shaped relationship between LVEF and the hazard ratio of the primary endpoint in women, but such relationship was not observed in men (p for interaction=0.037). ConclusionsIn women, not only lower LVEF but also snLVEF were associated with worse long-term outcomes. Additionally, sex-related differences in the GDMT implementation for HFmrEF highlight the need for sex-specific guidelines to optimize HF management.