Abstract
Background: An important knowledge gap remains on sex-related differences in heart failure (HF) management. Recently, it has been recognized that patients, particularly women, with supra-normal left ventricular ejection fraction (snLVEF) are at high risk of adverse outcomes. Aims: We sought to evaluate the sex related differences of long-term outcomes across the spectrum of LVEF in acute decompensated HF (ADHF) patients. Methods: We analyzed 3943 ADHF patients (age 77 years; 59.8% male) who were enrolled in WET-HF multicenter registry in Japan from 2006 to 2017. The association of long-term outcomes across the spectrum of LVEF were compared between men and women. Results: In both HF with reduced EF (HFrEF; LVEF < 50%) and preserved EF (HFpEF), female patients were older and had lower body mass index, lower prevalence of ischemic etiology, and smaller LV chamber size. In HFrEF, implementation of guideline-directed medical therapy such as the combination of renin-angiotensin-system inhibitor (RASi), β-blocker and mineralocorticoid receptor antagonist (MRA) was significantly lower in women at discharge, even after adjustment for covariates (RASi + β-blocker : odds ratio [OR], 0.80, p=0.049; RASi + β-blocker + MRA: OR, 0.73, p=0.016). Female patients showed higher incidence of the primary endpoint, defined as the composite of cardiac death and ADHF readmission during 1,000 days after discharge ( p = 0.009, log-rank test). However, female sex did not remain significant after adjustment for covariates. Restricted cubic spline analysis demonstrated a U-shaped relationship with a nadir at LVEF 60% between LVEF and the hazard ratio of the primary endpoint in women, but this relationship was not observed in men ( p for interaction = 0.048, Figure A, B ). This trend was more evident after excluding patients with valvular heart disease ( p for interaction = 0.014, Figure C, D ). Conclusions: In women, not only low LVEF but also snLVEF were associated with worse long-term outcomes.
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