Sex Differences in Patients With Chronic Heart Failure With Reference to Left Ventricular Ejection Fraction

Background: Data on sex differences in heart failure (HF) with reference to left ventricular ejection fraction (LVEF) are limited. Methods and Materials: We examined 4683 consecutive patients (mean 69 years) with HF in the CHART-2 study. Results: Compared to men (N = 3188), women with HF (N = 1495) were older and had a lower prevalence of ischemic heart disease and cancer, received less implementation of evidence-based treatment, and were characterized by more severe HF in terms of higher New York Heart Association (NYHA) functional class and increased brain natriuretic peptide (BNP) levels, despite greater preservation of LVEF. During the median 6.3-year follow-up, all-cause mortality was comparable between women and men (32.8% vs 33.2%, P = .816), while women had higher cardiovascular mortality, particularly among those with LVEF ≥50%. Although no sex differences existed in cause of death among patients with LVEF ≤ 40% and 41% to 49%, women had a higher proportion of cardiovascular death and lower proportion of noncardiovascular death than men among those with LVEF ≥ 50%. Multivariable Cox regression models showed that women with HF had reduced risk of both cardiovascular and noncardiovascular death, regardless of LVEF category. Beta-blockers were associated with improved mortality in women but not men with LVEF ≤ 40%, while renin–angiotensin system inhibitors were not associated with improved mortality in women with LVEF ≥ 50% but were in men. Conclusion: In addition to sex-specific differences in the age of onset, etiology and response to treatment, women with heart failure and preserved left ventricular ejection fraction (LVEF ≥ 50%) have higher cardiovascular mortality than men. Sex-related management of congestive heart failure should include a consideration of LVEF.