Sex-related heart failure mortality influenced by left ventricular ejection fraction

4th January 2022

Sex-related differences in mortality after heart-failure hospitalisation is influenced by the left ventricular ejection fraction

Sex-related differences in mortality in patients with heart failure hospitalisations appear to be affected by the left ventricular ejection fraction according to researchers from the Cardiology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain.

Although the risk of heart failure (HF) is similar between men and women, there are some notable sex-related differences, with men being predisposed to HF with reduced ejection fraction and women with preserved ejection fraction.

Although there is some evidence that women with HF live longer than men, they experience more psychological and physical disability. However, much of the available data is derived from patients with stable HF and what is less clear, is if there are any sex-related prognostic differences among patients hospitalised following decompensated heart failure.

For the present study, the Spanish team retrospectively examined gender differences in mortality across the left ventricular ejection fraction spectrum in a cohort of patients after a hospitalisation for acute HF.

The researchers used a multi-centre prospective registry of those hospitalised and collected demographics, medical history, laboratory and echocardiographic parameters and followed patients over a 6-month period.

The primary study endpoints were all-cause, cardiovascular and HF-related mortality. Cardiovascular death was considered secondary to a worsening of HF, acute myocardial infarction, stroke or transient ischaemic attack, whereas HF-related deaths were considered secondary to a worsening of the HF or a sudden cardiac death.

Findings

A total of 4812 patients with a mean age of 74.2 years (46.6% women) were included in the analysis. The proportion of patients with a left ventricular ejection fraction (LVEF) of < 40%, 41 – 49% and > 50% was 31.5%, 14.3% and 54.2% respectively. Women were generally older with a mean age of 76.8 years compared to 71.9 years for men and had a higher preserved ejection fraction (70.5% vs 39.9%, female vs male, p < 0.001).

After 6 months, 645 (13.4%) of the patients had died with mortality rates of 13.3% and 13.5% (women vs men, p = 0.82) and there were no significant sex-related differences in all-cause mortality. Moreover, LVEF was not an independent predictor of mortality (HR = 1.02, 95% CI 0.99 – 1.05, p = 0.13). Similarly, rates of cardiovascular mortality were not different between the sexes.

However, there was a significant interaction between sex and levels of LVEF (p for interaction = 0.030) and women had a significantly lower risk of cardiovascular mortality at lower LVEF levels (< 25%). There were also no differences between the sexes in HF-related mortality although as with cardiovascular mortality, there were differences across the levels of LVEF and women had a reduced risk of HR-related death.

For example, compared to men, women had a reduced risk of HF death at a LVEF of < 43% (HR = 0.77, 95% CI 0.59 – 0.99) In contrast, this risk of death in women became higher as the LVEF increased above 80%.

Commenting on these findings, the authors noted that while sex was not a determinant of 6 month all-cause mortality, women had a lower risk of cardiovascular and HR-related mortality where the LVEF was < 25% and < 43% but higher where the LVEF was > 80%.

They concluded that further work is required to confirm these findings and to evaluate the potential negative implications of a supra-normal LVEF in women with a preserved ejection fraction.

Citation

Santas E et al. Sex-Related Differences in Mortality Following Admission for Acute Heart Failure Across the Left Ventricular Ejection Fraction Spectrum J Am Heart Assoc 2021.