Over the past few years, more attention has been paid to the ways gender may affect cardiovascular disease. Early clinical cardiovascular studies tended to underrepresent women. This failing resulted in several challenges to physicians, including the lack of appreciation for the differences in clinical characteristics between men and women with regard to cardiovascular disease. In addition, this underrepresentation of women placed limitations on the ability to analyze clinical and laboratory variables that could help determine survival in women with heart failure. Investigators in the Beta-Blocker Evaluation of Survival Trial placed special emphasis on recruiting women with heart failure. Ghali and colleagues evaluated the influence of gender on baseline characteristics, response to treatment, and prognosis in patients with heart failure.

The study population was recruited from Veterans Affairs hospitals and other sites. Patients were eligible if they had New York Heart Association class III or IV heart failure with a left ventricular ejection fraction of 0.35 or less. Ischemic etiology of the heart failure was established at each center if patients had documented coronary artery disease (CAD) or previous myocardial infarction.

Participants were randomized to receive the beta blocker bucindolol or placebo. The primary outcome measure was all-cause mortality with secondary outcomes including cardiovascular mortality, all-cause and heart failure hospitalizations, the combination of death and heart transplant, and left ventricular ejection fraction at three and 12 months. The mean follow-up period for the study was two years.

The study included 593 women and 2,115 men. In the study, women with heart failure were younger and more likely to be black, and had a higher prevalence of nonischemic etiology. In addition, women had higher right and left ventricular ejection fractions, higher heart rate, greater cardiothoracic ratio, a higher prevalence of left bundle branch block, a lower prevalence of atrial fibrillation, and a lower level of plasma norepinephrine. The presence of an ischemic etiology and severity of heart failure were predictors of prognosis in women and men. Sex differences were noted, with the presence of CAD and left ventricular ejection fraction being stronger predictors of prognosis in women. If the etiology of heart failure was nonischemic, women had a significantly better survival rate than men.

The authors conclude that there is a significant gender difference in prognostic values in patients with advanced heart failure. They add that survival advantage is limited to women without an ischemic etiology for heart failure. They point out that because of these gender differences, information obtained from studying men with heart failure may not be extrapolated easily to women. Including more women in heart failure trials is important to understand how best to treat their heart failure.