Aims: We investigated the gender-based differences in the association between heart failure (HF) during acutecoronary syndrome (ACS) and post-discharge, long-term cardiovascular (CV) mortality.

Methods and results: The present study included 557 patients enrolled in three intensive coronary care units anddischarged alive. HF during ACS was evaluated by Killip class and left ventricular ejection fraction (LVEF). Inter-action between gender and HF after 15 years of follow up was studied using Cox models including a formal inter-action term. Median age was 67 (interquartile range [IQR], 59–75) years, 29% were females, 37% had non-STelevation myocardial infarction and 32% Killip classN1, and median LVEF was 53% (IQR 46–61). All butfive pa-tients were followed up to 15 years, representing 5332 person-years. Of these, 40.2% died of CV-related causes.Crude CV mortality rate was higher among women (52.2%) than men (35.3%;Pb0.0001). At a univariablelevel, a negative interaction between female gender and Killip class for CV mortality was found [hazard ratio(HR) = 0.51 (0.34–0.77),P=0.002].Infive multivariable models after controlling for age, main CV risk factors,clinical features, post-discharge medical treatment, and mechanical coronary reperfusion, the interaction wassignificant across all models [HR = 0.63 (0.42–0.95),P= 0.02 in the fully adjusted model]. LVEF showed no sig-nificant hazard associated with female gender on univariable analysis [HR = 1.4 (0.9–0.2.0),P= 0.11] but did soin all adjusted models [HR = 1.7 (1.2–2.5),P= 0.005 in the fully adjusted model].

Conclusion: Gender is a consistent, independent effect modifier in the association between HF and long-term CVmortality after ACS.

Keywords: Gender, Heart failure, Killip class, LVEF, Acute coronary syndrome, Cardiovascular mortality, Surviving analysis