With increasingly large sample sizes required to demonstrate event reduction, heart failure outcome trials are no longer being performed in a small group of selected patients and countries, but at a global scale with worldwide contribution of patients from countries with considerable differences in background therapy, socioeconomic status and healthcare practices. Recent studies have highlighted how socioeconomic determinants rather than geographical factors may underlie the heterogeneity of patient populations across the globe. Therefore, in this review, we evaluated (i) regional differences in patient characteristics and outcomes in recent epidemiologic studies; (ii) regional differences in worldwide representativeness of clinical trial populations; and (iii) the role of socioeconomic determinants in driving country differences in heart failure trial enrolment and clinical outcomes.

Aims Although left ventricular ejection fraction (LVEF) is routinely used to categorize patients with heart failure (HF), whether it predicts outcomes after hospitalization for acute heart failure (AHF) is uncertain. Consequently, we assessed the relationship between LVEF and cardiovascular (CV) outcomes in a large, well characterized cohort of patients hospitalized for AHF. Methods and results The 6128 patients from the RELAX‐AHF‐2 trial who had LVEF measured during AHF hospitalization were separated into LVEF quartiles and the relationship between LVEF and a composite of CV mortality and rehospitalization for HF or renal failure through 180 days was assessed. We found progressively lower risk for this composite outcome as LVEF increased (hazard ratio 0.95, 95% confidence interval 0.93–0.98 per 5% LVEF increase, P < 0.001) that was driven predominantly by decreased risk for rehospitalization. The smoothed spline curve depicting risk remained stable as LVEF decreased until reaching approximately 40%, at which point risk increased progressively with further reductions in LVEF. Significant differences between LVEF quartiles for post‐discharge CV risk were seen in patients with an ischaemic aetiology or with a history of HF preceding index hospitalization, but were less robust in patients with non‐ischaemic aetiology and absent in those with de novo HF. Conclusion In patients hospitalized with AHF, CV events over 180 days were more frequent in patients with lower LVEF. This was due predominantly to a significant increase in risk for HF/renal failure rehospitalization but not in either CV or all‐cause mortality. LVEF had greater prognostic value in patients with ischaemic aetiology or pre‐existing HF.