Heart failure with preserved ejection fraction: current insights and emerging therapeutic directions

Abstract

Heart failure with preserved ejection fraction (HFpEF), defined by clinical heart failure with left ventricular ejection fraction ≥ 50%, represents more than half of heart failure cases in Asia and carries a one-year composite hospitalization and mortality rate of approximately 12.1%. Recent landmark trials have transformed the therapeutic landscape: Sodium-glucose cotransporter 2 inhibitors emerged as treatment for HFpEF, shown beneficial in EMPEROR-preserved and DELIVER. Empagliflozin significantly reduced the risk of cardiovascular death or heart failure hospitalization and dapagliflozin demonstrated comparable efficacy across regions. Furthermore, glucagon-like peptide-1 receptor agonist such as semaglutide have shown promising improvements in functional capacity and symptom burden in obesity-related HF-pEF. Asian HFpEF phenotypes often exhibit high rates of hypertension and diabetes, alongside lower average body mass index compared to Western cohorts. In numerous respects, the clinical and pathophysiological features of HFpEF in Asian populations diverge from those traditionally observed in Western cohorts. In this brief review, we will focus on therapeutics approved for HFpEF and agents currently under clinical trial, as well as the distinctive characteristics of HFpEF patients observed in Asia and the key considerations for future therapeutic development in this region.