Approximately half of all patients with heart failure have preserved ejection fraction (HFpEF), a syndrome for which no treatment has proven to be effective in clinical trials. The pathophysiology of HFpEF is heterogeneous, with multiple individual mechanisms frequently coexisting within the same patient to cause symptomatic heart failure. In this Review, Barry Borlaug discusses the current understanding of the pathophysiological mechanisms underlying HFpEF, and how they might be mechanistically related to typical risk factors for HFpEF, including ageing, obesity, and hypertension.
