Abstract
•In clinical practice, significant treatment heterogeneity exists among patients with heart failure with preserved ejection fraction (HFpEF).•The heterogeneity of HFpEF has also been demonstrated via responder analyses in neutral HFpEF trials.•Identification of responder and nonresponder groups in HFpEF trials can provide novel insights into HFpEF pathophysiology.•Atrial shunt and splanchnic nerve ablation trials have identified novel latent pulmonary vascular disease and preload subtypes, respectively.•Stress-based phenotyping (e.g., exercise) should be considered in future HFpEF trials to help uncover pathophysiologic subtypes.