EDN1 and pulmonary arterial hypertension: Despite mechanistic similarities between PH-HFpEF and WHO Group I pulmonary arterial hypertension (PAH), such as elevated endothelin 1 (ET-1), lack of nitric oxide (NO), and decreased prostacyclin (PGI2), previous clinical trials that therapeutically targeted these pathways were beneficial in PAH, but demonstrated minimal or no effects in patients with PH-LHD (1).