Chowdhury MA, Moukarbel GV, Gupta R, et al. - In this single-center prospective cohort study, researchers examined patients with heart failure with preserved ejection fraction (HFpEF) along with pulmonary hypertension (PH) in order to determine the role of big endothelin 1, endothelin 1 (ET1), and neprilysin in these individuals. This study included 90 HFpEF patients. Of these, 30 had no PH, 30 had postcapillary PH, and 30 had combined post- and precapillary PH. Increased ET1 in pulmonary veins (endothelin from the wedge; ET1W) was detected in patients with HFpEF-PH vs controls. The link of ET1W levels with both PH and pulmonary vascular resistance was identified. One-year heart failure hospitalization in HFpEF patients was predicted by ET1W and ET1 gradient (ET1G), while long-term mortality in HFpEF was reported in relation to elevated ET1G levels. The role of ET1 in developing PH in HFpEF patients was emphasized and the potential of ET1 as a prognostic biomarker was explored in this study.