Typically, chronic PH-LHD secondary to MR development leads to persistent PVR and fibrosis and the remolding of pulmonary vascular via pulmonary arterial and arteriole vasoconstriction and thickening characterized by endothelial injury and/or dysfunction, resulting in excessive collagen deposition, an imbalance in the endothelial production of nitric oxide (NO) and endothelin-1 (ET-1) [42]. Here, EDN1 is linked to miotic rate.