EDN1 and Myocardial fibrosis: We previously demonstrated that increased RV pressure-load induces biventricular myocardial fibrosis and apoptosis in association with ET-1, TGF-β1 and CTGF signaling.[8,18] In the current study, we show that these effects, especially fibrosis, can be ameliorated by the dual endothelin receptor blocker macitentan, in association with improved biventricular function and independent of its effects on pulmonary vascular resistance.