Pulmonary hypertension and associated heart failure: New insights on emerging signalling pathways

Abstract Pulmonary hypertension associated with left heart disease (PH‐LHD) represents the hemodynamic condition at rest resulting from pathologies that affect the left ventricle and/or the left atrium. Among the left heart diseases, heart failure is the most frequent cause of PH. PH‐LHD is the most common cause of PH, accounting for 65–80% of diagnoses. Several drugs targeting specific signalling pathways involved in the pulmonary remodelling in PH‐LHD, including nitric oxide, MAP kinase and endothelin‐1, have been tested in randomized clinical trials (RCTs), with disappointing results in terms of efficacy and safety. Therefore, PH‐LHD still remains orphan of specific therapies able to counteract the pre‐ and post‐capillary remodelling of the pulmonary circulation. In this article, we will discuss the pathophysiology and molecular mechanisms of PH‐LHD. We will focus on the emerging signalling pathways involved in the pathophysiology of PH‐LHD that could suggest novel molecular targets for the treatment of this condition.