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Among the left heart diseases, heart failure is the most frequent cause of PH. PH\u2010LHD is the most common cause of PH, accounting for 65\u201380% of diagnoses. Several drugs targeting specific signalling pathways involved in the pulmonary remodelling in PH\u2010LHD, including nitric oxide, MAP kinase and endothelin\u20101, have been tested in randomized clinical trials (RCTs), with disappointing results in terms of efficacy and safety. Therefore, PH\u2010LHD still remains orphan of specific therapies able to counteract the pre\u2010 and post\u2010capillary remodelling of the pulmonary circulation. In this article, we will discuss the pathophysiology and molecular mechanisms of PH\u2010LHD. We will focus on the emerging signalling pathways involved in the pathophysiology of PH\u2010LHD that could suggest novel molecular targets for the treatment of this condition.<\/jats:p>","DOI":"10.1111\/eci.70038","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T20:49:45Z","timestamp":1743367785000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pulmonary hypertension and associated heart failure: New insights on emerging signalling pathways"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7877-0035","authenticated-orcid":false,"given":"Rosalinda","family":"Madonna","sequence":"first","affiliation":[{"name":"Department of Surgical, Medical and Molecular Pathology and Critical Area, Cardiology Division University of Pisa  Pisa 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