{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T09:15:09Z","timestamp":1782983709703,"version":"3.54.5"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Pulmonary arterial hypertension (PAH) is a rare but life-threatening disease that presents particular therapeutic challenges in children. It is characterized by pulmonary vasoconstriction and vascular remodeling, leading to right ventricular strain and eventually right heart failure. Although advances in pharmacotherapy have improved outcomes, treatment options remain limited. This review aims to evaluate the potential role of sotatercept, a novel fusion protein recently approved for adult PAH, and to assess the translatability of adult data to the pediatric population. Methods: A narrative synthesis of preclinical studies and randomized controlled trials was conducted to summarize the current evidence on sotatercept. In addition, pathophysiological, developmental, and therapeutic differences between adult and pediatric PAH were critically examined to assess relevance and applicability to younger patients. Results: Clinical trials in adults (PULSAR, STELLAR, ZENITH, HYPERION) confirm sotatercept\u2019s efficacy on background therapy, with significant reductions in pulmonary vascular resistance, improvements in 6 min walk distance, enhanced right ventricular function, and risk reductions in clinical worsening events. However, extrapolation to pediatric PAH faces challenges including etiological differences (e.g., PAH-CHD predominance, PPHN in infants), age-inappropriate endpoints (e.g., 6MWD infeasible in young children), variable growth-related pharmacokinetics, and compensatory RV physiology delaying overt failure. Safety concerns are manageable in adults but raise pediatric-specific alarms: activin inhibition\u2019s theoretical tumorigenic potential (dual tumor suppressor\/promoter role), pubertal\/fertility disruption (FSH suppression, gonadal maturation delay), and skeletal growth interference\u2014unproven clinically yet demanding long-term monitoring. The ongoing MOONBEAM trial will provide initial pharmacokinetic\/safety data in children. Conclusions: Sotatercept represents a promising, first-in-class therapeutic option for PAH with the potential to transform disease management. Nevertheless, dedicated pediatric studies are crucial to confirm safety, efficacy, and appropriate dosing and to define its role in the long-term treatment of children with PAH.<\/jats:p>","DOI":"10.3390\/children13040465","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:40:52Z","timestamp":1774878052000},"page":"465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sotatercept in Children with Pulmonary Hypertension\u2014A Narrative Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2268-0774","authenticated-orcid":false,"given":"Johanna","family":"Schulz","sequence":"first","affiliation":[{"name":"Pediatric Cardiology, Children\u2019s Heart Clinic, University Heart & Vascular Center Hamburg, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3978-1804","authenticated-orcid":false,"given":"Veronika C.","family":"Stark","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Children\u2019s Heart Clinic, University Heart & Vascular Center Hamburg, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Harbaum","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, Department of Internal Medicine II, University Medical Centre Hamburg-Eppendorf Hamburg, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6222-2683","authenticated-orcid":false,"given":"Rainer","family":"Kozlik-Feldmann","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Children\u2019s Heart Clinic, University Heart & Vascular Center Hamburg, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8337-5187","authenticated-orcid":false,"given":"Thomas S.","family":"Mir","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Children\u2019s Heart Clinic, University Heart & Vascular Center Hamburg, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fridrike","family":"Stute","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Children\u2019s Heart Clinic, University Heart & Vascular Center Hamburg, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4449-7739","authenticated-orcid":false,"given":"Jakob","family":"Olfe","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Children\u2019s Heart Clinic, University Heart & Vascular Center Hamburg, Martinistra\u00dfe 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/S2213-2600(15)00543-3","article-title":"A global view of pulmonary hypertension","volume":"4","author":"Hoeper","year":"2016","journal-title":"Lancet Respir. 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