{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:59:40Z","timestamp":1791381580484,"version":"4.3.3"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) carries a poor prognosis, and treatment decisions are often complicated by coexisting left-heart disease, lung disease, chronic thromboembolic disease, or pulmonary veno-occlusive disease-like vasculopathy. The role of sotatercept as part of initial therapy in treatment-naive SSc-PAH has not been established. We report a 60-year-old man with diffuse cutaneous systemic sclerosis, first recognized at referral 3 years after the onset of skin symptoms, and high-risk precapillary PAH. Careful evaluation showed no clinically significant parenchymal lung disease, chronic thromboembolic disease, or post-capillary physiology. Upfront therapy was started with macitentan, tadalafil, and sotatercept, with short-term dobutamine support for low-output hemodynamics. After 3 months, right heart catheterization showed marked improvement: pulmonary vascular resistance decreased from 12.6 to 3.7 Wood units, mean pulmonary arterial pressure decreased from 43 to 30 mmHg, and cardiac index increased from 1.50 to 2.90 L\/min\/m\u00b2. World Health Organization functional class improved from III to II, and risk status shifted to low risk by REVEAL Lite 2, COMPERA 2.0, and the Japanese Circulation Society\/Japanese Pulmonary Circulation and Pulmonary Hypertension Society 2025 model. No sotatercept-related adverse events were observed. This case documents the short-term course of upfront sotatercept-based triple therapy in carefully selected high-risk precapillary SSc-PAH.<\/jats:p>","DOI":"10.3389\/fcvm.2026.1956123","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:39:18Z","timestamp":1791380358000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Upfront sotatercept-based triple therapy in high-risk systemic sclerosis-associated pulmonary arterial hypertension"],"prefix":"10.3389","volume":"13","author":[{"given":"Yuichi","family":"Tamura","sequence":"first","affiliation":[{"name":"Pulmonary Hypertension Center, International University of Health and Welfare Mita Hospital","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarasa","family":"Isobe","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Center, International University of Health and Welfare Mita Hospital","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Fujii","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Center, International University of Health and Welfare Mita Hospital","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Shirai","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Kuwana","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1164\/rccm.200909-1331PP","article-title":"Systemic sclerosis-associated pulmonary arterial hypertension","volume":"181","author":"Le Pavec","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2200879","DOI":"10.1183\/13993003.00879-2022","article-title":"2022 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"61","author":"Humbert","year":"2023","journal-title":"Eur Respir J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-25-1144","article-title":"JCS\/JPCPHS 2025 guideline on pulmonary hypertension and pulmonary embolism\/deep vein thrombosis","author":"Tamura","year":"2026","journal-title":"Circ J"},{"key":"B4","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1136\/annrheumdis-2019-216274","article-title":"Initial combination therapy of ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) in the modified intention-to-treat population of the AMBITION study: post hoc analysis","volume":"79","author":"Kuwana","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1056\/NEJMoa2213558","article-title":"Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension","volume":"388","author":"Hoeper","year":"2023","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1056\/NEJMoa2415160","article-title":"Sotatercept in patients with pulmonary arterial hypertension at high risk for death","volume":"392","author":"Humbert","year":"2025","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1056\/NEJMoa2508170","article-title":"Sotatercept for pulmonary arterial hypertension within the first year after diagnosis","volume":"393","author":"McLaughlin","year":"2025","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"01209","DOI":"10.1183\/23120541.01209-2025","article-title":"Initial triple combination therapy including sotatercept in a patient with severe idiopathic pulmonary arterial hypertension: a case report","volume":"12","author":"Park","year":"2026","journal-title":"ERJ Open Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"92","DOI":"10.5301\/jsrd.5000235","article-title":"Complex pathophysiology of pulmonary hypertension associated with systemic sclerosis: potential unfavorable effects of vasodilators","volume":"2","author":"Shirai","year":"2017","journal-title":"J Scleroderma Relat Disord"},{"key":"B10","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/S2213-2600(24)00425-9","article-title":"Future treatment paradigms in pulmonary arterial hypertension: a personal view from physicians, health authorities, and patients","volume":"13","author":"Rahaghi","year":"2025","journal-title":"Lancet Respir Med"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1956123\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:39:20Z","timestamp":1791380360000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1956123\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":10,"alternative-id":["10.3389\/fcvm.2026.1956123"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1956123","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"1956123"}}