{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:22:18Z","timestamp":1793499738655,"version":"4.5.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 HL084946"],"award-info":[{"award-number":["P50 HL084946"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL114910"],"award-info":[{"award-number":["HL114910"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23HL90038491"],"award-info":[{"award-number":["K23HL90038491"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is a rare disease characterized by a very dismal response to therapy and poor survival. We assessed the effects of up-front combination PAH therapy in patients with SSc-PAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective, multicenter, open-label trial, 24 treatment-naive patients with SSc-PAH received ambrisentan 10 mg and tadalafil 40 mg daily for 36 weeks. Functional, hemodynamic, and imaging (cardiac magnetic resonance imaging and echocardiography) assessments at baseline and 36 weeks included changes in right ventricular (RV) mass and pulmonary vascular resistance as co\u2013primary endpoints and stroke volume\/pulmonary pulse pressure ratio, tricuspid annular plane systolic excursion, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide as secondary endpoints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At 36 weeks, we found that treatment had resulted in significant reductions in median (interquartile range [IQR]) RV mass (28.0 g [IQR, 20.6\u201332.9] vs. 32.5 g [IQR, 23.2\u201341.4]; P\u2009&amp;lt;\u20090.05) and median pulmonary vascular resistance (3.1 Wood units [IQR, 2.0\u20135.7] vs. 6.9 Wood units [IQR, 4.0\u201312.9]; P\u2009&amp;lt;\u20090.0001) and in improvements in median stroke volume\/pulmonary pulse pressure ratio (2.6 ml\/mm Hg [IQR, 1.8\u20133.5] vs. 1.4 ml\/mm Hg [IQR 8.9\u20132.4]; P\u2009&amp;lt;\u20090.0001) and mean (\u2009\u00b1\u2009SD) tricuspid annular plane systolic excursion (2.2\u2009\u00b1\u20090.12 cm vs. 1.65\u2009\u00b1\u20090.11 cm; P\u2009&amp;lt;\u20090.0001), 6-minute walk distance (395\u2009\u00b1\u200999 m vs. 343\u2009\u00b1\u2009131 m; P\u2009=\u20090.001), and serum N-terminal pro-brain natriuretic peptide (647\u2009\u00b1\u20091,127 pg\/ml vs. 1,578\u2009\u00b1\u20092,647 pg\/ml; P\u2009&amp;lt;\u20090.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Up-front combination therapy with ambrisentan and tadalafil significantly improved hemodynamics, RV structure and function, and functional status in treatment-naive patients with SSc-PAH and may represent a very effective therapy for this patient population. In addition, we identified novel hemodynamic and imaging biomarkers that could have potential value in future clinical trials.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT01042158).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201507-1398oc","type":"journal-article","created":{"date-parts":[[2015,9,11]],"date-time":"2015-09-11T16:14:31Z","timestamp":1441988071000},"page":"1102-1110","source":"Crossref","is-referenced-by-count":155,"title":["Ambrisentan and Tadalafil Up-front Combination Therapy in Scleroderma-associated Pulmonary Arterial Hypertension"],"prefix":"10.1093","volume":"192","author":[{"given":"Paul M.","family":"Hassoun","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roham T.","family":"Zamanian","sequence":"additional","affiliation":[{"name":"Division of Pulmonary & Critical Care Medicine, 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Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia L.","family":"Hulme","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Traci","family":"Housten","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Pisanello","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica H.","family":"Pullins","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia P.","family":"Corona-Villalobos","sequence":"additional","affiliation":[{"name":"Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan L.","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Gashouta","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar A.","family":"Minai","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, The Cleveland Clinic, Cleveland, 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