{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:10:07Z","timestamp":1793419807746,"version":"4.5.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","funder":[{"name":"Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, USA"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,5,12]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Combined post- and precapillary pulmonary hypertension in heart failure with preserved ejection fraction involves remodeling in both the heart and pulmonary vasculature. Despite significant mortality, there are no proven therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>In this multicenter, randomized, placebo-controlled, phase 2 trial, adults received sotatercept (0.3 or 0.7 mg\/kg) or placebo every 3 weeks. The primary end point was change in pulmonary vascular resistance at week 24. Hodges-Lehmann shift estimates described placebo-adjusted changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      A total of 164 patients were randomized 54:55:55 to sotatercept 0.3 mg\/kg, 0.7 mg\/kg, and placebo, and baseline median pulmonary vascular resistance was 5.2 (interquartile range, 4.0\u20136.9) Wood units. The median change from baseline in pulmonary vascular resistance at week 24 was \u22120.67 Wood units in the sotatercept 0.3 mg\/kg group, \u22120.33 Wood units in the sotatercept 0.7 mg\/kg group, and 0.26 Wood units in the placebo group. The Hodges-Lehmann shift estimates in pulmonary vascular resistance were \u22121.02 Wood units (95% CI, \u22121.81 to \u22120.23;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.004) for 0.3 mg\/kg and \u22120.75 Wood units (95% CI, \u22121.52 to 0.03;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.024) for 0.7 mg\/kg sotatercept. Reductions were observed in mean pulmonary arterial pressure (0.3 and 0.7 mg\/kg: \u22129.19 mm\u2009Hg [95% CI, \u221213.00 to \u22125.38] and \u22129.22 [95% CI, \u221212.97 to \u22125.46]) and pulmonary arterial wedge pressure (0.3 and 0.7 mg\/kg: \u22123.04 mm\u2009Hg [95% CI, \u22125.77 to \u22120.32] and \u22122.53 [95% CI, \u22125.33 to 0.28]). Changes in 6-minute walk distance were 20.3 m (95% CI, 1.5\u201339.1) for 0.3 mg\/kg and 5.8 m (95% CI, \u221217.3 to 28.9) for 0.7 mg\/kg sotatercept. The most common adverse events with sotatercept (both groups) were increased hemoglobin and diarrhea.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These findings provide proof of concept for improved pulmonary vascular and cardiac hemodynamics after activin signaling inhibition with sotatercept in patients with combined post- and precapillary pulmonary hypertension in heart failure with preserved ejection fraction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT04945460.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.126.079918","type":"journal-article","created":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T16:00:30Z","timestamp":1774800030000},"page":"1446-1459","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Sotatercept for Combined Post- and Precapillary Pulmonary Hypertension Associated With Heart Failure: Results From the Phase 2, Randomized, Placebo-Controlled CADENCE Study"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0482-4560","authenticated-orcid":true,"given":"Mardi","family":"Gomberg-Maitland","sequence":"first","affiliation":[{"name":"Department of Medicine, Section of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (M.G-M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9045-7722","authenticated-orcid":true,"given":"Ryan J.","family":"Tedford","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston (R.J.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6495-0094","authenticated-orcid":true,"given":"David","family":"Langleben","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Cardiology, Center for Pulmonary Vascular Disease, Azrieli Heart Center, Jewish General Hospital, McGill University, Montreal, Canada (D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6237-1470","authenticated-orcid":true,"given":"Stephan","family":"Rosenkranz","sequence":"additional","affiliation":[{"name":"Heart Center, Department of Cardiology, Cologne University Hospital, Cologne Cardiovascular Research Center, Germany (S.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Miller","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc, Rahway, NJ (B.M., A.D.J., A.U., C.J.M., A.G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8302-8943","authenticated-orcid":true,"given":"Aaron D.","family":"Jones","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc, Rahway, NJ (B.M., A.D.J., A.U., C.J.M., A.G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9824-2398","authenticated-orcid":true,"given":"Alessia","family":"Urbinati","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc, Rahway, NJ (B.M., A.D.J., A.U., C.J.M., A.G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciaran J.","family":"McMullan","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc, Rahway, NJ (B.M., A.D.J., A.U., C.J.M., A.G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra G.","family":"Cornell","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc, Rahway, NJ (B.M., A.D.J., A.U., C.J.M., A.G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Vachiery","sequence":"additional","affiliation":[{"name":"Department of Cardiology, H\u00f4pital Universitaire de Bruxelles Erasme, Brussels, Belgium (J-L.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab368"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.320257"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00879-2022"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac237"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2024.107817"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.09.942"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01344-2024"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2026.01.024"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1053\/pcad.2002.130041"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26094265"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM195605032541803"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2025.1579112"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201503-0529OC"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30317-9"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac184"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy809"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01886-2017"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.124.069340"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.2024"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv336"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024277"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2213558"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2415160"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2508170"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1064290"},{"key":"e_1_3_3_27_2","volume-title":"Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels","author":"Dolgin M","unstructured":"Dolgin M, Fox AC, Gorlin R, Levin RI, New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Little, Brown-1994.","edition":"9"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1198\/tast.2010.08121"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1214\/aoms\/1177704575"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0197-2456(99)00022-7"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1177\/0962280206074463"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1080\/10629360600810434"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780040211"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201801-0081PP"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2013.12.012"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad195"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01107-2023"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.123.011227"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.065134"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2026.02.5103"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2010.10.006"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8101757"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13051265"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.126.079918","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T18:06:07Z","timestamp":1782151567000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.126.079918"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":42,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,5,12]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.126.079918"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.126.079918","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,12]]},"assertion":[{"value":"2026-02-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}