{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:31:52Z","timestamp":1790105512194,"version":"4.0.1"},"reference-count":0,"publisher":"European Respiratory Society (ERS)","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/publications.ersnet.org\/user-licence"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K23HL164901"],"award-info":[{"award-number":["K23HL164901"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2025,12,3]]},"abstract":"\n Background<\/jats:title>\n Pulmonary vasodilators increase cardiac output (CO) in group 1 PH and can cause high CO with unclear implications.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To describe pathophysiology of high CO in group 1 PH.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Clinical characteristics were compared among PVDOMICS group 1 PH participants by low (cardiac index (CI) <2.2\u2005L\n \u00b7<\/jats:italic>\n min\n \u22121<\/jats:sup>\n \u00b7m\n \u22122<\/jats:sup>\n ),normal, or high output (CO>8\u2005L\u00b7min\n \u22121<\/jats:sup>\n or CI>4\u2005L\n \u00b7<\/jats:italic>\n min\n \u22121<\/jats:sup>\n \u00b7m\n \u22122<\/jats:sup>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Measurements and Main Results<\/jats:title>\n \n Of 449 group 1 PH participants, 23%(n=103) had low output, 68%(n=304) had normal CO and 9%(n=42) had high output. Increasing CO was associated with more intensive vasodilator use (triple therapy 11\/19\/33%,p=0.0008), with progressively lower PVR (p<0.0001). High output was associated with the lowest systemic vascular resistance (p<0.0001), with greater LV and LA enlargement (p<0.001 for all). High flow resulted in increase in LV and RV work at rest, and absolute\/relative RV work during exercise (p<0.0001 for all). Despite greater exercise O\n 2<\/jats:sub>\n delivery (p<0.0001), peripheral O\n 2<\/jats:sub>\n utilization was impaired by O\n 2<\/jats:sub>\n extraction ratio (p=0.001) and AVO\n 2<\/jats:sub>\n difference (p=0.005), without incremental functional or survival benefit compared to normal output PH. After adjusting for baseline risk, high output had increased risk of death\/transplant compared to normal output [adjusted HR 2.1 (95% 1.2\u20133.7), p=0.007]. In a validation cohort (n=37), 93% had normal CO at diagnosis, with the high output state developing in follow-up after vasodilator initiation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n 1 in 10 patients with group 1 PH has a high output state which is most common in prevalent PH and related to vasodilator intensity, with adverse cardiac remodeling and myocardial workload. Further studies are needed to determine optimal vasodilator dosing with high output, and therapeutic interaction with vasodilator sparing therapies such as sotatercept.<\/jats:p>\n <\/jats:sec>","DOI":"10.1183\/13993003.01871-2025","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T16:35:27Z","timestamp":1771518927000},"page":"2501871","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Pathophysiology and prevalence of high output heart failure in group 1 pulmonary hypertension"],"prefix":"10.1183","author":[{"given":"Yogesh N. V.","family":"Reddy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4128-3978","authenticated-orcid":false,"given":"Robert P.","family":"Frantz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revati","family":"Varma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Hassoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna R.","family":"Hemnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Horn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane A.","family":"Leopold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Rischard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika B.","family":"Rosenzweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas S.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serpil C.","family":"Erzurum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald J.","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar","family":"Farha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Emanuel","family":"Finet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Jellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-7209","authenticated-orcid":false,"given":"Stephen","family":"Mathai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. H. Wilson","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry A","family":"Borlaug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the PVDOMICS Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2026,2,19]]},"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.01871-2025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T16:35:27Z","timestamp":1771518927000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.01871-2025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":0,"alternative-id":["10.1183\/13993003.01871-2025"],"URL":"https:\/\/doi.org\/10.1183\/13993003.01871-2025","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]}}}