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To test this, we performed metabolomic analyses on 30\u00a0PH individuals and 12 controls. Furthermore, using 2\u2010[18F]fluoro\u20102\u2010deoxy\u2010D\u2010glucose positron emission tomography, we dichotomized PH patients into metabolic phenotypes of high and low right ventricle (RV) glucose uptake and followed them longitudinally. In support of metabolic alterations in PH and its progression, the high RV glucose group had higher RV systolic pressure (p\u2009&lt;\u20090.001), worse RV function as measured by RV fractional area change and peak global longitudinal strain (both p\u2009&lt;\u20090.05) and may be associated with poorer outcomes (33% death or transplantation in the high glucose RV uptake group compared to 7% in the low RV glucose uptake group at five years follow\u2010up, log\u2010ranked p\u2009=\u20090.07). Pathway enrichment analysis identified key metabolic pathways including fructose catabolism, arginine\u2010nitric oxide metabolism, tricarboxylic acid cycle, and ketones metabolism. Integrative human protein\u2010protein interactome network analysis of metabolomic and transcriptomic data identified key pathobiological pathways: arginine biosynthesis, tricarboxylic acid cycle, purine metabolism, hypoxia\u2010inducible factor 1, and apelin signaling. These findings identify a PH metabolomic endophenotype, and for the first time link this to disease severity and outcomes.<\/jats:p>","DOI":"10.1177\/20458940211054325","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T17:28:16Z","timestamp":1633714096000},"page":"1-12","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Metabolic endophenotype associated with right ventricular glucose uptake in pulmonary hypertension"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4800-8928","authenticated-orcid":false,"given":"Samar","family":"Farha","sequence":"first","affiliation":[{"name":"Lerner Research Institute Cleveland Clinic Cleveland OH USA"},{"name":"Respiratory Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzy","family":"Comhair","sequence":"additional","affiliation":[{"name":"Lerner Research Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Hou","sequence":"additional","affiliation":[{"name":"Lerner Research Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M.","family":"Park","sequence":"additional","affiliation":[{"name":"Lerner Research Institute Cleveland Clinic Cleveland OH USA"},{"name":"Heart Vascular and Thoracic Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Sharp","sequence":"additional","affiliation":[{"name":"Lerner Research Institute Cleveland Clinic Cleveland OH USA"},{"name":"Heart Vascular and Thoracic Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Peterson","sequence":"additional","affiliation":[{"name":"Lerner Research Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"Willard","sequence":"additional","affiliation":[{"name":"Lerner Research Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lerner Research Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank P.","family":"DiFilippo","sequence":"additional","affiliation":[{"name":"Imaging Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Neumann","sequence":"additional","affiliation":[{"name":"Imaging Institute Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.H. 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