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Group 1 PH + high HFpEF probability was associated with enhanced tryptophan metabolism with higher downstream kynurenine metabolite concentrations and lower serotonin concentrations (FDR P\u2009&amp;lt;\u20090.002 for all, n\u2009=\u2009193, t test). Linoleate (precursor to arachidonic acid and prostaglandins) and arginine and homoarginine (precursors to nitric oxide) were all lower in group 1 PH + high HFpEF probability (FDR P\u2009&amp;lt;\u20090.03 for all, n\u2009=\u2009193, t test). Metabolome changes in group 1 PH + high HFpEF probability overlapped with clinical HFpEF (n\u2009=\u2009240) but were abnormal relative to control subjects (n\u2009=\u200985) (P\u2009&amp;lt;\u20090.0001 for all, n\u2009=\u2009456, t test). There was no evidence of differential transpulmonary uptake\/release of most metabolites, suggesting probable nonpulmonary origin (except for serotonin, interaction P\u2009=\u20090.04; and kynurenine, interaction P\u2009=\u20090.03; n\u2009=\u2009433, mixed model).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with group 1 PH + high HFpEF probability have a unique metabolome characterized by enhanced tryptophan-kynurenine pathway breakdown, deficiency of amino acids (such as glycine and serine), lower serotonin, and decreased prostaglandin and nitric oxide precursors. Despite fulfilling clinical criteria for group 1 PH, these metabolome changes were comparable with clinical HFpEF, supporting biological overlap between these two forms of PH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202501-0034oc","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T16:48:25Z","timestamp":1749833305000},"page":"1701-1713","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":11,"title":["Metabolomic Evidence of Biological Overlap with Heart Failure with Preserved Ejection Fraction in a Subset of Pulmonary Arterial Hypertension"],"prefix":"10.1093","volume":"211","author":[{"given":"Yogesh N. 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