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Haemodynamics and oxygen transport responses were compared. HFpEF patients were then categorized a priori into previously-proposed, non-exclusive descriptive clinical trait phenogroups, including cardiometabolic, pulmonary vascular disease, left atrial myopathy, and vascular stiffening phenogroups based on clinical and haemodynamic profiles to contrast pathophysiology and clinical risk. Overall, patients with HFpEF (n\u2009=\u2009643) had impaired cardiac output reserve with exercise (2.3 vs. 2.8\u2009L\/min, p\u2009=\u20090.025) and greater reliance on peripheral oxygen extraction augmentation (4.5 vs. 3.8\u2009ml\/dl, p\u2009&amp;lt;\u20090.001) compared to dyspnoeic controls (n\u2009=\u2009219). Most (94%) patients with HFpEF met criteria for at least one clinical phenogroup, and 67% fulfilled criteria for multiple overlapping phenogroups. There was greater impairment in peripheral limitations in the cardiometabolic group and greater cardiac output limitations and higher pulmonary vascular resistance during exertion in the other phenogroups. Increasing trait multiplicity within a given patient was associated with worse exercise haemodynamics, poorer exercise capacity, lower cardiac output reserve, and greater risk for heart failure hospitalization or death (hazard ratio 1.74, 95% confidence interval 1.08\u20132.79 for 0\u20131 vs. \u22652 phenogroup traits present).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Though cardiac output response to exercise is limited in patients with HFpEF compared to those with non-cardiac dyspnoea, the relative contributions of cardiac and peripheral limitations vary with differing numbers and types of clinical phenotypic traits present. Patients fulfilling criteria for greater multiplicity and diversity of HFpEF phenogroup traits have poorer exercise capacity, worsening haemodynamic perturbations, and greater risk for adverse outcome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3105","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T06:04:16Z","timestamp":1703829856000},"page":"564-577","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Clinical Phenogroup Diversity and Multiplicity: Impact on Mechanisms of Exercise Intolerance in Heart Failure with Preserved Ejection Fraction"],"prefix":"10.1093","volume":"26","author":[{"given":"Kathryn","family":"Larson","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massar","family":"Omar","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , Rochester, MN ,","place":["USA"]},{"name":"Department of Cardiology, Odense University Hospital , Odense ,","place":["Denmark"]},{"name":"Steno Diabetes Center, Odense University Hospital , Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidemi","family":"Sorimachi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , Rochester, MN ,","place":["USA"]},{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine , Maebashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Omote","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Alogna","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , Rochester, MN ,","place":["USA"]},{"name":"Deutsches Herzzentrum der Charit\u00e9, Department of Cardiology, Angiology and Intensive Care Medicine, Campus Virchow-Klinikum , Berlin ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejana","family":"Popovic","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , Rochester, MN 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