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Many patients with HFpEF demonstrate an abnormal pulmonary haemodynamic response to exercise that is not identifiable at rest. This can be estimated non-invasively by the mean pulmonary artery pressure\u2013cardiac output relationship (mPAP\/CO slope). We sought to characterize the pathophysiology of disproportionate exercise-induced PH in relation to CO (DEi-PH) and its prognostic impact in patients with HFpEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>A total of 345 patients (166 HFpEF and 179 controls) underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. DEi-PH was defined as the mPAP\/CO slope\u2009&amp;gt;5.2\u2009mmHg\/L\/min (median value). At rest, there were no differences in right ventricular (RV) function and severity of PH between HFpEF patients with and without DEi-PH. Compared with controls (n = 179) and HFpEF without DEi-PH (n = 83), HFpEF with DEi-PH (n = 83) demonstrated worse exercise capacity (lower peak oxygen consumption), depressed RV systolic function, impaired RV\u2013pulmonary artery coupling, limitation in CO augmentation, more right-sided congestion, and worse ventilatory efficiency (higher minute ventilation vs. carbon dioxide volume) during peak exercise. Kaplan\u2013Meier analyses showed that HFpEF patients with DEi-PH had higher rates of composite outcomes of all-cause mortality or heart failure events than those without (log-rank p = 0.0002).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients with HFpEF and DEi-PH demonstrated distinct pathophysiologic features that become apparent only during exercise. These data suggest that DEi-PH is a pathophysiologic phenotype of HFpEF and reinforce the importance of exercise stress echocardiography for detailed characterization of HFpEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2821","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T01:59:15Z","timestamp":1678759155000},"page":"792-802","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Disproportionate Exercise-Induced Pulmonary Hypertension in Relation to Cardiac Output in Heart Failure with Preserved Ejection Fraction: A Non-Invasive Echocardiographic Study"],"prefix":"10.1093","volume":"25","author":[{"given":"Yuki","family":"Saito","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine , Maebashi ,","place":["Japan"]},{"name":"Division of Cardiology, Department of Medicine, Nihon University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Obokata","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine , Maebashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonari","family":"Harada","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine , Maebashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Kagami","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine , Maebashi ,","place":["Japan"]},{"name":"Division of Cardiovascular Medicine, National Defense Medical College , Tokorozawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidemi","family":"Sorimachi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine , Maebashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Yuasa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine , Maebashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimitsu","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine , Maebashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Gunma University Graduate School of Medicine , Maebashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Okumura","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Nihon University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine , Maebashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"2026010913092937300_ejhf2821-bib-0001","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cpcardiol.2015.12.002","article-title":"Heart failure with preserved ejection fraction","volume":"41","author":"Reddy","year":"2016","journal-title":"Curr Probl Cardiol"},{"key":"2026010913092937300_ejhf2821-bib-0002","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jcmg.2018.12.034","article-title":"Diastolic dysfunction and heart failure with preserved ejection fraction: understanding mechanisms by using noninvasive methods","volume":"13","author":"Obokata","year":"2020","journal-title":"JACC Cardiovasc Imaging"},{"key":"2026010913092937300_ejhf2821-bib-0003","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1161\/CIRCULATIONAHA.116.021884","article-title":"Phenotype-specific treatment of heart failure with preserved ejection fraction","volume":"134","author":"Shah","year":"2016","journal-title":"Circulation"},{"key":"2026010913092937300_ejhf2821-bib-0004","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.jacc.2008.11.051","article-title":"Pulmonary hypertension in heart failure with preserved ejection fraction. 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