{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:03:23Z","timestamp":1789005803511,"version":"build-2803163510"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,8,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In the FUEL (Fontan Udenafil Exercise Longitudinal) trial, a positive treatment effect was identified for outcomes at the ventilatory anaerobic threshold but not for the primary outcome, oxygen consumption (V\n              <jats:sc>o<\/jats:sc>\n              <jats:sub>2<\/jats:sub>\n              ) at peak exercise. This disparate response may be explained by the physiologic challenge of improving peak V\n              <jats:sc>o<\/jats:sc>\n              <jats:sub>2<\/jats:sub>\n              in participants with near\u2010normal baseline exercise performance.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Participants were divided into subgroups by baseline predicted peak V\n              <jats:sc>o<\/jats:sc>\n              <jats:sub>2<\/jats:sub>\n              (&lt;80% versus \u226580%). Treatment effect was evaluated in those with a baseline peak V\n              <jats:sc>o<\/jats:sc>\n              <jats:sub>2<\/jats:sub>\n              &lt;80% predicted and linear regression was performed to examine the interaction between subgroup and response to therapy for the primary and secondary outcomes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Of the 379 participants with paired exercise data, 302 (80%) had a baseline peak V\n              <jats:sc>o<\/jats:sc>\n              <jats:sub>2<\/jats:sub>\n              &lt;80% predicted. In this subgroup, the primary outcome of peak V\n              <jats:sc>o<\/jats:sc>\n              <jats:sub>2<\/jats:sub>\n              improved significantly after 6 months of udenafil treatment, when compared with placebo (0.23\u00b14.17\u2009mL\/kg per min versus \u22120.90\u00b13.74\u2009mL\/kg per min;\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.021). Secondary outcome measures, including V\n              <jats:sc>o<\/jats:sc>\n              <jats:sub>2<\/jats:sub>\n              at ventilatory anaerobic threshold (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.023), work at ventilatory anaerobic threshold (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.032), and the myocardial performance index (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.007) were all significantly improved as well. A significant interaction was found between exercise subgroups and response to udenafil for peak V\n              <jats:sc>o<\/jats:sc>\n              <jats:sub>2<\/jats:sub>\n              (\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.036) but not for other outcomes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In this post hoc subgroup analysis, after exclusion of patients with Fontan circulation with near\u2010normal baseline peak V\n              <jats:sc>o<\/jats:sc>\n              <jats:sub>2<\/jats:sub>\n              , a positive treatment effect of udenafil was identified for the primary outcome of peak V\n              <jats:sc>o<\/jats:sc>\n              <jats:sub>2<\/jats:sub>\n              . The interaction between baseline peak V\n              <jats:sc>o<\/jats:sc>\n              <jats:sub>2<\/jats:sub>\n              and treatment may have influenced the outcome of the FUEL trial.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\">https:\/\/clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT0274115.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.125.041348","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T11:28:22Z","timestamp":1754998102000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Revisiting the Effect of Udenafil on Exercise Performance in Patients With Fontan Circulation: Results of a Post Hoc Analysis of the FUEL Trial"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4194-2067","authenticated-orcid":false,"given":"David J.","family":"Goldberg","sequence":"first","affiliation":[{"name":"The Children\u2019s Hospital of Philadelphia, Perelman School of Medicine","place":["Philadelphia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Zak","sequence":"additional","affiliation":[{"name":"Carelon Research","place":["Newton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenwei","family":"Hu","sequence":"additional","affiliation":[{"name":"Carelon Research","place":["Newton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6401-9980","authenticated-orcid":false,"given":"Adam M.","family":"Lubert","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine","place":["Cincinnati, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7149-5421","authenticated-orcid":false,"given":"Rahul H.","family":"Rathod","sequence":"additional","affiliation":[{"name":"Harvard Medical School","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Penny","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3810-7132","authenticated-orcid":false,"given":"Robert","family":"Whitehill","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8659-736X","authenticated-orcid":false,"given":"Kurt R.","family":"Schumacher","sequence":"additional","affiliation":[{"name":"C.S. 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