{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T15:47:44Z","timestamp":1776440864819,"version":"3.51.2"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Imaging"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>The FUEL trial (Fontan Udenafil Exercise Longitudinal) demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle function in this cohort has not been studied.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>The 400 enrolled participants were randomized 1:1 to udenafil or placebo. Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil\/placebo. Linear regression compared change from baseline indices of single ventricle systolic, diastolic and global function, atrioventricular valve regurgitation, and mean Fontan fenestration gradient in the udenafil cohort versus placebo, controlling for ventricular morphology (left ventricle versus right ventricle\/other) and baseline value.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              The udenafil participants (n=191) had significantly improved between baseline and 26 weeks visits compared to placebo participants (n=195) in myocardial performance index (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.03, adjusted mean difference [SE] of changes between groups \u22120.03[0.01]), atrioventricular valve inflow peak E (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.009, 3.95 [1.50]), and A velocities (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.034, 3.46 [1.62]), and annular Doppler tissue imaging-derived peak e\u2032 velocity (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.008, 0.60[0.23]). There were no significant differences in change in single ventricle size, systolic function, atrioventricular valve regurgitation severity, or mean fenestration gradient. Participants with a dominant left ventricle had significantly more favorable baseline values of indices of single ventricle size and function (lower volumes and areas, E\/e\u2032 ratio, systolic:diastolic time and atrioventricular valve regurgitation, and higher annular s\u2032 and e\u2032 velocity).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and\/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\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: NCT02741115.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circimaging.121.013676","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T19:00:40Z","timestamp":1668538840000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants"],"prefix":"10.1161","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct02741115","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0346-8517","authenticated-orcid":true,"given":"Michael V.","family":"Di Maria","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO (M.V.D.M.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA (D.J.G., S.M.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Zak","sequence":"additional","affiliation":[{"name":"Healthcore, Watertown, MA (V.Z., C.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenwei","family":"Hu","sequence":"additional","affiliation":[{"name":"Healthcore, Watertown, MA (V.Z., C.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6401-9980","authenticated-orcid":true,"given":"Adam M.","family":"Lubert","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital, Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine, OH (A.M., B.H.G., E.M.U.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreea","family":"Dragulescu","sequence":"additional","affiliation":[{"name":"Hospital for Sick Children, Toronto, Ontario, Canada (A.D.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew S.","family":"Mackie","sequence":"additional","affiliation":[{"name":"Stollery Children\u2019s Hospital, University of Alberta, Edmonton, Canada (A.S.M.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"McCrary","sequence":"additional","affiliation":[{"name":"Duke University, Durham, NC (A.M.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5712-6470","authenticated-orcid":true,"given":"Angela","family":"Weingarten","sequence":"additional","affiliation":[{"name":"Vanderbilt Heart and Vascular Institute, Nashville, TN (A.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anitha","family":"Parthiban","sequence":"additional","affiliation":[{"name":"Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX (A.P., P.E.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Goot","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI (B.G., M.S., P.C.F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8508-9523","authenticated-orcid":true,"given":"Bryan H.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital, Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine, OH (A.M., B.H.G., E.M.U.)."},{"name":"UPMC Children\u2019s Hospital of Pittsburgh, University of Pittsburgh, PA (B.H.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn","family":"Taylor","sequence":"additional","affiliation":[{"name":"Shawn Jenkins Children\u2019s Hospital, Medical University of South Carolina, Charleston, SC (C.T.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9173-2458","authenticated-orcid":true,"given":"Christopher","family":"Lindblade","sequence":"additional","affiliation":[{"name":"Phoenix Children\u2019s Hospital, University of Arizona, Phoenix, AZ (C.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9939-3048","authenticated-orcid":true,"given":"Christopher J.","family":"Petit","sequence":"additional","affiliation":[{"name":"Children\u2019s Heart Center, Emory University School of Medicine, Atlanta, GA (C.J.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Spurney","sequence":"additional","affiliation":[{"name":"Children\u2019s National Hospital, Washington, DC (C.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Harrild","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital, MA (D.M.H.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5640-6777","authenticated-orcid":true,"given":"Elaine M.","family":"Urbina","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital, Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine, OH (A.M., B.H.G., E.M.U.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9106-8486","authenticated-orcid":true,"given":"Eleanor","family":"Schuchardt","sequence":"additional","affiliation":[{"name":"Rady Children\u2019s Hospital, University of California San Diego, CA (E.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gi","family":"Beom Kim","sequence":"additional","affiliation":[{"name":"Seoul National University Children\u2019s Hospital, Seoul National University College of Medicine, South Korea (G.B.K.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6104-5259","authenticated-orcid":true,"given":"Ja","family":"Kyoung Yoon","sequence":"additional","affiliation":[{"name":"Sejong Hospital Cardiovascular Center, Department of Pediatrics, Bucheon, South Korea (J.K.Y.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie N.","family":"Colombo","sequence":"additional","affiliation":[{"name":"St. Louis Children\u2019s Hospital, Washington University School of Medicine, St Louis, MO (J.N.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew D.","family":"Files","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Hospital, University of Washington, Seattle, WA (M.D.F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Schoessling","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI (B.G., M.S., P.C.F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Ermis","sequence":"additional","affiliation":[{"name":"Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX (A.P., P.E.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3794-5887","authenticated-orcid":true,"given":"Pierre C.","family":"Wong","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Los Angeles, Keck School of Medicine of USC, Los Angeles, CA (P.C.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruchira","family":"Garg","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute, Cedars-Sinai, Los Angeles, CA (R.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara K.","family":"Swanson","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital and Medical Center, Omaha, NE (S.K.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaji C.","family":"Menon","sequence":"additional","affiliation":[{"name":"Primary Children\u2019s Hospital, University of Utah, Salt Lake City, UT (S.C.M.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shubhika","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Nemours, AI DuPont, Wilmington, DE (S.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thor","family":"Thorsson","sequence":"additional","affiliation":[{"name":"C.S. Mott Children\u2019s Hospital, University of Michigan Congenital Heart Center, Ann Arbor, MI (T.T.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffanie R.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Riley Children\u2019s Hospital (Prairieland), Indianapolis, IN (T.R.J.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5733-6096","authenticated-orcid":true,"given":"Usha S.","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Columbia University Irving Medical Center, Morgan Stanley Children\u2019s Hospital of New York, NY (U.S.K.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3330-0598","authenticated-orcid":true,"given":"Stephen M.","family":"Paridon","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA (D.J.G., S.M.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter C.","family":"Frommelt","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI (B.G., M.S., P.C.F.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the Pediatric Heart Network","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.26.3.240"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2015-307467"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hfc.2013.09.010"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.117.004515"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1510\/icvts.2009.218594"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.02.081"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.12.054"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-009-9580-5"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2007.11.009"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2007.09.050"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.03.582"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq356"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2017.01.056"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.738559"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.07.065"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-005-1151-9"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.044352"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2018.03.015"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2012.08.005"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/heart.83.4.420"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(91)90195-q"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.79.6.1247"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(93)90784-x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2019.5459"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0894-7317(97)70090-7"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/echo.14169"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.110.944694"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.983866"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-7133.2008.00026.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-012-0400-y"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-012-0196-9"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.113.001243"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01144.2004"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1080\/00031305.2016.1154108"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.66.5.375"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2009.12.020"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2004.051789"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.109.931592"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.117.004571"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.85.4.1447"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2015-309042"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1136\/openhrt-2020-001434"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2017.04.073"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-020-02424-w"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2016.07.016"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2011.08.011"}],"container-title":["Circulation: Cardiovascular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCIMAGING.121.013676","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T13:07:10Z","timestamp":1749042430000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCIMAGING.121.013676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":46,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1161\/CIRCIMAGING.121.013676"],"URL":"https:\/\/doi.org\/10.1161\/circimaging.121.013676","relation":{},"ISSN":["1941-9651","1942-0080"],"issn-type":[{"value":"1941-9651","type":"print"},{"value":"1942-0080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11]]},"assertion":[{"value":"2021-10-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}