{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:55:12Z","timestamp":1780322112022,"version":"3.54.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>An endothelin-1 receptor blocker, shown to be effective in patients with pulmonary arterial hypertension, might decrease pulmonary vascular resistance to increase cardiac filling and consequently improve exercise capacity in Fontan patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>This was a prospective, multicentre randomized open label trial in Fontan patients. One group received bosentan for 6 months. The other group did not receive study medication for the first 3 months, followed by bosentan for 6 months. The primary endpoint was exercise capacity, and secondary endpoints were NT-proBNP level, cardiac output, SF-36 (Short Form-36) quality of life (QoL), and NYHA class. Forty-two adults (median age 29 (range 18\u201356) years, 52% male, 88% NYHA class I\u2013II) from five tertiary referral centres participated in the study. Ten patients were on diuretics. Ten patients were not motivated to finish the study. Analysis of all 32 patients who finished the study at 6 months of treatment showed that mean peak V\u2019O2 (24 vs. 25 mL\/kg\/min), median SQUASH score (6614 vs. 6390), median NT-proBNP (314 vs. 274 ng\/L), and mental QoL (50 vs. 51) remained unchanged as compared with baseline (P = NS, for all). After treatment, NYHA class had improved in 6 (19%), was unchanged in 24 (75%), and declined in 2 (6%) patients. Subgroup analysis on age, ventricular morphology, type of Fontan circulation, or baseline NT-proBNP level did not reveal efficacy of bosentan. Six transient adverse effects were reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>An increased NT-proBNP level was present in the majority of Fontan patients. Six months of bosentan treatment was not beneficial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>NTR1557<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjhf\/hft017","type":"journal-article","created":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T23:42:25Z","timestamp":1359502945000},"page":"690-698","source":"Crossref","is-referenced-by-count":126,"title":["Impact of Bosentan on Exercise Capacity in Adults After the Fontan Procedure: A Randomized Controlled Trial"],"prefix":"10.1093","volume":"15","author":[{"given":"Mark J.","family":"Schuuring","sequence":"first","affiliation":[{"name":"Department of Cardiology, Academic Medical Centre , Meibergdreef 9, 1105, AZ Amsterdam ,","place":["The Netherlands"]},{"name":"Interuniversity Cardiology Institute of the Netherlands , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen C.","family":"Vis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Academic Medical Centre , Meibergdreef 9, 1105, AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie P.J.","family":"van Dijk","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Nijmegen Medical Centre , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost P.","family":"van Melle","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert W.","family":"Vliegen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Leiden University Medical Centre , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petronella G.","family":"Pieper","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertjan T.","family":"Sieswerda","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Utrecht , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rianne H.A.C.M.","family":"de Bruin-Bon","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Academic Medical Centre , Meibergdreef 9, 1105, AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.M.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Academic Medical Centre , Meibergdreef 9, 1105, AZ Amsterdam ,","place":["The Netherlands"]},{"name":"Interuniversity Cardiology Institute of the Netherlands , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berto J.","family":"Bouma","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Academic Medical Centre , Meibergdreef 9, 1105, AZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,27]]},"reference":[{"key":"2026011921150059800_ejhfhft017-bib-0001","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1510\/icvts.2009.218594","article-title":"The Fontan circulation: who controls cardiac output?","volume":"10","author":"Gewillig","year":"2010","journal-title":"Interact Cardiovasc Thorac Surg"},{"key":"2026011921150059800_ejhfhft017-bib-0002","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1161\/CIRCULATIONAHA.110.981746","article-title":"Impact of oral sildenafil on exercise performance in children and young adults after the fontan operation: a randomized, double-blind, placebo-controlled, crossover trial","volume":"123","author":"Goldberg","year":"2011","journal-title":"Circulation"},{"key":"2026011921150059800_ejhfhft017-bib-0003","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1093\/eurheartj\/ehi396","article-title":"The spectrum of adult congenital heart disease in Europe: morbidity and mortality in a 5 year follow-up period. 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