{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:12:46Z","timestamp":1785798766514,"version":"3.56.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,3,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Patients who have undergone the Fontan procedure are at high risk of circulatory failure. In an exploratory analysis we aimed to determine the prognostic value of blood biomarkers in a young cohort who have undergone the Fontan procedure.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In multicenter prospective studies patients who have undergone the Fontan procedure underwent blood sampling, cardiopulmonary exercise testing, and stress cardiac magnetic resonance imaging. Several biomarkers including NT\u2010proBNP (N\u2010terminal pro\u2010B\u2010type natriuretic peptide), GDF\u201015 (growth differentiation factor 15), Gal\u20103 (galectin\u20103), ST2 (suppression of tumorigenicity 2), DLK\u20101 (protein delta homolog 1), FABP\u20104 (fatty acid\u2010binding protein 4), IGFBP\u20101 (insulin\u2010like growth factor\u2010binding protein 1), IGFBP\u20107, MMP\u20102 (matrix metalloproteinase 2), and vWF (von Willebrand factor) were assessed in blood at 9.6 (7.1\u201312.1) years after Fontan completion. After this baseline study measurement, follow\u2010up information was collected on the incidence of adverse cardiac events, including cardiac death, out of hospital cardiac arrest, heart transplantation (listing), cardiac reintervention (severe events), hospitalization, and cardioversion\/ablation for arrhythmias was collected and the relation with blood biomarkers was assessed by Cox proportional hazard analyses. The correlation between biomarkers and other clinical parameters was evaluated. We included 133 patients who have undergone the Fontan procedure, median age 13.2 (25th, 75th percentile 10.4\u201315.9) years, median age at Fontan 3.2 (2.5\u20133.9) years. After a median follow\u2010up of 6.2 (4.9\u20136.9) years, 36 (27.1%) patients experienced an event of whom 13 (9.8%) had a severe event. NT\u2010proBNP was associated with (all) events during follow\u2010up and remained predictive after correction for age, sex, and dominant ventricle (hazard ratio, 1.89; CI, 1.32\u20132.68). The severe event\u2010free survival was better in patients with low levels of GDF\u201015 (\n              <jats:italic>P<\/jats:italic>\n              =0.005) and vWF (\n              <jats:italic>P<\/jats:italic>\n              =0.008) and high levels of DLK\u20101 (\n              <jats:italic>P<\/jats:italic>\n              =0.041). There was a positive correlation (\u03b2=0.33,\n              <jats:italic>P<\/jats:italic>\n              =0.003) between DLK\u20101 and stress cardiac magnetic resonance imaging functional reserve.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">NT\u2010proBNP, GDF\u201015, vWF, DLK\u20101, ST\u20102 FABP\u20104, and IGFBP\u20107 levels relate to long\u2010term outcome in young patients who have undergone the Fontan procedure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.015022","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T10:13:17Z","timestamp":1614161597000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Associations Between Blood Biomarkers, Cardiac Function, and Adverse Outcome in a Young Fontan Cohort"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2832-8377","authenticated-orcid":false,"given":"Eva","family":"van den Bosch","sequence":"first","affiliation":[{"name":"Division of Pediatric Cardiology Department of Pediatrics Erasmus University Medical Center Rotterdam The Netherlands"},{"name":"Department of Radiology Erasmus University Medical Center Rotterdam The Netherlands"},{"name":"Netherlands Heart Institute Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjoerd S. 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P. J.","family":"Breur","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arend D. J.","family":"Ten Harkel","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology Department of Pediatrics Leiden University Medical Center The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Kapusta","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Sourasky Medical Center Tel Aviv University Tel Aviv Israel"},{"name":"Division of Pediatric Cardiology Department of Pediatrics Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3151-2474","authenticated-orcid":false,"given":"Beatrijs","family":"Bartelds","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology Department of Pediatrics Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0153-5934","authenticated-orcid":false,"given":"Arno A. 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