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This exploratory study reports biomarker profiles in unrepaired tetralogy of Fallot (TOF), repaired TOF (rTOF), hypoplastic left heart syndrome (HLHS) following Fontan surgery, and healthy controls. We compared circulating biomarker patterns between TOF, rTOF, HLHS, and control groups, aiming to characterize potential disease-specific profiles and generate hypotheses for future research. We prospectively enrolled subjects and collected single-time blood samples for analysis. We measured: microRNA-21 (miR-21), soluble suppression of tumorigenicity-2 (sST-2), galectin-3 (Gal-3), procollagen type-I carboxy-terminal pro-peptide (PICP), procollagen type-III amino-terminal pro-peptide (PIIINP), metalloproteinases (MMP-1\/MMP-9), and NT-proBNP. We included 207 patients: TOF (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200975), rTOF (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200960), HLHS (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200911), and healthy controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200960). Compared to the younger controls, TOF patients had higher PICP, MMP-1, and NT-proBNP. Compared to older controls, rTOF patients had higher PIIINP, MMP-1, MMP-9, and NT-proBNP; and HLHS patients had higher PIIINP and MMP-1. Collagen metabolism biomarkers and MMP-1 were elevated across disease groups. Gal-3 was associated with age in HLHS. No disease-specific patterns were observed; however, differences from controls suggest cardiac remodeling in TOF and HLHS.\n                  <\/jats:p>","DOI":"10.1007\/s00246-025-03935-0","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T22:51:47Z","timestamp":1751928707000},"page":"1552-1561","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring Serum Biomarker Levels in Tetralogy of Fallot, Hypoplastic Left Heart Syndrome, and Healthy Children"],"prefix":"10.1007","volume":"47","author":[{"given":"Ariel","family":"Vargas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Galan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriyana","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeli","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nkecha","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"DeCost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh D.","family":"Mai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique M.","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mercer-Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"issue":"3","key":"3935_CR1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/S2352-4642(19)30402-X","volume":"4","author":"MS Zimmerman","year":"2020","unstructured":"Zimmerman MS, Smith AGC, Sable CA, Echko MM, Wilner LB, Olsen HE et al (2020) Global, regional, and national burden of congenital heart disease, 1990\u20132017: a systematic analysis for the global burden of disease study 2017. 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