{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:43:09Z","timestamp":1793036589501,"version":"4.5.0"},"reference-count":45,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":284,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Carcinoid heart disease (CHD) is a severe fibrotic complication affecting cardiac valves in patients with neuroendocrine neoplasms (NENs). Early detection is crucial to improve prognosis. The value of the recommended screening biomarker, NT-proBNP, is uncertain. Biomarkers reflecting extracellular matrix (ECM) remodeling may capture early fibrogenesis. We aimed to evaluate circulating ECM biomarkers for the detection of CHD and to compare their performance with NT-proBNP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and methods<\/jats:title>\n                    <jats:p>In this cross-sectional study, we prospectively included patients with disseminated small intestinal NENs (siNENs). We performed transthoracic echocardiography (TTE) for CHD diagnosis, and blood samples were analyzed for 10 ECM biomarkers. Biomarker levels were compared between patients with and without CHD, and diagnostic performance was assessed using the area under the receiver operating characteristic (AUROC) curve.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 98 patients, 16 (16%) had CHD. PRO-C3 levels were significantly elevated in patients with CHD compared with patients without CHD (median: 19.3 ng\/mL (IQR: 15.6\u201324.0) vs 14.3 ng\/mL (IQR: 12.4\u201317.5), P = 0.002). The AUROC curve of PRO-C3 for CHD detection was 0.77 (95% CI: 0.64\u20130.90). At a cutoff level of 15.4 ng\/mL, the sensitivity was 85%, the specificity was 56%, the positive predictive value was 27%, and the negative predictive value was 95%. In the direct comparison between PRO-C3 and NT-proBNP, PRO-C3 did not outperform NT-proBNP (P = 0.09).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PRO-C3, reflecting collagen type III formation, demonstrated good performance in CHD detection and may represent a complementary or potentially earlier marker than NT-proBNP. However, the performance of PRO-C3 was insufficient as a stand-alone tool, and further evaluation and exploration of new biomarkers in larger cohorts is required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/eo-26-0059","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:47:51Z","timestamp":1791823671000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-15","source":"Crossref","is-referenced-by-count":0,"title":["Circulating extracellular matrix biomarkers in the detection of carcinoid heart disease"],"prefix":"10.1530","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1354-9601","authenticated-orcid":true,"given":"Tobias Stemann","family":"Lau","sequence":"first","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Aarhus University Hospital 1 , ,","place":["Aarhus, Denmark"]},{"name":"ENETS Center of Excellence, Aarhus University Hospital 2 , ,","place":["Aarhus, Denmark"]},{"name":"Department of Clinical Medicine, Aarhus University 3 , ,","place":["Aarhus, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4104-909X","authenticated-orcid":true,"given":"Elisavet","family":"Angeli","sequence":"additional","affiliation":[{"name":"Nordic Bioscience A\/S 4 , ,","place":["Herlev, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2127-6871","authenticated-orcid":true,"given":"Riina Karoliina","family":"Oksjoki","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital 5 , ,","place":["Aarhus, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8813-5252","authenticated-orcid":true,"given":"Vibeke Guldbrand","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital 5 , ,","place":["Aarhus, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1984-1881","authenticated-orcid":true,"given":"Federica","family":"Genovese","sequence":"additional","affiliation":[{"name":"Nordic Bioscience A\/S 4 , ,","place":["Herlev, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3456-2485","authenticated-orcid":true,"given":"Linda Skibsted","family":"Kornerup","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Aarhus University Hospital 1 , ,","place":["Aarhus, Denmark"]},{"name":"ENETS Center of Excellence, Aarhus University Hospital 2 , ,","place":["Aarhus, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8998-7910","authenticated-orcid":true,"given":"Henning","family":"Gr\u00f8nb\u00e6k","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Aarhus University Hospital 1 , ,","place":["Aarhus, Denmark"]},{"name":"ENETS Center of Excellence, Aarhus University Hospital 2 , ,","place":["Aarhus, Denmark"]},{"name":"Department of Clinical Medicine, Aarhus University 3 , ,","place":["Aarhus, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3526-0171","authenticated-orcid":true,"given":"Gitte","family":"Dam","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Aarhus University Hospital 1 , ,","place":["Aarhus, Denmark"]},{"name":"ENETS Center of Excellence, Aarhus University Hospital 2 , ,","place":["Aarhus, Denmark"]},{"name":"Department of Clinical Medicine, Aarhus University 3 , ,","place":["Aarhus, 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