{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:16:20Z","timestamp":1793085380336,"version":"4.5.0"},"reference-count":34,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Society of Finland (Finska L\u00e4kares\u00e4llskapet)","award":["TYH2021231"],"award-info":[{"award-number":["TYH2021231"]}]},{"name":"Medical Society of Finland (Finska L\u00e4kares\u00e4llskapet)","award":["TYH2022311"],"award-info":[{"award-number":["TYH2022311"]}]},{"name":"Ida Montin Foundation","award":["TYH2021231"],"award-info":[{"award-number":["TYH2021231"]}]},{"name":"Ida Montin Foundation","award":["TYH2022311"],"award-info":[{"award-number":["TYH2022311"]}]},{"name":"K. Albin Johansson Stiftelse","award":["TYH2021231"],"award-info":[{"award-number":["TYH2021231"]}]},{"name":"K. Albin Johansson Stiftelse","award":["TYH2022311"],"award-info":[{"award-number":["TYH2022311"]}]},{"name":"Wilhelm and Else Stockmann Foundation","award":["TYH2021231"],"award-info":[{"award-number":["TYH2021231"]}]},{"name":"Wilhelm and Else Stockmann Foundation","award":["TYH2022311"],"award-info":[{"award-number":["TYH2022311"]}]},{"name":"Medicinska underst\u00f6dsf\u00f6reningen Liv och H\u00e4lsa r.f.","award":["TYH2021231"],"award-info":[{"award-number":["TYH2021231"]}]},{"name":"Medicinska underst\u00f6dsf\u00f6reningen Liv och H\u00e4lsa r.f.","award":["TYH2022311"],"award-info":[{"award-number":["TYH2022311"]}]},{"name":"Sigrid Juselius Foundation","award":["TYH2021231"],"award-info":[{"award-number":["TYH2021231"]}]},{"name":"Sigrid Juselius Foundation","award":["TYH2022311"],"award-info":[{"award-number":["TYH2022311"]}]},{"name":"Finnish governmental grant","award":["TYH2021231"],"award-info":[{"award-number":["TYH2021231"]}]},{"name":"Finnish governmental grant","award":["TYH2022311"],"award-info":[{"award-number":["TYH2022311"]}]},{"name":"University of Helsinki","award":["TYH2021231"],"award-info":[{"award-number":["TYH2021231"]}]},{"name":"University of Helsinki","award":["TYH2022311"],"award-info":[{"award-number":["TYH2022311"]}]},{"name":"Minerva Foundation","award":["TYH2021231"],"award-info":[{"award-number":["TYH2021231"]}]},{"name":"Minerva Foundation","award":["TYH2022311"],"award-info":[{"award-number":["TYH2022311"]}]},{"name":"Academy of Finland","award":["TYH2021231"],"award-info":[{"award-number":["TYH2021231"]}]},{"name":"Academy of Finland","award":["TYH2022311"],"award-info":[{"award-number":["TYH2022311"]}]},{"DOI":"10.13039\/501100003756","name":"Helsinki University Hospital government research funds","doi-asserted-by":"publisher","award":["TYH2021231"],"award-info":[{"award-number":["TYH2021231"]}],"id":[{"id":"10.13039\/501100003756","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003756","name":"Helsinki University Hospital government research funds","doi-asserted-by":"publisher","award":["TYH2022311"],"award-info":[{"award-number":["TYH2022311"]}],"id":[{"id":"10.13039\/501100003756","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Small intestinal neuroendocrine tumors (SI-NETs) are characterized by carcinoid syndrome and carcinoid heart disease (CHD). The aim of the present study was to identify early risk markers for carcinoid heart disease and survival in a prospective median-term follow-up setting. Methods: We measured 5-HIAA and cumulative 5-HIAA exposure (Cum-5-HIAA) based on repeated measurements, proBNP, vascular function, hepatic tumor load, and transthoracic echocardiography (TTE) at baseline and during the median 5-year follow-up. Of 65 patients with SI-NETs, 54 patients underwent a prospective follow-up. In addition, survival was evaluated during the median follow-up of 6 years. Results: At baseline, three patients had CHD. During the median follow-up of 5 years, two patients (4%) developed CHD. Cum-5-HIAA and proBNP correlated with CHD (Westberg score, Spearman\u2019s \u03c1 = 0.32 and 0.31, respectively). Cum-5-HIAA had a superior diagnostic capability, predicting CHD in receiver operator characteristic analysis with an AUC of 0.98 (95% CI: 0.94\u20131.00) and outperformed proBNP, chromogranin A (CgA), and individual serum 5-HIAA measurements (AUC = 0.75, 0.85, and 0.91, respectively). Minor changes in valve regurgitation were frequently detected but did not correlate with vascular function. Regurgitation increased or decreased in 29% of tricuspid and 30% of pulmonic valves. CHD, hepatic tumor load, serum 5-HIAA, and elevated aortic pulse wave velocity (PWV) were associated with increased mortality in SI-NET patients. Conclusions: Cum-5-HIAA is a promising biomarker for CHD risk and outperformed other biomarkers. CHD and hepatic tumor load are the strongest predictors of mortality. PWV is a novel predictor of survival. The incidence of CHD was low among the SI-NET patients, probably reflecting successful treatment regimens.<\/jats:p>","DOI":"10.3390\/cancers16233896","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T06:11:54Z","timestamp":1732169514000},"page":"3896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Value of Repeat 5-HIAA Measurements as a Predictor of Carcinoid Heart Disease: A Prospective 5-Year Follow-Up Study in Patients with Small Intestinal Neuroendocrine Tumors"],"prefix":"10.3390","volume":"16","author":[{"given":"Iiro","family":"Kostiainen","sequence":"first","affiliation":[{"name":"Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, ENDO-ERN (European Reference Network on Rare Endocrine Conditions), 00280 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piia","family":"Simonen","sequence":"additional","affiliation":[{"name":"Cardiology, Heart and Lung Center, Helsinki University Hospital and University of Helsinki, 00280 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katri","family":"Aaltonen","sequence":"additional","affiliation":[{"name":"Cardiology, Heart and Lung Center, Helsinki University Hospital and University of Helsinki, 00280 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riikka","family":"Lind\u00e9n","sequence":"additional","affiliation":[{"name":"Radiology, HUS Diagnostic Center, Helsinki University Hospital and University of Helsinki, ENDO-ERN (European Reference Network on Rare Endocrine Conditions), 00260 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noora","family":"Karppinen","sequence":"additional","affiliation":[{"name":"Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, ENDO-ERN (European Reference Network on Rare Endocrine Conditions), 00280 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gordin","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Abdominal Center, Helsinki University Hospital and University of Helsinki, 00280 Helsinki, Finland"},{"name":"Minerva Institute for Medical Research, 00290 Helsinki, Finland"},{"name":"Joslin Diabetes Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne","family":"Rapola","sequence":"additional","affiliation":[{"name":"Cardiology, Heart and Lung Center, Helsinki University Hospital and University of Helsinki, 00280 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2428-0161","authenticated-orcid":false,"given":"Camilla","family":"Schalin-J\u00e4ntti","sequence":"additional","affiliation":[{"name":"Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, ENDO-ERN (European Reference Network on Rare Endocrine Conditions), 00280 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0041-1240","authenticated-orcid":false,"given":"Niina","family":"Matikainen","sequence":"additional","affiliation":[{"name":"Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, ENDO-ERN (European Reference Network on Rare Endocrine Conditions), 00280 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1159\/000443170","article-title":"ENETS Consensus Guidelines Update for Neuroendocrine Neoplasms of the Jejunum and Ileum","volume":"103","author":"Niederle","year":"2016","journal-title":"Neuroendocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13146","DOI":"10.1111\/jne.13146","article-title":"European Neuroendocrine Tumor Society (ENETS) 2022 Guidance Paper for Carcinoid Syndrome and Carcinoid Heart Disease","volume":"34","author":"Davar","year":"2022","journal-title":"J. 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