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
How to cite: Kostiainen, I.; Simonen, P.; Aaltonen, K.; Lindén, R.; Karppinen, N.; Gordin, D.; Rapola, J.; Schalin-Jäntti, C.; Matikainen, N. 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. Preprints 2024, 2024101685. https://doi.org/10.20944/preprints202410.1685.v1 Kostiainen, I.; Simonen, P.; Aaltonen, K.; Lindén, R.; Karppinen, N.; Gordin, D.; Rapola, J.; Schalin-Jäntti, C.; Matikainen, N. 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. Preprints 2024, 2024101685. https://doi.org/10.20944/preprints202410.1685.v1
Abstract
Background Small intestinal neuroendocrine tumors (SI-NETs) are characterized by carcinoid syndrome and carcinoid heart disease (CHD). The aim of 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, cumulative 5-HIAA exposure (Cum-5-HIAA) based on repeat measurements, proBNP, vascular function, hepatic tumor load and transthoracic echocardiography (TTE) were assessed at baseline and during median 5-year follow-up. Of 65 patients with SI-NETs; 54 patients underwent prospective follow-up. In addition, survival was evaluated during median follow-up of 6 years. Results At baseline three patients had CHD. During median follow-up of 5 years, two patients (4%) developed CHD. Cum-5-HIAA and proBNP correlated with CHD (Westberg Score, Spearman’s ρ = 0.32 and 0.31, respectively). Cum-5-HIAA had a superior diagnostic capability, predicting CHD in receiver operator characteristics analysis with AUC of 0.98 (95% CI: 0.94–1.00) and outperformed proBNP, chromogranin A (CgA), as well as 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. In 29% of tricuspid and 30% of pulmonic valves regurgitation increased or decreased. CHD, hepatic tumor load, serum 5-HIAA, and elevated aortic pulse wave velocity (PWV) 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 strongest predictors of mortality. PWV is a novel predictor of survival. The incidence of CHD was small among the SI-NET patients, probably reflecting successful treatment regimens.
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