Circulating Extracellular Matrix Biomarkers in the Detection of Carcinoid Heart Disease

Carcinoid heart disease (CHD) is a severe fibrotic complication affecting cardiac valves in patients with neuroendocrine neoplasms (NEN). 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 detection of CHD and to compare their performance with NT-proBNP.

In this cross-sectional study, we prospectively included patients with disseminated small intestinal NEN (siNEN). 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 characteristics (AUROC).

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: 15.6-24.0) vs 14.3 ng/ml (IQR: 12.4-17.5), p = 0.002). The AUROC of PRO-C3 for CHD detection was 0.77 (95% CI: 0.64-0.90). At a cut-off level of 15.4 ng/ml, the sensitivity was 85 %, the specificity 56 %, the positive predictive value 27 %, and the negative predictive value 95 %. In the direct comparison between PRO-C3 and NT-proBNP, PRO-C3 did not outperform NT-proBNP (p = 0.09).

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.