Peripheral Serotonergic Activation in Severe Aortic Stenosis: A Biochemical Perspective

The involvement of the serotoninergic system in the pathogenesis of calcific aortic stenosis introduced a novel dimension to our understanding of this complex cardiovascular condition. This study aimed to assess serotonin (5-HT) and its main metabolite, 5-Hydroxyindoleacetic acid (5-HIAA) in patients with severe aortic valve stenosis (AS). The study employed a case-control design, including 76 patients who underwent transthoracic echocardiography, computed tomography (CT), and peripheral blood sampling. Serum concentrations of 5-HT and 5-HIAA were quantified using enzyme-linked immunosorbent assay (ELISA). The severe aortic valve stenosis group exhibited significantly elevated levels of 5-HT and 5-HIAA compared to the control group (5-HT 1066.5 ng/mL (IQR = 961.9-1112 ng/mL) vs. 977.4 ng/mL (IQR = 394.3-1097.9 ng/mL); p = 0.034 and 5-HIAA 57 ± 12.7 ng/mL vs. 47.5 ± 15.3 ng/mL; p = 0.004, respectively). Receiver operating characteristic (ROC) analysis revealed that 5-HT predicted severe AS with a sensitivity of 73.7% and specificity of 50% at a cut-off level > 973.5 ng/mL, whereas 5-HIAA exhibited a sensitivity of 86.8% and specificity of 47.4% when a cut-off level > 45.49 ng/mL was used. This study showed a significant elevation in the 5-HT and 5-HIAA among patients with severe AS, further supporting the potential involvement of the peripheral serotonergic system in the pathophysiology of this condition.