Circulating Extracellular Matrix-Remodeling Biomarkers in Children with Bicuspid Aortic Valve: An Exploratory Cross-Sectional Study.

Background/Objectives: Bicuspid aortic valve (BAV) is frequently associated with valvular dysfunction and aortic remodeling. This exploratory study examined cross-sectional associations between circulating extracellular matrix-related biomarkers and concurrent echocardiographic characteristics in children with BAV. Methods: We included 43 pediatric participants-26 with BAV and 17 with tricuspid aortic valves (TAV). All participants underwent clinical assessment, transthoracic echocardiography, and serum biomarker quantification at the same study visit. MMP-2, MMP-9, TIMP-1, and TGF-β1 were measured using ELISA. Biomarker levels were compared between the BAV and TAV groups and, within the BAV group, according to the presence of concurrent aortopathy, aortic stenosis, and aortic regurgitation. Results: MMP-9, TIMP-1, and the MMP-9/TIMP-1 ratio were higher in the BAV group than in the TAV comparison group. Within the BAV cohort, none of the investigated biomarkers differed significantly between participants with and without aortopathy. TGF-β1 was higher in BAV patients with aortic stenosis, whereas the MMP-9/TIMP-1 ratio showed a borderline difference according to aortic regurgitation status; these subgroup findings are exploratory and limited by small sample size and multiple comparisons. Conclusions: In this selected pediatric cohort, circulating MMP-9 and TIMP-1 levels differed between children with BAV and the TAV comparison group. However, none of the investigated biomarkers differed significantly between BAV patients with and without aortopathy. These cross-sectional findings describe exploratory associations with the BAV phenotype but do not establish diagnostic, predictive, or prognostic utility. Larger longitudinal studies including the broader clinical spectrum of BAV and independent validation cohorts are required.