Purpose: The aim of our study was to evaluate the modulation of exosomal miRNAs in patients with severe AS, after release of LV pressure overload by TAVI.

Methods: Blood samples were obtained from AS patients at baseline, 30', 1h, 24h and 30 days after TAVI. Circulating exosomes were isolated from plasma samples using the Exosomes Isolation Kit (Thermo Fisher) and characterized using NTA (NanoSight). MiRNAs were isolated from purified exosomes using the miRVana Kit (Thermo Fisher) and evaluated by spectrophotometry (Bioanalyzer 2100). A miRNA differential expression profile was obtained comparing baseline samples with matched 24h samples (Affymetrix's GeneChip miRNA 3.0). The miRNAs with the largest differential expression between the two study groups were selected for validation by means of qRT-PCR.

Results: Samples from the first 16 patients were analysed, showing early halving of exosome concentration 1h after the procedure (p= 0.007), followed by a progressive increase at 24h (p= 0.09) and 30 days (p= 0.001) of follow up. The differential miRNA expression profile revealed significant modulation of several miRNA at 24h after TAVI compared to pre-treatment values. Among those differentially regulated, the miR-320b (p= 0.003), miR-141–3p (p= 0.041), miR-937–50 (p= 0.034), miR-1908 (p= 0.018) and miR-4508 (p= 0.008) were significantly upregulated, while the miR-199a (p= 0.048), miR-548ad (p= 0.008), miR-33a (p= 0.017 and miR-185 (p= 0.044) were significantly downregulated.