Biological remodeling and integration of TAVI bioprostheses across distinct anatomical zones and their correlation with hemodynamic outcomes at 180 days

Abstract Background Regional differences in biological healing after transcatheter aortic valve implantation (TAVI) may impact long-term prosthesis function. This study aimed to quantitatively evaluate tissue integration across distinct anatomical zones of the valve and explore its relationship with hemodynamic outcomes. Methods This preclinical study involved 22 sheep undergoing TAVI, with a follow-up period of 180 days. Postmortem histological analysis was performed on the explanted valves. Three anatomical zones of the bioprosthesis were analyzed: inflow, outflow, and the frame–aorta interface—the area of contact between the stent frame and aortic wall. Hemodynamic valve performance was evaluated at day 180 using transthoracic echocardiography, including measurements of mean and peak transvalvular gradients. Results Neointimal thickness was significantly greater in the inflow compared to the outflow zone (p=0.0009). Inflow neointimal thickness correlated significantly with both PGmean (p=0.031) and PGmax (p=0.019). Similarly, outflow thickness showed significant correlations with PGmean (p=0.022) and PGmax (p=0.018), as visualized in Fig. 1. Maturity of the neointima differed significantly between inflow and outflow regions (p=0.021), whereas neointimal length did not show a significant difference (p=0.08). Frame neointima maturity moderately correlated with inflow maturity (p=0.022). However, histological parameters at the frame–aorta interface (fibrin, macrophages, mineralization, neointima maturity) did not significantly correlate with valve hemodynamics. A multivariable linear regression model including all biological variables revealed no significant predictors of PGmean or PGmax. Conclusions Marked anatomical variation in biological integration was associated with transvalvular hemodynamic performance. These findings support the concept of designing anatomically adapted TAVI prostheses optimized for zone-specific healing. The next step involves developing a multi-parameter histopathological scoring system to enable standardized comparison of valve regions.PG vs neointima in/out zonesFor image description, please refer to the figure legend and surrounding text.