Abstract 385: Characterization of Cellular Infiltrate in Bioprosthetic Aortic and Mitral Valves

Abstract

Background: Bioprosthetic xenogeneic valves tend to deteriorate over time, termed structural valve deterioration (SVD), leading to valvular dysfunction. Several studies have hypothesized that SVD is a result of a chronic immune-mediated rejection process; however, a paucity of data exists demonstrating this conclusively. Objectives: Demonstrate that valves explanted for SVD contain a significantly greater burden of immune cellular infiltrate compared to normal human heart valves. Methods: Adult patients undergoing bioprosthetic aortic or mitral valve explantation secondary to a diagnosis of SVD were included in this study. A control arm included valves explanted from hearts without valvular disease considered for transplantation that were not utilized. Specimens underwent immunohistochemical staining using standard techniques utilizing the following primary monoclonal antibodies: anti-CD68, anti-CD20, and anti-CD3. Results: Eighteen valves explanted for SVD were analyzed along with 4 control valves. All valves were explanted from male patients with a mean age of 62-years. Overall, 12% (n=1) of patients had diabetes mellitus, 50% (n=4) had hypertension, 12% (n=1) had renal dysfunction and 38% (n=3) were on a lipid-lowering medication. Our results demonstrate that valves developing SVD have a cellular infiltrate containing significantly more immune cells than normal human valves. Specifically, there are significantly more CD3+ T-cells (p<0.05) and CD68+ macrophages (p<0.05) present in the cellular infiltrate of the SVD valves compared to the normal controls. Furthermore, while the cellular infiltrate of the SVD valves contains CD20+ B-cells, plasma cells, and neutrophils, none of these cells are present on the normal control valves (all p-values <0.05). Conclusions: Our data suggest a significantly greater immune cell infiltrate can be found in explanted bioprosthetic valves developing SVD than normal human valves, providing support for the chronic-immune mediated rejection hypothesis. This study will ultimately lead to a better understanding of the immune mechanisms responsible for SVD in bioprosthetic xenograft valves and will contribute to our goal of developing novel therapeutic techniques to mitigate development of SVD.