Bioprosthetic heart valve structural degeneration associated with metabolic syndrome: Mitigation with polyoxazoline modification

Abstract

Bioprosthetic heart valves (BHV), made from glutaraldehyde-fixed xenografts, are widely used for surgical and transcatheter valve interventions but suffer from limited durability due to structural valve degeneration (SVD). We focused on metabolic syndrome (MetS), a risk factor for SVD and a highly prevalent phenotype in patients affected by valvular heart disease with a well-recognized cluster of comorbidities. Multicenter patient data (N = 251) revealed that patients with MetS were at significantly higher risk of accelerated SVD and required BHV replacement sooner. Using a next-generation proteomics approach, we identified significantly differential proteomes from leaflets of explanted BHV from MetS and non-MetS patients (N = 24). Given the significance of protein infiltration in MetS-induced SVD, we then demonstrated the protective effects of polyoxazoline modification of BHV leaflets to mitigate MetS-induced BHV biomaterial degeneration (calcification, tissue cross-linking, and microstructural changes) in an ex vivo serum model and an in vivo with MetS rat subcutaneous implants.

Challenges and Opportunities in Valvular Heart Disease: From Molecular Mechanisms to the Community

“…Interestingly, young recipient age, hypertension, and metabolic syndrome are clinical risk factors for structural valve degeneration and may provide insight into specific failure mechanisms and potential mitigation strategies. 29 Indeed, given the rising demand for bioprosthetic valve implantation worldwide, new strategies to reduce immunogenicity of animal tissues used for their fabrication with adequate removal of residual antigens following decellularization are sorely needed. 30 While transcatheter valve replacement rates, which are governed by expanded approval into low- and medium-risk patients, the availability of novel devices, and the potential for repeat procedures (ie, valve-in-valve), are on the rise, further understanding mechanisms of bioprosthetic valve failure is mandated.…”