Age-related enhanced degeneration of bioprosthetic valves due to leaflet calcification, tissue crosslinking, and structural changes

Bioprosthetic heart valves (BHV), made from glutaraldehyde-fixed heterograft materials, are subject to more rapid structural valve degeneration (SVD) in pediatric and young adult patients. Differences in blood biochemistries and propensity for disease accelerate SVD in these patients, which results in multiple re-operations with compounding risks. The goal of this study is to investigate the mechanisms of BHV biomaterial degeneration and present models for studying SVD in young patients and juvenile animal models.We studied SVD in clinical BHV explants from pediatric and young adult patients, juvenile sheep implantation model, rat subcutaneous implants, and an ex vivo serum incubation model. BHV biomaterials were analyzed for calcification, collagen microstructure (alignment and crimp), and crosslinking density. Serum markers of calcification and tissue crosslinking were compared between young and adult subjects. We demonstrated that immature subjects were more susceptible to calcification, microstructural changes, and advanced glycation end products formation. In vivo and ex vivo studies comparing immature and mature subjects mirrored SVD in clinical observations. The interaction between host serum and BHV biomaterials leads to significant structural and biochemical changes which impact their functions.There is an increased risk for accelerated SVD in younger subjects, both experimental animals and patients. Increased calcification, altered collagen microstructure with loss of alignment and increased crimp periods, and increased crosslinking are three main characteristics in BHV explants from young subjects leading to SVD. Together, our studies establish a basis for assessing the increased susceptibility of BHV biomaterials to accelerated SVD in young patients.Bioprosthetic heart valves (BHV) are the predominant treatment option for valvular heart diseases. However, the main drawback of BHV is their limited durability. Although it has been widely acknowledged that young patients are more susceptible to BHV degeneration and have shorter implant durations, the underlying mechanisms remain elusive. We examined the BHV degeneration process in clinical BHV explants from young and older patients, juvenile sheep implantation model, rat subcutaneous implant model, and ex vivo serum incubation model. These comprehensive basic to translational studies highlighted that BHV degeneration is significantly associated with age related risk factors. These studies also shed light on understanding the degeneration of a variety of xenografts and lay the foundation for future studies on mitigating device degeneration in young patients.