Alpha-gal xenoantigens in bioprosthetic valve recipients: clinical implications for bioprosthesis longevity

BACKGROUND: Structural valve degeneration (SVD) is a key limitation of bioprosthetic heart valves (BHVs). The underlying mechanisms for this degeneration and pathophysiology remains only partially defined. Emerging evidence implicates a xenogeneic carbohydrate epitope, galactose-α-1,3-galactose (Alpha-gal), as a potential driver of immune-mediated valve deterioration. This review explores the current knowledge on alpha-gal (AG) sensitization and evidence linking it to SVD and the potential clinical implications. METHODS: A literature search was conducted using Embase, PubMed and Scopus, using variants of the following keywords, such as "alpha-gal", "bioprosthetic valve", and "degeneration". Studies included reported human subject findings and focused on BHVs. Only original works were permitted, published between January 2014 and December 2025. RESULTS: Six studies met the inclusion criteria. Case reports demonstrated heterogenous clinical outcomes with, rapid SVD observed in some alpha-gal sensitized patients, while other patients showed tolerance to bioprosthetic implantation in the perioperative and short-term period. The only study with longitudinal follow-up demonstrated that anti-AG IgG responses were associated with increased SVD and calcification. Another study found no perioperative adverse valvular outcomes, although follow-up was limited to in-hospital assessment. Overall, his manuscript identifies that AG sensitization may contribute to SVD in certain patients, however, its broader significance remains uncertain. CONCLUSIONS: Immune recognition of AG may contribute to SVD based on the limited available evidence. Larger prospective investigations are required to clarify a causal relationship and to assist in guiding potential preventative strategies. Recognition of this mechanism may ultimately inform management of valve replacement and bioprosthesis selection plans.