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

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.

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.

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.

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.