Human leukocyte antigen-DR and ABO mismatch are associated with accelerated homograft valve failure in children: Implications for therapeutic interventions

Objective: This study examines the incidence and factors associated with the failure of homograft valves and identifies those factors that are modifiable. Methods: From 1990 to 2001, 96 homograft valves were implanted in the right ventricular outflow tract of 83 children (mean age 5.1 +/- 5.6 years). Clinical and blinded serial echocardiographic follow-up was performed on all 90 valves in the 77 survivors. Results: Eighteen homograft valves were replaced as the result of pulmonary insufficiency (3), stenosis (9), or both (6). Freedom from reoperation was 71% at 9 years (95% confidence interval, 58%-84%). Forty-eight valves developed progressive pulmonary insufficiency of at least 2 grades, 26 valves developed transvalvular gradients of 50 mm Hg or greater, and 14 of these valves were also insufficient. The freedom from echocardiographic failure (progressive pulmonary insufficiency greater than or equal to2 grades or greater than or equal to50 mm Hg gradient) was only 27% at 5 years (95% confidence interval, 17%-37%). In a multivariate analysis (Cox regression), use of an aortic homograft (P = .001) and short antibiotic preservation time (P = .04) were associated with reoperation. Younger age (P = .01), ABO mismatch (P = .04), and diagnosis (P = .005) were associated with echocardiographic failure. In the subanalysis of patients with human leukocyte antigen typing, age (P = .002), aortic homograft (P = .04), and human leukocyte antigen-DR mismatch (P = .03) were associated with echocardiographic valve failure. Conclusion: Many homografts rapidly become insufficient and require replacement. In our analysis of both reoperation and echocardiographic failure, several immunologic factors are consistently associated with homograft failure. Matching for human leukocyte antigen-DR, blood group, and avoiding short preservation times (thus minimizing antigenicity) offers the potential to extend the life of these valves.