| Valved allografts are frequently used in the repair of congenital heart defects in children. Although the longevity of these grafts is generally very good, there continue to be ongoing problems with allograft stenosis, allograft valve insufficiency, and subsequent allograft failure, particularly in younger children. Investigators have put forth many possible etiologies for valved allograft failure in children. Risk factors for allograft degeneration are younger recipient or donor age, longer donor ischemic times, significant allograft size mismatch (donor size < 2 standard deviations below recipient size), and aortic valved allograft type rather than pulmonary valved allograft type. In broad terms, allograft degeneration may be due to factors related to or unrelated to immunologic injury. Factors unrelated to immunologic injury would include smaller size or ischemic injury. Factors related to immunologic injury include ABO incompatibility and HLA incompatibility. Pathologically, some investigators have failed to demonstrate any evidence of an inflammatory response in explanted valved allografts in adults. These studies describe explanted valved allografts as having minimal, if any viable cells, but retain the original collagen network. More recently, investigators have demonstrated significant cellular infiltration with T cell and B cells in failed explanted valved allografts in children. It has been established by multiple studies that allograft placement for repair of congenital heart defects induces a broadly reactive HLA antibody response that is persistent in many patients for up to 15 years after implantation. It has also been shown by analysis of HLA specificity of patient's serum and donor allografts that the antibody response is directed against HLA antigens present on the implanted allograft. Although the clinical effect of this antibody response is still unknown, we suspect that the vigorous antibody response demonstrated in children after implantation has the potential for harmful effects. Work from our institution has shown that 3 months of post-operative mycophenolic mofetil, but not azathioprine, suppresses the HLA response to valved allograft implantation, and that this response persists for up to 2 years. |
