Increasing numbers of infants are undergoing complete repair rather than palliation of congenital heart defects that requires placement of a cryopreserved valved allograft in the pulmonary position. Allograft implantation results in the production of HLA antibodies that contribute to the development of conduit stenosis and regurgitation and ultimately the need for replacement. In fact, 60 -100% of infant implants fail within 5 years, offsetting the success of an early complete repair since subsequent surgeries are needed. In addition, some of these children develop end-stage heart disease and may be listed for heart transplantation, If panel reactive antibodies (PRA) are >10%, prospective cross matching is required, limiting the donor pool and increasing both morbidity and mortality. Furthermore, despite successful prospective cross-matching, the incidence of graft rejection is higher in sensitized children than in children who do not have HLA antibodies. Thus, abrogating antibody production and prolonging the durability of the allograft would reduce the number of conduit replacement surgeries along with the associated surgical morbidity and mortality, economic burden, family stress, and negative effect of multiple hospitalizations on growth and development. It would also decrease the transplantation risk in the subset of children who develop end-stage heart disease. Pharmacological abrogation of the antibody response with a brief course of immunosuppression using mycophenolate mofetil (MMF) appeared successful and safe in a pilot study involving a small number of children who received a first time cryopreserved valved allograft. Before widespread use can be recommended, however, a randomized trial with adequate power is needed. The overall goal of this prospective randomized trial is to evaluate the proportion of subjects with PRA <10% in a group receiving MMF compared with a group receiving standard therapy only. In addition, echocardiographic endpoints of allograft failure will be evaluated along with their association with PRA. Drug safety will be determined by monitoring adverse events and specific blood tests. This study is being proposed to the Pediatric Heart Network because it requires several centers to provide an adequate number of subjects and because the required tests and procedures are widely used in clinical practice so each center will have the needed equipment and personnel to implement the protocol and obtain the studies and samples required for evaluation by core laboratories. Lay summary: Infants with heart defects who need a conduit placed between their right-sided heart pump and the blood vessel that goes to the lungs have early failure of that conduit and need additional surgeries to replace it each time it fails. This research will determine if a drug (mycophenolate mofetil) given for a short time after the conduit is first put in will safely decrease the body's reaction to the conduit and make it last longer so the child will not need as many operations. (End of Abstract).
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