Improving outcomes in paediatric heart transplantation

For patients with end-stage heart failure, heart transplantation remains the only viable long-term option. During the last fifty years, the procedure has become more successful, and the majority of candidates can now expect to recover and lead relatively normal day-to-day lives. Unfortunately, however, it is not a perfect cure. Daily lifelong immunosuppression is required to protect against rejection, and current drug regimens have substantial side-effects including infection, renal failure and hypertension, all of which further shorten life expectancy. Current post-transplant graft survival is estimated at 15 to 20 years, after which re-transplantation is indicated; with donation rates decreasing, and potential recipient numbers increasing, this is by no means certain. This thesis represents a body of work aiming to show improving outcomes for children at different stages of the transplant journey. Pre-transplant diagnosis has long been thought a predictor of outcome, with worse results for patients transplanted for congenital heart disease than cardiomyopathy. This work showed that with increasing specific surgical expertise, this bias has now largely disappeared. Restrictive cardiomyopathy, pre-transplant extra-corporeal membranous oxygenation and extreme donor:recipient weight ratio were all shown to increase the need for extra-corporeal life support as a rescue therapy in the immediate post-operative phase; this was associated with excellent medium-term survival in patients surviving to hospital discharge. Preimplantation use of the induction immunosuppression basiliximab was evaluated, indicating a reduction in acute rejection and mortality in the first 6 months posttransplant. Maintenance immunotherapy was also investigated, suggesting an improved side-effect profile seen in children taking tacrolimus rather than ciclosporin. Finally, cytomegalovirus was linked to the most important cause of death for patients over five years post-transplant – namely coronary allograft vasculopathy – as well as morphological and functional impairment in the systemic vasculature of heart transplant recipients. In summary, this thesis indicates an improving outcome for children at every stage of the post-transplant journey