Outcomes following heart transplantation in children

Abstract 

After nearly 30 years of heart transplantation in children, following the introduction of cyclosporine, it is clear that early and intermediate survival following transplantation is good. Actuarial survival at one year, 5 years, 10 years are 85%, 75%, and 64% respectively. Fifteen year actuarial survival in the ISHLT Registry is approximately 47%. Naturally, late survival reflects early experience with transplantation in children and a worst case scenario. Recent studies show that survival is improving owing almost entirely to reduced early mortality after transplant. Survival at five years in the current era, 2001–2005, is 77% compared to 72% for the era 1993–2000. Multiple factors may account for this reduced early mortality including better peri-operative management, improved immunosuppression but also better case selection and earlier referral. However, despite improving results and reduced early mortality, there is an ongoing constant phase of mortality, approximately 3% per year, resulting in decreasing survival with time. This ongoing risk of death has persisted but may be less in the current era due to improvements in immunosuppression.

Important differences in survival exist between patients of different age at transplant. While early survival in infants is less than in older children, late survival and overall survival is better. For those infants surviving at least one year after transplant subsequent ten year survival is approximately 80% compared to 70% for children 1–10 years of age and 60% for children 11–17 years of age. Of note, the constant hazard for death appears to be less the younger the infant is at transplant, compared to older children. This may represent a degree of conditional tolerance in the youngest infant. Patients with congenital heart disease have good survival following transplant but less than patients with cardiomyopathy or myocarditis. However, for patients with failed Fontan palliation for single ventricle survival is comparable to other patients with congenital heart disease. Outcomes for patients requiring mechanical support are poor for patients bridged to transplant with ECMO but are equivalent to other Status 1 patients for those on left ventricular assist devices (Thoratec, HeartMate, Abiomed, etc.). Outcomes of bridge to transplant with Berlin EXCOR appear to be superior to ECMO but a multi-center study is underway.

Despite discouraging late survival estimates based on historical experience, improving survival in more recent eras will probably result in improved long term survival in future years. Development of new strategies for immunosuppression, particularly those aimed at reducing graft loss from chronic rejection, may also significantly improve long term survival. In addition, tailoring therapy to those who are at high risk, including those with high risk due to elevated PRA and those with other risk factors may improve long term survival.

Keywords: Heart transplant, Cardiac, Heart disease, Antibodies