Our long-term goal is to understand early graft events that lead to the shortened lifespan of children receiving heart transplants. Understanding the risk factors for adverse graft outcomes will help determine the best opportunities for prevention and management of factors that lead to shortened life expectancy. In broad terms, we know that donor-specific antibodies (DSA; circulating proteins in the blood that attach to the graft and damage it) lead to poorer long-term graft outcomes. However, not all antibodies are equally damaging.

In Aim 1 of this study, we determine which pediatric heart transplant recipients have DSA in their blood before and after transplant and in year 1 of the study, we have performed multiple additional specialized tests to determine the special characteristics of all these antibodies in order to help us determine which ones are most damaging to the new heart. We believe this will help define a target population for more intensive therapies to prevent and treat “bad” antibody development.

In Aim 2, we use highly sophisticated and novel pathology techniques to look at biopsies of the transplanted heart of transplant recipients. We believe that studying the small blood vessels in the heart (graft capillaries) within 6 months of the transplant using automated pathology techniques with special stains, we may be able to identify those patients with early damage to blood vessels that may indicate the potential for adverse longer-term outcomes. We also believe that these damaged capillaries will be associated with certain antibodies as identified in Aim 1. In year 1, we obtained all the biopsy slides, stained them with special stains and made whole slide images of all materials for automated computer analysis that will occur in year 2.

Aim 3 will use the results of the tests in Aims 1 and 2 to create a computer model to predict which recipients are at highest risk for adverse outcomes such as rejection or graft loss. This analysis will occur in the last 6 months of the study per the original study timeline. In summary, we achieved the goals we set out in year one and anticipate that the studies will be completed on time at the end of year 2. We are hopeful that this model can help the child’s care team earlier in the post-transplant period to personalize their care to improve the child’s long-term outcomes.

Specific Aim 1: Perform detailed analysis of DSA in the pre and early post-transplant period after pediatric heart transplantation.

Specific Aim 2: To develop an automated transport based-based morphometry system that can be easily and widely applied to routine endomyocardial biopsies (EMB) early after heart transplant with the goal of predicting late graft outcomes.

Specific Aim 3: To develop a risk prediction model that incorporates all clinical information from CTOTC-09, combined with results from aims 1-2 above, and that can be applied in the first six months after transplantation to predict late (3 and 5 year) graft outcomes among early post-transplant survivors.