• Composite endpoint of death, graft loss, or rejection with hemodynamic compromise [ Time Frame: At Month 12 post-transplantation ] [ Designated as safety issue: Yes ]
  

• Overall participant and graft survival [ Time Frame: At Month 12 ] [ Designated as safety issue: Yes ]
  
• Frequency and time to acute rejection [ Time Frame: At Month 12 ] [ Designated as safety issue: Yes ]
  
• C4d on EMB [ Time Frame: At Month 12 ] [ Designated as safety issue: No ]
  
• Re-hospitalizations [ Time Frame: At Month 12 ] [ Designated as safety issue: No ]
  
• Severe infections [ Time Frame: At Month 12 ] [ Designated as safety issue: Yes ]
  
• Time to diagnosis of chronic rejection [ Time Frame: Through Month 36 ] [ Designated as safety issue: Yes ]
  
• Time to post-transplantation lymphoproliferative disorder [ Time Frame: At Month 36 ] [ Designated as safety issue: Yes ]
  
• Time to new-onset diabetes mellitus [ Time Frame: At Month 36 ] [ Designated as safety issue: Yes ]
  
• Wait-list mortality [ Time Frame: Measured up to 3 years post-transplant ] [ Designated as safety issue: Yes ]
  
• Time from listing to transplantation, death or delisting [ Time Frame: Measured up to 3 years post-transplant ] [ Designated as safety issue: Yes ]
  
• Panel reactivity of IgG allo-antibodies by AHG CDC-PRA [ Time Frame: Measured up to 3 years post-transplant ] [ Designated as safety issue: No ]
  
• Presence and quantification of anti-HLA IgG antibodies by ELISA and Luminex assay [ Time Frame: Measured up to 3 years post-transplant ] [ Designated as safety issue: No ]
  
• Presence of anti-MICA antibodies by Luminex assay [ Time Frame: Measured up to 3 years post-transplant ] [ Designated as safety issue: No ]
  

There is currently a renewed interest in allo-antibodies in transplantation. In 1966, Kissmeyer and colleagues reported that pre-existing antibodies directed against donor cells could cause hyperacute rejection of the renal allograft. Three years later, in a landmark study, Patel and Terasaki showed that a lymphocytotoxic assay to identify donor-specific antibodies was highly predictive of acute graft failure. These observations led to the practice of performing prospective, donor-specific cross matches by lymphocytotoxicity assay for all kidney transplants and for heart and lung transplants when the candidate has a positive panel reactive antibody assay. A concept evolved that transplantations should not be performed across a positive cytotoxicity cross-match. The purpose of this study is to determine the clinical outcomes of sensitized pediatric heart transplant recipients with a positive donor-specific cytotoxicity cross-match and to compare them with outcomes in non-sensitized heart transplant recipients.

This study will enroll 370 pediatric heart transplant recipients over a period of 3 years. The follow-up period will last up to 3 years. All participants will be enrolled pre-transplant. In the pre-transplant phase, visits will occur every 6 months. These routine visits will continue up until transplant or the end of the study. They will coincide with routine pre-transplant status visits. At the time of transplant, the participants will be assigned to one of two groups. Group A participants will be allo-antibody negative (<10% by AHG CDC-PRA and ELISA in all DTT-treated serum samples). Group B participants will have the presence of a DTT-treated AHG CDC-PRA of ≥10% and/or an ELISA-PRA ≥10% in any pre-transplant sample.

Both groups will receive standard transplantation care. This study has no interventions. All participants will undergo regular blood tests, but those in the sensitized group will have additional blood testing done after the transplant and lasting until the end of the study. Visits post-transplant will occur while participants are recovering in the hospital; at Months 1, 3, and 6; and annually until the study closes.

The information collected for the study include data from a physical exam, routine testing, adverse and serious adverse events assessments, and blood collection. Each time a biopsy is done, the study will ask to review the biopsy tissue and to collect a sample. If stored tissue is not available, none will be collected.