Determining the Association of Microvascular Disease as Assessed by PET and Graft Injury by Donor Derived Cell Free DNA

The goal of this research study is to understand if a blood test in people who have had heart transplants can detect and predict the following: * Blockages in the small blood vessels of the heart. * Whether small blockages can turn into more severe blockages in the future. Participants will undergo blood draws once every 3 months in the first year of the study (4 blood draws total, taking 15 minutes each) and their medical records will be reviewed for 3 years after the date they are enrolled in the study.

A prospective, single center, assessment of donor derived cell free DNA in subjects who are post-heart transplant to assess correlation with microvascular flow as assessed by myocardial flow reserve (MFR) on positron emission tomography (PET). Study design: This prospective, single center registry will enroll up to 88 subjects at Yale New Haven Health System (YNHHS). Patients who get PET scans for routine post-transplant surveillance will be included in the study. Up to an anticipated 44 subjects with low MFR and up to an anticipated 44 subjects with normal MFR will have dd-cf DNA drawn every 3 months for a year. Patient population: A total of 88 adults referred to have an annual PET stress test as part of routine post-transplant surveillance for cardiac allograft vasculopathy and who are at least 3 years from heart transplantation and meet all eligibility criteria will be enrolled. Diagnostic assessment: All subjects will have quarterly blood draws during the first year of enrollment to assess the levels of dd- cf DNA. All subjects will also undergo standard of care annual PET scans. Subject follow up: All subjects will have routine follow-up as clinically necessary based on standard of care. Screening and follow-up data collection will occur through the electronic medical record. Follow up duration: 3 years after enrollment. Primary endpoint: Elevated dd-cf DNA levels in subjects with low MFR compared to normal MFR at up to one year follow-up post-enrollment. Secondary Endpoints: The following secondary endpoints will be reported at 3 years post-enrollment based on the routine post-transplant standard of care: * Combined clinical events of rejection, reduction in ejection fraction, need for revascularization, myocardial infarction, heart failure admissions and death or need for retransplantation. * All-cause, cardiovascular, and non-cardiovascular mortality * Myocardial infarction (Fourth Universal Definition) * Revascularization (PCI or CABG) * Hospitalization for heart failure * Rejection * Decrease in ejection fraction from baseline echo to 3 years follow up. * Retransplantation Procedure summary: Patients will undergo routine post-transplant surveillance and management per the discretion of the treating physician and per YNHHS post-heart transplant protocols. Quarterly study blood draws will be conducted in the first year of the study and will include dd-cf DNA measurements. These results will not be available to study team or the patients. All study participants will be blinded to these results.