Superiority Assessment of Donor-derived Cell-FreE DNA ( Deoxyribonucleic Acid) for Cardiac Allograft REjection Monitoring

Heart transplantation (HTx) remains the gold-standard treatment for patients with end-stage heart failure refractory to the medical management, offering the best survival and quality of life. In the absence of a reliable non-invasive biomarker, international guidelines recommend to screen for cardiac allograft rejection during the first-year post-transplant using iterative protocol endomyocardial biopsies, a stressful and invasive procedure at risk of periprocedural complications. This invasive strategy suffers from multiple limitations and is increasingly being questioned. Recently, circulating donor-derived cell-free DNA (dd-cfDNA) ""Donor-derived cell-FreE Deoxyribonucleic Acid"", has been proposed as a reliable non-invasive biomarker of rejection in solid organ transplantation. Strong associations between allograft rejection and dd-cfDNA have been found in observational studies. Although donor-derived cell-free DNA (dd-cfDNA) is considered as the most promising non-invasive biomarker of allograft injury by international experts, no interventional trial has ever confirmed the efficiency and the safety of the non-invasive monitoring of rejection using dd-cfDNA. This prospective validation is mandatory and represents an important unmet medical need.We hypothesize that a non-invasive dd-cfDNA-based strategy might be superior to an invasive biopsy-based strategy for the screening of rejection in terms of patients' survival, allograft function and quality of life.

Inclusion Criteria: 1. Male or female, age 18 years or older at the time of signing informed consent, 2. Heart transplant recipient at 30 to 40 days post-transplant, discharged from the intensive care unit, 3. With at least one endomyocardial biopsy showing no signs of significant ongoing allograft rejection (ACR "Acute Cellular Rejection" ≥ 2R and/or pAMR "pathologic Antibody-Mediated Rejection" ≥ pAMR2 according to ISHLT "International Society for Heart and Lung Transplantation" working formulations), 4. Able to read, understand and provide written informed consent, 5. Able to understand and read French 6. Able and willing to comply with the study visit schedule, study procedures and study requirements, 7. Affiliation to a social security regime Exclusion Criteria: 1. Heart transplantation has been performed for more than 40 days. 2. Concurrent multiple solid organ or tissue transplant 3. Prior history of any solid organ or cellular transplantation (other than the current heart transplantation). 4. Planned use of other commercially available or investigational dd-cfDNA or gene expression profile assays. 5. Pregnancy and/or breastfeeding. 6. Hemodynamically unstable or other serious medical condition that may adversely affect the subject's ability to participate in the study. 7. Patient non discharged from ICU within 40 days post-transplant 8. Significant allograft rejection (ACR ≥ 2R and/or pAMR ≥ pAMR2) between transplantation and inclusion / randomization. 9. Under legal protection measure (tutorship or curatorship) and patient deprived of freedom 10. Participation in another interventional clinical trial