Advancements in Heart Transplantation: Donor-Derived Cell-Free DNA as Next-Generation Biomarker.

Heart failure, particularly in its advanced stages, significantly impacts quality of life. Despite progress in Guideline-Directed Medical Therapy (GDMT) and invasive treatments, heart transplantation (HT) remains the primary option for severe cases. However, complications such as graft rejection present significant challenges that necessitate effective monitoring. Endomyocardial biopsy (EMB) is the gold standard for detecting rejection, but its invasive nature, associated risks, and healthcare costs have shifted interest in non-invasive techniques. Donor-derived cell-free DNA (dd-cfDNA) has gained attention as a promising non-invasive biomarker for monitoring graft rejection. Compared to EMB, dd-cfDNA detects graft rejection early and enables clinicians to adjust immunosuppression promptly. Despite its advantages, dd-cfDNA testing faces challenges, such as the need for specialized technology and potential inaccuracies due to other clinical conditions. Additionally, dd-cfDNA cannot yet differentiate between types of graft rejection, and its effectiveness in chronic rejection remains unclear. Research is ongoing to set precise standards for dd-cfDNA levels, which would enhance its diagnostic accuracy and help in clinical decisions. The article also points to the future of HT monitoring, which may involve combining dd-cfDNA with other biomarkers and integrating artificial intelligence to improve diagnostic capabilities and personalize patient care. Furthermore, it emphasizes both global and racial inequalities in dd-cfDNA testing and the ethical issues related to its use in transplant medicine.