Rejection Surveillance: Integrating Cell-Free DNA and Gene Expression Panels to Decrease Invasiveness in Routine Monitoring of Heart Transplant Recipients

Post-transplant rejection surveillance remains a cornerstone of heart transplant care. Although endomyocardial biopsy has long been the gold standard for monitoring rejection, its invasiveness and limitations have driven innovations in noninvasive techniques. Molecular diagnostics, including gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA), have emerged as promising alternatives with demonstrated utility. GEP excels in identifying immune activation with high negative predictive value, while dd-cfDNA provides insights into allograft injury, with sensitivity up to 81% and specificity of 85%. Complementary cardiac imaging such as echocardiography and cardiac magnetic resonance enhance graft assessment by providing structural and functional data. Together, these investigations offer a multimodal approach to rejection surveillance, reducing the frequency of endomyocardial biopsy and improving overall care for transplant recipients.