Biomarker-Based Surveillance in Heart Transplant Rejection.

Post-transplant rejection surveillance remains a cornerstone of heart transplant care. Although endomyocardial biopsy (EMB) has long been the gold standard for detecting rejection, its invasive nature, interobserver variability in histologic interpretation, and limitations in distinguishing between acute cellular rejection (ACR) and antibody-mediated rejection have prompted interest in noninvasive techniques. Traditional biomarkers- such as troponin, C-reactive protein, brain natriuretic peptide, and donor-specific antibodies- offer supplementary assessments of graft function but lack the specificity and sensitivity required to be standalone markers. In contrast, commercially available molecular diagnostics and gene expression profiling tests have emerged as promising noninvasive biomarkers that reduce reliance on EMB while maintaining and improving diagnostic accuracy. These biomarkers enable longitudinal, non-invasive monitoring and may detect rejection earlier, enhancing overall care for transplant recipients. Complementary cardiac imaging modalities, including advanced echocardiography techniques, cardiac magnetic resonance, and positron emission tomography, further enhance graft assessment by providing detailed, structural, functional, and metabolic information. Despite these advancements, challenges remain in fully integrating these noninvasive approaches into the standardized care pathway of heart transplant patients. Additionally, emerging biomarkers, such as microRNAs, transcriptomic signatures, proteomic patterns, and metabolomic profiles, are under active investigation and hold the potential to further transform the landscape of rejection surveillance. This manuscript reviews the current standards in heart transplant rejection monitoring, highlights the promise of emerging molecular and imaging technologies, and explores the potential of multimodal strategies to personalize and improve long-term transplant outcomes.