Transforming heart transplantation care with multi-omics insights

Heart transplantation (HTx) remains the definitive treatment for patients with end-stage heart disease. Despite the number of HTx performed annually in worldwide continues to increase, complications of HTx still impact the quality of life and long-term prognosis, including rejection, infection, and allograft dysfunction. Endomyocardial biopsy remains the gold standard for monitoring cardiac allograft rejection post-heart transplantation, yet its invasiveness and interobserver error in histologic grading necessitate the development of novel noninvasive biomarkers to elucidate rejection mechanisms and progression. Cardiac allograft vasculopathy, a critical determinant of long-term outcomes, is challenging to detect early via intravascular ultrasound, underscoring the potential of plasma biomarkers for disease surveillance. Omic technologies usually refers to the application of multiple high-throughput screening technologies enabling comprehensive analysis of biological systems at a molecular level. Multi-omics technologies, including genomics(donor-derived cell-free DNA), transcriptomics(microRNAs panels, gene expression profiling), proteomics(cell signaling molecule), and metabolomics(ex situ heart perfusion), have demonstrated significant promise in post-transplant monitoring. These approaches provide personalized risk stratification and mechanical insights into cardiac allograft rejection, primary graft dysfunction, and cardiac allograft vasculopathy. Single-cell omics technologies and machine learning algorithms further resolve cellular heterogeneity and improve predictive modeling, thereby enhancing the clinical translatability of multi-omics data. This comprehensive review synthesizes these advances and highlights the transformative potential of integrating multi-omics with advanced analytics to achieve precision monitoring and therapy in HTx, ultimately improving long-term patient outcomes.