Serum biomarkers in cardiac allograft vasculopathy: A systematic review

• CAV remains a leading cause of graft failure and death in heart transplant recipients, necessitating robust, non-invasive diagnostic strategies due to the absence of angina symptoms in denervated hearts. • Biomarkers with strong diagnostic and prognostic performance are well-supported in the literature but remain largely absent from clinical guidelines. • Emerging technologies, including AI-driven histopathology, SOMAscan proteomics, and machine learning integration of multimodal biomarker data, are enhancing CAV risk stratification and may help develop future diagnostic approaches. Cardiac Allograft Vasculopathy (CAV) is a progressive manifestation of chronic allograft rejection in heart transplant recipients. While current diagnostic tools involve invasive and non-invasive imaging of coronary arterial anatomy and blood flow, circulating biomarkers can lead to earlier detection non-invasively. The aim of this systematic review is to synthesize existing literature of prognostic and diagnostic circulating peripheral biomarkers of CAV. A thorough literature search was performed on Pubmed, CINAHL, Scopus and Medline using the terms “cardiac allograft vasculopathy,” “CAV,” and “biomarkers.” The search yielded 1648 studies; 109 were included for the final review. Quality of evidence and risk of bias varied across the studies. Multiple circulating biomarkers could help diagnose and prognosticate in the presence of CAV with variable diagnostic accuracy and predictability. The role of incorporating these biomarkers in traditional coronary imaging diagnostic paradigm of CAV remains to be studied.