Revisiting Biomarkers of Cardiac Allograft Vasculopathy: Addressing the Achilles Heel of Heart Transplantation

Nearly half of heart transplant recipients will be diagnosed with cardiac allograft vasculopathy (CAV) within five years after transplantation. Advanced CAV can lead to worsening heart failure as well as arrhythmias and sudden cardiac death. The only curative therapy for end-stage CAV is re-transplantation. Current diagnostic methods are invasive and limited by poor sensitivity in early disease. Despite its high prevalence in the post-transplantpopulation, the underlying pathophysiology of this condition has yet to be fully described. It is thought to be primarily related to endothelial dysfunction, immune activation, and cardiometabolic disease. Biomarkers reflecting these underlying processes, particularly endothelial injury and immune activation, have shown early promise in discriminating prevalent CAV. Next-generation sequencing technologies such as proteomic and transcriptomic profiling have also provided further insight into the pathophysiology of CAV through the identification of novel biomarkers. Ultimately, these biomarkers may have a role in not only diagnosing CAV but also highlighting potential targets for disease-specific therapies. In this article, we review the current data for biomarkers in CAV and discuss future directions for biomarker identification..