Cardiac Allograft Vasculopathy: Past, Present and Future!

Cardiac Allograft Vasculopathy (CAV) is a serious complication after heart transplantation in adults as well as children and once developed irreversibly compromises the outcome of the recipients. Human leukocyte antigen mismatches, number and duration of rejection episodes, type of immunosuppression and presence of antibody -mediated rejection are among the most relevant immunological risk factors for CAV. Hypertension, hyperlipidemia, diabetes and metabolic syndrome, cytomegalovirus infection, mode of donor brain death, donor age, obesity, smoking and ischemia/reperfusion injury are among the most important non immunological risk factors. The combination of, non immunological and immunological risk factors facilitates the more rapid CAV development and progression towards a severe disease. Endothelial injury/dysfunction is the first event triggering the disease process. Inflammation is the central process of CAV development and progression. In order to more effectively affect CAV outcome and prolong survival, treatment with statins is recommended, and novel approaches needed. New immunosuppressive treatments to reduce CAV like mammalian target of rapamycin inhibitors (sirolimus and everolimus) are promptly required. Therapies effective in improving the allograft microvasculature like heparin -induced extracorporeal low density lipoprotein apheresis, or reducing the ischemia/reperfusion related damage like fibrin peptide Bß15-42 need to be introduced as possible new ways of treatment. Future perspectives for early CAV detection and prevention are: individual CAV risk stratification (immunohistochemistry, risk factor profiles), identification of novel early biomarkers, and a better understanding of antibody mediated rejection. All unknowns need to be resolved to better and more effectively prevent CAV development and/or reduce CAV progression.