Cardiac Allograft Vasculopathy: Past, Present and Future! - Abstract
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.