Cardiac allograft vasculopathy: advances in understanding its pathophysiology, prevention, and treatment.
OBJECTIVE
To discuss the current understanding of the pathogenesis, natural history, and diagnosis of cardiac allograft vasculopathy, and to outline new preventive and treatment strategies.


RESULTS
The central event in the development of allograft vasculopathy is the inflammatory response to immune or nonimmune-mediated endothelial damage. This response is characterized by the release of inflammatory cytokines, upregulation of cell-surface adhesion molecules, and the subsequent binding of leukocytes. Once induced, vascular smooth muscle cells proliferate and migrate from the media to form a neointima. Circulating progenitor cells are recruited to sites of arterial injury where they may then differentiate into smooth muscle cells. Because of its diffuse nature, allograft vasculopathy is best detected by intravascular ultrasound. Noninvasive tests, such as dobutamine echocardiography, are gaining in favor. Although the only definitive treatment is retransplantation, the immunosuppressant rapamycin can limit disease progression. Its synthetic derivative, everolimus, effectively prevented intimal hyperplasia in de novo transplant recipients.


CONCLUSIONS
These advances have provided hope that allograft vasculopathy may finally be manageable.
Pinney
Sean P
SP
Division of Circulatory Physiology, Columbia University, New York, New York, USA.
Mancini
Donna
D
D000924:Anticholesteremic Agents / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000209:etiology / Q000517:prevention & control / Q000628:therapy; D003331:Coronary Vessels / Q000473:pathology*; D004452:Echocardiography; D000068338:Everolimus; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D012086:Reoperation; D012307:Risk Factors; D019821:Simvastatin / Q000627:therapeutic use; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives*; D014184:Transplantation, Homologous; D018084:Ultrasonography, Interventional
D000924:Anticholesteremic Agents; D007166:Immunosuppressive Agents; D000068338:Everolimus; D019821:Simvastatin; D020123:Sirolimus