Evolving concepts and treatment strategies for cardiac allograft vasculopathy.

OPINION STATEMENT: The central event in the development of allograft vasculopathy is the inflammatory response to immune-mediated and nonimmune-mediated endothelial damage. This response is characterized by the release of inflammatory cytokines, upregulation of cell-surface adhesion molecules, and subsequent binding of leukocytes. Growth factors stimulate smooth muscle cell proliferation and circulating progenitor cells are recruited to sites of arterial injury leading to neointima formation. Because of its diffuse nature, intravascular ultrasound is more sensitive than angiography for early diagnosis. Proliferation signal inhibitors (PSIs) have the capacity to slow vasculopathy progression by inhibiting smooth muscle cell proliferation, but its side effects profile makes its use as a first line agent difficult. Retransplantation is still the only definitive therapy but is available only in selected cases. The current hope is that immunomodulation at the time of transplant could induce long-term tolerance and graft accommodation, leading to less vasculopathy.