However, in CAV, histology specimens typically show concentric thickening of the intimal layer of the main coronary arteries on the surface of the heart and in intramyocardial arteries which can become obliterated within a few years. There is smooth muscle cell migration, foamy macrophages and lymphocytic infiltrates. This can be seen to affect the whole length of the coronary arteries and often the smaller arteries. Calcification does not always occur in CAV and if it does appear, it happens late. The compensatory arterial dilation does not occur in CAV. Unlike in nontransplanted people with coronary artery disease due to atherosclerosis, in CAV occlusion with thrombus of the vessel lumen is rare.Inflammation and endothelial injury can be triggered by the donor arrest, organ procurement, and allograft ischaemia and reperfusion. Diagnosis
As symptoms are so variable and often absent, diagnosis has been a challenge. Hence, regular follow-up and monitoring of the allograft for early signs of disease is advocated. Coronary angiography
Surveillance is performed by regularly repeating coronary angiography in the cardiac catheterization laboratory, the diagnostic test of choice. This is typically performed annually for the first five years after transplantation. Angiography in CAV characteristically demonstrates diffuse stenoses in large coronary arteries and a reduced number of smaller coronary arteries, also known as "peripheral pruning". However, because CAV frequently affects the entire length of the coronary artery, CAV may not be apparent by angiography alone.
History
Unlike rejection and infection, CAV in the transplanted heart was not initially a predicted outcome. Early survivors of heart transplants soon developed this form of vasculopathy of their coronary arteries, initially identified at post-mortems. There were early suggestions that preventing cytomegalovirus (CMV) infection could decrease the prevalence of CAV. The impact of CAV has changed over time, with early recipients being younger, having more rejection and cardiovascular risk factors and less use of statins. Later recipients used statins routinely and were introduced to the immunosuppressive agent mycophenolate mofetil (MMF) and CMV prophylaxis. In addition, the later recipients were monitored for antibody-mediated cardiac allograft rejection (AMR).Before 2010 there was no uniform international standards for the nomenclature of CAV. A consensus statement on a standard language for CAV was first published in 2010 by the ISHLT. This was devised in a similar way to the earlier acute rejection grading system by endomyocardial biopsy. Research directions
Antibody-mediated cardiac allograft rejection (AMR) is a significant factor leading to the rapid progression of CAV. Future research directions in this area may include prospective databases that correlate clinical factors with surveillance of the incidence and severity of AMR, the frequency of CMV infection, and the use of immunosuppressants. The role of inducing immune tolerance has yet to be established. == References ==