Coronary cardiac allograft vasculopathy versus native atherosclerosis: difficulties in classification

Abstract

Cardiac allograft vasculopathy is regarded as a progressive and diffuse intimal hyperplastic lesion of arteries and veins that leads to insidious vessel narrowing and to allograft ischemic disease, such as acute myocardial infarction or sudden cardiac death. The coronary lesions in transplanted hearts are considered as a particular type of arteriosclerosis with many similarities but also significant differences compared to native coronary atherosclerosis. It is particularly difficult for pathologists to systematically classify the lesions and to elucidate their origins, since over time, the allograft immune responses cause vascular pathology characterized by not only the onset of de novo fibrocellular lesions but also remodeling of already-existing native atherosclerotic lesions in the donor heart. Intraplaque hemorrhages, which result from newly formed leaky microvessels, may cause rapid increase of stenosis and generate a substrate for plaque destabilization. Comparing cardiac allograft vasculopathy from explanted hearts at autopsy with native coronary atherosclerosis from hearts removed at transplantation has revealed that ongoing intraplaque hemorrhages are also an important feature of cardiac allograft vasculopathy and may be important factors in the rapid progression of cardiac allograft vasculopathy.

Late Failing Heart Allografts: Pathology of Cardiac Allograft Vasculopathy and Association With Antibody-Mediated Rejection

“…Experimental data from mouse models have demonstrated that alloantibodies may induce the development of fibrous intimal thickening of coronary arteries, a hallmark of human cardiac allograft vasculopathy (CAV). CAV is a multifaceted disease (8)(9)(10), with a complex pathophysiology involving either nonimmune and/or immune factors (11)(12)(13).…”

Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After Heart Transplantation

“…As in native atherosclerosis (18,19), these components of plaque instability can be encountered in CAV lesions, too, (7,20,21) and some of them (particularly increased lipid-rich, necrotic core and dense calcium) are associated with adverse clinical events in heart transplant recipients, such as recurrent acute cellular rejection, CAV progression, and need for revascularization (7,22). A histopathological study also demonstrated that in contrast to fibro-cellular plaques associated with different inflammatory cell subtypes in CAV versus native atherosclerosis (fewer macrophages and more lymphocytes in CAV), fibro-lipid plaques had the same inflammatory patterns between the 2 pathologies (23). That study also showed that intraplaque hemorrhage – another risk factor for plaque progression and instability in native atherosclerosis – was seen more frequently in CAV lesions than in native atherosclerosis and were colocalized with lipids and necrotic cores in these lesions.…”

“…Previous studies have demonstrated an association of acute cellular rejection in the early post-transplant period with inflammatory plaque (increased necrotic core and dense calcium contents) and CAV progression late after heart transplantation (3, 7,12). Immunohistochemical studies also suggested that typical CAV lesions display a similar pattern of inflammatory changes when compared to the inflamed myocardium during acute cellular rejection (23,26). The current study used serial IVUS in the early post-transplant period and showed that early acute cellular rejection can also affect plaque destabilization (ASP progression) during the first year, supporting the major contribution of inflammatory pathways to the etiology of CAV.…”

Association of periarterial neovascularization with progression of cardiac allograft vasculopathy and long-term clinical outcomes in heart transplant recipients

“…After heart transplantation, the transmural inflammation related to CAV often extends from the coronary artery intima to adventitia, and can even reach the perivascular tissues, (21,22) while inflammation is usually limited to the intima in atherosclerotic plaques. This widespread inflammation, which includes the tissue surrounding the blood vessels, may be associated with allograft rejection.…”