Abstract 9910: Chronic Inflammatory Responses to Polymer Can Evoke Both Late Restenosis and Very Late Stent Thrombosis After Sirolimus-Eluting Stent Implantation in Human Coronary Arteries

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Background: Sirolimus-eluting stents (SES) can reduce the rate of restenosis by marked inhibition of neointimal hyperplasia. However, late adverse events occurring more than 1 year (Y) after SES implantation, in-stent late luminal loss (LLL) and very late stent thrombosis (VLST), have been reported. The detailed mechanisms of these events are poorly understood at present. Methods and Results: Postmortem histopathological investigation of late vascular responses of coronary arteries was performed in 32 consecutive patients (pts) more than 1 Y after SES implantation. Although most simple lesions with a single SES showed gradual endothelial coverage (80 to 90%) after 1 Y, there was considerable inflammatory reaction involving T lymphocytes (T cells), macrophages (MΦ) and multinucleated giant cells adjacent to the struts. Furthermore, 14 cases showed necrotic core formation with numerous circumferential cholesterol clefts and pronounced infiltration by lipid-laden MΦ that were immunoreactive for collagen-degrading matrix metalloproteinases around the struts. In 3 of these arteries, the luminal surface was focally ruptured and massive thrombi composed of platelets and fibrin were observed. Furthermore, in 2 pts who died of VLST more than 2 Y after SES implantation, the arterial wall of SES segments was aneurysmally dilated with an extensive inflammatory infiltrate involving the intima, media and adventitia consisting predominantly of T cells and eosinophils, and occasional giant cells. Furthermore, 2 other pts developing coronary aneurysms in the stented segments demonstrated diffuse restenosis. Granulomatous inflammatory reaction with mild to moderate inflammatory cell infiltration but remarkable smooth muscle cell proliferation was clearly observed in the restenotic regions in these pts. Conclusions: These findings suggest that the polymer of SES can evoke significant chronic destructive and/or proliferative inflammatory responses followed by severe adverse clinical events such as LLL or VLST, depending on the intensity of inflammation. Although relatively milder inflammatory changes induce intimal hyperplasia, vessel wall destruction by severe inflammation can lead to aneurysm formation in extreme cases.