Abstract 4724: Pathological Mechanisms of Very Late Stent Thrombosis After Drug-Eluting Stent Implantation in Human Coronary Arteries
Although the postulated causes of very late stent thrombosis (VLST) after drug-eluting stent implantation include delayed intimal healing and endothelialization, the precise mechanisms have not yet been clarified. We histopathologically investigated necropsied coronary arteries from 36 consecutive patients with 42 lesions (les) after sirolimus-eluting stent (SES) implantation. The interval between stenting and death was distributed as follows: <6 months (M), 12 les; 6 M-1 year (Y), 10 les; 1–2 Y, 11 les; 2–3 Y, 5 les; and >3 Y, 4 les. Even at 6 M, >60% of the SES segment was not yet covered by neointima composed of smooth muscle cells (SMCs) and extracellular matrix. Remarkable fibrin deposition and infiltration of inflammatory cells (T lymphocytes and macrophages (MΦ)) surrounding the stent struts were present. In 2 patients with sudden died by stent thrombosis after cessation of antiplatelet therapy, >40% of the SES surface was not yet reendothelialized 10 M after stenting, and these uncovered struts served as a nidus for mural thrombus formation. Although most simple lesions with a single SES showed gradual endothelial coverage (80 to 90%) after 1 Y, in complex lesions, such as bifurcation with side-branch SES stenting, stent struts across the ostium were not entirely covered by neointima after more than 1.5 Y. In neointima with reendothelialization more than 1.5 Y post-SES stenting, the SMCs had become atrophic and abundant proliferation of collagen fibers was evident. However, heavy infiltration by lipid-laden MΦ was observed around the struts, which were immunoreactive for collagen-degrading matrix metalloproteinases. In 2 of these arteries, the luminal surface at stent sites was focally eroded and massive thrombi consisting of platelets and fibrin were observed at these sites. These findings suggest that severe peri-strut chronic inflammatory cells may accelerate neointimal vulnerability followed by post-SES VLST, despite endothelial coverage and continuous antiplatelet therapy. Thus, administration of a drug capable of stabilizing atheromatous plaque, such as statin, might prevent VLST after SES implantation.