Abstract 2159: Medial Necrosis Due to Sirolimus-Eluting Stent Implantation in Human Coronary Arteries
Background: Sirolimus-eluting stents (SES) have been proven to reduce the rates of restenosis by a striking inhibition of neointimal hyperplasia. However, unusual vessel responses to SES, such as late-acquired incomplete stent apposition (ISA) have been observed, and the precise mechanism of late ISA has not been clarified.
Methods and Results: To examine the mechanism of late ISA, the temporal mode of vascular responses after SES (3 days (D) to 12 months (M), 14 lesions) and bare metal stent (BMS; 2 D to 12 M, 24 lesions) implantation was investigated histopathologically in necropsied coronary arteries. In arteries that had been implanted with SES for 4 M, the stent struts were focally covered by thin membranous tissue mainly composed of fibrin deposition. Complete coverage of BMS by neointimal tissue composed of smooth muscle cells (SMC) and extracellular matrix (ECM) was documented after 1.5 M. Only mild neointimal thickening with focal endothelialization was observed around the circumference of the lumen at the stented site of atherosclerotic plaque-free segment in 4 of 9 lesions after 4 to 12 M. In these lesions, expansion of the stent strut forced the struts contiguous to the medial layer. Remarkable loss of medial SMCs was evident not only at the sites of the stent struts that had contacted and focally compressed the medial layer, but also at the sites where there was bowing of the media into the intima between the struts. In contrast, only restricted and incomplete medial SMC depletion was observed in the BMS segments where struts compressed the medial layer. We could observe that the medial SMC depletion was present only in the portions where SES struts directly contacted the medial wall layers. Depletion of medial SMC was not clearly observed even in DES segment between 3 D and 1 M.
Conclusions: Therefore, it is possible that these phenomena concerning elimination of medial SMCs were elicited by not only mechanical injury due to stent expansion but also by the pharmacological effect of sirolimus itself. The cytostatic effects of sirolimus on neointimal formation could be complicated by these local cytotoxic effects followed by a decrease in arterial wall tension, causing stent malapposition.