The Cypher and Taxus DES result in delayed arterial healing when compared with BMS of similar implant duration. The cause of DES LST is multifactorial with delayed healing in combination with other clinical and procedural risk factors playing a role.

Background-The long-term safety of drug-eluting stents (DES) for acute myocardial infarction (AMI) remains uncertain.Using autopsy data, we evaluated the pathological responses of the stented segment in patients treated with DES for AMI and compared with patients with stable angina. Methods and Results-From the CVPath Registry of 138 DES autopsies, we identified 25 patients who presented with AMI and had an underlying necrotic core with a ruptured fibrous cap. Twenty-six patients who had stable angina with thick-cap fibroatheroma treated by DES were selected as controls. Histomorphometric analysis was performed in patients with Ͼ30-day stent duration. We compared the response to stenting at the culprit site in these 2 groups and to nonculprit sites within each stent.

Veins grafted into an arterial environment undergo a complex vascular remodeling process. Pathologic vascular remodeling often results in stenosed or occluded conduit grafts. Understanding this complex process is important for improving the outcome of patients with coronary and peripheral artery disease undergoing surgical revascularization. Using in vivo murine cell lineage-tracing models, we show that endothelial-derived cells contribute to neointimal formation through endothelial to mesenchymal transition (EndMT), which is dependent upon early activation of the Smad2/3-Slug signaling pathway. Antagonism of TGF-β signaling by TGF-β neutralizing antibody, shRNA-mediated Smad3 or Smad2 knockdown, Smad3 haploinsufficiency, or endothelial cell-specific Smad2 deletion resulted in decreased EndMT and less neointimal formation compared to controls. Histological examination of postmortem human vein graft tissue corroborated the changes observed in our mouse vein graft model, suggesting that EndMT is operative during human vein graft remodeling. These data establish that EndMT is an important mechanism underlying neointimal formation in interpositional vein grafts, and identifies the TGF-β/Smad2/3-Slug signaling pathway as a potential therapeutic target to prevent clinical vein graft restenosis.

Objectives Human coronary bare metal stents (BMS) and drug-eluting stents (DES) from autopsy cases with implant durations >30 days were examined for the presence of neointimal atherosclerotic disease. Background Neointimal atherosclerotic change (neoatherosclerosis) following BMS implantation is rarely reported and usually occurs beyond 5 years. The incidence of neoatherosclerosis following DES implantation has not been reported. Methods All available cases from the CVPath stent registry (n=299 autopsies), which includes a total of 406 lesions (197 BMS, 209 DES [103 sirolimus-eluting stents (SES), and 106 paclitaxel-eluting stents (PES)]) with implant duration >30 days were examined. Neoatherosclerosis was recognized as clusters of lipid-laden foamy macrophages within the neointima with or without necrotic core formation. Results The incidence of neoatherosclerosis was significantly greater in DES (31%) than BMS (16%) lesions (p<0.001). The median stent duration with neoatherosclerosis was shorter in DES than BMS (DES; 420 [361–683], BMS; 2160 [1800–2880] days, p<0.001). Unstable lesions characterized as thin-cap fibroatheromas or plaque rupture were more frequent in BMS (n=7, 4%) than DES (n=3, 1%) (p=0.17), with relatively shorter implant durations for DES (1.5±0.4 years) compared to BMS (6.1±1.5 years). Independent determinants of neoatherosclerosis identified by multiple logistic regression included younger age (p<0.001), longer implant durations (p<0.001), SES usage (p<0.001), PES usage (p=0.001), and underlying unstable plaques (p=0.004). Conclusions Neoatherosclerosis is a frequent finding in DES and occurs earlier than in BMS. Unstable features of neoatherosclerosis are identified for both BMS and DES with shorter implant durations for the latter. The development of neoatherosclerosis may be yet another rare contributing factor to late thrombotic events.

Background Clinical trials have demonstrated that second-generation cobalt-chromium everolimus-eluting stent (CoCr-EES) is superior to first-generation paclitaxel-eluting stent (PES) and is non-inferior or superior to sirolimus-eluting stent (SES) in terms of safety and efficacy. It remains unclear whether vascular responses to CoCr-EES are different from SES and PES, since the pathology of CoCr-EES has not been described in humans. Methods and Results A total of 204 lesions (SES=73, PES=85, CoCr-EES=46) from 149 autopsy cases with duration of implant >30 days and ≤3 years were pathologically analyzed, where comparison of vascular responses was corrected for duration of implant. The observed frequency of late and very late stent thrombosis (LST/VLST) was less in CoCr-EES (4%) versus SES (21%, p=0.029) and PES (26%, p=0.008). Neointimal thickness was comparable among the groups, while the percent uncovered struts was strikingly lower in CoCr-EES (median=2.6%) versus SES (18.0%, p≤0.0005) and PES (18.7%, p<0.0005). CoCr-EES showed less inflammation score (with no hypersensitivity) and less fibrin deposition versus SES and PES. The observed frequency of neoatherosclerosis, however, did not differ significantly among the groups (CoCr-EES=29%, SES=35%, PES=19%). CoCr-EES had the least frequency of stent fracture (CoCr-EES=13%, SES=40%, PES=19%; p=0.007 for CoCr-EES versus SES), whereas fracture-related restenosis or thrombosis was comparable among the groups (CoCr-EES=6.5%, SES=5.5%, PES=1.2%). Conclusions CoCr-EES demonstrated greater strut coverage with less inflammation, less fibrin deposition, and less LST/VLST as compared to SES and PES in human autopsy analysis. Nevertheless, the observed frequencies of neoatherosclerosis and fracture-related adverse pathologic events were comparable in these devices, indicating that careful long-term follow-up remains important even after CoCr-EES placement.