Background— Stent thrombosis may occur late after drug-eluting stent (DES) implantation, and its cause remains unknown. The present study investigated differences of the stented segment between patients with and without very late stent thrombosis with the use of intravascular ultrasound. Methods and Results— Since January 2004, patients presenting with very late stent thrombosis (>1 year) after DES implantation underwent intravascular ultrasound. Findings in patients with very late stent thrombosis were compared with intravascular ultrasound routinely obtained 8 months after DES implantation in 144 control patients, who did not experience stent thrombosis for ≥2 years. Very late stent thrombosis was encountered in 13 patients at a mean of 630±166 days after DES implantation. Compared with DES controls, patients with very late stent thrombosis had longer lesions (23.9±16.0 versus 13.3±7.9 mm; P <0.001) and stents (34.6±22.4 versus 18.6±9.5 mm; P <0.001), more stents per lesion (1.6±0.9 versus 1.1±0.4; P <0.001), and stent overlap (39% versus 8%; P <0.001). Vessel cross-sectional area was similar for the reference segment (cross-sectional area of the external elastic membrane: 18.9±6.9 versus 20.4±7.2 mm 2 ; P =0.46) but significantly larger for the in-stent segment (28.6±11.9 versus 20.1±6.7 mm 2 ; P =0.03) in very late stent thrombosis patients compared with DES controls. Incomplete stent apposition was more frequent (77% versus 12%; P <0.001) and maximal incomplete stent apposition area was larger (8.3±7.5 versus 4.0±3.8 mm 2 ; P =0.03) in patients with very late stent thrombosis compared with controls. Conclusions— Incomplete stent apposition is highly prevalent in patients with very late stent thrombosis after DES implantation, suggesting a role in the pathogenesis of this adverse event.

As compared with paclitaxel-eluting stents, the use of sirolimus-eluting stents results in fewer major adverse cardiac events, primarily by decreasing the rates of clinical and angiographic restenosis.

Background-Intravascular ultrasound of drug-eluting stent (DES) thrombosis (ST) reveals a high incidence of incomplete stent apposition (ISA) and vessel remodeling. Autopsy specimens of DES ST show delayed healing and hypersensitivity reactions. The present study sought to correlate histopathology of thrombus aspirates with intravascular ultrasound findings in patients with very late DES ST. Methods and Results-The study population consisted of 54 patients (28 patients with very late DES ST and 26 controls).Of 28 patients with very late DES ST, 10 patients (1020Ϯ283 days after implantation) with 11 ST segments (5 sirolimus-eluting stents, 5 paclitaxel-eluting stents, 1 zotarolimus-eluting stent) underwent both thrombus aspiration and intravascular ultrasound investigation. ISA was present in 73% of cases with an ISA cross-sectional area of 6.2Ϯ2.4 mm 2 and evidence of vessel remodeling (index, 1.6Ϯ0.3). Histopathological analysis showed pieces of fresh thrombus with inflammatory cell infiltrates (DES, 263Ϯ149 white blood cells per high-power field) and eosinophils (DES, 20Ϯ24 eosinophils per high-power field; sirolimus-eluting stents, 34Ϯ28; paclitaxel-eluting stents, 6Ϯ6; P for sirolimus-eluting stents versus paclitaxel-eluting stentsϭ0.09). The mean number of eosinophils per high-power field was higher in specimens from very late DES ST (20Ϯ24) than in those from spontaneous acute myocardial infarction (7Ϯ10), early bare-metal stent ST (1Ϯ1), early DES ST (1Ϯ2), and late bare-metal stent ST (2Ϯ3; P from ANOVAϭ0.038). Eosinophil count correlated with ISA cross-sectional area, with an average increase of 5.4 eosinophils per high-power field per 1-mm 2 increase in ISA cross-sectional area. Conclusions-Very

Implantation of a BMS does not affect physiologic response to exercise proximal and distal to the stent. However, SESs are associated with exercise-induced paradoxic coronary vasoconstriction of the adjacent vessel segments, although vasodilatory response to nitroglycerin is maintained. These observations suggest (drug-induced) endothelial dysfunction as the underlying mechanism.

Background— The prognostic relevance of the collateral circulation is still controversial. The goal of this study was to assess the impact on survival of quantitatively obtained, recruitable coronary collateral flow in patients with stable coronary artery disease during 10 years of follow-up. Methods and Results— Eight-hundred forty-five individuals (age, 62±11 years), 106 patients without coronary artery disease and 739 patients with chronic stable coronary artery disease, underwent a total of 1053 quantitative, coronary pressure–derived collateral measurements between March 1996 and April 2006. All patients were prospectively included in a collateral flow index (CFI) database containing information on recruitable collateral flow parameters obtained during a 1-minute coronary balloon occlusion. CFI was calculated as follows: equation where P occl is mean coronary occlusive pressure, P ao is mean aortic pressure, and CVP is central venous pressure. Patients were divided into groups with poorly developed (CFI <0.25) or well-grown collateral vessels (CFI ≥0.25). Follow-up information on the occurrence of all-cause mortality and major adverse cardiac events after study inclusion was collected. Cumulative 10-year survival rates in relation to all-cause deaths and cardiac deaths were 71% and 88%, respectively, in patients with low CFI and 89% and 97% in the group with high CFI ( P =0.0395, P =0.0109). Through the use of Cox proportional hazards analysis, the following variables independently predicted elevated cardiac mortality: age, low CFI (as a continuous variable), and current smoking. Conclusions— A well-functioning coronary collateral circulation saves lives in patients with chronic stable coronary artery disease. Depending on the exact amount of collateral flow recruitable during a brief coronary occlusion, long-term cardiac mortality is reduced to one fourth compared with the situation without collateral supply.

In this relatively large population with chronic stable coronary artery disease undergoing quantitative collateral measurement, the beneficial impact of well developed collateral vessels on the occurrence of future major cardiac ischemic events is clearly demonstrated.

Even in patients with few coronary collaterals, the myocardial adaptation to repetitive ischemia is closely related to collateral recruitment. Pharmacologic preconditioning using a treatment with i.c. adenosine before angioplasty does not occur. The variable responses of ECG signs of ischemic adaptation to collateral channel opening suggest that ischemic preconditioning is a relevant factor in the development of ischemic tolerance.

Compared with PES, SES more effectively reduced MACE and TLR in small-vessel disease. Differences between SES and PES appear less pronounced in patients with large- and mixed-vessel disease. (The SIRTAX trial; http://clinicaltrials.gov/ct/show/NCT00297661?order=1; NCT00297661).