Search

Background: Long-term outcome after bifurcation stenting with drug-eluting stents (DES) for obstructive coronary artery disease is poorly understood. In this study, we report 6-9-month angiographic follow-up and long-term clinical outcomes after implantation of drug-eluting stents by crush and kissing stent technique for coronary bifurcation lesions., Methods: Consecutive patients undergoing bifurcation stenting with DES by crush or kissing stent technique were enrolled in a prospective registry. Angiographic follow-up was obtained at 6-9 months and clinical follow-up completed for a median of 38 months., Results: A total of 86 patients participated in the study. Bifurcation stenting by crush technique was performed in 73 (85%) and by kissing stent in 13 (15%) patients. Stenting of left main bifurcation was applied in 24 (28%) patients. Angiographic follow-up was completed in 75 (87%) patients and showed restenosis in the main for 8 (11%) and side branch for 20 (27%) patients. Clinical follow-up was available for a median duration of 38 months. During follow-up, 2 (2%) patients died, 4 (5%) experienced myocardial infarction (MI), and 11 (13%) underwent target vessel revascularization (TVR) with an overall major adverse cardiac event (MACE) rate of 16%. In left main cohort, angiographic restenosis occurred in 9 (37%) patients, and 3 (12%) patients required TVR. There were no deaths or stent thrombosis. A comparison of crush and kissing stent technique showed significantly higher angiographic restenosis with crush (26% vs 13% in kissing stent patients, P = 0.046) and 95% of restenosis in crush group involved ostium of the side branch. There was no difference in clinical outcomes between the crush and kissing stent groups. Final kissing balloon dilatation (FKB) was successful in 65 (89%) patients in the crush group and associated with a significant reduction in MACE (8% in FKB successful vs 37% in FKB unsuccessful, P = 0.04) during follow-up., Conclusion: Bifurcation stenting with crush or kissing stent technique is safe and associated with a low rate of TLR and MACE on long-term follow-up. Crush stenting is associated with a significantly higher rate of side branch restenosis compared to kissing stent technique. FKB is associated with significant reduction in MACE during follow-up., (© 2013, Wiley Periodicals, Inc.)

Objectives: We sought to examine angiographic and clinical outcomes with sirolimus-eluting stents (SES) in total coronary occlusion (TCO) revascularization., Background: Despite evaluation of drug-eluting stents beyond approved indications, few studies have evaluated their clinical benefit in TCO revascularization., Methods: Among 15 centers in North America, 200 consecutive TCO patients (78.8% >6 weeks TCO age) were enrolled for treatment with SES. The primary end point was 6-month angiographic binary restenosis within the treated segment., Results: Patient characteristics included: diabetes, 24.5%; prior infarction, 33.5%; and stent length, 45.9 mm median (quartile 1, 30.2 mm; quartile 2, 62.1 mm). A total of 199 patients (99.5%) were treated with SES, and procedural success was 98.0%. The 6-month binary restenosis rates were 9.5% in-stent, 12.4% in-segment, and 22.6% in-"working length" representing the entire treatment segment. Rates of 1-year target lesion revascularization, myocardial infarction, and target vessel failure were 9.8%, 1.0%, and 10.9%, respectively. Stent thrombosis occurred in 2 patients (1.0%). Using logistic regression modeling with propensity score adjustment, the absolute reduction in binary restenosis with SES compared with a historical bare-metal stent control was 37.7% (95% confidence interval [CI]: 27.2% to 48.3%, p < 0.001; odds ratio: 0.17, 95% CI: 0.09 to 0.30, p < 0.0001). Among 32 patients (16%) identified with stent fracture, target lesion revascularization was more common than patients without fracture (25.0% vs. 6.7%, p = 0.005)., Conclusions: Despite greater lesion complexity than prior TCO trials, percutaneous revascularization with SES appears safe and results in substantial reductions in angiographic restenosis and failed patency and a low rate of repeat revascularization. These findings support the use of SES in TCO revascularization. (The ACROSS/TOSCA Trial; NCT00378612).

Purpose: The objective of this study was to determine the effects of different doses of gamma-emitting radioactive stents on intimal hyperplasia in a porcine coronary stent model at 28 days., Methods: Sixty-four bare stents and those coated with palladium-103 [activities of 0 (control), 0.5, 1.0, 2.0, and 4.0 mCi] were implanted in the coronary arteries of 32 pigs. Stented segments were evaluated by histomorphometry at 28 days., Results: There was significantly more intima in the 0.5- and 1-mCi stents than in controls (4.27+/-0.52 and 4.71+/-1.13 vs. 1.71+/-0.61 mm(2); P<.0001). Neointimal formation in 2-mCi stents was similar to that in controls, while that in 4-mCi stents was reduced compared to that in controls (2.34+/-1.61 and 0.82+/-0.25 vs. 1.71+/-0.61 mm(2); P=NS and P<.05, respectively). Stent margin neointimal response was representative of that within the stent body, with nonsignficant modest increases in intimal area at adjacent nonstented segments in radioactive stent groups. There was a dose-dependent increase in inflammation scores. Radioactive stents had lower intimal smooth muscle and higher fibrin scores. There was an increase in adventitial fibrosis in 1- and 2-mCi stents versus controls (1.26+/-0.99, and 2.25+/-1.27 vs. 0.21+/-0.31; P<.001)., Conclusion: Dose-response inhibition of in-stent hyperplasia with minimal "edge effects" occurs with low-energy gamma-emitting stents. An increased inflammatory response at higher doses in palladium-103 stents indicates that later follow-up studies are necessary.

Despite continued advances in the prevention and treatment of coronary artery disease, there are still a large number of patients who are not candidates for the conventional revascularization techniques of balloon angioplasty and stenting, or coronary artery bypass grafting (CABG). Therapeutic angiogenesis, in the form of the administration of growth factor protein or gene therapy, has emerged as a promising new method of treatment for patients with coronary artery disease. The goal of this strategy is to promote the development of supplemental blood conduits that will act as endogenous bypass vessels. New vessel formation occurs through the processes of angiogenesis, vasculogenesis, and arteriogenesis, under the control of growth factors such as those that belong to the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and angiopoeitin (Ang) families of molecules. Preclinical studies have suggested that such an approach is both feasible and effective; however many questions remain to be answered. This review will address the elements of pharmacologic revascularization, focusing on gene and protein-based therapy. The important growth factors, the vector (for gene therapy), routes of delivery, the desired therapeutic effect, and quantifiable clinical end points for trials of angiogenesis will all be addressed., (Copyright 2003 Wiley-Liss, Inc.)

Background: The non-uniform extent and distribution of atherosclerotic plaque at bifurcations have been described by necropsy studies and they are related to local blood-flow disturbances. Systematic evaluation of plaque extent and distribution upstream and downstream of major coronary side-branches has not yet been evaluated in vivo., Methods: We used intravascular ultrasound imaging in 41 patients with atherosclerotic disease to study the region of 73 major coronary side-branches at 2 mm increments proximal and distal to the side-branch (657 images: 73 at origin of side-branch; 292 proximal; 292 distal). The maximum (MXT) and minimum (MINT) plaque thickness and the plaque burden percentage (% PB) were measured in all the segments. The angle of distribution of maximum plaque thickness with respect to the origin of the side-branch was determined in each cross-section and assigned to S1 when located on the semicircle in the direction of the origin of the side-branch and to S2 when located on the opposite wall., Results: The mean value of maximum plaque thickness and the plaque burden percentage were similar at the origin and in the two adjacent segments proximal and distal to the side-branch (1.0 +/- 0.48 mm, 1.06 +/- 0.48 mm and 0.98 +/- 0.48 mm; 45 +/- 19%, 46 +/- 19% and 44 +/- 18%). In distal sites of analysis, the plaque was more frequently eccentric in comparison to proximal sites (presence of an arc of plaque-free wall: 79% versus 62% in very distal and in very proximal sites respectively; p < 0.05). The prevalence of maximum plaque in S2 was higher at the origin (84%) and in adjacent distal segments (86%) as compared with the adjacent proximal segments (60%; p < 0.0001)., Conclusions: The distribution of plaque is influenced by the origin of a major coronary side-branch in patients with coronary atherosclerosis: in distal sites the location of maximum plaque is almost always eccentrically distributed on the wall opposite the take-off.

A novel approach of cell seeding of stents using xenotransplanted endothelium is proposed. The advantages of this approach are that these doubly transgenic animals will provide a limitless supply of endothelial cells producing controllable levels of active compound. These foreign cells will act as Trojan horses, graciously accepted at face value by the host organism, but capable of modifying the pathophysiological response to vessel damage, typified by the process of restenosis. Once implanted, the production of the bioactive compound is under exogenous control by means of 'designer' genes coding for modified cell surface receptors, which are introduced with the transgene to provide controllable levels of compound. Interaction of an orally administered compound with the modified cell receptor will switch on the transgene, while in its absence the transgene remains dormant. We have been able to show the feasibility this type of approach has for other animal species, and it shows great potential for application to humans.

Background: Demonstration and quantification of site-specific intracoronary administration of compounds has been confined thus far to the experimental animal laboratory. The aim of this study was to describe a scintigraphic method to demonstrate site-specific intracoronary drug delivery in humans. The methods allow on-line visualization and off-line quantification of site-specifically infused gamma-emitting compounds., Methods and Results: In 12 patients after balloon angioplasty, 99mTc-labeled heparin was administered at the site of dilatation by use of a coil balloon. Both the infusion period and the washout period after the end of infusion were monitored with a gamma-camera. A curve of counts per pixel as a function of time was derived that showed an accumulation phase during infusion followed by washout phase after the end of infusion. Both phases were fitted by regression analysis and showed a linear accumulation pattern and a biexponential washout pattern. After correction for background counts, 99mTc decay, and body attenuation, peak heparin amount and regional bioavailability were calculated. Peak amount was defined as the initial point of the slow washout component of the biexponential curve (elimination component), and regional bioavailability was defined as the area under the curve of accumulation and washout phase. Half-life and retention time, define as seven half-lives, were obtained by use of the elimination component after correction for 99mTc decay. Mean peak delivered amount was 45 +/- 44 IU (236 +/- 228 micrograms), corresponding to an efficiency of delivery ranging from 1% to 8% of the totally infused dose. Total regionally bioavailable heparin reached 244 +/- 194 IU.h (1.28 +/- 1.01 mg.h). Retention time varied from 12 to 90 hours (mean, 50:33 +/- 22:50 hours:minutes)., Conclusions: Site-specific intracoronary heparin delivery after angioplasty by means of the coil balloon was demonstrated in humans, and regional pharmacokinetics was quantified by use of a radioisotopic technique.

The use of 2-dimensional intravascular ultrasound (2-D IVUS) to improve the outcome of coronary stenting has gained clinical acceptance, and recently 3-D IVUS has been introduced to clinical practice. However, there have been no comprehensive studies comparing the measurements of the coronary dimensions after stenting obtained by the different approaches of IVUS and quantitative coronary angiography. We examined the minimal luminal cross-sectional area of 38 stents using 2-D IVUS, 3-D IVUS, and 2 standard methods of quantitative coronary angiography, edge detection (ED) and videodensitometry (VD). Correlations between 2-D IVUS and ED (r = 0.72; p < 0.0001), VD (r = 0.87; p < 0.0001), and 3-D IVUS (r = 0.81; p < 0.0001) were higher than the correlations seen between 3-D IVUS and ED (r = 0.58; p < 0.0005) and VD (r = 0.70; p < 0.0001). The measurements by 2-D and 3-D IVUS (8.32 +/- 2.50 mm2 and 8.05 +/- 2.66 mm2) were larger than the values obtained by the quantitative angiographic techniques ED and VD (7.55 +/- 2.22 mm2 and 7.27 +/- 2.21 mm2). Thus, concordance was seen among all of the 4 techniques, confirming the validity of using IVUS for determination of the minimal luminal cross-sectional area after coronary stenting. A particularly good correlation was found between VD and IVUS, perhaps because measurement of the luminal area is the basic quantification approach of both techniques, whereas the lower correlations of ED with IVUS and VD may be explained by the dependence of ED on the angiographic projections used, which is especially important in eccentric stent configurations.