http://repub.eur.nl/res/aut/6892/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/26646/ 2011-11-01T00:00:00Z Objective: To assess the safety and efficacy of the Genous™ endothelial progenitor cell (EPC) capturing stent in conjunction with HmG-CoA-reductase inhibitors (statins) to stimulate EPC recruitment, in the treatment of patients with de novo coronary artery lesions. Methods and results: The HEALING IIB study was a multi-center, prospective trial, including 100 patients. The primary efficacy endpoint was late luminal loss by QCA at 6-month follow-up (FU). Although statin therapy increased relative EPC levels by 5.6-fold, the angiographic outcome at 6 month FU was not improved in patients with an overall in-stent late luminal loss of 0.76 ± 0.50 mm. The composite major adverse cardiac events (MACE) rate was 9.4%, whereas 6.3% clinically justified target lesion revascularizations (TLRs) were observed. 2 Patients died within the first 30 days after stent implantation due to angiographically verified in-stent thrombosis. At 12 month FU, MACE and TLR increased to 15.6% and 11.5% respectively and stabilized until 24 month FU. 18 Month angiographic FU showed a significant decrease in late luminal loss (0.67 ± 0.54, 11.8% reduction or 10% by matched serial analysis, P= 0.001). Conclusion: The HEALING IIB study suggests that statin therapy in combination with the EPC capture stent does not contribute to a reduction of in-stent restenosis formation for the treatment of de novo coronary artery disease. Although concomitant statin therapy was able to stimulate EPC recruitment, it did not improve the angiographic outcome of the bio-engineered EPC capture stent. Remarkably, angiographic late loss was significantly reduced between 6 and 18 months. http://repub.eur.nl/res/pub/26647/ 2011-07-18T00:00:00Z Objective: To assess the safety and efficacy of the Genous™ endothelial progenitor cell (EPC) capturing stent in conjunction with HmG-CoA-reductase inhibitors (statins) to stimulate EPC recruitment, in the treatment of patients with de novo coronary artery lesions. Methods and results: The HEALING IIB study was a multi-center, prospective trial, including 100 patients. The primary efficacy endpoint was late luminal loss by QCA at 6-month follow-up (FU). Although statin therapy increased relative EPC levels by 5.6-fold, the angiographic outcome at 6 month FU was not improved in patients with an overall in-stent late luminal loss of 0.76 ± 0.50 mm. The composite major adverse cardiac events (MACE) rate was 9.4%, whereas 6.3% clinically justified target lesion revascularizations (TLRs) were observed. 2 Patients died within the first 30 days after stent implantation due to angiographically verified in-stent thrombosis. At 12 month FU, MACE and TLR increased to 15.6% and 11.5% respectively and stabilized until 24 month FU. 18 Month angiographic FU showed a significant decrease in late luminal loss (0.67 ± 0.54, 11.8% reduction or 10% by matched serial analysis, P = 0.001). Conclusion: The HEALING IIB study suggests that statin therapy in combination with the EPC capture stent does not contribute to a reduction of in-stent restenosis formation for the treatment of de novo coronary artery disease. Although concomitant statin therapy was able to stimulate EPC recruitment, it did not improve the angiographic outcome of the bio-engineered EPC capture stent. Remarkably, angiographic late loss was significantly reduced between 6 and 18 months. http://repub.eur.nl/res/pub/26476/ 2011-04-19T00:00:00Z Objectives: The purpose of this study was to evaluate the safety, device performance, and clinical outcome up to 2 years for patients undergoing transcatheter aortic valve implantation (TAVI). Background: The role of TAVI in the treatment of calcific aortic stenosis evolves rapidly, but mid- and long-term results are scarce. Methods: We conducted a prospective, multicenter, single-arm study with symptomatic patients undergoing TAVI for treatment of severe aortic valve stenosis using the 18-F Medtronic CoreValve (Medtronic, Minneapolis, Minnesota) prosthesis. Results: In all, 126 patients (mean age 82 years, 42.9% male, mean logistic European System for Cardiac Operative Risk Evaluation score 23.4%) with severe aortic valve stenosis (mean gradient 46.8 mm Hg) underwent the TAVI procedure. Access was transfemoral in all but 2 cases with subclavian access. Retrospective risk stratification classified 54 patients as moderate surgical risk, 51 patients as high-risk operable, and 21 patients as high-risk inoperable. The overall technical success rate was 83.1%. Thirty-day all-cause mortality was 15.2%, without significant differences in the subgroups. At 2 years, all-cause mortality was 38.1%, with a significant difference between the moderate-risk group and the combined high-risk groups (27.8% vs. 45.8%, p = 0.04). This difference was mainly attributable to an increased risk of noncardiac mortality among patients constituting the high-risk groups. Hemodynamic results remained unchanged during follow-up (mean gradient: 8.5 ± 2.5 mm Hg at 30 days and 9.0 ± 3.4 mm Hg at 2 years). Functional class improved in 80% of patients and remained stable over time. There was no incidence of structural valve deterioration. Conclusions: The TAVI procedure provides sustained clinical and hemodynamic benefits for as long as 2 years for patients with symptomatic severe aortic stenosis at increased risk for surgery. http://repub.eur.nl/res/pub/25151/ 2011-03-17T00:00:00Z BACKGROUND: Previous studies have shown that among patients undergoing multivessel revascularization, coronary-artery bypass grafting (CABG), as compared with percutaneous coronary intervention (PCI) either by means of balloon angioplasty or with the use of bare-metal stents, results in greater relief from angina and improved quality of life. The effect of PCI with the use of drug-eluting stents on these outcomes is unknown. METHODS: In a large, randomized trial, we assigned 1800 patients with three-vessel or left main coronary artery disease to undergo either CABG (897 patients) or PCI with paclitaxeleluting stents (903 patients). Health-related quality of life was assessed at baseline and at 1, 6, and 12 months with the use of the Seattle Angina Questionnaire (SAQ) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The primary end point was the score on the angina-frequency subscale of the SAQ (on which scores range from 0 to 100, with higher scores indicating better health status). RESULTS: The scores on each of the SAQ and SF-36 subscales were significantly higher at 6 and 12 months than at baseline in both groups. The score on the angina-frequency subscale of the SAQ increased to a greater extent with CABG than with PCI at both 6 and 12 months (P = 0.04 and P = 0.03, respectively), but the between-group differences were small (mean treatment effect of 1.7 points at both time points). The proportion of patients who were free from angina was similar in the two groups at 1 month and 6 months and was higher in the CABG group than in the PCI group at 12 months (76.3% vs. 71.6%, P = 0.05). Scores on all the other SAQ and SF-36 subscales were either higher in the PCI group (mainly at 1 month) or were similar in the two groups throughout the follow-up period. CONCLUSIONS: Among patients with three-vessel or left main coronary artery disease, there was greater relief from angina after CABG than after PCI at 6 and 12 months, although the extent of the benefit was small. (Funded by Boston Scientific; ClinicalTrials.gov number, NCT00114972.). Copyright http://repub.eur.nl/res/pub/24649/ 2009-06-01T00:00:00Z AimsTo report the 4-month angiographic and 6-month clinical follow-up in first-in-man study using the tacrolimus-eluting bioabsorbable polymer-coated cobalt-chromium MAHOROBA™ stent.Methods and resultsA total of 47 patients with either stable angina or unstable angina, or silent myocardial ischaemia, based on a de novo coronary stenosis that could be covered by a single 18 mm stent in a native coronary artery with a diameter between 3.0 and 3.5 mm were enrolled at three sites. The primary endpoint was in-stent late loss at 4 months. The secondary endpoints include volume obstruction of the stents assessed by intravascular ultrasound (IVUS) at 4 months and major adverse cardiac events (MACE) at 6 months. Forty-seven patients were enrolled. Procedural success was achieved in 97.9. At 4-month follow-up, in-stent late loss was 0.99 ± 0.46 mm, whereas in-stent volume obstruction in IVUS was 34.8 ± 15.8. At 6 months, there were no deaths, but 2 patients suffered from a myocardial infarction and 11 patients required ischaemia-driven repeat revascularization. The composite MACE rate was 23.4.ConclusionThis tacrolimus-eluting stent failed to prevent neointimal hyperplasia, despite the theoretical advantages of the tacrolimus, which has less inhibitory effects on endothelial cells than smooth muscle cells. http://repub.eur.nl/res/pub/4636/ 2004-10-06T00:00:00Z OBJECTIVES: We sought to demonstrate the safety and performance of the actinomycin D-coated Multilink-Tetra stent(Guidant Corp., Santa Clara, California) in the treatment of patients with single de novo native coronary lesions. BACKGROUND: Drug-eluting stents (DES) releasing sirolimus or paclitaxel dramatically reduce restenosis. The anti-proliferative drug, actinomycin D, which is highly effective in reducing neointimal proliferation in preclinical studies, was selected for clinical evaluation. METHODS: The multi-center, single-blind, three-arm ACTinomycin-eluting stent Improves Outcomes by reducing Neointimal hyperplasia (ACTION) trial randomized 360 patients to receive a DES (2.5 or 10 microg/cm(2) of actinomycin D) or metallic stent (MS). The primary end points were major adverse cardiac events (MACE) at 30 days, diameter stenosis by angiography, tissue effects, and neointimal volume by intravascular ultrasound (IVUS) at six months. When early monitoring revealed an increased rate of repeat revascularization, the protocol was amended to allow for additional follow-up for DES patients. Angiographic control of MS patients was no longer mandatory. RESULTS: The biased selection of DES patients undergoing IVUS follow-up invalidated the interpretation of the IVUS findings. The in-stent late lumen loss and that at the proximal and distal edges were higher in both DES groups than in the MS group and resulted in higher six-month and one-year MACE (34.8% and 43.1% vs. 13.5%), driven exclusively by target vessel revascularization without excess death or myocardial infarction. CONCLUSIONS: The results of the ACTION trial indicate that all anti-proliferative drugs will not uniformly show a drug class effect in the prevention of restenosis. http://repub.eur.nl/res/pub/5056/ 1996-12-01T00:00:00Z Background. Thrombin is a key enzyme in thrombogenesis. In animals, specific antithrombotic therapy at the time of coronary angioplasty reduced the incidence of subacute occlusion and inhibited the restenosis response. Argatroban is a highly selective synthetic thrombin antagonist that binds in a competitive manner. This is a report of a dose-verification study, assessing the safety and feasibility of intravenous Argatroban administration in patients undergoing percutaneous transluminal coronary angioplasty. Methods. Before angioplasty an intravenous bolus of 30 g/kg argatroban was administered, followed by a continuous infusion of 3.5 g/kg/min for 72 hours. Bolus injection was repeated, and the infusion rate was increased in order to achieve an activated coagulation time (ACT) of over 300 seconds. Following interim analysis, the bolus and initial infusion rate for the subsequent treatment groups was determined. Study endpoints were the occurrence of adverse events, coagulation tests, and qualitative angiogram reading. Patients were monitored by continuous 12-lead electrocardiographic recording over 24 hours, and underwent control angiography 18–24 hours following angioplasty. Results. Four treatment groups, comprised of 2, 8, 9, and 11 patients, respectively, were studied. The first two patients were excluded from analysis, since the initial dose was ineffective to attain an ACT-authorizing coronary angioplasty. The group with the highest dosage received a 250 g/kg intravenous bolus of argatroban, followed by a 4 hour infusion of 15 g/kg/min. At 4 hours the infusion rate was lowered to 3.8 g/kg/min and was continued for 68 hours without adjustment for catheter removal. The adverse event profile included myocardial infarction, aortocoronary bypass graft, bailout procedures, and repeat coronary angioplasty. Thrombin-time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT) were significantly related to argatroban plasma concentration, as demonstrated by regression analyses (R-square 0.64, 0.71, and 0.84, respectively). Prothrombin fragments 1 and 2 and thrombin-antithrombin III complex did not fit into a mathematical model, but showed slightly increased levels after reduction or cessation of the infusion rate. Conclusions. This dose-verification study, including 30 patients at four dose levels, indicated that argatroban infusion in coronary angioplasty patients can be administered safely, and results in an adequate and predictable level of anticoagulation. http://repub.eur.nl/res/pub/5048/ 1996-02-01T00:00:00Z Objectives. This study sought to determine the 1-year clinical follow-up of patients included in the Benestent trial. Background. The Benestent trial is a randomized study comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in patients with stable angina and a de novo coronary artery lesion. Seven-month follow-up data have shown a decreased rate of restenosis and fewer clinical events in the stent group. It is not established whether this favorable clinical outcome is maintained for longer periods or whether coronary stenting defers restenosis and its subsequent clinical manifestations. Methods. To clarify this uncertainty, we updated clinical information on all but 1 of 516 patients enrolled in the Benestent trial (257 in balloon group, 259 in stent group) at least 12 months after the intervention. Major clinical events (primary clinical end point) were tabulated according to the intention to treat principle myocardial infarction, the need for bypass surgery or a further percutaneous intervention in the previously treated lesion. Results. After 1 year, no significant differences in mortality (1.2% vs. 0.8%), stroke (0.0% vs 0.8%), myocardial infarction (5.0% vs. 4.2%) or coronary bypass graft surgery (6.9% vs. 5.1%) were found between the stent and balloon angioplasty groups, respectively. However, the requirement for a repeat angioplasty procedure was significantly lower in the stent group (10%) than the balloon angioplasty group (21%, relative risk [RR] 0.49, 95% confidence interval [CI] 0.31 to 0.75, p = 0.001), and overall primary end points were less frequently reached by stent group patients (23.2%) than those in the balloon group (31.5%, RR 0.74, 95% CI 0.55 to 0.98, p = 0.04). No differences were found between groups with respect to functional class angina and prescribed medication at the time of follow-up. Conclusions. These clinical follow-up data show that the benefit of elective native coronary artery stenting in patients with stable angina is maintained to at least 1 year after the procedure and results in a significantly reduced requirement for repeat intervention. http://repub.eur.nl/res/pub/4607/ 1994-01-01T00:00:00Z A European coronary angioscopy working group has been established to create and evaluate a classification system for angioscopic observation. The 'Ermenonville' classification features items, graded in 3-5 categories, such as lumen diameter, shape of narrowing, colours of surface, atheroma, dissection, thrombus, etc. Inter- and intra-observer agreement on the interpretation of angioscopic images, using this classification system, was studied within the working group. Kappa values for chance-corrected intra-observer agreement of the diagnostic items were 0.51-0.67. The mean kappa values for inter-observer agreement were very low at 0.13-0.29. The important items, such as red thrombus and dissection were studied after recoding as either present or absent. These items proved to have a good intra-observer agreement, and an acceptable inter-observer agreement after recoding. Other angioscopic diagnoses should be made with caution. Multicentre angioscopy studies should make use of an angioscopy core laboratory. A set of definitions for coronary angioscopy is proposed, and this working group will re-evaluate observer agreements using these definitions. http://repub.eur.nl/res/pub/4612/ 1994-01-01T00:00:00Z OBJECTIVES: This study was undertaken to compare coronary angioscopy with angiography for the detection of intimal dissection and intracoronary thrombus. BACKGROUND. It has been demonstrated previously that coronary angioscopy provides more intravascular detail than cineangiography. Both imaging methods have to be compared directly to assess the additional diagnostic value of angioscopy. METHODS. The angiograms and videotapes of 52 patients who had undergone angioscopy were reviewed independently by two observers unaware of other findings. Classic angiographic definitions were used for dissection and thrombus. Angioscopic dissection was defined as visible cracks or fissures on the lumen surface or mobile protruding structures that are contiguous with the vessel wall. Angioscopic thrombus was defined as a red, white or mixed red and white intraluminal mass. RESULTS. Angiography and angioscopy were in agreement in 40.4% of cases in the absence of thrombus and in 11.5% in the presence of thrombus. No fewer than 25 (48.1%) angioscopically observed thrombi remained undetected at angiography. With angioscopy as the standard, although the specificity of angiography for thrombus was 100%, sensitivity was very low at 19%. Angioscopic dissection was present in 40 patients (76.9%) versus angiographic dissection in 15 patients (28.8%). With regard to dissection, there was no correlation between the two imaging methods (r phi = 0.15, p = 0.29). CONCLUSIONS. Coronary angiography underestimates the presence of intracoronary thrombus. Angioscopy and angiography are complementary techniques for detecting and grading intimal dissections.