http://repub.eur.nl/res/aut/1314/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/35822/ 2007-04-01T00:00:00Z Aims: To understand wound healing after drug-eluting stents (DES) placement in humans, we studied the histology of in-stent restenosis (ISR) tissue obtained by atherectomy from bare metal stents (BMS) and DES in comparison with de novo atherosclerosis. Methods and results: The tissue was retrieved from ISR in ten sirolimus-eluting stents (SES) and nine paclitaxel-eluting stents (PES), six BMS, and nine stenotic de novo atherosclerotic lesions and processed for histology and immunocytochemistry. Patients with ISR in PES showed a significantly higher incidence of unstable angina upon presentation for re-intervention (P = 0.046). De novo tissue tended to be more collagen rich, whereas ISR tissue tended to be more proteoglycan rich. In all groups, cell content consisted almost exclusively of smooth muscle cells. Histology showed that fibrinoid in ISR tissue was present only in DES (P = 0.004), as late as 2 years following DES placement, indicating a persistent incomplete healing response. The amount of fibrinoid, given as a percentage of total tissue in each atherectomy specimen, was greater in PES than in SES (17 vs. 5%, P = 0.026). Conclusion: ISR in DES shows incomplete neointimal healing as late as 2 years after implantation. Patients with ISR in PES presented with more unstable angina and showed more pronounced signs of delayed healing than SES. http://repub.eur.nl/res/pub/8356/ 2005-01-01T00:00:00Z OBJECTIVES: To determine the long term outcome after intracoronary beta radiation therapy (IRT). SETTING: Tertiary referral centre. METHODS: The rate of major adverse cardiac events (MACE) was retrospectively determined in 301 consecutive patients who were treated with IRT. MACE was defined as death, myocardial infarction, or any reintervention. Long term clinical outcome was obtained from an electronic database of hospital records and from questionnaires to the patients and referring physicians. Long term survival status was assessed by written inquiries to the municipal civil registries. RESULTS: The mean (SD) follow up was 3.6 (1.2) years. The cumulative incidence of MACE at six months was 19.1%, at one year 36.4%, and at four years 58.3%. The target lesion revascularisation (TLR) rate at six months was 12.9%, at one year 28.3%, and at four years 50.4%. From multivariate analysis, dose < 18 Gy was the most significant predictor of TLR. At four years the cumulative incidence of death was 3.8%, of myocardial infarction 13.4%, and of coronary artery bypass surgery 11.3%. Total vessel occlusion was documented in 12.3% of the patients. CONCLUSIONS: In the long term follow up of patients after IRT, there are increased adverse cardiac events beyond the first six months. http://repub.eur.nl/res/pub/39856/ 2004-09-22T00:00:00Z Percutaneous Coronary Interventions Percutaneous coronary angioplasty was first introduced by Andreas Gruentzig in 1977 as a non surgical method for coronary artery revascularization. Although initially restricted to stable patients with single, discrete, concentric, noncalcified stenoses, percutaneous revascularization is now routinely applied to patients with multivessel disease, multiple lesions, complex lesions, acute coronary syndromes, and left ventricular dysfunction. Refinement of the equipment used to perform angioplasty and utilization of adjunctive periprocedural medications, together with time and growing experience played a major role in the explosive growth and popularity of percutaneous coronary interventions (PCI). The most important advancement in the field of percutaneous coronary interventions was the introduction of coronary stents, which reduce both the acute risk of major complications and the incidence of restenosis. With modern techniques, procedural success > 90% is readily achieved, and the risk of sudden arterial occlusion and subsequent myocardial infarction is very low. Long-term survival has been shown to be not different from that achieved with bypass surgery, therefore in many countries percutaneous coronary interventions have become the preferred strategy for coronary revascularization. Restenosis Restenosis, defined as the vessel lumen renarrowing following a successful percutaneous coronary intervention, represents the principal limitation to the long-term outcome of coronary angioplasty. Restenosis is a pathobiological process caused by the arterial healing response after vessel injury, and is due to varying degrees of elastic recoil, vascular remodeling, and neointimal hyperplasia. The only widely accepted means of reducing restenosis is the coronary stent, which virtually eliminates vessel elastic recoil and negative remodeling following balloon dilatation. However, the efficacy of this purely “mechanical” approach to the prevention of restenosis has been hampered by the development of a new iatrogenic disease: in-stent restenosis, which is predominantly due to neointima formation. In-stent restenosis has been reported to occur in 10 to 50% of the patients in several series, 7 depending upon a number of clinical, angiographic, and procedural variables. Furthermore, treatment of ISR is frequently a challenging clinical problem, with recurrent restenosis being reported in up to 80% of the patients in the most complex cases. The development of neointimal tissue is thought to relate to a combination of coagulation cascade activation, platelet deposition, organization of thrombus, growth factor stimulation, and is due mainly to smooth muscle cell proliferation and migration, and excessive extracellular matrix production. 9 Smooth muscle cell proliferation has therefore become the main target in the effort to prevent or reduce in-stent restenosis. http://repub.eur.nl/res/pub/4653/ 2004-07-01T00:00:00Z Abstract The purpose of this study was to compare the mid-term clinical outcome of sirolimus-eluting stent (SES) implantation and vascular brachytherapy (VBT) for in-stent restenosis (ISR). We assessed the 9-month occurrence of major adverse cardiac events (MACE) in 44 consecutive patients with ISR treated with SES implantation and 43 consecutive patients treated with VBT in the period immediately prior. Baseline clinical and angiographic characteristics of the two groups were similar. During follow-up, three patients (7%) died in the VBT group and none in the SES group. The incidence of myocardial infarction was 2.3% in both groups. Target lesion revascularization was performed in 11.6% of the VBT patients and 16.3% of the SES patients (P = NS). The 9-month MACE-free survival was similar in both groups (79.1% VBT vs. 81.5% SES; P = 0.8 by log rank). The result of this nonrandomized study suggests that sirolimus-eluting stent implantation is at least as effective as vascular brachytherapy in the treatment of in-stent restenosis. http://repub.eur.nl/res/pub/13390/ 2004-06-08T00:00:00Z BACKGROUND: Rupture of thin-cap fibroatheromatous plaques is a major cause of acute myocardial infarction (AMI). Such plaques can be identified in vitro by 3D intravascular palpography with high sensitivity and specificity. We used this technique in patients undergoing percutaneous intervention to assess the incidence of mechanically deformable regions. We further explored the relation of such regions to clinical presentation and to C-reactive protein levels. METHOD AND RESULTS: Three-dimensional palpograms were derived from continuous intravascular ultrasound pullbacks. Patients (n=55) were classified by clinical presentation as having stable angina, unstable angina, or AMI. In every patient, 1 coronary artery was scanned (culprit vessel in stable and unstable angina, nonculprit vessel in AMI), and the number of deformable plaques assessed. Stable angina patients had significantly fewer deformable plaques per vessel (0.6+/-0.6) than did unstable angina patients (P=0.0019) (1.6+/-0.7) or AMI patients (P<0.0001) (2.0+/-0.7). Levels of C-reactive protein were positively correlated with the number of mechanically deformable plaques (R2=0.65, P<0.0001). CONCLUSIONS: Three-dimensional intravascular palpography detects strain patterns in human coronary arteries that represent the level of deformation in plaques. The number of highly deformable plaques is correlated with both clinical presentation and levels of C-reactive protein. Further studies will assess the potential role of the technique to identify patients at risk of future clinical events http://repub.eur.nl/res/pub/4666/ 2004-04-01T00:00:00Z Long-length stenting has a poor outcome when bare metal stents are used. The safety and efficacy of the sirolimus-eluting stent (SES) in long lesions has not been evaluated. Therefore, the aim of the present study was to evaluate the clinical and angiographic outcomes of SES implantation over a very long coronary artery segment. Since April 2002, all patients treated percutaneously at our institution received a SES as the device of choice as part of the Rapamycin Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. During the RESEARCH registry, stents were available in lengths of 8, 18, and 33 mm. The present report includes a predefined study population consisting of patients treated with >36-mm-long stented segments. Patients had a combination of >or=2 overlapping stents at a minimum length of 41 mm (i.e., one 33-mm SES overlapping an 8-mm SES) to treat native de novo coronary lesions. The incidence of major cardiac adverse events (death, nonfatal myocardial infarction, and target lesion revascularization) was evaluated. The study group comprised 96 consecutive patients (102 lesions). Clinical follow-up was available for all patients at a mean of 320 days (range 265 to 442). In all, 20% of long-stented lesions were chronic total occlusions, and mean stented length per lesion was 61.2 +/- 21.4 mm (range 41 to 134). Angiographic follow-up at 6 months was obtained in 67 patients (71%). Binary restenosis rate was 11.9% and in-stent late loss was 0.13 +/- 0.47 mm. At long-term follow-up (mean 320 days), there were 2 deaths (2.1%), and the overall incidence of major cardiac events was 8.3%. Thus, SES implantation appears safe and effective for de novo coronary lesions requiring multiple stent placement over a very long vessel segment. http://repub.eur.nl/res/pub/4667/ 2004-04-01T00:00:00Z The purpose of this study was to assess the safety and effectiveness of sirolimus-eluting stent (SES) postdilatation with largely oversized balloons. We evaluated the clinical outcome of 68 consecutive patients enrolled in the Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry who underwent percutaneous coronary intervention with SES implantation and further postdilatation with balloons > 1 mm larger than the stent nominal size. Angiographic follow-up was either scheduled for selected subgroups or clinically driven. Overall, 75 lesions were treated. The procedure was successful in 98.5% of the cases. One patient (1.5%) underwent emergency coronary bypass surgery for acute vessel occlusion. During 10.1 +/- 1.7 months of follow-up, three patients (4.5%) died, one (1.5%) had acute myocardial infarction, and four (6%) had target vessel revascularization. At angiographic follow-up, loss index was 0.13 +/- 0.34 and restenosis rate was 7.7%. Although not routinely recommended in every patient, SES postdilatation with largely oversized balloons appears a safe and effective strategy for selected patients. http://repub.eur.nl/res/pub/13314/ 2004-03-23T00:00:00Z BACKGROUND: The factors associated with the occurrence of restenosis after sirolimus-eluting stent (SES) implantation in complex cases are currently unknown. METHODS AND RESULTS: A cohort of consecutive complex patients treated with SES implantation was selected according to the following criteria: (1) treatment of acute myocardial infarction, (2) treatment of in-stent restenosis, (3) 2.25-mm diameter SES, (4) left main coronary stenting, (5) chronic total occlusion, (6) stented segment >36 mm, and (7) bifurcation stenting. The present study population was composed of 238 patients (441 lesions) for whom 6-month angiographic follow-up data were obtained (70% of eligible patients). Significant clinical, angiographic, and procedural predictors of post-SES restenosis were evaluated. Binary in-segment restenosis was diagnosed in 7.9% of lesions (6.3% in-stent, 0.9% at the proximal edge, 0.7% at the distal edge). The following characteristics were identified as independent multivariate predictors: treatment of in-stent restenosis (OR 4.16, 95% CI 1.63 to 11.01; P<0.01), ostial location (OR 4.84, 95% CI 1.81 to 12.07; P<0.01), diabetes (OR 2.63, 95% CI 1.14 to 6.31; P=0.02), total stented length (per 10-mm increase; OR 1.42, 95% CI 1.21 to 1.68; P<0.01), reference diameter (per 1.0-mm increase; OR 0.46, 95% CI 0.24 to 0.87; P=0.03), and left anterior descending artery (OR 0.30, 95% CI 0.10 to 0.69; P<0.01). CONCLUSIONS: Angiographic restenosis after SES implantation in complex patients is an infrequent event, occurring mainly in association with lesion-based characteristics and diabetes mellitus. http://repub.eur.nl/res/pub/4672/ 2004-03-01T00:00:00Z A total of 91 patients with 112 lesions received 2.25-mm sirolimus-eluting stents (SESs), and these lesions were compared with those treated with SESs of ≥2.5-mm diameter in the same procedure (n = 109). The reference diameters were 1.88 ± 0.34 and 2.52 ± 0.57 mm, respectively (p <0.01). At follow-up, the late lumen loss was 0.07 ± 0.48 mm for the 2.25-mm SES versus 0.03 ± 0.38 mm for the larger SES (p = 0.5), and the binary restenosis rate was 10.7% versus 3.9%, respectively (p = 0.1). The 12-month target lesion revascularization rate was 5.5%. In conclusion, 2.25-mm SESs were associated with low rates of clinical and angiographic late complications. http://repub.eur.nl/res/pub/13279/ 2004-01-20T00:00:00Z BACKGROUND: The effectiveness of sirolimus-eluting stents in unselected patients treated in the daily practice is currently unknown. METHODS AND RESULTS: Sirolimus-eluting stent implantation has been used as the default strategy for all percutaneous procedures in our hospital as part of the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. Consecutive patients with de novo lesions (n=508) treated exclusively with sirolimus-eluting stents (SES group) were compared with 450 patients who received bare stents in the period just before (pre-SES group). Patients in the SES group more frequently had multivessel disease, more type C lesions, received more stents, and had more bifurcation stenting. At 1 year, the cumulative rate of major adverse cardiac events (death, myocardial infarction, or target vessel revascularization) was 9.7% in the SES group and 14.8% in the pre-SES group (hazard ratio [HR], 0.62 [95% CI, 0.44 to 0.89]; P=0.008). The 1-year risk of clinically driven target vessel revascularization in the SES group and in the pre-SES group was 3.7% versus 10.9%, respectively (HR, 0.35 [95% CI, 0.21 to 0.57]; P<0.001). CONCLUSIONS: Unrestricted utilization of sirolimus-eluting stents in the "real world" is safe and effective in reducing both repeat revascularization and major adverse cardiac events at 1 year compared with bare stent implantation. http://repub.eur.nl/res/pub/8304/ 2004-01-01T00:00:00Z AIMS: To investigate the effect on risk of major adverse cardiac events (MACE) of lipid lowering treatment with fluvastatin 80 mg/day after a first percutaneous coronary intervention in patients with stable and unstable angina. METHOD AND RESULTS: This prespecified subgroup analysis of the LIPS (Lescol intervention prevention study) analysed 1658 patients with documented diagnosis; 824 had unstable angina (417 randomly assigned to fluvastatin, 407 to placebo) and 834 had stable angina (including silent ischaemia; fluvastatin, 418; placebo, 416). Median follow up was 3.9 years. There was no significant effect of anginal status on long term risk of MACE. Fluvastatin treatment reduced the risk of MACE by 28% compared with placebo (p = 0.03) among patients with unstable angina, with no difference between patients with stable and patients with unstable angina (relative risk 1.07, 95% confidence interval 0.87 to 1.30, p = 0.53). Fluvastatin reduced coronary atherosclerotic events (MACE excluding restenosis) by 36% (p = 0.006) among patients with unstable angina and 31% (p = 0.02) among patients with stable angina. Fluvastatin caused similar reductions in total cholesterol and low density lipoprotein cholesterol concentrations in both patient groups. CONCLUSION: Treatment with fluvastatin 80 mg/day produced significant reductions in MACE and coronary atherosclerotic events after percutaneous coronary intervention in patients with average cholesterol concentrations. The beneficial effects of fluvastatin are observed in patients with unstable or stable angina alike. http://repub.eur.nl/res/pub/13250/ 2003-10-21T00:00:00Z BACKGROUND: Sirolimus-eluting stents (SES) have recently been proven to reduce restenosis and reintervention compared with bare stents. Safety and effectiveness of SES in acute myocardial infarction remain unknown. METHODS AND RESULTS: Since April 16, 2002, a policy of routine SES implantation has been instituted in our hospital, with no clinical or anatomic restrictions, as part of the RESEARCH (Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital) registry. During 6 months of enrollment, 96 patients with ST-elevation acute myocardial infarction underwent percutaneous recanalization and SES implantation; these patients comprise the study population. The incidence of major adverse cardiac events (death, nonfatal myocardial infarction, reintervention) was evaluated. Six-month angiographic follow-up was scheduled per protocol. At baseline, diabetes mellitus was present in 12.5% and multivessel disease in 46.9%. Primary angioplasty was performed in 89 patients (92.7%). Infarct location was anterior in 41 (42.7%) of the cases, and 12 patients (12.5%) had cardiogenic shock. Postprocedural TIMI-3 flow was achieved in 93.3% of the cases. In-hospital mortality was 6.2%. One patient (1.1%) had reinfarction and target lesion reintervention the first day as a result of distal dissection and acute vessel occlusion. During follow-up (mean follow-up of 218+/-75 days), 1 patient died (1.1%), no patient had recurrent myocardial infarction, and there were no additional reinterventions. No early or late stent thromboses were documented. At angiographic follow-up (70%), late loss was -0.04+/-0.25, and no patient presented angiographic restenosis. CONCLUSIONS: In this study, sirolimus-eluting stent implantation for patients with ST-elevation acute myocardial infarction was safe without documented angiographic restenosis at 6 months. http://repub.eur.nl/res/pub/13177/ 2003-07-22T00:00:00Z BACKGROUND: We describe the clinical and morphological patterns of restenosis after sirolimus-eluting stent (SES) implantation. METHODS AND RESULTS: From 121 patients with coronary angiography obtained >30 days after SES implantation, restenosis (diameter stenosis >50%) was identified in 19 patients and 20 lesions (located at the proximal 5-mm segment in 30% or within the stent in 70%). Residual dissection after the procedure or balloon trauma outside the stent was identified in 83% of the proximal edge lesions. Lesions within the stent were focal, and stent discontinuity was identified in some lesions evaluated by intravascular ultrasound. CONCLUSIONS: Sirolimus-eluting stent edge restenosis is frequently associated with local trauma outside the stent. In-stent restenosis occurs as a localized lesion, commonly associated with a discontinuity in stent coverage. Local conditions instead of intrinsic drug-resistance to sirolimus are likely to play a major role in post-SES restenosis.