http://repub.eur.nl/res/aut/2052/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/12947/ 2001-09-01T00:00:00Z BACKGROUND: There are limited data regarding the immediate and long-term effect of balloon angioplasty on the coronary flow reserve evaluated in a multicentre setting. METHODS AND RESULTS: A total of 86 patients with one-vessel disease and normal left ventricular function were analysed before and after optimal balloon angioplasty (diameter stenosis <35%) and at 6-month follow-up. Coronary flow reserve was assessed with a Doppler guide wire. A low coronary flow reserve (<or=2.5) after PTCA, due to an increased baseline blood flow velocity, was encountered in 42 of the 86 patients (49%). Recurrence of angina and target lesion revascularization were more frequent in these patients than in patients with a coronary flow reserve >2.5 (46% vs 23% and 36% vs 16%, respectively; P<0.05) due to a trend towards restenosis (29% vs 16%; P=0.15) or a low coronary flow reserve at follow-up due to persistent elevated baseline blood flow velocity. Patients without restenosis showed a decrease or increase of coronary flow reserve during follow-up, determined by alterations of hyperaemic blood flow velocity. CONCLUSIONS: Patients with an impaired coronary flow reserve directly after optimal balloon angioplasty showed a higher target lesion revascularization rate compared to patients with a coronary flow reserve >2.5. This patient group consists of patients prone to develop restenosis, while other patients are characterized by a persistently low coronary flow reserve, probably secondary to disturbed autoregulation and/or diffuse mild coronary atherosclerosis. Coronary flow reserve alterations in patients without restenosis were related to changes in hyperaemic blood flow velocity, suggesting that this phenomenon relates to epicardial remodelling. http://repub.eur.nl/res/pub/12838/ 2000-03-15T00:00:00Z AIMS: Evaluation of angiographical and intracoronary Doppler-derived parameters of coronary stenosis severity. METHODS AND RESULTS: A total of 225 patients with one-vessel disease were studied before PTCA and at 6 months follow-up. Exercise electrocardiography was performed to document presence (n = 157) or absence (n = 138) of an ST segment shift (> or =0.1 mV). Intracoronary blood flow velocity analysis was performed to determine the proximal/distal flow velocity ratio, the distal diastolic/systolic flow velocity ratio and coronary flow velocity reserve. Receiver operator characteristic curves were calculated to assess the predictive value of these variables compared with the exercise test. The distal coronary flow velocity reserve demonstrated the best linear correlation for both percentage diameter stenosis and minimum lumen diameter (r = 0.67 and r = 0.66; P<0.01), compared to the diastolic/systolic flow velocity ratio (r = 0.19 and r = 0.14; P<0.01) and the proximal/distal flow velocity ratio (r = 0.03 and r = 0.07; not significant). The areas under the curve were 0. 84+/-0.02; 0.82+/-0.03 and 0.83+/-0.03 for diameter stenosis, minimum lumen diameter and coronary flow velocity reserve, respectively. Logistic regression analysis revealed that the percentage diameter stenosis or minimum lumen diameter and coronary flow velocity reserve were independent predictors for the result of stress testing. CONCLUSIONS: The distal coronary flow velocity reserve is the best intracoronary Doppler parameter for evaluation of coronary narrowings. Angiographical estimates of coronary lesion severity and distal coronary flow velocity reserve are good and independent predictors for the assessment of functional severity of coronary stenosis, emphasizing the complementary role of these parameters for clinical decision making. http://repub.eur.nl/res/pub/4973/ 1997-01-01T00:00:00Z Background The aim of this prospective, multicenter study was the identification of Doppler flow velocity measurements predictive of clinical outcome of patients undergoing single-vessel balloon angioplasty with no previous Q-wave myocardial infarction. Methods and Results In 297 patients, a Doppler guidewire was used to measure basal and maximal hyperemic flow velocities proximal and distal to the stenosis before and after angioplasty. In 225 patients with an angiographically successful percutaneous transluminal coronary angioplasty (PTCA), postprocedural distal coronary flow reserve (CFR) and percent diameter stenosis (DS%) were correlated with symptoms and/or ischemia at 1 and 6 months, with the need for target lesion revascularization, and with angiographic restenosis (defined as DS 50% at follow-up). Logistic regression and receiver operator characteristic curve analyses were applied to determine the prognostic cutoff value of CFR and DS separately and in combination. Optimal cutoff criteria for predictors of these clinical events were DS, 35%; CFR, 2.5. A distal CFR after angioplasty >2.5 with a residual DS 35% identified lesions with a low incidence of recurrence of symptoms at 1 month (10% versus 19%, P=.149) and at 6 months (23% versus 47%, P=.005), a low need for reintervention (16% versus 34%, P=.024), and a low restenosis rate (16% versus 41%, P=.002) compared with patients who did not meet these criteria. Conclusions Measurements of distal CFR after PTCA, in combination with DS%, have a predictive value, albeit modest for the short- and long-term outcomes after PTCA, and thus may be used to identify patients who will or will not benefit from additional therapy such as stent implantation. http://repub.eur.nl/res/pub/5551/ 1997-01-01T00:00:00Z AIMS: Angiographic studies on the natural course of both focal and diffuse coronary atherosclerosis have not been performed before, but can both be assessed by quantitative coronary angiography. The objective of this study was to describe the natural course of focal and diffuse coronary atherosclerosis over time. METHODS AND RESULTS: In 129 patients with mild coronary artery disease, but not on lipid-lowering medication, three coronary angiograms were made each 2 years apart. Nine hundred and sixty five angiographically diseased and non-diseased segments were analysed by quantitative coronary angiography. Mean lumen diameter and minimal lumen diameter were used as measures of diffuse and focal coronary atherosclerosis. Mean lumen diameter and minimum lumen diameter decreased by 0.02 and 0.03 mm per year. The rate of progression was similar in the angiographically non-diseased, as in the mildly and moderately diseased segments. Progression of diffuse coronary atherosclerosis was largest in severely stenosed lesions (percentage diameter stenosis > or = 50%) and in the right coronary artery with a loss of 0.19 mm and 0.16 mm in mean lumen diameter. Progression of focal disease was most prominent in new and mild lesions and the right coronary artery, with a decrease in minimum lumen diameter of 0.34 mm and 0.22 mm. In most subgroups, progression occurred gradually over time. On a per segment level, progression and the occurrence of new lesions occurred in 4.4% and 4.2%. Regression and disappearance of a lesions was found in 2.3% and 1.9%. On a per patient level, 36% were progressors, 12% had a mixed response, 36% were stable, and 16% were regressors. CONCLUSION: Diffuse and focal coronary atherosclerosis progressed at the same rate in the first and second 2 years in stenosed and non-stenosed segments. The rate of coronary atherosclerosis progression was small, but was higher for focal than for diffuse disease. A minority of lesions progressed and spontaneous regression was rare. http://repub.eur.nl/res/pub/5046/ 1996-01-01T00:00:00Z Background The use of stents improves the result after balloon coronary angioplasty. Thrombogenicity of stents is, however, a concern. In the present study, we compared stents with an antithrombotic coating with regular stents. Methods and Results Regular stents were placed in coronary arteries of pigs receiving no aspirin (group 1; n=8) or aspirin over 4 weeks (group 2, n=10) or 12 weeks (group 3, n=9). Stents coated with heparin (antithrombin III uptake, 5 pmol/stent) were placed in 7 pigs that did not receive aspirin (group 4). The other animals received aspirin and coated stents with a heparin activity of 12 pmol antithrombin III/stent (group 5, n=10) or 20 pmol/stent (group 6, n=10; group 7, n=10). Quantitative arteriography was performed at implantation and after 4 (groups 1, 2, and 4 through 6) or 12 weeks (groups 3 and 7). In an additional 5 animals, five regular and five coated stents (20 pmol/stent) were placed and explanted after 5 days for examination of the early responses to the implants. Thrombotic occlusion of the regular stent occurred in 9 of 27 in groups 1 through 3. However, in 0 of 30 of the animals receiving high-activity heparin-coated stents (groups 5 through 7), thrombotic stent occlusion was observed (P<.001). Histological analysis at 4 weeks showed that the neointima in group 6 was thicker compared with its control group 2 (259±104 and 117±36 µm, P<.01), but at 12 weeks the thickness was similar (152±61 and 198±49 µm, respectively). Comparison at 5 days suggested delayed endothelialization of the coating. http://repub.eur.nl/res/pub/5047/ 1996-01-01T00:00:00Z Background The purpose of the Benestent-II Pilot Study was to evaluate the safety of delaying and eliminating anticoagulant therapy in patients receiving a heparin-coated stent in conjunction with antiplatelet drugs. Methods and Results The study consisted of three initial phases (I, II, III) during which resumption of heparin therapy after sheath removal was progressively deferred by 6, 12, and 36 hours. In phase IV, coumadin and heparin were replaced by 250 mg ticlopidine and 100 mg aspirin. Of the 207 patients with stable angina pectoris and a de novo lesion in whom heparin-coated stent implantation was attempted, implantation was successful in 202 patients (98%). Stent thrombosis did not occur during all four phases, and the overall clinical success rate at discharge was 99%. Bleeding complications requiring blood transfusion or surgery fell from 7.9% in phase I to 5.9%, 4%, and 0% in the three following phases. Hospital stay was 7.4, 6.1, 7.2, and 3.1 days for the consecutive phases. The restenosis rate for the combined four phases was 13% (15% in phase I, 20% in phase II, 11% in phase III, and 6% in phase IV). The overall rate of reintervention for the four phases was 8.9%. At 6 months, 84%, 75%, 94%, and 92% of the patients of phases I to IV, respectively, were event free. For the four phases, the event-free rate was 86%, which compares favorably with the rate observed in the Benestent-I study (80%; relative risk, 0.68 [0.45 to 1.04]). Conclusions The implantation of stents coated with polyamine and end-point–attached heparin in stable patients with one significant de novo coronary lesion is well tolerated, is associated with no (sub)acute stent thrombosis, and results in a favorable event-free survival after 6 months. http://repub.eur.nl/res/pub/4616/ 1994-01-01T00:00:00Z BACKGROUND. Balloon-expandable coronary-artery stents were developed to prevent coronary restenosis after coronary angioplasty. These devices hold coronary vessels open at sites that have been dilated. However, it is unknown whether stenting improves long-term angiographic and clinical outcomes as compared with standard balloon angioplasty. METHODS. A total of 520 patients with stable angina and a single coronary-artery lesion were randomly assigned to either stent implantation (262 patients) or standard balloon angioplasty (258 patients). The primary clinical end points were death, the occurrence of a cerebrovascular accident, myocardial infarction, the need for coronary-artery bypass surgery, or a second percutaneous intervention involving the previously treated lesion, either at the time of the initial procedure or during the subsequent seven months. The primary angiographic end point was the minimal luminal diameter at follow-up, as determined by quantitative coronary angiography. RESULTS. After exclusions, 52 patients in the stent group (20 percent) and 76 patients in the angioplasty group (30 percent) reached a primary clinical end point (relative risk, 0.68; 95 percent confidence interval, 0.50 to 0.92; P = 0.02). The difference in clinical-event rates was explained mainly by a reduced need for a second coronary angioplasty in the stent group (relative risk, 0.58; 95 percent confidence interval, 0.40 to 0.85; P = 0.005). The mean (+/- SD) minimal luminal diameters immediately after the procedure were 2.48 +/- 0.39 mm in the stent group and 2.05 +/- 0.33 mm in the angioplasty group; at follow-up, the diameters were 1.82 +/- 0.64 mm in the stent group and 1.73 +/- 0.55 mm in the angioplasty group (P = 0.09), which correspond to rates of restenosis (diameter of stenosis, > or = 50 percent) of 22 and 32 percent, respectively (P = 0.02). Peripheral vascular complications necessitating surgery, blood transfusion, or both were more frequent after stenting than after balloon angioplasty (13.5 vs. 3.1 percent, P < 0.001). The mean hospital stay was significantly longer in the stent group than in the angioplasty group (8.5 vs. 3.1 days, P < 0.001). CONCLUSIONS. Over seven months of follow-up, the clinical and angiographic outcomes were better in patients who received a stent than in those who received standard coronary angioplasty. However, this benefit was achieved at the cost of a significantly higher risk of vascular complications at the access site and a longer hospital stay. http://repub.eur.nl/res/pub/4625/ 1994-01-01T00:00:00Z It has been shown repeatedly in animal and clinical studies that heparin coating reduces thrombotic complications of several surfaces in contact with flowing blood. The demonstration that implantation of heparin-coated coronary stents is also effective in prevention of subacute thrombotic occlusion in a pig model offers the perspective of a clinical role of this treatment too. In order to put this to the test, the Benestent II pilot trial has been designed. This study will be conducted in a stepwise fashion in order to explore the feasibility of delaying deep anticoagulation as much as possible. Therefore, the primary goal is to minimize or exclude the need for heparin treatment following stent implantation. In addition, the effects on the need for revascularization procedures during follow-up will be recorded as well as the late morphological consequences as measured with quantitative coronary angiography. http://repub.eur.nl/res/pub/4507/ 1993-01-01T00:00:00Z The use of miniaturized pressure and velocity sensors mounted on angioplasty guidewires allows the simultaneous measurement of coronary blood flow velocity and transstenotic pressure gradient, 2 parameters that, combined, should perfectly characterize stenosis hemodynamics. The aim of this article is assessment of the changes in coronary blood flow velocity observed with a Doppler-tipped angioplasty guidewire in 35 patients undergoing balloon angioplasty. We also report our initial experience in 16 patients with the combined use of sensor-tip pressure and Doppler guidewires, and we discuss the application of new methodologic approaches for the study of the coronary circulation allowed by these techniques, such as the instantaneous assessment of the flow velocity/pressure and pressure gradient/flow velocity relations. Before and after angioplasty, flow velocity measurements were obtained distal to the stenosis, both in baseline conditions and after intracoronary injection of 8-12.5 mg of papaverine. The Doppler guidewire was left in place during the dilation procedure and the Doppler signal was continuously recorded during balloon inflation and after deflation to monitor the development of collateral flow, the restoration of flow after balloon deflation, the phase of postocclusive reactive hyperemia, and, incidently, the development of flow-limiting complications. Merits and pitfalls of several flow velocity parameters (average peak velocity, coronary flow velocity reserve, diastolic/systolic velocity ratio), as well as of parameters derived from the combination of pressure and velocity measurements (transstenotic pressure gradient/flow velocity relation and instantaneous diastolic hyperemic flow velocity/pressure relation) were evaluated in 35 patients with, and 37 without, significant coronary stenoses.(ABSTRACT TRUNCATED AT 250 WORDS) http://repub.eur.nl/res/pub/4521/ 1993-01-01T00:00:00Z A fiberoptic pressure sensor mounted on an 0.018-inch guidewire (Pressure Guide) was used to measure the transstenotic pressure gradient in 30 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) with lesions considered suitable for quantitative coronary angiographic (QCA) assessment. The aim of the study was to correlate pressure gradients with parameters obtained with QCA. After intracoronary injection of 125 micrograms of nitroglycerin, multiple angiographic views were taken of the lesion. The Pressure Guide fiberoptic sensor was then positioned distal to the stenosis and the pressure gradients were recorded before and after PTCA. There was a significant correlation between mean pressure gradients (delta P) and percent diameter stenosis (r = 0.73; p < 0.001) and absolute stenosis diameter (r = -0.67; p < 0.001) and with percent area stenosis (r = 0.69; p < 0.001) and absolute stenosis area (r = -0.63; p < 0.001). The closest relationship, though, was found with stenotic flow reserve (SFR), which is an integrated parameter calculated from QCA. This relationship can be described by the equation: delta P = 65.2 - 12.6.SFR (r = -0.79; p < 0.001). With a measured gradient of > 15 mm Hg, the sensitivity was 94% and the specificity 96% to predict an SFR < 3.5. In conclusion, a statistically significant relationship could be found between stenosis pressure gradients and angiographic parameters in this study with lesions without complicated morphology. The independent information obtained by pressure gradient measurement may be of particular value in intermediately severe lesions or in stenoses where the angiographic assessment otherwise is difficult. http://repub.eur.nl/res/pub/4531/ 1993-01-01T00:00:00Z http://repub.eur.nl/res/pub/4548/ 1993-01-01T00:00:00Z BACKGROUND. Ketanserin is a serotonin S2-receptor antagonist that inhibits the platelet activation and vasoconstriction induced by serotonin and also inhibits the mitogenic effect of serotonin on vascular smooth muscle cells. METHODS AND RESULTS. We conducted a randomized, double blind, placebo-controlled trial to assess the effect of ketanserin in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received either ketanserin (loading dose, 40 mg 1 hour before PTCA; maintenance dose, 40 mg bid for 6 months) or matched placebo. In addition, all patients received aspirin for 6 months. Coronary angiograms before PTCA, after PTCA, and at 6 months were quantitatively analyzed. Six hundred fifty-eight patients were entered into the intention-to-treat analysis. The primary clinical end point of the study was the occurrence between PTCA and 6 months of any one of the following: cardiac death, myocardial infarction, the need for repeat angioplasty, or bypass surgery. It also included the need for revascularization actuated by findings at 6-month follow-up angiography. The primary clinical end point was reached by 92 (28%) patients in the ketanserin group and 104 (32%) in the placebo group (RR, 0.89; 95% CI, 0.70, 1.13; P = .38). Quantitative angiography after PTCA and at follow-up was available in 592 patients (ketanserin, 287; control, 305). The mean difference in minimal lumen diameter between post-PTCA and follow-up angiogram (primary angiographic end point) was 0.27 +/- 0.49 mm in the ketanserin group and 0.24 +/- 0.52 mm in the control group (difference, 0.03 mm; 95% CI, -0.05, 0.11; P = .50). CONCLUSIONS. Ketanserin at the dose administered in this trial failed to reduce the loss in minimal lumen diameter during follow-up after PTCA and did not significantly improve the clinical outcome. http://repub.eur.nl/res/pub/4470/ 1992-01-01T00:00:00Z BACKGROUND. Cilazapril is a novel angiotensin converting enzyme inhibitor with antiproliferative effects in the rat model after balloon injury. METHODS AND RESULTS. We conducted a randomized, double-blind placebo-controlled trial to assess the effect of cilazapril in angiographic restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received cilazapril 2.5 mg in the evening after successful PTCA and 5 mg b.i.d. for 6 months or matched placebo. In addition, all patients received aspirin for 6 months. Coronary angiograms before PTCA, after PTCA, and at 6-month follow-up were quantitatively analyzed. In 94% of 735 recruited patients, PTCA was successful and all inclusion and exclusion criteria were met. For the per-protocol analysis, quantitative angiography after PTCA and at follow-up was available in 595 patients who complied with the treatment regimen (309 control, 286 cilazapril). The mean difference in minimal coronary lumen diameter between post-PTCA and follow-up angiogram (primary end point) was -0.29 +/- 0.49 mm in the control group and - 0.27 +/- 0.51 mm in the cilazapril group. Clinical events during 6- month follow-up, analyzed on an intention-to-treat basis, were ranked according to the most serious clinical event ranging from death (control, two; cilazapril, three), nonfatal myocardial infarction (control, eight; cilazapril, 5), coronary revascularization (control, 51; cilazapril, 53), or recurrent angina requiring medical therapy (control, 67; cilazapril, 68) to none of the above (control, 224; cilazapril, 212). There were no significant differences in ranking. CONCLUSIONS. Long-term angiotensin converting enzyme inhibition with cilazapril in a dose of 5 mg b.i.d. does not prevent restenosis and does not favorably influence the overall clinical outcome after PTCA. http://repub.eur.nl/res/pub/4480/ 1992-01-01T00:00:00Z OBJECTIVES: The objective of this study was to examine the relation between an angiographically visible coronary dissection immediately after successful coronary balloon angioplasty and a subsequent restenosis and long-term clinical outcome. BACKGROUND. The study population comprised all 693 patients who participated in the MERCATOR trial (randomized, double-blind, placebo-controlled restenosis prevention trial of cilazapril, 5 mg two times a day). METHODS. Cineangiographic films were processed and analyzed at a central angiographic core laboratory, without knowledge of clinical data, with use of an automated interpolated edge detection technique. Dissection was judged according to the National Heart, Lung, and Blood Institute classification. Angiographic follow-up was obtained in 94% of patients with 778 lesions. Two approaches were used to assess the restenosis phenomenon: 1) categoric, using the traditional cutoff criterion of greater than 50% diameter stenosis at follow-up, and 2) continuous, defined as absolute change in minimal lumen diameter (mm) between the postcoronary angioplasty and follow-up, adjusted for the vessel size (relative loss). Clinical outcome was ranked according to the most serious adverse clinical event per patient during the 6-month follow-up period, ranging from death, nonfatal myocardial infarction, coronary revascularization and recurrent angina requiring medical therapy to none of these. RESULTS. Dissection was present in 247 (32%) of the 778 dilated lesions. The restenosis rate was 29% in lesions with and 30% in lesions without dissection (relative risk 0.97; 95% confidence interval 0.77 to 1.23). The relative loss in both groups was 0.10 (mean difference 0; 95% confidence interval -0.03 to 0.03). Clinical outcome ranged from death in 4 patients (0.9%) without dissection and 1 patient (0.4%) with dissection; nonfatal myocardial infarction in 4 (0.9%) without and 8 (3.2%) with dissection; coronary revascularization in 73 (16.6%) without and 32 (12.7%) with dissection; recurrent angina requiring medical therapy in 88 (20%) without and 47 (18.7%) with dissection to no serious adverse event in 272 (61.7%) without and 114 (65.1%) with dissection. CONCLUSIONS. These data indicate that a successfully dilated coronary lesion with an angiographically visible dissection is no more likely to develop restenosis, and is not associated with a worse clinical outcome, at 6-month follow-up than is a dilated lesion without visible dissection on the post-balloon angioplasty angiogram.