Enlarging the Arsenal of Test Species for Sediment Quality Assessment.

Since only a few standard benthic test species are available for sediment quality, our study aimed to employ multiple test species representing different sensitivity categories in the quality assessment of contaminated sediments. To this end three macroinvertebrate species, Sericostoma personatum (caddisfly, sensitivity category 10), Asellus aquaticus (isopod, category 3) and Chironomus riparius (chironomid, category 2), were exposed to sediments originating from various contamination sources in whole sediment bioassays using intact sediment cores. The agricultural sediment caused insect mortality, the agricultural and urban sediment caused isopod growth reduction and the urban and Wastewater Treatment Plant (WWTP) sediment affected chironomid emergence time. It is concluded that the arsenal of standard species can be successfully expanded by non-standard species, reducing over- or underestimation of the risks of contaminated sediments.

Angiographic and clinical one-year follow-up of the Cordis tantalum coil stent in a multicenter international study demonstrating improved restenosis rates when compared to pooled PTCA and BENESTENT-I data: the European Antiplatelet Stent Investigation (EASI).

The Cordis tantalum coil stent was assessed in a nonrandomized multicenter trial: 275 patients with stable or unstable angina were entered. Clinical follow-up was for 1 year, with repeat angiography at 6 months. The major adverse cardiac event rates (MACE) were 3%, 14%, and 17% at 1, 7, and 13 months, respectively. The procedural success rate was 96% and the subacute occlusion rate 1.5%, in a group of patients over 60% of whom had ACC/AHA type B2 or C lesions. The binary restenosis rate at 6 months was 17.3%. Minimum lumen diameter increased from 1.07 +/- 0.28 mm preprocedure to 2.93 +/- 0.34 mm poststenting and at 6 months was 1.99 +/- 0.69 mm. These results demonstrate that the Cordis tantalum stent can be used to treat complex lesions with good procedural success and low rates of subacute thrombosis and restenosis at 6 months.

Total occlusion trial with angioplasty by using laser guidewire. The TOTAL trial.

AIMS: A randomized trial was performed to assess the safety and efficacy of a laser guidewire, in the treatment of chronic coronary occlusions. METHODS AND RESULTS: In 18 European centres, 303 patients with a chronic coronary occlusion were randomized to treatment with either the laser guidewire (n=144) or conventional guidewires (mechanical guidewire, n=159). The primary end-point of the study was treatment success, defined as reaching the true lumen distal to the occlusion by the allocated wire within 30 min of fluoroscopic time: laser guidewire vs mechanical guidewire; 52.8% (n=76) vs 47.2% (n=75), P=0.33. Serious adverse events following the initial guidewire attempt were 0% (laser guidewire) and 0.6% (mechanical guidewire), respectively. Angioplasty (performed following successful guidewire crossing) was successful in 179 patients (91%, laser guidewire n=79, mechanical guidewire n=100), followed by stent implantation in 149 (79%). At the 6-month angiographic follow-up, the difference in binary restenosis rate (laser guidewire vs mechanical guidewire; 45.5% vs 38.3 %, P=0.72) or reocclusion rate (25.8% vs 16.1%, P=0.15) did not reach statistical significance. At 1, 6 and 12 months, angina and event-free survival were 69%, 35% and 24% (laser guidewire) vs 74%, 40% and 31% (mechanical guidewire). CONCLUSION: Although laser guidewire technology was safe, the increase in crossing success did not reach statistical significance.

Influence of a history of smoking on short term (six month) clinical and angiographic outcome after successful coronary angioplasty.

OBJECTIVES: To assess the influence of smoking on restenosis after coronary angioplasty. DESIGN AND PATIENTS: The incidence of smoking on restenosis was investigated in 2948 patients. They were prospectively enrolled in four major restenosis trials in which quantitative angiography was used before and immediately after successful angioplasty and again at six months. RESULTS: Within the study population there were 530 current smokers, 1690 ex-smokers, and 728 non-smokers. Smokers were more likely to be men (85.9% v 87. 5% v 65.3%, current v ex- v non-, p < 0.001), to be younger (54.0 (9. 0) v 57.0 (9.1) v 59.9 (9.4) years, p < 0.001), to have peripheral vascular disease (7.2% v 5.5% v 2.3%, p < 0.001), and have sustained a previous myocardial infarction (42.9% v 43.9% v 37.9%, p = 0.022), but were less likely to be diabetic (9.1% v 9.5% v 12.6%, p = 0.043) or hypertensive (24.9% v 29.3% v 37.2, p < 0.001). There was no significant difference in the categorical restenosis rate (> 50% diameter stenosis) at six months (35.28% v 35.33% v 37.09%, current v ex- v non-), or the absolute loss (0.29 (0.54) v 0.33 (0.52) v 0. 35 (0.55) mm, respectively; p = 0.172). CONCLUSIONS: Although smokers have a lower incidence of known predisposing risk factors for atherosclerosis, they require coronary intervention almost six years earlier than non-smokers and three years earlier than ex-smokers. Once they undergo successful coronary angioplasty, there appears to be no evidence that smoking influences their short term (six month) outcome, but because of the known long term effects of smoking, patients should still be encouraged to discontinue the habit.

Carvedilol for prevention of restenosis after directional coronary atherectomy : final results of the European carvedilol atherectomy restenosis (EUROCARE) trial.

BACKGROUND: In addition to its known properties as a competitive, nonselective beta and alpha-1 receptor blocker, carvedilol directly inhibits vascular myocyte migration and proliferation and exerts antioxidant effects that are considerably greater than those of vitamin E or probucol. This provides the basis for an evaluation of carvedilol for the prevention of coronary restenosis. METHODS AND RESULTS: In a prospective, double-blind, randomized, placebo-controlled trial, 25 mg of carvedilol was given twice daily, starting 24 hours before scheduled directional coronary atherectomy and continuing for 5 months after a successful procedure. The primary end point was the minimal luminal diameter as determined during follow-up angiography 26+/-2 weeks after the procedure. Of 406 randomized patients, 377 underwent attempted atherectomy, and in 324 (88.9%), a

Does angiography six months after coronary intervention influence management and outcome? Benestent II Investigators.

OBJECTIVES: This study was performed to assess whether angiography six months after coronary balloon angioplasty or stent implantation has an influence on clinical management and one-year outcome. BACKGROUND: The Benestent II study randomized 827 patients to balloon angioplasty or stent implantation. A subrandomization was undertaken allocating patients to six-month clinical follow-up (CF) or clinical and angiographic follow-up (AF). METHODS: Seven hundred and six patients (349 CF and 357 AF) had no intercurrent angiography, so that restenosis and disease progression elsewhere remained unknown until the time of six-month follow-up. These two groups, which were well matched at enrolment, were compared with respect to symptoms, medication and major cardiac events defined as death, myocardial infarction and need for revascularization at six and 12 months. RESULTS: At six-month follow-up, 53 (15%) of the CF and 76 (21%) of the AF patients had stable angina (p = 0.041), while 5 (1%) and 4 (1%) had symptoms of unstable angina. At 12-month follow-up, 44 (13%) patients in both groups had stable angina, and only 1 patient in the CF group had unstable angina. Seventy-seven patients (27 CF and 50 AF; p < 0.01) had major cardiac events between 6 and 12 months. Of the 349 patients in the CF group, 21 underwent repeat percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery between 6 and 12 months, compared with 44 of the 357 patients in the AF group (relative risk 2.05 [1.24 to 3.37], p = 0.003). CONCLUSIONS: Patients who had AF six months after balloon angioplasty or stent implantation experienced more repeat revascularization procedures than those who had CF. They also had significantly more angina at six-month follow-up but this may be due to bias.

Anticoagulant properties, clinical efficacy and safety of efegatran, a direct thrombin inhibitor, in patients with unstable angina.

AIMS: Thrombin plays a key role in the clinical syndrome of unstable angina. We investigated the safety and efficacy of five dose levels of efegatran sulphate, a direct thrombin inhibitor, compared to heparin in patients with unstable angina. METHODS: Four hundred and thirty-two patients with unstable angina were enrolled. Five dose levels of efegatran were studied sequentially, ranging from 0.105 mg. kg(-1). h(-1)to 1.2 mg. kg(-1). h(-1)over 48 h. Safety was assessed clinically, with reference to bleeding and by measuring clinical laboratory parameters. Efficacy was assessed by the number of patients experiencing any episode of recurrent ischaemia as measured by computer-assisted continuous ECG ischaemia monitoring. Clinical end-points were: episodes of recurrent angina, myocardial infarction, coronary intervention (PTCA or CABG), and death. RESULTS: Efegatran demonstrated dose dependent ex-vivo anticoagulant activity with the highest dose level of 1.2 mg. kg(-1). h(-1)resulting in steady state mean activated partial thromboplastin time values of approximately three times baseline. Thrombin time was also increased. Neither of the efegatran doses studied were able to suppress myocardial ischaemia during continuous ECG ischaemia monitoring to a greater extent than that seen with heparin. There were no statistically significant differences in clinical outcome or major bleeding between the efegatran and heparin groups. Minor bleeding and thrombophlebitis occurred more frequently in the efegatran treated patients. CONCLUSION: Administration of efegatran sulphate at levels of at least 0.63 mg. kg(-1). h(-1)provided an anti-thrombotic effect which is at least comparable to an activated partial thromboplastin time adjusted heparin infusion. There was no excess of major bleeding. The level of thrombin inhibition by efegatran, as measured by activated partial thromboplastin time, appeared to be more stable than with heparin. Thus, like other thrombin inhibitors, efegatran sulphate is easier to administer than heparin. However, no clinical benefits of efegatran over heparin were apparent.

A randomized placebo-controlled trial of fluvastatin for prevention of restenosis after successful coronary balloon angioplasty; final results of the fluvastatin angiographic restenosis (FLARE) trial.

BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors competitively inhibit biosynthesis of mevalonate, a precursor of non-sterol compounds involved in cell proliferation. Experimental evidence suggests that fluvastatin may, independent of any lipid lowering action, exert a greater direct inhibitory effect on proliferating vascular myocytes than other statins. The FLARE (Fluvastatin Angioplasty Restenosis) Trial was conceived to evaluate the ability of fluvastatin 40 mg twice daily to reduce restenosis after successful coronary balloon angioplasty (PTCA). METHODS: Patients were randomized to either placebo or fluvastatin 40 mg twice daily beginning 2-4 weeks prior to planned PTCA and continuing after a successful PTCA (without the use of a stent), to follow-up angiography at 26+/-2 weeks. Clinical follow-up was completed at 40 weeks. The primary end-point was angiographic restenosis, measured by quantitative coronary angiography at a core laboratory, as the loss in minimal luminal diameter during follow-up. Clinical end-points were death, myocardial infarction, coronary artery bypass graft surgery or re-intervention, up to 40 weeks after PTCA. RESULTS: Of 1054 patients randomized, 526 were allocated to fluvastatin and 528 to placebo. Among these, 409 in the fluvastatin group and 427 in the placebo group were included in the intention-to-treat analysis, having undergone a successful PTCA after a minimum of 2 weeks of pre-treatment. At the time of PTCA, fluvastatin had reduced LDL cholesterol by 37% and this was maintained at 33% at 26 weeks. There was no difference in the primary end-point between the treatment groups (fluvastatin 0.23+/-0.49 mm vs placebo 0.23+/-0.52 mm, P=0.95) or in the angiographic restenosis rate (fluvastatin 28%, placebo 31%, chi-square P=0.42), or in the incidence of the composite clinical end-point at 40 weeks (22.4% vs 23.3%; logrank P=0.74). However, a significantly lower incidence of total death and myocardial infarction was observed in six patients (1.4%) in the fluvastatin group and 17 (4.0%) in the placebo group (log rank P=0.025). CONCLUSION: Treatment with fluvastatin 80 mg daily did not affect the process of restenosis and is therefore not indicated for this purpose. However, the observed reduction in mortality and myocardial infarction 40 weeks after PTCA in the fluvastatin treated group has not been previously reported with statin therapy. Accordingly, a priori investigation of this finding is indicated and a new clinical trial with this intention is already underway.

Reduction of recurrent ischemia with abciximab during continuous ECG-ischemia monitoring in patients with unstable angina refractory to standard treatment (CAPTURE).

BACKGROUND: In the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina) trial, 1265 patients with refractory unstable angina were treated with abciximab or placebo, in addition to standard treatment from 16 to 24 hours preceding coronary intervention through 1 hour after intervention. To investigate the incidence of recurrent ischemia and the ischemic burden, a subset of 332 patients (26%) underwent continuous vector-derived 12-lead ECG-ischemia monitoring. METHODS AND RESULTS: Patients were monitored from start of treatment through 6 hours after coronary intervention. Ischemic episodes were detected in 31 (18%) of the 169 abciximab and in 37 (23%) of the 163 placebo patients (NS). Only 9 (5%) of abciximab versus 22 (14%) of placebo patients had >/=2 ST episodes (P<0.01). In patients with ischemia, abciximab significantly reduced total ischemic burden (P<0.02), which was calculated alternatively as the total duration of ST episodes per patient, the area under the curve of the ST vector magnitude during episodes, or the sum of the areas under the curves of 12 leads during episodes. Twenty-one patients (6%) suffered a myocardial infarction (MI) (18) or died (3) within 5 days of treatment. The presence of asymptomatic and symptomatic ST episodes during the monitoring period preceding coronary intervention was associated with an increased relative risk of these events of 3.2 (95% CI 1.4, 7.4) and 4.1 (95% CI 1.4, 12.2), respectively. CONCLUSIONS: Recurrent ischemia predicts MI or death within 5 days of follow-up. Treatment with abciximab is associated with a reduction of frequent ischemia and a reduction of total ischemic burden in patients with refractory unstable angina. As such, patients with ischemia derive particularly high benefit from abciximab.

Clinical and angiographic comparison of matched patients with successful directional coronary atherectomy or stent implantation for primary coronary artery lesions.

OBJECTIVES: This study was designed to compare the long-term clinical and angiographic effects of successful directional atherectomy and stent implantation and to examine whether restenosis is related to the mechanism of lumen improvement as well as the extent of lumen gain. BACKGROUND: Directional atherectomy and coronary stent implantation have been shown to achieve a more optimal immediate result that may lead to a more favorable long-term angiographic outcome and fewer target vessel revascularizations than does angioplasty. However, it remains to be determined whether one of the devices used in these interventions provides consistently better results than the other. METHODS: To allow meaningful comparisons a prospectively collected series of 117 patients successfully treated with atherectomy were individually matched with a prospectively collected series of 117 patients successfully treated with stent implantation. Matching for baseline characteristics identified patients with identical lesion location and lesion severity, and immediate and late angiographic and clinical outcome were compared. To evaluate the possibility of a procedure effect on restenosis, patients were further matched for both immediate angiographic outcome and baseline characteristics, providing 150 matched patients for comparison. As confirmatory analysis, multivariate models were constructed to predict late lumen diameter. RESULTS: Matching resulted in two comparable groups with equivalent baseline clinical and stenosis characteristics (n = 117 pairs). Atherectomy led to a smaller immediate gain than stenting and, because late loss was similar in both groups, stenting resulted in a larger late lumen (1.96 +/- 0.51 vs. 1.66 +/- 0.55 mm, p < 0.0001). When patients were matched for immediate gain and baseline characteristics (n = 75 pairs), lumen loss was more pronounced after atherectomy, and thus the minimal lumen diameter at follow-up differed significantly between the two groups (1.66 +/- 0.53 vs. 1.90 +/- 0.47 mm, p = 0.004). This beneficial angiographic effect of stenting was accompanied by a reduced need for repeat interventions. Multivariate analysis confirmed the independent effect of the interventional device used, whereby less loss and greater lumen diameter at follow-up were predicted for stent implantation than for atherectomy. CONCLUSIONS: Successful stent implantation provided a more favorable long-term angiographic outcome and lower rates of restenosis and need for target lesion revascularization than did atherectomy. This favorable effect of stenting not only is related to a larger, immediate gain, but also seems to attenuate late lumen loss.

Short- and long-term clinical and quantitative angiographic results with the new, less shortening Wallstent for vessel reconstruction in chronic total occlusion: a quantitative angiographic study.

OBJECTIVES: This study was designed to examine whether oversized implantation of the new, less shortening Wallstent provides a more favorable long-term clinical and angiographic outcome in chronic total occlusions than does conventional coronary balloon angioplasty. BACKGROUND: Restenosis and reocclusion remain major limitations of balloon angioplasty for chronic total occlusions. Enforced mechanical remodeling by implantation of the oversized Wallstent may prevent elastic recoil and improve accommodation of intimal hyperplasia. METHODS: Lumen dimension was measured by a computer-based quantitative coronary angiography system (CAAS II). These measurements (before and after intervention and at 6-month follow-up) were compared between the groups with Wallstent implantation (20 lesions, 20 patients) and conventional balloon angioplasty (266 lesions, 249 patients) for treatment of chronic total occlusion. Acute gain (minimal lumen diameter after intervention minus that before intervention), late loss (minimal lumen diameter after intervention minus that at follow-up) and net gain (acute gain minus late loss) were examined. RESULTS: Wallstent deployment was successful in all patients. High pressure intra-Wallstent balloon inflation (mean +/- SD 14 +/- 3 atm) was performed in all lesions. Although vessel size did not differ between the Wallstent and balloon angioplasty groups, acute gain was significantly greater in the Wallstent group (2.96 +/- 0.55 vs. 1.61 +/- 0.34 mm, p < 0.0001). Although late loss was also significantly larger in the Wallstent group (0.81 +/- 0.95 vs. 0.43 +/- 0.68 mm, p < 0.05), net gain was still significantly greater in this group (2.27 +/- 1.00 vs. 1.18 +/- 0.69 mm, p < 0.0001). Angiographic restenosis (> or = 50% diameter stenosis) occurred at 6 months in 29% of lesions in the Wallstent group and in 45% of those in the balloon angioplasty group (p = 0.5150). CONCLUSIONS: Implantation of the oversized Wallstent, with full coverage of the lesion length, ensures resetting of the vessel size to its original caliber before disease and allows greater accommodation of intimal hyperplasia and chronic vessel recoil. Wallstent implantation provides a more favorable short- and long-term clinical and angiographic outcome than does conventional balloon angioplasty for chronic total occlusions.

Contributions of frequency distribution analysis to the understanding of coronary restenosis. A reappraisal of the gaussian curve.

BACKGROUND: Clinical restenosis after balloon angioplasty can be categorized by use of dichotomous terms based on the presence or absence of recurrent myocardial ischemia. In contrast, recent investigations have concluded that late luminal renarrowing, documented through angiographic imaging, occurs to a variable extent in nearly all stenoses. This process has been characterized by a gaussian or normal frequency distribution, with restenosis simply representing an extreme form of this delayed remodeling. In the current study, frequency distribution analysis was used to examine the process of coronary restenosis in a large cohort of patients at risk. METHODS AND RESULTS: Quantitative coronary angiographic analysis was applied to 9279 cineangiograms obtained in 3093 patients before and immediately after angioplasty and after 6-month follow-up. Late loss, defined as the change in minimum lumen diameter of the target stenosis from postdilation to follow-up, did not statistically conform to a normal distribution (P<.0001 by both chi2 statistic and Kolmogorov-Smirnov test), even after the exclusion of the 236 stenoses that displayed total occlusions at follow-up angiography. Examination of deviation from a normal curve revealed an excessively high frequency of stenoses that experienced either little change (0.0+/-0.3 mm) or marked change (1.0 to 2.0 mm) in late loss, with a low frequency of stenoses with intermediate values (0.3 to 1.0 mm). Similarly, although the distribution of percent diameter stenosis of the target lesion was statistically normal immediately after dilation, this gaussian distribution disappeared during the follow-up period. Other angiographic indexes of restenosis also failed to approximate a normal curve. In an attempt to improve the goodness of fit, a probabilistic model of late loss was created on the basis of deconvolution of the observed data distribution. Two theoretical, discrete populations of stenoses were identified, one with and one without overall late luminal narrowing. Unlike the gaussian distribution, this model provided a good representation of the observed data (P=NS for lack of fit). CONCLUSIONS: The frequency distributions of angiographic indexes of restenosis often superficially resemble a gaussian curve, an appearance that is artifactually enhanced by the measurement imprecision of current quantitative techniques. Nevertheless, standard indexes of coronary restenosis fail to conform statistically to a normal distribution. The pattern of deviations observed supports the possible existence of discrete subpopulations of lesions, each with a different propensity toward the development of restenosis after coronary intervention.

Role of angiographically identifiable thrombus on long-term luminal renarrowing after coronary angioplasty: a quantitative angiographic analysis.

BACKGROUND: Experimental studies suggest that mural thrombus may be involved in postangioplasty restenosis. The aim of our study was to examine the role of angiographically identifiable thrombus in the clinical situation. METHODS AND RESULTS: The study population comprised 2950 patients (3583 lesions). The presence of angiographically identifiable thrombus either before or after the procedure was defined as the presence of a generalized haziness or filling defect within the arterial lumen. Restenosis was assessed by both a categorical (> 50% diameter stenosis at follow-up) and a continuous approach (absolute and relative losses). The study population included 160 lesions with and 3423 lesions without angiographically identifiable thrombus. The categorical restenosis rate was significantly higher in lesions containing angiographically identifiable thrombus: 43.1% versus 34.4%, P < .01; relative risk, 1,449; CI, 1.051 to 1.997. The absolute and relative losses were also higher in lesions containing angiographically identifiable thrombus (absolute loss, 0.43 +/- 0.66 versus 0.32 +/- 0.52; relative loss, 0.16 +/- 0.26 versus 0.13 +/- 0.21; both P < .05). The higher restenosis in these lesions was due primarily to an increased incidence of occlusion at follow-up angiography in this group: 13.8% versus 5.7%, P < .001. When lesions that went on to occlude by the time of follow-up angiography were excluded from the analysis, the restenosis rate between the two groups was similar by both the categorical (34.1% versus 30.4%, P=NS; relative risk, 1.183; CI, 0.824 to 1.696) and continuous (absolute loss, 0.23 +/- 0.46 versus 0.24 +/- 0.42, P=NS; relative loss, 0.09 +/- 0.17 versus 0.09 +/- 0.16, P=NS) approaches. CONCLUSIONS: Our results indicate that the presence of angiographically identifiable thrombus at the time of the angioplasty is associated with higher restenosis. The mechanism by which this occurs is through vessel occlusion at follow-up angiography. Measures aimed at improving outcome in this group of patients should be focused in this direction.

Immediate and late outcome of excimer laser and balloon coronary angioplasty: a quantitative angiographic comparison based on matched lesions.

OBJECTIVES: This study sought to compare acute lumen changes and late lumen narrowing during and after excimer laser-assisted balloon angioplasty, measured by quantitative coronary angiography, with the immediate and long-term outcome of balloon angioplasty alone. BACKGROUND: Although excimer laser coronary angioplasty is used as an adjunct or alternative to balloon angioplasty, limited comparative data exist regarding the immediate and long-term efficacy of excimer laser-assisted balloon angioplasty versus balloon angioplasty alone. METHODS: A series of 53 lesions in 47 consecutive patients successfully treated with excimer laser-assisted balloon angioplasty were individually matched after completion of 6-month follow-up angiography with 53 successfully treated balloon angioplasty lesions according to vessel location, preprocedural minimal lumen diameter and reference diameter. Immediate and long-term angiographic results were assessed by an automated lumen contour detection algorithm. RESULTS: Before intervention in the laser and balloon angioplasty groups, respectively, minimal lumen diameter (mean +/- SD) was 0.73 +/- 0.47 and 0.74 +/- 0.46 mm, and reference diameter was 2.71 +/- 0.42 and 2.72 +/- 0.41 mm. Laser angioplasty was followed by adjunctive balloon dilation in 50 lesions. Mean balloon diameter at maximal inflation was similar in both treatment groups (2.61 +/- 0.32 and 2.65 +/- 0.38 mm, respectively), resulting in similar minimal lumen diameters after intervention of 1.77 +/- 0.41 and 1.78 +/- 0.34 mm, respectively. At follow-up angiography, minimal lumen diameter after excimer laser-assisted balloon angioplasty was 1.17 +/- 0.63 mm, and that after balloon angioplasty alone was 1.46 +/- 0.67 mm (p = 0.02). The angiographic restenosis rates at follow-up using the 50% diameter stenosis cutoff criterion were 57% and 34%, respectively (p = 0.02). CONCLUSIONS: Quantitative angiographic analysis of a matched group of 106 successfully treated coronary lesions showed a similar immediate outcome but reduced long-term efficacy of excimer laser-assisted balloon angioplasty compared with that after balloon angioplasty alone.

Differences in restenosis propensity of devices for transluminal coronary intervention. A quantitative angiographic comparison of balloon angioplasty, directional atherectomy, stent implantation and excimer laser angioplasty. CARPORT, MERCATOR, MARCATOR, PARK, and BENESTENT Trial Groups.

With the increasing clinical application of new devices for percutaneous coronary revascularization, maximization of the acute angiographic result has become widely recognized as a key factor in maintained clinical and angiographic success. What is unclear, however, is whether the specific mode of action of different devices might exert an additional independent effect on late luminal renarrowing. The purpose of this study was to investigate such a difference in the degree of provocation of luminal renarrowing (or 'restenosis propensity') by different devices, among 3660 patients, who had 4342 lesions successfully treated by balloon angioplasty (n = 3797), directional coronary atherectomy (n = 200), Palmaz-Schatz stent implantation (n = 229) or excimer laser coronary angioplasty (n = 116) and who also underwent quantitative angiographic analysis pre- and post-intervention and at 6-month follow-up. To allow valid comparisons between the groups, because of significant differences in coronary vessel size (balloon angioplasty = 2.62 +/- 0.55 mm, directional coronary atherectomy = 3.28 +/- 0.62 mm, excimer laser coronary angioplasty = 2.51 +/- 0.47 mm, Palmaz-Schatz = 3.01 +/- 0.44 mm; P < 0.0001), the comparative measurements of interest selected were the 'relative loss' in luminal diameter (RLoss = loss/vessel size) to denote the restenosis process, and the 'relative lumen at follow-up' (RLfup = minimal luminal diameter at follow up/vessel size) to represent the angiographic outcome. For consistency, lesion severity pre-intervention was represented by the 'relative lumen pre' (RLpre = minimal luminal diameter pre/vessel size) and the luminal increase at intervention was measured as 'relative gain' (relative gain = gain/ vessel size). Differences in restenosis propensity between devices was evaluated by univariate and multivariate analysis. Multivariate models were constructed to determine relative loss and relative lumen at follow-up, taking account of relative lumen pre-intervention, lesion location, relative gain, vessel size and the device used. In addition, model-estimated relative loss and relative lumen at follow-up at given relative lumen pre-intervention relative gain and vessel size, were compared among the four groups. Significant differences were detected among the groups both with respect to these estimates, as well as in the degree of influence of progressively increasing relative gain, on the extent of renarrowing (relative loss) and angiographic outcome (relative lumen at follow-up), particularly at higher levels of luminal increase (relative gain). Specifically, lesions treated by balloon angioplasty or Palmaz-Schatz stent implantation (the predominantly 'dilating' interventions) were associated with more favourable angiographic profiles than directional atherectomy or excimer laser (the mainly 'debulking' interventions). Significant effects of lesion severity and location, as well as the well known influence of luminal increase on both luminal renarrowing and late angiographic outcome were also noted. These findings indicate that propensity to restenosis after apparently successful intervention is influenced not only by the degree of luminal enlargement achieved at intervention, but by the device used to achieve it. In view of the clinical implications of such findings, further evaluation in larger randomized patient populations is warranted.

Long-term luminal renarrowing after successful elective coronary angioplasty of total occlusions. A quantitative angiographic analysis.

BACKGROUND: The long-term angiographic outcome after successful dilatation of coronary occlusions remains unclear. The objective of this study was to examine long-term restenosis after successful balloon dilatation of coronary occlusions at a predetermined time interval with quantitative angiography and compare this with a control population of stenoses. METHODS AND RESULTS: The study population comprised 2950 patients (3583 lesions) prospectively enrolled in and successfully completing four major restenosis trials (86% quantitative angiographic follow-up). Cineangiographic films were processed and analyzed at a central core laboratory with the use of an automated interpolated edge detection technique. The study population comprised 266 occlusions (7%) defined as total when there was absent anterograde filling beyond the lesion (109 lesions) and functional (157 lesions) when faint, late anterograde opacification of the distal segment was seen in the absence of a discernible luminal continuity; 3317 lesions were defined as stenoses (93%). Restenosis was significantly higher after successful dilatation of occlusions than of stenoses. With the categorical (> 50% diameter stenosis at follow-up) approach, the restenosis rate was 44.7% in occlusions compared with 34.0% in stenoses (P < .001; relative risk, 1.575; CI, 1.224 to 2.027). Similarly, the absolute loss (defined as the change in minimal lumen diameter between post coronary angioplasty and follow-up; in millimeters, mean +/- SD) (0.43 +/- 0.68) in occlusions was significantly higher than in stenoses (0.31 +/- 0.51, P < .001), as was the relative loss, defined as the change in minimal lumen diameter between postangioplasty and follow-up, adjusted for the vessel size (0.17 +/- 0.28 versus 0.12 +/- 0.20, P < .001). The higher restenosis rate in the occlusions group was due predominantly to an increased number of occlusions at follow-up angiography in this group (19.2% compared with 5.0% for stenoses, P < .001). Within the occlusions group, there were no significant differences in long-term outcome between total and functional occlusions (restenosis rate, 45.0% versus 44.6%; reocclusion rate, 23.9% versus 15.9%; absolute loss, 0.53 +/- 0.69 versus 0.36 +/- 0.67; relative loss, 0.21 +/- 0.28 versus 0.15 +/- 0.28; P = NS). CONCLUSIONS: These results indicate that successfully dilated coronary occlusions, both total and functional, have a higher rate of angiographic restenosis at 6 months than stenoses. This is due chiefly to a higher rate of occlusion at follow-up angiography in this group of lesions. Measures aimed at reducing restenosis after successful dilatation of coronary occlusion should be focused in this direction.

Quantitative angiographic comparison of elastic recoil after coronary excimer laser-assisted balloon angioplasty and balloon angioplasty alone.

OBJECTIVES: Coronary lumen changes during and after excimer laser-assisted balloon angioplasty were measured by quantitative coronary angiography, and the results were compared with the effects of balloon angioplasty alone. BACKGROUND: Reduction of atherosclerotic tissue mass by laser ablation in the treatment of coronary artery disease may be more effective in enlarging the lumen than balloon angioplasty alone. METHODS: A series of 57 consecutive coronary lesions successfully treated by xenon chloride excimer laser-assisted balloon angioplasty were individually matched with 57 coronary artery lesions successfully treated by balloon angioplasty alone. The following variables were measured by quantitative coronary analysis: 1) ablation by laser, 2) stretch by balloon dilation, 3) elastic recoil, and 4) acute gain. RESULTS: Matching by stenosis location, reference diameter and minimal lumen diameter resulted in two comparable groups of 57 lesions with identical baseline stenosis characteristics. Minimal lumen diameter before excimer laser-assisted balloon angioplasty and balloon angioplasty alone were (mean +/- SD) 0.73 +/- 0.44 and 0.74 +/- 0.43 mm, respectively. Laser ablation significantly improved minimal lumen diameter by 0.56 +/- 0.44 mm before adjunctive balloon dilation. In both treatment groups, similar-sized balloon catheters (2.59 +/- 0.35 and 2.56 +/- 0.40 mm, respectively) were used. After laser-assisted balloon angioplasty, elastic recoil was 0.84 +/- 0.30 mm (32% of balloon size), which was identical to that after balloon angioplasty alone, namely, 0.82 +/- 0.32 mm (32%). Consequently, both interventions resulted in similar acute gains of 1.02 +/- 0.52 and 1.00 +/- 0.56 mm, respectively. Minimal lumen diameter after intervention was equal in both groups: 1.75 +/- 0.35 and 1.75 +/- 0.34 mm, respectively. The statistical power of this study in which a 25% difference in elastic recoil (0.2 mm) between groups was considered clinically important was 95%. CONCLUSIONS: In matched groups of successfully treated coronary lesions, xenon chloride excimer laser ablation did not reduce immediate elastic recoil after adjunctive balloon dilation or improve the final angiographic outcome compared with balloon angioplasty alone using similar-sized balloon catheters.

Optimal use of directional coronary atherectomy is required to ensure long-term angiographic benefit: a study with matched procedural outcome after atherectomy and angioplasty.

OBJECTIVES: This study was designed to examine whether restenosis is related to the extent or mechanism of lumen improvement and to explore angiographic determinants of optimal atherectomy. BACKGROUND: Directional atherectomy induces a greater extent of immediate gain and late loss but has not been found to yield a better late angiographic lumen than angioplasty in randomized trials. The difference in lumen renarrowing may be related to either the extent or the mechanism of immediate gain. The design of previous studies has precluded the detection of a device-specific effect on restenosis. METHODS: A retrospective analysis was based on matching a prospectively collected series of 80 native coronary arteries successfully treated with atherectomy with a prospectively collected series of 80 native coronary arteries successfully treated with balloon angioplasty. Angiographic analysis was performed in 160 lesions to explore whether a specific device-related effect exists. Multivariate analyses were performed to determine the correlates of minimal lumen diameter at follow-up and late lumen loss and to identify the procedural characteristics for optimal atherectomy. RESULTS: Matching resulted in two comparable groups with equivalent baseline clinical and stenosis characteristics. By study design, atherectomy and angioplasty resulted in similar mean (+/- SD) immediate lumen gain (1.15 +/- 0.44 vs. 1.10 +/- 0.40 mm, p = 0.50). However, lumen loss was more pronounced after atherectomy, and, thus, the minimal lumen diameter at follow-up differed significantly between the two groups (1.78 +/- 0.57 vs. 2.00 +/- 0.56 mm, p = 0.001). Device type was retained in the multivariate analysis as an independent predictor of late minimal lumen diameter and lumen loss. Multivariate analysis identified vessel size and immediate gain as determinants of optimal atherectomy. CONCLUSIONS: Restenosis is a consequence not only of the extent of lumen improvement but also of the mechanism of vessel wall injury (debulking vs. dilating). While performing atherectomy, the operator should strive for an optimal procedural result to accommodate an increased intimal hyperplastic response.

Influence of serum cholesterol and cholesterol subfractions on restenosis after successful coronary angioplasty. A quantitative angiographic analysis of 3336 lesions.

BACKGROUND: Previous reports have suggested that hyperlipidemia may be associated with increased restenosis after successful coronary angioplasty. These studies have been compromised, however, by their retrospective nature, the small numbers involved, differences in the definition of restenosis, and inadequate quantitative angiographic follow-up at a prespecified time interval. The objective of the study was to examine the relation between serum cholesterol and long-term restenosis after coronary angioplasty, using quantitative angiography, at a predetermined time interval. METHODS AND RESULTS: The study population comprised 2753 patients (3336 lesions) prospectively enrolled and successfully completing four major restenosis trials. Cineangiographic films were processed and analyzed at a central angiographic core laboratory with the use of an automated interpolated edge-detection technique. Serum total cholesterol was measured at trial entry and at 6 months. Hypercholesterolemia was defined as total cholesterol > 7.8 mmol.L-1 at trial entry. Two approaches were used to assess restenosis: first, a categorical approach using the cutoff point of > 50% diameter stenosis at follow-up and second, a continuous approach examining changes in minimal luminal dimensions, the absolute loss (change in minimum luminal diameter after PTCA to follow-up, in mm) and relative loss (absolute loss corrected for vessel size), which may give a better understanding of the underlying pathological process involved. One hundred sixty patients with 191 lesions (5.73%) had hypercholesterolemia (total cholesterol, > 7.8 mmol.L-1; mean +/- SD, 8.46 +/- 0.75 mmol.L-1) and 2593 patients with 3145 lesions (94.27%) normal cholesterol (5.67 +/- 1.06 mmol.L-1). The restenosis rate was similar in patients with and without hypercholesterolemia (31.9% versus 33.7%, respectively; relative risk, 0.975; 95% CI, 0.882 to 1.077; P = .68). Similarly, there was no difference in either the absolute or relative loss between patients with and without hypercholesterolemia (0.31 +/- 0.53 versus 0.32 +/- 0.53 mm and 0.12 +/- 0.20 versus 0.13 +/- 0.21, respectively, P = NS for both). Conversely, the total serum cholesterol in patients with restenosis (using the categorical definition) was similar to those without restenosis (5.84 +/- 1.24 versus 5.81 +/- 1.22 mmol/L, respectively, P = NS). Dividing the population into deciles according to total cholesterol and examining the categorical restenosis rate (by chi 2) as well as the absolute and relative loss by ANOVA again revealed no significant differences between deciles. Subgroup analysis of 579 patients (667 lesions) with HDL and LDL cholesterol levels available again revealed no differences in the categorical restenosis rate (by chi 2) or the absolute or relative loss between deciles according to LDL, HDL, or LDL:HDL ratio, suggesting no influence of these cholesterol subfractions on restenosis. CONCLUSIONS: Our results indicate that there is no association between cholesterol and restenosis by either a categorical or continuous approach, suggesting that measures aimed at reducing total cholesterol are unlikely to significantly influence postangioplasty restenosis.

Influence of coronary vessel size on renarrowing process and late angiographic outcome after successful balloon angioplasty.

BACKGROUND: Although coronary angioplasty is increasingly applied in the treatment of multivessel disease and a broadening range of vessel size, the influence of vessel size itself on the late results of intervention is unresolved. An influence of vessel size on late outcome would carry implications for the application and evaluation of interventional devices, which are selectively used in larger or smaller vessels. The purpose of the present study was to investigate the influence of vessel size on both the restenosis process and late angiographic outcome in a large homogeneous patient group after successful percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: The study population comprised 3072 patients with 3736 successfully dilated native primary coronary artery lesions and satisfactory quantitative angiographic analysis in multiple identical projections before and after PTCA and at a 6-month follow-up. Late luminal loss, minimal luminal diameter (MLD) at follow-up, and net luminal gain, as well as percent diameter stenosis at follow-up, net gain in percent diameter stenosis, restenosis rates (according to three definitions), and net gain index, were all compared among nine equally sized groups (noniles) according to vessel size. A direct influence of vessel size on continuous measures of late result was also evaluated by linear regression. These evaluations provided conflicting information with no consistent influence of vessel size emerging. To elucidate the independent influence of vessel size on the restenosis process (late loss) and late angiographic outcome (MLD at follow-up), multiple linear regression analysis was performed taking into account luminal gain, preprocedural MLD, and lesion location. In this manner, vessel size was found to be exert a significantly positive influence on MLD at follow-up (P < .0001) and an equally negative effect on loss. Correcting for vessel size by using percent stenosis measurements led to an anticipated neutralization of this influence. Lesion location in the left anterior descending coronary artery was found to be independently associated with greater loss and smaller MLD at follow-up (P < .0001). CONCLUSIONS: Increasing coronary vessel size was found to be independently predictive of decreasing late luminal loss and increasing follow-up MLD after successful balloon angioplasty. Apparently superior or inferior late angiographic results of new interventional devices may thus be explained in part by preferential use in larger or smaller vessels, respectively. Devices that can safely optimize the short-term result of intervention may realize their ultimate long-term value in larger coronary vessels.