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Aims: The BRIE trial is a registry evaluating the safety and performance of (90)Sr delivered locally (Beta-Cath TM system of Novoste) to de-novo and restenotic lesions in patients with up to two discrete lesions in different vessels., Methods and Results: In total, 149 patients (175 lesions) were enrolled; 62 treated with balloons and 113 with stents. The restenosis rate, the minimal luminal diameter and the late loss were determined in three regions of interest: (a) in a subsegment of 5mm containing the original minimal luminal diameter pre-intervention termed target segment; (b) the irradiated segment, 28 mm in length, and (c) the entire analysed segment, 42 mm in length, termed the vessel segment. Binary restenosis was 9.9% for the target segment, 28.9% for the irradiated segment, and 33.6% for the vessel segment. These angiographic results include 5.3% total occlusions. Excluding total occlusions binary restenosis was 4.9%, 25% and 29.9%, respectively. At 1 year the incidence of major adverse cardiac events placed in a hierarchical ranking were: death 2%, myocardial infarction 10.1%, CABG 2%, and target vessel revascularization 20.1%. The event-free survival rate was 65.8%. Non-appropriate coverage of the injured segment by the radioactive source termed geographical miss affected 67.9% of the vessels, and increased edge restenosis significantly (16.3% vs 4.3%, P=0.004). It accounted for 40% of the treatment failures., Conclusion: The results of this registry reflect the learning process of the practitioner. The full therapeutic potential of this new technology is reflected by the restenosis rate at the site of the target segment. It can only be unravelled once the incidence of late vessel occlusion and geographical miss has been eliminated by the prolonged use of thienopyridine, the appropriate training of the operator applying this new treatment for restenosis prevention, and the use of longer sources., (Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.)

Aims: Intracoronary radiation is a promising therapy potentially reducing restenosis following catheter-based interventions. Currently, only limited data on this treatment are available. The feasibility and outcome in daily routine practice, however, is unknown., Methods and Results: In 100 consecutive patients, intracoronary beta-radiation was performed with a (90)Strontium system (Novoste Beta-Cathtrade mark) following angioplasty. Predominantly complex (73% type B2 and C) and long lesions (length 24.3+/-15.3 mm) were included (37% de novo, 19% restenotic and 44% in-stent restenotic lesions). Radiation success was 100%. Mean prescribed dose was 19.8+/-2.5 Gy. A pullback procedure was performed in 19% lesions. Geographic miss occurred in 8% lesions. Periprocedural thrombus formation occurred in four lesions, dissection in nine lesions. During hospital stay, no death, acute myocardial infarction, or repeat revascularization was observed. Major adverse cardiac events occurred predominantly between 6 and 12 months after the index procedure with major adverse cardiac event-free survival of 66% at 12 months (one death, 10 Q-wave myocardial infarctions, 23 target vessel revascularizations; ranked for worst event)., Conclusion: Routine catheter-based intracoronary beta-radiation therapy after angioplasty is safe and feasible with a high acute procedural success. The clinical 1-year follow-up showed delayed occurrence of major adverse cardiac events between 6 and 12 months after the index procedure., (Copyright 2001 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.)

Aims: We sought to compare the effect of intracoronary beta-radiation on the vessel dimensions in de novo lesions using three-dimensional intravascular ultrasound quantification after balloon angioplasty and stenting., Methods and Results: Forty patients (44 vessels; 28 balloon angioplasty and 16 stenting) treated with catheter-based beta-radiation and 18 non-irradiated control patients (18 vessels; 10 balloon angioplasty and 8 stenting) were investigated by means of three-dimensional volumetric intravascular ultrasound analysis post-procedure and at 6-8 months follow-up. Total vessel (EEM) volume enlarged after both balloon angioplasty and stenting (+37 mm(3) vs +42 mm(3), P=ns), but vessel wall volume (plaque plus media) also increased similarly (+33 mm(3) vs +49 mm(3), P=ns) in the irradiated patients. Lumen volume remained unchanged in both groups (+3 mm(3) vs -7 mm(3), P=ns). In the stent-covered segments, neointima at follow-up was significantly smaller in the irradiated group than the control group (8 mm(3) vs 27 mm(3), P=0.001, respectively), but the total amount of tissue growth was similar in both groups (33 mm(3) vs 29 mm(3), P=ns)., Conclusions: Intracoronary beta-radiation induces vessel enlargement after balloon angioplasty and/or stenting, accommodating tissue growth. Additional stenting may not play an important role in the prevention of constrictive remodelling in the setting of catheter-based intracoronary beta-radiotherapy., (Copyright 2002 The European Society of Cardiology.)

Aims: Coronary stenting is limited by a 10%-60% restenosis rate due to neointimal hyperplasia. Sirolimus is a macrocyclic lactone agent that interacts with cell-cycle regulating proteins and inhibits cell division between phases G1 and S1. The hypothesis tested in this study is that local delivery of sirolimus with an eluting stent can prevent restenosis., Methods and Results: Fifteen patients were treated with 18 mm sirolimus eluting BX VELOCITY stents. Quantitative angiography and three-dimensional quantitative intravascular ultrasound were performed at implantation and at the 6 months follow-up. All stent implantations were successful. One patient died on day 2, of cerebral haemorrhage and one patient suffered a subacute stent occlusion due to edge dissection (re-PTCA, CKMB 42). At 9 months no further adverse events had occurred and all patients were angina free. Quantitative coronary angiography revealed no change in minimal lumen diameter and percent diameter stenosis and hence no in-lesion or in-stent restenosis. Quantitative intravascular ultrasound showed that intimal hyperplasia volume and percent obstruction volume at follow-up were negligible at 5.3 mm(3)and 1.8%, respectively. No edge effect was observed in the segments proximal and distal to the stents., Conclusion: Implantation of a sirolimus-eluting stent seems to effectively prevent intimal hyperplasia., (Copyright 2001 The European Society of Cardiology.)

Background: Radioactive stents have been reported to reduce in-stent neointimal thickening. An unexpected increase in neointimal response was observed, however, at the stent-to-artery transitions, the so-called "edge effect." To investigate the factors involved in this edge effect, we studied stents with 1 radioactive half and 1 regular nonradioactive half, thereby creating a midstent radioactive dose-falloff zone next to a nonradioactive stent-artery transition at one side and a radioactive stent-artery transition at the other side., Methods and Results: Half-radioactive stents (n=20) and nonradioactive control stents (n=10) were implanted in the coronary arteries of Yucatan micropigs. Animals received aspirin and clopidogrel as antithrombotics. After 4 weeks, a significant midstent stenosis was observed by angiography in the half-radioactive stents. Two animals died suddenly because of coronary occlusion at this mid zone at 8 and 10 weeks. At 12-week follow-up angiography, intravascular ultrasound and histomorphometry showed a significant neointimal thickening at the midstent dose-falloff zone of the half-radioactive stents, but not at the stent-to-artery transitions at both extremities. Such a midstent response (mean angiographic late loss 1.0 mm) was not observed in the nonradioactive stents (mean loss 0.4 to 0.6 mm; P< 0.01)., Conclusions: The edge effect of high-dose radioactive stents in porcine coronary arteries is associated with the combination of stent injury and radioactive dose falloff.

Background: Edge restenosis is a major problem after radioactive stenting. The cold-end stent has a radioactive mid-segment (15.9 mm) and non-radioactive proximal and distal 5.7 mm segments. Conceptually this may negate the impact of negative vascular remodelling at the edge of the radiation., Method and Results: ECG-gated intravascular ultrasound with three-dimensional reconstruction was performed post-stent implantation and at the 6-month follow-up to assess restenosis within the margins of the stent and at the stent edges in 16 patients. Angiographic restenosis was witnessed in four patients, all in the proximal in-stent position. By intravascular ultrasound in-stent neointimal hyperplasia, with a >50% stented cross-sectional area, was seen in eight patients. This was witnessed proximally (n=2), distally (n=2) and in both segments (n=4). Echolucent tissue, dubbed the 'black hole' was seen as a significant component of neointimal hyperplasia in six out of the eight cases of restenosis. Neointimal hyperplasia was inhibited in the area of radiation: Delta neointimal hyperplasia=3.72 mm3 (8.6%); in-stent at the edges of radiation proximally and distally Delta neointimal hyperplasia was 7.9 mm3 (19.0%) and 11.4 mm3 (25.6%), respectively (P=0.017). At the stent edges there was no significant change in lumen volume., Conclusions: Cold-end stenting results in increased neointimal hyperplasia in in-stent non-radioactive segments., (Copyright 2001 The European Society of Cardiology.)

Aims: This study is the contribution by the Thoraxcenter, Rotterdam, to the European(32)P Dose Response Trial, a non-randomized multicentre trial to evaluate the safety and efficacy of the radioactive Isostent in patients with single coronary artery disease., Methods and Results: The radioactivity of the stent at implantation was 6--12 microCi. All patients received aspirin indefinitely and either ticlopidine or clopidogrel for 3 months. Quantitative coronary angiography measurements of both the stent area and the target lesion (stent area and up to 5 mm proximal and distal to the stent edges) were performed pre- and post-procedure and at the 5-month follow-up. Forty-two radioactive stents were implanted in 40 patients. Treated vessels were the left anterior descending coronary artery (n=20), right coronary artery (n=10) or left circumflex artery (n=10). Eight patients received additional non-radioactive stents. Lesion length measured 10+/-3 mm with a reference diameter of 3.07+/-0.69 mm. Minimal lumen diameter increased from 0.98+/-0.53 mm pre-procedure to 2.29+/-0.52 mm (target lesion) and 2.57+/-0.44 mm (stent area) post-procedure. There was one procedural non-Q wave myocardial infarction, due to transient thrombotic closure. Thirty-six patients returned for angiographical follow-up. Two patients had a total occlusion proximal to the radioactive stent. Of the patent vessels, none had in-stent restenosis. Edge restenosis was observed in 44%, occurring predominantly at the proximal edge. Target lesion revascularization was performed in 10 patients and target vessel revascularization in one patient. No additional clinical end-points occurred during follow-up. The minimal lumen diameter at follow-up averaged 1.66+/-0.71 mm (target lesion) and 2.12+/-0.72 (stent area); therefore late loss was 0.63+/-0.69 (target lesion) and 0.46+/-0.76 (stent area), resulting in a late loss index of 0.65+/-1.15 (target lesion) and 0.30+/-0.53 (stent area)., Conclusion: These results indicate that the use of radioactive stents is safe and feasible, however, the high incidence of edge restenosis makes this technique currently clinically non-applicable., (Copyright 2001 The European Society of Cardiology.)

AIMS: The BiodivYsio trade mark stent (Biocompatibles Ltd, Farnham, UK) is coated with a phosphorylcholine (PC)-containing copolymer to confer biocompatibility. The SOPHOS (Study Of PHosphorylcholine coating On Stents) study was designed to assess the safety and efficacy of this novel coronary stent and by indirect comparison to indicate equivalence with other formal stent studies. METHODS AND RESULTS: Patients with angina and a single short (#x2A7F;12 mm) de novo lesion in a native coronary artery of >/=2.75 mm diameter were included. A total of 425 patients were allocated in 24 centers. Clinical data were collected at one-, six- and nine-month follow-up. Angiography was performed before and after the stent implantation. In addition, in the first 200 patients (SOPHOS A) angiography was routinely performed at six months. The following 225 patients (SOPHOS B) were merely followed up clinically. The primary end-point of the study, the six-month MACE-rate (MACE = Major Adverse Cardiac Events) was 13.4% (two cardiac death; five Q-wave/nine non-Q-wave myocardial infarctions (MI); nine CABG and 32 target lesion revascularization (TLR), which is similar to the calculated 15% MACE-rate in comparable reference studies. Secondary end-points included among others restenosis at six months in the SOPHOS A population. The target vessel diameter was 2.98 +/- 0.48 mm. Minimal lumen diameter pre/post procedure and at follow-up was 1.00 +/- 0.32, 2.69 +/- 0.37, 1.91 +/- 0.71 mm, respectively. The binary restenosis rate (>/=50% diameter stenosis at follow-up) was 17.7%. CONCLUSION: The coronary BiodivYsio stent is safe and effective as a primary device for the treatment of native coronary artery lesions in patients with stable or unstable angina pectoris. Clinical and angiographic results are in the statistical range of equivalence with comparable studies with other current stents.

Mechanisms of in-stent restenosis are not fully understood. Shear stress is known to play a role in plaque and thrombus formation and is sensitive to changes in regional vessel geometry. Hence, we evaluated the regional changes in 3-D geometry and shear stress induced by stent placement in coronary arteries of pigs.Methods. 3-D reconstruction was performed, applying a combined angiographic and IVUS technique (ANGUS), from seven Wallstents (diameter 3.5 (n=3) and 5mm (n=4)), which were implanted in seven coronary arteries of five pigs. This 3-D geometry was used to calculate locally the curvature, while the shear stress distribution was obtained by computational fluid dynamics. Local changes in shear stress were obtained at the entrance and exit of the stent for baseline (0. 65+/-0.22 ml/s) and hyperemic flow (2.60+/-0.86 ml/s) conditions. Results. After stent implantation, the curvature increased by 121% at the entrance and by 100% at the exit of the stent, resulting in local changes in shear stress. In general, at the entrance of the stent local maxima in shear stress were generated, while at the exit both local maxima and minima in shear stress were observed (p<0.05). Additionally, the shear stress at the entrance and exit of the stent were correlated with the local curvature (r: 0.30-0.84).Conclusion. Stent implantation changes 3-D vessel geometry in such a way that regions with decreased and increased shear stress occur close to the stent edges. These changes might be related to the asymmetric patterns of in-stent restenosis.

The aim of the study was to assess the safety and feasibility of implantation of the Scimed Radius stent. Secondary objectives were to assess the result of stent placement by quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). The ESSEX study was a prospective, multicenter, observational study in which candidates for a single elective stent implantation, in a de novo or restenotic lesion, reference diameter 2.75-4.00 mm and target lesion < 14 mm in length, were enrolled. QCA at baseline, postprocedure, and 6-month follow-up was performed. IVUS was used to assess optimal stent implantation. One hundred and three patients were enrolled. Forty-four percent of the patients had unstable angina. Stent implantation was technically successful in all patients. Additional stents were implanted in 17 patients for procedural dissection (16) and spasm (1). Ninety-seven percent of patients were event-free at 1 month and 76% at 6-month follow-up. Angiographic restenosis rates for de novo lesions and for all patients were 19% and 21%, respectively. Clinical events occurred at 1- and 6-month follow-up in 2.9% and 24.3% of patients, respectively. No patients suffered subacute thrombosis. Retrospective analysis of peak balloon inflation pressure (< or = 12 and > 12 atm) as a determinant of clinical, QCA, and IVUS outcomes suggested no benefit or detrimental effect from optimization with high-pressure balloon inflation. Implantation of the self-expanding Radius stent is safe and efficacious. Based on registry data, clinical, angiographic, and IVUS, data comparable with modern balloon-expandable stents were obtained.

Background: True 3D reconstruction of coronary arteries in patients based on intravascular ultrasound (IVUS) may be achieved by fusing angiographic and IVUS information (ANGUS). The clinical applicability of ANGUS was tested, and its accuracy was evaluated quantitatively. METHODS AND REUSLTS: In 16 patients who were investigated 6 months after stent implantation, a sheath-based catheter was used to acquire IVUS images during an R-wave-triggered, motorized stepped pullback. First, a single set of end-diastolic biplane angiographic images documented the 3D location of the catheter at the beginning of pullback. From this set, the 3D pullback trajectory was predicted. Second, contours of the lumen or stent obtained from IVUS were fused with the 3D trajectory. Third, the angular rotation of the reconstruction was optimized by quantitative matching of the silhouettes of the 3D reconstruction with the actual biplane images. Reconstructions were obtained in 12 patients. The number of pullback steps, which determines the pullback length, closely agreed with the reconstructed path length (r=0.99). Geometric measurements in silhouette images of the 3D reconstructions showed high correlation (0.84 to 0.97) with corresponding measurements in the actual biplane angiographic images., Conclusions: With ANGUS, 3D reconstructions of coronary arteries can be successfully and accurately obtained in the majority of patients.

Background: Inhomogeneity of dose distribution and anatomic aspects of the atherosclerotic plaque may influence the outcome of irradiated lesions after balloon angioplasty (BA). We evaluated the influence of delivered dose and morphological characteristics of coronary stenoses treated with beta-radiation after BA., Methods and Results: Eighteen consecutive patients treated according to the Beta Energy Restenosis Trial 1.5 were included in the study. The site of angioplasty was irradiated with the use of a beta-emitting (90)Sr/(90)Y source. With the side branches used as anatomic landmarks, the irradiated area was identified and volumetric assessment was performed by 3D intracoronary ultrasound imaging after treatment and at 6 months. The type of tissue, the presence of dissection, and the vessel volumes were assessed every 2 mm within the irradiated area. The minimal dose absorbed by 90% of the adventitial volume (D(v90)Adv) was calculated in each 2-mm segment. Diffuse calcified subsegments and those containing side branches were excluded. Two hundred six coronary subsegments were studied. Of those, 55 were defined as soft, 129 as hard, and 22 as normal/intimal thickening. Plaque volume showed less increase in hard segments as compared with soft and normal/intimal thickening segments (P<0.0001). D(v90)Adv was associated with plaque volume at follow-up after a polynomial equation with linear and nonlinear components (r = 0.71; P = 0.0001). The multivariate regression analysis identified the independent predictors of the plaque volume at follow-up: plaque volume after treatment, D(v90)Adv, and type of plaque., Conclusions: Residual plaque burden, delivered dose, and tiss composition play a fundamental role in the volumetric outcome at 6-month follow-up after beta-radiation therapy and BA.

Background: A recognized limitation of endovascular beta-radiation therapy is the development of new stenosis at the edges of the irradiated area. The combination of injury and low-dose radiation may be the precursor of this phenomenon. We translated the radio-oncological concept of "geographic miss" to define cases in which the radiation source did not fully cover the injured area. The aims of the study were to determine the incidence and causes of geographic miss and evaluate the impact of this inadequate treatment on the outcome of patients treated with intracoronary beta-radiation., Methods and Results: We analyzed 50 consecutive patients treated with beta-radiation after percutaneous coronary intervention. The prescribed dose ranged between 12 and 20 Gy at 2 mm from the source axis. By means of quantitative coronary angiography, the irradiated segment (IRS) and both edges were studied before and after intervention and at 6-month follow-up. Edges that were injured during the procedure constituted the geographic miss edges. Twenty-two edges were injured during the intervention, mainly because of procedural complications that extended the treatment beyond the margins of the IRS. Late loss was significantly higher in geographic miss edges than in IRSs and uninjured edges (0.84+/-0.6 versus 0.15+/-0.4 and 0.09+/-0.4 mm, respectively; P<0.0001). Similarly, restenosis rate was significantly higher in the injured edges (10% within IRS, 40.9% in geographic miss edges, and 1.9% in uninjured edges; P<0.001)., Conclusions: These data support the hypothesis that the combination of injury and low-dose beta-radiation induces deleterious outcome.

Intracoronary radiation is a promising therapy to decrease restenosis after percutaneous intervention. The aim of this pilot study was to determine the mechanism of intracoronary beta-radiation after balloon angioplasty and stenting in a double-blind placebo-controlled randomized fashion. Twenty-six patients were randomized to either placebo (n = 6) or 3 doses (28, 35 and 42 Gy) of beta-radiation (n = 20) using the Guidant brachytherapy system (27 mm long 32P source wire). Of these, 21 patients underwent post-procedure and 6-month follow-up three-dimensional intravascular ultrasound (IVUS) assessment. Volumetric quantification was performed by means of a semi-automated contour detection system after an ECG-gated motorized pullback IVUS imaging and three-dimensional reconstruction. We compared the volumetric changes (Delta) of total vessel volume (TVV), plaque volume (PV) and lumen volume (LV) after 6 months between placebo (dummy wire) and irradiated patients. In addition, the volume of neointimal hyperplasia was quantified within the stented segments. There was an opposite behavior of TVV and LV change between placebo (DeltaTVV = -24 mm3 and DeltaLV = -42 mm3) and irradiated (DeltaTVV = +18 mm3 and (DeltaLV = +5 mm3) patients. The mean neointimal formation within the stented segment in the irradiated patients (n = 7) was 1.9 mm3 (1.5%). Our results suggest that beta-radiation affects vessel remodeling after percutaneous intervention and inhibit neointimal formation in stented patients.

Purpose: The use of endovascular coronary brachytherapy to prevent restenosis following percutaneous transluminal coronary angioplasty (PTCA) began in April 1997 at the Department of Interventional Cardiology of the Thoraxcenter at the University Hospital of Rotterdam. This article reviews the more than 250 patients that have been treated so far., Methods and Materials: The Beta-Cath System (Novoste), a manual, hydraulic afterloader with 12 90Sr seeds, was used in the Beta Energy Restenosis Trial (BERT-1.5, n = 31), for compassionate use (n = 25), in the Beta-Cath System trial (n = 27) and in the Beta Radiation in Europe (BRIE, n = 14). Since the Beta-Cath System has been commercialized in Europe, 57 patients have been treated and registered in RENO (Registry Novoste). In the Proliferation Reduction with Vascular Energy Trial (PREVENT), 37 patients were randomized using the Guidant-Nucletron remote control afterloader with a 32P source wire and a centering catheter. Radioactive 32P coated stents have been implanted in 102 patients. In the Isostent Restenosis Intervention Study 1 (IRIS 1), 26 patients received a stent with an activity of 0.75-1.5 microCi, and in the IRIS 2 (European 32P dose response trial), 40 patients were treated with an activity of 6-12 microCi. In two consecutive pilot trials, radioactive stents with non-radioactive ends (cold-end stents) and with ends containing higher levels of activity (hot-end stents) were implanted in 21 and 17 patients, respectively., Results: In the BERT-1.5 trial, the radiation dose, prescribed at 2 mm from the source train (non-centered), was 12 Gy (10 patients), 14 Gy (10 patients) and 16 Gy (11 patients). At 6-month follow-up, 8 out of 28 (29%) patients developed restenosis. The target lesion revascularization rate (TLR) was 7 out of 30 (23%) at 6 months and 8 out of 30 (27%) at 1 year. Two patients presented with late thrombosis in the first year. For compassionate use patients, a restenosis rate (RR) of 53% was observed. In the PREVENT trial, 34 of 37 patients underwent an angiographic 6-month follow-up. The doses prescribed at 0.5 mm depth into the vessel wall were 0 Gy (8), 28 Gy (9), 35 Gy (11) and 42 Gy (8). TLR was 14% in the irradiated patients and 25% in the placebo group. One patient developed late thrombosis. In the IRIS 1 trial, 23 patients showed an RR of 17% (in-stent). In the IRIS 2 trial, in-stent restenosis was not seen in 36 patients at 6-month follow-up. However, a high RR (44%) was observed at the stent edges., Conclusions: The integration of vascular brachytherapy in the catheterization laboratory is feasible and the different treatment techniques that are used are safe. Problems, such as edge restenosis and late thrombotic occlusion, have been identified as limiting factors of this technique. Solutions have been suggested and will be tested in future trials.

Background: This study represents the Heart Center Rotterdam's contribution to the Isostents for Restenosis Intervention Study, a nonrandomized multicenter trial evaluating the safety and feasibility of the radioactive Isostent in patients with single coronary artery disease. Restenosis after stent implantation is primarily caused by neointimal hyperplasia. In animal studies, beta-particle-emitting radioactive stents decrease neointimal hyperplasia by inhibiting smooth muscle cell proliferation., Methods and Results: The radioisotope (32)P, a beta-particle emitter with a half-life of 14.3 days, was directly embedded into the Isostent. The calculated range of radioactivity was 0.75 to 1.5 microCi. Quantitative coronary angiography measurements were performed before and after the procedure and at 6-month follow-up. A total of 31 radioactive stents were used in 26 patients; 30 (97%) were successfully implanted, and 1 was embolized. Treated lesions were in the left anterior descending coronary artery (n=12), the right coronary artery (n=8), or the left circumflex coronary artery (n=6). Five patients received additional, nonradioactive stents. Treated lesion lengths were 13+/-4 mm, with a reference diameter of 2.93+/-0. 47 mm. Minimum lumen diameter increased from 0.87+/-0.28 mm preprocedure to 2.84+/-0.35 mm postprocedure. No in-hospital adverse cardiac events occurred. All patients received aspirin indefinitely and ticlopidine for 4 weeks. Twenty-three patients (88%) returned for 6-month angiographic follow-up; 17% of them had in-stent restenosis, and 13% had repeat revascularization. No restenosis was observed at the stent edges. Minimum lumen diameter at follow-up averaged 1.85+/-0.69 mm, which resulted in a late loss of 0.99+/-0. 59 mm and a late loss index of 0.53+/-0.35. No other major cardiac events occurred during the 6-month follow-up., Conclusions: The use of radioactive stents with an activity of 0.75 to 1.5 microCi is safe and feasible.

Background: Abnormal endothelium-dependent coronary vasomotion has been reported after balloon angioplasty (BA), as well as after intracoronary radiation. However, the long-term effect on coronary vasomotion is not known. The aim of this study was to evaluate the long-term vasomotion of coronary segments treated with BA and brachytherapy., Methods and Results: Patients with single de novo lesions treated either with BA followed by intracoronary beta-irradiation (according to the Beta Energy Restenosis Trial-1.5) or with BA alone were eligible. Of these groups, those patients in stable condition who returned for 6-month angiographic follow-up formed the study population (n=19, irradiated group and n=11, control group). Endothelium-dependent coronary vasomotion was assessed by selective infusion of serial doses of acetylcholine (ACh) proximally to the treated area. Mean luminal diameter was calculated by quantitative coronary angiography both in the treated area and in distal segments. Endothelial dysfunction was defined as a vasoconstriction after the maximal dose of ACh (10(-6) mol/L). Seventeen irradiated segments (89.5%) demonstrated normal endothelial function. In contrast, 10 distal nonirradiated segments (53%) and 5 control segments (45%) demonstrated endothelium-dependent vasoconstriction (-19+/-17% and -9.0+/-5%, respectively). Mean percentage of change in mean luminal diameter after ACh was significantly higher in irradiated segments (P=0.01)., Conclusions: Endothelium-dependent vasomotion of coronary segments treated with BA followed by beta-radiation is restored in the majority of stable patients at 6-month follow-up. This functional response appeared to be better than those documented both in the distal segments and in segments treated with BA alone.

We report a case of late stent malapposition occurring 6 months after intracoronary beta-irradiation detected by three-dimensional intravascular ultrasound, in spite of good apposition immediately after the procedure. Volumetric quantification revealed that stent volume remained unchanged, whereas total vessel volume increased by 13% after 6 months within the stent area. The increase of the vessel volume took place mainly in the proximal part of the stent, where the malapposition was located.

Background: Endovascular radiation appears to inhibit intimal thickening after overstretching balloon injury in animal models. The effect of brachytherapy on vascular remodeling is unknown. The aim of the study was to determine the evolution of coronary vessel dimensions after intracoronary irradiation after successful balloon angioplasty in humans., Methods and Results: Twenty-one consecutive patients treated with balloon angioplasty and beta-radiation according to the Beta Energy Restenosis Trial-1.5 were included in the study. Volumetric assessment of the irradiated segment and both edges was performed after brachytherapy and at 6-month follow-up. Intravascular ultrasound images were acquired by means of ECG-triggered pullback, and 3-D reconstruction was performed by automated edge detection, allowing the calculation of lumen, plaque, and external elastic membrane (EEM) volumes. In the irradiated segments, mean EEM and plaque volumes increased significantly (451+/-128 to 490.9+/-159 mm(3) and 201.2+/-59 to 241.7+/-74 mm(3); P=0.01 and P=0.001, respectively), whereas luminal volume remained unchanged (250.8+/-91 to 249.2+/-102 mm(3); P=NS). The edges demonstrated an increase in mean plaque volume (26.8+/-12 to 32. 6+/-10 mm(3), P=0.0001) and no net change in mean EEM volume (71. 4+/-24 to 70.9+/-24 mm(3), P=NS), resulting in a decrease in mean luminal volume (44.6+/-16 to 38.3+/-16 mm(3), P=0.01)., Conclusions: A different pattern of remodeling is observed in coronary segments treated with beta-radiation after successful balloon angioplasty. In the irradiated segments, the adaptive increase of EEM volume appears to be the major contributor to the luminal volume at follow-up. Conversely, both edges showed an increase in plaque volume without a net change in EEM volume.

Recurrent in-stent restenosis after balloon angioplasty poses a serious management problem. Previously g-radiation has been shown to be effective in patients with in-stent restenosis. The aim of the study was to determine the feasibility and safety of b-radiation in patients with recurrent in-stent restenosis. From May 1997 to December 1998, 18 patients were treated with balloon angioplasty (n = 8) or laser (n = 10), followed by intracoronary b-radiation at a prescribed dose of 16 Gray at 2 mm from the source, for reference diameters by quantitative coronary angiography < 3.25 mm or 20 Gray for reference diameters > or =3.25 mm. Vessels treated were as follows: left anterior descending: (n = 5); circumflex: (n = 4); right coronary artery: (n = 6); saphenous vein graft: (n = 3). Average recurrence rate was 2.4 +/- 0.7 and the restenotic length was 16 +/- 7 mm. b-radiation was successfully delivered in all patients. Two patients presented complications related to laser debulking: a non-Q wave myocardial infarction in one and a re-angioplasty due to uncovered distal dissection in another. Geographical miss, defined as an area which has been injured but not covered by the radiation source, was demonstrated in 8 patients. Seventeen patients (94%) completed the 6-month angiographic follow-up. Restenosis (> 50% Diameter Stenosis) was observed in 9 patients (53%), leading to target lesion revascularization in 8 patients (47%). Six of the 9 restenoses were located in areas with geographical miss. Intracoronary b-radiation for recurrent in-stent restenosis appears to be a safe and feasible management strategy. However, the mismatch between injured and irradiated area may lead to failure of this therapy.

Background: Intracoronary brachytherapy appears to be a promising technology to prevent restenosis. Presently, limited data are available regarding the late safety of this therapeutic modality. The aim of the study was to determine the incidence of late (>1 month) thrombosis after PTCA and radiotherapy., Methods and Results: From April 1997 to March 1999, we successfully treated 108 patients with PTCA followed by intracoronary beta-radiation. Ninety-one patients have completed at least 2 months of clinical follow-up. Of these patients, 6.6% (6 patients) presented with sudden thrombotic events confirmed by angiography 2 to 15 months after intervention (2 balloon angioplasty and 4 stent). Some factors (overlapping stents, unhealed dissection) may have triggered the thrombosis process, but the timing of the event is extremely unusual. Therefore, the effect of radiation on delaying the healing process and maintaining a thrombogenic coronary surface is proposed as the most plausible mechanism to explain such late events., Conclusions: Late and sudden thrombosis after PTCA followed by intracoronary radiotherapy is a new phenomenon in interventional cardiology.

Percutaneous therapy of coronary bifurcated lesions is associated with greater risk of acute complications and late restenosis. Numerous innovative techniques using various stent types have been proposed. We report the first clinical use of a truly bifurcated stent (Bard XT Carina). The implantation procedure, favorable medium-term angiographic and 1-year clinical follow-up of the first human use in a 43-year-old female are illustrated with angiography and intravascular ultrasound. As a single prosthesis that effectively covers the bifurcation, this stent presents appealing alternative for the treatment of coronary bifurcation lesions when compared to methods that involve multiple-stent implantation. Cathet. Cardiovasc. Intervent. 47:361-369, 1999., (Copyright 1999 Wiley-Liss, Inc.)

Purpose: We present in this paper the comparison, by simulation, of different treatment strategies based either on beta- or gamma-sources, both with and without a centering device. Ionizing radiation to prevent restenosis is an emerging modality in interventional cardiology. Numerous clinical studies are presently being performed or planned, but there is variability in dose prescription, and both gamma- and beta-emitters are used, leading to a wide range of possible dose distributions over the arterial vessel wall. This paper discusses the potential merits of dose-volume histograms (DVH) based on three-dimensional (3-D) reconstruction of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) to compare brachytherapy treatment strategies., Materials and Methods: DVH describe the cumulative distribution of dose over three specific volumes: (1) at the level of the luminal surface, a volume was defined with a thickness of 0.1 mm from the automatically detected contour of the highly echogenic blood-vessel interface; (2) at the level of the IVUS echogenic media-adventitia interface (external elastic lamina [EEL]), an adventitial volume was computed considering a 0.5-mm thickness from EEL; and (3) the volume encompassed between the luminal surface and the EEL (plaque + media). The IVUS data used were recorded in 23 of 31 patients during the Beta Energy Restenosis Trial (BERT) conducted in our institution., Results: On average, the minimal dose in 90% of the adventitial volume was 37 +/- 16% of the prescribed dose; the minimal dose in 90% of the plaque + media volume was 58 +/- 24% and of the luminal surface volume was 67 +/- 31%. The minimal dose in the 10% most exposed luminal surface volume was 296 +/- 42%. Simulations of the use of a gamma-emitter and/or a radioactive source train centered in the lumen are reported, with a comparison of the homogeneity of the dose distribution., Conclusions: It is possible to derive DVH from IVUS, to evaluate the dose delivered to different parts of the coronary wall. This process should improve our understanding of the mechanisms of action of brachytherapy.

Objective: To compare percutaneous transluminal coronary angioplasty (PTCA) and stent implantation with respect to the long-term changes they induce in the newly formed endothelium in porcine coronary arteries by studying both morphological and functional parameters of the endothelium at 2 weeks and 3 months after intervention., Background: Problems affecting PTCA or stent implantation have been overcome to a large extent by means of better techniques and the availability of new drugs. Late problems, however, still exist in that restenosis affects a large number of patients. With an increasing number of patients being treated with stents, the problem of in-stent restenosis is of even greater concern, as this seems difficult to treat. A functional endothelial lining is thought to be important in controlling the growth of the underlying vascular tissue. We hypothesized that the enhanced neointimal hyperplasia observed after stenting is associated with a more pronounced and prolonged endothelial dysfunction., Methods: Arteries were analyzed using a dye-exclusion test and planimetry of permeable areas. Thereafter, the arteries were processed for light and scanning electron microscopy for assessment of morphology and proliferative response., Results: Leakage of the endothelium for molecules such as Evans blue-albumin as well as prolonged endothelial proliferation is observed as late as 3 months after the intervention, and is more pronounced after stenting. Permeability is associated with distinct morphologic characteristics: endothelial retraction, the expression of surface folds, and the adhesion of leukocytes., Conclusions: Stenting especially decreases long-term vascular integrity with respect to permeability and endothelial proliferation, and is associated with distinct morphologic characteristics.

Application of ionizing radiation to prevent restenosis in atherosclerotic vessels treated by balloon angioplasty is a new treatment under investigation in interventional cardiology and radiology. There is variability in dose prescription, and both gamma- and beta-emitters are used, leading to a wide range of dose distribution over the arterial vessel wall. We present a new modality of dosimetry based on a method that three-dimensional (3-D) image reconstruction of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) images. Dose volume histograms (DVH) are used to describe the cumulative distribution of dose over two specific volumes: i) at the level of the luminal surface, defined with a thickness of 0.1 mm from the automatically detected contour of the highly echogenic blood-vessel interface, and ii) the adventitia volume is computed considering a 0.5-mm thickness from the echogenic media-adventitia interface. DVH provide a tool for reporting the actual delivered dose at the site believed to be the target: the adventitia, and to detect excessive radiation which could lead to vascular complications. Simulation of a gamma-emitter or of a radioactive source train in the center of the lumen are possible. The data obtained from the first ten patients included in the beta-irradiation trial (BERT 1.5) conducted in our institution are presented, supporting the use of DVH based on quantitative IVUS measurements for optimal dose prescription in vascular interventional radiation therapy.

For several decades, synthetic polymers have been the subject of study for vascular applications. Several materials have been tested to date, both for coating and replacing metal stents. While conflicting data between some of these studies exist, these may in part be related to characteristics secondary to the synthetic polymer itself: surface characteristics (roughness, porosity, contaminants), bulk, fragmentation and degradation rate in the case of bioabsorbable polymers. Knowledge of the healing characteristics of the coated stents or stent grafts are essential for successful long-term results.

The development of the end-point attached HC stent should be regarded against the early unfavourable results with uncoated stents in the pre-IVUS- and pre-ticlopidine era. Despite this, results of pilot- and randomized trials show a surprising low incidence of (sub)acute stent thrombosis under challenging circumstances like acute coronary events. Considering the quite low incidence of early complications of non-coated second generation stents it may require very large trials to test the clinical efficacy of the HC coating against non-coated devices. However, even if the 'added value' of the HC coating is never scientifically proven, it has helped to a large degree to enhance the penetration of stent-therapy in interventional cardiology. Unlike the situation in 1992, very few cardiologists will now oppose the statement that stents contribute to the state of the art treatment of patients with angina pectoris or acute myocardial infarction.

In an effort to overcome the limitations of local drug delivery associated with the use of catheters, drug-loaded stents have been developed. Loading of such stents is achieved through either drug absorption (incorporation into a matrix) or drug adsorption (surface layering). The type of drug binding determines the elution profile/release kinetics of the drug, while the therapeutic target determines both the choice of drug used and the manner in which it is bound, i.e. eluting or non-eluting. While non-eluting stents have clinically reduced thrombotic complications following stent implantation, current experimental work concentrates on the use of eluting stents to combat restenosis.

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

Biomimicry is in its earliest stages and is being considered in the realm of tissue engineering. If arterial implants are to limit neointimal thickening, purely passive structures cannot succeed. Bioactivity must be present, either by pharmacologic intervention or by fabricating a 'living stent' that contains active cellular material. As tissue engineering evolves, useful solutions will emerge from applying this knowledge directly to vascular biologic problems resulting from angioplasty, stenting, and vascular prosthesis research.

Background: The multicentre, randomised Benestent-II study investigated a strategy of implantation of a heparin-coated Palmar-Schatz stent plus antiplatelet drugs compared with the use of balloon angioplasty in selected patients with stable or stabilised unstable angina, with one or more de-novo lesions, less than 18 mm long, in vessels of diameter 3 mm or more., Methods: 827 patients were randomly assigned stent implantation (414 patients) or standard balloon angioplasty (413 patients). The primary clinical endpoint was event-free survival at 6 months, including death, myocardial infarction, and the need for revascularisation. The secondary endpoints were the restenosis rate at 6 months and the cost-effectiveness at 12 months. There was also one-to-one subrandomisation to either clinical and angiographic follow-up or clinical follow-up alone. Analyses were by intention to treat., Findings: Four patients (one stent group, three angioplasty group) were excluded from analysis since no lesion was found. At 6 months, a primary clinical endpoint had occurred in 53 (12.8%) of 413 patients in the stent group and 79 (19.3%) of 410 in the angioplasty group (p=0.013). This significant difference in clinical outcome was maintained at 12 months. In the subgroup assigned angiographic follow-up, the mean minimum lumen diameter was greater in the stent group than in the balloon-angioplasty group, (1.89 [SD 0.65] vs 1.66 [0.57] mm, p=0.0002), which corresponds to restenosis rates (diameter stenosis > or =50%) of 16% and 31% (p=0.0008). In the group assigned clinical follow-up alone, event-free survival rate at 12 months was higher in the stent group than the balloon-angioplasty group (0.89 vs 0.79, p=0.004) at a cost of an additional 2085 Dutch guilders (US$1020) per patient., Interpretation: Over 12-month follow-up, a strategy of elective stenting with heparin-coated stents is more effective but also more costly than balloon angioplasty.

In view of the side effects of ticlopidine, stenting with the sole use of aspirin as post-stent treatment, has been attempted under the guidance of intravascular imaging to guarantee the optimization of the deployment. It was also hypothesized that optimal stenting under IVUS guidance would subsequently reduce the restenosis rate. With these aims the WEST-2 trial using the ACS MULTI-LINK stent was designed. This stent is composed of multiple corrugated rings connected to multiple links Ñ a design that combines radial strength, flexibility and conformability. In WEST-2, between February 1996 and August 1996, 18 centers enrolled 165 patients with stable or stabilized unstable angina and a single de novo lesion in vessel sizes ³ 2.75 mm. Optimal stenting was assessed using predefined QCA (DS% post-stent ³ 15% and stent/artery ratio ³ 1) and IVUS criteria. Patients fulfilling all criteria were treated with aspirin alone. MACE (death, MI, target lesion revascularization) as well as the restenosis rate were assessed at 6 months. In view of the results it may be concluded that the use of aspirin alone as post-stent treatment is safe when preset IVUS criteria are achieved. The target lesion revascularization rate, the restenosis percentage and the incidence of MACE encountered in this registry are among the lowest observed so far.

Aims: There is increased late loss in luminal diameter following long-term coronary stenting, compared with balloon angioplasty. We evaluated short- and long-term vessel wall injury after experimental implantation of two stent designs as well as balloon angioplasty and their relationship to neointimal hyperplasia., Methods and Results: Wiktor stents and Palmaz-Schatz stents were implanted in normal coronary arteries of pigs (balloon/artery ratio: 0.9-1.1). In control coronary arteries, balloon angioplasty was performed. At 1, 4 and 12 weeks, the vessel injury score, neointimal thickness and inflammatory response were assessed by histology. The vessel injury score increased over time in both Wiktor and Palmaz-Schatz stents: 0.9 +/- 0.1, 1.5 +/- 0.5 and 1.7 +/- 0.6 (mean +/- SD) for Wiktor stents and 0.7 +/- 0.2, 1.0 +/- 0.1 and 1.2 +/- 0.3 for Palmaz-Schatz stents at 1, 4 and 12 weeks follow-up, respectively. No increase in injury was seen in balloon angioplasty controls. Inflammation was seen in both stented groups but was absent 12 weeks after balloon angioplasty. No strong correlation between injury and neointimal thickness was apparent., Conclusion: Stents induce chronic injury in contrast to balloon angioplasty. Stent design (coil vs slotted tube) as well as inflammation may influence vessel response.

Histopathologic studies have demonstrated that vessels enlarge to compensate for an increase in plaque burden; this has been confirmed in vivo using intravascular ultrasound (IVUS). The initial studies suggested a biphasic course of lesion formation with (1) preservation of lumen dimensions up to a plaque burden of approximately 40%, and (2) luminal narrowing as plaque burden further increases. In this study, we used IVUS and angiography to assess the extent of left main (LM) atherosclerosis in 107 patients undergoing catheter-based procedures of the left anterior descending or left circumflex coronary arteries. Using IVUS, atherosclerotic plaques were found in all LM arteries, but only 26 (24%) had varying degrees of luminal narrowing on the angiogram. Nevertheless, there was an inverse relation (r = -0.62, p <0.0001) between the minimal lumen area and the plaque burden (i.e., plaque + media divided by total vessel area) that was not restricted to plaque burden values >40% (or >30%), but persisted at plaque burden values of 20% to 40%. In addition, LM arteries with a plaque burden <40% had a similar total vessel area as did LM arteries with a plaque burden > or =40% (22.9 +/- 6.1 vs 21.8 +/- 4.8 mm2, p = 0.30). These data suggest that lumen dimensions may not be preserved even if plaque occupies no more than 20% to 40% of the total vessel area. Thus, there is more variation in remodeling response during earlier stages of plaque accumulation within the LM artery than is commonly suggested.

Objective: This study evaluates the feasibility, reliability and reproducibility of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) image acquisition during automated transducer withdrawal and automated three-dimensional (3D) boundary detection for assessing on-line the result of coronary stenting., Background: Systolic-diastolic image artifacts frequently limit the clinical applicability of such automated analysis systems., Methods: In 30 patients, after successful angiography-guided implantation of 34 stents in 30 target lesions, we carried out IVUS examinations on-line with the use of ECG-gated automated 3D analyses and conventional manual analyses of two-dimensional images from continuous pullbacks. These on-line measurements were compared with off-line 3D reanalyses. The adequacy of stent deployment was determined by using ultrasound criteria for stent apposition, symmetry and expansion., Results: Gated image acquisition was successfully performed in all patients to allow on-line 3D analysis within 8.7 +/- 0.6 min (mean +/- SD). Measurements by on-line and off-line 3D analyses correlated closely (r > or = 0.95), and the minimal stent lumen differed only minimally (8.6 +/- 2.8 mm2 vs. 8.5 +/- 2.8 mm2, p = NS). The conventional analysis significantly overestimated the minimal stent lumen (9.0 +/- 2.7 mm2, p < 0.005) in comparison with results of both 3D analyses. Fourteen stents (41%) failed to meet the criteria by both 3D analyses, all of these not reaching optimal expansion, but only 7 (21%) were detected by conventional analysis (p < 0.02). Intraobserver and interobserver comparison of stent lumen measurements by the automated approach revealed minimal differences (0.0 +/- 0.2 mm2 and 0.0 +/- 0.3 mm2) and excellent correlations (r = 0.99 and 0.98, respectively)., Conclusions: ECG-gated image acquisition after coronary stent deployment is feasible, permits on-line automated 3D reconstruction and analysis and provides reliable and reproducible measurements; these factors facilitate detection of the minimal lumen site.

The use of coronary stents decreases the morbidity associated with acute closure and restenosis after balloon angioplasty. Intracoronary ultrasound (ICUS) guidance of stent implantation has been advocated to improve stent deployment and thereby to further improve the clinical outcome after stenting, over and above balloon angioplasty. Whereas the merits of intracoronary ultrasound in this respect still remain to be proven, the present paper illustrates that ICUS itself may also entail complications. This paper reports on three cases of stent damage induced or aggravated by the ICUS procedure.

Background: With the thrombogenic tendency and permanent implant nature of metallic stents, synthetic polymers have been proposed as candidate materials for stents and local drug delivery designs. We investigated the biocompatibility of several synthetic polymers after experimental placement in the coronary artery., Methods and Results: Five different biodegradable polymers (polyglycolic acid/polylactic acid [PGLA], polycaprolactone [PCL], polyhydroxybutyrate valerate [PHBV], polyorthoester [POE], and polyethyleneoxide/polybutylene terephthalate [PEO/ PBTP]) and three nonbiodegradable polymers (polyurethane [PUR], silicone [SIL], and polyethylene terephthalate [PETP]) were tested as strips deployed longitudinally across 90 degrees of the circumferential surface of coil wire stents. Appropriately sized polymer-loaded stents were implanted in porcine coronary arteries of 2.5- to 3.0-mm diameter. Four weeks after implantation, stent patency was assessed by angiography followed by microscopic examination of the coronary arteries. The biodegradable PCL, PHBV, and POE and the nonbiodegradable PUR and SIL evoked extensive inflammatory responses and fibrocellular proliferation (thickness of tissue response: 0.79 +/- 0.22, 1.12 +/- 0.01, 2.36 +/- 0.60, 1.24 +/- 0.36, and 1.43 +/- 0.15 mm, respectively). Less but still severe responses were observed for the biodegradable PGLA and PEO/PBTP (0.46 +/- 0.18 and 0.61 +/- 0.23 mm, respectively) and for the nonbiodegradable PETP (0.46 +/- 0.11 mm)., Conclusions: An array of both biodegradable and nonbiodegradable polymers has been demonstrated to induce a marked inflammatory reaction within the coronary artery with subsequent neointimal thickening, which was not expected on the basis of in vitro tests. The observed tissue response may be attributable to a combination of parent polymer compound, biodegradation products, and possibly implant geometry.

Objectives: We sought to determine the role of stent implantation in vein grafts by evaluating the long-term clinical outcome and estimated event-free survival at 5 years in 62 patients and by comparing our data with those of other treatment modalities previously reported., Background: Patients with recurrent angina after coronary artery bypass graft surgery pose a problem. Stent implantation has been advocated in an effort to avoid repeat operation and to address the limitations of balloon angioplasty., Methods: Patients undergoing stenting of a vein graft were entered into a dedicated data base. They were screened for death, infarction, bypass surgery and repeat angioplasty. Procedure-related events were included in the follow-up analysis. Survival and event-free survival curves were constructed by the Kaplan Meier method., Results: A total of 93 stents (84 Wallstent and 9 Palmaz-Shatz) were implanted in 62 patients. During the in-hospital period seven patients (11%) sustained a major cardiac event: two deaths (3%), two myocardial infarctions (3%) and three urgent bypass surgeries (5%). The clinical success rate, therefore, was 89%. During the follow-up period (median 2.5 years, range 0 to 5.9), another five patients (8%) died, 14 (23%) sustained a myocardial infarction, 12 (20%) underwent bypass surgery, and 14 (23%) underwent angioplasty. The estimated 5-year survival and event-free survival rates (free from infarction, repeat surgery and repeat angioplasty) were (mean +/- SD) 83 +/- 5% (95% confidence interval [CI] 73% to 93%) and 30 +/- 7% (95% CI 16% to 44%), respectively., Conclusions: The in-hospital outcome of patients who underwent stent implantation in a vein graft is acceptable, but the long-term clinical outcome is poor. It is unlikely that mechanical intervention alone will provide a satisfactory or definite answer for the patient with graft sclerosis over the long term.

Background: The new, less shortening, self-expanding Wallstent is characterized by longitudinal flexibility, a protective membrane, a low profile, and a customized range of diameters (3.5 to 6.0 mm). The recent modification of the braiding angle of the Wallstent has resulted in a new device with less shortening on expansion and a concomitant reduction in radial force. We hypothesized that the enforced mechanical remodeling produced by the selection of an oversized Wallstent might result in improved accommodation of subsequent reactive intimal hyperplasia and prevention of chronic recoil of the vessel., Methods and Results: To prove this hypothesis, we recently implanted 44 new, less shortening Wallstents in 35 native coronary arteries in 35 patients with acute or threatened closure after balloon angioplasty, according to a strategy of oversizing of Wallstent diameter and complete coverage of the lesion length. The initial and 6-month follow-up angiograms were analyzed with a computer-based quantitative coronary angiography (QCA) system. Acute gain (minimal luminal diameter [MLD] post minus MLD pre) and late loss (MLD post minus MLD at follow-up) were examined. Stent deployment was successful in 44 of 44 attempts (100%). Nominal stent diameter used was 1.40 mm larger than the maximal vessel diameter. One patient (3%) with a dilated but unstented lesion proximal to the stented segment sustained a subacute occlusion on day 1 associated with myocardial infarction. Event-free survival at 30 days after stent implantation was 97% (34 of 35 patients). Of the 34 patients eligible for 6-month angiographic follow-up, 3 who were asymptomatic declined repeat angiography. MLD (and percent diameter stenosis [% DS]) changed from 0.83 +/- 0.50 mm (72%) pre through 3.06 +/- 0.48 mm (15%) post to 2.27 +/- 0.74 mm (28%) at follow-up. Acute gain was 2.23 +/- 0.63 mm, and late loss was 0.78 +/- 0.61 mm. Angiographic restenosis ( > 50% DS) was observed in 5 of 31 patients (16%) at 6 months, all of whom underwent repeat angioplasty. Thus, the overall event-free survival at 6-month follow-up was 83% (29 of 35 patients)., Conclusions: The oversized Wallstent implantation with complete coverage of the lesion length conveyed a favorable 6-month clinical and angiographic outcome. The large acute gain obtained by the Wallstent afforded greater accommodation of the subsequent late loss. The enforced mechanical remodeling by oversized new Wallstents may result in prevention of acute and chronic recoil of the vessel wall and subsequently a lower restenosis rate at follow-up.

Optimized stent expansion by high-pressure inflations of oversized balloons has initially been derived from experience obtained with the Palmaz-Schatz stent, whereas there is little experience with this strategy in the Wallstent. By using this approach with quantitative coronary angiographic guidance, 20 Wallstents and 20 Palmaz-Schatz stents were implanted in 34 patients and consecutively examined by conventional two-dimensional (2D) intracoronary ultrasound (ICUS) and three-dimensional (3D) ICUS on the basis of the application of a pattern recognition algorithm. Ultrasound criteria of adequate stent expansion were defined as a complete apposition of the stent to the vessel wall, a stent symmetry index (SSI = minimum/maximum lumen diameter) > or = O.7, and a stent-reference lumen area ratio (SRR = Minimum intrastent lumen area/Average of proximal and distal reference lumen area) > or = O.8. In all cases a smooth angiographic lumen and a negative diameter stenosis, on the basis of a distal reference, was achieved. For the Wallstents ICUS showed a higher SSI (2D, 0.95 +/- 0.04 vs 0.85 +/- 0.09; p < 0.001; 3D, 0.90 +/- 0.09 vs 0.82 +/- 0.11, p < 0.05) and a lower SRR (2D, 0.66 +/- 0.12 vs 0.81 +/- 0.13, p < 0.005; 3D, 0.63 +/- 0.14 vs 0.74 +/- 0.15, p < 0.05) than for the Palmaz-Schatz stents. Ninety percent of failure in meeting these criteria resulted from a low SRR. The incidence of incomplete stent apposition (one in both stents) or SSI <0.7 was low and generally associated with an SRR <0.8. The Wallstents met the ICUS criteria less often (2D, 2(1O%) vs 10(50%), p < 0.01; 3D, 3(15%) vs 9(45%), p < 0.05), were significantly longer (35.1 +/- 7.7 mm and 14.3 +/- 3.3 mm, p < 0.0001), and generally demonstrated a larger vessel tapering, measured as proximal minus distal ICUS reference lumen area (1.33 +/- 2.91 mm2 vs 0.44 +/- 1.97 mm(2), not significant). Wallstents meeting the ICUS criteria, however, showed less vessel tapering (0.18 +/- 1.64 mm(2)). Thus optimized stent expansion was followed by excellent angiographic results for both Palmaz-Schatz and Wallstent. Although angiographic results and visual assessment of the ICUS examination suggested a good outcome, few Wallstents met the ICUS criteria in contrast to the Palmaz-Schatz stents. The low value of the SRR in the Wallstents is likely to be caused by vessel tapering, suggesting that this criterion may be unsuitable in assessing the adequacy of the expansion of relatively long stents such as the Wallstent.

A practical and rapid method was developed to study vascular pathology after implantation of metal endoprostheses (stents) that are used as internal splinting devices of tube-like structures. This method obviates the need for time-consuming grinding of thick sawing sections or removal of the prosthesis prior to histological processing, allowing for detailed analysis of the tissue in general, but especially of the stent-tissue interface. The vessels, with the metal stents still in place, were dehydrated in graded series of ethanol and embedded in methyl methacrylate. Using a motor-driven rotary microtome, 3- to 5-μm sections were easily cut. After deplastination, routine and special histological stainings were performed according to standard protocols for paraffin sections. This method proved to save time, compared with sawing sections, while allowing for a more complete examination of the stenttissue interface than is possible with routine paraffin techniques.

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 microns, P < .01), but at 12 weeks the thickness was similar (152 +/- 61 and 198 +/- 49 microns, respectively). Comparison at 5 days suggested delayed endothelialization of the coating., Conclusions: High-activity heparin coating of stents eliminates subacute thrombosis in porcine coronary arteries.

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.

Background: Inefficacy of systemic drug administration for restenosis prevention may partially relate to insufficient local drug concentration. This study aimed to evaluate the acute feasibility and long-term outcome of using an infusion-perfusion coil balloon, Dispatch., Methods and Results: In 22 patients after balloon angioplasty, the coil balloon was studied for (1) feasibility of local heparin delivery, (2) symptoms and signs of ischemia during prolonged deployment compared with angioplasty balloon occlusion, (3) coronary pressure and flow distal to the inflated device, and (4) long-term clinical and angiographic results. During prolonged intracoronary deployment of the coil balloon (29 +/- 8 minutes), 5 of 22 patients developed mild chest pain versus 20 of 22 during angioplasty (275 +/- 283 seconds). Neither hemodynamic nor vectorcardiographic signs of ischemia were detected, in contrast to angioplasty balloon occlusion. Baseline flow across the coil balloon was 44 +/- 31 mL/min, increasing by a factor of 1.8 +/- 0.7 during pharmacologically induced hyperemia. A mean volume of 14.2 +/- 6.1 mL containing 1416 +/- 608 IU of heparin was infused locally at a pressure of 122 +/- 54 mm Hg. At 7 +/- 1-month follow-up, 1 asymptomatic patient had died, and of the remaining 21, 17 (81%) were asymptomatic. Angiographic follow-up was obtained in 15 of 21 patients (71%), including all 4 symptomatic patients. Mean minimal luminal diameter after the procedure was 2.16 +/- 0.49 mm and at follow-up, 1.89 +/- 0.45 mm, which corresponds to a restenosis rate (diameter stenosis > or = 50%) of 7% (1/15)., Conclusions: Intracoronary use of the coil balloon after balloon angioplasty proved to be feasible and subjectively as well as objectively well tolerated during prolonged deployment by virtue of its perfusion properties. High volumes of heparin solution can be infused locally at very low pressure. No unfavorable clinical or angiographic long-term effects were observed.

Background: Balloon angioplasty damages endothelial cells and stimulates smooth muscle cell proliferation. The effects of local cytotoxic drug therapy on formation of neointima and late endothelial function are not known. This study was designed to determine whether direct infusion of mitomycin C via a microporous balloon catheter could significantly reduce formation of neointima after angioplasty. Furthermore, we investigated whether endothelial cell function is normal 7 weeks after the initial microporous angioplasty procedure., Methods: In 34 New Zealand white rabbits, bilateral external iliac arteries underwent balloon angioplasty, followed by either high-dose (0.66 mg/kg) or low-dose (0.025 mg/kg) mitomycin C in one iliac artery and saline infusion in the contralateral artery, and a control group was given saline in both vessels. Formation of neointima was measured in the iliac arteries after 7 weeks by morphometry. Before sacrifice of 17 'angioplasty' rabbits and three undamaged rabbits, graded doses of acetylcholine and isosorbide dinitrate were infused in the distal aorta, and the iliac artery diameter was measured by computerized quantitative angiography., Results: No significant differences in the absolute area of the intima or the intima: media ratio were demonstrated between control arteries and arteries that were directly infused with either high-dose or low-dose mitomycin. However, within the high-dose group, the mitomycin-treated vessel had a significantly lesser extent of formation of intimal hyperplasia (0.17 +/- 0.03 versus 0.27 +/- 0.03 mm2, P < 0.03) and lower intima: media area ratio (0.60 +/- 0.31 versus 1.09 +/- 0.42, P < 0.03) than the contralateral saline-treated vessel. Significant increases in mean luminal iliac artery diameter [0.18 mm (10.5%) at 1 min and 0.23 mm (13%) at 3 min, P < 0.05)] from baseline values following acetylcholine were observed in previously damaged iliac arteries. This vasodilatory response was not different from that in undamaged arteries., Conclusions: Local delivery of mitomycin C had no favorable effect on the inhibition of intimal hyperplasia compared with control saline-treated arteries. Normal endothelial function, determined on the basis of dilatory response to acetylcholine, can be demonstrated 7 weeks after balloon angioplasty injury.