Stent Edge Restenosis Research Articles

The SIRIUS‐DIRECT trial: A multi‐center study of direct stenting using the sirolimus‐eluting stent in patients with de novo native coronary artery lesions

To assess the safety and efficacy of direct stenting using the sirolimus-eluting BX Velocitytrade mark stent in patients with coronary lesions. Although direct coronary stenting has become a widespread practice, there have been no systematic assessments of direct stenting with drug-eluting stents. Total of 225 patients with identical inclusion and exclusion criteria as the original SIRIUS trial were enrolled in this prospective single-arm study. They were compared in a no-inferiority design with 412 similar patients from the SIRIUS trial who had sirolimus-eluting stents deployed after predilatation and were preassigned to angiographic follow-up evaluation. Direct stenting was successful in 85.8% of the patients. Compared with the predilatation group, direct stenting was associated with shorter median procedure duration (33 min vs. 45 min, P < 0.001). Angiographic follow-up at 8 months revealed similar late loss (in-stent-0.19 +/- 0.47 mm vs. 0.17 +/- 0.44 mm, and in-lesion-0.23 +/- 0.41 mm vs. 0.24 +/- 0.47 mm) and similar frequency of binary restenosis (in-stent-4.6% vs. 3.2% and in-lesion-6.1% vs. 8.9%) between the two treatment strategies. However, stent-edge restenosis was lower with direct stenting than in the predilatation control group (2.1% vs. 6.9%, P = 0.02). At 12-months, there were no significant differences in target lesion revascularization (3.7% vs. 5.1%, P = ns) or composite major adverse cardiac events (7.0% vs. 8.3%, P = ns). In patients similar to those treated in the SIRIUS trial, direct stenting using sirolimus-eluting stents achieves excellent short- and long-term clinical and angiographic results with shorter procedure time and less frequent stent edge restenosis compared with predilation stent implantation techniques.

Intravascular ultrasound findings in patients with restenosis of sirolimus- and paclitaxel-eluting stents

Objective We used intravascular ultrasound (IVUS) to compare restenotic sirolimus-eluting (SES) vs paclitaxel-eluting (PES) stents. Background Little is known about the IVUS pattern and mechanisms of restenosis, in the two widely available drug-eluting stent (DES) platforms. Methods Volumetric IVUS analysis was performed in patients with clinical restenosis in DES ( n = 29 SES and 11 PES respectively). Results Despite similar vessel volumes (347.5 ± 155.6 vs 356.5 ± 164.1 mm 3, p = 0.84) and stent volumes (175.6 ± 74.57 vs 179.7 ± 84.24 mm 3, p = 1.0), IVUS analysis showed that neointimal hyperplasia volume was significantly greater in PES restenoses than in SES restenoses (40.0 ± 44.2 vs 19.3 ± 11.4 mm 3, p = 0.02) without any significant difference in distribution over the stent length. This leads to a higher percent of volume obstruction (intimal hyperplasia volume divided by stent volume: 18.5 ± 13.7% vs 11.8 ± 7.7%, p = 0.045). Minimal stent area was smaller in SES than in PES (4.3 ± 1.2 vs 5.6 ± 1.2 mm 2, p = 0.06) and stent underexpansion was more frequently observed in SES stents: minimal stent area < 4.5 mm 2 (65% in SES vs 27% in PES, p = 0.04). Stent edge restenosis occured in 1/29 SES (3%) vs 3/11 PES (27%) stents, p = 0.056. Conclusion The magnitude of neointimal hyperplasia was greater in PES than in SES while stent underexpansion appeared to be more common in SES.

Is Stent Underexpansion the Main Cause of In-Stent Restenosis after Sirolimus-Eluting Stent Implantation?: An Intravascular Ultrasound Study

Background and Objectives:Intravascular ultrasound (IVUS) can be useful for assessing the causes of in-stent restenosis (ISR) after sirolimus-eluting stent (SES) implantation. We used IVUS to evaluate the causes of ISR after SES implantation. Subjects and Methods:SES implantation was performed in 502 patients with 670 coronary lesions. Of these patients, 27 patients had angiographic ISR in 28 lesions. We evaluated the patterns of ISR and we wanted to elucidate the possible mechanism of ISR after SES implantation with using IVUS analysis. Results:The ISR pattern was focal in 26 lesions, and diffuse in 2 lesions, including 1 total occlusion. When analyzing the 21 IVUS-applicable lesions, stent underexpansion [the minimal stent cross-sectional area (CSA) was <5 mm and it was <4.5 mm in the cases of small coronary arteries (reference vessel diameter <2.8 mm)] was observed in 10 lesions (48%). Stent fracture (defined as non-visualization of the struts on IVUS at the restenotic segments) and edge restenosis was identified in the 3 (14%) and 3 lesions (14%), respectively. Except for edge stenosis, stent underexpansion was observed in 55% of the intra-stent restenotic lesions and it was more prominent in the small coronary arteries (7/8 small coronary artery lesions). Stent underexpansion, stent fracture or edge restenosis were not related to the 7 ISR lesions (33%) in which profound intimal hyperplasia within the stent occurred. Conclusion:Our observation of ISR after SES implantation with using IVUS showed that most ISR lesions have mechanical problems, especially stent underexpansion. However, one third of the ISR lesions were associated with profound intimal hyperplasia within the stent. (Korean Circulation J 2007;37:58-63)

Effect of Plaque Volume on Subsequent Vessel Remodeling at Edges of Sirolimus-Eluting Stents

Serial (baseline and 9-month follow-up) intravascular ultrasound analysis was performed at 5-mm reference segments immediately proximal and distal to the sirolimus-eluting stent (SES) in 33 lesions. Proximal and distal reference segments were divided into 1-mm subsegments. Between postintervention and follow-up intravascular ultrasound studies, there were significant decreases in the lumen and increases in plaque & media areas in the subsegment closest to the distal edge, with no change in external elastic membrane area. There was no significant change in external elastic membrane, lumen, and plaque & media areas within the other subsegments. At the nearest 1-mm subsegment from the proximal and distal edges, baseline plaque & media area was associated with subsequent vessel remodeling. In conclusion, a large amount of plaque at the SES edge may be a risk of negative remodeling at follow-up (stent edge restenosis). It supports the importance of "normal-to-normal" SES deployment.

Gadolinium neutron capture brachytherapy (GdNCB), a new treatment method for intravascular brachytherapy

Restenosis is a major problem after balloon angioplasty and stent implantation. The aim of this study is to introduce gadolinium neutron capture brachytherapy (GdNCB) as a suitable modality for treatment of stenosis. The utility of GdNCB in intravascular brachytherapy (IVBT) of stent stenosis is investigated by using the GEANT4 and MCNP4B Monte Carlo radiation transport codes. To study capture rate, Kerma, absorbed dose and absorbed dose rate around a Gd-containing stent activated with neutrons, a 30 mm long, 5 mm diameter gadolinium foil is chosen. The input data is a neutron spectrum used for clinical neutron capture therapy in Studsvik, Sweden. Thermal neutron capture in gadolinium yields a spectrum of high-energy gamma photons, which due to the build-up effect gives an almost flat dose delivery pattern to the first 4 mm around the stent. The absorbed dose rate is 1.33 Gy/min, 0.25 mm from the stent surface while the dose to normal tissue is in order of 0.22 Gy/min, i.e., a factor of 6 lower. To spare normal tissue further fractionation of the dose is also possible. The capture rate is relatively high at both ends of the foil. The dose distribution from gamma and charge particle radiation at the edges and inside the stent contributes to a nonuniform dose distribution. This will lead to higher doses to the surrounding tissue and may prevent stent edge and in-stent restenosis. The position of the stent can be verified and corrected by the treatment plan prior to activation. Activation of the stent by an external neutron field can be performed days after catherization when the target cells start to proliferate and can be expected to be more radiation sensitive. Another advantage of the nonradioactive gadolinium stent is the possibility to avoid radiation hazard to personnel.

Analysis of stent edge restenosis with different forms of brachytherapy

Brachytherapy is a new technique to prevent or treat in-stent restenosis.1–7 However, there is a disturbing incidence of late lumen loss at the stent edges.8–11 Although “geographic miss” and low-dose radiation (at margins of β-emitting stents) may contribute to this problem, little is known about the serial changes responsible for stent edge restenosis across protocols.10,12 This study examines the relative contribution of remodeling and neointimal hyperplasia to edge restenosis in patients treated as part of various brachytherapy protocols who subsequently presented with stent edge restenosis.

Extent and distribution of in-stent intimal hyperplasia and edge effect in a non-radiation stent population

Intimal hyperplasia within the body of the stent is the primary mechanism for in-stent restenosis; however, stent edge restenosis has been described after brachytherapy. Our current understanding about the magnitude of in vivo intimal hyperplasia and edge restenosis is limited to data obtained primarily from select, symptomatic patients requiring repeat angiography. The purpose of this study was to determine the extent and distribution of intimal hyperplasia both within the stent and along the stent edge in relatively nonselect, asymptomatic patients scheduled for 6-month intravascular ultrasound (IVUS) as part of a multicenter trial: Heparin Infusion Prior to Stenting. Planar IVUS measurements 1 mm apart were obtained throughout the stent and over a length of 10 mm proximal and distal to the stent at index and follow-up. Of the 179 patients enrolled, 140 returned for repeat angiography and IVUS at 6.4 ± 1.9 months and had IVUS images adequate for analysis. Patients had 1.2 ± 0.6 Palmaz-Schatz stents per vessel. There was a wide individual variation of intimal hyperplasia distribution within the stent and no mean predilection for any location. At 6 months, intimal hyperplasia occupied 29.3 ± 16.2% of the stent volume on average. Lumen loss within 2 mm of the stent edge was due primarily to intimal proliferation. Beyond 2 mm, negative remodeling contributed more to lumen loss. Gender, age, vessel location, index plaque burden, hypercholesterolemia, diabetes, and tobacco did not predict luminal narrowing at the stent edges, but diabetes, unstable angina at presentation, and lesion length were predictive of in-stent intimal hyperplasia. In a non-radiation stent population, 29% of the stent volume is filled with intimal hyperplasia at 6 months. Lumen loss at the stent edge is due primarily to intimal proliferation.