Washington Radiation For In-Stent Restenosis Trial Research Articles

Intracoronary radiation therapy using a novel beta emitter for in-stent restenosis

Intracoronary beta-radiation therapy reduces in-stent restenosis (ISR). We aimed to determine the safety and feasibility of intracoronary radiation therapy (IRT) utilizing tungsten (188W), a beta emitter. A total of 30 patients with angiographic evidence of ISR in a previously treated native coronary artery underwent percutaneous coronary intervention (PCI; balloon angioplasty, ablation by atherectomy, or laser angioplasty). After the intervention, a noncentered delivery catheter with a side guide 0.014-in. wire carrying a tungsten (188W) coil, with an active length of 33 mm, was inserted. Patients were randomized to a radiation dose of 18, 22, or 25 Gy at 2 mm from the center of the source. Aspirin and Plavix, at 300 mg loading dose, were administered prior to intervention. Plavix 75 mg/day was prescribed for 6 months after the procedure. At 6 months follow-up, the overall binary angiographic restenosis rate was 18.8%. Target vessel revascularization (TVR) was 23% and target lesion revascularization related major adverse cardiac events (TLR-MACE) was 13.3%, without any intergroup differences. A comparison with the original Washington Radiation for In-stent restenosis Trial (WRIST) radiation cohort utilizing an 192Iridium source (prescription dose 15 Gy at 2 mm from the source) showed similar TVR and TLR-MACE rates of 30% and 18%, respectively. The TVR and TLR-MACE rates in the WRIST placebo cohort were 70% and 66%, respectively. Vascular brachytherapy with tungsten (188W) is feasible and safe. The 6-month clinical outcomes are similar to the original WRIST radiation group.

Cardiovascular News

Cardiovascular News

Cutting Balloon Angioplasty versus Conventional Balloon Angioplasty for In-Stent Restenosis Treated by Intracoronary Radiation Therapy

Background: Cutting Balloon angioplasty (CBA) may be a useful treatment modality for in-stent restenosis (ISR) as it maintains a stable position during dilatation and results in potentially less injury than plain old balloon angioplasty (POBA). The purpose of this study was to compare CBA and POBA with intracoronary radiation therapy (IRT) for in-stent restenosis (ISR). Methods: We selected 157 consecutive patients from the WRIST (Wa- shington Radiation for In-stent restenosis Trial) series of gamma radiation trials using both gamma and beta emitters for ISR of native coronaries or saphenous vein grafts, who were treated with CBA or POBA as the only treatment strategy before intracoronary radiation therapy. Patients in the CBA (N=64) and POBA (N=93) groups were matched for baseline demographic and procedural characteristics. Radiation was delivered successfully in all cases. Results: At angiographic follow up, acute gain was higher in the CBA group than the POBA group (1.7±0.7 mm vs. 1.4±0.9 mm, p=0.03). The angiographic restenosis rate (17.1% vs. 23.5%, p=NS) and edge restenosis rate (6.3% vs. 12.2%, p=NS) were not significantly lower in the cutting balloon cohort. At a 6 month clinical follow up, the CBA group showed a statistically decreased rate of clinically driven target vessel revascu- larization compared to the POBA group (5.7% vs.18.3%, p=0.038). Conclusions: Cutting balloon angioplasty is a reasonable treatment strategy for in-stent restenosis prior to intracoronary radiation therapy. (Korean Circulation J

Impact of the acute results on the long-term outcome after the treatment of in-stent restenosis: a serial intravascular ultrasound study.

The current study used serial (postintervention and follow-up) intravascular ultrasound (IVUS) to assess the impact of acute results on long-term follow-up of patients with in-stent restenosis (ISR). All patients (n = 180) with serial IVUS studies of ISR lesions from the following gamma-irradiation brachytherapy trials were included: Washington Radiation for In-Stent Restenosis Trial (WRIST), Gamma-1, and Angiorad Radiation Technology for In-Stent Restenosis Trial in Native Coronaries (ARTISTIC). There were 106 irradiated and 74 placebo patients. Quantitative analysis was performed according to the American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of IVUS. Images were acquired using motorized transducer pullback, cross-sectional analysis was performed every 1 mm, and volumetric and mean planar dimensions were calculated. The independent predictors for the absolute follow-up minimum lumen area (MLA) were the postintervention MLA, the postintervention minimum stent area, and the use of brachytherapy. Placebo patients lost 45% of the postintervention MLA while irradiated patients lost only 17% of the MLA. The independent predictors of the follow-up percent intimal hyperplasia (intimal hyperplasia volume divided by stent volume) and the independent predictors of the absolute increase in intimal hyperplasia were the postintervention percent intimal hyperplasia and the use of brachytherapy. Serial IVUS analysis shows that the follow-up MLA and percent intimal hyperplasia are dependent on the results obtained during the treatment of ISR lesions.

Additional stenting promotes intimal proliferation and compromises the results of intravascular radiation therapy: an intravascular ultrasound study

Background Vascular brachytherapy (VBT) reduces in-stent restenosis (ISR). However, additional stenting at the time of radiation may be associated with a worse outcome. Methods and results Intravascular ultrasound (IVUS) was performed after VBT and at 6 months follow-up in 79 native artery ISR patients treated with γ-radiation who participated in the Washington Radiation for In-Stent restenosis Trial (WRIST), Gamma-1, and Angiorad Radiation Technology for In-Stent restenosis Trial in Coronaries (ARTISTIC) trials. Patients were treated with 192Ir at 14 or 15 Gy at 2 mm from the source. Additional stents were used to treat the ISR lesions in 45 patients; these patients were then compared with the 34 patients treated without restenting. Paired measurements included stent, lumen, and intimal hyperplasia volumes. After the VBT procedure, intimal hyperplasia volume was smaller in the group treated with additional stents (54 ± 33 mm 3 vs 34 ± 33 mm 3, P = .012), but minimal lumen area was similar between the 2 groups (4.3 ± 1.5 mm 2 vs 4.7 ± 1.4 mm 2 respectively, P = NS). Between the time of the VBT procedure and follow-up, intimal hyperplasia volume increased by 27 ± 19 mm 3 in the restented group and by 9 ± 21 mm 3 in the group treated without additional stents ( P = .014). At 6 months, intimal volume was similar in the 2 groups, but minimal lumen area was slightly smaller in the group treated with additional stents (3.4 ± 1.8 mm 2 vs 4.2 ± 1.7 mm 2, P = .053). Patients treated with additional stents had more target lesion revascularizations than the group treated without additional stents (38% vs 15%, P = .02). Conclusions Additional stenting reduces intimal hyperplasia within the stents acutely. However, it compromises the benefit of VBT by promoting higher intimal regrowth within months after radiation.

Serial volumetric intravascular ultrasound assessment of native coronary artery versus saphenous vein grafts in-stent restenosis lesions after conventional catheter-based treatment

Stent implantation reduces restenosis in both native coronary arteries and saphenous vein grafts (SVG), 1– 4 but in-stent restenosis has become a signifi cant clinical problem. Conventional catheter-based interventions are associated with high recurrence rates in both locations; however, previous studies have not addressed whether SVG in-stent restenosis lesions have a higher recurrence rate compared with native arteries. The present study used serial (postintervention and followup) volumetric intravascular ultrasound (IVUS) imaging to compare patients on placebo who had native artery and SVG in-stent restenosis lesions selected from 2 randomized brachytherapy trials: Washington Radiation For In-stent Restenosis Trial (WRIST), which included both native artery and SVG lesions, and Saphenous Vein Graft (SVG- WRIST), which enrolled only patients with SVG in-stent restenosis. The purpose was to determine whether SVG in-stent restenosis lesions had a higher recurrence rate than native artery in-stent restenosis lesions.

Relationship between neointimal regrowth and mechanism of acute lumen gain during the treatment of in-stent restenosis with or without supplementary intravascular radiation.

We investigated whether neointimal regrowth is related to the mechanism of acute lumen gain during the treatment of in-stent restenosis (ISR) lesions both with and without adjunct intravascular brachytherapy. From the WRIST (Washington Radiation for In-Stent Restenosis Trial) cohort, 54 ISR patients ((192)Ir, 29; placebo, 25) were treated with nonrepeat stenting percutaneous interventions (excimer laser, rotational atherectomy, and/or balloon angioplasty) prior to (192)Ir or placebo therapy. Using Simpson's method, serial volumetric intravascular ultrasound (IVUS) analyses (pre- and posttreatment and 6-month follow-up) were analyzed to obtain stent, lumen, and intimal hyperplasia (IH) volumes that were then adjusted for stent length to create stent, lumen, and IH volume indexes. In the placebo group, the acute reduction of neointima (1.6 +/- 1.4 mm(3)/mm) was counteracted by intimal regrowth (2.1 +/- 1.7 mm(3)/mm). The amount of intimal regrowth correlated directly with the intimal reduction due to the intervention (r = 0.76; P < 0.001), but not with the amount of additional stent expansion. In the (192)Ir-treated group, intimal regrowth was significantly less than in the placebo group (-0.3 +/- 0.1 vs. 2.1 +/- 1.7 mm(3)/mm; P < 0.001) despite a similar initial intimal reduction (1.3 +/- 0.9 vs. 1.6 +/- 1.4 mm(3)/mm; P = NS). No correlation was found between intimal reduction at the time of the procedure and intimal regrowth in the (192)Ir group. In this study, neointimal regrowth following treatment of ISR lesions correlates directly with the extent of acute intimal volume reduction, but not with the extent of additional stent expansion. This relation is not seen in ISR segments treated with radiation, where intimal regrowth is substantially inhibited.

Comparison of intracoronary gamma radiation for in-stent restenosis in saphenous vein grafts versus native coronary arteries

Intracoronary gamma radiation is effective in reducing recurrent in-stent restenosis (ISR) involving native coronary arteries. This study compares the effectiveness and safety of intracoronary gamma radiation for the treatment of ISR in saphenous vein grafts (SVGs) versus native coronary arteries. In the Washington Radiation for In-Stent restenosis Trial (WRIST) series of gamma radiation trials, 1,142 patients with ISR (230 in SVG and 912 in native coronary arteries) completed 6-month clinical follow-up. All patients underwent balloon angioplasty, atherectomy, and/or restenting. Different ribbon lengths containing 6 to 23 seeds of iridium-192 were used to cover lesion lengths <80 mm. The prescribed radiation doses were 14 or 15 Gy at 2-mm radial distance from the center of the source. Baseline demographics showed that patients with SVGs were older (65 ± 13 vs 61 ± 11 years, p <0.001), more likely male (79% vs 64%, p <0.001), had more multivessel coronary disease (81% vs 50%, p <0.001), and less diffuse lesions (17 ± 10 vs 24 ± 12 mm, p <0.001). At 6 months, event-free survival was similar for patients with SVG ISR and native coronary ISR (82% vs 84%, p = 0.35). The SVG ISR population had a low rate of late total occlusion (4.6%) and late thrombosis (3.5%). Thus, treatment of ISR with gamma radiation in SVGs had similar outcome to native coronary arteries. The use of gamma radiation for the treatment of ISR should expand to SVGs.

12 vs. 6 months of clopidogrel to reduce major cardiac events in patients undergoing γ-radiation therapy for in-stent restenosis. Washington radiation for in-stent restenosis trial (WRIST) 12 vs. WRIST plus

12 vs. 6 months of clopidogrel to reduce major cardiac events in patients undergoing γ-radiation therapy for in-stent restenosis. Washington radiation for in-stent restenosis trial (WRIST) 12 vs. WRIST plus

Dose heterogeneity may not affect the neointimal proliferation after gamma radiation for in-stent restenosis: A volumetric intravascular ultrasound dosimetric study

ObjectivesThe goal of this study was to use serial (postirradiation and follow-up) volumetric intravascular ultrasound (IVUS): 1) to evaluate the actual distribution of gamma radiation in human in-stent restenosis (ISR) lesions, and 2) to analyze the relationship between neointimal regrowth and the delivered radiation dose. BackgroundThe relationship between the neointimal regrowth and delivered dose during the treatment of ISR remains unknown. MethodsWe analyzed 20 actively (gamma emitter) treated, native artery ISR patients from the Washington Radiation for In-Stent restenosis Trial (WRIST) that met the following criteria: on both postirradiation and six-month follow-up IVUS imaging, ≥80% of the external elastic membrane circumference could be identified throughout the treated length including the lesion and proximal and distal reference segments. Intravascular ultrasound images were digitized every 1 mm. Proximal and distal reference and stented segment luminal and adventitial contours were imported and reconstructed. The source was placed circumferentially at the site of the IVUS catheter and longitudinally according to the relationship between the radioactive seeds and stent edges. Using Monte Carlo simulations, dose volume histograms for the adventitia and intima were calculated. The relationship between the neointimal regrowth and calculated doses were evaluated. ResultsThere was large dose heterogeneity at both the intimal and adventitial levels. Most of the sites (93%) received >4 Gy at the adventitia, and all of the sites received >4 Gy at the intima. There was no relationship between neointimal regrowth and radiation dose. ConclusionsAlthough there may be large dose heterogeneity, gamma irradiation (using a fixed dose prescription) appears to deliver a sufficient dose to prevent neointimal regrowth.

Quantitative angiographic methods for appropriate end-point analysis, edge-effect evaluation, and prediction of recurrent restenosis after coronary brachytherapy with gamma irradiation

ObjectivesThe study was done to investigate the relationship between clinical restenosis and the relative angiographic location of the recurrent restenotic lesion, after treatment of in-stent restenosis with vascular brachytherapy in the Washington Radiation for In-Stent Restenosis Trial (WRIST). BackgroundIntracoronary radiation therapy reduces recurrence of in-stent restenosis. We investigated the above objective in patients enrolled in WRIST. MethodsThe WRIST study randomized 130 patients to double-blinded therapy with gamma irradiation (iridium-192 [192Ir]) versus placebo after interventional treatment of diffuse in-stent restenosis. After the intervention and at follow-up, three vessel segments were individually analyzed with quantitative coronary angiography: 1) the “stent,” 2) the “radiation ribbon,” and 3) the “ribbon+margin” segment (including 5 mm on either end of the injured or radiation-ribbon segment). Receiver operator curves (ROC) were used to assess the value of the follow-up percent diameter stenosis (DS) for each of the three analyzed segments in predicting target vessel revascularization (TVR). Results192Ir reduced recurrent restenosis (23.7% vs. 60.7%, p < 0.001) and the length of recurrent restenosis (8.99 ± 4.34 mm vs. 17.54 ± 10.48 mm, p < 0.001) at follow-up compared to placebo. Isolated stent edge (3.4%) and ribbon edge (1.7%) restenoses were infrequent in both groups. The best angiographic surrogate of TVR was the 50% follow-up DS obtained from the ribbon+margin analysis (ROC area 0.806). ConclusionsIn WRIST, not only was 192Ir therapy effective in reducing restenosis, but it also reduced the lesion length of treatment failures by 50%, and it was not associated with edge proliferation. The restenosis rate obtained from the vessel segment inclusiveof the dose fall-off zones was the best correlate of TVR and should become a standard analysis site in all vascular brachytherapy trials.

Safety and efficacy of manual stepping and overlapping of β-emitter for diffuse in-stent restenosis lesions

Background: The effects of overlapping β-emitter sources on the treatment of in-stent restenosis (ISR) lesions as a result of manual stepping are unknown. Methods and results: In the BETA WRIST (Beta Washington Radiation for In-stent Restenosis Trial), 17 out of the 50 patients who received radiation treatment had diffuse ISR in native coronaries that required manual stepping of the β-emitter ( 90Y) source in order to cover the lesion and the edges. Fourteen of those patients received radiation with an overlap of up to 3 mm in the middle of the stented segment. The prescribed dose was 20.6 Gy to a distance of 1.0 mm from the surface of the inflated balloon, and the calculated dose to the vessel wall at the overlapped area did not exceed 75 Gy. There was no difference in late total occlusion (7.1% vs. 9.0%, P=NS) and target lesion revascularization (28.5% vs. 27.2%, P=NS) between patients with stepping and those without stepping. At 6 months, there was no evidence of perforation or aneurysm at the overlapped segments. Quantitative coronary angiographic (QCA) analysis revealed significantly reduced late loss in the overlapped segment compared to the adjacent segment ( P=.04). Serial (postradiation vs. follow-up) IVUS measurement showed larger mean lumen cross-sectional area (CSA) ( P=.0035) and smaller mean intimal hyperplasia (IH) CSA ( P=.0010) in the overlapped segment compared to the adjacent segment. Conclusion: Manual stepping of β-emitter source with a short overlapped segment is safe for diffuse ISR. Further increase in lumen dimension and reduction in IH formation are observed at the overlapped segment.

Three-year follow-up after intracoronary gamma radiation therapy for in-stent restenosis: Original WRIST

Background: The Washington Radiation for In-Stent Restenosis Trial (WRIST) is a double-blinded randomized study evaluating the effects of intracoronary radiation therapy (IRT) in patients with in-stent restenosis (ISR). Methods: One hundred and thirty patients with ISR (100 native coronary and 30 vein grafts) underwent PTCA, laser ablation, rotational atherectomy, and/or additional stenting (36% of lesions). Patients were randomized to either Iridium-192 IRT or placebo, with a prescribed dose of 15 Gy to a 2-mm radial distance from the center of the source. Results: Angiographic restenosis (27% vs. 56%, P=.002) and target vessel revascularization (TVR; 26% vs. 66%, P<.001) were dramatically reduced at 6 months in IRT patients. Between 6 and 36 months, IRT compared to placebo patients had more target lesion revascularization (TLR; IRT=17% vs. placebo=2%, P=.002) and TVR (IRT=17% vs. placebo=3%, P=.009). At 3 years, the major adverse cardiac event (MACE) rate was significantly reduced with IRT (39% vs. 65%, P=.003). Conclusions: In WRIST, patients with ISR treated with IRT using 192Ir had a marked reduction in the need for repeat target lesion and vessel revascularization at 6 months, with the clinical benefit maintained at 3 years.

Two-year follow-up after beta and gamma intracoronary radiation therapy for patients with diffuse in-stent restenosis

In-stent restenosis (ISR) has become a major challenge as the use of stents has increased. 1 Casterella P.J. Teirstein P.S. Prevention of coronary restenosis. Cardiol Rev. 1999; 7: 219-231 Crossref PubMed Scopus (63) Google Scholar The recurrence rate after treatment for ISR remains high (>30%), and is not influenced by the device used in the interventional procedure. 2 Hoffmann R. Mintz G.S. Dussaillant G.R. Popma J.J. Pichard A.D. Satler L.F. Kent K.M. Griffin J. Leon M.B. Patterns and mechanisms of in-stent restenosis. A serial intravascular ultrasound study. Circulation. 1996; 94: 1247-1254 Crossref PubMed Scopus (1230) Google Scholar , 3 Reimers B. Moussa I. Akiyama T. Tucci G. Ferraro M. Martini G. Blengino S. Di Mario C. Colombo A. Long-term clinical follow-up after successful repeat percutaneous intervention for stent restenosis. J Am Coll Cardiol. 1997; 30: 186-192 Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar , 4 Mehran R. Mintz G.S. Satler L.F. Pichard A.D. Kent K.M. Bucher T.A. Popma J.J. Leon M.B. Treatment of in-stent restenosis with excimer laser coronary angioplasty mechanisms and results compared with PTCA alone. Circulation. 1997; 96: 2183-2189 Crossref PubMed Scopus (238) Google Scholar , 5 Baim D.S. Levine M.J. Leon M.B. Levine S. Ellis S.G. Schatz R.A. Management of restenosis within the Palmaz-Schatz coronary stent (the U.S. multicenter experience). The U.S. Palmaz-Schatz Stent Investigators. Am J Cardiol. 1993; 71: 364-366 Abstract Full Text PDF PubMed Scopus (185) Google Scholar The predominant mechanism of ISR is neointimal tissue proliferation. 6 Gordon P.C. Gibson C.M. Cohen D.J. Carrozza J.P. Kuntz R.E. Baim D.S. Mechanisms of restenosis and redilation within coronary stents-quantitative angiographic assessment. J Am Coll Cardiol. 1993; 21: 1166-1174 Abstract Full Text PDF PubMed Scopus (224) Google Scholar Preclinical and clinical studies have shown efficacy of intracoronary radiation delivered by catheter-based systems after intervention in reducing ISR using beta and gamma emitters. 7 Wiedermann J.G. Marboe C. Amols H. Schwartz A. Weinberger J. Intracoronary irradiation markedly reduces restenosis after balloon angioplasty in a porcine model. J Am Coll Cardiol. 1994; 23: 1491-1498 Abstract Full Text PDF PubMed Scopus (297) Google Scholar , 8 Waksman R. Robinson K.A. Crocker I.R. Gravanis M.B. Cipolla G.D. King III, S.B. Endovascular low-dose irradiation inhibits neointima formation after coronary artery balloon injury in swine. A possible role for radiation therapy in restenosis prevention. Circulation. 1995; 91: 1533-1539 Crossref PubMed Scopus (361) Google Scholar , 9 Waksman R. Robinson K.A. Crocker I.R. Wang C. Gravanis M.B. Cipolla G.D. Hillstead R.A. King III, S.B. Intracoronary low-dose β-irradiation inhibits neointima formation after coronary artery balloon injury in the swine restenosis model. Circulation. 1995; 92: 3025-3031 Crossref PubMed Scopus (265) Google Scholar The Beta Washington Radiation for In-Stent restenosis Trial (WRIST) using 90-yttrium (90Y) showed inhibition of angiographic and clinical restenosis compared with placebo at 6 months follow-up with similar outcomes in the gamma radiation arm (iridium-192 [192Ir]) of WRIST. 10 Waksman R. Bhargava B. White L. Chan R.C. Mehran R. Lansky A.J. Mintz G.S. Satler L.F. Pichard A.D. Leon M.B. Kent K.M. Intracoronary β-radiation therapy inhibits recurrence of in-stent restenosis. Circulation. 2000; 101: 1895-1898 Crossref PubMed Scopus (312) Google Scholar The long-term impact and safety of this technology is unknown, with concerns of late thrombosis, aneurysm formation, accelerated vascular disease, and perforation. 11 Teirstein P.S. Massullo V. Jani S. Popma J.J. Russo R.J. Schatz R.A. Guarneri E.M. Steuterman S. Sirkin K. Cloutier D.A. Leon M.B. Tripuraneni P. Three-year clinical and angiographic follow-up after intracoronary radiation results of a randomized clinical trial. Circulation. 2000; 101: 360-365 Crossref PubMed Scopus (333) Google Scholar In this study, we report a 2-year clinical follow-up of the beta and gamma WRIST cohorts.

Serial intravascular ultrasound analysis of edge recurrence after intracoronary gamma radiation treatment of native artery in-stent restenosis lesions

In the Washington Radiation for In-Stent restenosis Trial (WRIST), patients were first treated with conventional techniques and then randomized to either γ-irradiation ( 192Ir) or placebo (dummy seeds). In the 192Ir group with native coronary in-stent restenosis, we identified 8 patients with edge recurrence and compared them with 21 patients with no recurrence. Serial (postirradiation and follow-up) intravascular ultrasound analysis was performed according to conventional methods. When compared with nonrecurring lesions, lesions with distal edge recurrence had (1) greater decrease in mean distal lumen cross-sectional area (−3.0 ± 1.2 vs −0.7 ± 1.0 mm 2, p = 0.0002), (2) no change in mean distal external elastic membrane cross-sectional area versus an increase in mean distal cross-sectional area of 1.0 ± 0.9 mm 2 in nonrecurring lesions (p = 0.0047), and (3) a greater increase in mean distal plaque + media cross-sectional area (2.9 ± 1.2 mm vs 1.7 ± 0.6 mm 2, p = 0.0103). Within the stented segment, the nonrecurring lesions had no decrease in mean lumen and no increase in mean intimal hyperplasia cross-sectional area. Conversely, lesions with distal edge recurrence had a significant decrease in mean intrastent lumen cross-sectional area (−1.7 ± 1.7 mm 2) and a significant increase in mean intrastent intimal hyperplasia cross-sectional area (1.6 ± 1.6 mm 2). Lesions with distal edge recurrence also had a greater decrease in mean proximal lumen cross-sectional area (−1.7 ± 1.3 vs −0.3 ± 0.8 mm 2, p = 0.0213), with a trend toward a greater increase in mean proximal plaque + media cross-sectional area. Thus, edge recurrence after 192Ir treatment of in-stent restenosis is the result of neointimal hyperplasia (part of generalized treatment failure) and the absence of radiation-induced positive remodeling.

Edge stenosis and geographical miss following intracoronary gamma radiation therapy for in-stent restenosis

OBJECTIVESWe sought to determine the relationship between geographical miss (GM) and edge restenosis (ERS) following intracoronary radiation therapy.BACKGROUNDEdge restenosis may be a limitation of intracoronary irradiation to prevent in-stent restenosis (ISR). Inadequate radiation source coverage of the injured segment (GM) has been proposed as a cause of ERS. We studied the relationship between GM and ERS following 192Ir treatment of ISR.METHODSThere were 100 patients with native vessel ISR in WRIST (Washington Radiation for In-Stent Restenosis Trial), in which patients with ISR were first treated with conventional techniques and then randomized to gamma irradiation (192Ir) or placebo. Geographical miss was defined as segments proximal or distal to the treated lesion that were subjected to injury during primary intervention but were not covered by the radiation source.RESULTSGeographical miss was documented in 56 of 164 edges (34%). Edge restenosis was noted at eight of 80 radiated edges and in four of 84 placebo edges. In the irradiated group, ERS was observed in 21% of edges with GM and in 4% of edges without GM (p = 0.035). In contrast, in the placebo group, ERS was observed in only 7% of edges with GM and in 4% of edges without GM (p = NS). The late edge lumen loss was higher in the irradiated group with GM as compared to placebo with GM (0.74 ± 0.57 vs. 0.41 ± 0.50 mm, p = 0.016).CONCLUSIONSEdge restenosis following gamma irradiation treatment of ISR is related to GM: a mismatch between the segment of artery injured during the primary catheter-based intervention and the length of the radiation source.

Intracoronary radiation for patients with refractory in-stent restenosis: An analysis from the wrist-crossover trial

Background. In-stent restenosis (ISR) is a limitation of intracoronary stent implantation. In animal models and clinical trials, ionizing radiation has been shown to decrease in-stent neointimal formation. Methods and Materials. In the Washington Radiation for In-stent Restenosis Trial (WRIST), patients with in-stent restenosis were first treated with conventional catheter-based techniques and then randomized to gamma irradiation ( 192Ir, 15 Gy at 2 mm from the source) or placebo. Patients randomized to placebo that developed recurrent ISR and presented with anginal symptoms were crossed-over to active therapy. We compared the clinical and angiographic outcomes of 39 patients in the crossover group with 65 patients treated primarily with radiation. The primary clinical endpoints were mortality, morbidity, and repeat target lesion revascularization (TLR) at 6 months. Results. Procedural success was 100%. In-hospital and 30-day complications were minimal. At 6 months, the rate for any multiple adverse cardiac events (MACE: death, MI, or TLR) was 25.6% in the crossover group vs. 29.2% in the primary treatment group ( p = 0.86). Three patients in the crossover group and four in the primary treatment group died ( p = NS). There were no Q-wave myocardial infarction. Ten (9.6%) of the patients presented with late thrombosis and total occlusion: 6.2% (4/65) in the primary treatment group vs. 15.4% (6/39) in the crossover group ( p = 0.13). Conclusions. Patients who fail conventional catheter-based intervention without radiation can be treated with 192Ir with results similar to those who initially receive brachytherapy. This is of specific importance with respect to patients initially assigned to the placebo arm of randomized clinical trials.