Usefulness of Intracoronary Brachytherapy for Patients With Resistant Drug-Eluting Stent Restenosis.

In-stent restenosis (ISR) remains a concern even in the drug-eluting stent (DES) era and carries a high risk of recurrence. Brachytherapy is being used as an alternative treatment for resistant ISR, yet the safety and efficacy of this approach has not been well studied. We analyzed the outcomes of 101 patients who underwent coronary brachytherapy for resistant DES ISR. Baseline demographic, clinical, procedural, and outcome data were collected by phone and from electronic records. Comorbidities and overt cardiovascular disease were highly prevalent. Median previous stent layers were 2 with a maximum of 5 layers. Procedural angiographic success rate was 97% and median time to discharge was 1 day after brachytherapy. The primary outcome of target vessel revascularization was 24% at 1 year, 32% at 2 years, and 42% at 3 years. The rate of nonfatal myocardial infarction was 0% at 1 year, 3.5% at 2 years, and 6% at 3 years. The rate of all-cause mortality was 8.5% at 1 year, 12% at 2 years, and 16% at 3 years. We observed only 1 case of late stent thrombosis. After multivariable adjustment, female gender (hazard ratio 2.37, 95% confidence interval 1.02 to 5.52, p = 0.04) and diffuse ISR pattern (hazard ratio 2.95, 95% confidence interval 1.21 to 7.17, p = 0.01) were independently associated with the primary outcome. In conclusion, brachytherapy is feasible for the treatment of resistant DES ISR and is associated with high immediate procedural success and reasonable efficacy in a complex patient population. This approach might be used as an alternative for these patients.

From basic biology to randomized clinical trial: the Beta Radiation for Arteriovenous Graft Outflow Stenosis (BRAVO II).

The BRAVO-II study was a randomized controlled study of endovascular radiation therapy as compared to sham radiation therapy, following angioplasty of a thrombosed PRFE graft. The results did not show a benefit of endovascular radiation therapy, albeit in the context of an early termination of the study at less than 50% enrollment due to business reasons. Emphasis is laid on the fact that there may still be a role for radiation therapy in specific clinical settings associated with dialysis vascular access dysfunction.

Radiation therapy for dialysis access stenosis: unfulfilled promise or false expectations.

Hemodialysis vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population at a cost of well over $1 billion per annum. Venous stenosis (due to venous neointimal hyperplasia [VNH]) is the most common cause of polytetrafluroethylene PTFE) dialysis access graft and arteriovenous fistula (AVF) failure. Despite the magnitude of the clinical problem, however, there are currently no effective therapies for this condition. We and others have previously demonstrated that VNH in PTFE dialysis grafts and AVF is composed of smooth muscle cells/myofibroblasts, endothelial cells within neointimal microvessels, and peri-graft macrophages. Radiation therapy blocks the proliferation and activation of all these cell types. The current review will dissect out the available in vitro, experimental, and clinical data on the use of radiation therapy for vascular stenosis in general, and for dialysis access dysfunction in particular. It is important to try and identify whether there is still a role for radiation therapy in this specific clinical setting. We believe that this is a critically important question to answer in view of the huge unmet clinical need that is currently associated with hemodialysis vascular access dysfunction.

External beam radiation therapy for PTFE dialysis grafts: a pilot study.

PURPOSE: The aim of this study was to identify the effects of external beam radiation on PTFE dialysis graft dysfunction. METHODS: Seven patients who underwent PTFE dialysis graft angioplasty were randomized to receive either two 8 Gy doses of external beam radiation or no radiation. The primary endpoint was time to graft thrombosis with a secondary endpoint of time to first intervention. RESULTS: There was no statistically significant difference between the two groups in either of the endpoints, although grafts in the radiation group had a shorter time to thrombosis or intervention. CONCLUSIONS: Our results demonstrate technical feasibility for use of external beam radiation in the setting of dialysis vascular access graft dysfunction. Larger randomized studies are required to identify whether there is a clinical benefit from this intervention.

Inhibition of neointimal hyperplasia after stent placement with rhenium 188-filled balloon dilation in a canine iliac artery model.

PURPOSE: To evaluate the efficacy of beta-irradiation therapy with rhenium 188 ((188)Re) mercaptoacetyltriglycine (MAG3)-filled balloon dilation to prevent neointimal hyperplasia after stent placement in a canine iliac artery model. MATERIALS AND METHODS: A total of 15 stents were implanted into the iliac arteries of eight dogs (one or two stents in each dog). Rhenium 188 MAG3-filled balloon dilation was performed immediately after placement of 10 bare stents-20 Gy in group II (n = 5) and 40 Gy in group III (n = 5)-and conventional balloon dilation was performed immediately after placement of the remaining five bare stents (group I). A follow-up angiogram was obtained 8 weeks after the procedure, and percentage of luminal stenosis was calculated for the proximal and distal ends of each stent. Neointimal thickening (expressed as the neointimal area divided by the sum of neointimal area and media area) was assessed for microscopic examination. RESULTS: All eight dogs survived until they were euthanized 8 weeks after the procedures. The mean luminal stenosis measurements at 8-week follow-up angiography in groups I, II, and III were 26.63%, -0.44%, and 10.53%, respectively. The mean neointimal thickening measurements in groups I, II, and III were 0.77, 0.21, and 0.34, respectively. The mean percentage of luminal stenosis and neointimal thickening differed significantly among the three groups (P < .05). CONCLUSIONS: beta-Irradiation with (188)Re-MAG3-filled balloon dilation has the potential to reduce neointimal hyperplasia secondary to stent placement in a canine iliac artery model. A dose of 20 Gy may be preferable versus a dose of 40 Gy to reduce neointimal hyperplasia.

Intravascular radiation therapy with a Re-188 liquid-filled balloon in patients with in-stent restenosis.

OBJECTIVE: The aim of this study was to evaluate the feasibility and safety of intravascular radiation therapy (IVRT) using Re-188 filled balloon system in patients with in-stent stenosis. METHODS: A total of 39 patients with in-stent restenosis were enrolled as the IVRT (22 patients) and control groups (17 patients) of this study after a successful coronary angioplasty. For irradiation the angioplasty balloon was replaced by a noncompliant balloon of the same diameter but 10 mm longer in length with a proximal and distal radio-opaque marker to deliver the dose of 18 Gy at 0.5 mm depth from the surface of the balloon into the vessel wall. Angiographic follow-up was performed after 6 months. RESULTS: The length of the irradiated segment was between 9.14 and 22 mm and the diameter between 2.5 and 3 mm. In the IVRT group, two patients who did not receive antiplatelet therapy had myocardial infarction. Four patients who presented with stable angina earlier also had angiographically documented in-stent occlusion (two patients) and edge stenosis (two patients) of the target lesion and received angioplasty (18.1%). In the control group, three patients with recurrent angina and four asymptomatic patients had documented in-stent occlusion angiographically at 6 months and these seven patients underwent target lesion revascularization (41.2%). The overall restenosis rate in the IVRT and control groups were 23.91 and 39.86%, respectively (P=0.013). No complications were documented, except anginal pain and ST segment changes. CONCLUSION: Our results indicated that the Re-188 liquid-filled balloon is feasible, safe, and effective in patients with in-stent restenosis.

A meta-analysis of randomized controlled trials of intracoronary gamma- and beta-radiation therapy for in-stent restenosis.

We assessed the effectiveness of intracoronary brachytherapy and compared treatment effects for the two radiation sources as well as the performance of the procedure in saphenous vein grafts (SVG) and native coronary arteries. Five randomized controlled trials comparing intracoronary brachytherapy with placebo involving a total of 1310 patients were reviewed for a meta-analysis. Risk differences (RD) for major adverse cardiac events (MACE), target vessel revascularization, target lesion revascularization, and angiographic binary restenosis at 6-12 months were computed, and a meta-regression analysis of MACE was performed. For MACE, the RD was 0.19 (95% confidence interval [CI], 0.09%-0.29%; P value, 0.00); there was significant between-study variance of 0.2395. In univariate meta-regression analyses, diabetes was a significant factor for the between-study variance (P value, 0.000). In multivariate meta-regression analyses adjusted for diabetes and lesion length, neither gamma-radiation source nor SVG was a significant factor for the between-study variance (P value, 0.675 and 0.433, respectively); the adjusted between-study variance was 0.000. Intra-coronary brachytherapy is effective compared with placebo at mid-term follow up. Neither procedure in SVG (gamma radiation) nor difference in radiation source (beta or gamma) in native coronary arteries was a significant factor in brachytherapy effectiveness compared to placebo.

Intravascular brachytherapy versus drug-eluting stents for the treatment of patients with drug-eluting stent restenosis.

Drug-eluting stents (DESs), although promising technology, still are associated with restenosis; therefore, we evaluated the safety and efficacy of intravascular radiation therapy for the treatment of DES in-stent restenosis (ISR). Treatment of DES ISR has not been established, although intravascular radiation therapy is an effective treatment for patients with ISR of bare metal stents. Other modalities are conventional percutaneous coronary intervention (PCI), including restenting with DES. Radiation for Eluting Stents in Coronary FailUrE (RESCUE) is an international, Internet-based registry of 61 patients who presented with ISR of a DES and were assigned to intravascular radiation therapy with commercially available systems after PCI. Outcomes of these patients were compared with those of a consecutive series of 50 patients who presented with ISR of a DES and were assigned to repeat DES (r-DES) treatment. Baseline clinical and angiographic characteristics were similar between groups, except for more Cypher stents as the initial DES that restenosed in the r-DES group than in the intravascular radiation therapy group (88.5% vs 69%, p = 0.01). At 8 months there were fewer overall major adverse cardiac events in the intravascular radiation therapy group compared with the r-DES group (9.8% vs 24%, p = 0.044). The need for target vessel and target lesion revascularizations was similar in the 2 groups at 8 months. There has been no report of subacute thrombosis in either group. In conclusion, intravascular radiation therapy as adjunct therapy to PCI for patients presenting with ISR of a DES is safe and should be considered an alternative therapeutic option for this difficult subset of patients.

BRAVO I: A pilot study of vascular brachytherapy in polytetrafluoroethylene dialysis access grafts.

Hemodialysis vascular access dysfunction owing to stenosis and thrombosis in polytetrafluoroethylene dialysis access grafts is a huge clinical problem for which there are currently no long lasting durable therapies. Vascular brachytherapy has been used successfully for the prevention of coronary restenosis following angioplasty and stent placement. The Beta Radiation for Treatment of Arterial-Venous Graft Outflow I study was a pilot study of vascular brachytherapy in hemodialysis patients with patent but dysfunctional grafts. Twenty-five patients were randomized to receive either radiation therapy (a single dose of 18.4 Gy) or sham radiation, following angioplasty. The primary efficacy end point of the study was target lesion primary patency at 6 months. The primary safety end point was a composite of death, emergency surgery on the graft, venous rupture, or aneurysm formation. Forty-two percent of the radiated grafts achieved the target lesion primary patency end point at 6 months as compared to 0% of the control group (P = 0.015), but this did not translate into an improvement in secondary patency at either 6 or 12 months. Radiation therapy was found to be safe in the setting of hemodialysis vascular access dysfunction. Our results suggest that vascular brachytherapy is an intervention that is worthy of further examination in the setting of non-thrombosed dialysis access grafts.

Intracoronary beta-brachytherapy using a rhenium-188 filled balloon catheter in restenotic lesions of native coronary arteries and venous bypass grafts.

PURPOSE: We have previously demonstrated the efficacy of intracoronary beta-brachytherapy using a liquid (188)Re-filled balloon in a randomised trial including de novo lesions. Percutaneous coronary interventions in restenotic lesions and in stenoses of venous bypass grafts are characterised by a high recurrence rate for restenosis and re-interventions. Against this background, we wanted to assess the impact of intracoronary beta-brachytherapy using a liquid (188)Re-filled balloon in restenotic lesions in native coronary arteries and venous bypass grafts. METHODS: In 243 patients, beta-brachytherapy with 22.5 Gy was applied at a tissue depth of 0.5 mm. Patients were followed up angiographically after 6 months and clinically for 12 months. The primary clinical endpoint was the incidence of MACE (death, myocardial infarction, target vessel revascularisation). Secondary angiographic endpoints were late loss and binary restenosis rate in the total segment. RESULTS: All irradiation procedures were successfully performed. A total of 222 lesions were in native coronary arteries; 21 were bypass lesions. Mean irradiation length was 41.6+/-17.3 mm (range 20-150 mm) in native coronary arteries and 48.1+/-33.9 mm (range 30-180 mm) in bypass lesions; the reference diameter was 2.57+/-0.52 mm and 2.83+/-0.76 mm, respectively. There was no vessel thrombosis during antiplatelet therapy. Angiographic/clinical follow-up rate was 84%/100%. MACE rate was 17.6% in the native coronary artery group and 38.1% in the CABG group (p<0.03). Binary restenosis rate was 22.5% and 55.6% (p<0.01), and late loss was 0.38+/-0.72 mm and 1.33+/-1.11 mm (p<0.001), respectively. CONCLUSIONS: We conclude that intracoronary beta-brachytherapy with a liquid (188)Re-filled balloon using 22.5 Gy at a tissue depth of 0.5 mm in restenotic lesions is safe. It is associated with a low binary restenosis rate, resulting in a low occurrence rate of MACE within 12 months in restenotic lesions in native coronary arteries but not in vein grafts.

Clinical results of intracoronary brachytherapy (ICBT) for multiple in-stent restenosis.

BACKGROUND AND PURPOSE: Treatment of in-stent restenosis (ISR) with percutaneous coronary intervention (PCI) alone is often followed by early re-restenosis. The present study focused on the effect of intracoronary brachytherapy (ICBT) on multiple in-stent restenosis (MISR) after repeated PCI. PATIENTS AND METHODS: 40 patients (27 male, 13 female, age: 66 +/- 9 years) with MISR (two to six ISRs, median three ISRs) were retrospectively analyzed. All patients were treated by using the Novoste((R)) Beta-Cathtrade mark 3.5F System after PCI. The target vessel received 18.4-25.3 Gy of radiation at a depth of 2 mm from the center of the source. The restenosis-free survival and overall survival were calculated by Kaplan-Meier analysis (log-rank). The time interval between last PCI without ICBT and the consecutive recurrence was compared with the follow-up time after PCI with ICBT. RESULTS: The 3-year overall survival rate after ICBT was 93%. The 0.5-, 1-, 2-, and 3-year ISR-free survival rates after PCI + ICBT were 81%, 72%, 52%, and 38%, respectively. After PCI alone, the 0.5-, 1-, and 2-year ISR-free survival rates were 30%, 13%, and 0%, respectively. This difference was highly significant (p < 0.0001). Patients with more than three ISRs before ICBT had a better outcome (3-year ISR-free survival: 80%) than patients with only two or three ISRs before ICBT (3-year ISR-free survival: 25%; p < 0.05). CONCLUSION: ICBT is highly effective and safe in patients with ISR. The results of this study are in accordance with the WRIST and BETA-WRIST data. After 6 months both studies revealed an ISR-free survival rate of 86% (WRIST) and 66% (BETA-WRIST), respectively. The ISR rates in the own control group (70%) were comparable to the placebo groups in WRIST (68%) and BETA-WRIST (72%). Interestingly, patients with more than three ISRs before ICBT had the lowest ISR rate after ICBT.

Three-year follow-up after intracoronary beta-radiation therapy for in-stent restenosis.

BACKGROUND: Most studies that proved intracoronary radiation therapy (IRT) to be highly effective to reduce recurrent restenosis after treatment of in-stent restenosis (ISR) have looked at time periods up to 12 months. Whether the beneficial effect from radiation is sustained during long-term follow-up remains a concern. This study sought to evaluate the effectiveness of IRT using a beta-emitter during a 3-year follow-up period. METHODS: One hundred twenty-eight consecutive symptomatic patients (mean age, 63 +/- 11 years) with 134 in-stent restenotic lesions were treated for ISR with IRT (noncentred beta-emitter, Novoste; radiation dosis 21.1 +/- 3.1 Gy). Six-month angiographic follow-up was obtained in 104 patients (81%) with 105 lesions (78%). All patients underwent 36-month clinical follow-up. RESULTS: Six-month angiographic restenosis rate was 22% in stent (29% in lesion) with an in-stent late loss of 0.49 +/- 0.62 mm. Target lesion resvascularization (TLR) at 6-month follow-up was performed in 23 cases (18%). MACE (death, myocardial infarction, and target vessel revascularisation) was observed in 24 patients (19%). At 36-month follow-up, TLR increased to 36 cases (28%) and MACE was observed in 47 patients (37%). In a multivariate analysis, minimal lumen diameter before treatment of ISR using IRT was the only predictor of recurrent TLR at 36 months (OR = 0.131; 95% CI, 0.068-0.254; p = 0.002). In a subgroup of patients (N = 15) without restenosis at 6-month angiography but with clinically driven recurrent late angiography (mean, 18 +/- 7 months); in-lesion late loss increased from 0.47 +/- 0.54 mm at 6 months to 1.27 +/- 0.76 mm at repeated angiography (p = 0.005). CONCLUSION: There is a considerable number of delayed recurrent restenosis post IRT for ISR. This is due to ongoing late loss more than 6-month post IRT. The minimal lumen diameter before IRT predicts the need for recurrent TLR at 36 months.

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.

Clinical applications of 188Re-labelled radiopharmaceuticals for radionuclide therapy.

188Re is a radionuclide in which there is widespread interest for therapeutic purposes because of its favourable physical characteristics. Moreover, it can be eluted from an on-site installable 188W/188Re generator, which has a useful shelf-life of several months. Most of the clinical experiences gained with 188Re concern the use of 188Re-1,1-hydroxyethylidenediphosphonate (188Re-HEDP) for bone pain palliation in patients suffering prostate cancer. The maximum tolerated activity was 3.3 GBq 188Re-HEDP and if the platelet count exceeded 200 x 10(9) l(-1), the administration of 4.4 GBq appeared safe. Evidence for repeated administrations of 188Re-HEDP rather than single injections was established. In general, pain palliation occurs in 60-92% of patients with only moderate transient toxicity, mainly related to changes in blood counts. Also in haematology, radioimmunotherapy by means of 188Re might play a role by selectively targeting the bone marrow in patients undergoing conditioning prior to haematopoetic stem cell transplantation. The feasibility of such an approach was proven using a Re-labelled monoclonal antibody directed toward the CD66-antigen. More recently, encouraging safety data on locoregional treatment of primary liver tumours using 188Re-labelled lipiodol were reported. The normal organs at greatest risk for toxicity are the normal liver and the lungs. About 50% of the patients reported mild and transient side effects, mainly consisting of low grade fever, right hypochondrial discomfort or aggravation of pre-existing liver impairment. Besides the applications in oncology 188Re-based therapies have also been pioneered for benign condition such as prevention of re-stenosis following angioplasty and for radiosynovectomy in cases of refractory arthritis.

Effective dose for patients undergoing coronary and femoral intravascular radiotherapy involving an HDR 192Ir source.

Effective dose equivalent (EDE), and effective dose (ED) for coronary and femoral Intravascular brachytherapy (IVBT) procedures involving a 370 GBq (10 Ci) HDR 192Ir gamma source are tabulated. MIRD stylised models and the MCNP Monte Carlo code were used for the calculations. For coronary irradiation, the normalised EDE is 0.18 mSv (GBq min)(-1) and the ED is 0.056 mSv (GBq min)(-1). For femoral IVBT, the normalised EDE is 0.01629 mSv (GBq min)(-1) and the ED is 0.01195 mSv (GBq min)(-1). Although the medical benefits to a patient undergoing IVBT are often significant and justified, patient doses are high compared with dose limits for radiation protection purposes. As IVBT is becoming a routine procedure, data in this paper could be useful to manage the procedures efficiently.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Vascular brachytherapy with tungsten (188W) is feasible and safe. The 6-month clinical outcomes are similar to the original WRIST radiation group.

Beta radiation in the treatment of in-stent restenosis of an in situ saphenous vein bypass graft A case report.

We describe a case of instent restenosis in a femoral-distal saphenous vein bypass graft successfully treated with brachytherapy. A 45-year-old insulin-requiring diabetic woman underwent an in-situ femoral-anterior tibial bypass graft for a non-healing ischemic ulcer. Despite a technically successful percutaneous transluminal angioplasty and endovascular stenting of a retained valve within the threatened graft, the wound failed to heal. At the 1-month follow-up, instent restenosis was documented and successful cutting balloon angioplasty, complemented by adjunctive beta-irradiation was successfully performed. Clinical and hemodynamic success was achieved, with prompt ulcer healing and intermediate-term graft patency maintained on surveillance duplex ultrasound follow-up. We review the literature on radiation therapy in the management of peripheral arterial disease and discuss therapeutic options in the management of restenosis.

Vascular brachytherapy with 192Ir after femoropopliteal stent implantation in high-risk patients: twelve-month follow-up results from the Vienna-5 trial.

PURPOSE: To prospectively evaluate the effectiveness of endovascular brachytherapy in the prevention of restenosis after femoropopliteal stent implantation in high-risk patients. MATERIALS AND METHODS: Patients provided written informed consent to participate in this study, which was approved by the ethics committee. A total of 88 patients (mean age, 67.7 years +/- 10.1; 57 men [65%], 31 women [35%]) with femoropopliteal lesions (mean treatment length, 16.8 cm +/- 7.3) were included. Patients underwent percutaneous transluminal angioplasty (PTA) and stent implantation and were randomized in a double-blind fashion to undergo either gamma brachytherapy with an iridium 192 source or treatment with nonradioactive seeds. A 14-Gy dose of iridium 192 was prescribed at 2 mm into the arterial wall (target depth equals vessel radius plus 2 mm). The primary end point of the study was angiographic binary restenosis of more than 50% at 6-month follow-up. Secondary end point was either percutaneous or surgical target lesion revascularization after 6 months. Continuous data are presented as mean +/- standard deviation. Categorical data are expressed as percentages. Student t test was used to compare continuous data; chi(2) test was used to compare categorical values. Survival function was calculated with the Kaplan-Meier method. Multivariate Cox proportional hazard regression analysis was performed to enable evaluation of multivariate predictors of recurrence at 6- and 12-month follow-up. Variables included brachytherapy, clinical stage, lesion length, de novo and recurrent lesion, vessel run off, prior stenosis or occlusion, diabetes mellitus, and stent model. RESULTS: Revascularization and brachytherapy were accomplished successfully in all patients. The overall 6-month recurrence rate was 35% in patients who underwent only stent implantation and 33% in patients who underwent both stent implantation and brachytherapy (P = .89). Nine (10%) patients developed early reocclusion in the segment treated with a stent (two patients [4%] in the stent group and seven [17%] in the stent and brachytherapy group); of these patients, three in the stent and brachytherapy group experienced reocclusion within 24 hours of the intervention. Late (>30 days after intervention) thrombotic occlusion was observed in three patients (7%) in the stent and brachytherapy group. CONCLUSION: Brachytherapy does not improve 6-month patency after femoropopliteal stent implantation in high-risk patients because of a high incidence of early and late thrombotic occlusion.

Different responses by cultured aortic and venous smooth muscle cells to gamma radiation.

BACKGROUND: Stenosis of hemodialysis arteriovenous grafts is usually focal and caused by the proliferation of vascular smooth muscle cells (SMCs). External radiation of the graft is a potential strategy to prevent stenosis; however, the relative responsiveness of arterial and venous SMCs to radiation is unknown. METHODS: Human aortic and saphenous vein SMCs were cultured in a medium containing growth factors and serum and treated with 0 to 50 Gy in a gamma irradiator. At 2 to 20 days post-irradiation, cell counting, methylthiazoletetrazolium dye reduction, [(3)H]-thymidine uptake, and bromodeoxyuridine (BrdU) incorporation assays were performed. RESULTS: All assays showed that 1 to 50 Gy inhibited the proliferation of both aortic and venous SMCs in a dose-dependent manner. Importantly, venous cells were less susceptible to radiation in all assays, compared to aortic cells. At day 10, 1 to 50 Gy of radiation inhibited the increase in the number of aortic cells by 24% to 66% and venous cells by 8% to 25% (P < 0.01) (aortic vs. venous). The differences between aortic and venous cells varied among different assays and were most pronounced in the BrdU assay. CONCLUSION: Inasmuch as myointimal hyperplasia occurs at both arterial and venous anastomoses, future strategies using radiation to prevent hemodialysis vascular access stenosis should take these differences into consideration.

Three-year follow-up after intravascular gamma-radiation for in-stent restenosis in saphenous vein grafts.

The Washington Radiation for In-Stent Restenosis Trial in Saphenous Vein Grafts (SVG WRIST) demonstrated safety and efficacy of intravascular radiation therapy (IRT) for the treatment of in-stent restenosis (ISR) in SVG at 12 months. In this study, we aimed to examine whether the safety and efficacy of IRT is durable up to 36 months. One hundred twenty patients with diffuse ISR in SVG underwent balloon angioplasty, laser or atherectomy ablation, and/or additional stenting. After successful intervention, patients were randomly assigned in a double-blind fashion to intravascular treatment with a ribbon containing either iridium (Ir)-192 (n = 60) or nonradioactive seeds (n = 60). The prescribed dose at 2 mm from the source was either 14 or 15 Gy in vessels 2.5-4.0 mm or 18 Gy in vessels > 4.0 mm in diameter. At 36 months, target lesion revascularization (TLR; 43% vs. 66%; P = 0.02) and target lesion revascularization-major adverse cardiac event (TLR-MACE; 49% vs. 71%; P = 0.02) rates continued to be lower in the IRT group, but both target vessel revascularization (TVR; 59% vs. 71%; P = 0.17) and TVR-MACE (63% vs. 77%; P = 0.11) rates were not. In SVG WRIST, patients with ISR treated with IRT had a marked reduction in the need for repeat TLR at 36 months, with sustained clinical benefit at 3 years despite late recurrences, which were more pronounced in the radiation group.