strontium-radioisotopes and Coronary-Restenosis

Based on therapeutic approach for benign diseases, vascular brachytherapy decreases smooth vascular muscle cells proliferation and multiplication which lead to the formation of the neo-intima. The radioactive positive action affects arterial recoil due to post angioplasty vessel injury. Randomised studies has shown good angiographic results up to 6 months of follow-up, with 50% in-stent restenosis rate decrease and on the analysed segment as well. Decrease on Mace and TLR show statistically significance. Results don't correlate with emitter and bêta emitters had been introduced in France recently. Vascular brachytherapy is actually indicated for in-stent restenosis, there is no evidence to perform this treatment for de novo lesion. Geographic miss, source centering, late thrombosis and pullback procedure may interfere with treatment quality. IVUS allows best target volume determination to a higher quality level. Internationals guidelines such as Eva-Gec-Estro recommendations could increase treatment safety and enable development of an optimal technique.

Topics: Angioplasty, Balloon, Coronary; Beta Particles; Brachytherapy; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Restenosis; France; Gamma Rays; Half-Life; Humans; Iridium Radioisotopes; Multicenter Studies as Topic; Phosphorus Radioisotopes; Radiopharmaceuticals; Stents; Strontium Radioisotopes; Treatment Outcome; Yttrium Radioisotopes

Restenosis remains a vexing problem in patients undergoing percutaneous coronary interventions (PCI). This phenomenon is related to a combination of events, including elastic recoil, negative remodeling and fibrointimal tissue proliferation. While stenting (bare metal and drug eluting) has made a dramatic impact in preventing recoil and remodeling, restenosis still occurs. Once restenosis occurs, it presents its own set of challenges due to the excess tissue proliferation. Major predicators of restenosis include diabetes, small stent diameter and long stented lesions. Vascular brachytherapy is the only proven therapy associated with a significant reduction in angiographic restenosis and the need for target vessel revascularization for the treatment of in-stent restenosis.

Topics: Angioplasty, Balloon, Coronary; Brachytherapy; Coronary Restenosis; Humans; Patient Selection; Stents; Strontium Radioisotopes

Recent trials with different designs indicated that drug-eluting stents may be superior to vascular brachytherapy (VBT) for the treatment of in-stent restenosis (ISR). We performed a randomised, double-centre, clinical, quantitative coronary angiographic (QCA) and intravascular ultrasound (IVUS) acute and 3-years comparison of 90Sr/90Y-VBT and sirolimus-eluting stent implantation (SES) for ISR.. Ninety-one (91) consecutive patients were included. By QCA, SES led to a higher acute gain (2.08 ± 0.41 mm vs. 1.54 ± 0.70 mm, p < 0.0001), higher postprocedural minimum lumen diameter (2.76 ± 0.39 mm vs. 2.39 ± 0.52 mm; p < 0.0001), lower late lumen loss at follow-up (0.09 ± 0.29 vs. 0.39 ± 0.79 mm, p = 0.042), and a higher net lumen gain of the target lesion (2.05 ± 0.51 vs 1.18 ± 1.08 mm, p < 0.0001). By IVUS, the smaller acute gain following VBT was the result of residual intima hyperplasia, the intima hyperplasia formation following SES was extremely low, and the edge-effect was virtually absent after SES, respectively. At 6-month follow-up, both the angiographic restenosis rate (4.7 vs. 22.7%; p < 0.0001) and target lesion revascularisation rate (2.3 vs. 10.4%; p = 0.025) were lower in SES. Importantly, SES showed a stable clinical course at 3-year follow-up while VBT was associated with a sustained incidence of target vessel failure (11.6 vs. 46.7%; p < 0.0001).. SES for ISR is associated with superior QCA, IVUS and clinical results at 6-month and 3-year of follow-up when compared with VBT.

Topics: Aged; Angioplasty, Balloon, Coronary; Brachytherapy; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Germany; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Strontium Radioisotopes; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Yttrium Radioisotopes

We report a double-blind, randomized clinical trial of intracoronary beta-radiation for prevention of restenosis after stent implantation in native coronary de novo lesions in diabetic patients.. After successful stent implantation in native coronary de novo lesions, 106 lesions in 89 diabetic patients were randomly allocated to treatment with beta-radiation with 18 Gy at 1 mm vessel depth (n = 53) or placebo treatment (n = 53).. Angiographic analysis at 9 month follow-up revealed a late lumen loss of 0.7+/-0.9 mm in the radiotherapy group versus 1.2+/-0.8 mm in the control group at the injured segment (P = 0.006), 0.9+/-1.0 versus 1.3+/-0.7 mm at the radiated segment (P = 0.02), and 0.9+/-1.0 versus 1.3+/-0.7 mm at the target segment (P = 0.04) (defined as active source length plus 5mm on proximal and distal sites). Binary restenosis rates were significantly lower in the radiation group in all subsegments (injured segment: 10.9 versus 37.3%, P = 0.003; radiated segment: 21.7 versus 49.0%, P = 0.005; target segment: 23.9 versus 49.0%, P = 0.01). Target lesion revascularization for restenosis was required in nine lesions (17.6%) in the radiotherapy group versus 18 (34.0%) in the placebo group (P = 0.05). Late thrombosis occurred in four radiated patients (after premature discontinuation of antiplatelet therapy in all), resulting in a major adverse clinical event rate of 37.2% in the brachytherapy group versus 38.6% in the placebo group (P = ns).. In diabetic patients with de novo coronary lesions, intracoronary radiation after stent implantation significantly reduced restenosis. However, this clinical benefit was reduced by the frequent occurrence of late thrombosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Beta Particles; Brachytherapy; Coronary Disease; Coronary Restenosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Membrane Glycoprotein IIb; Prospective Studies; Regression Analysis; Stents; Strontium Radioisotopes; Treatment Outcome; Yttrium

It is an ongoing concern that intracoronary brachytherapy may possibly just delay the problem of in-stent restenosis ("late catch up"). For gamma-radiation, 3 placebo-controlled studies have shown the maintenance of the initially positive effect after 2 years, but similar data do not exist for beta-radiation. STents And Restenosis Trial (START) was the first placebo-controlled randomized trial for in-stent restenosis with beta-radiation; herein, we report the 2-year clinical follow-up.. Two hundred and forty-four patients were randomized to active treatment, 232 patients to placebo (nonactive source train) treatment. The primary end point of efficacy was target vessel revascularization (TVR); primary safety end point was any major adverse cardiac event (MACE) at 8 months and 2 years. Two-year clinical outcome in patients receiving brachytherapy was based on 195 of 244 original patients (79.9%) and in the placebo arm on 183 of 232 original patients (78.9%). TVR was significantly reduced by 25%; from 36.6% (placebo) to 27.5% (brachytherapy) remained significant after 2 years (RR .7 [.57-.98], 95% CI -9.2 [-17.5-0.8]). The Kaplan-Meier analysis for TVR and MACE showed improvement beginning approximately 90 days after radiation and remained almost constant for the 2 following years. Freedom from TVR was significantly increased from 62.4% +/- 3.8% to 71.6% +/- 3.3% (P = .027) and freedom from MACE from 58.9% +/- 3.7% to 68.0% +/- 3.4% (P = .035).. The START trial shows for the first time that the initial beneficial effects of intracoronary brachytherapy with beta-radiation using 90 Sr/ 90 Y are maintained at 2-year clinical follow-up period.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Beta Particles; Brachytherapy; Coronary Angiography; Coronary Disease; Coronary Restenosis; Diabetes Complications; Disease-Free Survival; Female; Follow-Up Studies; Humans; Life Tables; Male; Middle Aged; Prognosis; Stents; Strontium Radioisotopes; Thrombophilia; Treatment Outcome; Yttrium Radioisotopes

We sought to determine the correlates of failure following intracoronary radiation therapy (IRT) with Sr-90 using the Novoste Beta-Cath system for the treatment of in-stent restenosis (ISR) in a broad range of patients. IRT has been shown to be more efficacious compared to placebo for the treatment of ISR in large randomized trials. However, even in patients treated with IRT, major adverse cardiac events occur in approximately 20% of cases on follow-up. This trial sought to elucidate the correlates of failure following successful IRT for ISR. To determine the correlates of IRT failure, we retrospectively compared the demographics, lesion characteristics, and clinical outcomes of 102 consecutive patients with ISR treated with Sr-90 from September 1998 to July 2001. IRT failure was defined as death, myocardial infarction (MI), or target vessel revascularization (TVR) due to repeat ISR on follow-up. A comparison of the clinical and angiographic profile of IRT failures (n = 16) vs. IRT successes (n = 86) revealed that a history of smoking (75% vs. 40%; P = 0.012), current use of calcium channel blockers (84% vs. 45%; P = 0.013), ostial location of target lesion (44% vs. 16%; P = 0.020), and mean posttreatment minimal luminal diameter (MLD; 1.64 +/- 0.19 vs. 2.21 +/- 0.29 mm; P < 0.001), respectively, were correlated with failure using univariate analysis. After multivariate regression analysis, the correlates of failure that remained significant were treatment of an ostial lesion (OR = 31.2; 95% CI = 2.6-382.7; P = 0.007) and final posttreatment MLD (P < 0.001). Ostial location of target lesion and smaller posttreatment MLD are correlated with subsequent death, MI, and TVR following therapy with Sr-90 for ISR.

Topics: Aged; Beta Particles; Blood Vessel Prosthesis Implantation; Brachytherapy; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Endpoint Determination; Female; Follow-Up Studies; Humans; Illinois; Incidence; Male; Middle Aged; Multivariate Analysis; Randomized Controlled Trials as Topic; Retrospective Studies; Severity of Illness Index; Statistics as Topic; Stents; Strontium Radioisotopes; Treatment Failure

The management of diabetic patients with restenosis after percutaneous coronary intervention remains a significant challenge. Diabetic patients remain at significant risk of restenosis despite stent implantation. This retrospective analysis was performed to determine the extent to which vascular brachytherapy improves late clinical and angiographic outcomes in diabetic patients compared to conventional therapy and compared to patients' nondiabetic counterparts.. Pooled data from two studies (START [Stents and Radiation Trial] and START-40 trials) of patients (204 diabetic, 477 nondiabetic) receiving vascular brachytherapy (VBT) with a (90)Sr/(90)Y source after conventional percutaneous coronary intervention for in-stent restenosis comprise the study population. The radiation delivery system used in both studies was the Beta-Cath system. The prescribed dose at 2 mm from the centerline of the source axis was 18.4 Gy or 23 Gy, depending on vessel diameter. The reference vessel diameter, minimal lumen diameter, and percent diameter stenosis were measured before the intervention, at the conclusion of the procedure, and at the 8-month follow-up examination. The Breslow-Day test was used to formally assess the similarity of treatment effect between diabetic and nondiabetic patients.. Target lesion and target vessel revascularization rates and angiographic restenosis rates in diabetic and nondiabetic patients treated with beta radiation or placebo were analyzed. Diabetic patients were more likely to have longer and more complex coronary lesions. In-hospital outcomes in diabetic and nondiabetic patients were similar, irrespective of treatment status. At 8 months, patients treated with beta radiation exhibited less target lesion revascularization (diabetic: 10.9% vs. 22.7%, p = 0.02; nondiabetic: 12.8% vs. 22.3%, p = 0.007) and less target vessel revascularization (diabetic: 14.7% vs. 25.3%, p = 0.06; nondiabetic: 16.6% vs. 23.6%, p = 0.06) compared to placebo. In-stent binary angiographic restenosis was lower in irradiated patients (diabetic: 19.4% vs. 37.3% for placebo, p = 0.01; nondiabetic: 12.9% vs. 43% for placebo, p < 0.001). However, restenosis beyond the stent site reduced the impact of VBT, regardless of diabetic status. The magnitude of the treatment effect for target lesion and target vessel revascularization rates was similar between diabetic and nondiabetic patients.. Previously published institutional experiences have suggested that diabetic patients benefit from the use of VBT in the management of in-stent restenosis. This analysis now provides direct evidence to support the role of beta radiation VBT in this patient population. Diabetic patients undergoing this therapy are just as likely to benefit from it as their nondiabetic counterparts.

Topics: Beta Particles; Brachytherapy; Coronary Angiography; Coronary Restenosis; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Retrospective Studies; Stents; Strontium Radioisotopes; Yttrium Radioisotopes

Postcoronary angioplasty vascular brachytherapy (VBT) has emerged as a successful intervention for restenosis prevention in some clinical scenarios. Longer-term follow-up after VBT in de novo nonstented lesions has not been reported.. Thirty patients treated with post-percutaneous transluminal coronary angioplasty (PTCA) VBT with Sr90 underwent clinical and angiographic follow-up at 6 and 24 months. Specific vessel segment quantitative coronary angiographic analyses were performed to identify radiation edge effects. Nineteen patients who had not undergone index procedure stenting or target vessel revascularization (TVR) over the 2-year period were analyzed separately. Of the 30 patients, 3 underwent TVR by 6-month follow-up. An additional 4 patients required TVR between 6 and 24 months. In the total cohort of 26 patients undergoing angiographic follow-up at 6 and 24 months, an increase in minimal lumen diameter of the initial target segment was noted at 6 months compared with postprocedure analysis (2.31+/-0.48 versus 2.04+/-0.43 mm, P<0.05). At 24 months, this was no longer significant (2.19+/-0.61 mm). In the proximal segments of the entire cohort and the nonintervened subgroup, the principal late loss occurred over the first 6 months with no additional late loss at 2-year follow-up. The distal segments remained stable over the entire follow-up period.. Although some late failures of post-PTCA VBT are seen between 6 and 24 months, most treated vessels remain stable with no late loss or additional luminal increase beyond the 6-month period. This suggests that late aneurysm formation and significant late edge restenosis are unlikely in VBT after PTCA of de novo lesions for up to 2 years.

Topics: Angioplasty, Balloon, Coronary; Brachytherapy; Cohort Studies; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Dose-Response Relationship, Radiation; Female; Follow-Up Studies; Humans; Male; Secondary Prevention; Strontium Radioisotopes; Survival Rate; Treatment Outcome; Vascular Patency

After conventional treatment of in-stent restenosis, the incidence of recurrent clinical restenosis may approach 40%. We report the first multicenter, blinded, and randomized trial of intracoronary radiation with the use of a 90Sr/90Y beta-source for the treatment of in-stent restenosis.. After successful catheter-based treatment of in-stent restenosis, 476 patients were randomly assigned to receive an intracoronary catheter containing either 90Sr/90Y (n=244) or placebo (n=232) sources. The prescribed dose 2 mm from the center of the source was 18.4 Gy for vessels between 2.70 and 3.35 mm in diameter and 23.0 Gy for vessels between 3.36 and 4.0 mm. The primary end point, ie, clinically driven target-vessel revascularization by 8 months, was observed in 56 (26.8%) of the patients assigned to placebo and 39 (17.0%) of the patients assigned to radiation (P=0.015). The incidence of the composite including death, myocardial infarction, and target-vessel revascularization was observed in 60 (28.7%) of the patients assigned to placebo and 44 (19.1%) of the patients assigned to radiation (P=0.024). Binary 8-month angiographic restenosis (> or =50% diameter stenosis) within the entire segment treated with radiation was reduced from 45.2% in the placebo-treated patients to 28.8% in the 90Sr/90Y-treated patients (P=0.001). Stent thromboses occurred in 1 patient assigned to placebo <24 hours after the procedure and in 1 patient assigned to 90Sr/90Y at day 244.. The results of this study demonstrated that beta-radiation using 90Sr/90Y is both safe and effective for preventing recurrence in patients with in-stent restenosis.

Topics: Beta Particles; Brachytherapy; Cardiac Catheterization; Cineangiography; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Radiotherapy Dosage; Secondary Prevention; Stents; Strontium Radioisotopes; Survival Rate; Treatment Outcome; Vascular Patency; Yttrium Radioisotopes

Topics: Angioplasty, Balloon, Coronary; Beta Particles; Blood Platelets; Brachytherapy; CD40 Ligand; Clopidogrel; Coronary Restenosis; Coronary Thrombosis; Female; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Membrane Glycoprotein IIb; Prospective Studies; Stents; Strontium Radioisotopes; Ticlopidine; Yttrium Radioisotopes

We report our initial experience in 10 consecutive patients who underwent transradial coronary brachytherapy for in-stent restenosis using a 90Sr/Y source and the Novoste Beta-Rail system. In all patients, procedures were successfully completed using a right transradial approach. We performed the procedures with the Beta-Rail catheter using 7 Fr (Zuma II, Medtronic, MN; n = 5) or 8 Fr (Cordis, Miami, FL; n = 5) guiding catheters. All lesions were successfully dilated and no additional stent was inserted. We used a 40 mm source (n = 3) or a 60 mm source (n = 7) with manual stepping in four cases. In three cases, we did one stepping, and in one case, we did three steppings. The mean dwell time was 195 plus minus 44 sec. The mean delivered dose was 23 +/- 3 Gy at 2 mm distance from the source. No radiation treatment was interrupted. Mean fluoroscopy time was 26 +/- 13 min. Procedural success was achieved in all patients. Three patients had mild CK elevations (< 3 times upper normal limit). All patients were pretreated with clopidogrel (300 mg) and combined treatment with aspirin + clopidogrel is to be continued for at least 1 year. Clinical follow-up up to 3 months has not yielded any complication and all patients have remained free from angina.

Topics: Aged; Angioplasty, Balloon, Coronary; Brachytherapy; Cardiac Catheterization; Coronary Restenosis; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Radial Artery; Stents; Strontium Radioisotopes; Treatment Outcome; Ultrasonography, Interventional

Since late vessel failure has been speculated as a significant limitation of vascular brachytherapy (VBT), we conducted a prospective clinical evaluation at 6, 12, 24, 36 and 60 months follow-up after irradiation with (90)Sr/(90)Y for in-stent restenosis (ISR) regardless of the patient's symptomatic status. Complete five-year follow-up is reported for 104 consecutive patients. The cumulative rate of death was 13.5% (6 months: 0.96%; 12 months: 2.88%; 24 months: 4.81%; 36 months: 7.69%), of acute myocardial infarction 4.81% (2.88%; 4.81%; 4.81%; 4.81%), of late thrombotic occlusion 4.81% (3.85%; 4.81%; 4.81%; 4.81%), of target lesion revascularization (TLR) 27.9% (8.65%; 12.5%; 17.3%; 21.2%), of target vessel revascularization (TVR) 43.3% (12.5%; 19.2%; 22.1%; 29.8%), and of all major adverse cardiovascular events (MACE) 61.5% (16.3%; 26.9%; 31.7%; 42.3%), respectively. Considered that the annual incidence of TVR after the first year following drug-eluting stenting for in-stent restenosis has been reported as approximately 3% per year, an incidence of 5.8% per year following VBT of our study population clearly indicates a more pronounced, delayed and, even in the fifth year after the index procedure, ongoing restenotic process following beta-irradiation of in-stent restenotic lesions associated with clinically relevant adverse cardiovascular events.

Topics: Aged; Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Brachytherapy; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Heart; Humans; Male; Middle Aged; Prospective Studies; Stents; Strontium Radioisotopes; Treatment Outcome; Yttrium Radioisotopes

Cardiac disease is one of the most important causes of death in the world. Coronary artery stenosis is a very common cardiac disease. Intravascular brachytherapy (IVBT) is one of the radiotherapy methods which have been used recently in coronary artery radiation therapy for the treatment of restenosis. (90)Sr/(90)Y, a beta-emitting source, is a proper option for cardiovascular brachytherapy. In this research, a Monte Carlo simulation was done to calculate dosimetry parameters and effective equivalent doses to the heart and its surrounding tissues during IVBT. The results of this study were compared with the published experimental data and other simulations performed by different programs but with the same source of radiation. A very good agreement was found between results of this work and the published data. An assessment of the risk for cardiac and other sensitive soft tissues surrounding the treated vessel during (90)Sr/(90)Y IVBT was also performed in the study.

Topics: Algorithms; Beta Particles; Brachytherapy; Computer Simulation; Coronary Restenosis; Heart; Humans; Monte Carlo Method; Phantoms, Imaging; Radiometry; Radiotherapy Dosage; Relative Biological Effectiveness; Strontium Radioisotopes; Yttrium Radioisotopes

The purpose of this study was to identify potential predictors, including clinical, procedural, angiographic, and intravascular ultrasound (IVUS) parameters, for recurrent in-stent restenosis (ISR) following beta-radiation 90Strontium/Yttrium (90Sr/Y) in a large multicenter trial.. Although adjunct brachytherapy reduces recurrent ISR after primary catheter-based intervention, recurrence of stenosis after brachytherapy still occurs.. We analyzed 185 IVUS cohort patients in the STent And Restenosis Therapy (START) 40/20 trial where a 40-mm, 90Sr/Y, radioactive source train was exclusively used for treatment of ISR to be treatable with a 20-mm balloon.. Thirty-nine patients underwent target lesion revascularization. Preliminary univariate analysis showed that age, smoking, balloon/artery ratio, geographic miss, minimum lumen diameter, and diameter stenosis at baseline were associated with target lesion revascularization, while none of IVUS variables were (minimum lumen area, minimum stent area, or residual plaque burden). The multivariate logistic regression analysis showed that younger age, lower balloon/artery ratio, and presence of geographic miss were independent predictors of target lesion revascularization.. Even with adjunct beta-radiation therapy, initial mechanical optimization, such as appropriate balloon sizing and positioning, may be critical for the prevention of recurrent ISR.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Angioplasty, Balloon, Coronary; Beta Particles; Blood Vessel Prosthesis Implantation; Brachytherapy; Coronary Angiography; Coronary Artery Bypass; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Radiopharmaceuticals; Recurrence; Stents; Strontium Radioisotopes; Treatment Outcome; Ultrasonography, Interventional; Yttrium Radioisotopes

Topics: Adult; Aged; Aged, 80 and over; Beta Particles; Brachytherapy; Coronary Restenosis; Female; Humans; Male; Middle Aged; Stents; Strontium Radioisotopes; Yttrium Radioisotopes

Because late vessel failure has been speculated as a possible limitation of vascular brachytherapy, we conducted a prospective clinical evaluation at 6, 12, 24, and 36 months of follow-up after irradiation with strontium-90/yttrium-90 for in-stent restenosis, regardless of the patient's symptomatic status. We report complete 3-year follow-up data for 106 consecutive patients. The cumulative rate of death at 6, 12, 24, and 36 months was 0.9%, 0.9%, 0.9%, and 1.9% respectively. The corresponding rates for acute ST-elevation myocardial infarction were 2.8%, 4.7%, 4.7%, and 4.7%, respectively. The cumulative rate of late thrombotic occlusion at 6, 12, 24, and 36 months was 3.8%, 4.7%, 4.7%, and 4.7%, respectively. The corresponding rates of target lesion revascularization and target vessel revascularization were 8.5% and 12.3% (p = 0.046), 14.2% (p = 0.157) and 18.0% (p = 0.046), 12.3% and 18.9% (p = 0.008), and 21.7% (p = 0.083) and 29.2% (p = 0.005), respectively. The cumulative rate of all major adverse cardiovascular events at 6, 12, 24, and 36 months was 16.1%, 24.5% (p = 0.003), 27.4% (p = 0.083), and 35.8% (p = 0.003), respectively. In conclusion, these results indicate a delayed and, even in the third year after the index procedure, continued restenotic process after beta irradiation of in-stent restenotic lesions.

Topics: Aged; Blood Vessel Prosthesis Implantation; Brachytherapy; Coronary Angiography; Coronary Restenosis; Disease-Free Survival; Female; Follow-Up Studies; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Radiopharmaceuticals; Stents; Strontium Radioisotopes; Treatment Outcome; Yttrium Radioisotopes

Accurate patient-specific dosimetry in intravascular brachytherapy (IVBT) is generally difficult due to the extremely high-dose gradient, complexity of treatment device, and patient-specific geometry (e.g., calcification, stent, curvature, movement of target). The purpose of this study is to analyze quantitatively and systematically the dose effects of calcification, stent, guidewire, and source curvature on clinical dosimetry in an IVBT procedure, and propose a method that can be used to assess these effects in routine clinical practice.. Monte Carlo techniques were used to calculate 3-D dose distribution in both homogeneous and inhomogeneous media for three most commonly used IVBT sources: (90)Sr beta (Novoste), (192)Ir gamma (Cordis/Best), and (32)P beta (Guidant). Dosimetric perturbations in the presence of metallic stents, calcified plaques, metallic guide wires, and source curvature were studied for situations commonly encountered in the clinic. The importance of each of these perturbations and their practical influence on patient-specific dosimetry were analyzed. Factors (plaque, stent, guidewire, and curvature) that may be used to correct/reduce these perturbations were introduced to prevent dosimetric cold spots during IVBT. Practical methods of using these correction factors are proposed.. Dose perturbations are significant due to the presence of source curvature, metallic stents, calcified plaques, and metallic guide wires, especially for beta sources. These perturbations can be as high as 30% under normal clinical conditions, although they can be much higher in extreme situations. Empirical relationships of plaque factor with the thickness of calcified plaque, stent factor with stent metallic surface area, guidewire with guidewire thickness, and curvature factor with the bending angle are derived. These relationships are found to be useful in improving clinical dose accuracy in IVBT treatment planning or dose evaluation after treatment.. Significant dose perturbations due to the presence of source curvature, metallic stents, calcified plaques, and guide wires have been found in IVBT for in-stent restenosis. Because it has been reported that, with the current prescriptions for IVBT, higher doses consistently improve treatment outcomes, the empirical method derived from this work can be used to assess cold spots dosimetrically, thus improving patient-specific dosimetry for IVBT.

Topics: Blood Vessel Prosthesis Implantation; Brachytherapy; Calcinosis; Combined Modality Therapy; Coronary Restenosis; Dose Fractionation, Radiation; Equipment Design; Humans; Iridium Radioisotopes; Monte Carlo Method; Phosphorus Radioisotopes; Radiotherapy Planning, Computer-Assisted; Stents; Strontium Radioisotopes

Intracoronary brachytherapy after percutaneous transluminal coronary angioplasty (PTCA) is usually performed with catheter-based treatment techniques in a straight vessel segment. There is a growing interest for treatment of bifurcations, which requires consecutive positioning of the source in main vessel and side branch.. In-house developed software (IC-BT doseplan) is used to explore the optimal positioning of the source in modelled bifurcations with different shape for the source types available in our hospital, i.e. (90)Sr/(90)Y, (32)P and (192)Ir. The results were summarised in look-up tables. The usefulness of these look-up tables was tested on various clinical examples.. Tabulated results for the modelled bifurcations yield an estimation of the distance between the sources (gap width) in relation to the geometry and source type: (90)Sr/(90)Y gap range 3-8.5 mm, (32)P gap range 2-7 mm and (192)Ir gap range 3.5-8 mm. The average dose relative to 2 mm from the source axis is: (90)Sr/(90)Y, (mean+/-SD) 120+/-40%; (32)P, 125+/-50% and (192)Ir, 120+/-22%. The look-up tables also provide the coarse location and value of maximum and minimum dose: (90)Sr/(90)Y, 220-60%, (32)P, 230-55% and (192)Ir, 170-85%. It appeared that the look-up tables provide a good approximation of the optimal gap width in the clinical examples.. Tabulated optimal gap widths are very useful for quick estimation of the required gap width for a given bifurcation and source type, in case the prescribed dose in both vessels is the same. In unfavourable geometries there is a risk of local underdosage. Individual treatment planning using a program such as IC-BT doseplan is then recommended.

Topics: Angioplasty, Balloon, Coronary; Beta Particles; Brachytherapy; Coronary Restenosis; Coronary Vessels; Humans; Iridium Radioisotopes; Models, Biological; Phosphorus Radioisotopes; Radiotherapy Dosage; Strontium Radioisotopes; Yttrium Radioisotopes

The purpose of this analysis was to evaluate if overdosage during intracoronary irradiation due to overlapped source stepping may result in long-term morphologic changes in vessel anatomy.. Baseline angiograms of patients with in-stent restenosis undergoing coronary reintervention followed by intracoronary irradiation with source stepping were analyzed. Overlapping was considered present for the segment with overlapped reference isodose length (RIL) (RIL = segment with > or = 90% of reference dose at 1 mm vessel wall depth). Baseline and 6-months follow-up volumetric intravascular ultrasound (IVUS) analysis were performed for the overlapped segment and for proximal and distal segments of equal length.. Overlapping was found in six patients (three patients: (32)P treatment; three patients: (90)Sr/Y treatment); final analysis was performed in four patients. Comparison of the baseline and follow-up IVUS volumetric parameters revealed no significant change in lumen or vessel volumes at segments of overlaps in comparison to proximal and distal reference segments.. Increased dosage due to overlapping during source stepping is not associated with morphologic changes in vessel anatomy at follow-up.

Topics: Angioplasty, Balloon; Coronary Restenosis; Coronary Vessels; Dose-Response Relationship, Radiation; Humans; Imaging, Three-Dimensional; Phosphorus Radioisotopes; Prospective Studies; Strontium Radioisotopes; Ultrasonography, Interventional

Intravascular brachytherapy (IVBT) has been recognized as a preferred treatment for coronary in-stent restenosis (ISR) in routine practice. Stents made of high-Z materials will inevitably perturb the dose distribution of IVBT. In this work, we have conducted a systematic study on these dose perturbations for three commercially available IVBT sources.. The EGSnrc Monte Carlo codes were used to calculate the dose distributions for the 90Sr, 32P, and 192Ir IVBT sources with and without a metallic stent in place. The ring stent type made of different material and with different strut size, metallic surface area (MSA), and radius was studied.. Calculations show that dose enhancement of 5% to 20% occurs inside stent in the region close to the stent struts (luminal side) for all three sources. In the region outside stent (adventitial side), dose reduction of 5% to 20% is observed for a beta source, whereas the dose effect is negligible for the gamma source. For a given stent design, the tantalum stent yields a larger dose effect than other stents made of steel, Ti, Ni, or nitinol. It is found that the dose effect significantly depends on strut thickness, and it is strongly correlated to MSA. The MSA may be used to characterize the dose effect of a stent. Sample empiric equations to relate the dose perturbations to MSA for a given source, a stent material, and a strut thickness were derived.. The dose perturbations due to the presence of metallic stents were found to be significant in IVBT for ISR. The dose effects of a stent can be estimated from its MSA based on derived empiric equations. The data presented are practically useful to consider the dose effects of stents in dose evaluation/treatment planning for using IVBT to treat ISR.

Topics: Brachytherapy; Coronary Restenosis; Equipment Design; Half-Life; Humans; Iridium Radioisotopes; Monte Carlo Method; Phosphorus Radioisotopes; Radiotherapy Dosage; Stents; Strontium Radioisotopes

Although randomized clinical trials have demonstrated efficacy of coronary irradiation versus placebo for the treatment of in-stent restenosis (ISR), durable long-term benefit in community practice is less well defined. From January 1, 2001, through June 30, 2002, consecutive percutaneous coronary intervention (n = 3,869) were analyzed at our center with a total of 330 patients undergoing coronary irradiation for ISR (53, Ir192; 12, P32; 265 Novoste Sr90). Novoste Sr90 was successfully performed in 265 of 270 (98%) of patients attempted by 10 operators. The mean patient age was 63 years (range 35 90) with 55% male (145/265) and 45% female (120/265). ISR anatomic subsets included multi-lesion (45/265; 17%), multi-vessel (27/265; 10.0%) and saphenous vein graft (16/265; 6.0%) interventions. At a mean follow-up of 10.5 2.8 (SD) months, fifty-three (20%) of the Novoste Sr90 treated patients had returned for symptoms requiring repeat angiography. Of these, 23 patients had repeat percutaneous coronary intervention (PCI) including 2 target site revascularizations (TSR), twelve non-TSR (distinct from the radiated segment of the target vessel), and 9 non-target vessel revascularizations (TVR). Coronary artery bypass surgery was performed in 11 total patients, 4 due to TSR, and 7 due to non-TVR. Clinical TSR was 2.3% (6/265) and TVR was 6.8% (18/265). In conclusion, the Novoste SR90 Beta-Cath System for the treatment of ISR is associated with a high procedural success rate and low TSR and TVR. Revascularization in follow-up is predominantly due to progressive disease outside the radiated segment and aggressive secondary prevention, especially prolonged anti-platelet therapy, appear critical to long-term procedural success.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Beta Particles; Community Health Services; Coronary Disease; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ohio; Radiography; Stents; Strontium Radioisotopes; Treatment Outcome

Coronary artery brachytherapy may require treatment of lesions longer than a single source length. A treatment option is tandem positioning of the single source. This study presents relative dosimetric measurements of a cardiovascular brachytherapy source and the dosimetric characteristics in the junction region of tandem treatments. Measurements were carried out using a Novoste Beta Cath 90Sr/90Y 40 mm beta source in a plastic water phantom. Radiochromic MD-55-2 film, calibrated using both 6 MV photon and 6 MeV electron beams from a linear accelerator, was used as the dosimeter. Dose distributions around a single source and in the junction region of tandem irradiation were measured. Measurements of the near field dose as close as 1.2 mm from the source are presented. Significant over- or underdoses in the junction region of tandem irradiation were quantified. At a radial distance of 2 mm from the longitudinal axis of the source, the dose value in the middle of the junction region, normalized to the dose at 2 mm midline single source, was about 182% for a 2-seed overlap and 16% for a 2-seed gap, respectively. Dose distributions in the junction region as a function of source overlap and radial distance have fairly high gradients and exhibit characteristic patterns. The fraction of prescription dose was found to have a sigmoidal dependence on overlap size, for radial distances ranging between 1.2 and 3 mm. The parameters of these sigmoids, quantified as functions of radial distance, could be used to provide quick and reasonable over/underdose estimates, given any potential overlap or gap in the junction area, with an uncertainty within 10%.

Topics: Beta Particles; Brachytherapy; Coronary Restenosis; Film Dosimetry; Humans; Piperazines; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Computer-Assisted; Reproducibility of Results; Sensitivity and Specificity; Strontium Radioisotopes; Vascular Diseases; Yttrium Radioisotopes

In-stent restenotic lesions have been problematic for many patients with the need for multiple repeat percutaneous coronary interventions (PCI). The need for repeat PCI has been significantly reduced in patients since the advent of vascular brachytherapy. In-stent restenosis resulting in bifurcation presents even more of a challenge. The use of radiation therapy for the treatment of this kind of lesion has not yet been reported. The purpose of this paper is to present five cases of radiation therapy in bifurcation in-stent restenotic lesions using the intraluminal beta radiation catheter delivery system (Beta-Cath System, Novoste Corporation, Norcross, Georgia).. We reviewed the database of patients enrolled in our Compassionate Use Registry between August 1999 and April 2002. The data is reported for 5 patients who received radiation in both branches of bifurcation lesions with the Beta-Cath catheter system.. The mean diameter of the vessels was 3.1 mm 0.5 mm. The dose administered was from 18.3 to 23 Gy, with an overlap of 3.3 to 10.3 mm; the hinge angle between the branches went from 43.3 to 65.4 . Angiographic follow-up was obtained at 6 months in 4 patients, with a single patient showing a focal (< 5 mm) edge lesion treated by balloon angioplasty (TVR no TLR). No aneurysms or zones of ectasia were noted.. Beta radiation with the Beta-Cath catheter system appears to be safe, secure and clinically useful in in-stent restenotic bifurcation lesions.

Topics: Angioplasty, Balloon; Beta Particles; Brachytherapy; Canada; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Humans; Iridium Radioisotopes; Male; Middle Aged; Prospective Studies; Radiometry; Stents; Strontium Radioisotopes; Treatment Outcome

Three radiation sources have been approved for commercial use in vascular brachytherapy. The beta sources ((90)Strontium and (32)Phosphorous) are more popular because of less radiation protection concerns than gamma sources. Because (90)Strontium has a longer half-life than (32)Phosphorous, it requires less frequent source exchanges. Also, because (90)Strontium is more penetrating, a similar benefit can be achieved with lower delivered doses. Based on these advantages, (90)Strontium is the preferred isotope for vascular brachytherapy.

Topics: Angioplasty, Balloon, Coronary; Brachytherapy; Coronary Restenosis; Humans; Iridium Radioisotopes; Phosphorus Radioisotopes; Strontium Radioisotopes; Yttrium Radioisotopes

Topics: Animals; Brachytherapy; Coronary Restenosis; Cricetinae; Dyspnea; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Models, Animal; Patient Compliance; Point-of-Care Systems; Stents; Strontium Radioisotopes; Treatment Outcome

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.. 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Brachytherapy; Coronary Artery Disease; Coronary Restenosis; Female; Humans; Male; Middle Aged; Stents; Strontium Radioisotopes; Survival Analysis; Treatment Outcome; Yttrium Radioisotopes

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Beta Particles; Brachytherapy; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Female; Follow-Up Studies; Humans; Male; Middle Aged; Radiotherapy Dosage; Safety; Stents; Strontium Radioisotopes; Treatment Outcome; Ultrasonography, Interventional; Yttrium Radioisotopes

To evaluate the safety and efficacy of a 40-mm 90Strontium/90Yttrium source train in the management of in-stent restenosis within native coronary arteries.. This multicenter, prospective registry was designed to compare the results of patients with in-stent restenosis treated with a 40-mm source train to the placebo arm of the previously reported randomized Stents and Radiation Trial (START). All patients entered in the registry were treated with repeat balloon angioplasty followed by intravascular brachytherapy. Radiation dose was prescribed based on vessel size. 18 Gy was delivered at 2 mm for vessel diameters between 2.75 and 3.35 mm, and 23 Gy was used for vessels between 3.36 and 4.0 mm. The efficacy endpoints for the START 40 registry included a reduction in the target lesion revascularization (TLR) rate, target vessel revascularization rates, and target vessel failure (TVF) at 8 months. Secondary angiographic efficacy endpoints were binary restenosis at 8 months, in-stent minimum luminal diameter (MLD), and late loss. The safety endpoints included major adverse cardiac events as well as late aneurysm formation. The registry was designed to allow a statistically valid comparison of these results to the placebo group of the START 30 trial. Quantitative angiographic analysis was performed on the 8-month follow-up examination. Rates of restenosis were evaluated for various segments of the treated vessel. A separate analysis was performed to evaluate the relationship between vessel injury length and the radiated segment.. A total of 207 patients were entered into the START 40 registry. The postprocedure angiographic results, including the postprocedure MLD and percent diameter stenosis, were similar between the START 40 patients and the placebo group from the START trial in the stented segment of the treated vessel. Eight-month angiographic follow-up was available on 150 patients from the registry. The TLR rate was significantly reduced when compared to the placebo group (11% vs. 22.4% respectively, p = 0.008). A similar reduction was seen in terms of target vessel revascularization (15.9% vs. 24.1%, p = 0.03). The 8-month MLD was found to be significantly larger in the START 40 patients (1.85 mm vs. 1.47 mm, p < 0.0001). The difference seen in the clinical endpoint of TVF (19.3% vs. 25.9%) did not reach statistical significance (p = 0.1). Analysis of the procedural angiograms revealed mismatch between the length of vessel injured and the location of the 90% isodose in 46% of the treated cases. Angiographic analysis revealed that geographic miss was associated with a higher rate of binary restenosis (32% vs. 18% p = 0.04) in the analysis segment.. This multicenter registry demonstrates the safety and efficacy of a 40-mm 90Strontium/90Yttrium source train in the management of patients with in-stent restenosis. Restenosis rates were lowered with the use of this longer source train when compared to the placebo arm of the START trial for lesions with a maximum vessel injury length of 20 mm. Angiographic analysis identified the importance of the accurate delineation of injury length and correct source positioning. These results support the continued use of beta radiation for the treatment of this disease process.

Topics: Brachytherapy; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Registries; Stents; Strontium Radioisotopes; Treatment Outcome; Yttrium Radioisotopes

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.. 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).. 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.

Topics: Aged; Angioplasty, Balloon, Coronary; Beta Particles; Brachytherapy; Coronary Restenosis; Disease-Free Survival; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Strontium Radioisotopes

Intravascular brachytherapy requires that the dose be specified within millimeters of the source. High dose gradients near brachytherapy sources require that the source-detector distance be accurately known for dosimetry purposes. Solid phantoms can be designed to accommodate these stringent requirements. This study reports dosimeter readings from 90Sr-90Y sources measured in water, A150, polystyrene and in an epoxy-based water-equivalent plastic. Measurements showed that while A150 and the epoxy-based plastic agreed well with water when the surface of the source contacted the detector housing, the relative response in the phantoms decreased with increasing depth in phantom, falling to approximately 0.55 those of water at a depth of 5 mm. Readings in polystyrene were within 4% of those in water between 1 and 2 mm depth. However, while polystyrene followed water more closely than the other two materials, at greater depths the relative response in polystyrene to water varied from 0.65 to 1.34. When the density of the materials is accounted for, the relative response in A150 is nearly constant with increasing areal density. Furthermore, the response in A150 shows the closest agreement with that in water of any of the solid materials for higher areal densities. For values below 0.3 g/cm2, polystyrene shows the closest agreement with water.

Topics: Angioplasty; Biophysical Phenomena; Biophysics; Brachytherapy; Coronary Restenosis; Humans; Phantoms, Imaging; Plastics; Polystyrenes; Radiometry; Radiotherapy Planning, Computer-Assisted; Strontium Radioisotopes; Water; Yttrium Radioisotopes