Intracoronary Radiation Research Articles

Repeat intracoronary β-brachytherapy using a rhenium-188-filled balloon catheter for recurrent restenosis in patients who failed intracoronary radiation therapy

Conventional percutaneous coronary intervention (PCI) in restenotic lesions after brachytherapy failure is associated with a high recurrence rate of restenoses and revascularizations. Intracoronary brachytherapy using a liquid rhenium-188-filled balloon in de novo or restenotic lesions safely and effectively reduced restenosis rates. We report clinical and angiographic data regarding the safety and efficacy of rhenium-188 brachytherapy in restenoses after brachytherapy failure. Fourteen patients with restenosis after brachytherapy failure received rhenium-188 beta-brachytherapy. Follow-up was performed angiographically after 6 months and clinically after 12 months. Primary clinical endpoint was the incidence of major adverse cardiac events (MACE) defined as any death, myocardial infarction or repeat revascularization in the target vessel within 12 months. Secondary angiographic endpoints were the binary restenosis rate and late loss in the total segment including edge effects at 6 months. The prescribed dose of 22.5 Gy (n=12) or 30 Gy (n=2) was successfully delivered in all patients. In two lesions, a bare-metal stent was implanted. The mean length of the irradiated segment was 40.0+/-15.7 mm. The mean diameter of the irradiation balloon was 2.96+/-0.37 mm. Angiographic follow-up was done in 13 of 14 patients. There was no edge stenosis or coronary aneurysm. Within the total segment, late loss was 0.39+/-0.64 mm and late loss index was 0.18+/-0.40 with a binary restenosis rate of 23%. Twelve months' clinical follow-up was available in all patients, which showed a MACE rate of 7% due to one target lesion revascularization (TLR). Intracoronary beta-brachytherapy with a liquid rhenium-188-filled balloon in restenoses after intracoronary radiation therapy failure including 12 months combined antiplatelet therapy is safe with respect to vessel thrombosis, late coronary occlusion or aneurysm formation. With limited use of stenting, angiographic and clinical follow-up for repeat brachytherapy were favorable and it is associated with low restenosis and target vessel revascularization rate.

Late Late Stent Thrombosis after Intracoronary Brachytherapy: Learning from Brachytherapy Experiences in the Drug-Eluting Stent Era

Stent thrombosis is generally a fatal complication after percutaneous coronary intervention. Combined antiplatelet therapy is recommended to prevent stent thrombosis in those patients who have undergone stenting. However, there are conflicting opinions on the appropriate duration of instituting antiplatelet treatment, especially after intracoronary radiation therapy or drug-eluting stent implantation, which are two situations closely associated with an increased risk of stent thrombosis. We report here on 2 cases of late stent thrombosis that occurred despite giving combined antiplatelet therapy, and these maladies developed more than 4 years after intracoronary brachytherapy. (Korean Circulation J 2006;36:324-327)

Randomized blinded clinical trial of intracoronary brachytherapy with 90Sr/Y beta-radiation for the prevention of restenosis after stent implantation in native coronary arteries in diabetic patients

Background We report a double-blind, randomized clinical trial of intracoronary β-radiation for prevention of restenosis after stent implantation in native coronary de novo lesions in diabetic patients. Methods After successful stent implantation in native coronary de novo lesions, 106 lesions in 89 diabetic patients were randomly allocated to treatment with β-radiation with 18 Gy at 1 mm vessel depth ( n=53) or placebo treatment ( n=53). Results 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 5 mm 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). Conclusions 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.

Comparison Between Sirolimus-Eluting Stents and Intracoronary Catheter-Based Beta Radiation for the Treatment of In-Stent Restenosis

We report the outcomes of patients who had in-stent restenosis (IRS) that was treated with intravascular brachytherapy (IVBT) or sirolimus-eluting stent (SES) implantation. The benefit of IVBT for treating ISR is well documented. SES implantation decreases first-time ISR and, in preliminary reports, has been used to treat ISR. Fifty consecutive patients who had ISR were treated; the first 25 patients underwent SES implantation and the next 25 patients were treated with IVBT using a beta-Cath System (a 40-mm strontium-90/yttrium-90 source). Quantitative angiographic and intravascular ultrasound follow-up were performed at 5.2 +/- 1.1 and 12.1 +/- 1.2 months; clinical follow-up was performed at 15 months. SES deployment and IVBT were successful in all patients. At 12-month follow-up, 8 patients who underwent IVBT had angiographic recurrence (4 in the stent and 4 at the stent edge); only 1 patient who underwent SES implantation developed recurrent ISR. At 12 months, in-stent late luminal loss was similar between the SES and IVBT groups (0.35 +/- 0.45 vs 0.34 +/- 0.46 mm, p = 0.9); however, in-stent net luminal gain was higher in the SES group than in the IVBT group (1.32 +/- 0.13 vs 0.57 +/- 0.19 mm, p <0.0001), and in-lesion late luminal loss was higher in the IVBT group (0.48 +/- 0.32 vs 0.16 +/- 0.42 mm, p = 0.004). At 12 months, intravascular ultrasound stent volume obstruction was higher after IVBT versus than after SES implantation (38.7% vs 6.7%, p <0.0001). At 15-month clinical follow-up, 64% and 96% (p <0.01) of patients who underwent IVBT and SES implantation, respectively, were free of major adverse cardiac events. In conclusion SES implantation for the treatment of ISR was effective and superior to catheter-based IVBT in preventing recurrent neointimal proliferation and angiographic restenosis at 1-year follow-up.

Optimizing dosimetry with high-dose intracoronary gamma radiation (21 Gy) for patients with diffuse in-stent restenosis

The efficacy of intracoronary gamma radiation (IRT-gamma) in reducing recurrent in-stent restenosis (ISR) is well established using doses of 14-18 Gy. We sought to examine whether an escalation in dose to 21 Gy is safe and confers additional benefit in reducing repeat revascularization and major adverse cardiac events (MACE) in patients with diffuse ISR. Forty-seven patients with diffuse ISR (lesion length 20-80 mm) in native coronary arteries (n=25) and saphenous vein grafts (n=22) underwent percutaneous transluminal coronary angioplasty and/or additional stents followed by IRT-gamma using the Checkmate system (Cordis) with a dose of 21 Gy. All patients were discharged with clopidogrel for 12 months and aspirin indefinitely. Six-month angiographic and 12-month clinical outcomes of these patients were compared to 120 patients treated with 18 Gy using the same system. At baseline, patients in the 21-Gy group had more multivessel, vein graft disease and history of prior myocardial infarctions and coronary artery bypass grafts (P<.001). The use of debulking devices and stents was less in this group (P<.001). Procedural and in-hospital complications were similar. Follow-up at 6 months revealed nonsignificant but lower late loss (in-stent, 0.33+/-0.7 mm; in-lesion, 0.41+/-0.6 mm) in the 21-Gy group compared to the 18-Gy group; follow-up at 12 months revealed a trend toward less overall myocardial infarction, although repeat revascularization and MACE rates were similar. IRT-gamma therapy for diffuse ISR lesions with a 21-Gy dose is clinically safe and feasible with marked reduction in late loss but does not confer additional benefit with regard to repeat revascularization and MACE when compared to a dose of 18 Gy.

Intracoronary Brachytherapy for Treatment of In-Stent Restenosis

Randomized, double-blind, placebo-controlled trials have demonstrated that intracoronary brachytherapy is more efficacious than placebo in reducing death, myocardial infarction, and target vessel revascularization at long-term follow up of patients with in-stent restenosis. Intracoronary brachytherapy is efficacious in treating totally occluded in-stent restenotic lesions, in treating de novo and in-stent restenotic lesions in saphenous vein grafts, in treating diffuse in-stent restenosis, in treating native coronary ostial in-stent restenotic lesions, in treating patients with diabetes with in-stent restenosis, in treating patients at high-risk for recurrence of restenosis, in treating elderly patients, and in treating patients who failed intracoronary radiation. Beta and gamma intracoronary brachytherapy are equally effective in treating in-stent restenosis. Long-term aspirin and clopidogrel should be administered for at least 1 year to reduce late vessel thrombosis. Inadequate radiation may cause edge stenosis.

Long-term clinical outcomes of dissections after intracoronary β-radiation with rhenium-188-diethylene triamine penta-acetic acid-filled balloon system

Background Intracoronary radiation with a rhenium-188 ( 188Re)-filled balloon is safe and efficiently reduces restenosis, but there is a potential risk of a 188Re-filled balloon induced dissection. Little is known about the effect of radiation on dissection resolution and the late clinical outcome of dissection after brachytherapy. Methods After successful catheter-based treatments of de novo or restenotic lesion, 256 patients were randomly assigned to the radiation or control group. The 188Re-filled balloon system was designed to deliver 17.6 Gy in 1.0-mm tissue depth. Results Dissections were identified in 15 patients among the 138 patients of the radiation group (10.9%). Additional stents were deployed in 10 patients to cover the flow-limiting dissection. Binary restenosis rate (53.3% vs. 16.3%, p=0.001) and target vessel revascularization (TVR) rate (53.3% vs. 11.1%, p<0.001) were significantly higher in patients with the dissection at 9 months. Geographic miss (GM) was identified in 4 of the 10 patients who underwent additional stenting. Binary restenosis rate in the GM group (100%; 4 of 4 patients) was significantly higher than the non-GM group (33.3%; 2 of 6 patients, p=0.02). Long-term follow-up of the patients with dissections who had not undergone TVR ( n=7, mean follow-up duration: 640.7±387.3 days) has demonstrated persistent unhealed dissections. Conclusions Intracoronary radiation impairs the healing process after vessel injury and residual dissection after brachytherapy leads to adverse clinical outcomes, which was mainly due to GM in case of stent implantation.

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.

NF-κB decoy potentiates the effects of radiation on vascular smooth muscle cells by enhancing apoptosis

NF-kappaB promotes cell survival against external stress such as radiation. We examined whether NF-kappaB decoy transfection enhances the antiproliferative effects of radiation on vascular smooth muscle cells (VSMCs) in vitro. The irradiation induced activation or nuclear translocation of NF-kappaB p65 in VSMCs was confirmed by immunofluorescence. NF-kappaB decoy transfection resulted in inhibition of the radiation-induced NF-kappaB activation in VSMCs and the subsequent reduction of transcription and translocation of ICAM, iNOS, and TNF-alpha, downstream molecules under the control of NF-kappaB. By using MTT assay, NF-kappaB decoy augmented the antiproliferative effects of radiation, where the effect of low dose radiation (2 and 8-Gy) of the cells transfected with NF-kappaB decoy was equivalent to the high dose (16-Gy) irradiated non-transfected cells at 48 h after irradiation: 1.06+/-0.16, 1.11+/-0.22, 1.20+/-0.25, respectively. The decrease in proliferation and survival of the radiation treated cells by flow cytometry analysis showed that NF-kappaB inhibition did not show any additive effects on the cell cycle of the irradiated VSMCs, while apoptosis was significantly increased after NF-kappaB decoy transfection in the irradiated VSMCs (apoptosis fraction: 13.33+/-2.08% vs. 26.29+/-7.43%, for radiation only vs. radiation+NF-kappaB decoy transfection, P < 0.05). In addition, at 48 h, NF-kappaB decoy transfection dose dependently (10 microM vs. 20 microM) inhibited proliferation of 16Gy-irradiated VSMCs, and showed greater antiproliferative efficacy than 100 microM sulfasalazine, a specific NF-kappaB inhibitor. These results indicate that NF-kappaB inhibition reduces proliferation and survival of irradiated VSMCs, likely by increased apoptosis rather than additive cell cycle arrest and suggest the possibility of adjunctive gene therapy using NF-kappaB decoy to improve efficacy and to decrease the adverse effects of intracoronary radiation therapy.

Drug-eluting stents for the treatment of in-stent restenosis

Treatment of in-stent restenosis (ISR) remains problematic despite the widespread application of drug-eluting stents (DES). Challenging lesion cohorts such as diffuse ISR and restenosis after failed intracoronary radiation therapy (IRT) maybe best treated with DES. The overall benefit of DES appears inferior to their utility in treating de novo coronary lesions. Randomised trials comparing DES and IRT will soon be available to determine the optimal therapy for ISR. The challenge to treat ISR in the DES era is the next frontier of interventional cardiology.

Angiographic and clinical outcomes of late total occlusion versus treatment failure without late total occlusion in patients after intracoronary radiation therapy for in-stent restenosis

This study aimed to compare the outcomes of patients with late total occlusion (LTO) versus patients with recurrence in the absence of LTO after intracoronary radiation therapy for in-stent restenosis. LTO, especially in the context of acute myocardial infarction, after intracoronary radiation therapy for in-stent restenosis, is associated with negative clinical outcomes after 6 and 12 months compared with in-stent restenosis without LTO.

Angiographic and three-dimensional intravascular ultrasound analysis of combined intracoronary beta radiation and self-expanding stent implantation in human coronary arteries

This study tested the combination of vascular brachytherapy (VBT) and self-expanding Wallstent implantation in coronary lesions of patients at high risk for restenosis as assessed angiographically by quantitative coronary analysis and by 3-dimensional intravascular ultrasound analysis. Twenty-nine "de novo" lesions were managed with a self-expanding stent alone (n = 19) or with a self-expanding stent after beta-VBT (n = 10) in 27 patients who had been identified by high levels of plasma angiotensin-converting enzyme as being prone to myointimal growth after stent implantation. At 6 months, the increase in stent strut diameter was similar in the 2 groups by quantitative coronary analysis and 3-dimensional intravascular ultrasound (Delta mean stent strut diameter -0.33 +/- 0.3 vs -0.40 +/- 0.3 mm, p = 0.5; Delta stent area -11.8 +/- 6.1 vs -12.0 +/- 6.1 mm(2), p = 0.9; Delta stent volume -96.9 +/- 112 vs -83.5 +/- 73 mm(3), p = 0.7; for groups treated with VBT and self-expanding stents and only self-expanding stents, respectively). In-stent neointimal proliferation was decreased in the group treated with VBT and self-expanding stents (minimal luminal diameter 2.5 +/- 0.8 vs 1.88 +/- 0.8 mm, p = 0.04) by quantitative coronary analysis (minimal luminal area 6.7 +/- 2.5 vs 4.1 +/- 1.9 mm(2), p = 0.01), by intravascular ultrasound, and proliferation volume (84.6 +/- 66.4 vs 159.2 +/- 103.5 mm(3), p = 0.05) by 3-dimensional intravascular ultrasound. Positive vessel and luminal remodelings were observed in 50% of the group treated with VBT and self-expanding stents and in 11% of the group treated only with self-expanding stents (p = 0.02). The combined use of VBT and self-expanding stents is a novel approach that enlarges vascular lumen by preventing vessel constriction and neointimal proliferation. The feasibility and good results of this experimental approach suggest that the simultaneous use of these 2 technologies may be an interesting alternative for difficult vascular districts with high restenosis rates, such as peripheral circulation in the lower limbs.

Two‐year clinical follow‐up results of intracoronary radiation therapy with rhenium‐188‐diethylene triamine penta‐acetic acid‐filled balloon

We investigated the 2-year clinical follow-up results as well as 6-month angiographic and clinical follow-up results of intracoronary radiation therapy using a rhenium-188-diethylene triamine penta-acetic acid ((188)Re-DTPA)-filled balloon system. The study comprised of 161 patients with significant de novo (83%) or in-stent restenosis (17%) lesions. Irradiation to deliver 17.6 Gy at a depth of 1.0 mm into the vessel wall was carried out after successful intervention. At 6-month follow-up, binary restenosis developed with significantly lower frequency in the radiation group than in the control group (24.3% vs. 46.3%; P = 0.009), although target lesion revascularization rate did not show significant benefit. At 2-year follow-up, cumulative target lesion revascularization rate was not significantly different between radiation group (n = 86) and control group (n = 75; 20.0% vs. 26.0%; P = 0.368). The rate of major adverse cardiac events including death, myocardial infarction, and target lesion revascularization did not show significant difference between two groups either (22.3% vs. 30.1%; P = 0.266). In conclusion, although significant reduction in restenosis rate was noted at 6-month angiographic follow-up, intracoronary radiation therapy mostly in patients with de novo lesion did not show significant clinical benefit in 6-month and 2-year follow-up results. The benefit was noted only in a small subgroup of patients with in-stent restenosis.

Two-year outcomes of repeated brachytherapy in patients with restenosis after intracoronary radiation therapy

This study compared the 2-year outcomes of repeat brachytherapy (n = 10) and conventional percutaneous intervention (n = 14) in patients with restenosis after intracoronary brachytherapy with a rhenium-188-filled balloon system. The short-term target lesion revascularization rate was significantly lower in the repeat brachytherapy group (0% vs 36%, p = 0.038), and additional target lesion revascularization was required in 2 patients with repeat brachytherapy during 2-year follow-up. There were no vascular complications related to repeat brachytherapy.

Brachytherapy: Potential therapy for refractory coronary spasm

We sought to demonstrate that brachytherapy reduces coronary spasm in refractory and highly symptomatic variant angina. In some patients with variant angina due to extensive vasoconstriction, intensive drug therapy fails to sufficiently relieve symptoms. In 18 patients with frequent angina episodes despite triple anti-anginal therapy, coronary spasm was induced by intracoronary acetylcholine (ACh) infusion. Five patients had spasm in a second vessel. Intracoronary radiation (20 Gy) was applied to vasospastic segments using a beta-emitting ((32)P) wire source centered within a Galileo balloon. Parameters of vessel function before and after brachytherapy were investigated. Before brachytherapy, artery diameters decreased (p < 0.0001) from 2.8 +/- 0.4 mm to 1.0 +/- 0.4 mm for the first vessels and from 3.1 +/- 0.3 mm to 1.0 +/- 0.2 mm for the second vessels. After brachytherapy (143 +/- 106 and 80 +/- 52 days for first and second vessels, respectively), ACh-induced vasoconstriction was significantly reduced. The ACh-induced changes in artery diameter before and after brachytherapy were -1.5 +/- 0.5 mm and -0.5 +/- 0.3 mm (p < 0.0001) for the first vessels and -1.4 +/- 0.3 mm and -0.4 +/- 0.2 mm (p < 0.01) for the second vessels, respectively. In non-irradiated spastic vessels, ACh-induced vasoconstriction remained unchanged (e.g., -1.7 +/- 0.6 mm, -1.6 +/- 0.3 mm, and -1.5 +/- 0.5 mm for second vessels, at first investigation, first follow-up, and immediately before brachytherapy, respectively). Angina frequency decreased from 15.6 +/- 6.0 to 2.2 +/- 2.4 angina episodes/week (p < 0.001) in treated patients. Brachytherapy is a potential therapy in patients with highly symptomatic variant angina.

Comparison of acute and long-term results and underlying mechanisms from sirolimus-eluting stent implantation for the treatment of in-stent restenosis and recurrent in-stent restenosis in patients in whom intracoronary radiation failed as assessed by intravascular ultrasound

In-stent restenosis (ISR), especially after vascular brachytherapy, is a therapeutic challenge. Sirolimus-eluting stent implantation is a promising new option for the treatment of patients with ISR. The efficacy of sirolimus-eluting stent implantation for the treatment of patients with their first episodes of ISR and with recurrent ISR due to the failure of vascular brachytherapy was compared using intravascular ultrasound imaging.

The role of brachytherapy and Cutting Balloon angioplasty in the current treatment of stent restenosis.

The Gamma I, START and INHIBIT trials conclusively demonstrate the feasibility, safety and efficacy of intracoronary radiation as the treatment of choice for stent restenosis. Further reports confirm this finding and extend the indications. Vascular brachytherapy should be made available for all patients with diffuse stent restenosis. Specific devices such as cutting balloons may improve the procedure but does not seem to have an impact alone on the evolution.

The Cutting Balloon for In‐Stent Restenosis:

Extraordinary advances have been made in the prevention, medical treatment, and the surgical and percutaneous intervention of coronary artery disease. However, despite the vast contribution of coronary artery stenting, coronary artery disease remains a major health problem. The massive treatment of symptomatic coronary artery disease with non-drug-eluting stents in the past, accounts for a large incidence of in-stent restenosis (ISR). We know today that in the following days after coronary artery angioplasty, new layers of intimal cells, called neo-intima, scaffold the endothelium forming a rubbery membrane. Numerous attempts have been made, and are still ongoing, to prevent the formation or to remove the neo-intima with suboptimal results and cost-effectiveness. Drug-eluting stents seem to be the most promising approach to date, however, the high cost of these devices may limit their use. In the mean time, new cases of ISR present to our cardiology practices. Because of its lower cost and identical technique to a regular balloon, the cutting balloon has emerged in numerous observational studies, and in a few randomized studies as a practical alternative to treat ISR. Although a few randomized studies have compared angioplasty with the cutting balloon versus angioplasty with a regular balloon, there are no randomized or economic studies comparing this device to excimer laser or intracoronary radiation in the treatment of this complication of coronary stenting. We reviewed the most prominent studies to date, on the performance of the cutting balloon in the treatment of ISR.

Effectiveness of sirolimus-eluting stent implantation for treatment of in-stent restenosis after brachytherapy failure

The impact of the use of sirolimus-eluting stents (SESs) in the treatment of in-stent restenosis in previously irradiated sites has not been adequately evaluated. Fifteen consecutive patients who underwent percutaneous coronary interventions using SESs in lesion sites previously intervened with intracoronary radiation therapy were identified. All stents were implanted successfully, and there were no major in-hospital complications. At 30-day follow-up, there was 1 case of subacute thrombosis that led to target lesion revascularization (TLR). At 6 months, 2 patients underwent TLR because of recurrent angina with angiographic restenosis, and 1 patient underwent target vessel revascularization distally to the SES site; no other major adverse cardiac events occurred at long-term follow-up (mean 17 ± 8 months).

Increased dosage during intracoronary irradiation due to overlapped source stepping shows no long-term adverse changes in vessel morphology.

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.