Intracoronary Radiation Research Articles

Endovascular brachytherapy to prevent restenosis after angioplasty

Endovascular radiotherapy is the first effective prophylaxis of restenosis after percutaneous transluminal angioplasty (PTA) and stenting. The FDA recently approved two devices for the delivery of intracoronary radiation following coronary artery stenting. Published multicenter, double-blind, randomized trials of intracoronary radiation therapy report good results for preventing in-stent restenosis, while the data for the peripheral circulation are still inconclusive. Beta-emitters are easier applicable and probably also safer, whereas gamma-emitters have been more extensively evaluated clinically so far. Primary indication for endovascular brachytherapy are patients at high risk for restenosis, such as previous restenoses, in-stent hyperplasia, long stented segment, long PTA lesion, narrow residual vascular lumen and diabetes. Data from coronary circulation suggest a safety margin of at least 4 to 10 mm at both ends of the angioplastic segment to avoid edge restenosis. To prevent late thrombosis of the treated coronary segment, antiplatelet therapy with clopidogrel and aspirin are recommended for at least 6 months after PTA and for 12 months after a newly implanted stent. An established medication regimen after radiotherapy of peripheral arteries is still lacking.

Impact of intracoronary radiation on in‐stent restenosis involving ostial lesions

The aim of this study was to compare 6-month clinical outcomes of patients with in-stent restenosis (ISR) involving the ostium treated with intracoronary radiation therapy (IRT) compared to placebo therapy, and also to nonostial lesions treated with IRT. Coronary interventions in ostial lesions have a high rate of recurrence of restenosis. The impact of IRT on ostial ISR has been inadequately characterized. We assessed patients enrolled in gamma (192-iridium) and beta (90-yttrium, 32-phosphorus) radiation trials for ISR at the Washington Hospital Center. Of patients receiving IRT, 105 (8%) patients had ostial ISR and 1,289 (92%) patients had nonostial ISR. Twenty-seven patients had ostial ISR and received placebo therapy. Baseline demographic and angiographic and procedural details were similar, except ostial IRT patients had a trend toward shorter lesions (15.4 +/- 10.8 vs. 24.1 +/- 12.2 mm; P < 0.001) and had a higher rate of saphenous vein graft disease (46% vs. 19%; P < 0.001) compared to nonostial IRT patients. At 6 months, ostial lesions treated with IRT for ISR had a reduced rate of target lesion revascularization (TLR) compared to ostial lesions treated with placebo (15% vs. 43%; P = 0.004). Outcomes at 6 months were similar for the ostial and nonostial IRT groups including TLR (15% vs. 14%; P = 0.80) and composite major adverse cardiac events (18% vs. 15%; P = 0.46). Intracoronary radiation therapy is effective for ostial in-stent restenotic lesions and should be comfortably used for this challenging anatomic location.

Predictors of late cardiac events following treatment with Sr-90 β-irradiation for instent restenosis

Background: Intracoronary radiation therapy (IRT) with Sr-90 using the Novoste Beta-Cath system has been shown to be an effective therapy for instent restenosis (ISR), but the temporal occurrence of cardiac events and the predictors of late complications require further investigation. Methods: We analyzed the demographics, lesion characteristics and clinical outcomes of 138 consecutive patients with ISR treated with IRT from September 1998 to March 2002. Major adverse cardiac events (MACE) were defined as death, myocardial infarction (MI) or target vessel revascularization (TVR). Characteristics of early (≤8 months) and late (>8 months) failures were analyzed. Results: Thirty-two (23.1%) of 138 patients had MACE on follow-up; 25% (8/32) of failures occurred late after treatment with IRT. A comparison of the clinical and angiographic profile of early and late failures using univariate analysis indicates no correlations to late failure following IRT. Duration to failure after IRT was 14.25±3.69 months in the late group compared to 4.63±2.86 months in the early group ( P<.001). Conclusions: Late MACE after IRT with Sr-90 for ISR occur beyond the traditional period for clinical restenosis in 25% of cases and are difficult to predict. Further study is warranted to identify patients at risk for the development of late complications after IRT.

Disappearance of intima over the stent and ulcer formation after intracoronary radiation for in-stent restenosis.

Little is known about the alterations of the vascular surface after radiation therapy for in-stent restenosis in humans, even though animal experiments suggest that delayed healing of the neointima is a cause of late thrombosis. Coronary angioscopy, together with coronary angiography, was performed at 3 months follow-up of 7 patients with in-stent restenosis who underwent beta-radiation therapy. Minimal lesion diameter (MLD) of the lesion increased from 1.00+/-0.30 mm (immediately before) to 2.44+/-0.39 mm (immediately after) and the MLD was well maintained 3 months later (2.34+/-0.62 mm) without any cases of restenosis. In 5 patients, the intima was so thin that some stent struts could be seen through it on angioscopy and in 2 of those, the intima over the stent had disappeared and 1 patient showed ulceration of the vascular wall beneath the stent. After intracoronary radiation therapy, the intima can become so thin that some stent struts are exposed to the lumen, which may be related to the occurrence of late thrombosis. Accordingly, patients who are treated with intracoronary radiation therapy may need long-term antiplatelet therapy.

Angiographic Outcomes and Predictors of Recurrent Restenosis after Cutting Balloon Angioplasty for the Treatment of In-Stent Restenosis

Background and Objectives:The optimal treatment for in-stent restenosis (ISR) is controversial, although intracoronary radiation therapy (ICRT) has provided the most consistent results to date. This study was designed to assess the early and late angiographic results, and to find independent predictors of recurrent restenosis, following cutting balloon angioplasty (CBA) for ISR. Subjects and Methods:Eighty patients (87 lesions) with first time ISR underwent CBA and systematic follow-up (FU) angiography. A conventional balloon was used before, or after, the CBA, if required. ICRT was used in 18 lesions (21%). A multivariate logistic regression analysis was performed. (Why?) Results:The ISR was focal (n=32, 37%), diffuse or proliferative (n=51, 58%) and occlusive (n=4, 5%). Procedural success was achieved in all 87 lesions (100%). No significant edge dissection occurred. The preand post-procedural diameter stenoses (DS) were 81.5±10.8% and 6.7±6.0%, respectively, and the preand post-procedural MLD (Define MLD?) 0.71±0.44 mm and 2.85±0.32 mm, respectively, with 2.14±0.44 mm of acute gain. A FU angiography was performed in 54 (78%) of the 69 lesions treated with CBA alone. The overall angiographic restenosis rate was 24% (13/54), with 9% (2/22) in the focal ISR and 34% (11/32) in the diffuse or occlusive ISR. The FU DS and MLD were 32.0±23.4% and 2.1±0.7 mm, respectively, with 0.79±0.69 mm of late loss. The length of a restenotic lesion (OR 12.2, 95% CI:1.3115.2, p=0.0286) was an independent predictor of recurrent restenosis. Conclusion:CBA is a simple and efficient first line treatment for ISR, with an acceptable restenosis rate, and the length of a restenotic lesion is an independent predictor of recurrent restenosis. In diffuse or occlusive ISR, more definite treatment modalities, such as ICRT combined with CBA or debulking techniques, might be required to reduce recurrent restenosis. (Korean Circulation J 2003;33 (3):196-204)

Long-Term Follow-Up Results of Intracoronary Beta-Radiation Therapy with a Rhenium-188 Diethylene Triamine Penta-Acetic Acid-Filled Balloon

Background and Objectives:Intracoronary irradiation has emerged as a successful intervention for the treatment of restenosis. However, the radiation process is complex, difficult and hard to perform. On the contrary, intracoronary radiation therapy using a Re-DTPA-filled balloon system is simple and inexpensive. The short-term follow-up results of this system have been reported, but the long-term results remain to be elucidated. The object of this study is to evaluate the short and long-term follow-up results of intracoronary radiation using a ReDTPA-filled balloon system in restenotic lesions. Subjects and Methods:Thirty-eight patients, with restenotic lesion after previous percutaneous coronary intervention, were selected from the SPARE trial (Seoul National University Post-Angioplasty RhEnium irradiation trial). There were 27 cases in the irradiation group, with 11 in the control group. Irradiation was performed in the restenotic lesions after successful interventions. The results of 6month angiographic and 6-month and 3-year clinical follow-up data were compared between the two groups. Results:A 6-month angiographic follow-up was performed in 33 patients (87%), 25 in the radiation group and 8 in control. Binary restenosis developed in 1 of 25 (4%) and 4 of 8 (50%) in the radiation and control groups, respectively (p=0.008). At the 6-month clinical follow-up, there were no significant differences in the event rates between the two groups. At the 3-year clinical follow-up, there was a significant difference in the target vessel revascularization:2 of 27 (7.4%) and 5 of 11 (45.4%) in the radiation and control groups, respectively (p=0.017). There were no deaths or myocardial infarctions. Conclusion:Radiation therapy using a ReDTPA-filled balloon system is feasible, and may be effective in improving the long-term outcomes in restenotic lesions. (Korean Circulation J 2003;33 (8):723-729)

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

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

Long-term outcome of patients treated with repeat percutaneous coronary intervention after failure of gamma-brachytherapy for the treatment of in-stent restenosis.

Although (192)Ir intracoronary brachytherapy has been demonstrated to dramatically reduce the recurrence of in-stent restenosis, up to 24% of these patients will still require repeat target-vessel revascularization. The short- and long-term outcomes of repeat percutaneous intervention in this population have not been characterized. Analysis was performed of all patients enrolled in the GAMMA-I and GAMMA-II brachytherapy trials who underwent repeat percutaneous target lesion revascularization (TLR) because of restenosis. Subjects were divided into 2 cohorts: those who had received (192)Ir brachytherapy and those randomized to placebo. Forty-five (17.6%) of a total of 256 patients whose index treatment was intracoronary radiation therapy and 36 (29.8%) of 121 patients whose index treatment was placebo required repeat percutaneous TLR. The mean time to this first TLR was 295+/-206 days in the irradiated group and 202+/-167 days in the placebo group (P=0.03). Acute procedural success occurred in 100% of irradiated patients and 94% of placebo controls (P=0.19). After the first TLR, a subsequent TLR was required in 15 (33.3%) of 45 brachytherapy patients versus 17 (47.2%) of 36 placebo failure patients (P=0.26). There was no significant difference in time to second TLR between the 2 groups. Other long-term major adverse event rates in both groups were comparable to those of other contemporary angioplasty/stenting series. In those patients who "fail" (192)Ir intracoronary brachytherapy for in-stent restenosis, treatment with (192)Ir delays the time to first TLR. Additionally, repeat percutaneous intervention in these patients is safe and efficacious in the short term, with acceptable long-term results.

Delivered dose and vascular response after beta-radiation for in-stent restenosis: retrospective dosimetry and volumetric intravascular ultrasound analysis.

Observations from previous intracoronary radiation therapy trials noted a considerable discrepancy between the prescribed radiation dose and the dose actually delivered. The aims of this study were to investigate the effect of actual delivered dose on vascular changes and to test the appropriateness of the current dose prescription. Serial volumetric intravascular ultrasound (IVUS) analysis was performed in 30 in-stent restenosis cases treated with a 40-mm (90)Sr/Y source train. The fixed dose was prescribed at 2 mm from the centerline of the source train (18.4 Gy at 2 mm for reference diameter < or =3.35 mm and 23 Gy for diameter > or =3.36 mm). Only stent segments with full radiation coverage and device injury were enrolled and divided into 2-mm-long subsegments (n=202). D(S90)EEM (the minimum dose absorbed by 90% of the external elastic membrane surface) was calculated as the delivered dose corresponding to each segment, assuming that the radiation catheter occupied the same position in the vessel as the IVUS catheter. Mean D(S90)EEM of 23.5+/-5.82 Gy (range 12.3 to 41.7 Gy) was delivered to these subsegments. Overall, intimal hyperplasia volume remained constant from postintervention to follow-up (2.23+/-1.10 to 2.32+/-1.09 mm3/m; P=NS). Regression analysis revealed there was no correlation between delivered dose intensity and changes in intimal hyperplasia volume. No particular dose-dependent complications were appreciated in this delivered dose range. The current dose-prescription protocol of (90)Sr/Y radiation to native in-stent restenosis lesions may provide substantial inhibition of neointimal reproliferation regardless of the actual delivered dose intensity.

Geographical miss during intracoronary irradiation: impact on restenosis and determination of required safety margin length

ObjectivesThe goal of this study was to evaluate the incidence and effects of underdosage of injured segments during intracoronary irradiation and to define the minimal length of safety margin required to avoid mismatched source placement. BackgroundUnderdosage of injured segments due to misplacement of active source has been suggested as the underlying mechanism for the occurrence of edge restenosis. MethodsBaseline angiograms of 112 vessels in 109 patients with in-stent restenosis undergoing coronary reintervention followed by intracoronary irradiation (192Ir: Checkmate, Cordis, Miami, Florida; 32P: Gallileo, Guidant, Houston, Texas; 90Sr/Y: Beta-Cath, Novoste, Norcross, Georgia) were analyzed. The distances between the outermost injury and outermost end of “reference isodose length” (RIL), defined as a segment with ≥90% of reference dose at 1 mm vessel wall depth, were measured. “Safety margin” was defined as the distance between the outermost injury and outermost end of the RIL, “geographical miss” (GM) as a complete injured segment not being covered by the RIL, and “restenosis” as the percent diameter stenosis >50%. ResultsBaseline angiographic analysis was performed for 224 edges in 112 vessels. Geographical miss was found in 46 (20.6%) edges. The incidence of target lesion restenosis within the 78 vessels with available follow-up was 43.3% for patients with GM versus 14.9% for patients with no GM (p = 0.005). Analysis of various injured segments exposed highest restenosis rates in injured segments with negligible irradiation (27.8%) in comparison with injured segments with dose fall-off (16.7%) or injured segments with full-dose irradiation (7.7%) (p = 0.006). Receiver operating curve analysis revealed a safety margin of 10 mm required per vessel (i.e., 5-mm safety margin/edge) to achieve 95% specificity of GM. ConclusionsGeographical miss is associated with a higher incidence of restenosis at the corresponding edges. Restenosis was more pronounced in injured segments with negligible irradiation than in injured segments at the dose fall-off zones. We recommend a safety margin of 10 mm per vessel to minimize GM.

Can we prevent in-stent restenosis?

Nowadays stent placement has replaced balloon angioplasty as the most commonly performed percutaneous coronary interventional procedure, mainly because of its better acute and chronic outcome. As a result, in-stent restenosis (ISR) has become a widespread problem. The incidence of ISR varies from 10% to 50% and depends on the absence or presence of several risk factors, such as small vessel size, longer lesions, and diabetes. Intravascular ultrasound studies have demonstrated that ISR is mainly caused by neointimal proliferation; consequently, this pathologic process has become the target of many preventive and therapeutic approaches. This article provides an overview of such management strategies, highlighting the rather disappointing experiences with mechanical and systemic drug therapies; the relative merits and disadvantages of intracoronary radiation; and the exciting yet realistic promise, embodied by the recent advancements in drug-eluting stent technology, of potentially eradicating ISR in the near future.

Effectiveness of radioactive tungsten source in the prevention of restenosis in stented porcine coronary arteries

Purpose : Intracoronary radiation has shown the potential to inhibit neointimal proliferation in porcine models of restenosis. The objective of this study was to determine whether intracoronary radiation using a new coiled wire of tungsten-188 ( 188W), a pure β emitter (half-life 69.4 days) is safe. In addition, a dose of 0 Gy, 18 Gy, or 25 Gy prescribed to 2 mm from the center of the source and delivered intraluminally is sufficient to prevent restenosis and free from adverse effects. Methods and Materials : Ten domestic swine underwent 13-mm stent implantation (SI) into two arteries, left anterior descending plus either the left circumflex or right coronary artery. After SI, a closed-end lumen radiation catheter was inserted to the treated artery and a 40-mm coiled 188W source was manually delivered to cover the stented segment and its margins. A total of 20 arteries were randomized to treatment with a radiation dose of 0, 18 Gy, or 25 Gy delivered to 2 mm depth from the center of the source. Four weeks after the procedure, the swine underwent angiography and intravascular ultrasound using automated pullback at 0.5 mm/s. before being killed and the arteries perfusion fixed. Histopathologic and histomorphometric analyses were performed at 28 days after injury and radiation. Results : Irradiation with 188W at a dose of 25 Gy after SI significantly inhibited neointima formation (intimal area: 1.05 ± 0.64 vs. 2.75 ± 0.99 mm 2, p < 0.01) and at an 18 Gy dose of radiation (intimal area: 1.73 ± 0.49 vs. 2.75 ± 0.99 mm 2), as compared to controls. One artery receiving 18 Gy and two arteries receiving 25 Gy were totally occluded at follow-up due to thrombus formation but no edge stenosis was observed in any of the irradiated arteries. Conclusions : Intracoronary radiation therapy using a new coiled wire of 188W source delivered after SI appeared to be safe and well tolerated. The radiation doses demonstrated efficacy in reducing neointima formation in the porcine coronary stent injury model.

Effect of catheter-based iridium-192 gamma brachytherapy on the added risk of restenosis from diabetes mellitus after intervention for in-stent restenosis (subanalysis of the GAMMA I Randomized Trial)

Catheter-based intracoronary radiation therapy using iridium-192 (Ir-192) has been shown to be effective in reducing recurrent coronary restenosis after initial percutaneous treatment of in-stent restenosis. Patients with diabetes mellitus (DM) have a higher risk of recurrent restenosis than nondiabetics for nonstented and in-stent restenosis coronary lesions. The use of Ir-192 for preventing recurrent restenosis in such patients remains undefined. The GAMMA I trial was a prospective, randomized, double-blind, multicenter trial of 252 patients with in-stent restenosis who underwent percutaneous coronary intervention and were assigned to receive either Ir-192 (131 patients) or catheter-based placebo (121 patients). DM was present in 79 patients (31%) (41 patients received Ir-192 and 38 patients received placebo) and was absent in 173 patients (90 patients received Ir-192 and 83 patients received placebo). At 6-month follow-up in the GAMMA I trial, the angiographic in-lesion binary restenosis rate was lower in the Ir-192 arm than in the placebo arm (32.4 vs 55.3, p = 0.01). When patients were stratified by the presence of DM, the antirestenosis effect of Ir-192 was larger for diabetic patients than for nondiabetic patients (absolute in-lesion restenosis rate was reduced by 40% for diabetics and 16% for nondiabetics). Thus, adjunctive Ir-192 intracoronary radiation therapy reduces recurrent restenosis after intervention for in-stent restenosis in patients with and without DM. The relative impact of this treatment is more pronounced in diabetic patients because it appears to neutralize the added risk of recurrent restenosis seen in proliferative diabetic lesions.

Localized intracoronary beta radiation therapy to inhibit recurrence of in-stent restenosis

Background In-stent restenosis presents a major limitation of intracoronary stenting. Ionizing radiation has been shown to reduce the recurrence of restenosis after stent placement. We are reporting the effects of intracoronary radiation therapy versus placebo for the clinical and angiographic outcomes of patients with diffuse in-stent restenosis. Methods A total of 332 patients with in-stent restenosis underwent successful coronary intervention, then were blindly randomized to receive either intracoronary beta radiation using a 32P source (RT) or a sham placebo treatment (C) delivered into a centering balloon catheter via an automatic afterloader. Longer lesions (> 22 mm of dilated length) were treated with tandem positioning of the study wire. The primary safety endpoint was the composite occurrence of major adverse cardiac events (MACE) defined as death, myocardial infarction (MI), and repeat target lesion revascularization (TLR) at nine months. The primary efficacy endpoint was binary angiographic restenosis rate in the analysis segment during the nine-month follow-up. The secondary endpoints were MACE with target vessel revascularization (TVR) and angiographic endpoints of restenosis and the magnitude of late lumen loss indices. Findings Procedural success, in-hospital and 30 days complications were similar among the groups. For the primary safety endpoint, freedom from death, myocardial infarction, and repeat target lesion revascularization through 290 days was better in the radiated group (86 % RT vs. 69 % C, p = 0.0006). The binary angiographic restenosis rate was lower in the radiated group for the entire analyzed segment (26 % RT vs. 52 % C, p < 0.0001) – radiation also reduced the target lesion revascularization in long lesions (14 % RT vs. 37 % C, p = 0.005). Interpretation Vascular brachytherapy using pure-emitter 32P delivered into a centering catheter via an automatic afterloader reduced the overall revascularization in patients undergoing treatment for diffuse in-stent restenosis.

Visual assessment of procedural results following treatment with Sr-90 β-radiation for instent restenosis

Background: Visual assessment (VA) of postprocedural % diameter stenosis (DS) is used routinely in clinical practice to determine the adequacy of coronary intervention. Although VA has been shown to underestimate final %DS after balloon angioplasty compared to quantitative coronary angiography (QCA), the impact of this effect on clinical outcomes following treatment with intracoronary radiation therapy (IRT) with Sr-90 for instent restenosis (ISR) is unknown. Methods: To determine the effect of VA on the rate of major adverse cardiac events (MACEs) after IRT for ISR, we compared the clinical outcomes of 102 consecutive patients based on postprocedural %DS by QCA vs. %DS by VA. MACE was defined as death, MI or need for target vessel revascularization (TVR). Results: MACE rates for the 102 consecutive patients grouped according to postprocedural %DS by QCA and VA were compared. The mean %DS by QCA was 30.7%, while the mean %DS by VA was 12.5%. The mean %DS by VA across the QCA subgroups were 13.67%, 10.71% and 13.37%, respectively ( P=.244). Fifty-two patients (51.0%) had %DS ≥30% by QCA with the highest MACE percentage occurring in this subgroup. Conclusion: VA underestimated the %DS compared to QCA, and it was associated with worse MACE following treatment with Sr-90 for ISR.

Routine intracoronary beta-irradiation. Acute and one year outcome in patients at high risk for recurrence of stenosis.

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.

The “shielding” effect of the guide wire during coronary brachytherapy with P-32 source

Intracoronary beta irradiation (use of beta radiation for intracoronary irradiation) is an effective method in reducing neointimal proliferation after successful angioplasty and stent implantation. However, long-term results may be influenced by absolute dose and by the homogeneity in dose distribution. In our study, we investigated dose perturbation due to the presence of a conventional guide wire during irradiation. The Galileo III centering catheter and P-32 beta source were used. The 55 MD GAF Chromic foil was positioned within a phantom made of PMMA. The dose distribution at cylindrical surfaces has been assessed using GAF Chromic dosimetric foil MD55 (Nuclear Associates, USA). Our study demonstrated the significant dose reduction of 46% in the most “shaded” area. The dose reduction to 80% or less occupy the 60° sector. This phenomenon can cause progression of late restenosis. In conclusion, the results suggest that technical improvements in centering catheter construction should be made to eliminate the “shielding” effect of the guide wire.

The effect of intracoronary radiation for the treatment of recurrent in-stent restenosis in patients with diabetes mellitus

ObjectivesThe purpose of this study was to examine the effect of intracoronary radiation therapy (IRT) in diabetic patients with in-stent restenosis (ISR). BackgroundDiabetic patients are at an increased risk for restenosis, repeat revascularization procedures and late mortality after percutaneous coronary interventions and stenting. Intracoronary radiation therapy, utilizing both gamma and beta-emitters, has been shown to reduce the rate of ISR. MethodsThe study group consisted of 749 consecutive patients with ISR who were treated with either IRT or placebo in randomized trials and registries at our center. Diabetic patients (252 radiation and 51 placebo) were compared with nondiabetic patients (371 radiation and 75 placebo). ResultsIn-hospital outcomes were similar between diabetic and nondiabetic patients treated with and without radiation. At six-month clinical and angiographic follow-up, there was a significant reduction in the binary restenosis (63.8% vs. 15.7%, p < 0.0001), target lesion revascularization (66.7% vs. 17.6%, p < 0.0001) and target vessel revascularization (TVR) (70.6% vs. 22.9%, p < 0.0001) rates in diabetic patients treated with radiation compared to placebo. Comparisons between the placebo arms detected a trend towards higher restenosis (63.8% vs. 48.4% p = 0.13) and TVR (70.6% vs. 56.0%, p = 0.14) in diabetic versus nondiabetic patients. In contrast, diabetic and nondiabetic patients treated with IRT experienced similar restenosis (15.6% vs. 10.7% p = 0.33) and TVR (22.9% vs. 28.2% p = 0.41) rates. ConclusionsIn diabetic patients with ISR, intracoronary radiation significantly reduced the recurrence of ISR compared to placebo. Additionally, similar rates of restenosis and revascularization procedures were achieved in irradiated diabetic and nondiabetic patients. In view of these results, IRT should be considered as a valuable therapeutic alternative in all diabetic patients with ISR.

Five-Year Clinical Follow-Up After Intracoronary Radiation

Several clinical trials indicate that intracoronary radiation is safe and effective for treatment of restenotic coronary arteries. We previously reported 6-month and 3-year clinical and angiographic follow-up demonstrating significant decreases in target lesion revascularization (TLR) and angiographic restenosis after gamma radiation of restenotic lesions. The objective of this study was to document the clinical outcome 5 years after treatment of restenotic coronary arteries with catheter-based iridium-192 (192Ir). A double-blind, randomized trail compared 192Ir to placebo sources in patients with restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192Ir and 29 to placebo. At 5-year follow-up, TLR was significantly lower in the 192Ir group (23.1% versus 48.3%; P=0.05). There were 2 TLRs between years 3 and 5 in patients in the 192Ir group and none in patients in the placebo group. The 5-year event-free survival rate (freedom from death, myocardial infarction, or TLR) was greater in 192Ir-treated patients (61.5% versus 34.5%; P=0.02). Despite apparent mitigation of efficacy over time, there remains a significant reduction in TLR at 5 years and an improvement in event-free survival in patients treated with intracoronary 192Ir. The early clinical benefits after intracoronary gamma radiation with 192Ir seem durable at 5-year clinical follow-up.

Monte Carlo dose simulation for intracoronary radiation therapy with a rhenium 188 solution-filled balloon with contrast medium

Background. The therapeutic efficacy of percutaneous transluminal coronary angioplasty is limited by the incidence of restenosis. Intracoronary irradiation has shown to be effective in restenosis control by inhibiting the neointimal proliferation. Methods and Results. Monte Carlo simulation has been performed to calculate the dose to the vessel wall for intracoronary irradiation with a rhenium 188 solution-filled balloon for restenosis inhibition. With a 3-mm-diameter and 30-mm-long balloon, the radiation dose at 1 mm from the balloon surface was 5.3% lower when the balloon structure was included in geometric modeling of the angioplasty catheter, as compared with that obtained by ignoring the structure. The additional dose reduction due to Hexabrix 320 contrast medium added in 30% of volume ratio was 4.7%. With regard to axial dose distribution, the dose was uniform over the balloon length except near the balloon end, at which the dose was reduced by 35% at a 1-mm-deep layer in the vessel wall. With the Re-188 solution mixed with 30% of Hexabrix 320 in volume ratio, the Re-188 activity to be injected for delivery of 15 Gy to the 1-mm-deep layer by 1-minute irradiation was 27.3 GBq/mL. Conclusions. Dose estimates produced in this study should be helpful in determining the Re-188 activity to be injected or the irradiation time for a varying situation in terms of length and diameter of the irradiated arterial segment and depth of the target layer. (J Nucl Cardiol 2002;9:312-18.)