Intracoronary Radiation Research Articles

Intracoronary radiotherapy with a 188rhenium liquid-filled PTCA balloon system in in-stent restenosis: acute and long-term angiographic results, as well as 1-year clinical follow-up

Background: Intracoronary radiotherapy with β- and γ-emitters has been shown to reduce the risk of restenosis after balloon angioplasty and after coronary stenting. The present study addresses the question whether intracoronary radiotherapy using the 188rhenium liquid-filled PTCA balloon system is feasible, safe and effective in cases of in-stent restenosis. Acute and long-term angiographic results as well as clinical events within 1 year after the procedure were evaluated. Methods and results: From September 1999 to April 2000, 41 patients (mean age 60±10 years, 33 male, 8 female) with symptomatic in-stent restenosis underwent repeat PTCA and immediate intracoronary brachytherapy. After successful repeat PTCA (residual stenosis less than 30% in diameter), a second standard PTCA catheter was inflated with liquid 188rhenium in the redilated in-stent restenosis for 315–880, mean 540±155 s with low pressure (3 atm) in order to reach 30 Gy at 0.5 mm depth of the vessel wall. In all patients with successful reintervention, intracoronary radiotherapy was unproblematically performed; in 16 patients, 21 new stents were implanted during the procedure—either immediately before or after radiation therapy. During follow-up, four episodes of stent thrombosis with subsequent myocardial infarction occurred in three patients (8 days, 37 days, 5 months and 6 months after the procedure, respectively). This complication was seen exclusively in patients with newly implanted stents. One patient of the stent group died suddenly 46 days after the procedure. All 40 surviving patients underwent repeat angiography in cases of repeat angina or routinely 6 months after brachytherapy, respectively. In the redilated target vessels without new stenting, restenosis (stenosis >50% in diameter) or reocclusion was observed in only 5 of 25 (=20%) cases, but in the restented target lesions, in 10 of 15 (=67%). Event-free survival (death, myocardial infarction, TVR) at 1 year after repeat dilatation and subsequent brachytherapy was 80% for patients not newly stented, but only 44% for patients with new stents. Conclusions: Intracoronary radiation therapy with the liquid-filled β-emitting 188rhenium balloon is a safe and effective therapy in cases of in-stent restenosis. The positive effect of irradiation, however, is abolished if a new stent is needed. In the not newly stented patients, 1-year follow-up is encouraging.

Long-term outcomes after treatment of diffuse in-stent restenosis with rotational atherectomy followed by beta-radiation therapy with a 188Re-MAG 3-filled balloon

Background: Intracoronary radiation therapy for in-stent restenosis has been demonstrated to reduce restenosis and major adverse cardiac events. However, long-term angiographic and clinical outcomes after beta radiation therapy have not been sufficiently evaluated. Methods: We evaluated the long-term angiographic and clinical outcomes of 50 consecutive patients who had received beta-radiation therapy with a 188Re-MAG 3-filled balloon after rotational atherectomy for diffuse in-stent restenosis (lesion length>10 mm) in native coronary arteries. The radiation dose was 15 Gy at a depth of 1.0 mm into the vessel wall. Results: The mean lesion length was 25.6±12.7 mm. Radiation was delivered successfully to all patients without any procedural or in-hospital complications. At the 6-month angiogram, the restenosis rates was 10% (5/50). There were no major adverse cardiac events (MACE), such as death, myocardial infarction, and target lesion revascularization (TLR) by 6-month follow-up. Long-term clinical follow-up data were obtained in all patients during 30.1±4.5 months. No myocardial infarction and one noncardiac death occurred during follow-up. Two-year follow-up angiogram was performed in 26 (58%) of 45 patients who showed a patent radiation segment at the 6-month angiogram. Significant narrowing of diameter stenosis of more than 50% occurred in 6 (23%) of 26 patients between 6 and 24 months after beta-radiation. Late TLR was performed in 6 patients. The rate of 30-month death-free survival and MACE-free survival were 98.0±2.0% and 86.9±5.0%. Conclusion: Beta-radiation using a 188Re-MAG 3-filled balloon after rotational atherectomy is associated with favorable long-term angiographic and clinical outcomes.

Predictors of 32P β brachytherapy failure in patients with high-risk in-stent restenosis

Background The effectiveness of coronary radiation therapy for the treatment of in-stent restenosis (ISR) has been established in several randomized clinical trials. The efficacy of this treatment in the general population is less well established. Methods and materials We report our experience in 118 consecutive patients with nonselected high-risk ISR who had undergone successful percutaneous coronary intervention and brachytherapy with 32P β-irradiation and who were prospectively enrolled in a quantitative angiographic and clinical follow-up protocol at 7 months after the index procedure. The aim of this study was to investigate the independent predictor of angiographic restenosis after 32P brachytherapy treatment. Results Of the patients, 28.8% were diabetics. The mean lesion and mean radiated lengths were, respectively, 30.1 ± 17.2 and 43.8 ± 16.9 mm. The ISR pattern was diffuse in 96% of the treated lesions; in particular, 22.1% presented an occlusive pattern and 37.1% a proliferative pattern. At follow-up angiographic, restenosis and major adverse cardiac events (MACE) rates were, respectively, 20.8% and 29.6%. The univariate predictors of angiographic restenosis were procedural geographic miss, pattern IV ISR, manual pullback maneuver of the radiation source, preprocedural lesion percentage stenosis and preprocedural lesion MLD. At logistic regression analysis, only geographic miss and pattern IV ISR were independent predictors of post intracoronary radiation therapy (IRT) angiographic restenosis. Conclusion These data indicate that 7-month angiographic restenosis after 32P IRT in complex patients with ISR is not a frequent event and is predicted mainly by an occlusive lesion at baseline and by procedural geographical miss.

Five-year follow-up after intracoronary gamma radiation therapy for In-stent restenosis

Five-year follow-up after intracoronary gamma radiation therapy for In-stent restenosis

Evolution of angiographic restenosis rate and late lumen loss after intracoronary beta radiation for In-Stent restenotic lesions

The aim of this study was to investigate the time course of angiographic restenosis rate and late loss after successful percutaneous coronary intervention and vascular brachytherapy with β-irradiation using strontium-90/yttrium-90 in 98 patients who were prospectively enrolled into a quantitative angiographic and clinical follow-up protocol at 6, 12, and 24 months after the index procedure, regardless of their symptom status. Actuarial restenosis rates measured 11.2 ± 5% at 6 months of follow-up, 24.5 ± 5% at 12 months, and 28.5 ± 6% at 24 months, respectively. Late loss of the stent segment during the first 6 months measured 0.38 ± 0.40 mm (6 to 12 months: 0.25 ± 0.38 mm; 12 to 24 months: 0.16 ± 0.32 mm), of the injured segment 0.27 ± 0.21 mm (6 to 12 months: 0.21 ± 0.26 mm; 12 to 24 months: 0.13 ± 0.24 mm), of the irradiated segment 0.18 ± 0.29 mm (6 to 12 months: 0.19 ± 0.31 mm; 12 to 24 months: 0.11 ± 0.27 mm), and of the analysis segment 0.18 ± 0.36 mm (6 to 12 months: 0.17 ± 0.29 mm; 12 to 24 months: 0.11 ± 0.20 mm). Restenosis after angioplasty and β-irradiation of in-stent restenotic lesions is not complete within 6 months but is sustained with a gradual decrease over 24 months.

864-6 Prolonged clopidogrel treatment reduces lesion cell proliferation after balloon injury and intracoronary radiation

864-6 Prolonged clopidogrel treatment reduces lesion cell proliferation after balloon injury and intracoronary radiation

1080-64 Late total occlusion versus treatment failure without late thrombotic occlusion in patients after intracoronary radiation: Angiographic and clinical outcomes

1080-64 Late total occlusion versus treatment failure without late thrombotic occlusion in patients after intracoronary radiation: Angiographic and clinical outcomes

880-5 Optimizing dosimetry with high dose intracoronary gamma radiation 21 Gy for patients with diffuse in-stent restenosis

880-5 Optimizing dosimetry with high dose intracoronary gamma radiation 21 Gy for patients with diffuse in-stent restenosis

880-1 Repeat intracoronary gamma radiation for patients with in-stent restenosis who failed radiation therapy: Results from the re-WRIST clinical trial

880-1 Repeat intracoronary gamma radiation for patients with in-stent restenosis who failed radiation therapy: Results from the re-WRIST clinical trial

880-6 Three-year follow-up after intracoronary gamma radiation for in-stent restenosis in saphenous vein grafts

880-6 Three-year follow-up after intracoronary gamma radiation for in-stent restenosis in saphenous vein grafts

1080-63 The real-world clinical practice of intracoronary radiation therapy as compared to investigational trials

1080-63 The real-world clinical practice of intracoronary radiation therapy as compared to investigational trials

1155-100 Intracoronary radiation therapy using a novel beta emitter for in-stent restenosis: Tungsten WRIST

1155-100 Intracoronary radiation therapy using a novel beta emitter for in-stent restenosis: Tungsten WRIST

Usefulness of periprocedural creatinine phosphokinase-MB release to predict adverse outcomes after intracoronary radiation therapy for in-stent restenosis

We aimed to analyze periprocedural creatinine phosphokinase (CPK)-MB elevation in patients treated with intracoronary radiation therapy (IRT) for in-stent restenosis (ISR) to risk stratify these patients. The clinical significance of periprocedural CPK-MB elevation after IRT for ISR is unknown. An elevated CPK-MB has been associated with increased mortality after conventional angioplasty. We evaluated 1,326 patients who were enrolled in radiation trials for ISR at the Washington Hospital Center using γ- and β- emitters. Patients were analyzed according to degree of CPK-MB increase within 24 hours of the index IRT procedure (normal CPK-MB, CPK-MB 1 to 3 times the upper limit of normal, or CPK-MB >3 times the upper limit of normal). Patients with CPK-MB >3 times the upper limit of normal were older (64 ± 12 years, p = 0.04), more likely to be smokers (64%, p = 0.04), hypertensive (85%, p <0.01), and diabetic (49%, p = 0.04). The cohort with the highest CPK-MB release (CPK-MB >3 times the upper limit of normal) had significantly higher rates of adverse clinical events at 12 months (major adverse cardiac events 40%, p <0.01), including death (9.3%, p <0.01) and late thrombosis (6.3%, p <0.01). Periprocedural CPK-MB elevation is of prognostic importance in patients treated with IRT for ISR, and its analysis appears to be mandatory to risk stratify these patients. The impact of glycoprotein IIb/IIIa antagonists in reducing periprocedural CPK-MB release awaits evaluation.

Cardiovascular News

Cardiovascular News

Real-world clinical practice of intracoronary radiation therapy as compared to investigational trials

Intracoronary radiation therapy (IRT) is well established in clinical practice as an effective treatment for in-stent restenosis. We aimed to determine if the 6-month clinical outcome of patients treated postapproval for marketing [commercial radiation (CR)] is equivalent to those patients enrolled in the Washington Radiation for In-Stent Restenosis Trials [Gamma WRIST and Beta WRIST; investigational radiation (IR)]. The 6-month clinical outcome of 110 consecutive patients with 125 lesions who received IRT (gamma, (192)Ir, 15-18 Gy, n = 6; or beta, (32)P, 20 Gy, n = 20; or (90)Sr/Y, 18.4-23.0 Gy, n = 99) in CR was compared with the 6-month clinical outcome of 117 patients with 117 lesions who received IRT ((192)Ir, 15 Gy, n = 65, in Gamma WRIST; and (90)Y, 20.6 Gy, n = 52, in Beta WRIST) in IR. Patients in CR were treated with wider radiation margins. The CR received antiplatelet therapy for at least 6 months and the IR for 1 month. The baseline characteristics of both groups were similar. Use of atheroablation devices was less in CR than IR (15.2% vs. 32.8%, respectively; P = 0.001). The overall major adverse cardiac events (death, Q-wave myocardial infarction, and target vessel revascularization; 18.2% vs. 29.1% in IR; P = 0.05) were significantly lower in the CR when compared with patients in the IR. The real-world clinical practice of IRT demonstrates lower events and better clinical outcomes. This is most likely a result of implementation of the lessons learned from the clinical trials such as optimizing the dosimetry by using a higher dose, treating wider margins to minimize edge effect, and administering prolonged antiplatelet therapy to abolish late thrombosis.

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

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

Repeat intracoronary radiation for recurrent in-stent restenosis in patients who failed intracoronary radiation

Repeat intracoronary radiation for recurrent in-stent restenosis in patients who failed intracoronary radiation

Chronic total occlusion due to diffuse in-stent restenosis: is brachytherapy the solution?

Percutaneous coronary intervention of chronic total occlusions (CTO) is associated with a significantly higher incidence of reocclusion and restenosis compared with non-total occlusions. Randomized and observational trials have demonstrated the effectiveness of intracoronary brachytherapy (ICBT) for the prevention of recurrent in-stent restenosis. However, limited data are available on the effectiveness of ICBT in patients with totally occluded in-stent restenosis. The authors assessed the long-term outcome of patients treated with intracoronary gamma radiation for totally occluded in-stent restenotic lesions. Percutaneous coronary intervention and subsequent catheter-based irradiation with iridium-192 was performed in 100 patients (103 vessels) with diffuse in-stent restenosis. At baseline, CTO of the target vessel at the site of the stent was present in 15 vessels (14.5%). Follow-up data were collected during follow-up visits and from telephone interviews. Repeat coronary angiography was performed in symptomatic patients with clinical restenosis. Clinical and angiographic characteristics were similar between the two groups, although there was a trend towards more unstable angina at the index procedure in CTO patients (66.7% versus 41.4%; p = 0.12) compared with patients without non-total occlusions. A higher percentage of patients (53.3%) with CTO required longer radiation sources (14 seeds, covering a length of 55 mm), compared with 23.9% of patients with non-total occlusion (p = 0.04). With a mean follow-up period of 47.5 +/- 24.0 months, major adverse cardiac events (MACE) were observed in 10 of 15 patients (66.7%) with CTO compared with 25 out of 88 patients (28.4%) without CTO (p = 0.009). According to multivariate analysis, total occlusion of the target vessel at baseline was the single independent predictor of MACE at one-year follow-up (relative risk 16.2, 95% confidence interval 4.2-62.9; p < 0.0001). This study shows that the use of gamma radiation for the prevention of recurrence of in-stent restenosis in patients with CTO does not seem to be as effective as in patients with non-total occlusions. Furthermore, CTO was an independent predictor of worse outcome at long-term follow-up in this study.

Intracoronary Radiation Therapy (IRT) for In-Stent Restenosis

The efficacy of beta and gamma emitters in reducing clinical and angiographic restenosis in patients with in-stent restenosis has been confirmed by a number of studies. This review is intended to give an overview of the individual trials, summarize pertinent lessons that have been learned and give insight into the future of intracoronary radiation. The encouraging results from the clinical trials have established vascular brachytherapy as a

Coronary restenosis: a review of mechanisms and management

Percutaneous coronary interventions represent an attractive alternative to surgical revascularization; nevertheless, these techniques continue to be characterized by their propensity to elicit restenosis. Despite an exhaustive search for an effective pharmacotherapy to treat or prevent restenosis, hundreds of clinical trials have failed to identify an agent with proven therapeutic benefit. Recently, however, the Food and Drug Administration approved intracoronary radiation (brachytherapy) as a viable therapeutic option for in-stent stenosis. In addition, recent randomized trials have shown encouraging results for drug-eluting stents. This article reviews the pathophysiology of restenosis, along with current and future treatment options.