Intracoronary radiotherapy with a 188Rhenium liquid-filled angioplasty balloon system in in-stent restenosis: a single-center, prospective, randomized, placebo-controlled, double-blind evaluation

BACKGROUND: In cases of in-stent restenosis, intracoronary radiotherapy with beta-emitters and gamma-emitters has been shown to reduce the risk of repeat restenosis. The present randomised, placebo-controlled study addresses the question of whether intracoronary radiotherapy applied by the easy-to-handle Rhenium liquid-filled angioplasty balloon system is also able to reduce the angiographic re-restenosis rate in stents. METHODS AND RESULTS: At our center, from May 2000 to December 2003, 165 patients (mean age 64+/-10, median 65 years; 127 men, 38 women) with symptomatic in-stent restenosis underwent either intracoronary brachytherapy or sham procedure. Index clinical and angiographic parameters were largely comparable in both groups. Radiation therapy was performed with a standard percutaneous transluminal coronary angioplasty (PTCA) balloon catheter inflated with liquid Rhenium in the redilated in-stent restenosis for 240-890, mean 384+/-125 s with low pressure (3 atm) in order to reach 30 Gy at 0.5 mm depth of the vessel wall. In 82 patients, intracoronary radiotherapy was carried out without complications, but one of the 83 patients who underwent sham procedure suffered small myocardial infarction. During follow-up, stent thrombosis with subsequent non-Q-wave myocardial infarction occurred in one patient in each group (6 days and 8 months after the procedure, respectively). At 6 months after the index procedure, repeat angiography was performed in 156 of the 164 patients with successful procedure (rate 95%): restenosis (stenosis >50% in diameter) or reocclusion was observed in only 19 of 78 (=24%) patients of the radiation but in 31 of 78 (=40%) patients of the sham procedure group (P=0.04). Event-free survival (free of death, myocardial infarction, target vessel revascularization) at 1 year was 87% for patients being radiated and 74% for patients having undergone sham procedure (P=0.05). CONCLUSIONS: Intracoronary radiation therapy with the liquid-filled beta-emitting Rhenium balloon is not only easy to perform, safe, and comparably inexpensive but also an effective option to prevent repeat restenosis and the need for target vessel revascularization in cases of in-stent restenosis.     

Usefulness of intracoronary brachytherapy for in-stent restenosis with a 188Re liquid-filled balloon

The objective of this randomized pilot trial with 21 patients was to evaluate the effectiveness of a rhenium-188 liquid-filled balloon system to prevent recurrent restenosis after percutaneous transluminal coronary angioplasty for in-stent restenosis. A significant benefit from brachytherapy was seen at 6-month repeat angiography, as well as during the clinical follow-up of 12 months.     

Treatment of in-stent restenosis with sirolimus-eluting-stents -- a six month clinical and angiographic follow-up

Summary Treatment of in-stent restenosis (ISR) remains a therapeutic challenge since many pharmacological and mechanical approaches have shown disappointing results except for brachytherapy. Drug-eluting stents (DES) have been reported to effectively reduce ISR in de novo lesions. We studied 55 consecutive patients with ISR in native coronary arteries and 7 with ISR in saphenous vein grafts (SVG) with elective indication for percutaneous coronary intervention (PCI), who underwent successful implantation with DES. No in-hospital postprocedural major adverse cardiac events were observed. All but one patient (n=61) underwent an angiographic follow-up at 183±30 days. Grade of stenosis was assessed by quantitative coronary angiography (QCA) at index procedure and at control angiography. Restenosis (>50%) occurred in 5 patients (8.2%). Target vessel revascularization was performed in an additional 4 patients. Minimal intimal hyperplasia was observed in all segments covered by DES (late loss 0.08±0.37 mm, loss index 0.11±0.47). One patient suffered from subacute stent thrombosis due to discontinuation of clopidogrel medication. At six month follow-up two patients had died. Death was not related to a restenosis in the treated segment. Conclusion Our experiences with DES treatment of ISR lesions show good angiographic and clinical results at index procedure and at the 6 month follow-up with low sub acute thrombosis rate as compared with existing treatment modalities. Restenosis rate seems to be at least as low as reported for brachytherapy.      

Comparison of angiographic and clinical outcomes between rotational atherectomy versus balloon angioplasty followed by radiation therapy with a rhenium-188-mercaptoacetyltriglycine-filled balloon in the treatment of diffuse in-stent restenosis

BACKGROUND: The purpose of this study was to compare the efficacy of rotational atherectomy (RA) with simple balloon angioplasty, prior to beta-radiation therapy with a rhenium-188-mercaptoacetyltriglycine (188Re-MAG3)-filled balloon for diffuse in-stent restenosis (ISR). METHODS: After completing 50 cases with RA prior to beta-radiation (Group I), we performed optimal balloon angioplasty followed by beta-radiation in the next 53 consecutive patients (Group II) for the treatment of diffuse ISR. The radiation dose was 15 Gy at a depth of 1.0 mm into the vessel wall. RESULTS: The baseline clinical and angiographic characteristics were similar between the two groups. The mean length of the lesion was 25.6+/-12.7 mm in Group I and 22.9+/-8.6 mm in Group II (p=0.26). Radiation was successfully delivered to all patients, with a mean irradiation time of 179+/-55 s. The 6-month angiographic restenosis rate was 10% (5/50) in Group I versus 33% (17/51) in Group II (p=0.007). No adverse event including myocardial infarction, death, or stent thrombosis occurred during the 1-year follow-up period. The risk of a target lesion revascularization or a major adverse cardiac event was significantly lower in Group I than in Group II (two patients in Group I vs. nine patients in Group II; OR, 0.20; 95% CI, 0.04-0.96; p=0.04). CONCLUSION: Concomitant treatment with rotational atherectomy and beta-irradiation using a 188Re-MAG3-filled balloon for diffuse ISR has a synergistic effect, in terms of 6-month angiographic restenosis and 1-year cardiac event-free survival.     

Intracoronary beta-radiation of de novo coronary lesions using a (186)Re liquid-filled balloon system: six-month results from a clinical feasibility study.

Vascular brachytherapy has shown to be effective for in-stent restenosis, but efficacy in de novo lesions remains uncertain. We evaluated feasibility and outcome of intracoronary beta-radiation therapy in de novo coronary lesions using a (186)Re liquid-filled balloon system. Thirty-three patients received 20 Gy (186)Re beta-radiation immediately after balloon angioplasty. The 6-month restenosis rate was 41% (12/29) and restenosis was located within the target lesion in eight patients and at the edges of the injured and irradiated segment, outside the target lesion, in four patients. At 6 months, four patients (12%), all stented during the initial procedure, had experienced a late (> 30 days) total occlusion. Intracoronary beta-radiation therapy of de novo coronary lesions using (186)Re is technically feasible. No reduction in restenosis was observed. The high incidence of late total occlusions may have been prevented by avoiding new stent implantation and prolonging double antiplatelet therapy.     

Stenting the stent: initial results and long-term clinical and angiographic outcome of coronary stenting for patients with in-stent restenosis

Stent restenosis constitutes a therapeutic challenge affecting an increasing number of patients. Conventional angioplasty and debulking techniques are currently used in these patients. However, the potential role of a second stent implantation in this setting (stenting the stent) remains unknown. Therefore, 65 consecutive patients (12 women, aged 62 +/- 11 years) undergoing stent implantation (42 elective and 23 unplanned) for the treatment of in-stent restenosis (diffuse [> 10 mm] in 39 [60%]) were studied. Angiographic success was obtained in all patients. Three patients developed hospital complications: 1 died from refractory heart failure and 2 suffered non-Q-wave myocardial infarctions. During follow-up (mean 17 +/- 11 months) 1 patient died (noncardiac cause) and only 9 (14%) required target vessel revascularization. Kaplan-Meier event-free survival (freedom from death, myocardial infarction, and target vessel revascularization) at 1 year was 84%. Using Cox analysis, patients with unstable symptoms, a short time to stent restenosis, nonelective stenting, and B2-C lesions tended to have poorer prognosis. After adjustment, nonelective stenting was associated (adjusted RR 2.9, 95% confidence interval [CI] 0.82 to 10.3, p = 0.09) with an adverse clinical outcome. On quantitative angiography (core lab) restenosis was found in 13 of 43 patients (30%) (75% of those eligible). Logistic regression analysis identify restenosis length (adjusted RR 1.43, 95% CI 1.04 to 2.14, p = 0.04), and time to restenosis (adjusted RR 0.67, 95% CI 0.47 to 0.94, p = 0.01) as the only independent predictors of recurrent restenosis. Thus, repeat coronary stenting is a safe and efficacious strategy for the treatment of patients with in-stent restenosis. Both elective and nonelective stenting provide excellent initial results. The long-term clinical and angiographic outcome of these patients is also favorable.     

Three-year clinical follow-up results of intracoronary radiation therapy using a rhenium-188-diethylene-triamine-penta-acetic-acid-filled balloon system.

BACKGROUND: Intracoronary radiation therapy (IRT) prevents recurrent in-stent restenosis, but its long-term safety and efficacy remain uncertain. In the present study, the long-term clinical outcome of IRT using the rhenium-188 ((188)Re)-filled balloon system was evaluated. METHODS AND RESULTS: After successful catheter-based treatment of either a de novo or restenotic lesion, 187 patients were randomly assigned to either the radiation (N=104) or the control (N=83) group. The (188)Re-filled balloon system was designed to deliver 17.6 Gy to 1.0-mm tissue depth. Angiographic restenosis was significantly reduced with IRT at 9 months (18.9% vs 45.9%, p<0.001), but the incidence of major adverse cardiac events (MACE) including death, myocardial infarction, and target-vessel revascularization (TVR) by 3 years showed no difference. Lack of clinical benefit might be related to TVR caused by geographic miss (6/22, 28.6%), balloon-induced unhealed dissection (3/22, 13.6%) and late thrombosis (2/22, 9.1%). In the restenotic subgroup (N=39), the MACE rate within 3 years was significantly reduced with IRT (14.3% vs 54.5%, p=0.01). CONCLUSIONS: IRT using the (188)Re -filled balloon system is safe and technically feasible. Although IRT failed to show favorable outcomes for de novo lesion, the clinical benefits for restenotic lesions seem durable for 3 years. Furthermore, preventing geographic miss and dissection might improve long-term outcomes.     

Long-term clinical and angiographic outcome of patients with occlusive in-stent restenosis treated with (32P) beta-brachytherapy.

The objective of this study was to determine the safety and efficacy of (32)P beta-brachytherapy in totally occlusive in-stent restenosis (ISR). Patients with occlusive ISR were generally excluded from the randomized clinical trials on intracoronary brachytherapy (utilizing either gamma- or beta-sources) that have shown reductions in restenosis rate and need for revascularization procedures. We analyzed short- and long-term effects of (32)P beta-brachytherapy (20 Gy) in 27 patients (28 lesions) with occlusive ISR and 84 (99 lesions) patients with nonocclusive high-risk ISR. The primary outcome measure was frequency of in-lesion angiographic binary restenosis at 7 months. Secondary endpoints were rates of major adverse cardiac events (MACE), target vessel revascularization (TVR), clinically driven TVR, and target lesion revascularization (TLR). (32)P beta-brachytherapy was feasible and safe and provided similar postprocedural angiographic results in the two clinically comparable groups. However, the 7-month binary restenosis rate was higher in the occlusive group, as were the MACE and late total occlusion rates. Multivariate logistic analysis of the overall population indicated occlusive pattern to be the only independent predictor of angiographic restenosis. In both groups, recurrent lesions most often showed a focal pattern with significant reduction of length. Although safe and effective in high-risk ISR, (32)P brachytherapy at 20 Gy does not appear to be sufficient to avoid long-term restenosis in patients with occlusive lesions. Further studies should determine the most suitable source and dosage of brachytherapy for patients with occlusive ISR.     

Treatment of in-stent restenosis using a paclitaxel-eluting stent: acute results and long-term follow-up of a matched-pair comparison with intracoronary {beta}-radiation therapy

Aims Intracoronary radiation therapy (ICR) has significantlyimproved the long-term outcome after treatment of diffuse in-stentrestenosis (ISR). The efficacy of drug eluting stents in thissetting remains less well defined. This matched-pair analysiscompared the procedural and long-term clinical and angiographicoutcome after treatment of diffuse ISR using a paclitaxel-elutingstent (PES) with intracoronary ß-radiation therapy. Methods and Results Twenty-two patients receiving 25 PES (ACHIEVE^TM,Cook, 3.1 µg paclitaxel per square millimeter, non-polymerbased coating) for ISR underwent 6-month angiographic and 12-monthclinical follow-up. From a database including 141 patients (174lesions) undergoing intracoronary ß-radiation forISR, 25 lesions (25 patients) were pair-matched with the formergroup for lesion length and vessel size. PES implantation andICR were successfull in all patients with a significantly lowerpostprocedural in-stent diameter stenosis in the PES group (8±12%vs. 18±8%, ). Angiographic binary in-lesion restenosis at 6 month was 20% (5/25 lesions) in thePES group and 16% (4/25) in the ICR group (). PES implantation resulted in significantly higher in-stent MLDat FU (2.10±0.71 vs. 1.75±0.36, ) and a higher in-stent net gain (PES: 1.19±0.69, ICR:0.84±0.49, ). Two patients in the PES group and 6 patients in the ICR group experienced a targetlesion revascularisation at 12-month follow-up (). Conclusion Implantation of a non-polymer based paclitaxel-elutionstent and conventional ICR therapy for complex ISR lead to comparableacute and long-term clinical and angiographic follow-up results.     

Intracoronary irradiation and stent placement in a chronic total coronary occlusion: long-term clinical, angiographic, and intracoronary ultrasound follow-up.

Intracoronary irradiation emerges as a promising method in a variety of restenosis prone coronary lesions. We report the acute and long-term clinical, angiographic, and ICUS follow-up of a patient who underwent a successful angioplasty with stent placement in a chronic coronary occlusion with adjuvant gamma-intracoronary radiation.     

Use of Taxus polymer-coated paclitaxel-eluting stents for treatment of in-stent restenosis in real world patients: results of clinical and angiographic follow-up at six months in a single-center registry.

OBJECTIVE: To evaluate the safety and efficacy of Taxus paclitaxel-eluting stents in a real world group of unselected patients with coronary in-stent restenosis (ISR) lesions. METHODS: This is a prospective single-center registry of a consecutive series of 94 patients with 104 ISR lesions, without previous brachytherapy, over a period of 1 year. Quantitative coronary angiographic analyses were performed at baseline and at 6-month angiographic follow-up. Clinical follow-up were obtained at 6 months. RESULTS: Pre-intervention mean reference vessel diameter was 2.62 +/- 0.50 mm and mean lesion length was 13.95 +/- 6.78 mm. Baseline ISR patterns were mostly either Type I focal (32.7%) or Type II diffuse intrastent (48.1%). At 6-month angiographic follow-up, the in-stent and in-segment binary restenosis was 3.8% (4/105) and 7.6% (8/105) respectively, and the in-stent and in-segment late loss was 0.30 +/- 0.50 mm and 0.57 +/- 0.54 mm, respectively. Seven of these eight restenosed lesions had a diffuse or proliferative ISR pattern prior to intervention. Lesions that restenosed had longer mean stent length per lesion (37.3 mm vs. 22.5 mm in nonrestenosed group; P = 0.001) and more likely to have had a pattern of total occlusion pre-intervention (25.0% vs. 3.1% in nonrestenosed group; P = 0.046). At 6-month clinical follow-up, the MACE rate was 8.5% and target lesion revascularization rate was 7.4%. There was no death but subacute stent thrombosis occurred in 1 patient (1.1%) at 3 days after intervention. CONCLUSIONS: Paclitaxel-eluting Taxus stent for the treatment of ISR effectively suppresses recurrent neointimal proliferation, and was safe and efficacious at 6-month follow-up.     

Comparison of acute results of prophylactic intraaortic balloon pumping with cardiopulmonary support for percutaneous transluminal coronary angioplasty (PTCA)

High-risk patients not eligible for coronary artery bypass grafting (CABG) are being considered for percutaneous coronary interventions, using cardiopulmonary support (CPS) or intraaortic balloon pump (IABP). However, few data are available regarding case selection and outcome with various support devices. Over a 4-yr period, 149 patients underwent high-risk coronary angioplasty, using elective placement of support devices. Based on physician preference, 58 patients underwent CPS and 91 underwent IABP support prior to the angioplasty. Patients selected for CPS-assisted angioplasty were more likely to be males, and to have a history of chronic angina, congestive heart failure, and lower ejection fraction (26 ± 13% vs. 32 ± 14%, P = 0.01). Multivessel disease was present in 95% of CPS patients and 89% of IABP patients (P = 0.35). Multivessel angioplasty was performed more frequently in the CPS group (40% vs. 20%, P = 0.01), and angioplasty success was higher in the CPS groups (99% vs. 87%, P = 0.005). Major cardiac events such as myocardial infarction, bypass surgery, stroke, and death did not differ between the groups. Peripheral vascular complications such as hematomas (36% vs. 24%, P = 0.16), vascular repair (14% vs. 3%, P = 0.03), and transfusions (60% vs. 27%, P = 0.0001) were higher in the CPS group. In conclusion, despite a higher risk profile, CPS allowed longer balloon inflations and higher PTCA success rates compared to IABP. However, peripheral vascular complications were higher in the CPS group, and major cardiac events were similar to those in IABP-treated patients. These data suggest that either method of support may be acceptable during high-risk PTCA. Cathet. Cardiovasc. Diagn. 45:115–119, 1998. © 1998 Wiley-Liss, Inc.     

Angiographic and clinical outcomes at 8 months of cutting balloon angioplasty and beta-brachytherapy for native vessel in-stent restenosis (BETACUT): results from a stopped randomized controlled trial.

The objective of this study was to assess angiographic and clinical outcomes of cutting balloon (CB) angioplasty and concomitant Sr/Y-90 beta-brachytherapy as a treatment modality for patients with native vessel in-stent restenosis (ISR). Procedural advantages over the standard balloon (SB) have been claimed for the CB. Intracoronary brachytherapy preceded by SB angioplasty is regarded as the treatment of choice in patients with ISR. In an interim analysis of a prospective randomized trial designed for 652 patients, 100 consecutive patients with ISR were assigned to treatment with SB angioplasty (n = 51) or CB angioplasty (n = 49), followed in either case by Sr/Y-90 beta-brachytherapy. Quantitative coronary angiography at baseline, postintervention, and at 8 months was performed by an independent central laboratory. More than 90% of target lesions in the overall patient population were diffuse, with 14% of stents totally occluded. Procedural parameters and immediate angiographic outcomes were essentially the same in either study arm. At 8 months, no statistically significant differences were observed in recurrent angiographic restenosis (SB = 26.1%; CB = 29.5%; P = 0.82), target lesion revascularizations (SB = 13.7%; CB = 8.2%; P = 0.53), and major adverse cardiac events (SB = 15.7%; CB = 8.2%; P = 0.36). In this interim analysis, there was no indication of a beneficial effect of CB use over SB use in terms of angiographic or clinical outcomes at 8-month follow-up. CB angioplasty appears to be as safe and efficacious as SB angioplasty in beta-radiation treatment of patients with predominantly diffuse native vessel ISR. It was decided to discontinue the trial.     

Percutaneous mitral valvuloplasty with a single rubber-nylon balloon (Inoue balloon): long-term results in 71 patients

The first 71 patients with rheumatic mitral stenosis who successfully underwent single rubber-nylon balloon (Inoue balloon) percutaneous mitral valvuloplasty (PMV) from November 1985 to August 1988 had a mean follow-up period of 27.1 +/- 11.6 months (range, 14 to 48 months). Functional status before PMV was New York Heart Association (NYHA) functional class IV in two, class III in 38, and class II in 31. Pre and post PMV and follow-up mean diastolic mitral gradient by catheter method was 17.5 +/- 6.9, 2.7 +/- 3.5, and 3.3 +/- 3.4 mm Hg (p less than 0.001 pre versus post PMV and pre PMV versus follow-up; and p greater than 0.005 post PMV versus follow-up). By Doppler method the mean diastolic gradient was 17.4 +/- 5.5, 8.5 +/- 4.7, and 9.2 +/- 4.1 mm Hg, respectively (p less than 0.001 pre versus post PMV and pre PMV versus follow-up; and p greater than 0.05 post PMV versus follow-up). Mitral valve area was 1.12 +/- 0.26, 2.04 +/- 0.41, and 1.92 +/- 0.45 cm2, respectively (p greater than 0.001 pre versus post PMV and pre PMV versus follow-up; and p less than 0.05 post PMV versus follow-up). The phonocardiographic and vectorcardiographic studies and cardiopulmonary exercise testing showed significant improvement after PMV and at follow-up. At follow-up the NYHA functional class was 1 in 57 patients, class II in 13, and class III in one patient with severe mitral valve calcification and subvalvular fusion, in whom restenosis occurred 18 months after PMV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Optimal coronary balloon angioplasty with provisional stenting versus primary stent (OCBAS): Immediate and long-term follow-up results

Objective. This study sought to compare two strategies of revascularization in patients obtaining a good immediate angiographic result after percutaneous transluminal coronary angioplasty (PTCA): elective stenting versus optimal PTCA. A good immediate angiographic result with provisional stenting was considered to occur only if early loss in minimal luminal diameter (MLD) was documented at 30 min post-PTCA angiography.Background. Coronary stenting reduces restenosis in lesions exhibiting early deterioration (>0.3 mm) in MLD within the first 24 hours (early loss) after successful PTCA. Lesions with no early loss after PTCA have a low restenosis rate.Methods. To compare angiographic restenosis and target vessel revascularization (TVR) of lesions treated with coronary stenting versus those treated with optimal PTCA, 116 patients were randomized to stent (n = 57) or to optimal PTCA (n = 59). After randomization in the PTCA group, 13.5% of the patients crossed over to stent due to early loss (provisional stenting).Results. Baseline demographic and angiographic characteristics were similar in both groups of patients. At 7.6 months, 96.6% of the entire population had a follow-up angiographic study: 98.2% in the stent and 94.9% in the PTCA group. Immediate and follow-up angiographic data showed that acute gain was significantly higher in the stent than in the PTCA group (1.95 vs. 1.5 mm; p < 0.03). However, late loss was significantly higher in the stent than the PTCA group (0.63 ± 0.59 vs. 0.26 ± 0.44, respectively; p = 0.01). Hence, net gain with both techniques was similar (1.32 ± 0.3 vs. 1.24 ± 0.29 mm for the stent and the PTCA groups, respectively; p = NS). Angiographic restenosis rate at follow-up (19.2% in stent vs. 16.4% in PTCA; p = NS) and TVR (17.5% in stent vs. 13.5% in PTCA; p = NS) were similar. Furthermore, event-free survival was 80.8% in the stent versus 83.1% in the PTCA group (p = NS). Overall costs (hospital and follow-up) were US $591,740 in the stent versus US $398,480 in the PTCA group (p < 0.02).Conclusions. The strategy of PTCA with delay angiogram and provisional stent if early loss occurs had similar restenosis rate and TVR, but lower cost than primary stenting after PTCA.