Repeated intracoronary beta radiation for recurrent in-stent restenosis.

More than 70% of percutaneous coronary interventions are followed by a stent implantation. In-stent restenosis still occurs in 20-30% of patients and remains a therapeutic challenge. At present only vascular brachytherapy has been shown to be an effective treatment option. We report here one case of recurrent in-stent restenosis after vascular brachytherapy that was successfully treated by a second beta radiation treatment.     

Endovascular brachytherapy for treatment of bilateral renal artery in-stent restenosis.

Percutaneous transluminal angioplasty of renal artery stenosis is an attractive alternative to surgical therapy. However, even with endovascular stenting, the overall rate of restenosis is 21%. While brachytherapy for coronary in-stent restenosis has proven efficacy, its use for renal artery in-stent restenosis has not been formally evaluated. We report a case of bilateral in-stent renal artery restenosis treated with endovascular brachytherapy.     

Treatment of reoccurring instent restenosis following reintervention after stent-supported renal artery angioplasty.

BACKGROUND: Reoccurrence of restenosis following angioplasty of renal instent restenosis is a considerable drawback of stent-supported angioplasty of renal artery stenosis especially in small vessel diameters. We therefore prospectively studied the long-term outcome of different techniques of endovascular treatment of reoccurrence of instent renal artery restenosis after primarily successful reangioplasty focusing on the impact of covered and drug eluting stents, respectively. PATIENTS AND METHODS: The study included 31 consecutive patients (33 lesions) presenting with their at least second instent restenosis following renal artery stenting who were included in a prospective follow-up program (mean follow-up 36+/-25 months, range 1-85). Primary endpoint of the study was the reoccurrence rate of instent stenosis after primarily successful treatment of instent restenosis determined by duplex ultrasound. RESULTS: Primary success rate was 100%, no major complication occurred. Seven lesions were treated with balloon angioplasty (21%, group 1), 7 lesions with stent-in-stent placement (21%, group 2), 6 lesions with placement of a covered stent (18%, group 3), 3 lesions with a cutting balloon (9%, group 4), and 10 lesions with placement of a drug eluting stent (31%, group 5). During follow-up, overall 12 lesions (36%) developed reoccurrence of instent restenosis: n=5 in group 1 (reoccurrence rate 71%), n=3 in group 2 (43%), n=1 in group3 (17%), 3 in group 4 (100%), and n=0 in group 5 (0%). Treatment with a cutting balloon was the only significant predictor of restenosis (hazard ratio 32.3 (95% CI, 3.3-315.0); P<0.001). CONCLUSION: Treatment of at least second renal artery instent restenosis is feasible and safe. Balloon angioplasty and the implantation of a bare metal stent, a covered stent, or a drug eluting stent seemed to offer favorable long-term patency, whereas cutting balloon angioplasty resulted in a very high rate of restenoses and should therefore be discouraged for this indication.     

Long-term angiographic follow-up after successful repeat balloon angioplasty for in-stent restenosis

BACKGROUND: Coronary stent implantation is associated with improved angiographic short-term and mid-term clinical outcome. However, restenosis rate still remains between 20 and 30%. HYPOTHESIS: The purpose of the study, performed as a prospective angiographic follow-up to detect restenosis, was to evaluate the immediate and the 6-month angiographic results of repeat balloon angioplasty for in-stent restenosis. METHODS: From April 1996 to September 1997, 335 stenting procedures performed in 327 patients underwent prospectively 6-month control angiography. Of the 96 lesions that showed in-stent restenosis (> 50% diameter stenosis) (29%), 72 underwent balloon angioplasty. RESULTS: The primary success rate was 100%. Follow-up angiogram at a mean of 6.9 +/- 2.4 months was obtained in 54 patients. Recurrent restenosis was observed in 24 of the 55 stents (44%). Repeat intervention for diffuse and body location in-stent restenosis before repeat intervention was associated with significantly higher rates of recurrent restenosis (p < 0.001 and p < 0.05, respectively). Of the 19 patients who underwent further balloon angioplasty (100% success rate), coronary angiography was performed in 18 (95%) at a mean of 8.2 +/- 2.0 months and showed recurrent restenosis in 12 patients (67%). Further repeat intervention for diffuse and severe in-stent restenosis before the second repeat intervention was associated with significantly higher rates of further recurrent restenosis (p < 0.05 and p < 0.005, respectively). CONCLUSIONS: Although balloon angioplasty can be safely, successfully, and repeatedly performed after stent restenosis, it carries a progressively high recurrence of angiographic restenosis rate during repeat 6-month follow-ups. The subgroup of patients with diffuse, severe, and/or body location in-stent restenosis proved to be at higher risk of recurrent restenosis.     

Treatment of instent restenosis following stent-supported renal artery angioplasty.

OBJECTIVES: We prospectively studied the long-term outcome of endovascular treatment of instent renal artery stenosis (IRAS). BACKGROUND: Restenosis is a considerable drawback of stent-supported angioplasty of renal artery stenosis especially in small vessel diameters. The appropriate treatment strategy is not yet defined. PATIENTS AND METHODS: During a 10-year period 56 consecutive patients (65 lesions) with their first IRAS were included in a prospective follow-up program (mean follow-up 53 +/- 25 months, range 6-102). Primary endpoint of the study was the reoccurence of IRAS (>or= 70%) after primarily successful treatment of the first IRAS determined by duplex ultrasound. RESULTS: Primary success rate was 100%, no major complication occurred. Nineteen lesions were treated with plain balloon angioplasty (group 1, 30%), 42 lesions with stent-in-stent placement (group 2, 65%) using various bare metal balloon expandable stents, and 4 lesions with drug-eluting stent angioplasty (group 3, 6%). During follow-up, overall 21 lesions (32%) developed reoccurence of IRAS: n = 7/19 in group 1 (37%), n = 14/42 in group 2 (33%), and n = 0/4 in group 3 (0%; P = 0.573). Reoccurence of IRAS was more likely to occur in smaller vessel diameters than in larger ones [3-4mm: 4/7 (57%); 5 mm: 11/26 (42%); 6 mm: 5/25 (20%); 7 mm: 1/7 (14%), P = 0.088]. Multivariable analysis found bilateral IRAS and IRAS of both renal arteries of the same side in case of multiple ipsilateral renal arteries as independent predictors for reoccurence of IRAS. CONCLUSION: Treatment of IRAS is feasible and safe. The data demonstrate a nonsignificant trend towards lower restenosis with restenting of IRAS versus balloon angioplasty of IRAS. Individual factors influence the likelihood of reoccurence of IRAS.     

Drug-eluting stent implantation for treatment of recurrent renal artery in-stent restenosis.

Percutaneous renal artery stenting has become the treatment of choice for renal artery stenosis. In-stent restenosis (ISR) still remains a persistent problem. Drug eluting stents have significantly reduced the incidence of ISR in coronary arteries. We report a case in which recurrent renal ISR was successfully treated with paclitaxel-eluting stent implantation, using intravascular ultrasound guidance, with maintained stent patency at 6 months.     

Balloon-based radiation therapy for treatment of in-stent restenosis in human coronary arteries: results from the BRITE I study.

Catheter-based intracoronary radiation therapy demonstrated reduction of the recurrence rate of in-stent restenosis by 35%-50% when compared to conventional therapy. The objectives of this study were to determine the safety and feasibility of a new balloon-shaped source design and a higher applied dose to reduce the restenosis rates. Thirty-two patients with in-stent restenosis who met study eligibility criteria were successfully treated with standard PCI techniques. Following a successful intervention, a P-32 beta-balloon source was positioned to cover the angioplasty site and a dose of a 20 Gy at 1 mm from the surface of the source was administered. The primary endpoint was a composite of major adverse cardiac events (any death, MI, emergent CABG, or repeat target vessel revascularization) during 6 months of follow-up. At 6 months, only one patient underwent repeat PTCA to the target vessel (3%). There were no instances of death, emergency surgery, late thrombosis, total occlusions, or MI. Binary restenosis measured by QCA at the stented segment was 0% and for the whole analysis vessel was 7.5%. Beta-radiation delivered with a balloon P-32 source design for patients with in-stent restenosis results in lower than expected rate of angiographic and clinical restenosis and the absence of late complications.     

Cutting balloon angioplasty vs. conventional balloon angioplasty in patients receiving intracoronary brachytherapy for the treatment of in-stent restenosis.

The objective of this study was to evaluate the safety and efficacy of cutting balloon angioplasty (CBA) for the treatment of in-stent restenosis prior to intracoronary brachytherapy (ICB). Cutting balloon angioplasty may reduce the incidence of uncontrolled dissection requiring adjunctive stenting and may limit "melon seeding" and geographic miss in patients with in-stent restenosis who are subsequently treated with ICB. We performed a retrospective case-control analysis of 134 consecutive patients with in-stent restenosis who were treated with ICB preceded by either CBA or conventional balloon angioplasty. We identified 44 patients who underwent CBA and ICB, and 90 control patients who underwent conventional percutaneous transluminal coronary angioplasty (PTCA) and ICB for the treatment of in-stent restenosis. Adjunctive coronary stenting was performed in 13 patients (29.5%) in the CBA/ICB group and 41 patients (45.6%; P < 0.001) in the PTCA/ICB group. There was no difference in the injury length or active treatment (ICB) length. The procedural and angiographic success rates were similar in both groups. There were no statistically significant differences in the incidence of death, myocardial infarction, recurrent angina pectoris, subsequent target lumen revascularization, or the composite endpoint of all four clinical outcomes (P > 0.05). Despite sound theoretical reasons why CBA may be better than conventional balloon angioplasty for treatment of in-stent restenosis with ICB, and despite a reduction in the need for adjunctive coronary stenting, we were unable to identify differences in clinical outcome.     

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.     

Elderly patients have a favorable outcome after intracoronary radiation for in-stent restenosis.

Intracoronary radiation therapy (IRT) reduces recurrent in-stent restenosis (ISR) by inhibition of smooth muscle cell proliferation. The ability of these cells to replicate is limited with age due to changes in the telomeres. The purpose of this study was to assess the effect of age on outcomes following IRT for ISR. We evaluated 1,088 patients with 6-month clinical follow-up who were enrolled in radiation trials for ISR using gamma- and beta-emitters. Patients were analyzed within and between IRT (n = 861) or placebo therapy (n = 227) in four age groups (< 55, 55-65, 66-75, > 75 years). Baseline characteristics were similar within each age group of IRT patients, except elderly patients (> 75 years) had a lower rate of diabetes (28% in patients > 75 years; P = 0.008) and a higher rate of previous CABG (59% in patients > 75 years; P < 0.001). The rate of target lesion revascularization (TLR) was reduced in the elderly. TLR at 6 months was 18% in patients < 55 years, 21% in 55-65 years, 12% in 66-75 years, and 10% in patients > 75 (P = 0.009). The MACE rate at 6 months was 21% in patients < 55 years, 29% in 55-65 years, 26% in 66-75 years, and 17% in patients > 75 (P = 0.03). No effect of age was seen in placebo patients. IRT-treated patients had reduced MACE compared to placebo in all age groups, driven by reduced target vessel revascularization. Age was an independent predictor of MACE at 6 months (OR = 0.8; CI = 0.70-0.93; P = 0.004). Angiographic restenosis was not clearly associated with need for TLR in patients > 75 years. In elderly patients (> 75 years) treated with IRT for ISR, the rate of TLR was significantly reduced compared to younger patients. However, this reduction in TLR was not associated with a reduction in angiographic restenosis, suggesting that TLR should not be used as a surrogate for angiographic evaluation.     

Mechanism of cutting balloon angioplasty for in-stent restenosis: an intravascular ultrasound study.

We investigated by intravascular ultrasound (IVUS) the mechanism of action of cutting balloon (CB) angioplasty in patients with in-stent restenosis. Seventy-one consecutive restenotic lesions of 66 patients were studied by quantitative coronary angiography (QCA) and IVUS before, immediately after, and, in 20 cases, at 24-hr time interval after CB. CB was selected according to 1:1 CB-to-stent ratio and inflated at 8 atm for 60-90 sec. Both IVUS planar and volumetric (Simpson's rule, 25 patients) analysis were carried out. IVUS measurements included external elastic membrane area (EEMA), stent area (SA), minimal lumen area (MLA), and restenosis area (RA). Following CB, QCA analysis showed increase of minimal lumen diameter (1.17 +/- 0.46 vs. 2.45 +/- 0.51 mm; P < 0.0001) and decrease of diameter stenosis (64% +/- 13% vs. 21% +/- 9%; P < 0.0001). IVUS measurements showed a significant increase of MLA (2.18 +/- 0.80 vs. 7.31 +/- 1.8 mm(2); P < 0.0001), SA (9.62 +/- 2.6 vs. 10.7 +/- 2.75 mm(2); P < 0.0001), and EEMA (17.27 +/- 5 vs. 18.1 +/- 5 mm(2); P < 0.0001) and a decrease of RA (7.43 +/- 2.63 vs. 3.45 +/- 1.39 mm(2); P < 0.0001). No significant change was observed in the original plaque + media area (7.65 +/- 3 vs. 7.38 +/- 2.9 mm(2); P = NS). Thus, of the total lumen enlargement (5.13 +/- 1.85 mm(2)), 23% was the result of increase in mean SA, whereas 77% was the result of a decrease in mean RA. These changes were associated with a 5% increase in EEMA. IVUS volumetric changes paralleled planar variations. Angiographic and IVUS changes were well maintained at 24 hr. CB enlarges coronary lumen mainly by in-stent tissue reduction associated with a moderate degree of additional stent expansion. Favorable QCA and IVUS acute results are maintained at 24 hr.     

Coronary stent strut avulsion in aorto-ostial in-stent restenosis: potential complication after cutting balloon angioplasty.

We report a case of stent strut avulsion by the cutting balloon during the withdrawal of the deflated balloon catheter in aorto-ostial in-stent restenosis, which was managed successfully by another stent. The proposed mechanisms and recommendations to avoid this rare complication are provided.     

Long-term follow-up of brachytherapy for treatment of allograft in-stent restenosis.

The experience of brachytherapy in the treatment of in-stent restenosis of allograft arteries is limited. We present two cases of in-stent restenosis treated with brachytherapy with favorable angiographic follow-up at 10 months in one patient and at 17 months in the other.     

Peripheral vascular disease: carotid and vertebral brachytherapy for in-stent restenosis.

For years, intra-arterial brachytherapy has been a recognized method for treating recurrent stenosis after percutaneous transluminal angioplasty and stent placement. However, its use in arteries supplying the brain has not been described to date. We report a case treated with intra-arterial brachytherapy for high-grade recurrent stenoses of the high cervical internal carotid artery and the proximal vertebral artery. At 2-year follow-up, the outcome was successful.     

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.     

Combined cutting balloon angioplasty and intracoronary beta radiation for treatment of in-stent restenosis: clinical outcomes and effect of pullback radiation for long lesions.

Intracoronary beta (beta) radiation decreases the incidence of target lesion revascularization after percutaneous intervention (PCI) for in-stent restenosis (ISR). Cutting balloon (CB) angioplasty may also be superior to other percutaneous techniques for the treatment of ISR. We sought to study the outcomes of patients with ISR who underwent both CB angioplasty and intracoronay beta radiation and compare them to patients with ISR who underwent other PCI techniques without concomitant radiation. We also sought to evaluate the safety and efficacy of pullback intracoronary beta radiation for the treatment of long ISR lesions. Between January 2001 and November 2001, 102 patients (mean age = 55 +/- 13 years) with ISR underwent both CB angioplasty and intracoronay beta radiation. beta radiation was delivered using the Beta Cath (Novoste) 30 mm system, and pullback radiation was performed in 41 patients. A comparison group included a total of 393 patients with ISR who underwent other PCI techniques without concomitant intracoronary radiation therapy. Follow-up was obtained in 99 patients (97%) in the CB angioplasty with intracoronary radiation group and 377 patients (96%) in the comparison group. At follow-up, both target vessel revascularization (TVR) and major adverse cardiovascular events (MACE) occurred significantly less in the CB angioplasty with intracoronary radiation group than in the comparison group (7% vs. 18% for TVR, and 14% vs. 24% for MACE; P < 0.05 for both). In the pullback radiation group, TVR was performed in five patients (12%), and MACE occurred in eight patients (20%). A combination of CB angioplasty and intracoronay beta radiation for ISR seems to yield low rates of subsequent target vessel revascularization and adverse cardiac events. In addition, pullback beta radiation using the Beta Cath (Novoste) 30 mm system is safe and can be used to treat long ISR lesions effectively. Further randomized trials are needed to confirm these findings.     

Restenosis after stenting of atherosclerotic renal artery stenosis: Is there a rationale for the use of drug‐eluting stents?

Percutaneous stent-angioplasty has become an accepted therapy for the treatment of atherosclerotic renal artery stenosis (RAS) because of higher acute and long-term success rates compared with balloon angioplasty alone. Restenosis rates after successful renal stent placement vary from 6 to 20% and depend mainly on the definition of restenosis and the vessel diameter of the renal artery or stent. We recommend that restenosis should be defined as >70%. The safety and efficacy of drug-eluting stents for the treatment of RAS is poorly defined. The currently partially published GREAT study (Palmaz Genesis peripheral stainless steel balloon expandable stent: comparing a sirolimus-coated vs. a bare stent in REnal Artery Treatment) examined the effect of a sirolimus-coated stent on restenosis rate in 102 patients and found a relative risk reduction of angiographic binary in-stent restenosis by 50% (7% versus 14%, P = ns). Given the lack of outcome data, the considerable expenses associated with drug-eluting stents, morbidity, and cost associated with prolonged dual antithrombotic therapy, the use of drug-eluting stents in RAS should be restricted to clinical trials. This is a review on restenosis rate following renal stenting, its definition, and the potential use for implantation of a drug-eluting stent in RAS, which so far for this indication is not yet commercially available.