Intracoronary brachytherapy: Initial Australasian experience with the Novoste Beta-Cath system

Background: Coronary artery stenting is now performed in the vast majority of percutaneous interventional procedures worldwide. In-stent restenosis remains the major limitation of this technology and responds poorly to conventional interventional therapies. The only available treatment shown to impact upon this unfavourable response is endovascular radiation. In this paper we describe the initial Australasian experience with the Novoste Beta-Cath device, designed specifically for the delivery of beta radiation to the coronary artery.

Methods: Patients were considered eligible for intracoronary brachytherapy if they had symptomatic diffuse in-stent restenosis, or restenosis within a vessel that was not suitable for stenting. Brachytherapy was provided as a clinical procedure following successful percutaneous transterminal coronary angioplasty (PTCA). Clinical and procedural details were collected at hospital admission, and patients were contacted a median of 9 months following the procedure. Information was collected on recurrent hospital presentations and details verified by retrieving patient records.

Results: From June 1999 to July 2000, intracoronary brachytherapy was performed in 17 vessels in 16 patients and was technically successful in all cases. A single late stent thrombosis occurred 80 days following brachytherapy. This patient died of a subarachnoid haemorrhage 186 days later. There were three presentations with chest pain during the follow-up period, one associated with scintigraphic abnormality consistent with clinical restenosis. There was no documented angiographic restenosis.

Conclusions: Intracoronary brachytherapy with the Beta-Cath device is simple to apply and has yielded promising intermediate term results in our patient cohort. Its application appears most appropriate to diffuse in-stent restenotic lesions in vessels ranging from 2.5 to 3.5 mm in diameter. In these patients, adjunctive brachytherapy currently provides the best available option for ensuring an enduring result following repeat percutaneous revascularisation.     

Intracoronary brachytherapy in the treatment of in-stent restenosis. Initial experience in Brazil

Intracoronary brachytherapy using beta or gamma radiation is currently the most efficient type of therapy for preventing the recurrence of coronary in-stent restenosis. Its implementation depends on the interaction among interventionists, radiotherapists, and physicists to assure the safety and quality of the method. The authors report the pioneering experience in Brazil of the treatment of 2 patients with coronary in-stent restenosis, in whom beta radiation was used as part of the international multicenter randomized PREVENT study (Proliferation REduction with Vascular ENergy Trial). The procedures were performed rapidly and did not require significant modifications in the traditional techniques used for conventional angioplasty. Alteration in the radiological protection devices of the hemodynamic laboratory were also not required, showing that intracoronary brachytherapy using beta radiation can be incorporated into the interventional tools of cardiology in our environment.     

Intracoronary brachytherapy for treatment of in-stent restenosis

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

Intracoronary brachytherapy for in-stent restenosis using long sources reduces restenosis

Edge restenosis (candy wrapper effect) and late thrombosis remain a problem in various randomized intracoronary brachytherapy (ICBT) trials for the treatment of in-stent restenosis (ISR). Target vessel revascularization (TVR) due to target lesion revascularization (TLR) and edge restenosis can be decreased with the use of longer ICBT sources and debulking devices and has not been systematically studied. We analyzed 226 patients with ISR (240 vessels of 264 lesions; average lesion length 17.5+/-8.9 mm) who had lesion debulking followed by 90 Strontium (Sr) beta-irradiation using the Novoste Betacath system (30 mm source in 144 vessels and 40 mm source in 96 vessels). Dual antiplatelet therapy was recommended for one year. At follow-up of 12+/-2 months, clinical TVR occurred in 9.7%, with TLR in 7.1% and non-TLR in 2.6% of cases. There was no delayed or late subacute thrombosis. Beta-irradiation using a longer 90Sr source after lesion modification with cutting balloon (CB) and or rotational atherectomy (RA), along with the use of long-term dual antiplatelet therapy is safe and associated with single-digit clinical restenosis.     

Intracoronary brachytherapy with beta-radiation for the treatment of long diffuse in-stent restenosis

OBJECTIVE: To assess the efficacy of intracoronary brachytherapy with beta-radiation (Sr/Y) for the treatment of long diffuse in-stent restenosis (ISR). METHODS: As recurrent ISR depends on intimal injury after coronary angioplasty, long in-stent restenotic lesions were defined as lesions with a treatment length >26 mm (lesion length >20 mm plus a treatment margin of 3 mm at each end). Seventy-eight patients with long ISR were treated at our institution with beta-brachytherapy after coronary angioplasty. Patients were irradiated with either an approximate dose of 12 Gy at 1 mm vessel wall depth or with 18 Gy at 1 mm vessel wall depth. Clinical follow-up was available for 69 patients and angiographic follow-up for 65 patients. Late lumen loss (LLL), binary restenosis (stenosis >50%), target lesion revascularization (TLR) and major adverse cardiac events (MACE) were assessed for a follow-up time of 6.6+/-2.2 months. RESULTS: Mean interventional treatment length was 46+/-18 mm. TLR was performed in all 23 patients with binary restenosis (33%). Death of cardiac cause was reported for two patients, one of whom did not undergo TLR. Thus, overall MACE rate was 35%. Recurrent ISR was significantly more frequent in patients with geographic miss. Comparison of the different radiation dose regimens revealed significantly lower LLL in patients irradiated with the higher dose (0.20+/-0.68 mm compared with 0.65+/-0.96 mm, P=0.03). CONCLUSION: Intracoronary brachytherapy with beta-radiation (Sr/Y) is a safe and effective therapeutic option for the reduction of recurrent ISR in long diffuse lesions. We recommend a high-dose irradiation with 18 Gy at 1 mm vessel wall depth.     

Carotid brachytherapy for in-stent restenosis.

Carotid stenting has emerged as an alternative revascularization modality to endarterectomy for the treatment of carotid artery disease. Restenosis of a carotid stent may be occasionally seen. Our experience in intravascular radiation therapy for coronary restenosis has provided us the opportunity to explore this treatment strategy for carotid restenosis. We report our initial experience with brachytherapy for the treatment of restenosis after carotid stenting.     

Intracoronary radiation therapy for multi-drug resistant in-stent restenosis: initial clinical experience.

While randomized clinical trials have demonstrated the excellent efficacy of sirolimus-eluting stents (SES) for de novo lesions, the optimal treatment for SES-restenosis is not known. Management may include stand-alone balloon angioplasty, repeat SES implantation, or placement of a drug-eluting stent (DES) with an alternative antiproliferative agent (i.e., a paclitaxel-eluting stent, PES). The appropriate management strategy for recurrent restenosis after PES implantation for SES restenosis is even less clear. We report the initial clinical experience with intracoronary radiation therapy (ICRT) for multi-DES resistant restenosis. We performed ICRT in five patients with recurrent restenosis after treatment with both SES and PES. Over a median follow-up of 256 days (range 75-489 days), one patient had a target lesion revascularization at 182 days and subsequently died at 483 days following the procedure. Our findings support the further study of this management approach.     

Treatment of in-stent restenosis in a gastroepiploic artery coronary bypass graft with brachytherapy

The pedicled right gastroepiploic artery is used as an arterial conduit in a select group of patients undergoing coronary artery bypass grafting with favorable patency and survival rates. Myocardial ischemia can occur, especially secondary to distal anastomotic stenosis. Percutaneous coronary interventions have been successful in treating these stenoses, precluding further challenging and higher risk operations. The restenosis rate of such interventions is unknown. We describe a case of distal right gastroepiploic graft anastomotic stenosis that was initially treated with percutaneous angioplasty, but later required stenting for restenosis. Subsequent in-stent restenosis was successfully treated with angioplasty and brachytherapy via the left axillary approach.     

Treatment of in-stent restenosis.

Although in-stent restenosis is the result of neointimal hyperplasia, mechanical problems (e.g. stent underexpansion) that occurred during implantation may result in restenosis at follow-up. The treatment of in-stent restenosis, begins with identification of these occult mechanical problems. Thereafter, in-stent restenosis can be treated with PTCA, atheroablation, or additional stent implantation; it is nuclear which technique is superior. Not all in-stent restenosis lesions have a similar risk of recurrence. Recurrence appears to depend on several markers of biologic activity: focal vs diffuse in-stent restenosis, the first episode vs recurrent in-stent restenosis, and early vs late recurrence. Vascular brachytherapy has emerged as the most promising way to treat high-risk lesion subsets.     

Intracoronary brachytherapy for the treatment of recurrent drug-eluting stent in-stent restenosis: A systematic review and meta-analysis

BACKGROUNDWe performed a meta-analysis on observational studies since randomized control trials are not available. We studied intracoronary brachytherapy (ICBT) and recurrent drug eluting stent in-stent restenosis (DES-ISR) to evaluate the procedural success, target lesion revascularization (TLR), incidence of myocardial infarction (MI) and all-cause mortality at 2 years follow-up.AIMTo perform meta-analysis for patients undergoing ICBT for recurrent DES-ISR.METHODSWe performed a systematic search of the PubMed/MEDLINE, Cochrane and DARE databases to identify relevant articles. Studies were excluded if intra-coronary brachytherapy was used as a treatment modality for initial ISR and studies with bare metal stents. We used a random-effect model with DerSimonian & Laird method to calculate summary estimates. Heterogeneity was assessed using I² statistics.RESULTSA total of 6 observational studies were included in the final analysis. Procedural angiographic success following intra-coronary brachytherapy was 99.8%. Incidence of MI at 1-year was 2% and 4.1% at 2-years, respectively. The incidence of TLR 14.1% at 1-year and 22.7% at 2-years, respectively. All-cause mortality at 1- and 2-year follow-up was 3% and 7.5%, respectively.CONCLUSIONGiven the observational nature of the studies included in the analysis, heterogeneity was significantly higher for outcomes. While there are no randomized controlled trials or definitive guidelines available for recurrent ISR associated with DES, this analysis suggests that brachytherapy might be the alternative approach for recurrent DES-ISR. Randomized controlled trials are required to confirm results from this study.     

Intracoronary optical coherence tomography for the assessment of in-stent restenosis

Optical coherence tomography (OCT) is a novel imaging modality in interventional cardiology. With its clear image quality, it has attracted considerable attention as a tool to accurately evaluate atherosclerosis and coronary stents in vivo. It has a 10-fold higher resolution compared to intravascular ultrasound and utilises near-infrared light that requires temporary blood clearance during image acquisition. We present a case of in-stent restenosis in a patient five years after percutaneous intervention. Optical coherence tomography clearly showed the mechanism behind the stent failure and helped appropriately plan the subsequent repeat intervention. The technology heralds an exciting advance in the invasive assessment of the coronary arteries that will improve our understanding of heart disease into the future.     

Intracoronary radiation to treat in-stent restenosis in six cardiac transplant patients.

Transplant vasculopathy significantly limits the survival of cardiac transplant patients and occurs in 50% of patients by 5 years posttransplant. We report our experience with six cardiac transplant patients who underwent intracoronary brachytherapy for in-stent restenosis. At four centers, six patients underwent intracoronary radiation for in-stent restenosis. All patients received extended antiplatelet therapy with clopidogrel and aspirin. Follow-up angiography was performed in all patients. Two of the six patients underwent subsequent target lesion revascularization. Patient 1 presented with total occlusion of her radiated lesion. She had a complex procedure requiring stenting for a dissection after the radiation dwell. Patient 2 had high-grade restenosis following brachytherapy. Patient 3 had a 50% restenotic lesion. Patients 4, 5, and 6 had follow-up angiography that showed no evidence of restenosis. There are few good options to treated accelerated transplant vasculopathy. Radiation therapy may be a viable option in this difficult patient population.     

Histopathology of coronary in-stent restenosis following gamma brachytherapy

The histopathology of in-stent restenosis (ISR) following gamma brachytherapy is described. Such histology has not been reported previously. An 82 year old man presented with recurrent ISR three months after gamma brachytherapy to an area of ISR within a native circumflex vessel. The recurrent ISR was treated with directional coronary atherectomy; the histopathology of this directional coronary atherectomy specimen is discussed. These histopathological examinations showed abundant extracellular matrix material. Surprisingly, there was a relatively small cellular (myofibroblastic) component, with an absence of endothelial cells and little evidence of active proliferation. ISR after gamma brachytherapy may be a pathologically distinct entity.     

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.     

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.