Intracoronary Brachytherapy for Restenosis: 20 Years of Follow-Up.

BACKGROUND/PURPOSE: Intracoronary brachytherapy (ICB) has mainly been used to treat in-stent restenosis following percutaneous coronary intervention and was virtually abandoned about 20 years ago. However, patients treated with this strategy are still alive and some teams continue to perform this therapy. We aimed to investigate the very long-term clinical outcome of patients treated with ICB. METHODS/MATERIALS: A total of 173 consecutive patients who had been treated with ICB at a large tertiary referral centre between 1998 and 2003 were included. The primary endpoint of the study was all-cause mortality. The secondary endpoints were as follows: occurrence of major adverse cardiac events (MACE, defined as all-cause death, non-fatal myocardial infarction, or target vessel revascularization), cardiac death, and presence of angina at the end of follow-up. RESULTS: Patients' mean age at the time of ICB was 64 ± 10 years and 77 % were male. Restenosis (bare metal stent vs. balloon angioplasty) was the only indication for ICB. Unstable angina was present in 34 % of the patients. Follow-up was available for 166 patients. After a mean follow-up of 20 ± 1.3 years, 66 % of the patients had died (including 74 patients (67 %) with cardiac death). Cumulative MACE rate at 20 years was 96 %. CONCLUSIONS: Very long-term follow-up of patients with in-stent restenosis treated with ICB confirmed a high all-cause mortality rate mainly due to cardiac causes and MACEs.

The Contemporary Use of Intracoronary Brachytherapy for In-Stent Restenosis: A Review.

In-stent restenosis (ISR) has been a major limitation in interventional cardiology and constitutes nearly 10 % of all percutaneous coronary interventions in the United States. Drug-eluting stent (DES) restenosis proves particularly difficult to manage and poses a high risk of recurrence and repeat intervention. Intra-coronary brachytherapy (IBT) has been traditionally viewed as a potential treatment modality for ISR. However, its use was hindered by procedural complexity, cost, and the advent of newer-generation DES. Recent data suggests promising results regarding IBT for the treatment of resistant DES-ISR. This review addresses the mechanism of action of IBT, procedural details, and associated risks and complications of its use. It will also highlight the available clinical evidence supporting the use of IBT and the future directions of its utilization in the treatment of ISR.

Failure patterns after intravascular brachytherapy for in-stent coronary restenosis.

INTRODUCTION: One strategy to improve the effectiveness of intravascular brachytherapy (IVBT) is to study its failures. Previous investigations described mostly discrete, focal recurrences, typically at the proximal or distal edges of the irradiated segment after plain angioplasty or bare metal stents. We reviewed failure patterns of 30 unselected drug-eluting stent (DES) patients who had follow-up angiograms for recurrence within their IVBT-treated vessel. METHODS: Records of 53 unselected IVBT patients treated between 2016 and 2021 were reviewed. Thirty of the 53 patients had at least one subsequent percutaneous intervention (PCI) for in-stent restenosis (ISR) after IVBT. Angiographic findings of those 30 patients with ISR within their previously irradiated vessel are reported here. RESULTS: Of the 30 patients, 21 (70%) developed recurrent ISR within the irradiated segment. Six of the 21 patients who failed within the irradiated segment also experienced ISR proximal or distal to the irradiated segment. Only 15 patients (50%) failed exclusively within the irradiated segment. In nine patients (30%), restenosis occurred proximally and/or distally to the irradiated segment, but not inside of the irradiated segment itself. CONCLUSIONS: We have shown here that 50% of failures after coronary IVBT for DES ISR occur exclusively within the irradiated segment. An additional 20% of patients had failure within and outside of the irradiated segment. These percentages suggest that a higher radiation dose might improve the long-term patency rates, a conclusion that should be tempered by the lack of universal follow-up.

Coronary intravascular brachytherapy for in-stent restenosis: A review of the contemporary literature.

Intracoronary stent restenosis (ISR) is a clinically relevant challenge in the modern era. Heterogeneity in patient- and lesion-specific factors can further compound this clinical challenge. Coronary intravascular brachytherapy (IVBT) was the standard therapeutic approach for ISR prior to the advent of drug-eluting stents (DES). Despite prospective data describing the superiority of DES over IVBT for treating de novo ISR, IVBT remains a treatment option for patients with complex disease. The purpose of this review is to evaluate the historical and contemporary literature surrounding IVBT in order to elucidate its role in modern cardiac care and to describe opportunities for future investigations to improve patient selection. Herein, we provide a review of the contemporary literature describing IVBT as a safe and effective treatment option for patients with recurrent, refractory ISR after multilayer DES and no good surgical or mechanical option. Combination therapy with emerging technologies such as DCBs may further increase efficacy.

An in-depth review of retrospective studies to assess the role of vascular brachytherapy for the treatment of complex patients with multiple risk factors for DES-ISR.

BACKGROUND: Vascular brachytherapy (VBT) used to be an effective treatment modality for management of in-stent stenosis but was superceded by drug eluting stents (DES) which had shown a greater efficacy. However, there is no clear evidence to support superior management for in-stent restenosis (ISR) which continues to be a challenge. METHODS: We conducted a systematic review of the literature and appraised PubMed, Medline, Web of science, ProQuest and Cochrane databases from 2000 to 2020. We assessed comparative outcomes including efficacy (as assessed by measuring major adverse cardiac events, target vessel revascularisation, target lesion revascularisation, all-cause mortality, target lesion myocardial infarction and stent thrombosis) and safety of VBT. RESULTS: Of 1083 records obtained, a total of 8 retrospective studies met the inclusion criteria. In the included studies, major adverse cardiac events (MACE) rates ranged from 10% to 17.5% in the VBT group compared to 14.1% to 28.2% in the re-DES group at one year follow up. There were lower rates of target vessel revascularisation (VBT 10-22.8%; control 18-22.9%) and target lesion revascularisation (VBT 10-14.1%, Control 8-22.1%) between the VBT and re-DES groups. There were significantly low rates of all-cause mortality (1-5.4%), target lesion myocardial infarction (0-7%) and stent thrombosis (0-2.1%) in the VBT group at one year. CONCLUSIONS: VBT is considered to be an effective and safe treatment strategy in complex patients with multiple risk factors for DES-ISR in initial reports. There are no long-term comparison studies available beyond 1 year. There is a need for randomised controlled trials to objectively assess the role of VBT compared to DES and drug coated balloons.

Is Coronary Brachytherapy Staging a Comeback for the Treatment of In-Stent Restenosis?

PURPOSE OF REVIEW: The catheter-based coronary intervention has become a well-established therapeutic modality for obstructive coronary artery disease. However, in-stent restenosis remains a significant limitation of coronary intervention despite the use of newer devices. Intravascular brachytherapy was introduced to treat recurrent in-stent restenosis but only modestly adopted. This review will discuss the mechanism of intracoronary brachytherapy, available clinical evidence of brachytherapy in recurrent in-stent restenosis treatment, and the future of coronary brachytherapy in coronary intervention. RECENT FINDINGS: Drug-eluting stents have an inherent limitation as they leave a permanent metal layer inside an artery when deployed. Recently, drug-coated balloon technology has emerged to treat coronary artery disease as a combination of balloon angioplasty and local drug delivery without leaving a metal layer behind. Recent European guidelines recommended using drug-coated balloons when treating in-stent restenosis treatment, while the US guidelines have not yet addressed the use of drug-coated balloons in such cases. Coronary brachytherapy is a valuable addition to treat these challenging diseases despite several logistic issues. If there are newer technologies with easier setup, such as drug-coated balloons, coronary brachytherapy resurgence is improbable in the contemporary era, although it may not become obsolete.

Intravascular coronary brachytherapy combined with a drug-coated balloon.

BACKGROUND: Coronary artery disease leads to stenosis of the major cardiac vessels, resulting in ischemia and infarction. Percutaneous intervention (PCI) with balloon angioplasty can re-open stenosed vessels. Drug eluting stents (DES) and intravascular brachytherapy (IVBT) and drug-coated balloons (DCBs) are proven to decrease the likelihood of another restenosis after PCI, but neither is completely effective. Due to the limited long-term effectiveness of IVBT or DCB used separately for salvage PCI, we combined the two in some poor prognosis patients. METHODS: Combined IVBT+DCB was intended for a total of 36 patients from 2015-2020. PCI with some combination of ballooning, laser and directional/rotational atherectomy was used to maximally open the stenotic region prior to IVBT+DCB. Beta-radiation brachytherapy for all patients was done with a Novoste Beta-Cath. Lutonix 4.0 x 40 mm paclitaxel-coated balloons (Bard, Murray Hill, NJ) were employed. RESULTS: Overall survival at two years was 88%. Nine patients had follow-up angiograms, all for cardiac symptoms. Time from IVBT+DCB to follow-up angiography ranged from 4 to 33 months. The average months PCI-free interval before brachy therapy was 11.1 mos (95% CI 1.03-23.25) versus 23.3 mos after VBT (23.3 95% CI 12.3-32.3). The mean difference was 11.2 mos (95% CI 1.06-21.4, p < 0.031). None of the follow-up angiographic procedures displayed evidence of what could be interpreted as radiation damage. CONCLUSIONS: In this uncontrolled series, IVBT plus DCB appeared to lengthen the ISR-free interval relative to what had been achieved prior to the combined intervention. We view these results as mildly encouraging, worthy of further study.

The birth, decline, and contemporary re-emergence of endovascular brachytherapy for prevention of in-stent restenosis.

Despite the advent of drug-eluting stents and dual antiplatelet therapy in the interventional management of cardiovascular disease, restenosis rates remain high with significant sequelae. Endovascular brachytherapy-popular in the 1990s and early 2000s-has recently resurfaced as a cost-effective treatment option. In this work, we outline the history of endovascular brachytherapy starting with its earliest promise in the 1990s. We discuss the development of drug-eluting stents and dual antiplatelet strategies and their impact on the perceived benefit of endovascular brachytherapy. For the contemporary era, we propose novel roles for endovascular brachytherapy in complex coronary artery disease and in high-risk patients managed with drug-eluting stents. We discuss the impetus for reducing the requirement and duration of dual antiplatelet therapy using endovascular brachytherapy. We also review innovative opportunities for endovascular brachytherapy after bare-metal stent placement in both coronary and noncoronary territories and offer economic arguments in favor of endovascular brachytherapy. Trials of endovascular brachytherapy in these regimes are merited.

Long-term outcome of brachytherapy treatment for coronary in-stent restenosis: Ten-year follow-up.

OBJECTIVES: The objective of this study was to determine the long-term major adverse cardiac events (MACE) in patients treated with intracoronary brachytherapy (ICBT) for coronary in-stent restenosis (ISR). BACKGROUND: ICBT was commonly used to treat coronary ISR prior to the availability of drug-eluting stents (DES). The long-term outcomes of ICBT for ISR remain unknown. METHODS: Six hundred and eighty consecutive patients who underwent ICBT treated for ISR between September 1998 and April 2005 were included in the study. Clinical and angiographic data were collected and the long-term MACE were measured for all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR) at 10-year follow-up. RESULTS: Patients were 63 ± 11 years old (66% male). The majority of patients were treated with a bare metal stent 670/680 (99%) prior to ICBT. Significant baseline clinical findings include high incidence of smokers 479/680 (70%), hyperlipidemia 638/680 (94%), and multivessel disease 526/680 (77%). The majority of target lesions were diffuse 407/680 (60%), and either in the left anterior descending 258/680 (38%) or right coronary artery 215/680 (32%). At 10-year follow-up, the rate of death was 25%, MI was 22.4%, and TVR was 48%. CONCLUSION: MACE at 10-year follow-up following ICBT for ISR indicates steady rate of death and MI and declining rate of TVR after 5 years.

Intravascular Brachytherapy for the Management of Repeated Multimetal-Layered Drug-Eluting Coronary Stent Restenosis.

BACKGROUND: Because of the widespread acceptance of percutaneous coronary intervention with drug-eluting stents as an effective treatment strategy for in-stent restenosis, it is common to encounter multimetal layer stent restenosis in the recent years. This study aimed to evaluate the clinical outcomes of such patients treated with intravascular brachytherapy (IVBT) in comparison with other percutaneous options. METHODS AND RESULTS: We enrolled patients who underwent percutaneous coronary intervention during the period between 2011 and 2015 for recurrent drug-eluting stents in-stent restenosis with at least 2 layers of stents at the lesion site. This analysis compared patients who underwent treatment with IVBT and those who did not (non-IVBT group). The primary end point measured was major adverse cardiac events defined as a composite of target lesion revascularization, myocardial infarction, and all-cause mortality at 12 months. Adjusted associations were measured using propensity score matching. A total of 328 percutaneous coronary intervention patients met the eligibility criteria, of which 197 patients received IVBT, and 131 patients underwent routine percutaneous intervention. The primary end point was significantly lower in patients undergoing IVBT (13.2% and 28.2%; P=0.01). A propensity score matching for risk factors of in-stent restenosis identified 182 patients. The advantages of IVBT with regard to 1-year major adverse cardiac events were confirmed in this matched cohort (13.2% and 30.8%; adjusted hazard ratio [95% CI]: 0.37 [0.18-0.73]; P<0.01). CONCLUSIONS: In this analysis, IVBT led to significantly lower major adverse cardiac events in patients with multilayered drug-eluting stents restenosis when compared with other percutaneous options at 1-year follow-up.

Usefulness of Intracoronary Brachytherapy for Patients With Resistant Drug-Eluting Stent Restenosis.

In-stent restenosis (ISR) remains a concern even in the drug-eluting stent (DES) era and carries a high risk of recurrence. Brachytherapy is being used as an alternative treatment for resistant ISR, yet the safety and efficacy of this approach has not been well studied. We analyzed the outcomes of 101 patients who underwent coronary brachytherapy for resistant DES ISR. Baseline demographic, clinical, procedural, and outcome data were collected by phone and from electronic records. Comorbidities and overt cardiovascular disease were highly prevalent. Median previous stent layers were 2 with a maximum of 5 layers. Procedural angiographic success rate was 97% and median time to discharge was 1 day after brachytherapy. The primary outcome of target vessel revascularization was 24% at 1 year, 32% at 2 years, and 42% at 3 years. The rate of nonfatal myocardial infarction was 0% at 1 year, 3.5% at 2 years, and 6% at 3 years. The rate of all-cause mortality was 8.5% at 1 year, 12% at 2 years, and 16% at 3 years. We observed only 1 case of late stent thrombosis. After multivariable adjustment, female gender (hazard ratio 2.37, 95% confidence interval 1.02 to 5.52, p = 0.04) and diffuse ISR pattern (hazard ratio 2.95, 95% confidence interval 1.21 to 7.17, p = 0.01) were independently associated with the primary outcome. In conclusion, brachytherapy is feasible for the treatment of resistant DES ISR and is associated with high immediate procedural success and reasonable efficacy in a complex patient population. This approach might be used as an alternative for these patients.

Treatment of in-stent restenosis with excimer laser coronary angioplasty: benefits over scoring balloon angioplasty alone.

Treatment of in-stent restenosis (ISR) is associated with a high incidence of recurrence. This study evaluated the clinical safety and 6-month efficacy of excimer laser coronary angioplasty (ELCA) before scoring balloon dilatation for the treatment of ISR. Twenty-three patients with ISR were included and treatment strategy of ISR was dependent on each operator. Twelve patients among those were treated with ELCA before scoring balloon dilatation (ELCA group) and 11 patients were treated with scoring balloon alone (non-ELCA group). Acute procedural results were evaluated by quantitative coronary angiography (QCA) and frequency domain optical coherence tomography (FD-OCT). Follow-up angiography was performed in all patients and the incidence of recurrent ISR and target lesion revascularization (TLR) was determined at 6 months after initial ISR treatment. Procedural success was achieved in all patients. Baseline clinical and angiographic characteristics were similar between groups. Maximum dilatation pressure of scoring balloon was significantly lower in the ELCA group than in the non-ELCA group (9.0 ± 3.1 vs. 14.9 ± 4.3 atm, p = 0.001). In follow-up angiography, the occurrence of TLR was similar between groups (16.7 vs. 45.5 %, p = 0.09), but the late luminal loss was significantly lower in the ELCA group (0.7 ± 0.6 vs. 1.3 ± 0.7 mm, p = 0.03). ELCA is a safe and feasible technique for the treatment of ISR and associated with a relatively low recurrent restenosis in comparison with scoring balloon dilatation alone.

Vascular brachytherapy versus drug-eluting stents in the treatment of in-stent restenosis: A meta-analysis of long-term outcomes.

INTRODUCTION: Clinical trials have shown a short-term benefit of drug-eluting stents (DES) compared to vascular brachytherapy (VBT) for treatment of in-stent restenosis (ISR). The long-term benefits of DES vs. VBT are conflicting in the literature. This study aimed to do a meta-analysis of long-term outcomes of DES compared to VBT for treatment of ISR. METHODS: PubMed, EMBASE, Cochrane Central and unpublished data were searched for cohort studies and randomized controlled trials (RCTs) that directly compared VBT to DES for the treatment of ISR. We evaluated the following outcomes at 2-5 years of follow-up: target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), stent thrombosis, cardiovascular (CV) mortality, and overall mortality. Heterogeneity was defined as I(2) values > 25%. Review Manager 5.1 was used for statistical analysis. RESULTS: We included 1,375 patients from five studies, of which three were RCTs. VBT was used to treat ISR in 685 (49.8%) patients. After a 2-5 year follow-up, no significant differences were found between treatment groups regarding MI (P = 0.49), stent thrombosis (P = 0.86), CV mortality (P = 0.35), and overall mortality (P = 0.71). TLR (OR 2.37; CI 1.55-3.63; P < 0.001) and TVR (OR 2.23; CI 1.01-4.94; P = 0.05) were significantly increased in patients who received VBT. CONCLUSION: This study suggests that DES are associated with decreased long-term revascularization procedures when compared to VBT for the treatment of ISR. This benefit does not appear to be associated with a significant reduction in mortality or myocardial infarction.

Late results (>10 years) of intracoronary beta brachytherapy for diffuse in-stent restenosis.

INTRODUCTION: Until the development of drug-eluting stents (DES), diffuse in-stent restenosis (ISR) was the main limitation of bare-metal stents in percutaneous coronary intervention (PCI). Among the different treatments available, intracoronary brachytherapy (BT) emerged as one of the most promising, although it was almost abandoned with the increasing use of DES. OBJECTIVE: To assess the Portuguese experience with 90Sr/90Y beta brachytherapy for the treatment of diffuse ISR regarding long-term (>10 years) major adverse cardiac events (MACE) and angiographic restenosis. METHODS: This single-center, retrospective, observational study included 12 consecutive patients treated between January and June 2001, mean age 58.6±9.9 years (range 43-77 years), 11 male. All had chronic stable angina, 75% had dyslipidemia, 58% had hypertension, 50% had peripheral arterial disease, 42% had diabetes and 50% had multivessel disease. Recurrent ISR was present in half of the patients and 11 had normal left ventricular function. After balloon dilatation, BT was performed using an Sr90/Y90 (Novoste Beta-CathTM) beta radiation source. All patients remained under dual antiplatelet therapy until scheduled nine-month follow-up angiography. Patients were followed for the occurrence of death (all-cause and cardiovascular), non-fatal myocardial infarction (MI), revascularization, stent thrombosis and angiographic restenosis. MACE were defined as the combined incidence of cardiac death, MI and urgent target vessel revascularization. RESULTS: In all cases there was both clinical and angiographic success. In a mean follow-up of 10.9±2.5 years, 19 events occurred in seven patients: death in three (25%), only one cardiac (8.3%); ST-elevation MI in one (related to a non-target vessel) (8.3%); and 15 revascularizations in five (42%), of which nine were of the target vessel (mainly in the first two years). There was only one case of probable stent thrombosis. Angiographic restenosis at nine months was 27% (three out of 11 patients), of which two were total occlusions. Ten-year MACE-free survival was 42% (5 patients). CONCLUSIONS: Intracoronary beta brachytherapy for the treatment of diffuse ISR in this small cohort of patients proved to be safe and efficacious, with no late adverse events related to intracoronary radiation.

Absorbed dose assessment of cardiac and other tissues around the cardiovascular system in brachytherapy with 90Sr/90Y source by Monte Carlo simulation.

Cardiac disease is one of the most important causes of death in the world. Coronary artery stenosis is a very common cardiac disease. Intravascular brachytherapy (IVBT) is one of the radiotherapy methods which have been used recently in coronary artery radiation therapy for the treatment of restenosis. (90)Sr/(90)Y, a beta-emitting source, is a proper option for cardiovascular brachytherapy. In this research, a Monte Carlo simulation was done to calculate dosimetry parameters and effective equivalent doses to the heart and its surrounding tissues during IVBT. The results of this study were compared with the published experimental data and other simulations performed by different programs but with the same source of radiation. A very good agreement was found between results of this work and the published data. An assessment of the risk for cardiac and other sensitive soft tissues surrounding the treated vessel during (90)Sr/(90)Y IVBT was also performed in the study.