Long-term clinical outcomes of dissections after intracoronary beta-radiation with rhenium-188-diethylene triamine penta-acetic acid-filled balloon system

BACKGROUND: Intracoronary radiation with a rhenium-188 ((188)Re)-filled balloon is safe and efficiently reduces restenosis, but there is a potential risk of a (188)Re-filled balloon induced dissection. Little is known about the effect of radiation on dissection resolution and the late clinical outcome of dissection after brachytherapy. METHODS: After successful catheter-based treatments of de novo or restenotic lesion, 256 patients were randomly assigned to the radiation or control group. The (188)Re-filled balloon system was designed to deliver 17.6 Gy in 1.0-mm tissue depth. RESULTS: Dissections were identified in 15 patients among the 138 patients of the radiation group (10.9%). Additional stents were deployed in 10 patients to cover the flow-limiting dissection. Binary restenosis rate (53.3% vs. 16.3%, p=0.001) and target vessel revascularization (TVR) rate (53.3% vs. 11.1%, p<0.001) were significantly higher in patients with the dissection at 9 months. Geographic miss (GM) was identified in 4 of the 10 patients who underwent additional stenting. Binary restenosis rate in the GM group (100%; 4 of 4 patients) was significantly higher than the non-GM group (33.3%; 2 of 6 patients, p=0.02). Long-term follow-up of the patients with dissections who had not undergone TVR (n=7, mean follow-up duration: 640.7+/-387.3 days) has demonstrated persistent unhealed dissections. CONCLUSIONS: Intracoronary radiation impairs the healing process after vessel injury and residual dissection after brachytherapy leads to adverse clinical outcomes, which was mainly due to GM in case of stent implantation.     

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.     

Repeat intracoronary beta-brachytherapy using a rhenium-188-filled balloon catheter for recurrent restenosis in patients who failed intracoronary radiation therapy.

BACKGROUND: Conventional percutaneous coronary intervention (PCI) in restenotic lesions after brachytherapy failure is associated with a high recurrence rate of restenoses and revascularizations. Intracoronary brachytherapy using a liquid rhenium-188-filled balloon in de novo or restenotic lesions safely and effectively reduced restenosis rates. We report clinical and angiographic data regarding the safety and efficacy of rhenium-188 brachytherapy in restenoses after brachytherapy failure. METHODS: Fourteen patients with restenosis after brachytherapy failure received rhenium-188 beta-brachytherapy. Follow-up was performed angiographically after 6 months and clinically after 12 months. Primary clinical endpoint was the incidence of major adverse cardiac events (MACE) defined as any death, myocardial infarction or repeat revascularization in the target vessel within 12 months. Secondary angiographic endpoints were the binary restenosis rate and late loss in the total segment including edge effects at 6 months. RESULTS: The prescribed dose of 22.5 Gy (n=12) or 30 Gy (n=2) was successfully delivered in all patients. In two lesions, a bare-metal stent was implanted. The mean length of the irradiated segment was 40.0+/-15.7 mm. The mean diameter of the irradiation balloon was 2.96+/-0.37 mm. Angiographic follow-up was done in 13 of 14 patients. There was no edge stenosis or coronary aneurysm. Within the total segment, late loss was 0.39+/-0.64 mm and late loss index was 0.18+/-0.40 with a binary restenosis rate of 23%. Twelve months' clinical follow-up was available in all patients, which showed a MACE rate of 7% due to one target lesion revascularization (TLR). CONCLUSIONS: Intracoronary beta-brachytherapy with a liquid rhenium-188-filled balloon in restenoses after intracoronary radiation therapy failure including 12 months combined antiplatelet therapy is safe with respect to vessel thrombosis, late coronary occlusion or aneurysm formation. With limited use of stenting, angiographic and clinical follow-up for repeat brachytherapy were favorable and it is associated with low restenosis and target vessel revascularization rate.     

Treatment of diffuse in-stent restenosis with rotational atherectomy followed by radiation therapy with a rhenium-188-mercaptoacetyltriglycine-filled balloon

OBJECTIVES: This study was done to evaluate the feasibility and efficacy of beta-radiation therapy with a rhenium-188-mercaptoacetyltriglycine ((188)Re-MAG(3))-filled balloon after rotational atherectomy for diffuse in-stent restenosis (ISR). BACKGROUND: Rotational atherectomy has been shown to be safe and efficient for the treatment of ISR, but the recurrence rate is still high. Intracoronary beta-irradiation after rotational atherectomy may be a reasonable approach to prevent recurrent ISR. METHODS: Fifty consecutive patients with diffuse ISR (length >10 mm) in native coronary arteries underwent rotational atherectomy and adjunctive balloon angioplasty, followed by beta-irradiation using a (188)Re-MAG(3)-filled balloon catheter. The radiation dose was 15 Gy at a depth of 1.0 mm into the vessel wall. RESULTS: The mean lengths of the lesion and irradiated segment were 25.6 +/- 12.7 mm and 37.6 +/- 11.2 mm, respectively. Radiation was delivered successfully to all patients, with a mean irradiation time of 201.8 +/- 61.7 s. No adverse event, including myocardial infarction, death or stent thrombosis, occurred during the follow-up period (mean 10.3 +/- 3.7 months), and nontarget vessel revascularization was needed in one patient. The six-month binary angiographic restenosis rate was 10.4%, and the loss index was 0.17 +/- 0.31. CONCLUSIONS: Beta-irradiation using a (188)Re-MAG(3)-filled balloon after rotational atherectomy is safe and feasible in patients with diffuse ISR, and it may improve their clinical and angiographic outcomes. Further prospective, randomized trials are warranted to evaluate the synergistic effect of debulking and irradiation in patients with diffuse ISR.     

Intravascular ultrasound analysis of nonstented adjacent segments in diffuse in-stent restenosis treated with radiation therapy with a rhenium-188-filled balloon.

The effects of beta-radiation therapy on nonstented adjacent segments in in-stent restenosis have not been sufficiently evaluated. beta-radiation therapy for in-stent restenosis was performed with a (188)Re-MAG(3)-filled balloon. We evaluated the effects of beta-radiation therapy on nonstented adjacent segments in in-stent restenosis by intravascular ultrasound (IVUS) analysis in 50 patients who received radiation therapy vs. 9 control patients. The changes (Delta = follow-up - postintervention) of the external elastic membrane (EEM), the lumen, and other IVUS variables were compared between the segments that received radiation therapy and the control segments. The significant differences between the two groups were as follows: Delta EEM area was 0.3 mm(2) in the radiation vs. -1.0 mm(2) in the control (P = 0.005) and Delta lumen area was 0.2 mm(2) vs. -1.3 mm(2), respectively (P < 0.001). In conclusion, compared with the changes of vessel shrinkage in the control group, significant vessel enlargement occurred in the nonstented adjacent segments that received radiation therapy.     

Intracoronary beta-irradiation with liquid rhenium-188: results of the Taiwan radiation in prevention of post-pure balloon angioplasty restenosis study

STUDY OBJECTIVE: To assess the feasibility and short-term outcome of intracoronary irradiation after pure balloon angioplasty (POBA) of de novo and post-POBA restenotic lesions with a liquid beta-emitter (188)Re-filled balloon. DESIGN AND SETTING: Nonrandomized prospective study with contemporaneous control group in a single medical center. PATIENTS AND METHODS: In the Taiwan Radiation in Prevention of Post-Pure Balloon Angioplasty Restenosis study, 40 patients underwent 14-Gy irradiation and 15 patients underwent 20-Gy irradiation at a tissue depth of 0.5 mm after POBA. Thirty control patients received a 5-min inflation with a perfusion balloon catheter after POBA. RESULTS: No procedural or in-hospital complications, or 30-day major adverse cardiac events were noted. Six-month angiographic restenosis rates were 49% in the 14-Gy group, 20% in the 20-Gy group, and 57% in the control group (p = 0.05, 20-Gy group vs control group). In the lesions with an arc of calcification of < 180 degrees, restenosis occurred in 15 of the 34 lesions (44%) in the 14-Gy group and in none of the 11 lesions (0%) in the 20-Gy group (p = 0.007). In a vessel with a reference diameter < 3.0 mm, restenosis occurred in 1 of the 8 lesions (13%) in the 20-Gy group, and in 8 of the 11 lesions (73%) in the control group (p = 0.02). In the post-POBA restenotic lesions, restenosis occurred in none of the six lesions (0%) in the 20-Gy group, and in five of the six lesions (83%) in the control group (p = 0.008). CONCLUSIONS: Post-POBA, catheter-based brachytherapy in nonstented native coronary artery with a (188)Re-filled balloon can effectively reduce target lesion restenosis with 20-Gy irradiation at a tissue depth of 0.5 mm and seems to be more effective in the treatment of lesions with an arc of calcification < 180 degrees, in a vessel with a reference diameter of < 3.0 mm, and in post-POBA restenotic lesions.     

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.     

Two-year outcomes of repeated brachytherapy in patients with restenosis after intracoronary radiation therapy

This study compared the 2-year outcomes of repeat brachytherapy (n = 10) and conventional percutaneous intervention (n = 14) in patients with restenosis after intracoronary brachytherapy with a rhenium-188-filled balloon system. The short-term target lesion revascularization rate was significantly lower in the repeat brachytherapy group (0% vs 36%, p = 0.038), and additional target lesion revascularization was required in 2 patients with repeat brachytherapy during 2-year follow-up. There were no vascular complications related to repeat brachytherapy.     

Two-year follow-up intravascular ultrasound analysis after bare metal stent implantation in 120 lesions.

The objective of this study was to examine long-term changes after bare metal stent implantation in a relatively large number of patients. There are few reports of intravascular ultrasound (IVUS) studies performed on stented and nonstented (reference) segments beyond 6 months after bare metal stenting. Using IVUS, we evaluated serial changes in stented and reference segments between 6 and 24 months after stent implantation in 110 patients with 120 lesions. Serial IVUS images were acquired at five equidistant intrastent sites and at two different reference segment sites. Measurements were made of the external elastic membrane (EEM), stent, lumen, and intimal hyperplasia (IH = stent - lumen) area. For the whole patient group, between 6 and 24 months, the mean IH area in stented segments decreased from 2.6 +/- 1.0 to 2.3 36+/- 0.9 mm2 (P < 0.001), and the mean lumen area increased from 6.2 +/- 2.0 to 6.5 +/- 1.9 mm2 (P < 0.001). The mean IH area decreased in 91 lesions (76%) and increased in 29 lesions (24%) between 6 and 24 months. There were no significant changes in EEM or lumen area in the reference segments. Late angiographic restenosis (diameter stenosis > or = 50%) occurred in three lesions between 6 and 24 months. A late target lesion revascularization was performed for one lesion. In the period of time between 6 and 24 months after stenting, IH regression occurred in most (76%) stent lesions, resulting in late lumen increase. However, IH progression was observed in 24% of in-stent lesions. No significant changes of EEM or lumen area occurred in the reference segments.     

Impact of radiation dose on late clinical outcome after intracoronary radiation therapy: three-year follow-up of Long WRIST.

To determine the safety and efficacy, including the impact, on the late recurrence rate of an incremental gamma-radiation dose from 15 to 18 Gy, we report the 3-year clinical outcome of Washington Radiation for In-Stent Restenosis Trial for Long Lesions (Long WRIST). One hundred eighty patients with recurrent in-stent restenosis (ISR) were enrolled in the Long WRIST series and treated with (192)Ir with 1 month of antiplatelet therapy. Between 6 months and 3 years, the need for repeat revascularization was low and similar among the three groups. At 3 years, target lesion revascularization (TLR) and major adverse cardiac events (MACE) were less frequent in the 18 Gy group than in the 15 Gy group (P = 0.12 for TLR, P < 0.05 for MACE) and less frequent in the 15 Gy group as compared to the placebo group (P < 0.05 for TLR and MACE). At 3 years, a higher dose of 18 Gy with (192)Ir continues to improve the outcome of patients treated for ISR when compared to patients treated with 15 Gy or placebo.     

Long-term results of 60 patients with pathologic stage I & IIA Hodgkin's disease treated with exclusive mantle radiation therapy.

Between January 1972 and December 1982 60 patients with pathological stage IA and IIA Hodgkin's disease (HD) were submitted to Mantle irradiation only. Twenty-five were in stage I (32.1%) and 35 in stage II (67.9%). All patients were submitted to staging laparotomy. Cases with large mediastinal mass were excluded from this series. Delivered doses were 44 Gy in involved areas, 40 Gy on the mediastinum and 36 Gy on uninvolved sites. Twenty-four patients in stage I (96%) and 33 in stage II (94.2%) obtained complete remission. Actuarial 10- and 20-yr overall (OS) rates were 86% and 79.1%, respectively. Event-free (EFS) and relapse-free (RFS) survival rates at 10 and 20 yr were 67.5% and 62.1%, respectively. The occurrence of disease relapse resulted in the only statistical significant prognostic factor for OS in both univariate and multivariate analysis. Distant and extranodal recurrences were significantly (P<0.01) related to a reduced OS. On multivariate analysis stage was the only determinant factor for increased RFS. Extended field RT proved to be an effective curative modality for stage I HD patients, whereas 15 out of 33 patients in stage II relapsed requiring salvage therapy. Long-term analysis of survival and treatment-related morbidity rates will improve our knowledge and assist the physicians to choose the therapeutic option to offer to HD patients.     

Successful treatment of distal coronary guidewire-induced perforation with balloon catheter delivery of intracoronary thrombin.

Distal coronary artery perforation with a coronary guidewire is a relatively rare but potentially fatal complication during PTCA. Historically, these types of perforations have been easy to control with reversal of heparin anticoagulation combined with prolonged distal balloon inflation. In the modern era, with widespread use of potent glycoprotein IIb/IIIa inhibitors, this type of distal wire perforation has become more difficult to manage and potentially lethal. In this article, we report two cases of guidewire-related distal coronary artery perforation, successfully treated using a new technique using localized, distal intracoronary thrombin injection. During prolonged low-pressure balloon inflation, a small dose of thrombin was injected just proximal to the wire perforation site via the lumen of a coronary balloon catheter. This approach appears to be a relatively rapid and effective way to control this troublesome complication.     

Continuous coronary perfusion balloon catheters in coronary dissections after percutaneous transluminal coronary angioplasty: Acute clinical results and 6-months follow-up

The purpose of the study was to evaluate prospectively the effectof a continuous perfusion balloon catheter (‘High FlowCPC Mainz’, SchneiderlPfizer Europe AG, CH-8052 Zurich,Switzerland) on tolerated inflation time during elective PTCA(n=31), and its usefulness in cases of unsatisfactory morphologicalor functional results after PTCA (n=42). Sixty-five patientswere male, eight female; their mean age was 57.6 ± 8.85years. The target vessel was the LAD in 39 patients, the RCAin 29, the LCX in three, and bypass grafts in two. Seven patientshad type A lesions, 44 type B and 22 type C, respectively. Thetarget lesion was in the proximal third of the coronary arteryin 41 patients, in the mid-third in 30, and in the distal thirdin two. Side branches were involved in 24 patients. The mediansize of the standard PTCA balloon was 3.00 mm and 3.5 mm forthe CPC. Tolerated inflation time rose from 36 ±21 sto 213 ± 108 s (P<0.01). Additionally, the CPC catheterwas used in 42 patients with symptomatic dissections (ST segmentelevation, chest pain, or impaired contrast run-off) after PTCA.Wall wrapping by CPC was successful in 24 (57%) and unsuccessfulin 18 (43%) patients. A significant difference was found forthe inflation times tolerated between patients with successful(265 ± 99 s) and unsuccessful wall wrapping (161 ±108 s; P<0.01). Of the 18 patients with unsuccessful wallwrapping, 11 (61%) required an intracoronary stent, and sixpatients (30%) could be managed by medical treatment alone.One patient, included in the study with TIM10 flow after intravenousthrombolysis for acute myocardial infarction, died in cardiogenicshock. Follow-up over 186 ± 39 days revealed no significantdifferences in clinical outcome between patients treated bythe perfusion catheter alone, by acute stent implantation orconservative treatment. Symptomatic dissections can be managed in a large number ofpatients by using continuous perfusion PTCA catheters. However,further larger studies will have to show if clinical outcomediffers between patients treated with CPC catheters, stents,or acute bypass grafting after failed PTCA and which treatmentis most suitable for the individual patient.     

冠状动脉支架术后医生电话随访对患者依从性的影响

目的探讨医生电话随访对冠状动脉粥样硬化性心脏病(冠心病)患者戒烟依从性、服药依从性及冠状动脉支架术后复查造影的依从性的影响。方法将160例冠状动脉支架术后患者按随机数字表法随机分为随访组(80例)和对照组(80例)两组。出院时都叮嘱入选患者术后必须戒烟、长期服药和1年内返院复查冠状动脉造影。出院后只对随访组进行电话随访,出院1年后评定两组患者的依从性。结果随访组患者的戒烟依从性[90.32%(56/62)vs.75.00%(45/60),χ2=5.02,P<0.05]、服药依从性[91.25%(73/80)vs.77.50%(62/80),χ2=5.74,P<0.05]及冠状动脉支架术后复查造影依从性[90.00%(72/80)vs.76.25%(61/80),χ2=5.39,P<0.05]均较对照组高,差异有统计学意义(P<0.05)。结论医生电话随访对提高冠心病患者戒烟依从性、服药依从性及冠状动脉支架术后复查造影的依从性具有一定的临床意义。     

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.