Late Total Occlusion Research Articles

Pathological findings of late total occlusion after Zilver PTX stent implantation in restenosis lesion of bare-metal nitinol stent for superficial femoral artery.

Pathological findings of late total occlusion after Zilver PTX stent implantation in restenosis lesion of bare-metal nitinol stent for superficial femoral artery.

In-stent late total occlusion following left main coronary artery stenting

In-stent late total occlusion following left main coronary artery stenting

3D-conformal radiotherapy for prevention of carotid recurrent in-stent restenosis: Initial experience

To investigate 3D-conformal external beam radiotherapy for prevention of recurrent instent restenosis after carotid artery angioplasty. Between Oct 2000 and Sep 2001 five patients with recurrent carotid artery in-stent restenosis of more than 50% lumen loss diagnosed with duplex sonography were enrolled. After successful revascularization, radiotherapy treatment planning was performed, which was based on the angioplasty protocol and all images documenting the intervention. A single dose of 5 Gy was prescribed to the 100% isodose. The treatment started on day one after angioplasty. In total, 4 fractions were given within 3 days. All patients tolerated the treatment well. No acute radiotherapy associated side effects were observed. Two patients developed recurrence within four months after therapy. In both cases, late total occlusion of the stent was noticed. One patient died and one developed a severe stroke. The other three patients remained asymptomatic with evidence of less than 50% restenosis. 3D-conformal radiotherapy is a feasible treatment option for highly selected patients with carotid artery in-stent restenosis. These preliminary results from a very small group of patients do show some potential for radiotherapy to prevent restenosis. However, due to the risk of late stent thrombosis, radiotherapy for the prevention of recurrent carotid artery in-stent restenosis is not recommended.

Angiographic and clinical outcomes of late total occlusion versus treatment failure without late total occlusion in patients after intracoronary radiation therapy for in-stent restenosis

This study aimed to compare the outcomes of patients with late total occlusion (LTO) versus patients with recurrence in the absence of LTO after intracoronary radiation therapy for in-stent restenosis. LTO, especially in the context of acute myocardial infarction, after intracoronary radiation therapy for in-stent restenosis, is associated with negative clinical outcomes after 6 and 12 months compared with in-stent restenosis without LTO.

Long‐term clinical and angiographic outcome of patients with occlusive in‐stent restenosis treated with (32P) β‐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.

1080-64 Late total occlusion versus treatment failure without late thrombotic occlusion in patients after intracoronary radiation: Angiographic and clinical outcomes

1080-64 Late total occlusion versus treatment failure without late thrombotic occlusion in patients after intracoronary radiation: Angiographic and clinical outcomes

Incidence and predictors of late total occlusion following coronary stenting

To determine the incidence and predictors of total occlusion in-stent restenosis, we reviewed three randomized stent vs. stent trials and one stent registry, which provided 955 coronary artery lesions with 6-month angiographic follow-up. Fifteen (1.6%) of the 955 stented lesions were totally occluded at 6-month follow-up. Most patients with total occlusion presented with recurrent angina at the time of repeat angiography (60.0%) while no patient presented with an acute ST segment elevation myocardial infarction. The univariate predictors of total occlusion following elective coronary stenting included stenting for restenosis after a previous percutaneous intervention (P = 0.001), longer stent length (P < 0.001), longer lesion length (P < 0.001), smaller reference vessel diameter (P = 0.022), smaller preprocedure minimum lumen diameter (MLD; P = 0.004), and smaller postprocedure MLD (P = 0.036). Stepwise multiple logistic regression analysis demonstrated that stenting for restenotic lesions (P = 0.004), longer stent length (P < 0.001), and smaller preprocedure MLD (P = 0.012) were independent predictors of total occlusion following coronary stenting.

Use of restenting should be minimized with intracoronary radiation therapy for in-stent restenosis.

Restenting at the time of intracoronary radiation therapy (IRT) for in-stent restenosis (ISR) potentially increases the risk of late total occlusion (LTO) of the treated vessel. Prolonged antiplatelet therapy with clopidogrel (6 months) has been shown to be effective in reducing LTO risk. The purpose of this study was to assess the impact of restenting on clinical outcomes following IRT for ISR with 6 months of clopidogrel. We retrospectively evaluated 1,275 patients with 6-months clinical follow-up who were enrolled in radiation trials for ISR using gamma- and beta-emitters conducted at Washington Hospital Center. Patients were analyzed according to whether additional stents were deployed at the time of IRT. The predominant indication for restenting was to optimize the final angiographic result in the event of tissue prolapse or to cover edge dissections. All patients received a minimum of 6 months of clopidogrel. Baseline clinical and angiographic characteristics were similar between the restented and nonrestented groups. Radiation was delivered successfully in all cases. At 6 months, patients treated with additional stents and IRT had a significantly higher rate of target vessel revascularization than patients without additional stents (24.6% vs. 18.7%; P = 0.011). Restenting caused more frequent late thrombosis, late total occlusion, and Q-wave myocardial infarction than no restenting (4.0% vs. 2.2%, P = 0.09; 6.1% vs. 4.3%, P = 0.14; and 1.9% vs. 0.4%, P = 0.009, respectively). Restenting for the treatment of ISR is associated with increased adverse events and should be avoided after intracoronary radiation therapy for in-stent restenosis, as restenting results in a higher recurrence rate and the potential for increased late total occlusion.

Time course of stent endothelialization after intravascular radiation therapy in rabbit iliac arteries.

Late total occlusion after vascular brachytherapy (VBT) continues to be a serious complication. Delayed reendothelialization was suggested as a pivotal cause, but the time course for complete healing is unknown. Seventy-two rabbit iliac arteries underwent stent implantation and were treated with gamma-radiation using 192Ir. The prescribed doses were 0 Gy (controls, n=24 arteries), 15 Gy (n=24), or 30 Gy (n=24) at 2 mm. Animals were killed at 1 month (n=24), 3 months (n=24), or 6 months (n=24) and were analyzed for histomorphometry or scanning electron microscopy. Intimal area was reduced after VBT at 3 months with 15 and 30 Gy (0.66+/-0.07 and 0.66+/-0.04 mm2, respectively) compared with controls (1.01+/-0.11 mm2, P<0.05) and at 6 months with 30 Gy (0.75+/-0.09 versus 1.28+/-0.26 mm2 in controls, P<0.01). Intimal area was similar at 6 months between 15 Gy and controls. At 1 month, 92+/-4% of the control stented segment was covered with endothelial cells, whereas only 37+/-4% and 37+/-8% was covered in the 15- and 30-Gy arteries, respectively. Similarly, at 3 and 6 months, there was a difference in the extent of reendothelialized areas (at 3 months, 95+/-2%, 32+/-12%, and 29+/-13%; and at 6 months, 98+/-2%, 40+/-8%, and 35+/-12% in control, 15-Gy, and 30-Gy arteries, respectively). Excess platelets and leukocytes were seen in irradiated arteries without complete coverage of endothelium. Reendothelialization after VBT is not completed at 6 months after VBT. Special care with prolonged antiplatelet therapy should be considered beyond that time point.

Comparison of intracoronary gamma radiation for in-stent restenosis in saphenous vein grafts versus native coronary arteries

Intracoronary gamma radiation is effective in reducing recurrent in-stent restenosis (ISR) involving native coronary arteries. This study compares the effectiveness and safety of intracoronary gamma radiation for the treatment of ISR in saphenous vein grafts (SVGs) versus native coronary arteries. In the Washington Radiation for In-Stent restenosis Trial (WRIST) series of gamma radiation trials, 1,142 patients with ISR (230 in SVG and 912 in native coronary arteries) completed 6-month clinical follow-up. All patients underwent balloon angioplasty, atherectomy, and/or restenting. Different ribbon lengths containing 6 to 23 seeds of iridium-192 were used to cover lesion lengths <80 mm. The prescribed radiation doses were 14 or 15 Gy at 2-mm radial distance from the center of the source. Baseline demographics showed that patients with SVGs were older (65 ± 13 vs 61 ± 11 years, p <0.001), more likely male (79% vs 64%, p <0.001), had more multivessel coronary disease (81% vs 50%, p <0.001), and less diffuse lesions (17 ± 10 vs 24 ± 12 mm, p <0.001). At 6 months, event-free survival was similar for patients with SVG ISR and native coronary ISR (82% vs 84%, p = 0.35). The SVG ISR population had a low rate of late total occlusion (4.6%) and late thrombosis (3.5%). Thus, treatment of ISR with gamma radiation in SVGs had similar outcome to native coronary arteries. The use of gamma radiation for the treatment of ISR should expand to SVGs.

A prospective single-center registry for the use of intracoronary gamma radiation in patients with diffuse in-stent restenosis.

Based on single-center prospective registry data, the study evaluates short- and long-term results of intracoronary gamma radiation in patients with diffuse in-stent restenosis in the reality of routine clinical practice. Percutaneous coronary intervention and subsequent catheter-based irradiation with iridium-192 was performed in 84 vessels (81 patients) with diffuse in-stent restenosis. Repeat coronary angiography was performed in 35 patients with clinical restenosis. With a mean follow-up of 12.0 +/- 0.5 months, major adverse cardiac events were observed in 29 (34.5%) patients, including 2 cases of cardiac death, 3 myocardial infarctions, 21 target lesion revascularizations, and 4 target vessel revascularizations. Five of six patients with total occlusion of the target vessel at baseline developed target lesion restenosis. Late total occlusion of the target vessel was observed in four patients. The 1-year event-free survival rate was 69.8%. Total occlusion of the target vessel at baseline was the single independent predictor of cardiac events at 1-year follow-up (P < 0.001). In patients with a target lesion in the left anterior descending artery, predictors of cardiac events also included female sex (P = 0.014), current smoking (P = 0.014), stenting during brachytherapy session (P = 0.02), and smaller reference vessel diameter at baseline (P = 0.01). The results of our registry are similar to those of randomized trials. As applied in routine clinical practice, intracoronary gamma radiation is a feasible, safe, and effective tool in the treatment of diffuse in-stent restenosis. Late events in the entire group were predicted by total occlusion at baseline.

Wrist 12 versus wrist plus: twelve versus six months of clopidogrel for prevention of late total occlusion after gamma radiation therapy for in-stent restenosis

Wrist 12 versus wrist plus: twelve versus six months of clopidogrel for prevention of late total occlusion after gamma radiation therapy for in-stent restenosis

Takayasu's arteritis

THE LANCET • Vol 359 • February 16, 2002 • www.thelancet.com 557 11 Teirstein PS, Massullo V, Jani S, et al. Catheter-based radiotherapy to inhibit restenosis after coronary stenting. N Engl J Med 1997; 336: 1697–703. 12 Waksman R, White RL, Chan RC, et al. Intracoronary radiation therapy after angioplasty inhibits recurrence in patients with in-stent restenosis. Circulation 2000; 101: 2165–71. 13 Leon MB, Teirstein PS, Moses JW, et al. Localized intracoronary gamma radiation therapy to inhibit the recurrence of restenosis after stenting N Engl J Med 2001; 344: 250–56. 14 Kleiman NS, Califf RM. Results from late-breaking clinical trials sessions at ACCIS 2000 and ACC 2000. JACC 2000; 36: 310–25. 15 Waksman R, Bhargava B, White L, et al. Intracoronary beta-radiation therapy inhibits recurrence of in-stent restenosis. Circulation 2000; 101: 1895–98. 16 Raizner AE, Oesterle S, Waksman R, et al. The PREVENT trial, a feasibility study of intracoronary brachytherapy in the prevention of restenosis: an interim report. Circulation 1998; 98: 3423. 17 Waksman R, Bhargava B, Mintz GS, et al. Late total occlusion after intracoronary brachytherapy for patients with in-stent restenosis. J Am Coll Cardiol 2000; 36: 65–68. 18 Waksman R, Ajani EA, White L, et al. Prolonged antiplatelet therapy to prevent late thrombosis after intracoronary radiation in patients with in-stent restenosis: Washington radiation for in-stent restenosis trial plus 6 months of clopidogrel (WRIST PLUS). Circulation 2001; 103: 2328–31. 19 Kim HS, Waksman R, Cottin Y, et al. Edge stenosis and geographical miss following intracoronary gamma radiation therapy for in-stent restenosis. J Am Coll Cardiol 2000; 37: 1026–30. 20 Verin V, Popowski Y, De Bruyne B, et al. Endoluminal beta radiation therapy for the prevention of coronary restenosis after balloon angioplasty. N Engl J Med 2001; 344: 243–49.

Safety and efficacy of manual stepping and overlapping of β-emitter for diffuse in-stent restenosis lesions

Background: The effects of overlapping β-emitter sources on the treatment of in-stent restenosis (ISR) lesions as a result of manual stepping are unknown. Methods and results: In the BETA WRIST (Beta Washington Radiation for In-stent Restenosis Trial), 17 out of the 50 patients who received radiation treatment had diffuse ISR in native coronaries that required manual stepping of the β-emitter ( 90Y) source in order to cover the lesion and the edges. Fourteen of those patients received radiation with an overlap of up to 3 mm in the middle of the stented segment. The prescribed dose was 20.6 Gy to a distance of 1.0 mm from the surface of the inflated balloon, and the calculated dose to the vessel wall at the overlapped area did not exceed 75 Gy. There was no difference in late total occlusion (7.1% vs. 9.0%, P=NS) and target lesion revascularization (28.5% vs. 27.2%, P=NS) between patients with stepping and those without stepping. At 6 months, there was no evidence of perforation or aneurysm at the overlapped segments. Quantitative coronary angiographic (QCA) analysis revealed significantly reduced late loss in the overlapped segment compared to the adjacent segment ( P=.04). Serial (postradiation vs. follow-up) IVUS measurement showed larger mean lumen cross-sectional area (CSA) ( P=.0035) and smaller mean intimal hyperplasia (IH) CSA ( P=.0010) in the overlapped segment compared to the adjacent segment. Conclusion: Manual stepping of β-emitter source with a short overlapped segment is safe for diffuse ISR. Further increase in lumen dimension and reduction in IH formation are observed at the overlapped segment.

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.

Is 6 months of plavix enough to prevent late total occlusion after gamma radiation for in-stent restenosis?: Ron Waksman, Andrew E. Ajani, Han-Soo Kim, Roxana Mehran, Alexandra J. Lansky, Regina Deible, Maeve Taaffe, Gary S. Mintz, Lowell F. Satler, Kenneth M. Kent, Augusto D. Pichard. Washington Hospital Center, Washington, DC

Is 6 months of plavix enough to prevent late total occlusion after gamma radiation for in-stent restenosis?: Ron Waksman, Andrew E. Ajani, Han-Soo Kim, Roxana Mehran, Alexandra J. Lansky, Regina Deible, Maeve Taaffe, Gary S. Mintz, Lowell F. Satler, Kenneth M. Kent, Augusto D. Pichard. Washington Hospital Center, Washington, DC

Late total occlusion after intracoronary brachytherapy for patients with in-stent restenosis

OBJECTIVESThe study sought to determine the incidence and predictors of late total occlusion (LTO, >30 days) in-patients with in-stent restenosis who were treated with intracoronary radiation.BACKGROUNDIntracoronary radiation both with beta and gamma emitters has been shown to reduce recurrent in-stent restenosis.METHODSWe reviewed the records of 473 patients who presented with in-stent restenosis and who were enrolled in various radiation protocols, whether randomized to placebo versus radiation or entered into registries. There were 165 placebo and 308 radiated patients, including both gamma and beta emitters. Maximum dose to the vessel wall was 30 to 55 Gy. Following radiation, all patients received antiplatelet therapy with aspirin and either ticlopidine or clopidogrel for one month. All patients completed at least six months of angiographic follow-up.RESULTSThe LTO was documented in 28 patients (9.1%) from the irradiated group versus 2 placebo patients (1.2%), p < 0.0001. The LTO rates were similar across studies and emitters. In the irradiated group, LTO presented as acute myocardial infarction in 12 patients (43%), unstable angina in 14 (50%), and asymptotic in 2 (7%). Mean time to LTO was 5.4 ± 3.2 months in the irradiated group versus 4.5 ± 2.1 in placebo patients (p = NS). The overall rate of restenting for the entire study group at the time of radiation was 48.6%. Importantly, new stents were placed in 82% of the irradiated and in 100% of the placebo patients who presented with LTO. Multivariate analysis determined that new stenting was the main predictor of LTO.CONCLUSIONSIntracoronary radiation for patients with in-stent restenosis is associated with a high rate of LTO. Restenting may contribute late thrombosis. Prolonged antiplatelet therapy (up to six months) should be considered for these patients.

Late Thrombosis After Radiation

Five years after Condado et al1 first treated human coronary arteries with brachytherapy, there is ongoing clinical investigation into its safety and efficacy in preventing restenosis. As with any novel technique, unexpected complications may dampen early high expectations and result in pessimism and skepticism. However, time, experience, and complete data analysis will determine the reality. Costa and coworkers2 may be reacting prematurely by reporting a new phenomenon in interventional cardiology entitled “late, sudden thrombosis after PTCA plus radiotherapy.” They report 6 (6.6%) of 91 patients who presented with late total occlusion/thrombosis at angiographic follow-up; these patients were enrolled into different radiation protocols using different β-emitters at different prescribed doses. Late total occlusion or late thrombosis is a valid concern, especially when associated with acute myocardial infarction (MI). However, can we really draw any conclusion from 6 heterogeneous case reports taken from a small cohort of patients in the absence of a control group? Is this announcement based on too few data, and is it premature? An editorial based on a Brief Rapid Communication mandates the editorialist to gather additional information, disclose his own insights, and provide the readers (the jury in this case) with as much information as possible. Acute thrombosis occurs during or early after intervention, and subacute thrombosis occurs within the subsequent 30 days. Both usually present with unstable symptoms and angiographic evidence of thrombus. However, the definition of late thrombosis may be problematic. It may not present with symptoms. It may be detected only when follow-up angiography shows a late total occlusion, which could also be the result of progressive intimal hyperplasia. Late total occlusion/thrombosis should be defined as any angiographically documented total occlusion >30 days after the procedure. For patients who have a patent treatment site at 6 months and subsequently develop a total …