phosphorus-radioisotopes and Graft-Occlusion--Vascular

Brachytherapy by implantation of a radioactive stent is an alternative approach to catheter-based systems to reduce restenosis. The pilot clinical trials using 32P radioactive b-emitting stents at low-to-intermediate activity (0.5Eth 3.0 mCi) showed that restenosis at 6 months was not different from that of currently available non-radioactive stents. The evaluation of the efficacy in reducing restenosis of radioactive stents with higher activities (3Eth 24 mCi) started in Europe (Milan, Rotterdam and Vienna) between 1998 and 1999. In the Milan and Rotterdam experience, 32P radioactive stents with an activity of 3Eth 12 mCi demonstrated a reduction of intra-stent restenosis to < 4%. However, a high-edge restenosis > 30% was observed in the first 1Eth 3 mm outside the stent margins. This edge effect might be due to a low dose of radiation at the stent margins combined with systematic balloon injury in the reference segments. The hypothesis that a further increase in stent activity (12Eth 21 mCi) associated with a reduced balloon injury outside the stent could solve the problem of edge restenosis was not confirmed by the Milan experience; edge restenosis still occurred in 26% of the lesions treated by a single 32P radioactive stent, even if a nonaggressive stent implantation strategy was used. Two approaches under investigation to solve the problem of edge restenosis are: 1) lengthening the stent with a non-radioactive stent (cold-ends stent) to prevent negative remodeling; and 2) extending the area of irradiation beyond the balloon-injured area by an increased activity at the stent ends (hot-ends stent).

Topics: Blood Vessel Prosthesis Implantation; Brachytherapy; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Disease; Coronary Vessels; Dose-Response Relationship, Radiation; Equipment Safety; Europe; Graft Occlusion, Vascular; Humans; Phosphorus Radioisotopes; Stents

Radioactive stents with an activity of 0.75 to 12 microCi have shown >40% edge restenosis due to neointimal hyperplasia and negative remodeling. This trial evaluated whether radioactive Cold Ends stents might resolve edge restenosis by preventing remodeling at the injured extremities.. The 25-mm long (15-mm radioactive center and 5-mm nonradioactive ends) Cold Ends stents had an activity of 3 to 12 microCi at implantation. Forty-three stents were implanted in 43 patients with de novo native coronary artery disease. Two procedural, 1 subacute, and 1 late stent thrombosis occurred. A restenosis rate of 22% was observed with a shift of the restenosis, usually occurring at the stent edges of radioactive stents, into the Cold Ends stents. The most severe restenosis occurred at the transition zone from radioactive to nonradioactive segments, a region located in dose fall-off.. Cold Ends stents did not resolve edge restenosis.

Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; Blood Vessel Prosthesis Implantation; Brachytherapy; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Dose-Response Relationship, Radiation; Female; Fibrinolytic Agents; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Platelet Aggregation Inhibitors; Stents; Treatment Outcome

Restenosis after conventional stenting is almost exclusively caused by neointimal hyperplasia. Beta-particle-emitting radioactive stents decrease in-stent neointimal hyperplasia at 6-month follow-up. The purpose of this study was to evaluate the 1-year outcome of (32)P radioactive stents with an initial activity of 6 to 12 microCi using serial quantitative coronary angiography and volumetric ECG-gated 3D intravascular ultrasound (IVUS).. Of 40 patients undergoing initial stent implantation, 26 were event-free after the 6-month follow-up period and 22 underwent repeat catheterization and IVUS at 1 year; they comprised half of the study population. Significant luminal deterioration was observed within the stents between 6 months and 1 year, as evidenced by a decrease in the angiographic minimum lumen diameter (-0.43+/-0.56 mm; P:=0.028) and in the mean lumen diameter in the stent (-0.55+/-0. 63 mm; P:=0.001); a significant increase in in-stent neointimal hyperplasia by IVUS (18.16+/-12.59 mm(3) at 6 months to 27.75+/-11. 99 mm(3) at 1 year; P:=0.001) was also observed. Target vessel revascularization was performed in 5 patients (23%). No patient experienced late occlusion, myocardial infarction, or death. By 1 year, 21 of the initial 40 patients (65%) remained event-free.. Neointimal proliferation is delayed rather than prevented by radioactive stent implantation. Clinical outcome 1 year after the implantation of stents with an initial activity of 6 to 12 microCi is not favorable when compared with conventional stenting.

Topics: Adult; Aged; Brachytherapy; Coronary Angiography; Coronary Disease; Endosonography; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Radiation Dosage; Stents; Treatment Failure; Treatment Outcome

This study represents the Heart Center Rotterdam's contribution to the Isostents for Restenosis Intervention Study, a nonrandomized multicenter trial evaluating the safety and feasibility of the radioactive Isostent in patients with single coronary artery disease. Restenosis after stent implantation is primarily caused by neointimal hyperplasia. In animal studies, beta-particle-emitting radioactive stents decrease neointimal hyperplasia by inhibiting smooth muscle cell proliferation.. The radioisotope (32)P, a beta-particle emitter with a half-life of 14.3 days, was directly embedded into the Isostent. The calculated range of radioactivity was 0.75 to 1.5 microCi. Quantitative coronary angiography measurements were performed before and after the procedure and at 6-month follow-up. A total of 31 radioactive stents were used in 26 patients; 30 (97%) were successfully implanted, and 1 was embolized. Treated lesions were in the left anterior descending coronary artery (n=12), the right coronary artery (n=8), or the left circumflex coronary artery (n=6). Five patients received additional, nonradioactive stents. Treated lesion lengths were 13+/-4 mm, with a reference diameter of 2.93+/-0. 47 mm. Minimum lumen diameter increased from 0.87+/-0.28 mm preprocedure to 2.84+/-0.35 mm postprocedure. No in-hospital adverse cardiac events occurred. All patients received aspirin indefinitely and ticlopidine for 4 weeks. Twenty-three patients (88%) returned for 6-month angiographic follow-up; 17% of them had in-stent restenosis, and 13% had repeat revascularization. No restenosis was observed at the stent edges. Minimum lumen diameter at follow-up averaged 1.85+/-0.69 mm, which resulted in a late loss of 0.99+/-0. 59 mm and a late loss index of 0.53+/-0.35. No other major cardiac events occurred during the 6-month follow-up.. The use of radioactive stents with an activity of 0.75 to 1.5 microCi is safe and feasible.

Topics: Adult; Aged; Aspirin; Beta Particles; Brachytherapy; Coronary Angiography; Coronary Disease; Feasibility Studies; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Patient Selection; Phosphorus Radioisotopes; Platelet Aggregation Inhibitors; Stents; Ticlopidine

We report a case of obstructive in-stent restenosis in a diffusely diseased saphenous vein graft complicated by a non-ST-elevation myocardial infarction. With tirofiban infusion, the extensively occluded saphenous bypass was reperfused, establishing a TIMI flow 3, and then entirely irradiated with a beta source (32P) without any complication. At 7 months the patient was asymptomatic and the control angiogram did not reveal any restenosis. In conclusion, 32P beta brachytherapy may be extremely effective not only in case of native vessel in-stent restenosis but also in cases of high-risk vein graft in-stent restenosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Aspirin; Beta Particles; Blood Vessel Prosthesis; Brachytherapy; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Female; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Myocardial Infarction; Phosphorus Radioisotopes; Reoperation; Saphenous Vein; Stents; Ticlopidine; Tirofiban; Tyrosine

Intracoronary radiation has shown the potential to reduce formation of neointima in porcine models of restenosis.. To investigate the feasibility, safety, and efficacy of a new 'deployable-balloon' device with radioisotope 32P integrated into the balloon material.. Ten swine were subjected to balloon-overstretching injury in 20 coronary arteries and were randomly allocated to receive a radiation dose of 0, 15, or 20Gy prescribed to 1 mm from the surface of the radioactive balloon material. The animals were killed 4 weeks after the procedure. Their coronaries were perfusion fixed and stained. Vessel parameters (area of intima and length of fracture) and area of thrombus area were analyzed by computer-aided histomorphometry.. Radiation treatment with the new 32P balloon device was performed without complications. The lengts of fracture for the three groups were similar (NS). Formation of neointima after balloon injury was less in members of the radiated groups than it was in controls (area of intima/length of fracture was 0.70 +/-0.12 mm for controls, 0.08+/-0.13mm with 15 Gy, and 0.07+/-0.17 mm with 20 Gy; P < 0.001). Vessels treated with 20 Gy had a greater total area of thrombus (0.00+/-0.00 versus 0.51+/-0.98 mm2, P< 0.01).. Intracoronary radiation therapy using a new 32P deployable-balloon system is feasible and safe. A radiation dose of 15 Gy was sufficient to inhibit neointimal response in the porcine coronary-balloon-injury model.

Topics: Angioplasty, Balloon, Coronary; Animals; Brachytherapy; Coronary Disease; Coronary Vessels; Feasibility Studies; Graft Occlusion, Vascular; Phosphorus Radioisotopes; Random Allocation; Secondary Prevention; Swine; Tunica Intima

A recognized limitation of radioactive stents is the development of restenosis at the stent edges, known as the "candy-wrapper" effect. The mechanisms of this effect remain incompletely understood and controversial. The aim of this study is to assess the effect of endovascular irradiation on neointima formation and vascular remodeling. (32)P Palmaz-Schatz stents (1.5-4 microCi) were implanted in 11 patients with restenosis after previous percutaneous transluminal coronary angioplasty (PTCA). Intravascular ultrasound (IVUS) images of target sites and adjunct vessel segments were acquired both during intervention and after 6 months. The angiographic restenosis rate was 54%, and the MLD decreased from 2.21 +/- 0.6 mm to 1.38 +/- 0.4 mm at follow-up (P < 0.01). IVUS analysis demonstrated that late lumen loss was the result of neointimal tissue proliferation, which was nonuniformly distributed and exaggerated at both the central articulation and the distal stent edges. Negative remodeling did not contribute to restenosis. In contrast, we found a linear relationship between increase of area stenosis and a positive remodeling index (r = 0.84, P < 0.0001). Restenosis after implantation of (32)P Palmaz-Schatz stents was mainly the result of neointimal tissue proliferation which tended to be nonuniformly distributed in the stent articulation and edges. Negative remodeling or stent recoil was not observed. Cathet Cardiovasc Intervent 2001;54:41-48.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Endothelium, Vascular; Female; Graft Occlusion, Vascular; Humans; Hyperplasia; Male; Middle Aged; Phosphorus Radioisotopes; Stents; Ultrasonography, Interventional

Topics: Brachytherapy; Coronary Disease; Graft Occlusion, Vascular; Humans; Phosphorus Radioisotopes; Stents

Radioactive stents have been reported to reduce in-stent neointimal thickening. An unexpected increase in neointimal response was observed, however, at the stent-to-artery transitions, the so-called "edge effect." To investigate the factors involved in this edge effect, we studied stents with 1 radioactive half and 1 regular nonradioactive half, thereby creating a midstent radioactive dose-falloff zone next to a nonradioactive stent-artery transition at one side and a radioactive stent-artery transition at the other side.. Half-radioactive stents (n=20) and nonradioactive control stents (n=10) were implanted in the coronary arteries of Yucatan micropigs. Animals received aspirin and clopidogrel as antithrombotics. After 4 weeks, a significant midstent stenosis was observed by angiography in the half-radioactive stents. Two animals died suddenly because of coronary occlusion at this mid zone at 8 and 10 weeks. At 12-week follow-up angiography, intravascular ultrasound and histomorphometry showed a significant neointimal thickening at the midstent dose-falloff zone of the half-radioactive stents, but not at the stent-to-artery transitions at both extremities. Such a midstent response (mean angiographic late loss 1.0 mm) was not observed in the nonradioactive stents (mean loss 0.4 to 0.6 mm; P< 0.01).. The edge effect of high-dose radioactive stents in porcine coronary arteries is associated with the combination of stent injury and radioactive dose falloff.

Topics: Animals; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Vessels; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Radiation; Drug Implants; Female; Graft Occlusion, Vascular; Implants, Experimental; Phosphorus Radioisotopes; Stents; Swine, Miniature; Tunica Intima; Vascular Patency

Balloon-expandable beta-particle-emitting ((32)P) stents inhibit within-stent neointimal hyperplasia but induce lumen narrowing beyond the stent margins, ie, the so-called "edge effects.". We prospectively investigated the performance of novel stents impregnated with the gamma-emitting isotope (103)Pd, designed to reduce edge effects, in 24 rabbits. The stents had a length of 18 mm and were mounted on 20-mm-long delivery balloons for deployment. Angiograms were obtained immediately and 1 month after direct implantation of control and 1-, 2-, and 4-mCi (103)Pd stents into the iliac arteries without predilatation or postdilatation. Late lumen loss was measured with quantitative angiography. Neointimal hyperplasia and vascular remodeling were evaluated by histomorphometry. Late lumen loss was inhibited within (103)Pd stents (control 0.18 mm, 1 mCi 0.08 mm, 2 mCi 0.05 mm, and 4 mCi -0.03 mm, P<0.05 all activities versus control). Conversely, late lumen loss occurred at the edges of (103)Pd stents, correlating with areas of high balloon/artery ratios and vessel overstretch injury. Edge effects were primarily due to neointimal hyperplasia but were also caused by negative vessel remodeling at high stent activities.. Edge effects after implantation of radioisotope stents can occur independently of the isotope chosen for stent impregnation.

Topics: Angiography; Animals; Blood Vessel Prosthesis Implantation; Dose-Response Relationship, Radiation; Drug Implants; Female; Gamma Rays; Graft Occlusion, Vascular; Iliac Artery; Implants, Experimental; Palladium; Phosphorus Radioisotopes; Prospective Studies; Rabbits; Radioisotopes; Radiometry; Stents; Tunica Intima; Vascular Patency