Serial intravascular ultrasound analysis of the impact of lesion length on the efficacy of intracoronary gamma-irradiation for preventing recurrent in-stent restenosis.
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BACKGROUND: The relation between lesion length and effectiveness of brachytherapy is not well studied. METHODS AND RESULTS: We compared serial (postintervention and follow-up) intravascular ultrasound findings in 66 patients with native coronary artery in-stent restenosis (ISR) who were treated with (192)Ir (15 Gy delivered 2 mm away from the radiation source). Patients were enrolled in the Washington Radiation for In-Stent Restenosis Trial (WRIST; ISR length, 10 to 47 mm; n=36) or Long WRIST (ISR length, 36 to 80 mm; n=30). External elastic membrane, stent, lumen, and intimal hyperplasia (IH; stent minus lumen) areas and source-to-target (intravascular ultrasound catheter to external elastic membrane) distances were measured. Postintervention stent areas were larger in WRIST and smaller in Long WRIST patients (P:<0.0001). At follow-up, maximum IH area significantly increased in both WRIST and Long WRIST patients (P:<0.0001 for both), but this increase was greater in Long WRIST patients (P:=0.0006). Similarly, minimum lumen cross-sectional area significantly decreased in both WRIST and Long WRIST patients (P:<0.05 and P:<0.0001, respectively), but this decrease was more pronounced in Long WRIST patients (P:=0.0567). The maximum source-to-target distance was longer in Long WRIST than in WRIST, and it correlated directly with ISR length (r=0.547, P:<0.0001). Overall, the change in minimum lumen area and the change in maximum IH area correlated with the maximum source-to-target distance (r=0.352, P:=0.0038 and r=0.523, P:<0.0001 for WRIST and Long WRIST, respectively). The variability (maximum/minimum) in IH area at follow-up also correlated with the maximum source-to-target distance (r=0.378, P:<0.0001). CONCLUSIONS: Brachytherapy may be less effective in longer ISR lesions because of the greater variability and longer source-to-target distances in diffuse ISR. (+info)
Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: a quantitative coronary angiography and three-dimensional intravascular ultrasound study.
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BACKGROUND: Restenosis remains an important limitation of interventional cardiology. Therefore, we aimed to determine the safety and efficacy of sirolimus (a cell-cycle inhibitor)-coated BX Velocity stents. METHODS AND RESULTS: Thirty patients with angina pectoris were electively treated with 2 different formulations of sirolimus-coated stents (slow release [SR], n=15, and fast release [FR], n=15). All stents were successfully delivered, and patients were discharged without clinical complications. Independent core laboratories analyzed angiographic and 3D volumetric intravascular ultrasound data (immediately after procedure and at 4-month follow-up). Eight-month clinical follow-up was obtained for all patients. There was minimal neointimal hyperplasia in both groups (11.0+/-3.0% in the SR group and 10.4+/-3.0% in the FR group, P:=NS) by ultrasound and quantitative coronary angiography (in-stent late loss, 0.09+/-0.3 mm [SR] and -0.02+/-0.3 mm [FR]; in-lesion late loss, 0.16+/-0.3 mm [SR] and -0.1+/-0.3 mm [FR]). No in-stent or edge restenosis (diameter stenosis >or=50%) was observed. No major clinical events (stent thrombosis, repeat revascularization, myocardial infarction, or death) had occurred by 8 months. CONCLUSIONS: The implantation of sirolimus-coated BX Velocity stents is feasible and safe and elicits minimal neointimal proliferation. Additional placebo-controlled trials are required to confirm these promising results. (+info)
Oral anticoagulant therapy during and after coronary angioplasty the intensity and duration of anticoagulation are essential to reduce thrombotic complications.
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BACKGROUND: In the randomized Balloon Angioplasty and Anticoagulation Study (BAAS), the addition of oral anticoagulants to aspirin significantly reduced early and late events after coronary angioplasty. However, bleeding episodes were increased. The present report studied the intensity and the duration of anticoagulation as predictors of thrombotic and bleeding events. METHODS AND RESULTS: A total of 530 patients, 34% of whom received a stent, were treated with aspirin plus coumarins. Half of the patients were randomized to angiographic follow-up. The target international normalized ratio (INR) was 2.1 to 4.8 during angioplasty and 6-month follow-up. Thrombotic events were death, myocardial infarction, target lesion revascularization, and thrombotic stroke. Bleeding complications were hemorrhagic stroke, major extracranial bleeding, and false aneurysm. "Optimal" anticoagulation was defined as an INR in the target range for at least 70% of the follow-up time. There were 17 early thrombotic events (3.2%), 7 early bleeding episodes (1.3%), and 10 false aneurysms (1.9%). The incidence rate for both early thrombotic and bleeding events was lowest in patients in the target range. A total of 61 late thrombotic events occurred (11.6%). Optimal anticoagulation was an independent predictor of late thrombotic events (relative risk, 0.33; 95% CI, 0.19 to 0.57) and was associated with a 0.21 mm (95% CI, 0.17 to 0.42) larger vessel lumen at 6 months. Late bleeding episodes (1.4%) were lowest in patients in the target range. CONCLUSIONS: Coumarins started before coronary angioplasty with a target INR of 2.1 to 4.8 led to the lowest procedural event rate, without an increase in bleeding episodes. During follow-up, optimal anticoagulation was associated with a decrease in the incidence of late events by 67% and a significant improvement in 6-month angiographic outcome. (+info)
Relation of a common methylenetetrahydrofolate reductase mutation and plasma homocysteine with intimal hyperplasia after coronary stenting.
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BACKGROUND: Hyperhomocysteinemia has been identified as an independent risk factor for coronary artery disease. Recent studies have shown that a common mutation (nucleotide 677 C-->T) in the methylenetetrahydrofolate reductase (MTHFR) gene may contribute to mild hyperhomocysteinemia and, therefore, to the incidence of coronary artery disease. No information exists, however, regarding the association between the mutation of the MTHFR gene or plasma homocysteine levels and morphological analysis of coronary atherosclerosis using intravascular ultrasound. METHODS AND RESULTS: To examine the potential influence of MTHFR genotype and homocysteine on coronaryarteries morphologically, we screened 62 patients with 65 lesions that were treated with 93 Palmaz-Schatz stents. The plasma homocysteine levels in the patients with the TT genotype were not significantly higher than those in the patients with non-TT (CC+CT) genotypes (13.1 +/- 5.5 versus 11.5 +/- 3.1 mmol/L, P=0.16). Angiographic analysis showed that the percent diameter stenosis in the patients with the TT genotype was significantly greater than that in those with non-TT genotypes (43.7 +/- 17.8% versus 29.0 +/- 22.0%, P=0.015). Intravascular ultrasound analysis showed that the TT genotype was significantly associated with greater intimal hyperplasia area (5.70 +/- 1.94 versus 3.72 +/- 1.38 mm2, P=0.001). In multiple stepwise regression analysis, the number of the T alleles was the only independent predictor of intimal hyperplasia after intervention (r2=0.21, P=0.004). CONCLUSIONS: The homozygous mutant genotype of the MTHFR gene may increase the risk of in-stent restenosis more than does the normal homozygous or heterozygous genotype. (+info)
Long-term effects of intracoronary beta-radiation in balloon- and stent-injured porcine coronary arteries.
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BACKGROUND: The data on the long-term safety and efficacy of intracoronary beta-radiation in animal models are limited. METHODS AND RESULTS: A total of 30 coronary arteries in 15 swine were subjected to balloon or stent injury followed by beta-radiation from a centered 32P source (2000 cGy to 1 mm beyond lumen surface) or a sham radiation procedure. The animals received aspirin for 6 months and ticlopidine for 30 days. Five of the 10 animals subjected to radiation died (at 5 days, 7 days, 3 months [n = 2], and 4 months) as a result of layered, occlusive thrombus at the intervention site (3 stent and 2 balloon injury sites). No deaths occurred in the control group. In the surviving animals, balloon-injured and irradiated vessels showed a trend toward larger lumens than controls (2.15 +/- 0.17 versus 1.80 +/- 0.08 mm2, P=0.06) and larger external elastic lamina areas (3.32 +/- 0.21 versus 2.62 +/- 0.10 mm2, P=0.003). In the stent-injured vessels from surviving animals, lumen, neointimal, and external elastic lamina areas were 3.58 +/- 0.33, 3.16 +/- 0.35, and 8.12 +/- 0.42 mm2 for irradiated vessel segments; these values were not different from those in controls (3.21 +/- 0.15, 2.84 +/- 0.27, and 7.76 +/- 0.28 mm2, respectively). Histologically, healing was complete in most survivors, although intramural fibrin and hemorrhage were occasionally seen. CONCLUSION: In the long-term (6 month) porcine model of restenosis, the inhibition by intracoronary beta-radiotherapy of the neointimal formation that is known to be present at 1 month is not sustained. This lack of effect on neointimal formation after balloon and stent arterial injury is accompanied by subacute and late thrombosis that leads to cardiac death on a background of continuous aspirin but relatively brief ticlopidine treatment. (+info)
Lipid peroxidation may predict restenosis after coronary balloon angioplasty.
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The present study assessed whether lipid peroxidation in plasma might predict restenosis after coronary balloon angioplasty. A total of 87 patients, who had undergone successful coronary balloon angioplasty using standard techniques, were enrolled. Fasting blood samples before the intervention were measured for plasma levels of thiobarbituric acid reactive substances (TBARS, an indicator of lipid peroxidation). Angiography was carried out before and 15 min after angioplasty, and at follow-up (4 months after angioplasty), and evaluated using a quantitative approach. There were 23 patients with restenosis (group R) and 64 patients without restenosis (group N) after coronary balloon angioplasty. The plasma TBARS level (mean+/-SEM) of 4.3+/-0.1 micromol/L in group R was significantly higher than that of 3.2+/-0.1 micromol/L in group N (p<0.01). There were no significant differences in other parameters, including plasma lipid levels, between the 2 groups. The plasma level of TBARS positively correlated with lumen loss of the coronary artery at the time of follow-up angiography (r=0.57, p<0.01). Our results suggest that oxidative stress contributes to restenosis and indicate that an elevated plasma level of TBARS may be a reliable predictor of restenosis. (+info)
Histopathologic evaluation of coronary artery thrombi obtained by directional coronary atherectomy in patients with restenosis-induced unstable angina pectoris.
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The pathogenesis of unstable angina pectoris (UAP) following percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy (DCA) has not been adequately investigated, so the present study aimed to determine whether thrombi are present in restenotic lesions. The study group comprised 14 patients (16 arterial branches) with angina pectoris in whom either PTCA or DCA was performed and who had developed UAP associated with restenosis, and who then underwent DCA of the restenosed lesion (R-UAP group). The control groups comprised individuals with UAP undergoing DCA with no prior history of PTCA or DCA (P-UAP group; n=29, 29 branches), patients with acute myocardial infarction (AMI group; n=34, 34 branches), and patients with stable angina pectoris (SAP group; n=31, 33 branches). The presence of thrombi was determined by light microscopy of histologic specimens. Thrombus was present in only 1 of the 16 (6.3%) branches in the R-UAP group. 21 of the 29 (72.4%) branches in the P-UAP group, and in 25 of the 34 (73.5%) in the AMI group. In the SAP group, it was detected in only 2 of the 33 (7.1%) branches. The incidence of thrombus was significantly lower in the R-UAP group than in the P-UAP group. In conclusion, the role of thrombus is limited in causing post-interventional UAP at restenosed sites. (+info)
Intracoronary brachytherapy in the treatment of in-stent restenosis. Initial experience in Brazil.
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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. (+info)