Two-year follow-up after catheter-based radiotherapy to inhibit coronary restenosis.

BACKGROUND: Although early trials indicate the treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The possibility of late untoward consequences, such as aneurysm formation, perforation, and accelerated vascular disease, is of significant concern. Furthermore, it is not known whether the beneficial effects of radiation therapy will be durable or whether radiation will only delay restenosis. METHODS AND RESULTS: A double-blind, randomized trial was undertaken to compare 192Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Patients were randomly assigned to receive a 0.76-mm (0. 03-in) ribbon containing sealed sources of either 192Ir or placebo. All patients underwent repeat coronary angiography at 6 months. All living patients were contacted 24 months after their index study procedure. Patients were assessed with respect to the need for target-lesion revascularization or nontarget-lesion revascularization, occurrence of myocardial infarction, or death. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192Ir and 29 to placebo. Follow-up was obtained in 100% of living patients at a minimum of 24 months. Target-lesion revascularization was significantly lower in the 192Ir group (15.4% versus 44.8%; P<0. 01). Nontarget-lesion revascularization was similar in 192Ir and placebo patients (19.2% versus 20.7%; P=NS). There were 2 deaths in each group. The composite end point of death, myocardial infarction, or target-lesion revascularization was significantly lower in 192Ir-treated versus placebo-treated patients (23.1% versus 51.7%; P=0.03). No patient in the 192Ir group sustained a target-lesion revascularization later than 10 months. CONCLUSIONS: At 2-year clinical follow-up, treatment with 192Ir demonstrates significant clinical benefit. Although further follow-up (including late angiography) will be necessary, no clinical events have occurred to date in the 192Ir group to suggest major untoward effects of vascular radiotherapy. At the intermediate follow-up time point, vascular radiotherapy continues to be a promising new treatment for restenosis.

Three-year clinical and angiographic follow-up after intracoronary radiation : results of a randomized clinical trial.

BACKGROUND: Although several early trials indicate treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The objective of this report is to document angiographic and clinical outcome 3 years after treatment of restenotic stented coronary arteries with catheter-based (192)Ir. METHODS AND RESULTS: A double-blind, randomized trial compared (192)Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to (192)Ir and 29 to placebo. At 3-year follow-up, target-lesion revascularization was significantly lower in the (192)Ir group (15. 4% versus 48.3%; P<0.01). The dichotomous restenosis rate at 3-year follow-up was also significantly lower in (192)Ir patients (33% versus 64%; P<0.05). In a subgroup of patients with 3-year angiographic follow-up not subjected to target-lesion revascularization by the 6-month angiogram, the mean minimal luminal diameter between 6 months and 3 years decreased from 2.49+/-0.81 to 2.12+/-0.73 mm in (192)Ir patients but was unchanged in placebo patients. CONCLUSIONS: The early clinical benefits observed after treatment of coronary restenosis with (192)Ir appear durable at late follow-up. Angiographic restenosis continues to be significantly reduced in (192)Ir-treated patients, but a small amount of late loss was observed between the 6-month and 3-year follow-up time points. No events occurred in the (192)Ir group to suggest major untoward effects of vascular radiotherapy. At 3-year follow-up, vascular radiotherapy continues to be a promising new treatment for restenosis.

The effect of ovariectomy on spine bone mineral density in rhesus monkeys.

As part of a study on the effects of hormones on uterine biology and estrogen metabolism, 12 normal female rhesus (Macaca mulatta) monkeys were ovariectomized, and treated intermittently with estradiol and progesterone. In order to determine whether there were changes in bone density as a result of ovariectomy despite the hormone therapy, spine bone mineral density (BMD) was measured by dual-photon absorptiometry. The mean +/- SE time from ovariectomy was 26 +/- 3 months, the mean estrogen treatment time was 3.5 +/- 0.4 months and the mean time from last hormonal treatment was 4.1 +/- 0.6 months. In these 12 monkeys aged 7.7 +/- 0.2 years, the mean spine BMD, 0.825 +/- 0.008 g/cm2, was significantly less, p = 0.0011, than the spine BMD, 0.863 +/- 0.007 g/cm2, in 12 intact female rhesus of similar age, 7.6 +/- 0.1 years and weight. Ovariectomy in female rhesus monkeys results in a relatively rapid diminution of spine BMD which is not prevented by intermittent hormonal replacement. This species may be an excellent model for studies of human osteoporosis.

A subgroup analysis of the Scripps Coronary Radiation to Inhibit Proliferation Poststenting Trial.

INTRODUCTION: In the Scripps Coronary Radiation to Inhibit Proliferation Poststenting (SCRIPPS) Trial, 192Ir significantly reduced angiographic, ultrasonographic, and clinical endpoints of restenosis. The objective of this analysis was to quantitate the impact of patient, lesion and technical characteristics on late angiographic outcome. METHODS: Patients with restenotic, stented coronary lesions were randomized to receive either 192Ir or placebo sources. Late luminal loss and loss index were calculated for several patient subgroups, including patients with diabetes, in-stent restenosis, multiple previous percutaneous transluminal coronary angioplasty (PTCA) procedures, longer lesion lengths, saphenous vein grafts, small vessel diameters, and minimum dose exposures < 8.00 Gy. Two-factor analysis of variance was used to test for an interaction between patient characteristics and treatment effect. RESULTS: In the treated group, late loss was particularly low in patients with diabetes (0.19 mm), in-stent restenosis (0.17 mm), reference vessel diameters < 3.0 mm (0.07 mm), and patients who received a minimum radiation dose to the entire adventitial border of at least 8.00 Gy. The loss index in each of these subgroups was similarly low at -0.02, 0.03, -0.02, and 0.03, respectively. By 2-factor analysis of variance, a significant interaction between subgroup characteristic and treatment effect (late loss) was found in patients with in-stent restenosis (p = 0.035), and patients receiving a minimum dose of 8.00 Gy to the adventitial border (p = 0.009). CONCLUSION: In this pilot study, patient characteristics associated with a more aggressive proliferative response to injury appeared to confer an enhanced response to radiotherapy. Furthermore, a dose threshold response to 192Ir was found with an enhanced response occurring when the entire circumference of the adventitial border was exposed to at least 8.00 Gy.

Quantitative angiographic analysis of stent restenosis in the Scripps Coronary Radiation to Inhibit Intimal Proliferation Post Stenting (SCRIPPS) Trial.

To identify luminal dimension changes occurring within the stent alone and within the stent + margin segment, we reviewed the quantitative angiographic results obtained from the Scripps Coronary Radiation to Inhibit Proliferation Post Stenting (SCRIPPS) trial, a prospective randomized trial assessing the effect of iridium-192 (Ir-192) on the prevention of stent restenosis. Fifty-five patients were randomly assigned to receive Ir-192 or placebo sources after successful intervention. Procedural and 6-month follow-up cineangiograms were quantitatively reviewed in 52 patients to identify changes within the stent and the stent + margin segment. The percent diameter stenosis was lower within the stent than within the stent + margin segment after the procedure (6 +/- 22% vs 21+/- 15%, p <0.0001) and at follow-up (28 +/- 29% vs 42 +/- 21%, p <0.0001). As a result, a lower restenosis rate was found within the stent than within the stent + margin (25% vs 37%, p <0.0001); isolated stent margin restenosis occurred in 11.5% of lesions. Treatment with Ir-192 reduced restenosis within the stent (8% vs 39%; p = 0.010) and within the stent + margin segment (17% vs 54%; p = 0.010); the reduction in restenosis at the margin only (8.3% vs 14.3%, p = 0.503) was not significant. The lowest relative risk for restenosis resulting from Ir-192 occurred within the stent (0.21; 95% confidence interval [CI] 0.05 to 0.86) compared with the stent + margin segment (0.31; 95% CI 0.12 to 0.81) or the stent margin (0.58; 95% CI 0.12 to 2.91). In the SCRIPPS trial, 32% of restenosis occurred at the stent margins. Treatment with Ir-192 reduced restenosis primarily within the stent rather than the margin. Whether extending the treatment length to fully include the stent margins will further reduce restenosis requires further study.

Radiation safety of personnel during catheter-based Ir-192 coronary brachytherapy.

Catheter-based brachytherapy using Ir-192 seed sources has shown significant reduction in the rate of restenosis among patients with coronary in-stent restenosis. High-energy gamma rays from Ir-192 raise some radiation safety issues of personnel. The aim of this study was to fully analyze the radiation safety issues associated with Ir-192 brachytherapy in the cardiac cath lab environment. Measurements were made to assess the penetrating ability of Ir-192 gamma rays through tissues, concrete and lead. Radiation exposure levels were measured around a large number of patients undergoing Ir-192 brachytherapy. Personnel were carefully monitored for any additional dose received from brachytherapy for the last five years covering > 500 cases. Our results showed that with a proper radiation safety program in place, the dose to cath lab staff was negligible. It was concluded that radiation safety of personnel was easy to maintain during catheter-based coronary brachytherapy using Ir-192 seed sources.

Physics and safety aspects of a coronary irradiation pilot study to inhibit restenosis using manually loaded 192Ir ribbons.

Radiation therapy has been successfully used in controlling some forms of benign tissue growth. A pilot study has been launched to evaluate the usefulness of localized radiation therapy in reducing restenosis after coronary angioplasty. In this randomized, double-blind study, patients with known restenosis received balloon angioplasty or additional stent implantation and were then randomized to receive either radiation or placebo treatment. Active sources consisted of 192Ir in the form of cylindrical seeds (0.3 x 0.05 cm). The seeds are embedded in a nylon ribbon. The nylon ribbon is passed through an indwelling coronary catheter. For this pilot trial, radioactive sources were exposed to blood elements and, therefore, required sterilization. A method of sterilization is described. A working team was developed to perform coronary radiation procedures at our institution. A description of the procedure is provided.

Ultrasound attenuation of the os calcis in women with osteoporosis and hip fractures.

Bone ultrasound attenuation of the calcaneus, and vertebral and femoral bone density measured by dual photon absorption were determined in 22 women with osteoporosis, 10 women with hip fractures, and 29 normal, age-matched controls to determine the utility of the ultrasound technique as an indicator of axial osteopenia. Vertebral and femoral neck density and bone ultrasound attenuation were significantly decreased (P less than 0.01) in the women with osteoporosis and those with hip fractures. The sensitivity and specificity of bone ultrasound attenuation was 80% at a value of 50 dB/MHz. At 90% specificity the sensitivity of bone ultrasound attenuation was 65%. The results of this pilot study suggest that ultrasound attenuation, a safe, simple, and radiation-free procedure, may be utilized as an indicator of decreased axial bone mass.

Catheter-based radiotherapy to inhibit restenosis after coronary stenting.

BACKGROUND: In animal models of coronary restenosis, intracoronary radiotherapy has been shown to reduce the intimal hyperplasia that is a part of restenosis. We studied the safety and efficacy of catheter-based intracoronary gamma radiation plus stenting to reduce coronary restenosis in patients with previous restenosis. METHODS: Patients with restenosis underwent coronary stenting, as required, and balloon dilation and were then randomly assigned to receive catheter-based irradiation with iridium-192 or placebo. Clinical follow-up was performed, with quantitative coronary angiographic and intravascular ultrasonographic measurements at six months. RESULTS: Fifty-five patients were enrolled; 26 were assigned to the iridium-192 group and 29 to the placebo group. Angiographic studies were performed in 53 patients (96 percent) at a mean (+/-SD) of 6.7+/-2.2 months. The mean minimal luminal diameter at follow-up was larger in the iridium-192 group than in the placebo group (2.43+/-0.78 mm vs. 1.85+/-0.89 mm, P=0.02). Late luminal loss was significantly lower in the iridium-192 group than in the placebo group (0.38+/-1.06 mm vs. 1.03+/-0.97 mm, P=0.03). Angiographically identified restenosis (stenosis of 50 percent or more of the luminal diameter at follow-up) occurred in 17 percent of the patients in the iridium-192 group, as compared with 54 percent of those in the placebo group (P= 0.01). There were no apparent complications of the treatment. CONCLUSIONS: In this preliminary, short-term study of patients with previous coronary restenosis, coronary stenting followed by catheter-based intracoronary radiotherapy substantially reduced the rate of subsequent restenosis.