Clinical and angiographic acute and follow up results of intracoronary beta brachytherapy in saphenous vein bypass grafts: a subgroup analysis of the multicentre European registry of intraluminal coronary beta brachytherapy (RENO).

OBJECTIVE: To assess clinically and angiographically the feasibility, safety, and effectiveness of vascular brachytherapy (VBT) in saphenous vein bypass grafts (SVG). PATIENTS AND METHODS: 67 of 1098 (6.1%) consecutive patients of the European registry of intraluminal coronary beta brachytherapy underwent treatment for 68 SVG lesions by VBT using a Sr/Y(90) source train (BetaCath). Clinical follow up data were obtained for all of them after a mean (SD) of 6.3 (2.4) months and angiographic follow up was performed in 61 patients (91.0%) after 6.9 (2.0) months. RESULTS: 58 (86.6%) patients were men, their mean (SD) age was 66 (10) years, 28 (41.8%) had unstable angina, and 21 (31.3%) had diabetes. Fifty three (77.9%) lesions were in-stent restenosis, 13 (19.1%) de novo lesions, and 2 (3.0%) non-stented restenotic lesions. Mean (SD) reference diameter before the intervention was 4.19 (0.52) mm, mean (SD) lesion length was 23.56 (20.38) mm, and mean (SD) minimum lumen diameter measured 0.73 (0.62) mm. Mean (SD) acute gain was 3.02 (0.88) mm. The prescribed radiation dose was 20.1 (3.2) Gy. Pullback manoeuvres were performed in 17 (25.0%) of cases. Most patients received combined aspirin and thienopyridin treatment for 6 or 12 months after the procedure. Technical success was obtained in 62 (91.2%) treated lesions and in-hospital major adverse cardiac events occurred in 4.5%. At follow up, mean (SD) reference diameter was 4.20 (0.53) mm, minimum lumen diameter 2.94 (1.50) mm, and late loss 0.86 (1.25) mm. The overall major adverse cardiac events rate was 26.7%. CONCLUSION: VBT of SVG is feasible and safe. At follow up the reintervention rate and cardiac morbidity and mortality seem to be favourable, considering that interventions in SVG usually are associated with the highest risks.

The effects of intracoronary brachytherapy on the natural history of postangioplasty dissections.

OBJECTIVES: The aim of this study was to determine the natural history of postangioplasty intravascular ultrasound (IVUS)-detected dissections and to assess the influence of intracoronary beta-radiation on dissection resolution. BACKGROUND: Intracoronary radiotherapy is considered to impair exaggerated vessel healing. Conversely, excessive healing impairment may increase the risk of complications due to unhealed dissection. Alternatively, residual dissection may represent an innocent marker of adequate therapy. METHODS: Immediate postangioplasty and six-month follow-up IVUS studies of 94 patients in the IVUS substudy of the MultiVitamins and Probucol (MVP) trial and 26 nonstented patients in the Beta Energy Restenosis Trial (BERT) were analyzed for the presence or absence of dissection. RESULTS: Of the 28 patients with postangioplasty dissections in MVP, only one had evidence of residual dissection at six months (95% confidence interval [CI] for failure rate 0.2%; 20.2%). Conversely, 9 of 16 dissections had healed in BERT (95% CI for failure rate 30.6%; 79.2%) (p < 0.0002). Nevertheless, an index based on dissection arc and length demonstrated improvement in the irradiated patients. Irradiated patients with residual dissections showed significant increase in lumen area at six-months (5.10 +/- 0.98 to 7.11 +/- 2.61 mm2, p < 0.02) not noted when there was resolution of the dissection (6.03 +/- 2.38 to 6.36 +/- 3.33 mm2, p = NS). In both groups the external elastic membrane area was unchanged at follow-up. CONCLUSIONS: Resolution appears to be the natural history of IVUS-detected dissections in most cases. Significant resolution of dissection occurs following intracoronary beta-radiation as reflected in reduced dissection index at six-months in these patients, although significant impairment of vessel wall healing was noted.

Influence of postangioplasty beta-irradiation on endothelial function in porcine coronary arteries.

BACKGROUND: Postangioplasty (PTCA) intracoronary radiation therapy (ICRT) has been demonstrated to limit restenosis. The consequences of these procedures on coronary reactivity are unknown. METHODS AND RESULTS: Porcine coronary arteries were studied after PTCA immediately (n=5) and 6 weeks (n=5) after ICRT (n=5 and 5, respectively), after combined PTCA+ICRT (n=5 and 7, respectively), and after no intervention (n=11). A 3-cm-long source train of Sr/Y(90) was used in vivo to deliver 16 Gy at a depth of 2 mm from the source center, as used in clinical trials. Arterial rings were mounted on myographs to record isometric tension. After achieving steady-state contraction to depolarizing physiological solution containing 40 mmol/L KCl, measured baseline tension was significantly elevated immediately after all interventions. It returned to normal levels 6 weeks after PTCA and ICRT alone but was significantly reduced if combined. Active contractions induced by 40 mmol/L KCl were maintained after combined therapy both immediately after and at 6 weeks. In these depolarizing conditions, nitric oxide-dependent relaxation to substance P was trivial after PTCA+ICRT and reduced after ICRT, whereas in the presence of physiological solution and N(omega)-nitro-L-arginine, substance P-induced relaxation was reduced after PTCA and abolished after PTCA+ICRT 6 weeks after intervention. In rings without endothelium, the relaxation mediated by sodium nitroprusside (0.1 micromol/L) was reduced immediately after PTCA and at 6 weeks. CONCLUSIONS: PTCA+ICRT altered the passive mechanical properties of porcine coronary arterial wall. Furthermore, at 6 weeks, receptor-operated release of endothelium-derived nitric oxide and endothelium-derived hyperpolarizing factor was reduced by ICRT and PTCA alone, respectively, and was prevented by their combination.

Double vessel occlusions after balloon angioplasty treated by stenting and subsequently by abciximab infusion.

Stent thrombosis is a serious complication after percutaneous coronary intervention. A patient is presented with a double vessel occlusion after balloon angioplasty and subsequent stenting. He was then managed by abciximab therapy alone. Control angiography showed complete resolution of the thrombotic occlusions. His subsequent clinical course was uneventful.

Effects of intracoronary beta-radiation therapy after coronary angioplasty: an intravascular ultrasound study.

BACKGROUND: Endovascular radiation is emerging as a potential solution for the prevention and treatment of restenosis. Its effects on the morphology of unstented vessels cannot be determined by angiography and therefore require the use of intravascular ultrasound. METHODS AND RESULTS: Through a 5F noncentered catheter for delivery of a 90Sr/Y source train, 12, 14, or 16 Gy at 2 mm was delivered to native coronary arteries after successful balloon angioplasty in 30 patients. Four patients required stent deployment in the first week. Quantitative coronary angiography and IVUS were performed during the initial procedure and at 6-month follow-up. Binary angiographic restenosis was present in 3 of 30 patients, with target lesion and vessel revascularization performed in 3 and 5 patients, respectively. Angiographic late loss was -0.02+/-0.60 mm, with a -0.09+/-0.46 loss index. IVUS demonstrated no significant reduction in lumen area (from 5.69+/-1.72 mm2 after treatment to 6. 04+/-2.63 mm2 at follow-up), with no significant change in external elastic membrane area (13.71+/-4.54 to 14.22+/-4.71 mm2) over the 6-month follow-up. Wall area was 8.01+/-3.85 mm2 after radiation therapy and 8.19+/-3.44 mm2 at follow-up (P=NS). No significant differences were noted between the different dose groups. CONCLUSIONS: beta-Radiation therapy resulted in a low restenosis rate with negligible late loss by angiography. By IVUS, beta-radiation was shown to inhibit neointima formation, with no reduction of total vessel area at 6-month follow-up.

Efficacy of beta radiation in prevention of post-angioplasty restenosis. An interim report from the beta energy restenosis trial.

UNLABELLED: Restenosis remains a major limitation of coronary angioplasty in spite of major advances in techniques and technology. Recent studies have demonstrated that ionizing radiation may limit the degree of this problem. Gamma radiation has been shown to be effective in reducing in stent restenosis in humans, and beta radiation following encouraging results in animals has been shown to be feasible in humans. The objective of this study was to assess the feasibility of a 5 F non-centered catheter to deliver beta radiation emitting seeds to the lesion site post angioplasty and its effect on restenosis. Following successful angioplasty, patients were randomized to treatment with 12, 14 or 16 Gy at the angioplasty site. This was delivered with a 5 F non-centered catheter. Twelve beta radiation emitting seeds (90Sr/Y) were delivered to an area 3 cm in length to cover the angioplasty site. Angiographic follow-up was performed at 6 months. Baseline and follow-up angiograms were performed by blinded investigators at a core laboratory. This interim report comprises the first 35 patients to complete 6-month angiographic follow-up. There were no major radiation incidents. Four patients had evidence of angiographic restenosis. The MLD (mm) and percent stenosis were 0.77 +/- 0.27/72.5 +/- 8.6 pre angioplasty, 2.08 +/- 0.4/25.7 +/- 9.8 post angioplasty and radiation and 2.05 +/- 0.59/25.7 +/- 19.8 at follow-up respectively. CONCLUSION: Beta radiation can be feasibly and safely delivered post coronary angioplasty with a very encouraging reduction of restenosis.

Local Delivery of TGF-b Antibodies to Prevent Neointima Formation after Balloon Injury in a Pig Coronary Artery Model.

BACKGROUND: The formation of neointima after vessel injury results from smooth muscle cell proliferation and extracellular matrix secretion. This process is activated by multiple growth factor release. Among these, Transforming Growth Factor-b (TGF-b) has been shown to play an important role. We hypothesized that local delivery of TGF-b antibodies could reduce neointima formation after balloon angioplasty. METHODS AND RESULTS: Using autoperfusion double-balloon catheters (Baxter, Irvine, California), we infused polyclonal TGF-b antibodies in 30 minutes, immediately after oversized balloon angioplasty in pig coronary arteries. Eleven coronary arteries received 100 m anti-TGF-b and thirteen served as controls. Animals were sacrificed 10 weeks later; coronary segments were harvested and processed for histologic quantitative assessment of the neointima. The extent of injury was similar in treated versus control vessels (39% +/- 5% vs. 30% +/- 4%) and there was no difference in intimal thickening (0.63 +/- 0.19 mm for treated vs. 0.52 +/- 0.12 mm for controls). A previously validated restenosis injury index (ratio of neointimal area to total wall area over extent of injury) was also similar in both groups, 1.46 +/- 0.15 for treated versus 1.55 +/- 0.14 for controls. CONCLUSION: Local delivery of a single dose of TGF-b antibodies failed to demonstrate a benefit on neointima formation in a pig coronary artery model.

Salmonella mycotic aneurysm of the aortic arch: case report and review.

Salmonella mycotic aneurysms of the thoracic aorta are exceedingly rare. We describe what we believe is only the third reported case involving the aortic arch. The patient was treated with surgical intervention and a prolonged course of antibiotics, which resulted in long-term survival. We review 13 previously reported cases of salmonella mycotic aneurysms of the thoracic aorta. The overall outcome was abysmal, with 10 of 13 patients dying within 1 month after the diagnosis was made. We discuss the pathogenesis, clinical presentation, diagnostic approach, and management (including surgical intervention and duration of antibiotic therapy) of this condition on the basis of the findings in these cases.

Plasma cell dyscrasia with marrow fibrosis. A reversible syndrome mimicking agnogenic myeloid metaplasia.

BACKGROUND: The interrelation between plasma cell dyscrasia and myelofibrosis or agnogenic myeloid metaplasia (AMM) is unclear. The existence of two distinct syndromes has been proposed: (1) plasma cell dyscrasia associated with simple marrow fibrosis caused by the secretion of lymphokines and (2) myeloma coexisting with AMM representing two distinct clonal diseases. METHODS: The authors report the case of a 68 year-old man seen initially with severe anemia, massive splenomegaly, a leuko-erythroblastic blood morphology, and myelofibrosis coexisting with massive bone marrow infiltration with IgA lambda-producing plasmacytoid cells. RESULTS: Cyclic therapy with vincristine, carmustine, cyclophosphamide, melphalan, and prednisone resulted in clinical remission of the myeloma lasting for 2 years and complete resolution of all the clinical features resembling AMM. CONCLUSIONS: The authors' observations and the report of two other patients in whom remission of AMM has been observed after myeloma treatment underline the broad spectrum of secondary abnormalities ranging from moderate bone marrow fibrosis to the full clinical expression of a syndrome closely mimicking AMM. These secondary abnormalities are potentially reversible even in the presence of advanced bone marrow fibrosis and massive splenomegaly.