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Biomedical subjects

Roswitha Wolfram

Publications and source records attributed to Roswitha Wolfram.

12 recordsLinked to original sources
PubMed2003

Repeat intracoronary radiation for recurrent in-stent restenosis in patients who failed intracoronary radiation.

BACKGROUND: Intracoronary radiation therapy (IRT) is the only proven treatment for in-stent restenosis (ISR). It is, however, associated with a significant failure rate. The present study evaluated the outcomes of patients who underwent repeat intracoronary radiation for recurrent ISR. METHODS AND RESULTS: Fifty-one consecutive patients who failed a previous radiation treatment, presented with angina and angiographic evidence of ISR, and were treated with percutaneous coronary intervention (PCI) and repeat radiation to the same segment were studied. Twenty-five patients were treated with gamma radiation in a dose of 15 Gy, and 26 were treated with beta radiation doses of 18.3 to 23 Gy. The mean cumulative dose for this cohort was 39.5+/-11.9 Gy (range, 29 to 75.6 Gy). The outcomes of those patients were compared with outcomes of 299 patients who also failed initial radiation but were treated with repeat conventional PCI to a previously irradiated segment without repeat radiation. At 9 months after treatment, the repeat-IRT group had lower rates of target lesion revascularization (23.5% versus 54.6%; P<0.001) and major adverse cardiac events, including target vessel revascularization (29.4% versus 61.3%; P<0.001). At 9 months, patients with repeat IRT were free of angiographic and clinical events related to the radiation therapy. CONCLUSIONS: Repeat gamma or beta radiation to treat failed IRT for ISR after conventional PCI is safe and effective at 9 months and should be considered as a therapeutic option for this difficult patient subset.

Angina Pectoris↗
PubMed2003

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.

Brachytherapy↗
PubMed2003

Endovascular Brachytherapy in Peripheral Arteries: Solution for Restenosis or False Hope?

Endovascular brachytherapy with gamma-radioactive source ((192)iridium ) significantly reduces the restenosis after femoropopliteal angioplasty for both de novo and recurrent lesions. Increased arterial patency after additional stenting and brachytherapy was also achieved with the same approach. This was found as a result of single-center studies performed in Frankfurt, Germany, Vienna, Austria, and Bern, Switzerland. However, until recently, only one multicenter investigation was published that also underlined this positive effect of brachytherapy. A definitive role of radiotherapy in restenosis prevention should be established after the results of three multicenter, phase III trials (ie, Paris, Vienna-3, and Swiss) are presented in early 2003. These investigations recruited approximately 630 patients with recurrent and de novo lesions without stent placement. Another important phase III study, the results of which are also expected at the beginning of 2003, is the Vienna-5 trial. This study had the same inclusion criteria as the Paris and Vienna-3 trials, but angioplasty was combined in all patients with stenting. The patients were then randomized for brachytherapy or sham irradiation. Endovascular brachytherapy has shown to be a safe treatment modality. The only clinically relevant impediment was the late sudden thrombosis or occlusion that occurred after stenting and radiation. These events can present up to 1 year after brachytherapy, and in some cases even later. Prolonged antiplatelet medication with clopidogrel (at least 12 months) has solved this problem completely. No other major adverse effects were seen. If gamma radiation is used, the patients must be transported after intervention to the brachytherapy suite, owing to radiation safety regulations. Although no negative consequences during transportation were observed in all performed studies, this represents an additional risk. To shorten the whole procedure, studies using beta sources ((32)phosphorus, (90)strontium) are ongoing, whereas those with beta-radioactive sources of brachytherapy can be performed in the catheterization laboratory. Emerging approaches using drug-eluting stents with antiproliferative substances such as rapamycin and paclitaxel are being investigated as well; however, the safety and efficacy for restenosis prophylaxis must be proven in large clinical trials.

Journal Article↗
PubMed2003

Understanding and preventing the edge effect.

Edge stenosis, combining neointimal proliferation and negative remodeling, remains a serious limitation of vascular brachytherapy. This review comprehensively presents terminology, definitions, mechanisms, and treatment strategies to better understand the complexities of edge narrowing. The major contributors to this phenomenon are known; understanding the practical solutions will enable us to further minimize the problem of the edge effect.

Brachytherapy↗
PubMed2003

Late thrombosis: a problem solved?

Late thrombosis (angiographic total occlusion associated with an acute coronary syndrome) is a potentially life-threatening complication after intracoronary radiation therapy. This review is intended to explore the preclinical and clinical evidence for late thrombosis, to discuss the etiology, and to provide guidelines for future management. Although we have gained a greater understanding of this complex entity, further research is required in a quest to curtail late thrombosis rates.

Animals↗
PubMed2002

Muscular side effects of statins.

Lipid lowering has been shown to be effective in preventing primary and recurrent cardiovascular events and to save life. Statins almost exclusively used for this purpose meanwhile became one of the most widely prescribed families of drugs world-wide. Myopathies--mainly not well characterized--are the major group of side effects. We here review different types of clinical appearances, localizations, symptoms and the biochemical background. The data indicate that severe muscular side effects are rare. Patients and their doctors, however, easily overlook mild ones. Myopathic symptoms without any known biochemical correlate are not rare. No general guideline exists about exact diagnosis and differential diagnosis. Strict adherence to the measures of life-style change and performance of regular exercise can even further enhance significantly these side effects. Much more research should be directed onto the pathophysiological (genetic?) background to finally evaluate possible therapeutic consequences rather than simply to withdraw or change the respective statin.

Adult↗
PubMedDate not supplied

The initial course of in-stent restenosis influences the response to vascular brachytherapy.

BACKGROUND: Vascular brachytherapy (VBT) reduces the rate of recurrence of in-stent restenosis (ISR) by inhibiting intimal proliferation. However, the rate of cell proliferation, reflected by the speed of ISR development, is variable in ISR lesions and might influence the responsiveness of ISR to radiation. The aim of this study was to determine the influence of the initial ISR course on the clinical outcome of patients undergoing VBT. METHODS: In 1165 patients treated for ISR with VBT in the WRIST studies, we determined the time for ISR (time between initial stent implantation and restenosis), the time for VBT treatment (time between stent implantation and VBT), and previous ISR treatment with conventional strategies. Target lesion revascularization (TLR) at 6 months was available in all patients. RESULTS: Previous ISR treatment did not influence the result of VBT (TLR was 17% vs. 16% without previous angioplasty). Time to ISR influences the outcome of patients undergoing VBT; TLR decreased when ISR occurred later. TLR was 18.2%, 16.7%, and 11.1% when time to ISR was <90, 90-2700, and >270 days, respectively, P=.03. Early ISR (time for ISR <90 days) is a factor for radiation failure (OR=2.1, P<.05). In patients with early ISR, TLR is lower when VBT is delayed; TLR was 11% if performed 90 days after stent implantation as compared to 22% if VBT is performed early (<90 days), P<.05. CONCLUSION: The course of ISR development affects the long-term efficacy of VBT. Early restenosis remains a factor of treatment failure in the VBT era. Delaying VBT beyond 90 days after stent implantation reduces the rate of subsequent revascularization in these patients.

Aged↗
PubMedDate not supplied

The proximal location of stenosis in the left anterior descending coronary artery is not a predictive factor of worse outcome in the era of the stent.

BACKGROUND: Patients treated for lesions in the proximal left anterior descending coronary artery (P-LAD) have worse outcome after balloon angioplasty as compared to patients treated for lesions in the distal left anterior descending coronary artery (D-LAD). We sought to examine if this discrepancy was still observed after stenting. METHODS: A total of 676 consecutive patients with a symptomatic monovessel disease in the LAD artery who underwent angioplasty with stenting were prospectively entered into a dedicated database. Among this cohort, 322 lesions were located in P-LAD and 354 in D-LAD. Patients with total occlusion, acute myocardial infarction (MI) or restenosis were excluded. RESULTS: Procedural characteristics were similar in the two groups. Procedural success was high with the same rates of in-hospital death and Q-wave MI for patients treated in P-LAD and D-LAD. At 1 year, the rate of target lesion revascularization (TLR) was 13.9% in the P-LAD group and 16.3% in the D-LAD group (P = .79), and the rate of event-free survival was 81.9% and 81% (P = .67), respectively. The treatment of ostial lesions (n = 23) was not related to worse outcome. In multivariate analysis, lesion location was not a predictor of major adverse cardiac events (MACE). CONCLUSION: This study shows that stenting of lesions in the P-LAD is as effective and safe as treatment of lesions located in D-LAD. Therefore, when stenting is feasible, the location of the lesion in the LAD is not predictive of worse outcome and, consequently, should not be taken into account in the choice of the revascularization strategy.

Aged↗
PubMedDate not supplied

Antioxidants attenuate atherosclerotic plaque development in a balloon-denuded and -radiated hypercholesterolemic rabbit.

BACKGROUND: Oxidation of lipoproteins is considered to be a key contributor to atherogenesis. Antioxidants are potential antiatherogenic agents because they can inhibit lipoprotein oxidation. Radiation has been shown to increase oxidative stress leading to increased atherogenesis. This study is designed to test the potential of antioxidants to inhibit atherosclerotic plaque progression in balloon-denuded and -radiated rabbits. METHODS AND RESULTS: Two groups of New Zealand white rabbits (n=36) were fed with 1% cholesterol diet (control diet) or with 1% cholesterol diet containing a mixture of various antioxidants for 1 week. Iliac arteries in all the animals were balloon denuded and continued to fed with 0.15% cholesterol diet or 0.15% cholesterol diet containing antioxidants (antioxidant diet). Four weeks after balloon denudation one iliac artery in 12 animals from each group was radiated and all the animals were continued to be fed with the same diet. Four weeks after radiation animals were sacrificed and morphometric analysis of iliac arteries (n=12) in nonradiated and radiated animals were performed. Plaque area (PA) in the rabbits that were fed with cholesterol diet is 0.2+/-0.12 mm2, and it is increased by 2.75-fold (P<.05) in the radiated arteries of animals fed with cholesterol diet. Plaque area in the animals fed with antioxidant diet is 50% less then the one in the animals fed with cholesterol diet. Similarly, plaque area in radiated arteries of the animals fed with antioxidant diet is 50% less then the animals fed with cholesterol diet. CONCLUSION: Antioxidants significantly attenuate atherosclerotic plaque progression in balloon-injured and -radiated hypercholesterolemic rabbits.

Animals↗
PubMedDate not supplied

Oral rapamycin inhibits growth of atherosclerotic plaque in apoE knock-out mice.

INTRODUCTION: Inflammatory and immunological responses of vascular cells are known to play significant roles in atherosclerotic plaque development. Rapamycin with antiinflammatory, immunosuppressive and antiproliferative properties has been shown to reduce neointima formation when coated on stents. This study is designed to test the potential of oral rapamycin to inhibit atherosclerotic plaque development. METHODS: Eight-week-old apoE knock-out mice were fed with 0.25% cholesterol supplemented diet (control diet), control diet containing 50 microg/kg rapamycin (low-dose rapamycin) or 100 microg/kg rapamycin (high-dose rapamycin) for 4 or 8 weeks. Subsets of mice from each group (n=10) were weighed and euthanized. Whole blood rapamycin levels were determined using HPLC-MS/MS, and histological analyses of atherosclerotic lesions in the aortic root were performed. RESULTS: Mice fed with high-dose rapamycin did not gain weight (18.5+/-1.5 vs. 20.6+/-0.9 g, P=.01). Blood levels of rapamycin 117+/-7 pg/ml were detected in the blood of mice fed with high-dose rapamycin for 8 weeks. The plaque area in mice fed with high dose oral rapamycin is significantly less as compared to control (0.168+/-0.008 vs. 0.326+/-0.013 mm2, P=.001 at 4 weeks; 0.234+/-0.013 vs. 0.447+/-0.011 mm2, P=.001 at 8 weeks). Lumen area was inversely proportional to the plaque area. CONCLUSIONS: The results indicate that oral rapamycin is effective in attenuating the progression of atherosclerotic plaque in the mice.

Administration, Oral↗