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Since late vessel failure has been speculated as a significant limitation of vascular brachytherapy (VBT), we conducted a prospective clinical evaluation at 6, 12, 24, 36 and 60 months follow-up after irradiation with 90Sr/90Y for in-stent restenosis (ISR) regardless of the patient's symptomatic status. Complete five-year follow-up is reported for 104 consecutive patients. The cumulative rate of death was 13.5% (6 months: 0.96%; 12 months: 2.88%; 24 months: 4.81%; 36 months: 7.69%), of acute myocardial infarction 4.81% (2.88%; 4.81%; 4.81%; 4.81%), of late thrombotic occlusion 4.81% (3.85%; 4.81%; 4.81%; 4.81%), of target lesion revascularization (TLR) 27.9% (8.65%; 12.5%; 17.3%; 21.2%), of target vessel revascularization (TVR) 43.3% (12.5%; 19.2%; 22.1%; 29.8%), and of all major adverse cardiovascular events (MACE) 61.5% (16.3%; 26.9%; 31.7%; 42.3%), respectively. Considered that the annual incidence of TVR after the first year following drug-eluting stenting for in-stent restenosis has been reported as approximately 3% per year, an incidence of 5.8% per year following VBT of our study population clearly indicates a more pronounced, delayed and, even in the fifth year after the index procedure, ongoing restenotic process following beta-irradiation of in-stent restenotic ||lesions associated with clinically relevant adverse cardiovascular events. [ABSTRACT FROM AUTHOR]

Selective inhibitors of cyclooxygenase-2 (COX-2, ‘coxibs’) are highly effective anti-inflammatory and analgesic drugs that exert their action by preventing the formation of prostanoids. Recently some coxibs, which were designed to exploit the advantageous effects of non-steroidal anti-inflammatory drugs while evading their side effects, have been reported to increase the risk of myo cardial infarction and atherothrombotic events. This has led to the withdrawal of rofecoxib from global markets, and warnings have been issued by drug authorities about similar events during the use of celecoxib or valdecoxib/parecoxib, bringing about questions of an inherent atherothrombotic risk of all coxibs and consequences that should be drawn by health care professionals. These questions need to be addressed in light of the known effects of selective inhibition of COX-2 on the cardiovascular system. Although COX-2, in contrast to the cyclooxygenase-1 (COX-1) isoform, is regarded as an inducible enzyme that only has a role in pathophysiological processes like pain and inflammation, experimental and clinical studies have shown that COX-2 is constitutively expressed in tissues like the kidney or vascular endothelium, where it executes important physiological functions. COX-2-dependent formation of prostanoids not only results in the mediation of pain or inflammatory signals but also in the maintenance of vascular integrity. Especially prostacyclin (PGI2), which exerts vasodilatory and antiplatelet properties, is formed to a significant extent by COX-2, and its levels are reduced to less than half of normal when COX-2 is inhibited. This review outlines the rationale for the development of selective COX-2 inhibitors and the pathophysiological consequences of selective inhibition of COX-2 with special regard to vasoactive prostaglandins. It describes coxibs that are current ly available, evaluates the current knowledge on the risk of atherothrombotic events associated with their intake and critically discusses the consequences that should be drawn from these insights. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In-stent restenosis (ISR), especially after vascular brachytherapy, is a therapeutic challenge. Sirolimus-eluting stent implantation is a promising new option for the treatment of patients with ISR. The efficacy of sirolimus-eluting stent implantation for the treatment of patients with their first episodes of ISR and with recurrent ISR due to the failure of vascular brachytherapy was compared using intravascular ultrasound imaging. [Copyright &y& Elsevier]

The aim of this study was to investigate the time course of angiographic restenosis rate and late loss after successful percutaneous coronary intervention and vascular brachytherapy with β-irradiation using strontium-90/yttrium-90 in 98 patients who were prospectively enrolled into a quantitative angiographic and clinical follow-up protocol at 6, 12, and 24 months after the index procedure, regardless of their symptom status. Actuarial restenosis rates measured 11.2 ± 5% at 6 months of follow-up, 24.5 ± 5% at 12 months, and 28.5 ± 6% at 24 months, respectively. Late loss of the stent segment during the first 6 months measured 0.38 ± 0.40 mm (6 to 12 months: 0.25 ± 0.38 mm; 12 to 24 months: 0.16 ± 0.32 mm), of the injured segment 0.27 ± 0.21 mm (6 to 12 months: 0.21 ± 0.26 mm; 12 to 24 months: 0.13 ± 0.24 mm), of the irradiated segment 0.18 ± 0.29 mm (6 to 12 months: 0.19 ± 0.31 mm; 12 to 24 months: 0.11 ± 0.27 mm), and of the analysis segment 0.18 ± 0.36 mm (6 to 12 months: 0.17 ± 0.29 mm; 12 to 24 months: 0.11 ± 0.20 mm). Restenosis after angioplasty and β-irradiation of in-stent restenotic lesions is not complete within 6 months but is sustained with a gradual decrease over 24 months. [Copyright &y& Elsevier]

Coronary flow velocity reserve (CFVR) (maximum/baseline flow velocity, 16 μg adenosine) was compared with dobutamine stress echocardiography (DSE) (5 to 40 μg/kg/min) to assess the progression of angiographically silent cardiac allograft vasculopathy (CAV). As a reference for the morphologic assessment of CAV, serial intracoronary ultrasound (ICUS) measurements were performed. An increase in CFVR could be observed in all transplant patients despite morphologic or functional progression of CAV or non-progressive CAV as assessed by ICUS or DSE. Thus, serial intracoronary Doppler flow analysis is not useful to predict morphologic or functional progression of CAV. [ABSTRACT FROM AUTHOR]

Background: The survival of heart transplant patients is limited by cardiac allograft vasculopathy (CAV). Intravascular ultrasound (IVUS) and IVUS-derived radiofrequency plaque composition analysis (IVUS-RF) provide further information about the process of coronary atherosclerosis. Methods: In this study we aimed to assess the time-dependent differences in disease progression in patients with CAV. Fifty-six patients were divided into three groups according to time interval after transplantation (Group I: 1 to 3 months, 18 patients; Group II, 1 to 5 years, 20 patients; Group III: 5 to 15 years, 18 patients). Results: IVUS-RF revealed time-dependent increases in all plaque components. The largest increase was shown for fibrotic, fibrofatty and necrotic tissue between Groups I and II. Dense calcium area increased uniformly in all groups. IVUS-RF–derived plaque type analysis revealed predominantly fibrotic plaques in all groups with a decrease of frequency over time. Fibrolipidic and fibrotic–calcific plaques increased uniformly. High-risk lesions, such as thick-cap fibroatheromas (FAs), increased in Groups I and II and decreased in Group III. Thin-cap FAs were detected only in Group III. Conclusions: IVUS-RF, as compared with gray-scale IVUS, provides better detailed information about the development of CAV by plaque morphology and composition analysis in different stages after heart transplantation. Serial IVUS-RF analysis in these patients may improve the stratification of heart transplant recipients. [Copyright &y& Elsevier]

Background: Cardiac allograft vasculopathy (CAV) is the major limitation in survival of patients after heart transplantation. Cardiac allograft vasculopathy is angiographically silent in the early phase after operation. Intravascular ultrasound (IVUS) is a more sensitive method to detect the early stages of CAV and provides information about its development. Recent IVUS studies demonstrated a rapid progression of CAV within the first year after transplantation as a predictor of morbidity and mortality. Objectives: This study assessed the plaque composition of early atherosclerosis in transplant patients by radiofrequency analysis. Methods: Coronary angiography and IVUS with Virtual Histology (VH) software (Real-Time VH, Volcano Corp, Rancho Cordova, CA) were used to assess 18 patients early after heart transplantation (1.71 ± 0.47 months). The plaque composition was determined by IVUS radiofrequency data analysis. Tissue maps were reconstructed from radiofrequency data using VH-IVUS software. The VH-IVUS acquisition was performed with standardized IVUS (EagleEye catheter; 2.9F/20MHz; Volcano Corp) and the VH-IVUS console (Volcano Corp). Results: Coronary angiography did not show any wall irregularities. Intravascular ultrasound demonstrated donor-transmitted atherosclerosis in 6 of 18 patients (33.33%). The incidence, amount of plaque burden, and plaque composition was significantly related to donor age. By VH-IVUS analysis, the plaque composition consisted mainly of fibrotic tissue. Conclusions: Donor-transmitted coronary atherosclerosis is present early after heart transplantation and cannot be detected by coronary angiography. VH-IVUS gives detailed information about the plaque distribution and the plaque composition. [Copyright &y& Elsevier]

Because late vessel failure has been speculated as a possible limitation of vascular brachytherapy, we conducted a prospective clinical evaluation at 6, 12, 24, and 36 months of follow-up after irradiation with strontium-90/yttrium-90 for in-stent restenosis, regardless of the patient’s symptomatic status. We report complete 3-year follow-up data for 106 consecutive patients. The cumulative rate of death at 6, 12, 24, and 36 months was 0.9%, 0.9%, 0.9%, and 1.9% respectively. The corresponding rates for acute ST-elevation myocardial infarction were 2.8%, 4.7%, 4.7%, and 4.7%, respectively. The cumulative rate of late thrombotic occlusion at 6, 12, 24, and 36 months was 3.8%, 4.7%, 4.7%, and 4.7%, respectively. The corresponding rates of target lesion revascularization and target vessel revascularization were 8.5% and 12.3% (p = 0.046), 14.2% (p = 0.157) and 18.0% (p = 0.046), 12.3% and 18.9% (p = 0.008), and 21.7% (p = 0.083) and 29.2% (p = 0.005), respectively. The cumulative rate of all major adverse cardiovascular events at 6, 12, 24, and 36 months was 16.1%, 24.5% (p = 0.003), 27.4% (p = 0.083), and 35.8% (p = 0.003), respectively. In conclusion, these results indicate a delayed and, even in the third year after the index procedure, continued restenotic process after β irradiation of in-stent restenotic lesions. [Copyright &y& Elsevier]

Background: Intravascular ultrasound (IVUS) is the reference method for in vivo assessment of vessel dimensions and coronary plaque composition, which can influence device selection as well as stent sizing. Objectives: The objective of this prospective multicenter-study was to test the application, safety, and feasibility of a new combined IVUS and stent delivery system. Methods: A total of 32 patients with planned direct stent implantation under IVUS guidance were included in the study. Procedural as well as angiographical and IVUS characteristics of the stent implantation with the combined IVUS and stent delivery system were assessed and compared to a historical control cohort where IVUS-guided stenting was performed with a separate IVUS catheter. Results: Direct stent placement was successfully performed in all patients and no malfunctions of the system were noted. A postinterventional IVUS assessment was possible in 27 (87%) of the 31 patients. The IVUS information led to a change in therapeutic strategy in 16 (50%) of the 32 patients. In the study group, both the procedural time and the amount of contrast dye were significantly lower than in the historical IVUS-guided stenting control group. A clinical 12-month follow-up revealed a 89% event-free survival and a target vessel revascularization rate of 7%. Conclusion: The use of a combined IVUS and stent delivery device is safe, easy to handle, and can provide helpful additional information to guide a percutaneous coronary interventions procedure. Beyond angiography, these informations had significant impact on the interventional strategy in these patients, which resulted in a low rate of major adverse cardiac events. The concept of combining IVUS information and a stent delivery system may be increasingly attractive with evolving imaging modalities like virtual histology or a combination with drug-eluting stents. [ABSTRACT FROM AUTHOR]

Cocaine use is a major problem worldwide and there are numerous reports about cocaine-associated myocardial infarction. Nevertheless minimal data are available from randomised clinical trials to suggest evidence-based approaches to the management of cocaine-associated myocardial ischemia. Moreover, most reports have been limited to conservative management of cocaine-associated myocardial infarction. We report a case of a young male cocaine user with acute myocardial infarction, undergoing diagnostic coronary angiography and intravascular ultrasound revealing severe atherosclerosis, followed by successful stent implantation. [Copyright &y& Elsevier]

BACKGROUND: DSE and SPECT are two well-established methods to non-invasively investigate the functional significance of coronary artery stenoses in patients with coronary artery disease. The measurement of Fractional Flow Reserve has emerged a new invasive reference standard for lesion specific quantification of coronary artery stenoses. The objective of our prospective study was to compare sensitivity and specificity of Dobutamine Stress Echocardiography (DSE) and Single Photon Emission Computer tomography (SPECT) with the pressure derived Fractional Flow Reserve (FFR) for the identification of hemodynamic relevant cororonary lesions in patients with predominantely coronary multivessel disease and angiographically intermediate stenoses. METHODS: Inclusion criteria were a coronary lesion of 50-75% diameter stenosis by visual assessment in patients with known or suspected CAD. SPECT, DSE and FFR testing was performed within one week of coronary angiography RESULTS: The study comprised 48 consecutive symptomatic patients. In 41 cases, a coronary multivessel disease was present. Mean FFR was 0.80 ± 0.13 (0.41-1.0). Overall sensitivity of DSE and SPECT was 67% and 69% whereas specificity reached 77% and 87%. However, sensitivity was significantly reduced if the target lesion was located distally. DSE showed poor results if the lesions were located in the circumflex artery or if a history of prior myocardial infarctions was present. CONCLUSION: DSE and SPECT are both useful methods for the non-invasive assessment of coronary artery disease. DSE showed reasonable combination of sensitivity and specificity even in patients with multivessel disease. Although use of noninvasive stress tests is only limited in patients with prior myocardial infarctions and invasive stress testing should be preferred in these patients. (Int J Cardiovasc Intervent 2004; 6: 142-147) [ABSTRACT FROM AUTHOR]

Pathogenic events leading to in-stent restenosis (ISR) are still incompletely understood. Among others, inflammation, immune reactions, deregulated cell death and growth have been suggested. Therefore, atherectomy probes from 21 patients with symptomatic ISR were analyzed by immunohistochemistry for pathogen burden and compared to primary target lesions from 20 stable angina patients. While cytomegalovirus, herpes simplex virus, Epstein-Barr virus and Helicobacter pylori were not found in ISR, acute and/or persistent chlamydial infection were present in 6/21 of these lesions (29%). Expression of human heat shock protein 60 was found in 8/21 of probes (38%). Indicated by distinct signals of CD68, CD40 and CRP, inflammation was present in 5/21 (24%), 3/21 (14%) and 2/21 (10%) of ISR cases. Cell density of ISR was significantly higher than that of primary lesions (977 ± 315 vs. 431 ± 148 cells/mm2; p < 0.001). There was no replicating cell as shown by Ki67 or PCNA. TUNEL+ cells indicating apoptosis were seen in 6/21 of ISR specimens (29%). Quantitative analysis revealed lower expression levels for each intimal determinant in ISR compared to primary atheroma (all p < 0.05). In summary, human ISR at the time of clinical presentation is characterized by low frequency of pathogen burden and inflammation, but pronounced hypercellularity, low apoptosis and absence of proliferation. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In-stent restenosis (ISR), especially after vascular brachytherapy, is a therapeutic challenge. Sirolimus-eluting stent implantation is a promising new option for the treatment of patients with ISR. The efficacy of sirolimus-eluting stent implantation for the treatment of patients with their first episodes of ISR and with recurrent ISR due to the failure of vascular brachytherapy was compared using intravascular ultrasound imaging. [ABSTRACT FROM AUTHOR]

Introduction and methods: The reaction of superoxide anions and NO not only results in a decreased availability of NO, but also leads to the formation of peroxynitrite, the role of which in the cardiovascular system is still discussed controversially. In cultured human endothelial cells, we studied whether there is a significant interaction between endothelial NO and neutrophil-derived superoxide anions in terms of endothelial peroxynitrite formation. We particularly studied whether a significantly higher redox-stress can be found in those endothelial cells directly adjacent to an activated neutrophil. Results: A considerable part of the 2,7-dihydrodichlorofluoresceine signal in endothelial cells was due to oxidation by peroxynitrite. Providing superoxide radicals by enzymatic source or by the neutrophil respiratory burst increased the fluorescence, which was attenuated by blockade of endothelial NO-synthase, suggesting that peroxynitrite was formed from neutrophil- or extracellular enzyme-derived superoxide and endothelial NO. Considerably higher fluorescence intensity was observed in endothelial cells in direct neighborhood to a neutrophil. This was particularly pronounced in the presence of a NO-donor and was accompanied by a strong activation of NF-κB and increased expression of E-selectin in these cells. Conclusion: Endothelial cells adjacent to neutrophils may have elevated levels of peroxynitrite that result in an increased expression of adhesion molecules. Such cells might represent a preferential site for adhesion and migration of additional neutrophils when simultaneously high concentrations of NO and neutrophil-derived superoxide are present. [Copyright &y& Elsevier]