Suchergebnisse

Part 7: Perceptional Systems ; International audience ; The increase of life expectancy in the European Union, and the high risk of cardiovascular diseases associated with age, are some of the main factors to contribute to the rise of healthcare costs. An intelligent stent (e-stent), capable of obtaining and transmitting real-time measurements of physiological parameters for its clinical consultation, can be a useful tool for long-term monitoring, diagnostic, and early warning system for arterial blockage without patient hospitalization. In this paper, a behavioural model of capacitive Micro-Electro-Mechanical (MEMS) pressure sensor is proposed and simulated under several restenosis conditions. Special attention has been given to the need of an accurate fault model, obtained from realistic finite-element simulations,to ensure long-term reliability; particularly for those faults whose behavior cannot be easily described by an analytical model.

In-stent restenosis (ISR) is one of the main limitations of percutaneous coronary intervention (PCI) therapy with drug-eluting stents (DES) implantation. The aim of this study was to determine if circulating microRNAs (miRNAs) have diagnostic capability for determining ISR in a cohort of matched patients. Blood samples were collected from 55 patients who underwent previously PCI and were readmitted for a new coronary angiography. Patients were divided into subgroups comprising patients who presented ISR or not (non-ISR). A microarray analysis determined that up to 49 miRNAs were differentially expressed between ISR and non-ISR patients. Of these, 10 miRNAs are related to vascular smooth muscle and endothelial cells proliferation, migration, and differentiation, well-known hallmarks of vascular remodeling. Additionally, we identified that the expression of miR-30b-5p is significantly lower in serum samples of ISR patients, as compared to non-ISR. A further analysis demonstrated that miR-30b-5p provides better values of the receiver operator characteristic curve than other miRNAs and biochemical parameters. Finally, the in-silico analysis suggests that miR-30b-5p is predicted to target 62 genes involved in different signaling pathways involved in vascular remodeling. In conclusion, we determined for the first time that circulating mi-R30b-5p can reliably prognose restenosis in patient with implanted DES, which could be potentially helpful in the establishment of an early diagnosis and therapy of ISR. ; This research was funded by the INSTITUTE OF CARLOS III, grant number: PI18/01197); AGENCIA ESTATAL DE INVESTIGACIÓN, grant number: PID2019-104084GB-C22/ AEI/10.13039/501100011033); the ANDALUSIA GOVERNMENT, grant number: PI-0313-2016. This study was co-financed by FEDER Funds.

Background and aim: Obstructive coronary disease is one of the most important causes of death worldwide. Percutaneous coronary intervention is one of the most important treatments of this pathology. Using of coronary artery stents represented a major advance in interventional cardiology. While bare metal stents (BMS) set the reference point for improved safety over balloon-angioplasty, first-generation drug-eluting stents demonstrated significant improvements in efficacy, but not necessarily safety, and further technologic developments have focused on optimizing both. Methods: We studied 228 patients with STEMI in the last 6 months, divided in 2 groups – in the first group are 122 patients (53.5%) who developed in stent restenosis and the second group has 106 patients had no signs of restenosis (46.5%). The mean time of performing the angiographic reevaluation was 111 days for the first group and 154 days for the second group. The clinical signs that indicate the need of coronary reevaluation was stable angina (116, 50.87%), acute coronary syndrome (58, 25.4%) and asymptomatic patients (64, 28.9%). The cardiovascular risk factors correlate with high risk of restenosis was diabetes (24.3% in first group and 12.2% in the second one, p=0.004), active smoking (p=0.010) and metabolic syndrome (p=0.003). The stent's length >28mm, stent's diameter ≤ 2.5 mm and chronic occlusion correlate with high risk of in-stent restenosis in BMS. Conclusion: Understanding the importance of risk factors control, will reduce the risk of restenosis, of other cardiovascular event, even sudden death.

Zhen-hua Zhou,1 Jing Peng,1 Zhao-you Meng,1 Lin Chen,1 Jia-Lu Huang,1 He-qing Huang,1 Li Li,2 Wen Zeng,2 Yong Wei,2 Chu-Hong Zhu,2 Kang-Ning Chen1 1Department of Neurology, Cerebrovascular Disease Research Institute, Southwest Hospital, 2Department of Anatomy, Key Laboratory for Biomechanics of Chongqing, Third Military Medical University, Chongqing, People's Republic of China Background: Carotid artery stenosis is a major risk factor for ischemic stroke. Although carotid angioplasty and stenting using an embolic protection device has been introduced as a less invasive carotid revascularization approach, in-stent restenosis limits its long-term efficacy and safety. The objective of this study was to test the anti-restenosis effects of local stent-mediated delivery of the A20 gene in a porcine carotid artery model.Materials and methods: The pCDNA3.1EHA20 was firmly attached onto stents that had been collagen coated and treated with N-succinimidyl-3-(2-pyridyldithiol)propionate solution and anti-DNA immunoglobulin fixation. Anti-restenosis effects of modified vs control (the bare-metal stent and pCDNA3.1 void vector) stents were assessed by Western blot and scanning electron microscopy, as well as by morphological and inflammatory reaction analyses.Results: Stent-delivered A20 gene was locally expressed in porcine carotids in association with significantly greater extent of re-endothelialization at day 14 and of neointimal hyperplasia inhibition at 3 months than stenting without A20 gene expression.Conclusion: The A20-gene-eluting stent inhibits neointimal hyperplasia while promoting re-endothelialization and therefore constitutes a novel potential alternative to prevent restenosis while minimizing complications. Keywords: restenosis, A20, gene therapy, stent, endothelialization

This is an, un-copyedited, author manuscript that has been accepted for publication in the Frontiers in Bioscience ; Atherosclerosis and related forms of cardiovascular disease (CVD) are associated with several genetic and environmental risk factors, including hypercholesterolemia, diabetes mellitus (DM), hypertension, obesity and smoking. Human DM is a multisystem disorder that results from progressive failure of insulin production and insulin resistance. Most diabetic patients die from complications of atherosclerosis and CVD, and DM is also associated with increased risk of restenosis post-angioplasty. Furthermore, the incidence of DM, particularly type 2-DM, is expected to increase significantly during the next decades owing to the unhealthy effects of modern life-style habits (e.g., obesity and lack of physical exercise). Thus, it is of utmost importance to develop novel preventive and therapeutic strategies to reduce the social and health-care burden of CVD and DM. Although a number of physiological alterations thought to promote atherosclerosis have been identified in diabetic patients, the precise molecular mechanisms that link DM and atherosclerosis are largely unknown. Thus, the aim of this review is to discuss current murine models of combined DM and atherosclerosis and to explore how these experimental systems are being utilized to gain mechanistic insights into diabetes-induced neointimal lesion development, as well as their potential use in evaluating the efficacy of new therapies. Our discussion includes models generated by streptozotocin treatment and those resulting from naturally occurring or targeted mutations in the mouse. ; Work in the laboratory of the authors is supported by grants from the Spanish Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares RECAVA, Red de Grupos G03/212), and from the Spanish Ministry of Education and Science and the European Regional Development Fund (SAF2004-03057, SAF2005-06058). H. G.-N. is supported by an European Union Marie Curie postdoctoral fellowship. ; Peer reviewed

Background: The risk of stroke associated with carotid artery restenosis after stenting or endarterectomy is unclear. We aimed to compare the long-term risk of restenosis after these treatments and to investigate if restenosis causes stroke in a secondary analysis of the International Carotid Stenting Study (ICSS). Methods: ICSS is a parallel-group randomised trial at 50 tertiary care centres in Europe, Australia, New Zealand, and Canada. Patients aged 40 years or older with symptomatic carotid stenosis measuring 50% or more were randomly assigned either stenting or endarterectomy in a 1:1 ratio. Randomisation was computer-generated and done centrally, with allocation by telephone or fax, stratified by centre, and with minimisation for sex, age, side of stenosis, and occlusion of the contralateral carotid artery. Patients were followed up both clinically and with carotid duplex ultrasound at baseline, 30 days after treatment, 6 months after randomisation, then annually for up to 10 years. We included patients whose assigned treatment was completed and who had at least one ultrasound examination after treatment. Restenosis was defined as any narrowing of the treated artery measuring 50% or more (at least moderate) or 70% or more (severe), or occlusion of the artery. The degree of restenosis based on ultrasound velocities and clinical outcome events were adjudicated centrally; assessors were masked to treatment assignment. Restenosis was analysed using interval-censored models and its association with later ipsilateral stroke using Cox regression. This trial is registered with the ISRCTN registry, number ISRCTN25337470. This report presents a secondary analysis, and follow-up is complete. Findings: Between May, 2001, and October, 2008, 1713 patients were enrolled and randomly allocated treatment (855 were assigned stenting and 858 endarterectomy), of whom 1530 individuals were followed up with ultrasound (737 assigned stenting and 793 endarterectomy) for a median of 4·0 years (IQR 2·3–5·0). At least moderate restenosis (≥50%) occurred in 274 patients after stenting (cumulative 5-year risk 40·7%) and in 217 after endarterectomy (29·6%; unadjusted hazard ratio [HR] 1·43, 95% CI 1·21–1·72; p<0·0001). Patients with at least moderate restenosis (≥50%) had a higher risk of ipsilateral stroke than did individuals without restenosis in the overall patient population (HR 3·18, 95% CI 1·52–6·67; p=0·002) and in the endarterectomy group alone (5·75, 1·80–18·33; p=0·003), but no significant increase in stroke risk after restenosis was recorded in the stenting group (2·03, 0·77–5·37; p=0·154; p=0·10 for interaction with treatment). No difference was noted in the risk of severe restenosis (≥70%) or subsequent stroke between the two treatment groups. Interpretation: At least moderate (≥50%) restenosis occurred more frequently after stenting than after endarterectomy and increased the risk for ipsilateral stroke in the overall population. Whether the restenosis-mediated risk of stroke differs between stenting and endarterectomy requires further research. Funding: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, and the European Union.

BACKGROUND: The risk of stroke associated with carotid artery restenosis after stenting or endarterectomy is unclear. We aimed to compare the long-term risk of restenosis after these treatments and to investigate if restenosis causes stroke in a secondary analysis of the International Carotid Stenting Study (ICSS). METHODS: ICSS is a parallel-group randomised trial at 50 tertiary care centres in Europe, Australia, New Zealand, and Canada. Patients aged 40 years or older with symptomatic carotid stenosis measuring 50% or more were randomly assigned either stenting or endarterectomy in a 1:1 ratio. Randomisation was computer-generated and done centrally, with allocation by telephone or fax, stratified by centre, and with minimisation for sex, age, side of stenosis, and occlusion of the contralateral carotid artery. Patients were followed up both clinically and with carotid duplex ultrasound at baseline, 30 days after treatment, 6 months after randomisation, then annually for up to 10 years. We included patients whose assigned treatment was completed and who had at least one ultrasound examination after treatment. Restenosis was defined as any narrowing of the treated artery measuring 50% or more (at least moderate) or 70% or more (severe), or occlusion of the artery. The degree of restenosis based on ultrasound velocities and clinical outcome events were adjudicated centrally; assessors were masked to treatment assignment. Restenosis was analysed using interval-censored models and its association with later ipsilateral stroke using Cox regression. This trial is registered with the ISRCTN registry, number ISRCTN25337470. This report presents a secondary analysis, and follow-up is complete. FINDINGS: Between May, 2001, and October, 2008, 1713 patients were enrolled and randomly allocated treatment (855 were assigned stenting and 858 endarterectomy), of whom 1530 individuals were followed up with ultrasound (737 assigned stenting and 793 endarterectomy) for a median of 4·0 years (IQR 2·3-5·0). At least moderate restenosis (≥50%) occurred in 274 patients after stenting (cumulative 5-year risk 40·7%) and in 217 after endarterectomy (29·6%; unadjusted hazard ratio [HR] 1·43, 95% CI 1·21-1·72; p<0·0001). Patients with at least moderate restenosis (≥50%) had a higher risk of ipsilateral stroke than did individuals without restenosis in the overall patient population (HR 3·18, 95% CI 1·52-6·67; p=0·002) and in the endarterectomy group alone (5·75, 1·80-18·33; p=0·003), but no significant increase in stroke risk after restenosis was recorded in the stenting group (2·03, 0·77-5·37; p=0·154; p=0·10 for interaction with treatment). No difference was noted in the risk of severe restenosis (≥70%) or subsequent stroke between the two treatment groups. INTERPRETATION: At least moderate (≥50%) restenosis occurred more frequently after stenting than after endarterectomy and increased the risk for ipsilateral stroke in the overall population. Whether the restenosis-mediated risk of stroke differs between stenting and endarterectomy requires further research. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, and the European Union.

BACKGROUND: Coronary stent
restenosis is a neointimal hyperplasia, which leads to the
obstruction of the previously treated lesion. Its incidence
is around 10%. The treatment is a new intervention with
balloon angioplasty and implantation of a new stent to
reestablish blood flow. OBJECTIVE: To determine if there is
a difference between the different treatment strategies
against intrastent restenosis such as the bioabsorbable
endoprosthesis, drug-eluting stent and drug-eluting
balloon, evaluated by angiography after 12 months of being
treated an intrastent stenosis. MATERIALS AND METHODS:
Observational, ambispective, crosssectional and comparative
study consisting of the evaluation of patients with
angina-compatible disease in the following 12 months to the
treatment for intrastent stenosis. We reviewed the
angiographies of the patients who entered the Cath Lab of
the Hospital Central Militar for evaluation of intrastent
restenosis due to previous balloon angioplasty or previous
coronary intervention with implantation of a drug-eluting
or bioabsorbable stent after angina. RESULTS: Three groups
were treated with intrastent stenosis, the first using
bioabsorbable stent, the second with drug-eluting stent and
another group treated with a medicated balloon; in the
control angiographies performed on patients with angina, a
statistically significant difference was found in the
therapy used for intrastent stenosis (15.7%, 65.1%, 70%, p
< 0.001), with a higher success rate in bioabsorbable
stent group in relation to the other two therapies.
However, there was no difference in the treatment of
intrastent stenosis with the use of drug-eluting stents vs.
medicated balloon (65.1%, 70%, p < 0.75).

Importance of the Exercise Test Follow-up Programme for Patients with Coronary Artery Disease who Underwent Percutaneous Coronary Intervention
The clinical course and prognosis of coronary heart disease (CHD) can be modified favourably with percutaneous coronary intervention (PCI) in combination with medication. A follow-up programme was developed in the Latvian Centre of Cardiology, which included a stress electrocardiogram for patients after PCI. This is the first study in Latvia, and provides wide opportunities to evaluate functional status of patients, treatment effectiveness, possible risks and prognosis after PCI. Exercise tests are widely used for the evaluation and diagnostics of CHD. This method has been successfully implemented in diagnostics of restenosis in coronary arteries, a process which pathophysiologically differs from primary atherosclerosis. A total of 7,300 patients with CHD were followed-up in one year after PCI. An exercise test was conducted one, three, six and twelve months after PCI. Clinical and functional status of patients and risk of restenosis were evaluated and corrections in medications were made. Seventeen percent of patients had chest pain and 13% had significant ST-segment changes in electrocardiogram. Restenosis of coronary arteries in angiography were established in 6.4%. In half of those patients above restenosis was diagnosed early — three to six months after PCI. We established a patient subgroup (22%) with "silent" ischemia (positive exercise test without chest pain), out of whom 41% had restenosis. For left main (LM) disease patients 50% of all restenosis diagnoses also were diagnosed early (three to six month after PCI). Restenosis was associated with ST-segment deviation in the exercise electrocardiogram. A lower Robinson index (RI) was registered in the same group of patients. A focussed follow-up programme performing exercise test allows to determine timely possible risk of restenosis, to adapt medication doses, to reduce risk factors and to influence positively patients' compliance.

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Cardiovascular Research following peer review. The definitive publisher-authenticated version Cardiovasc Res. 75 (4):803-12. is available online at: http://cardiovascres.oxfordjournals.org/cgi/content/full/75/4/803 ; OBJECTIVE: The tumor suppressor p53 regulates cell proliferation and apoptosis, two key processes in the pathogenesis of occlusive vascular disease. Here, we examined the consequences of heightening p53 function on neointimal lesion formation in the setting of atherosclerosis and mechanical injury. METHODS: (1) Immunohistopathological characterization of neointimal lesions in atherosclerosis-prone apolipoprotein E-null mice with normal p53 gene dosage (apoEKO) and carrying a p53 transgene (Super-p53/apoE-KO); (2) molecular studies in macrophages and smooth muscle cells (SMCs) obtained from these mice. RESULTS: The p53 transgene conferred p53 gain-of-function in cultured cells and mice. In vitro, survival of irradiated Super-p53 macrophages and femoral SMCs was reduced, but only Super-p53 SMCs exhibited attenuated proliferation. In vivo, whereas the size of spontaneously formed and diet-induced aortic atheromas was undistinguishable in apoE-KO and Super-p53/apoE-KO mice, the latter exhibited attenuated neointimal thickening in mechanically-injured femoral artery. In both models, neither apoptosis nor cell proliferation were affected by additional p53 gene dosage when examined in established neointimal lesions. However, at 2 days after mechanical injury when neointimal lesions were not formed yet, cell proliferation was significantly attenuated within medial SMCs of Super-p53/apoEKO mice. CONCLUSION: Heightening p53 function has differential effects on in vitro proliferation of macrophages (unaffected) versus SMCs (reduced), and on native atherosclerosis (unaffected) versus mechanically-induced neointimal thickening (reduced) in apoE-KO mice. The protective effect of p53 in mechanically-injured femoral artery coincided with limited medial SMC proliferation at early time points preceding neointima formation, but neither medial nor neointimal cell proliferation was affected in vessels with established occlusive lesions. These findings corroborate p53 gain-of-function as a promising therapeutic strategy to limit post-angioplasty restenosis but not native atherosclerosis. ; Work financed by grants from Ministerio de Sanidad y Consumo/Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares, RECAVA), from the Regional Government of Valencia (GV04B-288) and from Ministerio de Educación y Ciencia and the European Regional Development Fund (SAF2004-03057). S.M.S.-G. and J.M.G received salary support from Instituto de Salud Carlos III, and J.J.F. from CSIC-I3P predoctoral fellowship program cosponsored by the European Social Fund. ; Peer reviewed

Intro -- Authored Books -- By Author -- Preface -- Acknowledgments -- Contents -- Contributors -- Chapter 1: 1950-1970s: Where We Came From -- References -- Chapter 2: 1970s: Growth and Innovation -- References -- Chapter 3: 1980s: Expanding the Practice -- Adjunctive Therapy for PTCA -- Leadership Changes -- Directional Coronary Atherectomy -- PTCA and CABG -- Contrast Nephropathy -- Imaging and Radiation Exposure -- Vasodilators -- References -- Chapter 4: 1990s: Another Move -- Directional Coronary Atherectomy -- Excimer Laser -- Rotational Atherectomy -- Restenosis -- Development of Animal Laboratory Practice -- Acute Ischemic Syndromes: Pathophysiology -- Patient Subsets Undergoing Intervention -- Chronic Total Occlusion -- Treatment of Multivessel CAD -- Mobile Cardiac Cath Lab -- Facility Expansion -- Disappointments -- References -- Chapter 5: 1980-1990: Structural Heart Interventions -- Aortic Balloon Valvuloplasty -- Mitral Balloon Valvuloplasty -- Atrial Septal Defects -- Atrial Septostomy -- Education and Teaching -- Cardiac Imaging -- Summary -- References -- Chapter 6: 2000s: New Field of Focus -- Acute Ischemic Syndromes -- Stent Implantation -- Randomized Clinical Trials and Multicenter Registries -- Mayo Clinic PTCA Registry -- Carotid Stenting -- Restenosis -- Stents, Restenosis, and Vascular Brachytherapy -- Stent Thrombosis -- Procedural Risk and Strategies of Care -- Radial Access -- Imaging Advances -- Practice Advancements -- Traning and Education -- Leadership -- References -- Chapter 7: 2000s: Structural Heart Disease -- Percutaneous Balloon Mitral Valvuloplasty -- Balloon Aortic Valvuloplasty -- Transcatheter Aortic Valve Replacement -- Early TAVR -- Paravalvular Leak Closure -- Mitral Edge-to-Edge Repair -- Importance of Hemodynamic Assessment -- Left Atrial Appendage Occlusion.

To follow up the restenosis in arteries stented during an angioplasty is an important current clinical problem. A new approach to monitor the growth of neointimal tissue inside the stent is proposed on the basis of electrical impedance spectroscopy (EIS) sensors and the oscillation-based test (OBT) circuit technique. A mathematical model was developed to analytically describe the histological composition of the neointima, employing its conductivity and permittivity data. The bioimpedance model was validated against a finite element analysis (FEA) using COMSOL Multiphysics software. A satisfactory correlation between the analytical model and FEA simulation was achieved in most cases, detecting some deviations introduced by the thin "double layer" that separates the neointima and the blood. It is hereby shown how to apply conformal transformations to obtain bioimpedance electrical models for stack-layered tissues over coplanar electrodes. Particularly, this can be applied to characterize the neointima in real-time. This technique is either suitable as a main mechanism for restenosis follow-up or it can be combined with proposed intelligent stents for blood pressure measurements to auto-calibrate the sensibility loss caused by the adherence of the tissue on the micro-electro-mechanical sensors (MEMSs). ; This work was carried out in collaboration with the Cardiology Department of the UHMV Hospital, Santander (Spain) and was funded by the Spanish Government's "Ministerio de Economía, Industria y Competitividad" under the joint projects TEC2013-46242-C3-1-P and TEC2013-46242-C3, co-financed with FEDER.

Existing biodegradable Magnesium Alloy Stents (MAS) have several drawbacks, such as high restenosis, hasty degradation, and bulky cross-section, that limit their widespread application in a current clinical practice. To find the optimum stent with the smallest possible cross-section and adequate scaffolding ability, a 3D finite element model of 25 MAS stents of different cross-sectional dimensions were analysed while localized corrosion was underway. For the stent geometric design, a generic sine-wave ring of biodegradable magnesium alloy (AZ31) was selected. Previous studies have shown that the long-term performance of MAS was characterized by two key features: Stent Recoil Percent (SRP) and Stent Radial Stiffness (SRS). In this research, the variation with time of these two features during the corrosion phase was monitored for the 25 stents. To find the optimum profile design of the stent subjectively (without using optimization codes and with much less computational costs), radial recoil was limited to 27 % (corresponding to about 10 % probability of in-stent diameter stenosis after an almost complete degradation) and the stent with the highest radial stiffness was selected.The comparison of the recoil performance of 25 stents during the heterogeneous corrosion phase showed that four stents would satisfy the recoil criterion and among these four, the one having a width of 0.161 mm and a thickness of 0.110 mm, showed a 24 % – 49 % higher radial stiffness at the end of the corrosion phase. Accordingly, this stent, which also showed a 23.28 % mass loss, was selected as the optimum choice and it has a thinner cross-sectional profile than commercially available MAS, which leads to a greater deliverability and lower rates of restenosis.