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Biomedical subjects

Valentin Fuster

Publications and source records attributed to Valentin Fuster.

At least 109 records · Page 6Linked to original sources
PubMed2004

Quantification of human atherosclerotic plaques using spatially enhanced cluster analysis of multicontrast-weighted magnetic resonance images.

One of the current limitations of magnetic resonance imaging (MRI) is the lack of an objective method to classify plaque components. Here we present a cluster analysis technique that can objectively quantify and classify MR images of atherosclerotic plaques. We obtained three-dimensional (3D) images from 12 human coronary artery specimens on a 9.4T imaging system using multicontrast-weighted fast spin-echo (T1-, proton density-, and T2-weighted) imaging with an isotropic voxel size of 39 micro. Spatially enhanced cluster analysis (SECA) was performed on multicontrast MR images, and the resulting segmentation was evaluated against histological tracings. To visualize the overall structure of plaques, the MR images were rendered in 3D. The specimens exhibited lesions of American Heart Association (AHA) plaque classification types I-VI. Both MR images and histological sections were independently reviewed, categorized, and compared. Overall, the classification obtained from the cluster-analyzed MR and histopathology images showed very good agreement for all AHA types (92%, Cohen's kappa = 0.89, P < 0.0001). All plaque types were identified and quantified by SECA with a high degree of correlation between cluster-analyzed MR and manually traced histopathology data. MRI combined with SECA provides an objective method for atherosclerotic plaque component characterization and quantification.

Analysis of Variance↗
PubMed2004

Magnetic resonance imaging and computed tomography in assessment of atherosclerotic plaque.

The two most promising noninvasive imaging modalities for the study of atherosclerosis are magnetic resonance imaging (MRI) and computed tomography (CT). Both have been shown to be capable of imaging vessel wall structures and differentiating various stages of atherosclerotic wall changes. MRI has been applied in various in vivo human studies to image atherosclerotic plaques in coronary arteries, carotid arteries, and aorta. The latest generation of multidetector row computed tomography (MDCT) systems allows for the noninvasive characterization of different plaque components in various vascular structures. MDCT allows evaluation of the whole arterial vasculature. In addition, MDCT has the ability to visualize the vessel wall and to give a quantitative measurement of calcified and noncalcified plaque. Using either technique, the repeatable, noninvasive study of atherosclerotic disease during its natural history and after therapeutic intervention will enhance our understanding of disease progression and regression. MDCT and MRI, therefore, may help in selecting appropriate treatments.

Carotid Artery Diseases↗
PubMed2004

Terminology for high-risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece.

A group of investigators met for two days in Santorini, Greece, to discuss progress in the field of identification and treatment of high risk/vulnerable atherosclerotic plaques and patients. Many differences in the manner in which terms are being utilized were noted. It was recognized that increased understanding of the pathophysiology of coronary thrombosis and onset of acute coronary syndromes has created the need for agreement on nomenclature. The participants spent considerable time discussing the topic and reached agreement on their own usage of the terms as described below. It is the hope that this usage might be of value to the larger community of scientists working in this field, and that widespread adoption of a common nomenclature would accelerate progress in the prevention of acute coronary events.

Calcinosis↗
PubMed2004

Atherothrombosis: a widespread disease with unpredictable and life-threatening consequences.

Atherothrombosis, characterised by atherosclerotic lesion disruption with superimposed thrombus formation, is the major cause of acute coronary syndromes (ACS) and cardiovascular death. It is the leading cause of mortality in the industrialised world. Atherosclerosis is a diffuse process that starts early in childhood and progresses asymptomatically through adult life. Later in life, it is clinically manifested as coronary artery disease, stroke, transient ischaemic attack, and peripheral arterial disease. From the clinical point of view, we should envision this disease as a single pathologic entity that affects different vascular territories. Available antithrombotic therapy is very safe and efficient but the morbidity and mortality due to atherothrombosis is still unacceptably high. Recent evidence suggests that inhibition of tissue factor or elements in the tissue factor pathway (i.e., factors VIIa and Xa, or thrombin) has the potential to further improve outcomes in atherothrombosis. Here, we will review the most important concepts and advances in the pathogenesis, prevention, and antithrombotic treatment of this widespread disease.

Arteriosclerosis↗
PubMed2004

Evolving concepts in the triad of atherosclerosis, inflammation and thrombosis.

Recent developments into antherothrombosis, the leading cause of morbidity and mortality in Western Society, may help to change our treatment strategy to a more casual approach. The composition of the atherosclerotic plaque, rather than the percent stenosis, appears to be a critical predictor for both risk of plaque rupture and subsequent thrombogenicity. A large lipid core, rich in tissue factor (TF) and inflammatory cells including macrophages, and a thin fibrous cap with compromise of its structural integrity by matrix degrading enzymes, such as metalloproteinases (MMPs), render a lesion susceptible to rupture and subsequent acute thrombosis. Thrombosis may lead to a complete occlusion or, in the case of mural thrombus or intraplaque hemorrhage, to plaque progression. Disruption of a vulnerable or unstable plaque (type IV and Va lesions of the AHA classification) with a subsequent change in plaque geometry and thrombosis may result in an acute coronary syndrome. The high-risk plaque tend to be relatively small, but soft or vulnerable to "passive" disruption because of high lipid content. Inflammatory processes are important components of all stages of atherosclerotic development, including plaque initiation and disruption. As such the early steps in atherosclerotic lesion formation are the over expression of endothelial adhesive protein (i.e. selectins, VCAM and ICAM), chemotactic factors (MCP-1), growth factors (M-CSF), and cytokines (IL-2) that will facilitate the recruitment, internalization and survival of blood-borne inflammatory cells into the vascular wall. Macrophages, following what appears to be a defense mission by protecting the vessel wall from excess lipid accumulation, may eventually undergo apoptosis with release of MMPs and TF. Specific cell recruitment in the vessel wall and build-up of the extracellular matrix are coordinated by a wide variety of stimulators and inhibitors. Active interaction of immune competent cells within the atherosclerotic lesions appears to play a pivotal role in the control of atherosclerotic plaque evolution and, therefore, deserves particular attention from the research community with the ultimate goal of improving preventive and therapeutic medical approaches. Inflammation, thrombosis and atherosclerosis are interdependent and define a triad within the complex pathogenic process of atherothrombosis.

Arteriosclerosis↗
PubMed2004

Technology insight: targeting of biological molecules for evaluation of high-risk atherosclerotic plaques with magnetic resonance imaging.

Identification of high-risk atherosclerotic lesions prone to rupture and thrombosis may greatly decrease the morbidity and mortality associated with atherosclerosis. The development of magnetic resonance imaging contrast agents that specifically target components of the atherosclerotic plaque might enable non-invasive detection of high-risk lesions. This review discusses a variety of molecules present in atherosclerotic plaque that could serve as targets for specific contrast agents. Ultimately, such agents may allow the identification of high-risk atherosclerotic lesions in patients and enable treatment of these patients before lesion progression and complications.

Animals↗
PubMed2004

Molecular, cellular and functional imaging of atherothrombosis.

Recent years have seen a dramatic expansion in our knowledge of the events of atherogenesis and in the availability of drugs that can retard the progression - and even induce the regression - of this disease process. Our understanding has been advanced considerably by developments in genetics and molecular biology and by the use of genetically modified mouse models that have provided key mechanistic insights. Increasingly sophisticated imaging techniques will capitalize on these advances by bringing forward diagnosis, enhancing disease characterization and providing more precise evaluation of the effects of treatment. In this review, techniques for imaging atherosclerosis and thrombosis will be discussed. Particular attention will be given to magnetic resonance imaging techniques that enable lesion characterization and allow the targeted imaging of cells, molecules and biological processes. Emphasis is given to the potential contribution of magnetic resonance imaging methods to therapeutic monitoring, drug delivery and drug discovery.

Animals↗
PubMed2004

Tissue factor coagulation pathway: a new therapeutic target in atherothrombosis.

Atherothrombosis, defined as atherosclerotic lesion disruption with superimposed thrombus formation, is the major cause of acute coronary syndromes and cardiovascular deaths. It is the leading cause of morbidity and mortality in the industrialized world. Plaque composition, rather than luminal stenosis, is recognized as the major determinant of this disease. Since tissue factor is found within atheroma and also in the bloodstream of atherosclerotic patients, it likely plays a key role in determining both plaque and blood thrombogenicity. Ongoing clinical and preclinical studies are evaluating the therapeutic possibilities of specific inhibition of the tissue factor pathway. Here, we will review the role of tissue factor in atherothrombosis and therapeutic applications.

Arteriosclerosis↗
PubMed2004

Peroxisome proliferator-activated receptor ligands in atherosclerosis.

In this review, the effect of peroxisome proliferator-activated receptor (PPAR) ligands on atherosclerosis is examined. The PPAR-gamma agonist thiazolidinediones are currently indicated for the management of Type 2 diabetes mellitus, and the PPAR-alpha agonist fibrates are used in dyslipidaemia. Here their mechanism of action and the pre-clinical and clinical evidence for the use of these medications for the prevention and treatment of atherosclerotic disease is explored. In addition, the role of PPAR-delta and the possibilities for the role of dual-binding agonists are examined.

Animals↗
PubMed2004

Clinical and experimental experience with factor Xa inhibitors.

Cardiovascular disease is the major cause of mortality in the industrial world today. We are constantly moving towards new and better ways of fighting this epidemic. Advances have been made in various fields such as patient education, imaging techniques, interventional cardiology, and novel therapeutic agents. In particular, antithrombotics are being studied with great interest and hope. Amid this class of agents, factor Xa inhibitors have already begun to show promising results in trials involving patients with acute coronary syndromes. Whereas DX-9065a is in late stage clinical trials, fondaparinux sodium is available for clinical use. Promising results have been obtained with fondaparinux sodium in patients with coronary artery disease in the PENTUA (Pentasaccharide in Unstable Angina) and PENTALYSE (Pentasaccharide as an Adjunct to Fibrinolysis in ST-Elevation Acute Myocardial Infarction) trials. Besides having a direct effect on the coagulation cascade, they have shown properties that indirectly influence the remodeling of plaques in the coronary circulation. Available evidence on factor Xa inhibitors does not ensure a remedy to acute coronary syndromes but it gives hope of improving current treatments and reducing the morbidity and mortality of cardiovascular disease. The efficacy and tolerability of fondaparinux sodium in the prevention and treatment of deep vein thrombosis (with or without pulmonary embolism) has been established in several large trials such as PENTATHLON (Pentasaccharide in Total Hip Replacement Surgery), PENTAMAKS (Pentasaccharide in Major Knee Surgery), EPHESUS (European Pentasaccharide Hip Elective Surgery), PENTHIFRA (Pentasaccharide in Hip-Fracture Surgery), and PENTHIFRA-Plus. Whereas fondaparinux sodium offers benefits over low molecular weight heparins and unfractionated heparin, the incidence of bleeding complications was greater with fondaparinux sodium than with unfractionated heparin. Treatment with factor VIIa can reverse the anticoagulant effect of fondaparinux sodium and this may be particularly important in patients who need to undergo emergency surgical procedures. Fondaparinux sodium has been recently approved for use, in conjunction with warfarin, in patients with symptomatic deep vein thrombosis or acute pulmonary embolism based on the results of two large trials conducted by the Matisse investigators. In conclusion, these observations strongly suggest the clinical potential of this class of agents in preventing arterial and venous thrombosis.

Anticoagulants↗
PubMed2004

Update in atherothrombotic disease.

Crucial advances in our understanding of the pathogenesis of atherothrombosis, defined as atherosclerosis and its thrombotic complications, have been achieved during the past two decades. The historical hypothesis of pathogenesis ("lipid accumulation") has evolved to integrate several factors contributing to the initiation and evolution of this complex disease. Endothelial dysfunction is considered to be the earliest event in atherogenesis. Inflammation and apoptosis play critical roles in its progression and onset. Tissue factor is postulated to be a central actor in determining plaque thrombogenicity. A hyperreactive state of the blood ("vulnerable blood") may be responsible for one-third of all the acute coronary syndromes. This review will discuss emerging concepts in the pathogenesis of and therapeutic approaches to atherothrombotic disease.

Acute Disease↗
PubMed2004

Anticoagulation in pregnant women with prosthetic heart valves.

The combination of heart disease and pregnancy can present a formidable challenge to the clinician entrusted to care for both the mother and fetus. Since most data is retrospective, a definitive prognosis for such a patient may be difficult to obtain. Nevertheless, certain cardiac conditions carry greater risks of maternal mortality than do others. However, even for certain preexisting conditions, a tremendous amount of debate persists with respect to risks during pregnancy and optimal peripartum management. One such area of controversy concerns anticoagulation in pregnant women with prosthetic heart valves. For patients who require anticoagulation for mechanical valves, the choice of some combination of warfarin, unfractionated heparin, and low-molecular-weight heparin (LMWH) has resulted in many small-scale trials, which have not yet provided definite guidance as to the best course of action. Even more controversial has been the recent labeling change that advises against the use of LMWH in all patients with prosthetic heart valves, as a result of two cases of prosthetic valve thrombosis in women using LMWH while pregnant. Although the latest product labeling, in the summer of 2003, was changed to a less restrictive recommendation, debate persists. A discussion of the available data on anticoagulation in pregnant women with prosthetic heart valves is presented here, to inform the clinician and the patient of the risks and benefits of the options presently available.

Anticoagulants↗
PubMed2003

ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias--executive summary. a report of the American college of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (writing committee to develop guidelines for the management of patients with supraventricular arrhythmias) developed in collaboration with NASPE-Heart Rhythm Society.

Explore the source record for details and available documents.

Anti-Arrhythmia Agents↗