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      ESC Working Group on Coronary Pathophysiology and Microcirculation position paper on ‘coronary microvascular dysfunction in cardiovascular disease’

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          Abstract

          Although myocardial ischaemia usually manifests as a consequence of atherosclerosis-dependent obstructive epicardial coronary artery disease, a significant percentage of patients suffer ischaemic events in the absence of epicardial coronary artery obstruction. Experimental and clinical evidence highlight the abnormalities of the coronary microcirculation as a main cause of myocardial ischaemia in patients with ‘normal or near normal’ coronary arteries on angiography. Coronary microvascular disturbances have been associated with early stages of atherosclerosis even prior to any angiographic evidence of epicardial coronary stenosis, as well as to other cardiac pathologies such as myocardial hypertrophy and heart failure. The main objectives of the manuscript are (i) to provide updated evidence in our current understanding of the pathophysiological consequences of microvascular dysfunction in the heart; (ii) to report on the current knowledge on the relevance of cardiovascular risk factors and comorbid conditions for microcirculatory dysfunction; and (iii) to evidence the relevance of the clinical consequences of microvascular dysfunction. Highlighting the clinical importance of coronary microvascular dysfunction will open the field for research and the development of novel strategies for intervention will encourage early detection of subclinical disease and will help in the stratification of cardiovascular risk in agreement with the new concept of precision medicine.

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          Most cited references103

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          Human epicardial adipose tissue is a source of inflammatory mediators.

          Inflammatory mediators that originate in vascular and extravascular tissues promote coronary lesion formation. Adipose tissue may function as an endocrine organ that contributes to an inflammatory burden in patients at risk of cardiovascular complications. In this study, we sought to compare expression of inflammatory mediators in epicardial and subcutaneous adipose stores in patients with critical CAD. Paired samples of epicardial and subcutaneous adipose tissues were harvested at the outset of elective CABG surgery (n=42; age 65+/-10 years). Local expression of chemokine (monocyte chemotactic protein [MCP]-1) and inflammatory cytokines (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha) was analyzed by TaqMan real-time reverse transcription-polymerase chain reaction (mRNA) and by ELISA (protein release over 3 hours). Significantly higher levels of IL-1beta, IL-6, MCP-1, and TNF-alpha mRNA and protein were observed in epicardial adipose stores. Proinflammatory properties of epicardial adipose tissue were noted irrespective of clinical variables (diabetes, body mass index, and chronic use of statins or ACE inhibitors/angiotensin II receptor blockers) or plasma concentrations of circulating biomarkers. In a subset of samples (n=11), global gene expression was explored by DNA microarray hybridization and confirmed the presence of a broad inflammatory reaction in epicardial adipose tissue in patients with coronary artery disease. The above findings were paralleled by the presence of inflammatory cell infiltrates in epicardial adipose stores. Epicardial adipose tissue is a source of several inflammatory mediators in high-risk cardiac patients. Plasma inflammatory biomarkers may not adequately reflect local tissue inflammation. Current therapies do not appear to eliminate local inflammatory signals in epicardial adipose tissue.
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            Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction.

            Coronary endothelial dysfunction is characterized by vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. Although endothelial dysfunction is considered an early phase of coronary atherosclerosis, there is a paucity of information regarding the outcome of these patients. Thus, this study was designed to evaluate the outcome of patients with mild coronary artery disease on the basis of their endothelial function. Follow-up was obtained in 157 patients with mildly diseased coronary arteries who had undergone coronary vascular reactivity evaluation by graded administration of intracoronary acetylcholine, adenosine, and nitroglycerin and intracoronary ultrasound at the time of diagnostic study. Patients were divided on the basis of their response to acetylcholine into 3 groups: group 1 (n=83), patients with normal endothelial function; group 2 (n=32), patients with mild endothelial dysfunction; and group 3 (n=42), patients with severe endothelial dysfunction. Over an average 28-month follow-up (range, 11 to 52 months), none of the patients from group 1 or 2 had cardiac events. However, 6 (14%) with severe endothelial dysfunction had 10 cardiac events (P<0.05 versus groups 1 and 2). Cardiac events included myocardial infarction, percutaneous or surgical coronary revascularization, and/or cardiac death. Severe endothelial dysfunction in the absence of obstructive coronary artery disease is associated with increased cardiac events. This study supports the concept that coronary endothelial dysfunction may play a role in the progression of coronary atherosclerosis.
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              Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries.

              Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a puzzling clinical entity with no previous evaluation of the literature. This systematic review aims to (1) quantify the prevalence, risk factors, and 12-month prognosis in patients with MINOCA, and (2) evaluate potential pathophysiological mechanisms underlying this disorder.
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                Author and article information

                Journal
                Cardiovascular Research
                Oxford University Press (OUP)
                0008-6363
                1755-3245
                February 08 2020
                February 08 2020
                Affiliations
                [1 ]Cardiovascular Program-ICCC, Research Institute Hospital Santa Creu i Sant Pau, Barcelona, Spain
                [2 ]Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV) Instituto de Salud Carlos III, Madrid, Spain
                [3 ]Cardiovascular Research Chair, Autonomous University Barcelona (UAB), Barcelona, Spain
                [4 ]Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
                [5 ]Division of Cardiology, Department of Medicine, State University of New York at Buffalo, Buffalo, NY, USA
                [6 ]Division of Cardiology, Maggiore della Carità Hospital, Eastern Piedmont University , Novara, Italy
                [7 ]Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, Cardiovascular Research Institute COEUR, Erasmus University Medical Center, Rotterdam, The Netherlands
                [8 ]Department of Physiology, Amsterdam Cardiovascular Science Institute, Amsterdam University Medical Centres, Amsterdam, The Netherlands
                [9 ]Department of Translational Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary
                [10 ]Department of Physiology, New York Medical College, Valhalla, NY, USA
                [11 ]First Department of Cardiology, Hippokration Hospital, University of Athens Medical School, Athens, Greece
                [12 ]Department of Cardiology, University Clinical Center of Serbia; and School of Medicine, University of Belgrade, Belgrade, Serbia
                [13 ]University Clinic of Cardiology, Medical Faculty, Ss' Cyril and Methodius University, Skopje, Republic of Macedonia
                [14 ]Institut für Physiologie, Universität zu Lübeck, Lübeck, Germany
                [15 ]DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Lübeck, Germany
                Article
                10.1093/cvr/cvaa003
                7825482
                32034397
                6b6dec0f-77d4-4d18-943a-6afbfca39af1
                © 2020

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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