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      Coronary microvascular dysfunction: a key step in the development of uraemic cardiomyopathy?

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          Abstract

          The syndrome of uraemic cardiomyopathy, characterised by left ventricular hypertrophy, diffuse fibrosis and systolic and diastolic dysfunction, is common in chronic kidney disease and is associated with an increased risk of cardiovascular morbidity and mortality. The pathophysiological mechanisms leading to uraemic cardiomyopathy are not fully understood. We suggest that coronary microvascular dysfunction may be a key mediator in the development of uraemic cardiomyopathy, a phenomenon that is prevalent in other myocardial diseases that share phenotypical similarities with uraemic cardiomyopathy such as hypertrophic cardiomyopathy and heart failure with preserved ejection fraction. Here, we review the current understanding of uraemic cardiomyopathy, highlight different methods of assessing coronary microvascular function and evaluate the current evidence for coronary microvascular dysfunction in chronic kidney disease.

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          Evolving concepts in the pathogenesis of uraemic cardiomyopathy

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            Arterial disease in chronic kidney disease.

            End stage renal disease is associated with a very high risk of premature cardiovascular death and morbidity. Early stage chronic kidney disease (CKD) is also associated with an increased frequency of cardiovascular events and is a common but poorly recognised and undertreated risk factor. Cardiovascular disease in CKD can be attributed to two distinct but overlapping pathological processes, namely atherosclerosis and arteriosclerosis. While the risk of athero-thrombotic events such as myocardial infarction is elevated, arteriosclerosis is the predominant pathophysiological process involving fibrosis and thickening of the medial arterial layer. This results in increased arterial stiffness causing left ventricular hypertrophy and fibrosis and the exposure of vulnerable vascular beds such as the brain and kidney to high pressure fluctuations causing small vessel disease. These pathophysiological features are manifest by a high risk of lethal arrhythmia, congestive heart failure, myocardial infarction and stroke. Recent work has highlighted the importance of aldosterone and disordered bone mineral metabolism.
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              Quantitative Assessment of Coronary Microvascular Function: Dynamic Single-Photon Emission Computed Tomography, Positron Emission Tomography, Ultrasound, Computed Tomography, and Magnetic Resonance Imaging.

              A healthy, functional microcirculation in combination with nonobstructed epicardial coronary arteries is the prerequisite of normal myocardial perfusion. Quantitative assessment in myocardial perfusion and determination of absolute myocardial blood flow can be achieved noninvasively using dynamic imaging with multiple imaging modalities. Extensive evidence supports the clinical value of noninvasively assessing indices of coronary flow for diagnosing coronary microvascular dysfunction; in certain diseases, the degree of coronary microvascular impairment carries important prognostic relevance. Although, currently positron emission tomography is the most commonly used tool for the quantification of myocardial blood flow, other modalities, including single-photon emission computed tomography, computed tomography, magnetic resonance imaging, and myocardial contrast echocardiography, have emerged as techniques with great promise for determination of coronary microvascular dysfunction. The following review will describe basic concepts of coronary and microvascular physiology, review available modalities for dynamic imaging for quantitative assessment of coronary perfusion and myocardial blood flow, and discuss their application in distinct forms of coronary microvascular dysfunction.
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                Author and article information

                Journal
                Heart
                Heart
                heartjnl
                heart
                Heart
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                1355-6037
                1468-201X
                September 2019
                25 June 2019
                : 105
                : 17
                : 1302-1309
                Affiliations
                [1 ] departmentBirmingham Cardio-Renal Group, Institute of Cardiovascular Sciences , University of Birmingham , Birmingham, UK
                [2 ] departmentDepartment of Cardiology , Queen Elizabeth Hospital Birmingham , Birmingham, UK
                [3 ] departmentDepartment of Nephrology , Queen Elizabeth Hospital Birmingham , Birmingham, UK
                [4 ] departmentGreen Lane Cardiovascular Service , Auckland City Hospital , Auckland, New Zealand
                Author notes
                [Correspondence to ] Professor Jonathan N Townend; john.townend@ 123456uhb.nhs.uk
                Author information
                http://orcid.org/0000-0003-2352-8353
                Article
                heartjnl-2019-315138
                10.1136/heartjnl-2019-315138
                6711343
                31239278
                ad7f311c-4bfe-41ca-a00a-e404db77688e
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

                History
                : 26 March 2019
                : 05 May 2019
                : 02 June 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000274, British Heart Foundation;
                Funded by: Birmingham Health Partners;
                Categories
                Review
                1506
                Custom metadata
                unlocked

                Cardiovascular Medicine
                myocardial disease
                Cardiovascular Medicine
                myocardial disease

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