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      Coronary Microvascular Dysfunction: What Clinicians and Investigators Should Know

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          Abstract   

          Purpose of Review

          Abnormal structure and function of the coronary microvasculature have been implicated in the pathophysiology of multiple cardiovascular disease processes. This article reviews recent research progress related to coronary microvascular dysfunction (CMD) and salient clinical takeaways.

          Recent Findings

          CMD is prevalent in patients with signs and symptoms of ischemia and no obstructive epicardial coronary artery disease (INOCA), particularly in women. CMD is associated with adverse outcomes, including most frequently the development of heart failure with preserved ejection fraction. It is also associated with adverse outcomes in patient populations including hypertrophic cardiomyopathy, dilated cardiomyopathy, and acute coronary syndromes. In patients with INOCA, stratified medical therapy guided by invasive coronary function testing to define the subtype of CMD leads to improved symptoms.

          Summary

          There are invasive and non-invasive methodologies to diagnose CMD that provide prognostic information and mechanistic information to direct treatment. Available treatments improve symptoms and myocardial blood flow; ongoing investigations aim to develop therapy to improve adverse outcomes related to CMD.

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          Most cited references97

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          2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes

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            Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association

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              A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation.

              Over the past decade, myocardial structure, cardiomyocyte function, and intramyocardial signaling were shown to be specifically altered in heart failure with preserved ejection fraction (HFPEF). A new paradigm for HFPEF development is therefore proposed, which identifies a systemic proinflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations. The new paradigm presumes the following sequence of events in HFPEF: 1) a high prevalence of comorbidities such as overweight/obesity, diabetes mellitus, chronic obstructive pulmonary disease, and salt-sensitive hypertension induce a systemic proinflammatory state; 2) a systemic proinflammatory state causes coronary microvascular endothelial inflammation; 3) coronary microvascular endothelial inflammation reduces nitric oxide bioavailability, cyclic guanosine monophosphate content, and protein kinase G (PKG) activity in adjacent cardiomyocytes; 4) low PKG activity favors hypertrophy development and increases resting tension because of hypophosphorylation of titin; and 5) both stiff cardiomyocytes and interstitial fibrosis contribute to high diastolic left ventricular (LV) stiffness and heart failure development. The new HFPEF paradigm shifts emphasis from LV afterload excess to coronary microvascular inflammation. This shift is supported by a favorable Laplace relationship in concentric LV hypertrophy and by all cardiac chambers showing similar remodeling and dysfunction. Myocardial remodeling in HFPEF differs from heart failure with reduced ejection fraction, in which remodeling is driven by loss of cardiomyocytes. The new HFPEF paradigm proposes comorbidities, plasma markers of inflammation, or vascular hyperemic responses to be included in diagnostic algorithms and aims at restoring myocardial PKG activity. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                merz@cshs.org
                Journal
                Curr Atheroscler Rep
                Curr Atheroscler Rep
                Current Atherosclerosis Reports
                Springer US (New York )
                1523-3804
                1534-6242
                20 June 2023
                20 June 2023
                2023
                : 25
                : 8
                : 435-446
                Affiliations
                [1 ]GRID grid.512369.a, Cedars-Sinai Medical Center, , Smidt Heart Institute, ; Los Angeles, CA USA
                [2 ]GRID grid.50956.3f, ISNI 0000 0001 2152 9905, Cedars-Sinai Medical Center, , Barbra Streisand Women’s Heart Center, Smidt Heart Institute, ; 127 S. San Vicente Blvd, Los Angeles, CA 90048 USA
                Author information
                http://orcid.org/0000-0002-9933-5155
                Article
                1116
                10.1007/s11883-023-01116-z
                10412671
                37338666
                5c2c8928-81b5-4c68-bb49-70ef7725cdef
                © The Author(s) 2023, corrected publication 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 1 June 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100017540, NHLBI Division of Intramural Research;
                Award ID: N01HV68161
                Award ID: N01HV68162
                Award ID: N01HV68163
                Award ID: N01HV68164
                Award ID: U01HL64829
                Award ID: U01HL64914
                Award ID: U01HL64924
                Award ID: K23HL105787
                Award ID: K23 HL125941
                Award ID: K23HL127262
                Award ID: K23HL151867
                Award ID: T32HL69751
                Award ID: T32HL116273
                Award ID: R01HL090957
                Award ID: R01HL033610
                Award ID: R01HL056921
                Award ID: R01HL146158
                Award ID: R01 HL146158-04S1
                Award ID: R01 HL153500
                Award ID: UM1HL087366
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000049, National Institute on Aging;
                Award ID: R03AG032631
                Award ID: U54AG065141
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000097, National Center for Research Resources;
                Award ID: M01RR000425
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100006108, National Center for Advancing Translational Sciences;
                Award ID: UL1TR000124
                Award ID: UL1TR000064
                Award ID: UL1TR001427
                Award Recipient :
                Funded by: Cedars-Sinai Medical Center
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                © Springer Science+Business Media, LLC, part of Springer Nature 2023

                Immunology
                coronary microvascular dysfunction,microvascular angina,coronary function testing,coronary flow reserve,ischemia with no obstructive coronary artery disease

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