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      Micro-computed tomography (micro-CT) for the assessment of myocardial disarray, fibrosis and ventricular mass in a feline model of hypertrophic cardiomyopathy

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          Abstract

          Micro-computed tomography (micro-CT) is a high-resolution imaging modality that provides accurate tissue characterization. Hypertrophic cardiomyopathy (HCM) occurs as a spontaneous disease in cats, and is characterized by myocardial hypertrophy, disarray and fibrosis, as in humans. While hypertrophy/mass (LVM) can be objectively measured, fibrosis and myocyte disarray are difficult to assess. We evaluated the accuracy of micro-CT for detection and quantification of myocardial disarray and fibrosis by direct comparison with histopathology. 29 cat hearts (12 normal and 17 HCM hearts) underwent micro-CT and pathologic examination. Myocyte orientation was assessed using structure tensor analysis by determination of helical angle (HA), fractional anisotropy (FA) and myocardial disarray index (MDI). Fibrosis was segmented and quantified based on comparison of gray-scale values in normal and fibrotic myocardium. LVM was obtained by determining myocardial volume. Myocardial segments with low FA, low MDI and disruption of normal HA transmural profile on micro-CT were associated with myocardial disarray on histopathology. FA was consistently lower in HCM than normal hearts. Assessment of fibrosis on micro-CT closely matched the histopathologic evaluation. LVM determined by micro-CT was higher in HCM than normal hearts. Micro-CT can be used to detect and quantify myocardial disarray and fibrosis and determine myocardial mass in HCM.

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          Most cited references27

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          Etiology of Sudden Death in Sports: Insights From a United Kingdom Regional Registry.

          Accurate knowledge of causes of sudden cardiac death (SCD) in athletes and its precipitating factors is necessary to establish preventative strategies.
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            Cardiomyopathy prevalence in 780 apparently healthy cats in rehoming centres (the CatScan study).

            Hypertrophic cardiomyopathy (HCM) appears to be common in cats and, based on pilot data, a prevalence of 15% has been hypothesized. The objectives were to screen a large population of apparently healthy adult cats for cardiac disease, and identify factors associated with a diagnosis of HCM.
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              Echocardiographic assessment of spontaneously occurring feline hypertrophic cardiomyopathy. An animal model of human disease.

              Necropsy studies in domestic cats have suggested the occurrence of a primary cardiac disease resembling hypertrophic cardiomyopathy (HCM) in humans. We used two-dimensional echocardiography to define morphological and functional features of HCM during life in 46 domestic cats evaluated in a subspecialty veterinary clinic. Cats were 8 months to 14 years old (mean, 6 years). During the follow-up period of as long as 49 months, 18 cats died (or were euthanatized) due to congestive heart failure, peripheral embolization, or both, and 3 other cats experienced out-of-hospital sudden, unexpected death. Echocardiography showed a small left ventricular cavity, associated with a variety of patterns of hypertrophy. Wall thickening was most often diffuse (involving ventricular septum and free wall) in 31 cats (67%) and segmental in 15 (33%), including 12 with thickening confined to anterior septum; wall thickening was judged to be asymmetrical in 42 and symmetrical (concentric) in 4. In 30 cats (65%), marked mitral valve systolic anterior motion produced dynamic obstruction to left ventricular outflow (Doppler estimated gradients, 25 to 110 mm Hg). Compared with survivors, cats with HCM that died with heart failure had greater left ventricular thickness (8.1 +/- 1.5 versus 7.3 +/- 0.9 mm; P < .05) and larger left atria (20.1 +/- 4.6 versus 16.8 +/- 3.4 mm; P = .01) and more often had the nonobstructive form (89% versus 48%; P < .01). A spontaneously occurring disease of domestic cats was identified by echocardiography and was similar in its phenotypic expression to HCM in humans; it was characterized by unexplained left ventricular hypertrophy in a variety of patterns with or without evidence of outflow obstruction. Unfavorable prognosis was associated with greater magnitude of hypertrophy and absence of outflow obstruction. Feline HCM may prove to be a valuable animal model of the human disease.
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                Author and article information

                Contributors
                jms330@cam.ac.uk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                19 November 2020
                19 November 2020
                2020
                : 10
                : 20169
                Affiliations
                [1 ]GRID grid.20931.39, ISNI 0000 0004 0425 573X, Clinical Sciences and Services, , Royal Veterinary College, ; London, UK
                [2 ]GRID grid.10403.36, Institut D’Investigacions Biomèdiques August Pi I Sunyer, ; Barcelona, Spain
                [3 ]GRID grid.83440.3b, ISNI 0000000121901201, Institute of Cardiovascular Science, , University College London, ; London, UK
                [4 ]GRID grid.451052.7, ISNI 0000 0004 0581 2008, Department of Histopathology, Great Ormond Street Hospital for Children, , NHS Foundation Trust, ; London, UK
                [5 ]GRID grid.451052.7, ISNI 0000 0004 0581 2008, Department of Radiology, Great Ormond Street Hospital for Children, , NHS Foundation Trust, ; London, UK
                [6 ]GRID grid.451056.3, ISNI 0000 0001 2116 3923, National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, ; London, UK
                [7 ]Finn Pathologists, Norfolk, UK
                Article
                76809
                10.1038/s41598-020-76809-5
                7678873
                33214588
                5c7dc8b8-711d-448a-bbba-734ff98db6c6
                © The Author(s) 2020

                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
                : 4 August 2020
                : 2 November 2020
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                cardiac hypertrophy,cardiovascular biology
                Uncategorized
                cardiac hypertrophy, cardiovascular biology

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