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      Evaluation of cardiac hypertrophy in the setting of sudden cardiac death

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          Abstract

          Ventricular hypertrophy is a common pathological finding at autopsy that can act as a substrate for arrhythmogenesis. Pathologists grapple with the significance of ventricular hypertrophy when assessing the sudden and unexpected deaths of young people and what it could mean for surviving family members. The pathological spectrum of left ventricular hypertrophy (LVH) is reviewed herein. This article is oriented to the practicing autopsy pathologist to help make sense of various patterns of increased heart muscle, particularly those that are not clearly cardiomyopathic, yet present in the setting of sudden cardiac death. The article also reviews factors influencing arrhythmogenesis as well as genetic mutations most commonly associated with ventricular hypertrophy, especially those associated with hypertrophic cardiomyopathy (HCM).

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          Most cited references79

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          Mechanisms of physiological and pathological cardiac hypertrophy

          Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number, individual cardiomyocytes increase in size, and the heart develops hypertrophy to reduce ventricular wall stress and maintain function and efficiency in response to an increased workload. There are two types of hypertrophy: physiological and pathological. Hypertrophy initially develops as an adaptive response to physiological and pathological stimuli, but pathological hypertrophy generally progresses to heart failure. Each form of hypertrophy is regulated by distinct cellular signalling pathways. In the past decade, a growing number of studies have suggested that previously unrecognized mechanisms, including cellular metabolism, proliferation, non-coding RNAs, immune responses, translational regulation, and epigenetic modifications, positively or negatively regulate cardiac hypertrophy. In this Review, we summarize the underlying molecular mechanisms of physiological and pathological hypertrophy, with a particular emphasis on the role of metabolic remodelling in both forms of cardiac hypertrophy, and we discuss how the current knowledge on cardiac hypertrophy can be applied to develop novel therapeutic strategies to prevent or reverse pathological hypertrophy.
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            Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction.

            Characterization of myocardial structural changes in heart failure with preserved ejection fraction (HFpEF) has been hindered by the limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction, and myocardial fibrosis may contribute to HFpEF pathophysiology.
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              Slow conduction in the infarcted human heart. 'Zigzag' course of activation.

              Ventricular tachycardias occurring in the chronic phase of myocardial infarction are caused by reentry. Areas of slow conduction, facilitating reentry, are often found in the infarcted zone. The purpose of this study was to elucidate the mechanism of slow conduction in the chronic infarcted human heart. Spread of activation was studied in infarcted papillary muscles from hearts of patients who underwent heart transplantation because of infarction. Recordings were carried out on 10 papillary muscles that were superfused in a tissue bath. High-resolution mapping was performed in areas revealing slow conduction. Activation delay between sites perpendicular to the fiber direction and 1.4 mm apart could be as long as 45 milliseconds. Analysis of activation times revealed that activation spread in tracts parallel to the fiber direction. Conduction velocity in the tracts was between 0.6 and 1 m/s. Although tracts were separated from each other over distances up to 8 mm, they often connected with each other at one or more sites, forming a complex network of connected tracts. In this network, wave fronts could travel perpendicular to the fiber direction. Separation of tracts was due to collagenous septa. At sites where tracts were interconnected, the collagenous barriers were interrupted. Slow conduction perpendicular to the fiber direction in infarcted myocardial tissue is caused by a "zigzag" course of activation at high speed. Activation proceeds along pathways lengthened by branching and merging bundles of surviving myocytes ensheathed by collagenous septa.
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                Author and article information

                Journal
                Forensic Sci Res
                Forensic Sci Res
                TFSR
                tfsr20
                Forensic Sciences Research
                Taylor & Francis
                2096-1790
                2471-1411
                2019
                19 August 2019
                : 4
                : 3 , Special Issue on Sudden Cardiac Death; Guest Editor: Joaquín Lucena Romero
                : 223-240
                Affiliations
                [a ]Department of Laboratory Medicine and Pathobiology , Ontario Forensic Pathology Service, University of Toronto , Toronto, Canada;
                [b ]University Health Network, Division of Cardiology – Electrophysiology , University of Toronto , Toronto, Canada;
                [c ]Fred A. Litwin Family Centre in Genetic Medicine and Inherited Arrhythmia Clinic , University Health Network & Mount Sinai Hospital, University of Toronto , Toronto, Canada
                Author notes
                CONTACT Kristopher S. Cunningham kris.cunningham@ 123456ontario.ca
                Author information
                http://orcid.org/0000-0002-2513-1627
                Article
                1633761
                10.1080/20961790.2019.1633761
                6713129
                31489388
                da5b66e5-7488-4222-a1d6-b11b65bddede
                © 2019 The Author(s). Published by Taylor & Francis Group on behalf of the Academy of Forensic Science.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 October 2018
                : 17 June 2019
                : 17 June 2019
                Page count
                Figures: 0, Tables: 2, Pages: 27, Words: 14237
                Categories
                Reviews

                forensic sciences,forensic pathology,ventricular hypertrophy,arrhythmia,sudden cardiac death,genetics

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