Arrhythmogenic cardiomyopathy: pathogenesis, pro-arrhythmic remodelling, and novel approaches for risk stratification and therapy
van der Voorn, Stephanie M; Te Riele, Anneline S J M; Basso, Cristina; Calkins, Hugh; Remme, Carol Ann; van Veen, Toon A B
(2020) Cardiovascular research, volume 116, issue 9, pp. 1571 - 1584
(Article)
Abstract
Arrhythmogenic cardiomyopathy (ACM) is a life-threatening cardiac disease caused by mutations in genes predominantly encoding for desmosomal proteins that lead to alterations in the molecular composition of the intercalated disc. ACM is characterized by progressive replacement of cardiomyocytes by fibrofatty tissue, ventricular dilatation, cardiac dysfunction, and heart failure but mostly
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dominated by the occurrence of life-threatening arrhythmias and sudden cardiac death (SCD). As SCD appears mostly in apparently healthy young individuals, there is a demand for better risk stratification of suspected ACM mutation carriers. Moreover, disease severity, progression, and outcome are highly variable in patients with ACM. In this review, we discuss the aetiology of ACM with a focus on pro-arrhythmic disease mechanisms in the early concealed phase of the disease. We summarize potential new biomarkers which might be useful for risk stratification and prediction of disease course. Finally, we explore novel therapeutic strategies to prevent arrhythmias and SCD in the early stages of ACM.
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Keywords: Cardiomyopathy • Arrhythmia, Cardiology and Cardiovascular Medicine, Physiology (medical), Physiology, Journal Article
ISSN: 0008-6363
Publisher: Oxford University Press
Note: Funding Information: This work was supported by a grant from the Netherlands Cardio Vascular Research Initiative (CVON): the Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences (CVON-eDETECT 2015-12, CVON-PREDICT2 2018-30 (S.M.v.d.V., C.A.R., T.A.B.v.V.) and the Registry for Cardio-Cerebro-Vascular Pathology, Veneto Region, Venice, Italy, Ministry of Health (RF 2013_I 02356762 and RF-2016-02363774), PRIN Ministry of Education, University and Research (2015ZLNETW_001 and 20173ZWACS), Rome, Italy, and the CARIPARO Foundation, Padua, Italy (C.B.). Publisher Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
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