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Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy.

Miles, C; Finocchiaro, G; Papadakis, M; Gray, B; Westaby, J; Ensam, B; Basu, J; Parry-Williams, G; Papatheodorou, E; Paterson, C; et al. Miles, C; Finocchiaro, G; Papadakis, M; Gray, B; Westaby, J; Ensam, B; Basu, J; Parry-Williams, G; Papatheodorou, E; Paterson, C; Malhotra, A; Robertus, JL; Ware, JS; Cook, SA; Asimaki, A; Witney, A; Chis Ster, I; Tome, M; Sharma, S; Behr, ER; Sheppard, MN (2019) Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy. Circulation. ISSN 1524-4539
SGUL Authors: Behr, Elijah Raphael Witney, Adam Austin Chis Ster, Delizia Irina Tome, Maria Teresa Asimaki, Angeliki

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BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by myocardial fibro-fatty replacement and an increased risk of sudden cardiac death (SCD). Originally described as a right ventricular (RV) disease, ACM is increasingly recognized as a biventricular entity. We evaluated pathological, genetic, and clinical associations in a large SCD cohort. METHODS: We investigated 5205 consecutive cases of SCD referred to a national cardiac pathology center between 1994 and 2018. Hearts and tissue blocks were examined by expert cardiac pathologists. Following comprehensive histological evaluation, 202 cases (4%) were diagnosed with ACM. Of these, 15 (7%) were diagnosed ante-mortem with dilated cardiomyopathy (DCM)(n=8) or ACM (n=7). Prior symptoms, medical history, circumstances of death, and participation in competitive sport were recorded. Post-mortem genetic testing was undertaken in 24/202 (12%). Rare genetic variants were classified according to American College of Medical Genetics and Genomics (ACMG) criteria. RESULTS: Of 202 ACM decedents (35.4±13.2 years; 82% male), 157 (78%) reported no prior cardiac symptoms. Forty-one decedents (41/202; 20%) were participants in competitive sport. The adjusted odds of dying during physical exertion were higher in males than females (OR 4.58; 95% CI 1.54-13.68; p=0.006) and in competitive athletes compared with non-athletes (OR 16.62; 95% CI 5.39-51.24; p<0.001). None of the decedents with an ante-mortem diagnosis of DCM fulfilled definite 2010 Task Force criteria. Macroscopic appearance of the heart was normal in 40/202 (20%) cases. There was left ventricular (LV) histopathological involvement in 176/202 (87%). Isolated RV disease was seen in 13%, isolated LV disease in 17%, and biventricular involvement in 70%. Among whole hearts, the most common areas of fibro-fatty infiltration were the LV posterobasal (68%) and anterolateral walls (58%). Post-mortem genetic testing yielded pathogenic variants in ACM-related genes in 6/24 (25%) decedents. CONCLUSIONS: SCD due to ACM affects males predominantly, most commonly occurring during exertion in athletic individuals in the absence of prior reported cardiac symptoms. LV involvement is observed in the vast majority of SCD cases diagnosed with ACM at autopsy. Current Task Force criteria may fail to diagnose biventricular ACM prior to death.

Item Type: Article
Additional Information: © 2018 The Authors. Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
Keywords: arrhythmogenic cardiomyopathy, left ventricular arrhythmogenic cardiomyopathy, 1103 Clinical Sciences, 1102 Cardiovascular Medicine And Haematology, 1117 Public Health And Health Services, Cardiovascular System & Hematology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Circulation
ISSN: 1524-4539
Language: eng
31 January 2019Published Online
2 January 2019Accepted
Publisher License: Creative Commons: Attribution 4.0
Project IDFunderFunder ID
FS/18/28/33549British Heart Foundation
UNSPECIFIEDRobert Lancaster Memorial FundUNSPECIFIED
1122330National Health and Medical Research Council
UNSPECIFIEDNational Institute for Health Research
PubMed ID: 30700137
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