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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; Ster, IC; Tome, M; Sharma, S; Behr, ER; Sheppard, MN (2019) Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy. Circulation, 139 (15). pp. 1786-1797. ISSN 1524-4539
SGUL Authors: Behr, Elijah Raphael Witney, Adam Austin Papadakis, Michael Sharma, Sanjay Chis Ster, Delizia Irina Sheppard, Mary Noelle Tome, Maria Teresa Ensam, Bode Miles, Christopher Jason Asimaki, Angeliki Gray, Belinda Ruth

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BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by myocardial fibrofatty replacement and an increased risk of sudden cardiac death (SCD). Originally described as a right ventricular 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. After comprehensive histological evaluation, 202 cases (4%) were diagnosed with ACM. Of these, 15 (7%) were diagnosed antemortem with dilated cardiomyopathy (n=8) or ACM (n=7). Previous symptoms, medical history, circumstances of death, and participation in competitive sport were recorded. Postmortem genetic testing was undertaken in 24 of 202 (12%). Rare genetic variants were classified according to American College of Medical Genetics and Genomics criteria. RESULTS: Of 202 ACM decedents (35.4±13.2 years; 82% male), no previous cardiac symptoms were reported in 157 (78%). Forty-one decedents (41/202; 20%) had been participants in competitive sport. The adjusted odds of dying during physical exertion were higher in men than in women (odds ratio, 4.58; 95% CI, 1.54-13.68; P=0.006) and in competitive athletes in comparison with nonathletes (odds ratio, 16.62; 95% CI, 5.39-51.24; P<0.001). None of the decedents with an antemortem diagnosis of dilated cardiomyopathy fulfilled definite 2010 Task Force criteria. The macroscopic appearance of the heart was normal in 40 of 202 (20%) cases. There was left ventricular histopathologic involvement in 176 of 202 (87%). Isolated right ventricular disease was seen in 13%, isolated left ventricular disease in 17%, and biventricular involvement in 70%. Among whole hearts, the most common areas of fibrofatty infiltration were the left ventricular posterobasal (68%) and anterolateral walls (58%). Postmortem genetic testing yielded pathogenic variants in ACM-related genes in 6 of 24 (25%) decedents. CONCLUSIONS: SCD attributable to ACM affects men predominantly, most commonly occurring during exertion in athletic individuals in the absence of previous reported cardiac symptoms. Left ventricular 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 before death.

Item Type: Article
Additional Information: © 2019 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 right ventricular dysplasia, cardiomyopathies, death, sudden, cardiac, 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
9 April 2019Published
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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