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Diagnostic Yield of Genetic Testing in Young Athletes with T-wave Inversion.

Sheikh, N; Papadakis, M; Wilson, M; Malhotra, A; Adamuz, C; Homfray, T; Monserrat, L; Behr, ER; Sharma, S (2018) Diagnostic Yield of Genetic Testing in Young Athletes with T-wave Inversion. Circulation, 138 (12). pp. 1184-1194. ISSN 1524-4539 https://doi.org/10.1161/CIRCULATIONAHA.118.034208
SGUL Authors: Behr, Elijah Raphael Papadakis, Michael Sharma, Sanjay

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Abstract

Background -T-wave inversion (TWI) is common in patients with cardiomyopathy. However, up to 25% of athletes of African/Afro-Caribbean descent (black athletes) and 5% of white athletes also have TWI of unclear clinical significance despite comprehensive clinical evaluation and long-term follow-up. The aim of this study was to determine the diagnostic yield from genetic testing, beyond clinical evaluation, when investigating athletes with TWI. Methods -We investigated 50 consecutive asymptomatic black and 50 white athletes aged 14-35-years-old with TWI and a normal echocardiogram who were referred to a UK tertiary center for cardiomyopathy and sports cardiology. Subjects underwent exercise testing, 24-hour ECG, signal-averaged ECG, cardiac magnetic resonance imaging, and a blood-based analysis of a comprehensive 311 gene panel for cardiomyopathies including hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, left ventricular non-compaction, and ion channel disorders such as long QT syndrome and Brugada syndrome. Results -In total, 21 athletes (21%) were diagnosed with cardiac disease on the basis of comprehensive clinical investigations. Of these, 8 (38.1%) were gene positive (MYPBC3, MYH7, GLA, and ACTC1 genes) and 13 (61.9%) were gene negative. Of the remaining 79 athletes (79%), 2 (2.5%) were gene positive (TTR and SCN5A genes) in the absence of a clinical phenotype. The prevalence of newly diagnosed cardiomyopathy was higher in white athletes compared with black athletes (30.0% vs. 12%, P=0.027). Hypertrophic cardiomyopathy accounted for 90.5% of all clinical diagnoses. All black athletes and 93.3% of white athletes with a clinical diagnosis of cardiomyopathy or a genetic mutation capable of causing cardiomyopathy exhibited lateral TWI as opposed to isolated anterior or inferior TWI; the genetic yield of diagnoses from lateral TWI was 14.0%. Conclusions -Up to 10% of athletes with TWI revealed mutations capable of causing cardiac disease. Despite the substantial cost, the positive diagnostic yield from genetic testing was one-half of that from clinical evaluation (10% vs. 21%) and contributed to additional diagnoses in only 2.5% of athletes with TWI in the absence of a clear clinical phenotype, making it of negligible use in routine clinical practice.

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 Non-Commercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.
Keywords: T-wave inversion, cardiomyopathy, ethnicity, exercise, genetic testing, screening, T-wave inversion, cardiomyopathy, ethnicity, exercise, genetic testing, screening, 1103 Clinical Sciences, 1102 Cardiovascular Medicine And Haematology, 1117 Public Health And Health Services, Cardiovascular System & Hematology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Circulation
ISSN: 1524-4539
Language: eng
Dates:
DateEvent
18 September 2018Published
24 July 2018Published Online
8 May 2018Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
PG/11/122/29310British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
PubMed ID: 29764897
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109841
Publisher's version: https://doi.org/10.1161/CIRCULATIONAHA.118.034208

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