Genetic Testing in Young Athletes With T-Wave Inversion

Study Questions:

What is the diagnostic yield from genetic testing, beyond clinical evaluation, when investigating athletes with T-wave inversion (TWI)?


A cohort of 50 consecutive asymptomatic athletes of African/Afro-Caribbean descent (black athletes) and 50 white athletes aged 14-35 years with TWI and a normal echocardiogram who had been referred to a UK tertiary center for cardiomyopathy and sports cardiology were investigated. Subjects underwent exercise testing, 24-hour electrocardiography (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 noncompaction, and ion channel disorders such as long QT syndrome and Brugada syndrome.


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%. The cost of testing per athlete increased from US$1,084 for comprehensive clinical evaluation to $3,267 with genetic testing; with a cost of $109,150 per athlete to make an additional diagnosis based only on genetic testing.


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.


TWI is common among patients with cardiomyopathy. However, up to 25% of black athletes and 5% of white athletes also have TWI of unclear clinical significance. This study found that the prevalence of cardiomyopathy among white athletes with TWI was higher than among black athletes with TWI; that the diagnostic yield of genetic testing among young athletes with TWI was only 10%—one-half the yield (21%) of clinical evaluation; and that genetic testing contributed to additional diagnoses in only 2.5% of athletes with TWI and a negative comprehensive clinical evaluation. The relatively low diagnostic yield and high cost of genetic testing suggest that genetic testing probably is not justified in the routine evaluation of asymptomatic athletes with TWI and no family history of a heritable cardiac condition.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Sports and Exercise Cardiology, Implantable Devices, EP Basic Science, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Prevention, Lipid Metabolism, Acute Heart Failure, Magnetic Resonance Imaging, Exercise, Sports and Exercise and Congenital Heart Disease and Pediatric Cardiology, Sports and Exercise and ECG and Stress Testing, Sports and Exercise and Imaging

Keywords: Arrhythmias, Cardiac, Arrhythmogenic Right Ventricular Dysplasia, Athletes, Brugada Syndrome, Cardiomyopathy, Dilated, Cardiomyopathy, Hypertrophic, Electrocardiography, Exercise, Exercise Test, Genetic Testing, Heart Failure, Ion Channels, Long QT Syndrome, Magnetic Resonance Imaging, Mutation, Phenotype, Prevalence, Sports

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