Genetic testing in athletes with T-wave inversion provided a diagnostic yield of 10% versus 21% from clinical evaluation, adding diagnoses in only 2.5% of those without a clinical phenotype.
Observational (n=100)
No
Does genetic testing improve the diagnostic yield beyond comprehensive clinical evaluation in asymptomatic young athletes with T-wave inversion?
Routine genetic testing in asymptomatic athletes with T-wave inversion and normal echocardiograms provides negligible additional diagnostic yield beyond comprehensive clinical evaluation.
Absolute Event Rate: 10% vs 21%
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 14 to 35 years of age 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 ambulatory ECG, signal-averaged ECG, cardiac magnetic resonance imaging, and a blood-based analysis of a comprehensive 311-gene panel for cardiomyopathies and ion channel disorders associated with TWI, including hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, left ventricular noncompaction, 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 (myosin binding protein C MYBPC3, myosin heavy chain 7 MYH7, galactosidase alpha GLA, and actin alpha, cardiac muscle 1 ACTC1 genes) and 13 (61.9%) were gene negative. Of the remaining 79 athletes (79%), 2 (2.5%) were gene positive (transthyretin TTR and sodium voltage-gated channel alpha subunit 5 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% versus 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 12.3%. 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 that from clinical evaluation (10% versus 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.
Sheikh et al. (Tue,) conducted a observational in T-wave inversion (n=100). Genetic testing (311-gene panel) vs. Clinical evaluation was evaluated on Diagnostic yield. Genetic testing in athletes with T-wave inversion provided a diagnostic yield of 10% versus 21% from clinical evaluation, adding diagnoses in only 2.5% of those without a clinical phenotype.