Dr Nabeel Sheikh discusses the role of genetic testing when evaluating athletes with abnormal ECG results.

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

Sheikh N et al., Diagnostic Yield of Genetic Testing in Young Athletes With T-Wave Inversion. Circulation 2018;May 15


Regular intensive exercise is associated with a number of changes in the heart which include enlargement of the chambers, thickening (hypertrophy) of the muscle, and slowing of the heart rate. These changes can be detected on an athlete’s electrical tracing (ECG) and ultrasound scan (echocardiogram). In the vast majority of athletes, such changes are well within what we would class as normal for a highly athletic individual.

However, a small number of athletes and particularly those of African/Afro Caribbean (black) ethnicity exhibit changes on their ECG called T-wave inversion (TWI) which are commonly seen in several inherited (genetic) heart conditions implicated in exercise-related sudden death. The presence of TWI on an athlete’s ECG therefore invariably raises concerns and prompts several investigations to ensure the athlete does not harbour one of these inherited heart conditions.

Up until now, studies have shown that in a small number of athletes with TWI, a heart condition is indeed found, either after initial routine tests or after subsequent tests during follow-up over a number of years. This is important to determine, as affected individuals can then be given the appropriate treatment and advice about whether to exercise or not, as well as treatment and lifestyle advice that can lower the risk of sudden cardiac death (SCD). However, in the vast majority of athletes with TWI, a cardiac condition is not found, despite comprehensive investigations and follow-up. This results in uncertainty about whether these athletes have a sinister heart condition or not.

So far, all of the studies investigating athletes with TWI have used routine clinical tests such as an echocardiogram and cardiac MRI scan to try to detect whether an athlete has a heart condition. However, as mentioned, most of the heart conditions associated with TWI are genetic, meaning they arise due to a spelling mistake in a gene containing information about the heart’s structure. Therefore one unanswered question has been whether searching for these spelling mistakes by gene testing athletes will help us determine whether their TWI is due to a genetic heart condition or not. Some of the drawbacks with gene testing are that it is very expensive to do and that the results can take a long time to process. In addition, when results do arrive, in some cases they can be difficult to interpret because changes of uncertain significance are uncovered.

In our study, we added genetic testing to the comprehensive routine clinical evaluation of 50 black and 50 white athletes to see whether this would help us find out the cause of TWI in those athletes whose clinical investigations were all normal. The results from our study show that firstly, comprehensive clinical evaluation can result in a diagnosis over one-fifth of athletes with TWI (21%) after a first evaluation. From this perspective, cardiac MRI appears to be the most useful investigation and athletes with TWI in the lateral ECG leads appear to be the ones who harbour a cardiac condition. In addition, cardiac conditions are identified in more than twice the number of white athletes with TWI compared to black athletes with TWI (30% versus 12%). Conversely, the results of genetic testing are only positive in 10% of athletes yet triple the cost of evaluation: routine clinical testing alone cost $1,084 per athlete evaluated, but the addition of genetic testing put this cost up to $3,267 per athlete. Furthermore, genetic testing contributed to addition diagnoses beyond routine clinical testing in only 2.5% of athletes with T-wave inversion despite the substantial cost, and caused diagnostic uncertainty in a minority of athletes.

The results from our study provide the answer to a long awaited question: whether genetic testing can help in the evaluation of athletes with TWI. Our study shows that such a strategy in not useful in day-to-day clinical practice and that routine clinical investigation alone (particularly cardiac MRI) outperforms genetic testing in determining the cause of TWI in athletes. Our study also shows that TWI is associated with cardiac disease in 20% of athletes.