Utility of genetic testing in athletes

Abstract

Athletes are some of the fittest members of our society, yet paradoxically carry an increased risk of sudden cardiac death (SCD). The athlete's underlying risk of SCD in sports may be increased due to a number of underlying structural, arrhythmic and inherited cardiac conditions (ICCs). There are also physiological adaptations, which occur in the cardiovascular system in athletes as a result of high-level athletic activity and may be misinterpreted as pathology. Differentiation of "athlete's heart" from heart disease may be challenging due to the effects of exercise on the electrical and structural cardiac remodeling. Features such as prolongation of the QT interval, left ventricular hypertrophy and cavity dilatation, create significant overlap between physiology and inherited channelopathies and cardiomyopathies. Most inherited cardiac conditions have an underlying genetic basis to disease and genetic testing in an athlete can have diagnostic, prognostic and therapeutic implications, including guiding exercise recommendations. Therefore, genetic testing can be a useful diagnostic tool when used carefully and appropriately by a trained cardio-genetics expert.

Keywords: athlete; athlete's heart; cardiomyopathy; channelopathy; genetics; sudden cardiac death.

Figure 1

Utility of genetic testing in athletes suspected of an underlying inherited cardiac condition (Modified from Gray, Papadakis 2019).18 Red: Not recommended, Orange: May be considered, Green: Should be considered. Key: LQTS‐ Long QT Syndrome, CPVT‐ Catecholaminergic Polymorphic Ventricular Tachycardia, ACM‐ Arrhythmogenic Cardiomyopathy, HCM‐ Hypertrophic Cardiomyopathy, QTc‐ corrected QT interval, PVB‐ premature ventricular beats, VT‐ ventricular tachycardia, LVWT‐ left ventricular wall thickness, SCD‐ sudden cardiac death. ^± Structural heart disease, coronary artery disease and electrolyte abnormalities should be excluded. * Symptoms, documented polymorphic arrhythmias, paradoxical prolongation of the QT interval during exercise, T‐wave alternans, T wave notching, congenital deafness, family history of unexplained SCD.19 ^§ According to the 2010 Task Force criteria, excluding genetic testing result.20 ^# High propensity to ventricular arrhythmias (eg, high burden of PVCs from RVOT or multifocal PVCs on holter), symptoms (eg, syncope), family history of SCD in a first‐degree relative under the age of 40 years, presence of scar on MRI, RV structural changes with borderline ECG abnormalities (eg, T‐wave inversion in anterior chest leads). ~ Symptoms (eg, syncope), family history of SCD in a first‐degree relative under the age of 40 years, ECG abnormalities (particularly inferolateral T‐wave inversion), asymmetric hypertrophy, myocardial scar on cardiac MRI, blunted blood pressure response to exercise

Figure 2

Summary flow diagram outlining the genetic testing process