PREPARE · PREcision medicine to Prevent ARrhythmic Events in athletes

Regular physical activity is known to be beneficial for health, can prevent cardiovascular disease and reduce overall mortality. However, high intensity exercise can promote the development of arrhythmias and cause sudden cardiac death. Recently the Prof.Peter Schwartz’s group discovered the phenomenon of exercise-induced Long QT Syndrome (exiLQTS). Affected athletes develop significant QT interval prolongation and repolarization abnormalities on the electrocardiogram during training periods and normalisation occurs during detraining. Clinically, these athletes resemble patients with congenital LQTS, who are known to be severely at risk for life-threatening arrhythmias, but no pathogenic genetic variants in main genes responsible for LQTS were found. Data on how exercise could trigger pathogenic QT prolongation and arrhythmias is limited and thus the possibilities to evaluate potential risks and prevent sudden cardiac death in these young athletes are currently absent. This project will use a precision medicine approach to reveal molecular culprits of exiLQTS by:i)demonstrating that the disease could be recapitulated in vitro using athlete-specific induced pluripotent stem cell-derived cardiomyocytes models;ii)creating a statistical model integrating genetic, electrophysiological, and molecular data;iii)discovering major factors responsible for exiLQTS development and identifying molecular targets for risk stratification and therapy.Results of the study will shed the light on mysterious exercise-related QT prolongation and will contribute to better risk assessment and clinical management of arrhythmias in young athletes.