Sudden cardiac death in young athletes, although rare, has a major emotional and societal impact. In some cases, dangerous heart rhythm problems occur during intense training in people who otherwise appear healthy. One condition that may contribute to this risk is exercise-induced Long QT Syndrome (exiLQTS). Long QT Syndrome (LQTS) is a disorder of the heart’s electrical system in which the QT interval on the electrocardiogram is prolonged, increasing the risk of life-threatening arrhythmias. In most cases, LQTS is genetically mediated and the QT prolongation is persistent. In exercise-induced LQTS, however, the abnormal electrical pattern appears only during intense training and reverses with detraining. The mechanisms behind this phenomenon were largely unknown, creating uncertainty in clinical decision-making and risk assessment.
The PREPARE project aimed to uncover why some athletes develop exercise-induced QT prolongation and what are the potential targets for the future therapies. The project focused on the molecular and cellular mechanisms underlying cardiac function. To achieve this, PREPARE used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), a technology that allows to generate cardiomyocytes in the laboratory from individual athletes. This approach makes it possible to study athlete-specific cardiac cells under controlled “exercise-like” conditions in vitro.
The project combined multiple levels of analysis, including clinical data, advanced genetic testing, functional measurements of hiPSC-CMs electrophysiology and large-scale transcriptomic (gene expression) analysis.
By integrating these data, PREPARE generated new mechanistic insights into how exercise can trigger reversible electrical abnormalities. Although these discoveries are not immediately translated into clinical treatments, they provide a strong scientific foundation for improved risk stratification, future therapeutic development, and personalized approaches in cardiology.
