Electromechanical Presages of Sudden Cardiac Death in the Young: integrating imaging, modelling and genetics for patient stratification

Research focus: In the young (<40 years), sudden cardiac death (SCD) is often the first manifestation of a genetic cardiac disease causing lethal arrhythmias. Both male gender and physical exercise are known risk factors for SCD in this vulnerable population. Current mechanistic understanding of how gender-related and environmental factors such as exercise interact with a pro-arrhythmic tissue substrate and trigger ventricular arrhythmias or accelerate the evolution of arrhythmic diseases is limited, which makes the identification of those at risk for SCD extremely difficult. The EMPATHY project aims to unravel the complex pro-arrhythmic electro-mechanical interactions in the apparently healthy yet vulnerable hosts of genetic cardiac diseases by combining three different but highly complementary scientific fields, being clinical cardiac imaging (OSLO), genetics and cellular electrophysiology (MILAN), and multi-scale computational modelling (MAASTRICHT). We expect that the integrative EMPATHY approach will reveal novel genetic and electro-mechanical signatures of arrhythmogenic diseases, enabling earlier disease recognition, lifesaving therapy and effective prevention of SCD in the young.

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Sudden cardiac death (SCD) is responsible for half of the deaths related to heart disease. In the young (<40 years), SCD is often the first manifestation of a genetic cardiac disease causing lethal arrhythmias. Both male gender and physical exercise are known risk factors for SCD in this vulnerable population. Current mechanistic understanding of how exercise- and gender-related factors facilitate the occurrence of ventricular arrhythmias is limited, which makes the identification of those at risk for SCD extremely difficult. The EMPATHY project aims to unravel the complex pro-arrhythmic electro-mechanical interactions in the apparently healthy yet vulnerable hosts of genetic cardiac diseases by combining three different but highly complementary scientific fields, being clinical cardiac imaging (OSLO), genetics and cellular electrophysiology (MILAN), and multi-scale computational modelling (MAASTRICHT). Data will be obtained from aetiologically different populations, including cardiomyopathy and channelopathy patients as well as athletes with exercise-induced QT prolongation, all having the influence of exercise on disease occurrence/progression and a male predominance for phenotypic manifestations in common. These data will be used to create virtual patient models for well-controlled in silico evaluation of disease-specific proarrhythmic mechanisms related to exercise and gender. We expect that the integrative EMPATHY approach will reveal novel genetic and electro-mechanical signatures of arrhythmogenic diseases, enabling more effective prevention of SCD in the young.