Human in silico clinical trials in post myocardial infarction: mechanistic investigations into phenotypic electromechanical variability and response to treatment

Patients surviving a myocardial infarction (MI) suffer from a damaged heart and are at risk of sudden death and impaired cardiac pumping action. Risk stratification for sudden death is primarily based on ventricular pumping efficiency. However, a significant number of sudden deaths occur in patients with relatively preserved ejection fraction, and patients with low ejection fraction often do not experience serious arrhythmic events. 

I will investigate mechanisms explaining the links between arrhythmic risk and mechanical dysfunction in patients who have had an MI and how they are modulated by pharmacological treatments. We will construct computer models of populations of human ventricles to simulate their electrophysiological and mechanical function, considering variability in ionic, cellular and tissue properties. We will calibrate and validate them using rich experimental and clinical datasets. 

Our findings will inform the identification of more effective methods for risk stratification and improve treatment of patients at risk of sudden death after an MI.