Abstract

Many drugs fail to reach the market due to adverse side effects on the heart, and this translates into important socio-economic costs. A major concern for society, regulatory agencies and industry is that drug-induced alterations in cardiac function can increase the risk of development of potentially life threatening arrhythmias, such as Torsades de Pointes. Given the limitations of in vitro and in vivo testing in preclinical prediction of drug cardiotoxicity, there is increasing interest in in silico methods to supplement experimental methods. This presentation will describe how advanced computational techniques are developed and used in our group to investigate the mechanisms of drug action on cardiac electrophysiological function, from the ionic to the ECG level. Our main aim is to unravel the mechanisms of drug-induced arrhythmic risk in the context of high inter-subject electrophysiological variability, and to propose novel arrhythmic risk biomarkers based on this research.