- Non cardiac drugs can unintentionally interfere with cardiac electrophysiology and pose risks of arrhythmogenicity. This cardiac toxicity is a major concern for pharmaceutical industry, regulatory agencies and society, having a huge socio-economic impact
- Identification of cardiotoxic compounds as early as possible in the drug research and development process is mandatory
- As attested by the high attrition rate, prediction of drug-induced pro-arrhythmic risk using solely experiments is challenging both preclinically and clinically due to the complexity of the mechanisms of drug-induced pro-arrhythmia and the existence of significant animal species differences in drug-induced effects on cardiac electrophysiology
- Computational modeling and simulation has significantly contributed to the understanding of cardiac electrophysiology and arrhythmias over the last 40 years.
- In order to estimate proarrhythmia score of a preclinical compound, the recent CiPA initiative (Comprehensive in vitro proarrhythmia assay, led by FDA, HESI and SPS) is based on in silico cellular simulation of multiscale effects of compounds on cardiac ionic currents allowing the detection of cardiac action potential abnormalities