Computational Cardiac Safety Testing

In recent years, computational cardiac electrophysiology simulations using mathematical models have begun to be used in industrial and regulatory assessment of the proarrhythmic risk of candidate drug compounds. The aim of this chapter is to equip the reader with the background necessary to critically engage with academic journal articles and reports on this topic. We provide an introduction to the basis for these models, discuss how compound action is modeled, and examine the simulated emergent properties that can correlate with proarrhythmic risk. We discuss important principles around uncertainty, how to assess simulation reliability and reproducibility, and therefore how to establish trust in model predictions. We examine applications of simulations to date, particularly in the context of the comprehensive in vitro proarrhythmia Assay (CiPA). The chapter concludes with a discussion of future avenues for research.