Lethal arrhythmias with a QT prolongation account for 21% of total cardiac toxicities141. QT prolongation is an adverse effect related to human Ether-a-go-go Related Gene (hERG) channels. Cardiac safety testing has been mainly dependent on the hERG assay, because blocking the hERG current is considered to be associated with the deadly ventricular arrhythmia named torsades de pointes (or TdP). It has been discovered that 40–60% of drugs that inhibit hERG channel current do not cause QT prolongation142,143. These false positive results from the hERG assay have hindered the development of promising drugs. Preclinical strategies have been proposed to detect drug-induced electrophysiological cardiotoxicity using in vitro human ion channel assays, human-based in silico reconstructions, and human stem cell-derived cardiomyocytes144. Recent efforts have shown that multi-electrode arrays (MEA) assays using human iPSC-derived cardiomyocytes may offer a reliable, cost-effective surrogate for preclinical in vitro testing145 that could be used to assess pro-arrhythmic risk146.
