Key result
The in vitro hERG assay provides sensitive but non-specific prediction of drug-induced arrhythmogenic potential, while the CiPA initiative improves specificity compared to hERG plus TQT studies.
Why the study?
The predictive value of the in vitro hERG assay for anticipating clinical outcomes of drug-related arrhythmogenic potential remains a matter of debate.
This review highlights the evolution of preclinical proarrhythmia risk assessment from the sensitive but non-specific hERG assay to the more specific CiPA initiative incorporating AI and hiPSC-derived cardiomyocytes.
• QT prolongation and torsades de pointes are significant cardiac safety concerns. • The ICH S7B (non-clinical) and E14 (clinical) guidelines identify proarrhythmic risk. • The in vitro hERG assay is a sensitive measurement but it is not specific. • CiPA initiative improved specificity compared with the hERG assay plus TQT study. • AI and hiPSC-derived cardiomyocytes are key for drug testing. A prolonged QT interval is a risk factor for developing torsades de pointes – a potentially fatal drug-related ventricular arrhythmia. The in vitro hERG assay plays a relevant part in this context, presenting predictive value for anticipating the arrhythmogenic potential of new drugs. However, its value for predicting clinical outcomes remains a matter of debate. This review article addresses the several milestones in the field, highlighting the International Council for Harmonization (ICH) S7B and E14 guidelines, and the comprehensive in vitro proarrhythmia assay (CiPA), as well as the current limitations and future challenges.
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Matos et al. (2026) conducted a review in Drug-induced proarrhythmia and QT prolongation. hERG assay and CiPA initiative was evaluated. The in vitro hERG assay provides sensitive but non-specific prediction of drug-induced arrhythmogenic potential, while the CiPA initiative improves specificity compared to hERG plus TQT studies.
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