Cardiac safety assays

• Drug-induced ‘Torsades de pointes’ arrhythmias are a major adverse effect of many drugs.
• Current proarrhythmia liability assays mainly assess hERG inhibition and QT-interval prolongation.
• We review recent literature highlighting challenges in using established proarrhythmia assays.
• Promising novel assays, including zebrafish, IPSC, and computer modeling are discussed.

Cardiac safety, including the risk of drug-induced ‘torsades de pointes’ (TdP) arrhythmia, is a major concern in the development, approval and prescription of new drugs. Assessment of surrogate markers of TdP-risk, such as QT-interval prolongation or inhibition of the rapid delayed-rectifier K+-current (IKr) encoded by the human ether-a-go-go-related gene (hERG), is therefore required before drug approval. Here, we review some methodologies employed to assess proarrhythmia liability of drugs, discuss the challenges involved in this process, and highlight promising novel cardiac-safety assays.