A 2015 focus on preventing drug-induced arrhythmias

Expert Rev Cardiovasc Ther. 2016;14(2):245-53. doi: 10.1586/14779072.2016.1116940. Epub 2015 Nov 26.


Drug-induced Torsade de Pointes arrhythmia is a life-threatening adverse effect feared by pharmaceutical companies. For the last decade, the cardiac safety guidelines have imposed human ether-a-go-go-related gene channel blockade and prolongation of QT interval as surrogates for proarrhythmic risk propensity of a new chemical entity. Suffering from a lack of specificity, this assessment strategy led to a great amount of false positive outcomes. Therefore, this review will discuss new pharmaceutical strategies: the cardiac safety proposal that recently emerged, the Comprehensive in vitro Proarrhythmia Assay, combining in vitro assays that integrate effects on main cardiac ion channels, with computational models of human ventricular action potential as well as assays using human stem cell-derived cardiomyocytes for an improved prediction of drug's proarrhythmic liability, alternative pharmacological perspectives as well as the current treatment of drug-induced long QT syndrome.

Keywords: Cardiac arrhythmias; animal models; cardiac safety; drugs; electrophysiology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / prevention & control*
  • Computer Simulation
  • Electrocardiography
  • Heart Ventricles / physiopathology
  • Humans
  • Ion Channels / metabolism
  • Long QT Syndrome / chemically induced
  • Long QT Syndrome / prevention & control*
  • Myocytes, Cardiac / metabolism
  • Torsades de Pointes / chemically induced
  • Torsades de Pointes / prevention & control*


  • Ion Channels