title: A 2015 focus on preventing drug-induced arrhythmias.
abstract: 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.
authors.affiliation: a Department of Medical Physiology, Division Heart & Lungs , University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Bossu
authors.affiliation: a Department of Medical Physiology, Division Heart & Lungs , University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: M A G
authors.initials: MA
authors.lastname: van der Heyden
authors.affiliation: a Department of Medical Physiology, Division Heart & Lungs , University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: T P
authors.initials: TP
authors.lastname: de Boer
authors.affiliation: a Department of Medical Physiology, Division Heart & Lungs , University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Vos
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D003198:Computer Simulation; D004562:Electrocardiography; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008133:Long QT Syndrome / Q000139:chemically induced / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000378:metabolism; D016171:Torsades de Pointes / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D007473:Ion Channels
keywords: Cardiac arrhythmias; animal models; cardiac safety; drugs; electrophysiology