QT prolongation is an unreliable predictor of ventricular arrhythmia.
Not all drugs that prolong the QT interval are proarrhythmic, and absence of QT prolongation is no guarantee for lack of proarrhythmia. Thus, QT prolongation is an unreliable predictor of ventricular arrhythmia. Development of drugs based on the absence of QT prolongation may stop development of some of the safest agents (with respect to arrhythmias). Conversely, drug-induced shortening of the QT interval may facilitate reentry, which might have lethal consequences in vulnerable patients. If QT prolongation and QT shortening must be avoided, then the pharmaceutical industry faces a mission impossible. Cardiac safety is better evaluated in terms of lambda, TRIaD (Triangulation, Reverse use dependence, Instability, and Dispersion), and disturbances of automaticity.
Hondeghem
Luc M
LM
Department of Pharmacology, Katholieke Universiteit Leuven, Leuven, Belgium. Luc.Hondeghem@screenQT.com
D000200:Action Potentials; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D006352:Heart Ventricles / Q000294:innervation* / Q000473:pathology; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D011379:Prognosis; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D016171:Torsades de Pointes / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*