The QT interval as it relates to the safety of non-cardiac drugs
1 Main Line Health Heart Center, Lankenau Hospital, 558 Medical Office Building East, 100 Lancaster Avenue, Wynnewood, PA 19096, USA
2 University of London, London, UK
3 St Paul's Cardiac Electrophysiology, London, UK
* Corresponding author. Tel: +1 610 645 3398; fax: +1 610 896 0643. E-mail address: koweypr{at}mlhheart.org
The ability of some non-cardiac drugs to alter cardiac repolarization and thereby increase the likelihood of cardiac arrhythmias, in particular life-threatening torsades de pointes, has led regulatory agencies to request that modifications of the QT interval, manifesting repolarization changes, should be intensively investigated in every drug developed. However, although prolongation of the QT interval is a relatively easily measured marker of repolarization changes, it is widely viewed as a poor surrogate of the arrhythmogenic potential of a drug. Despite intensive and costly investigation, the prediction of pro-arrhythmic risk based on pre-clinical and clinical data therefore remains imperfect. How QT interval relates to the safety of non-cardiac drugs, and how physicians can best integrate pre-clinical and clinical information in assessment of the risk profile of a drug, remain somewhat open questions.
Key Words: QT study • QT/QTc prolongation • Drug safety • Pro-arrhythmia • Torsade de pointes • Delayed repolarization