The QT interval and torsade de pointes

The QT interval on the electrocardiogram is the time from the onset of ventricular depolarisation (the Q wave) to completion of repolarisation (the end of the T wave). It is influenced by heart rate, autonomic factors, electrolyte levels, gender and age. A prolonged QT interval indicates an increased risk of developing malignant ventricular tachyarrhythmias, particularly torsade de pointes. QT prolongation may be primary (inherited, familial, congenital, idiopathic) or caused by disease, drugs or toxins. Drugs that have been associated with the development of torsade de pointes include antiarrhythmic, antibacterial and psychotropic agents and antihistamines. Several of these drugs depress myocardial ion channels, particularly the rapidly activating delayed rectifier (repolarising) potassium current (I-Kr). Overdosage of drugs that affect the delayed rectifier (repolarising) potassium currents (I-K), or coadministration of these drugs with another medication that inhibits their metabolism (e.g. an antihistamine such as terfenadine with an antifungal agent such as ketoconazole, which inhibits the cytochrome P450 3A4 hepatic enzyme), can induce torsade de pointes. Torsade de pointes is a potentially life-threatening ventricular tachyarrhythmia and the risks of administering drugs that can induce this condition must be carefully considered.