Clinical meaning
The QT interval on the ECG represents ventricular depolarization and repolarization — from the beginning of the QRS complex to the end of the T wave. It is corrected for heart rate using Bazett's formula (QTc = QT / √RR interval). Normal QTc is < 440 ms in males and < 460 ms in females. QTc prolongation (> 500 ms is highest risk) predisposes to torsades de pointes (TdP), a polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation and sudden cardiac death. Mechanism: prolonged repolarization creates unequal recovery of excitability across the ventricular myocardium, leading to early afterdepolarizations (EADs) that trigger re-entrant circuits. Drug-induced QT prolongation occurs through blockade of the hERG (IKr) potassium channel, which is responsible for the rapid delayed rectifier potassium current critical for phase 3 repolarization. Major drug categories causing QT prolongation include: antiarrhythmics (sotalol, amiodarone, procainamide, dofetilide), antipsychotics (haloperidol, ziprasidone, thioridazine), antibiotics (fluoroquinolones, macrolides, azole antifungals), antiemetics (ondansetron, droperidol), and methadone. Risk factors for TdP include female sex, hypokalemia, hypomagnesemia, bradycardia, congenital long QT syndrome, structural heart disease, and the combination of multiple QT-prolonging drugs. Management of TdP: IV magnesium sulfate 2g bolus (first-line), temporary overdrive pacing or isoproterenol to increase heart rate and shorten repolarization, and defibrillation if pulseless.