Etiology
The most common form of congenital LQTS (LQTS type 1) is caused by a defect in the slow delayed rectifier voltage-gated potassium channel.
Acquired LQTS
A prolonged QT interval indicates delayed ventricular de- or repolarization, most commonly caused by drugs (mainly via inhibition of potassium efflux) or electrolyte imbalances.
- Drug-induced LQTS: Usually substances that block potassium outflow during the rapid repolarization phase
- Macrolides & fluoroquinolones
- Antiemetics (eg, ondansetron)
- Azoles (eg, fluconazole)
- Antipsychotics, TCAs & SSRIs
- Some opioids (eg, methadone, oxycodone)
- Class Ia antiarrhythmics (eg, quinidine)
- Class III antiarrhythmics (eg, dofetilide, sotalol)
- Electrolyte imbalances: hypokalemia, hypomagnesemia, hypocalcemia
- Hypokalemia: Inhibits the IKr (rapid delayed rectifier K+) current. Slows Phase 3 (repolarization) by reducing K+ efflux.
- Hypomagnesemia: Directly inhibits K+ channels (like IKr) and promotes renal K+ wasting, often causing concurrent hypokalemia. Slows Phase 3 (repolarization).
- Hypocalcemia: Delays inactivation of L-type Ca2+ channels. Prolongs Phase 2 (plateau) of the action potential.
- Endocrine disorders: hypothyroidism
Complications
- Ventricular tachycardia (torsades de pointes)
- Ventricular fibrillation
- Asystole
- Sudden cardiac death