What can cause torsades de pointes?

Causes of Torsades de Pointes

Torsades de pointes (TdP) is most commonly caused by QT-prolonging medications, electrolyte abnormalities, bradycardia, and congenital long QT syndrome, with drug-induced cases accounting for the majority of acquired TdP episodes. 1

Medication-Related Causes

• Class IA antiarrhythmic drugs with high risk (1-10% incidence): quinidine, disopyramide, procainamide 1, 2
• Class III antiarrhythmic drugs with high risk (1-10% incidence): sotalol, dofetilide, ibutilide 1, 3
• Other antiarrhythmic drugs: amiodarone (less frequent risk) 1
• Anti-infective agents: clarithromycin, erythromycin, halofantrine, pentamidine, sparfloxacin 1
• Antiemetics: domperidone, droperidol 1
• Antipsychotics: chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide 1, 4
• Opioid dependence agents: methadone 1
• Other medications: arsenic trioxide, bepridil, cisapride 1

Electrolyte Abnormalities

• Hypokalemia (potassium <4 mEq/L) 1
• Hypomagnesemia (particularly severe) 1, 5
• Hypocalcemia 1

Cardiac Conditions

• Bradycardia (including sinus bradycardia and heart block) 1
• Recent conversion from atrial fibrillation 1
• Congestive heart failure 1, 3
• Left ventricular hypertrophy 1
• Congenital long QT syndrome 1
• Digitalis toxicity 1

Risk Factors and Predisposing Conditions

• Female gender 1
• Advanced age (especially hospitalized elderly patients) 1
• Baseline QT prolongation (QT intervals >500 ms) 1
• Genetic factors: certain DNA polymorphisms even without clinical congenital LQTS 1
• Rapid intravenous drug administration of QT-prolonging medications 1
• High drug concentrations (often due to drug interactions or impaired metabolism) 1
• Renal or hepatic dysfunction affecting drug clearance 2
• Combination of multiple QT-prolonging drugs 1
• Combination of QT-prolonging drug with its metabolic inhibitor 1

ECG Features Predicting Torsades de Pointes

• Marked QTc prolongation >500 ms (with exceptions for amiodarone and verapamil) 1
• Prominent U waves and QT-U prolongation, especially after pauses 1
• Short-long-short R-R cycle pattern before TdP onset 1
• T-wave alternans (macroscopic) 1
• Ventricular ectopy and couplets 1

Clinical Pitfalls and Management Considerations

• Drug combinations can significantly increase risk even when individual drugs pose minimal risk 1

• Hospital settings may increase risk due to concurrent illness, electrolyte disorders, and IV drug administration 1

• Proton pump inhibitors can contribute to TdP risk through induction of hypomagnesemia with prolonged use (>2 weeks) 5

• Immediate management includes:

  • Discontinuation of offending agent(s) 1
  • IV magnesium sulfate 2g (even with normal magnesium levels) 1, 6
  • Correction of electrolyte abnormalities (potassium to 4.5-5 mmol/L) 1
  • Temporary pacing to increase heart rate if TdP recurs despite other measures 1
  • Immediate cardioversion for sustained TdP 1

• Prevention strategies include careful ECG monitoring for QT prolongation in high-risk patients and avoiding combinations of QT-prolonging drugs 1