What causes QT (QT interval) prolongation?

Causes of QT Prolongation

QT interval prolongation is primarily caused by medications, electrolyte abnormalities, cardiac conditions, and genetic factors, with medications being the most frequent cause of acquired QT prolongation. 1

Medication-Related Causes

High-Risk Medications

• Antiarrhythmic agents: Particularly Class IA (quinidine, procainamide, disopyramide) and Class III (sotalol, dofetilide, ibutilide, amiodarone) 2
• Antimicrobials:
  • Macrolides (erythromycin, clarithromycin) 1
  • Fluoroquinolones 1
• Psychiatric medications:
  • Antipsychotics (especially thioridazines) 2
  • Tricyclic antidepressants 3
• Gastrointestinal medications:
  • Prokinetics (cisapride) 2
  • Proton pump inhibitors 4
• Other medications:
  • Antihistamines 3
  • Antifungal agents 3
  • Molecular targeted drugs 4

Multiple QT-prolonging medications have an additive effect, with each additional QT-prolonging drug adding approximately 3-11 ms to the QTc interval 5.

Electrolyte Abnormalities

• Hypokalemia: Very strong evidence for QT prolongation 6
• Hypomagnesemia: Commonly seen in patients with vomiting or diarrhea 2
• Hypocalcemia: Produces distinctive lengthening of the ST segment 2

Cardiac Conditions

• Heart disease: Especially left ventricular hypertrophy, ischemia, or low left ventricular ejection fraction 2
• Bradyarrhythmias: Including complete heart block and sinus pauses 2
• Myocardial infarction 1
• Heart failure 1

Other Medical Conditions

• Central nervous system abnormalities 2, 1
• Thyroid disease: Particularly hypothyroidism 1
• Renal failure 1
• Hepatic failure 1
• Autoimmune diseases: With anti-Ro/SSA antibodies (in neonates) 2, 1

Patient-Specific Risk Factors

• Female sex: Women have QTc intervals approximately 16 ms longer than men 5, 2
• Advanced age: QTc interval increases with age 5, 2
• Genetic predisposition: Congenital Long QT Syndrome (LQTS) 2
• Recent conversion from atrial fibrillation 1

Drug Overdose Considerations

• Opiates: Particularly methadone can cause QT prolongation 2
• Cocaine: Prolongs QT interval for several days after ingestion 2
• Psychotropic drugs: Overdose of tricyclic antidepressants or thioridazines 2

Risk Factors for Progression to Torsades de Pointes

QT prolongation can lead to torsades de pointes, a life-threatening ventricular arrhythmia, particularly when:

• QTc exceeds 500 ms 1
• Sudden bradycardia or long pauses occur 2
• T wave alternans or polymorphic ventricular premature beats develop 2
• Short-long-short cycle length sequences occur 2

Clinical Implications

• Monitor QT interval in the same ECG lead over time 2
• Document QTc before initiating QT-prolonging drugs and at least every 8 hours thereafter 2
• In patients who develop QTc >500 ms, discontinue the offending drug and continue ECG monitoring until QTc decreases 2
• Be particularly vigilant with patients who have multiple risk factors for QT prolongation 7
• Consider alternative medications with similar efficacy but lower risk of QT prolongation when appropriate 1

The combination of multiple QT-prolonging factors significantly increases the risk of torsades de pointes, making it essential to identify and address all modifiable risk factors 7.