What are the causes of prolonged QT (QT interval)?

From the Guidelines

Prolonged QT interval can be caused by various factors, including medications, electrolyte abnormalities, and genetic conditions, with the most recent and highest quality study suggesting that medications such as antiarrhythmics, antipsychotics, antibiotics, and antidepressants are common causes of QT prolongation 1.

Causes of Prolonged QT Interval

The causes of prolonged QT interval can be categorized into several groups, including:

• Medications: certain antiarrhythmics (amiodarone, sotalol), antipsychotics (haloperidol, quetiapine), antibiotics (macrolides like azithromycin, fluoroquinolones like ciprofloxacin), and antidepressants (citalopram, escitalopram) are known to cause QT prolongation 1.
• Electrolyte abnormalities: hypokalemia, hypomagnesemia, and hypocalcemia are significant contributors to QT prolongation 1.
• Genetic conditions: Long QT Syndrome (LQTS) represents inherited cardiac channelopathies that affect cardiac repolarization 1.
• Other causes: structural heart disease, hypothyroidism, hypothermia, and severe bradycardia can also contribute to QT prolongation 1.

Management of Prolonged QT Interval

When managing patients with prolonged QT, it's essential to:

• Correct electrolyte abnormalities
• Review and potentially discontinue offending medications
• Monitor the QT interval regularly
• For genetic causes, beta-blockers are often prescribed as first-line therapy 1.

Importance of Prompt Identification and Management

The danger of prolonged QT lies in its association with torsades de pointes, a potentially fatal ventricular arrhythmia, which is why prompt identification and management of the underlying cause is crucial 1.

From the FDA Drug Label

In post marketing experience, there were cases reported of QT prolongation in patients who overdosed on quetiapine [see OVERDOSAGE (10. 1)] , in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval [see DRUG INTERACTIONS (7.1)] Erythromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia

The cause of prolonged QT can be:

• Overdose of certain medications, such as quetiapine 2
• Concomitant illness 2
• Medicines known to cause electrolyte imbalance or increase QT interval, such as erythromycin 3
• Arrhythmia associated with erythromycin 3
• Electrolyte imbalance, such as hypokalemia or hypomagnesemia 2 3
• Concomitant use of other drugs that prolong the QTc interval 2
• Congenital prolongation of the QT interval 2
• Cardiovascular disease 2
• Family history of QT prolongation 2
• The elderly 2 3
• Congestive heart failure 2
• Heart hypertrophy 2

From the Research

Causes of Prolonged QT Interval

• Prolonged QT interval can be caused by various factors, including:
  • Hypokalemia (low potassium levels) 4, 5, 6
  • Hypomagnesemia (low magnesium levels) 4, 5, 6
  • Female sex 4, 5, 6
  • Advancing age 4
  • Genetic predisposition 4, 5, 7
  • Heart failure 4
  • Bradycardia (slow heart rate) 4
  • Use of QT-interval-prolonging drugs, such as antiarrhythmic agents (e.g. quinidine, sotalol, amiodarone) 4, 5, 7, 8
  • Drug-drug interactions 4, 5, 6
  • Electrolyte disturbances 7, 6
  • Myocardium heterogeneity 7
  • Genetic polymorphism 7

Drug-Induced QT Interval Prolongation

• Certain drugs can prolong the QT interval, including:
  • Antiarrhythmic agents (e.g. quinidine, sotalol, amiodarone) 4, 5, 7, 8
  • Quetiapine 6
  • Other cardiovascular drugs 5
• The risk of drug-induced QT interval prolongation can be increased by factors such as:
  • Dosage 8
  • Coexisting medical conditions 8
  • Electrolyte imbalances 8
  • Other risk factors (e.g. age, sex) 8

Mechanisms of QT Interval Prolongation

• The QT interval can be prolonged by factors that delay the repolarization phase 3, including:
  • Blocking of the ion channel cavity of HERG 7
  • Abnormal protein trafficking required for the location of HERG subunits in cell membrane 7
  • Impairment of the I(Kr) current 7
• Other factors can also play a role in QT interval prolongation, including:
  • Myocardium heterogeneity 7
  • Drug-drug interaction 7
  • Genetic polymorphism 7
  • Electrolyte disturbances 7