From the Guidelines
QT interval prolongation is primarily caused by medications, electrolyte abnormalities, and certain medical conditions, with the most significant risk factors being the use of QT-prolonging medications, hypokalemia, hypomagnesemia, and congenital long QT syndrome. The causes of QT interval prolongation can be categorized into several key areas, including:
- Medications: antiarrhythmics (amiodarone, sotalol, procainamide), certain antibiotics (macrolides like azithromycin, fluoroquinolones like ciprofloxacin), antipsychotics (haloperidol, quetiapine), antidepressants (citalopram, escitalopram), and antiemetics (ondansetron) 1
- Electrolyte abnormalities: hypokalemia (potassium <3.5 mEq/L), hypomagnesemia (magnesium <1.8 mg/dL), and hypocalcemia 1
- Medical conditions: congenital long QT syndrome, structural heart disease, hypothyroidism, and liver or kidney dysfunction 1
- Other factors: female gender, advanced age, bradycardia, and genetic predisposition 1
The mechanism of QT prolongation involves delayed ventricular repolarization due to blockade of potassium channels or enhancement of inward sodium or calcium currents, which extends the action potential duration 1. This prolongation can lead to early afterdepolarizations and trigger potentially fatal arrhythmias like Torsades de Pointes. The risk of adverse events increases in patients with long QT syndrome with prolongation of the QTc >500 ms, and QT-prolonging medications should not be used in patients with long QT syndrome unless there is no suitable alternative 1.
Key risk factors for drug-induced torsades de pointes include female gender, hypokalemia, bradycardia, recent conversion from atrial fibrillation, congestive heart failure, digitalis therapy, high drug concentrations, and baseline QT prolongation 1. Intravenous magnesium can suppress episodes of torsades de pointes without necessarily shortening QT, even when serum magnesium is normal 1. Temporary pacing is highly effective in managing torsades de pointes that is recurrent after potassium repletion and magnesium supplementation 1.
From the FDA Drug Label
Factors contributing to QTC prolongation (especially hypokalemia, hypomagnesemia, and hypocalcemia) should be sought out and (if possible) aggressively corrected Proarrhythmia, primarily torsade de pointes (TdP), has been associated with prolongation by amiodarone HCl injection of the QTc interval to 500 ms or greater. Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation
The causes of QT interval prolongation include:
- Electrolyte imbalances:
- Hypokalemia
- Hypomagnesemia
- Hypocalcemia
- Medications:
From the Research
Causes of QT Interval Prolongation
The QT interval can be prolonged due to various factors, including:
- Congenital long QT syndrome, which is caused by inherited gene mutations in cardiac ion channels 4
- The use of certain medications, such as:
- Antiarrhythmic drugs (e.g. quinidine, sotalol, amiodarone) 5, 6, 7
- Antibiotics (e.g. macrolide and fluoroquinolone antibiotics) 7, 8
- Antihistamines 5
- Antidepressants (e.g. bupropion, duloxetine, fluoxetine, paroxetine) 7, 8
- Antipsychotic drugs 7
- Serotonin agonists of the triptan class 7
- Cisapride 7
- Dolasetron 7
- Electrolyte disorders, such as:
- Other factors, such as:
- Myocarditis 4
- Endocrine and nutritional disorders 4
- Advanced age 8
- Female sex 4, 8
- Acute myocardial infarction 8
- Heart failure with reduced ejection fraction 8
- Bradycardia 8
- Treatment with diuretics 8
- Elevated plasma concentrations of QTc interval-prolonging drugs due to drug interactions 8
- Inadequate dose adjustment of renally eliminated drugs in patients with kidney disease 8
- Rapid intravenous administration 8