What causes prolonged QTc (QT interval corrected) interval?

From the Guidelines

Prolonged QTc interval can cause life-threatening cardiac arrhythmias, particularly Torsades de Pointes (TdP), which may progress to ventricular fibrillation and sudden cardiac death, and its management involves identifying and correcting underlying causes, discontinuing offending medications, normalizing electrolytes, and in some cases, using beta-blockers or implanting cardiac defibrillators for high-risk patients, as recommended by the 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1.

Causes of Prolonged QTc Interval

• Medications (such as certain antipsychotics, antibiotics like macrolides and fluoroquinolones, antiarrhythmics, and antihistamines)
• Electrolyte abnormalities (especially hypokalemia, hypomagnesemia, and hypocalcemia)
• Structural heart disease
• Genetic disorders like Long QT Syndrome
• Endocrine disorders

Management of Prolonged QTc Interval

• Identifying and correcting underlying causes
• Discontinuing offending medications
• Normalizing electrolytes
• Using beta-blockers or implanting cardiac defibrillators for high-risk patients
• Regular ECG monitoring is essential for those with known QTc prolongation or who are taking medications known to affect the QT interval, as suggested by the 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1.

Important Considerations

• The risk of adverse events increases in patients with long QT syndrome with prolongation of the QTc >500 ms, as stated in the 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1.
• QT-prolonging medications should not be used in patients with long QT syndrome unless there is no suitable alternative, and careful monitoring of the QTc during therapy is recommended, as advised by the 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1.
• Attention to maintaining normal potassium and magnesium balance when medications or situations that promote depletion are encountered is an important component of management, as emphasized by the 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1.

From the FDA Drug Label

In post marketing experience, there were cases reported of QT prolongation in patients who overdosed on quetiapine, in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval. The use of quetiapine should be avoided in combination with other drugs that are known to prolong QTc including Class 1A antiarrythmics (e.g., quinidine, procainamide) or Class III antiarrythmics (e.g., amiodarone, sotalol), antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone) Quetiapine should also be avoided in circumstances that may increase the risk of occurrence of torsade de pointes and/or sudden death including (1) a history of cardiac arrhythmias such as bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval Caution should also be exercised when quetiapine is prescribed in patients with increased risk of QT prolongation (e.g., cardiovascular disease, family history of QT prolongation, the elderly, congestive heart failure, and heart hypertrophy)

Prolonged QTc causes include:

• Overdose on quetiapine
• Concomitant illness
• Medicines known to cause electrolyte imbalance or increase QT interval
• Combination with other drugs that prolong QTc, such as:

• Class 1A antiarrythmics (e.g., quinidine, procainamide)
• Class III antiarrythmics (e.g., amiodarone, sotalol)
• Antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine)
• Antibiotics (e.g., gatifloxacin, moxifloxacin)

• Circumstances that increase the risk of torsade de pointes and/or sudden death, including:

• History of cardiac arrhythmias (e.g., bradycardia)
• Hypokalemia or hypomagnesemia
• Concomitant use of other drugs that prolong the QTc interval
• Presence of congenital prolongation of the QT interval

• Increased risk of QT prolongation due to:

• Cardiovascular disease
• Family history of QT prolongation
• Elderly patients
• Congestive heart failure
• Heart hypertrophy 2

From the Research

Prolonged QTc Interval Causes

Prolonged QTc interval is a significant risk factor for torsades de pointes (TdP), a life-threatening arrhythmia. Several studies have identified various risk factors that contribute to QTc interval prolongation.

• Demographic Factors:
  • Female sex: Women have a longer QTc interval compared to men 3
  • Advancing age: The QTc interval increases with increasing age, but the difference between men and women diminishes 3
• Electrolyte Imbalances:
  • Hypokalemia: A significant risk factor for QTc interval prolongation 4, 3, 5
  • Hypomagnesemia: A risk factor for QTc interval prolongation 4, 5
  • Hypocalcemia: An independent risk factor that significantly prolongs the QTc interval 3
• Medications:
  • QT-prolonging drugs: The use of certain drugs can prolong the QTc interval, including antipsychotic drugs, antiarrhythmic drugs, and diuretics 4, 3, 5, 6, 7
  • Drug-drug interactions: Interactions between medications can increase the risk of QTc interval prolongation 4, 7
• Comorbidities:
  • Heart failure: A risk factor for QTc interval prolongation 4
  • Bradycardia: A risk factor for QTc interval prolongation 4
  • Renal failure: No significant evidence found for an association with QTc interval prolongation 5
  • Diabetes: No significant evidence found for an association with QTc interval prolongation 5