What can cause a prolonged QT (quantum time) interval?

From the Guidelines

Prolonged QT interval can be caused by various factors, including medications, electrolyte abnormalities, and certain medical conditions, with medications such as antiarrhythmics, antibiotics, antipsychotics, and antidepressants being common culprits, as well as electrolyte disturbances like hypokalemia and hypomagnesemia, and medical conditions like congenital long QT syndrome and structural heart disease. The list of medications that can cause QT prolongation is extensive and includes antiarrhythmics like amiodarone, sotalol, and quinidine 1, as well as certain antibiotics such as macrolides and fluoroquinolones, antipsychotics like haloperidol, and some antidepressants. Electrolyte disturbances, particularly hypokalemia and hypomagnesemia, are significant contributors to QT prolongation, and medical conditions associated with QT prolongation include congenital long QT syndrome, structural heart disease, hypothyroidism, and liver or kidney dysfunction. Other factors that can contribute to QT prolongation include female gender, advanced age, bradycardia, and recent conversion from atrial fibrillation, and it is essential to monitor for QT prolongation as it increases the risk of developing torsades de pointes, a potentially fatal ventricular arrhythmia 1. Key risk factors for drug-induced torsades de pointes are listed in Table 10 of the acc/aha/esc 2006 guidelines and include female gender, hypokalemia, bradycardia, and recent conversion from atrial fibrillation, among others 1. In patients with long QT syndrome, the risk of adverse events increases with QTc prolongation >500 ms, and QT-prolonging medications should be avoided unless there is no suitable alternative, with careful monitoring of the QTc during therapy recommended 1. Maintaining normal potassium and magnesium balance is crucial, especially when medications or situations that promote depletion are encountered, and rare case reports exist of fever prolonging the QT interval in patients with long QT syndrome type 2, highlighting the importance of reducing fever with antipyretics 1. Overall, careful medication review and electrolyte monitoring are essential in high-risk patients to prevent QT prolongation and the associated risk of torsades de pointes. Some of the key medications to avoid in patients at risk of QT prolongation include disopyramide, dofetilide, ibutilide, procainamide, quinidine, sotalol, and ajmaline, as well as certain anti-infectives, antiemetics, antipsychotics, and opioid dependence agents 1. Intravenous magnesium can suppress episodes of torsades de pointes without necessarily shortening QT, even when serum magnesium is normal, and temporary pacing is highly effective in managing torsades de pointes that is recurrent after potassium repletion and magnesium supplementation 1. Given the potential for QT prolongation to lead to life-threatening arrhythmias, it is critical to be aware of the medications and conditions that can contribute to this condition and to take steps to mitigate these risks. The most recent guidelines recommend careful monitoring of the QTc during therapy with QT-prolonging medications and avoiding these medications in patients with long QT syndrome unless there is no suitable alternative 1. By prioritizing the prevention and management of QT prolongation, healthcare providers can help reduce the risk of torsades de pointes and other life-threatening arrhythmias in high-risk patients. In clinical practice, it is essential to consider the potential for QT prolongation when prescribing medications, particularly in patients with underlying heart conditions or electrolyte disturbances, and to monitor these patients closely for signs of QT prolongation. The use of online resources, such as www.torsades.org and www.qtdrugs.org, can provide up-to-date information on medications that can prolong the QT interval and help healthcare providers make informed decisions about medication use in high-risk patients 1. Ultimately, the key to preventing QT prolongation and associated arrhythmias is a combination of careful medication management, electrolyte monitoring, and awareness of the potential risks and benefits of different medications in high-risk patients.

From the FDA Drug Label

Cases of sudden death, QT-prolongation, and Torsades de pointes have been reported in patients receiving haloperidol. Higher than recommended doses of any formulation of haloperidol appear to be associated with a higher risk of QT-prolongation and Torsades de pointes Although cases have been reported even in the absence of predisposing factors, particular caution is advised in treating patients with other QT-prolonging conditions (including electrolyte imbalance [particularly hypokalemia and hypomagnesemia], drugs known to prolong QT, underlying cardiac abnormalities, hypothyroidism, and familial long QT-syndrome)

• Prolonged QT interval can be caused by:
  • Higher than recommended doses of haloperidol
  • Electrolyte imbalance (particularly hypokalemia and hypomagnesemia)
  • Drugs known to prolong QT
  • Underlying cardiac abnormalities
  • Hypothyroidism
  • Familial long QT-syndrome
  • Other QT-prolonging conditions 2

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 or Class III antiarrythmics, antipsychotic medications, antibiotics, or any other class of medications known to prolong the QTc interval.

• Prolonged QT interval can also be caused by:
  • Overdose of 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
    • Class III antiarrythmics
    • Antipsychotic medications
    • Antibiotics
    • Other medications known to prolong QTc 3

From the Research

Causes of Prolonged QT Interval

• Drug-induced QT interval prolongation is a common cause of prolonged QT interval, with various drugs such as antiarrhythmic drugs (e.g. sotalol, quinidine) and non-antiarrhythmic drugs (e.g. certain antihistamines, antimicrobial drugs, psychiatric drugs) implicated in this condition 4, 5, 6.
• Certain medical conditions, such as congenital long QT syndrome, heart disease, hypokalemia, hypomagnesemia, and hypocalcemia, can also contribute to a prolonged QT interval 4, 7, 8.
• Demographic factors, including female sex and advanced age, have been identified as risk factors for QTc interval prolongation 7, 8.
• Other risk factors for QTc interval prolongation include the use of loop diuretics, bradycardia, and treatment with diuretics 7, 8.

Drug-Related Risk Factors

• The coadministration of drugs that inhibit the metabolism of QT-prolonging drugs, such as ketoconazole, itraconazole, and erythromycin, can increase the risk of QT interval prolongation 4.
• Pharmacokinetic drug interactions, such as those involving antifungal agents, macrolide antibiotics, and drugs to treat human immunodeficiency virus, can also increase the risk of TdP 8.
• The use of multiple QT-prolonging drugs can have a cumulative effect on the QTc interval, with patients using two QT-prolonging drugs having a longer QTc interval compared to those using one QT-prolonging drug 7.

Clinical Implications

• Patients with a prolonged QT interval are at increased risk of ventricular arrhythmias, such as torsade de pointes (TdP), and sudden death 4, 5, 6.
• Measurement of the QT interval before and during treatment is recommended in high-risk patients, particularly those with a history of heart disease or those taking QT-prolonging drugs 4.
• Close monitoring and evaluation of patients, particularly those in the intensive care unit, is necessary to prevent and manage QT interval prolongation 6.