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

From the Guidelines

Prolonged QTc interval can be caused by various factors including medications, electrolyte abnormalities, and underlying cardiac conditions, with the most critical factor being the use of QT-prolonging medications, as stated in the 2018 AHA/ACC/HRS guideline 1. The causes of prolonged QTc interval can be categorized into several groups, including:

• Medications: antiarrhythmics (amiodarone, sotalol, procainamide), certain antibiotics (macrolides like azithromycin, fluoroquinolones like ciprofloxacin), antipsychotics (haloperidol, quetiapine), and antidepressants (citalopram, escitalopram) 1
• Electrolyte abnormalities: hypokalemia, hypomagnesemia, and hypocalcemia, which can significantly increase the risk of QT prolongation 1
• Underlying cardiac conditions: congenital long QT syndrome, heart failure, and bradycardia can also cause QT prolongation 1 Other contributing factors include:
• Hypothyroidism
• Hypothermia
• Advanced age
• Female gender
• Liver or kidney disease The mechanism typically involves delayed repolarization of cardiac myocytes due to alterations in ion channel function, particularly potassium channels, as described in the 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1. When managing patients with prolonged QTc, it's essential to correct electrolyte abnormalities, review and potentially modify medications, and address underlying conditions to reduce the risk of dangerous cardiac events, as recommended in the 2018 AHA/ACC/HRS guideline 1. Key recommendations for managing patients with prolonged QTc include:
• Avoidance of QT-prolonging drugs 1
• Correction of electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia) 1
• Beta-blockers are recommended in patients with a clinical diagnosis of LQTS 1
• ICD implantation with the use of beta-blockers is recommended in LQTS patients with previous cardiac arrest 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)] . 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). Erythromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving erythromycin. Fatalities have been reported Erythromycin should be avoided in patients with known prolongation of the QT interval, patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents

Causes of prolonged QTc include:

• Overdose on quetiapine 2
• Concomitant illness 2
• Medicines known to cause electrolyte imbalance or increase QT interval 2
• Class 1A antiarrythmics (e.g., quinidine, procainamide) 2
• Class III antiarrythmics (e.g., amiodarone, sotalol) 2
• Antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine) 2
• Antibiotics (e.g., gatifloxacin, moxifloxacin) 2
• Erythromycin 3
• History of cardiac arrhythmias such as bradycardia 2
• Hypokalemia or hypomagnesemia 2
• Concomitant use of other drugs that prolong the QTc interval 2
• Presence of congenital prolongation of the QT interval 2
• Cardiovascular disease 2
• Family history of QT prolongation 2
• The elderly 2
• Congestive heart failure 2
• Heart hypertrophy 2

From the Research

Causes of Prolonged QTc

The causes of prolonged QTc can be attributed to various factors, including:

• Patient-related risk factors, such as female sex, age >65 years, and uncorrected electrolyte disturbances 4
• Certain medications, including antipsychotics like risperidone and quetiapine, which can induce QTc interval prolongation 5, 6, 7
• Co-prescribed medicines that can increase the risk of QTc prolongation 4, 6
• Comorbidities, such as heart disease, hypokalemia, and bradycardia 5, 8
• Electrolyte imbalances, including hypokalemia and hypomagnesemia 5, 8

Medication-Related Risk Factors

Medications can play a significant role in QTc prolongation, with certain drugs being more likely to cause this condition than others. For example:

• Risperidone has been associated with QTc interval prolongation, particularly in adult women and older adults 5, 7
• Quetiapine has also been linked to QTc prolongation, especially in critically ill patients receiving concomitant medications known to prolong the QTc interval 6
• Other medications, such as diuretics, antiarrhythmic drugs, and QTc-prolonging drugs, can also increase the risk of QTc prolongation 4, 8

Demographic and Clinical Risk Factors

Certain demographic and clinical factors can also contribute to the risk of QTc prolongation, including:

• Female sex, which has been identified as a risk factor for QTc prolongation 4, 5
• Older age, particularly >65 years, which can increase the risk of QTc prolongation 4, 5
• Uncorrected electrolyte disturbances, such as hypokalemia, which can contribute to QTc prolongation 4, 5
• Heart disease, which can increase the risk of QTc prolongation and Torsades de Pointes 5, 8