What are the causes of a prolonged QT interval?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: January 11, 2026View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Causes of Prolonged QT Interval

Prolonged QT interval results from medications (most common and preventable), electrolyte abnormalities, structural heart disease, congenital channelopathies, and bradyarrhythmias, with drug-induced causes being the predominant etiology in clinical practice. 1

Medication-Induced QT Prolongation

Drug-induced QT prolongation represents the most common and preventable cause, requiring systematic evaluation of all medications 1:

Antiarrhythmic Drugs

  • Class IA agents (quinidine, procainamide, disopyramide) require monitoring for QTc prolongation 1
  • Class III agents (sotalol, dofetilide, ibutilide, amiodarone) necessitate monitoring particularly 4-5 hours post-administration 1, 2

Psychiatric Medications

  • Antipsychotics including thioridazine, pimozide, haloperidol, ziprasidone, and chlorpromazine cause QT prolongation 1, 3, 2
  • Quetiapine causes moderate QT prolongation (approximately 6 ms on average), though less than thioridazine 4, 5
  • The FDA label for quetiapine specifically warns to avoid combination with other QT-prolonging drugs and in patients with cardiac arrhythmias, hypokalemia, hypomagnesemia, or congenital QT prolongation 5
  • Antidepressants including venlafaxine and citalopram contribute to QT prolongation, particularly in polypharmacy scenarios 6, 7

Antibiotics

  • Macrolides (clarithromycin) and fluoroquinolones (gatifloxacin, moxifloxacin) cause QT prolongation 1, 2

Other High-Risk Medications

  • Methadone causes significant dose-dependent QT prolongation; baseline and follow-up ECGs are recommended, with additional evaluation if daily dosage exceeds 100 mg 1, 3, 5
  • Chemotherapy agents including arsenic trioxide (26-93% incidence) and vandetanib 1
  • Antiemetics such as ondansetron and domperidone 6, 2

Critical Drug Interaction Considerations

  • CYP3A4 inhibitors (verapamil) combined with QT-prolonging drugs increase risk through metabolic inhibition 1
  • Polypharmacy with multiple QT-prolonging medications creates additive effects that are frequently underrecognized 4, 6, 7

Electrolyte Abnormalities

Electrolyte disturbances represent critical correctable risk factors requiring aggressive correction 1:

  • Hypokalemia is a significant risk factor, particularly in women, and commonly results from diuretic therapy 1, 3
  • Hypomagnesemia contributes to QT prolongation and requires monitoring 1
  • Hypocalcemia potentiates drug-induced QT prolongation 1
  • Diuretic-induced hypokalemia creates compounded risk when combined with underlying cardiac conditions, requiring vigilant electrolyte monitoring 1

Cardiac Structural Disease

Structural heart abnormalities increase baseline QT prolongation risk 1:

  • Left ventricular hypertrophy and heart hypertrophy 1, 5
  • Low left ventricular ejection fraction and heart failure (particularly reduced ejection fraction) 1, 3
  • Myocardial ischemia (both acute and chronic, including previous myocardial infarcts) prolongs QT and predisposes to sudden cardiac death 1
  • Inherited cardiomyopathies (hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy) 1
  • Congenital heart diseases and surgical sequelae 1

Congenital Long QT Syndrome

Hereditary channelopathies create baseline QT prolongation 3:

  • Prevalence of 1 in 2,500-5,000 live births 1, 3
  • KCNQ1 (LQT1) affecting IKs current is the most common mutation 1, 3
  • De novo mutations account for 30% of cases with unaffected parents 1, 3
  • Autoimmune-related cases occur in neonates born to mothers with anti-Ro/SSA antibodies 1, 3
  • Genetically determined ion-channel dysfunction creates baseline prolongation that overlaps considerably with healthy individuals 1

Bradyarrhythmias

Slow heart rates prolong QTc and predispose to torsades de pointes 1:

  • Sinus bradycardia and heart block 1
  • AV nodal blocking agents (adenosine, calcium channel blockers, digoxin, beta-blockers) should be avoided in pre-excited atrial fibrillation as they may paradoxically increase ventricular response 1

Patient-Specific Risk Factors

Individual characteristics modify QT prolongation risk 1:

  • Female sex: Women have inherently longer QT intervals post-puberty 1
  • Older age increases susceptibility to drug-associated QT effects 1
  • Central nervous system abnormalities can produce QT prolongation and T wave inversion 3

Critical Thresholds and Warning Signs

QTc ≥500 ms or increase ≥25% from baseline mandates immediate discontinuation of offending agents and continuous monitoring until washout occurs 1:

  • Enhanced U waves 1
  • T-wave alternans 1
  • Polymorphic ventricular premature beats or couplets 1
  • Nonsustained polymorphic ventricular tachycardia 1
  • Sudden bradycardia or long pauses 1

Common Clinical Pitfalls

  • Failing to recognize additive effects of multiple QT-prolonging medications 4
  • Assuming all psychiatric medications carry equal QT prolongation risk (valproate does NOT prolong QT) 4
  • Neglecting to monitor electrolytes in patients on diuretics receiving QT-prolonging drugs 1
  • Overlooking drug-drug interactions involving CYP3A4 inhibitors 1

References

Guideline

QTc Prolongation Causes and Risk Factors

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

QT Prolongation and Associated Diseases

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

QT Prolongation Risk with Psychiatric Medications

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Multifactorial QT interval prolongation.

Cardiology journal, 2010

Research

Prolonged QT Interval in Patients Receiving Psychotropic Medications.

Journal of the American Psychiatric Nurses Association, 2020

Related Questions

Does Compazine (prochlorperazine) prolong the QT interval?
Is it safe to administer lorazepam (Ativan) to a patient with a prolonged QT interval?
What anxiety medications have a low risk of QT (QT interval) prolongation?
Can ivabradine and amiodarone together prolong the corrected QT interval in an adult patient being treated for heart‑rate control or atrial arrhythmias?
Can a patient with a prolonged QT interval take phentermine (anorexiant)
What are the management strategies for a patient with heart failure, including those with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF)?
What is the best approach to improve lung function in patients with respiratory conditions or recent surgical intervention using incentive spirometry (IS)
What is the best treatment approach for an elderly patient with COVID-19 (Coronavirus Disease 2019)?
What is the best course of management for a non-smoker patient with mild scarring and bronchiectasis in the parasinusal region on the right lobe, normal Pulmonary Function Tests (PFTs), and normal lab work?
What is the most likely diagnosis for a 41-week gestation pregnant woman with severe headaches, bilateral lower-extremity pitting edema, clonus, hypertension (elevated blood pressure), thrombocytopenia (low platelet count), impaired liver function (elevated liver enzymes), and proteinuria (high total urine protein-creatinine ratio)?
Is septoplasty medically necessary for a patient with a long-standing history of difficulty breathing through the nose, obstructive sleep apnea, CPAP (Continuous Positive Airway Pressure) intolerance, deviated nasal septum, nasal turbinate abnormalities, and nasal turbinate hypertrophy, who has not undergone a trial of medical management with intranasal steroids, such as fluticasone (fluticasone), or mechanical treatments like nasal strips or nasal cones?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.