Long QT Interval



  • QT interval: the interval from the beginning of the QRS complex to the end of the T wave on the surface electrocardiogram (ECG). This represents the period from the onset of ventricular depolarization to completion of repolarization of the ventricular myocardium, or ventricular systole. The QT interval is normal if it is <50% of the RR interval.
  • Corrected QT interval (QTc): The QT interval has an inverse relationship with heart rate. The QTc is the QT interval corrected for heart rate, and it estimates the QT interval at a heart rate of 60 beats/min. See formulas.
  • Prolonged QTc is generally defined as >450 ms for adult males and >470 ms for adult females:
    • 430 to 450 ms considered borderline in men
    • 450 to 470 ms considered borderline in women (1)
    • 440 to 460 ms considered borderline in children aged 1 to 15 years
  • Most cases of prolonged QT are acquired, but several genetic mutations cause inherited long QT syndrome (LQTS) (1).
  • Prolonged QTc from any cause can precipitate polymorphic ventricular tachycardia (VT) called torsade de pointes (TdP), leading to dizziness, syncope, and sudden cardiac death from ventricular fibrillation (VF).


Often presents in childhood, but may present as early as newborn period or go undiagnosed until middle age. The mean onset age is 14 years.

Incidence of medication-induced QTc prolongation and TdP varies with medication and a host of other factors. Exact incidences are difficult to estimate but may be 1/2,000 to 1/2,500.

Congenital LQTS is estimated to occur in 1/2,500 to 1/7,000 births. The true incidence of mutations in the population is likely much higher.

Etiology and Pathophysiology

  • Acquired
    • Demographics: increasing age, female sex
    • Electrolyte abnormalities: hypokalemia, hypocalcemia, and hypomagnesemia
    • Noncardiac disease: hypothyroidism, renal impairment, and hepatic impairment
    • Cardiac disease: heart failure, LVH, and myocardial ischemia
    • Scenarios: rapid increase in the QT interval >60 ms, conversion from atrial fibrillation/bradycardia
    • Medications (*denotes “high-risk” medication for TdP 25.) (1)
      • Antiarrhythmic medications (quinidine, procainamide, dronedarone, dofetilide, sotalol, disopyramide, and amiodarone)
      • Antipsychotic medications: especially if given IV (haloperidol*, chlorpromazine*, thioridazine*, pimozide*)
      • Antidepressants: most commonly used drugs responsible (SSRIs, SNRIs, trazodone, TCAs)
      • Antibiotics/antivirals/antifungals/antiprotozoals/antimalarials: macrolides (clarithromycin*, erythromycin* also CYP3A4 inhibitors), fluoroquinolones, quinine, and chloroquine
      • Antiemetics: metoclopramide, ondansetron, promethazine
      • Opioids: methadone*, buprenorphine
      • Antihistamines: cetirizine, hydroxyzine, diphenhydramine
      • Decongestants: pseudoephedrine, phenylephrine
      • Stimulants: albuterol, phentermine
      • Misc: chloroquine*, pentamidine*, various antimuscarinics, and anticonvulsants
  • Congenital
    • >13 genes have been identified that encode for subunits of various ion membrane channels
    • Mutations of KCNQ1 (LQTS1), KCNH2 (LQTS2), and SCN5A (LQTS3) genes account for >90% of cases.
    • Loss of function mutations in several potassium ion membrane channels or gain of function mutations in the sodium or calcium ion membrane channels in cardiac myocytes
  • Pathophysiology
    • Depolarization (phase 0) of the myocardium results from the rapid influx of sodium through sodium channels (INa) causing myocyte contraction during systole; seen on ECG as the QRS complex
    • Repolarization occurs through the efflux of potassium from the cell (phases 2 and 3) by rapid (IKr) and slow (IKs) components of the delayed rectifier; represented by the T wave on an ECG
    • Drug-induced QT prolongation most often due to blockade of the IKr channel leading to delay in phase 3 rapid repolarization.
    • In both cases, deviation from normal ion channel function leads to transmural dispersion of repolarization currents across the myocardium, triggering early after depolarizations which may devolve into TdP (1).
    • Prolonged QT interval alone does not denote imminent risk for TdP; TdP is often self-limited, but TdP can cause syncope or degrade to VF.


  • >13 distinct genotypes are linked to LQTS. LQT1 is most common cause of congenital LQTS.
  • Penetrance is highly variable making both diagnosis and management challenging (1).

Risk Factors

For the feared complication, TdP, risk factors include the following:

  • Female (~2 times increased risk), QTc >500 ms (2 to 3 times increased risk), QTc >60 ms over previous baseline (for every 10 ms increase in the QTc, there is a 5–7% increased risk for developing TdP), history of syncope or presyncope, history of TdP, bradycardia, liver or kidney disease (by increasing blood levels of QT-prolonging medications), medications that cause QTc prolongation (high doses, fast infusions, combination of medications), medications that inhibit CYP3A4, electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia)
  • For congenital LQTS
    • Catecholamine surges from exercise, emotional stress, loud noises, postpartum depression.

General Prevention

  • Avoid (or use with caution) causative medications, including combinations with potentially additive effects.
  • Replete electrolytes (goal: Mg >2 mg/dL, K = 4.5 to 5.0 mEq/L).
  • Treat underlying diseases.
  • Avoid strenuous sports and other stimulating activities, like amusement park rides or jumping into cold water, in LQTS.
  • Avoid sudden loud noises in LQTS (alarm clocks, doorbells, telephones).

Commonly Associated Conditions

  • Illnesses with associated severe vomiting and/or diarrhea leading to electrolyte disturbances
  • Eating disorders—anorexia nervosa, bulimia
  • Romano-Ward syndrome
  • Andersen-Tawil syndrome (LQTS type 7)—prolonged QT interval, muscle weakness, facial dysmorphism
  • Timothy syndrome (LQTS type 8)—prolonged QT interval, hand/foot, facial, and neurodevelopment features
  • Jervell and Lange-Nielsen syndrome—associated with profound sensorineural hearing loss

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