Description

• The pathophysiology is complex and incompletely understood:
  • Alteration in cardiac sodium, potassium, or calcium ion flow
  • Imbalance in the sympathetic innervation of the heart
• Prolonged ventricular repolarization results in lengthening of QT interval on surface ECG:
  • “Pause-dependent” lengthening due to short–long–short sequence in which a sinus beat is followed by an extrasystole (short), then a postextrasystolic pause (long), concluding with a ventricular extrasystole (short)
  • “Adrenergic-dependent” pauses found in congenital cases
• Symptoms often preceded by vigorous exercise, emotional stress, or loud noise
• Nocturnal bradycardia can lengthen QT interval, causing sleep-related symptoms
• Re-entrant rhythm can lead to torsades de pointes, ventricular tachycardia, and ventricular fibrillation
• Hemodynamic compromise following dysrhythmia leads to syncope or death
• Independent risk factor for sudden cardiac death

Risk Factors

• 20 genes linked to long QT syndrome:
  • Autosomal recessive form associated with deafness (Jervell and Lange–Nielsen syndromes)
  • Autosomal dominant form not associated with deafness (Romano–Ward syndrome)
  • Adrenergic stimulation (fright, exertion, delirium tremens, and loud auditory stimulus) becomes prodysrhythmic in certain genotypes, while sleep-related symptoms are found in others
• 10–15% of carriers have baseline normal QTc
• Specific genetic mutations increase risk of cardiac events
• Death occurs in 1–2% of untreated patients per year
  • Drug-induced QT prolongation may also have a genetic background
  • Congenital form occurs in 1 in 3,000–5,000, with mortality of 6% by age 40 yr

• Diagnosis suspected in the young with syncope, cardiac arrest, or sudden death
• Syncope following emotional stress or exercise suggestive
• Death occurs without preceding symptoms in 10% of pediatric patients

Etiology

• Drugs:
  • Complete list at http://www.crediblemeds.org
  • Class Ia antidysrhythmics – quinidine, procainamide, disopyramide
  • Class III antidysrhythmics – sotalol, ibutilide, amiodarone
  • Antibiotics – erythromycin, pentamidine, chloroquine, trimethoprim–sulfamethoxazole
  • Antifungal agents – ketoconazole, itraconazole
  • Psychotropic drugs – phenothiazines, haloperidol, risperidone, STCAs
  • Cisapride
  • Antihistamines
  • Organophosphates
  • Narcotics – methadone
• Electrolyte abnormalities:
  • Hypokalemia
  • Hypomagnesemia
  • Hypocalcemia
• Cardiac:
  • Bradyarrhythmias
  • Arteriovenous block
  • Mitral valve prolapse
  • Myocarditis
  • Myocardial ischemia
• CNS:
  • Subarachnoid hemorrhage
  • Stroke
  • Raised intracranial pressure
• Congenital (idiopathic)
• Other
  • Protein-sparing fasting
  • Anorexia nervosa
  • Hypothyroidism
  • Hypothermia