Qt Syndrome, Prolonged

Basics

Description

A disorder of myocardial repolarization characterized by a prolonged QT interval on the ECG and associated with increased risk of polymorphic ventricular tachycardia (VT)

  • The pathophysiology is complex and varied among acquired and congenital long ST syndrome (LQTS):
    • 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” precipitated by a short RR interval followed by a long RR interval typically caused by a premature ventricular contraction followed by compensatory pause
    • “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
  • Reentrant rhythm can lead to torsades de pointes, VT, and ventricular fibrillation
  • Hemodynamic compromise following dysrhythmia leads to syncope or death
  • Independent risk factor for sudden cardiac death
  • While QTc longer than 500 represents greatest
  • Risk of reentrant rhythms, otherwise poorly understood which asymptomatic patients are at highest risk of dysrhythmia

Risk Factors

Genetics

  • LQTS has 13 subtypes based on genetic mutation types, most common are types 1–3:
    • Type 1: Mutation in KCNQ1, impairs QT shortening in response to tachycardia → arrhythmia, torsades, and SCD
    • Type 2: Mutation in KCNH2 impacts voltage-gated K+ channels, associated with cardiac events postpartum
    • Type 3: Mutation in SCNA5 gene, mutation results in prolonged action potential duration and ECG can mimic Brugada syndrome, at risk for cardiac events while patient is asleep or at rest:
      • 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 (lifetime risk of syncope or sudden cardiac arrest as high as 50% with some mutations):
    • Drug-induced QT prolongation may also have a genetic background
    • Congenital form suspected 1 in 2, with mortality of 6% by age 40 yr

Pediatric Considerations

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

Athletes

  • Physiologic QT prolongation associated with chronic exercise training
  • Differentiation between physiologic and pathologic requires exercise testing or genetic testing

Etiology

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

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