Long QT syndrome

Long QT syndrome (LQTS) is a congenital or acquired heart condition in which the QT interval (i.e., ventricular depolarization and repolarization) is prolonged. Most patients with LQTS are asymptomatic, but some present with seizures, syncope, or even life-threatening arrhythmias and sudden death. Treatment depends on the underlying cause: Beta blockers and implantable cardioverter defibrillator (ICD) insertion are commonly used for congenital LQTS, whereas treatment of the underlying cause (drug, electrolyte abnormality, etc.) is the first-line therapy for acquired LQTS.

A prolonged QT interval may be congenital or acquired.

Congenital LQTS

• Congenital LQTS arises from mutations in genes that code for ion channels within myocytes
• These mutations all cause ventricular action potentials to be prolonged, resulting in a lengthened QT interval on ECG. ^[1]
• LQTS type 1
  • Most common type of congenital LQTS
  • Defect: loss of function mutation on the KCNQ1 gene located on chromosome 11p → defective slow delayed rectifier voltage-gated potassium channel
  • Subtypes
    • Jervell and Lange-Nielsen syndrome ^[2]
      • Associated with congenital deafness
      • Autosomal recessive
      • Associated with ventricular tachyarrhythmias
    • Romano-Ward syndrome ^[3]
      • No associated deafness
      • Autosomal dominant
      • Associated with ventricular tachyarrhythmias

Acquired LQTS

• Drugs: Usually substances that block potassium outflow during the rapid repolarization phase ^[4]
  • Antiarrhythmics: especially class IA and class III antiarrhythmics
    • Compared to other class III antiarrhythmics, amiodarone rarely causes torsades de pointes.
  • Psychiatric medications: especially tricyclic antidepressants and haloperidol
  • Antibiotics (e.g., macrolides, fluoroquinolones)
  • Antihistamines (e.g., diphenhydramine)
  • Antimalarial medications
  • Antiparkinson medications
  • Opioids
• Electrolyte imbalances (e.g., hypokalemia, hypomagnesemia, hypocalcemia)
• Endocrine disorders (e.g., hypothyroidism)
• Nutritional deficiencies (e.g., anorexia nervosa)
• Ischemic stroke or intracranial hemorrhage

References:^{[5][6][7][8][9][10][11]}

• Often asymptomatic, especially if the QT interval is only minutely prolonged
• Some patients present with:
  • Palpitations
  • Dizziness
  • Syncope
  • Cardiac arrest

References:^[5]

• Diagnosis of LQTS can be difficult because a slightly prolonged QT interval can be a normal variant (i.e., not congenital LQTS), and some patients with LQTS do not have a prolonged QT interval.
• The primary finding in LQTS is a long QT interval corrected for heart rate (QTc) interval.
  • Males: > 440 ms
  • Females: > 460 ms
• Other diagnostic criteria take patient history and ECG findings into account.

	Finding	Score
History	Congenital deafness	0.5
	Family history of LQTS	1
	Family history of sudden cardiac death	0.5
	Syncope	1 (without stress) or 2 (with stress)
ECG	460–469 ms	2
	450– 459 ms	1
	Torsade de pointes	2
	T-wave alternans	1
	Notched T wave in 3 leads	1
	Bradycardia	0.5

• Genetic testing confirms the diagnosis of LQTS.

References:^[6][12]

• Both congenital and acquired LQTS
  • Avoid activities that stress the heart
  • Avoid cold temperatures (e.g., swimming, diving, skiing)
• Congenital LQTS
  • First line: beta blockers (e.g., propranolol)
  • Left cardiac sympathetic denervation (stellectomy): patients not responsive to beta blockers
  • High-risk patients (recurrent syncope despite medical therapy, survival of cardiac arrest): implantable cardioverter defibrillator (ICD)
• Acquired LQTS: treat cause; (remove offending drug, fix electrolyte imbalances, etc.)

All treatment modalities aim to reduce the risk and severity of cardiac events!

References:^[6]

• Ventricular tachycardia (torsade de pointes)
• Ventricular fibrillation
• Asystole
• Sudden cardiac death

References:^[13]

We list the most important complications. The selection is not exhaustive.