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 ^[2]
  • Most common type of congenital LQTS
  • Loss of function mutation on the KCNQ1 gene located on chromosome 11p → defective slow delayed rectifier voltage-gated potassium channel → affected repolarization phase ^[3]
  • Subtypes
    • Jervell and Lange-Nielsen syndrome ^[4][5]
      • Associated with congenital deafness
      • Autosomal recessive
      • Associated with ventricular tachyarrhythmias
    • Romano-Ward syndrome ^[6]
      • No associated deafness
      • Autosomal dominant
      • Associated with ventricular tachyarrhythmias

Acquired LQTS ^{[7][8][9][10]}

• Drug-induced LQTS: Usually substances that block potassium outflow during the rapid repolarization phase ^[11]
  • Antiarrhythmics ^[12]
    • Class Ia (e.g., quinidine, disopyramide, procainamide)
    • Class III (e.g., sotalol; uncommonly, amiodarone)
  • Antibiotics (e.g., macrolides, fluoroquinolones)
  • Antihistamines (e.g., diphenhydramine)
  • Antidepressants (most tricyclic antidepressants and tetracyclic antidepressants, some SSRIs, lithium
  • Antipsychotics (e.g., haloperidol, ziprasidone)
  • Anticonvulsants (e.g., fosphenytoin, felbamate)
  • Antiemetics (ondansetron)
  • Antifungals (e.g., azoles)
  • Antiparkinson medications
  • Opioids
• Electrolyte imbalances: hypokalemia, hypomagnesemia, hypocalcemia
• Acute CNS insult: Ischemic stroke or intracranial hemorrhage ^[13][14]
• Endocrine disorders: hypothyroidism
• Nutritional deficiencies: severe vitamin D deficiency (uncommon) ^[15][16]

Compared to other class III antiarrhythmics, amiodarone uncommonly causes torsades de pointes.

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

• 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.

• Genetic testing confirms the diagnosis of LQTS.

• 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.

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

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

1. Herold G. Internal Medicine. Herold G ; 2014
2. Moss AJ, Kass RS. Long QT syndrome: from channels to cardiac arrhythmias. J Clin Invest. 2005; 115 (8): p.2018-2024. doi: 10.1172/jci25537 . | Open in Read by QxMD
3. Jervell and Lange-Nielsen Syndrome.
4. Jervell and Lange-Nielsen syndrome. http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=12056&Disease_Disease_Search_diseaseGroup=jervell&Disease_Disease_Search_diseaseType=Pat&Krankheite(n)/Krankheitsgruppe=Jervell-Lange-Nielsen-Syndrom&title=Jervell-Lange-Nielsen-Syndrom&search=Disease_Search_Simple. Updated: October 1, 2009. Accessed: December 6, 2017.
5. Jervell and Lange-Nielsen Syndrome. https://ghr.nlm.nih.gov/condition/jervell-and-lange-nielsen-syndrome. Updated: November 7, 2017. Accessed: November 13, 2017.
6. Romano-Ward Syndrome. http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=14727&Disease_Disease_Search_diseaseGroup=romano&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Romano-Ward-syndrome&title=Romano-Ward-syndrome&search=Disease_Search_Simple. Updated: October 1, 2009. Accessed: December 6, 2017.
7. Fazio G, Vernuccio F, Grutta G, Re GL. Drugs to be avoided in patients with long QT syndrome: Focus on the anaesthesiological management. World J Cardiol. 2013; 5 (4): p.87-93. doi: 10.4330/wjc.v5.i4.87 . | Open in Read by QxMD
8. van Noord C, Eijgelsheim M, Stricker BH. Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol. 2010; 70 (1): p.16-23. doi: 10.1111/j.1365-2125.2010.03660.x . | Open in Read by QxMD
9. Thomas SHL, Behr ER. Pharmacological treatment of acquired QT prolongation and torsades de pointes. Br J Clin Pharmacol. 2015; 81 (3): p.420-427. doi: 10.1111/bcp.12726 . | Open in Read by QxMD
10. Yap YG, Camm AJ. Drug induced QT prolongation and torsades de pointes. Heart. 2003; 89 (11): p.1363–1372.
11. Berul CI. Acquired Long QT Syndrome: Definitions, Causes, and Pathophysiology. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/acquired-long-qt-syndrome .Last updated: January 3, 2018. Accessed: December 6, 2017.
12. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. J Am Coll Cardiol. 2018; 72 (14): p.e91-e220. doi: 10.1016/j.jacc.2017.10.054 . | Open in Read by QxMD
13. Lele A, Lakireddy V, Gorbachov S, Chaikittisilpa N, Krishnamoorthy V, Vavilala MS. A Narrative Review of Cardiovascular Abnormalities After Spontaneous Intracerebral Hemorrhage. J Neurosurg Anesthesiol. 2019; 31 (2): p.199-211. doi: 10.1097/ANA.0000000000000493 . | Open in Read by QxMD
14. Fure B, Bruun Wyller T, Thommessen B. Electrocardiographic and troponin T changes in acute ischaemic stroke.. J Intern Med. 2006; 259 (6): p.592-7. doi: 10.1111/j.1365-2796.2006.01639.x . | Open in Read by QxMD
15. Halawa A, Dave I, Gautam S. Torsade de Pointes with severe vitamin D deficiency, an unusual presentation of a common problem. Journal of Cardiology Cases. 2019; 20 (4): p.132-134. doi: 10.1016/j.jccase.2019.07.003 . | Open in Read by QxMD
16. Frederiksen TC, Krogh Christiansen M, Charmoth Østergaard P, et al. QTc Interval and Risk of Cardiac Events in Adults With Anorexia Nervosa. Circulation: Arrhythmia and Electrophysiology. 2018; 11 (8). doi: 10.1161/circep.117.005995 . | Open in Read by QxMD