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long QT syndrome

Etiology: - some are inherited - most are acquired - risk factors - hypokalemia, hypomagnesemia - structural heart disease - medications - macrolides & fluoroquinolones (especially moxifloxacin) - antipsychotics & antidepressants - antifungals - class Ia antiarrhythmics & class III antiarrhythmics - methadone - donepezil Epidemiology: 1) uncommon 2) more common in women than in men Pathology: - disorder of myocardial repolarization Genetics: long QT syndrome genotyping* - LTQ1: associated with mutation in KvLQ1 gene - pathogenic variant of the C-terminus [5] - LTQ2: associated with mutation in HERG gene [5] - LTQ3: associated with mutation in SCN5A gene - LTQ4: associated with mutation in ANK2 gene - LTQ5: associated with mutation in KCNE1 gene - LTQ6: associated with mutation in KCNE2 gene - LTQ7: associated with mutation in KCNJ2 gene - aLQTS: (acquired) defects in ALG10B may reduce susceptibility * referral for electrophysiological testing takes preference to genotyping [2] Clinical manifestations: 1) occurrence of symptoms in otherwise young healthy patients a) syncope - often follows stressful situation b) seizures c) sudden death 2) congenital deafness 3) family members with long QT syndrome or history of sudden death at a young age Special laboratory: 1) electrocardiogram: (scoring system for diagnosis) a) parameters - degree of QT prolongation (QTc > 530 msec)* - torsades de pointes - T-wave alternans - notched T-waves in 3 leads - low heart rate relative to age b) possible scores: 0-9 - < 2 low probability - 2-3 intermediate probability - > 3 high probability 2) electrophysiological testing (referral) [2] * QTc > 460 msec, > 500 msec [2] Complications: 1) increased risk of torsades de pointes* 2) increased risk of sudden cardiac death* * risk increased with physical or emotional stress Management: 1) beta-blockers [2,3,6] a) symptomatic without history of syncope b) non-selective beta-blockers generally recommended 1] propranolol 2] nadolol c) selective beta-1 antagonists may be equally effective 1] atenolol 2] metoprolol d) titrate to significantly blunt heart rate response during exercise e) amiodarone is contraindicated as it may further increase the QTc interval 2) cardioverter-defibrillator implantation - survivors of cardiac arrest - recurrent syncope while taking beta-blocker - QTc interval > 500 msec 3) surgical antiadrenergic therapy 3) exercise restriction [2]

Interactions

disease interactions

Related

QT interval QT prolongation short QT syndrome

Specific

long QT syndrome type 1 (LQT1, Romano-Ward syndrome) long QT syndrome type 2 long QT syndrome type 3 long QT syndrome type 4 (sick sinus syndrome with bradycardia) long QT syndrome type 5 long QT syndrome type 6 long QT syndrome type 7 (Andersen syndrome, Andersen cardiodysrhythmic periodic paralysis, LQT7) long QT syndrome type 9 long QT syndrome type 10 long QT syndrome type 11 (LQT11) long QT syndrome type 14 (LQT14) long QT syndrome type 14 (LQT15)

General

cardiac conduction disorder genetic disease of the heart

Database Correlations

OMIM 152427 MORBIDMAP 152427

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 125
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018, 2023.
  3. Hobbs JB et al, Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long-QT syndrome. JAMA 2006, 296:1249 PMID: 16968849
  4. Goldenberg I, Moss AJ. Long QT syndrome. J Am Coll Cardiol. 2008 Jun 17;51(24):2291-300. PMID: 18549912
  5. Shimizu W, Makimoto H, Yamagata K et al Association of Genetic and Clinical Aspects of Congenital Long QT Syndrome With Life-Threatening Arrhythmias in Japanese Patients. JAMA Cardiol. Published online February 13, 2019 PMID: 30758498 https://jamanetwork.com/journals/jamacardiology/fullarticle/2724694 - Zareba W Sex and Genotype in Long QT Syndrome Risk Stratification. JAMA Cardiol. Published online February 13, 2019 PMID: 30758500 https://jamanetwork.com/journals/jamacardiology/fullarticle/2724693
  6. European Society of Cardiology Ventricular Arrhythmia Clinical Practice Guidelines (ESC, 2022) Medscape. Sept 30, 2022 https://reference.medscape.com/viewarticle/981520 - Zeppenfeld K, Tfelt-Hansen J, de Riva M et al 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. European Heart Journal, Volume 43, Issue 40, 21 October 2022, Pages 3997-4126 PMID: 36017572 https://academic.oup.com/eurheartj/article/43/40/3997/6675633
  7. Roden DM Clinical practice. Long-QT syndrome. N Engl J Med 2008;358:169-76. PMID: 18184962 https://www.nejm.org/doi/pdf/10.1056/NEJMcp0706513
  8. Genedis; Note: congenital long QT syndrome website http://www.tau.ac.il/lifesci/bioinfo/genedis/heart/long_qt.html