Long QT Syndrome Treatment & Management

  • Author: Ali A Sovari, MD, FACP; Chief Editor: Jeffrey N Rottman, MD   more...
 
Updated: Jan 10, 2012
 

Medical Care

All patients with long QT syndrome (LQTS) should avoid drugs that prolong the QT interval or reduce their serum potassium or magnesium levels. Potassium and magnesium deficiency should be corrected.

Although treating asymptomatic patients is somewhat controversial, a safe approach is to treat all patients with congenital LQTS because sudden cardiac death can be the first manifestation of LQTS.

Beta-blockers are drugs of choice for patients with LQTS. The protective effect of beta-blockers is related to their adrenergic blockade that diminishes the risk of cardiac arrhythmias. They may also reduce the QT interval in some patients.

Although for years the recommended dosage of beta-blockers was relatively large (eg, propranolol 3 mg/kg/d, or 210 mg/d in a 70-kg individual), recent data suggest that dosages lower than this have a protective effect similar to that of large dosages.

  • Beta-blockers are effective in preventing cardiac events in approximately 70% of patients, whereas cardiac events continue to occur despite beta-blocker therapy in the remaining 30%. Response to beta blocker therapy may vary depending on the trigger event. A study by Goldenberg et al found that in patients with LQT1, beta blocker therapy is effective when exercise triggers the event but it is ineffective if the event happens during sleep or arousal.[10]
  • Propranolol and nadolol are the beta-blockers most frequently used, though atenolol and metoprolol are also prescribed in patients with LQTS. Different beta-blockers demonstrate similar effectiveness in preventing cardiac events in patients with LQTS.

The implantable cardioverter-defibrillator (ICD) was shown to be highly effective to prevent sudden cardiac death (SCD) in high-risk patients. In a study of 125 patients with LQTS with ICDs, there was 1.3% death in high-risk ICD patients, compared with 16% in non-ICD patients during mean 8-year follow-up (p=0.07).[11] High-risk patients are defined as those with aborted cardiac arrest or recurrent cardiac events (eg, syncope or torsade de pointes) despite conventional therapy (ie, beta-blocker alone) and those with very prolonged QT interval (>500 ms).

  • An alternative is beta-blockade in combination with a pacemaker and/or stellectomy in some patients. Use of an ICD may be considered as primary therapy if the patient has a strong family history of SCD. However, since some studies showed that family history of SCD is not an independent risk factor[12] , some experts do not recommend ICD therapy based on only a family history of SCD[13] . Early ICD therapy should be considered in high-risk patients with Jervell and Lange-Nielsen syndrome, because the efficacy of beta-blockers was found to be more limited in these patients.[14]
  • The usefulness of implanted cardiac pacemakers is based on the premise that pacing eliminates arrhythmogenic bradycardia, decreases heart-rate irregularities (eliminating short-long-short sequences), and decreases repolarization heterogeneity, diminishing the risk of torsade de pointes ventricular tachycardia. Pacemakers are particularly helpful in patients with documented pause-bradycardia–induced torsade de pointes and in patients with LQT3.
  • However, recent data indicate that cardiac events continue to occur in high-risk patients with cardiac pacing. Because newer models of ICDs include a cardiac pacing function, cardiac pacing (without defibrillators) is unlikely to be used in patients with LQTS. Pacing alone may be used in low-risk patients with LQT3.

Left cervicothoracic stellectomy is another antiadrenergic therapeutic measure used in high-risk patients with LQTS, especially in those with recurrent cardiac events despite beta-blocker therapy.

  • Stellectomy decreases the risk of cardiac events in high-risk patients with LQTS, and it is more effective in patients with LQT1 than those with other types of LQTS.
  • Although this technique decreases the risk of cardiac events, it does not eliminate the risk. Therefore, ICD is superior therapy to cervicothoracic stellectomy.
  • Cervicothoracic stellectomy may be indicated in some high-risk patients and in patients who have several ICD discharges while being treated with beta-blockade and an ICD.

The triggering effect of exercise and tachycardia, and therefore the protective effect of beta-blockers, varies depending on the type of LQTS.

  • Exercise and tachycardia trigger LQT1 events. Therefore, patients with LQT1 should avoid strenuous exercise, and beta-blockers are expected to provide excellent help by preventing cardiac events. Syncope and sudden cardiac death during swimming or diving are strongly related to LQT1. Therefore, patients with LQT1 should avoid swimming with no supervision.
  • LQT2 is also exercise induced but to a lesser degree than LQT1.
  • Tachycardia and exercise do not trigger LQT3; events typically happen during sleep. Because tachycardia is not a trigger, the role of beta-blockers in preventing the cardiac events of LQT3 is debated. Mexiletine, a sodium channel blocker, may improve protection in this subgroup of the patients. Some experts suggest the use of a beta-blocker combined with mexiletine in patients with LQT3.

Gene-specific therapy is an area under investigation. For example, since LQT3 is associated with gain of function mutations in Na+ channels, antiarrhythmic agents with Na+ channel blocking properties have been suggested as gene-specific therapy for patients with LQTS3. Nevertheless, this area is complex and requires further investigations and studies. For instance, Ruan and colleagues found that mexiletine, an Na+ channel blocker, can facilitate F1473 mutant protein trafficking resulting in a net effect of further increase in Na current and worsening of QT prolongation in a subset of patients with LQTS3 with this specific mutation.[15]

Trigger-specific risk stratification and therapy has been suggested by some studies. For example, Kim and colleagues showed that certain types of mutations in LQT2 are associated with certain trigger events (exercise triggers vs arousal triggers vs nonarousal/nonexercise triggers) and that patients with exercise trigger events respond to the treatment with beta-blockers.[16]

A summary of guidelines suggested by the American College of Cardiology, the American Heart Association, and the European Society of Cardiology, in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society for management of patients with LQTS include:[17, 18]

  • No participation in competitive sports for patients with the diagnosis established by means of genetic testing only.
  • Beta-blockers should be given to patients who have QTc-interval prolongation (>460 ms in women and >440 ms in men) and is recommended (class IIa) for patients with a normal QTc interval.
  • ICD should be implanted for survivors of cardiac arrest and is recommended (class IIa) for patients with syncope while receiving beta-blockers. ICD therapy can be considered (class IIb) for primary prevention in patients with characteristics that suggest high risk; these include LQT2, LQT3, and QTc interval greater than 500 ms.
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Consultations

A cardiologist and a cardiac electrophysiologist are typically consulted when patients with long QT syndrome (LQTS) are evaluated.

In families of patients with genotypically confirmed LQTS, genetic counseling of patients and family members should be considered.

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Activity

Physical activity, swimming, and stress-related emotions frequently trigger cardiac events in patients with long QT syndrome (LQTS). Therefore, discourage patients from participating in competitive sports. This recommendation is most important for patients with LQT1 or LQT2. See also the Medical Care section.

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Contributor Information and Disclosures
Author

Ali A Sovari, MD, FACP  Clinical and Research Fellow in Cardiovascular Medicine, Section of Cardiology, University of Illinois College of Medicine; Staff Physician and Hospitalist, St John Regional Medical Center, Cogent Healthcare, Inc

Ali A Sovari, MD, FACP is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Heart Association, American Medical Association, American Physiological Society, and Heart Rhythm Society

Disclosure: Nothing to disclose.

Coauthor(s)

Abraham G Kocheril, MD, FACC, FACP, FHRS  Professor of Medicine, University of Illinois College of Medicine

Abraham G Kocheril, MD, FACC, FACP, FHRS is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Heart Association, American Medical Association, Cardiac Electrophysiology Society, Central Society for Clinical Research, Heart Failure Society of America, and Illinois State Medical Society

Disclosure: Nothing to disclose.

Ramin Assadi, MD  Senior Fellow, Department of Cardiology, Loma Linda University School of Medicine

Ramin Assadi, MD is a member of the following medical societies: American College of Cardiology, American College of Physicians, and American Medical Association

Disclosure: Nothing to disclose.

Arnold S Baas, MD, FACC, FACP  Assistant Professor of Medicine, Division of Cardiology, University of California, Los Angeles School of Medicine; Attending Physician, UCLA Santa Monica Hospital and UCLA Westwood Hospital

Arnold S Baas, MD, FACC, FACP is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Federation for Medical Research, and American Society of Echocardiography

Disclosure: Nothing to disclose.

Specialty Editor Board

Justin D Pearlman, MD, ME, PhD, FACC, MA  Chief, Division of Cardiology, Director of Cardiology Consultative Service, Director of Cardiology Clinic Service, Director of Cardiology Non-Invasive Laboratory, Director of Cardiology Quality Program KMC, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School

Justin D Pearlman, MD, ME, PhD, FACC, MA is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Federation for Medical Research, International Society for Magnetic Resonance in Medicine, and Radiological Society of North America

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Brian Olshansky, MD  Professor of Medicine, Department of Internal Medicine, University of Iowa College of Medicine

Brian Olshansky, MD is a member of the following medical societies: American Autonomic Society, American College of Cardiology, American College of Chest Physicians, American College of Physicians, American College of Sports Medicine, American Federation for Clinical Research, American Heart Association, Cardiac Electrophysiology Society, Heart Rhythm Society, and New York Academy of Sciences

Disclosure: Guidant/Boston Scientific Honoraria Speaking and teaching; Medtronic Honoraria Speaking and teaching; Guidant/Boston Scientific Consulting fee Consulting; Novartis Honoraria Speaking and teaching; Novartis Consulting fee Consulting

Amer Suleman, MD  Private Practice

Amer Suleman, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Institute of Stress, American Society of Hypertension, Federation of American Societies for Experimental Biology, Royal Society of Medicine, and Society of Cardiac Angiography and Interventions

Disclosure: Nothing to disclose.

Chief Editor

Jeffrey N Rottman, MD  Professor of Medicine and Pharmacology, Vanderbilt University School of Medicine; Chief, Department of Cardiology, Nashville Veterans Affairs Medical Center

Jeffrey N Rottman, MD is a member of the following medical societies: American Heart Association and North American Society of Pacing and Electrophysiology (NASPE)

Disclosure: Nothing to disclose.

References

  1. Vatta M, Ackerman MJ, Ye B, Makielski JC, Ughanze EE, Taylor EW, et al. Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation. Nov 14 2006;114(20):2104-12. [Medline].

  2. Rajab A, Straub V, McCann LJ, Seelow D, Varon R, Barresi R, et al. Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. PLoS Genet. Mar 12 2010;6(3):e1000874. [Medline].

  3. Border WL, Benson DW. Sudden infant death syndrome and long QT syndrome: the zealots versus the naysayers. Heart Rhythm. Feb 2007;4(2):167-9. [Medline].

  4. Medeiros A, Kaku T, Tester DJ, et al. Sodium channel B4 subunit mutation causes congenital long QTsyndrome. Heart Rhythm. 2006;3:S34.

  5. Wu G, Ai T, Kim JJ, et al. Alpha-1-Syntrophin Mutation and the Long QT Syndrome: a disease of sodium channel disruption. Circulation. May 28, 2008;Online, ahead of print.

  6. Buber J, Mathew J, Moss AJ, et al. Risk of Recurrent Cardiac Events After Onset of Menopause in Women With Congenital Long-QT Syndrome Types 1 and 2. Circulation. Jun 21 2011;123(24):2784-91. [Medline].

  7. [Best Evidence] Hinterseer M, Beckmann BM, Thomsen MB, Pfeufer A, Dalla Pozza R, Loeff M, et al. Relation of increased short-term variability of QT interval to congenital long-QT syndrome. Am J Cardiol. May 1 2009;103(9):1244-8. [Medline].

  8. Schwartz PJ, Moss AJ, Vincent GM. Diagnostic criteria for the long QT syndrome: an update. Circulation. 1993;88:782-4. [Medline].

  9. Viskin S, Postema PG, Bhuiyan ZA, Rosso R, Kalman JM, Vohra JK, et al. The Response of the QT Interval to the Brief Tachycardia Provoked by Standing A Bedside Test for Diagnosing Long QT Syndrome. J Am Coll Cardiol. Jan 22 2010;[Medline].

  10. Goldenberg I, Thottathil P, Lopes CM, et al. Trigger-specific ion-channel mechanisms, risk factors, and response to therapy in type 1 long QT syndrome. Heart Rhythm. Jan 2012;9(1):49-56. [Medline].

  11. Zareba W, Moss AJ, Daubert JP, Hall WJ, Robinson JL, Andrews M. Implantable cardioverter defibrillator in high-risk long QT syndrome patients. J Cardiovasc Electrophysiol. Apr 2003;14(4):337-41. [Medline].

  12. Goldenberg I, Moss AJ, Peterson DR, McNitt S, Zareba W, Andrews ML, et al. Risk factors for aborted cardiac arrest and sudden cardiac death in children with the congenital long-QT syndrome. Circulation. Apr 29 2008;117(17):2184-91. [Medline].

  13. Goldenberg I, Moss AJ. Long QT syndrome. J Am Coll Cardiol. Jun 17 2008;51(24):2291-300. [Medline].

  14. Goldenberg I, Moss AJ, Zareba W, McNitt S, Robinson JL, Qi M, et al. Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome. J Cardiovasc Electrophysiol. Nov 2006;17(11):1161-8. [Medline].

  15. Ruan Y, Denegri M, Liu N, Bachetti T, Seregni M, Morotti S, et al. Trafficking Defects and Gating Abnormalities of a Novel SCN5A Mutation Question Gene-Specific Therapy in Long QT Syndrome Type 3. Circ Res. Mar 25 2010;Epub-ahead of print. [Medline].

  16. Kim JA, Lopes CM, Moss AJ, McNitt S, Barsheshet A, Robinson JL, et al. Trigger-specific risk factors and response to therapy in long QT syndrome type 2. Heart Rhythm. Dec 2010;7(12):1797-805. [Medline].

  17. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. Sep 5 2006;114(10):e385-484. [Medline].

  18. Roden DM. Long QT Syndrome. N Engl J Med. Jan 2008;358(2):169-76. [Medline].

  19. Ackerman MJ. Genotype-phenotype relationships in congenital long QT syndrome. J Electrocardiol. Oct 2005;38(4 Suppl):64-8. [Medline].

  20. Ali RH, Zareba W, Moss AJ, et al. Clinical and genetic variables associated with acute arousal and nonarousal-related cardiac events among subjects with long QT syndrome. Am J Cardiol. Feb 15 2000;85(4):457-61. [Medline].

  21. Antzelevitch C. Arrhythmogenic mechanisms of QT prolonging drugs: is QT prolongation really the problem?. J Electrocardiol. 2004;37 Suppl:15-24. [Medline].

  22. Antzelevitch C, Oliva A. Amplification of spatial dispersion of repolarization underlies sudden cardiac death associated with catecholaminergic polymorphic VT, long QT, short QT and Brugada syndromes. J Intern Med. Jan 2006;259(1):48-58. [Medline].

  23. Chiang CE, Roden DM. The long QT syndromes: genetic basis and clinical implications. J Am Coll Cardiol. Jul 2000;36(1):1-12. [Medline].

  24. Ching CK, Tan EC. Congenital long QT syndromes: clinical features, molecular genetics and genetic testing. Expert Rev Mol Diagn. May 2006;6(3):365-74. [Medline].

  25. Gowda RM, Khan IA, Wilbur SL, Vasavada BC, Sacchi TJ. Torsade de pointes: the clinical considerations. Int J Cardiol. Jul 2004;96(1):1-6. [Medline].

  26. Kao LW, Furbee RB. Drug-induced q-T prolongation. Med Clin North Am. Nov 2005;89(6):1125-44, x. [Medline].

  27. Lankipalli RS, Zhu T, Guo D, Yan GX. Mechanisms underlying arrhythmogenesis in long QT syndrome. J Electrocardiol. Oct 2005;38(4 Suppl):69-73. [Medline].

  28. Modell SM, Lehmann MH. The long QT syndrome family of cardiac ion channelopathies: a HuGE review. Genet Med. Mar 2006;8(3):143-55. [Medline].

  29. Moss AJ, Robinson J. Clinical features of the idiopathic long QT syndrome. Circulation. Jan 1992;85(1 Suppl):I140-4. [Medline].

  30. Moss AJ, Schwartz PJ, Crampton RS, et al. The long QT syndrome. Prospective longitudinal study of 328 families. Circulation. Sep 1991;84(3):1136-44. [Medline].

  31. Moss AJ, Zareba W, Benhorin J, et al. ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. Circulation. Nov 15 1995;92(10):2929-34. [Medline].

  32. Moss AJ, Zareba W, Hall WJ, et al. Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation. Feb 15 2000;101(6):616-23. [Medline].

  33. Napolitano C, Bloise R, Priori SG. Long QT syndrome and short QT syndrome: how to make correct diagnosis and what about eligibility for sports activity. J Cardiovasc Med (Hagerstown). Apr 2006;7(4):250-6. [Medline].

  34. Rashba EJ, Zareba W, Moss AJ, et al. Influence of pregnancy on the risk for cardiac events in patients with hereditary long QT syndrome. LQTS Investigators. Circulation. Feb 10 1998;97(5):451-6. [Medline].

  35. Roden DM. Acquired long QT syndromes and the risk of proarrhythmia. J Cardiovasc Electrophysiol. Aug 2000;11(8):938-40. [Medline].

  36. Roden DM. Long QT syndrome: reduced repolarization reserve and the genetic link. J Intern Med. Jan 2006;259(1):59-69. [Medline].

  37. Schwartz PJ. The congenital long QT syndromes from genotype to phenotype: clinical implications. J Intern Med. Jan 2006;259(1):39-47. [Medline].

  38. Schwartz PJ, Locati EH, Moss AJ, et al. Left cardiac sympathetic denervation in the therapy of congenital long QT syndrome. A worldwide report. Circulation. Aug 1991;84(2):503-11. [Medline].

  39. Schwartz PJ, Priori SG, Spazzolini C, et al. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation. Jan 2 2001;103(1):89-95. [Medline].

  40. Vincent GM, Timothy KW, Leppert M, Keating M. The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome. N Engl J Med. Sep 17 1992;327(12):846-52. [Medline].

  41. Zareba W, Moss AJ, le Cessie S, et al. Risk of cardiac events in family members of patients with long QT syndrome. J Am Coll Cardiol. Dec 1995;26(7):1685-91. [Medline].

  42. Zareba W, Moss AJ, Schwartz PJ, et al. Influence of genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group. N Engl J Med. Oct 1 1998;339(14):960-5. [Medline].

 
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Marked prolongation of QT interval in a 15-year-old male adolescent with long QT syndrome (LQTS) (R-R = 1.00 s, QT interval = 0.56 s, QT interval corrected for heart rate [QTc] = 0.56 s). Abnormal morphology of repolarization can be observed in almost every lead (ie, peaked T waves, bowing ST segment). Bradycardia is a common feature in patients with LQTS.
Genetically confirmed long QT syndrome (LQTS) with borderline values of QT corrected for heart rate (QTc) duration (R-R = 0.68 s, QT interval = 0.36 s, QT interval corrected for heart rate [QTc] = 0.44 s) in a 12-year-old girl. Note the abnormal morphology of the T wave (notches) in leads V2-V4.
ECG of a 13-year-old female who had a syncopal event while running to a school bus. She awoke after a few seconds, and her subsequent clinical course was uneventful.
Table 1. Genetic Background of Inherited Forms of LQTS (Romano-Ward syndrome: LQT1-6, Anderson syndrome: LQT7, Timothy syndrome: LQT8, and Jervell and Lang-Nielsen syndrome: JLN1-2)
Type of LQTSChromosomal LocusMutated GeneIon Current Affected
LQT111p15.5KVLQT1 or KCNQ1 (heterozygotes)Potassium (IKs)
LQT27q35-36HERG, KCNH2Potassium (IKr)
LQT33p21-24SCN5ASodium (INa)
LQT44q25-27ANK2, ANKBSodium, potassium and calcium
LQT521q22.1-22.2KCNE1 (heterozygotes)Potassium (IKs)
LQT621q22.1-22.2MiRP1, KNCE2Potassium (IKr)
LQT7 (Anderson syndrome)17q23.1-q24.2KCNJ2Potassium (IK1)
LQT8 (Timothy syndrome)12q13.3CACNA1CCalcium (ICa-Lalpha)
LQT93p25.3CAV3Sodium (INa)
LQT1011q23.3SCN4BSodium (INa)
LQT117q21-q22AKAP9Potassium (IKs)
LQT12SNTAISodium (INa)
JLN111p15.5KVLQT1 or KCNQ1 (homozygotes)Potassium (IKs)
JLN221q22.1-22.2KCNE1 (homozygotes)Potassium (IKs)
Table 2. Diagnostic Criteria for LQTS
CriterionPoints
ECG findings *
QTc, ms†>4803
460-4692
450-459 in male patient1
Torsade de pointes‡2
T-wave alternans1
Notched T wave in 3 leads1
Low heart rate for age§0.5
Clinical history
Syncope║With stress2
Without stress1
Congenital deafness0.5
Family history
A. Family members with definite LQTS#1
B. Unexplained sudden cardiac death < 30 y in an immediate family member0.5
*In the absence of medications or disorders known to affect these electrocardiographic features.



†QTc calculated by Bazett's formula



‡Mutually exclusive



§Resting heart rate below the second percentile for the age.



||Mutually exclusive



¶The same family member cannot be counted in A and B.



#Definite LQTS is defined by an LQTS score of more than 3 (≥ 4).



Table 3. Definition of QTc Based on Age- and Sex-Specific Criteria
GroupProlonged QTc, sBorderline QTc, sReference Range, s
Children and adolescents (< 15 y)>0.460.44-0.46< 0.44
Men>0.450.43-0.45< 0.43
Women>0.460.45-0.46< 0.45
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