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Pediatric Long QT Syndrome Workup

  • Author: Sreekanth S Raghavan, MBBS, , FACC; Chief Editor: Stuart Berger, MD  more...
 
Updated: Jun 26, 2014
 

Approach Considerations

Laboratory studies in patients with suspected long QT syndrome should rule out dyselectrolytemias, especially those involving potassium, ionized calcium, and magnesium.

Epinephrine QT stress testing is an effective diagnostic tool used to unmask concealed long QT syndrome. Two protocols are followed: the Shimizu protocol and the Mayo protocol. These protocols are especially useful in patients with LQT1. Unique responses have also been observed in patients with LQT2 and LQT3, making this test invaluable in the diagnostic workup of long QT syndrome.[8]

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Electrocardiography

The QT interval in the surface ECG is one of the most often used risk stratifiers in families with congenital long QT syndrome. (See the images below.)

Marked prolongation of QT interval in a 15-year-ol Marked prolongation of QT interval in a 15-year-old male adolescent with long QT syndrome. 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 long QT syndrome. R-R = 1 s; QT interval = 0.56 s; QT interval corrected for heart rate (QTc) = 0.56 s.
Genetically confirmed long QT syndrome with border Genetically confirmed long QT syndrome with borderline values of QT corrected for heart rate (QTc) duration in a 12-year-old girl. Note the abnormal morphology of the T wave (notches) in leads V2-V4. R-R = 0.68 s; QT interval = 0.36 s; QTc = 0.44 s.

QTc is the best diagnostic and prognostic ECG parameter in families with long QT syndrome (see Table 2, below). A single measurement should be obtained in lead II (if measurable) and then in left precordial leads (preferably V5) as a second choice. (A second opinion is recommended when the QTc is borderline.)

In a study by Mönnig et al, the predictive power for identifying carriers in families with long QT syndrome was found to be highest in leads II and V5. The investigators also found that these ECG leads were optimal for risk stratification.[9]

Table 2. Genetic Basis of Long QT Syndrome (Open Table in a new window)

Group Prolonged QTc (s) Borderline QTc (s) Reference Range (s)
Children and adolescents (< 15 y) >0.46 0.44-0.46 < 0.44
Men >0.45 0.43-0.45 < 0.43
Women >0.46 0.45-0.46 < 0.45

All ECGs in family members of a patient with long QT syndrome need to be reviewed, along with detailed histories and physical examinations. An absence of ECG findings that suggest long QT syndrome in family members must not be construed to exclude long QT syndrome in a patient. More recently, magneto-cartography-derived QT interval has been used along with the heart rate to determine long QT syndrome in fetuses.[10, 11]

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Genetic Testing

Genetic testing for known mutations in DNA samples confirms the diagnosis with high specificity but low sensitivity, because only 50% of patients with long QT syndrome have known mutations. The remaining half of patients with long QT syndrome may have mutations of yet unknown genes.

However, this technology is valuable because it can help in predicting the course of the disease in these patients and aid in risk stratification. A study by Moss et al found that in patients with KCNQ1 mutations, the Cox proportional hazards survivorship model indicated an increased risk for cardiac events in patients with transmembrane versus C-terminus mutations (hazard ratio, 2.06), as well as in patients with mutations resulting in dominant-negative versus haploinsufficiency ion channel effects (hazard ratio, 2.26). The investigators found these risks to be independent of traditional clinical risk factors.[12]

Arnestad M et al suggested that 9.5% of the patients with sudden infant death syndrome had relevant LQTS mutations.[13] On the basis of their functional effect, 8 mutations and 7 rare variants were found in 19 of 201 cases; these mutations were likely contributors to sudden death in those patients.

Tester et al sought to determine the spectrum and prevalence of long QT syndrome–associated mutations in a large cohort of autopsy-negative, sudden unexplained death cases.[14] Long QT syndrome–associated mutations (4 novel) were found in 20% of these individuals. Sudden death was the sentinel event in two thirds of the cases. This underscores the importance of postmortem long QT syndrome genetic testing for sudden unexplained death in the pediatric population.

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Contributor Information and Disclosures
Author

Sreekanth S Raghavan, MBBS, , FACC Consulting Pediatric Cardiologist, Head and Director of Pediatric Cardiac Services, Manipal Heart Institute, India

Sreekanth S Raghavan, MBBS, , FACC is a member of the following medical societies: American College of Cardiology, American Society of Echocardiography, Pediatric Cardiac Society of India

Disclosure: Nothing to disclose.

Chief Editor

Stuart Berger, MD Medical Director of The Heart Center, Children's Hospital of Wisconsin; Associate Professor, Department of Pediatrics, Section of Pediatric Cardiology, Medical College of Wisconsin

Stuart Berger, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American College of Chest Physicians, American Heart Association, Society for Cardiovascular Angiography and Interventions

Disclosure: Nothing to disclose.

Acknowledgements

John W Moore, MD, MPH Professor of Clinical Pediatrics, Section of Pediatric Cardiology, Department of Pediatrics, University of California San Diego School of Medicine; Director of Cardiology, Rady Children's Hospital

John W Moore, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, and Society for Cardiac Angiography and Interventions

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References
  1. Taggart NW, Haglund CM, Tester DJ, Ackerman MJ. Diagnostic miscues in congenital long-QT syndrome. Circulation. 2007 May 22. 115(20):2613-20. [Medline].

  2. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome. An update. Circulation. 1993 Aug. 88(2):782-4. [Medline].

  3. Gupta A, Lawrence AT, Krishnan K, Kavinsky CJ, Trohman RG. Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes. Am Heart J. 2007 Jun. 153(6):891-9. [Medline].

  4. Hobbs JB, Peterson DR, Moss AJ, et al. Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long-QT syndrome. JAMA. 2006 Sep 13. 296(10):1249-54. [Medline].

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

  6. Albertella L, Crawford J, Skinner JR. Presentation and outcome of water-related events in children with long QT syndrome. Arch Dis Child. 2011 Aug. 96(8):704-7. [Medline].

  7. Hintsa T, Keltikangas-Jarvinen L, Puttonen S, et al. Depressive symptoms in the congenital long QT syndrome. Ann Med. 2009 Jun 23. 1-6. [Medline].

  8. Vyas H, Ackerman MJ. Epinephrine QT stress testing in congenital long QT syndrome. J Electrocardiol. 2006 Oct. 39(4 Suppl):S107-13. [Medline].

  9. Monnig G, Eckardt L, Wedekind H, et al. Electrocardiographic risk stratification in families with congenital long QT syndrome. Eur Heart J. 2006 Sep. 27(17):2074-80. [Medline].

  10. Cuneo BF, Strasburger JF, Yu S, Horigome H, Hosono T, Kandori A. In utero diagnosis of long QT syndrome by magnetocardiography. Circulation. 2013 Nov 12. 128(20):2183-91. [Medline].

  11. Mitchell JL, Cuneo BF, Etheridge SP, Horigome H, Weng HY, Benson DW. Fetal heart rate predictors of long QT syndrome. Circulation. 2012 Dec 4. 126(23):2688-95. [Medline].

  12. Moss AJ, Shimizu W, Wilde AA, et al. Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation. 2007 May 15. 115(19):2481-9. [Medline].

  13. Arnestad M, Crotti L, Rognum TO, et al. Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation. 2007 Jan 23. 115(3):361-7. [Medline].

  14. Tester DJ, Ackerman MJ. Postmortem long QT syndrome genetic testing for sudden unexplained death in the young. J Am Coll Cardiol. 2007 Jan 16. 49(2):240-6. [Medline].

  15. [Guideline] Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008 May 27. 51(21):e1-62. [Medline]. [Full Text].

  16. Bar-Cohen Y, Silka MJ. Congenital Long QT Syndrome: Diagnosis and Management in Pediatric Patients. Curr Treat Options Cardiovasc Med. 2006 Sep. 8(5):387-395. [Medline].

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  21. Chockalingam P, Crotti L, Girardengo G, Johnson JN, Harris KM, van der Heijden JF. Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol. J Am Coll Cardiol. 2012 Nov 13. 60(20):2092-9. [Medline].

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  24. Hofman N, Wilde AA, Tan HL. Diagnostic criteria for congenital long QT syndrome in the era of molecular genetics: do we need a scoring system?. Eur Heart J. 2007 Jun. 28(11):1399. [Medline].

 
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Marked prolongation of QT interval in a 15-year-old male adolescent with long QT syndrome. 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 long QT syndrome. R-R = 1 s; QT interval = 0.56 s; QT interval corrected for heart rate (QTc) = 0.56 s.
Genetically confirmed long QT syndrome with borderline values of QT corrected for heart rate (QTc) duration in a 12-year-old girl. Note the abnormal morphology of the T wave (notches) in leads V2-V4. R-R = 0.68 s; QT interval = 0.36 s; QTc = 0.44 s.
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 Basis of Long QT Syndrome, Including Jervell and Lang-Nielsen (JLN) Syndrome
Type of Long QT Syndrome Chromosomal Locus Mutated Gene Ion Current Affected
LQT1 11p15.5 KVLQT1or KCNQ1 (heterozygotes) Potassium (IKs)
LQT2 7q35-36 HERG, KCNH2 Potassium (IKr)
LQT3 3p21-24 SCN5A Sodium (INa)
LQT4 4q25-27 ANK2, ANKB Sodium, potassium and calcium
LQT5 21q22.1-22.2 KCNE1 (heterozygotes) Potassium (IKs)
LQT6 21q22.1-22.2 MiRP1, KNCE2 Potassium (IKr)
LQT7 (Andersen syndrome) 17q23 KCNJ2 Potassium (IK1)
LQT8 (Timothy syndrome) 12q13.3 CACNA1C Calcium (ICa-Lalpha)
JLN1 11p15.5 KVLQT1or KCNQ1 (homozygotes) Potassium (IKs)
JLN2 21q22.1-22.2 KCNE1 (homozygotes) Potassium (IKs)
Table 2. Genetic Basis of Long QT Syndrome
Group Prolonged QTc (s) Borderline QTc (s) Reference Range (s)
Children and adolescents (< 15 y) >0.46 0.44-0.46 < 0.44
Men >0.45 0.43-0.45 < 0.43
Women >0.46 0.45-0.46 < 0.45
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