European Journal of Pediatrics

, Volume 168, Issue 9, pp 1107–1115 | Cite as

QT interval prolongation and risk for cardiac events in genotyped LQTS-index children

  • H. Wedekind
  • D. Burde
  • S. Zumhagen
  • V. Debus
  • G. Burkhardtsmaier
  • G. Mönnig
  • G. Breithardt
  • E. Schulze-Bahr
Original Paper


Congenital long-QT syndrome (LQTS) is an inherited cardiac disorder with a disturbance in repolarization characterized by a prolonged QT interval on the surface electrocardiogram and life-threatening ventricular tachycardia. Publications from the International LQTS Registry have provided information that the cardiac risk may be influenced by gender, genotype, exposure to arrhythmia triggers, and previous cardiac events. In children, early-onset of disease, changes in life style, and medical treatment is a sensitive issue and significant, gender-related differences of a first life-threatening event were reported. Thus, we investigated the clinical features of a large genotyped population of LQTS-index children (age ≤16 years) upon a single-center experience and determined risk factors for symptoms. Of 83 children [mean corrected QT interval (QTc) 510 ± 74 ms], 89% had LQT1, -2, or -3. Nine patients (11%) were identified as having Jervell and Lange-Nielsen syndrome. Among symptomatic children (n = 51, 61%), syncope was the most prevalent symptom at initial presentation (49%); however, aborted cardiac arrest (ACA) occurred in 33% and sudden cardiac death (SCD) in 18%, respectively, as the initial manifestation. During a mean follow-up period of 5.9 ± 4.7 years, 31% of the children developed symptoms while on therapy (86% syncope, 9% ACA, 5% SCD). Statistical analyses of risk factors for cardiac events showed that the QTc >500 ms was a strong and significant predictor for cardiac events during follow-up (p = 0.02). Furthermore, a prior syncope [hazard ratio (HR), 4.05; 95% confidence interval (CI), 1.1 to 15.0; p = 0.03] or an ACA (HR, 11.7; 95% CI, 3.1 to 43.4; p = <0.001) identified children with an increased risk for recurrent cardiac events compared to asymptomatic LQT children. LQTS-index children manifest with a high percentage of severe symptoms. Among presently validated risk factors for LQTS, a QTc interval >500 ms and a history of prior syncope or ACA were strong predictors for recurrent cardiac events.


Children Arrhythmias Genetics Long QT syndrome Treatment 



This work was supported in part by grants from the Dr. Adolf Schilling Foundation, Münster, Germany; the Deutsche Forschungsgemeinschaft, Bonn, Germany (SFB 656-C1, Schu1082/3-1, and 3-2); and the Fondation Leducq, Paris, France.

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Bazett JC (1920) An analysis of time relation of electrocardiograms. Heart 7:353–367Google Scholar
  2. 2.
    Beinder E, Grancay T, Menendez T, Singer H, Hofbeck M (2001) Fetal sinus bradycardia and the long QT syndrome. Am J Obstet Gynecol 185:743–747PubMedCrossRefGoogle Scholar
  3. 3.
    Etheridge SP, Sanatani S, Cohen MI, Albaro CA, Saarel EV, Bradley DJ (2007) Long QT syndrome in children in the era of implantable defibrillators. J Am Coll Cardiol 50:1335–1340PubMedCrossRefGoogle Scholar
  4. 4.
    Garson A Jr, Dick M 2nd, Fournier A, Gillette PC, Hamilton R, Kugler JD, van Hare GF 3rd, Vetter V, Vick GW 3rd (1993) The long QT syndrome in children. An international study of 287 patients. Circulation 87:1866–1872PubMedGoogle Scholar
  5. 5.
    Goldenberg I, Mathew J, Moss AJ, McNitt S, Peterson DR, Zareba W, Benhorin J, Zhang L, Vincent GM, Andrews ML, Robinson JL, Morray B (2006) Corrected QT variability in serial electrocardiograms in long QT syndrome: the importance of the maximum corrected QT for risk stratification. J Am Coll Cardiol 48:1047–1052PubMedCrossRefGoogle Scholar
  6. 6.
    Goldenberg I, Moss AJ, Peterson DR, McNitt S, Zareba W, Andrews ML, Robinson JL, Locati EH, Ackerman MJ, Benhorin J, Kaufman ES, Napolitano C, Priori SG, Qi M, Schwartz PJ, Towbin JA, Vincent GM, Zhang L (2008) Risk factors for aborted cardiac arrest and sudden cardiac death in children with the congenital long-QT syndrome. Circulation 117:2184–2191PubMedCrossRefGoogle Scholar
  7. 7.
    Goldenberg I, Moss AJ, Bradley J, Polonsky S, Peterson DR, McNitt S, Zareba W, Andrews ML, Robinson JL, Ackerman MJ, Benhorin J, Kaufman ES, Locati EH, Napolitano C, Priori SG, Qi M, Schwartz PJ, Towbin JA, Vincent GM, Zhang L (2008) Long-QT syndrome after age 40. Circulation 117:2192–2201PubMedCrossRefGoogle Scholar
  8. 8.
    Hobbs JB, Peterson DR, Moss AJ, McNitt S, Zareba W, Goldenberg I, Qi M, Robinson JL, Sauer AJ, Ackerman MJ, Benhorin J, Kaufman ES, Locati EH, Napolitano C, Priori SG, Towbin JA, Vincent GM, Zhang L (2006) Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long-QT syndrome. JAMA 296:1249–1254PubMedCrossRefGoogle Scholar
  9. 9.
    Hofbeck M, Ulmer H, Beinder E, Sieber E, Singer H (1997) Prenatal findings in patients with prolonged QT interval in the neonatal period. Heart 77:198–204PubMedCrossRefGoogle Scholar
  10. 10.
    Locati EH, Zareba W, Moss AJ, Schwartz PJ, Vincent GM, Lehmann MH, Towbin JA, Priori SG, Napolitano C, Robinson JL, Andrews M, Timothy K, Hall WJ (1998) Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry. Circulation 97:2237–2244PubMedGoogle Scholar
  11. 11.
    Loddenkötter B, Becker K, Hohoff C, Brinkmann B, Bajanowski T (2005) Real-time quantitative PCR assay for the detection of Helicobacter pylori: no association with sudden infant death syndrome. Int J Legal Med 119:202–206PubMedCrossRefGoogle Scholar
  12. 12.
    Mönnig G, Eckardt L, Wedekind H, Haverkamp W, Gerss J, Milberg P, Wasmer K, Kirchhof P, Assmann G, Breithardt G, Schulze-Bahr E (2006) Electrocardiographic risk stratification in families with congenital long QT syndrome. Eur Heart J 17:2074–2080CrossRefGoogle Scholar
  13. 13.
    Moss AJ, Zareba W, Hall WJ, Schwartz PJ, Crampton RS, Benhorin J, Vincent GM, Locati EH, Priori SG, Napolitano C, Medina A, Zhang L, Robinson JL, Timothy K, Towbin JA, Andrews ML (2000) Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation 101:616–623PubMedGoogle Scholar
  14. 14.
    Moss AJ, Shimizu W, Wilde AA, Towbin JA, Zareba W, Robinson JL, Qi M, Vincent GM, Ackerman MJ, Kaufman ES, Hofman N, Seth R, Kamakura S, Miyamoto Y, Goldenberg I, Andrews ML, McNitt S (2007) Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation 115:2481–2489PubMedCrossRefGoogle Scholar
  15. 15.
    Petko C, Bradley DJ, Tristani-Firouzi M, Cohen MI, Sanatani S, Saarel EV, Albaro CA, Etheridge SP (2008) Congenital long QT syndrome in children identified by family screening. Am J Cardiol 101:1756–1758PubMedCrossRefGoogle Scholar
  16. 16.
    Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, Vicentini A, Spazzolini C, Nastoli J, Bottelli G, Folli R, Cappelletti D (2003) Risk stratification in the long-QT syndrome. N Engl J Med 348:1866–1874PubMedCrossRefGoogle Scholar
  17. 17.
    Priori SG, Napolitano C, Schwartz PJ, Grillo M, Bloise R, Ronchetti E, Moncalvo C, Tulipani C, Veia A, Bottelli G, Nastoli J (2004) Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. JAMA 292:1341–1344PubMedCrossRefGoogle Scholar
  18. 18.
    Sauer AJ, Moss AJ, McNitt S, Peterson DR, Zareba W, Robinson JL, Qi M, Goldenberg I, Hobbs JB, Ackerman MJ, Benhorin J, Hall WJ, Kaufman ES, Locati EH, Napolitano C, Priori SG, Schwartz PJ, Towbin JA, Vincent GM, Zhang L (2007) Long QT syndrome in adults. J Am Coll Cardiol 49:329–337PubMedCrossRefGoogle Scholar
  19. 19.
    Schulze-Bahr E, Schwarz M, Hauenschild S, Wedekind H, Funke H, Haverkamp W, Breithardt G, Pongs O, Isbrandt D (2001) A novel long-QT 5 gene mutation in the C-terminus (V109I) is associated with a mild phenotype. J Mol Med 79:504–509PubMedCrossRefGoogle Scholar
  20. 20.
    Schwartz PJ (1985) Idiopathic long QT syndrome: progress and questions. Am Heart J 109:399–411PubMedCrossRefGoogle Scholar
  21. 21.
    Schwartz PJ, Moss AJ, Vincent GM, Crampton RS (1993) Diagnostic criteria for the long QT syndrome. An update. Circulation 88:782–784PubMedGoogle Scholar
  22. 22.
    Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, Denjoy I, Guicheney P, Breithardt G, Keating MT, Towbin JA, Beggs AH, Brink P, Wilde AA, Toivonen L, Zareba W, Robinson JL, Timothy KW, Corfield V, Wattanasirichaigoon D, Corbett C, Haverkamp W, Schulze-Bahr E, Lehmann MH, Schwartz K, Coumel P, Bloise R (2001) Genotype-phenotype correlation in the long-QT syndrome. Circulation 103:89–95PubMedGoogle Scholar
  23. 23.
    Schwartz PJ, Garson A Jr, Paul T, Stramba-Badiale M, Vetter VL, Wren C, European Society of Cardiology (2002) Guidelines for the interpretation of the neonatal electrocardiogram. A task force of the European Society of Cardiology. Eur Heart J 23:1329–1344PubMedCrossRefGoogle Scholar
  24. 24.
    Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K, Shkolnikova M, Berul CI, Bitner-Glindzicz M, Toivonen L, Horie M, Schulze-Bahr E, Denjoy I (2006) The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. Circulation 113:783–790PubMedCrossRefGoogle Scholar
  25. 25.
    Schwartz PJ, Crotti L (2008) Ion channel diseases in children: manifestations and management. Curr Opin Cardiol 23:184–191PubMedCrossRefGoogle Scholar
  26. 26.
    Villain E, Denjoy I, Lupoglazoff JM, Guicheney P, Hainque B, Lucet V, Bonnet D (2004) Low incidence of cardiac events with beta-blocking therapy in children with long QT syndrome. Eur Heart J 25:1405–1411PubMedCrossRefGoogle Scholar
  27. 27.
    Weintraub RG, Gow RM, Wilkinson JL (1990) The congenital long-QT syndromes in childhood. J Am Coll Cardiol 16:674–680PubMedCrossRefGoogle Scholar
  28. 28.
    Zareba W, Moss AJ, Schwartz PJ, Vincent GM, Robinson JL, Priori SG, Benhorin J, Locati EH, Towbin JA, Keating MT, Lehmann MH, Hall WJ (1998) Influence of the genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group. N Engl J Med 339:960–965PubMedCrossRefGoogle Scholar
  29. 29.
    Zareba W, Moss AJ (2001) Long QT syndrome in children. J Electrocardiol 34(Suppl):167–171PubMedCrossRefGoogle Scholar
  30. 30.
    Zareba W, Moss AJ, Locati EH, Lehmann MH, Peterson DR, Hall WJ, Schwartz PJ, Vincent GM, Priori SG, Benhorin J, Towbin JA, Robinson JL, Andrews ML, Napolitano C, Timothy K, Zhang L, Medina A, International Long QT Syndrome Registry (2003) Modulating effects of age and gender on the clinical course of long QT syndrome by genotype. J Am Coll Cardiol 42:103–109PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • H. Wedekind
    • 1
    • 2
    • 5
  • D. Burde
    • 1
  • S. Zumhagen
    • 1
  • V. Debus
    • 3
  • G. Burkhardtsmaier
    • 4
  • G. Mönnig
    • 1
  • G. Breithardt
    • 1
    • 2
  • E. Schulze-Bahr
    • 1
    • 2
  1. 1.Department of Cardiology and AngiologyUniversity Hospital of MünsterMünsterGermany
  2. 2.Leibniz Institute for Arteriosclerosis Research at the University of MünsterMünsterGermany
  3. 3.Department of Pediatric CardiologyUniversity Hospital of MünsterMünsterGermany
  4. 4.Department of Medical Informatics and BiomathematicsUniversity Hospital of MünsterMünsterGermany
  5. 5.St. Marien-Hospital HammKlinik für Kardiologie und IntensivmedizinHammGermany

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