The diagnosis and treatment of cardiac ion channelopathies: Congenital long QT syndrome and Brugada syndrome

  • Ryan G. Aleong
  • David J. Milan
  • Patrick T. Ellinor

Opinion statement

Sudden cardiac death in young adults can be due to a range of conditions including coronary disease, hypertrophic or dilated cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Although each of these disorders has typical pathologic findings, some victims display no overt abnormalities and are presumed to have died from a primary cardiac arrhythmia. Increasingly, these malignant arrhythmias have been demonstrated to be due to mutations in ion channels. In this review we focus on the two most common of these disorders, termed ion channelopathies, namely congenital long QT syndrome and Brugada syndrome.


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References and Recommended Reading

  1. 1.
    Modell SM, Lehmann MH: The long QT syndrome family of cardiac ion channelopathies: a HuGE review. Genet Med 2006, 8:143–155.PubMedCrossRefGoogle Scholar
  2. 2.
    Roden DM, Spooner PM: Inherited long QT syndromes: a paradigm for understanding arrhythmogenesis. J Cardiovasc Electrophysiol 1999, 10:1664–1683.PubMedCrossRefGoogle Scholar
  3. 3.
    Mohler PJ, Schott JJ, Gramolini AO, et al.: Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature, 2003, 421:634–639.PubMedCrossRefGoogle Scholar
  4. 4.
    Tristani-Firouzi M, Jensen JL, Donaldson MR, et al.: Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest 2002, 110:381–388.PubMedGoogle Scholar
  5. 5.
    Splawski I, Timothy KW, Decher N, et al.: Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci U S A 2005, 102:8089–8096; discussion 8086–8088.PubMedCrossRefGoogle Scholar
  6. 6.
    Schwartz PJ, Moss AJ, Vincent GM, Crampton RS: Diagnostic criteria for the long QT syndrome. An update. Circulation 1993, 88:782–784.PubMedGoogle Scholar
  7. 7.
    Vyas H, Hejlik J, Ackerman MJ: Epinephrine QT stress testing in the evaluation of congenital long-QT syndrome: diagnostic accuracy of the paradoxical QT response. Circulation 2006, 113:1385–1392.PubMedCrossRefGoogle Scholar
  8. 8.
    Takenaka K, Ai T, Shimizu W, et al.: Exercise stress test amplifies genotype-phenotype correlation in the LQT1 and LQT2 forms of the long-QT syndrome. Circulation 2003, 107:838–844.PubMedCrossRefGoogle Scholar
  9. 9.
    Wang Q, Shen J, Splawski I, et al.: SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 1995, 80:805–811.PubMedCrossRefGoogle Scholar
  10. 10.
    Priori SG, Schwartz PJ, Napolitano C, et al.: Risk stratification in the long-QT syndrome. N Engl J Med 2003, 348:1866–1874.PubMedCrossRefGoogle Scholar
  11. 11.
    Brugada P, Brugada J: Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol 1992, 20:1391–1396.PubMedCrossRefGoogle Scholar
  12. 12.
    Nademanee K, Veerakul G, Nimmannit S, et al.: Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men. Circulation 1997, 96:2595–2600.PubMedGoogle Scholar
  13. 13.
    Priori SG, Napolitano C, Gasparini M, et al.: Natural history of Brugada syndrome: insights for risk stratification and management. Circulation 2002, 105:1342–1347.PubMedCrossRefGoogle Scholar
  14. 14.
    London BM, Sanyal S, Michalec M, et al.: A mutation in the glycerol-3-phosphate dehydrogenase 1-like gene (GPD1L) causes Brugada syndrome [abstract]. Heart Rhythm 2006, 3:S32.CrossRefGoogle Scholar
  15. 15.
    Antzelevitch C, Fish J: Electrical heterogeneity within the ventricular wall. Basic Res Cardiol 2001, 96:517–527.PubMedCrossRefGoogle Scholar
  16. 16.
    Wilde AA, Antzelevitch C, Borggrefe M, et al.: Proposed diagnostic criteria for the Brugada syndrome. Eur Heart J 2002, 23:1648–1654.PubMedGoogle Scholar
  17. 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 2006, 114:e385–e484.PubMedCrossRefGoogle Scholar
  18. 18.
    Roberts R, Brugada R: Genetics and arrhythmias. Annu Rev Med 2003, 54:257–267.PubMedCrossRefGoogle Scholar
  19. 19.
    Tester DJ, Ackerman MJ: Genetic testing for cardiac channelopathies: ten questions regarding clinical considerations for heart rhythm allied professionals. Heart Rhythm 2005, 2:675–677.PubMedCrossRefGoogle Scholar
  20. 20.
    Phillips KA, Ackerman MJ, Sakowski J, Berul CI: Cost-effectiveness analysis of genetic testing for familial long QT syndrome in symptomatic index cases. Heart Rhythm 2005, 2:1294–1300.PubMedCrossRefGoogle Scholar
  21. 21.
    Moss AJ, Zareba W, Hall WJ, et al.: Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation 2000, 101:616–623.PubMedGoogle Scholar
  22. 22.
    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, 296:1249–1254.PubMedCrossRefGoogle Scholar
  23. 23.
    Schwartz PJ, Priori SG, Spazzolini C, et al.: Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 2001, 103:89–95.PubMedGoogle Scholar
  24. 24.
    Tan HL, Bardai A, Shimizu W, et al.: Genotype-specific onset of arrhythmias in congenital long-QT syndrome: possible therapy implications. Circulation 2006, 114:2096–2103.PubMedCrossRefGoogle Scholar
  25. 25.
    Voigt A, Shalaby A, Saba S: Rising rates of cardiac rhythm management device infections in the United States: 1996 through 2003. J Am Coll Cardiol 2006, 48:590–591.PubMedCrossRefGoogle Scholar
  26. 26.
    Taheri S, Murphy K, Cohen M, et al.: The effects of centrally administered apelin-13 on food intake, water intake and pituitary hormone release in rats. Biochem Biophys Res Commun 2002, 291:1208–1212.PubMedCrossRefGoogle Scholar
  27. 27.
    Al-Khatib SM, Lucas FL, Jollis JG, et al.: The relation between patients’ outcomes and the volume of cardioverter-defibrillator implantation procedures performed by physicians treating Medicare beneficiaries. J Am Coll Cardiol 2005, 46:1536–1540.PubMedCrossRefGoogle Scholar
  28. 28.
    Gandelman G, Frishman WH, Wiese C, et al.: Intravascular device infections: epidemiology, diagnosis, and management. Cardiol Rev 2007, 15:13–23.PubMedCrossRefGoogle Scholar
  29. 29.
    Schwartz PJ, Priori SG, Cerrone M, et al.: Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome. Circulation 2004, 109:1826–1833.PubMedCrossRefGoogle Scholar
  30. 30.
    Ouriel K, Moss AJ: Long QT syndrome: an indication for cervicothoracic sympathectomy. Cardiovasc Surg 1995, 3:475–478.PubMedCrossRefGoogle Scholar
  31. 31.
    Mizusawa Y, Sakurada H, Nishizaki M, Hiraoka M: Effects of low-dose quinidine on ventricular tachyarrhythmias in patients with Brugada syndrome: low-dose quinidine therapy as an adjunctive treatment. J Cardiovasc Pharmacol 2006, 47:359–364.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Ryan G. Aleong
  • David J. Milan
  • Patrick T. Ellinor
    • 1
  1. 1.Cardiac Arrhythmia Service and Cardiovascular Research CenterMassachusetts General HospitalBostonUSA

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