GENETICALLY DETERMINED CARDIAC ARRHYTHMIAS

Genetic factors play an important role in pathogenesis of many diseases. It has been shown that potential-dependent Na, K, and Ca channels have common characteristics in their molecular structure, which should be taken into account when assessing physiological functioning of these channels. Hereditary diseases due to channel pathology are called channelopathies, or primary electrical heart disorders (long QT interval syndrome, short QT interval syndrome, Brugada syndrome, catecholamine-dependent ventricular tachycardia, idiopathic ventricular fibrillation, Lenegre disease, hereditary Wolf-Parkinson-White syndrome, hereditary atrial fibrillation). The second leading cause of sudden cardiac death (SCD), after coronary heart disease, is secondary hereditary electrical disorders (hypertrophic cardiomyopathy, dilated cardiomyopathy, right ventricular arrhythmogenic dysplasia, isolated left ventricular non-compaction). Genetically determined cardiac arrhythmias (CA), with or without structural heart pathology, manifest in young age (with an exception of Brugada syndrome) and have specific phenotypic and genotypic characteristics. Timely diagnostics of these diseases should be based on ECG screening (ideally performed before 3 years of age) and EchoCG. In addition, examination of families with high SCD risk has an important diagnostic value. High total SCD risk in treated patients with genetically determined CA is an indication for cardioverter-defibrillator implantation. Optimal strategy of SCD prevention in patients with genetically determined CA includes baseline risk assessment and ongoing monitoring, according to the individual risk profile. This review describes clinical and molecular features of genetically determined CA, SCD risk criteria, and modern views on diagnostics and treatment of these patients.

Cardiac arrhythmias, genetic etiology, risk criteria, clinical manifestation, diagnostics, treatment

1. Габрусенко С. А. Современные подходы к лечению больных гипертрофической кардиомиопатией/ С. А. Габрусенко, Ю. В. Сафрыгина, В. Г. Наумов и др. Лечащий врач. 2004; № 2: 32-37.

2. Школьникова М. А. Первичные электрические заболевания сердца как причина внезапной смерти. Доктор.ru. 2008; 3: 25-32.

3. Школьникова М. А. Прогнозирование риска развития жизнеугрожающих состояний и внезапной смерти при нарушениях сердечного ритма у детей, принципы профилактики. Автореферат докт. дисс. М.-1993.-106с.

4. Школьникова М. А. Жизнеугрожающие аритмии у детей. Москва, Нефтяник, 1999.

5. AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram Part IV: The ST Segment, T and U Waves, and the QT Interval A Scientific Statement From the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society Endorsed by the International Society for Computerized Electrocardiology. Pentti M. Rautaharju, MD, PhD; Borys Surawicz, MD, FAHA, FACC; Leonard S. Gettes, MD, FAHA, FACC. J.Am.Coll.Cardiol. published online Feb 19, 2009.

6. Ankerman M. Cardiac causes of sudden unexpected death in children and their relationship to seizures and syncope: genetic testing for cardiac electropathies. Semin. Pediatr. Neurol. 2005; 12:52-58.

7. Antzelevitch C., Burashnikov A., Di Diego J. Mechanisms of cardiac arrhythmia. 2008. pp 65-133.

8. Antzelevitch C., Pollevick G., Cordeiro J., et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation. 2007; 115:442-449.

9. Bellocq C., Van Ginneken A., Bezzina C., et al. Mutation in KCNQ1 gene leading to the short QT-interval syndrome. Circulation. 2004; 109:2394-2397.

10. Chen P., Priori S. The Brugada Syndrome. JACC. 2008; 51(12): 1176-1180.

11. Crotti L., Celano G., Dagradi F., et al. Congenital long QT syndrome. Orphanet J Rare Diseases 2008, 3:18.

12. Denjoy I, Lupoglazoff J., Guicheney P., et al. Arrhythmic sudden death in children. Archives of Cardiovascular Diseases. 2008; 101:121-125.

13. Donaldson M, R., Yoon G., Fu Y. H. et al. Andersen-Tawil syndrome: a model of clinical variability, pleiotropy, and genetic heterogeneity. Ann Med. 2004; 36 (Suppl 1): 92–7.

14. Engberding R., Stollberger C., Ong P. et al. Isolated Non-Compaction Cardiomyopathy Dtsch Arztebl Int. 2010 March; 107(12): 206–213.

15. Gussak I., Antzelevitch C. Electrical diseases of the heart. Genetics, mechanisms, treatment, prevention. Springer. 2008. pp.461-654, 705-719.

16. Keating M., Atkinson D., Dunn C., et al. Linkage of a cardiac arrhythmia, the long QT syndrome, and the Harvey ras-1 gene. Science. 1991 May 3; 252(5006):704–706.

17. Leenhard A., Lucet V., Denjoy I. et al. Cateholaminergic polymorphic ventricular tachycardia in children. A 7-year follow up of 21 patients. Circulation. 1995; 91: 1512-1519.

18. Marks M. L., Trippel D. L., Keating M. T. Long QT syndrome associated with syndactyly identified in females. Am J Cardiol. 1995; 76:744-745.

19. Maron B. J., Towbin J. A., Thiene G., et al. Contemporary Definitions and Classification of the Cardiomyopathies: An American Heart Association Scientific Statement From the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. 8722; 2006; 113: 1807-1816.

20. McKenna W. J., Behr E. R. Hypertrophic cardiomyopathy: management, risk stratification, and prevention of sudden death. Heart. 2002; 87:169-176.

21. Moss A. J. Liu J. E. Gottlieb S. et al. Efficacy of permanent pacing in the management of high-risk patient with long QT syndrome. Circulation 1991; 84: 1524-1529.

22. Patel Ch., Antzelevich Ch. Pharmacological approach to the treatment of long and short QT syndromes. Pharmacology and Therapeutices, 2008; 3(118): 138-151.

23. Priori S. G., Antzelevitch C.: Inherited arrhythmogenic diseases. In Sudden Cardiac Death / Ed. by Silvia G. Priori, Douglas P. Zipes. 2006.

24. Priori S., Pandit S., Rivolta I., et al. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res. 2005; 96: 800-807.

25. Sansone V., Tawil R. Management and treatment of Andersen-Tawil syndrome. Neurotherapeutics. 2007; 4(2):233-237.

26. Sauer A., Moss A., McNitt S., et al. Long QT syndrome in adults. J Am Coll Cardiol, 49: 329-337, 2007.

27. Schimpf R., Wolpert Ch., Gaita F. et al. Short QT syndrome. Cardiovascular research. 2005; 67: 357-364.

28. Schwartz P.J., Moss A.J., Vincent G.M., et al. Diagnostic criteria for the long QT syndrome. An update. Circulation. 1993; 88: 782-784.

29. Schwartz P. J., Spazzolini C., Crotti L., et al. The Jervell and Lange-Nielsen Syndrome. Natural history, molecular basis, and clinical outcome. Circulation 2006; 113:783-790.

30. Schwartz P.J., Priori S.G., Locati E.H., et al. Long QT syndrome patients with mutations on the SCN5A and HERG genes have differential responses to Na+ channel blockage and to increases in heart rate. Implications for gene-specific therapy. Circulation. 1955; 92: 3381-6.

31. Schwartz P.J., Priori S.G., 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.

32. Splawski I., Timothy K.W., Sharpe L.M., et al. Ca (V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004; 119:19-31.

33. Weisz S.H., Limongelli G., Pacileo G. et al. Left ventricular non compaction in children. Congenit Heart Dis. 2010; 5(5):284-297.

34. Zareba W., Moss A.J., Schwartz P.J. 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. 1998; 339: 960-5.

35. Zipes D.P., Jalife J. Cardiac electrophysiology. From cell to bedside. Elsevier. Fifth edition. 2009. Ventricular arrhythmias: mechanisms, features, and, management. pp 675-699, 723-779.