The Modern State of the Problem of Congenital Long QT Syndrome
https://doi.org/10.31550/1727-2378-2024-23-1-38-45
Abstract
Aim. To summarize the currently available information on the pathophysiological mechanisms, clinical management, diagnosis and therapeutic approaches in congenital long QT syndrome.
Key points. Congenital long QT syndrome is a hereditary disease characterized by an increased ventricles repolarization time, and, consequently, a lengthening of the QT interval on the electrocardiogram. It is accompanied by fatal cardiac arrhythmias, episodes of syncope and cases of sudden cardiac death. Sixteen genes associated with hereditary long QT syndrome have been described, and genetic testing has become an integral part of the diagnosis of this pathology and risk stratification.
Conclusion. New knowledge about the structure of these proteins contributes to a deeper understanding of the problem of channelopathy, in particular, long QT syndrome, which is the most well-studied of this group of diseases. In addition, continued progress in understanding the genetic basis and mechanisms of development of long QT syndrome leads to the emergence of more effective, targeted, individualized treatment strategies for the syndrome.
About the Authors
T. G. Tedeev
S.M. Kirov Military Medical Academy
Russian Federation
Russian Federation
6 Academician Lebedev Str., St. Petersburg, 194044
D. V. Cherkashin
S.M. Kirov Military Medical Academy
Russian Federation
Russian Federation
6 Academician Lebedev Str., St. Petersburg, 194044
G. G. Kutelev
S.M. Kirov Military Medical Academy
Russian Federation
Russian Federation
6 Academician Lebedev Str., St. Petersburg, 194044
V. A. Kachnov
S.M. Kirov Military Medical Academy
Russian Federation
Russian Federation
6 Academician Lebedev Str., St. Petersburg, 194044
N. T. Mirzoev
S.M. Kirov Military Medical Academy
Russian Federation
Russian Federation
6 Academician Lebedev Str., St. Petersburg, 194044
References
1. Jervell A., Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of the QT interval, and sudden death. Am. Heart J. 1957;54(1):59–68. DOI: 10.1016/0002-8703(57)90079-0
2. Romano C., Gemme G., Pongiglione R. Rare cardiac arrhythmias of the pediatric age. I. Repetitive paroxysmal tachycardia. Minerva Pediatr. 1963;15:1155–64.
3. Ward O. A new familial cardiac syndrome in children. J. Ir. Med. Assoc. 1964;54:103–6.
4. Mironov N.Yu., Lajovich L.Yu., Golitsyn S.P. Ventricular arrhythmias and sudden cardiac death. M.: MIA; 2018. 112 p. (in Russian)
5. Mazzanti A., Maragna R., Vacanti G., Monteforte N. et al. Interplay between genetic substrate, QTc duration and arrhythmia risk in patients with long QT syndrome. J. Am. Coll. Cardiol. 2018;71(15):1663–71. DOI: 10.1016/j.jacc.2018.01.078
6. Bohnen M., Peng G., Robey S., Terrenoire C. et al. Molecular pathophysiology of congenital long QT syndrome. Physiol. Rev. 2017;97(1):89–134. DOI: 10.1152/physrev.00008.2016
7. Barsheshet A., Dotsenko O., Goldenberg I. Congenital long QT syndromes: prevalence, pathophysiology and management. Paediatr. Drugs. 2014;16(6):447–56. DOI: 10.1007/s40272-014-0090-4
8. Priori S., Napolitano C., Cantù F., Brown A.M. et al. Differential response to Na+ channel blockade, β-adrenergic stimulation and rapid pacing in a cellular model mimicking the SCN5A and HERG defects present in the long QT syndrome. Circ. Res. 1996;78(6):1009–15. DOI: 10.1161/01.res.78.6.1009
9. Bhuiyan Z. Clinical and genetic spectrum of hereditary cardiac arrhythmia syndromes. PhD thesis. University of Amsterdam; 2016. 16 p.
10. Barro-Soria R., Rebolledo S., Liin S.I., Perez M.E. et al. KCNE1 divides the voltage sensor movement in KCNQ1/KCNE1 channels into two steps. Nat. Commun. 2014;5:3750. DOI: 10.1038/ncomms4750
11. Schwartz P.J., Gnecchi M., Dagradi F., Castelletti S. et al. From patientspecific induced pluripotent stem cells to clinical translation in long QT syndrome type 2. Eur. Heart J. 2019;40(23):1832–6. DOI: 10.1093/eurheartj/ehz023
12. Bos J.M., Crotti L., Rohatgi R.K., Castelletti S. et al. Mexiletine shortens the QT interval in patients with potassium channelmediated type 2 long QT syndrome. Circ. Arrhythm. Electrophysiol. 2019;12(5):e007280. DOI: 10.1161/CIRCEP.118.007280
13. Adler A., Novelli V., Amin A.S., Abiusi E. et al. An international, multicentered reappraisal of genes reported to cause congenital long QT syndrome. Circulation. 2020;141(6):418–28. DOI: 10.1161/circulationaha.119.043132
14. Antzelevitch C., Nesterenko V., Shryock J.S., Rajamani S. et al. The role of late INa in development of cardiac arrhythmias. Handb. Exp. Pharmacol. 2014;221:137–68. DOI: 10.1007/978-3-642-41588-3_7
15. Mohler P.J., Schott J.J., Gramolini A.O., Dilly K.W. et al. Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature. 2003;421(6923):634–9. DOI: 10.1038/nature01335
16. Abbott G.W., Sesti F., Splawski I., Buck M.E. et al. MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell. 1999;97(2):175–87. DOI: 10.1016/s00928674(00)80728-x
17. Bauer R., Timothy K., Golden A. Update on the molecular genetics of Timothy syndrome. Front. Pediatr. 2021;9:668546. DOI: 10.3389/fped.2021.668546
18. Wu G., Ai T., Kim J.J., Mohapatra B. et al. Alpha-1-syntrophin mutation and the long-QT syndrome: a disease of sodium channel disruption. Circ. Arrhythm. Electrophysiol. 2008;1(13):193–201. DOI: 10.1161/CIRCEP.108.769224
19. Yang Y., Yang Y., Liang B., Liu J. et al. Identification of a Kir3.4 mutation in congenital long QT syndrome. Am. J. Hum. Genet. 2010;86(6):872–80. DOI: 10.1016/j.ajhg.2010.04.017
20. Boczek N.J., Gomez-Hurtado N., Ye D., Calvert M.L. et al. Spectrum and prevalence of CALM1-, CALM2- and CALM3-encoded calmodulin variants in long QT syndrome and functional characterization of a novel long QT syndrome-associated calmodulin missense variant, E141G. Circ. Cardiovasc. Genet. 2016;9(2):136–46. DOI: 10.1161/CIRCGENETICS.115.001323
21. Rohatgi R.K., Sugrue A.M., Bos J.M., Cannon B.C. et al. Contemporary outcomes in patients with long QT syndrome. J. Am. Coll. Cardiol. 2017;70(4):453–62. DOI: 10.1016/j.jacc.2017.05.046
22. Beach S.R., Celano C.M., Sugrue A.M., Adams C. et al. QT prolongation, Torsades de Pointes, and psychotropic medications: a 5-year update. Psychosomatics. 2018;59(2):105–22. DOI: 10.1016/j.psym.2017.10.009
Review
For citations:
Tedeev T.G., Cherkashin D.V., Kutelev G.G., Kachnov V.A., Mirzoev N.T. The Modern State of the Problem of Congenital Long QT Syndrome. Title. 2024;23(1):38-45. (In Russ.) https://doi.org/10.31550/1727-2378-2024-23-1-38-45
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