perinatologyРоссийский вестник перинатологии и педиатрииRossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics)1027-40652500-2228Ltd. “The National Academy of Pediatric Science and Innovation”10.21508/1027-4065-2025-70-2-30-37perinatology-2182Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESБлокаторы натриевых каналов в терапии третьего варианта синдрома удлиненного интервала Q–TSodium channel blocker in therapy of type 3 long Q–T syndromehttps://orcid.org/0000-0002-1780-3518ИльдароваР. А.IldarovaR. A.

Ильдарова Рукижат Абдул-Гафуровна — к.м.н., ст. науч. сотр. отдела детской кардиологии и аритмологии

125412 Москва, ул. Талдомская, д. 2 

Moscow 

https://orcid.org/0000-0002-2119-169XБерезницкаяВ. В.BereznitskayaV. V.

Березницкая Вера Васильевна — к.м.н., зав. детским кардиологическим отделением нарушений сердечного ритма 

125412 Москва, ул. Талдомская, д. 2 

Moscow 

https://orcid.org/0000-0001-7115-0186ШкольниковаМ. А.ShkolnikovaM. A.

Школьникова Мария Александровна — д.м.н., проф., Почетный президент Ассоциации детских кардиологов России 

125412 Москва, ул. Талдомская, д. 2 

Moscow 

ОСП «Научно-исследовательский клинический институт педиатрии и детской хирургии им. академика Ю.Е. Вельтищева» (Институт Вельтищева) ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава РоссииРоссияVeltischev Research and Clinical Institute for pediatrics and pediatric surgery at the Pirogov Russian National Research Medical UniversityRussian Federation2025140520257023037Copyright © Ltd. “The National Academy of Pediatric Science and Innovation”, 20252025Ltd. “The National Academy of Pediatric Science and Innovation”Ltd. “The National Academy of Pediatric Science and Innovation”https://www.ped-perinatology.ru/jour/about/submissions#copyrightNoticehttps://www.ped-perinatology.ru/jour/article/view/2182

Синдром удлиненного интервала Q–T, обусловленный мутацией в гене SCN5A, является третьим по распространенности молекулярно-генетическим вариантом синдрома. Аритмические события при этом варианте синдрома ассоциированы с высоким риском летального исхода, а терапия бета-адреноблокаторами недостаточно эффективна. С учетом нарушения инактивации натриевого канала кардиомиоцитов вследствие вариантов в гене SCN5A в качестве геноспецифической терапии предложены блокаторы натриевого канала.Цель исследования. Оценка эффективности и безопасности терапии блокатором натриевых каналов лаппаконитина гидробромидом в когорте детей с третьим вариантом синдрома удлиненного интервала Q–T.Материалы и методы. В исследование включены 16 пациентов из 11 неродственных семей, получавшие комбинированную терапию бета-адреноблокатором и лаппаконитина гидробромидом в течение 48±37 мес.Результаты. Основным показанием к назначению лаппаконитина гидробромида было выраженное удлинение интервала Q–T (у 81,25% пациентов). Продолжительность интервала Q–Tc достоверно уменьшалась после назначения лаппаконитина гидробромида как по данным стандартной электрокардиографии (с 507±20,7 до 451±26,0 мс; р=0,000003), так и при холтеровском мониторировании (ХМ) электрокардиограммы — ЭКГ (средний Q–Tc с 536±16,2 до 489±24,9 мс; р=0,0002). Спонтанных аритмических событий на фоне комбинированной антиаритмической терапии не отмечено.Заключение. Блокатор натриевых каналов лаппаконитина гидробромид у больных с третьим вариантом синдрома удлиненного интервала Q–T влияет на такой фактор риска внезапной сердечной смерти, как интервал Q–Tc, достоверно уменьшая его продолжительность. Препарат может быть рекомендован к назначению в дополнение к терапии бета-адреноблокатором при Q–Tc ≥500 мс на стандартной ЭКГ или среднего Q–Tc при ХМ ЭКГ у больных с III вариантом синдрома.

Long QT syndrome caused by a mutation in the SCN5A gene is the third most common molecular genetic type of the syndrome. Cardiac events in long QT syndrome type 3 are associated with a high risk of death, and beta-blocker therapy is not effective enough. Given the impaired inactivation of the cardiomyocyte sodium channel due to variants in the SCN5A gene, sodium channel blockers have been proposed as gene-specific therapy.The aim of this study was to evaluate the efficacy and safety of therapy with the sodium channel blocker lappaconitine hydrobromide in a cohort of children with type 3 long QT syndrome.Materials and methods. The study included 16 patients from 11 unrelated families who received combination therapy with a betablocker and lappaconitine hydrobromide for 48±37 months.Results. The main indication for the use of lappaconitine hydrobromide was a pronounced prolongation of the QT interval (in 81.25% of cases). The duration of the QTc interval significantly decreased after the administration of lappaconitine hydrobromide both according to the standard ECG (from 507±20.7 to 451±26.0 ms; p=0.000003) and during Holter monitoring (mean QTc from 536±16.2 to 489±24.9 ms; p=0.0002). No spontaneous arrhythmic events were noted during combined antiarrhythmic therapy.Conclusion. The sodium channel blocker lappaconitine hydrobromide in patients with type 3 long QT syndrome affects such a risk factor for sudden cardiac death as the QTc interval by significantly reducing its duration. The drug can be recommended for use in addition to beta-blocker therapy for QTc ≥ 500 ms on a standard ECG or mean QTc during Holter monitoring in patients with type 3 of the syndrome.

детисиндром удлиненного интервала Q–Tвнезапная сердечная смертьблокатор натриевых каналовгеноспецифическая терапияchildrenlong Q–T syndromesudden cardiac deathsodium-channel blockergene-specific therapyReferencesZhu W., Bian X., Lv J. From genes to clinical management: A comprehensive review of long QT syndrome pathogenesis and treatment. Heart Rhythm O2. 2024; 5(8): 573–586. DOI: 10.1016/j.hroo.2024.07.006Zhu W., Bian X., Lv J. From genes to clinical management: A comprehensive review of long QT syndrome pathogenesis and treatment. Heart Rhythm O2. 2024; 5(8): 573–586. DOI: 10.1016/j.hroo.2024.07.006Wallace E., Howard L., Liu M., O’Brien T., Ward D., Shen S., Prendiville T. Long QT Syndrome: Genetics and Future Perspective. Pediatr Cardiol 2019; 40(7): 1419–1430. DOI: 10.1007/s00246–019–02151-xWallace E., Howard L., Liu M., O’Brien T., Ward D., Shen S., Prendiville T. Long QT Syndrome: Genetics and Future Perspective. Pediatr Cardiol 2019; 40(7): 1419–1430. DOI: 10.1007/s00246–019–02151-xGeorge A.L. Jr. Inherited disorders of voltage-gated sodium channels. J Clin Invest 2005; 115(8): 1990–1999. DOI: 10.1172/JCI25505George A.L. Jr. Inherited disorders of voltage-gated sodium channels. J Clin Invest 2005; 115(8): 1990–1999. DOI: 10.1172/JCI25505Zareba W., Moss A.J., Schwartz P.J., Vincent G.M., Robinson J.L., Priori S.G., et al. Influence of the genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group. N Engl J Med 1998; 339(14): 960–965. DOI: 10.1056/NEJM199810013391404Zareba W., Moss A.J., Schwartz P.J., Vincent G.M., Robinson J.L., Priori S.G., et al. Influence of the genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group. N Engl J Med 1998; 339(14): 960–965. DOI: 10.1056/NEJM199810013391404Moss A.J., Goldenberg I. Importance of Knowing the Genotype and the Specific Mutation When Managing Patients with Long QT Syndrome. Circ Arrhythm Electrophysiol 2008; 1(3): 213–226. DOI: 10.1161/CIRCEP.108.796599Moss A.J., Goldenberg I. Importance of Knowing the Genotype and the Specific Mutation When Managing Patients with Long QT Syndrome. Circ Arrhythm Electrophysiol 2008; 1(3): 213–226. DOI: 10.1161/CIRCEP.108.796599Priori S.G., Napolitano C., Schwartz P.J., Grillo M., Bloise R., et al. Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. JAMA 2004; 292(11): 1341–1344. DOI: 10.1001/jama.292.11.1341Priori S.G., Napolitano C., Schwartz P.J., Grillo M., Bloise R., et al. Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. JAMA 2004; 292(11): 1341–1344. DOI: 10.1001/jama.292.11.1341Wilde A.A.M., Moss A.J., Kaufman E.S., Shimizu W., Peterson D.R., Benhorin J., et al. Clinical Aspects of Type 3 Long-QT 27 Syndrome: An International Multicenter Study. Circulation 2016; 134: 872–882. DOI: 10.1161/CIRCULATIONAHA.116.021823Wilde A.A.M., Moss A.J., Kaufman E.S., Shimizu W., Peterson D.R., Benhorin J., et al. Clinical Aspects of Type 3 Long-QT 27 Syndrome: An International Multicenter Study. Circulation 2016; 134: 872–882. DOI: 10.1161/CIRCULATIONAHA.116.021823Zeppenfeld K., Tfelt-Hansen J., de Riva M., Winkel B.G., Behr E.R., Blom N.A., et al; ESC Scientific Document Group. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J 2022; 43(40): 3997–4126. DOI: 10.1093/eurheartj/ehac262Zeppenfeld K., Tfelt-Hansen J., de Riva M., Winkel B.G., Behr E.R., Blom N.A., et al; ESC Scientific Document Group. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J 2022; 43(40): 3997–4126. DOI: 10.1093/eurheartj/ehac262Ahn J., Kim H.J., Choi J.-I., Lee K.N., Shim J., Ahn H.S., et al. Effectiveness of beta-blockers depending on the 24 genotype of congenital long-QT syndrome: A meta-analysis. Aalto-Setala K, ed: PLoS 25 ONE 2017; 12: e0185680. DOI: 10.1371/journal.pone.0185680Ahn J., Kim H.J., Choi J.-I., Lee K.N., Shim J., Ahn H.S., et al. Effectiveness of beta-blockers depending on the 24 genotype of congenital long-QT syndrome: A meta-analysis. Aalto-Setala K, ed: PLoS 25 ONE 2017; 12: e0185680. DOI: 10.1371/journal.pone.0185680Школьникова М.А., Ильдарова Р.А. Современные подходы к лечению наследственных жизнеугрожающих аритмий у детей. Педиатрия им. Г.Н. Сперанского 2018; 97(3): 133–141.Shkolnikova M.A., Ildarova R.A. Modern approaches to hereditary life-threatening arrhythmias treatment in children. Pediatriya im. G.N. Speranskogo 2018; 97(3): 133–141. (in Russ.)Schwartz P.J., Priori S.G., Locati E.H., Napolitano C., Cantu F., Towbin J.A., et al. Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate: IMPLICATIONS for gene-specific therapy. Circulation 1995; 92: 3381–3386. DOI: 10.1161/01.cir.92.12.3381Schwartz P.J., Priori S.G., Locati E.H., Napolitano C., Cantu F., Towbin J.A., et al. Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate: IMPLICATIONS for gene-specific therapy. Circulation 1995; 92: 3381–3386. DOI: 10.1161/01.cir.92.12.3381Priori S.G., Napolitano C., Cantu F., Brown A.M., Schwartz P.J. Differential response to Na+ channel blockade, beta-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: 1009–1015. DOI: 10.1161/01.res.78.6.1009Priori S.G., Napolitano C., Cantu F., Brown A.M., Schwartz P.J. Differential response to Na+ channel blockade, beta-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: 1009–1015. DOI: 10.1161/01.res.78.6.1009Ruan Y., Liu N., Bloise R., Napolitano C., Priori S.G. Gating properties of SCN5A mutations and the response to mexiletine in long-QT syndrome type 3 patients. Circulation 2007; 116(10): 1137–1144. DOI: 10.1161/CIRCULATIONAHA.107.707877Ruan Y., Liu N., Bloise R., Napolitano C., Priori S.G. Gating properties of SCN5A mutations and the response to mexiletine in long-QT syndrome type 3 patients. Circulation 2007; 116(10): 1137–1144. DOI: 10.1161/CIRCULATIONAHA.107.707877Ildarova R.A., Shkolnikova M.A., Kharlap M., Bereznitskaya V., Kalinin L. Sodium-channel blockers might contribute to the prevention of ventricular tachycardia in patients with long QT syndrome type 2: a description of 4 cases. J Electrocardiol 2012; 45(3): 237–243. DOI: 10.1016/j.jelectrocard.2012.01.008Ildarova R.A., Shkolnikova M.A., Kharlap M., Bereznitskaya V., Kalinin L. Sodium-channel blockers might contribute to the prevention of ventricular tachycardia in patients with long QT syndrome type 2: a description of 4 cases. J Electrocardiol 2012; 45(3): 237–243. DOI: 10.1016/j.jelectrocard.2012.01.008Mazzanti A., Maragna R., Faragli A., Monteforte N., Bloise R., Memmi M., et al. Genespecific therapy with mexiletine reduces arrhythmic events in patients with long QT syndrome type 3. J Am Coll Cardiol 2016; 67: 1053–1058. DOI: 10.1016/j.jacc.2015.12.033Mazzanti A., Maragna R., Faragli A., Monteforte N., Bloise R., Memmi M., et al. Genespecific therapy with mexiletine reduces arrhythmic events in patients with long QT syndrome type 3. J Am Coll Cardiol 2016; 67: 1053–1058. DOI: 10.1016/j.jacc.2015.12.033Benhorin J., Taub R., Goldmit M., Kerem B., Kass R.S., Windman I., Medina A. Effects of flecainide in patients with new SCN5A mutation. Mutation specific therapy for long QT syndrome. Circulation 2000; 101: 1698–1706. DOI: 10.1161/01.cir.101.14.1698Benhorin J., Taub R., Goldmit M., Kerem B., Kass R.S., Windman I., Medina A. Effects of flecainide in patients with new SCN5A mutation. Mutation specific therapy for long QT syndrome. Circulation 2000; 101: 1698–1706. DOI: 10.1161/01.cir.101.14.1698Windle J.R., Getelka R.C., Moss A.J., Zareba W., Atkins D.L. Normalization of ventricular repolarization with flecainide in long QT syndrome patients with SCN5A: DeltaKPQ mutation. Ann Noninvasive Electrocardiol 2001; 6: 153–158. DOI: 10.1111/j.1542–474x.2001.tb00100.xWindle J.R., Getelka R.C., Moss A.J., Zareba W., Atkins D.L. Normalization of ventricular repolarization with flecainide in long QT syndrome patients with SCN5A: DeltaKPQ mutation. Ann Noninvasive Electrocardiol 2001; 6: 153–158. DOI: 10.1111/j.1542–474x.2001.tb00100.xChorin E., Hu D., Antzelevitch C., Hochstadt A., Belardinelli L., Zeltser D., et al. Ranolazine for Congenital Long-QT Syndrome Type III: Experimental and Long-Term Clinical Data. Circ Arrhythm Electrophysiol 2016; 9(10): e004370. DOI: 10.1161/CIRCEP.116.004370Chorin E., Hu D., Antzelevitch C., Hochstadt A., Belardinelli L., Zeltser D., et al. Ranolazine for Congenital Long-QT Syndrome Type III: Experimental and Long-Term Clinical Data. Circ Arrhythm Electrophysiol 2016; 9(10): e004370. DOI: 10.1161/CIRCEP.116.004370Chorin E., Taub R., Medina A., Flint N., Viskin S., Benhorin J. Long-term flecainide therapy in type 3 long QT syndrome. Europace 2018; 20(2): 370–376. DOI: 10.1093/europace/euw439Chorin E., Taub R., Medina A., Flint N., Viskin S., Benhorin J. Long-term flecainide therapy in type 3 long QT syndrome. Europace 2018; 20(2): 370–376. DOI: 10.1093/europace/euw439Hermida A., Gourraud J.B., Denjoy I., Fressart V., Kyndt F., Maltret A., et al. Type 3 long QT syndrome: Is the effectiveness of treatment with beta-blockers population-specific? Heart Rhythm 2024; 21(3): 313–320. DOI: 10.1016/j.hrthm.2023.11.007Hermida A., Gourraud J.B., Denjoy I., Fressart V., Kyndt F., Maltret A., et al. Type 3 long QT syndrome: Is the effectiveness of treatment with beta-blockers population-specific? Heart Rhythm 2024; 21(3): 313–320. DOI: 10.1016/j.hrthm.2023.11.007Veldkamp M.W., Wilders R., Baartscheer A., Zegers J.G., Bezzina C.R., Wilde A.A. Contribution of sodium channel mutations to bradycardia and sinus node dysfunction in LQT3 families. Circ Res 2003; 92(9): 976–983. DOI: 10.1161/01.RES.0000069689.09869.A8Veldkamp M.W., Wilders R., Baartscheer A., Zegers J.G., Bezzina C.R., Wilde A.A. Contribution of sodium channel mutations to bradycardia and sinus node dysfunction in LQT3 families. Circ Res 2003; 92(9): 976–983. DOI: 10.1161/01.RES.0000069689.09869.A8Schwartz P.J., Priori S.G., Cerrone M., Spazzolini C., Odero A., Napolitano C., et al. Left cardiac sympathetic denervation in the management of high-risk patients affected by the long QT syndrome. Circulation 2004; 109: 1826–1833. DOI: 10.1161/01.CIR.0000125523.14403.1EPSchwartz P.J., Priori S.G., Cerrone M., Spazzolini C., Odero A., Napolitano C., et al. Left cardiac sympathetic denervation in the management of high-risk patients affected by the long QT syndrome. Circulation 2004; 109: 1826–1833. DOI: 10.1161/01.CIR.0000125523.14403.1EPVaseghi M., Barwad P., Malavassi Corrales F.J., Tandri H., Mathuria N., Shah R., et al. Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias. J Am Coll Cardiol 2017; 69(25): 3070–3080. DOI: 10.1016/j.jacc.2017.04.035Vaseghi M., Barwad P., Malavassi Corrales F.J., Tandri H., Mathuria N., Shah R., et al. Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias. J Am Coll Cardiol 2017; 69(25): 3070–3080. DOI: 10.1016/j.jacc.2017.04.035Соколов С.Ф., Беляева М.М., Бакалов С.А., Голицын С.П. Лаппаконитина гидробромид и его пролонгированная форма при желудочковой экстрасистолии у больных без органической патологии сердца: эффективность и безопасность. Кардиология: Новости. Мнения. Обучение 2018; 2(17). URL: https://cyberleninka.ru/article/n/lappakonitina-gidrobromid-i-ego-prolongirovannaya-forma-pri-zheludochkovoy-ekstrasistolii-u-bolnyh-bez-organicheskoy-patologii-serdtsaSokolov S.F., Belyaeva M.M., Bakalov S.A., Golitsyn S.P. Lappaconitine hydrobromide and its prolonged form in ventricular extrasystole in patients without organic heart disease: efficacy and safety. Cardiology: News, Opinions, Training 2018; 2(17) (in Russ.) URL: https://cyberleninka.ru/article/n/lappakonitina-gidrobromid-i-ego-prolongirovannaya-forma-pri-zheludochkovoy-ekstrasistolii-u-bolnyh-bez-organicheskoy-patologii-serdtsa

The authors declare that there are no conflicts of interest present.