Cardiac ArrhythmiasCardiac ArrhythmiasCardiac ArrhythmiasCardiac Arrhythmias2782-42842782-4233Eco-Vector56818010.17816/cardar568180Case reportsКлинические случаиResearch ArticleClinical and genetic characterization of patients with catecholaminergic polymorphic ventricular tachycardia: a case seriesКлиническая и генетическая характеристика пациентов с катехоламинергической полиморфной желудочковой тахикардией (серия случаев)https://orcid.org/0000-0001-9917-59328023-5308KomissarovaSvetlana M.КомиссароваСветлана Михайловна
Belarus

MD, Dr. Sci. (Med.), Associate Professor, chief researcher, Laboratory of Chronic Heart Failure, State Institution Republican Scientific and Practical Centre “Cardiology”

д-р мед. наук, доцент, главный научный сотрудник лаборатории хронической сердечной недостаточности ГУ «РНПЦ «Кардиология»

kom_svet@mail.ruhttps://orcid.org/0000-0002-1986-13672782-2270RineiskaNadiia M.РинейскаяНадежда Михайловна
Belarus

Cand. Sci. (Med.), junior researcher, Laboratory of Chronic Heart Failure, State Institution Republican Scientific and Practical Centre “Cardiology”

канд. мед. наук, младший научный сотрудник лаборатории хронической сердечной недостаточности ГУ «РНПЦ „Кардиология”»

nadya.rin@gmail.comhttps://orcid.org/0000-0003-4721-91095682-1497ChakovaNatalya N.ЧаковаНаталья Николаевна
Belarus

Cand. Sci. (Biol.), PhD, leading researcher, Laboratory of Animal Genetics, Institute of Genetics and Cytology of Belarus National Academy of Sciences

канд. биол. наук, ведущий научный сотрудник лаборатории генетики животных ГНУ «Институт генетики и цитологии НАН Беларуси»

chaknat@mail.ruhttps://orcid.org/0000-0002-3566-76441093-1793NiyazovaSvetlana S.НиязоваСветлана Сергеевна
Belarus

junior researcher, Laboratory of Animal Genetics, Institute of Genetics and Cytology of Belarus National Academy of Sciences

младший научный сотрудник лаборатории генетики животных ГНУ «Институт генетики и цитологии НАН Беларуси»

kruglenko_sveta@tut.byhttps://orcid.org/0000-0001-8815-35432666-1270PlashchinskayaLarisa I.ПлащинскаяЛариса Иосифовна
Belarus

Cand. Sci. (Med.), leading researcher, Laboratory of Cardiac Arrhythmias, State Institution Republican Scientific and Practical Centre “Cardiology”

канд. мед. наук, ведущий научный сотрудник лаборатории нарушений сердечного ритма ГУ «РНПЦ «Кардиология»

lario2001@mail.ruhttps://orcid.org/0000-0002-5180-79509413-7121BarsukevichVeronika Ch.БарсукевичВероника Чеславовна
Belarus

Cand. Sci. (Med.), leading researcher, Laboratory of Cardiac Arrhythmias, State Institution Republican Scientific and Practical Centre “Cardiology”

канд. мед. наук, ведущий научный сотрудник лаборатории нарушений сердечного ритма ГУ «РНПЦ «Кардиология»

barsukevich.v@gmail.comhttps://orcid.org/0000-0002-7162-37371617-8500PodpalovaOlga V.ПодпаловаОльга Владиславовна
Belarus

Cand. Sci. (Med.), researcher, Laboratory of Cardiac Arrhythmias, State Institution Republican Scientific and Practical Centre “Cardiology”

канд. мед. наук, научный сотрудник лаборатории нарушений сердечного ритма ГУ «РНПЦ «Кардиология»

olgapodpalova22@gmail.comState Institution Republican Scientific and Practical Centre “Cardiology”Республиканский научно-практический центр «Кардиология»Institute of Genetics and Cytology of Belarus National Academy of SciencesИнститут генетики и цитологии НАН Беларуси31102023271120233327400908202303102023Copyright ©; 2023, Eco-VectorCopyright ©; 2023, Эко-ВекторCopyright ©; 2023,2023Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0https://journals.eco-vector.com/cardar/article/view/568180

AIM: of the study was to evaluate the clinical and genetic characteristics, including the development of adverse events and outcomes in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT).

MATERIALS AND METHODS: The clinical phenotype of eight patients with CPVT, two of whom were relatives of probands, was observed over 4 years. The clinical and instrumental study included ECG-12, 24-hour Holter ECG monitoring, genealogical history collection and family history of sudden cardiac death (SCD), transthoracic echocardiography and cardiac magnetic resonance imaging to detect structural myocardial changes, electrophysiologic study according to indications, and ICD monitoring. High-throughput sequencing (NGS) was utilized to search for mutations in genes linked to the onset of channelopathies and other inherited rhythm disorders.

RESULTS: In 8 patients, nucleotide variants of pathogenicity classes III-V were identified according to the ACMG (2015) criteria in the RYR2 gene associated with CPVT. Pathogenic (IV-V class) and likely pathogenic (IV class) mutations in the RYR2 gene were found in 6 (75%) probands, variants with uncertain clinical significance (VUS, class III) were found in 2 patients. At the time of diagnosis, transient QTc interval prolongation of more than 480 ms was detected in 4 (50%) patients; bradycardia less than 54 beats/min — in 2 (25%) patients, sequences of supraventricular tachycardia and ventricular tachyarrhythmia — in 2 (25%) patients. The most severe form of the disease with marked clinical manifestations and an episode of clinical death with subsequent resuscitation, as well as a transient QTc interval prolongation exceeding 500 ms was observed in patients with mutations c.11814C > A (p.Ser3938Arg, rs794728704); c.463G > A (p.Gly155Arg) and c.14876G > A (p.Arg4959Gln, rs794728811) in the RYR2 gene. Three (37.5%) patients underwent ICD implantation; one for primary SCD prevention and two for secondary prevention.

CONCLUSION: In this study, the spectrum of clinical manifestations in patients with genetically confirmed CPVT was examined. The findings highlight transient QTc interval extensions, significant sinus bradycardia, and sequences of supraventricular tachyarrhythmias, which can escalate into life-threatening ventricular tachyarrhythmias in CPVT patients.

Цель исследования — оценить клиническую и генетическую характеристику, включая развитие неблагоприятных событий и исходов у пациентов с катехоламинергической полиморфной желудочковой тахикардией (КПЖТ).

Материалы и методы. Обследовано 8 пациентов с КПЖТ, двое из которых были родственниками пробандов, наблюдаемых в течение 4 лет. Клинико-инструментальное исследование включало регистрацию электрокардиограммы в 12 отведениях, суточное электрокардиографическое мониторирование, сбор генеалогического анамнеза и выявление случаев внезапной сердечной смерти в семье или наличия семейной формы заболевания, эхокардиографическое исследование и магнитно-резонансную томографию сердца для исключения структурных изменений миокарда, проведение эндокардиального электрофизиологического исследования по показаниям, мониторинг имплантируемого кардиовертера-дефибриллятора. Поиск мутаций в кодирующих последовательностях генов, ассоциированных с развитием каналопатий и других наследственных нарушений ритма, проводили методом высокопроизводительного секвенирования.

Результаты. У 8 пациентов выявлены нуклеотидные варианты III–V классов патогенности согласно критериям ACMG (2015) в гене RYR2, ассоциированным с КПЖТ. У 6 (75 %) пробандов обнаружены диагностически значимые мутации (IV–V класса патогенности) в гене RYR2, у 2 пациентов были обнаружены варианты с неопределенной клинической значимостью (VUS, III класс). На момент постановки диагноза транзиторное удлинение интервала QTc более 480 мс было выявлено у 4 (50 %) пациентов; брадикардия менее 54 уд/мин — у 2 (25 %), суправентрикулярная тахикардия, которая сменялась желудочковой тахиаритмией — у 2 (25 %) пациентов. Наиболее тяжелая форма заболевания с выраженными клиническими проявлениями и эпизодом клинической смерти с последующими реанимационными мероприятиями, а также транзиторным удлинением интервала QTc, превышающим 500 мс, наблюдалось у пациентов с мутациями c.11814C > A (p.Ser3938Arg, rs794728704); c.463G > A (p.Gly155Arg) и c.14876G > A (p.Arg4959Gln, rs794728811) в гене RYR2. Имплантация кардиовертера-дефибриллятора потребовалась 3 (37,5 %) пациентам, в том числе 1 пациенту с целью первичной профилактики ВСС и 2 (25 %) — с целью вторичной профилактики.

Заключение. В настоящем исследовании изучен спектр клинических проявлений у пациентов с генетически подтвержденной КПЖТ. Транзиторное удлинение интервала QTc, выраженная синусовая брадикардия и суправентрикулярная тахиаритмия, сменяющиеся жизнеугрожающей желудочковой тахиаритмией с высокой частотой представлены у пациентов с КПЖТ.

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