Possible proarrhythmic stimuli in Y4734C-RYR2 variant
associated with idiopathic ventricular fibrillation

a 2023

Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation

BÉBAROVÁ, Markéta; Olga ŠVECOVÁ; Martin KRÁL; Štefan ZELENÁK; Jiří PACHERNÍK et. al.

Basic information

Original name

Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation

Authors

BÉBAROVÁ, Markéta (203 Czech Republic, guarantor, belonging to the institution); Olga ŠVECOVÁ (203 Czech Republic, belonging to the institution); Martin KRÁL (203 Czech Republic, belonging to the institution); Štefan ZELENÁK (703 Slovakia, belonging to the institution); Jiří PACHERNÍK (203 Czech Republic); Tomáš BÁRTA (203 Czech Republic, belonging to the institution); Samuel LIETAVA (703 Slovakia, belonging to the institution); Iva SYNKOVÁ (203 Czech Republic); Jana ZÍDKOVÁ (203 Czech Republic, belonging to the institution) and Tomáš NOVOTNÝ (203 Czech Republic)

Edition

47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology, 2023

Other information

Language

English

Type of outcome

Conference abstract

Field of Study

30201 Cardiac and Cardiovascular systems

Country of publisher

Denmark

Confidentiality degree

is not subject to a state or trade secret

RIV identification code

RIV/00216224:14110/23:00134665

Organization unit

Faculty of Medicine

Keywords in English

proarrhythmic stimuli; Y4734C-RYR2; idiopathic ventricular fibrillation

Abstract

In the original language

Background: The RYR2 variant Y4734C was identified in a patient suffering from idiopathic ventricular fibrillation. To investigate its pathogenic character, functional analysis has been started. Here, we present the pilot data on potential proarrhythmic stimuli in this variant. Material and Methods: The recordings of the spontaneous electrical activity of Y4734C-RYR2 (Y4734C) and unrelated healthy control (WT) hiPSC-CM (5 and 3 measured samples, respectively) were performed using the multielectrode array (MEA) technique at 37°C. Besides the evaluation of the cycle length (CL), the short-term variability of CL (STVCL) was calculated. Since some data were not normally distributed, the median ± interquartile range (IQR) and non-parametric statistical tests were used. Results: In the control Tyrode solution (5 mM K+ Tyr), CL significantly differed in WT and Y4734C (1.36±0.22 and 0.53±0.14 s, respectively; P  0.05), but STVCL was the same (8.0 ms). Subsequently, the possible proarrhythmic impact of additively applied hypokalaemia (3 mM K+), β-adrenergic stimulation (1 µM isoprenaline), and high temperature (40°C) was tested. In Y4734C, STVCL slightly decreased in 3 mM K+ and then gradually increased when 1 µM isoprenaline was added, first alone and later in combination with 40°C (4.1, 22.4, and 39.3 ms, respectively; P  0.05). In contrast, STVCL in WT was considerably higher only in the concurrent presence of 3 mM K+ and 1 µM isoprenaline (30.7 ms vs. 13.3 ms in 3 mM K+ and 9.3 ms in the presence of all the stimuli; P  0.05). Conclusions: The pilot data showed non-significant differences between the effect of three selected proarrhythmic stimuli, namely hypokalaemia, β-adrenergic stimulation, and high temperature, on the spontaneous electrical activity of WT- and Y4734C-RYR2 hiPSC-CM.

Links

MUNI/A/1343/2022, interní kód MU

Name: Zátěže kardiovaskulárního systému od A po Z

Investor: Masaryk University, Loads on the cardiovascular system from A to Z

NU22-02-00348, research and development project

Name: Funkční hodnocení genetických variant u případů klinicky „skutečné“ idiopatické fibrilace komor: in vitro a in silico modelování s cílem odhalit arytmogenní mechanismus

Investor: Ministry of Health of the CR, Subprogram 1 - standard

Cite

BÉBAROVÁ, Markéta; Olga ŠVECOVÁ; Martin KRÁL; Štefan ZELENÁK; Jiří PACHERNÍK; Tomáš BÁRTA; Samuel LIETAVA; Iva SYNKOVÁ; Jana ZÍDKOVÁ and Tomáš NOVOTNÝ. Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation. In 47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology. 2023.

@proceedings{2334064,
   author = {Bébarová, Markéta and Švecová, Olga and Král, Martin and Zelenák, Štefan and Pacherník, Jiří and Bárta, Tomáš and Lietava, Samuel and Synková, Iva and Zídková, Jana and Novotný, Tomáš},
   booktitle = {47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology},
   keywords = {proarrhythmic stimuli; Y4734C-RYR2; idiopathic ventricular fibrillation},
   language = {eng},
   title = {Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation},
   year = {2023}
}

TY  - CONF
ID  - 2334064
AU  - Bébarová, Markéta - Švecová, Olga - Král, Martin - Zelenák, Štefan - Pacherník, Jiří - Bárta, Tomáš - Lietava, Samuel - Synková, Iva - Zídková, Jana - Novotný, Tomáš
PY  - 2023
TI  - Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation
KW  - proarrhythmic stimuli
KW  - Y4734C-RYR2
KW  - idiopathic ventricular fibrillation
N2  - Background: The RYR2 variant Y4734C was identified in a patient suffering from idiopathic ventricular fibrillation. To investigate its pathogenic character, functional analysis has been started. Here, we present the pilot data on potential proarrhythmic stimuli in this variant. Material and Methods: The recordings of the spontaneous electrical activity of Y4734C-RYR2 (Y4734C) and unrelated healthy control (WT) hiPSC-CM (5 and 3 measured samples, respectively) were performed using the multielectrode array (MEA) technique at 37°C. Besides the evaluation of the cycle length (CL), the short-term variability of CL (STVCL) was calculated. Since some data were not normally distributed, the median ± interquartile range (IQR) and non-parametric statistical tests were used. Results: In the control Tyrode solution (5 mM K+ Tyr), CL significantly differed in WT and Y4734C (1.36±0.22 and 0.53±0.14 s, respectively; P  0.05), but STVCL was the same (8.0 ms). Subsequently, the possible proarrhythmic impact of additively applied hypokalaemia (3 mM K+), β-adrenergic stimulation (1 µM isoprenaline), and high temperature (40°C) was tested. In Y4734C, STVCL slightly decreased in 3 mM K+ and then gradually increased when 1 µM isoprenaline was added, first alone and later in combination with 40°C (4.1, 22.4, and 39.3 ms, respectively; P  0.05). In contrast, STVCL in WT was considerably higher only in the concurrent presence of 3 mM K+ and 1 µM isoprenaline (30.7 ms vs. 13.3 ms in 3 mM K+ and 9.3 ms in the presence of all the stimuli; P  0.05). Conclusions: The pilot data showed non-significant differences between the effect of three selected proarrhythmic stimuli, namely hypokalaemia, β-adrenergic stimulation, and high temperature, on the spontaneous electrical activity of WT- and Y4734C-RYR2 hiPSC-CM.
ER  -

BÉBAROVÁ, Markéta; Olga ŠVECOVÁ; Martin KRÁL; Štefan ZELENÁK; Jiří PACHERNÍK; Tomáš BÁRTA; Samuel LIETAVA; Iva SYNKOVÁ; Jana ZÍDKOVÁ and Tomáš NOVOTNÝ. Possible proarrhythmic stimuli in Y4734C-RYR2 variant associated with idiopathic ventricular fibrillation. In \textit{47th Meeting of the European Working Group on Cardiac Cellular Electrophysiology}. 2023.

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