Unexplained cardiac arrest (idiopathic ventricular fibrillation): clinical and genetic characteristics

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Abstract

AIM: The study was to evaluate the clinical and genetic characteristics of inherited arrhythmias in patients who survived unexplained cardiac arrest.

MATERIALS AND METHODS: 20 patients (10 male and 10 female) aged 15 to 55 years (median age 36 [28; 44] years) with documented VT/VF on ECG were observed for 3 years. The clinical and instrumental study included registration of 12-lead ECG, 24-hour Holter ECG, genealogical history collection and family history of sudden cardiac death with ECG assessment of all family members, transthoracic echocardiography, 2D Speckle Tracking echocardiography and cardiac magnetic resonance imaging to exclude structural myocardial changes. 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 4 (20 %) of the 20 probands included in the study, likely pathogenic variants were identified (pathogenicity class IV), and in 7 (35 %) patients, variants with unknown clinical significance (pathogenicity class III) in 10 genes associated with channelopathies (KCNQ1, KCNH2, SCN5A, AKAP9, ANK2, SCN10А, RYR2) and cardiomyopathies (MYH7, JPH2, RBM20). Several genetic variants were found in 3 cases. No significant genetic changes were detected in 9 (45 %) probands. The clinical diagnosis was established during the follow-up period and was verified due to the genetic testing in 5 (25 %) patients. From their ECGs, a prolonged QTc > 460 ms was found in 1 patient, Brugada pattern in 2 individuals, and a shortening of QTc up to 323 ms in 1 proband. Subclinical structural changes associated with cardiomyopathies were revealed in 2 patients. In 15 (75 %) patients, it was unfeasible to establish a distinct clinical phenotype. In 6 (30 %) probands, the diagnosis was clarified due to detected genetic variants.

CONCLUSION: Clinical manifestations and diverse genetic variants have been studied in patients who have survived unexplained cardiac arrest. In the course of genotyping patients who suffered unexplained cardiac arrest, genetic changes associated with LQTS were detected in 30 % of cases, while the QTc in most cases did not exceed 440 ms, which makes it difficult to establish a diagnosis at an early stage before the development of life-threatening arrhythmic events. The data from our study confirm the idea that in patients with idiopathic ventricular fibrillation, who have suffered unexplained cardiac arrest, cardiac channelopathy or subclinical manifestations of cardiomyopathy are commonly the cause. This phenomenon imposes a need for genetic testing in this category of patients.

About the authors

Svetlana M. Komissarova

“Cardiology” State Institution Republican Scientific and Practical Centre

Email: kom_svet@mail.ru
ORCID iD: 0000-0001-9917-5932
SPIN-code: 8023-5308

MD, Dr. Sci. (Med.), professor

Belarus, Minsk

Natalya N. Chakova

Institute of Genetics and Cytology of Belarus National Academy of Sciences

Email: chaknat@mail.ru
ORCID iD: 0000-0003-4721-9109
SPIN-code: 5682-1497

Cand. Sci. (Biol.)

Belarus, Minsk

Nadiia M. Rineiska

“Cardiology” State Institution Republican Scientific and Practical Centre

Author for correspondence.
Email: nadya.rin@gmail.com
ORCID iD: 0000-0002-1986-1367
SPIN-code: 2782-2270

MD, Cand. Sci. (Med.), researcher, Laboratory of Chronic Heart Failure

Belarus, Minsk

Svetlana S. Niyazova

Institute of Genetics and Cytology of Belarus National Academy of Sciences

Email: kruglenko_sveta@tut.by
ORCID iD: 0000-0002-3566-7644
SPIN-code: 1093-1793

junior researcher

Belarus, Minsk

Tatyana V. Dolmatovich

Institute of Genetics and Cytology of Belarus National Academy of Sciences

Email: t.dolmatovich@igc.by
ORCID iD: 0000-0001-7562-131X

Cand. Sci. (Biol.)

Belarus, Minsk

Veronika Ch. Barsukevich

“Cardiology” State Institution Republican Scientific and Practical Centre

Email: barsukevich.v@gmail.com
ORCID iD: 0000-0002-5180-7950
SPIN-code: 9413-7121

MD, Cand. Sci. (Med.)

Belarus, Minsk

Larisa I. Plashchinskaya

“Cardiology” State Institution Republican Scientific and Practical Centre

Email: lario2001@mail.ru
ORCID iD: 0000-0001-8815-3543
SPIN-code: 2666-1270

MD, Cand. Sci. (Med.)

Belarus, Minsk

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Supplementary files

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1. JATS XML
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2. Fig. 1. 12-lead ECG of proband 873c. Prolonged QTc interval — 482 ms, ventricular premature beat (red ellipse)

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3. Fig. 2. 24-hour Holter ECG of patient 829. Ventricular premature beats and paroxysms of nonsustained ventricular tachycardia

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4. Fig. 3. Pedigree of the proband 799’s family with mutations p.Glu48Lys in SCN5A gene and p.Ala143Thr in JUP gene. The proband is indicated by an arrow. Clinically affected individuals are indicated by the shaded symbols

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5. Fig. 4. 12-lead ECG of patient 732 with Brugada pattern type 1 (“coved”), showing a “vaulted” ST elevation of more than 2 mm in V1–V2, followed by a negative T-wave

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6. Fig. 5. 24-hour Holter ECG of patient 642с. Ventricular premature beat, R on T pattern (red asterisk), initiated a paroxysm of ventricular tachycardia with transformation into ventricular fibrillation

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7. Fig. 6. 2D Speckle Tracking Echocardiography of patient 816. Left ventricular global longitudinal strain — 13,6 %

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