Twelve-Lead ECG, Holter Monitoring Parameters, and Genetic Testing in Brugada Syndrome: Insights from Analysis of Multigenerational Family with a History of Sudden Cardiac Arrest during Physical Activity

Paweł T Matusik; Piotr Bijak; Magdalena Kaźnica-Wiatr; Marek Karpiński; Patrycja S Matusik; Andrzej Maziarz; Piotr Podolec; Jacek Lelakowski

doi:10.3390/jcm12206581

Twelve-Lead ECG, Holter Monitoring Parameters, and Genetic Testing in Brugada Syndrome: Insights from Analysis of Multigenerational Family with a History of Sudden Cardiac Arrest during Physical Activity

J Clin Med. 2023 Oct 18;12(20):6581. doi: 10.3390/jcm12206581.

Authors

Paweł T Matusik^{1

2}, Piotr Bijak³, Magdalena Kaźnica-Wiatr⁴, Marek Karpiński⁵, Patrycja S Matusik^{6

7}, Andrzej Maziarz², Piotr Podolec^{1

4}, Jacek Lelakowski^{1

2}

Affiliations

¹ Institute of Cardiology, Faculty of Medicine, Jagiellonian University Medical College, 31-202 Kraków, Poland.
² Department of Electrocardiology, The John Paul II Hospital, 31-202 Kraków, Poland.
³ Cardiology Outpatient Clinic, The John Paul II Hospital, 31-202 Kraków, Poland.
⁴ Department of Cardiac and Vascular Diseases, The John Paul II Hospital, 31-202 Kraków, Poland.
⁵ Genetic Counselling Outpatient Clinic, The John Paul II Hospital, 31-202 Kraków, Poland.
⁶ Department of Diagnostic Imaging, University Hospital, 30-688 Kraków, Poland.
⁷ Chair of Radiology, Jagiellonian University Medical College, 31-501 Kraków, Poland.

Abstract

Brugada syndrome (BrS) is an arrhythmogenic disorder increasing the risk of syncopal episodes and sudden cardiac death. BrS usually runs through families with reduced penetrance and variable expression. We analyzed the multigenerational family of a patient who died after sudden cardiac arrest with post-mortem diagnosis of BrS. We analyzed clinical history, comprehensive arrhythmic risk, genetic findings, and additional tests, including electrocardiogram (ECG), detailed 24-hour Holter ECG results, and standard echocardiography findings, and followed up the patients in the ambulatory clinic. We analyzed a pedigree of 33 members of four generations of the family (19 male and 14 female patients). In this family, we identified 7 patients with BrS (median Modified Shanghai Score and Sieira model: 4.5 (4-6) and 1 (0-4) points, respectively), including both parents of the deceased patient, and 8 relatives with negative sodium channel blocker drug challenge test. Genetic testing revealed a novel mutation in sodium voltage-gated channel alpha subunit 5 (SCN5A) c.941A>G, (p.Tyr314Cys) inherited from the father of the proband. Patients with BrS were characterized by longer P-wave duration (120 (102-155) vs. 92.5 (88-110) ms, p = 0.013) and longer PR intervals (211.3 ±26.3 vs. 161.6 ± 18.9 ms, p = 0.001), along with more frequent positive aVR sign, but did not differ in terms of QRS duration or T-wave characteristics in resting ECGs. BrS patients were characterized by lower mean, minimal, and maximal (for all p ≤ 0.01) heart rates obtained from Holter ECG monitoring, while there was no difference in arrhythmias among investigated patients. Moreover, visual diurnal variability of ST segment changes and fragmented QRS complexes were observed in patients with BrS in Holter ECG monitoring. There were no major arrhythmic events during median follow-up of 68.7 months of alive BrS patients. These results suggest ECG features which may be associated with a diagnosis of BrS and indicate a novel SCN5A variant in BrS patients. Twelve-lead Holter ECG monitoring, with modified precordial leads placement, may be useful in BrS diagnostics and risk stratification in personalized medicine.

Keywords: Brugada syndrome; ECG; Holter ECG monitoring; atrioventricular conduction; diagnosis; electrocardiogram; family screening; genes; heart rate; next-generation sequencing.

Abstract

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