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March 24, 2025Journal of Cardiovascular ElectrophysiologyOpen Access

SCN5A pathogenic variants were independently associated with a significantly higher risk of cardiac events in patients with Brugada syndrome (OR 11.2).

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Why the study?

Interpretation and management of benign or variants of unknown clinical significance in SCN5A remain challenging in Brugada syndrome, prompting investigation into their relationship with clinical symptoms.

Does the presence of specific SCN5A variants affect the risk of cardiac events and clinical symptoms in patients with Brugada syndrome?

Population

239 patients diagnosed with BrS at Hiroshima University Hospital

Comparison

BrS patients with SCN5A variants vs those without

Design

Observational genetic and clinical association study

Key result

SCN5A pathogenic variants were independently associated with a significantly higher risk of cardiac events in patients with Brugada syndrome (OR 11.2).

Authors

SOSho OkamuraHOHidenori OchiMNMika Nakashima

Discussion

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Member takes

Overview

SCN5A pathogenic variants independently predict cardiac events in BrS; supports incorporating them into risk assessment while VUS prognostic value remains uncertain.

Study Design

Type

Observational (n=239)

Multicenter

No

Structured PICO

Does the presence of specific SCN5A variants affect the risk of cardiac events and clinical symptoms in patients with Brugada syndrome?

P
Population
239 predominantly male patients with Brugada syndrome were retrospectively evaluated to determine the association between SCN5A variants and cardiac events.
E
Exposure
Presence of SCN5A variants (pathogenic or variants of unknown clinical significance [VUS])
C
Comparator
Patients without SCN5A variants or with benign variants
O
Outcome
Cardiac events and clinical symptomshard clinical

Main Result

Odds Ratio: 11.2 (95% CI 1.5–227.4)

Absolute Event Rate: 85.7% vs 17.7%

p-value: p=0.037

SCN5A pathogenic variants are independent risk factors for cardiac events in Brugada syndrome, and signal-averaged ECG is useful for risk stratification in patients with variants of unknown significance.

Limitations

  • Retrospective study design
  • Single center study
  • Small sample size, particularly for patients with SCN5A VUS or pathogenic variants
  • Late potentials were evaluated from the results of only one signal-averaged ECG
  • Sequence analysis was performed only on the exon of the SCN5A gene, not fully evaluating introns

Cite This Study

Okamura et al. (2025) conducted an observational in Brugada syndrome (n=239). SCN5A pathogenic variants vs. No SCN5A variants was evaluated on Symptomatic Brugada syndrome (cardiac events) (OR 11.2, 95% CI 1.5-227.4, p=0.037). SCN5A pathogenic variants were independently associated with a significantly higher risk of cardiac events in patients with Brugada syndrome (OR 11.2).

synapsesocial.com/papers/6a9b75a59fa83f7ab06be8f8https://doi.org/10.1111/jce.16643
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