Related Experiment Video
Updated: Jan 20, 2026
In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
Sudden cardiac death in families with premature cardiovascular disease
Caroline Bruikman1, Maurice W J de Ronde1,2, Ahmed Amin3
1Department of Vascular Medicine, Amsterdam UMC, Amsterdam, The Netherlands.
Insights
Brugada syndrome is common in families with sudden cardiac death (SCD) and premature atherosclerosis (PAS). While SCN5A mutations are rare in these families, genetic predisposition to arrhythmias may still cause SCD at older ages.
Area of Science:
- Cardiology
- Genetics
- Inherited Arrhythmia Syndromes
Background:
- Sudden cardiac death (SCD) in families with premature atherosclerosis (PAS) is often linked to myocardial infarction-induced arrhythmias.
- Non-ischaemic inherited conditions can also predispose to lethal arrhythmias.
Purpose of the Study:
- To investigate the prevalence of Brugada syndrome in families experiencing SCD with premature atherosclerosis.
- To determine if Brugada syndrome is a significant factor in SCD within these families.
Main Methods:
- Retrospective analysis of patients undergoing Ajmaline testing for Brugada syndrome screening.
- Cohort divided into groups with and without a family history of PAS.
- Screening for SCN5A mutations in individuals with positive Ajmaline tests.
Main Results:
- Brugada syndrome prevalence was similar in families with SCD and PAS (22%) compared to those with SCD alone (19%).
- Families with SCD and PAS had more SCD cases (2.34 vs 1.63) occurring at an older age (42 vs 36 years).
- SCN5A mutation prevalence was lower in families with SCD and PAS (3% vs 18%).
Conclusions:
- Brugada syndrome is similarly prevalent in families with SCD and PAS as in those with SCD alone.
- SCD in families with PAS may stem from genetic arrhythmia predispositions other than SCN5A mutations.
- Screening for Brugada syndrome in families with SCD and PAS is recommended.
Objective:
Sudden cardiac death (SCD) in families with premature atherosclerosis (PAS) is generally attributed to lethal arrhythmias during myocardial infarction. Yet, such arrhythmias may also arise from non-ischaemic inherited susceptibility. We aimed to test the hypothesis that Brugada syndrome is prevalent among families with PAS in which SCD occurred.
Methods:
We investigated all patients who underwent Ajmaline testing to screen them for Brugada syndrome because of unexplained familial SCD in the Amsterdam University Medical Centers between 2004 and 2017. We divided the cohort into two groups based on a positive family history for PAS. All individuals with a positive Ajmaline test were screened for SCN5A-mutation.
Results:
In families with SCD and PAS, the prevalence of positive Ajmaline test was similar to families with SCD alone (22% vs 19%). The number of SCD cases in families with SCD and PAS was higher (2.34 vs 1.63, p<0.001) and SCD occurred at older age in families with SCD and PAS (42 years vs 36 years, p<0.001), while the prevalence of SCN5A mutations was lower (3% vs 18%, p<0.05).
Conclusions:
Brugada syndrome has a similar prevalence in families with SCD and PAS as in families with SCD alone, although SCD in families with SCD and PAS occurs in more family members and at older age, while SCN5A mutations in these families are rare. This suggests that the SCD occurring in families with PAS could be related to an underlying genetic predisposition of arrhythmias, with a different genetic origin. It could be considered to screen families with SCD and PAS for Brugada syndrome.
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