Gender Differences in Prognosis and Risk Stratification of Brugada Syndrome: A Pooled Analysis of 4,140 Patients From 24 Clinical Trials

Yuan, Mengchen; Tian, Chao; Li, Xinye; Yang, Xinyu; Yang, Yihan; Liu, Nian; Kusano, Kengo; Barajas-Martínez, Héctor; Hu, Dan; Shang, Hongcai; Gao, Yonghong; Xing, Yanwei

doi:10.3389/fphys.2018.01127

Cited by 20 publications

(20 citation statements)

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“…The search strategies contained a combination of two search terms by using the Boolean operator “and” (ie, Brugada syndrome and SCN5A ). In addition, we further searched the reference lists of previous meta‐analyses to identify additional studies. The full electronic search strategy is shown in Table S1.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, we further searched the reference lists of previous metaanalyses 6,[19][20][21] to identify additional studies. The full electronic search strategy is shown in Table S1.…”

Section: Literature Search and Inclusion Criteriamentioning

confidence: 99%

“…Thereinto, BrS is a rare heritable arrhythmia syndrome which is characterized by a coved‐type ST‐segment elevation in the right precordial leads on electrocardiogram (ECG), it has been suggested that Brugada syndrome increased the risk of sudden cardiac death (SCD) . Most BrS patients are males, who have a higher risk of arrhythmic events than females . While more than 20 BrS‐associated genes have been identified, only SCN5A has sufficient genetic evidence suggesting that it is a genetic cause of disease, accounting for 20%‐25% of BrS cases, Despite these advances, genetic testing is still not recommended for BrS risk stratification .…”

Section: Introductionmentioning

confidence: 99%

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Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta‐analysis

et al. 2019

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Whether the presence of SCN5A mutation is a predictor of BrS risk remains controversial, and patient selection bias may have weakened previous findings. Therefore, we performed this study to clarify the clinical characteristics and outcomes of BrS probands with SCN5A mutations. We systematically retrieved eligible studies published through October 2018. A total of 17 studies enrolling 1780 BrS patients were included. Overall, our results found that compared with BrS patients without SCN5A mutations, patients with SCN5A mutations exhibited a younger age at the onset of symptoms and higher rate of the spontaneous type-1 electrocardiogram pattern, more pronounced conduction or repolarization abnormalities, and increased atrial vulnerability. In addition, the presence of SCN5A mutations was associated with an elevated risk of major arrhythmic events in both Asian (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.07-3.11; P = .03) and Caucasian (OR = 2.24, 95% CI 1.02-4.90; P = .04) populations. In conclusions, patients with SCN5A mutations exhibit more pronounced electrophysiological defects and more severe prognosis.Clinicians should be cautious when utilizing genetic testing for risk stratification or treatment guidance before determining whether the causal relationship regarding SCN5A mutation status is an independent predictor of risk.

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Section: Methodsmentioning

confidence: 99%

“…In addition, we further searched the reference lists of previous metaanalyses 6,[19][20][21] to identify additional studies. The full electronic search strategy is shown in Table S1.…”

Section: Literature Search and Inclusion Criteriamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta‐analysis

et al. 2019

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“…In Southeast Asia, BrS seems to affect almost exclusively male adults [7]. Pooled analyses indicated that a spontaneous type 1 ECG is an independent risk factor for SCD in males, but not in females, and that male patients are at higher risk of arrhythmic events [8,9]. However, BrS is found throughout the world and in both genders, to whom studies have shown it is transmitted equally [5] as an autosomal dominant disease with incomplete penetrance [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Brugada Syndrome: Oligogenic or Mendelian Disease?

Monasky

Micaglio

Ciconte

et al. 2020

IJMS

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Brugada syndrome (BrS) is diagnosed by a coved-type ST-segment elevation in the right precordial leads on the electrocardiogram (ECG), and it is associated with an increased risk of sudden cardiac death (SCD) compared to the general population. Although BrS is considered a genetic disease, its molecular mechanism remains elusive in about 70-85% of clinically-confirmed cases. Variants occurring in at least 26 different genes have been previously considered causative, although the causative effect of all but the SCN5A gene has been recently challenged, due to the lack of systematic, evidence-based evaluations, such as a variant's frequency among the general population, family segregation analyses, and functional studies. Also, variants within a particular gene can be associated with an array of different phenotypes, even within the same family, preventing a clear genotype-phenotype correlation. Moreover, an emerging concept is that a single mutation may not be enough to cause the BrS phenotype, due to the increasing number of common variants now thought to be clinically relevant. Thus, not only the complete list of genes causative of the BrS phenotype remains to be determined, but also the interplay between rare and common multiple variants. This is particularly true for some common polymorphisms whose roles have been recently re-evaluated by outstanding works, including considering for the first time ever a polygenic risk score derived from the heterozygous state for both common and rare variants. The more common a certain variant is, the less impact this variant might have on heart function. We are aware that further studies are warranted to validate a polygenic risk score, because there is no mutated gene that connects all, or even a majority, of BrS cases. For the same reason, it is currently impossible to create animal and cell line genetic models that represent all BrS cases, which would enable the expansion of studies of this syndrome. Thus, the best model at this point is the human patient population. Further studies should first aim to uncover genetic variants within individuals, as well as to collect family segregation data to identify potential genetic causes of BrS.

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“…Brugada syndrome is about 7-10 times more prevalent in men, and male gender is associated with a higher incidence of ventricular arrhythmias and SCD at diagnosis and follow-up. 17,37,38 However, despite the less favourable prognosis generally observed in men, gender alone may not be an independent prognostic indicator and the majority of men remain asymptomatic. 17,19 Risk stratification in women with Brugada syndrome has been more challenging as most studies have mainly consisted of male participants.…”

Section: Gender-specific Riskmentioning

confidence: 99%