Facilitatory and inhibitory effects of SCN5A mutations on atrial fibrillation in Brugada syndrome

Amin, Ahmad S.; Boink, Gerard J.J.; Atrafi, Florence; Spanjaart, Anne M.; Asghari-Roodsari, Alaleh; Molenaar, Remco J.; Wilde, Arthur A.M.; Tan, Hanno L.

doi:10.1093/europace/eur011

Cited by 37 publications

(30 citation statements)

References 25 publications

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“…Toh et al 53 found significantly prolonged atrial conduction times and increased left atrial volumes in Brugada patients with SCN5A mutations compared with those without. Similar to Amin et al's 28 findings, however, left atrial diameter was not significantly different between the two groups, suggesting that left atrial volume may be a more accurate measurement of asymmetric remodeling of the atrium. Increased atrial structural remodeling in SCN5A loss‐of‐function mutation carriers compared with noncarriers is also consistent with the observation by Amin et al 28 that the prevalence of persistent AF tended to be higher in the former group.…”

Section: Pathophysiology and Predictors Of Af In Brssupporting

confidence: 85%

“…Similar to Amin et al's 28 findings, however, left atrial diameter was not significantly different between the two groups, suggesting that left atrial volume may be a more accurate measurement of asymmetric remodeling of the atrium. Increased atrial structural remodeling in SCN5A loss‐of‐function mutation carriers compared with noncarriers is also consistent with the observation by Amin et al 28 that the prevalence of persistent AF tended to be higher in the former group. This view of the substrate is supported by experiments in mice with a single null allele of the SCN5A gene, demonstrating age‐related development of myocardial fibrosis and progressive slowing of atrial and ventricular conduction velocities.…”

Section: Pathophysiology and Predictors Of Af In Brssupporting

confidence: 85%

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Atrial fibrillation in Brugada syndrome: Current perspectives

Vlachos

Mascia

Martin

et al. 2020

Cardiovasc electrophysiol

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The incidence of atrial fibrillation (AF) in Brugada syndrome (BrS) has been reported at between 9% and 53% by different series, but the true prevalence is unknown. However, AF may be the presenting feature in some patients. The underlying mechanisms for AF may be a combination of multiple factors, genetic or acquired, that may impact upon autonomic function, atrial structure, and conduction velocities or other unknown factors. The presence of AF has been associated with a more malignant course, with a greater incidence of syncope and ventricular arrhythmias, thus acting as marker of more advanced disease. Regarding the management of patients with AF, antiarrhythmic drugs effective in preventing malignant arrhythmias in BrS such as quinidine or invasive treatment with pulmonary vein isolation (PVI) may be useful in AF treatment. In this review, we aim to present the current perspectives regarding the genetics, pathophysiology, management, and prognosis of AF in patients with BrS.

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Section: Pathophysiology and Predictors Of Af In Brssupporting

confidence: 85%

Section: Pathophysiology and Predictors Of Af In Brssupporting

confidence: 85%

Atrial fibrillation in Brugada syndrome: Current perspectives

Vlachos

Mascia

Martin

et al. 2020

Cardiovasc electrophysiol

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“…BrS has been associated with an increased risk for AF. Amin et al showed that loss of function SCN5A mutations in BrS are associated with intra-atrial conduction slowing, a substrate for AF maintenance, and decreased atrial ectopic activity, which may inhibit the trigger for AF initiation [62]. Similar to what is observed in LQT-3, gain of function mutations result in increased late sodium current and prolongation of the action potential duration thereby triggering early afterdepolarizations, not only in ventricular cardiomyocytes but also in atrial cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

Reduced Penetrance and Variable Expression of SCN5A Mutations and the Importance of Co-inherited Genetic Variants: Case Report and Review of the Literature

Robyns

Nuyens

Casteren

et al. 2014

Indian Pacing and Electrophysiology Journal

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Mutations in the SCN5A gene are responsible for multiple phenotypical presentations including Brugada syndrome, long QT syndrome, progressive familial heart block, sick sinus syndrome, dilated cardiomyopathy, lone atrial fibrillation and multiple overlap syndromes. These different phenotypic expressions of a mutation in a single gene can be explained by variable expression and reduced penetrance. One of the possible explanations of these phenomena is the co-inheritance of genetic variants. We describe a family where the individuals exhibit a compound heterozygosity in the SCN5A gene including a mutation (R1632H) and a new variant (M858L). Individuals with both the mutation and new variant present with a more severe phenotype including spontaneous atrial tachyarrhythmia at young age. We give an overview of the different phenotypes of "SCN5A disease" and discuss the importance of co-inherited genetic variants in the expression of SCN5A disease.

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“…Loss-of-function mutations in SCN5A diminish the magnitude of the inward sodium current (I Na ) and can clinically manifest as progressive cardiac conduction disorders (PCCD) (1,2) or as arrhythmic syndromes, which include Brugada syndrome (BrS) (3) and atrial fibrillation (4). In addition to electrophysiological dysfunction, SCN5A mutations are also associated with myocardial fibrosis that can be regionally localized or diffuse, manifesting as a global cardiomyopathy (5).…”

Section: Introductionmentioning

confidence: 99%