Fibrosis and Conduction Abnormalities as Basis for Overlap of Brugada Syndrome and Early Repolarization Syndrome

Boukens, Bastiaan J.; Potse, Mark; Coronel, Ruben

doi:10.3390/ijms22041570

Cited by 14 publications

(10 citation statements)

References 56 publications

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“…In addition, RT is the summation of local activation time and local duration of repolarization, and in our ex vivo and in silico experiments, we studied heterogeneity in repolarization duration. RT heterogeneity may also result from heterogeneity in activation, for example, due to zigzag conduction through small conducting channels within the permanently inexcitable scar ( 24 ), sodium channel abnormalities ( 25 ), or post-repolarization refractoriness ( 26 ). Considering these various sources of “excitability heterogeneity” would allow us to extend our reasoning to other myocardial substrates or even arrhythmias of other electromechanical organs.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive detection of spatiotemporal activation-repolarization interactions that prime idiopathic ventricular fibrillation

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Noninvasive detection of spatiotemporal activation-repolarization interactions that prime idiopathic ventricular fibrillation

et al. 2021

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“…There have been several excellent studies regarding the overlap between BrS and other cardiac pathologies, including early repolarization syndrome (5), arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) (6-9), progressive cardiac conduction defect (Lenègre syndrome) (10,11), LQTS (12)(13)(14), Wolff-Parkinson-White (15,16), hypertrophic cardiomyopathy (17,18), atrial flutter (19), and atrial fibrillation (20)(21)(22)(23). Therefore, whatever mechanisms that ultimately lead to the development of the BrS ECG pattern may also be involved in other pathways that result in other cardiac pathologies.…”

Section: Brugada Syndrome and Cardiac Disorders Overlapmentioning

confidence: 99%

“…The typical symptoms of BrS are syncope and cardiac arrest due to ventricular fibrillation (VF) or ventricular tachycardia (VT), in the absence of overt cardiac structural changes, typically between 30 and 50 years of age (3,4). BrS has been associated with several other cardiac disorders, such as early repolarization syndrome (5), arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) (6)(7)(8)(9), progressive cardiac conduction defect (Lenègre syndrome) (10,11), LQTS (12)(13)(14), Wolff-Parkinson-White (15,16), hypertrophic cardiomyopathy (17,18), atrial flutter (19), and atrial fibrillation (20)(21)(22)(23). In addition, BrS has also been associated with non-cardiac pathologies, such as epilepsy, thyroid disorders, cancer, skeletal muscle sodium channelopathies, laminopathies, and diabetes.…”

Section: Introductionmentioning

confidence: 99%

Brugada Syndrome: Warning of a Systemic Condition?

D'Imperio

Monasky

Micaglio

et al. 2021

Front. Cardiovasc. Med.

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Brugada syndrome (BrS) is a hereditary disorder, characterized by a specific electrocardiogram pattern and highly related to an increased risk of sudden cardiac death. BrS has been associated with other cardiac and non-cardiac pathologies, probably because of protein expression shared by the heart and other tissue types. In fact, the most commonly found mutated gene in BrS, SCN5A, is expressed throughout nearly the entire body. Consistent with this, large meals and alcohol consumption can trigger arrhythmic events in patients with BrS, suggesting a role for organs involved in the digestive and metabolic pathways. Ajmaline, a drug used to diagnose BrS, can have side effects on non-cardiac tissues, such as the liver, further supporting the idea of a role for organs involved in the digestive and metabolic pathways in BrS. The BrS electrocardiogram (ECG) sign has been associated with neural, digestive, and metabolic pathways, and potential biomarkers for BrS have been found in the serum or plasma. Here, we review the known associations between BrS and various organ systems, and demonstrate support for the hypothesis that BrS is not only a cardiac disorder, but rather a systemic one that affects virtually the whole body. Any time that the BrS ECG sign is found, it should be considered not a single disease, but rather the final step in any number of pathways that ultimately threaten the patient's life. A multi-omics approach would be appropriate to study this syndrome, including genetics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, and glycomics, resulting eventually in a biomarker for BrS and the ability to diagnose this syndrome using a minimally invasive blood test, avoiding the risk associated with ajmaline testing.

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“…Nademanee et al showed an increased collagen content in the right ventricular outflow tract (RVOT) that shows epicardial surface and intramyocardial fibrosis, in addition to diminished gap junction protein expression. This fibrosis was associated with conduction delay in the RVOT [ 33 , 34 ]. Our results go in the same direction as these articles and seem to indicate that despite being an arrhythmogenic disease there are certain structural abnormalities in this syndrome.…”

Section: Discussionmentioning

confidence: 99%

Searching for genetic modulators of the phenotypic heterogeneity in Brugada syndrome

et al. 2022

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In Brugada syndrome, even within the same family where all affected individuals share the same mutation, phenotypic variation is prominent, with variable penetrance and expressivity, presenting different degrees of involvement. It is difficult to establish a direct correlation between genotype and phenotype to predict prognosis in complications and risk of sudden death. The factors that modulate this inter- and intra-familial phenotypic variability remain to be determined. With the intention of testing whether other genetic factors, in addition to the causal mutation in SCN5A, may have a modulating effect on the Brugada phenotype and the risk of sudden death, we have studied 8 families with a causal variant in SCN5A with at least two affected individuals, one of whom has suffered cardiac arrest or sudden death. Whole exome sequencing was performed looking for additional variants that modify the phenotype and allow us to predict a better or worse prognosis for the evolution of the disease. The results did not show any clear genetic modifier; nevertheless, highlight the possible implication of the cholesterol and fibrosis pathways, as well as the circadian rhythm, as possible modulators of Brugada syndrome phenotype.

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Fibrosis and Conduction Abnormalities as Basis for Overlap of Brugada Syndrome and Early Repolarization Syndrome

Cited by 14 publications

References 56 publications

Noninvasive detection of spatiotemporal activation-repolarization interactions that prime idiopathic ventricular fibrillation

Noninvasive detection of spatiotemporal activation-repolarization interactions that prime idiopathic ventricular fibrillation

Brugada Syndrome: Warning of a Systemic Condition?

Searching for genetic modulators of the phenotypic heterogeneity in Brugada syndrome

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