Brugada Syndrome: Clinical, Genetic, Molecular, Cellular, and Ionic Aspects☆
Section snippets
Clinical Characteristics and Diagnostic Criteria
Brugada syndrome (BrS) typically manifests in the third or fourth decade of life (average age of 41 ± 15 years), although patients have been diagnosed with the syndrome at an age as young as 2 days and as old as 84 years. Prevalence of BrS electrocardiograph (ECG) in the general population varies significantly among continents, countries, and ethnic groups.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 The prevalence of the disease is the highest in Southeast
Genetic Basis
Inheritance of BrS is via an autosomal dominant mode of transmission. Mutations in 19 genes have been identified as associated with the Brugada phenotype (Table 1). These mutations cause either a decrease in inward sodium or calcium current or an increase in outward potassium currents, resulting in an outward shift in the balance of current active during the early phases of the AP.
Indrajit Choudhuri, MD: At the time of printing, this review provides a complete and up-to-date list of currently
Cellular and Ionic Basis
An outward shift in the balance of currents active during phases 1 and 2 of the epicardial AP via either a reduction of inward current (INa or ICa) or increase in outward current (IKr or IK-ATP) allows the already prominent Ito to accentuate phase 1 repolarization (FIG 2, FIG 3). When phase 1 is repolarized beyond the voltage range in which L-type Ca2+ channels activate, the Ca2+ channels fail to activate, resulting in loss of the AP plateau, predominantly in the RV subepicardial cells, where I
Approach to Therapy
Table 3 lists device and pharmacologic therapies suggested on the basis of clinical experience or experimental studies.
Funding Sources
This study was supported by grant HL47678 from NHLBI (CA), NYSTEM grant no. C026424 (CA), and the Masons of New York, Florida, Massachusetts, Connecticut, Maryland, Delaware, New Hampshire, and Wisconsin.
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Dr Antzelevith is a consultant to Gilead Sciences in Foster City, CA, and has received research support from Gilead Sciences and the Buchang Group in Xi’an, China.