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  • zip cost br Genetic basis Similar to other

    2019-06-15


    Genetic basis Similar to other arrhythmia syndromes, Brugada and early repolarization syndromes are inherited diseases that are usually transmitted in an autosomal-dominant manner [26]. To date, 13 genes have been associated with Brugada syndrome. Loss-of-function mutations in SCN5A, encoding the cardiac predominant sodium channel α-subunit, are the most frequent genotype and account for ∼20% of patients with Brugada syndrome (Table 4) [13,27]. Other genes, including SCN1B[28], SCN3B[29], GPD1L[30], MOG1 [31], and SLMAP[32], encoding proteins that modify the sodium channel function, are also causative genes of Brugada syndrome. The importance of sodium channel genes in the pathogenesis of Brugada syndrome and the similarities of early repolarization syndrome to Brugada syndrome led us to find SCN5A mutations in patients with early repolarization syndrome (Table 4) [23]. These two diseases have further common genetic backgrounds, including calcium channel genes such as CACNA1C, CACNB2b, and CACNA2D1, as well as KCNJ8, which encodes the ATP-sensitive potassium channel [24,33–35]. In fact, all of the five causative genes reported for early repolarization syndrome are also causative genes of Brugada syndrome. In early repolarization syndrome, an ion channel dysfunction of a pathogenic genetic background results in either the decrease of inward zip cost currents (Na+ and Ca2+ currents) or the increase of outward currents (K+ currents), both of which can cause shortening of the zip cost duration, consistent with a relatively short QT interval.
    Treatment Implantable cardioverter defibrillator is the only proven effective treatment to prevent sudden cardiac death in patients with Brugada syndrome and those with early repolarization syndrome. The arrhythmogenicity of vagal stimulation has been reported, and the β-adrenergic agonist isoproterenol has been found effective for treating electrical storm in both diseases. To date, quinidine has been the only drug to show efficacy in preventing recurrent episodes of ventricular fibrillation in patients with Brugada syndrome [36]. Quinidine has been also effective in patients with early repolarization syndrome [16]. These similarities in responses to drugs between patients with Brugada syndrome and those with early repolarization syndrome suggest the presence of common electrophysiological abnormalities that have a critical role in the formation of arrhythmogenic substrates.
    Introduction Brugada syndrome [1,2] is an arrhythmogenic disorder associated with a high risk of sudden cardiac death in individuals with structurally normal hearts. The syndrome is characterized by a coved pattern of ST-segment elevation in electrocardiogram (ECG) leads V1 to V2. Such ECG findings have been reported to be dynamic and are often concealed [3–8]. However, they become unmasked by intravenous or oral administration of class IC antiarrhythmic drugs such as pilsicainide and propafenone [9–12]. Accordingly, temporal use of these drugs has been introduced as an effective technique (namely, a pharmacological challenge test) for identifying patients at risk of Brugada syndrome and for patients with concealed forms of Brugada-type ECGs [13,14]. However, the predictive accuracy of such drug administration for risk stratification remains unknown. Class IC antiarrhythmic drugs have generally been used to manage paroxysmal atrial tachyarrhythmias (ATs) in clinical practice and are highly effective for preventing AT attacks [15–17]. However, there are no available data on the prevalence and prognosis of patients with paroxysmal AT without a history of Brugada syndrome who show Brugada-type ECGs on use of class IC antiarrhythmic drugs.
    Methods
    Results
    Discussion The 12-lead ECG pattern typical of Brugada syndrome is known to be dynamic and is often concealed in high-risk groups [1]. Although its mechanism has not been fully clarified, a pharmacological challenge test using sodium channel blockers, in particular class IC antiarrhythmic drugs, has been used to identify the manifestation of Brugada syndrome and to identify the patients at risk of aborted cardiac sudden death or lethal ventricular arrhythmias [13,14]. However, the specificity and sensitivity of this technique for risk stratification remains unknown in patients with no history of Brugada-type ECGs.