Brugada syndrome BS is a hereditary
Brugada syndrome (BS) is a hereditary arrhythmogenic disease characterized by a coved- or saddleback-type ST elevation in the right precordial lead on a 12-lead electrocardiogram (ECG) and ventricular fibrillation (VF) occurring mainly at night. During the past 2 decades, since Brugada and Brugada first described this peculiar condition, there has been notable progress in our understanding of this syndrome with respect to genetics, epidemiology, electrophysiology, and clinical findings. Hundreds of mutations in more than 12 genes that encode sodium, potassium, or calcium ion ruthenium red Supplier have been identified in individuals with this condition. The prevalence, incidence, and short-term prognosis of this syndrome have also been clarified. However, the exact reason for its predominance in men and Asian individuals remains unknown, although the effect of testosterone and the higher expression of the transient outward potassium (Ito) current in the right ventricular (RV) epicardium in men and polymorphisms that are found only in Asian individuals are believed to be responsible for this predominance.
The pathophysiological mechanism of this syndrome also remains a matter of debate. There are 2 main theories that explain the mechanism of ST elevation and ventricular arrhythmias: the repolarization hypothesis and the depolarization hypothesis. The repolarization hypothesis has been supported by studies using animal models and relies on Ito-mediated transmural dispersion of repolarization between the RV endocardium and epicardium. This theory provides an explanation for the trigger (phase 2 reentry) underlying the development of VF, ST segment elevation by calcium channel blockers or potassium channel openers, ST segment normalization by quinidine or isoproterenol, and the strong association between spontaneous type 1 ECG and cardiac events. In contrast, the depolarization hypothesis relies on conduction delay in the RV outflow tract caused by structural abnormalities. Although this theory has not been demonstrated in experimental models, various data supporting the existence of RV conduction delay have been obtained from electrophysiological studies (EPS) and clinical studies involving signal-averaged ECGs and body surface, epicardial, and endocardial mapping. Furthermore, Nademanee et al. recently demonstrated that abnormal low-voltage, prolonged, and fractionated late potentials exist in the epicardial aspect of the RV outflow tract in selected BS patients who received multiple shocks by an implantable cardioverter-defibrillator (ICD). It is unknown whether these abnormalities exist in every BS patient and which hypothesis is more reliable. Further research is needed to clarify these issues as well as to determine the efficacy of catheter ablation in patients with BS. The value of VF inducibility by EPS is still a controversial topic for risk stratification in BS. Although many studies have failed to demonstrate the usefulness of EPS, a good association between VF inducibility and patient outcome may be obtained by using specific standardized stimulation protocols, as reported by Makimoto et al. .
Introduction Brugada syndrome (BS) is a clinical entity that causes sudden death because of ventricular fibrillation (VF) in patients with apparently structurally normal hearts, and it is characterized by coved ST-segment elevation in the right precordial leads (V1–V3) [1,2]. A similar clinical condition, which brings sudden death mainly at night in young and middle-aged men, has been known in Asian countries by different names such as “pokkuri” in Japan, “lai-tai” in Thailand, and “bangungut” in the Philippines. Several cases of pokkuri or idiopathic VF that showed coved ST elevation just after resuscitation were reported in Japan [3,4] in 1990 (Fig. 1) before Brugada et al. first described this condition in 1992. In 1990, we also reported that some patients demonstrate a peculiar ST elevation in the leads V1–V3 and develop a syncopal attack at midnight or early morning in a series of four cases with idiopathic VF .