Genetic variants in SCN5A gene were identified in patients with various arrhythmogenic conditions including Brugada syndrome. Despite significant progress of last decades in studying the molecular mechanism of arrhythmia-associated SCN5A mutations, the understanding of relationship between genetics, electrophysiological consequences and clinical phenotype is lacking. We have found a novel genetic variant Y739D in the SCN5A-encoded sodium channel Nav1.5 of a male patient with Brugada syndrome (BrS). The objective of the study was to characterize the biophysical properties of Nav1.5-Y739D and provide possible explanation of the phenotype observed in the patient. The WT and Y739D channels were heterologously expressed in the HEK-293T cells and the whole-cell sodium currents were recorded. Substitution Y739D reduced the sodium current density by 47 ± 2% at -20 mV, positively shifted voltage-dependent activation, accelerated both fast and slow inactivation, and decelerated recovery from the slow inactivation. The Y739D loss-of-function phenotype likely causes the BrS manifestation. In the hNav1.5 homology models, which are based on the cryo-EM structure of rat Nav1.5 channel, Y739 in the extracellular loop IIS1-S2 forms H-bonds with K1381 and E1435 and pi-cation contacts with K1397 (all in loop IIIS5-P1). In contrast, Y739D accepts H-bonds from K1397 and Y1434. Substantially different contacts of Y739 and Y739D with loop IIIS5-P1 would differently transmit allosteric signals from VSD-II to the fast-inactivation gate at the N-end of helix IIIS5 and slow-inactivation gate at the C-end of helix IIIP1. This may underlie the atomic mechanism of the Y739D channel dysfunction.

A 38-year-old man with a diagnosis of Brugada syndrome had a recurrence of monomorphic ventricular tachycardia 6 years after successful epicardial right ventricular outflow tract ablation by the use of subxiphoid access. Preprocedural and intraprocedural investigations suggested that the pathologic substrate of the right ventricular outflow tract had not been eliminated completely. Therefore, the patient underwent a hybrid electrophysiology-guided video-assisted thoracoscopic ablation. (Level of Difficulty: Advanced.).

We describe the case of a 14-year-old boy hospitalized for multisystem inflammatory syndrome in children who developed atrial fibrillation during the acute phase and a transient Brugada type 1 pattern in the subacute phase. Eight months later, a provocative test with ajmaline confirmed the suspicion of Brugada syndrome. (Level of Difficulty: Intermediate.).

Abnormalities of an athlete\'s electrocardiogram may be the result of an underlying heart disease and may carry a risk of sudden death. It is important that electrocardiographic abnormalities are correctly distinguished. We present the case of a young marathon athlete presenting with syncope and incomplete right bundle block pattern suggestive of a type 2 Brugada pattern. (Level of Difficulty: Advanced.).

An asymptomatic patient presented at our hospital exhibiting a Brugada electrocardiography pattern with coronary artery fistulas. Coronary artery fistula is a congenital or acquired rare abnormal condition with increased symptoms and complications over time. In the absence of the therapeutic consensus, we discuss the association and management for this condition. (Level of Difficulty: Advanced.).

A 32-year-old woman with anorexia nervosa experienced ventricular tachycardia while on therapeutic-dose amitriptyline despite normal blood tests, imaging, and intracardiac recordings. Electrocardiograms over several years featured the Type 1 Brugada pattern. Careful electrocardiogram monitoring should be made if using high doses of amitriptyline, especially in those with low body weight. (Level of Difficulty: Intermediate.).

Conduction delay in the right ventricular outflow tract as manifested in the electrocardiogram constitutes a high-risk predictor of ventricular arrhythmias in patients with Brugada syndrome. We present a case with a right QRS axis between -90° and ±180°. This feature has never been reported in the context of Brugada syndrome. (Level of Difficulty: Advanced.).

This case outlines the dynamic and often concealed electrocardiographic findings associated with Brugada syndrome and explores its important relationship with early repolarization syndrome as part of a spectrum of inherited J-wave syndromes. (Level of Difficulty: Beginner.).

A 37-year-old man with Brugada syndrome and frequent appropriate implantable cardioverter-defibrillator shocks received an epicardial substrate ablation. During the procedure to eliminate delayed potentials, transient, marked ST-segment elevation in lead V2 was observed, particularly in the anterior right ventricle with a borderline between normal and low-voltage areas. (Level of Difficulty: Intermediate.).

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