Diagnostic's experience and ten-year tretment outcomes of patients with brugada syndrome
Objective. To carry out mutations search of SCN5A gene in patients with Brugada syndrome (BrS) using DNA method, to study genotype-phenotype relationship of BrS patients with mutation (genotype-positive) and without it (genotype-negative) in the SCN5A gene encoding the cardiac voltage-gated sodium (Na) channel. Today, mutations in 21 genes have been associated with BrS, but only mutations in SCN5A gene account for the vast majority. If a genotype-phenotype relationship exists, this might facilitate screening, optimize the cost of valuable diagnostic studies and future management of these patients. Material and methods. The study included 46 individuals (31 males, mean age 41.8±12.8 years). Among them 19 patients had spontaneous type 1 BrS ECG pattern, and 27 patients with type 2-3 BrS ECG pattern showed a type 1 BrS after intravenous administration of Na-blocking drugs and programmed electrical stimulation induced ventricular tachycardia. Sinus node dysfunction (SND) was observed in 13 (28%) subjects. Mutations in SCN5A gene were identified in 14 (30%) probands. Phenotype-genotype correlation was studied in SCN5A-positive and SCN5A-negative patients. Results. Genotype-positive patients have more frequently registered spontaneous type 1 BrS ECG pattern (71%, р<0.001), also the number of patients with family history of sudden cardiac death is higher (64%, р<0.002). SCN5A-linked Brugada patients are associated with a higher incidence of SND (6 of 14) than non-SCN5A-linked Brugada patients (7 of 32) and significantly longer conduction intervals on the baseline ECG (P-Q and QRS). According to electrophysiological studies A-H and H-V intervals as well as corrected sinus node recovery time were reliably longer for subjects with mutations in the SCN5A gene (р<0.001). Conclusion. BrS patients with and without SCN5A mutation can be differentiated by phenotypical differences. During investigation we frequently found SND and conduction disorders in patients with mutations in the SCN5A gene. These results fit with the observed loss of function of mutated BrS-related sodium channels. For this reason revealing cardiac conduction defects, drug-induced abnormal increasing of QRS duration for patients with type 1 BrS ECG pattern are strongly connected with increasing probability of SCN5A mutation.