Sodium Channel Blockers Identify Risk for Sudden Death in Patients With ST-Segment Elevation and Right Bundle Branch Block but Structurally Normal Hearts

TLDR

Brugada syndrome, characterized by right bundle branch block and ST‑segment elevation in V1‑V3, is linked to SCN5A mutations and often presents with transient ECG changes. This study aimed to assess arrhythmic risk in overt and concealed Brugada syndrome and to evaluate whether sodium‑channel blockers can unmask the syndrome to identify at‑risk patients. Intravenous ajmaline, procainamide, or flecainide were administered to 34 patients with transient ECG normalization, 19 family members (11 mutation carriers, 8 non‑carriers), and 53 controls to observe ECG responses. All patients with transient or persistent Brugada syndrome and all mutation carriers developed ST‑segment elevation and RBBB after drug challenge, whereas non‑carriers and controls did not; follow‑up revealed no difference in arrhythmia incidence between transient and persistent phenotypes, confirming the blockers’ diagnostic utility and similar arrhythmic risk.

Abstract

Background —A mutation in the cardiac sodium channel gene (SCN5A) has been described in patients with the syndrome of right bundle branch block, ST-segment elevation in leads V1 to V3, and sudden death (Brugada syndrome). These electrocardiographic manifestations are transient in many patients with the syndrome. The present study examined arrhythmic risk in patients with overt and concealed forms of the disease and the effectiveness of sodium channel blockers to unmask the syndrome and, thus, identify patients at risk. Methods and Results —The effect of intravenous ajmaline (1 mg/kg), procainamide (10 mg/kg), or flecainide (2 mg/kg) on the ECG was studied in 34 patients with the syndrome and transient normalization of the ECG (group A), 11 members of 3 families in whom a SCN5A mutation was associated with the syndrome and 8 members in whom it was not (group B), and 53 control subjects (group C). Ajmaline, procainamide, or flecainide administration resulted in ST-segment elevation and right bundle branch block in all patients in group A and in all 11 patients with the mutation in group B. A similar pattern could not be elicited in the 8 patients in group B who lacked the mutation or in any person in group C. The follow-up period (37±33 months) revealed no differences in the incidence of arrhythmia between the 34 patients in whom the phenotypic manifestation of the syndrome was transient and the 24 patients in whom it was persistent (log-rank, 0.639). Conclusions —The data demonstrated a similar incidence of potentially lethal arrhythmias in patients displaying transient versus persistent ST-segment elevation and right bundle branch block, as well as the effectiveness of sodium channel blockers to unmask the syndrome and, thus, identify patients at risk.