Novel therapeutic strategies for the management of ventricular arrhythmias associated with the Brugada syndrome

Abstract

Introduction: The Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome characterized by prominent J waves appearing as distinct coved type ST segment elevation in the right precordial leads of the electrocardiogram (ECG). It is associated with a high risk for sudden cardiac death.

Areas covered: We discuss: i) ECG manifestations of BrS, which can be unmasked or aggravated by sodium channel blockers, febrile states, vagotonic agents, as well as tricyclic and tetracyclic antidepressants; ii) genetic basis of BrS; iii) ionic and cellular mechanisms underlying BrS; iv) therapy involving devices including an implantable cardioverter defibrillator; v) therapy involving radiofrequency ablation; and vi) therapy involving pharmacological therapy, which is aimed at producing an inward shift in the balance of the currents active during Phase I of the right ventricular action potential either by boosting calcium channel current (isoproterenol, cilostazol and milrinone) or by inhibition of transient outward current I_to (quinidine, bepridil and the Chinese herb extract Wenxin Keli).

Expert opinion: This review provides an overview of the clinical and molecular aspects of BrS with a focus on approaches to therapy. Available data suggest that agents capable of inhibiting the transient outward current I_to can exert an ameliorative effect regardless of the underlying cause.

Keywords:

• arrhythmias
• Brugada syndrome
• isoproterenol
• pharmacology
• phophdiesterase III inhibitors
• quinidne
• sudden cardiac death

Declaration of interest

This work was supported by grants from the NHLBI (number HL47678) and NYSTEM (number CO26424). C Antzelevitch has also received grant support from the Buchang Group for work related to Wenxin Keli and is a consultant for Gilead Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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