Arrhythmogenic Brugada syndrome substrate: a proof of principle

The Brugada syndrome is an inherited, arrhythmogenic entity affecting predominantly young men without structural heart disease.¹ It is associated with a specific ECG pattern of coved-type ST-segment elevation in right precordial leads (Figure 1). Patients are at increased risk for sudden cardiac death often triggered by vagal influence and many times occurring at rest. After its description as a distinct entity in 1992, a first genetic link was identified in 1998.² The Brugada syndrome has a complex electrophysiological substrate, and several aspects are important for understanding its pathology. Many lines of evidence suggest a central role of I_to in the genesis of the Brugada syndrome. First, the balance of de- and repolarizing forces during the cardiac action potential is disturbed, leading to a loss of dome in epicardial action potentials and to increased dispersion of refractoriness. Reduced depolarizing (sodium current, I_Na, or calcium current, I_Ca) or increased repolarizing ion currents (transient outward …

*Corresponding author. Tel: +49 69 6301 83661, fax: +49 69 6301 4037. E-mail address: j.ehrlich{at}em.uni-frankfurt.de