Editorial Drug Therapy For Preventing Ventricular Arrhythmia In Brugada syndrome: Do We Have The Answers Yet?

After the first description of Brugada syndrome [1] and its genetic mutation in SCN5A gene [2], the understanding of this, often fatal, genetic abnormality has greatly increased. Electrophysiologically, ventricular myocardium is composed of three distinct cell types, namely epicardial, endocardial, and M cells [3]. Action potentials recorded from epicardial and M cells display a spike-and-dome morphology, because of prominent transient outward current-mediated phase 1, which is not prominent in the endocardial cells. In Brugada syndrome, different genetic mutations in the SCN5A gene, which encodes for the α subunit of the cardiac sodium channel, causes a loss of function in the INa channel, resulting in a loss of the action potential dome in epicardial myocytes. Accentuated Ito-mediated action potential notch and the loss of action potential dome in the epicardium, but not endocardium of the right ventricular outflow tract, gives rise to a transmural voltage gradient. This causes ST segment elevation in leads V1- V3 and induction of ventricular fibrillation (VF) due to phase 2 reentry [4-8]. Agents that reduce outward currents (e.g. Ito, IK-ATP, IKs, IKr) or boost inward currents (e.g. ICa-L) at the end of phase 1 of AP can attenuate ST segment elevation and suppress episodes o