New Insights Into Brugada Syndrome From High Density Epicardial Mapping

BACKGROUND PATHOGENESIS IN BRUGADA SYNDROME The pathophysiological basis of Brugada syndrome (BrS) is controversial. Two are the main theories which explain the electrocardiographic findings localized typically in the right precordial leads and the susceptibility of BrS patients to develop life-threatening ventricular arrhythmias: the first is that BrS is the result of a trouble in the repolarization of myocardial cells, the latter instead links BrS to depolarization and conduction abnormalities. Both theories have a common end-point in the fact that BrS patients share an anatomical and/or a functional lieu which predispose them to reentry related ventricular tachyarrhythmias and consequently to sudden cardiac death.

The repolarization theory suggests that an outward shift in the balance of currents active during phases 1 and 2 of the right ventricular (RV) epicardial action potential (AP) via either a reduction of inward current (INa or ICa) or increase in outward current (Ito, IKr, or IK-ATP) allows the intrinsically prominent Ito in RV epicardium to accentuate phase 1 repolarization. When phase 1 repolarizes to a voltage below that needed to activate the L-type Ca+2 channels, the Ca+2 channels fail to activate, resulting in loss of the AP plateau in the RV subepicardial cells where Ito is most prominent. Loss of the AP dome is commonly heterogeneous so that loss of the dome at some epicardial sites but not others creates an epicardial, as well as transmural dispersion of repolarization. Conduction of the AP dome from epicardial sites at which it is maintained to sites at which it is lost might result in the development of a closely coupled extrasystole, a phenomenon termed phase 2 reentry, which precipitates ventricular tachycardia and fibrillation (VT and VF)(1).

The depolarization hypothesis is based on the assumption that BrS patients' electrocardiographic pattern and their predisposition to develop VT/VF is related to the presence of fibrosis and to a reduced density of connexin 43 proteins in the gap-junctions of the RVOT and of other regions of the RV.

Even if both theories appear reasonable and sound, the depolarization one has obtained more consensus in the scientific community, thanks to frequent association of BrS pattern with atrioventricular conduction abnormalities and to the recent studies on epicardial mapping and radiofrequency ablation of BrS patients. The repolarization theory has been proven only in the experimental setting and is waiting for confirmation in human studies.

Two groups of scientists have shed light on the topic (i.e. epicardial mapping of BrS patient).