Drug-induced Brugada Syndrome

Yee Guan Yap; Elijah R. Behr; A. John Camm

Disclosures

Europace. 2009;11(8):989-994. 

In This Article

Patho-mechanism of Brugada Syndrome

The exact electrophysiological mechanism of this syndrome has not yet been fully elucidated. Three mechanisms are proposed for ST-segment elevation in Brugada syndrome: local conduction abnormality, local ventricular depolarization, and early repolarization abnormality.[10,11] The latter hypothesis postulates an accentuation of the action potential notch in the right ventricular epicardium carried by the transient outward current (Ito) via a reduction in the fast sodium inward current (INa). In theory, a reduction in INa or L-type ICa or an increase in Ito (dominant at epicardium) would produce a striking abbreviation of the epicardial action potential, which would lead to an epicardial–endocardial heterogeneity of repolarization that would cause ST-segment elevation. Thus, a genetic defect in the cardiac sodium channel gene SCN5A may lead to a reduction in the transmural sodium voltage gradient, which is normally responsible for the inscription of the J wave, giving rise to a saddleback-form ST-segment elevation if the epicardial repolarization precedes repolarization in mid- and endocardial regions. Further accentuation of the notch accompanied by a prolongation of the epicardial action potential may lead to the development of a coved-type ST-segment elevation. Ultimately, a loss of the action potential dome at some epicardial sites may result. As a consequence, marked intramural dispersion of repolarization may be responsible for local re-excitation via phase 2 re-entry.[10] When coupled with extrasystoles capable of initiating circus movement, a re-entry arrhythmia can be triggered. Pharmacological agents that primarily block I Na but not I to (flecainide, ajmaline, and procainamide) can further diminish sodium current already reduced by the Brugada mutations. This hypothesis may explain the use of sodium channel blockers to unmask concealed forms of the Brugada syndrome and the potential pro-arrhythmic adverse effects of these and other pharmacological agents.

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