Delay in right ventricular activation contributes to Brugada syndrome.
BACKGROUND
Although Brugada syndrome revolves around reduced net depolarizing force, the electrophysiological mechanisms of its defining features (right precordial ST-segment elevation and ventricular tachyarrhythmias) remain unresolved. Two proposed mechanisms are (1) right ventricular (RV) conduction delay and (2) selective and significant RV subepicardial action potential shortening. Both mechanisms must cause disparate contractile changes: delay in RV contraction and reduction of contractile force, respectively. We aimed to establish the electrophysiological mechanism of Brugada syndrome by studying the timing and force of RV contraction.


RESULTS
Using tissue Doppler echocardiography, we studied how these contractile variables change on induction of the characteristic ST-segment changes of Brugada syndrome by flecainide challenge. Accordingly, we studied patients in whom flecainide induced these changes (inducible) and those in whom these changes were not induced (control). We found that (1) the occurrence of a positive response (coved-type ST elevation) after flecainide coincides with delay in the onset of contraction between the RV and left ventricle (LV); (2) the extent of contraction delay between RV and LV correlates with the magnitude of ST elevation; and (3) RV ejection time (duration of RV ejection phase) shortens as the Brugada ECG pattern emerges.


CONCLUSIONS
These results indicate that both proposed mechanisms of Brugada syndrome may be operative.
Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Raymond
R
Tukkie
Peter
P
Sogaard
Jim
J
Vleugels
Irma K L M
IK
de Groot
Arthur A M
AA
Wilde
Hanno L
HL
Tan
D000200:Action Potentials; D000328:Adult; D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type / Q000502:physiology; D015150:Echocardiography, Doppler / Q000379:methods; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005424:Flecainide; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D017136:Ion Transport; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D013577:Syndrome; D017180:Tachycardia, Ventricular / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; D005424:Flecainide