TY - JOUR
T1 - Mechanism of right precordial ST-segment elevation in structural heart disease: Excitation failure by current-to-load mismatch
AU - Hoogendijk, Mark G.
AU - Potse, Mark
AU - Linnenbank, André C.
AU - Verkerk, Arie O.
AU - den Ruijter, Hester M.
AU - van Amersfoorth, Shirley C. M.
AU - Klaver, Eva C.
AU - Beekman, Leander
AU - Bezzina, Connie R.
AU - Postema, Pieter G.
AU - Tan, Hanno L.
AU - Reimer, Annette G.
AU - van der Wal, Allard C.
AU - ten Harkel, Arend D. J.
AU - Dalinghaus, Michiel
AU - Vinet, Alain
AU - Wilde, Arthur A. M.
AU - de Bakker, Jacques M. T.
AU - Coronel, Ruben
PY - 2010
Y1 - 2010
N2 - BACKGROUND The Brugada sign has been associated with mutations in SCN5A and with right ventricular structural abnormalities. Their role in the Brugada sign and the associated ventricular arrhythmias is unknown. OBJECTIVE The purpose of this study was to delineate the role of structural abnormalities and sodium channel dysfunction in the Brugada sign. METHODS Activation and repolarization characteristics of the explanted heart of a patient with a loss-of-function mutation in SCN5A (G752R) and dilated cardiomyopathy were determined after induction of right-sided ST-segment elevation by ajmaline. In addition, right ventricular structural discontinuities and sodium channel dysfunction were simulated in a computer model encompassing the heart and thorax. RESULTS In the explanted heart, disappearance of local activation in unipolar electrograms at the basal right ventricular epicardium was followed by monophasic ST-segment elevation. The local origin of this phenomenon was confirmed by coaxial electrograms. Neither early repolarization nor late activation correlated with ST-segment elevation. At sites of local ST-segment elevation, the subepicardium was interspersed with adipose tissue and contained more fibrous tissue than either the left ventricle or control hearts. In computer simulations entailing right ventricular structural discontinuities, reduction of sodium channel conductance or size of the gaps between introduced barriers resulted in subepicardial excitation failure or delayed activation by current-to-load mismatch and in the Brugada sign on the ECG. CONCLUSION Right ventricular excitation failure and activation delay by current-to-load mismatch in the subepicardium can cause the Brugada sign. Therefore, current-to-load mismatch may underlie the ventricular arrhythmias in patients with the Brugada sign
AB - BACKGROUND The Brugada sign has been associated with mutations in SCN5A and with right ventricular structural abnormalities. Their role in the Brugada sign and the associated ventricular arrhythmias is unknown. OBJECTIVE The purpose of this study was to delineate the role of structural abnormalities and sodium channel dysfunction in the Brugada sign. METHODS Activation and repolarization characteristics of the explanted heart of a patient with a loss-of-function mutation in SCN5A (G752R) and dilated cardiomyopathy were determined after induction of right-sided ST-segment elevation by ajmaline. In addition, right ventricular structural discontinuities and sodium channel dysfunction were simulated in a computer model encompassing the heart and thorax. RESULTS In the explanted heart, disappearance of local activation in unipolar electrograms at the basal right ventricular epicardium was followed by monophasic ST-segment elevation. The local origin of this phenomenon was confirmed by coaxial electrograms. Neither early repolarization nor late activation correlated with ST-segment elevation. At sites of local ST-segment elevation, the subepicardium was interspersed with adipose tissue and contained more fibrous tissue than either the left ventricle or control hearts. In computer simulations entailing right ventricular structural discontinuities, reduction of sodium channel conductance or size of the gaps between introduced barriers resulted in subepicardial excitation failure or delayed activation by current-to-load mismatch and in the Brugada sign on the ECG. CONCLUSION Right ventricular excitation failure and activation delay by current-to-load mismatch in the subepicardium can cause the Brugada sign. Therefore, current-to-load mismatch may underlie the ventricular arrhythmias in patients with the Brugada sign
U2 - https://doi.org/10.1016/j.hrthm.2009.10.007
DO - https://doi.org/10.1016/j.hrthm.2009.10.007
M3 - Article
C2 - 20022821
SN - 1547-5271
VL - 7
SP - 238
EP - 248
JO - Heart Rhythm
JF - Heart Rhythm
IS - 2
ER -