Mechanism of right precordial ST-segment elevation in structural heart disease: Excitation failure by current-to-load mismatch

Mark G. Hoogendijk; Mark Potse; Andre C. Linnenbank; Arie O Verkerk; Hester M. den Ruijter; Shirley C. M. van Amersfoorth; Eva C. Klaver; Leander Beekman; Connie R Bezzina; Pieter G. Postema; Hanno L. Tan; Annette G. Reimer; Allard C. van der Wal; Arend D. J. ten Harkel; Michiel Dalinghaus; Alain Vinet; Arthur A. M. Wilde; Jacques M. T. de Bakker; Ruben Coronel

doi:10.1016/j.hrthm.2009.10.007

Mechanism of right precordial ST-segment elevation in structural heart disease: Excitation failure by current-to-load mismatch

Mark G. Hoogendijk^*, Mark Potse, Andre C. Linnenbank, Arie O Verkerk, Hester M. den Ruijter, Shirley C. M. van Amersfoorth, Eva C. Klaver, Leander Beekman, Connie R Bezzina, Pieter G. Postema, Hanno L. Tan, Annette G. Reimer, Allard C. van der Wal, Arend D. J. ten Harkel, Michiel Dalinghaus, Alain Vinet, Arthur A. M. Wilde, Jacques M. T. de Bakker, Ruben Coronel

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.The purpose of this study was to delineate the role of structural abnormalities and sodium channel dysfunction in the Brugada sign.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.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.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.

Original language	English
Pages (from-to)	238-248
Journal	Heart Rhythm
Volume	7
Issue number	2
DOIs	https://doi.org/10.1016/j.hrthm.2009.10.007
Publication status	Published - Feb 2010

Keywords

Arrhythmia
Electrocardiography
Excitation
Structure
ST-segment elevation

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10.1016/j.hrthm.2009.10.007

Cite this

Hoogendijk, M. G., Potse, M., Linnenbank, A. C., Verkerk, A. O., den Ruijter, H. M., van Amersfoorth, S. C. M., Klaver, E. C., Beekman, L., Bezzina, C. R., Postema, P. G., Tan, H. L., Reimer, A. G., van der Wal, A. C., ten Harkel, A. D. J., Dalinghaus, M., Vinet, A., Wilde, A. A. M., de Bakker, J. M. T., & Coronel, R. (2010). Mechanism of right precordial ST-segment elevation in structural heart disease: Excitation failure by current-to-load mismatch. Heart Rhythm, 7(2), 238-248. https://doi.org/10.1016/j.hrthm.2009.10.007

@article{990fd2553f674a06b8744ee958fdb0ac,

title = "Mechanism of right precordial ST-segment elevation in structural heart disease: Excitation failure by current-to-load mismatch",

abstract = "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.The purpose of this study was to delineate the role of structural abnormalities and sodium channel dysfunction in the Brugada sign.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.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.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.",

keywords = "Arrhythmia, Electrocardiography, Excitation, Structure, ST-segment elevation",

author = "Hoogendijk, {Mark G.} and Mark Potse and Linnenbank, {Andre C.} and Verkerk, {Arie O} and {den Ruijter}, {Hester M.} and {van Amersfoorth}, {Shirley C. M.} and Klaver, {Eva C.} and Leander Beekman and Bezzina, {Connie R} and Postema, {Pieter G.} and Tan, {Hanno L.} and Reimer, {Annette G.} and {van der Wal}, {Allard C.} and {ten Harkel}, {Arend D. J.} and Michiel Dalinghaus and Alain Vinet and Wilde, {Arthur A. M.} and {de Bakker}, {Jacques M. T.} and Ruben Coronel",

year = "2010",

month = feb,

doi = "10.1016/j.hrthm.2009.10.007",

language = "English",

volume = "7",

pages = "238--248",

journal = "Heart Rhythm",

issn = "1547-5271",

publisher = "Elsevier Science",

number = "2",

}

Hoogendijk, MG, Potse, M, Linnenbank, AC, Verkerk, AO, den Ruijter, HM, van Amersfoorth, SCM, Klaver, EC, Beekman, L, Bezzina, CR, Postema, PG, Tan, HL, Reimer, AG, van der Wal, AC, ten Harkel, ADJ, Dalinghaus, M, Vinet, A, Wilde, AAM, de Bakker, JMT & Coronel, R 2010, 'Mechanism of right precordial ST-segment elevation in structural heart disease: Excitation failure by current-to-load mismatch', Heart Rhythm, vol. 7, no. 2, pp. 238-248. https://doi.org/10.1016/j.hrthm.2009.10.007

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, Andre 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 - 2010/2

Y1 - 2010/2

N2 - 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.The purpose of this study was to delineate the role of structural abnormalities and sodium channel dysfunction in the Brugada sign.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.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.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 - 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.The purpose of this study was to delineate the role of structural abnormalities and sodium channel dysfunction in the Brugada sign.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.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.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.

KW - Arrhythmia

KW - Electrocardiography

KW - Excitation

KW - Structure

KW - ST-segment elevation

U2 - 10.1016/j.hrthm.2009.10.007

DO - 10.1016/j.hrthm.2009.10.007

M3 - Article

SN - 1547-5271

VL - 7

SP - 238

EP - 248

JO - Heart Rhythm

JF - Heart Rhythm

IS - 2

ER -