Early repolarization in mice causes overestimation of ventricular activation time by the QRS duration

Bas J. Boukens*, Mark G. Hoogendijk, Arie O. Verkerk, Andre Linnenbank, Peter Van Dam, Carol Ann Remme, Jan W. Fiolet, Tobias Opthof, Vincent M. Christoffels, Ruben Coronel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

37 Citations (Scopus)


Aims Transgenic mice are frequently used to investigate the role of genes involved in cardiac conduction. The QRS duration calculated from the electrocardiogram (ECG) is a commonly used measure for ventricular conduction time. However, the relation between ventricular activation and QRS duration calculated from a mouse surface ECG is not well understood. We aim to relate ventricular activation and repolarization patterns with the mouse ECG.Methods and resultsVentricular activation and repolarization patterns generated by high-density optical mapping and a six-lead pseudo-ECG were compared in isolated mouse hearts. In addition, mouse ECGs were simulated in silico. Right-ventricular activation ends later than left-ventricular activation. Final activation coincided with the end of the QRS complex in leads III and aVF, but not in leads I, II, aVR, and aVL. The pattern of early repolarization (at 20% of repolarization, RT20) but not of RT50 or RT80 followed the activation pattern. After sodium channel blockade by ajmaline, total ventricular activation time increased by 10.0 ms, whereas QRS duration increased by only 2.1 ms. In mice carrying a mutation in Scn5a (1798insD), ventricular activation ended after the end of the QRS complex (12.9 ± 0.1 vs. 10.8 ± 0.3).ConclusionIn the mouse, ventricular myocardium activation and early repolarization waves are simultaneously present. This hampers unequivocal interpretation of the duration of the QRS complex as a measure of ventricular activation duration, especially when conduction is slowed. Under these conditions mapping of local activation and repolarization patterns is required for correct interpretation of the ECG.

Original languageEnglish
Pages (from-to)182-191
Number of pages10
JournalCardiovascular Research
Issue number1
Publication statusPublished - 1 Jan 2013
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants from STW (project 10959 to A.L. and P.v.D.) and the Netherlands Heart Foundation (2010B205 and 2008B062 to V.M.C. and R.C. and 2007B018 to R.C.)


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