Electrocardiographic patterns of early repolarization attributable to increased transient outward current in the subepicardial region. A simulation study

A.D. Corlan1, B. Amuzescu2, I. Milicin3, L. De Ambroggi 4

1University Emergency Hospital - Bucharest - Romania,
2University of Bucharest - Bucharest - Romania,
3Scalacalc Laboratory, Quattro Electronic Design - Bucharest - Romania,
4IRCCS Policlinico San Donato, University of Milan - San Donato Milanese - Italy,

European Heart Journal (2009), 30 (Abstract Supplement), p. 491

[Poster (PDF)] On the ESC site: [Abstract] [Poster]
Archived by WebCite® at http://www.webcitation.org/67gWEjdlB Accessed: 2012-05-15.

Background

An association between the presence of ECG patterns of early repolarization (prominent J wave and/or QRS slurring) and occurrence of malignant ventricular arrhythmias has been reported.

Purpose

We aimed to characterize the effect on body surface ECG potentials of one of the proposed causes of early repolarization: the increased maximal conductance for the transient outward current in the subepicardial region.

Methods

We simulated single cardiac cycle electrocardiograms using 3D finite element models of the ventricular myocardium, with six strata in each ventricle. Action potentials were simulated with modified Luo-Rudy dynamic models, with parameters adjusted for the human myocytes. 370 surface electrograms were computed on a human thorax-shaped volume conductor. Pairs of simulations were run with the same maximal conductivities for the fast and slow K, the ATP-dependent K, plateau K, T and L-type Ca and Na/Ca exchanger currents. In one member of the pair the maximal conductance of the transient outward current was 0, while in the other it had a randomly assigned value between 0.076 and 0.190 nS/pF in the subepicardial stratum. In each of 1000 pairs of simulations random values in a range of ±60% from literature reference values were used for the channels other than transient outward. The body surface effect of the Ito (ItoECG) was computed in each pair by substracting the ECG of the non-Ito case from that of the Ito case.

Results

The maximal amplitude of the root mean square (RMS) of the ItoECG was 28±4% of the maximal amplitude of the RMS of the non-Ito QRS. The ItoECG reached this maximum 28 ms before the J point It was correlated (R=0.97) and linearly related with the Ito maximal conductance but not with any other maximal conductances, except slightly with that of the plateau K current (R=-0.11, p < 0.001). At the end of ventricular activation (the J point) the ItoECG contribution to the RMS of the J point was 5.5±2.9% of the QRS RMS amplitude, then ItoECG continued to decrease for 21±2.4 ms. ItoECG was constant during the rest of the ST and then increased again in amplitude during the T wave.

Conclusions

Parameters of the simulated effect of physiological levels of Ito on the body surface potentials are consistent with ECG observations of the early repolarization phenomenon. Most of the Ito effect was superimposed on the last part of the depolarization.