Increased transient outward current in the subepicardial region is sufficient to explain the slurring of the QRS. A simulation study

Alexandru Dan Corlan; Bogdan Amuzescu; Ivan Milicin; Luigi Deambroggi

Increased transient outward current in the subepicardial region is sufficient to explain the slurring of the QRS. A simulation study

Alexandru Dan Corlan, Bogdan Amuzescu, Ivan Milicin, Luigi Deambroggi,

:-, 2009

ABSTRACT

BACKGROUND. QRS slurring was statistically associated with a history of malignant arrhythmias. Clarification of the possible mechanisms of this easily detectable feature is needed to increase its predictive value. METHODS. We built a finite element model of the ventricles with 27000 elements organised in six myocardial strata for each ventricle. The shape of the action potential was computed in each stratum using a modified Luo Rudy dynamic model with parameters extracted from the literature for the human myocardium. Activation times were assigned with a cellular automaton model and tuned to reproduce the well known recordings by D. Durrer et al. Electrograms were computed for 370 electrodes positioned on a surface with the shape of a human thorax in a uniform volume conductor around the ventricle (electrode positions were kindly provided by R. Macleod from Utah University). Two simulations were compared one without an Ito current and one with a maximum transient outward conductance (gIto) assigned randomly in the 0.076-0.19 nS/pF interval in the subepicardial layer. QRS slurring was measured by the decrease of the second derivative of the potential in time on each lead between the Ito and the non-Ito cases at the end of ventricular activation. 1000 such pairs of simulations were run with maximal conductances for the rapid and slow K (gKrgKs) the ATP-dependent K (gKATP) plateau K (gKp) T and L-type Ca (gCaT gCaL) Na/Ca exchanger (gNaCa) currents in a 40-160% range from the reference value. RESULTS. Adding the Ito current produced a QRS slurring aspect in 322+/-2.4 of the 370 leads. The magnitude of the slurring was strongly associated with gIto (r=0.75). Of the other maximum current conductances studied only gCaT (r=0.47) and gKp (r=-0.38) had a limited influence. CONCLUSION. The QRS slurring aspect on the electrocardiogram was reliably produced by the increase of the gIto in the subepicardial layer.