Generation of the T wave in the electrocardiogram:
lessons to be learned from long-QT syndromes.

Mark Potse, Ghayath Baroudi, Paola A. Lanfranchi, and Alain Vinet.
Can. J. Cardiol. 2007, 23 Suppl. C.:238C.

Poster presented at the Canadian Cardiovascular Congress, October 2007.



Meeting abstracts in Can. J. Cardiol. 2007, 23 Supplement C


introduction  The electrocardiographic T wave is caused by heterogeneity of repolarization time and action potential shape in the ventricles. In the normal ECG, most T waves are concordant, i.e. they have the same sign as the QRS complex. This is only possible if there is a negative correlation between depolarization and repolarization times. This requires heterogeneity of action potential duration (APD), which is thought to result from differences in ion-channel density. Candidate channels include those responsible for the rapid and slow components of the delayed rectifier current (IKr and IKs) and the L-type calcium current (ICaL). Of these, only IKs has been demonstrated to be heterogeneous. We investigated whether this heterogeneity explains T-wave concordance in the 12-lead ECG.

methods  The experimentally observed heterogeneity of IKs and other currents was implemented in a detailed computer model of the human heart. Action potentials were simulated with a reaction-diffusion equation, at 0.25-mm resolution. The ECG was computed from the action potentials with an inhomogeneous torso model. Details of these models were published previously. Simulations were repeated with a loss-of-function mutation (L251P) in KCNQ1, which is associated with an LQT1 syndrome.

results  The experimentally observed heterogeneity of IKs alone led to T-wave concordance only in the right precordial leads. With the addition of an endocardial-to-epicardial gradient in IKs, concordance was obtained in all 12 leads. Introduction of the L251P mutation, which decimates IKs globally, led to QT prolongation and reduction of T-wave amplitude, both with and without the additional gradient.

discussion  T-wave concordance necessitates heterogeneity of APD. A transmural APD gradient is often assumed. This hypothesis is attractive because transmural heterogeneity of cell types has been demonstrated. However, we have shown that the known ionic heterogeneities do not suffice to explain the normal T wave, which is concordant in all standard ECG leads. Only with an additional difference between endocardial and epicardial layers can this concordance be obtained. Moreover, a strong reduction of IKs, such as it occurs in some LQT1 syndromes, reduces the amplitude of the T wave so obtained. This is in disagreement with the observation that LQT1 syndromes are associated with normal or increased T-wave amplitude. To explain this observation, we must assume that heterogeneity in IKs opposes T-wave concordance, rather than causing it. This suggests an important role of IKr and ICaL in the generation of the T wave.


Computational resources for this work were provided by the Réseau québécois de calcul de haute performance (RQCHP). M. Potse was supported by a postdoctoral research award from the Groupe de recherche en sciences et technologie biomédicale (GRSTB), École Polytechnique and Université de Montréal; and by the Research Center of Sacré-Coeur Hospital, Montréal, Québec, Canada.