Section: New Results

Medical applications of numerical models

• Influence of Transmural Slow-Conduction Zones on the Long-Time Behaviour Of Atrial Arrhythmia. A Numerical Study with a Human Bilayer Atrial Model. [20] , [31] , [16]

  Atrial fibrosis is known to be a factor in the perpetuation of atrial arrhythmia. Despite the thinness of atrial tissue, the fibrosis distribution may not be homogeneous through the entire thickness of the atria. The aim of this study is twofold. 1) We want to elucidate the respective influences of a transmural and a non-transmural distribution of fibrosis, described as a slow conduction zone, on the perpetuation of a rotor-like arrhythmic episode, compared to a control situation. 2) We aim to assess which is the more efficient ablation protocol between a) a lesion-box ablation, b) an ablation line connecting the fibrotic zone to the closest anatomical obstacle, c) ablation spots.

  We used a bilayer monodomain representation of the atria that included transmural heterogeneities of fibre organisation, and an arrhythmic scenario composed of a rotor initiated near the pulmonary veins. This model allowed long simulations for a sustainable computational load. We observed that when the fibrosis was transmural, the centre of the rotor was anchored in the slow conduction zone and was stable during a 10 seconds simulation, whereas the other simulations showed meandering rotors that disappeared after a few seconds. In our model framework, only a transmural fibrosis distribution had a stabilizing effect on reentrant circuits. Furthermore, the lesion-box ablation and the line ablation were able to stop the arrhythmia, unlike the spot lesions. The bilayer model proved to be a good trade-off between accuracy and speed for observing the influence of transmural heterogeneities on atrial arrhythmia over long periods.

• Effects of L-type Calcium channel and hERG blockers on the electrical activity of the human heart: A simulation study.

  Class III and IV drugs affect cardiac hERG (IKr) and L-type calcium (ICaL) channels, resulting in complex alterations in repolarization with both anti and pro-arrhythmic consequences. Interpretation of their effects on cellular and ECG-based biomarkers for risk stratification is challenging. As pharmaceutical compounds often exhibit multiple ion channel effects, our goal is to investigate the simultaneous effect of ICaL and IKr block on human ventricular electrophysiology from ionic to ECG level. ECG simulations show that ICaL block results in shortening of the QT interval, ST elevation and reduced T wave amplitude, caused by reduction in APD and AP amplitude during the plateau phase, and in repolarization times. In contrast, IKr block results in QT prolongation and reduced T wave amplitude. Combined ICaL and IKr block are combined, the degree of ICaL block strongly determines QT interval whereas the effect of IKr block is more pronounced on the T wave amplitude.