Abstract:

Ongoing developments in cardiac modelling have resulted, in particular, in the development of advanced and increasingly complex computational frameworks for simulating cardiac tissue electrophysiology. The goal of these simulations is often to represent the detailed physiology and pathologies of the heart using codes that exploit the computational potential of high-performance computing architectures. These developments have rapidly progressed the simulation capacity of cardiac virtual physiological human style models; however, they have also made it increasingly challenging to verify that a given code provides a faithful representation of the purported governing equations and corresponding solution techniques. This study provides the first cardiac tissue electrophysiology simulation benchmark to allow these codes to be verified. The benchmark was successfully evaluated on 11 simulation platforms to generate a consensus gold-standard converged solution. The benchmark definition in combination with the gold-standard solution can now be used to verify new simulation codes and numerical methods in the future.

Abstract:

Persistent atrial fibrillation (AF) patients show a 50% recurrence after pulmonary vein isolation (PVI), and no consensus is established for following treatment. The aim of our i-STRATIFICATION study is to provide evidence for optimal stratification of recurrent AF patients to pharmacological versus ablation therapy, through insilico trials in 800 virtual atria. The cohort presents variability in anatomy, electrophysiology, and tissue structure (low voltage areas, LVA), and is developed and validated against experimental and clinical data from ionic currents to ECG. AF maintenance is evaluated prior-and post-PVI, and atria with sustained arrhythmia after PVI are independently subjected to seven state-of-the-art treatments for AF. The results of the i-STRATICICATION study show that the right and left atrial volume dictate the success of ablation therapy in structurally-healthy atria. On the other hand, LVA ablation, both in the right and left atrium, is required for atria presenting LVA remodelling and short refractoriness. This atrial refractoriness, mainly modulated by L-type Ca2+ current, ICaL, and fast Na+ current, INa, determines the success of pharmacological therapy. Therefore, our study suggests the assessment of optimal treatment selection using the above-mentioned patient characteristics. This provides digital evidence to integrate human in-silico trials into clinical practice.

Abstract:

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is mainly sustained by reentrant circuits and rapid ectopic activity. In the present study, we performed computer simulations using a 3D human atrial model including fibre orientation, electrophysiological heterogeneities and tissue anisotropy. Membrane kinetics were described as in the human atrial action potential model by Maleckar et al., including AF-induced ionic remodeling. The impact of ionic changes on reentrant activity was investigated by characterizing arrhythmia stability, rotor dynamics and dominant frequency (DF). Our simulations show that reentrant circuits tend to organize around the pulmonary veins and the right atrial appendage. Simulated IK1 and INa blocks lead to slower DF in the whole atria, expanded wave meandering and reduction of secondary wavelets. INaK block slightly reduces DF and does not notably change the propagation pattern. Regularity and coupling indices of electrograms are usually higher in the right atrium than in the left atrium, entailing a higher likelihood of arrhythmia generation in the latter, as occurs in AF patients.