PIEMAP: Personalized Inverse Eikonal Model from cardiac Electro-Anatomical Maps

Electroanatomical mapping, a keystone diagnostic tool in cardiac electrophysiology studies, can provide high-density maps of the local electric properties of the tissue. It is therefore tempting to use such data to better individualize current patient-specific models of the heart through a data assimilation procedure and to extract potentially insightful information such as conduction properties. Parameter identification for state-of-the-art cardiac models is however a challenging task. In this work, we introduce a novel inverse problem for inferring the anisotropic structure of the conductivity tensor, that is fiber orientation and conduction velocity along and across fibers, of an eikonal model for cardiac activation. The proposed method, named PIEMAP, performed robustly with synthetic data and showed promising results with clinical data. These results suggest that PIEMAP could be a useful supplement in future clinical workflows of personalized therapies.Comment: 12 pages, 4 figures, 1 tabl

Bioactive peptides and antinutrients in chickpea: description and properties (a review)

Legumes are a rich source of many different biologically active substances, such as fiber, proteins, vitamins and minerals. Chickpea (Cicer arietinum L.) is the third most important leguminous plant in the world: it has high nutritional value and is a source of a wide range of bioactive compounds. Bioactive peptides of chickpea seeds have antioxidant, ACE-inhibiting, cholesterollowering, antihypertensive, antimicrobial, antithrombotic, immunomodulatory, and opioid activities as well as the ability to bind minerals. But despite the benefits and high nutritional value, chickpea seeds contain antinutrients that reduce their nutritional and biological advantages. These antinutritional factors include condensed tannins, raffinose, and phytic acid. Research has shown that cooking, pregermination or fermentation can effectively reduce the indigestible content of chickpea seeds. For this purpose, it is recommended to use certain physical, chemical or biological methods: heat treatment, soaking and/or germination, enzymatic hydrolysis, irradiation, etc.This review article presents the world’s results of research aimed at studying bioactive chickpea peptides derived from chickpea seeds and ways of their formation as well as methods for elimination of antinutritional factors

Spatial Relationship Between Atrial Fibrillation Drivers and the Presence of Repetitive Conduction Patterns Using Recurrence Analysis on In-Silico Models

Catheter ablation treatment for atrial fibrillation (AF) is still suboptimal, possibly due to the difficulty to identify AF drivers. Recurrence analysis can be used to detect and eventually locate repetitive patterns that tend to be generated by AF drivers. In this study, we aimed to understand the spatial relationship between repetitiveness in recurrence analysis and rotor positions in an in-silico AF model. AF was simulated in a detailed three-dimensional model of the atria considering different degrees of endomysial fibrosis (0% and 70%). Rotors driving AF were tracked based on phase singularities obtained from transmembrane potentials. Activation-phase signals calculated from electrograms (4x4 electrode grid, 3 mm spacing) were used for recurrence analysis. Intervals with and without longlasting sources inside the electrode coverage area were determined; the recurrence in both groups of intervals was quantified and compared with each other by calculating the recurrence rate (RR) per AF cycle length. RRs were lower during intervals with sources for both 0% and 70% fibrosis groups (0.56 [0.36;0.85] vs. 0.90 [0.80;0.97], p < 0:001 and 0.73 [0.41;0.84] vs. 0.87 [0.76;0.92], p < 0:001, respectively). These results indicate that recurrences are found in the area adjacent to the sources but not on the sources themselves, thus suggesting that recurrence analysis could contribute to guide ablation therapy

Application of phase coherence in assessment of spatial alignment of electrodes during simultaneous endocardial-epicardial direct contact mapping of atrial fibrillation

AIMS: Mapping and interpretation of wave conduction patterns recorded during simultaneous mapping of the electrical activity on both endocardial and epicardial surfaces are challenging because of the difficulty of reconstruction of reciprocal alignment of electrodes in space. Here, we suggest a method to overcome this difficulty using a concept of maximized endo-epicardial phase coherence. METHODS AND RESULTS: Endo-epicardial mapping was performed in six humans during induced atrial fibrillation (AF) in right atria using two sets of 8 × 8 electrode plaques. For each electrode, mean phase coherence (MPC) with all electrodes on the opposite side of the atrial wall was calculated. Localization error was defined as a distance between the directly opposing electrode and the electrode with the maximal MPC. Overall, there was a linear correlation between MPC and distance between electrodes with R(2) = 0.34. Localization error obtained for electrodes of the plaque in six patients resulted in a mean 2.3 ± 1.9 mm for 25 s electrogram segment length. Eighty-four per cent of the measurements resulted in error smaller than 3.4 mm. The duration of the recording used to compute MPC was negatively correlated with localization error; however, the effect reached plateau for segment durations longer than 15 s. CONCLUSION: Application of the concept of maximized endo-epicardial phase coherence to electrograms during AF allows reconstruction of reciprocal alignment of the electrodes on the opposite side of the atrial wall. This approach may be especially useful in settings where the spatial position of endo- and epicardial electrodes for intracardiac mapping cannot otherwise be determined

Synergistic antiarrhythmic effect of inward rectifier current inhibition and pulmonary vein isolation in a 3D computer model for atrial fibrillation

International audienceAims: Recent clinical studies showed that antiarrhythmic drug (AAD) treatment and pulmonary vein isolation (PVI) synergistically reduce atrial fibrillation (AF) recurrences after initially successful ablation. Among newly developed atrial-selective AADs, inhibitors of the G-protein-gated acetylcholine-activated inward rectifier current (IKACh) were shown to effectively suppress AF in an experimental model but have not yet been evaluated clinically. We tested in silico whether inhibition of inward rectifier current or its combination with PVI reduces AF inducibility. Methods and results: We simulated the effect of inward rectifier current blockade (IK blockade), PVI, and their combination on AF inducibility in a detailed three-dimensional model of the human atria with different degrees of fibrosis. IK blockade was simulated with a 30% reduction of its conductivity. Atrial fibrillation was initiated using incremental pacing applied at 20 different locations, in both atria. IK blockade effectively prevented AF induction in simulations without fibrosis as did PVI in simulations without fibrosis and with moderate fibrosis. Both interventions lost their efficacy in severe fibrosis. The combination of IK blockade and PVI prevented AF in simulations without fibrosis, with moderate fibrosis, and even with severe fibrosis. The combined therapy strongly decreased the number of fibrillation waves, due to a synergistic reduction of wavefront generation rate while the wavefront lifespan remained unchanged. Conclusion: Newly developed blockers of atrial-specific inward rectifier currents, such as IKAch, might prevent AF occurrences and when combined with PVI effectively supress AF recurrences in human

Fibrillation Patterns Creep and Jump in a Detailed Three-Dimensional Model of the Human Atria

Activation mapping in animal models of atrial fibrillation (AF) has shown that activation patterns can repeat for several cycles and then be followed by different changing or repetitive patterns. Subsequent clinical studies have suggested a similar type of activity in human AF. Our purpose was to investigate whether a computer model of human AF can reproduce this behavior. We used a three-dimensional model of the human atria consisting of 0.2-mm volumetric elements with a detailed representation of bundle structures and fiber orientations. Propagating activation was simulated over 9 seconds with a monodomain reaction-diffusion model using human atrial membrane dynamics. AF was induced by rapid pacing. Pattern recurrence was quantified using a similarity measure based on transmembrane voltage at 1000 uniformly distributed points in the model. Recurrence plots demonstrated a continuous evolution of patterns, but the speed of evolution varied considerably. Groups of upto 15 similar cycles could be recognized, separated by rapid changes. In a few cases truly periodic patterns developed, which were related to macroscopic anatomical reentry. The drivers of non-periodic patterns could not be clearly identified. For example, a spiral wave could appear or disappear without an obvious impact on the similarity between cycles. We conclude that our model can indeed reproduce strong variations in similarity between subsequent cycles, but true periodicity only in case of anatomical reentry.L'Institut de Rythmologie et modélisation Cardiaqu

Short P-Wave Duration is a Marker of Higher Rate of Atrial Fibrillation Recurrences after Pulmonary Vein Isolation: New Insights into the Pathophysiological Mechanisms Through Computer Simulations

BackgroundShort ECG P-wave duration has recently been demonstrated to be associated with higher risk of atrial fibrillation (AF). The aim of this study was to assess the rate of AF recurrence after pulmonary vein isolation in patients with a short P wave, and to mechanistically elucidate the observation by computer modeling.Methods and ResultsA total of 282 consecutive patients undergoing a first single-pulmonary vein isolation procedure for paroxysmal or persistent AF were included. Computational models studied the effect of adenosine and sodium conductance on action potential duration and P-wave duration (PWD). About 16% of the patients had a PWD of 110 ms or shorter (median PWD 126 ms, interquartile range, 115 ms-138 ms; range, 71 ms-180 ms). At Cox regression, PWD was significantly associated with AF recurrence (P=0.012). Patients with a PWD = 140 (HR, 1.87, 95% CI, 1.06-3.30; P=0.031) had a nearly 2-fold increase in risk with respect to the other group. In the computational model, adenosine yielded a significant reduction of action potential duration 90 (52%) and PWD (7%). An increased sodium conductance (up to 200%) was robustly accompanied by an increase in conduction velocity (26%), a reduction in action potential duration 90 (28%), and PWD (22%).ConclusionsOne out of 5 patients referred for pulmonary vein isolation has a short PWD which was associated with a higher rate of AF after the index procedure. Computer simulations suggest that shortening of atrial action potential duration leading to a faster atrial conduction may be the cause of this clinical observation

A two layers monodomain model of cardiac electrophysiology of the atria

Numerical simulations of the cardiac electrophysiology in the atria are often based on the standard bidomain or monodomain equations stated on a two-dimensional manifold. These simulations take advantage of the thinness of the atrial tissue, and their computational cost is reduced, as compared to three-dimensional simulations. However, these models do not take into account the heterogeneities located in the thickness of the tissue, like dis-continuities of the fibre direction, although they can be a substrate for atrial arrhythmia [Hocini et al., 2002, Ho et al., 2002, Nattel, 2002]. We investigate a two-dimensional model with two coupled, superimposed layers that allows to introduce three-dimensional heterogeneities, but retains a reasonable computational cost. We introduce the mathematical derivation of this model and error estimates with respect to the three-dimensional model. We give some numerical illustrations of its interest: we numerically show its convergence for vanishing thickness, introduce an optimization process of the coupling coefficient and assess its validity on physiologically relevant geometries. Our model would be an efficient tool to test the influence of three-dimensional fibre direction heterogeneities in reentries or atrial arrhythmia without using three-dimensional models.Modèles numériques haute résolution de l'électrophysiologie cardiaqueL'Institut de Rythmologie et modélisation Cardiaqu

Computational models in cardiology

The treatment of individual patients in cardiology practice increasingly relies on advanced imaging, genetic screening and devices. As the amount of imaging and other diagnostic data increases, paralleled by the greater capacity to personalize treatment, the difficulty of using the full array of measurements of a patient to determine an optimal treatment seems also to be paradoxically increasing. Computational models are progressively addressing this issue by providing a common framework for integrating multiple data sets from individual patients. These models, which are based on physiology and physics rather than on population statistics, enable computational simulations to reveal diagnostic information that would have otherwise remained concealed and to predict treatment outcomes for individual patients. The inherent need for patient-specific models in cardiology is clear and is driving the rapid development of tools and techniques for creating personalized methods to guide pharmaceutical therapy, deployment of devices and surgical interventions