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The clinical spectrum of atrial fibrillation means that a patient-individualised approach is required to ensure optimal treatment. Cardiac computed tomography can accurately delineate atrial structure and function and could contribute to a personalised care pathway for atrial fibrillation patients. The imaging modality offers excellent spatial resolution and has been utilised in pre-, peri- and post-procedural care for patients with atrial fibrillation. Advances in temporal resolution, acquisition times and analysis techniques suggest potential expanding roles for cardiac computed tomography in the future management of patients with atrial fibrillation. The aim of the current review is to discuss the use of cardiac computed tomography in atrial fibrillation in pre-, peri- and post-procedural settings. Potential future applications of cardiac computed tomography including atrial wall thickness assessment and epicardial fat volume quantification are discussed together with emerging analysis techniques including computational modelling and machine learning with attention paid to how these developments may contribute to a personalised approach to atrial fibrillation management.

Background: The lack of thermally and mechanically performant biomaterials represents the major limit for 3D-printed surgical guides, aimed at facilitating complex surgery and ablations. Methods: Cryosurgery is a treatment for cardiac arrhythmias. It consists of obtaining cryolesions, by freezing the target tissue, resulting in selective and irreversible damage. MED625FLX and TPU95A are two biocompatible materials for surgical guides; however, there are no data on their response to cryoenergy delivery. The study purpose is to evaluate the biomaterials' thermal properties, examining the temperature changes on the porcine muscle samples (PMS) when the biomaterials are in place during the cryoablation. Two biomaterials were selected, MED625FLX and TPU95A, with two thicknesses (1.0 and 2.5 mm). To analyze the biomaterials' behavior, the PMS temperatures were measured during cryoablation, firstly without biomaterials (control) and after with the biomaterials in place. To verify the biomaterials' suitability, the temperatures under the biomaterial samples should not exceed a limit of -30.0 °C. Furthermore, the biomaterials' geometry after cryoablation was evaluated using the grid paper test. Results: TPU95A (1.0 and 2.5 mm) successfully passed all tests, making this material suitable for cryoablation treatment. MED625FLX of 1.0 mm did not retain its shape, losing its function according to the grid paper test. Further, MED625FLX of 2.5 mm is also suitable for use with a cryoenergy source. Conclusions: TPU95A (1.0 and 2.5 mm) and MED625FLX of 2.5 mm could be used in the design of surgical guides for cryoablation treatment, because of their mechanical, geometrical, and thermal properties. The positive results from the thermal tests on these materials and their thickness prompt further clinical investigation. ispartof: JOURNAL OF CLINICAL MEDICINE vol:12 issue:3 ispartof: location:Switzerland status: published

We present an open-source software pipeline to create patient-specific left atrial (LA) models with fibre orientations and a fibrosis map, suitable for electrophysiology simulations. The semi-automatic pipeline takes as input a contrast enhanced magnetic resonance angiogram, and a late gadolinium enhanced (LGE) contrast magnetic resonance (CMR). Five operators were allocated 20 cases each from a set of 50 CMR datasets to create a total of 100 models to evaluate inter/intra-operator variability. Each output model consisted of (1) a labelled surface mesh open at the pulmonary veins (PV) and mitral valve (MV), (2) fibre orientations mapped from a diffusion tensor MRI human atlas, (3) fibrosis map from the LGE-CMR scan, and (4) simulation of local activation time (LAT) and phase singularity (PS) mapping. We evaluated reproducibility in our pipeline by comparing agreement in shape of the output meshes, fibrosis distribution in the LA body, and fibre orientations; simulations outputs were evaluated comparing total activation times of LAT maps, mean conduction velocity (CV), and structural similarity index measure (SSIM) of PS maps. Our workflow allows a single model to be created in 16.72 +/- 12.25 minutes. Results in this abstract are reported as inter/intra. Shape only differed noticeably with users' selection of the MV and the length of the PV from the ostia to the distal end; fibrosis agreement (0.91/0.99 ICC) and fibre orientation agreement (60.63/71.77 %) were high. LAT maps showed good agreement, the median of the absolute difference of the total activation times was 2.02ms/1.37ms. The average of the mean CV difference was -4.04mm/s / 2.1mm/s. PS maps showed a moderately good agreement with SSIM of 0.648/0.608. Although we found notable differences in the models due to user input, our tests show that operator variability was comparable to that of image resolution or fibre estimation., Comment: 17 pages, 7 figures, submitted for review at Journal of Computers in Biology and Medicine (in press)

There is increasing evidence to suggest that atrial fibrillation is associated with a heightened risk of dementia. The mechanism of interaction is unclear. Atrial fibrillation-induced cerebral infarcts, hypoperfusion, systemic inflammation, and anticoagulant therapy-induced cerebral microbleeds, have been proposed to explain the link between these conditions. An understanding of the pathogenesis of atrial fibrillation-associated cognitive decline may enable the development of treatment strategies targeted towards the prevention of dementia in atrial fibrillation patients. The aim of this review is to explore the impact that existing atrial fibrillation treatment strategies may have on cognition and the putative mechanisms linking the two conditions. This review examines how components of the ‘Atrial Fibrillation Better Care pathway’ (stroke risk reduction, rhythm control, rate control, and risk factor management) may influence the trajectory of atrial fibrillation-associated cognitive decline. The requirements for further prospective studies to understand the mechanistic link between atrial fibrillation and dementia and to develop treatment strategies targeted towards the prevention of atrial fibrillation-associated cognitive decline, are highlighted.

Patient-specific three-dimensional (3D) printed models have been increasingly used in many medical fields, including cardiac surgery for which they are used as planning and communication tools. To locate and plan the correct region of interest for the bypass placement during coronary artery bypass graft (CABG) surgery, cardiac surgeons can pre-operatively rely on different medical images. This article aims to present a workflow for the production of a patient-specific 3D-printed surgical guide, from data acquisition and image segmentation to final prototyping. The aim of this surgical guide is to help visualize the region of interest for bypass placement during the operation, through the use of dedicated surgical holes. The results showed the feasibility of this surgical guide in terms of design and fitting to the phantom. Further studies are needed to assess material biocompatibility and technical properties. ispartof: BIOENGINEERING-BASEL vol:9 issue:5 ispartof: location:Switzerland status: published

In some persistent atrial fibrillation (AF) patients, localized drivers may sustain AF and thus could represent possible ablation targets. In this work, we test in silico the feasibility of locating AF drivers from high-density electrode grid catheter mapping. A volumetric 3D atrial model was used to simulate 8 AF episodes driven by a stable reentry around a region of scar tissue (5 left atrium [LA], 3 right atrium [RA]). Sequential mapping in 1s segments was performed with a high-density electrode grid, starting from 20 uniformly distributed regions (12 LA, 8 RA). Conduction velocities estimated for each AF cycle were used to obtain temporal and directional parameters of the propagation. Trajectories of connected activation times were used to detect reentries or radial spread of activations. If no pattern was detected, the electrode array was moved in 5mm steps upstream of the propagation direction. The algorithm obtained accuracy, sensitivity, and precision of 87.2%, 23.4%, and 56.3% for reentries and 87.0%, 8.5%, and 26.8% for radial spread of activations, respectively. Reentries were found in average within 1.52 steps15 mm from the initial position of the grid. The results indicate that propagation patterns may be sufficient to track localized AF drivers sequentially during high-density mapping.

Aims 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.

Background Short 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 Results A 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 P =0.007) and 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%). Conclusions One 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.

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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.

Aims Electric conduction in the atria is direction-dependent, being faster in fibre direction, and possibly heterogeneous due to structural remodelling. Intracardiac recordings of atrial activation may convey such information, but only with high-quality data. The aim of this study was to apply a patient-specific approach to enable such assessment even when data are scarce, noisy, and incomplete. Methods and results Contact intracardiac recordings in the left atrium from nine patients who underwent ablation therapy were collected before pulmonary veins isolation and retrospectively included in the study. The Personalized Inverse Eikonal Model from cardiac Electro-Anatomical Maps (PIEMAP), previously developed, has been used to reconstruct the conductivity tensor from sparse recordings of the activation. Regional fibre direction and conduction velocity were estimated from the fitted conductivity tensor and extensively cross-validated by clustered and sparse data removal. Electrical conductivity was successfully reconstructed in all patients. Cross-validation with respect to the measurements was excellent in seven patients (Pearson correlation r > 0.93) and modest in two patients (r = 0.62 and r = 0.74). Bland–Altman analysis showed a neglectable bias with respect to the measurements and the limit-of-agreement at –22.2 and 23.0 ms. Conduction velocity in the fibre direction was 82 ± 25 cm/s, whereas cross-fibre velocity was 46 ± 7 cm/s. Anisotropic ratio was 1.91±0.16. No significant inter-patient variability was observed. Personalized Inverse Eikonal model from cardiac Electro-Anatomical Maps correctly predicted activation times in late regions in all patients (r = 0.88) and was robust to a sparser dataset (r = 0.95). Conclusion Personalized Inverse Eikonal model from cardiac Electro-Anatomical Maps offers a novel approach to extrapolate the activation in unmapped regions and to assess conduction properties of the atria. It could be seamlessly integrated into existing electro-anatomic mapping systems. Personalized Inverse Eikonal model from cardiac Electro-Anatomical Maps also enables personalization of cardiac electrophysiology models.

International audience; 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.

Aims Atrial fibrillation (AF) is a progressive arrhythmia characterized by structural alterations that increase its stability. Both clinical and experimental studies showed a concomitant loss of antiarrhythmic drug efficacy in later stages of AF. The mechanisms underlying this loss of efficacy are not well understood. We hypothesized that structural remodelling may explain this reduced efficacy by making the substrate more three-dimensional. To investigate this, we simulated the effect of sodium (Nathorn)-channel block on AF in a model of progressive transmural uncoupling. Methods and results In a computer model consisting of two cross-connected atrial layers, with realistic atrial membrane behaviour, structural remodelling was simulated by reducing the number of connections between the layers. 100% of endoepicardial connectivity represented a healthy atrium. At various degrees of structural remodelling, we assessed the effect of 60% sodium channel block on AF stability, endo-epicardial electrical activity dissociation (EED), and fibrillatory conduction pattern complexity quantified by number of waves, phase singularities (PSs), and transmural conduction ('breakthrough', BT). Sodium channel block terminated AF in non-remodelled but not in remodelled atria. The temporal excitable gap (EG) and AF cycle length increased at all degrees of remodelling when compared with control. Despite an increase of EED and EG, sodium channel block decreased the incidence of BT because of transmural conduction block. Sodium channel block decreased the number of waves and PSs in normal atrium but not in structurally remodelled atrium. Conclusion This simple atrial model explains the loss of efficacy of sodium channel blockers in terminating AF in the presence of severe structural remodelling as has been observed experimentally and clinically. Atrial fibrillation termination in atria with moderate structural remodelling in the presence of sodium channel block is caused by reduction of AF complexity. With more severe structural remodelling, sodium channel block fails to promote synchronization of the two layers of the model.

Aims P-wave beat-to-beat morphological variability can identify patients prone to paroxysmal atrial fibrillation (AF). To date, no computational study has been carried out to mechanistically explain such finding. The aim of this study was to provide a pathophysiological explanation, by using a computer model of the human atria, of the correlation between P-wave beat-to-beat variability and the risk of AF.Methods and results A physiological variability in the earliest activation site (EAS), on a beat-to-beat basis, was introduced into a computer model of the human atria by randomizing the EAS location. A methodology for generating multi-scale, spatially-correlated regions of heterogeneous conduction was developed. P-wave variability in the presence of such regions was compared with a control case. Simulations were performed with an eikonal model, for the activation map, and with the lead field approach, for P-wave computation. The methodology was eventually compared with a reference monodomain simulation. A total of 60 P-waves were simulated for each sinus node exit location (12 in total), and for each of the 15 patterns of heterogeneous conduction automatically generated by the model. A P-wave beat-to-beat variability was observed in all cases. Variability was significantly increased in presence of heterogeneous slow conducting regions, up to two-fold the variability in the control case. P-wave variability increased non-linearly with respect to the EAS variability and total area of slow conduction. Distribution of the heterogeneous conduction was more effective in increasing the variability when it surrounded the EAS locations and the fast conducting bundles. P-waves simulated by the eikonal approach compared excellently with the monodomain-based ones.Conclusion P-wave variability in patients with paroxysmal AF could be explained by a variability in sinoatrial node exit location in combination with slow conducting regions.

International audience; Introduction Recent work has shown that the transition from persistent to permanent AF in goats coincides with an increase in fibrosis in the outer millimeter of the atrial wall. Macroscopically this leads to reduced electrical conductivity orthogonal to the dominant fiber orientation. A causal relation has not been established yet. Our purpose was to test if epicardial fibrosis can explain the increased incidence of transmural conduction (breakthroughs), which is also observed in permanent AF. Methods We constructed a detailed geometry of the human atria including epicardial layer and all major endocardial bundle structures. The model also includes realistic one to three layers of fiber orientations, corresponding to their location in the atrium. Computer simulations were run with a mesh of 0.2 mm resolution and Courtemanche human atrial cell model. Epicardial fibrosis was modeled by assigning zero transverse conductivity to a random selection of model elements in the epicardial layer. Simulations were performed with 0, 50, and 70% affected elements. Results The numbers of waves, phase singularities, and breakthroughs (BTs) were quantified at different degrees of fibrotic tissue. Increase in the “fibrotic” volume from zero (Control) to moderate (50% Fibrotic), and severe (70% Fibrotic) increased both the number of waves and the number of phase singularities. Along with the increase in fibrosis, the endo-epicardial electrical activity dyssynchrony increased from 8.6% to 18.6%, and 38.4%. Fibrosis increased the incidence of BTs. Conclusion: This model is the first anatomical atrial model to display BTs, a common and conspicuous feature in experimental studies on AF. Epicardial fibrosis in this model increases the degree of endo-epicardial electrical activity dyssynchrony and the incidence of BTs, thus increasing the complexity of fibrillatory conduction. The model offers the opportunity to study transmural conduction, which frequently occurs during AF, in more detail.

AIMS: Structural alterations during atrial fibrillation (AF) not only lead to electrical dissociation within the epicardial layer, but also between the epicardial layer and the endocardial bundle network. The aim of the study was to investigate the role of transmural conduction in the stability of AF episodes using a dual-layer computer model. METHODS AND RESULTS: A proof-of-principle dual-layer model was developed in which connections between the layers can be introduced or removed at any time during the simulation. Using an S1-S2 protocol, a spiral wave was initiated in one of the layers, which degenerated into a complex AF pattern after connection with the other layer at six randomly chosen sites. After 6 s, connections were either retained (dual-layer simulations) or removed (single-layer simulations). Dual-layer simulations were more complex, as indicated by the higher number of waves and phase singularities. Tracking waves through both layers revealed that the number of waves in dual-layer simulations was significantly higher than in the single-layer simulations, reflecting more opportunities for reentry and a concomitant increase in AF stability. In the dual-layer model, only 12% of the AF episodes died out within 6 s, while 59% died out in the single-layer model. CONCLUSION: Atrial fibrillation patterns are more complex and AF episodes are more stable in a dual-layer model. This study indicates an important role for endo-epicardial conduction for the stabilization of AF.

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.