Abstract:

Ventricular coordinates are widely used as a versatile tool for various applications that benefit from a description of local position within the heart. However, the practical usefulness of ventricular coordinates is determined by their ability to meet application-specific requirements. For regression-based estimation of biventricular position, for example, a consistent definition of coordinate directions in both ventricles is important. For the transfer of data between different hearts as another use case, the coordinate values are required to be consistent across different geometries. Existing ventricular coordinate systems do not meet these requirements. We first compare different approaches to compute coordinates and then present Cobiveco, a consistent and intuitive biventricular coordinate system to overcome these drawbacks. A novel one-way mapping error is introduced to assess the consistency of the coordinates. Evaluation of mapping and linearity errors on 36 patient geometries showed a more than 4-fold improvement compared to a state-of-the-art method. Finally, we show two application examples underlining the relevance for cardiac data processing. Cobiveco MATLAB code is available under a permissive open-source license.

Abstract:

Electrocardiographic imaging (ECGI) strongly relies on a priori assumptions and additional information to overcome ill-posedness. The major challenge of obtaining good reconstructions consists in finding ways to add information that effectively restricts the solution space without violating properties of the sought solution. In this work, we attempt to address this problem by constructing a spatio-temporal basis of body surface potentials (BSP) from simulations of many focal excitations. Measured BSPs are projected onto this basis and reconstructions are expressed as linear combinations of corresponding transmembrane voltage (TMV) basis vectors. The novel method was applied to simulations of 100 atrial ectopic foci with three different conduction velocities. Three signal-to-noise ratios (SNR) and bases of six different temporal lengths were considered. Reconstruction quality was evaluated using the spatial correlation coefficient of TMVs as well as estimated local activation times (LAT). The focus localization error was assessed by computing the geodesic distance between true and reconstructed foci. Compared with an optimally parameterized Tikhonov-Greensite method, the BSP basis reconstruction increased the mean TMV correlation by up to 22, 24, and 32% for an SNR of 40, 20, and 0 dB, respectively. Mean LAT correlation could be improved by up to 5, 7, and 19% for the three SNRs. For 0 dB, the average localization error could be halved from 15.8 to 7.9 mm. For the largest basis length, the localization error was always below 34 mm. In conclusion, the new method improved reconstructions of atrial ectopic activity especially for low SNRs. Localization of ectopic foci turned out to be more robust and more accurate. Preliminary experiments indicate that the basis generalizes to some extent from the training data and may even be applied for reconstruction of non-ectopic activity.

Abstract:

Large-scale electrophysiological simulations to obtain electrocardiograms (ECG) carry the potential to produce extensive datasets for training of machine learning classifiers to, e.g., discriminate between different cardiac pathologies. The adoption of simulations for these purposes is limited due to a lack of ready-to-use models covering atrial anatomical variability. We built a bi-atrial statistical shape model (SSM) of the endocardial wall based on 47 segmented human CT and MRI datasets using Gaussian process morphable models. Generalization, specificity, and compactness metrics were evaluated. The SSM was applied to simulate atrial ECGs in 100 random volumetric instances. The first eigenmode of our SSM reflects a change of the total volume of both atria, the second the asymmetry between left vs. right atrial volume, the third a change in the prominence of the atrial appendages. The SSM is capable of generalizing well to unseen geometries and 95% of the total shape variance is covered by its first 23 eigenvectors. The P waves in the 12-lead ECG of 100 random instances showed a duration of 104ms in accordance with large cohort studies. The novel bi-atrial SSM itself as well as 100 exemplary instances with rule-based augmentation of atrial wall thickness, fiber orientation, inter-atrial bridges and tags for anatomical structures have been made publicly available. The novel, openly available bi-atrial SSM can in future be employed to generate large sets of realistic atrial geometries as a basis for in silico big data approaches.

Abstract:

OBJECTIVE: Atrial flutter (AFl) is a common arrhythmia that can be categorized according to different self-sustained electrophysiological mechanisms. The non-invasive discrimination of such mechanisms would greatly benefit ablative methods for AFl therapy as the driving mechanisms would be described prior to the invasive procedure, helping to guide ablation. In the present work, we sought to implement recurrence quantification analysis (RQA) on 12-lead ECG signals from a computational framework to discriminate different electrophysiological mechanisms sustaining AFl. METHODS: 20 different AFl mechanisms were generated in 8 atrial models and were propagated into 8 torso models via forward solution, resulting in 1,256 sets of 12-lead ECG signals. Principal component analysis was applied on the 12-lead ECGs, and six RQA-based features were extracted from the most significant principal component scores in two different approaches: individual component RQA and spatial reduced RQA. RESULTS: In both approaches, RQA-based features were significantly sensitive to the dynamic structures underlying different AFl mechanisms. Hit rate as high as 67.7% was achieved when discriminating the 20 AFl mechanisms. RQA-based features estimated for a clinical sample suggested high agreement with the results found in the computational framework. CONCLUSION: RQA has been shown an effective method to distinguish different AFl electrophysiological mechanisms in a non-invasive computational framework. A clinical 12-lead ECG used as proof of concept showed the value of both the simulations and the methods. SIGNIFICANCE: The non-invasive discrimination of AFl mechanisms helps to delineate the ablation strategy, reducing time and resources required to conduct invasive cardiac mapping and ablation procedures.

Abstract:

The solution of the inverse problem of electrocardiology allows the reconstruction of the spatial distribution of the electrical activity of the heart from the body surface electrocardiogram (electrocardiographic imaging, ECGI). ECGI using the equivalent dipole layer (EDL) model has shown to be accurate for cardiac activation times. However, validation of this method to determine repolarization times is lacking. In the present study, we determined the accuracy of the EDL model in reconstructing cardiac repolarization times, and assessed the robustness of the method under less ideal conditions (addition of noise and errors in tissue conductivity). A monodomain model was used to determine the transmembrane potentials in three different excitation-repolarization patterns (sinus beat and ventricular ectopic beats) as the gold standard. These were used to calculate the body surface ECGs using a finite element model. The resulting body surface electrograms (ECGs) were used as input for the EDL-based inverse reconstruction of repolarization times. The reconstructed repolarization times correlated well (COR > 0.85) with the gold standard, with almost no decrease in correlation after adding errors in tissue conductivity of the model or noise to the body surface ECG. Therefore, ECGI using the EDL model allows adequate reconstruction of cardiac repolarization times. Graphical abstract Validation of electrocardiographic imaging for repolarization using forward calculated body surface ECGs from simulated activation-repolarization sequences.

Abstract:

Radiofrequency ablation (RFA) therapy is the gold standard in interventional treatment of many cardiac arrhythmias. A major obstacle are non transmural lesions, leading to recurrence of arrhythmias. Recent clinical studies have suggested intracardiac electrogram (EGM) criteria as a promising marker to evaluate lesion development. Seeking for a deeper understanding of underlying mechanisms, we established a simulation approach for acute RFA lesions. Ablation lesions were modeled by a passive necrotic core surrounded by a borderzone with properties of heated myocardium. Herein, conduction velocity and electrophysiological properties were altered. We simulated EGMs during RFA to study the relation between lesion formation and EGM changes using the bidomain model. Simulations were performed on a three dimensional setup including a geometrically detailed representation of the catheter with highly conductive electrodes. For validation, EGMs recorded during RFA procedures in five patients were analyzed and compared to simulation results. Clinical data showed major changes in the distal unipolar EGM. During RFA, the negative peak amplitude decreased up to 104% and maximum negative deflection was up to 88% smaller at the end of the ablation sequence. These changes mainly occurred in the first 10 s after ablation onset. Simulated unipolar EGM reproduced the clinical changes, reaching up to 83% negative peak amplitude reduction and 80% decrease in maximum negative deflection for transmural lesions. In future work, the established model may enable the development of further EGM criteria for transmural lesions even for complex geometries in order to support clinical therapy.

Abstract:

We suggest a new regularization method for reconstruction of cardiac transmembrane voltages (TMV) from body surface potentials that is based on imposing similarity between time-aligned TMVs. An iterative scheme is proposed to update the delays needed for time-alignment. Evaluation of the method using simulated ventricular pacings showed a clear improvement over second order Tikhonov.

Abstract:

ECG imaging estimates the cardiac electrical activity from body surface potentials. As this involves solving a severly ill-posed problem, additional information is required to get a unique and stable solution. Recent progress is based on introducing more problem-specific information by exploiting the structure of cardiac excitation. However, added information must be either certain or general enough to not impair the solution. We have recently developed a method that uses a spatio-temporal basis to restrict the solution space. In the present work, we analyzed this method with respect to one of the most fundamental assumptions made during basis creation: cardiac (an)isotropy. We tested the reconstruction using simulations of ventricular pacings and then applied it to clinical data. In simulations, the overall median localization error was smallest with a basis including fiber orientation. For the clinical data, however, the overall error was smallest with an isotropic basis. This observation suggests that modeling priors should be introduced with care, whereby further work is needed.

Abstract:

The boundary element method is widely used to solve the forward problem of electrocardiography, i.e. to calculate the body surface potentials (BSP) caused by the heart’s electrical activity. This requires discretization of boundary surfaces between compartments of a torso model. Often, the resolution of the surface bounding the heart is chosen above 1 mm, which can lead to spikes in resulting BSPs. We demonstrate that this artifact is caused by discontinuous propagation of the wavefront on coarse meshes and can be avoided by blurring cardiac sources before spatial downsampling. We evaluate different blurring methods and show that Laplacian blurring reduces the BSP error 5-fold for both transmembrane voltages and extracellular potentials downsampled to 3 different resolutions. We suggest a method to find the optimal blurring parameter without having to compute BSPs using a fine mesh.

Abstract:

ECG imaging aims to reconstruct the cardiac electrical activity from non-invasive measurements of body surface potentials (BSP) by finding unique and physiologically meaningful solutions to the inverse problem of electrocardiography. This can be accomplished using regularization, which reduces the space of admissible solutions by demanding solution properties that are already known beforehand. Messnarz et. al. proposed a regularization scheme that requires transmembrane voltages (TMV) to not decrease over time. We suggest a generalization of this method that forces TMVs to decrease only slowly and as a result can also be applied to irregular cardiac activity. We first develop the method using a simplified spherical geometry and then show its benefit for imaging fibrillatory activity on a realistic geometry of the atria.

Abstract:

Modelling the interaction of the heart and the vascular system allows to study the pumping efficiency of the heart in a controlled environment under various cardiac and vascular conditions such as arrhythmias, dyssynchronies, regions of stiffened myocardium, valvular stenoses or decreased vascular compliances. To pose realistic hemodynamic boundary conditions to a four-chambered elastomechanical heart model, we developed a lumped element model of the closed loop human vascular system. Systemic and pulmonary circulations were each represented by a three-element Windkessel model emptying into a venous compliance. Both circulations were coupled by connecting the venous compliances to the corresponding atrium via venous resistances. Cardiac valves were represented by ideal diodes and resistances. Strong coupling between the heart and the vascular system model was accomplished by estimating the cardiac pressures that lead to continuous flows across the model interfaces. Active regulatory mechanisms were not considered. Pressures, flows and volumes throughout the circulatory system were simulated until a steady state was reached and the effects of model parameters on these hemodynamic parameters were evaluated in a sensitivity analysis. Increasing the systemic peripheral resistance by 50% caused an 8% decrease in stroke volume (SV) and a 33% increase in mean arterial pressure. Increased venous resistance descreased the E/A wave ratio of the atrioventricular flow and led to a reduced SV by impeding passive cardiac filling. Increasing the arterial compliance decreased mean cardiac pressures, while only slightly reducing the SV. Larger arterial resistances mainly caused higher peak systolic pressures. Furthermore, we show that embedding the heart model into surrounding elastic tissue by forcing permanent contact at the pericardial surface leads to more realistic time courses of atrial volumes and atrial pressure-volume curves composed of an A and a V loop as found in measurements. In conclusion, this work enables simulations of diseases that involve significant cardiovascular interaction.

Abstract:

Electrocardiographic imaging (ECGI) could help in diagnosis and treatment of atrial fibrillation (AF), the most common life-threatening arrhythmia. Based on a previous work by Figuera et al. on the reconstruction of epicardial potentials (EP) during AF, we explore the performance of a Tikhonov regularization with two spatial constraints for transmembrane voltage (TMV) based ECGI. We develop a new method to impose epi-endocardial similarity and show its benefit for ECGI of atrial activity. Apart from TMVs, local activation times and dominant frequency are evaluated as target parameters. In the AF models studied, joint reconstruction of epi- and endocardial TMVs showed performance comparable to the previously reported EPs imaging.

Abstract:

Intracardiac electrograms are essential for the diagnosis and treatment of various cardiac arrhythmias. To gain reliable information about structural alterations of underlying tissue, it is necessary to interpret these electrograms correctly. Therefore it has to be understood how other parameters influence the signal. Realistic 3D geometries were created and simulated using the bidomain model. Based on these simulations, the influences of catheter orientation, tissue thickness and conduction velocity on the amplitudes of intracardiac electrograms were evaluated.

Abstract:

A variety of biophysical and phenomenological active tension models has been proposed during the last decade that show physiological behaviour on a cellular level. However, applying these models in a whole heart finite element simulation framework yields either unphysiological values of stress and strain or an insufficient deformation pattern compared to magnetic resonance imaging data. In this study, we evaluate how introducing an orthotropic active stress tensor affects the deformation pattern by conducting a sensitivity analysis regarding the active tension at resting length Tref and three orthotropic activation parameters (Kss, Ksn and Knn). Deformation of left ventricular contraction is evaluated on a truncated ellipsoid using four features: wall thickening (WT), longitudinal shortening (LS), torsion (Θ) and ejection fraction (EF). We show that EF, WT and LS are positively correlated with the parameters Tref and Knn while Kss reduces all of the four observed features. Introducing shear stress to the model has little to no effect on EF, WT and LS, although it reduces torsion by up to 3◦. We find that added stress in the normal direction can support healthy deformation patterns. However, the twisting motion, which has been shown to be important for cardiac function, reduces by up to 20◦.

Abstract:

Over the last decades, computational models have been applied in in-silico simulations of the heart biomechan- ics. These models depend on input parameters. In particular, four parameters are needed for the constitutive law of Guc- cione et al., a model describing the stress-strain relation of the heart tissue. In the literature, we could find a wide range of values for these parameters. In this work, we propose an optimization framework which identifies the parameters of a constitutive law. This framework is based on experimental measurements conducted by Klotz et al.. They provide an end-diastolic pressure-volume relation- ship. We applied the proposed framework on one heart model and identified the following elastic parameters to optimally match the Klotz curve: 𝐶 = 313 Pa, 𝑏𝑓 = 17.8, 𝑏𝑡 = 7.1 and 𝑏𝑓𝑡 = 12.4. In general, this approach allows to identify optimized param- eters for a constitutive law, for a patient-specific heart geome- try. The use of optimized parameters will lead to physiological simulation results of the heart biomechanics and is therefore an important step towards applying computational models in clinical practice.

Abstract:

Atrial flutter (AFl) is a common heart rhythm disor- der driven by different self-sustaining electrophysiological atrial mechanisms. In the present work, we sought to dis- criminate which mechanism is sustaining the arrhythmia in an individual patient using non-invasive 12-lead elec- trocardiogram (ECG) signals. Specifically, we analyse the influence of atrial and torso geometries for the success of such discrimination. 2,512 ECG were simulated and 151 features were extracted from the signals. Three clas- sification scenarios were investigated: random set clas- sification; leave-one-atrium-out (LOAO); and leave-one- torso-out (LOTO). A radial basis neural network classifier achieved test accuracies of 89.84%, 88.98%, and 59.82% for the random set classification, LOTO, and LOAO, re- spectively. The most discriminative single feature was the F-wave duration (74% test accuracy). Our results show that a machine learning approach can potentially identify a high number of different AFl mechanisms using the 12- lead ECG. More than the 8 atrial models used in this work should be included during training due to the significant influence that the atrial geometry has on the ECG signals and thus on the resulting classification. This non-invasive classification can help to identify the optimal ablation strategy, reducing time and resources required to conduct invasive cardiac mapping and ablation procedures.

Abstract:

Activation times (AT) describe the sequence of cardiac depolarization and represent one of the most important parameters for analysis of cardiac electrical activity. However, estimation of ATs can be challenging due to multiple sources of noise such as fractionation or baseline wander. If ATs are estimated from signals reconstructed using electrocardiographic imaging (ECGI), additional problems can arise from over-smoothing or due to ambiguities in the inverse problem. Often, resulting AT maps show falsely homogeneous regions or artificial lines of block. As ATs are not only important clinically, but are also commonly used for evaluation of ECGI methods, it is important to understand where these errors come from. We present results from a community effort to compare methods for AT estimation on a common dataset of simulated ventricular pacings. ECGI reconstructions were performed using three different surface source models: transmembrane voltages, epi-endo potentials and pericardial potentials, all using 2nd-order Tikhonov and 6 different regularization parameters. ATs were then estimated by the community participants and compared to the ground truth. While the pacing site had the largest effect on AT correlation coefficients (CC larger for lateral than for septal pacings), there were also differences between methods and source models that were poorly reflected in CCs. Results indicate that artificial lines of block are most severe for purely temporal methods. Compared to the other source models, ATs estimated from transmembrane voltages are more precise and less prone to artifacts.

Abstract:

Electrocardiographic Imaging (ECGI) requires robust ECG forward simulations to accurately calculate cardiac activity. However, many questions remain regarding ECG forward simulations, for instance: there are not common guidelines for the required cardiac source sampling. In this study we test equivalent double layer (EDL) forward simulations with differing cardiac source resolutions and different spatial interpolation techniques. The goal is to reduce error caused by undersampling of cardiac sources and provide guidelines to reduce said source undersampling in ECG forward simulations. Using a simulated dataset sampled at 5 spatial resolutions, we computed body surface potentials using an EDL forward simulation pipeline. We tested two spatial interpolation methods to reduce error due to undersampling triangle weighting and triangle splitting. This forward modeling pipeline showed high frequency artifacts in the predicted ECG time signals when the cardiac source resolution was too low. These low resolutions could also cause shifts in extrema location on the body surface maps. However, these errors in predicted potentials can be mitigated by using a spatial interpolation method. Using spatial interpolation can reduce the number of nodes required for accurate body surface potentials from 9,218 to 2,306. Spatial interpolation in this forward model could also help improve accuracy and reduce computational cost in subsequent ECGI applications.

Abstract:

Nowadays, a large share of the global population is affected by heart rhythm disorders. Computational modelling is a useful tool for understanding the dynamics of cardiac arrhythmias. Several recent clinical and experimental studies suggest that atrial fibrillation is maintained by re-entrant drivers (e.g. rotors). As a consequence, numerous works have addressed atrial arrhythmogenicity of a given electrophysiological model using different methods to simulate the perpetuation of re-entrant activity. However, no common procedure to test atrial fibrillation vulnerability has yet been defined. Here, we systematically evaluate and compare two state-of-the-art methods. The first one is rapid extrastimulus pacing from rim of the four pulmonary veins. The second consists of placing phase singularities in the atria, estimating an activation time map by solving the Eikonal equation and finally using this as initial condition for the electrical cardiac propagation simulation. In this way, we are forcing the wavefronts to follow re-entrant circuits with low computational cost thus less simulation time. We aim to identify a methodology to quantify arrhythmia vulnerability on patient-specific atrial geometries and substrates. We will proceed with in-silico experiments, comparing the results of these two methods to initiate re-entrant activity, checking the influence of the different parameters on the dynamics on the re-entrant drivers and finally extracting a valid set of parameters allowing to reliably assess re-entry vulnerability. The final objective is to come up with an easily reproducible minimal set of simulations to assess vulnerability of a particular atrial substrate (cellular and tissue model) or of distinct anatomical atrial geometries to arrhythmic episodes. Given the great need of exploring susceptibility to atrial arrhythmias, i.e. after a first ablation procedure, this study can provide a useful tool to test new treatment strategies and to learn how to prevent the onset and progression of atrial fibrillation.

Abstract:

The human heart is an organ of high complexity and hence, very challenging to simulate. To calculate the force developed by the human heart and therefore the tension of the muscle fibers, accurate models are necessary. The force generated by the cardiac muscle has physiologically imposed limits and depends on various characteristics such as the length, strain and the contraction velocity of the cardiomyocytes. Another characteristic is the activation time of each cardiomyocyte, which is a wave and not a static value for all cardiomyocytes. To simulate a physiologically correct excitation, the functionality of the cardiac simulation framework CardioMechanics was extended to incorporate inhomogeneous activation times. The functionality was then used to evaluate the effects of local activation times with two different tension models. The active stress generated by the cardiomyocytes was calculated by (i) an explicit function and (ii) an ode-based model. The results of the simulations showed that the maximum pressure in the left ventricle dropped by 2.3% for the DoubleHill model and by 5.3% for the Lumens model. In the right ventricle the simulations showed similar results. The maximum pressure in both the left and the right atrium increased using both models. Given that the simulation of the inhomogeneously activated cardiomyocytes increases the simulation time when used with the more precise Lumens model, the small drop in maximum pressure seems to be negligible in favor of a simpler simulation model.

Abstract:

Radiofrequency ablation (RFA) is a widely used clinical treatment for many types of cardiac arrhythmias. However, nontransmural lesions and gaps between linear lesions often lead to recurrence of the arrhythmia. Intrac- ardiac electrograms (IEGMs) provide real-time informa- tion regarding the state of the cardiac tissue surrounding the catheter tip. Nevertheless, the formation and inter- pretation of IEGMs during the RFA procedure is complex and yet not fully understood. In this in-silico study, we propose a computational model for acute ablation lesions. Our model consists of a necrotic scar core and a border zone, describing irreversible and reversible temperature induced electrophysiological phenomena. These phenom- ena are modeled by varying the intra- and extracellular conductivity of the tissue as well as a regulating zone factor. The computational model is evaluated regarding its feasibility and validity. Therefore, this model was com- pared to an existing one and to clinical measurements of ve patients undergoing RFA. The results show that the model can indeed be used to recreate IEGMs. We computed IEGMs arising from complex ablation scars, such as scars with gaps or two overlapping ellipsoid scars. For orthogo- nal catheter orientation, the presence of a second necrotic core in the near- eld of a punctiform acute ablation lesion had minor impact on the resulting signal morphology. The presented model can serve as a base for further research on the formation and interpretation of IEGMs.

Abstract:

Creating transmural ablation scars in a reliable way is a key issue in improvement of therapeutical pro- cedures for cardiac arrhythmias. About one third of the patients has to undergo several procedures till arrhythmic episodes are successfully treated. Morphological features of intracardiac electrograms might contribute to evaluate scar transmurality during the ablation procedure. We an- alyzed intracardiac signals before, during and after point- wise ablation in patients with atrial flutter. Unipolar elec- trograms of the distal electrode showed a relative decrease in amplitude of the second extremum of up to 99 % with a mean of 84±20.6 % after the endpoint of ablation.

Abstract:

Intracardiac electrograms are the key in under- standing, interpretation and treatment of cardiac arrhythmias. However, electrogram morphologies are strongly variable due to catheter position, orientation and contact. Simulations of intracardiac electrograms can improve comprehension and quantification of influencing parameters and therefore reduce misinterpretations. In this study simulated intracardiac electro- grams are analyzed regarding tilt angles of the catheter relative to the propagation direction, electrode tissue distances as well as clinical filter settings. Catheter signals are computed on a realistic 3D catheter geometry using bidomain simulations of cardiac electrophysiology. Thereby high conductivities of the catheter electrodes are taken into account. For validation, simulated electrograms are compared with in vivo electrograms recorded during an EP-study with direct annotation of catheter orientation and tissue contact. Good agreement was reached regarding timing and signal width of simulated and measured electrograms. Correlation was 0.92±0.07 for bipolar, 0.92±0.05 for unipolar distal and 0.80 ± 0.12 for unipolar proximal electrograms for different catheter orientations and locations.

Abstract:

Local activation time (LAT) maps help to understand the path of electrical excitation in cardiac arrhythmias. They can be generated automatically from intracardiac electrograms using various criteria provided by commercial electroanatomical mapping systems. This study compares existing criteria and a novel method based on the non-linear energy operator (NLEO) with respect to their precision and robustness.