A Review of Personalised Cardiac Computational Modelling Using Electroanatomical Mapping Data.

Computational models of cardiac electrophysiology have gradually matured during the past few decades and are now being personalised to provide patient-specific therapy guidance for improving suboptimal treatment outcomes. The predictive features of these personalised electrophysiology models hold the promise of providing optimal treatment planning, which is currently limited in the clinic owing to reliance on a population-based or average patient approach. The generation of a personalised electrophysiology model entails a sequence of steps for which a range of activation mapping, calibration methods and therapy simulation pipelines have been suggested. However, the optimal methods that can potentially constitute a clinically relevant in silico treatment are still being investigated and face limitations, such as uncertainty of electroanatomical data recordings, generation and calibration of models within clinical timelines and requirements to validate or benchmark the recovered tissue parameters. This paper is aimed at reporting techniques on the personalisation of cardiac computational models, with a focus on calibrating cardiac tissue conductivity based on electroanatomical mapping data.

Constructing bilayer and volumetric atrial models at scale.

To enable large in silico trials and personalized model predictions on clinical timescales, it is imperative that models can be constructed quickly and reproducibly. First, we aimed to overcome the challenges of constructing cardiac models at scale through developing a robust, open-source pipeline for bilayer and volumetric atrial models. Second, we aimed to investigate the effects of fibres, fibrosis and model representation on fibrillatory dynamics. To construct bilayer and volumetric models, we extended our previously developed coordinate system to incorporate transmurality, atrial regions and fibres (rule-based or data driven diffusion tensor magnetic resonance imaging (MRI)). We created a cohort of 1000 biatrial bilayer and volumetric models derived from computed tomography (CT) data, as well as models from MRI, and electroanatomical mapping. Fibrillatory dynamics diverged between bilayer and volumetric simulations across the CT cohort (correlation coefficient for phase singularity maps: left atrial (LA) 0.27 ± 0.19, right atrial (RA) 0.41 ± 0.14). Adding fibrotic remodelling stabilized re-entries and reduced the impact of model type (LA: 0.52 ± 0.20, RA: 0.36 ± 0.18). The choice of fibre field has a small effect on paced activation data (less than 12 ms), but a larger effect on fibrillatory dynamics. Overall, we developed an open-source user-friendly pipeline for generating atrial models from imaging or electroanatomical mapping data enabling in silico clinical trials at scale (https://github.com/pcmlab/atrialmtk).

Treatment of pathophysiologic propagation outside of the pulmonary veins in retreatment of atrial fibrillation patients: RECOVER AF study.

AIMS: RECOVER AF evaluated the performance of whole-chamber non-contact charge-density mapping to guide the ablation of non-pulmonary vein (PV) targets in persistent atrial fibrillation (AF) patients following either a first or second failed procedure. METHODS AND RESULTS: RECOVER AF was a prospective, non-randomized trial that enrolled patients scheduled for a first or second ablation retreatment for recurrent AF. The PVs were assessed and re-isolated if necessary. The AF maps were used to guide the ablation of non-PV targets through elimination of pathologic conduction patterns (PCPs). Primary endpoint was freedom from AF on or off antiarrhythmic drugs (AADs) at 12 months. Patients undergoing retreatment with the AcQMap System (n = 103) were 76% AF-free at 12 months [67% after single procedure (SP)] on or off AADs (80% free from AF on AADs). Patients who had only received a pulmonary vein isolation (PVI) prior to study treatment of non-PV targets with the AcQMap System were 91% AF-free at 12 months (83% SP). No major adverse events were reported. CONCLUSION: Non-contact mapping can be used to target and guide the ablation of PCPs beyond the PVs in persistent AF patients returning for a first or second retreatment with 76% freedom from AF at 12 months. The AF freedom was particularly high, 91% (43/47), for patients enrolled having only a prior de novo PVI, and freedom from all atrial arrhythmias for this cohort was 74% (35/47). These early results are encouraging and suggest that guiding individualized targeted ablation of PCPs may therefore be advantageous to target at the earliest opportunity in patients with persistent AF.

Tipping the scales of understanding: An engineering approach to design and implement whole-body cardiac electrophysiology experimental models.

The study of cardiac electrophysiology is built on experimental models that span all scales, from ion channels to whole-body preparations. Novel discoveries made at each scale have contributed to our fundamental understanding of human cardiac electrophysiology, which informs clinicians as they detect, diagnose, and treat complex cardiac pathologies. This expert review describes an engineering approach to developing experimental models that is applicable across scales. The review also outlines how we applied the approach to create a set of multiscale whole-body experimental models of cardiac electrophysiology, models that are driving new insights into the response of the myocardium to acute ischemia. Specifically, we propose that researchers must address three critical requirements to develop an effective experimental model: 1) how the experimental model replicates and maintains human physiological conditions, 2) how the interventions possible with the experimental model capture human pathophysiology, and 3) what signals need to be measured, at which levels of resolution and fidelity, and what are the resulting requirements of the measurement system and the access to the organs of interest. We will discuss these requirements in the context of two examples of whole-body experimental models, a closed chest in situ model of cardiac ischemia and an isolated-heart, torso-tank preparation, both of which we have developed over decades and used to gather valuable insights from hundreds of experiments.

Improving Generalization by Learning Geometry-Dependent and Physics-Based Reconstruction of Image Sequences.

Deep neural networks have shown promise in image reconstruction tasks, although often on the premise of large amounts of training data. In this paper, we present a new approach to exploit the geometry and physics underlying electrocardiographic imaging (ECGI) to learn efficiently with a relatively small dataset. We first introduce a non-Euclidean encoding-decoding network that allows us to describe the unknown and measurement variables over their respective geometrical domains. We then explicitly model the geometry-dependent physics in between the two domains via a bipartite graph over their graphical embeddings. We applied the resulting network to reconstruct electrical activity on the heart surface from body-surface potentials. In a series of generalization tasks with increasing difficulty, we demonstrated the improved ability of the network to generalize across geometrical changes underlying the data using less than 10% of training data and fewer variations of training geometry in comparison to its Euclidean alternatives. In both simulation and real-data experiments, we further demonstrated its ability to be quickly fine-tuned to new geometry using a modest amount of data.

Reconstruction of cardiac position using body surface potentials.

Electrocardiographic imaging (ECGI) is a noninvasive technique to assess the bioelectric activity of the heart which has been applied to aid in clinical diagnosis and management of cardiac dysfunction. ECGI is built on mathematical models that take into account several patient specific factors including the position of the heart within the torso. Errors in the localization of the heart within the torso, as might arise due to natural changes in heart position from respiration or changes in body position, contribute to errors in ECGI reconstructions of the cardiac activity, thereby reducing the clinical utility of ECGI. In this study we present a novel method for the reconstruction of cardiac geometry utilizing noninvasively acquired body surface potential measurements. Our geometric correction method simultaneously estimates the cardiac position over a series of heartbeats by leveraging an iterative approach which alternates between estimating the cardiac bioelectric source across all heartbeats and then estimating cardiac positions for each heartbeat. We demonstrate that our geometric correction method is able to reduce geometric error and improve ECGI accuracy in a wide range of testing scenarios. We examine the performance of our geometric correction method using different activation sequences, ranges of cardiac motion, and body surface electrode configurations. We find that after geometric correction resulting ECGI solution accuracy is improved and variability of the ECGI solutions between heartbeats is substantially reduced.

Combining endocardial mapping and electrocardiographic imaging (ECGI) for improving PVC localization: A feasibility study.

INTRODUCTION: Accurate reconstruction of cardiac activation wavefronts is crucial for clinical diagnosis, management, and treatment of cardiac arrhythmias. Furthermore, reconstruction of activation profiles within the intramural myocardium has long been impossible because electrical mapping was only performed on the endocardial surface. Recent advancements in electrocardiographic imaging (ECGI) have made endocardial and epicardial activation mapping possible. We propose a novel approach to use both endocardial and epicardial mapping in a combined approach to reconstruct intramural activation times. OBJECTIVE: To implement and validate a combined epicardial/endocardial intramural activation time reconstruction technique. METHODS: We used 11 simulations of ventricular activation paced from sites throughout myocardial wall and extracted endocardial and epicardial activation maps at approximate clinical resolution. From these maps, we interpolated the activation times through the myocardium using thin-plate-spline radial basis functions. We evaluated activation time reconstruction accuracy using root-mean-squared error (RMSE) of activation times and the percent of nodes within 1 ms of the ground truth. RESULTS: Reconstructed intramural activation times showed an RMSE and percentage of nodes within 1 ms of the ground truth simulations of 3 ms and 70%, respectively. In the worst case, the RMSE and percentage of nodes were 4 ms and 60%, respectively. CONCLUSION: We showed that a simple, yet effective combination of clinical endocardial and epicardial activation maps can accurately reconstruct intramural wavefronts. Furthermore, we showed that this approach provided robust reconstructions across multiple intramural stimulation sites.

Transient recovery of epicardial and torso ST-segment ischemic signals during cardiac stress tests: A possible physiological mechanism.

BACKGROUND: Acute myocardial ischemia has several characteristic ECG findings, including clinically detectable ST-segment deviations. However, the sensitivity and specificity of diagnosis based on ST-segment changes are low. Furthermore, ST-segment deviations have been shown to be transient and spontaneously recover without any indication the ischemic event has subsided. OBJECTIVE: Assess the transient recovery of ST-segment deviations on remote recording electrodes during a partial occlusion cardiac stress test and compare them to intramyocardial ST-segment deviations. METHODS: We used a previously validated porcine experimental model of acute myocardial ischemia with controllable ischemic load and simultaneous electrical measurements within the heart wall, on the epicardial surface, and on the torso surface. Simulated cardiac stress tests were induced by occluding a coronary artery while simultaneously pacing rapidly or infusing dobutamine to stimulate cardiac function. Postexperimental imaging created anatomical models for data visualization and quantification. Markers of ischemia were identified as deviations in the potentials measured at 40% of the ST-segment. Intramural cardiac conduction speed was also determined using the inverse gradient method. We assessed changes in intramyocardial ischemic volume proportion, conduction speed, clinical presence of ischemia on remote recording arrays, and regional changes to intramyocardial ischemia. We defined the peak deviation response time as the time interval after onset of ischemia at which maximum ST-segment deviation was achieved, and ST-recovery time was the interval when ST deviation returned to below thresholded of ST elevation. RESULTS: In both epicardial and torso recordings, the peak ST-segment deviation response time was 4.9±1.1 min and the ST-recovery time was approximately 7.9±2.5 min, both well before the termination of the ischemic stress. At peak response time, conduction speed was reduced by 50% and returned to near baseline at ST-recovery. The overall ischemic volume proportion initially increased, on average, to 37% at peak response time; however, it recovered to only 30% at the ST-recovery time. By contrast, the subepicardial region of the myocardial wall showed 40% ischemic volume at peak response time and recovered much more strongly to 25% as epicardial ST-segment deviations returned to baseline. CONCLUSION: Our data show that remote ischemic signal recovery correlates with a recovery of the subepicardial myocardium, whereas subendocardial ischemic development persists.

Pharmacological and simulated exercise cardiac stress tests produce different ischemic signatures in high-resolution experimental mapping studies.

OBJECTIVE: Test the hypothesis that exercise and pharmacological cardiac stressors create different electrical ischemic signatures. INTRODUCTION: Current clinical stress tests for detecting ischemia lack sensitivity and specificity. One unexplored source of the poor detection is whether pharmacological stimulation and regulated exercise produce identical cardiac stress. METHODS: We used a porcine model of acute myocardial ischemia in which animals were instrumented with transmural plunge-needle electrodes, an epicardial sock array, and torso arrays to simultaneously measure cardiac electrical signals within the heart wall, the epicardial surface, and the torso surface, respectively. Ischemic stress via simulated exercise and pharmacological stimulation were created with rapid electrical pacing and dobutamine infusion, respectively, and mimicked clinical stress tests of five 3-minute stages. Perfusion to the myocardium was regulated by a hydraulic occluder around the left anterior descending coronary artery. Ischemia was measured as deflections to the ST-segment on ECGs and electrograms. RESULTS: Across eight experiments with 30 (14 simulated exercise and 16 dobutamine) ischemic interventions, the spatial correlations between exercise and pharmacological stress diverged at stage three or four during interventions (p<0.05). We found more detectable ST-segment changes on the epicardial surface during simulated exercise than with dobutamine (p<0.05). The intramyocardial ischemia formed during simulated exercise had larger ST40 potential gradient magnitudes (p<0.05). CONCLUSION: We found significant differences on the epicardium between cardiac stress types using our experimental model, which became more pronounced at the end stages of each test. A possible mechanism for these differences was the larger ST40 potential gradient magnitudes within the myocardium during exercise. The presence of microvascular dysfunction during exercise and its absence during dobutamine stress may explain these differences.

Simultaneous Multi-Heartbeat ECGI Solution with a Time-Varying Forward Model: a Joint Inverse Formulation.

Electrocardiographic imaging (ECGI) is an effective tool for noninvasive diagnosis of a range of cardiac dysfunctions. ECGI leverages a model of how cardiac bioelectric sources appear on the torso surface (the forward problem) and uses recorded body surface potential signals to reconstruct the bioelectric source (the inverse problem). Solutions to the inverse problem are sensitive to noise and variations in the body surface potential (BSP) recordings such as those caused by changes or errors in cardiac position. Techniques such as signal averaging seek to improve ECGI solutions by incorporating BSP signals from multiple heartbeats into an averaged BSP with a higher SNR to use when estimating the cardiac bioelectric source. However, signal averaging is limited when it comes to addressing sources of BSP variability such as beat to beat differences in the forward solution. We present a novel joint inverse formulation to solve for the cardiac source given multiple BSP recordings and known changes in the forward solution, here changes in the heart position. We report improved ECGI accuracy over signal averaging and averaged individual inverse solutions using this joint inverse formulation across multiple activation sequence types and regularization techniques with measured canine data and simulated heart motion. Our joint inverse formulation builds upon established techniques and consequently can easily be applied with many existing regularization techniques, source models, and forward problem formulations.

The electrocardiographic forward problem: A benchmark study.

BACKGROUND: Electrocardiographic forward problems are crucial components for noninvasive electrocardiographic imaging (ECGI) that compute torso potentials from cardiac source measurements. Forward problems have few sources of error as they are physically well posed and supported by mature numerical and computational techniques. However, the residual errors reported from experimental validation studies between forward computed and measured torso signals remain surprisingly high. OBJECTIVE: To test the hypothesis that incomplete cardiac source sampling, especially above the atrioventricular (AV) plane is a major contributor to forward solution errors. METHODS: We used a modified Langendorff preparation suspended in a human-shaped electrolytic torso-tank and a novel pericardiac-cage recording array to thoroughly sample the cardiac potentials. With this carefully controlled experimental preparation, we minimized possible sources of error, including geometric error and torso inhomogeneities. We progressively removed recorded signals from above the atrioventricular plane to determine how the forward-computed torso-tank potentials were affected by incomplete source sampling. RESULTS: We studied 240 beats total recorded from three different activation sequence types (sinus, and posterior and anterior left-ventricular free-wall pacing) in each of two experiments. With complete sampling by the cage electrodes, all correlation metrics between computed and measured torso-tank potentials were above 0.93 (maximum 0.99). The mean root-mean-squared error across all beat types was also low, less than or equal to 0.10 mV. A precipitous drop in forward solution accuracy was observed when we included only cage measurements below the AV plane. CONCLUSION: First, our forward computed potentials using complete cardiac source measurements set a benchmark for similar studies. Second, this study validates the importance of complete cardiac source sampling above the AV plane to produce accurate forward computed torso potentials. Testing ECGI systems and techniques with these more complete and highly accurate datasets will improve inverse techniques and noninvasive detection of cardiac electrical abnormalities.

Quantifying the spatiotemporal influence of acute myocardial ischemia on volumetric conduction velocity.

INTRODUCTION: Acute myocardial ischemia occurs when coronary perfusion to the heart is inadequate, which can perturb the highly organized electrical activation of the heart and can result in adverse cardiac events including sudden cardiac death. Ischemia is known to influence the ST and repolarization phases of the ECG, but it also has a marked effect on propagation (QRS); however, studies investigating propagation during ischemia have been limited. METHODS: We estimated conduction velocity (CV) and ischemic stress prior to and throughout 20 episodes of experimentally induced ischemia in order to quantify the progression and correlation of volumetric conduction changes during ischemia. To estimate volumetric CV, we 1) reconstructed the activation wavefront; 2) calculated the elementwise gradient to approximate propagation direction; and 3) estimated conduction speed (CS) with an inverse-gradient technique. RESULTS: We found that acute ischemia induces significant conduction slowing, reducing the global median speed by 20 cm/s. We observed a biphasic response in CS (acceleration then deceleration) early in some ischemic episodes. Furthermore, we noted a high temporal correlation between ST-segment changes and CS slowing; however, when comparing these changes over space, we found only moderate correlation (corr. = 0.60). DISCUSSION: This study is the first to report volumetric CS changes (acceleration and slowing) during episodes of acute ischemia in the whole heart. We showed that while CS changes progress in a similar time course to ischemic stress (measured by ST-segment shifts), the spatial overlap is complex and variable, showing extreme conduction slowing both in and around regions experiencing severe ischemia.

Estimation and Validation of Cardiac Conduction Velocity and Wavefront Reconstruction Using Epicardial and Volumetric Data.

OBJECTIVE: In this study, we have used whole heart simulations parameterized with large animal experiments to validate three techniques (two from the literature and one novel) for estimating epicardial and volumetric conduction velocity (CV). METHODS: We used an eikonal-based simulation model to generate ground truth activation sequences with prescribed CVs. Using the sampling density achieved experimentally we examined the accuracy with which we could reconstruct the wavefront, and then examined the robustness of three CV estimation techniques to reconstruction related error. We examined a triangulation-based, inverse-gradient-based, and streamline-based techniques for estimating CV cross the surface and within the volume of the heart. RESULTS: The reconstructed activation times agreed closely with simulated values, with 50-70% of the volumetric nodes and 97-99% of the epicardial nodes were within 1 ms of the ground truth. We found close agreement between the CVs calculated using reconstructed versus ground truth activation times, with differences in the median estimated CV on the order of 3-5% volumetrically and 1-2% superficially, regardless of what technique was used. CONCLUSION: Our results indicate that the wavefront reconstruction and CV estimation techniques are accurate, allowing us to examine changes in propagation induced by experimental interventions such as acute ischemia, ectopic pacing, or drugs. SIGNIFICANCE: We implemented, validated, and compared the performance of a number of CV estimation techniques. The CV estimation techniques implemented in this study produce accurate, high-resolution CV fields that can be used to study propagation in the heart experimentally and clinically.

A Cardiac Shape Model for Segmentation Uncertainty Quantification.

Segmentation of cardiac images is a variable component of many patient specific computational pipelines, yet its impact on simulated results are still not fully understood. A hurdle to to exploring the impact of the segmentation variability is the technical challenge of building a statistical shape model of the ventricles. In this study, we improved open our previous shape analysis by creating a unified shape model including both the epicardium and endocardium. We tested four techniques within ShapeWorks to generate a ventricular shape model: standard, multidomain, hybrid multidomain, and geodesic distance. The multidomain and hybrid multidomain generated a shape model using all eleven segmentations, and the geodesic distance method generated a shape model using a subset of four segmentations. Each of the shape models captured spatially dependent characteristics of the segmentation variability, including wall thickness, annular diameter, and basal truncation. While each of the three methods have benefits, the hybrid multidomain approach provided the most accurate shape model with fewest points and may be most useful in a majority of applications.

High-Capacity Cardiac Signal Acquisition System for Flexible, Simultaneous, Multidomain Acquisition.

Capturing cardiac electrical propagation or electrocardiographic images demands simultaneous, multidomain recordings of electrocardiographic signals with adequate spatial and temporal resolution. Available systems can be cost-prohibitive or lack the necessary flexibility to capture signals from the heart and torso. We have designed and constructed a system that leverages affordable commercial products (Intantech, CA, USA) to create a complete, cardiac signal acquisition system that includes a flexible front end, analog signal conditioning, and defibrillation protection. The design specifications for this project were to (1) record up to 1024 channels simultaneously at a minimum of 1 kHz, (2) capture signals within the range of ± 30 mV with a resolution of 1 µV, and (3) provide a flexible interface for custom electrode inputs.We integrated the Intantech A/D conversion circuits to create a novel system, which meets all the required specifications. The system connects to a standard laptop computer under control of open-source software (Intantech). To test the system, we recorded electrograms from within the myocardium, on the heart surface, and on the body surface simultaneously from a porcine experimental preparation. Noise levels were comparable to both our existing, custom acquisition system and a commercial competitor. The cost per channel was $32 USD, totaling $33,800 USD for a complete system.

Novel Experimental Preparation to Assess Electrocardiographic Imaging Reconstruction Techniques.

Electrocardiographic imaging (ECGI) systems are still plagued by a myriad of controllable and uncontrollable sources of error, which makes studying and improving these systems difficult. To mitigate these errors, we developed a novel experimental preparation using a rigid pericardiac cage suspended in a torso-shaped electrolytic tank. The 256-electrode cage was designed to record signals 0.5-1.0 cm above the entire epicardial surface of an isolated heart. The cage and heart were fixed in a 192-electrode torso tank filled with electrolyte with predetermined conductivity. The resulting signals served as ground truth for ECGI performed using the boundary element method (BEM) and method of fundamental solutions (MFS) with three regularization techniques: Tikhonov zero-order (Tik0), Tikhonov second-order (Tik2), truncated singular value decomposition (TSVD). Each ECGI regularization technique reconstructed cage potentials from recorded torso potentials well with spatial correlation above 0.7, temporal correlation above 0.8, and root mean squared error values below 0.7 mV. The earliest site of activation was best identified by MFS using Tik0, which localized it to within a range of 1.9 and 4.8 cm. Our novel experimental preparation has shown unprecedented agreement with simulations and represents a new standard for ECGI validation studies.

Improving Localization of Cardiac Geometry Using ECGI.

INTRODUCTION: Electrocardiographic imaging (ECGI) requires a model of the torso, and inaccuracy in the position of the heart is a known source of error. We previously presented a method to localize the heart when body and heart surface potentials are known. The goal of this study is to extend this approach to only use body surface potentials. METHODS: We used an iterative coordinate descent optimization to estimate the positions of the heart for several consecutive heartbeats relying on the assumption that the epicardial potential sequence is the same in each beat. The method was tested with data synthesized using measurements from a isolated-heart, torso-tank preparation. Improvement was evaluated in terms of both heart localization and ECGI accuracy. RESULTS: The geometric correction resulted in cardiac geometries closely matching ground truth geometry. ECGI accuracy increased dramatically by all metrics using the corrected geometry. DISCUSSION: Future studies will employ more realistic animal models and then human subjects. Success could impact clinical ECGI by reducing errors from respiratory movement and perhaps decrease imaging requirements, reducing both cost and logistical difficulty of ECGI, widening clinical applicability.

Quantifying the Spatiotemporal Influence of Acute Myocardial Ischemia on Volumetric Conduction Speeds.

Acute myocardial ischemia compromises the ordered electrical activation of the heart, however, because of sampling limitations, volumetric changes in activation have not been measured. We used a large-animal experimental model and high-resolution volumetric mapping to study the effects of ischemia on conduction speeds (CS) throughout the myocardium. We estimated CS and electrocardiographic changes (ST segments) and evaluated the spatial and temporal correlations between them across 11 controlled episodes. We found that ischemia induces significant conduction slowing, reducing the global median speed by 25 cm/s. Furthermore, there was a high temporal correlation between the development of ischemic severity and CS (corr. = 0.93) through each episode. The spatial correlations between ST-segment changes and CS slowing were more spatially complex than expected with substantial slowing at the periphery of the zones that showed ST-segment changes. This is the first study that has documented in an experimental model volumetric changes of CS during acute myocardial ischemia and explored the relationships between ischemia development in space and time. We showed that conduction speed changes are spatiotemporally correlated to ischemic severity and illustrated the biphasic response long proposed from cellular studies.

Experimental Validation of a Novel Extracellular-Based Source Representation of Acute Myocardial Ischemia.

Electrocardiographic imaging (ECGI) based detection of myocardial ischemia requires an accurate formulation of the source model, which includes a relationship between extracellular and transmembrane potentials (TMPs). In this study, we used high-resolution intramural experimental recordings and forward modeling to examine the relationship between extracellular potentials and TMPs during myocardial ischemia. We measured extracellular electro-grams from intramural plunge needle arrays during seven controlled ischemia episodes in an animal model. We used three TMP source representations: (1) parameterized and distance-based (defined previously), (2) extracellular-based linear transform, and (3) extracellular-based sigmoidal transform. TMPs for each source formulation were then used to compute extracellular potentials by calculating the passive bidomain forward solution throughout the myocardium. We compared measured and computed potentials. Linear and sigmoidal approaches produced improved results compared to the parameterized method. The RMSE, SC, and TC of linear, sigmoidal, and parameterized methods were 0.85 mV, 1.21 mV, and 3.37 mV; 0.91, 0.88, and 0.47; 0.90, 0.77, and 0.33 respectively. We found extracellular-based calculations of TMPs produced superior forward computations compared to parameterized zones.

Effect of Myocardial Fiber Direction on Epicardial Activation Patterns.

Fiber structure governs the spread of excitation in the heart, however, little is known about the effects of physiological variability in the fiber orientation on epicardial activation. To investigate these effects, we used computer simulation to compare ventricular activation sequences initiated from stimulus sites at regularly spaced depths within the myocardium under varying rule-based fiber ranges. We compared the effects using four characteristics of epicardial breakthrough (BKT): location, area, shape (calculated via the axis ratio of a fitted ellipse), and orientation. Our results showed changes in the BKT characteristics as pacing depth increased, e.g., the area increased, the shape became more circular, and the orientation rotated counterclockwise, regardless of the fiber orientation. Furthermore, the maximal differences in epicardial activation from a single pacing site for location, area, axis ratio, and orientation were 1.2 mm, 74 mm 2 , 0.16, and 26°, respectively. Our results suggest that variability in fiber orientation has a negligible effect on the location, area, and shape of the BKT, while fluctuations were observed in the BKT orientation in response to the fiber fields, especially for epicardial stimulation sites. Our results suggest the fiber field orientation plays only a minor role in activation simulations of ectopic beats.