Cell to whole organ global sensitivity analysis on a four-chamber heart electromechanics model using Gaussian processes emulators.

Cardiac pump function arises from a series of highly orchestrated events across multiple scales. Computational electromechanics can encode these events in physics-constrained models. However, the large number of parameters in these models has made the systematic study of the link between cellular, tissue, and organ scale parameters to whole heart physiology challenging. A patient-specific anatomical heart model, or digital twin, was created. Cellular ionic dynamics and contraction were simulated with the Courtemanche-Land and the ToR-ORd-Land models for the atria and the ventricles, respectively. Whole heart contraction was coupled with the circulatory system, simulated with CircAdapt, while accounting for the effect of the pericardium on cardiac motion. The four-chamber electromechanics framework resulted in 117 parameters of interest. The model was broken into five hierarchical sub-models: tissue electrophysiology, ToR-ORd-Land model, Courtemanche-Land model, passive mechanics and CircAdapt. For each sub-model, we trained Gaussian processes emulators (GPEs) that were then used to perform a global sensitivity analysis (GSA) to retain parameters explaining 90% of the total sensitivity for subsequent analysis. We identified 45 out of 117 parameters that were important for whole heart function. We performed a GSA over these 45 parameters and identified the systemic and pulmonary peripheral resistance as being critical parameters for a wide range of volumetric and hemodynamic cardiac indexes across all four chambers. We have shown that GPEs provide a robust method for mapping between cellular properties and clinical measurements. This could be applied to identify parameters that can be calibrated in patient-specific models or digital twins, and to link cellular function to clinical indexes.

Impact of intraventricular septal fiber orientation on cardiac electromechanical function.

Cardiac fiber direction is an important factor determining the propagation of electrical activity, as well as the development of mechanical force. In this article, we imaged the ventricles of several species with special attention to the intraventricular septum to determine the functional consequences of septal fiber organization. First, we identified a dual-layer organization of the fiber orientation in the intraventricular septum of ex vivo sheep hearts using diffusion tensor imaging at high field MRI. To expand the scope of the results, we investigated the presence of a similar fiber organization in five mammalian species (rat, canine, pig, sheep, and human) and highlighted the continuity of the layer with the moderator band in large mammalian species. We implemented the measured septal fiber fields in three-dimensional electromechanical computer models to assess the impact of the fiber orientation. The downward fibers produced a diamond activation pattern superficially in the right ventricle. Electromechanically, there was very little change in pressure volume loops although the stress distribution was altered. In conclusion, we clarified that the right ventricular septum has a downwardly directed superficial layer in larger mammalian species, which can have modest effects on stress distribution.NEW & NOTEWORTHY A dual-layer organization of the fiber orientation in the intraventricular septum was identified in ex vivo hearts of large mammals. The RV septum has a downwardly directed superficial layer that is continuous with the moderator band. Electrically, it produced a diamond activation pattern. Electromechanically, little change in pressure volume loops were noticed but stress distribution was altered. Fiber distribution derived from diffusion tensor imaging should be considered for an accurate strain and stress analysis.

Calibration of a three-state cell death model for cardiomyocytes and its application in radiofrequency ablation.

Objective.Thermal cellular injury follows complex dynamics and subcellular processes can heal the inflicted damage if insufficient heat is administered during the procedure. This work aims to the identification of irreversible cardiac tissue damage for predicting the success of thermal treatments.Approach.Several approaches exist in the literature, but they are unable to capture the healing process and the variable energy absorption rate that several cells display. Moreover, none of the existing models is calibrated for cardiomyocytes. We consider a three-state cell death model capable of capturing the reversible damage of a cell, we modify it to include a variable energy absorption rate and we calibrate it for cardiac myocytes.Main results.We show how the thermal damage predicted by the model response is in accordance with available data in the literature on myocytes for different temperature distributions. When coupled with a computational model of radiofrequency catheter ablation, the model predicts lesions in agreement with experimental measurements. We also present additional experiments (repeated ablations and catheter movement) to further illustrate the potential of the model.Significance.We calibrated a three-state cell death model to provide physiological results for cardiac myocytes. The model can be coupled with ablation models and reliably predict lesion sizes comparable to experimental measurements. Such approach is robust for repeated ablations and dynamic catheter-cardiac wall interaction, and allows for tissue remodelling in the predicted damaged area, leading to more accurate in-silico predictions of ablation outcomes.

Mechanoelectric effects in healthy cardiac function and under Left Bundle Branch Block pathology.

Mechanoelectric feedback (MEF) in the heart operates through several mechanisms which serve to regulate cardiac function. Stretch activated channels (SACs) in the myocyte membrane open in response to cell lengthening, while tension generation depends on stretch, shortening velocity, and calcium concentration. How all of these mechanisms interact and their effect on cardiac output is still not fully understood. We sought to gauge the acute importance of the different MEF mechanisms on heart function. An electromechanical computer model of a dog heart was constructed, using a biventricular geometry of 500K tetrahedral elements. To describe cellular behavior, we used a detailed ionic model to which a SAC model and an active tension model, dependent on stretch and shortening velocity and with calcium sensitivity, were added. Ventricular inflow and outflow were connected to the CircAdapt model of cardiovascular circulation. Pressure-volume loops and activation times were used for model validation. Simulations showed that SACs did not affect acute mechanical response, although if their trigger level was decreased sufficiently, they could cause premature excitations. The stretch dependence of tension had a modest effect in reducing the maximum stretch, and stroke volume, while shortening velocity had a much bigger effect on both. MEF served to reduce the heterogeneity in stretch while increasing tension heterogeneity. In the context of left bundle branch block, a decreased SAC trigger level could restore cardiac output by reducing the maximal stretch when compared to cardiac resynchronization therapy. MEF is an important aspect of cardiac function and could potentially mitigate activation problems.

Meshfree Semi-Lagrangian Methods for Solving Surface Advection PDEs.

We analyze a class of meshfree semi-Lagrangian methods for solving advection problems on smooth, closed surfaces with solenoidal velocity field. In particular, we prove the existence of an embedding equation whose corresponding semi-Lagrangian methods yield the ones in the literature for solving problems on surfaces. Our analysis allows us to apply standard bulk domain convergence theories to the surface counterparts. In addition, we provide detailed descriptions for implementing the proposed methods to run on point clouds. After verifying the convergence rates against the theory, we show that the proposed method is a robust building block for more complicated problems, such as advection problems with non-solenoidal velocity field, inviscid Burgers' equations and systems of reaction advection diffusion equations for pattern formation.

Impact of electrode tip shape on catheter performance in cardiac radiofrequency ablation.

Background: The role of catheter tip shape on the safety and efficacy of radiofrequency (RF) ablation has been overlooked, although differences have been observed in clinical and research fields. Objective: The purpose of this study was to analyze the role of electrode tip shape in RF ablation using a computational model. Methods: We simulated 108 RF ablations through a realistic 3-dimensional computational model considering 2 clinically used, open-irrigated catheters (spherical and cylindrical tip), varying contact force (CF), blood flow, and irrigation. Lesions are defined by the 50°C isotherm contour and evaluated by means of width, depth, depth at maximum width, and volume. Ablations are deemed as safe, critical (tissue temperature >90°C), and pop (tissue temperature >100°C). Results: Tissue-electrode contact is less for the spherical tip at low CF but the relationship is inverted at high CF. At low CF, the cylindrical tip generates deeper and wider lesions and a 4-fold larger volume. With increasing CF, the lesions generated by the spherical tip become comparable to those generated by the cylindrical tip. The 2 tips feature different safety profiles: CF and power are the main determinants of pops for the spherical tip; power is the main factor for the cylindrical tip; and CF has a marginal effect. The cylindrical tip is more prone to pop generation at higher powers. Saline irrigation and blood flow effect do not depend on tip shape. Conclusion: Tip shape determines the performance of ablation catheters and has a major impact on their safety profile. The cylindrical tip shows more predictable behavior in a wide range of CF values.

Systematic Characterization of High-Power Short-Duration Ablation: Insight From an Advanced Virtual Model.

Background: High-power short-duration (HPSD) recently emerged as a new approach to radiofrequency (RF) catheter ablation. However, basic and clinical data supporting its effectiveness and safety is still scarce. Objective: We aim to characterize HPSD with an advanced virtual model, able to assess lesion dimensions and complications in multiple conditions and compare it to standard protocols. Methods: We evaluate, on both atrium and ventricle, three HPSD protocols (70 W/8 s, 80 W/6 s, and 90 W/4 s) through a realistic 3D computational model of power-controlled RF ablation, varying catheter tip design (spherical/cylindrical), contact force (CF), blood flow, and saline irrigation. Lesions are defined by the 50°C isotherm contour. Ablations are deemed safe or complicated by pop (tissue temperature >97°C) or charring (blood temperature >80°C). We compared HPSD with standards protocols (30-40 W/30 s). We analyzed the effect of a second HPSD application. Results: We simulated 432 applications. Most (79%) associated a complication, especially in the atrium. The three HPSD protocols performed similarly in the atrium, while 90 W/4 s appeared the safest in the ventricle. Low irrigation rate led frequently to charring (72%). High-power short-duration lesions were 40-60% shallower and smaller in volume compared to standards, although featuring similar width. A second HPSD application increased lesions to a size comparable to standards. Conclusion: High-power short-duration lesions are smaller in volume and more superficial than standards but comparable in width, which can be advantageous in the atrium. A second application can produce lesions similar to standards in a shorter time. Despite its narrow safety margin, HPSD seems a valuable new clinical approach.

A computational model of open-irrigated radiofrequency catheter ablation accounting for mechanical properties of the cardiac tissue.

Radiofrequency catheter ablation (RFCA) is an effective treatment for cardiac arrhythmias. Although generally safe, it is not completely exempt from the risk of complications. The great flexibility of computational models can be a major asset in optimizing interventional strategies if they can produce sufficiently precise estimations of the generated lesion for a given ablation protocol. This requires an accurate description of the catheter tip and the cardiac tissue. In particular, the deformation of the tissue under the catheter pressure during the ablation is an important aspect that is overlooked in the existing literature, which resorts to a sharp insertion of the catheter into an undeformed geometry. As the lesion size depends on the power dissipated in the tissue and the latter depends on the percentage of the electrode surface in contact with the tissue itself, the sharp insertion geometry has the tendency to overestimate the lesion obtained, which is a consequence of the tissue temperature rise overestimation. In this paper, we introduce a full 3D computational model that takes into account the tissue elasticity and is able to capture tissue deformation and realistic power dissipation in the tissue. Numerical results in FEniCS-HPC are provided to validate the model against experimental data and to compare the lesions obtained with the new model and with the classical ones featuring a sharp electrode insertion in the tissue.