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Catheter ablation therapy for persistent atrial fibrillation (AF) typically includes pulmonary vein isolation (PVI) and may include additional ablation lesions that target patient-specific anatomical, electrical, or structural features. Clinical centers employ different ablation strategies, which use imaging data together with electroanatomic mapping data, depending on data availability. The aim of this study was to compare ablation techniques across a virtual cohort of AF patients. We constructed 20 paroxysmal and 30 persistent AF patient-specific left atrial (LA) bilayer models incorporating fibrotic remodeling from late-gadolinium enhancement (LGE) MRI scans. AF was simulated and post-processed using phase mapping to determine electrical driver locations over 15 s. Six different ablation approaches were tested: (i) PVI alone, modeled as wide-area encirclement of the pulmonary veins; PVI together with: (ii) roof and inferior lines to model posterior wall box isolation; (iii) isolating the largest fibrotic area (identified by LGE-MRI); (iv) isolating all fibrotic areas; (v) isolating the largest driver hotspot region [identified as high simulated phase singularity (PS) density]; and (vi) isolating all driver hotspot regions. Ablation efficacy was assessed to predict optimal ablation therapies for individual patients. We subsequently trained a random forest classifier to predict ablation response using (a) imaging metrics alone, (b) imaging and electrical metrics, or (c) imaging, electrical, and ablation lesion metrics. The optimal ablation approach resulting in termination, or if not possible atrial tachycardia (AT), varied among the virtual patient cohort: (i) 20% PVI alone, (ii) 6% box ablation, (iii) 2% largest fibrosis area, (iv) 4% all fibrosis areas, (v) 2% largest driver hotspot, and (vi) 46% all driver hotspots. Around 20% of cases remained in AF for all ablation strategies. The addition of patient-specific and ablation pattern specific lesion metrics to the trained random forest classifier improved predictive capability from an accuracy of 0.73 to 0.83. The trained classifier results demonstrate that the surface areas of pre-ablation driver regions and of fibrotic tissue not isolated by the proposed ablation strategy are both important for predicting ablation outcome. Overall, our study demonstrates the need to select the optimal ablation strategy for each patient. It suggests that both patient-specific fibrosis properties and driver locations are important for planning ablation approaches, and the distribution of lesions is important for predicting an acute response.

Introduction: Timing of atrial, right (RV), and left ventricular (LV) stimulation in cardiac resynchronization therapy (CRT) is known to affect electrical activation and pump function of the LV. In this study, we used computer simulations, with input from animal experiments, to investigate the effect of varying pacing delays on both LV and RV electrical dyssynchrony and contractile function.Methods: A pacing protocol was performed in dogs with atrioventricular block (N = 6), using 100 different combinations of atrial (A)-LV and A-RV pacing delays. Regional LV and RV electrical activation times were measured using 112 electrodes and LV and RV pressures were measured with catheter-tip micromanometers. Contractile response to a pacing delay was defined as relative change of the maximum rate of LV and RV pressure rise (dP/dtmax) compared to RV pacing with an A-RV delay of 125 ms. The pacing protocol was simulated in the CircAdapt model of cardiovascular system dynamics, using the experimentally acquired electrical mapping data as input.Results: Ventricular electrical activation changed with changes in the amount of LV or RV pre-excitation. The resulting changes in dP/dtmax differed markedly between the LV and RV. Pacing the LV 10–50 ms before the RV led to the largest increases in LV dP/dtmax. In contrast, RV dP/dtmax was highest with RV pre-excitation and decreased up to 33% with LV pre-excitation. These opposite patterns of changes in RV and LV dP/dtmax were reproduced by the simulations. The simulations extended these observations by showing that changes in steady-state biventricular cardiac output differed from changes in both LV and RV dP/dtmax. The model allowed to explain the discrepant changes in dP/dtmax and cardiac output by coupling between atria and ventricles as well as between the ventricles.Conclusion: The LV and the RV respond in a opposite manner to variation in the amount of LV or RV pre-excitation. Computer simulations capture LV and RV behavior during pacing delay variation and may be used in the design of new CRT optimization studies.

BackgroundVirtual electrodes from structural/conductivity heterogeneities are known to elicit wavefront propagation, upon field-stimulation, and are thought to be important for defibrillation. In this work we investigate how the constitutive and geometrical parameters associated with such anatomical heterogeneities, represented by endo/epicardial surfaces and intramural surfaces in the form of blood-vessels, affect the virtual electrode patterns produced.Methods and resultsThe steady-state bidomain model is used to obtain, using analytical and numerical methods, the virtual electrode patterns created around idealized endocardial trabeculations and blood-vessels. The virtual electrode pattern around blood-vessels is shown to be composed of two dominant effects; current traversing the vessel surface and conductivity heterogeneity from the fibre-architecture. The relative magnitudes of these two effects explain the swapping of the virtual electrode polarity observed, as a function of the vessel radius, and aid in the understanding of the virtual electrode patterns predicted by numerical bidomain modelling. The relatively high conductivity of blood, compared to myocardium, is shown to cause stronger depolarizations in the endocardial trabeculae grooves than the protrusions.ConclusionsThe results provide additional quantitative understanding of the virtual electrodes produced by small-scale ventricular anatomy, and highlight the importance of faithfully representing the physiology and the physics in the context of computational modelling of field stimulation.

AimThe human right atrium and sinoatrial node (SAN) anatomy is complex. Optical mapping experiments suggest that the SAN is functionally insulated from atrial tissue except at discrete SAN-atrial electrical junctions called SAN exit pathways, SEPs. Additionally, histological imaging suggests the presence of a secondary pacemaker close to the SAN. We hypothesise that a) an insulating border-SEP anatomical configuration is related to SAN arrhythmia; and b) a secondary pacemaker, the paranodal area, is an alternate pacemaker but accentuates tachycardia. A 3D electro-anatomical computational model was used to test these hypotheses.MethodsA detailed 3D human SAN electro-anatomical mathematical model was developed based on our previous anatomical reconstruction. Electrical activity was simulated using tissue specific variants of the Fenton-Karma action potential equations. Simulation experiments were designed to deploy this complex electro-anatomical system to assess the roles of border-SEPs and paranodal area by mimicking experimentally observed SAN arrhythmia. Robust and accurate numerical algorithms were implemented for solving the mono domain reaction-diffusion equation implicitly, calculating 3D filament traces, and computing dominant frequency among other quantitative measurements.ResultsA centre to periphery gradient of increasing diffusion was sufficient to permit initiation of pacemaking at the centre of the 3D SAN. Re-entry within the SAN, micro re-entry, was possible by imposing significant SAN fibrosis in the presence of the insulating border. SEPs promoted the micro re-entry to generate more complex SAN-atrial tachycardia. Simulation of macro re-entry, i.e. re-entry around the SAN, was possible by inclusion of atrial fibrosis in the presence of the insulating border. The border shielded the SAN from atrial tachycardia. However, SAN micro-structure intercellular gap junctional coupling and the paranodal area contributed to prolonged atrial fibrillation. Finally, the micro-structure was found to be sufficient to explain shifts of leading pacemaker site location.ConclusionsThe simulations establish a relationship between anatomy and SAN electrical function. Microstructure, in the form of intercellular gap junction coupling, was found to regulate SAN function and arrhythmia.

Structural differences between ventricular regions may not be the sole determinant of local ventricular fibrillation (VF) dynamics and molecular remodeling may play a role.To define regional ion channel expression in myopathic hearts compared to normal hearts, and correlate expression to regional VF dynamics.High throughput real-time RT-PCR was used to quantify the expression patterns of 84 ion-channel, calcium cycling, connexin and related gene transcripts from sites in the LV, septum, and RV in 8 patients undergoing transplantation. An additional eight non-diseased donor human hearts served as controls. To relate local ion channel expression change to VF dynamics localized VF mapping was performed on the explanted myopathic hearts right adjacent to sampled regions. Compared to non-diseased ventricles, significant differences (p