Novel Computational Analysis of Left Atrial Anatomy Improves Prediction of Atrial Fibrillation Recurrence after Ablation

The left atrium (LA) can change in size and shape due to atrial fibrillation (AF)-induced remodeling. These alterations can be linked to poorer outcomes of AF ablation. In this study, we propose a novel comprehensive computational analysis of LA anatomy to identify what features of LA shape can optimally predict post-ablation AF recurrence. To this end, we construct smooth 3D geometrical models from the segmentation of the LA blood pool captured in pre-procedural MR images. We first apply this methodology to characterize the LA anatomy of 144 AF patients and build a statistical shape model that includes the most salient variations in shape across this cohort. We then perform a discriminant analysis to optimally distinguish between recurrent and non-recurrent patients. From this analysis, we propose a new shape metric called vertical asymmetry, which measures the imbalance of size along the anterior to posterior direction between the superior and inferior left atrial hemispheres. Vertical asymmetry was found, in combination with LA sphericity, to be the best predictor of post-ablation recurrence at both 12 and 24 months (area under the ROC curve: 0.71 and 0.68, respectively) outperforming other shape markers and any of their combinations. We also found that model-derived shape metrics, such as the anterior-posterior radius, were better predictors than equivalent metrics taken directly from MRI or echocardiography, suggesting that the proposed approach leads to a reduction of the impact of data artifacts and noise. This novel methodology contributes to an improved characterization of LA organ remodeling and the reported findings have the potential to improve patient selection and risk stratification for catheter ablations in AF

Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are effective in terminating AF

Correlation between P-wave morphology and origin of atrial focal tachycardia--insights from realistic models of the human atria and torso

Atrial arrhythmias resulting from abnormally rapid focal activity in the artia may be reflected in an altered P-wave morphology (PWM) in the ECG. Although clinically important, detailed relationships between PWM and origins of atrial focal excitations has not been established. To study such relationships, we developed computational models of the human atria and torso. The model simulation results were used to evaluate an extant clinical algorithm for locating the origin of atrial focal points from the ECG. The simulations showed that the algorithm was practical, and could predict the atrial focal locations with 85% accuracy. We proposed a further refinement of the algorithm to distinguish between focal locations within large atrial bundles

Electrophysiological models for the heterogeneous canine atria:computational platform for studying rapid atrial arrhythmias

Heterogeneity in the electrical action potential (AP) properties can provide a substrate for atrial arrhythmias, especially at rapid pacing rates. In order to quantify such substrates, we develop a family of detailed AP models for canine atrial cells. An existing model for the canine right atrial (RA) myocyte was modified based on electrophysiological data from dog to create new models for the canine left atrium (LA), the interatrial Bachmann’s bundle (BB), and the pulmonary vein (PV). The heterogeneous AP models were incorporated into a tissue strand model to simulate the AP propagation, and used to quantify conditions for conduction abnormalities (primarily, conduction block at rapid pacing rated) in the canine atria