Identifying locations susceptible to micro-anatomical reentry using a spatial network representation of atrial fibre maps.

Micro-anatomical reentry has been identified as a potential driver of atrial fibrillation (AF). In this paper, we introduce a novel computational method which aims to identify which atrial regions are most susceptible to micro-reentry. The approach, which considers the structural basis for micro-reentry only, is based on the premise that the accumulation of electrically insulating interstitial fibrosis can be modelled by simulating percolation-like phenomena on spatial networks. Our results suggest that at high coupling, where micro-reentry is rare, the micro-reentrant substrate is highly clustered in areas where the atrial walls are thin and have convex wall morphology, likely facilitating localised treatment via ablation. However, as transverse connections between fibres are removed, mimicking the accumulation of interstitial fibrosis, the substrate becomes less spatially clustered, and the bias to forming in thin, convex regions of the atria is reduced, possibly restricting the efficacy of localised ablation. Comparing our algorithm on image-based models with and without atrial fibre structure, we find that strong longitudinal fibre coupling can suppress the micro-reentrant substrate, whereas regions with disordered fibre orientations have an enhanced risk of micro-reentry. With further development, these methods may be useful for modelling the temporal development of the fibrotic substrate on an individualised basis.

Understanding the transition from paroxysmal to persistent atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhytmia, characterized by the chaotic motion of electrical wavefronts in the atria. In clinical practice, AF is classified under two primary categories: paroxysmal AF, short intermittent episodes separated by periods of normal electrical activity; and persistent AF, longer uninterrupted episodes of chaotic electrical activity. However, the precise reasons why AF in a given patient is paroxysmal or persistent is poorly understood. Recently, we have introduced the percolation-based Christensen-Manani-Peters (CMP) model of AF which naturally exhibits both paroxysmal and persistent AF, but precisely how these differences emerge in the model is unclear. In this paper, we dissect the CMP model to identify the cause of these different AF classifications. Starting from a mean-field model where we describe AF as a simple birth-death process, we add layers of complexity to the model and show that persistent AF arises from reentrant circuits which exhibit an asymmetry in their probability of activation relative to deactivation. As a result, different simulations generated at identical model parameters can exhibit fibrillatory episodes spanning several orders of magnitude from a few seconds to months. These findings demonstrate that diverse, complex fibrillatory dynamics can emerge from very simple dynamics in models of AF.

The microscopic relationships between triangular arbitrage and cross-currency correlations in a simple agent based model of foreign exchange markets.

Foreign exchange rates movements exhibit significant cross-correlations even on very short time-scales. The effect of these statistical relationships become evident during extreme market events, such as flash crashes. Although a deep understanding of cross-currency correlations would be clearly beneficial for conceiving more stable and safer foreign exchange markets, the microscopic origins of these interdependencies have not been extensively investigated. This paper introduces an agent-based model which describes the emergence of cross-currency correlations from the interactions between market makers and an arbitrager. The model qualitatively replicates the time-scale vs. cross-correlation diagrams observed in real trading data, suggesting that triangular arbitrage plays a primary role in the entanglement of the dynamics of different foreign exchange rates. Furthermore, the model shows how the features of the cross-correlation function between two foreign exchange rates, such as its sign and value, emerge from the interplay between triangular arbitrage and trend-following strategies. In particular, the interaction of these trading strategies favors certain combinations of price trend signs across markets, thus altering the probability of observing two foreign exchange rates drifting in the same or opposite direction. Ultimately, this entangles the dynamics of foreign exchange rate pairs, leading to cross-correlation functions that resemble those observed in real trading data.

Identifying Potential Re-Entrant Circuit Locations From Atrial Fibre Maps.

Re-entrant circuits have been identified as potential drivers of atrial fibrillation (AF). In this paper, we develop a novel computational framework for finding the locations of re-entrant circuits from high resolution fibre orientation data. The technique follows a statistical approach whereby we generate continuous fibre tracts across the tissue and couple adjacent fibres stochastically if they are within a given distance of each other. By varying the connection distance, we identify which regions are most susceptible to forming re-entrant circuits if muscle fibres are uncoupled, through the action of fibrosis or otherwise. Our results highlight the sleeves of the pulmonary veins, the posterior left atrium and the left atrial appendage as the regions most susceptible to re-entrant circuit formation. This is consistent with known risk locations in clinical AF. If the model can be personalised for individual patients undergoing ablation, future versions may be able to suggest suitable ablation targets.

Unified mechanism of local drivers in a percolation model of atrial fibrillation.

The mechanisms of atrial fibrillation (AF) are poorly understood, resulting in disappointing success rates of ablative treatment. Different mechanisms defined largely by different atrial activation patterns have been proposed and, arguably, this dispute has slowed the progress of AF research. Recent clinical evidence suggests a unifying mechanism of local drivers based on sustained reentrant circuits in the complex atrial architecture. Here, we present a percolation inspired computational model showing spontaneous emergence of AF that strongly supports, and gives a theoretical explanation for, the clinically observed diversity of activation. We show that the difference in surface activation patterns is a direct consequence of the thickness of the discrete network of heart muscle cells through which electrical signals percolate to reach the imaged surface. The model naturally follows the clinical spectrum of AF spanning sinus rhythm, paroxysmal AF, and persistent AF as the decoupling of myocardial cells results in the lattice approaching the percolation threshold. This allows the model to make the prediction that, for paroxysmal AF, reentrant circuits emerge near the endocardium, but in persistent AF they emerge deeper in the bulk of the atrial wall. If experimentally verified, this may go towards explaining the lowering ablation success rate as AF becomes more persistent.