The mechanism of atrial fibrillation (AF) is 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 based on sustained re-entrant circuits in the complex atrial architecture. Here, we present a simple 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 and persistent AF as the decoupling of myocardial cells results in the lattice approaching the percolation threshold. This allows the model to make additional predictions beyond the current clinical understanding, showing that for paroxysmal AF re-entrant circuits emerge near the endocardium, but in persistent AF they emerge deeper in the bulk of the atrial wall where endocardial ablation is less effective. If clinically confirmed, this may explain the lower success rate of ablation in long-lasting persistent AF.
Atrial fibrillation (AF) is the most common abnormal heart rhythm and the single biggest cause of stroke. Ablation, destroying regions of the atria, is applied largely empirically and can be curative but with a disappointing clinical success rate. We design a simple model of activation wavefront propagation on a structure mimicking the branching network architecture of heart muscle and show how AF emerges spontaneously as age-related parameters change. We identify regions responsible for the initiation and maintenance of AF, the ablation of which terminates AF. The simplicity of the model allo…
Atrial fibrillation (AF) consequences on the heart valve dynamics are usually studied along with a valvular disfunction or disease, since in medical monitoring the two pathologies are often concomitant. Aim of the present work is to study, through a stochastic lumped-parameter approach, the basic fluid dynamics variations of heart valves, when only paroxysmal AF is present with respect to the normal sinus rhythm (NSR) in absence of any valvular pathology. Among the most common parameters interpreting the valvular function, the most useful turns out to be the regurgitant volume. During AF both …
Mapping resolution has recently been identified as a key limitation in successfully locating the drivers of atrial fibrillation. Using a simple cellular automata model of atrial fibrillation, we demonstrate a method by which re-entrant drivers can be located quickly and accurately using a collection of indirect electrogram measurements. The method proposed employs simple, out of the box machine learning algorithms to correlate characteristic electrogram gradients with the displacement of an electrogram recording from a re-entrant driver. Such a method is less sensitive to local fluctuations in…
Università della Svizzera italiana（提契诺大学）；University of Pennsylvania（宾夕法尼亚大学）；Pontificia Universidad Católica de Chile（智利天主教大学）
Computational models of atrial fibrillation have successfully been used to predict optimal ablation sites. A critical step to assess the effect of an ablation pattern is to pace the model from different, potentially random, locations to determine whether arrhythmias can be induced in the atria. In this work, we propose to use multi-fidelity Gaussian process classification on Riemannian manifolds to efficiently determine the regions in the atria where arrhythmias are inducible. We build a probabilistic classifier that operates directly on the atrial surface. We take advantage of lower resolutio…
While spiral wave breakup has been implicated in the emergence of atrial fibrillation, its role in maintaining this complex type of cardiac arrhythmia is less clear. We used the Karma model of cardiac excitation to investigate the dynamical mechanisms that sustain atrial fibrillation once it has been established. The results of our numerical study show that spatiotemporally chaotic dynamics in this regime can be described as a dynamical equilibrium between topologically distinct types of transitions that increase or decrease the number of wavelets, in general agreement with the multiple wavele…
During episodes of atrial fibrillation, the heart's electrical activity becomes disorganized and shows fragmenting spiral waves. To systematically address how this pattern terminates using spatially extended simulations exceeds current computational resources. To circumvent this limitation, we treat the number of spiral waves as a stochastic population with a corresponding birth-death equation and use techniques from statistical physics to determine the mean episode duration of atrial fibrillation. We show that this duration can be computed for arbitrary geometries in minimal computational tim…
Atrial fibrillation (AF) is associated with cognitive impairment/dementia, independently of clinical cerebrovascular events (stroke/TIA). One of the plausible mechanisms is the occurrence of AF-induced transient critical hemodynamic events; however, it is presently unknown, if ventricular response rate during AF may impact on cerebral hemodynamics. AF was simulated at different ventricular rates (50, 70, 90, 110, 130 bpm) by two coupled lumped parameter validated models (systemic and cerebral circulation), and compared to corresponding control normal sinus rhythm simulations (NSR). Hemodynamic…
Background. Different mechanisms have been proposed to relate atrial fibrillation (AF) and coronary flow impairment, even in absence of relevant coronary artery disease (CAD). However, the underlying hemodynamics remains unclear. Aim of the present work is to computationally explore whether and to what extent ventricular rate during AF affects the coronary perfusion. Methods. AF is simulated at different ventricular rates (50, 70, 90, 110, 130 bpm) through a 0D-1D multiscale validated model, which combines the left heart-arterial tree together with the coronary circulation. Artificially-built …
Atrial fibrillation (AF) is associated with an increased risk of dementia and cognitive decline, independent of strokes. Several mechanisms have been proposed to explain this association, but altered cerebral blood flow dynamics during AF has been poorly investigated: in particular, it is unknown how AF influences hemodynamic parameters of the distal cerebral circulation, at the arteriolar and capillary level. Two coupled lumped-parameter models (systemic and cerebrovascular circulations, respectively) were here used to simulate sinus rhythm (SR) and AF. For each simulation 5000 cardiac cycles…
We study the interplay between traveling action potentials and spatial inhomogeneities in the FitzHugh-Nagumo model to investigate possible mechanisms for the occurrence of fibrillatory states in the atria of the heart. Different dynamical patterns such as ectopic foci, localized and meandering spiral waves are found depending on the characteristics of the inhomogeneities. Their appearance in dependence of the size and strength of the inhomogeneities is quantified by phase diagrams. Furthermore it is shown that regularly paced waves in a region R, that is connected by a small bridge connection…
Atrial fibrillation (AF) is a leading cause of morbidity and mortality. AF prevalence increases with age, which is attributed to pathophysiological changes that aid AF initiation and perpetuation. Current state-of-the-art models are only capable of simulating short periods of atrial activity at high spatial resolution, whilst the majority of clinical recordings are based on infrequent temporal datasets of limited spatial resolution. Being able to estimate disease progression informed by both modelling and clinical data would be of significant interest. In addition an analysis of the temporal d…
Background: The arrhythmogenic role of atrial complex morphology has not yet been clearly elucidated. We hypothesized that bumpy tissue geometry can induce action potential duration (APD) dispersion and wavebreak in atrial fibrillation (AF). Methods and Results: We simulated 2D-bumpy atrial model by varying the degree of bumpiness, and 3D-left atrial (LA) models integrated by LA computed tomographic (CT) images taken from 14 patients with persistent AF. We also analyzed wave-dynamic parameters with bipolar electrograms during AF and compared them with LA-CT geometry in 30 patients with persist…
An example of phase transition in natural complex systems is the qualitative and sudden change in the heart rhythm between sinus rhythm and atrial fibrillation (AF), the most common irregular heart rhythm in humans. While the system behavior is centrally controlled by the behavior of the sinoatrial node in sinus rhythm, the macro-scale collective behavior of the heart causes the micro-scale behavior in AF. To quantitatively analyze this causation shift associated with phase transition in human heart, we evaluated the causal architecture of the human cardiac system using the time series of mult…
Atrial fibrillation (AF) is the most common form of arrhythmia with accelerated and irregular heart rate (HR), leading to both heart failure and stroke and being responsible for an increase in cardiovascular morbidity and mortality. In spite of its importance, the direct effects of AF on the arterial hemodynamic patterns are not completely known to date. Based on a multiscale modelling approach, the proposed work investigates the effects of AF on the local arterial fluid dynamics. AF and normal sinus rhythm (NSR) conditions are simulated extracting 2000 $\mathrm{RR}$ heartbeats and comparing t…
Although atrial fibrillation (AF), a common arrhythmia, frequently presents in patients with underlying valvular disease, its hemodynamic contributions are not fully understood. The present work aimed to computationally study how physical conditions imposed by pathologic valvular anatomy act on AF hemodynamics. We simulated AF with different severity grades of left-sided valvular diseases and compared the cardiovascular effects that they exert during AF, compared to lone AF. The fluid dynamics model used here has been recently validated for lone AF and relies on a lumped parameterization of th…
Atrial fibrillation (AF) is the most common cardiac arrhythmia in human beings, and is associated with significant morbidity and mortality. The current standard of care includes interventional catheter ablation in selected patients, but the success rate is limited. The major limitation of the current approach to AF is the lack of fundamental understanding of its underlying mechanism. Specifically, it remains unclear whether human AF dynamics are a deterministic or a stochastic process. Here we assess for determinism in human AF by evaluating the properties of the symbolic representation of int…
Atrial fibrillation (AF) increases the risk of stroke by a factor of four to five and is the most common abnormal heart rhythm. The progression of AF with age, from short self-terminating episodes to persistence, varies between individuals and is poorly understood. An inability to understand and predict variation in AF progression has resulted in less patient-specific therapy. Likewise, it has been a challenge to relate the microstructural features of heart muscle tissue (myocardial architecture) with the emergent temporal clinical patterns of AF. We use a simple model of activation wavefront …
Aims. Clinical data indicating a heart rate (HR) target during rate control therapy for permanent atrial fibrillation (AF) and assessing its eventual relationship with reduced exercise tolerance are lacking. The present study aims at investigating the impact of resting HR on the hemodynamic response to exercise in permanent AF patients by means of a computational cardiovascular model. Methods. The AF lumped-parameter model was run to simulate resting (1 Metabolic Equivalent of Task-MET) and various exercise conditions (4 METs: brisk walking; 6 METs: skiing; 8 METs: running), considering differ…
There has recently been growing evidence that atrial fibrillation (AF), the most common cardiac arrhythmia, is independently associated with the risk of dementia. This represents a very recent frontier with high social impact for the number of individuals involved and for the expected increase in AF incidence in the next 40 years. Although a number of potential haemodynamic processes, such as microembolisms, altered cerebral blood flow, hypoperfusion and microbleeds, arise as connecting links between the two pathologies, the causal mechanisms are far from clear. An in silico approach is propos…
A network-based approach is presented to investigate the cerebrovascular flow patterns during atrial fibrillation (AF) with respect to normal sinus rhythm (NSR). AF, the most common cardiac arrhythmia with faster and irregular beating, has been recently and independently associated with the increased risk of dementia. However, the underlying hemodynamic mechanisms relating the two pathologies remain mainly undetermined so far; thus the contribution of modeling and refined statistical tools is valuable. Pressure and flow rate temporal series in NSR and AF are here evaluated along representative…
Atrial fibrillation (AF) is the most common cardiac arrhytmia, characterised 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 e…
Mathematical models of cardiac electrical excitation are increasingly complex, with multiscale models seeking to represent and bridge physiological behaviours across temporal and spatial scales. The increasing complexity of these models makes it computationally expensive to both evaluate long term (>60 seconds) behaviour and determine sensitivity of model outputs to inputs. This is particularly relevant in models of atrial fibrillation (AF), where individual episodes last from seconds to days, and inter-episode waiting times can be minutes to months. Potential mechanisms of transition between …
Background. Despite the routine prescription of rate control therapy for atrial fibrillation (AF), clinical evidence demonstrating a heart rate target is lacking. Aim of the present study was to run a mathematical model simulating AF episodes with a different heart rate (HR) to predict hemodynamic parameters for each situation. Methods. The lumped model, representing the pumping heart together with systemic and pulmonary circuits, was run to simulate AF with HR of 50, 70, 90, 110 and 130 bpm, respectively. Results. Left ventricular pressure increased by 56.7%, from 33.92+-37.56 mmHg to 53.15+-…
We consider the use of a running measure of power spectrum disorder to distinguish between the normal sinus rhythm of the heart and two forms of cardiac arrhythmia: atrial fibrillation and atrial flutter. This spectral entropy measure is motivated by characteristic differences in the spectra of beat timings during the three rhythms. We plot patient data derived from ten-beat windows on a "disorder map" and identify rhythm-defining ranges in the level and variance of spectral entropy values. Employing the spectral entropy within an automatic arrhythmia detection algorithm enables the classifica…
