Alessandro Cristoforetti

A novel approach to propagation pattern analysis in intracardiac atrial fibrillation signals

The purpose of this study is to investigate propagation patterns in intracardiac signals recorded during atrial fibrillation (AF) using an approach based on partial directed coherence (PDC), which evaluates directional coupling between multiple signals in the frequency domain. The PDC is evaluated at the dominant frequency of AF signals and tested for significance using a surrogate data procedure specifically designed to assess causality. For significantly coupled sites, the approach allows also to estimate the delay in propagation. The methods potential is illustrated with two simulation scenarios based on a detailed ionic model of the human atrial myocyte as well as with real data recordings, selected to present typical propagation mechanisms and recording situations in atrial tachyarrhythmias. In both simulation scenarios the significant PDCs correctly reflect the direction of coupling and thus the propagation between all recording sites. In the real data recordings, clear propagation patterns are identified which agree with previous clinical observations. Thus, the results illustrate the ability of the novel approach to identify propagation patterns from intracardiac signals during AF, which can provide important information about the underlying AF mechanisms, potentially improving the planning and outcome of arrhythmia ablation.

Anatomic Localization of Rapid Repetitive Sources in Persistent Atrial Fibrillation: Fusion of Biatrial CT Images With Wave Similarity/Cycle Length Maps

OBJECTIVES The aim of this study was to investigate the anatomic distribution of critical sources in patients with atrial fibrillation (AF) by fusion of biatrial computed tomography (CT) images with cycle length (CL) and wave similarity (WS) maps. BACKGROUND Experimental and clinical studies show that atrial fibrillation (AF) may originate from rapid and repetitive (RR) sources of activation. Localization of RR sources may be crucial for an effective ablation treatment. Atrial electrograms showing rapid and repetitive activations can be identified by combining WS and CL analysis. METHODS Patients with persistent AF underwent biatrial electroanatomic mapping and pre-procedural CT cardiac imaging. WS and CL maps were constructed in 17 patients by calculating the degree of repetitiveness of activation waveforms (similarity index [S]) and the cycle length at each atrial site. WS/CL maps were then integrated with biatrial 3-dimensional CT reconstructions by a stochastic approach. RESULTS Repetitive sources of activation (S ≥ 0.5) were present in most patients with persistent AF (94%) and were mainly located at the pulmonary veins (82% of patients), at the superior caval vein (41%), on the anterior wall of the right atrium (23%), and at the left atrial appendage (23%). Potential driver sources showing both rapid and repetitive activations (CL = 140.7 ± 25.1 ms, S = 0.65 ± 0.15) were present only in a subset of patients (65%) and were confined to the pulmonary vein region (47% of patients) and left atrial appendage (12%). Differently, the repetitive activity of the superior caval vein was characterized by a slow activation rate (CL = 184.7 ± 14.6 ms). CONCLUSIONS The identification and localization of RR sources is feasible by fusion of biatrial anatomic images with WS/CL maps. Potential driver sources are present only in a subset of patients with persistent AF and are mainly located in the pulmonary vein region.

Electroanatomic Mapping and Late Gadolinium Enhancement MRI in a Genetic Model of Arrhythmogenic Atrial Cardiomyopathy

Although atrial arrhythmias may have genetic causes, very few data are available on evaluation of the arrhythmic substrate in genetic atrial diseases in humans. In this study, we evaluate the nature and evolution of the atrial arrhythmic substrate in a genetic atrial cardiomyopathy.

The logical operator map identifies novel candidate markers for critical sites in patients with atrial fibrillation.

The identification of suitable markers for critical patterns during atrial fibrillation (AF) may be crucial to guide an effective ablation treatment. Single parameter maps, based on dominant frequency and complex fractionated electrograms, have been proposed as a tool for electrogram-guided ablation, however the specificity of these markers is debated. Experimental studies suggest that AF critical patterns may be identified on the basis of specific rate and organization features, where rapid organized and rapid fragmented activities characterize respectively localized sources and critical substrates. In this paper we introduce the logical operator map, a novel mapping tool for a point-by-point identification and localization of AF critical sites. Based on advanced signal and image processing techniques, the approach combines in a single map electrogram-derived rate and organization features with tomographic anatomical detail. The construction of the anatomically-detailed logical operator map is based on the time-domain estimation of atrial rate and organization in terms of cycle length and wave-similarity, the logical combination of these indexes to obtain suitable markers of critical sites, and the multimodal integration of electrophysiological and anatomical information by segmentation and registration techniques. Logical operator maps were constructed in 14 patients with persistent AF, showing the capability of the combined rate and organization markers to identify with high selectivity the subset of electrograms associated with localized sources and critical substrates. The precise anatomical localization of these critical sites revealed the confinement of rapid organized sources in the left atrium with organization and rate gradients towards the surrounding tissue, and the presence of rapid fragmented electrograms in proximity of the sources. By merging in a single map the most relevant electrophysiological and anatomical features of the AF process, the logical operator map may have significant clinical impact as a direct, comprehensive tool to understand arrhythmia mechanisms in the single patient and guide more conservative, step-wise ablation.

A stochastic approach for automatic registration and fusion of left atrial electroanatomic maps with 3D CT anatomical images

The integration of electroanatomic maps with highly resolved computed tomography cardiac images plays an important role in the successful planning of the ablation procedure of arrhythmias. In this paper, we present and validate a fully-automated strategy for the registration and fusion of sparse, atrial endocardial electroanatomic maps (CARTO maps) with detailed left atrial (LA) anatomical reconstructions segmented from a pre-procedural MDCT scan. Registration is accomplished by a parameterized geometric transformation of the CARTO points and by a stochastic search of the best parameter set which minimizes the misalignment between transformed CARTO points and the LA surface. The subsequent fusion of electrophysiological information on the registered CT atrium is obtained through radial basis function interpolation. The algorithm is validated by simulation and by real data from 14 patients referred to CT imaging prior to the ablation procedure. Results are presented, which show the validity of the algorithmic scheme as well as the accuracy and reproducibility of the integration process. The obtained results encourage the application of the integration method in post-intervention ablation assessment and basic AF research and suggest the development for real-time applications in catheter guiding during ablation intervention.

Registration and fusion of segmented left atrium CT images with CARTO electrical maps for the ablative treatment of atrial fibrillation

This study aims to extract the interior surface of the left atrium (LA) and pulmonary veins (PVs) from three dimensional tomographic data and to integrate it with LA CARTO electrical maps. The separation of LA and PVs from other overlapping structures of the heart was performed processing 3D CT data by marker-controlled watershed segmentation and surface extraction. CARTO maps were then registered on the LA internal surface by a stochastic optimization algorithm based on simulated annealing. The residual registration error resulted inferior to 3 mm. The integration between electrophysiological and high resolved anatomic information of LA results feasible and may constitute a significant support for mechanism investigation and treatment of atrial fibrillation.

A Fully Adaptive Multiresolution Algorithm for Atrial Arrhythmia Simulation on Anatomically Realistic Unstructured Meshes

Biophysically detailed and anatomically realistic atrial models are emerging as a valuable tool in the study of atrial arrhythmias, nevertheless clinical use of these models would be favored by a reduction of computational times. This paper introduces a novel adaptive mesh algorithm, based on multiresolution representation (MR), for the efficient integration of cardiac ordinary differential equation (ODE)-partial differential equation (PDE) systems on unstructured triangle meshes. The algorithm applies a dynamically adapted node-centered finite volume method (FVM) scheme for integration of diffusion. The method accuracy and efficiency were evaluated by simulating propagation scenarios of increasing complexity levels (pacing, stable spirals, atrial fibrillation) on tomography-derived three-dimensional monolayer atrial models, based on a monodomain reaction-diffusion formulation coupled with the Courtemanche atrial ionic model. All simulated propagation patterns were accurately reproduced with substantially reduced computational times (10%-30% of the full-resolution simulation time). The proposed algorithm, combining the MR computational efficiency with the geometrical flexibility of unstructured meshes, may favor the development of patient-specific multiscale models of atrial arrhythmias and their application in the clinical setting.

A Multi-Variate Predictability Framework to Assess Invasive Cardiac Activity and Interactions During Atrial Fibrillation

Objective: This study introduces a predictability framework based on the concept of Granger causality (GC), in order to analyze the activity and interactions between different intracardiac sites during atrial fibrillation (AF). Methods: GC-based interactions were studied using a three-electrode analysis scheme with multi-variate autoregressive models of the involved preprocessed intracardiac signals. The method was evaluated in different scenarios covering simulations of complex atrial activity as well as endocardial signals acquired from patients. Results: The results illustrate the ability of the method to determine atrial rhythm complexity and to track and map propagation during AF. Conclusion: The proposed framework provides information on the underlying activation and regularity, does not require activation detection or postprocessing algorithms and is applicable for the analysis of any multielectrode catheter. Significance: The proposed framework can potentially help to guide catheter ablation interventions of AF.

Fusion of Electrical Maps and MDCT Images for Validation of Left Atrium Ablation Points

Purpose Aims of this study are: a) the three-dimensional (3D) reconstruction of the left atrium (LA) and pulmonary veins (PVs) and its fusion with LA electrical map (LAEM); b) the validation of the real positions of the PVs ablation points (APs). Methods Eight patients underwent TAC 16 slices after PVs ablation for atrial fibrillation (AF). A marker-controlled “watershed segmentation” was developed for 3D LA reconstruction. LAEMs (CARTO) were registered on the 3D LA inner surface of the patients. On the “fusion maps”, we count offline the APs number inside the ostia of PVs. Results A percentage of 5,4% up to 17% of the total APs number was counted inside the left superior PV (LSPV) ostia and in particular on the anterior wall. A percentage of 4,5% up to 13,9% of the total APs number was counted inside the right inferior PV (RIPV) ostia. Conclusions Fusion maps allow validating the position of the APs on a real map of LA. This study shows that the area between LSPV ostium and LAA could be the critical points during AF ablation.

Modeling fibrosis distribution for the study of wave propagation patterns during atrial fibrillation

Experimental and clinical evidence suggests the role of fibrosis in the formation of a pro-arrhythmic substrate for atrial fibrillation (AF). This work presents a simulation model to investigate the interactions between excitation wavefronts and fibrosis. The Courtemanche-Ramirez-Nattel model of the human atrial potential was implemented on a sphere monolayer, and fibrosis was included replacing mesh nodes with non-excitable elements with no-flux boundary conditions. A stochastic algorithm was used to generate spatial patterns of fibrosis with specific density, patch dimension and orientation. Simulations run at different model parameters showed that the presence and spatial pattern of fibrosis could significantly alter the dynamics of propagating wavefronts, favoring the occurrence of reentrant activity and self-sustained propagation. Combined with more realistic atrial geometry, this simulation model may help to clarify the determinants of AF multifactorial substrate.