Maria S. Guillem

Noninvasive Localization of Maximal Frequency Sites of Atrial Fibrillation by Body Surface Potential Mapping

Background—Ablation of high-frequency sources in patients with atrial fibrillation (AF) is an effective therapy to restore sinus rhythm. However, this strategy may be ineffective in patients without a significant dominant frequency (DF) gradient. The aim of this study was to investigate whether sites with high-frequency activity in human AF can be identified noninvasively, which should help intervention planning and therapy. Methods and Results—In 14 patients with a history of AF, 67-lead body surface recordings were simultaneously registered with 15 endocardial electrograms from both atria including the highest DF site, which was predetermined by atrial-wide real-time frequency electroanatomical mapping. Power spectra of surface leads and the body surface location of the highest DF site were compared with intracardiac information. Highest DFs found on specific sites of the torso showed a significant correlation with DFs found in the nearest atrium (&rgr;=0.96 for right atrium and &rgr;=0.92 for left atrium) and the DF gradient between them (&rgr;=0.93). The spatial distribution of power on the surface showed an inverse relationship between the frequencies versus the power spread area, consistent with localized fast sources as the AF mechanism with fibrillatory conduction elsewhere. Conclusions—Spectral analysis of body surface recordings during AF allows a noninvasive characterization of the global distribution of the atrial DFs and the identification of the atrium with the highest frequency, opening the possibility for improved noninvasive personalized diagnosis and treatment.

Body surface localization of left and right atrial high-frequency rotors in atrial fibrillation patients: A clinical-computational study

BACKGROUND Ablation is an effective therapy in patients with atrial fibrillation (AF) in which an electrical driver can be identified. OBJECTIVE The aim of this study was to present and discuss a novel and strictly noninvasive approach to map and identify atrial regions responsible for AF perpetuation. METHODS Surface potential recordings of 14 patients with AF were recorded using a 67-lead recording system. Singularity points (SPs) were identified in surface phase maps after band-pass filtering at the highest dominant frequency (HDF). Mathematical models of combined atria and torso were constructed and used to investigate the ability of surface phase maps to estimate rotor activity in the atrial wall. RESULTS The simulations show that surface SPs originate at atrial SPs, but not all atrial SPs are reflected at the surface. Stable SPs were found in AF signals during 8.3% ± 5.7% vs. 73.1% ± 16.8% of the time in unfiltered vs. HDF-filtered patient data, respectively (P < .01). The average duration of each rotational pattern was also lower in unfiltered than in HDF-filtered AF signals (160 ± 43 ms vs. 342 ± 138 ms; P < .01), resulting in 2.8 ± 0.7 rotations per rotor. Band-pass filtering reduced the apparent meandering of surface HDF rotors by reducing the effect of the atrial electrical activity occurring at different frequencies. Torso surface SPs representing HDF rotors during AF were reflected at specific areas corresponding to the fastest atrial location. CONCLUSION Phase analysis of surface potential signals after HDF filtering during AF shows reentrant drivers localized to either the left atrium or the right atrium, helping in localizing ablation targets.

Noninvasive Assessment of the Complexity and Stationarity of the Atrial Wavefront Patterns During Atrial Fibrillation

A novel automated approach to quantitatively evaluate the degree of spatio-temporal organization in the atrial activity (AA) during atrial fibrillation (AF) from surface recordings, obtained from body surface potential maps (BSPM), is presented. AA organization is assessed by measuring the reflection of the spatial complexity and temporal stationarity of the wavefront patterns propagating inside the atria on the surface ECG, by means of principal component analysis (PCA). Complexity and stationarity are quantified through novel parameters describing the structure of the mixing matrices derived by the PCA of the different AA segments across the BSPM recording. A significant inverse correlation between complexity and stationarity is highlighted by this analysis. The discriminatory power of the parameters in identifying different groups in the set of patients under study is also analyzed. The obtained results present analogies with earlier invasive studies in terms of number of significant components necessary to describe 95% of the variance in the AA (four for more organized AF, and eight for more disorganized AF). These findings suggest that automated analysis of AF organization exploiting spatial diversity in surface recordings is indeed possible, potentially leading to an improvement in clinical decision making and AF treatment.

Functional mathematical model of dual pathway AV nodal conduction

Dual atrioventricular (AV) nodal pathway physiology is described as two different wave fronts that propagate from the atria to the His bundle: one with a longer effective refractory period [fast pathway (FP)] and a second with a shorter effective refractory period [slow pathway (SP)]. By using His electrogram alternance, we have developed a mathematical model of AV conduction that incorporates dual AV nodal pathway physiology. Experiments were performed on five rabbit atrial-AV nodal preparations to develop and test the presented model. His electrogram alternances from the inferior margin of the His bundle were used to identify fast and slow wave front propagations. The ability to predict AV conduction time and the interaction between FP and SP wave fronts have been analyzed during regular and irregular atrial rhythms (e.g., atrial fibrillation). In addition, the role of dual AV nodal pathway wave fronts in the generation of Wenckebach periodicities has been illustrated. Finally, AV node ablative modifications have been evaluated. The model accurately reproduced interactions between FP and SP during regular and irregular atrial pacing protocols. In all experiments, specificity and sensitivity higher than 85% were obtained in the prediction of the pathway responsible for conduction. It has been shown that, during atrial fibrillation, the SP ablation significantly increased the mean HH interval (204 ± 39 vs. 274 ± 50 ms, P < 0.05), whereas FP ablation did not produce significant slowing of ventricular rate. The presented mathematical model can help in understanding some of the intriguing AV node mechanisms and should be considered as a step forward in the studies of AV nodal conduction.

Presence and stability of rotors in atrial fibrillation: evidence and therapeutic implications

Rotor-guided ablation has opened new perspectives into the therapy of atrial fibrillation (AF). Analysis of the spatio-temporal cardiac excitation patterns in the frequency and phase domains has demonstrated the importance of rotors in research models of AF, however, the dynamics and role of rotors in human AF are still controversial. In this review, the current knowledge gained through research models and patient data that support the notion that rotors are key players in AF maintenance is summarized. We report and discuss discrepancies regarding rotor prevalence and stability in various studies, which can be attributed in part to methodological differences among mapping systems. Future research for validation and improvement of current clinical electrophysiology mapping technologies will be crucial for developing mechanistic-based selection and application of the best therapeutic strategy for individual AF patient, being it, pharmaceutical, ablative, or other approach.

Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study

Background Atrial remodeling as a result of long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction in the efficacy of antiarrhythmic treatments. Objective The purpose of this study was to identify the ionic current modifications that could destabilize reentries during chronic AF and serve to personalize antiarrhythmic strategies. Methods A population of 173 mathematical models of remodeled human atrial tissue with realistic intersubject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The relationship of each ionic current with AF maintenance and the dynamics of functional reentries (rotor meandering, dominant frequency) were evaluated by means of 3-dimensional simulations. Results Self-sustained reentries were maintained in 126 (73%) of the simulations. AF perpetuation was associated with higher expressions of INa and ICaL (P <.01), with no significant differences in the remaining currents. ICaL blockade promoted AF extinction in 30% of these 126 models. The mechanism of AF termination was related with collisions between rotors because of an increase in rotor meandering (1.71 ± 2.01cm2) and presented an increased efficacy in models with a depressed INa (P <.01). Conclusion Mathematical simulations based on a population of models representing intersubject variability allow the identification of ionic mechanisms underlying rotor dynamics and the definition of new personalized pharmacologic strategies. Our results suggest that the underlying mechanism of the diverging success of ICaL block as an antiarrhythmic strategy is dependent on the basal availability of sodium and calcium ion channel conductivities.

Noninvasive Estimation of Epicardial Dominant High‐Frequency Regions during Atrial Fibrillation

Ablation of high dominant frequency (DF) sources in patients with atrial fibrillation (AF) is an effective treatment option for paroxysmal AF. The aim of this study was to evaluate the accuracy of noninvasive estimation of DF and electrical patterns determination by solving the inverse problem of the electrocardiography.

Electrophysiological characteristics of permanent atrial fibrillation: insights from research models of cardiac remodeling.

Atrial fibrillation (AF) results in a remodeling of the electrical and structural characteristics of the cardiac tissue which dramatically reduces the efficacy of pharmacological and catheter-based ablation therapies. Recent experimental and clinical results have demonstrated that the complexity of the fibrillatory process significantly differs in paroxysmal versus persistent AF; however, the lack of appropriate research models of remodeled atrial tissue precludes the elucidation of the underlying AF mechanisms and the identification of appropriated therapeutic targets. Here, we summarize the different research models used to date, highlighting the lessons learned from them and pointing to the new doors that should be open for the development of innovative treatments for AF.

Role of atrial tissue remodeling on rotor dynamics an in vitro study

The objective of this article is to present an in vitro model of atrial cardiac tissue that could serve to study the mechanisms of remodeling related to atrial fibrillation (AF). We analyze the modification on gene expression and modifications on rotor dynamics following tissue remodeling. Atrial murine cells (HL-1 myocytes) were maintained in culture after the spontaneous initiation of AF and analyzed at two time points: 3.1 ± 1.3 and 9.7 ± 0.5 days after AF initiation. The degree of electrophysiological remodeling (i.e., relative gene expression of key ion channels) and structural inhomogeneity was compared between early and late cell culture times both in nonfibrillating and fibrillating cell cultures. In addition, the electrophysiological characteristics of in vitro fibrillation [e.g., density of phase singularities (PS/cm(2)), dominant frequency, and rotor meandering] analyzed by means of optical mapping were compared with the degree of electrophysiological remodeling. Fibrillating cell cultures showed a differential ion channel gene expression associated with atrial tissue remodeling (i.e., decreased SCN5A, CACN1C, KCND3, and GJA1 and increased KCNJ2) not present in nonfibrillating cell cultures. Also, fibrillatory complexity was increased in late- vs. early stage cultures (1.12 ± 0.14 vs. 0.43 ± 0.19 PS/cm(2), P < 0.01), which was associated with changes in the electrical reentrant patterns (i.e., decrease in rotor tip meandering and increase in wavefront curvature). HL-1 cells can reproduce AF features such as electrophysiological remodeling and an increased complexity of the electrophysiological behavior associated with the fibrillation time that resembles those occurring in patients with chronic AF.

Adaptive step ODE algorithms for the 3D simulation of electric heart activity with graphics processing units

In this paper we studied the implementation and performance of adaptive step methods for large systems of ordinary differential equations systems in graphics processing units, focusing on the simulation of three-dimensional electric cardiac activity. The Rush-Larsen method was applied in all the implemented solvers to improve efficiency. We compared the adaptive methods with the fixed step methods, and we found that the fixed step methods can be faster while the adaptive step methods are better in terms of accuracy and robustness.