Andreu M. Climent

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.

Global position paper on cardiovascular regenerative medicine

Authors/Task Force Members. Chairpersons: Francisco Fern andez-Avilés (Spain), Andre Terzic (USA); Basic Research Subcommittee: Lina Badimon (Spain), Kathleen Broughton (USA), Darcy L. DiFede (USA), Stefanie Dimmeler (Germany), Rosalinda Madonna (Italy), Marc S. Penn (USA), Mark A. Sussman (USA), Joost P.G. Sluijter (The Netherlands), Kai C. Wollert (Germany); Translational Research Subcommittee: Wayne Balkan (USA), Roberto Bolli (USA), Steven Chamuleau (The Netherlands), Dominique Charron (France),

PoincarÉ Surface Profiles of RR Intervals: A Novel Noninvasive Method for the Evaluation of Preferential AV Nodal Conduction During Atrial Fibrillation

The ventricular response during atrial fibrillation (AF) presents particular characteristics that may play a relevant role in the selection of the most appropriate treatment. Using different ECG signal processing techniques such as RR histogram analysis or histographic Poincare plots (PPs) (so-called 3-D PPs), clusters of RR intervals due to preferential atrioventricular (AV) node conduction can be observed. However, these methods are limited by the need for visual inspection and subjective interpretation of analysis results. The objective of this paper is to develop a method to automatically detect and quantify preferential clusters of RR intervals. This novel method, the Poincare surface profile (PSP), uses the information of histographic PPs to filter part of the AV node memory effects. PSP detected all RR populations present in RR interval histograms in 55 patients with persistent AF and also 67% additional RR populations. In addition, a reduction of beat-to-beat dependencies allowed a more accurate location of RR populations. This novel Poincare-plot-based analysis also allows monitoring of short-term variations of preferential conductions. We illustrate the capability of this short-time monitoring technique to evaluate the effects of rate control drugs on each preferential conduction.

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.

How Many Leads Are Necessary for a Reliable Reconstruction of Surface Potentials During Atrial Fibrillation

In this study, we aimed at determining how many leads are necessary for accurately reconstructing ECG potentials during atrial fibrillation (AF) on the body surface. Although the standard ECG is appropriate for the detection of this arrhythmia, its accuracy for extracting other diagnostic features or constructing surface potential maps may not be optimal. We evaluated the suitability of the standard ECG in AF and proposed a new lead system for improving the information content of AF signals in limited lead systems. We made use of 64-lead body surface potential mapping recordings of 17 patients during AF and 18 healthy subjects. Lead selection was performed by making use of a lead selection algorithm proposed by Lux, and error curves were calculated for increasing number of selected leads for QRS complexes and P waves from healthy subjects and AF signals. From our results, at least 23 leads are needed in order to have the same degree of accuracy in the derivation of AF waves as the 12-lead ECG for a normal QRS complex (25% error). The 12-lead ECG allows a reconstruction of surface potentials with 53% error. If a limited lead set is to be chosen, a repositioning of only four electrodes from the standard ECG reduces reconstruction error in 11%. This repositioning of electrodes may include more right anterior electrodes and one posterior electrode.

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.