Miguel Rodrigo

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.

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.

Technical considerations on phase mapping for identification of atrial reentrant activity in direct-And inverse-computed electrograms

Background: Phase mapping has become a broadly used technique to identify atrial reentrant circuits for ablative therapy guidance. This work studies the phase mapping process and how the signal nature and its filtering affect the reentrant pattern characterization in electrogram (EGM), body surface potential mapping, and electrocardiographic imaging signals. Methods and Results: EGM, body surface potential mapping, and electrocardiographic imaging phase maps were obtained from 17 simulations of atrial fibrillation, atrial flutter, and focal atrial tachycardia. Reentrant activity was identified by singularity point recognition in raw signals and in signals after narrow band-pass filtering at the highest dominant frequency (HDF). Reentrant activity was dominantly present in the EGM recordings only for atrial fibrillation and some atrial flutter propagations patterns, and HDF filtering allowed increasing the reentrant activity detection from 60% to 70% of time in atrial fibrillation in unipolar recordings and from 0% to 62% in bipolar. In body surface potential mapping maps, HDF filtering increased from 10% to 90% the sensitivity, although provoked a residual false reentrant activity ≈30% of time. In electrocardiographic imaging, HDF filtering allowed to increase ⩽100% the time with detected rotors, although provoked the apparition of false rotors during 100% of time. Nevertheless, raw electrocardiographic imaging phase maps presented reentrant activity just in atrial fibrillation recordings accounting for ≈80% of time. Conclusions: Rotor identification is accurate and sensitive and does not require additional signal processing in measured or noninvasively computed unipolar EGMs. Bipolar EGMs and body surface potential mapping do require HDF filtering to detect rotors at the expense of a decreased specificity.

Clinical Implications of Ablation of Drivers for Atrial Fibrillation: A Systematic Review and Meta-Analysis

Background: The outcomes from pulmonary vein isolation (PVI) for atrial fibrillation (AF) are suboptimal, but the benefits of additional lesion sets remain unproven. Recent studies propose ablation of AF drivers improves outcomes over PVI, yet with conflicting reports in the literature. We undertook a systematic literature review and meta-analysis to determine outcomes from ablation of AF drivers in addition to PVI or as a stand-alone procedure. Methods: Database search was done using the terms atrial fibrillation and ablation or catheter ablation and driver or rotor or focal impulse or FIRM (Focal Impulse and Rotor Modulation). We pooled data using random effects model and assessed heterogeneity with I2 statistic. Results: Seventeen studies met inclusion criteria, in a cohort size of 3294 patients. Adding AF driver ablation to PVI reported freedom from AF of 72.5% (confidence interval [CI], 62.1%–81.8%; P<0.01) and from all arrhythmias of 57.8% (CI, 47.5%–67.7%; P<0.01). AF driver ablation when added to PVI or as stand-alone procedure compared with controls produced an odds ratio of 3.1 (CI, 1.3–7.7; P=0.02) for freedom from AF and an odds ratio of 1.8 (CI, 1.2–2.7; P<0.01) for freedom from all arrhythmias in 4 controlled studies. AF termination rate was 40.5% (CI, 30.6%–50.9%) and predicted favorable outcome from ablation(P<0.05). Conclusions: In controlled studies, the addition of AF driver ablation to PVI supports the possible benefit of a combined approach of AF driver ablation and PVI in improving single-procedure freedom from all arrhythmias. However, most studies are uncontrolled and are limited by substantial heterogeneity in outcomes. Large multicenter randomized trials are needed to precisely define the benefits of adding driver ablation to PVI.

Highest dominant frequency and rotor positions are robust markers of driver location during noninvasive mapping of atrial fibrillation: A computational study

BACKGROUND Dominant frequency (DF) and rotor mapping have been proposed as noninvasive techniques to guide localization of drivers maintaining atrial fibrillation (AF). OBJECTIVE The purpose of this study was to evaluate the robustness of both techniques in identifying atrial drivers noninvasively under the effect of electrical noise or model uncertainties. METHODS Inverse-computed DFs and phase maps were obtained from 30 different mathematical AF simulations. Epicardial highest dominant frequency (HDF) regions and rotor location were compared with the same inverse-computed measurements after addition of noise to the ECG, size variations of the atria, and linear or angular deviations in the atrial location inside the thorax. RESULTS Inverse-computed electrograms (EGMs) individually correlated poorly with the original EGMs in the absence of induced uncertainties (0.45 ± 0.12) and were worse with 10-dB noise (0.22 ± 0.11), 3-cm displacement (0.01 ± 0.02), or 36° rotation (0.02 ± 0.03). However, inverse-computed HDF regions showed robustness against induced uncertainties: from 82% ± 18% match for the best conditions, down to 73% ± 23% for 10-dB noise, 77% ± 21% for 5-cm displacement, and 60% ± 22% for 36° rotation. The distance from the inverse-computed rotor to the original rotor was also affected by uncertainties: 0.8 ± 1.61 cm for the best conditions, 2.4 ± 3.6 cm for 10-dB noise, 4.3 ± 3.2 cm for 4-cm displacement, and 4.0 ± 2.1 cm for 36° rotation. Restriction of rotor detections to the HDF area increased rotor detection accuracy from 4.5 ± 4.5 cm to 3.2 ± 3.1 cm (P <.05) with 0-dB noise. CONCLUSION The combination of frequency and phase-derived measurements increases the accuracy of noninvasive localization of atrial rotors driving AF in the presence of noise and uncertainties in atrial location or size.

Solving Inaccuracies in Anatomical Models for Electrocardiographic Inverse Problem Resolution by Maximizing Reconstruction Quality

Electrocardiographic Imaging has become an increasingly used technique for non-invasive diagnosis of cardiac arrhythmias, although the need for medical imaging technology to determine the anatomy hinders its introduction in the clinical practice. This paper explores the ability of a new metric based on the inverse reconstruction quality for the location and orientation of the atrial surface inside the torso. Body surface electrical signals from 31 realistic mathematical models and four AF patients were used to estimate the optimal position of the atria inside the torso. The curvature of the L-curve from the Tikhonov method, which was found to be related to the inverse reconstruction quality, was measured after application of deviations in atrial position and orientation. Independent deviations in the atrial position were solved by finding the maximal L-curve curvature with an error of 1.7 ± 2.4 mm in mathematical models and 9.1 ± 11.5 mm in patients. For the case of independent angular deviations, the error in location by using the L-curve was 5.8±7.1° in mathematical models and 12.4° ± 13.2° in patients. The ability of the L-curve curvature was tested also under superimposed uncertainties in the three axis of translation and in the three axis of rotation, and the error in location was of 2.3 ± 3.2 mm and 6.4° ± 7.1° in mathematical models, and 7.9±10.7 mm and 12.1°±15.5° in patients. The curvature of L-curve is a useful marker for the atrial position and would allow emending the inaccuracies in its location.

Regularization Techniques for ECG Imaging during Atrial Fibrillation: A Computational Study.

The inverse problem of electrocardiography is usually analyzed during stationary rhythms. However, the performance of the regularization methods under fibrillatory conditions has not been fully studied. In this work, we assessed different regularization techniques during atrial fibrillation (AF) for estimating four target parameters, namely, epicardial potentials, dominant frequency (DF), phase maps, and singularity point (SP) location. We use a realistic mathematical model of atria and torso anatomy with three different electrical activity patterns (i.e., sinus rhythm, simple AF, and complex AF). Body surface potentials (BSP) were simulated using Boundary Element Method and corrupted with white Gaussian noise of different powers. Noisy BSPs were used to obtain the epicardial potentials on the atrial surface, using 14 different regularization techniques. DF, phase maps, and SP location were computed from estimated epicardial potentials. Inverse solutions were evaluated using a set of performance metrics adapted to each clinical target. For the case of SP location, an assessment methodology based on the spatial mass function of the SP location, and four spatial error metrics was proposed. The role of the regularization parameter for Tikhonov-based methods, and the effect of noise level and imperfections in the knowledge of the transfer matrix were also addressed. Results showed that the Bayes maximum-a-posteriori method clearly outperforms the rest of the techniques but requires a priori information about the epicardial potentials. Among the purely non-invasive techniques, Tikhonov-based methods performed as well as more complex techniques in realistic fibrillatory conditions, with a slight gain between 0.02 and 0.2 in terms of the correlation coefficient. Also, the use of a constant regularization parameter may be advisable since the performance was similar to that obtained with a variable parameter (indeed there was no difference for the zero-order Tikhonov method in complex fibrillatory conditions). Regarding the different targets, DF and SP location estimation were more robust with respect to pattern complexity and noise, and most algorithms provided a reasonable estimation of these parameters, even when the epicardial potentials estimation was inaccurate. Finally, the proposed evaluation procedure and metrics represent a suitable framework for techniques benchmarking and provide useful insights for the clinical practice.

Minimal configuration of body surface potential mapping for discrimination of left versus right dominant frequencies during atrial fibrillation.

Ablation of drivers maintaining atrial fibrillation (AF) has been demonstrated as an effective therapy. Drivers in the form of rapidly activated atrial regions can be noninvasively localized to either left or right atria (LA, RA) with body surface potential mapping (BSPM) systems. This study quantifies the accuracy of dominant frequency (DF) measurements from reduced‐leads BSPM systems and assesses the minimal configuration required for ablation guidance.