Ismael Hernandez-Romero

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.

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.