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

[EN] 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 degrees in mathematical models and 12.4 degrees +/- 13.2 degrees 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 degrees +/- 7.1 degrees in mathematical models, and 7.9 +/- 10.7 mm and 12.1 degrees +/- 15.5 degrees in patients. The curvature of L-curve is a useful marker for the atrial position and would allow emending the inaccuracies in its location.This work was supported in part by Generalitat Valenciana under Grant ACIF/2013/021, in part by the Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spain, under Grant PI13-01882, Grant PI13-00903, Grant PI14/00857, Grant TEC2013-46067-R, and Grant DTS16/00160, in part by the Spanish Society of Cardiology (Grant for Clinical Research in Cardiology 2015), and in part by the Spanish Ministry of Science and Innovation (Red RIC) under Grant PLE2009-0152.Rodrigo Bort, M.; Climent, AM.; Liberos Mascarell, A.; Hernández-Romero, I.; Arenal, A.; Bermejo, J.; Fernández-Avilés, F.... (2018). Solving Inaccuracies in Anatomical Models for Electrocardiographic Inverse Problem Resolution by Maximizing Reconstruction Quality. IEEE Transactions on Medical Imaging. 37(3):733-740. https://doi.org/10.1109/TMI.2017.2707413S73374037

Atrial location optimization by electrical measures for Electrocardiographic Imaging

[EN] Background: The Electrocardiographic Imaging (ECGI) technique, used to non-invasively reconstruct the epicardial electrical activity, requires an accurate model of the atria and torso anatomy. Here we evaluate a new automatic methodology able to locate the atrial anatomy within the torso based on an intrinsic electrical parameter of the ECGI solution. Methods: In 28 realistic simulations of the atrial electrical activity, we randomly displaced the atrial anatomy for +/- 2.5 cm and +/- 30 degrees on each axis. An automatic optimization method based on the L-curve curvature was used to estimate the original position using exclusively non-invasive data. Results: The automatic optimization algorithm located the atrial anatomy with a deviation of 0.5 +/- 0.5 cm in position and 16.0 +/- 10.7 degrees in orientation. With these approximate locations, the obtained electrophysiological maps reduced the average error in atrial rate measures from 1.1 +/- 1.1 Hz to 0.5 +/- 1.0 Hz and in the phase singularity position from 7.2 +/- 4.0 cm to 1.6 +/- 1.7 cm (p < 0.01). Conclusions: This proposed automatic optimization may help to solve spatial inaccuracies provoked by cardiac motion or respiration, as well as to use ECGI on torso and atrial anatomies from different medical image systems.This work was supported in part by: Generalitat Valenciana Grants [APOSTD/2017] and projects [GVA/2018/103]; Nvidia Corporation with GPU QUADRO P6000 donation.Gisbert Soler, V.; Jiménez-Serrano, S.; Roses-Albert, E.; Rodrigo Bort, M. (2020). Atrial location optimization by electrical measures for Electrocardiographic Imaging. Computers in Biology and Medicine. 127:1-8. https://doi.org/10.1016/j.compbiomed.2020.104031S18127Cuculich, P. S., Zhang, J., Wang, Y., Desouza, K. A., Vijayakumar, R., Woodard, P. K., & Rudy, Y. 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Computers in Biology and Medicine, 44, 15-26. doi:10.1016/j.compbiomed.2013.10.023Rodrigo, M., Climent, A. M., Liberos, A., Fernández-Avilés, F., Berenfeld, O., Atienza, F., & Guillem, M. S. (2017). Highest dominant frequency and rotor positions are robust markers of driver location during noninvasive mapping of atrial fibrillation: A computational study. Heart Rhythm, 14(8), 1224-1233. doi:10.1016/j.hrthm.2017.04.017Dolan, E. D., Lewis, R. M., & Torczon, V. (2003). On the Local Convergence of Pattern Search. SIAM Journal on Optimization, 14(2), 567-583. doi:10.1137/s1052623400374495Rodrigo, M., Guillem, M. S., Climent, A. M., Pedrón-Torrecilla, J., Liberos, A., Millet, J., … Berenfeld, O. (2014). Body surface localization of left and right atrial high-frequency rotors in atrial fibrillation patients: A clinical-computational study. Heart Rhythm, 11(9), 1584-1591. doi:10.1016/j.hrthm.2014.05.013Sanders, P., Berenfeld, O., Hocini, M., Jaïs, P., Vaidyanathan, R., Hsu, L.-F., … Haïssaguerre, M. (2005). Spectral Analysis Identifies Sites of High-Frequency Activity Maintaining Atrial Fibrillation in Humans. Circulation, 112(6), 789-797. doi:10.1161/circulationaha.104.517011Atienza, F., Almendral, J., Ormaetxe, J. M., Moya, Á., Martínez-Alday, J. D., Hernández-Madrid, A., … Jalife, J. (2014). Comparison of Radiofrequency Catheter Ablation of Drivers and Circumferential Pulmonary Vein Isolation in Atrial Fibrillation. Journal of the American College of Cardiology, 64(23), 2455-2467. doi:10.1016/j.jacc.2014.09.053Rodrigo, M., Climent, A. M., Liberos, A., Fernández-Avilés, F., Berenfeld, O., Atienza, F., & Guillem, M. S. (2017). Technical Considerations on Phase Mapping for Identification of Atrial Reentrant Activity in Direct- and Inverse-Computed Electrograms. 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N., Ramanathan, C., Ping Jia, & Rudy, Y. (2003). Heart-surface reconstruction and ecg electrodes localization using fluoroscopy, epipolar geometry and stereovision: application to noninvasive imaging of cardiac electrical activity. IEEE Transactions on Medical Imaging, 22(10), 1307-1318. doi:10.1109/tmi.2003.818263Lee, J., Thornhill, R. E., Nery, P., Robert deKemp, Peña, E., Birnie, D., … Ukwatta, E. (2019). Left atrial imaging and registration of fibrosis with conduction voltages using LGE-MRI and electroanatomical mapping. Computers in Biology and Medicine, 111, 103341. doi:10.1016/j.compbiomed.2019.103341Weiss, E., Wijesooriya, K., Dill, S. V., & Keall, P. J. (2007). Tumor and normal tissue motion in the thorax during respiration: Analysis of volumetric and positional variations using 4D CT. International Journal of Radiation Oncology*Biology*Physics, 67(1), 296-307. doi:10.1016/j.ijrobp.2006.09.009Wikström, K., Isacsson, U., Nilsson, K., & Ahnesjö, A. (2018). Reproducibility of heart and thoracic wall position in repeated deep inspiration breath holds for radiotherapy of left-sided breast cancer patients. Acta Oncologica, 57(10), 1318-1324. doi:10.1080/0284186x.2018.1490027Messinger-Rapport, B. J., & Rudy, Y. (1986). The Inverse Problem in Electrocardiography: A Model Study of the Effects of Geometry and Conductivity Parameters on the Reconstruction of Epicardial Potentials. IEEE Transactions on Biomedical Engineering, BME-33(7), 667-676. doi:10.1109/tbme.1986.325756Messinger-Rapport, B. J., & Rudy, Y. (1990). Noninvasive recovery of epicardial potentials in a realistic heart-torso geometry. Normal sinus rhythm. Circulation Research, 66(4), 1023-1039. doi:10.1161/01.res.66.4.1023Coll-Font, J., & Brooks, D. H. (2018). Tracking the Position of the Heart From Body Surface Potential Maps and Electrograms. Frontiers in Physiology, 9. doi:10.3389/fphys.2018.01727Van der Waal, J., Meijborg, V., Schuler, S., Coronel, R., & Oostendorp, T. (2020). In silico validation of electrocardiographic imaging to reconstruct the endocardial and epicardial repolarization pattern using the equivalent dipole layer source model. Medical & Biological Engineering & Computing, 58(8), 1739-1749. doi:10.1007/s11517-020-02203-yChamorro-Servent, J., Dubois, R., & Coudière, Y. (2019). Considering New Regularization Parameter-Choice Techniques for the Tikhonov Method to Improve the Accuracy of Electrocardiographic Imaging. Frontiers in Physiology, 10. doi:10.3389/fphys.2019.0027

The Impact of Torso Signal Processing on Noninvasive Electrocardiographic Imaging Reconstructions

Goal: To evaluate state-of-the-art signal processing methods for epicardial potential-based noninvasive electrocardiographic imaging reconstructions of single-site pacing data. Methods: Experimental data were obtained from two torso-tank setups in which Langendorff-perfused hearts (n = 4) were suspended and potentials recorded simultaneously from torso and epicardial surfaces. 49 different signal processing methods were applied to torso potentials, grouped as i) high-frequency noise removal (HFR) methods ii) baseline drift removal (BDR) methods and iii) combined HFR+BDR. The inverse problem was solved and reconstructed electrograms and activation maps compared to those directly recorded. Results: HFR showed no difference compared to not filtering in terms of absolute differences in reconstructed electrogram amplitudes nor median correlation in QRS waveforms (p > 0.05). However, correlation and mean absolute error of activation times and pacing site localization were improved with all methods except a notch filter. HFR applied post-reconstruction produced no differences compared to pre-reconstruction. BDR and BDR+HFR significantly improved absolute and relative difference, and correlation in electrograms (p < 0.05). While BDR+HFR combined improved activation time and pacing site detection, BDR alone produced significantly lower correlation and higher localization errors (p < 0.05). Conclusion: BDR improves reconstructed electrogram morphologies and amplitudes due to a reduction in lambda value selected for the inverse problem. The simplest method (resetting the isoelectric point) is sufficient to see these improvements. HFR does not impact electrogram accuracy, but does impact post-processing to extract features such as activation times. Removal of line noise is insufficient to see these changes. HFR should be applied post-reconstruction to ensure over-filtering does not occur

Non-invasive identification of atrial fibrillation drivers

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. Nowadays the fibrillatory process is known to be provoked by the high-frequency reentrant activity of certain atrial regions that propagates the fibrillatory activity to the rest of the atrial tissue, and the electrical isolation of these key regions has demonstrated its effectiveness in terminating the fibrillatory process. The location of the dominant regions represents a major challenge in the diagnosis and treatment of this arrhythmia. With the aim to detect and locate the fibrillatory sources prior to surgical procedure, non-invasive methods have been developed such as body surface electrical mapping (BSPM) which allows to record with high spatial resolution the electrical activity on the torso surface or the electrocardiographic imaging (ECGI) which allows to non-invasively reconstruct the electrical activity in the atrial surface. Given the novelty of these systems, both technologies suffer from a lack of scientific knowledge about the physical and technical mechanisms that support their operation. Therefore, the aim of this thesis is to increase that knowledge, as well as studying the effectiveness of these technologies for the localization of dominant regions in patients with AF. First, it has been shown that BSPM systems are able to noninvasively identify atrial rotors by recognizing surface rotors after band-pass filtering. Furthermore, the position of such surface rotors is related to the atrial rotor location, allowing the distinction between left or right atrial rotors. Moreover, it has been found that the surface electrical maps in AF suffer a spatial smoothing effect by the torso conductor volume, so the surface electrical activity can be studied with a relatively small number of electrodes. Specifically, it has been seen that 12 uniformly distributed electrodes are sufficient for the correct identification of atrial dominant frequencies, while at least 32 leads are needed for non-invasive identification of atrial rotors. Secondly, the effect of narrowband filtering on the effectiveness of the location of reentrant patterns was studied. It has been found that this procedure allows isolating the reentrant electrical activity caused by the rotor, increasing the detection rate for both invasive and surface maps. However, the spatial smoothing caused by the regularization of the ECGI added to the temporal filtering causes a large increase in the spurious reentrant activity, making it difficult to detect real reentrant patterns. However, it has been found that maps provided by the ECGI without temporal filtering allow the correct detection of reentrant activity, so narrowband filtering should be applied for intracavitary or surface signal only. Finally, we studied the stability of the markers used to detect dominant regions in ECGI, such as frequency maps or the rotor presence. It has been found that in the presence of alterations in the conditions of the inverse problem, such as electrical or geometrical noise, these markers are significantly more stable than the ECGI signal morphology from which they are extracted. In addition, a new methodology for error reduction in the atrial spatial location based on the curvature of the curve L has been proposed. The results presented in this thesis showed that BSPM and ECGI systems allows to non-invasively locate the presence of high-frequency rotors, responsible for the maintenance of AF. This detection has been proven to be unambiguous and robust, and the physical and technical mechanisms that support this behavior have been studied. These results indicate that both non-invasive systems provide information of great clinical value in the treatment of AF, so their use can be helpful for selecting and planning atrial ablation procedures.La fibrilación auricular (FA) es una de las arritmias cardiacas más frecuentes. Hoy en día se sabe que el proceso fibrilatorio está provocado por la actividad reentrante a alta frecuencia de ciertas regiones auriculares que propagan la actividad fibrilatoria en el resto del tejido auricular, y se ha demostrado que el aislamiento eléctrico de estas regiones dominantes permite detener el proceso fibrilatorio. La localización de las regiones dominantes supone un gran reto en el diagnóstico y tratamiento de la FA. Con el objetivo de poder localizar las fuentes fibrilatorias con anterioridad al procedimiento quirúrgico, se han desarrollado métodos no invasivos como la cartografía eléctrica de superficie (CES) que registra con gran resolución espacial la actividad eléctrica en la superficie del torso o la electrocardiografía por imagen (ECGI) que permite reconstruir la actividad eléctrica en la superficie auricular. Dada la novedad de estos sistemas, existe una falta de conocimiento científico sobre los mecanismos físicos y técnicos que sustentan su funcionamiento. Por lo tanto, el objetivo de esta tesis es aumentar dicho conocimiento, así como estudiar la eficacia de ambas tecnologías para la localización de regiones dominantes en pacientes con FA. En primer lugar, ha visto que los sistemas CES permiten identificar rotores auriculares mediante el reconocimiento de rotores superficiales tras el filtrado en banda estrecha. Además, la posición de los rotores superficiales está relacionada con la localización de dichos rotores, permitiendo la distinción entre rotores de aurícula derecha o izquierda. Por otra parte, se ha visto que los mapas eléctricos superficiales durante FA sufren una gran suavizado espacial por el efecto del volumen conductor del torso, lo que permite que la actividad eléctrica superficial pueda ser estudiada con un número relativamente reducido de electrodos. Concretamente, se ha visto que 12 electrodos uniformemente distribuidos son suficientes para una correcta identificación de frecuencias dominantes, mientras que son necesarios al menos 32 para una correcta identificación de rotores auriculares. Por otra parte, también se ha estudiado el efecto del filtrado en banda estrecha sobre la eficacia de la localización de patrones reentrantes. Así, se ha visto que este procedimiento permite aislar la actividad eléctrica reentrante provocada por el rotor, aumentando la tasa de detección tanto para señal obtenida de manera invasiva como para los mapas superficiales. No obstante, este filtrado temporal sobre la señal de ECGI provoca un gran aumento de la actividad reentrante espúrea que dificulta la detección de patrones reentrantes reales. Sin embargo, los mapas ECGI sin filtrado temporal permiten la detección correcta de la actividad reentrante, por lo el filtrado debería ser aplicado únicamente para señal intracavitaria o superficial. Por último, se ha estudiado la estabilidad de los marcadores utilizados en ECGI para detectar regiones dominantes, como son los mapas de frecuencia o la presencia de rotores. Se ha visto que en presencia de alteraciones en las condiciones del problema inverso, como ruido eléctrico o geométrico, estos marcadores son significativamente más estables que la morfología de la propia señal ECGI. Además, se ha propuesto una nueva metodología para la reducción del error en la localización espacial de la aurícula basado en la curvatura de la curva L. Los resultados presentados en esta tesis revelan que los sistemas de CES y ECGI permiten localizar de manera no invasiva la presencia de rotores de alta frecuencia. Esta detección es univoca y robusta, y se han estudiado los mecanismos físicos y técnicos que sustentan dicho comportamiento. Estos resultados indican que ambos sistemas no invasivos proporcionan información de gran valor clínico en el tratamiento de la FA, por lo que su uso puede ser de gran ayuda para la selección y planificaciLa fibril·lació auricular (FA) és una de les arítmies cardíaques més freqüents. Hui en dia es sabut que el procés fibrilatori està provocat per l'activitat reentrant de certes regions auriculars que propaguen l'activitat fibril·latoria a la resta del teixit auricular, i s'ha demostrat que l'aïllament elèctric d'aquestes regions dominants permet aturar el procés fibrilatori. La localització de les regions dominants suposa un gran repte en el diagnòstic i tractament d'aquesta arítmia. Amb l'objectiu de poder localitzar fonts fibril·latories amb anterioritat al procediment quirúrgic s'han desenvolupat mètodes no invasius com la cartografia elèctrica de superfície (CES) que registra amb gran resolució espacial l'activitat elèctrica en la superfície del tors o l'electrocardiografia per imatge (ECGI) que permet obtenir de manera no invasiva l'activitat elèctrica en la superfície auricular. Donada la relativa novetat d'aquests sistemes, existeix una manca de coneixement científic sobre els mecanismes físics i tècnics que sustenten el seu funcionament. Per tant, l'objectiu d'aquesta tesi és augmentar aquest coneixement, així com estudiar l'eficàcia d'aquestes tecnologies per a la localització de regions dominants en pacients amb FA. En primer lloc, s'ha vist que els sistemes CES permeten identificar rotors auriculars mitjançant el reconeixement de rotors superficials després del filtrat en banda estreta. A més, la posició dels rotors superficials està relacionada amb la localització d'aquests rotors, permetent la distinció entre rotors de aurícula dreta o esquerra. També s'ha vist que els mapes elèctrics superficials durant FA pateixen un gran suavitzat espacial per l'efecte del volum conductor del tors, el que permet que l'activitat elèctrica superficial pugui ser estudiada amb un nombre relativament reduït d'elèctrodes. Concretament, s'ha vist que 12 elèctrodes uniformement distribuïts són suficients per a una correcta identificació de freqüències dominants auriculars, mentre que són necessaris almenys 32 per a una correcta identificació de rotors auriculars. D'altra banda, també s'ha estudiat l'efecte del filtrat en banda estreta sobre l'eficàcia de la localització de patrons reentrants. Així, s'ha vist que aquest procediment permet aïllar l'activitat elèctrica reentrant provocada pel rotor, augmentant la taxa de detecció tant pel senyal obtingut de manera invasiva com per als mapes superficials. No obstant això, aquest filtrat temporal sobre el senyal de ECGI provoca un gran augment de l'activitat reentrant espúria que dificulta la detecció de patrons reentrants reals. A més, els mapes proporcionats per la ECGI sense filtrat temporal permeten la detecció correcta de l'activitat reentrant, per la qual cosa el filtrat hauria de ser aplicat únicament per a senyal intracavitària o superficial. Per últim, s'ha estudiat l'estabilitat dels marcadors utilitzats en ECGI per a detectar regions auriculars dominants, com són els mapes de freqüència o la presència de rotors. S'ha vist que en presència d'alteracions en les condicions del problema invers, com soroll elèctric o geomètric, aquests marcadors són significativament més estables que la morfologia del mateix senyal ECGI. A més, s'ha proposat una nova metodologia per a la reducció de l'error en la localització espacial de l'aurícula basat en la curvatura de la corba L. Els resultats presentats en aquesta tesi revelen que els sistemes de CES i ECGI permeten localitzar de manera no invasiva la presència de rotors d'alta freqüència. Aquesta detecció és unívoca i robusta, i s'han estudiat els mecanismes físics i tècnics que sustenten aquest comportament. Aquests resultats indiquen que els dos sistemes no invasius proporcionen informació de gran valor clínic en el tractament de la FA, pel que el seu ús pot ser de gran ajuda per a la selecció i planificació de procediments d'ablació auricular.Rodrigo Bort, M. (2016). Non-invasive identification of atrial fibrillation drivers [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/75346TESISPremios Extraordinarios de tesis doctorale

Cardiac anisotropy in boundary-element models for the electrocardiogram

The boundary-element method (BEM) is widely used for electrocardiogram (ECG) simulation. Its major disadvantage is its perceived inability to deal with the anisotropic electric conductivity of the myocardial interstitium, which led researchers to represent only intracellular anisotropy or neglect anisotropy altogether. We computed ECGs with a BEM model based on dipole sources that accounted for a “compound” anisotropy ratio. The ECGs were compared with those computed by a finite-difference model, in which intracellular and interstitial anisotropy could be represented without compromise. For a given set of conductivities, we always found a compound anisotropy value that led to acceptable differences between BEM and finite-difference results. In contrast, a fully isotropic model produced unacceptably large differences. A model that accounted only for intracellular anisotropy showed intermediate performance. We conclude that using a compound anisotropy ratio allows BEM-based ECG models to more accurately represent both anisotropies

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

[EN] 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 degrees 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 degrees 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 degrees 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.This work was supported in part by grants from Generalitat Valenciana (ACIF/2013/021); Instituto de Salud Carlos III-FEDER (Fondo Europeo de Desarrollo Regional) and Ministerio de Ciencia e Innovacion (PI13-01882, PI13-00903, PI14/00857, PI16/01123, IJCI-2014-22178, DTS16/00160 and Red RIC RD12.0042.0001); Spanish Society of Cardiology (Clinical Research Grant 2015); and the National Heart, Lung, and Blood Institute (P01-HL039707, P01-HL087226, and Q1 R01-HL118304). Dr. Atienza served on the advisory board of Medtronic and Sorin. Dr. Berenfeld received research support from Medtronic and St. Jude Medical; and is a cofounder and Scientific Officer of Rhythm Solutions, Inc., Research and Development Director for S.A.S. Volta Medical, and consultant to Acutus Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.Rodrigo Bort, M.; Climent, AM.; Liberos Mascarell, A.; Fernandez-Aviles, F.; Berenfeld, O.; Atienza, F.; Guillem Sánchez, MS. (2017). Highest dominant frequency and rotor positions are robust markers of driver location during noninvasive mapping of atrial fibrillation: A computational study. Heart Rhythm. 14(8):1224-1233. https://doi.org/10.1016/j.hrthm.2017.04.017S1224123314

Modeling Human Atrial Patho-Electrophysiology from Ion Channels to ECG - Substrates, Pharmacology, Vulnerability, and P-Waves

Half of the patients suffering from atrial fibrillation (AF) cannot be treated adequately, today. This thesis presents multi-scale computational methods to advance our understanding of patho-mechanisms, to improve the diagnosis of patients harboring an arrhythmogenic substrate, and to tailor therapy. The modeling pipeline ranges from ion channels on the subcellular level up to the ECG on the body surface. The tailored therapeutic approaches carry the potential to reduce the burden of AF