Mathematical modeling approaches for the diagnosis and treatment of reentrant atrial tachyarrhythmias

[EN] Atrial tachyarrhythmias present a high prevalence in the developed world, and several studies predict that in the coming decades it will be increased. Micro or macro-reentrant mechanisms of the electrical wavefronts that govern the mechanical behavior of the heart are one of the main responsibles for the maintenance of these arrhythmias. Atrial flutter is maintained by a macro-reentry around an anatomical or functional obstacle located in the atria. In the case of atrial fibrillation, the hypothesis which describes high frequency rotors as dominant sources of the fibrillation and responsible for the maintenance of the arrhythmia, has been gaining relevance in the last years. However, the therapies that target high frequency sources have a limited efficacy with current techniques. Radiofrequency ablation allows the destruction of parts of the cardiac tissue resulting in the interruption of the reentrant circuit in case of macro-reentries or the isolation of micro-reentrant circuits. The non-invasive location of reentrant circuits would increment the efficacy of these therapies and would shorten surgery interventions. In parallel, pharmacological therapies modify ionic expressions associated to the excitability and electrical refractoriness of the cardiac tissue with the objective of hindering the maintenance of reentrant behaviors. These therapies require a deep knowledge of the ionic mechanisms underlying the reentrant behavior and its properties in order to be effective. The research in these mechanisms allows the evaluation of new targets for the treatment and thus may improve the efficacy in atrial fibrillation termination. In this thesis, mathematical modeling is used to go forward in the minimization of the limitations associated to these treatments. Body surface potential mapping has been evaluated, both clinically and by means of mathematical simulations for the diagnosis and location of macro-reentrant circuits. The analysis of phase maps obtained from multiple lead electrocardiographic recordings distributed in the whole torso allowed the discrimination between different reentrant circuits. It is the reason why this technique is presented as a tool for the non-invasive location of macro and micro-reentrant circuits. A population of mathematical models designed in this thesis based on the action potentials recordings of atrial cardiomyocites from 149 patients, allowed the evaluation of the ionic mechanisms defining the properties of reentrant behaviors. This study has allowed us defining the blockade of ICaL as a target for the pharmacological treatment. The blockade of this current is associated with the increase of the movement in the core of the rotor which easies the collision of the rotor with other wavefronts or anatomical obstacles promoting the extinction of the reentry. The variability observed between patients modeled in our population has allowed showing and explaining the mechanisms promoting divergent results of a single treatment. This is why the introduction of populations of models will allow the prevention of side effects associated to inter-subject variability and to go forward in the development of individualized therapies. These works are built through a simulation platform of cardiac electrophysiology based in Graphic Processing Units (GPUs) and developed in this thesis. The platform allows the simulation of cellular models, tissues and organs with a realistic geometry and shows features comparable to that of the platforms used by the most relevant electrophysiology research groups at the moment.[ES] Las taquiarritmias auriculares tienen una alta prevalencia en el mundo desarrollado, además diversos estudios poblacionales indican que en las próximas décadas ésta se verá incrementada. Los mecanismos de micro o macro-reentrada de los frentes de onda eléctricos que rigen el comportamiento mecánico del corazón, se presentan como una de las principales causas del mantenimiento de estas arritmias. El flutter auricular es mantenido por un macro-reentrada alrededor de un obstáculo anatómico o funcional en las aurículas, mientras que en el caso de la fibrilación auricular la hipótesis que define a los rotores de alta frecuencia como elementos dominantes y responsables del mantenimiento de la arritmia se ha ido imponiendo al resto en los últimos años. Sin embargo, las terapias que tienen como objetivo finalizar o aislar estas reentradas tienen todavía una eficacia limitada. La ablación por radiofrecuencia permite eliminar zonas del tejido cardiaco resultando en la interrupción del circuito de reentrada en el caso de macro-reentradas o el aislamiento de comportamientos micro-reentrantes. La localización no invasiva de los circuitos reentrantes incrementaría la eficacia de estas terapias y reduciría la duración de las intervenciones quirúrgicas. Por otro lado, las terapias farmacológicas alteran las expresiones iónicas asociadas a la excitabilidad y la refractoriedad del tejido con el fin de dificultar el mantenimiento de comportamientos reentrantes. Este tipo de terapias exigen incrementar el conocimiento de los mecanismos subyacentes que explican el proceso de reentrada y sus propiedades, la investigación de estos mecanismos permite definir las dianas terapéuticas que mejoran la eficacia en la extinción de estos comportamientos. En esta tesis el modelado matemático se utiliza para dar un paso importante en la minimización de las limitaciones asociadas a estos tratamientos. La cartografía eléctrica de superficie ha sido testada, clínicamente y con simulaciones matemática,s como técnica de diagnóstico y localización de circuitos macro-reentrantes. El análisis de mapas de fase obtenidos a partir de los registros multicanal de derivaciones electrocardiográficas distribuidas en la superficie del torso permite diferenciar distintos circuitos de reentrada. Es por ello que esta técnica de registro y análisis se presenta como una herramienta para la localización no invasiva de circuitos macro y micro-reentrantes. Una población de modelos matemáticos, diseñada en esta tesis a partir de los registros de los potenciales de acción de 149 pacientes, ha permitido evaluar los mecanismos iónicos que definen las propiedades asociadas a los procesos de reentrada. Esto ha permitido apuntar al bloqueo de la corriente ICaL como diana terapéutica. Ésta se asocia al incremento del movimiento del núcleo que facilita el impacto del rotor con otros frentes de onda u obstáculos extinguiéndose así el comportamiento reentrante. La variabilidad entre pacientes reflejada en la población de modelos ha permitido además mostrar los mecanismos por los cuales un mismo tratamiento puede mostrar efectos divergentes, así el uso de poblaciones de modelos matemáticos permitirá prevenir efectos secundarios asociados a la variabilidad entre pacientes y profundizar en el desarrollo de terapias individualizadas. Estos trabajos se cimientan sobre una plataforma de simulación de electrofisiología cardiaca de basado en Unidades de Procesado Gráfico (GPUs) y desarrollada en esta tesis. La plataforma permite la simulación de modelos celulares cardiacos así como de tejidos u órganos con geometría realista, mostrando unas prestaciones comparables con las de las utilizadas por los grupos de investigación más potentes en el campo de la electrofisiología.[CA] Les taquiarítmies auriculars tenen una alta prevalença en el món desenvolupat, a més diversos estudis poblacionals indiquen que en les pròximes dècades aquesta es veurà incrementada. Els mecanismes de micro o macro-reentrada dels fronts d'ona elèctrics que regeixen el comportament mecànic del cor, es presenten com una de les principals causes del manteniment d'aquestes arítmies. El flutter auricular és mantingut per una macro-reentrada al voltant d'un obstacle anatòmic o funcional en les aurícules, mentre que en el cas de la fibril·lació auricular la hipòtesi que defineix als rotors d'alta freqüència com a elements dominants i responsables del manteniment de l'arítmia s'ha anat imposant a la resta en els últims anys. No obstant això, les teràpies que tenen com a objectiu finalitzar o aïllar aquestes reentrades tenen encara una eficàcia limitada. L'ablació per radiofreqüència permet eliminar zones del teixit cardíac resultant en la interrupció del circuit de reentrada en el cas de macro-reentrades o l'aïllament de comportaments micro-reentrants. La localització no invasiva dels circuits reentrants incrementaria l'eficàcia d'aquestes teràpies i reduiria la durada de les intervencions quirúrgiques. D'altra banda, les teràpies farmacològiques alteren les expressions iòniques associades a la excitabilitat i la refractaritat del teixit amb la finalitat de dificultar el manteniment de comportaments reentrants. Aquest tipus de teràpies exigeixen incrementar el coneixement dels mecanismes subjacents que expliquen el procés de reentrada i les seues propietats, la recerca d'aquests mecanismes permet definir les dianes terapèutiques que milloren l'eficàcia en l'extinció d'aquests comportaments. En aquesta tesi el modelatge matemàtic s'utilitza per a fer un pas important en la minimització de les limitacions associades a aquests tractaments. La cartografia elèctrica de superfície ha sigut testada, clínicament i amb simulacions matemàtiques com a tècnica de diagnòstic i localització de circuits macro-reentrants. L'anàlisi de mapes de fase obtinguts a partir dels registres multicanal de derivacions electrocardiogràfiques distribuïdes en la superfície del tors permet diferenciar diferents circuits de reentrada. És per açò que aquesta tècnica de registre i anàlisi es presenta com una eina per a la localització no invasiva de circuits macro i micro-reentrants. Una població de models matemàtics, dissenyada en aquesta tesi a partir dels registres dels potencials d'acció de 149 pacients, ha permès avaluar els mecanismes iònics que defineixen les propietats associades als processos de reentrada. Açò ha permès apuntar al bloqueig del corrent ICaL com a diana terapèutica. Aquesta s'associa a l'increment del moviment del nucli que facilita l'impacte del rotor amb altres fronts d'ona o obstacles extingint-se així el comportament reentrant. La variabilitat entre pacients reflectida en la població de models ha permès a més mostrar els mecanismes pels quals un mateix tractament pot mostrar efectes divergents, així l'ús de poblacions de models matemàtics permetrà prevenir efectes secundaris associats a la variabilitat entre pacients i aprofundir en el desenvolupament de teràpies individualitzades. Aquests treballs es fonamenten sobre una plataforma de simulació de electrofisiologia cardíaca basat en Unitats de Processament Gràfic (GPUs) i desenvolupada en aquesta tesi. La plataforma permet la simulació de models cel·lulars cardíacs així com de teixits o òrgans amb geometria realista, mostrant unes prestacions comparables amb les de les utilitzades per els grups de recerca més importants en aquesta área.Liberos Mascarell, A. (2016). Mathematical modeling approaches for the diagnosis and treatment of reentrant atrial tachyarrhythmias [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/62166TESI

Non-invasive Spatial Mapping of Frequencies in Atrial Fibrillation: Correlation With Contact Mapping

Introduction: Regional differences in activation rates may contribute to the electrical substrates that maintain atrial fibrillation (AF), and estimating them non-invasively may help guide ablation or select anti-arrhythmic medications. We tested whether non-invasive assessment of regional AF rate accurately represents intracardiac recordings. Methods: In 47 patients with AF (27 persistent, age 63 ± 13 years) we performed 57-lead non-invasive Electrocardiographic Imaging (ECGI) in AF, simultaneously with 64-pole intracardiac signals of both atria. ECGI was reconstructed by Tikhonov regularization. We constructed personalized 3D AF rate distribution maps by Dominant Frequency (DF) analysis from intracardiac and non-invasive recordings. Results: Raw intracardiac and non-invasive DF differed substantially, by 0.54 Hz [0.13 - 1.37] across bi-atrial regions (R2 = 0.11). Filtering by high spectral organization reduced this difference to 0.10 Hz (cycle length difference of 1 - 11 ms) [0.03 - 0.42] for patient-level comparisons (R2 = 0.62), and 0.19 Hz [0.03 - 0.59] and 0.20 Hz [0.04 - 0.61] for median and highest DF, respectively. Non-invasive and highest DF predicted acute ablation success (p = 0.04). Conclusion: Non-invasive estimation of atrial activation rates is feasible and, when filtered by high spectral organization, provide a moderate estimate of intracardiac recording rates in AF. Non-invasive technology could be an effective tool to identify patients who may respond to AF ablation for personalized therapy

Technical Considerations on Phase Mapping for Identification of Atrial Reentrant Activity in Direct- and Inverse-Computed Electrograms

[EN] [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.This study was supported, in part, by Universitat Politecnica de Valencia through its research initiative program; Generalitat Valenciana Grants (ACIF/2013/021); the Instituto de Salud Carlos III (Ministry of Economy and Competitiveness, Spain: PI13-01882, PI13-00903, PI14/00857, PI16/01123, TEC2013-46067-R, DTS16/0160, and IJCI-2014-22178); Spanish Society of Cardiology (Grant for Clinical Research in Cardiology 2015); Spanish Ministry of Science and Innovation (Red RIC RD12.0042.0001); and the National Heart, Lung, and Blood Institute (P01-HL039707, P01-HL087226, and Q1 R01-HL118304) and cofounded by FEDER.Rodrigo Bort, M.; Martínez Climent, A.; Liberos Mascarell, A.; Fernández-Avilés, F.; Berenfeld, O.; Atienza, F.; Guillem Sánchez, MS. (2017). Technical Considerations on Phase Mapping for Identification of Atrial Reentrant Activity in Direct- and Inverse-Computed Electrograms. Circulation Arrhythmia and Electrophysiology. 10(9):1-13. https://doi.org/10.1161/CIRCEP.117.005008S113109Allessie, M., & de Groot, N. (2014). CrossTalk opposing view: Rotors have not been demonstrated to be the drivers of atrial fibrillation. The Journal of Physiology, 592(15), 3167-3170. doi:10.1113/jphysiol.2014.271809Narayan, S. M., & Zaman, J. A. B. (2016). Mechanistically based mapping of human cardiac fibrillation. The Journal of Physiology, 594(9), 2399-2415. doi:10.1113/jp270513Guillem, M. S., Climent, A. M., Rodrigo, M., Fernández-Avilés, F., Atienza, F., & Berenfeld, O. (2016). Presence and stability of rotors in atrial fibrillation: evidence and therapeutic implications. Cardiovascular Research, 109(4), 480-492. doi:10.1093/cvr/cvw011Narayan, S. M., Krummen, D. E., Clopton, P., Shivkumar, K., & Miller, J. M. (2013). Direct or Coincidental Elimination of Stable Rotors or Focal Sources May Explain Successful Atrial Fibrillation Ablation. Journal of the American College of Cardiology, 62(2), 138-147. doi:10.1016/j.jacc.2013.03.021Berenfeld, O., Ennis, S., Hwang, E., Hooven, B., Grzeda, K., Mironov, S., … Jalife, J. (2011). Time- and frequency-domain analyses of atrial fibrillation activation rate: The optical mapping reference. Heart Rhythm, 8(11), 1758-1765. doi:10.1016/j.hrthm.2011.05.007Gray, R. A., Pertsov, A. M., & Jalife, J. (1998). Spatial and temporal organization during cardiac fibrillation. Nature, 392(6671), 75-78. doi:10.1038/32164Rodrigo, 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.2014.05.013Vijayakumar, R., Vasireddi, S. K., Cuculich, P. S., Faddis, M. N., & Rudy, Y. (2016). Methodology Considerations in Phase Mapping of Human Cardiac Arrhythmias. Circulation: Arrhythmia and Electrophysiology, 9(11). doi:10.1161/circep.116.004409Guillem, M. S., Climent, A. M., Millet, J., Arenal, Á., Fernández-Avilés, F., Jalife, J., … Berenfeld, O. (2013). Noninvasive Localization of Maximal Frequency Sites of Atrial Fibrillation by Body Surface Potential Mapping. Circulation: Arrhythmia and Electrophysiology, 6(2), 294-301. doi:10.1161/circep.112.000167Haissaguerre, M., Hocini, M., Denis, A., Shah, A. J., Komatsu, Y., Yamashita, S., … Dubois, R. (2014). Driver Domains in Persistent Atrial Fibrillation. Circulation, 130(7), 530-538. doi:10.1161/circulationaha.113.005421Dössel, O., Krueger, M. W., Weber, F. M., Wilhelms, M., & Seemann, G. (2012). Computational modeling of the human atrial anatomy and electrophysiology. Medical & Biological Engineering & Computing, 50(8), 773-799. doi:10.1007/s11517-012-0924-6Koivumäki, J. T., Seemann, G., Maleckar, M. M., & Tavi, P. (2014). In Silico Screening of the Key Cellular Remodeling Targets in Chronic Atrial Fibrillation. PLoS Computational Biology, 10(5), e1003620. doi:10.1371/journal.pcbi.1003620Garcia-Molla, V. M., Liberos, A., Vidal, A., Guillem, M. S., Millet, J., Gonzalez, A., … Climent, A. M. (2014). Adaptive step ODE algorithms for the 3D simulation of electric heart activity with graphics processing units. Computers in Biology and Medicine, 44, 15-26. doi:10.1016/j.compbiomed.2013.10.023Rodrigo, M., Climent, A. M., Liberos, A., Calvo, D., Fernández-Avilés, F., Berenfeld, O., … Guillem, M. S. (2016). Identification of Dominant Excitation Patterns and Sources of Atrial Fibrillation by Causality Analysis. Annals of Biomedical Engineering, 44(8), 2364-2376. doi:10.1007/s10439-015-1534-xPEDRÓN-TORRECILLA, J., RODRIGO, M., CLIMENT, A. M., LIBEROS, A., PÉREZ-DAVID, E., BERMEJO, J., … GUILLEM, M. S. (2016). Noninvasive Estimation of Epicardial Dominant High-Frequency Regions During Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 27(4), 435-442. doi:10.1111/jce.12931Zlochiver, S., Yamazaki, M., Kalifa, J., & Berenfeld, O. (2008). Rotor meandering contributes to irregularity in electrograms during atrial fibrillation. Heart Rhythm, 5(6), 846-854. doi:10.1016/j.hrthm.2008.03.010ALHUSSEINI, M., VIDMAR, D., MECKLER, G. L., KOWALEWSKI, C. A., SHENASA, F., WANG, P. J., … RAPPEL, W.-J. (2017). Two Independent Mapping Techniques Identify Rotational Activity Patterns at Sites of Local Termination During Persistent Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 28(6), 615-622. doi:10.1111/jce.1317

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

[EN] Background: 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. Methods: Nine uniformly distributed lead sets of eight to 66 electrodes were evaluated. BSPM signals were registered simultaneously with intracardiac electrocardiograms (EGMs) in 16 AF patients. DF activity was analyzed on the surface potentials for the nine leads configurations, and the noninvasive measures were compared with the EGM recordings. Results: Surface DF measurements presented similar values than panoramic invasive EGM recordings, showing the highest DF regions in corresponding locations. The noninvasive DFs measures had a high correlation with the invasive discrete recordings; they presented a deviation of 0.8 for leads configurations with 12 or more electrodes. Conclusions: Reduced-leads BSPM systems enable noninvasive discrimination between LA versus RA DFs with similar results as higher-resolution 66-leads system. Our findings demonstrate the possible incorporation of simplified BSPM systems into clinical planning procedures for AF ablation.This work was supported in part by Generalitat-Valenciana Grants [ACIF/2013/021]; Instituto de SaludCarlos III, Ministerio de Ciencia e Innovacion [PI13/00903, PI13-01882, PI14/00857, PI16/01123, TEC2013-46067-R, DTS16/0160 and IJCI-2014-22178] cofound by FEDER.; Spanish Society of Cardiology [Clinical research Grants 2015]; Ministerio de Ciencia e Innovacion [Red RICRD12.0042.0001]; and the National Heart, Lung, and Blood Institute [P01-HL039707, P01-HL087226 and R01-HL118304].Rodrigo Bort, M.; Climent Martínez, BA.; Liberos Mascarell, A.; Fernández-Avilés, F.; Atienza, F.; Guillem Sánchez, MS.; Berenfeld, O. (2017). Minimal configuration of body surface potential mapping for discrimination of left versus right dominant frequencies during atrial fibrillation. Pacing and Clinical Electrophysiology. 40(8):940-946. https://doi.org/10.1111/pace.13133S940946408Atienza, 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.2014.09.053Narayan, S. M., Krummen, D. E., Clopton, P., Shivkumar, K., & Miller, J. M. (2013). Direct or Coincidental Elimination of Stable Rotors or Focal Sources May Explain Successful Atrial Fibrillation Ablation. Journal of the American College of Cardiology, 62(2), 138-147. doi:10.1016/j.jacc.2013.03.021Haissaguerre, M., Hocini, M., Denis, A., Shah, A. J., Komatsu, Y., Yamashita, S., … Dubois, R. (2014). Driver Domains in Persistent Atrial Fibrillation. Circulation, 130(7), 530-538. doi:10.1161/circulationaha.113.005421Atienza, F., Almendral, J., Jalife, J., Zlochiver, S., Ploutz-Snyder, R., Torrecilla, E. G., … Berenfeld, O. (2009). Real-time dominant frequency mapping and ablation of dominant frequency sites in atrial fibrillation with left-to-right frequency gradients predicts long-term maintenance of sinus rhythm. Heart Rhythm, 6(1), 33-40. doi:10.1016/j.hrthm.2008.10.024Lim, H. S., Zellerhoff, S., Derval, N., Denis, A., Yamashita, S., Berte, B., … Haissaguerre, M. (2015). Noninvasive Mapping to Guide Atrial Fibrillation Ablation. Cardiac Electrophysiology Clinics, 7(1), 89-98. doi:10.1016/j.ccep.2014.11.004Rodrigo, 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.2014.05.013Guillem, M. S., Climent, A. M., Millet, J., Arenal, Á., Fernández-Avilés, F., Jalife, J., … Berenfeld, O. (2013). Noninvasive Localization of Maximal Frequency Sites of Atrial Fibrillation by Body Surface Potential Mapping. Circulation: Arrhythmia and Electrophysiology, 6(2), 294-301. doi:10.1161/circep.112.000167Lux, R. L., Smith, C. R., Wyatt, R. F., & Abildskov, J. A. (1978). Limited Lead Selection for Estimation of Body Surface Potential Maps in Electrocardiography. IEEE Transactions on Biomedical Engineering, BME-25(3), 270-276. doi:10.1109/tbme.1978.326332Finlay, D. D., Nugent, C. D., Donnelly, M. P., & Black, N. D. (2008). Selection of optimal recording sites for limited lead body surface potential mapping in myocardial infarction and left ventricular hypertrophy. Journal of Electrocardiology, 41(3), 264-271. doi:10.1016/j.jelectrocard.2008.02.009Guillem, M. S., Castells, F., Climent, A. M., Bodí, V., Chorro, F. J., & Millet, J. (2008). Evaluation of lead selection methods for optimal reconstruction of body surface potentials. Journal of Electrocardiology, 41(1), 26-34. doi:10.1016/j.jelectrocard.2007.07.001De la Salud Guillem, M., Bollmann, A., Climent, A. M., Husser, D., Millet-Roig, J., & Castells, F. (2009). How Many Leads Are Necessary for a Reliable Reconstruction of Surface Potentials During Atrial Fibrillation? IEEE Transactions on Information Technology in Biomedicine, 13(3), 330-340. doi:10.1109/titb.2008.2011894Castells, F., Mora, C., Rieta, J. J., Moratal-Pérez, D., & Millet, J. (2005). Estimation of atrial fibrillatory wave from single-lead atrial fibrillation electrocardiograms using principal component analysis concepts. Medical & Biological Engineering & Computing, 43(5), 557-560. doi:10.1007/bf02351028Narayan, S. M., & Jalife, J. (2014). CrossTalk proposal: Rotors have been demonstrated to drive human atrial fibrillation. The Journal of Physiology, 592(15), 3163-3166. doi:10.1113/jphysiol.2014.271031Allessie, M., & de Groot, N. (2014). CrossTalk opposing view: Rotors have not been demonstrated to be the drivers of atrial fibrillation. The Journal of Physiology, 592(15), 3167-3170. doi:10.1113/jphysiol.2014.271809Berenfeld, O., & Oral, H. (2012). The quest for rotors in atrial fibrillation: Different nets catch different fishes. Heart Rhythm, 9(9), 1440-1441. doi:10.1016/j.hrthm.2012.04.029PEDRÓN-TORRECILLA, J., RODRIGO, M., CLIMENT, A. M., LIBEROS, A., PÉREZ-DAVID, E., BERMEJO, J., … GUILLEM, M. S. (2016). Noninvasive Estimation of Epicardial Dominant High-Frequency Regions During Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 27(4), 435-442. doi:10.1111/jce.12931Uijen, G., van Oosterom, A., & Hoekema, R. (1999). The Number of Independent Signals in Body Surface Maps. 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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

From specialized to core course in Telecommunications degree: Experiences from digital electronic design and verification

[EN] The European Higher Education Area (EHEA) defines the competences for professional practice of a Telecommunications Engineer. The School of Telecommunication Engineering of the Universitat Politècnica de València (Valencia, Spain) provides an integrated education program consisting of a Graduate (GITST) + Master (MUIT). The GITST course offers four specialization tracks: Electronics, Telematics, Communication Systems and Multimedia for the proper acquisition of knowledge and competences of the future Telecommunications Engineers. In 2018, the graduate program has implemented a structural change in the organization of subjects for reinforcing important skills, in which a course on digital electronics design and verification (Integration of Digital Systems, ISDIGI) has been transformed into a core subject of the study plan. In this paper, we describe the methodology and adaptation of ISDIGI (i.e. a project-based learning intermediate HDL course that includes design and verification abilities) to the new GITST Curriculum. In addition, this paper describes the process of moving from specialized to core subject.Martínez Millana, A.; Liberos Mascarell, A.; Monzó Ferrer, JM.; Martínez Peiró, MA.; Martínez Pérez, JD.; Gadea Gironés, R. (2020). From specialized to core course in Telecommunications degree: Experiences from digital electronic design and verification. Editorial Universitat Politècnica de València. 229-238. https://doi.org/10.4995/INN2019.2019.10133OCS22923

Effects of Geometry in Atrial Fibrillation Markers Obtained With Electrocardiographic Imaging

[EN] Electrocardiographic imaging (ECGI) can characterise cardiac pathologies such as atrial fibrillation (AF) through specific markers based on frequency or phase analysis. In this study, the effect of the geometry of patients torso and atria in the ECGI resolution is studied. A realistic 3D atrial geometry was located on 30 patient torsos and ECGI signals were calculated for 30 different AF simulations in each torso. Dominant frequency (DF) and reentrant activity analysis were calculated for each scenario. Anatomical and geometrical measurements of each torso (30-80% of variability between patients) and atria were calculated and compared with the errors in the ECGI estimation versus the departing EGM maps. Results show evidences that big chest dimensions worsen the non-invasive calculation of AF markers (p<0.05). Also, higher number of visible electrodes from each atrial region improves ECGI characterization measured as lower DF deviations (0.64±0.26 Hz vs 0.72±0.27 Hz, p<0.05) and higher reentrant activity coincidence (10.1±12.2% vs 3.4±3.4%, p<0.05). Torso and atrial geometry affect the quality of the non-invasive reconstruction of AF markers such as DF or reentrant activity. Knowing the geometrical parameters that worsen non-invasive AF maps may help to measure each detected AF driver reliability.Supported in part by: Instituto de Salud Carlos III FEDER (Fondo Europeo de Desarrollo Regional; IJCI2014-22178, DTS16/00160; PI14/00857, PI16/01123; PI17/01059; PI17/01106), Generalitat Valenciana Grants (APOSTD/2017 and APOSTD/2018) and projects (GVA/2018/103) and EIT-Health 19600 AFFINE.Molero-Alabau, R.; Climent, AM.; Hernández-Romero, I.; Liberos, A.; Fernández-Avilés, F.; Atienza, F.; Guillem Sánchez, MS.... (2019). Effects of Geometry in Atrial Fibrillation Markers Obtained With Electrocardiographic Imaging. IEEE. 1-4. https://doi.org/10.22489/CinC.2019.3081

Body Surface Potential Propagation Maps During Macroreentrant Atrial Arrhythmias. A Simulation Study

Abstract Atrial flutter (AFL) i

Multi-GPU adaptation of a simulator of heart electric activity

[EN] The simulation of the electrical activity of the heart is calculated by solving a large system of ordinary differential equations; this takes an enormous amount of computation time. In recent years graphics processing unit (GPU) are being introduced in the field of high performance computing. These powerful computing devices have attracted research groups requiring simulate the electrical activity of the heart. The research group signing this paper has developed a simulator of cardiac electrical activity that runs on a single GPU. This article describes the adaptation and modification of the simulator to run on multiple GPU. The results confirm that the technique significantly reduces the execution time compared to those obtained with a single GPU, and allows the solution of larger problems.[ES] La simulación de la actividad eléctrica del corazón se calcula mediante la resolución de un gran sistema de ecuaciones diferenciales ordinarias, que necesita una enorme cantidad de tiempo de computación. Sin embargo, en los últimos años se están introduciendo, en el ámbito de la computación de alto rendimiento, las unidades de procesamiento gráfico (GPU). Estos potentes dispositivos han atraído a grupos de investigación que requieren simular la actividad eléctrica del corazón. El grupo de investigación que firma este artículo ha desarrollado un simulador de actividad eléctrica cardíaca que se ejecuta en una sola GPU. En este artículo se describe la adaptación y modificaciones de dicho simulador para su ejecución en múltiples GPU. Los resultados confirman que la técnica empleada permite reducir sensiblemente los tiempos de ejecución respecto a los que se obtienen con una sola GPU, además de permitir afrontar problemas mucho más grandes.Este trabajo ha sido financiado por la Universitat Politècnica de València a través de su Programa de Apoyo a la Investigación y Desarrollo (PAID-06-11) y (PAID-05-12), por la Generalitat Valenciana a través de los proyectos PROMETEO/2009/013 y Ayudas para la realización de proyectos de I+D para grupos de investigación emergentes GV/2012/039, y por el Ministerio Español de Economía y Competitividad y el fondo europeo de Desarrollo Regional (FEDER) de la Comunidad Europea través del proyecto TEC2012-38142-C04.García Mollá, VM.; Vidal Maciá, AM.; Liberos Mascarell, A.; Climent, AM. (2013). Adaptación para multiples GPU de un simulador de actividad eléctrica en el corazón. Revista Cubana de Ciencias Informáticas. 7(4):100-111. http://hdl.handle.net/10251/39802S1001117

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