Characterization and Modeling of Atrioventricular Conduction during Atrial Fibrillation

La fibrilación auricular (FA) es una de las arritmias cardiacas más comunes, la cual afecta alrededor del 10% de la población de más de 70 años. En FA, los impulsos eléctricos auriculares generados por el nodo sinusal son sustituidos por impulsos eléctricos desorganizados. Esto esta asociado con un bombardeo irregular de activaciones auriculares hacia el nodo AV. Dado que el nodo AV no puede conducir todas estas activaciones, algunas de ellas son bloqueadas en el nodo. Esta propiedad de filtrado que tiene el nodo es fundamental para mantener el ritmo cardiaco en un rango compatible con la vida. Sin embargo, la respuesta ventricular durante FA presenta intervalos RR (tiempo entre dos activaciones) más cortos e irregulares que durante ritmo sinusal. Al ser el nodo AV la única estructura responsable para la conducción de los latidos auriculares hacia los ventrículos, las estrategias terapéuticas para controlar el ritmo cardiaco durante FA tratan de utilizar y ajustar las propiedades de conducción del nodo. Sin embargo, sigue sin estar suficientemente entendido el papel que dichas propiedades de conducción juegan para controlar y modular la respuesta ventricular durante FA. Durante el desarrollo de la presente tesis se han investigado en diferentes especies y con diversas técnicas algunas de las principales características de la conducción del nodo AV con la intención de aportar mayor conocimiento sobre esta intrigante estructura del corazón. Específicamente, se ha analizado uno de los fenómenos más enigmáticos de la respuesta ventricular durante FA: la aparición de patrones de respuesta ventricular multimodales al construir histogramas de RR obtenidos a partir de registros de larga duración. En la literatura se han sugerido diversas teorías que pudiesen explicar la aparición de estos múltiples intervalos RR predominantes. En el desarrollo de la presente disertación se mostrarán algunos resultados incompatibles con dichas teorías, razón por la cual se presenta y defiende una nueva hipótesis que sugiere que los intervalos RR predominantes están relacionados con el proceso fibrilatorio auricular.Martínez Climent, BA. (2011). Characterization and Modeling of Atrioventricular Conduction during Atrial Fibrillation [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/10985Palanci

Optical imaging of voltage and calcium in isolated hearts: Linking spatiotemporal heterogeneities and ventricular fibrillation initiation

[EN] Background Alternans have been associated with the development of ventricular fibrillation and its control has been proposed as antiarrhythmic strategy. However, cardiac arrhythmias are a spatiotemporal phenomenon in which multiple factors are involved (e.g. calcium and voltage spatial alternans or heterogeneous conduction velocity) and how an antiarrhythmic drug modifies these factors is poorly understood. Objective The objective of the present study is to evaluate the relation between spatial electrophysiological properties (i.e. spatial discordant alternans and conduction velocity) and the induction of ventricular fibrillation (VF) when a calcium blocker is applied. Methods The mechanisms of initiation of VF were studied by simultaneous epicardial voltage and calcium optical mapping in isolated rabbit hearts using an incremental fast pacing protocol. The additional value of analyzing spatial phenomena in the generation of unidirectional blocks and reentries as precursors of VF was depicted. Specifically, the role of action potential duration (APD), calcium transients (CaT), spatial alternans and conduction velocity in the initiation of VF was evaluated during basal conditions and after the administration of verapamil. Results Our results enhance the relation between (1) calcium spatial alternans and (2) slow conduction velocities with the dynamic creation of unidirectional blocks that allowed the induction of VF. In fact, the administration of verapamil demonstrated that calcium and not voltage spatial alternans were the main responsible for VF induction. Conclusions VF induction at high activation rates was linked with the concurrence of a low conduction velocity and high magnitude of calcium alternans, but not necessarily related with increases of APD. Verapamil can postpone the development of cardiac alternans and the apparition of ventricular arrhythmias.This work was funded in part by the CIBERCV (Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares), Instituto de Salud Carlos III (PI14/00857, PI16/01123, DTS16/0160, PI17/01059, PI17/01106 and IJCI-2014-22178); Spanish Ministry of Ecomomy (TEC2013-46067-R); Generalitat Valenciana Grants (APOSTD/2017 and APOSTD/2018) and projects (GVA/2018/103), EIT-Health 19600 AFFINE and cofound by FEDER.Hernández-Romero, I.; Guillem Sánchez, MS.; Figuera, C.; Atienza, F.; Fernández-Avilés, F.; Martínez Climent, BA. (2019). Optical imaging of voltage and calcium in isolated hearts: Linking spatiotemporal heterogeneities and ventricular fibrillation initiation. PLoS ONE. 14(5):1-15. https://doi.org/10.1371/journal.pone.0215951S115145Hayashi, M., Shimizu, W., & Albert, C. M. (2015). The Spectrum of Epidemiology Underlying Sudden Cardiac Death. Circulation Research, 116(12), 1887-1906. doi:10.1161/circresaha.116.304521Karma, A. (1994). Electrical alternans and spiral wave breakup in cardiac tissue. Chaos: An Interdisciplinary Journal of Nonlinear Science, 4(3), 461-472. doi:10.1063/1.166024Weiss, J. N., Garfinkel, A., Karagueuzian, H. S., Qu, Z., & Chen, P.-S. (1999). Chaos and the Transition to Ventricular Fibrillation. Circulation, 99(21), 2819-2826. doi:10.1161/01.cir.99.21.2819Hayashi, H., Shiferaw, Y., Sato, D., Nihei, M., Lin, S.-F., Chen, P.-S., … Qu, Z. (2007). Dynamic Origin of Spatially Discordant Alternans in Cardiac Tissue. Biophysical Journal, 92(2), 448-460. doi:10.1529/biophysj.106.091009Pruvot, E. J., Katra, R. P., Rosenbaum, D. S., & Laurita, K. R. (2004). Role of Calcium Cycling Versus Restitution in the Mechanism of Repolarization Alternans. Circulation Research, 94(8), 1083-1090. doi:10.1161/01.res.0000125629.72053.95Opthof, T., Remme, C. A., Jorge, E., Noriega, F., Wiegerinck, R. F., Tasiam, A., … Cinca, J. (2017). Cardiac activation–repolarization patterns and ion channel expression mapping in intact isolated normal human hearts. Heart Rhythm, 14(2), 265-272. doi:10.1016/j.hrthm.2016.10.010Wilson, F. N., Macleod, A. G., Barker, P. S., & Johnston, F. D. (1934). The determination and the significance of the areas of the ventricular deflections of the electrocardiogram. American Heart Journal, 10(1), 46-61. doi:10.1016/s0002-8703(34)90303-3Ashman, R., & Byer, E. (1943). The normal human ventricular gradient. American Heart Journal, 25(1), 16-35. doi:10.1016/s0002-8703(43)90379-5Pastore, J. M., Girouard, S. D., Laurita, K. R., Akar, F. G., & Rosenbaum, D. S. (1999). Mechanism Linking T-Wave Alternans to the Genesis of Cardiac Fibrillation. Circulation, 99(10), 1385-1394. doi:10.1161/01.cir.99.10.1385Qu, Z., Garfinkel, A., Chen, P.-S., & Weiss, J. N. (2000). Mechanisms of Discordant Alternans and Induction of Reentry in Simulated Cardiac Tissue. Circulation, 102(14), 1664-1670. doi:10.1161/01.cir.102.14.1664Mironov, S., Jalife, J., & Tolkacheva, E. G. (2008). Role of Conduction Velocity Restitution and Short-Term Memory in the Development of Action Potential Duration Alternans in Isolated Rabbit Hearts. Circulation, 118(1), 17-25. doi:10.1161/circulationaha.107.737254Swissa, M., Qu, Z., Ohara, T., Lee, M.-H., Lin, S.-F., Garfinkel, A., … Chen, P.-S. (2002). Action potential duration restitution and ventricular fibrillation due to rapid focal excitation. American Journal of Physiology-Heart and Circulatory Physiology, 282(5), H1915-H1923. doi:10.1152/ajpheart.00867.2001Hirayama, Y., Saitoh, H., Atarashi, H., & Hayakawa, H. (1993). Electrical and mechanical alternans in canine myocardium in vivo. Dependence on intracellular calcium cycling. Circulation, 88(6), 2894-2902. doi:10.1161/01.cir.88.6.2894Riccio, M. L., Koller, M. L., & Gilmour, R. F. (1999). Electrical Restitution and Spatiotemporal Organization During Ventricular Fibrillation. Circulation Research, 84(8), 955-963. doi:10.1161/01.res.84.8.955Jin, Q., Dosdall, D. J., Li, L., Rogers, J. M., Ideker, R. E., & Huang, J. (2014). Verapamil reduces incidence of reentry during ventricular fibrillation in pigs. American Journal of Physiology-Heart and Circulatory Physiology, 307(9), H1361-H1369. doi:10.1152/ajpheart.00256.2014Lee, P., Yan, P., Ewart, P., Kohl, P., Loew, L. M., & Bollensdorff, C. (2012). Simultaneous measurement and modulation of multiple physiological parameters in the isolated heart using optical techniques. Pflügers Archiv - European Journal of Physiology, 464(4), 403-414. doi:10.1007/s00424-012-1135-6Wang, K., Lee, P., Mirams, G. R., Sarathchandra, P., Borg, T. K., Gavaghan, D. J., … Bollensdorff, C. (2015). Cardiac tissue slices: preparation, handling, and successful optical mapping. American Journal of Physiology-Heart and Circulatory Physiology, 308(9), H1112-H1125. doi:10.1152/ajpheart.00556.2014Laughner, J. I., Ng, F. S., Sulkin, M. S., Arthur, R. M., & Efimov, I. R. (2012). Processing and analysis of cardiac optical mapping data obtained with potentiometric dyes. American Journal of Physiology-Heart and Circulatory Physiology, 303(7), H753-H765. doi:10.1152/ajpheart.00404.2012Gizzi, A., Cherry, E. M., Gilmour, R. F., Luther, S., Filippi, S., & Fenton, F. H. (2013). Effects of Pacing Site and Stimulation History on Alternans Dynamics and the Development of Complex Spatiotemporal Patterns in Cardiac Tissue. Frontiers in Physiology, 4. doi:10.3389/fphys.2013.00071VISWESWARAN, R., McINTYRE, S. D., RAMKRISHNAN, K., ZHAO, X., & TOLKACHEVA, E. G. (2013). Spatiotemporal Evolution and Prediction of [Ca2+ ]i and APD Alternans in Isolated Rabbit Hearts. Journal of Cardiovascular Electrophysiology, 24(11), 1287-1295. doi:10.1111/jce.12200Bayly, P. V., KenKnight, B. H., Rogers, J. M., Hillsley, R. E., Ideker, R. E., & Smith, W. M. (1998). Estimation of conduction velocity vector fields from epicardial mapping data. IEEE Transactions on Biomedical Engineering, 45(5), 563-571. doi:10.1109/10.668746Liberos, A., Bueno-Orovio, A., Rodrigo, M., Ravens, U., Hernandez-Romero, I., Fernandez-Aviles, F., … Climent, A. M. (2016). Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study. Heart Rhythm, 13(12), 2358-2365. doi:10.1016/j.hrthm.2016.08.028Trujillo-Pino, A., Krissian, K., Alemán-Flores, M., & Santana-Cedrés, D. (2013). Accurate subpixel edge location based on partial area effect. Image and Vision Computing, 31(1), 72-90. doi:10.1016/j.imavis.2012.10.005Krummen, D. E., Ho, G., Villongco, C. T., Hayase, J., & Schricker, A. A. (2016). Ventricular fibrillation: triggers, mechanisms and therapies. Future Cardiology, 12(3), 373-390. doi:10.2217/fca-2016-0001Garfinkel, A., Kim, Y.-H., Voroshilovsky, O., Qu, Z., Kil, J. R., Lee, M.-H., … Chen, P.-S. (2000). Preventing ventricular fibrillation by flattening cardiac restitution. Proceedings of the National Academy of Sciences, 97(11), 6061-6066. doi:10.1073/pnas.090492697Nachimuthu, S., Assar, M. D., & Schussler, J. M. (2012). Drug-induced QT interval prolongation: mechanisms and clinical management. Therapeutic Advances in Drug Safety, 3(5), 241-253. doi:10.1177/2042098612454283Torres, V., Tepper, D., Flowers, D., Wynn, J., Lam, S., Keefe, D., … Somberg, J. C. (1986). QT prolongation and the antiarrhythmic efficacy of amiodarone. Journal of the American College of Cardiology, 7(1), 142-147. doi:10.1016/s0735-1097(86)80272-8Pueyo, E., Smetana, P., Caminal, P., deLuna, A. B., Malik, M., & Laguna, P. (2004). Characterization of QT Interval Adaptation to RR Interval Changes and Its Use as a Risk-Stratifier of Arrhythmic Mortality in Amiodarone-Treated Survivors of Acute Myocardial Infarction. IEEE Transactions on Biomedical Engineering, 51(9), 1511-1520. doi:10.1109/tbme.2004.828050Noujaim, S. F., Auerbach, D. S., & Jalife, J. (2007). Ventricular Fibrillation. Circulation Journal, 71(SupplementA), A1-A11. doi:10.1253/circj.71.a1Choi, B., & Salama, G. (2000). Simultaneous maps of optical action potentials and calcium transients in guinea‐pig hearts: mechanisms underlying concordant alternans. The Journal of Physiology, 529(1), 171-188. doi:10.1111/j.1469-7793.2000.00171.xCao, J.-M., Qu, Z., Kim, Y.-H., Wu, T.-J., Garfinkel, A., Weiss, J. N., … Chen, P.-S. (1999). Spatiotemporal Heterogeneity in the Induction of Ventricular Fibrillation by Rapid Pacing. Circulation Research, 84(11), 1318-1331. doi:10.1161/01.res.84.11.1318De Diego, C., Pai, R. K., Dave, A. S., Lynch, A., Thu, M., Chen, F., … Valderrábano, M. (2008). Spatially discordant alternans in cardiomyocyte monolayers. American Journal of Physiology-Heart and Circulatory Physiology, 294(3), H1417-H1425. doi:10.1152/ajpheart.01233.2007Aistrup, G. L., Kelly, J. E., Kapur, S., Kowalczyk, M., Sysman-Wolpin, I., Kadish, A. H., & Wasserstrom, J. A. (2006). Pacing-induced Heterogeneities in Intracellular Ca2+Signaling, Cardiac Alternans, and Ventricular Arrhythmias in Intact Rat Heart. Circulation Research, 99(7). doi:10.1161/01.res.0000244087.36230.bfChudin, E., Goldhaber, J., Garfinkel, A., Weiss, J., & Kogan, B. (1999). Intracellular Ca2+ Dynamics and the Stability of Ventricular Tachycardia. Biophysical Journal, 77(6), 2930-2941. doi:10.1016/s0006-3495(99)77126-2Sato, D., Bers, D. M., & Shiferaw, Y. (2013). Formation of Spatially Discordant Alternans Due to Fluctuations and Diffusion of Calcium. PLoS ONE, 8(12), e85365. doi:10.1371/journal.pone.0085365Zhou, X., Bueno-Orovio, A., Orini, M., Hanson, B., Hayward, M., Taggart, P., … Rodriguez, B. (2016). In Vivo and In Silico Investigation Into Mechanisms of Frequency Dependence of Repolarization Alternans in Human Ventricular Cardiomyocytes. Circulation Research, 118(2), 266-278. doi:10.1161/circresaha.115.307836Morotti, S., Grandi, E., Summa, A., Ginsburg, K. S., & Bers, D. M. (2012). Theoretical study of L-type Ca2+current inactivation kinetics during action potential repolarization and early afterdepolarizations. The Journal of Physiology, 590(18), 4465-4481. doi:10.1113/jphysiol.2012.231886Harada, M., Tsuji, Y., Ishiguro, Y. S., Takanari, H., Okuno, Y., Inden, Y., … Kodama, I. (2011). Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart. American Journal of Physiology-Heart and Circulatory Physiology, 300(2), H565-H573. doi:10.1152/ajpheart.00209.2010Hwang, G.-S., Hayashi, H., Tang, L., Ogawa, M., Hernandez, H., Tan, A. Y., … Chen, P.-S. (2006). Intracellular Calcium and Vulnerability to Fibrillation and Defibrillation in Langendorff-Perfused Rabbit Ventricles. Circulation, 114(24), 2595-2603. doi:10.1161/circulationaha.106.630509Wang, L., Myles, R. C., De Jesus, N. M., Ohlendorf, A. K. P., Bers, D. M., & Ripplinger, C. M. (2014). Optical Mapping of Sarcoplasmic Reticulum Ca 2+ in the Intact Heart. Circulation Research, 114(9), 1410-1421. doi:10.1161/circresaha.114.302505Wagner, S., Maier, L. S., & Bers, D. M. (2015). Role of Sodium and Calcium Dysregulation in Tachyarrhythmias in Sudden Cardiac Death. Circulation Research, 116(12), 1956-1970. doi:10.1161/circresaha.116.304678Chorro, F. J., Cánoves, J., Guerrero, J., Mainar, L., Sanchis, J., Such, L., & López-Merino, V. (2000). Alteration of Ventricular Fibrillation by Flecainide, Verapamil, and Sotalol. Circulation, 101(13), 1606-1615. doi:10.1161/01.cir.101.13.1606BANVILLE, I., & GRAY, R. A. (2002). Effect of Action Potential Duration and Conduction Velocity Restitution and Their Spatial Dispersion on Alternans and the Stability of Arrhythmias. Journal of Cardiovascular Electrophysiology, 13(11), 1141-1149. doi:10.1046/j.1540-8167.2002.01141.xSamie, F. H., Mandapati, R., Gray, R. A., Watanabe, Y., Zuur, C., Beaumont, J., & Jalife, J. (2000). A Mechanism of Transition From Ventricular Fibrillation to Tachycardia. Circulation Research, 86(6), 684-691. doi:10.1161/01.res.86.6.684Ikeda, T., Yoshino, H., Sugi, K., Tanno, K., Shimizu, H., Watanabe, J., … Kato, T. (2006). Predictive Value of Microvolt T-Wave Alternans for Sudden Cardiac Death in Patients With Preserved Cardiac Function After Acute Myocardial Infarction. Journal of the American College of Cardiology, 48(11), 2268-2274. doi:10.1016/j.jacc.2006.06.075Wiegerinck, R. F., Verkerk, A. O., Belterman, C. N., van Veen, T. A. B., Baartscheer, A., Opthof, T., … Coronel, R. (2006). Larger Cell Size in Rabbits With Heart Failure Increases Myocardial Conduction Velocity and QRS Duration. Circulation, 113(6), 806-813. doi:10.1161/circulationaha.105.56580

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. Methods of Information in Medicine, 38(02), 119-124. doi:10.1055/s-0038-1634176Ihara, Z., van Oosterom, A., Jacquemet, V., & Hoekema, R. (2007). Adaptation of the standard 12-lead electrocardiogram system dedicated to the analysis of atrial fibrillation. Journal of Electrocardiology, 40(1), 68.e1-68.e8. doi:10.1016/j.jelectrocard.2006.04.006Gerstenfeld, E. P., SippensGroenewegen, A., Lux, R. L., & Lesh, M. D. (2000). Derivation of an optimal lead set for measuring ectopic atrial activation from the pulmonary veins by using body surface mapping. Journal of Electrocardiology, 33, 179-185. doi:10.1054/jelc.2000.20307SippensGroenewegen, A., Peeters, H. A. P., Jessurun, E. R., Linnenbank, A. C., Robles de Medina, E. O., Lesh, M. D., & van Hemel, N. M. (1998). Body Surface Mapping During Pacing at Multiple Sites in the Human Atrium. Circulation, 97(4), 369-380. doi:10.1161/01.cir.97.4.369SALINET, J. L., TUAN, J. H., SANDILANDS, A. J., STAFFORD, P. J., SCHLINDWEIN, F. S., & NG, G. A. (2013). Distinctive Patterns of Dominant Frequency Trajectory Behavior in Drug-Refractory Persistent Atrial Fibrillation: Preliminary Characterization of Spatiotemporal Instability. Journal of Cardiovascular Electrophysiology, 25(4), 371-379. doi:10.1111/jce.12331Sanders, 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., Moreno, J., Vaidyanathan, R., Talkachou, A., Kalifa, J., … Berenfeld, O. (2006). Activation of Inward Rectifier Potassium Channels Accelerates Atrial Fibrillation in Humans. Circulation, 114(23), 2434-2442. doi:10.1161/circulationaha.106.63373

Clinical Characteristics and Electrophysiological Mechanisms Underlying Brugada ECG in Patients With Severe Hyperkalemia

[EN] Background-Several metabolic conditions can cause the Brugada ECG pattern, also called Brugada phenotype (BrPh). We aimed to define the clinical characteristics and outcome of BrPh patients and elucidate the mechanisms underlying BrPh attributed to hyperkalemia. Methods and Results-We prospectively identified patients hospitalized with severe hyperkalemia and ECG diagnosis of BrPh and compared their clinical characteristics and outcome with patients with hyperkalemia but no BrPh ECG. Computer simulations investigated the roles of extracellular potassium increase, fibrosis at the right ventricular outflow tract, and epicardial/endocardial gradients in transient outward current. Over a 6-year period, 15 patients presented severe hyperkalemia with BrPh ECG that was transient and disappeared after normalization of their serum potassium. Most patients were admitted because of various severe medical conditions causing hyperkalemia. Six (40%) patients presented malignant arrhythmias and 6 died during admission. Multiple logistic regression analysis revealed that higher serum potassium levels (odds ratio, 15.8; 95% CI, 3.1-79; P=0.001) and male sex (odds ratio, 17; 95% CI, 1.05-286; P=0.045) were risk factors for developing BrPh ECG in patients with severe hyperkalemia. In simulations, hyperkalemia yielded BrPh by promoting delayed and heterogeneous right ventricular outflow tract activation attributed to elevation of resting potential, reduced availability of inward sodium channel conductance, and increased right ventricular outflow tract fibrosis. An elevated transient outward current gradient contributed to, but was not essential for, the BrPh phenotype. Conclusions-In patients with severe hyperkalemia, a BrPh ECG is associated with malignant arrhythmias and all-cause mortality secondary to resting potential depolarization, reduced sodium current availability, and fibrosis at the right ventricular outflow tract.This work was funded in part by the CIBERCV (Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares), Instituto de Salud Carlos III (PI14/00857, DTS16/0160, PI17/1059, PI01106), Spanish Ministry of Ecomomy (TEC2013-46067-R) and the ERDF (European Regional Development Fund).Rivera-Juárez, A.; Hernández-Romero, I.; Puertas, C.; Zhang-Wang, S.; Sánchez-Álamo, B.; Martins, R.; Figuera, C.... (2019). Clinical Characteristics and Electrophysiological Mechanisms Underlying Brugada ECG in Patients With Severe Hyperkalemia. Journal of the American Heart Association. 8(3):1-15. https://doi.org/10.1161/JAHA.118.010115S11583Brugada, P., & Brugada, J. (1992). Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome. Journal of the American College of Cardiology, 20(6), 1391-1396. doi:10.1016/0735-1097(92)90253-jAntzelevitch, C., Brugada, P., Borggrefe, M., Brugada, J., Brugada, R., Corrado, D., … Wilde, A. (2005). Brugada Syndrome: Report of the Second Consensus Conference. Circulation, 111(5), 659-670. doi:10.1161/01.cir.0000152479.54298.51Priori, S. G., Wilde, A. A., Horie, M., Cho, Y., Behr, E. R., Berul, C., … Tracy, C. (2013). HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes. Heart Rhythm, 10(12), 1932-1963. doi:10.1016/j.hrthm.2013.05.014Bezzina, C. R., Barc, J., Mizusawa, Y., Remme, C. A., Gourraud, J.-B., Simonet, F., … Dagradi, F. (2013). Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death. Nature Genetics, 45(9), 1044-1049. doi:10.1038/ng.2712Frustaci, A., Priori, S. G., Pieroni, M., Chimenti, C., Napolitano, C., Rivolta, I., … Russo, M. A. (2005). Cardiac Histological Substrate in Patients With Clinical Phenotype of Brugada Syndrome. Circulation, 112(24), 3680-3687. doi:10.1161/circulationaha.105.520999Corrado, D., Zorzi, A., Cerrone, M., Rigato, I., Mongillo, M., Bauce, B., & Delmar, M. (2016). Relationship Between Arrhythmogenic Right Ventricular Cardiomyopathy and Brugada Syndrome. Circulation: Arrhythmia and Electrophysiology, 9(4). doi:10.1161/circep.115.003631Coronel, R., Casini, S., Koopmann, T. T., Wilms-Schopman, F. J. G., Verkerk, A. O., de Groot, J. R., … de Bakker, J. M. T. (2005). Right Ventricular Fibrosis and Conduction Delay in a Patient With Clinical Signs of Brugada Syndrome. Circulation, 112(18), 2769-2777. doi:10.1161/circulationaha.105.532614Probst, V., Veltmann, C., Eckardt, L., Meregalli, P. G., Gaita, F., Tan, H. L., … Wilde, A. A. M. (2010). Long-Term Prognosis of Patients Diagnosed With Brugada Syndrome. Circulation, 121(5), 635-643. doi:10.1161/circulationaha.109.887026Baranchuk, A., Nguyen, T., Ryu, M. H., Femenía, F., Zareba, W., Wilde, A. A. M., … Pérez-Riera, A. R. (2012). Brugada Phenocopy: New Terminology and Proposed Classification. Annals of Noninvasive Electrocardiology, 17(4), 299-314. doi:10.1111/j.1542-474x.2012.00525.xLittmann, L., Monroe, M. H., Taylor, L., & Brearley, W. D. (2007). The hyperkalemic Brugada sign. Journal of Electrocardiology, 40(1), 53-59. doi:10.1016/j.jelectrocard.2006.10.057Weiss, J. N., Qu, Z., & Shivkumar, K. (2017). Electrophysiology of Hypokalemia and Hyperkalemia. Circulation: Arrhythmia and Electrophysiology, 10(3). doi:10.1161/circep.116.004667Wilde, A. A. M., Postema, P. G., Di Diego, J. M., Viskin, S., Morita, H., Fish, J. M., & Antzelevitch, C. (2010). The pathophysiological mechanism underlying Brugada syndrome. Journal of Molecular and Cellular Cardiology, 49(4), 543-553. doi:10.1016/j.yjmcc.2010.07.012Zhang, J., Sacher, F., Hoffmayer, K., O’Hara, T., Strom, M., Cuculich, P., … Rudy, Y. (2015). Cardiac Electrophysiological Substrate Underlying the ECG Phenotype and Electrogram Abnormalities in Brugada Syndrome Patients. Circulation, 131(22), 1950-1959. doi:10.1161/circulationaha.114.013698Nademanee, K., Hocini, M., & Haïssaguerre, M. (2017). Epicardial substrate ablation for Brugada syndrome. Heart Rhythm, 14(3), 457-461. doi:10.1016/j.hrthm.2016.12.001Hoogendijk, M. G., Opthof, T., Postema, P. G., Wilde, A. A. M., de Bakker, J. M. T., & Coronel, R. (2010). The Brugada ECG Pattern. Circulation: Arrhythmia and Electrophysiology, 3(3), 283-290. doi:10.1161/circep.110.937029Hoogendijk, M. G., Potse, M., Linnenbank, A. C., Verkerk, A. O., den Ruijter, H. M., van Amersfoorth, S. C. M., … Coronel, R. (2010). Mechanism of right precordial ST-segment elevation in structural heart disease: Excitation failure by current-to-load mismatch. Heart Rhythm, 7(2), 238-248. doi:10.1016/j.hrthm.2009.10.007Tsuneoka, H., Takagi, M., Murakoshi, N., Yamagishi, K., Yokoyama, Y., … Xu, D. (2016). Long‐Term Prognosis of Brugada‐Type ECG and ECG With Atypical ST‐Segment Elevation in the Right Precordial Leads Over 20 Years: Results From the Circulatory Risk in Communities Study (CIRCS). Journal of the American Heart Association, 5(8). doi:10.1161/jaha.115.002899Babai Bigi, M. A., Aslani, A., & Shahrzad, S. (2007). aVR sign as a risk factor for life-threatening arrhythmic events in patients with Brugada syndrome. Heart Rhythm, 4(8), 1009-1012. doi:10.1016/j.hrthm.2007.04.017Van Oosterom, A. (2004). ECGSIM: an interactive tool for studying the genesis of QRST waveforms. Heart, 90(2), 165-168. doi:10.1136/hrt.2003.014662O’Hara, T., Virág, L., Varró, A., & Rudy, Y. (2011). Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation. PLoS Computational Biology, 7(5), e1002061. doi:10.1371/journal.pcbi.1002061Dutta, S., Mincholé, A., Quinn, T. A., & Rodriguez, B. (2017). Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions. Progress in Biophysics and Molecular Biology, 129, 40-52. doi:10.1016/j.pbiomolbio.2017.02.007Cardone-Noott, L., Bueno-Orovio, A., Mincholé, A., Zemzemi, N., & Rodriguez, B. (2016). Human ventricular activation sequence and the simulation of the electrocardiographic QRS complex and its variability in healthy and intraventricular block conditions. EP Europace, 18(suppl_4), iv4-iv15. doi:10.1093/europace/euw346Pelleg, A., Mitamura, H., Price, R., Kaplinsky, E., Menduke, H., Dreifus, L. S., & Michelson, E. L. (1989). Extracellular potassium ion dynamics and ventricular arrhythmias in the canine heart. Journal of the American College of Cardiology, 13(4), 941-950. doi:10.1016/0735-1097(89)90240-4Giudicessi, J. R., Ye, D., Tester, D. J., Crotti, L., Mugione, A., Nesterenko, V. V., … Ackerman, M. J. (2011). Transient outward current (Ito) gain-of-function mutations in the KCND3-encoded Kv4.3 potassium channel and Brugada syndrome. Heart Rhythm, 8(7), 1024-1032. doi:10.1016/j.hrthm.2011.02.021Garcia-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.2013.10.023Atienza, F., Almendral, J., Moreno, J., Vaidyanathan, R., Talkachou, A., Kalifa, J., … Berenfeld, O. (2006). Activation of Inward Rectifier Potassium Channels Accelerates Atrial Fibrillation in Humans. Circulation, 114(23), 2434-2442. doi:10.1161/circulationaha.106.633735Ettinger, P. O., Regan, T. J., & Oldewurtel, H. A. (1974). Hyperkalemia, cardiac conduction, and the electrocardiogram: A review. American Heart Journal, 88(3), 360-371. doi:10.1016/0002-8703(74)90473-6Anselm, D. D., Gottschalk, B. H., & Baranchuk, A. (2014). Brugada Phenocopies: Consideration of Morphologic Criteria and Early Findings From an International Registry. Canadian Journal of Cardiology, 30(12), 1511-1515. doi:10.1016/j.cjca.2014.09.023Guo, J., Massaeli, H., Xu, J., Jia, Z., Wigle, J. T., Mesaeli, N., & Zhang, S. (2009). Extracellular K+ concentration controls cell surface density of IKr in rabbit hearts and of the HERG channel in human cell lines. Journal of Clinical Investigation, 119(9), 2745-2757. doi:10.1172/jci39027Sakmann, B., & Trube, G. (1984). Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. The Journal of Physiology, 347(1), 641-657. doi:10.1113/jphysiol.1984.sp015088Bérubé, J., Chahine, M., & Daleau, P. (1999). Modulation of HERG potassium channel properties by external pH. Pfl�gers Archiv European Journal of Physiology, 438(3), 419-422. doi:10.1007/s004240050930Junttila, M. J., Gonzalez, M., Lizotte, E., Benito, B., Vernooy, K., Sarkozy, A., … Brugada, R. (2008). Induced Brugada-Type Electrocardiogram, a Sign for Imminent Malignant Arrhythmias. Circulation, 117(14), 1890-1893. doi:10.1161/circulationaha.107.746495Postema, P. G., Vlaar, A. P. J., DeVries, J. H., & Tan, H. L. (2011). Familial Brugada syndrome uncovered by hyperkalaemic diabetic ketoacidosis. Europace, 13(10), 1509-1510. doi:10.1093/europace/eur151Smits, J. P. ., Eckardt, L., Probst, V., Bezzina, C. R., Schott, J. J., Remme, C. A., … Wilde, A. A. . (2002). Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non–SCN5A-related patients. Journal of the American College of Cardiology, 40(2), 350-356. doi:10.1016/s0735-1097(02)01962-9Di Diego, J. M., Cordeiro, J. M., Goodrow, R. J., Fish, J. M., Zygmunt, A. C., Pérez, G. J., … Antzelevitch, C. (2002). Ionic and Cellular Basis for the Predominance of the Brugada Syndrome Phenotype in Males. Circulation, 106(15), 2004-2011. doi:10.1161/01.cir.0000032002.22105.7aGUILLEM, M. S., CLIMENT, A. M., MILLET, J., BERNE, P., RAMOS, R., BRUGADA, J., & BRUGADA, R. (2016). Spatiotemporal Characteristics of QRS Complexes Enable the Diagnosis of Brugada Syndrome Regardless of the Appearance of a Type 1 ECG. Journal of Cardiovascular Electrophysiology, 27(5), 563-570. doi:10.1111/jce.1293

Noninvasive Assessment of Complexity of Atrial Fibrillation Correlation With Contact Mapping and Impact of Ablation

[EN] Background: It is difficult to noninvasively phenotype atrial fibrillation (AF) in a way that reflects clinical end points such as response to therapy. We set out to map electrical patterns of disorganization and regions of reentrant activity in AF from the body surface using electrocardiographic imaging, calibrated to panoramic intracardiac recordings and referenced to AF termination by ablation. Methods: Bi-atrial intracardiac electrograms of 47 patients with AF at ablation (30 persistent, 29 male, 63 +/- 9 years) were recorded with 64-pole basket catheters and simultaneous 57-lead body surface ECGs. Atrial epicardial electrical activity was reconstructed and organized sites were invasively and noninvasively tracked in 3-dimension using phase singularity. In a subset of 17 patients, sites of AF organization were targeted for ablation. Results: Body surface mapping showed greater AF organization near intracardially detected drivers than elsewhere, both in phase singularity density (2.3 +/- 2.1 versus 1.9 +/- 1.6; P=0.02) and number of drivers (3.2 +/- 2.3 versus 2.7 +/- 1.7; P=0.02). Complexity, defined as the number of stable AF reentrant sites, was concordant between noninvasive and invasive methods (r(2)=0.5; CC=0.71). In the subset receiving targeted ablation, AF complexity showed lower values in those in whom AF terminated than those in whom AF did not terminate (P<0.01). Conclusions: AF complexity tracked noninvasively correlates well with organized and disorganized regions detected by panoramic intracardiac mapping and correlates with the acute outcome by ablation. This approach may assist in bedside monitoring of therapy or in improving the efficacy of ongoing ablation procedures.This article was supported in part by: Instituto de Salud Carlos III FEDER (Fondo Europeo de Desarrollo Regional; IJCI-2014-22178, DTS16/00160; PI14/00857, PI16/01123; PI17/01059; PI17/01106), Generalitat Valenciana Grants (APOSTD/2017 and APOSTD/2018) and projects (GVA/2018/103); National Institutes of Health (Dr Narayan: R01 HL85537; K24 HL103800); EITHealth 19600 AFFINE.Rodrigo Bort, M.; Martínez Climent, BA.; Hernández-Romero, I.; Liberos Mascarell, A.; Baykaner, T.; Rogers, AJ.; Alhusseini, M.... (2020). Noninvasive Assessment of Complexity of Atrial Fibrillation Correlation With Contact Mapping and Impact of Ablation. Circulation Arrhythmia and Electrophysiology. 13(3):236-246. https://doi.org/10.1161/CIRCEP.119.007700S236246133Calkins H Hindricks G Cappato R Kim YH Saad EB Aguinaga L Akar JG Badhwar VBrugada J Camm J etal 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensusstatement on catheter and surgical ablation of atrial fibrillation: Executive summary. J Arrhythm.2017;33:369-409Narayan SM Krummen DE Clopton P Shivkumar K Miller JM. Direct or coincidentalelimination of stable rotors or focal sources may explain successful atrial fibrillation ablation:on-treatment analysis of the CONFIRM trial (Conventional ablation for AF with or without focalHaissaguerre M Hocini M Denis A Shah AJ Komatsu Y Yamashita S Daly M Amraoui SZellerhoff S Picat MQ etal. Driver domains in persistent atrial fibrillation. Circulation.2014;130:530-8.Atienza F Almendral J Ormaetxe JM Moya A Martínez-Alday JD Hernández-Madrid ACastellanos E Arribas F Arias MÁ Tercedor L etal. Comparison of radiofrequency catheterablation of drivers and circumferential pulmonary vein isolation in atrial fibrillation: aAtienza, 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.2014.09.053Seitz J Bars C Théodore G Beurtheret S Lellouche N Bremondy M Ferracci A Faure JPenaranda G Yamazaki M etal. AF Ablation Guided by Spatiotemporal ElectrogramDispersion Without Pulmonary Vein Isolation: A Wholly Patient-Tailored Approach. J Am CollGuillem MS Climent AM Millet J Arenal Á Fernández-Avilés F Jalife J Atienza FBerenfeld O. Noninvasive localization of maximal frequency sites of atrial fibrillation by bodysurface potential mapping. Circ Arrhythm Electrophysiol. 2013;6:294-301.Ramirez FD Birnie DH Nair GM Szczotka A Redpath CJ Sadek MM Nery PB. Efficacyand safety of driver-guided catheter ablation for atrial fibrillation: A systematic review and metaRamirez, F. D., Birnie, D. H., Nair, G. M., Szczotka, A., Redpath, C. J., Sadek, M. M., & Nery, P. B. (2017). Efficacy and safety of driver-guided catheter ablation for atrial fibrillation: A systematic review and meta-analysis. Journal of Cardiovascular Electrophysiology, 28(12), 1371-1378. doi:10.1111/jce.13313Baykaner T Rogers AJ Meckler GL Zaman J Navara R Rodrigo M Alhusseini MKowalewski CAB Viswanathan MN Narayan SM etal. Clinical Implications of Ablation ofDrivers for Atrial Fibrillation: A Systematic Review and Meta-Analysis. Circ ArrhythmBrachmann J Hummel JD Wilber DJ Sarver AE Rapkin J Shpun S Szili-Torok T.Prospective randomized comparison of rotor ablation vs. conventional ablation for treatment ofVijayakumar R Vasireddi SK Cuculich PS Faddis MN Rudy Y. MethodologyConsiderations in Phase Mapping of Human Cardiac Arrhythmias. Circ ArrhythmAlhusseini M Vidmar D Meckler GL Kowalewski CA Shenasa F Wang PJ Narayan SMRappel WJ. Two Independent Mapping Techniques Identify Rotational Activity Patterns at Sitesof Local Termination During Persistent Atrial Fibrillation. J Cardiovasc Electrophysiol.2017;28:615-622.Miller JM Kalra V Das MK Jain R Garlie JB Brewster JA Dandamudi G. Clinical Benefitof Ablating Localized Sources for Human Atrial Fibrillation: The Indiana University FIRMZaman JAB Baykaner T Clopton P Swarup V Kowal RC Daubert JP Day JD Hummel JSchricker AA Krummen DE etal. Recurrent Post-Ablation Paroxysmal Atrial FibrillationShares Substrates With Persistent Atrial Fibrillation: An 11-Center Study. JACC ClinYushkevich PA Zhang H Gee JC. Continuous medial representation for anatomicalstructures. IEEE Trans Med Imaging. 2006;25:1547-64.Remondino F. 3-D reconstruction of static human body shape from image sequence.Remondino, F. (2004). 3-D reconstruction of static human body shape from image sequence. Computer Vision and Image Understanding, 93(1), 65-85. doi:10.1016/j.cviu.2003.08.006Eggert DW Lorusso A Fish RB. Estimating 3-D rigid body transformations: a comparisonRodrigo M Guillem MS Climent AM Pedrón-Torrecilla J Liberos A Millet J FernándezRodrigo, 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.2014.05.013Rodrigo M Climent AM Liberos A Fernández-Avilés F Berenfeld O Atienza F GuillemMS. Highest dominant frequency and rotor positions are robust markers of driver location duringMS. Technical Considerations on Phase Mapping for Identification of Atrial Reentrant Activityin Direct- and Inverse-Computed Electrograms. Circ Arrhythm Electrophysiol.2017;10:e005008.Castells F Mora C Rieta JJ Moratal-Pérez D Millet J. Estimation of atrial fibrillatory wavefrom single-lead atrial fibrillation electrocardiograms using principal component analysisconcepts. Med Biol Eng Comput. 2005;43:557-560.Rodrigo M Climent AM Liberos A Hernandez-Romero I Arenal A Bermejo J FernandezAviles F Atienza F Guillem MS. Solving Inaccuracies in Anatomical Models forElectrocardiographic Inverse Problem Resolution by Maximizing Reconstruction Quality. IEEERodrigo, M., Climent, A. M., Liberos, A., Hernandez-Romero, I., Arenal, A., Bermejo, J., … Guillem, M. S. (2018). Solving Inaccuracies in Anatomical Models for Electrocardiographic Inverse Problem Resolution by Maximizing Reconstruction Quality. IEEE Transactions on Medical Imaging, 37(3), 733-740. doi:10.1109/tmi.2017.2707413Honarbakhsh S Schilling RJ Providência R Dhillon G Sawhney V Martin CA Keating EFinlay M Ahsan S Chow A etal. Panoramic atrial mapping with basket catheters: Aquantitative analysis to optimize practice patient selection and catheter choice. J CardiovascElectrophysiol. 201;28:1423-1432Knecht S Sohal M Deisenhofer I Albenque JP Arentz T Neumann T Cauchemez BDuytschaever M Ramoul K Verbeet T etal. Multicentre evaluation of non-invasive biatrialmapping for persistent atrial fibrillation ablation: the AFACART study. Europace.2017;19:1302-1309.Metzner A Wissner E Tsyganov A Kalinin V Schlüter M Lemes C Mathew S Maurer THeeger CH Reissmann B etal. Noninvasive phase mapping of persistent atrial fibrillation inhumans: Comparison with invasive catheter mapping. Ann Noninvasive Electrocardiol.2018;23:e12527.Duchateau J Sacher F Pambrun T Derval N Chamorro-Servent J Denis A Ploux S HociniM Jaïs P Bernus O etal. Performance and limitations of noninvasive cardiac activationDuchateau, J., Sacher, F., Pambrun, T., Derval, N., Chamorro-Servent, J., Denis, A., … Dubois, R. (2019). Performance and limitations of noninvasive cardiac activation mapping. Heart Rhythm, 16(3), 435-442. doi:10.1016/j.hrthm.2018.10.010Rudy Y. Letter to the Editor-ECG imaging and activation mapping. Heart Rhythm. 2019;16:e50-e.Podziemski P Zeemering S Kuklik P van Hunnik A Maesen B Maessen J Crijns HJWillems S Verma A Betts TR Murray S Neuzil P Ince H Steven D Sultan A Heck PMHall MC etal. Targeting Nonpulmonary Vein Sources in Persistent Atrial Fibrillation IdentifiedLim HS Hocini M Dubois R Denis A Derval N Zellerhoff S Yamashita S Berte BMahida S Komatsu Y etal. Complexity and Distribution of Drivers in Relation to Duration ofCamm AJ Breithardt G Crijns H Dorian P Kowey P Le Heuzey JY Merioua I PedrazziniL Prystowsky EN Schwartz PJ etal. Real-life observations of clinical outcomes with rhythmand rate-control therapies for atrial fibrillation RECORDAF (Registry on Cardiac RhythmCamm, A. J., Breithardt, G., Crijns, H., Dorian, P., Kowey, P., Le Heuzey, J.-Y., … Weintraub, W. (2011). Real-Life Observations of Clinical Outcomes With Rhythm- and Rate-Control Therapies for Atrial Fibrillation. Journal of the American College of Cardiology, 58(5), 493-501. doi:10.1016/j.jacc.2011.03.034Kowalewski CAB Shenasa F Rodrigo M Clopton P Meckler G Alhusseini MI SwerdlowMA Joshi V Hossainy S Zaman JAB etal. Interaction of Localized Drivers and DisorganizedActivation in Persistent Atrial Fibrillation: Reconciling Putative Mechanisms Using MultipleChelu MG King JB Kholmovski EG Ma J Gal P Marashly Q AlJuaid MA Kaur G SilverMA Johnson KA etal. Atrial Fibrosis by Late Gadolinium Enhancement Magnetic ResonanceImaging and Catheter Ablation of Atrial Fibrillation: 5-Year Follow-Up Data. J Am Heart Assoc.2018;7:e006313.Guillem MS Bollmann A Climent AM Husser D Millet-Roig J Castells F. How manyleads are necessary for a reliable reconstruction of surface potentials during atrial fibrillation?De 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.2008.2011894Rodrigo M Climent AM Liberos A Fernández-Aviles F Atienza F Guillem MS BerenfeldO. Minimal configuration of body surface potential mapping for discrimination of left versu