There is evidence that rotors could be drivers that maintain atrial fibrillation. Complex fractionated atrial electrograms have been located in rotor tip areas. However, the concept of electrogram fractionation, defined using time intervals, is still controversial as a tool for locating target sites for ablation. We hypothesize that the fractionation phenomenon is better described using non-linear dynamic measures, such as approximate entropy, and that this tool could be used for locating the rotor tip. The aim of this work has been to determine the relationship between approximate entropy and fractionated electrograms, and to develop a new tool for rotor mapping based on fractionation levels. Two episodes of chronic atrial fibrillation were simulated in a 3D human atrial model, in which rotors were observed. Dynamic approximate entropy maps were calculated using unipolar electrogram signals generated over the whole surface of the 3D atrial model. In addition, we optimized the approximate entropy calculation using two real multi-center databases of fractionated electrogram signals, labeled in 4 levels of fractionation. We found that the values of approximate entropy and the levels of fractionation are positively correlated. This allows the dynamic approximate entropy maps to localize the tips from stable and meandering rotors. Furthermore, we assessed the optimized approximate entropy using bipolar electrograms generated over a vicinity enclosing a rotor, achieving rotor detection. Our results suggest that high approximate entropy values are able to detect a high level of fractionation and to locate rotor tips in simulated atrial fibrillation episodes. We suggest that dynamic approximate entropy maps could become a tool for atrial fibrillation rotor mapping.

Centro de Bioingeniería Universidad Pontificia Bolivariana Medellín Colombia

Czech Institute of Informatics Robotics and Cybernetics Czech Technical University Prague Prague Czech Republic

Czech Institute of Informatics Robotics and Cybernetics Czech Technical University Prague Prague Czech Republic; Department of Cybernetics Faculty of Electrical Engineering Czech Technical University Prague Prague Czech Republic

GI²B Instituto Tecnológico Metropolitano Medellín Colombia

I3BH Universitat Politècnica de València Valencia Spain

Institute of Biomedical Engineering Karlsruhe Institute of Technology Karlsruhe Germany

Medizinische Klinik 4 Staedtisches Klinikum Karlsruhe Karlsruhe Germany

PLoS One. 2015 Mar 05;10(3):e0118677. doi: 10.1371/journal.pone.0118677. PubMed

Zobrazit více v PubMed

Gupta A, Maheshwari A, Thakur R, Lokhandwala Y (2002) Cardiac mapping: utility or futility? Indian Pacing and Electrophysiology Journal 2:20–32. PubMed PMC

De Bakker J, Wittkampf F (2010) The pathophysiologic basis of fractionated and complex electrograms and the impact of recording techniques on their detection and interpretation. Circ Arrhythm Electrophysiol 3:204–213. PubMed

Nademanee K, McKenzie J, Kosar E, Schwab M, Sunsaneewitayakul B, et al. (2004) A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. Journal of the American College of Cardiology 43:2044–53. PubMed

Reddy V (2009) Atrial fibrillation: unanswered questions and future directions. Cardiology Clinics 27:201–216. PubMed

Jadidi A, Duncan E, Miyazaki S, Lellouche N, Shah A, et al. (2012) Functional nature of electrogram fractionation demonstrated by left atrial high-density mapping. Circulation Arrhythmia and electrophysiology 5:32–42. PubMed PMC

Ciaccio E, Biviano A, Whang W, Garan H (2012) Identification of recurring patterns in fractionated atrial electrograms using new transform coefficients. BioMedical Engineering OnLine 11:4. PubMed PMC

Ganesan A, Kuklik P, Lau D, Brooks A, Baumert M, et al. (2013) Bipolar electrogram shannon entropy at sites of rotational activation: implications for ablation of atrial fibrillation. Circ Arrhythm Electrophysiol 6:48–57. PubMed

Navoret N, Jacquir S, Laurent G, Binczak S (2013) Detection of complex fractionated atrial electrograms using recurrence quantification analysis. IEEE transactions on bio-medical engineering 60:1975–82. PubMed

Skanes A, Mandapati R, Berenfeld O, Davidenko J, Jalife J (1998) Spatiotemporal periodicity during atrial fibrillation in the isolated sheep heart. Circulation 98:1236–1248. PubMed

Navoret N, Jacquir S, Laurent G, Binczak S (2012) Relationship between complex fractionated atrial electrogram patterns and different heart substrate configurations materials numerical cell models method the modelled catheter is a thermocool irrigated tip. Computing in Cardiology 39:893–396.

Umapathy K, Masse S, Kolodziejska K, Veenhuyzen G, Chauhan V, et al. (2008) Electrogram fractionation in murine HL-1 atrial monolayer model. Heart rhythm: the official journal of the Heart Rhythm Society 5:1029–35. PubMed

Zlochiver S, Yamazaki M, Kalifa J, Berenfeld O (2008) Rotor meandering contributes to irregularity in electrograms during atrial fibrillation. Heart rhythm 5:846–854. PubMed PMC

Orozco-Duque A, Ugarte JP, Tobón C, Saiz J, Bustamante J (2013) Approximate entropy can localize rotors, but not ectopic foci during chronic atrial fibrilation: A simulation study. Computing in Cardiology 40:903–906.

Jalife J, Berenfeld O, Skanes A, Mandapati R (1998) Mechanisms of atrial fibrillation: mother rotors or multiple daughter wavelets, or both. Cardiovasc Electrophysiol 9:S2–12. PubMed

Narayan S, Patel J, Mulpuru S, Krummen D (2012) Focal impulse and rotor modulation ablation of sustaining rotors abruptly terminates persistent atrial fibrillation to sinus rhythm with elimination on follow-up A video case study. Heart rhythm 9:1436–1439. PubMed PMC

Narayan S, Shivkumar K, Krummen D, Miller J, Rappel WJ (2013) Panoramic electrophysiological mapping but not electrogram morphology identifies stable sources for human atrial fibrillation. Circ Arrhythm Electrotrophysiol 6(1):58–67. PubMed PMC

Tobón C, Ruiz-Villa C, Heidenreich E, Romero L, Hornero F, et al. (2013) A three-dimensional human atrial model with fiber orientation. electrograms and arrhythmic activation patterns relationship. PLoS ONE 8:e50883. PubMed PMC

Courtemanche M, Ramirez R, Nattel S (1998) Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model. The American Journal of Physiology 275:H301–21. PubMed

Kneller J, Zou R, Vigmond E, Wang Z, Leon L, et al. (2002) Cholinergic atrial fibrillation in a computer model of a two-dimensional sheet of canine atrial cells with realistic ionic properties. Circulation Research 90:E73–87. PubMed

Bosch R, Zeng X, Grammer J, Popovic K, Mewis C, et al. (1999) Ionic mechanisms of electrical remodeling in human atrial fibrillation. Cardiovascular research 44:121–31. PubMed

Workman A, Kane K, Rankin A (2001) The contribution of ionic currents to changes in refractoriness of human atrial myocytes associated with chronic atrial fibrillation. Cardiovascular research 52:226–35. PubMed

Van Wagoner D (2003) Electrophysiological remodeling in human atrial fibrillation. Pacing and clinical electrophysiology 26:1572–1575. PubMed

Zhang H, Garratt CJ, Zhu J, Holden A (2005) Role of up-regulation of ik1 in action potential shortening associated with atrial fibrillation in humans. Cardiovasc Res 66:493–502. PubMed

Roberge F, Vinet A, Victorri B (1986) Reconstruction of propagated electrical activity with a two-dimensional model of anisotropic heart muscle. Circ Res 58:461–475. PubMed

Heidenreich Ea, Ferrero JM, Doblaré M, Rodríguez JF (2010) Adaptive macro finite elements for the numerical solution of monodomain equations in cardiac electrophysiology. Annals of biomedical engineering 38:2331–45. PubMed

Narayan S, Krummen D, Rappel WJ (2012) Clinical mapping approach to diagnose electrical rotors and focal impulse sources for human atrial fibrillation. Journal of Cardiovascular Electrophysiology 23:447–454. PubMed PMC

Pincus S (1991) Approximate entropy as a measure of system complexity. Proceedings of the National Academy of Sciences of the United States of America 88:2297–301. PubMed PMC

Pincus S, Goldberger A (1994) Physiological time-series analysis: what does regularity quantify? American Journal of Physiology Heart and Circulatory Physiology 266:H1643–H1656. PubMed

Alcaraz R, Rieta J (2010) A review on sample entropy applications for the non-invasive analysis of atrial fibrillation electrocardiograms. Biomedical Signal Processing and Control 5:1–14.

Kremen V, Lhotská L, Macas M, Cihák R, Vancura V, et al. (2008) A new approach to automated assessment of fractionation of endocardial electrograms during atrial fibrillation. Physiological measurement 29:1371–81. PubMed

Kremen V, Kordik P, Lhotska L (2009) Comparison of several classifiers to evaluate endocardial electrograms fractionation in human. In: Engineering in Medicine and Biology Society, 2009. EMBC 2009. Annual International Conference of the IEEE. pp. 2502–2505. PubMed

Kremen V (2008) Automated assessment of endocardial electrograms fractionation in human. Ph.D. thesis, Czech Technical University in Prague Faculty of Electrical Engineering Department of Cybernetics.

Schilling C (2012) Analysis of Atrial Electrograms, volume 17. Karlrsruhe: KIT Scientific Publishing.

Pincus S (1992) Approximating Markov chains. Proceedings of the National Academy of Sciences of the United States of America 89:4432–6. PubMed PMC

Konings K, Smeets J, Penn O, Wellens H, Allessie M (1997) Configuration of unipolar atrial electrograms during electrically induced atrial fibrillation in humans. Circulation 95:1231–1241. PubMed

Jacquemet V, Virag N, Ihara Z, Dang L, Blanc O, et al. (2003) Study of Unipolar Electrogram Morphology in a Computer Model of Atrial Fibrillation. Journal of Cardiovascular Electrophysiology 14:S172–S179. PubMed

Navoret N, Xu B, Jacquir S, Binczak S (2010) Comparison of complex fractionated atrial electrograms at cellular scale using numerical and experimental models. Conference proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Conference 2010:3249–52. PubMed

Nademanee K, Lockwood E, Oketani N, Gidney B (2010) Catheter ablation of atrial fibrillation guided by complex fractionated atrial electrogram mapping of atrial fibrillation substrate. Journal of Cardiology 55:1–12. PubMed

Pincus S, Singer B (1996) Randomness and degrees of irregularity. Proceedings of the National Academy of Sciences of the United States of America 93:2083–8. PubMed PMC

Yentes J, Hunt N, Schmid K, Kaipust J, McGrath D, et al. (2012) The appropriate use of approximate entropy and sample entropy with short data sets. Annals of Biomedical Engineering 41:349–365. PubMed PMC

Richman J, Moorman J (2000) Physiological time-series analysis using approximate entropy and sample entropy. Am J Physiol Heart Circ Physiol 278:H2039–2049. PubMed

Hoekstra B, Diks C, Allessie M, DeGoede J (1995) Nonlinear analysis of epicardial atrial electrograms of electrically induced atrial fibrillation in man. J Cardiovasc Electrophysiol 6:419–440. PubMed

Novák D, Kremen V, Cuesta D, Schmidt K, Chudácek V, et al. (2009) Discrimination of endocardial electrogram disorganization using a signal regularity analysis. Conference proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Conference 2009:1812–5. PubMed

Anier A, Lipping T, Ferenets R, Puumala P, Sonkajärvi E, et al. (2012) Relationship between approximate entropy and visual inspection of irregularity in the EEG signal, a comparison with spectral entropy. British Journal of Anaesthesia 109:928–34. PubMed

Scherr D, Dalal D, Cheema A, Cheng A, Henrikson C, et al. (2007) Automated detection and characterization of complex fractionated atrial electrograms in human left atrium during atrial fibrillation. Heart Rhythm The Official Journal of the Heart Rhythm Society 4:1013–1020. PubMed

Grzęda R, Noujaim FS, Berenfeld O, Jalife J (2009) Complex fractionated atrial electrograms: properties of time- domain vs. frequency-domain methods. NIH Public Access 6:1475–1482. PubMed PMC

Hunter RJ, Diab I, Tayebjee M, Richmond L, Sporton S, et al. (2011) Characterization of fractionated atrial electrograms critical for maintenance of atrial fibrillation: A randomized, controlled trial of ablation strategies (the CFAE AF trial). Circulation Arrhythmia and electrophysiology 4:622–9. PubMed

Berenfeld O, Jalife J (2011) Complex fractionated atrail electrograms: is this the beast to tame in AF. NIH Public Access 4:426–428. PubMed PMC