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Characterisation of human AV-nodal properties using a network model

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Abstract

Characterisation of the AV-node is an important step in determining the optimal form of treatment for supraventricular tachycardias. To integrate and analyse patient-specific measurements, mathematical modelling has emerged as a valuable tool. Here we present a model of the human AV-node, consisting of a series of interacting nodes, each with separate dynamics in refractory time and conduction delay. The model is evaluated in several scenarios, including atrial fibrillation (AF) and clinical pacing, using simulated and measured data. The model is able to replicate signals derived from clinical ECG data as well as from invasive measurements, both under AF and pacing. To quantify the uncertainty in parameter estimation, 1000 parameter sets were sampled, showing that model output similar to data corresponds to limited regions in the model parameter space. The model is the first human AV-node model to capture both spatial and temporal dynamics while being efficient enough to allow interactive use on clinical timescales, as well as parameter estimation and uncertainty quantification. As such, it fills a new niche in the current set of published models and forms a valuable tool for both understanding and clinical research.

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References

  1. Billette J, Tadros R (2014) Integrated rate-dependent and dual pathway AV nodal functions: principles and assessment framework. Am J Physiol Heart Circ Physiol 306:H173

    Article  CAS  PubMed  Google Scholar 

  2. Botteron DW, Smith JM (1995) A technique for measurement of the extent of spatial organization of atrial activation during atrial fibrillation in the intact human heart. IEEE Trans Biomed Eng 42(6):579

    Article  CAS  PubMed  Google Scholar 

  3. Britton OJ, Bueno-Orovio A, Ammel KV, Lu HR, Towart R, Gallacher DJ, Rodriguez B (2013) Experimentally calibrated population of models predicts and explains intersubject variability in cardiac cellular electrophysiology. Proc Natl Acad Sci 110(23):E2098. doi:10.1073/pnas.1304382110. http://www.pnas.org/content/110/23/E2098

  4. Bueno-Orovio A, Sánchez C, Pueyo E, Rodriguez B (2014) Na/K pump regulation of cardiac repolarization: insights from a systems biology approach. Pflugers Arch 466(2):183. doi:10.1007/s00424-013-1293-1

    Article  CAS  PubMed  Google Scholar 

  5. Climent A, Guillem M, Zhang Y, Millet J, Mazgalev T (2011) Functional mathematical model of dual pathway AV nodal conduction. Am J Physiol Heart Circ Physiol 300(4):H1393

    Article  CAS  PubMed  Google Scholar 

  6. Cohen RJ, Berger RD, Dushane T (1983) A quantitative model for the ventricular response during atrial fibrillation. IEEE Trans Biomed Eng 30:769

    Article  CAS  PubMed  Google Scholar 

  7. Corino VDA, Sandberg F, Lombardi F, Mainardi L, Sörnmo L (2013) An atrioventricular node model for analysis of the ventricular response during atrial fibrillation. IEEE Trans Biomed Eng 8:1017

    Google Scholar 

  8. Corino VDA, Sandberg F, Mainardi LT, Sörnmo L, Trans IEEE (2011) An atrioventricular node model for analysis of the ventricular response during atrial fibrillation. IEEE Trans Biomed Eng 58:3386

    Article  PubMed  Google Scholar 

  9. Courtemanche M, Ramirez RJ, Nattel S (1998) Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model. Am J Physiol 275:H301

    CAS  PubMed  Google Scholar 

  10. Goldberger AL, Amaral LAN, Glass L, Hausdorff JM, Ivanov PCH, Mark RG, Mietus JE, Moody GB, Peng CK, Stanley HE (2000) Physiobank, physiotoolkit, and physionet: components of a new research resource for complex physiologic signals. Circulation 101(23):e215

    Article  CAS  PubMed  Google Scholar 

  11. Guevara MR, Ward G, Shrier A, Glass L (1984) Electrical alternance and period doubling bifurcations. In: Computers in cardiology. Salt Lake City, pp 167–170

  12. Henriksson M, Corino V, Sörnmo L, Sandberg F (2016) A statistical atrioventricular node model accounting for pathway switching during atrial fibrillation. IEEE Trans Biomed Eng 63:1842

    Article  PubMed  Google Scholar 

  13. Inada S, Boyett M, Dobrzynski H (2009) Mathematical models of human sinus and atrioventricular node action potentials. Comput Cardiol 2009:77–80

    Google Scholar 

  14. Inada S, Shibata N, Iwata M, Haraguchi R, Ashihara T, Ikeda T, Mitsui K, Dobrzynski H, Boyett M, Nakazawa K (2017) Simulation of ventricular rate control during atrial fibrillation using ionic channel blockers. J Arrhythm In press

  15. Jørgensen P, Schäfer C, Guerra PG, Talajic M, Nattel S, Glass L (2002) A mathematical model of human atrioventricular nodal function incorporating concealed conduction. Bull Math Biol 64:1083

    Article  PubMed  Google Scholar 

  16. Konukoglu E, Relan J, Cilingir U, Menze BH, Chinchapatnam P, Jadidi A, Cochet H, Hocini M, Delingette H, Ayache N et al (2011) Efficient probabilistic model personalization integrating uncertainty on data and parameters: application to eikonal-diffusion models in cardiac electrophysiology. Prog Biophys Mol Biol 107:134–146

    Article  PubMed  Google Scholar 

  17. Kurian T, Ambrosi C, Hucker W, Fedorov VV, Efimov IR (2010) Anatomy and electrophysiology of the human av node. Pacing Clin Electrophysiol 33:754

    Article  PubMed  PubMed Central  Google Scholar 

  18. Lagerholm M, Peterson C, Braccini G, Edenbrandt L, Sörnmo L (2000) Clustering ECG complexes using Hermite functions and self-organizing maps. IEEE Trans Biomed Eng 47(7):838. doi:10.1109/10.846677

    Article  CAS  PubMed  Google Scholar 

  19. Lian J, Müssig D, Lang V (2006) Computer modeling of ventricular rhythm during atrial fibrillation and ventricular pacing. IEEE Trans Biomed Eng 53:1512

    Article  PubMed  Google Scholar 

  20. Liu S, Olsson SB, Yang Y, Hertervig E, Kongstad O, Yuan S (2004) Concealed conduction and dual pathway physiology of the atrioventricular node. J Cardiovasc Electrophysiol 15(2):144. doi:10.1046/j.1540-8167.2004.03301.x

    Article  PubMed  Google Scholar 

  21. Mangin L, Vinet A, Page P, Glass L (2005) Effects of antiarrhythmic drug therapy on atrioventricular nodal function during atrial fibrillation in humans. Europace 7:S71

    Article  Google Scholar 

  22. Masè M, Glass L, Disertori M, Ravelli F (2012) Nodal recovery, dual pathway physiology, and concealed conduction determine complex AV dynamics in human atrial tachyarrhythmias. Am J Physiol Heart and Circ Physiol 303:H1219

    Article  Google Scholar 

  23. Masè M, Marini M, Disertori M, Ravelli F (2015) Dynamics of AV coupling during human atrial fibrillation: role of atrial rate. Am J Physiol Heart Circ Physiol 309:H198

    Article  PubMed  Google Scholar 

  24. Mendenhall G, Voigt A, Saba S (2013) Insights into atrioventricular nodal function from patients displaying dual conduction properties interactive and orthogonal pathways. Circ Arrhyth Electrophysiol 6:364

    Article  Google Scholar 

  25. Mitchell M (1996) An introduction to genetic algorithms. Complex adaptive systems. MIT Press, Cambridge

    Google Scholar 

  26. Mitchell C, Shaeffer D (2003) A two-current model for the dynamics of cardiac membrane. Bull Math Biol 65(5):767. doi:10.1016/S0092-8240(03)00041-7

    Article  CAS  PubMed  Google Scholar 

  27. Natale A, Klein G, Yee R, Thakur R (1994) Shortening of fast pathway refractoriness after slow pathway ablation. Effects of autonomic blockade. Circulation 89:1103

    Article  CAS  PubMed  Google Scholar 

  28. Ng J, Sehgal V, Ng JK, Gordon D, Goldberger JJ (2014) Iterative method to detect atrial activations and measure cycle length from electrograms during atrial fibrillation. IEEE Trans Biomed Eng 61:273–278

    Article  PubMed  Google Scholar 

  29. Podziemski P, Zebrowski J (2013) A simple model of the right atrium of the human heart with the sinoatrial and atrioventricular nodes included. J Clin Monit Comput 27:481

    Article  PubMed  PubMed Central  Google Scholar 

  30. Rashidi A, Khodarahmi I (2005) Nonlinear modeling of the atrioventricular node physiology in atrial fibrillation. J Theor Biol 232:545

    Article  PubMed  Google Scholar 

  31. Sandberg F, Corino V, Mainardi LT, Ulimoen S, Enger S, Tveit A, Platonov P, Sörnmo L (2015) Non-invasive assessment of the effect of beta blockers and calcium channel blockers on the AV node during permanent atrial fibrillation. J Electrocardiol 48(5):861

    Article  PubMed  Google Scholar 

  32. Sandberg F, Stridh M, Sörnmo L (2008) Frequency tracking of atrial fibrillation using hidden markov models. IEEE Trans Biomed Eng 55:502

    Article  PubMed  Google Scholar 

  33. Shkurovich S, Sahakian A, Swiryn S (1998) Detection of atrial activity from high-voltage leads of implantable ventricular defibrillators using a cancellation technique. IEEE Trans Biomed Eng 45(2):229

    Article  CAS  PubMed  Google Scholar 

  34. Shrier A, Dubarsky H, Rosengarten M, Guevara MR, Nattel S, Glass L (1987) Prediction of complex atrioventricular conduction rhythms in humans with use of the atrioventricular nodal recovery curve. Circulation 76(6): 1196. doi:10.1161/01.CIR.76.6.1196. http://circ.ahajournals.org/content/76/6/1196

  35. Stridh M, Sörnmo L (2001) Spatiotemporal QRST cancellation techniques for analysis of atrial fibrillation. IEEE Trans Biomed Eng 48(1):105. doi:10.1109/10.900266

    Article  CAS  PubMed  Google Scholar 

  36. Sun J, Amellal F, Glass L, Bilette J (1995) Alternans and period-doubling bifurcations in atrioventricular nodal conduc. J Theor Biol 173:79

    Article  CAS  PubMed  Google Scholar 

  37. Talajic M, Papadatos D, Villemaire C, Glass L, Nattel S (1991) A unified model of atrioventricular nodal conduction predicts dynamic changes in Wenckebach periodicity. Circ Res 68:1280

    Article  CAS  PubMed  Google Scholar 

  38. Ulimoen S, Enger S, Carlson J, Platonov P, Pripp A, Abdelnoor M, Arnesen H, Gjesdal K, Tveit A (2013) Comparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrillation. Am J Cardiol 111(2):225

    Article  CAS  PubMed  Google Scholar 

  39. Wallman M, Smith NP, Rodriguez B (2012) A comparative study of graph-based, eikonal, and monodomain simulations for the estimation of cardiac activation times. IEEE Trans Biomed Eng 59:1739

    Article  PubMed  Google Scholar 

  40. Wallman M, Smith NP, Rodriguez B (2014) Computational methods to reduce uncertainty in the estimation of cardiac conduction properties from electroanatomical recordings. Med Image Anal 18(1):228. doi:10.1016/j.media.2013.10.006

    Article  PubMed  Google Scholar 

  41. Wallman M, Sandberg F (2015) Characterization of AV-nodal properties during atrial fibrillation using a multilevel modelling approach. In: 2015 Computing in cardiology conference (CinC), pp 477–480. doi:10.1109/CIC.2015.7408690

  42. Zhang Y, Bharati S, Mowrey KA, Mazgalev TN (2003) His electrogram alternans reveal dual atrioventricular nodal pathway conduction during atrial fibrillation: the role of slow-pathway modification. Circulation 107:1059

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to Drs. Arnljot Tveit and Sara Ulimoen, Baerum Hospital, Drammen, Norway, for generously sharing the RATAF database. The authors acknowledge support from the Swedish Research Council, Grant No. 621-2014-6134.

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Correspondence to Mikael Wallman.

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Wallman, M., Sandberg, F. Characterisation of human AV-nodal properties using a network model. Med Biol Eng Comput 56, 247–259 (2018). https://doi.org/10.1007/s11517-017-1684-0

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