Development, in vitro validation and human application of a novel method to identify arrhythmia mechanisms: The stochastic trajectory analysis of ranked signals mapping method

Shohreh Honarbakhsh, Ross J Hunter, Malcolm Finlay, Waqas Ullah, Emily Keating, Andrew Tinker, Richard J Schilling, Shohreh Honarbakhsh, Ross J Hunter, Malcolm Finlay, Waqas Ullah, Emily Keating, Andrew Tinker, Richard J Schilling

Abstract

Introduction: Stochastic trajectory analysis of ranked signals (STAR) is a novel method for mapping arrhythmia. The aim was to describe its development and validation as a mapping tool.

Methods and results: The method ranks electrodes in terms of the proportion of the time they lead relative to neighboring electrodes and ascribes a predominant direction of activation between electrodes. This was conceived with the aim of mapping atrial fibrillation (AF) drivers. Validation of this approach was performed in stages. First, in vitro simultaneous multi-electrode array and optical mapping were performed on spontaneously fibrillating HL1 cell cultures, to determine if such a method would be able to determine early sites of activation (ESA). A clinical study acquiring unipolar electrograms using a 64-pole basket for the purposes of STAR mapping in patients undergoing atrial tachycardia (AT) ablation. STAR maps were analyzed by physicians to see if arrhythmia mechanisms could be correctly determined. Mapping was then repeated during atrial pacing. STAR mapping of in vitro activation sequences accurately correlated to the optical maps of planar and rotational activation. Thirty-two ATs were mapped in 25 patients. The ESA accurately identified focal/micro-reentrant ATs and the mechanism of macro-reentrant ATs was effectively demonstrated. STAR method accurately identified four pacing sites in all patients.

Conclusions: This novel STAR method correlated well with the gold standard of optical mapping in vitro and was able to accurately identify AT mechanisms. Further analysis is needed to determine whether the method might be of use mapping AF.

Keywords: atrial fibrillation; atrial tachycardia; catheter ablation; mapping method; optical mapping.

© 2019 Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
i‐iv, Shows a simplified method of calculating a STAR map. Five electrogram pairs are shown, (a‐e), and the electrograms derived from each electrode are shown below. Three representative patterns which together comprise 80% of the total recording time are shown (i‐iii): (i) accounting for 50% of the time electrode a is leading all other electrodes, (ii) a different activation sequence is illustrated, with electrode (c) leading, accounting for 20% of the time, (iii) is another activation sequence where electrode (e) leads, 10% of the time. Each electrode has a value associated with it based on the proportion of time that electrode is seen as "leading" its closest associated electrode as shown in (iv). A final process combines these data and superimposes these on a combined map, highlighting the leading electrodes. STAR, stochastic trajectory analysis of ranked signals
Figure 2
Figure 2
A, A STAR LA map in an anterior‐posterior view (GEPD = 6 cm) demonstrating a focal AT mapped to the septum. B, STAR LA map in a left lateral view (GEPD = 6 cm) demonstrating a mitral isthmus‐dependent AT whereby electrodes anteriorly are leading electrodes posteriorly, as a result, no electrode is leading 100% of the time as seen with a focal AT. AT, atrial tachycardia; GEPD, geodesic electrode pairing distance; STAR, stochastic trajectory analysis of ranked signals
Figure 3
Figure 3
A‐D, (Ai‐iv) 2D optical map demonstrating a planar wavefront moving from the top left corner of the map with the electrode that recorded the earliest activation highlighted with a red circle. B, electrograms recorded by the electrodes on the MEA, of note it highlights the noise experienced on the electrodes that were excluded from the analysis. C, 2D STAR map that shows the earliest activation at the electrode highlighted on the optical map and also shows the wavefront moving across the MEA as seen on the optical map. MEA, multi‐electrode array; STAR, stochastic trajectory analysis of ranked signals
Figure 4
Figure 4
A‐D, Demonstrates STAR maps during atrial pacing at 600ms in sinus rhythm at four different LA sites. A, LA roof. B, LA appendage. C, Endocardial distal CS distal. D, Endocardial proximal CS. The maps show the earliest site of activation near the pacing site as indicated by the yellow star. The STAR mapping method also implements arrows to demonstrate the direction of wavefront propagation. CS, coronary sinus; STAR, stochastic trajectory analysis of ranked signals
Figure 5
Figure 5
A‐D, Roof‐dependent flutter mapped with STAR and CARTO3 LAT maps. A, STAR map in a tilted LAO view that demonstrates the wavefront moving up the anterior wall, as indicated by the arrows that correlate to B, the LAT map in a tilted LAO view. C, STAR map in posterior‐anterior view that demonstrates the wavefront moving down the posterior wall that is supported by D, the LAT map. LAT, local activation time; STAR, stochastic trajectory analysis of ranked signals
Figure 6
Figure 6
A‐D, Focal/micro‐reentrant AT mapped with STAR and CARTO3 LAT maps. A, LAT map in a titled anterior‐posterior view demonstrating earliest activation at the septum. B, LAT map in a titled right lateral view supporting the spread of the AT from the septum across the LA. C, STAR map that shows the earliest site of activation at the septum that correlates to the focus of the AT. D, BARD electrograms that include the surface ECGs, CS, and map electrograms that shows an AT with a CL of 225 ms terminating to sinus rhythm on ablation at the earliest site of activation. AT, atrial tachycardia; LAT, local activation time; STAR, stochastic trajectory analysis of ranked signals
Figure 7
Figure 7
A‐B, Micro‐reentrant AT mapped with STAR and CARTO3 LAT map. A, LAT map in a titled anterior‐posterior view demonstrating a micro‐reentrant AT mapped to the low anterior wall with the arrows further highlighting the mechanism. B, STAR map in an anterior‐posterior view that shows two early sites of activation at the low anterior wall. Neither of these sites is leading 100% of the time as the electrodes closer to the circuit are leading these electrodes. The arrows demonstrate that the wavefront propagates away from these sites across the LA. AT, atrial tachycardia; LAT, local activation time; STAR, stochastic trajectory analysis of ranked signals
Figure 8
Figure 8
A‐B, STAR and CARTO 3 LAT maps of a focal right‐sided AT. A, A right atrial STAR map in anterior‐posterior view that demonstrates an early site of activation at the right atrial septum with the arrows highlighting the wavefront propagation from this site. B, LAT map of the focal AT. AT, atrial tachycardia; LAT, local activation time; STAR, stochastic trajectory analysis of ranked signals

References

    1. Narayan SM, Shivkumar K, Krummen DE, Miller JM, Rappel WJ. Panoramic electrophysiological mapping but not electrogram morphology identifies stable sources for human atrial fibrillation: stable atrial fibrillation rotors and focal sources relate poorly to fractionated electrograms. Circ Arrhythm Electrophysiol. 2013;6:58‐67.
    1. Lin T, Rillig A, Bucur T, et al. Focal impulse and rotor modulation using the novel 64‐electrode basket catheter: electrogram characteristics of human rotors. Europace. 2015;17:1791‐1797.
    1. Honarbakhsh S, Schilling RJ, Dhillon G, et al. A novel mapping system for panoramic mapping of the left atrium: application to detect and characterize localized sources maintaining atrial fibrillation. JACC Clin Electrophysiol. 2018;4:124‐134.
    1. Narayan SM, Baykaner T, Clopton P, et al. Ablation of rotor and focal sources reduces late recurrence of atrial fibrillation compared with trigger ablation alone: extended follow‐up of the CONFIRM trial (conventional ablation for atrial fibrillation with or without focal impulse and rotor modulation). J Am Coll Cardiol. 2014;63:1761‐1768.
    1. Hunter RJ, Diab I, Thomas G, et al. Validation of a classification system to grade fractionation in atrial fibrillation and correlation with automated detection systems. Europace. 2009;11:1587‐1596.
    1. Takahashi Y, O'Neill MD, Hocini M, et al. Characterization of electrograms associated with termination of chronic atrial fibrillation by catheter ablation. J Am Coll Cardiol. 2008;51:1003‐1010.
    1. Honarbakhsh S, Schilling RJ, Orini M, et al. Structural remodeling and conduction velocity dynamics in the human left atrium: relationship with reentrant mechanisms sustaining atrial fibrillation. Heart Rhythm. 2018;16:18‐25.
    1. Honarbakhsh S, Schilling RJ, Orini M, et al. Left atrial scarring and conduction velocity dynamics: rate dependent conduction slowing predicts sites of localized reentrant atrial tachycardias. Int J Cardiol. 2019;278:114‐119.
    1. Claycomb WC, Lanson NA, Jr. , Stallworth BS, et al. HL‐1 cells: a cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte. Proc Natl Acad Sci USA. 1998;95:2979‐2984.
    1. Dias P, Desplantez T, El‐Harasis MA, et al. Characterisation of connexin expression and electrophysiological properties in stable clones of the HL‐1 myocyte cell line. PLoS One. 2014;9:e90266.
    1. Xie C, Lin Z, Hanson L, Cui Y, Cui B. Intracellular recording of action potentials by nanopillar electroporation. Nat Nanotechnol. 2012;7:185‐190.
    1. Honarbakhsh S, Schilling RJ, Providencia R, et al. Characterization of drivers maintaining atrial fibrillation: correlation with markers of rapidity and organization on spectral analysis. Heart Rhythm. 2018;15:1296‐1303.
    1. Haissaguerre M, Hocini M, Denis A, et al. Driver domains in persistent atrial fibrillation. Circulation. 2014;130:530‐538.
    1. Mandapati R, Skanes A, Chen J, Berenfeld O, Jalife J. Stable microreentrant sources as a mechanism of atrial fibrillation in the isolated sheep heart. Circulation. 2000;101:194‐199.
    1. Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel WJ, Miller JM. Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (conventional ablation for atrial fibrillation with or without focal impulse and rotor modulation) trial. J Am Coll Cardiol. 2012;60:628‐636.
    1. Daoud EG, Zeidan Z, Hummel JD, et al. Identification of repetitive activation patterns using novel computational analysis of multielectrode recordings during atrial fibrillation and flutter in humans. JACC Clin Electrophysiol. 2017;3:207‐216.
    1. Vijayakumar R, Vasireddi SK, Cuculich PS, Faddis MN, Rudy Y. Methodology considerations in phase mapping of human cardiac arrhythmias. Circ Arrhythm Electrophysiol. 2016;9.

Source: PubMed

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