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. 2022 Nov 23;8(1):68-84.
doi: 10.1016/j.jacbts.2022.07.011. eCollection 2023 Jan.

Regions of Highly Recurrent Electrogram Morphology With Low Cycle Length Reflect Substrate for Atrial Fibrillation

Shin Yoo  1 , Markus Rottmann  1 , Jason Ng  1 , David Johnson  1 , Bassel Shanab  1 , Anna Pfenniger  1 , Gail Elizabeth Geist  1 , Suman Mandava  1 , Amy Burrell  1 , Wenwei Zhang  1 , J Andrew Wasserstrom  1 , Bradley P Knight  1 , Rod Passman  1 , Jeffrey J Goldberger  2 , Rishi Arora  1
Affiliations

Regions of Highly Recurrent Electrogram Morphology With Low Cycle Length Reflect Substrate for Atrial Fibrillation

Shin Yoo et al. JACC Basic Transl Sci. .

Abstract

Traditional anatomically guided ablation and attempts to perform electrogram-guided atrial fibrillation (AF) ablation (CFAE, DF, and FIRM) have not been shown to be sufficient treatment for persistent AF. Using biatrial high-density electrophysiologic mapping in a canine rapid atrial pacing model of AF, we systematically investigated the relationship of electrogram morphology recurrence (EMR) (Rec% and CLR) with established AF electrogram parameters and tissue characteristics. Rec% correlates with stability of rotational activity and with the spatial distribution of parasympathetic nerve fibers. These results have indicated that EMR may therefore be a viable therapeutic target in persistent AF.

Keywords: AF, atrial fibrillation; AI, anisotropy index; CFAE, complex fractionated atrial electrogram; CLR, cycle length of the most recurrent electrogram morphology; DF, dominant frequency; EGM, electrogram; EMR, electrogram morphology recurrence; FFT, fast Fourier transform; FI, fractionation interval; FIRM, focal impulse and rotor mapping; LAA, left atrial appendage; LAFW, left atrial free wall; LAT, local activation time; OI, organization index; PLA, posterior left atrium; PV, pulmonary vein; RAA, right atrial appendage; RAFW, right atrial free wall; RAP, rapid atrial pacing; Rec%, recurrence percentage; ShEn, Shannon’s entropy; arrhythmias; atrial fibrillation; fibrosis; mapping.

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Conflict of interest statement

Dr Arora is supported by National Institutes of Health grants R01 HL093490; R01 HL140061; an AHA Strategically Focused Research Networks AF Center grant; and by the NIH Center for Accelerated Innovations at Cleveland Clinic (NCAI-CC). Dr Arora has ownership interest in Rhythm Therapeutics. Dr Pfenniger is supported by grant KL2TR001424. All authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Examples of Recurrence Plots and Electrogram Signals and Regionally Variable Rec% and CLR (A) Illustration of a color-coded cross-correlation matrix of all activations (top) and electrogram signals (bottom) in 6 atrial regions. (B) Regional distribution of Rec% and CLRMin in 6 atrial regions. Data presented as mean ± SEM; n = 13. ∗∗P < 0.01; ∗∗∗P < 0.001. CLR = cycle length of the most recurrent electrogram morphology; LAA = left atrial appendage; LAFW = left atrial free wall; OI = organization index; PLA = posterior left atrium; PRA = posterior right atrium; RAA = right atrial appendage; RAFW = right atrial free wall; Rec% = recurrence percentage.
Figure 2
Figure 2
Close Correlation of Rec% and CLR With FI and ShEn But Not With DF (A) Example of correlation coefficient between electrograms (EGMs) in the LAA of animal 1. (B) Analysis of R values of Rec% (left) and CLR(right) with other EGMs in 6 atrial regions. The pie charts show proportion of animals with correlation factors R ≥ 0.5 (orange) and R < 0.5 (gray); n = 13. DF = dominant frequency; FI = fractional interval; ShEn = Shannon’s entropy (ShEn); other abbreviations as in Figure 1.
Figure 3
Figure 3
Strong Relation of Rec% With Stability of Rotational Activities (A) Examples of multiple interacting rotational activities in 6 atrial regions. (B) Comparison of stability of rotational activities in 6 atrial regions. Data are presented in box and whiskers plot. Kruskal-Wallis 1-way analysis of variance on ranks with Tukey’s post hoc method for all pairwise comparison; n = 13. ∗P < 0.05. (C) Correlation of stability of rotational activities with Rec%. Abbreviations as in Figure 1.
Figure 4
Figure 4
Poor Correlation of Rec% and CLR With Fibrosis (A) Representative images of Masson’s trichrome–stained tissue section and outcome of analysis in 6 atrial regions. Red indicates myocardium, and blue indicates fibrosis. (B) Regional differences in fibrosis. Data are presented in box and whiskers plot. Kruskal-Wallis 1-way analysis of variance on ranks with Tukey’s post hoc method for all pairwise comparison; n = 13. ∗P < 0.05. (C) Correlation of fibrosis with Rec%, CLRMin, FI, OI, DF, and ShEn. Abbreviations as in Figure 1.
Figure 5
Figure 5
No Correlation of Rec% and CLR With Myofiber Anisotropy (A) Example of fiber orientation measurements in LAFW and LAA. (B) Regional differences in anisotropy index (AI). Data are presented as mean ± SEM; n = 13. ∗∗∗P < 0.001. One-way analysis of variance with Holm-Sidak method for pairwise multiple comparison. (C) Correlation of AI with Rec%, CLRMin, FI, OI, DF, and ShEn. Abbreviations as in Figure 1.
Figure 6
Figure 6
Close Relation of Rec% With Spatial Distribution of Parasympathetic Nerve Fiber Representative micrographs of atrial regions with (A) high and (B) low standard deviation of parasympathetic nerve fiber density. Location of 4 random micrographs are denoted in mini map. Blue and brown arrows designate sympathetic and parasympathetic nerve fibers, respectively. Correlation of (C) Rec% and (D) SD of Rec% with SD of parasympathetic nerve fiber density. (E and F) Change of Rec% and CLR by atropine in 6 atrial regions. Data are presented as mean ± CI; n = 13. ∗∗∗P < 0.001. Using linear mixed models with a random intercept for dog, and both a fixed effect and a compound symmetric covariance structure for electrode, the effect of atropine was compared in 6 atrial regions.
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References

    1. Trayanova N.A. Mathematical approaches to understanding and imaging atrial fibrillation: significance for mechanisms and management. Circ Res. 2014;114:1516–1531. - PMC - PubMed
    1. Heijman J., Guichard J.B., Dobrev D., Nattel S. Translational challenges in atrial fibrillation. Circ Res. 2018;122:752–773. - PubMed
    1. Ganesan A.N., Shipp N.J., Brooks A.G., et al. Long-term outcomes of catheter ablation of atrial fibrillation: a systematic review and meta-analysis. J Am Heart Assoc. 2013;2 - PMC - PubMed
    1. Schotten U., Verheule S., Kirchhof P., Goethe A. Pathophysiological mechanisms of atrial fibrillation: a translational appraisal. Physiol Rev. 2011;91:265–325. - PubMed
    1. Haissaguerre M., Jais P., Shah D.C., et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998;339:659–666. - PubMed