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The role of fibroblasts in complex fractionated electrograms during persistent/permanent atrial fibrillation: implications for electrogram-based catheter ablation.

ABSTRACT: Electrogram-based catheter ablation, targeting complex fractionated atrial electrograms (CFAEs), is empirically known to be effective in halting persistent/permanent atrial fibrillation (AF). However, the mechanisms underlying CFAEs and electrogram-based ablation remain unclear.Because atrial fibrosis is associated with persistent/permanent AF, we hypothesized that electrotonic interactions between atrial myocytes and fibroblasts play an important role in CFAE genesis and electrogram-based catheter ablation.We used a human atrial tissue model in heart failure and simulated propagation and spiral wave reentry with and without regionally proliferated fibroblasts. Coupling of fibroblasts to atrial myocytes resulted in shorter action potential duration, slower conduction velocity, and lower excitability. Consequently, heterogeneous fibroblast proliferation in the myocardial sheet resulted in frequent spiral wave breakups, and the bipolar electrograms recorded at the fibroblast proliferation area exhibited CFAEs. The simulations demonstrated that ablation targeting such fibroblast-derived CFAEs terminated AF, resulting from the ablation site transiently pinning the spiral wave and then pushing it out of the fibroblast proliferation area. CFAEs could not be attributed to collagen accumulation alone.Fibroblast proliferation in atria might be responsible for the genesis of CFAEs during persistent/permanent AF. Our findings could contribute to better understanding of the mechanisms underlying CFAE-targeted AF ablation.

SUBMITTER: Ashihara T

PROVIDER: S-EPMC3313658 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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The role of fibroblasts in complex fractionated electrograms during persistent/permanent atrial fibrillation: implications for electrogram-based catheter ablation.

Ashihara Takashi T Haraguchi Ryo R Nakazawa Kazuo K Namba Tsunetoyo T Ikeda Takanori T Nakazawa Yuko Y Ozawa Tomoya T Ito Makoto M Horie Minoru M Trayanova Natalia A NA

Circulation research 20111215 2

<h4>Rationale</h4>Electrogram-based catheter ablation, targeting complex fractionated atrial electrograms (CFAEs), is empirically known to be effective in halting persistent/permanent atrial fibrillation (AF). However, the mechanisms underlying CFAEs and electrogram-based ablation remain unclear.<h4>Objective</h4>Because atrial fibrosis is associated with persistent/permanent AF, we hypothesized that electrotonic interactions between atrial myocytes and fibroblasts play an important role in CFAE ...[more]

PMID: 22179057

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Project description:Complex fractionated atrial electrograms (CFAEs) may represent a phenomenon associated with sources of atrial fibrillation (AF) and are being used increasingly as targets of catheter ablation. However, current methods have limited efficacy for characterizing CFAEs important to substrate arrhythmogenicity and do not measure electrogram morphology.The purpose of this study was to develop a methodology for quantifying the degree of morphologic heterogeneity in CFAE deflections, and to determine whether there are differences in this measurement between paroxysmal and persistent AF patients.Two successive bipolar CFAEs of length 8.4 seconds each were acquired during AF from two sites each at the ostia of the four pulmonary veins (PVs) and from the anterior and posterior left atrial free wall in patients with paroxysmal AF (N = 10) and long-standing persistent AF (N = 10). Extrinsic and intrinsic features of electrogram shape were used to characterize fractionation in CFAE sequences. The extrinsic parameters were the amplitude, upslope, downslope, and width of each deflection. The intrinsic parameter was the voltage profile as characterized by the sum of absolute values. These measurements were compared to the mean interval between CFAE deflections, a standard fractionation indicator.The variability of intrinsic/extrinsic morphologic parameters was higher in paroxysmal than persistent AF at the left superior PV (P < or =.003), the posterior left atrial free wall, anterior left atrial free wall, left inferior PV, and right superior PV (P <.05 for most parameters), and the right inferior PV (not significant). Mean CFAE deflection intervals were longer at all locations in paroxysmal AF but were significant only at the left superior PV and posterior left atrial free wall (P <.05). Quantitative morphologic parameters were not well correlated with dominant frequency (r(2) <0.32); thus, our new measures are robust to changes in activation rate.A novel method for quantifying CFAEs, independent of activation rate, has been developed. The method demonstrates greater significance in the difference between CFAE morphology in paroxysmal and long-standing AF compared with mean interval between CFAE deflections. The differences identified suggest that CFAE morphology may evolve as AF persists.

Project description:IntroductionMultiple groups have reported on the usefulness of ablating in atrial regions exhibiting abnormal electrograms during atrial fibrillation (AF). Still, previous studies have suggested that ablation outcomes are highly operator- and center-dependent. This study sought to evaluate a novel machine learning software algorithm named VX1 (Volta Medical), trained to adjudicate multipolar electrogram dispersion.MethodsThis study was a prospective, multicentric, nonrandomized study conducted to assess the feasibility of generating VX1 dispersion maps. In 85 patients, 8 centers, and 17 operators, we compared the acute and long-term outcomes after ablation in regions exhibiting dispersion between primary and satellite centers. We also compared outcomes to a control group in which dispersion-guided ablation was performed visually by trained operators.ResultsThe study population included 29% of long-standing persistent AF. AF termination occurred in 92% and 83% of the patients in primary and satellite centers, respectively, p = 0.31. The average rate of freedom from documented AF, with or without antiarrhythmic drugs (AADs), was 86% after a single procedure, and 89% after an average of 1.3 procedures per patient (p = 0.4). The rate of freedom from any documented atrial arrhythmia, with or without AADs, was 54% and 73% after a single or an average of 1.3 procedures per patient, respectively (p < 0.001). No statistically significant differences between outcomes of the primary versus satellite centers were observed for one (p = 0.8) or multiple procedures (p = 0.4), or between outcomes of the entire study population versus the control group (p > 0.2). Interestingly, intraprocedural AF termination and type of recurrent arrhythmia (i.e., AF vs. AT) appear to be predictors of the subsequent clinical course.ConclusionVX1, an expertise-based artificial intelligence software solution, allowed for robust center-to-center standardization of acute and long-term ablation outcomes after electrogram-based ablation.

Dataset Information

The role of fibroblasts in complex fractionated electrograms during persistent/permanent atrial fibrillation: implications for electrogram-based catheter ablation.

Publications

The role of fibroblasts in complex fractionated electrograms during persistent/permanent atrial fibrillation: implications for electrogram-based catheter ablation.

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