Temporal stability and specificity of high bipolar electrogram entropy regions in sustained atrial fibrillation: Implications for mapping

Abstract

Background: The potential utility of entropy (En) for atrial fibrillation (AF) mapping has been demonstrated in previous studies by multiple groups, where an association between high bipolar electrogram (EGM) entropy and the pivot of rotors has been shown. Though En is potentially attractive new approach to ablation, no studies have examined its temporal stability and specificity, which are critical to the application of entropy to clinical ablation. In the current study, we sought to objectively measure the temporal stability and specificity of bipolar EGM entropy in medium to long term recordings using three studies: i) a human basket catheter AF study, ii) a tachypaced sheep AF study and iii) a computer simulation study. Objective: To characterize the temporal dynamics and specificity of Approximate, Sample and Shannon entropy (ApEn/SampEn/ShEn) in human (H), sheep (S), and computer simulated AF. Methods: 64-electrode basket bi-atria sustained AF recordings (H:15 min; S:40 min) were separated into 5 s segments. ShEn/ApEn/SampEn were computed, and co-registered with NavX 3D maps. Temporal stability was determined in terms of: (i) global pattern stability of En and (ii) the relative stability the top 10% of En regions. To provide mechanistic insights into underlying mechanisms, stability characteristics were compared to models depicting various propagation patterns. To verify these results, cross-validation was performed across multiple En algorithms, across species, and compared with dominant frequency (DF) temporal characteristics. The specificity of En was also determined by looking at the association of En to rotors and areas of wave cross propagation. Results: Episodes of AF were analysed (H:26 epochs, 6040 s; S:15 epochs, 14,160 s). The global pattern of En was temporally unstable (CV-H:13.42% ± 4.58%; S:14.13% ± 8.13%; Friedman-H: p N 0.001; S: p N 0.001). However, within this dynamic flux, the top 10% of ApEn/SampEn/ShEn regions were relatively temporally stable (Kappa N0.6) whilst the top 10% of DF regions were unstable (Kappa b0.06). In simulated AF scenarios, the experimental data were optimally reproduced in the context of an AF pattern with stable rotating waves surrounded by wavelet breakup (Kappa: 0.610; p b 0.0001). Conclusion: En shows global temporal instability, however within this dynamic flux, the top 10% regions exhibited relative temporal stability. This suggests that high En regions may be an appealing ablation target. Despite this, high En was associated with not just the pivot of rotors but also with areas of cross propagation, which suggests the need for future work before clinical application is possible.

Renewal theory provides a universal quantitative framework to characterise the continuous regeneration of rotational events in cardiac fibrillation

“…Basket catheter recordings were performed as previously described (23). 64-electrode basket catheters (Constellation, Boston Scientific, MA, 48mm(4mm spacing), 60mm(5mm spacing)) were utilized, based on computed tomographic scan.…”

“…Ovine persistent AF was induced via atrial tachypacing for 16 weeks at ≥ 300 bpm per minute as described (23). Unipolar electrograms were obtained during electrophysiology study, using 64-electrode Constellation catheters (48mm).…”

“…Computer simulations were based on the Ten Tusscher-Panfilov model on 2-D, isotropic square grids (80x80) (23). Model calculations are in S2.…”

Spatial concentration and distribution of phase singularities in human atrial fibrillation: Insights for the AF mechanism

“…This study utilized a combined cohort from Flinders University and Hamburg University 20 . All data were obtained with written informed consent, with study approval provided by local human ethics committees.…”

Challenges Associated with Interpreting Mechanisms of AF

“…65 This highlights that the usefulness of DF for targeting ablation is questionable because the arrhythmia mechanism is unstable. 66,67 A key technical challenge for frequency mapping that needs to be taken into consideration is that the temporal resolution is limited by the short duration of cardiac recordings compared with the sampling rate.…”