Critical appraisal of technologies to assess electrical activity during atrial fibrillation: a position paper from the European heart rhythm association and European society of cardiology working group on ecardiology in collaboration with the heart rhythm society, Asia pacific heart rhythm society, Latin American Heart rhythm society and computing in cardiology

Abstract We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (I) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (I) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e. g. catheter­electrode combinations) for signal processing (e. g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future.

Analyzing the effect of electrode size on electrogram and activation map properties.

BACKGROUND: Atrial electrograms recorded from the epicardium provide an important tool for studying the initiation, perpetuation, and treatment of AF. However, the properties of these electrograms depend largely on the properties of the electrode arrays that are used for recording these signals. METHOD: In this study, we use the electrode's transfer function to model and analyze the effect of electrode size on the properties of measured electrograms. To do so, we use both simulated as well as clinical data. To simulate electrogram arrays we use a two-dimensional (2D) electrogram model as well as an action propagation model. For clinical data, however, we first estimate the trans-membrane current for a higher resolution 2D modeled cell grid and later use these values to interpolate and model electrograms with different electrode sizes. RESULTS: We simulate electrogram arrays for 2D tissues with 3 different levels of heterogeneity in the conduction and stimulation pattern to model the inhomogeneous wave propagation observed during atrial fibrillation. Four measures are used to characterize the properties of the simulated electrogram arrays of different electrode sizes. The results show that increasing the electrode size increases the error in LAT estimation and decreases the length of conduction block lines. Moreover, visual inspection also shows that the activation maps generated by larger electrodes are more homogeneous with a lower number of observed wavelets. The increase in electrode size also increases the low voltage areas in the tissue while decreasing the slopes and the number of detected deflections. The effect is more pronounced for a tissue with a higher level of heterogeneity in the conduction pattern. Similar conclusions hold for the measurements performed on clinical data. CONCLUSION: The electrode size affects the properties of recorded electrogram arrays which can respectively complicate our understanding of atrial fibrillation. This needs to be considered while performing any analysis on the electrograms or comparing the results of different electrogram arrays.

Mitochondrial Dysfunction Underlies Cardiomyocyte Remodeling in Experimental and Clinical Atrial Fibrillation.

Atrial fibrillation (AF), the most common progressive tachyarrhythmia, results in structural remodeling which impairs electrical activation of the atria, rendering them increasingly permissive to the arrhythmia. Previously, we reported on endoplasmic reticulum stress and NAD+ depletion in AF, suggesting a role for mitochondrial dysfunction in AF progression. Here, we examined mitochondrial function in experimental model systems for AF (tachypaced HL-1 atrial cardiomyocytes and Drosophila melanogaster) and validated findings in clinical AF. Tachypacing of HL-1 cardiomyocytes progressively induces mitochondrial dysfunction, evidenced by impairment of mitochondrial Ca2+-handling, upregulation of mitochondrial stress chaperones and a decrease in the mitochondrial membrane potential, respiration and ATP production. Atrial biopsies from AF patients display mitochondrial dysfunction, evidenced by aberrant ATP levels, upregulation of a mitochondrial stress chaperone and fragmentation of the mitochondrial network. The pathophysiological role of mitochondrial dysfunction is substantiated by the attenuation of AF remodeling by preventing an increased mitochondrial Ca2+-influx through partial blocking or downregulation of the mitochondrial calcium uniporter, and by SS31, a compound that improves bioenergetics in mitochondria. Together, these results show that conservation of the mitochondrial function protects against tachypacing-induced cardiomyocyte remodeling and identify this organelle as a potential novel therapeutic target.