Unveiling the impact of fibrosis presence in fibrillatory electrograms

Introduction Complexity and fragmentation presence in atrial fibrillation (AF) electrograms (EGMs) has been extensively studied in the literature, with areas exhibiting complex fractionated atrial electrograms (CFAEs) postulated as responsible for AF maintenance. Computational simulations based on in silico models are widely employed to support AF initiating and maintenance theories. However, they are still limited when trying to mimic the effect of fibrosis in live cardiac cells and its impact in the clinical context, i.e., EGM morphologies in electroanatomical mapping studies. Controlled experiments on cultivated cardiomyocytes and optical mapping signals can better explain the role of fibrosis and its effect on EGM recordings. Purpose To study the effect of fibrosis in fibrillatory scenarios by comparing the temporal and frequency domains of EGMs and Ca2+ transient signals in cardiomyocyte cell cultures. Methods A total of 51 HL1 cardiomyocytes cell line monolayers experiments were cultured until confluence. Optical mapping (OM) was performed to evaluate the electrophysiological activity of the samples through Ca2+ transient quantification under the effect of Rhod2 dye. Activation frequency and calcium transient signals were acquired, and virtual EGMs were calculated from the signals virtually after post-processing the cell cultures at 16 different positions in the culture, see Figure 1A. Results The DF ratio between the OM and the virtual EGMs obtained for the different fibrosis levels are summarized and represented in Figure 1B. The Pearson's correlation coefficient was adjusted for all the samples and the significance level was stablished at p-value<0.01. Conclusions Optical mapping signal morphologies strongly correlate with EGM recordings when a clear dominant frequency (DF) dominates the complete area of the cell culture and no fibrosis is present. However, for patchy distributions of the DF, usually associated with higher concentrations of fibrosis, morphologies do not correlate for increasing fibrosis levels, and DF measurements differ with poor match between EGM-DF and OM-DF. Results on higher fibrotic experiments, i.e., 40–50% fibrosis level, show that DF correlates due to the poor and degraded cardiac activity in the EGMs and optical mapping recordings. The results reveal the importance and impact of fibrosis in the remodeling of atrial tissue and the correct interpretation of endocardial EGMs in the presence of heterogeneous tissue. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III and Ministerio de Ciencia, Innovaciόn y Universidades