Lack of Full Transmurality in Atrial Fibrosis Distribution Promotes Local Arrhythmogenic Activity that Sustains Atrial Fibrillation (AF)

Introduction:: AF is the most prevalent heart disease that affects 2% of the world population. The AF mechanisms in persistent (PersAF) patients with fibrotic remodeling remain incompletely understood. Atrial fibrosis is visualized on Late Gadolinium Enhanced (LGE)-MRI, however it remains unknown what features of the fibrotic substrate are arrhythmogenic and likely to sustain AF reentrant drivers (RDs). Atria being thinner than ventricles, the 3D aspect of atrial fibrosis distribution and the resulting difference in epi- and endocardial activity has not been explored and it is unknown whether fibrosis transmurality plays a role in promoting RDs formation. The objective of this study is to elucidate the role of the 3D fibrosis distribution in AF substrate arrhythmogenicity using personalized computational modeling of patient atria.


Materials and Methods:: Three persAF patients underwent LGE-MRI scans. The scans were used to generate bi-atrial models with fibrosis distribution. Personalized computational modeling probed substrate arrhythmogenesis by pacing from 40 bi-atrial sites. Out of all 120 pacing sites, pacing from 27 sites induced 16 unique RDs in the substrate. Epi and endocardial electrophysiological (EP) activity was examined in the regions of RD formation. Transmurality of fibrosis was quantified statistically in these regions, which included the calculation of Dice Similarity Coefficient (DSC) to quantify the differences in epi- and endocardial fibrosis patterns.

Results, Conclusions, and Discussions:: A dissimilarity in EP activity between endo- and epicardium was observed in all atria, stemming from dissimilar endo-epi fibrosis patterns. Significant differences were found between endo- and epicardium fibrosis patterns in regions of RD formation (Fig. A, C.1). The dissimilar endo-epi EP activity was instrumental in RD formation. The lack of homogeneity between endo and epi EP activity derived from dissimilar fibrosis patterns allows for the wavefront to form preferential conduction pathways within the 3D substrate and causes rotational wave activity to persist around the patch of fibrosis with incomplete transmurality (Fig. B). A range of 22-31.5% local volumetric transmural fibrosis indicated a strong likelihood that an RD will form locally (Fig. C.2) if simultaneously accompanied by a low DSC of 0.15-0.32 in these regions thus confirming the significant differences in epi and endocardial fibrosis patterns (Fig. C.3).
Regions of highly dissimilar endo-epi LGE-MRI fibrosis are instrumental to the formation of RDs in the AF substrate and must be prioritized for PVI ablation to reduce AF recurrence in PersAF patients.

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