Abstract

Introduction: Late-gadolinium enhanced (LGE)-MRI has revealed atrial fibrotic remodeling in embolic stroke of undetermined source (ESUS) patients. Curiously, fibrosis levels in ESUS patients are the same as those observed in AF. A potential explanation is that ESUS patients have pre-clinical arrhythmic substrate, but lack the triggers needed to initiate AF. Hypothesis: Simulations in computational models reconstructed from LGE-MRI scans can determine if the fibrotic substrate of a particular ESUS patient has the capacity to sustain reentry. Methods: ESUS (per standard criteria) was verified by a neurologist. 45 ablation-naïve AF patients and 45 ESUS patients within three months of stroke underwent LGE-MRI for fibrosis assessment. Left atrial (LA) models were built from LGE-MRI scans. Fiber orientations were mapped into each LA model using universal atrial coordinates. Burst pacing from 15 sites was used to test inducibility of arrhythmia sustained by reentry (Fig A). Results: In 23/45 (51%) ESUS and 29/45 (64%) AF models, we observed sustained reentry. Fibrosis burden was significantly higher for patients in whom simulations suggested the existence of pre-clinical arrhythmic substrate; however, within the inducible and non-inducible sub-groups, there was no significant difference in fibrosis burden for ESUS vs. AF patients (Fig B). This suggests that the presence of pre-clinical substrate in ESUS is correlated with fibrosis burden, although exceptions to this supposition were not uncommon (i.e., inducible low-fibrosis and non-inducible high-fibrosis models; Fig C). Conclusions: In this modeling study, pro-arrhythmic properties of fibrosis in ESUS and AF are indistinguishable. This suggests that some ESUS patients have pre-clinical fibrotic substrate, but do not have AF due to a lack of suitable triggers. Ongoing clinical follow-up will test whether abundance of pre-clinical substrate is predictive of incident AF.

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