Computational modeling identifies embolic stroke of undetermined source patients with potential arrhythmic substrate

Cardiac magnetic resonance imaging (MRI) has revealed fibrosis in embolic stroke of undetermined source (ESUS) patients comparable to levels seen in atrial fibrillation (AFib). We used computational modeling to understand the absence of arrhythmia in ESUS despite the presence of putatively pro-arrhythmic fibrosis. MRI-based atrial models were reconstructed for 45 ESUS and 45 AFib patients. The fibrotic substrate’s arrhythmogenic capacity in each patient was assessed computationally. Reentrant drivers were induced in 24/45 (53%) ESUS and 22/45 (49%) AFib models. Inducible models had more fibrosis (16.7 ± 5.45%) than non-inducible models (11.07 ± 3.61%; p<0.0001); however, inducible subsets of ESUS and AFib models had similar fibrosis levels (p=0.90), meaning that the intrinsic pro-arrhythmic substrate properties of fibrosis in ESUS and AFib are indistinguishable. This suggests that some ESUS patients have latent pre-clinical fibrotic substrate that could be a future source of arrhythmogenicity. Thus, our work prompts the hypothesis that ESUS patients with fibrotic atria are spared from AFib due to an absence of arrhythmia triggers.