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 The heart usually beats with a regular rhythm to pump the blood that carries oxygen and nutrients to different organs. Sometimes, alterations in the heart’s rhythm known as arrhythmias can occur. Atrial fibrillation, also called AFib, is a type of arrhythmia in which the heart beats rapidly and irregularly, causing abnormal blood-flow that can lead to the formation of blood clots. If one of these blood clots travels to the brain, it can block a blood vessel, causing a stroke. However, many strokes occur without any evidence of AFib. One subset of strokes that are not associated with AFib are embolic strokes of undetermined source (ESUS), which account for 25% of all strokes. By definition ESUS and AFib do not occur together, but both are associated with similar elevated levels of disease-related remodeling (i.e., fibrosis) in the heart tissue, which appears when the heart is injured. Fibrosis impairs the heart’s normal electrical activity. Bifulco et al. wanted to determine whether there is some fundamental difference in fibrosis between people with AFib and those who have had an ESUS event. To do this, they used a computational approach to model the geometries and patterns of fibrosis of the hearts of 45 ESUS patients and 45 patients with AFib, essentially producing a virtual version of each patient’s heart. Bifulco et al. then applied a virtual pace-maker (working in overdrive mode) to each heart model to determine whether electrical inputs that can lead to AFib had different effects on ESUS and AFib patients. The results showed that the electrical inputs had similar effects in all of the heart models. This led Bifulco et al. to conclude that ESUS and AFib patients have indistinguishable patterns of fibrosis. The key difference is that ESUS patients are missing the trigger to initiate the fibrillation process – if atrial fibrosis is the proverbial tinderbox, these triggers are the spark needed to ignite a fire. Further research, including confirmation of Bifulco et al.’s findings in live patients, will be needed to confirm the hypothesis that ESUS patients lack AFib primarily due to an absence of triggers. If this is indeed the case, these findings may make it easier to identify ESUS patients at higher risk for AFib or further strokes. Additionally, a better understanding of fibrosis as a link between stroke and AFib will help clinicians provide better, more personalized treatments, for example guiding whether a patient should take blood thinners or undergo more rigorous cardiac monitoring.

Informations de copyright

© 2021, Bifulco et al.

Déclaration de conflit d'intérêts

SB, GS, SS, ZB, CR, SN, CM, PK, MM, DT, WL, NA, PB No competing interests declared