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Computational modeling identifies embolic stroke of undetermined source patients with potential arrhythmic substrate
Savannah F Bifulco1, Griffin D Scott1, Sakher Sarairah2
1Department of Bioengineering, University of Washington, Seattle, United States.
Elife
|May 4, 2021
Summary
Cardiac fibrosis in embolic stroke of undetermined source (ESUS) patients is similar to atrial fibrillation (AFib) patients. Computational models suggest ESUS patients may have latent fibrosis, potentially leading to future arrhythmias without triggers.
Area of Science:
- Cardiology
- Neurology
- Computational Biology
Background:
- Cardiac magnetic resonance imaging (MRI) reveals significant atrial fibrosis in embolic stroke of undetermined source (ESUS) patients, comparable to levels found in atrial fibrillation (AFib) patients.
- The presence of fibrosis, a known pro-arrhythmic substrate, raises questions about the absence of detectable arrhythmias in many ESUS patients.
Purpose of the Study:
- To computationally assess the arrhythmogenic capacity of atrial fibrosis in ESUS patients.
- To compare the intrinsic pro-arrhythmic properties of fibrosis between ESUS and AFib patients.
- To investigate the hypothesis that ESUS patients with fibrotic atria are protected from AFib by a lack of arrhythmia triggers.
Main Methods:
- Reconstruction of MRI-based atrial models for 45 ESUS and 45 AFib patients.
- Computational assessment of the arrhythmogenic potential of fibrotic substrates within these patient-specific models.
- Induction of reentrant drivers to evaluate substrate arrhythmogenicity.
Main Results:
- Reentrant drivers were computationally induced in 53% of ESUS models and 49% of AFib models.
- Models with inducible drivers exhibited significantly higher fibrosis percentages (16.7 ± 5.45%) compared to non-inducible models (11.07 ± 3.61%; p<0.0001).
- Crucially, the inducible subsets of ESUS and AFib models showed statistically indistinguishable levels of fibrosis (p=0.90), indicating similar intrinsic pro-arrhythmic substrate properties.
Conclusions:
- The fibrotic substrate in ESUS patients possesses intrinsic pro-arrhythmic properties comparable to those in AFib patients.
- ESUS patients may harbor latent, pre-clinical atrial fibrosis that represents a future arrhythmogenic risk.
- The absence of AFib in these ESUS patients could be attributed to a lack of initiating triggers, despite the presence of a susceptible substrate.
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