Embolic stroke of undetermined source correlates to atrial fibrosis without atrial fibrillation

Objective

To examine the hypothesis that atrial fibrosis and associated atrial cardiopathy may be in the causal pathway of cardioembolic stroke independently of atrial fibrillation (AF) by comparing atrial fibrosis burden between patients with embolic stroke of undetermined source (ESUS), patients with AF, and healthy controls.

Methods

We used late-gadolinium-enhancement MRI to compare atrial fibrosis in 10 patients with ESUS against 10 controls (no stroke, no AF) and 10 patients with AF. Fibrosis was compared between groups, controlling for stroke risk factors.

Results

Mean age was 51 ± 15 years, and 43% of participants were female. Patients with ESUS had more atrial fibrosis than controls (16.8 ± 5.7% vs 10.6 ± 5.7%, p = 0.019) and similar fibrosis compared to patients with AF (17.8 ± 4.8%, p = 0.65). Odds ratios of ESUS per quartile of fibrosis were 3.22 (95% CI [CI] 1.11–9.32, p = 0.031, unadjusted) and 3.17 (95% CI 1.05–9.52, p = 0.041, CHA₂DVASc score adjusted). Patients with >12% fibrosis had a higher percentage of ESUS (77.8% vs 27.3%, p = 0.02), and patients with >20% fibrosis had the highest proportion of ESUS (4 of 5).

Conclusions

Patients with ESUS exhibit similar atrial fibrosis compared to patients with AF and more fibrosis than healthy controls. Fibrosis is associated with ESUS after controlling for stroke risk factors, supporting the hypothesis that fibrosis is in the causal pathway of cardioembolic stroke independently of AF. Prospective studies are needed to assess the role of anticoagulation in primary and secondary stroke prevention in patients with high atrial fibrosis.