Abstract 4136863: Diffuse Functional and Structural Abnormalities in Fibrosis: Potential Structural Basis for Sustaining Atrial Fibrillation

Background: Structural remodeling is associated with atrial fibrillation (AF), but detailed structural and functional characteristics is not well defined. Goal: Using a novel transgenic goat model with cardiac-specific overexpression of TGF-β1 leading to increased cardiac fibrosis, we evaluated detailed structural and functional differences between fibrotic and healthy regions of the atria. Methods: Ex-vivo MRI and histology were used to evaluate fibrosis, fiber disarray, and structural anisotropy. Ex-vivo MRI intensity values were scaled to standard deviations around the mean. The functional analysis examined conduction speeds and direction heterogeneity. Conduction anisotropy was measured along the fiber direction obtained with diffusion tensor imaging. Results: The transgenic goats (n=12) had, on average, 21% of the left atria labeled as fibrotic determined from ex-vivo MRI. The histology samples taken from the labeled fibrotic regions had an increase in fibrosis percentage compared to labeled healthy regions (7.78±3.76% vs 2.80±1.86%, p<0.01). The structural anisotropy was lower in fibrotic regions (0.196±0.002 vs 0.244±0.002, p<0.01). Fiber disarray was greater in the fibrotic regions (20.3±0.2° vs 19.2±0.1°, p<0.01). The fibrotic regions had slower conduction speeds (0.78±0.02 m/s vs 1.12±0.02 m/s, p<0.01) and more aligned conduction directions (30.5±0.2° vs 31.6±0.1°, p<0.01), potentially developing unidirectional conduction block. Conduction anisotropy, measured on the fiber directions, was found to be lower in the fibrotic regions (1.86±0.05 vs 2.10±0.02, p=0.04). As scaled MRI intensity increased, the conduction speed, heterogeneity, and anisotropy all decreased. Conclusions: Functional and structural differences exist between fibrotic and healthy regions of the atria. Though statistically significant, the changes are not discrete. The correlation showed gradual functional abnormalities with MRI intensities. Fibrotic regions tended to have increased fiber disarray, slower conduction, and more unidirectional propagation with lower conduction and structural anisotropy. Diffuse functional and structural abnormalities may allow fibrotic regions to serve as a substrate to sustain AF.