Atrial Fibrosis Correlates with Slower Conduction in a Transgenic Goat Model

Eugene Kwan1, Elyar Ghafoori1, Wilson Good2, Rob MacLeod1, Edward Hsu1, Boyce Moon3, Jeffrey Fish3, Misha Regouski4, Irina Polejaeva4, Derek Dosdall1, Ravi Ranjan1
1University of Utah, 2The SCI Institute, 3Abbott, 4Utah State University


Introduction: Slow conduction zones in the left atrium (LA) may be regions of interest in sustaining, and thus ablating, atrial fibrillation (AF). Our goal was to measure the extent of slowed conduction speed and its relationship to zones of fibrosis, using a transgenic goat model. Methods: High-density electrophysiology mapping studies were performed on transgenic goats (n=10) with cardiac-specific overexpression of TGF-Beta 1 using a prototype high-density catheter and the Advisor™ HD Grid Mapping Catheter, Sensor Enabled,™ with the Ensite™ Precision Cardiac Mapping System (Abbott). LA activation times were collected during sinus rhythm and conduction velocity estimated using triangulation on the LA surface mesh. The animal received a gadolinium injection 20 minutes before sacrifice, and a T1-weighted delayed contrast-enhanced MRI was performed on the explanted heart using a 7T scanner to visualize areas of fibrosis. Calculated conduction speed was correlated with normalized MRI intensity. The high-intensity region was defined as normalized intensity >0.75. Masson trichrome staining of the tissue was performed to determine fibrosis content. Results: A mean of 899 ± 184 points per animal were used for conduction velocity calculations. The mean conduction speed for all animals was 0.75 m/s. The high-intensity regions had a mean conduction speed of 0.45 ± 0.24 m/s, slower than the value measured in low-intensity regions of 0.85 ± 0.28 m/s, (p<0.001). The high-intensity regions had a mean fibrosis percentage of 10.4% ± 4.0% while low-intensity regions had a mean fibrosis percentage of 4.5% ± 2.4%. Conclusion: We show reduced conduction speed in fibrotic regions suggesting that fibrosis plays a key role in conduction slowing in the atria and is likely important in allowing reentrant circuits to occur and sustain AF.