Atrial Structural Remodeling in Patients With Atrial Fibrillation Is a Diffuse Fibrotic Process: Evidence From High-Density Voltage Mapping and Atrial Biopsy

Background Low-voltage areas (LVAs) in the atria of patients with atrial fibrillation are considered local fibrosis. We hypothesized that voltage reduction in the atria is a diffuse process associated with fibrosis and that the presence of LVAs reflects a global voltage reduction. Methods and Results We examined 140 patients with atrial fibrillation and 13 patients with a left accessory pathway (controls). High-density bipolar voltage mapping was performed using a grid-mapping catheter during high right atrial pacing. Global left atrial (LA) voltage (V_GLA) in the whole LA and regional LA voltage (V_RLA) in 6 anatomic regions were evaluated with the mean of the highest voltage at a sampling density of 1 cm². Patients with atrial fibrillation were categorized into quartiles by V_GLA. LVAs were evaluated at voltage cutoffs of 0.1, 0.5, 1.0, and 1.5 mV. Twenty-eight patients with atrial fibrillation also underwent right atrial septum biopsy, and the fibrosis extent was quantified. Voltage at the biopsy site (V_biopsy) was recorded. V_GLA results by category were Q1 (<4.2 mV), Q2 (4.2-5.6 mV), Q3 (5.7-7.0 mV), and Q4 (≥7.1 mV). V_RLA at any region was reduced as V_GLA decreased. V_GLA and V_RLA did not differ between Q4 and controls. The presence of LVAs increased as V_GLA decreased at any voltage cutoff. Biopsies revealed 11±6% fibrosis, which was inversely correlated with both V_biopsy and V_GLA (r=-0.71 and -0.72, respectively). V_biopsy was correlated with V_GLA (r=0.82). Conclusions Voltage reduction in the LA is a diffuse process associated with fibrosis. Presence of LVAs reflects diffuse voltage reduction of the LA.