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 cm(2). 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.