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

Abstract

Development of atrial fibrillation（AF）is closely associated with the progression of atrial structural remodeling. Fibrosis is considered a hallmark of structural remodeling, resulting in a substrate vulnerable to AF. Low-voltage areas（LVAs）identified in the left atrium（LA）by bipolar voltage mapping during catheter ablation have been considered local fibrosis. However, we hypothesized that voltage reduction in the atria is a diffuse process and that the presence of LVAs reflects a global voltage reduction. High-density bipolar voltage mapping was performed during high right atrial pacing to evaluate the relationship between bipolar voltage reduction in the whole LA and LVA. The results confirmed that the presence of LVAs reflects diffuse voltage reduction of the whole LA. We also developed atrial biopsy and demonstrated that the extent of fibrosis was inversely correlated with both bipolar voltage at the biopsy site and global LA voltage. Subsequent studies have revealed that histological correlates of atrial structural remodeling include increased intercellular space preceding fibrosis, fibrosis, myofibrillar loss, and decreased nuclear density. Further analysis of the process of atrial remodeling will help to elucidate the pathogenesis of AF and atrial cardiomyopathy and develop new therapeutic targets.