Histological validation of atrial structural remodelling in patients with atrial fibrillation.

BACKGROUND AND AIMS: This study aimed to histologically validate atrial structural remodelling associated with atrial fibrillation. METHODS AND RESULTS: Patients undergoing atrial fibrillation ablation and endomyocardial atrial biopsy were included (n = 230; 67 ± 12 years old; 69 women). Electroanatomic mapping was performed during right atrial pacing. Voltage at the biopsy site (Vbiopsy), global left atrial voltage (VGLA), and the proportion of points with fractionated electrograms defined as ≥5 deflections in each electrogram (%Fractionated EGM) were evaluated. SCZtotal was calculated as the total width of slow conduction zones, defined as regions with a conduction velocity of <30 cm/s. Histological factors potentially associated with electroanatomic characteristics were evaluated using multiple linear regression analyses. Ultrastructural features and immune cell infiltration were evaluated by electron microscopy and immunohistochemical staining in 33 and 60 patients, respectively. Fibrosis, intercellular space, myofibrillar loss, and myocardial nuclear density were significantly associated with Vbiopsy (P = .014, P < .001, P < .001, and P = .002, respectively) and VGLA (P = .010, P < .001, P = .001, and P < .001, respectively). The intercellular space was associated with the %Fractionated EGM (P = .001). Fibrosis, intercellular space, and myofibrillar loss were associated with SCZtotal (P = .028, P < .001, and P = .015, respectively). Electron microscopy confirmed plasma components and immature collagen fibrils in the increased intercellular space and myofilament lysis in cardiomyocytes, depending on myofibrillar loss. Among the histological factors, the severity of myofibrillar loss was associated with an increase in macrophage infiltration. CONCLUSION: Histological correlates of atrial structural remodelling were fibrosis, increased intercellular space, myofibrillar loss, and decreased nuclear density. Each histological component was defined using electron microscopy and immunohistochemistry studies.

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 (VGLA) in the whole LA and regional LA voltage (VRLA) 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 VGLA. 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 (Vbiopsy) was recorded. VGLA 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). VRLA at any region was reduced as VGLA decreased. VGLA and VRLA did not differ between Q4 and controls. The presence of LVAs increased as VGLA decreased at any voltage cutoff. Biopsies revealed 11±6% fibrosis, which was inversely correlated with both Vbiopsy and VGLA (r=-0.71 and -0.72, respectively). Vbiopsy was correlated with VGLA (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.