Abstract 3370: Histological Substrate For Chronic Atrial Fibrillation
Background We hypothesize that significant neural and structural remodeling is present in the left atrium (LA), pulmonary veins (PVs) and LA-PV junction in patients with atrial fibrillation (AF).
Methods and Results A total of 23 biopsies were performed (8 of the right superior pulmonary vein (RSPV)-left atrium (LA) junction, 8 of the right inferior pulmonary vein (RIPV)-LA junction, and 7 of the right atrial appendage (RAA) in 5 patients with chronic AF and 3 patients in sinus rhythm (SR) (mean age 70.9±12.1 years, 75% women, mean LA diameter 51.3±7.1 mm, 87.5% NYHA class III-IV), who underwent cardiac surgery for mitral regurgitation (87.5%) or stenosis (12.5%). Specimens (average, 2.9±0.4 per patient) were preserved in Carnoy’s solution and processed for periodic acid-Schiff (PAS), trichrome and immunostaining for tyrosine hydroxylase (TH), growth-associated protein 43 (GAP43), cholineacetyltransferase (ChAT) and synaptophysin (SYN). Interstitial fibrosis was greater in AF (37±5.6 %) than SR patients (7.4±2.8%, p=0.009). Atrial myocarditis with lymphomononuclear infiltrates was observed in all AF patients and in 33% of SR patients (p=0.002). Intramyocardial and perivascular nerve twigs were found around areas of fibrosis, and the densities of TH-, GAP43-, SYN-, ChAT- positive nerves did not differ between AF and SR patients (5010±1545 vs 1782±276, 2503±723 vs 2521±1062, 2524±641 vs 3270±1272, 351±155 vs 424±170 μm2/mm2, respectively, p=NS). The density of TH-positive nerve twigs in AF patients was greater than the other nerve twigs (p=0.03). The subendocardial layer of PAS-positive cells did not differ in AF and SR patients (0.07±0.006 mm vs 0.08±0.02 mm, n = 5 and n = 3, respectively, p=NS). However, scattered subendocardial PAS-positive cells were present in 80% of AF patients and absent in SR patients (p=0.04).
Conclusions Patients with chronic AF have more fibrosis and myocarditis in LA and PVs than patients in SR. We also, for the first time, documented the presence of PAS-positive cells in human LA and PVs, and that these cells were scattered in the subendocardial layer in patients with AF but not in patients with SR.