Biatrial Inflammatory and Fibrotic Remodeling in Severe Aortic Stenosis Compared with CABG Controls

Background: Extensive prior work has established severe aortic stenosis as a whole-heart remodeling process involving chronic pressure overload, concentric hypertrophy, myocardial stiffness, and progressive ventricular fibrosis. However, direct paired histological characterization of both atria remains limited. Methods: This single-center observational comparative study included 28 patients with severe aortic stenosis referred for surgical aortic valve replacement and 14 coronary artery bypass grafting (CABG) controls without significant valvular disease, consecutively enrolled between 9 May 2024 and 28 April 2025. Left- and right-atrial tissue samples were collected intraoperatively. The relative expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta (TGF-beta) was quantified by RT-qPCR using pooled tissue samples and interpreted descriptively as a group-level molecular output. Atrial fibrosis was measured histologically at the patient level using Masson’s trichrome staining and digital image analysis. Results: Compared with CABG controls, patients with severe aortic stenosis demonstrated greater left-atrial fibrosis (median: 19.12% [IQR: 16.12–23.12] vs. 11.54% [9.53–14.29]; p < 0.0001) and right-atrial fibrosis (16.33% [15.07–19.13] vs. 8.40% [5.75–11.27]; p = 0.0001). Pooled RT-qPCR outputs descriptively suggested higher IL-6, TNF-alpha, and TGF-beta expression in both atria, although biological replication was insufficient for inferential testing. Echocardiographically, the aortic stenosis group showed higher aortic jet velocity and transvalvular gradients, thicker ventricular walls, a larger right-ventricular diameter, higher pulmonary artery systolic pressure, and a larger estimated left-atrial volume. A sensitivity analysis of 13 within-group correlations found that no correlation retained statistical significance at q < 0.05. Exploratory regressions restricted to patient-level histological outcomes suggested that severe aortic stenosis status remained associated with left- and right-atrial fibrosis after limited adjustment for age and sex. Conclusions: These findings complement the extensive ventricular fibrosis literature by providing paired human biatrial tissue evidence of greater atrial fibrosis in severe aortic stenosis compared with CABG controls. The pooled molecular findings remain descriptive and require validation using patient-level biological measurements.