Atrial Matrix Remodeling In Atrial Fibrillation Patients With Aortic Stenosis.

Introduction Atrial fibrillation (AF) is the most common cardiac arrhythmia with adverse clinical outcomes and diverse pathophysiological background. Aortic stenosis is the most prevalent valvular disease, with Aortic Valve Replacement (AVR) surgery remaining the gold standard treatment for severe symptomatic aortic stenosis, improving both quality of life and overall survival. However, the pathophysiology of AF in aortic stenosis is poorly understood. Evidence suggests atrial remodeling is associated with disease occurrence and progression, which involves specific molecular markers of fibrosis. Objectives This study aimed to evaluate atrium extracellular matrix remodeling in Atrial fibrillation (AF) patients with severe aortic stenosis, through histological fibrosis quantification and extracellular matrix gene expression analysis, as well as serum quantification of selected protein targets. Materials and Methods A posthoc analysis of a prospective study was performed in a cohort of aortic stenosis patients. Between 2014 and 2019, 56 patients with severe aortic stenosis submitted to Aortic valve replacement (AVR) surgery in a tertiary hospital were selected. Results Fibrosis was significantly increased in the AF group when compared to Sinus Rhythm (SR) patients (p=0.024). Moreover, cardiomyocyte area was significantly higher in AF patients vs SR patients (p=0.008). Conversely, collagen III gene expression was increased in AF patients (p=0.038). TIMP1 was less expressed in the atria of AF patients. MMP16/ TIMP4 ratio was significantly decreased in AF patients (p=0.006). TIMP1 (p=0.004) and TIMP2 (p=0.012) were significantly increased in the serum of AF patients. Aortic valve maximum (p=0.0159) and mean (p=0.031) gradients demonstrated a negative association with serum TIMP1. Conclusions Atrial fibrillation patients with severe aortic stenosis present increased atrial fibrosis and collagen type III synthesis, with extracellular matrix remodelling demonstrated by a decrease in the MMP16/TIMP4 ratio, along with an increased serum TIMP1 and TIMP2 proteins.