Atrial matrix remodeling in atrial fibrillation patients with aortic stenosis

Abstract

Background 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. 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 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 versus 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.

Severe Aortic Valve Stenosis and Pulmonary Hypertension: A Systematic Review of Non-Invasive Ways of Risk Stratification, Especially in Patients Undergoing Transcatheter Aortic Valve Replacement

“…It should mean that adverse cardiac remodeling associated with moderate to severe AS plays a central role in the development of other cardiovascular and cerebrovascular events, such as atrial fibrillation, TIA/stroke, acute coronary syndrome/acute myocardial infarction, conversion of HF with preserved ejection fraction to HF with reduced ejection fraction and fatal arrhythmias/sudden cardiac death [66,67]. PH is not only frequently accompanied by adverse cardiac remodeling, but it is also promoted by cumulative effects of HF, atrial fibrillation and other factors such as preload and afterload, skeletal muscle weakness and metabolic disease (diabetes, obesity and thyroid dysfunction) [68][69][70][71][72].…”

Pericardial NT-Pro-BNP and GDF-15 as Biomarkers of Atrial Fibrillation and Atrial Matrix Remodeling in Aortic Stenosis

“…cDNA (100 ng/µL) was synthesized using the SensiFAST TM cDNA Synthesis Kit from Meridian Bioscience Inc ® (Cincinnati, Ohio, United States), with reactions conducted in a T100 thermal cycler from Bio-Rad ® (Hercules, California, United States). RT-qPCR reactions were performed using the PikoReal TM Real-Time PCR System from Thermo Fisher Scientific ® (Waltham, Massachusetts, United States), using previously described protocols [19]. Before gene expression quantification using the 2 −∆CT method, PCR efficiency of each gene, including the internal control gene (18s RNA) was determined and it was assured they were identical.…”

Pericardial Fluid Annexin A1 Is a Marker of Atrial Fibrillation in Aortic Stenosis: A Proteomics Analysis

“…Myocardial hypertrophy may contribute to AF pathophysiology through abnormal calcium handling, causing ectopic triggers from delayed afterdepolarisations [3]. Recently, LA fibrosis and collagen type III gene expression were found increased in AF patients with AS, although the tissue inhibitor of metalloproteases (TIMPs) 1 and matrix metalloprotease (MMP) 16/TIMP4 ratio gene expression were decreased, suggesting extracellular matrix remodelling in this subset of patients [4]. Proteome analysis through mass spectrometry (MS) improved current medical research by allowing the identification of a large spectrum of proteins at once, excusing the need of mining scientific literature to select hypothetical biomarkers of a given disease.…”

“…However, to the best of our knowledge, biomarkers of AF in the setting of AS are yet to be identified, which could help stratify patients according to the risk of developing short-and long-term outcomes after surgery or in AS in general. Furthermore, classical biomarkers of AS severity, such as aortic valve maximum and mean gradients, are reduced in AF, with markers associated with fibrosis and remodelling predicting worse outcomes [4]. Moreover, former studies have low sample size, either in proteome discovery phase or in the subsequent validation stage, usually by Western blotting.…”