Atrial Cardiomyopathy in Valvular Heart Disease: From Molecular Biology to Clinical Perspectives

Abstract

This review discusses the evolving topic of atrial cardiomyopathy concerning valvular heart disease. The pathogenesis of atrial cardiomyopathy involves multiple factors, such as valvular disease leading to atrial structural and functional remodeling due to pressure and volume overload. Atrial enlargement and dysfunction can trigger atrial tachyarrhythmia. The complex interaction between valvular disease and atrial cardiomyopathy creates a vicious cycle of aggravating atrial enlargement, dysfunction, and valvular disease severity. Furthermore, atrial remodeling and arrhythmia can predispose to atrial thrombus formation and stroke. The underlying pathomechanism of atrial myopathy involves molecular, cellular, and subcellular alterations resulting in chronic inflammation, atrial fibrosis, and electrophysiological changes. Atrial dysfunction has emerged as an essential determinant of outcomes in valvular disease and heart failure. Despite its predictive value, the detection of atrial fibrosis and dysfunction is challenging and is not included in the clinical routine. Transthoracic echocardiography and cardiac magnetic resonance imaging are the main diagnostic tools for atrial cardiomyopathy. Recently published data have revealed that both left atrial volumes and functional parameters are independent predictors of cardiovascular events in valvular disease. The integration of atrial function assessment in clinical practice might help in early cardiovascular risk estimation, promoting early therapeutic intervention in valvular disease.

Novel Biomarkers and Advanced Cardiac Imaging in Aortic Stenosis: Old and New

“…The increased LA pressure and wall stretch lead to the renin-angiotensin-aldosterone system (RAAS) and leukocyte activation-the main pathways to atrial fibrosis and cardiomyocyte hypertrophy [38].…”

“…RAAS activation promotes the activation of hydrolysis phospholipase C (PLC), the activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the release of reactive oxygen species (ROS), and it regulates the expression of profibrotic factors (TGF, CTGF) [38]. PLC activation leads to intracellular Ca 2+ overload and fibroblast proliferation [38]. The mitogen-activated protein kinase is stimulated by Ang II-AT1-R interaction, further regulating the transcription of some genes: MMP, PAI-1, CTGF, and TGF-β [37].…”

“…Leukocyte activation is also triggered at the LA level with the subsequent release of inflammatory stimuli [38]. Fibroblast proliferation and differentiation into the myofibroblast phenotype are activated.…”

“…Fibroblast proliferation and differentiation into the myofibroblast phenotype are activated. Thus, the extracellular matrix (ECM) components are released, including fibronectin, procollagen, laminin, elastin, fibrillin, proteoglycans, glycoproteins matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs [38].…”

“…This finding may be explained by the Frank-Starling mechanism: although initially acting as a compensatory mechanism in response to LA dilation, it can also lead to a deterioration in LA function with time [49]. Additionally, LA dysfunction might appear before LA enlargement and LV damage [38]. Until recently, the main underlying mechanism of LA dysfunction in AS was considered to be the increase in LA afterload through higher LV diastolic pressures [50].…”