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Review
. 2023 Jul 6;12(13):1796.
doi: 10.3390/cells12131796.

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

Andrea Ágnes Molnár  1 , Attila Sánta  1 , Dorottya Tímea Pásztor  1 , Béla Merkely  1
Affiliations
Review

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

Andrea Ágnes Molnár et al. Cells. .

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.

Keywords: aortic valve stenosis; atrial cardiomyopathy; fibrosis; mitral valve regurgitation.

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Conflict of interest statement

The authors declare that the review was conducted in the absence of any commercial or financial relationships that could be construed as potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic illustration of atrial cardiomyopathy in valvular heart disease. Valvular heart disease, such as primary (organic) mitral valve (MV) regurgitation due to leaflet prolapse (white arrow), leads to atrial volume and/or pressure overload and consequent increased atrial wall stress (green arrows), which results in cardiomyocyte apoptosis, cardiomyocyte dedifferentiation, and atrial fibrosis. Atrial dysfunction and/or atrial dilatation with electrophysiological remodeling develops defined as atrial cardiomyopathy. Atrial cardiomyopathy leads to annular dilatation and exaggerates valve malcoaptation. Atrial fibrillation might develop and increase the risk of stroke. Notably, longstanding permanent atrial fibrillation without initial valvular heart disease may lead to atrial dilatation, subsequent annular dilatation, and secondary (functional) mitral or tricuspid valve regurgitation. Aortic stenosis may also promote atrial cardiomyopathy due to pressure overload. In advanced stages of aortic stenosis, functional mitral or tricuspid regurgitation can be detected due to mitral or tricuspid annulus dilatation. Heart failure symptoms develop when the adaptive mechanisms fail to further compensate the pathophysiological changes. LA: left atrium; LV: left ventricle.
Figure 2
Figure 2
Schematic illustration of cellular and molecular changes in valvular disease leading to atrial fibrosis and cardiomyocyte hypertrophy. Valvular disease leads to increased left atrial (LA) pressure and wall stretch resulting in renin–angiotensin–aldosterone system (RAAS) and leukocyte activation, which promote atrial fibrosis. NADPH: nicotinamide adenine dinucleotide phosphate; ROS: reactive oxygen species; MAPK: mitogen-activated protein kinase; Ca: calcium; AT-1R: angiotensin type 1 receptor; PLC: phospholipase C; IP3: inositol triphosphate 3; DAG: diacylglycerol; PKC: protein kinase C; TGF-β: transforming growth factor β; CTGF: connective tissue growth factor; ECM: extracellular matrix.
Figure 3
Figure 3
Representative image of left atrial strain analysis using two dimensional speckle tracking echocardiography in case of a normal subject (left panel) and valvular heart disease patient (right panel). The absolute values of reservoir, conduit, and contraction strain parameters are significantly decreased in the valvular heart disease case, suggesting left atrial dysfunction. LA: left atrium.
Figure 4
Figure 4
Representative two-dimensional transthoracic echocardiography image showing primary mitral regurgitation due to prolapse of posterior mitral valve leaflet (red arrow) leading to eccentric mitral regurgitation (white arrow). The left atrial reservoir function is decreased (1.) LA: left atrium; RA: right atrium; LV: left ventricle; RV: right ventricle; MV: mitral valve; (2.) conduit strain; (3.) contraction strain.
Figure 5
Figure 5
Representative two-dimensional transthoracic echocardiography image showing severe tricuspid regurgitation (white arrow) and decreased right atrial reservoir function. RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle.
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