Atrial Myopathy

Abstract

This paper discusses the evolving concept of atrial myopathy by presenting how it develops and how it affects the properties of the atria. It also reviews the complex relationships among atrial myopathy, atrial fibrillation (AF), and stroke. Finally, it discusses how to apply the concept of atrial myopathy in the clinical setting-to identify patients with atrial myopathy and to be more selective in anticoagulation in a subset of patients with AF. An apparent lack of a temporal relationship between episodes of paroxysmal AF and stroke in patients with cardiac implantable electronic devices has led investigators to search for additional factors that are responsible for AF-related strokes. Multiple animal models and human studies have revealed a close interplay of atrial myopathy, AF, and stroke via various mechanisms (e.g., aging, inflammation, oxidative stress, and stretch), which, in turn, lead to fibrosis, electrical and autonomic remodeling, and a pro-thrombotic state. The complex interplay among these mechanisms creates a vicious cycle of ever-worsening atrial myopathy and a higher risk of more sustained AF and strokes. By highlighting the importance of atrial myopathy and the risk of strokes independent of AF, this paper reviews the methods to identify patients with atrial myopathy and proposes a way to incorporate the concept of atrial myopathy to guide anticoagulation in patients with AF.

Keywords: 4D, 4 dimensional; AF, atrial fibrillation; APD, action potential duration; CMR, cardiac magnetic resonance; CRP, C-reactive protein; Ca2+, calcium; Cx, connexin; GDF, growth differentiation factor; IL, interleukin; K+, potassium; LA, left atrial; LAA, left atrial appendage; NADPH, nicotinamide adenine dinucleotide phosphate; NOX2, catalytic, membrane-bound subunit of NADPH oxidase; NT-proBNP, N-terminal pro B-type natriuretic peptide; OAC, oral anticoagulant; ROS, reactive oxygen species; TGF, transforming growth factor; TNF, tumor necrosis factor; atrial fibrillation; atrial myopathy; electrophysiology; thrombosis.

Graphical abstract

Central Illustration

Atrial Myopathy: Its Relationship Between Atrial Fibrillation and Strokes Atrial myopathy is typically caused by insults such as aging, inflammation, oxidative stress, and stretching of the atria. These myopathic changes alter the properties of myocardial electrophysiology and cardiac autonomic nervous system. They can also lead to architectural structural changes characterized by fibrosis. Furthermore, atrial myopathy results in endothelial dysfunction and stasis, thereby a prothrombotic state. Electrophysiological remodeling and fibrosis facilitate the development of atrial fibrillation, which leads to more inflammation, fibrosis and autonomic remodeling, all of which contribute to a worsening prothrombotic environment, mediated by circulating inflammatory cytokines, chemokines and other molecules such as C-reactive protein (CRP), interleukin (IL)- 2, -6 and -8, tumor necrosis factor (TNF)-α, etc. Atrial fibrillation and thrombosis can develop separately and interact closely to further aggravate the underlying atrial myopathic processes. CRP = C-reactive protein; vWF = von Willebrand's Factor; WBC = white blood cell.

Figure 1

Stages of Atrial Myopathy AF = atrial fibrillation.

Figure 2

Atrial 4D Flow CMR in Patients With AF (A) Atrial 4-dimensional (4D) flow cardiac magnetic resonance (CMR) for 2 patients with AF with comparable left atrial (LA) volume and identical CHA₂DS₂-VASc scores = 1 indicating low thromboembolic risk. Velocity histograms (C) quantify the LA velocity distribution inside the (B) LA. (D) LA stasis maps depict the relative amount of low LA flow velocities (<0.2 m/s). Note the substantially increased flow stasis (red) in subject #51 compared with subject #35 despite identical CHA₂DS₂-VASc scores. Ao = aorta; LV = left ventricle; PA = pulmonary artery; RA = right atrium; other abbreviation as in Figure 1.