Atrial Fibrosis, Ischaemic Stroke and Atrial Fibrillation

Abstract

Atrial fibrosis is an important component of the arrhythmic substrate in AF. Evidence suggests that atrial fibrosis also plays a role in increasing the risk of stroke in patients with the arrhythmia. Patients with embolic stroke of undetermined source (ESUS), who are suspected to have AF but are rarely shown to have it, frequently demonstrate evidence of atrial fibrosis; measured using late-gadolinium enhancement MRI, this manifests as atrial remodelling encompassing structural, functional and electrical properties. In this review, the authors discuss the available evidence linking atrial disease, including fibrosis, with the risk of ischaemic stroke in AF, as well as in the ESUS population, in whom it has been linked to recurrent stroke and new-onset AF. They also discuss the implications of this association on future research that may elucidate the mechanism of stroke and stroke prevention strategies in the AF and ESUS populations.

Matrix Metalloproteinases in Cardioembolic Stroke: From Background to Complications

“…The clinical implication of these findings is the fact that atria affected with the AF episode are more susceptible to consecutives arrhythmias, this was summarized with the concept that “AF begets AF”. Further stages of atrial remodeling include biomarkers activation, contractile dysfunction, enlargement of atrium and finally atrial walls fibrosis as a result of extracellular matrix activation, fibroblasts proliferation, oxidative stress, inflammation, apoptosis and necrosis [ 34 , 36 , 37 , 38 ]. During atrial fibrosis process, cardiomyocytes, lost as a result of apoptosis and necrosis in conditions of enhanced oxidative stress or inflammation, are replaced by compounds of ECM.…”

“…In abnormal conditions of blood stasis in the cavity of fibrillating atrium, blood coagulability enhances and consequently increases the risk of thrombus formation. The higher the burden of arrhythmia, the more probable risk of systemic thromboembolism and stroke [ 37 , 39 , 40 ].…”

Association Between Left Atrial Appendage Morphology and Function and the Risk of Ischaemic Stroke in Patients with Atrial Fibrillation

“…Atrial fibrosis in patients with AF may play a significant role in the development of electromechanical dysfunction leading to stasis and localised contractile dysfunction that may form the focus of thrombus formation. [ 50 ] Akoum et al used late gadolinium enhancement cardiac MRI to detect structural LAA dysfunction in patients with AF, finding that LAA fibrosis was associated with reduced LAA flow velocities, and thus with blood stasis, thrombus formation and the risk of stroke. [ 51 , 52 ]…”

Angiotensin‐receptor blocker losartan alleviates atrial fibrillation in rats by downregulating frizzled 8 and inhibiting the activation of WNT‐5A pathway

“…[6][7][8][9][10][11] Atrial fibrosis has the principal property of creating a substrate for AF, which results from the loss of myocytes and the replacement with collagen in the extracellular space leading to increased heterogeneity in the atrial tissues and an increased probability of arrhythmia initiation and sustenance. 12 These findings suggest that addressing atrial remodelling and atrial fibrosis are important for exploring the mechanism of AF and finding novel treatment approach.…”

“…Atrial fibrosis is a multi‐individual and multi‐factor process formed by the complex interaction mediated by cells and neurohormones leading to the redistribution of connective tissue and myocardial tissue, which is not only the stress response of the heart to various forms of injury, but also the end‐stage pathological manifestation of a variety of cardiovascular diseases 6–11 . Atrial fibrosis has the principal property of creating a substrate for AF, which results from the loss of myocytes and the replacement with collagen in the extracellular space leading to increased heterogeneity in the atrial tissues and an increased probability of arrhythmia initiation and sustenance 12 . These findings suggest that addressing atrial remodelling and atrial fibrosis are important for exploring the mechanism of AF and finding novel treatment approach.…”