Left Atrial Remodeling and Thromboembolic Risk in Patients With Atrial Fibrillation

Left atrial (LA) remodeling is a crucial substrate for atrial fibrillation (AF) and stroke. Increased pressure or volume results in overload in LA, which cause LA enlargement. LA enlargement and dysfunction lead to a prothrombotic condition characterized by blood stasis and endothelial dysfunction. LA fibrosis is another hallmark of structural remodeling and a substrate of AF. LA fibrosis also leads to increase of thromboembolic risk and contribute to subsequent thromboembolic events.

Kim et al.¹⁾ reported the results of their investigation of 139 patients with AF who underwent the first AF catheter ablation. The authors investigated association between spontaneous echo contrast (SEC) and multiple parameters of LA and LA appendage (LAA) remodeling measured from transesophageal echocardiography and cardiac magnetic resonance (CMR).

Remodeled LA forms the substrate for AF, then promotes AF progression. AF itself also promote LA structural remodeling. LA enlargement leads to further stasis and propensity to thrombosis. It is well known that LA size is an independent risk factor for stroke.²⁾ LA fibrosis is a marker for longstanding, progressed LA remodeling. Several studies reported that LA fibrosis was associated with increased risk of stroke.³⁾,⁴⁾ A previous research demonstrated that the presence of thrombus or SEC was associated with more severe LA late gadolinium enhancement (LGE) than those with normal findings.⁵⁾ King et al.³⁾ reported that advanced LA LGE was associated with increased risk of stroke or transient ischemic accidents. In a cross-sectional study among 387 patients with AF, presence of atrial fibrosis was more predictive of stroke than CHAD₂ risk score.⁶⁾ A recent article investigated the mechanisms that LA fibrosis leads to aberrant hemodynamics, contributing to increased stroke risk in AF patients.⁷⁾ Enlarged and fibrotic LA lead to impair LA function. LA function is important because it contributes 30% of the left ventricular (LV) stroke volume.⁸⁾ Impaired atrial contraction leads to stasis of blood flow, allowing blood clots to form in the LA or LAA, causing ischemic stroke. It is well known that impaired LA function is associated with increased risk of stroke and AF.⁹⁾ Impaired LA function was also associated with increased risk of stroke in non-AF patients.¹⁰⁾,¹¹⁾ In this study, LA size was related to SEC in patients with paroxysmal AF, and LA LGE was related to SEC in patients with persistent AF. Differences in AF duration may have contributed to these differences. Measurement of LA LGE is challenging because LA wall is very thin. However, recently advances in cardiac magnetic resonance techniques have made it possible to quantify LA LGE as a surrogate marker of LA fibrosis.¹²⁾ It is sometimes helpful for LA imaging assessment that the LA wall thickness in AF patients is thicker than in non-AF population. In this study, LA LGE was measured by experienced expert, and it was associated with SEC which was consistent with the results of previous reports.

LAA has been known as the most common site for clot formation in AF patients. Furthermore, it is well established that LAA anatomy and low blood flow in the LAA is associated with clot formation and stroke events in AF patients. Lee et al. reported that larger LAA orifice size and lower LAA flow velocity was associated with a high odds ratio of stroke in non-valvular AF patients with or without low CHA₂DS₂-VASc score.¹³⁾,¹⁴⁾ In this study, lower LAA emptying velocity was associated with SEC in persistent AF patients, which is consistent with previous reports.

The patient group included in this study did not have a very high CHA₂DS₂-VASc score. Although current guideline recommends initiation of oral anticoagulation in AF patients with a CHA₂DS₂-VASc score ≥2 (males) and ≥3 (females) for stroke prevention, stroke can occur even in patients with low and intermediate CHA₂DS₂-VASc score.¹⁵⁾ Current opinion statement of the European Society of Cardiology working group of cardiovascular pharmacotherapy and European Society of Cardiology Council on Stroke reported current opinion statement on oral anticoagulation in patients with AF, they suggest to consider additional thromboembolic risk factors, including increased LA size (LA volume ≥73 mL or diameter ≥4.7 cm) and decreased LAA emptying velocity <20 cm/s).¹⁶⁾

LA and LAA remodeling are significantly associated with thromboembolic risk (Figure 1), therefore these parameters should be considered along with CHA₂DS₂-VASc score to assess stroke risk stratification in patients with AF.

Figure 1. Association between left atrial remodeling and thromboembolic risk.

Left atrium and left atrial appendage remodeling are significantly associated with thromboembolic risk.