Left Atrial Structure and Function in Atrial Fibrillation: ENGAGE AF–TIMI 48

Study Questions:

What is the relationship between left atrial (LA) structure and function, type and burden of atrial fibrillation (AF), and stroke risk?


This study examined 971 patients from the echocardiographic substudy of the ENGAGE AF–TIMI 48 study, a multicenter randomized trial comparing two doses of edoxaban vs. warfarin in patients with a history of AF and moderate to high risk of stroke. LA size, LA emptying fraction (LAEF), and contraction were compared between groups based on electrical burden of AF (paroxysmal, persistent, or permanent) and stroke risk based on CHADS2 score. Patients with reversible AF, severe renal dysfunction, high bleeding risk, or at least moderate mitral stenosis were excluded.


There was an inverse linear relationship between LA size and LAEF (r = -0.57, p < 0.001), with a similar relationship observed in subjects with sinus rhythm or AF during echocardiography. The majority of patients (55%) had an enlarged LA volume index (LAVI) and reduced LAEF, while a significant cohort (19%) had a reduced LAEF despite normal LAVI, and only 17% had normal LAVI and LAEF. An increasing electrical burden of AF (paroxysmal, persistent, vs. permanent) was associated with an increase in LAVI (29.9 vs. 33.6 vs. 37.4 ml/m2, p-trend < 0.001), decrease in LA emptying fraction (41.5 vs. 37.5 vs. 35.0%, p-trend < 0.001), and decreased LA expansion index (75.9 vs. 63.3 vs. 57.6%, p-trend < 0.001). Higher CHADS2 scores were associated with increased LA size and decreased LAEF. After multivariable adjustment, an increased LAVI was associated with a higher CHADS2 score.


The authors concluded that the presence of increased electrical burden of AF and higher CHADS2 scores are associated with greater abnormalities in LA size and function.


Current anticoagulation strategies are generally simplified, with patients typically treated without regard for the frequency of AF or the anatomy and function of the LA. Interestingly, this study found that in patients with AF and normal LA size, over one half had reduced LAEF, with a consistent pattern observed regardless of whether patients were in AF or sinus rhythm at the time of the study. While prior literature examining the relationship between stroke risk and LA size has had inconsistent results, these findings suggest that further variables such as LA function may be helpful to improve our risk discrimination size alone. Further investigation may be merited to determine whether the addition of LA anatomy and function to clinical risk models can improve our ability to identify AF patients at increased risk of stroke.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Dyslipidemia, Noninvasive Imaging, Valvular Heart Disease, Lipid Metabolism, Novel Agents, Echocardiography/Ultrasound

Keywords: Blood Coagulation, Atrial Function, Left, Myocardial Infarction, Warfarin, Mitral Valve Stenosis, Cardiovascular Diseases, Thiazoles, Pyridines, Factor Xa, Echocardiography

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