Left Atrial Volume in Patients With Asymptomatic Aortic Valve Stenosis (the Simvastatin and Ezetimibe in Aortic Stenosis Study) Morten Dalsgaard, MD a, *, Kenneth Egstrup, MD, DMSc b , Kristian Wachtell, MD, PhD a , Eva Gerdts, MD, PhD c , Dana Cramariuc, MD c , Jesper Kjaergaard, MD, PhD a , and Christian Hassager, MD, DMSc a Left atrial (LA) size is known to increase with persistently increased left ventricular (LV) filling pressure. We therefore hypothesized that LA volume might reflect the severity of aortic valve stenosis (AS). Transthoracic echocardiography was performed in 1,758 pa- tients with asymptomatic AS (transaortic Doppler velocity >2.5 and <4 m/s) in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. LA volume was measured in end-systole in the apical 4-chamber view in 1,503 patients (85%), and aortic valve area (AVA) was estimated by the continuity equation and indexed by body surface area. Mean values for age and AVA were 67  10 years and 1.27  0.5 cm 2 , respectively, and 574 were women (38%). Mean value for LA volume indexed (LAVI) was 36  13 ml/m 2 . Enlarge- ment of LA volume (>32 ml/m 2 ) was found in 57% of patients. AVA indexed was significantly correlated to LAVI (r 0.1, p  0.0002). Multivariate analysis showed that LAVI was significantly related to AVA indexed (beta 4.1, p  0.007) in a model that also included mitral regurgitation (beta  2.8, p <0.0001), history of hypertension (beta  2.2, p  0.002), LV end-diastolic volume (beta  0.05, p <0.0001), presence of LV hypertrophy (beta  3.4, p <0.0001), and restrictive LV filling pattern (beta  3.5, p  0.01). Gender and LV ejection fraction were eliminated from the final model. In conclusion, LA volume is often enlarged in asymptomatic patients with AS. Furthermore, LA volume is related to AVA even when adjusting for other known risk factors for increased LA volume including of measurements of diastolic function. © 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;101:1030 –1034) Because left atrial (LA) size is known to increase with persistently increased left ventricular (LV) filling pressure, LA volume might reflect the severity of the disease in patients with aortic valve stenosis (AS). 1–3 The aim of this study was to investigate if LA volume is related to degree of stenosis in patients with asymptomatic AS and if LA vol- ume is related to structural LV changes known to occur in these patients. Methods This study is an echocardiographic baseline substudy to the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. SEAS is a multicenter, double-blinded, randomized, placebo- controlled study to evaluate the effect of ezetimibe and sim- vastatin on clinical outcome in patients with AS. Enrolled in the SEAS study were 1,873 patients 45 years of age with mild to moderate AS and preserved LV ejection fraction. Mild to moderate AS was defined as aortic valve thickening at echocardiographic evaluation accompanied by a Doppler- measured peak flow velocity 2.5 and 4.0 m/s across the valve. Echocardiographic parameters used were analyzed at the echocardiography core laboratory from digitalized video recordings using Tomtec Image-Arena (Unterschleissheim, Germany). Patients with clinically significant mitral valve stenosis or regurgitation or severe or predominant aortic regurgita- tion were excluded. Patients with LV systolic dysfunction, coronary heart disease, diabetes mellitus, renal insuffi- ciency, and history of stroke or peripheral vascular disease also were excluded. Details about the SEAS study protocol, design, and patient recruitment have recently been pub- lished. 4 Transthoracic echocardiogram was readable in 1,758 patients at baseline. LA volume measurements were possible in 1,503 patients (85%), constituting the study population used in the present study. Compared with this substudy population, the 370 ineligible patients did not differ in age, gender, body mass index, or aortic valve area (AVA; data not shown). The SEAS study was approved by regional ethics committees in all participating countries. All patients gave written informed consent to participate in the SEAS study. LA volume was measured in LV end-systole by the modified Simpson monoplane method in the apical 4-cham- ber view. 5 If possible, LA volume was measured by the biplane Simpson method in apical 2- and 4-chamber views (n = 948). 5 Measurements for LA volume were indexed a Department of Cardiology, Copenhagen University Hospital Rigshos- pitalet, Copenhagen, and b Department of Medicine, Svendborg Hospital, Svendborg, Denmark; and c Institute of Medicine, University of Bergen, Bergen, Norway. Manuscript received September 30, 2007; revised manu- script received and accepted November 21, 2007. This study was funded by Grant 06-10-B317-A1186-22339 from the Danish Heart Foundation (Copenhagen, Denmark) to Dr. Dalsgaard. *Corresponding author: Tel: 45-3545-3545; fax: 45-3545-2513. E-mail address: morten.dalsgaard@rh.regionh.dk (M. Dalsgaard). 0002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. www.AJConline.org doi:10.1016/j.amjcard.2007.11.048