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  1. 1. Predictive Value of Normal Left Atrial Volume in Stress EchocardiographyAhmed A. Alsaileek, Martin Osranek, Kaniz Fatema, Robert B. McCully, Teresa S. Tsang, and James B. Seward J. Am. Coll. Cardiol. published online Feb 8, 2006; doi:10.1016/j.jacc.2005.09.069 This information is current as of December 6, 2010 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://content.onlinejacc.org/cgi/content/full/j.jacc.2005.09.069v1 Downloaded from content.onlinejacc.org by on December 6, 2010
  2. 2. ARTICLE IN PRESSJournal of the American College of Cardiology Vol. 47, No. 5, 2006© 2006 by the American College of Cardiology Foundation ISSN 0735-1097/06/$32.00Published by Elsevier Inc. doi:10.1016/j.jacc.2005.09.069Predictive Value of Normal LeftAtrial Volume in Stress EchocardiographyAhmed A. Alsaileek, MD, Martin Osranek, MD, Kaniz Fatema, PHD, Robert B. McCully, MD,Teresa S. Tsang, MD, James B. Seward, MDRochester, Minnesota OBJECTIVES Our objective was to evaluate whether normal left atrial volume index (LAVI) is a predictor of a normal stress echocardiogram and thus a predictor of low ischemic risk. BACKGROUND Left atrial enlargement is closely related to the chronicity and intensity of the burden of increased ventricular filling pressure. Typically ischemic heart disease (IHD) has a long period of subclinical dysfunction. Increased filling pressure, reflected by enlarged LAVI, is hypoth- esized to mirror the burden of subclinical and overt IHD. We hypothesized that a normal LAVI might also be useful in predicting low IHD risk. METHODS One hundred eighty randomly selected patients (mean age, 63 15 years; 53% men) underwent outpatient exercise or dobutamine stress echocardiography for known or suspected coronary artery disease. Left atrial volume index was measured retrospectively with the biplane area-length method. The stress echocardiogram was interpreted as abnormal if wall motion abnormalities (WMAs) were noted at rest and/or with stress. RESULTS Left atrial volume index was categorized as 28 ml/m2 (normal), 28.1 to 32 ml/m2, 32.1 to 36 ml/m2, and 36 ml/m2. Abnormal stress echocardiography was identified in 57 patients (31.7%). The percentage of abnormal stress echocardiograms in each LAVI category was 5.7%, 21.9%, 38.7%, and 54.7%, respectively. The negative predictive value for LAVI 28 ml/m2 was 94.3%. CONCLUSIONS Normal resting LAVI ( 28 ml/m2) was strongly predictive of a normal stress echocardio- gram. Left atrial volume index might be a simple means of identifying patients with low ischemic risk and should be further evaluated as a complement to the assessment of ischemic risk. (J Am Coll Cardiol 2006;47:1024 – 8) © 2006 by the American College of Cardiology FoundationLeft atrial volume index (LAVI) is a preferred method for stress echocardiography database to identify patients whodetermining LA size and provides incremental prognostic had undergone clinically indicated outpatient exercise orinformation beyond that afforded by clinical risk factors (1,2). dobutamine stress echocardiography between February 1,Left atrial volume index reflects the chronicity and magnitude 2004, and March 31, 2004. The entry criterion was restingof the increased left ventricular (LV) filling pressure and is two-dimensional images appropriate for blinded retrospec-closely related to general cardiovascular risk burden (3–5). tive off-line measurement of LAVI. Exclusion criteria wereIschemic heart disease (IHD) has been demonstrated to cause images inadequate for measuring LAVI, an indeterminatesubclinical diastolic dysfunction before systolic dysfunction stress result, and denial of research authorization. Of 1,000becomes evident (6 – 8). patients, we randomly selected a sample of 200 subject Multiple studies have shown the value of normal LAVI studies with a computer algorithm.for the prediction of general cardiovascular risk (9 –14) and Data acquisition. Atrial volume, with the biplane area-a normal stress test for the prediction of low ischemic risk length method, was indexed to body surface area. With(15–18). Our study specifically addressed the hypothesis off-line rest images obtained before the stress test, LAVIthat a normal resting LAVI is also predictive of a normal was measured at the end of ventricular systole just beforestress echocardiogram and a low risk of IHD. In many opening of the mitral valve (1). Left atrial volume (LAV)clinical settings, stress testing might not be available, was calculated as follows:whereas it is often possible to obtain a focused echocardio-graphic examination, which could include measurement of Area4-chamber Area2-chamberLAVI. 0.85 Shortest lengthMETHODS Normal and abnormal LAVIs have been previously pub-Study population. Approval was obtained from the insti- lished (5,19,20). For this study, we used LAVI 28 ml/m2tutional review board of the Mayo Foundation. We used the as normal. As published previously (21,22), the stress echocardio- From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. grams were interpreted as normal if wall motion was normalDr. Osranek was supported by post-doctoral fellowships from the Austrian Science Fund both at rest and with stress. Wall motion abnormalities(Schrödinger Stipend) and the American Heart Association. Manuscript received May 23, 2005; revised manuscript received August 16, 2005, (WMAs) were divided into three groups: 1) fixed—WMAaccepted September 19, 2005. at rest, which remained unchanged with stress; 2) mixed— Downloaded from content.onlinejacc.org by on December 6, 2010
  3. 3. ARTICLE IN PRESSJACC Vol. 47, No. 5, 2006 Alsaileek et al. 1025March 7, 2006:1024–8 Predictive Value of Normal Left Atrial Volume LAVI measurement had not been obtained. Of the 180 Abbreviations and Acronyms remaining patients, 96 (53%) were men (mean age, 63 15 CAD coronary artery disease years; range, 27 to 89 years) and 47.8% underwent dobut- IHD ischemic heart disease amine stress echocardiography. The patients’ baseline char- LAV left atrial volume acteristics are presented in Table 1. LAVI left atrial volume index LV left ventricle/ventricular Normal LAVI. Normal LAVI (LAVI 28 ml/m2) was WMA wall motion abnormality found in 53 patients (29.4%) (mean age, 59 13 years; range, 27 to 85 years); 45% were men and 36% underwent dobutamine stress echocardiography (Table 2). The indica-WMA at rest and additional WMA with stress; and 3) new tions for stress testing in patients with normal LAVI wereWMA—no WMA at rest and new WMA with stress. chest pain and shortness of breath in 52.8%, preoperativeStatistical analysis. Results are presented as mean values assessment in 20.8%, known coronary artery disease (CAD)SD for continuous variables and as frequency percentages for in 11.3%, and other in 15%. Of 53 patients with normalcategorical variables. Group comparisons were performed with LAVI, 50 (94.3%) had completely normal stress echocar-a standard t test or chi-square test, as appropriate. Univariate diograms and 3 (5.7%) had fixed WMA of a small localizedassociations of stress echocardiographic (normal/abnormal area in the inferior wall (Fig. 1). No patient with LAVI 28test), LAVI, and clinical variables were assessed with logistic ml/m2 had stress echocardiography with ischemic or mixedmodels. The effect of LAVI on stress echocardiographic WMA (positive for ischemia). Normal LAVI had 94.7%variables was also estimated with a logistic model after sensitivity, 41% specificity, 94.3% negative predictive value,adjusting for age, gender, low ejection fraction ( 0.50), and 42.9% positive predictive value for abnormal stressLV end-diastolic diameter, and LV hypertrophy. Left atrial echocardiography.volume index was used as a dichotomous variable (LAVI LAVI and stress echocardiography results. Wall motion 28 ml/m2) in all the models. Significance was defined as p was interpreted as being entirely normal (no WMA) in 123 0.05 for all analyses. Some clinically significant variables patients (68.3%) and abnormal (any WMA) in 57 (31.7%).were forced into the model with an insignificant p value. The indications for stress echocardiography in normal andThe interobserver variability for LAV measurements was abnormal studies were chest pain and shortness of breath indetermined for 20 randomly selected studies. The LAV 43.1% versus 28.1%, preoperative assessment in 28.4%measurement was obtained by two independent observers, versus 33.3%, known CAD in 10% versus 29.8%, and otherand the interclass correlation was estimated to be 0.91 (95% in 18.5% versus 8.8%, respectively. For patients with normalconfidence interval, 0.82 to 0.96). wall motion, LAVI was 31.9 10.6 ml/m2 (range, 16.9 to 68.8 ml/m2), and for those with abnormal wall motion,RESULTS LAVI was 42.7 12.8 ml/m2 (range, 23.3 to 79.9 ml/m2)Of the 200 randomly selected patients, 20 (10%) were (p 0.0001) (Fig. 2). Left atrial volume index was largestexcluded because echocardiographic images suitable for for older patients with mixed WMA, 46.5 13.2 ml/m2.Table 1. Clinical and Echocardiographic Features of the Study Group, Categorized by Stress Echocardiography Results Myocardial Wall Motion Abnormal (n 57) Feature Normal (n 123) Ischemic (n 12) Fixed (n 19) Mixed (n 26)Age, yrs, mean SD (range) 61 15 (27–89) 63 14 (36–86) 67 12 (51–88) 72 9* (50–89)Men, % 46 50 63 80*WMSI, mean SD Resting 1.0 0.0 1.02 0.07 1.5 0.5* 1.5 0.4* At peak 1.0 0.0 1.2 0.3* 1.4 0.5* 1.7 0.5*LAVI, ml/m2, mean SD (range) 31.9 10.6 (16.9–68.8) 38.6 10.8* (29.2–61.4) 39.7 12.3* (23.3–77.3) 46.5 13.2* (30.2–80)Dobutamine echo, % 43 60 63 57LV wall thickness, mm Septal 9.5 1.3 10.4 1.1 9.6 1.7 9.9 1.3 Posterior wall 9.5 1.4 9.1 1.3 9.2 1.3 9.7 1.4LV dimensions, cm LVDD 4.6 0.4 4.8 0.6 5.2 0.6* 5.1 0.8* LVSD 3.1 0.3 3.3 1.0 4.0 0.7* 3.7 0.8*LVEF, % Resting 61.2 4.2 64.0 4.2 50.8 12.6* 50.0 13.4* At peak 74.0 5.6 71.7 7.8 61.4 14.3* 56.2 15.6**p 0.05 compared with the normal. EF ejection fraction; LAVI left atrial volume index; LV left ventricular; LVDD left ventricular end-diastolic; LVSD left ventricular end-systolic; WMSI wallmotion score index. Downloaded from content.onlinejacc.org by on December 6, 2010
  4. 4. ARTICLE IN PRESS1026 Alsaileek et al. JACC Vol. 47, No. 5, 2006 Predictive Value of Normal Left Atrial Volume March 7, 2006:1024–8Table 2. Clinical and Echocardiographic Features of the Study Group, Categorized by LAVI Results LAVI Categories, ml/m2 Feature <28 (n 53) 28.1–32 (n 32) 32.1–36 (n 31) >36 (n 64)Age, yrs, mean SD (range) 59 13 (27–85) 56 12 (32–80) 63 13 (35–86) 71 13* (44–89)Men, % 45 59 45 61BMI, kg/m2, mean SD 28.9 5.3 30.1 8.3 28.5 5.1 27.7 5.2WMSI, mean SD Resting 1.01 0.06 1.01 0.03 1.15 0.33 1.26 0.44* At peak 1.01 0.06 1.05 0.15 1.22 0.38 1.34 0.48*Dobutamine echo, % 36 50 39 61LV wall thickness, mm Septal 9.5 1.3 9.7 1.5 10.2 2.2 10.1 1.6 Posterior wall 9.3 1.3 9.4 1.5 9.6 1.7 9.9 1.6LV dimensions, cm LVDD 4.7 0.5 4.8 0.5 4.8 0.6 5.0 0.6* LVSD 3.0 0.4 3.2 0.8 3.9 0.8* 3.6 0.8*LVEF, % Resting 61.1 4.6 61.1 4.9 57.8 9.7 56.0 11.5* At peak 74.0 6.4 72.8 5.6 68.9 12.7 65.8 14.1**p 0.05 compared with LAVI 28 ml/m2. BMI body mass index; other abbreviations as in Table 1.Any WMA also increased in frequency relative to an the more likely the presence of abnormal wall motion (new,increase in LAVI (Fig. 1). With logistic regression (Table fixed, or mixed), which is consistent with data suggesting3), LAVI was an independent predictor of normal stress the greatest risk for IHD is in the mixed WMA subgroupechocardiography even after adjusting for age, gender, (21–23).resting ejection fraction, LV hypertrophy, and LV dimen- This study was designed to address the value of normalsions (p 0.0013). LAVI as an indicator of low general cardiovascular and ischemic risk. Left atrial volume index has been shown to beDISCUSSION highly predictive of general cardiovascular risk, including hypertension, atrial fibrillation, heart failure, stroke, deathThis study demonstrates that LAVI is strongly predictive of associated with dilated cardiomyopathy, and death afterstress echocardiographic results. Two observations deserve acute myocardial infarction (5,9 –14,24). Forty-seven pa-emphasis. First, a normal LAVI is strongly associated with tients (50%) with LAVI 32 ml/m2 had a normal stressa normal stress echocardiogram. Of the patients with LAVI echocardiogram. As we previously reported (5,25), increased 28 ml/m2, only three (5.7% of abnormal exams) had a LAVI is consistent with chronic elevation of filling pressureresting WMA and 100% had no stress-induced WMA. Inthree patients a fixed WMA was small and localized to the and increased general cardiovascular risk.basal inferior wall. Second, the more abnormal the LAVI, A normal stress echocardiogram is highly associated with a low risk of developing IHD within two to three years (15–18,21,23). The current study shows a strong relationFigure 1. The percentage of patients with a normal and abnormal stressechocardiogram with normal or abnormal (ischemic, fixed, or mixed) wall Figure 2. Mean SD left atrial volume index (LAVI) according tomotion for each category of left atrial volume index (LAVI). None of the different wall motion abnormality (WMA) results. Left atrial volume indexpatients with LAVI 28 ml/m2 had a positive stress echocardiogram (i.e., is significantly different between normal and any WMA (new, fixed, ornew wall motion abnormality), but three had a fixed wall motion abnor- mixed). An atrial volume 28 ml/m2 is associated with escalating cardio-mality localized to the inferior wall. vascular risk, including risk of ischemic heart disease. Downloaded from content.onlinejacc.org by on December 6, 2010
  5. 5. ARTICLE IN PRESSJACC Vol. 47, No. 5, 2006 Alsaileek et al. 1027March 7, 2006:1024–8 Predictive Value of Normal Left Atrial VolumeTable 3. Logistic Regression Showing the Effect of Normal changes in loading, which would accompany an acuteLAVI ( 28 ml/m2) on Normal Stress Echocardiography After ischemic event (33).Adjusting for Age, Gender, Low Resting EF ( 0.50), LVH, Conclusions. Patients with a normal stress echocardio-and LVDD gram are at low risk for the development of a coronary event Variable Odds Ratio 95% CI p Value within two years. A normal LAVI ( 28 ml/m2) stronglyAge 0.969 0.940–0.999 0.0438 predicted a normal stress echocardiogram. The magnitudeGender, male 0.441 0.190–1.025 0.0570 of increased LAVI is closely related to the magnitude ofLVDD, mm 0.495 0.193–1.275 0.1452 IHD detected. Left atrial volume index is also known toLow resting EF ( 0.50) 0.024 0.002–0.247 0.0017LVH 0.398 0.159–0.992 0.0481 predict low general cardiovascular risk. Left atrial volumeLAVI 28 ml/m2 8.632 2.325–32.043 0.0013 index should be assessed further for its complementary roleCI confidence interval; LVH left ventricular hypertrophy; other abbreviations as in stress testing as a means of enhancing prediction ofin Table 1. cardiovascular risk.between a normal LAVI and a normal stress echocardio- Reprint requests and correspondence: Dr. James B. Seward,gram. Thus, if validated, a normal resting LAVI could be Division of Cardiovascular Diseases, Mayo Clinic, 200 First Streetused as a predictor of low ischemic risk as well as general SW, Rochester, Minnesota 55905.cardiovascular risk. The chronicity and burden of decreased myocardial REFERENCEScompliance and increased filling pressure are thus reflectedin the magnitude of increased LAVI (5,26). Elevated filling 1. Lester SJ, Ryan EW, Schiller NB, Foster E. Best method in clinical practice and in research studies to determine left atrial size. 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  7. 7. Predictive Value of Normal Left Atrial Volume in Stress EchocardiographyAhmed A. Alsaileek, Martin Osranek, Kaniz Fatema, Robert B. McCully, Teresa S. Tsang, and James B. Seward J. Am. Coll. Cardiol. published online Feb 8, 2006; doi:10.1016/j.jacc.2005.09.069 This information is current as of December 6, 2010Updated Information including high-resolution figures, can be found at:& Services http://content.onlinejacc.org/cgi/content/full/j.jacc.2005.09.06 9v1References This article cites 37 articles, 24 of which you can access for free at: http://content.onlinejacc.org/cgi/content/full/j.jacc.2005.09.06 9v1#BIBLCitations This article has been cited by 4 HighWire-hosted articles: http://content.onlinejacc.org/cgi/content/full/j.jacc.2005.09.06 9v1#otherarticlesRights & Permissions Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://content.onlinejacc.org/misc/permissions.dtlReprints Information about ordering reprints can be found online: http://content.onlinejacc.org/misc/reprints.dtl Downloaded from content.onlinejacc.org by on December 6, 2010

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