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J Am Coll Cardiol, 2006; 47:1024-1028, doi:10.1016/j.jacc.2005.09.069 (Published online 8 February 2006). © 2006 by the American College of Cardiology Foundation CLINICAL RESEARCH: ECHOCARDIOGRAPHY Predictive Value of Normal Left Atrial Volume in Stress Echocardiography Ahmed A. Alsaileek, MD, Martin Osranek, MD1, Kaniz Fatema, PhD, Robert B. McCully, MD, Teresa S. Tsang, MD and James B. Seward, MD* Division of Cardiovascular Diseases, Mayo Clinic, Rochester, 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 hypothesized 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 echocardiogram. 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, 2004; 44:327-334, doi:10.1016/j.jacc.2004.03.062 © 2004 by the American College of Cardiology Foundation CLINICAL RESEARCH: PROGNOSTIC MARKERS IN ACUTE MI Long-term prognostic significance of left atrial volume in acute myocardial infarction Roy Beinart, MD*, Valentina Boyko, MSc , Ehud Schwammenthal, MD*, Rafael Kuperstein, MD*, Alex Sagie, MD , Hanoch Hod, MD, FACC*, Shlomo Matetzky, MD*, Solomon Behar, MD , Michael Eldar, MD, FACC* and Micha S. Feinberg, MD, FACC*,* * Heart Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel Neufeld Cardiac Research Institute, Sheba Medical Center, Tel Hashomer, Israel Cardiology Department, Rabin Medical Center, Petach Tiqvah, Israel * Reprint requests and correspondence: Dr. Micha S. Feinberg, Heart Institute, Sheba Medical Center, Tel Hashomer, Israel. [email protected] OBJECTIVES: The aim of this study was to evaluate the significance of increased left atrial (LA) volume determined within the first 48 h of admission as a long-term predictor of outcome in patients with acute myocardial infarction (MI). BACKGROUND: The LA volume reflects left ventricular (LV) diastolic properties. Whereas other LV Doppler diastolic characteristics are influenced by acute changes in LV function, LA volume is stable and reflects diastolic properties before MI. METHODS: Clinical and echocardiographic parameters were prospectively collected in 395 consecutive patients with acute MI. Patients with LA volume index (LAVI) >32 ml/m2 (normal + 2 standard deviations) were compared with those with LAVI 32 ml/m2. Independent clinical and echocardiographic prognostic risk factors for five years' mortality were determined by the Cox proportional hazard model. RESULTS: Left atrial volume index >32 ml/m2 was found in 63 patients (19%) who had a higher incidence of congestive heart failure on admission (24% vs. 12%, p < 0.01), a higher incidence of mitral regurgitation, increased LV dimensions, and reduced LV ejection fraction when compared with patients with LAVI 32 ml/m2. Their five-year mortality rate was 34.5% versus 14.2% (p < 0.001). Significant independent risk predictors of five years' mortality were age (10 years) (odds ratio [OR] 1.45; 95% confidence interval [CI]1.14 to 1.86), Killip class 2 on admission (OR 2.30; 95% CI 1.29 to 4.09), LAVI >32 ml/m2 (OR 2.22; 95% CI 1.25 to 3.96), diabetes (OR 1.94; 95% CI 1.15 to 3.28), and LV restrictive filling pattern (OR 1.89; 95% CI 1.09 to 3.31). CONCLUSIONS: In patients with acute MI, increased LA volume, determined within the first 48 h of admission, is an independent predictor of five-year mortality with incremental prognostic information to clinical and echocardiographic data. Circulation. 1999;99:400-405.) © 1999 American Heart Association, Inc. Clinical Investigation and Reports Impact of Preoperative Symptoms on Survival After Surgical Correction of Organic Mitral Regurgitation Rationale for Optimizing Surgical Indications Christophe M. Tribouilloy, MD; Maurice Enriquez-Sarano, MD; Hartzell V. Schaff, MD; Thomas A. Orszulak, MD; Kent R. Bailey, PhD; A. Jamil Tajik, MD; Robert L. Frye, MD From the Division of Cardiovascular Diseases and Internal Medicine (C.M.T., M.E.-S., A.J.T., R.L.F.), the Section of Cardiovascular Surgery (H.V.S., T.A.O.), and the Section of Biostatistics (K.R.B.), Mayo Clinic and Mayo Foundation, Rochester, Minn. Background—Surgical correction of mitral regurgitation in patients with no or mild symptoms remains controversial, particularly because the impact of preoperative symptoms on postoperative outcome is unknown. Methods and Results—The long-term outcome of 478 patients with organic mitral regurgitation (199 in NYHA functional class I/II and 279 in class III/IV before surgery) operated on between 1984 and 1991 was analyzed. In patients in NYHA class I/II before surgery compared with those in class III/IV, postoperative long-term survival was higher (at 10 years, 76±5% versus 48±4%, P<0.0001), with lower operative mortality (0.5% versus 5.4%, P=0.003) and better late survival (P<0.0001). Comparison of observed and expected survival showed identical curves in patients in class I/II before surgery (P=0.18), whereas excess mortality was observed in patients in class III/IV before surgery (P<0.0001). Excess mortality associated with severe symptoms was also confirmed in all subgroups (all P<0.003) and in multivariate analysis (P=0.0036; adjusted hazard ratio [95% CI], 1.81 [1.21 to 2.70]). Conclusions—In patients with organic mitral regurgitation, preoperative functional class III/IV symptoms are associated with excess short- and long-term postoperative mortality independently of all baseline characteristics. These data should lead to consideration of surgical correction of severe organic mitral regurgitation when no or minimal symptoms are present in patients at low operative risk, especially if repair is feasible. Published online before print December 18, 2006, doi:10.1161/01.HYP.0000254322.96189.85 (Hypertension. 2007;49:311.) © 2007 American Heart Association, Inc. Original Articles Left Atrial Size and Risk of Major Cardiovascular Events During Antihypertensive Treatment Losartan Intervention for Endpoint Reduction in Hypertension Trial Eva Gerdts; Kristian Wachtell; Per Omvik; Jan Erik Otterstad; Lasse Oikarinen; Kurt Boman; Björn Dahlöf; Richard B. Devereux From the Institute of Medicine (E.G., P.O.), University of Bergen, Bergen, Norway; the Department of Medicine (K.W.), Copenhagen County University Hospital, Glostrup, Denmark; the Department of Medicine (J.E.O.), Vestfold Central Hospital, Tönsberg, Norway; the Department of Cardiology (L.O.), Helsinki University Central Hospital, Helsinki, Finland; the Department of Medicine (K.B.), Skellefteå Hospital and Umeå University, Skellefteå, Sweden; the Department of Medicine (B.D.), Sahlgrenska University Hospital/Östra, Gothenburg, Sweden; and the Department of Medicine (R.B.D.), Weill Medical College of Cornell University, New York, NY. Correspondence to Eva Gerdts, Institute of Medicine, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway. E-mail [email protected] The influence of left atrial size on cardiovascular events during antihypertensive treatment has not been reported previously from a long-term, prospective, randomized hypertension treatment trial. We recorded left atrial diameter by annual echocardiography and cardiovascular events in 881 hypertensive patients (41% women) with electrocardiographic left ventricular hypertrophy aged 55 to 80 (mean: 66) years during a mean of 4.8 years of randomized losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint Reduction in Hypertension Study. During follow-up, a total of 88 primary end points (combined cardiovascular death, myocardial infarction, or stroke) occurred. In Cox regression, baseline left atrial diameter/height predicted incidence of cardiovascular events (hazard ratio: 1.98 per cm/m [95% CI: 1.02 to 3.83 per cm/m]; P=0.042) adjusted for significant effects of Framingham risk score and history of atrial fibrillation. Greater left atrial diameter reduction during follow-up was associated with greater reduction in left ventricular hypertrophy, absence of new-onset atrial fibrillation or mitral regurgitation during follow-up, and losartan-based treatment (B=–0.13±0.03 cm/m; P<0.001) in multiple linear regression, adjusting for baseline left atrial diameter/height. However, in time-varying Cox regression analysis, left atrial diameter reduction was not independent of left ventricular hypertrophy regression in predicting cardiovascular events during follow-up. In conclusion, left atrial diameter/height predicts risk of cardiovascular events independent of other clinical risk factors in hypertensive patients with left ventricular hypertrophy and may be useful in pretreatment clinical assessment of cardiovascular risk in these patients. J Am Coll Cardiol, 2006; 47:2357-2363, doi:10.1016/j.jacc.2006.02.048 © 2006 by the American College of Cardiology Foundation STATE-OF-THE-ART PAPER Left Atrial Size Physiologic Determinants and Clinical Applications Walter P. Abhayaratna, MBBS, FRACP*, James B. Seward, MD, FACC*, Christopher P. Appleton, MD, FACC , Pamela S. Douglas, MD, FACC , Jae K. Oh, MD, FACC*, A. Jamil Tajik, MD, FACC and Teresa S.M. Tsang, MD, FACC*,* Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota Division of Cardiovascular Diseases, Mayo Clinic, Scottsdale, Arizona Cardiovascular Medicine Division, Duke University, Durham, North Carolina. * Manuscript received November 18, 2005; revised manuscript received January 27, 2006, accepted February 7, 2006. Reprint requests and correspondence: Dr. Teresa S. M. Tsang, Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905. (Email: [email protected] ). * Left atrial (LA) enlargement has been proposed as a barometer of diastolic burden and a predictor of common cardiovascular outcomes such as atrial fibrillation, stroke, congestive heart failure, and cardiovascular death. It has been shown that advancing age alone does not independently contribute to LA enlargement, and the impact of gender on LA volume can largely be accounted for by the differences in body surface area between men and women. Therefore, enlargement of the left atrium reflects remodeling associated with pathophysiologic processes. In this review, we discuss the normal size and phasic function of the left atrium. Further, we outline the clinically important aspects and pitfalls of evaluating LA size, and the methods for assessing LA function using echocardiography. Finally, we review the determinants of LA size and remodeling, and we describe the evidence regarding the prognostic value of LA size. The use of LA volume for risk stratification is an evolving science. More data are required with respect to the natural history of LA remodeling in disease, the degree of LA modifiability with therapy, and whether regression of LA size translates into improved cardiovascular outcomes. Circulation. 2004;110:2320-2325.) © 2004 American Heart Association, Inc. Cardiovascular Surgery Atrial Fibrillation After Surgical Correction of Mitral Regurgitation in Sinus Rhythm Incidence, Outcome, and Determinants Steven J. Kernis, MD; Vuyisile T. Nkomo, MD, MPH; David Messika-Zeitoun, MD; Bernard J. Gersh, MBChB, DPhil; Thoralf M. Sundt, III, MD; Karla V. Ballman, PhD; Christopher G. Scott, MS; Hartzell V. Schaff, MD; Maurice Enriquez-Sarano, MD From the Division of Cardiovascular Diseases and Internal Medicine (S.J.K., V.T.N., D.M.-Z., B.J.G., M.E.S.), the Division of Cardiovascular Surgery (T.M.S., H.V.S.), and the Department of Health Science Research (K.V.B., C.G.S.), Mayo Clinic, Rochester, Minn. Correspondence to Maurice Enriquez-Sarano, MD, Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail [email protected] Received April 22, 2004; revision received July 24, 2004; accepted August 11, 2004. Background— The incidence, determinants, and outcome of postoperative atrial fibrillation (AF) after surgery for mitral regurgitation (MR) are poorly defined but may have important implications for timing of mitral valve surgery. Methods and Results— In 762 patients in sinus rhythm with no AF history undergoing MR surgical correction, we examined the rates and prognostic implications of postoperative AF for early AF (within 2 weeks postoperatively) and late AF (>2 weeks after surgery). During postoperative follow-up, 180 patients (24%) experienced new AF (early AF in 136 and late AF in 111). Isolated early AF without recurrence was observed in 69 patients characterized by high angina class and lower left ventricular ejection fraction but no significant left atrial (LA) enlargement. However, overall early AF predicted late AF: 62±5% of patients with early AF had late AF at 10 years compared with 9±1% of patients without early AF (P<0.0001). Large LA size strongly and independently predicted early AF (P=0.01) and late AF (P=0.003). For late AF, the predictive value of an enlarged LA was cumulative to that of early AF. Postoperative AF was associated with an increased subsequently higher risk of stroke or congestive heart failure (adjusted risk ratio=1.46 [1.04 to 2.05], P=0.03). Conclusions— Postoperative AF is common after surgical correction of MR in patients with no prior history of AF and is associated with increased subsequent morbidity. LA enlargement is independently predictive of postoperative AF and as such, should be integrated into the clinical decision-making process in patients with MR. Circulation. 2003;107:2207.) © 2003 American Heart Association, Inc. Clinical Investigation and Reports Left Atrial Volume A Powerful Predictor of Survival After Acute Myocardial Infarction Jacob E. Møller, MD, PhD; Graham S. Hillis, MBChB, PhD; Jae K. Oh, MD; James B. Seward, MD; Guy S. Reeder, MD; R. Scott Wright, MD; Seung W. Park, MD, PhD; Kent R. Bailey, PhD; Patricia A. Pellikka, MD From the Division of Cardiovascular Diseases (J.E.M., G.S.H., P.A.P., J.B.S., G.S.R., R.S.W., S.W.P., J.K.O.) and the Department of Biostatistics (K.R.B.), Mayo Clinic Rochester, Minn. Correspondence to Dr Patricia A. Pellikka, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail [email protected] Background— After acute myocardial infarction (AMI), diastolic function assessed by Doppler echocardiography provides important prognostic information that is incremental to systolic function. However, Doppler variables are affected by multiple factors and may change rapidly. In contrast, left atrial (LA) volume is less influenced by acute changes and reflects subacute or chronic diastolic function. This may be of importance when one assesses risk in patients with AMI. Methods and Results— Three hundred fourteen patients with AMI who had a transthoracic echocardiogram with assessment of left ventricular (LV) systolic and diastolic function and measurement of LA volume during admission were identified. The LA volume was corrected for body surface area, and the population was divided according to LA volume index of 32 mL/m2 (2 SDs above normal). LA volume index was >32 mL/m2 in 142 (45%). The primary study end point was all-cause mortality. During follow-up of 15 (range 0 to 33) months, 46 patients (15%) died. LA volume index was a powerful predictor of mortality and remained an independent predictor (hazard ratio 1.05 per 1-mL/m2 change, 95% CI 1.03 to 1.06, P<0.001) after adjustment for clinical factors, LV systolic function, and Doppler-derived parameters of diastolic function. Conclusions— Increased LA volume index is a powerful predictor of mortality after AMI and provides prognostic information incremental to clinical data and conventional measures of LV systolic and diastolic function. European Heart Journal Advance Access originally published online on September 1, 2005 © The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: [email protected] Left atrial volume predicts cardiovascular events in patients originally diagnosed with lone atrial fibrillation: three-decade follow-up Martin Osranek1, Francesca Bursi1, Kent R. Bailey2, Brandon R. Grossardt2, Robert D. Brown, Jr3, Stephen L. Kopecky1, Teresa S. Tsang1 and James B. Seward1,* 1 Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA Division of Biostatistics, Mayo Clinic, Rochester, MN, USA 3 Department of Neurology, Mayo Clinic, Rochester, MN, USA 2 Received 24 May 2005; revised 12 July 2005; accepted 11 August 2005; online publishahead-of-print 1 September 2005. * Corresponding author. Tel: +1 507 284 3581; fax: +1 507 284 3968. E-mail address: [email protected] See page 2487 for the editorial comment on this article (doi:10.1093/eurheartj/ehi578) Aims The objectives of this study were to determine the long-term outcome and the predictors of adverse events in patients originally diagnosed with lone atrial fibrillation (AF). Methods and results This population-based historical cohort study comprised 46 residents of Olmsted County, MN, USA, with well-documented, clinically defined lone AF and a complete two-dimensional echocardiographic examination. The original echocardiographic videotape recordings were analysed in a blinded fashion for left atrial volume (LAV) and left ventricular ejection fraction. With 1296 person-years of followup, the median duration of AF was 27 (first quartile=24, third quartile=33) years. Twentythree (50%) patients developed events. Cerebral infarction occurred in seven patients, myocardial infarction in 11, and congestive heart failure in 16. In a multivariable analysis, patients with indexed LAV 32 mL/m2 had a significantly worse event-free survival (adjusted HR, 4.46; 95% CI, 1.56–12.74; P=0.005). All cerebral infarctions occurred in patients with an indexed LAV >32 mL/m2. Conclusion Patients originally diagnosed with benign lone AF follow divergent courses based on LAV. Those originally diagnosed with lone AF and normal sized atria had a benign clinical course throughout the long-term follow-up. Patients with increased LAV at diagnosis or later during the follow-up experienced adverse events. Journal of the American College of Cardiology Volume 40, Issue 8 , 16 October 2002, Pages 1425-1430 doi:10.1016/S0735-1097(02)02305-7 Copyright © 2002 American College of Cardiology Foundation Published by Elsevier Inc. Clinical study: congestive heart failure Determinants and prognostic value of left atrial volume in patients with dilated cardiomyopathy Andrea Rossi MD*, , , Mariantonietta Cicoira MD*, Luisa Zanolla MD*, Rita Sandrini MD*, Giorgio Golia MD*, Piero Zardini MD* and Maurice EnriquezSarano MD, FACC† Dipartimento di Scienze Biomediche e Chirurgiche, Sezione di Cardiologia, Universita’ di Verona, Verona, Italy † Division of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota, USA * Received 4 February 2002; revised 30 April 2002; accepted 7 June 2002. Available online 15 October 2002. Abstract Objectives We aimed to investigate the determinants of left atrial (LA) volume and its prognostic value in patients with dilated cardiomyopathy (DCM). Background Enlargement of the LA is a marker of mortality in the general population. Patients with DCM are characterized by a wide range of LA sizes, but the clinical role of this observation has been played down. Methods A complete echocardiographic Doppler examination was performed in 337 patients (age 60 ± 13 years; 84% male) with the diagnosis of DCM. Left atrial maximal volume (LAmax) was measured at left ventricular (LV) end systole (four-chamber view; area– length method). Left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV) and ejection fraction (EF) were also measured. Mitral regurgitation (MR) was graded using a 5-point scale. Mitral E-wave (E) and A-wave (A) velocities, as well as their ratio (E/A), were measured off-line. Results Determinants of LAmax were: atrial fibrillation (r = 0.34, p < 0.0001), LVEDV (r = 0.46, p < 0.0001), EF (r = 0.40, p < 0.0001), MR (r = 0.39, p < 0.0001), and E/A ratio (r = 0.36, p < 0.0001). During follow-up (41 ± 29 months), 77 patients died and 12 underwent heart transplantation. Univariate Cox analysis showed that LAmax (hazard ratio [HR] 1.01, 95% confidence interval [CI] 1.007–1.013, p < 0.0001), LVESV (HR 1.003, CI 1.001–1.005, p = 0.0003), E/A ratio (HR 1.6, CI 1.3–2.005, p < 0.0001), and MR (HR 1.21, CI 1.03– 1.44, p = 0.02) were related to the outcome. On bivariate Cox analysis, LAmax predicted the prognosis independently of each determinant. Patients with a larger LA volume (LAmax/m2 >68.5 ml/m2) had a risk ratio of 3.8 compared with those with a smaller LA volume. Conclusions In patients with DCM, LA volume is associated with LV remodeling, diastolic dysfunction, and the degree of MR. The maximal volume of the LA has an independent and incremental prognostic value, compared with all its determinants.