Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Electrocardiography wikipedia , lookup
Cardiovascular disease wikipedia , lookup
Heart failure wikipedia , lookup
Cardiac contractility modulation wikipedia , lookup
Echocardiography wikipedia , lookup
Arrhythmogenic right ventricular dysplasia wikipedia , lookup
Jatene procedure wikipedia , lookup
Mitral insufficiency wikipedia , lookup
Effect of Age on Phasic Left Atrial Volume Original Article Acta Cardiol Sin 2012;28:34-41 Cardiac Imaging Association between Normal Aging and Phasic Left Atrial Volume as Assessed by Real-Time Three-Dimensional Echocardiography Wei-Wen Lin,1,2 Kuo-Yang Wang,1,3 Chi-Pin Lee,1 Taill-Lih Jou,5 Mei-Chun Chen,1,2 Chih-Tai Ting1,4 and Ying-Tsung Chen1,3,4,5 Background: Left atrial (LA) size is a good predictor of many cardiovascular outcomes, including atrial fibrillation, stroke and heart failure. Real-time 3D echocardiography (RT3DE) may be a superior index for estimating LA volume, compared with traditional M-mode and 2D methods. In this study, we used RT3DE to evaluate phasic LA volumes and functions among different age groups of healthy Taiwanese subjects. Methods: Sixty-eight healthy volunteers were divided into three groups according to age. Group 1: under 40 years old (n = 20); group 2: 40-60 years old (n = 24); and group 3: over 60 years old (n = 24). RT3DE of LA volume was acquired from the apical view. Three phasic LA volumes, including maximal LA volume (LAVmax), minimal LA volume (LAVmin) and LA volume before atrial contraction (LAVpreA) were measured. These phasic LA volumes were used to calculate the emptying volume and emptying fraction at different phases of one heart cycle. Results: There were significantly positive correlations between age and LA volumes (r = 0.639 for LAVmax, r = 0.642 for LAVpreA, r = 0.661 for LAVmin; all p < 0.001). Total LA empty volume (p < 0.001) and active LA empty volume (p = 0.001) also positively correlated with age. In contrast, total, passive and active LA emptying fractions were not significantly different among the three age groups. Conclusion: Aging has a significant effect on phasic LA volumes, but phasic LA empty fractions remain unchanged in healthy Taiwanese adults. Key Words: Aging · Left atrial function · Phasic LA volume · Real-time 3D echocardiography an important role in overall cardiac performance. 1 But due to a paucity of proper non-invasive tools to evaluate LA function within a three-dimensional structure, it has not been well studied. Increased LA diameter and area were related to many adverse cardiovascular outcomes, such as atrial fibrillation (AF), stroke, and heart failure.2-4 Assessment of LA diameter and area by M-mode and 2D echocardiography provides important physiologic and prognostic information in many different cardiovascular diseases. But LA area has a non-linear relationship to its volume. Morphology of LA may become less spherical and more elongated during its remodeling.5,6 Measurement of LA area by 2D echocardiography cannot actually reflect the true volume of LA, whereas LA volume evaluated by RT3DE may be a superior in- INTRODUCTION It is well-known that left atrial (LA) function plays Received: February 13, 2011 Accepted: June 28, 2011 1 Cardiovascular Center, Taichung Veterans General Hospital; 2 Department of Radiological Technology, Central Taiwan University of Science and Technology; 3Department of Medicine, Chung-Shan Medical University, Taichung; 4Cardiovascular Research Center, National Yang Ming University School of Medicine, Taipei; 5 Department of Internal Medicine, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan. Address correspondence and reprint requests to: Dr. Ying-Tsung Chen, Department of Internal Medicine, Tungs’ Taichung MetroHarbor Hospital, No. 699, Chungchi Rd., Sec. 1, Wuchi Township, Taichung County 435, Taiwan. Tel: 886-4-2658-1919; E-mail: ytchen@ livemail.tw Acta Cardiol Sin 2012;28:34-41 34 Effect of Age on Phasic Left Atrial Volume dex compared with other traditional methods.7-9 However, there are few studies in the literature on the relationship between changes in LA phasic volumes and cardiovascular outcomes. In this study, we used RT3DE with speckle tracking to evaluate phasic LA volumes in different age groups in a healthy Taiwanese population. Aging is often associated with myocardial fibrosis, stiffness and ventricular diastolic dysfunction.10 Impaired relaxation depresses the early diastolic mitral inflow volume, and the LA active emptying volume increases to maintain cardiac output.11 The compensatory changes of LA mechanical function secondary to aging LV are not well understood. The purpose of this study is to evaluate phasic LA function in different age groups of a healthy Taiwanese population. A better understanding of the different phases of LA volume in a cardiac cycle, and their contribution to cardiac output in healthy and disease hearts, may be of value in the development of future therapeutic and diagnostic modalities. for off-line speckle tracking analysis. Care was taken to ensure that the entire LA was visualized, without any dropout of the LA wall. In the parasternal long axis or short axis view, M-mode of the LA and LV chamber were measured for diameter and wall thickness. In the apical 4-chamber view, mitral inflow was recorded at the tip of the mitral leaflet. The peak velocities of early and late diastolic filling waves (E-wave, A-wave) and the E/A velocity ratio were measured. RT3DE datasets were analyzed using the 3D wall motion tracking software (Toshiba Medical Systems). In apical views (4-chamber and 2-chamber), LA endocardial boundaries were manually measured at the end diastolic phase. Then, the 3D endocardial surface was reconstructed and automatically tracked throughout the cardiac cycle. (Figure 1). Eight-one consecutive healthy volunteers without any history of cardiovascular disease were recruited in this study (including hospital employee and adult from health examination center). Thirteen volunteers were excluded due to poor imaging quality of the LA after RT3DE, and subjects with diabetes, hypertension or arrhythmia were also excluded. Subjects were divided into three groups according to their age, as follows: group 1: under 40 years old (n = 20); group 2: 40-60 years old (n = 24); and group 3: over 60 years old (n = 24). The study protocol was approved by the institutional review board of the hospital, and written informed consent was obtained from all subjects prior to the study. LA phasic volume measurement Three basic volumes were measured 9 (Figure 1, right): (a) maximal LA volume (LAVmax), at left ventricular (LV) end-systolic phase, just before mitral valve opening; (b) pre-atrial contraction volume (LAVpreA), before the P-wave on surface ECG; and (c) minimal LA volume (LAVmin), at LV end-diastolic phase, just before mitral valve closure. The LA volumes above were used to estimate the emptying volume and emptying fraction: LA empty volume (LAEV): LAVmax - LAVmin; LA emptying fraction (LAEF): (LAEV/LAVmax) ´ 100%. Four LA emptying parameters were derived: (a) LA passive empty volume: LAVmax - LAVpreA; (b) LA passive emptying fraction: (LAVmax - LAVpreA)/LAVmax ´ 100%; (c) LA active emptying volume: LAVpreA LAVmin; and (d) LA active emptying fraction: (LAVpreA - LAVmin)/LAVpreA ´ 100%. LA expansion index was calculated using the equation total LAEV/LAVmin ´ 100%. All the LA volume data were corrected for body surface area. Echocardiographic studies All patients were imaged in a left lateral decubitus position using Artida ultrasound system equipment (Toshiba Medical Systems Co., Tochigi, Japan) with a 3 MHz/PST-25SX probe. RT3DE with speckle tracking imaging was performed from the apical position by an experienced technician. The average frame rate for analysis was 25-30 frames/s. Three consecutive cardiac cycles during a single breath-hold were stored digitally Intraobserver and interobserver variability Intraobserver variability was determined by having an observer repeat the LA volume (LAVmax, LAVmin, and LAVpreA) measurements in 20 randomly selected subjects. Interobserver variability was determined by having an echocardiography specialist repeatedly measure these randomly selected subjects. Intraobserver and interobserver variabilities were presented by BlandAltman plot. METHODS 35 Acta Cardiol Sin 2012;28:34-41 Wei-Wen Lin et al. A B C D E Figure 1. (A) apical four-chamber strain and (B) two-chamber images via real-time 3D speckle tracking echocardiography. (C,D) Left atrium (LA) 3D reconstruction image in systolic and diastolic phase. (E) Left atrial volume (dash line, right y-axis) and displacement distance (solid line, left y-axis). Maximum LA volume (LAVmax), pre atrial contraction volume (LAVpreA) and minimal LA volume (LAVmin) (white arrows). Statistical analysis Continuous data were expressed as median (minimum, maximum). Comparisons among the three age groups were analyzed using the Kruskal-Wallis test. All 68 subjects were put together as a group, and a simple linear regression test was used to evaluate the correlation between phasic LA volume, stroke volume and age. A p value < 0.05 was considered statistically significant. < 0.001). However, there were no significant differences among the three age groups in the LV internal dimension at end-diastolic and end-systolic (LVIDd, LVIDs) phases and ejection fractions (EF). The mitral E/A ratios were lower in groups 2 and 3 than in group 1 (p < 0.001), suggesting greater diastolic dysfunction with increased age. Phasic LA volumes changes and correlations among age groups The three phasic LA volumes and calculated phasic LA emptying fractions are shown in Table 2 and Figure 2. LAVmax, LAVpreA and LAVmin were increased significantly in groups 2 and 3 as compared with group 1 (p < 0.05). Total and active LA empty volumes were greater in group 3 than in groups 1 and 2 (p < 0.05). In contrast to the increases in phasic LA volumes and empty volumes with age, total, passive and active LA emptying fractions were not significantly different among the age groups. Table 3 showed the correlations between age and phasic LA volumes and functions. There were direct RESULTS Demographic and M-mode, 2D echocardiography measurements The demographic and routine echocardiography measurement data are listed in Table 1. Aorta and LA diameters were significantly higher in groups 2 and 3 compared with group 1 (p < 0.001). LV chamber thickness (including ventricular septum and posterior wall) increased in groups 2 and 3 as compared with group 1 (p Acta Cardiol Sin 2012;28:34-41 36 Effect of Age on Phasic Left Atrial Volume Table 1. Basic demographic data Age (y/o) Sex (M/F) SBP (mmHg) DBP (mmHg) HR (beat/min) BSA (M2) AO (mm) LA (mm) IVSd (mm) LVIDd (mm) PWd (mm) LVIDs (mm) PA (mm) peak E (cm/sec) peak A (cm/sec) E/A ratio EF (%) Mean ± SD d p < 0.05 vs. 20-40 y/o k Kruskal-Wallis Test 20-40 y/o (n = 20) 40-60 y/o (n = 24) > 60 y/o (n = 24) p-value k 29.83 ± 7.010 12/8 .119 ± 11.4 71.2 ± 12.6 73.4 ± 14.5 1.51 ± 0.23 30.25 ± 2.950 31.71 ± 4.110 9.33 ± 1.52 45.88 ± 5.890 9.04 ± 1.30 29.25 ± 6.210 21.92 ± 3.540 80.17 ± 9.400 58.04 ± 13.20 1.47 ± 0.46 63.67 ± 3.800 49.21 ± 6.470 14/10 .120 ± 12.2 72.6 ± 10.8 71.3 ± 12.0 1.48 ± 0.32 d 34.04 ± 5.10d0 d 37.13 ± 5.33d0 d 12.13 ± 2.11d0 44.50 ± 5.540 d 11.42 ± 2.26d0 27.00 ± 4.670 d 24.25 ± 4.13d0 d 63.71 ± 14.73d d 76.46 ± 12.42d d 0.85 ± 0.21d 61.75 ± 4.200 68.15 ± 4.530 13/11 122.3 ± 17.60 76.4 ± 17.9 070.6 ± 14.33 1.55 ± 0.22 d 34.85 ± 4.02d0 d 37.55 ± 6.04d0 d 12.50 ± 1.57d0 45.70 ± 5.250 d 12.25 ± 1.68d0 25.15 ± 4.650 d 25.55 ± 4.55d0 d 63.60 ± 9.38d0 d 0 80.00 ± 16.27d0 0d0.83 ± 0.21d0 62.35 ± 4.120 NS NS NS NS < 0.0001 < 0.0001 < 0.0001 NS < 0.0001 NS < 0.0150 < 0.0001 < 0.0001 < 0.0001 NS Values are means ± SD, *p < 0.05 was considered significant. AO, aorta; LA, left atrium; IVSd, interventricular septum in diastole; LVIDd, left ventricular internal diameter in diastole; PWd, posterior wall in diastole; LVIDs, left ventricular internal diameter in systole; PA, pulmonary artery; LVEF, left ventricular ejection fraction; BSA, body surface area. Table 2. Phasic LA volume data Max LA volume (ml) Minimal LA volume (ml) Per A volume (ml) Max LA volume (ml/M2) Minimal LA volume (ml/M2) Per A volume (ml/M2) Total LA SV (MaxV-MinV) (ml/M2) Passive LA SV (MaxV- preA) (ml/M2) Active LA SV (preA-Min A) (ml/M2) Total LA EF (LASV/MaxV) ´ 100% Active LA EF (active LASV/preA V) ´ 100% Passive LA EF (passive LA SV/MaxV) ´ 100% LA expansion index (total LA SV/MinV) ´ 100% k Kruskal-Wallis Test d p < 0.05 vs. < 40 y/o y p < 0.05 vs. 40-60 y/o < 40 y/o (n = 20) 40-60 y/o (n = 24) > 60 y/o (n = 24) p-value k 36.71 ± 9.62 15.10 ± 4.32 23.82 ± 7.49 23.96 ± 5.51 10.00 ± 2.61 15.76 ± 4.52 13.96 ± 3.43 08.20 ± 2.79 05.76 ± 2.62 00.58 ± 0.06 00.36 ± 0.10 00.35 ± 0.09 01.44 ± 0.36 041.53 ± 10.00 18.21 ± 4.24 28.55 ± 7.09 d 28.67 ± 7.59d d 12.55 ± 3.12d d 19.70 ± 5.30d 16.12 ± 4.88 08.97 ± 3.95 07.14 ± 2.99 00.56 ± 0.04 00.36 ± 0.08 00.31 ± 0.09 01.29 ± 0.23 052.01 ± 12.58 23.31 ± 5.52 36.47 ± 8.55 dy 33.85 ± 8.56dy dy 15.14 ± 3.65dy dy 23.71 ± 5.72dy d 18.71 ± 5.46d 10.14 ± 4.49 0d8.56 ± 3.18d 00.55 ± 0.05 00.35 ± 0.10 00.29 ± 0.10 01.24 ± 0.26 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0060 < 0.1390 < 0.0030 < 0.0960 < 0.9920 < 0.1960 < 0.0960 Values are means ± SD, *p < 0.05 was considered significant. LA, left atrium; SV, stroke volume; EF, ejection fraction. 37 Acta Cardiol Sin 2012;28:34-41 Wei-Wen Lin et al. A B C D Figure 2. Phasic left atrial volume and stroke volume in different age groups. LAVmax: LA volume maximum; LAVpreA: LA volume pre atrial contraction; LAVmin: LA volume minimum; LASV: LA stroke volume. sive LA empty volumes (correlation coefficient = 0.384, p = 0.006). Table 3. Correlations of age with phasic left atrial volume and stroke volume age LA diameter (mm) LAVmax (ml/M2) LAVmin (ml/M2) LAVpreA (ml/M2) Total LAEV (ml/M2) Passive LAEV (ml/M2) Active LAEV (ml/M2) Correlation coefficient p-value Correlation coefficient p-value Correlation coefficient p-value Correlation coefficient p-value Correlation coefficient p-value Correlation coefficient p-value Correlation coefficient p-value Observer variabilities Intra- and inter-observer variability was present by Bland-Altman analysis (Table 4). 0.532 < 0.001 < 0.639 < 0.001 < 0.661 < 0.001 < 0.642 < 0.001 < 0.559 < 0.001 < 0.327 0.006 0.452 < 0.001 < DISCUSSION In people without cardiovascular disease, LA diameter and area continue to increase from childhood to old age.2,3 However, to the best of the authors’ knowledge, there are no data on the effect of age on phasic LA volume among healthy Taiwanese. Our study demonstrates that phasic LA volumes, including LAVmax, LAVpreA and LAVmin, increased with age in a clear linear fashion, and showed good correlations (Tables 2 and 3). Total and active LA empty volumes were also age-dependently higher in the older age groups, but the passive LA empty volumes did not correlate with age. Furthermore, LA total, active and passive emptying fraction were not significantly different among the three age groups. The results indicate that LAV, left atrial volume; LAEV, left atrial empty volume. positive correlations between LA diameter, phasic LA volumes (including LAVmax, LAVpreA and LAVmin) and age (p < 0.001). Moreover, age correlated well with total and active LA empty volumes (p < 0.001), though only a weak correlation was found between age and pasActa Cardiol Sin 2012;28:34-41 38 Effect of Age on Phasic Left Atrial Volume Table 4. Bland-Altman analysis for intra-observer and inter-observer variability Mean difference Max LA volume (ml) Minimal LA volume (ml) Pre A volume (ml) intra-observer inter-observer intra-observer inter-observer intra-observer inter-observer 1.36 2.35 0.69 -0.181.28 0.34 95% C.I. of the Difference 0.55 1.26 0.12 -0.930.65 -0.51- 2.16 3.43 1.26 0.57 1.91 1.18 p 0.002 0.000 0.019 0.622 0.000 0.417 although LA volume increases as age increases, LA systolic function may remain unchanged in healthy adults. which suggest that both LA diameter and phasic LA volumes increase with age (Table 3, Figure 2). Effect of age on phasic LA volume and mechanical function LA volume may be considered as a barometer of LV diastolic pressure. 12 Age increases ventricular myocardium fibrosis and stiffness, which leads to an increase in LV filling pressure.10 In the early LV diastolic phase, LA is exposed to the pressure of left ventricle just after the mitral valve opens, and the maximal or reserved LA volume may be related to the early LV filling pressure. As age increases, the increased LV filling pressure leads to greater reserved and pre-atrial contraction LA volumes. Consequently, the minimal LA volume may be related to the elevated end-diastolic pressure.13 In this study, age was significantly correlated with increased phasic LA volumes (Tables 2 and 3). The total and active LA empty volumes increase to provide adequate LV filling volume (Table 2). The passive LA empty volume (at conduit phase) is influenced by LV myocardium diastolic velocity and compliance, and is less influenced by the atrial function itself. But the dilated LA still functions as described by the FrankStarling mechanism12,13 and there is a normal emptying fraction (Table 2). Thomas et al.14 reported that LA diameter, LAVmax and LAVmin volume were not changed in normal age subjects. LA size increase is a pre-clinical pathology condition, but is not a part of normal aging. The results were in conflict with previous studies that atrial size increased with aging.2-4,15 The authors suggested that this difference may be attributed to the fact that they estimated LA volumes by using biplane methods of discs and 3D reconstruction from 2D images, without using M-mode methods. By using RT3DE, our observations were consistent with most of the recent studies,15,23-25 Phasic LA volumes and function in different cardiovascular diseases Associations between changes in phasic LA volumes and function with different cardiovascular diseases have been demonstrated in a recent report by Stefanadis et al. 16 In patients with hypertrophic cardiomyopathy, 17 LAVmax, LAVmin and LAVpreA were increased, but total, active and passive LA ejection were decreased. Changes in LA function may be secondary to LV myocardial fibrosis and diastolic dysfunction in these patients. In patients who suffered myocardial infarction with non-ST elevation, there were progressive increases in LAVmax and LAVmin, with decreased active and passive LA empty volumes.18 Phasic LA volume assessed by RT3DE and its clinical implication For years, M-mode and 2D echocardiography have been used to measure LA size, with good clinical implications in many diseases, including atrial fibrillation and heart failure. 19,20 They generally remain the standard procedure in daily practice. RT3DE is a relatively new ultrasound technique, with little information to prove its incremental clinical implications at the present time. However, by using more sophisticated echocardiographic tools in the future, such as the 3D measurement of strain, strain rate and torsion, the use of RT3DE may provide more substantial information about phasic LA volumes, and thus increase its value as a clinical instrument to practitioners. Study limitations There were some limitations of this study. First, in our study, LV wall thickness increased in the old age 39 Acta Cardiol Sin 2012;28:34-41 Wei-Wen Lin et al. 4. Gardin JM, McClelland R, Kitzman D, et al. M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the cardiovascular health study). Am J Cardiol 2001;87:1051-7. 5. Tsang T, Barnes M, Gersh B, et al. Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden. Am J Cardiol 2002;90:1284-9. 6. Tsang T, Abhayaratna W, Barnes M, et al. Prediction of cardiovascular outcomes with left atrial size: is volume superior to area or diameter? J Am Coll Cardiol 2006;47:1018-23. 7. Shin MS, Fukuda S, Song JM, et al. Relationship between left atrial and left ventricular function in hypertrophic cardiomyopathy: a real-time 3-dimensional echocardiographic study. J Am Soc Echocardiogr 2006;19:796-801. 8. Gottdiener JS, Kitzman DW, Aurigemma GP, et al. Left atrial volume, geometry, and function in systolic and diastolic heart failure of persons over 65 years of age (the cardiovascular health study). Am J Cardiol 2006;97:83-9. 9. Anwar AM, Soliman OI, Geleijnse ML, et al. Assessment of left atrial volume and function by real-time three-dimensional echocardiography. Int J Cardiol 2008;123:155-61. 10. Terman A, Brunk UT. The aging myocardium: roles of mitochondrial damage and lysosomal degradation. Heart Lung Circ 2005;14:107-14. 11. Daneshvar D, Wei J, Tolstrup K, et al. Diastolic dysfunction: improved understanding using emerging imaging techniques. Am Heart J 2010;160:394-404. 12. Stefanadis C, Dernellis J, Stratos C, et al. Assessment of left atrial pressure-area relation in humans by means of retrograde left atrial catheterization and echocardiographic automatic boundary detection: effects of dobutamine. J Am Coll Cardiol 1998;31:426-36. 13. Anwar AM, Geleijnse ML, Soliman OI, et al. Left atrial FrankStarling law assessed by real-time, three-dimensional echocardiographic left atrial volume changes. Heart 2007;93:1393-7. 14. Thomas L, Levett K, Boyd A, et al. Compensatory changes in atrial volumes with normal aging: is atrial enlargement inevitable? J Am Coll Cardiol 2002;40:1630-5. 15. Pan NH, Tsao HM, Chang NC, et al. Aging dilates atrium and pulmonary veins: implications for the genesis of atrial fibrillation. Chest 2008;133:190-6. 16. Stefanadis C, Dernellis J, Toutouzas P. A clinical appraisal of left atrial function. Eur Heart J 2001;22:22-36. 17. Eshoo S, Semsarian C, Ross DL, et al. Left atrial phasic volumes are modulated by the type rather than the extent of left ventricular hypertrophy. J Am Soc Echocardiogr 2010;23:538-44. 18. Boyd AC, Ng AC, Tran da T, et al. Left atrial enlargement and phasic function in patients following non-ST elevation myocardial infarction. J Am Soc Echocardiogr 2010;23:1251-8. 19. Psaty BM, Manolio TA, Kuller LH, et al. Incidence of and risk factors for atrial fibrillation in older adults. Circulation 1997; 96:2455-61. group. In the previous studies by others, LV mass increased as age increased.21,22 We cannot separate the effects of LV mass on LA size. Second, we did not evaluate backward flow in pulmonary veins, due to poor temporal and spatial resolution in RT3DE. LV diastolic function has been shown to be impaired as age increases. The active LAEV increase in our study may not totally increase during LV preload, and the pulmonary veins backward flow may also increase during atrial contraction. Third, due to a low frame rate (20-30 frames/s), some LA volume measurement were not entirely in the images before the p wave on the electrocardiogram. In some patients, we manually identified and measured the LA volumes closest to the pre-A point. CONCLUSION Phasic LA volumes were significantly and dosedependently associated with increased age in healthy Taiwanese adults, but phasic LA emptying fractions did not differ among the three age groups. These results carry important clinical and prognostic implications. Monitoring phasic LA volumes by real-time 3D echocardiography in healthy subjects, and for evaluation of different cardiovascular diseases in Taiwan, may be of considerable value in clinical practice and have an important public health impact. ACKNOWLEDGMENT This work was supported by the research grant TCVGH-993103B from the Taichung Veterans General Hospital, Taiwan, Republic of China. REFERENCES 1. Hawley RR, Dodge HT, Graham TP. Left atrial volume and its changes in heart disease. Circulation 1966;34:989-96. 2. Vaziri SM, Larson MG, Benjamin EJ, et al. Echocardiographic predictors of non-rheumatic atrial fibrillation. The Framingham Heart Study. Circulation 1994;89:724-30. 3. Benjamin EJ, D’Agostino RB, Belanger AJ, et al. Left atrial size and the risk of stroke and death. The Framingham Heart Study. Circulation 1995;92:835-41. Acta Cardiol Sin 2012;28:34-41 40 Effect of Age on Phasic Left Atrial Volume 20. Takemoto Y, Barnes ME, Seward JB, et al. Usefulness of left atrial volume in predicting first congestive heart failure in patients over 65 years of age with well-preserved left ventricular systolic function. Am J Cardiol 2005;96:832-6. 21. Savage DD, Levy D, Dannenberg AL, et al. Association of echocardiographic left ventricular mass with body size, blood pressure and physical activity (the Framingham Study). Am J Cardiol 1990;65:371-6. 22. Levy D, Garrison RJ, Savage DD, et al. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990;322:1561-6. 23. Nikitin NP, Witte KK, Thackray SD, et al. Effect of age and sex on left atrial morphology and function. Eur J Echocardiogr 2003;4:36-42. 24. Okamatsu K, Takeuchi M, Nakai H, et al. Effects of aging on left atrial function Assessed by two-dimensional speckle tracking echocardiography. J Am Soc Echocardiogr 2009;22:70-5. 25. Liang HY, Cheng WC, Chang KC. Mechanisms of right atrial pacing inducing left atrial and left ventricular dysfunction evaluated by strain echocardiography. Acta Cardiol Sin 2010;26: 157-64. 41 Acta Cardiol Sin 2012;28:34-41