© 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12645

Echocardiography

Left Atrial Asynchrony and Mechanical Function in Patients with Mitral Stenosis before and Immediately after Percutaneous Balloon Mitral Valvuloplasty: A Real Time Three-Dimensional Echocardiography Study Yan Deng, M.D., Sheng-lan Guo, M.D., Hong-yue Su, B.M., Qian Wang, B.M., Zhen Tan, B.M., Ji Wu, M.D., Ph.D., and Di Zhang, M.D. Department of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, China

Objective: This study evaluated the feasibility of assessing left atrium (LA) function and asynchrony in patients with rheumatic mitral stenosis (MS) before and immediately after percutaneous balloon mitral valvuloplasty (PBMV) by real time three-dimensional echocardiography (RT3DE). Methods: Thirty patients with rheumatic MS who underwent PBMV and 30 controls were enrolled. RT3DE was used to measure LA volume and function, the standard deviation of time to the minimal systolic volume divided into 16 segments, 12 segments, or 6 segments (Tmsv 16-SD, Tmsv 12-SD, Tmsv 6-SD), and the maximum differences (Tmsv 16-Dif, 12-Dif, 6-Dif) in RT3DE derived values in MS patients before and 2 days after PBMV were obtained and compared with those of normal controls. The associations between the LA asynchrony and heart volume, function, mitral valve area (MVA), maximum mitral valve gradient (MVGmax), mean mitral valve gradient (MVGmean), and mean LA pressure (MLAP) were investigated. Results: Left atrium asynchrony indexes were significantly larger, and LA function parameters were significantly lower in the MS group than in the controls (P < 0.05 for all). Of all the LA asynchrony indexes, LA Tmsv16-SD was most significantly correlated with the LA volume and function parameters, MVGmax, MVGmean, and MLAP (P < 0.05 for all). LA asynchrony indexes and LA volume significantly deceased, and LA function significantly increased post-PBMV (P < 0.05). Conclusion: Real time three-dimensional echocardiography is a reliable and reproducible method to quantify LA function and asynchrony. RT3DE revealed a significant, early improvement in LA function and asynchrony in MS patients after PBMV. (Echocardiography 2015;32:291–301) Key words: left atrium, real time three-dimensional echocardiography, asynchrony, atrial fibrillation, rheumatic mitral stenosis Rheumatic heart disease (RHD) is a leading cause of morbidity and mortality in much of the world and is associated with development of long-term valvular complications, especially mitral stenosis (MS).1 Patients with MS who are prone to developing atrial fibrillation (AF) have an increased risk of thromboembolism and acute pulmonary edema. Previous studies support the hypothesis that abnormalities in left atrial (LA) synchronicity and mechanical function increase This work was supported in part by grants from the Guangxi Health Ministry (Medicine) (Z2011363), Guangxi Department of Education (2013LX034), and Guangxi Natural Science Foundation (GXNSFA013138). The sponsors had no part in the research or writing of this article. Address for correspondence and reprint requests: Yan Deng, M.D., Department of Ultrasound, the First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, China. E-mail: [email protected]

the risk of AF and are a robust predictor of cardiovascular outcome.2,3 Several electrophysiological and echocardiographic techniques can be used to assess LA electrical and contractile functioning in such patients.4–10 However, their availability is limited by the invasive nature of electrophysiological studies and the unreliability and difficulty of obtaining echocardiographic indexes. Accurate quantification of LA function and asynchrony remains a challenging task. Recently, real time three-dimensional echocardiography (RT3DE) has been used to quantify left ventricular (LV) dysfunction and dyssynchrony but the usefulness of the technique in evaluating dyssynchronous LA contraction is still open to discussion. Percutaneous balloon mitral valvuloplasty (PBMV) is considered a safe and effective treatment to restore LA function and the conduction system in MS patients. To our knowledge, there 291

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have been no studies of RT3DE to assess LA function and asynchrony in MS patients before and immediately after PBMV. More important, the association between LA function, LA pressure, and asynchrony has not been investigated. The present study was designed to assess the feasibility and reproducibility of RT3DE to characterize LA pathophysiology in MS patients and to evaluate the results shortly after PBMV. Materials and Methods: Patient Population: A total of 30 patients (10 males and 20 females, with a mean age of 34.5  7.1 years) with moderate or severe pure rheumatic MS were recruited from a series diagnosed by transthoracic echocardiography and referred to the First Affiliated Hospital of Guangxi Medical University from October 2010 to March 2013 for PBMV (MS group). Patients were diagnosed with ≥ class II New York Heart Association (NYHA) heart failure. Wilkins scores were used to evaluate mitral valve lesions before carrying out PBMV and those with scores >10 were not eligible. The patients were not concurrently being treated with digitalis, b-blockers, or any other anti-arrhythmic drugs. Patients were excluded if they had moderate or severe aortic or mitral insufficiency, aortic stenosis, severe or bicommissural calcification, LA thrombi, diabetes mellitus, arterial hypertension, dyslipidemia, coronary artery disease, arrhythmias (i.e. a history of arrhythmia, or arrhythmia on ECG at selection, 4 hour Holter recording, or exercise treadmill ECG), LV systolic dysfunction, LV ejection fraction (LVEF) 11 mm), lung disease, or echocardiogram abnormalities. Thirty sex-, age-, and body mass index (BMI)-matched healthy volunteers without any known cardiovascular disease or cardiovascular risk factors were recruited as a control group. All patients and controls were in sinus rhythm during the study period. The Human Research Ethics Committee of the First Affiliated Hospital of Guangxi Medical University approved this study. All patients gave written informed consent before inclusion. Percutaneous Balloon Mitral Valvuloplasty (PBMV): The same experienced cardiologist performed all the PBMV procedures via an anterograde transvenous approach with a stepwise dilatation technique using a single Inoue balloon. He was not informed of the research purpose prior to the procedures. Mean left atrial pressure (MLAP) was measured before and immediately after PBMV. If the mitral valve area (MVA) was >1.5 cm2

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without moderate or severe mitral regurgitation after PBMV, the results were considered satisfactory. Transthoracic 2DE, Doppler, 2D Echocardiography, and RT3DE: Real time three-dimensional echocardiography and two-dimensional (2D) echocardiography were performed 1 day before (baseline), and at 2 days after PBMV with the subject in a left lateral decubitus position. A Philips iE33 ultrasound system (Philips Medical Systems, Andover, MA, USA) equipped with S5 phasedarray (frequency 1.0–5.0 Hz) and X3 matrixarray (frequency 1.0–3.0 Hz) transducers. Five cardiac cycles were stored in cine loop format for offline analysis. A 2-lead ECG was recorded continuously during echocardiography. Data were analyzed by 2 independent, experienced investigators who were blinded to the clinical information. Acquisition of 2DE and Doppler were performed using the S5 phased-array transducer. All standard echocardiographic parameters were measured following the recommendations of the American Society of Echocardiography. The LV dimensions, LVEF, septal and LV posterior wall diastolic thickness, and LA dimension were measured in the 2D guided M-mode in the parasternal long-axis view. LV mass was calculated as described by Devereux et al.11 and normalized for body surface area (BSA) (LV mass index). In all patients, the smallest cross-sectional orifice area was traced in the parasternal short-axis view at early diastole.12 Continuous-wave Doppler tracing of the mitral inflow was recorded with color Doppler guidance from the apical four-chamber view. Maximum mitral valve gradient mean mitral valve gradient (MVGmax), (MVGmean), and pressure half time (PHT) were calculated by the software package installed as part of the ultrasound imaging system. Real time three-dimensional echocardiography acquisition was performed using an X3 matrix-array transducer. The entire full-volume RT3DE dataset of the LA was obtained in the apical four-chamber view while the subjects were holding their breath. This required a stable inter-beat (RR) interval to minimize translation artifacts between the acquired subvolumes. Quantification of LA Volumes and Function: Real time three-dimensional echocardiography datasets were stored digitally, and 6 segment quantitative analysis was performed offline using a 3DQ advanced quantification plugin

Left Atrial Asynchrony and Function

(Q-Lab, Version 8.1, Philips Medical Systems) over a complete heart cycle. The apical fourand two-chamber views through the full-volume dataset were considered as fundamental planes (Fig. 1A). First, tracing was performed by marking 5 atrial points, the anterior, inferior, lateral, septal mitral annuli, and the midpoint of the LA posterior wall, in a fourchamber view. The end-diastolic and endsystolic frames during the cardiac cycle were selected for delineation. Then, the endocardial border of each frame was traced in sequence automatically. Manual adjustments could also be made to correct the automatic tracings, which allowed the endocardial border to fit well. Finally, the indexes of the LA volume and function were calculated from automatically generated time–volume curves. The LA volume and function parameters were calculated using previously published equations.13–16 LA volumes were described as follows: (1) LA maximum volume (LAVmax) at end systole when LA volume was maximal just before mitral valve opening, (2) LA minimum volume (LAVmin) at end diastole when the LA volume was the smallest just before mitral valve closure, (3) LA volume before atrial contraction (LAVpreA) as the last frame before mitral valve reopening or at the initiation of the P-wave on ECG, (4) total atrial stroke volume (TASV) as LAVmin, (5) passive atrial stroke volLAVmax LAVpreA, and (6) ume (PASV) as LAVmax active atrial stroke volume (AASV) as LAVmin. The LA volumes were norLAVpreA malized to BSA to make the measurements comparable. The resulting indexes were

expressed as: LAVmax index (LAVmaxI) = LAVmax/ BSA, LAVmin index (LAVminI) = LAVmin/BSA, LAVpreA index (LAVpreAI) = LAVpreA/BSA, TASV index (TASVI) = TASV/BSA; PASV index (PASVI) = PASV/BSA, and AASV index (AASVI) = AASV/ BSA. The LA functions were calculated with the following formulae: (1) total atrial emptying fraction (TAEF) = TASV/LAVmax 9 100%, (2) active atrial emptying fraction (AAEF) = AASV/LAVpreA 9 100%, and (3) passive atrial emptying fraction (PAEF) = PASV/LAVmax 9 100%. Measurement of LA Mechanical Asynchrony: Left atrium mechanical asynchrony was evaluated and quantified by RT3DE. A 3D model of the LA was generated for each dataset and the data was divided automatically by the software into 16, 12, or 6 segments. These segments were represented by different colors so that the global and regional time–volume curves could be represented and analyzed separately. Time–volume curves were generated for each of the 16 segments, and the time when minimal systolic volume (Tmsv) occurred in each segment was used to evaluate LA systolic asynchrony. The LA synchronicity parameters were calculated for the series of curves as previously described (Fig. 1B).13,14 These included the standard deviations (SDs) of the 16-, 12-, and 6-segment data intervals (Tmsv 16-SD, Tmsv 12-SD, and Tmsv 6-SD), and the maximal differences in the Tmsv for all 16-,12-, and 6-segment intervals (Tmsv 16-Dif, Tmsv 12-Dif, and Tmsv 6-Dif). To allow for comparisons to be made between data obtained from patients with different heart

Figure 1. Representative LA images and time–volume curves obtained with RT3DE. A. The endocardial border was detected automatically in the apical four-chamber, two-chamber, and short-axis views. Left atrial volume parameters (LAVmax, LAVmin, and LAVpreA) were calculated from time–volume curves generated from RT3DE data. B. The LA was automatically divided into 16 volumetric segments by Q-Lab to generate 16 regional time–volume curves. LA = left atrium.

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rates, each parameter of LA synchrony was corrected for the number of heart beats and expressed as a percentage of the (RR) interval within each of the datasets (i.e. consisting of 6, 12, or 16 segments). Statistical Analysis: A commercially available statistical analysis software package (SPSS version 17.0, SPSS, Inc., Chicago, IL, USA) was used for the statistical analyses. Continuous variables were expressed as means  SD, and nominal variables were expressed as percentages. Differences between the groups were analyzed with the unpaired t-test for continuous variables. Variables before and after PBMV were compared using paired samples t-tests. The v2 test was used to assess differences between categorical variables. Correlations between study variables were determined using Pearson’s r coefficient. For all tests, P-values 0.05 for all). Changes of LA Volume and Mechanical Function before and after PBMV: The RT3DE findings on LA volume and function variables are listed in Table III. At baseline, RT3DE revealed larger LA volume indexes in

Left Atrial Asynchrony and Function

TABLE II Two-Dimensional, Doppler Echocardiographic, and Pressure Variables in MS Patients before and Immediately after PBMV and in Controls MS (n = 30) Variable LVEDd (mm) LVESd (mm) IVST (mm) PWT (mm) LVM (g/m2) LVEF (%) LAD (mm) MVA (cm2) PHT (ms) MVGmax (mmHg) MVGmean (mmHg) MLAP (mmHg)

MS pre-PBMV (n = 30)

MS post-PBMV (n = 30)

Control (n = 30)

45.4  1.41

46.4  1.72

45.3  1.81

28.5  1.46

29.2  1.72

28.7  1.62

9.4  1.07

9.4  1.04

9.3  1.05

9.3  1.27

9.3  1.18

9.3  1.09

94.6  14.81

96.6  13.57

94.9  12.68

65.1  3.10 47.0  3.53*

64.2  3.75 43.0  3.44*†

67.2  3.49 3.25  1.1

0.88  0.20

1.61  0.28†

–

236.1  65.7 26.6  5.2

135.7  55.7† 11.4  3.9†

– –

16.3  4.2

6.4  2.4†

–

20.2  4.9

10.5  3.8†

–

LVEDd = left ventricular end-diastolic diameter; LVESd = left ventricular end-systolic diameter; IVST = inter ventricular septum thickness; PWT = left ventricular posterior wall diastolic wall thickness; LVM = left ventricular mass; LVEF = left ventricular ejection fraction; LAD = left atrial diameter; MS = mitral stenosis; MVA = mitral valve era; PHT = pressure half time; MVGmax = maximum mitral valve gradient; MVGmean = mean mitral valve gradient; MLAP = mean left atrial pressure, which was measured immediately before and after percutaneous balloon mitral valvuloplasty (PBMV). Data are expressed as mean  SD. *P < 0.05 versus control group. †P < 0.05 versus MS group pre-PBMV.

the MS group (LAVmaxI = 54.5  7.6 mL/m2, LAVpreAI = 46.7  7.4 mL/m2, LAVminI = 39.3  6.5 mL/m2) compared with the control group (LAVmaxI = 22.7  1.9 mL/m2, LAVpreAI = 13.7  2.7 mL/m2, LAVminI = 8.7  2.1 mL/m2). Immediately after PBMV, significant decreases in LA volumes were noted in the MS group (LAVmaxI = 41.5  5.9 mL/m2, LAVpreAI = 38.5  4.9 mL/m2, LAVminI = 27.87.1 mL/m2). Before PBMV, LA global, active, and passive emptying fractions were significantly lower in the MS group than in the healthy controls (P < 0.05). After PBMV significant increases in LA emptying fractions were observed in the MS group (P < 0.05). Compared with the control group, the MS group had smaller PASVI and TASVI, and higher AASVI (P < 0.05) before

PBMV. After PBMV, PASVI had increased and AASVI had decreased, resulting in a TASVI similar to that of the control group. Changes of LA Mechanical Asynchrony before and after PBMV: Left atrium systolic synchronicity derived from the atrial time–volume curves generated before and after PBMV is summarized in Table III for both patients and the controls. Before PBMV, the parameters indicative of atrial asynchrony were significantly higher in the MS group than in controls (P < 0.01). After PBMV, LA asynchrony parameters in the MS group had significantly decreased but the values remained significantly higher than in the controls (P < 0.01). The LA time–volume curves in MS patients and controls are shown in Figure 2(A–C) and illustrate the impact of PBMV on LA synchronicity. In the healthy control group, LA regional time–volume curves reached minimal volumes nearly simultaneously and were neatly ranked. However, in patients with severe MS, the curves had a haphazard organization, which is an indication of LA asynchrony. After PBMV, the time to minimal systolic volume was more homogeneous, indicating that LA emptying volume was more synchronous. Relationships of LA Asynchrony with Heart Structure, Function, and Pressure Variables in Patients with MS: The correlation analysis of LA asynchrony with heart structure and function evaluated by the echocardiographic methods used here are shown in Table IV. In MS patients, the LA volumes measured by RT3DE (LAVmaxI, LAVminI, and LAVpreAI), were positively correlated with the Tmsv-SD and Tmsv-Dif variables indicative of LA asynchrony (all P < 0.05). LA function measurements, including TAEF, PAEF, and AAEF, were negatively correlated with LA asynchrony variables (all P < 0.05). Significant positive correlations were also observed between MVGmean, MVGmax, MLAP, and LA asynchrony variables (all P < 0.05). On the other hand, no correlations were found between other echocardiographic and LA asynchrony variables. The strongest correlations were seen for Tmsv 16-SD and LAVmaxI (r = 0.689, P < 0.01), TAEF (r = 0.717, P < 0.01), and MLAP (r = 0.635, P < 0.01). Reproducibility of the RT3DE Measurements: Inter-and intra-observer variability is reported in Table V. The ICC values for inter- and intra-observer variability for the LA volume (LAVmax, LAVpreA, and LAVmin) and LA synchronicity variables (Tmsv 16-SD, Tmsv 12-SD, Tmsv 6-SD, Tmsv 16-Dif, Tmsv 12-Dif, Tmsv 6-Dif) showed 295

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TABLE III Left Atrium Volume, Mechanical Function, and Synchronicity Variables Measured by RT3DE Controls and in MS Patients before and Immediately after PBMV MS (n = 30) Variable LA volume and mechanical function variables LAVmax I (mL/m2) LAVmin I (mL/m2) LAVpreA I (mL/m2) TASVI (mL/m2) PASVI (mL/m2) AASVI (mL/m2) TAEF (%) AAEF (%) PAEF (%) LA synchronicity variables Tmsv 16-SD (%) Tmsv 12-SD (%) Tmsv 6-SD (%) Tmsv 16-Dif (%) Tmsv 12-Dif (%) Tmsv 6-Dif (%)

Pre-PBMV

54.5 39.3 46.7 12.5 6.5 8.0 28.5 11.4 16.5

        

7.6* 6.5* 7.4* 2.8* 1.8* 1.7* 5.7* 5.1* 4.7*

16.86 16.11 12.67 53.53 47.82 28.72

     

9.95* 7.70* 11.76* 16.46* 18.46* 19.64*

Post-PBMV

Control (n = 30)

41.5 27.8 38.5 15.5 8.6 6.5 42.1 21.6 20.5

        

5.9*† 7.1*† 4.9*† 3.7* 2.1* 1.6† 4.7*† 4.3*† 3.9*†

22.7 8.7 13.7 16.2 9.1 6.0 61.5 39.8 37.4

        

1.9 2.1 2.7 2.5 2.3 1.9 6.2 5.9 5.4

10.22 10.64 6.57 39.24 33.7 17.54

     

9.69*† 9.65*† 7.68*† 19.93*† 17.26*† 13.56*†

2.56 1.00 1.00 5.45 3.36 2.64

     

1.60 0.33 0.54 1.45 1.38 1.51

LA = left atrium; LAVmaxI = left atrium volume at end systole (largest atrial volume just before mitral valve opening) indexed for body surface area; LAVminI = left atrium volume at end diastole (smallest atrial volume before mitral valve closure) indexed for body surface area; LAVpreAI = left atrium volume at the last frame before mitral valve reopening or at the time of P wave on ECG, indexed for body surface area; TASVI = total atrial stroke volume indexed for body surface area; MS = mitral stenosis; PASVI = passive atrial stroke volume indexed for body surface area; AASVI = active atrial stroke volume indexed for body surface area; TAEF = total atrial emptying fraction; AAEF = active atrial emptying fraction; PAEF = passive atrial emptying fraction. Tmsv 16SD = SD of Tmsv of all 16 segments of the atrium; Tmsv 12-SD = SD of Tmsv of 12 segments of the atrium; Tmsv 6-SD = SD of Tmsv of 6 segments of the atrium; Tmsv 16-Dif = maximal difference of Tmsv among all 16 segments; Tmsv 12-Dif = maximal difference of Tmsv among 12 segments; Tmsv 6-Dif = maximum difference of Tmsv among 6 segments; PBMV = percutaneous balloon mitral valvuloplasty; RT3DE = real time three-dimensional echocardiography. Data are expressed as mean  SD. *P < 0.05 versus control group. †P < 0.05 versus MS group pre-PBMV.

excellent agreement (all ICC > 0.9, P < 0.05). CVs for intra-observer variability for the LA volume and LA synchronicity variables were adequate or clinically acceptable. CVs of interobserver variability for Tmsv 16-SD and Tmsv 12SD were clinically acceptable, but the CVs of Tmsv 6-SD, Tmsv 16-Dif, Tmsv 12-Dif, and Tmsv 6-Dif measurements were relatively large. CVs of intraand inter-observer variability for Tmsv 16-SD were smaller than for Tmsv 12-SD. Bland–Altman analyses for inter- and intra-observer variability in LA volume and LA synchronicity variables are shown in Table V and graphically in Figure 3. Discussion: The findings of the present study indicate that RT3DE can quantify LA function and asynchrony with good reproducibility in patients with MS. RT3DE reliably demonstrated (1) expansion of LA volume, deterioration of LA function, and increase in LA asynchrony in MS patients; (2) 296

significant adaptation of LA physiology and decrease in asynchrony accompanying hemodynamic changes that occurred following PBMV; and (3) positive correlation of LA asynchrony parameters with LA volume and pressure but a negative correlation with LAEF. Measurement of PBMV-Related Changes in LA Volume and Function by RT3DE: The assessment of LA volume and function is of great value for studying adverse cardiovascular events.21–24 RT3DE has been used to assess LA volume and function in many types of patients because it can rapidly and accurately detect phasic changes during the cardiac cycle.13,25,26 However, few RT3DE studies have included MS patients undergoing PBMV procedures. The LA is a reservoir, pump, and conduit, effectively modulating LV filling.27 In this study, the LA volume was significantly enlarged and the AASVI increased in MS patients, whereas the PAS-

Left Atrial Asynchrony and Function

Figure 2. Representative 16-segment LA time–volume curves from pre- and post-PBMV patients and the control group. A. In patients with severe MS, time–volume curves of LA segments were disperse, suggesting LA asynchrony. B. In patients after PBMV, systolic synchronicity was achieved as reflected by time–volume curves of LA segments that displayed a more orderly pattern. C. In controls, the time–volume curves of LA segments reached the minimal systolic volume simultaneously, indicating a synchronous pattern of contraction. PBMV = percutaneous balloon mitral valvuloplasty; LA = left atrium.

VI and LAEF passively decreased. This finding is in line with previous measurements using speckle tracking echocardiography (STE).28 This might be explained by MS functioning as an obstacle to LA emptying, thus leading to increase in LA afterload, LA pressure elevation, and eventual deterioration of conduit function. According to the Frank–Starling mechanism, as the LA stretches, AASVI increases as a compensatory mechanism to maintain a normal volume of blood pumped from the LA. However, increased LA pressure and stretch of myocardial fibers may shift the cardiac muscle to the descending portion of the Frank– Starling curve, leading to abnormal LA function. Left atrium volume significantly decreased after PBMV, leading to improvement in LA function. This may have been the result of PASVI normalization, which is largely dependent on the MVA-related afterload in patients with MS. Attenuation of the intrinsic contractility of the LA myo-

cardium caused by a decline of LAVpreA may explain the decrease in AASVI after the procedure. However, our findings reflected only the active process of physiological adaptation secondary to procedure-related hemodynamic changes, that is, an acute fall in LA pressure (or decrease in the pressure gradient through the mitral valve). Future randomized studies could provide additional insight into the relationship between the long-term effects of PBMV and LA remodeling. Assessment of LA Asynchrony by RT3DE: Mitral stenosis is a structural heart disease commonly associated with increased risk of AF.29 Recent trials2,3,30,31 have demonstrated that LA asynchrony detected by echocardiography techniques such as Doppler tissue imaging (DTI) or 2D STE during systole can predict new-onset or recurrent AF after defibrillation. However, assess297

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TABLE IV Relationships of left atrium synchronicity variables with heart structure, function and pressure variables in 30 patients with mitral stenosis (Pearson’s r coefficients) Variable

Tmsv 16-SD (%)

Tmsv 12-SD (%)

Tmsv 6-SD (%)

Tmsv16-Dif (%)

Tmsv 12-Dif (%)

Tmsv 6-Dif (%)

LAD MVA PHT MVGmean MVGmax MLAP LAVmax I LAVmin I LAVpreA I TASVI PASVI AASVI TAEF AAEF PAEF

0.232 –0.189 0.279 0.477* 0.513* 0.635* 0.689** 0.632** 0.638** 0.205 0.116 0.197 –0.717** –0.571** –0.640**

0.121 –0.138 0.124 0.322* 0.459* 0.519* 0.588** 0.658** 0.590** 0.146 0.135 0.114 –0.768** –0.612** –0.583**

0.052 –0.101 0.112 0.127 0.121 0.157 0.380* 0.424* 0.382* 0.097 0.082 0.079 –0.546* –0.370* –0.436*

0.127 –0.224 0.197 0.571* 0.393* 0.513 0.488** 0.612** 0.516** 0.059 0.087 0.028 –0.575** –0.467** –0.509**

0.093 –0.231 0.129 0.4619* 0.362* 0.397* 0.538** 0.651** 0.556** 0.003 0.002 0.001 –0.508** –0.443** –0.492**

0.055 –0.107 0.121 0.087 0.151 0.131 0.335* 0.400* 0.342* 0.004 0.030 0.001 –0.464* –0.404* –0.425*

LAD = left atrial diameter; MVA = mitral valve area; PHT = pressure half time; MVGmean = mean mitral valve gradient; MVGmax = maximum mitral valve gradient; LAVmaxI = left atrium volume at end-systole (largest atrial volume just before mitral valve opening) indexed for body surface area;LAVminI = left atrium volume at end-diastole (smallest atrial volume before mitral valve closure) indexed for body surface area;LAVpreAI = left atrium volume at the last frame before mitral valve reopening or at the time of P wave on ECG indexed for body surface area;TASVI = total atrial stroke volume indexed for body surface area; PASVI = passive atrial stroke volume indexed for body surface area; AASVI = active atrial stroke volume indexed for body surface area; TAEF = total atrial emptying fraction; AAEF = active atrial emptying fraction; PAEF = passive atrial emptying fraction. *P