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European Journal of Echocardiography 2004 5(6):407-415; doi:10.1016/j.euje.2004.03.002
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Copyright © 2004, The European Society of Cardiology

Mitral annular motion as a surrogate for left ventricular ejection fraction: real-time three-dimensional echocardiography and magnetic resonance imaging studies

Jian Xin Qin, Takahiro Shiota*, Hiroyuki Tsujino, Giuseppe Saracino, Richard D. White, Neil L. Greenberg, Jun Kwan, Zoran B. Popovic, Deborah A. Agler, William J. Stewart and James D. Thomas

Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA

Received 21 November 2003; received in revised form 26 February 2004; accepted after revision 2 March 2004.

* Corresponding author. Director, 3D Echocardiography, Department of Cardiovascular Medicine, Desk F15, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel.: +1-216-445-7287; fax: +1-216-445-4419. shiotat{at}ccf.org


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Notes
 References
 
Aims: To validate the accuracy of mitral annular motion assessed by real-time three-dimensional echocardiography (RT3DE) as a surrogate for determination of the left ventricular function in comparison with magnetic resonance imaging (MRI).

Methods and results: Forty-seven patients with a variety of cardiac pathologies underwent both RT3DE and MRI exams. After 3D data sets were transferred to a PC with a custom-made program, nine consecutive rotational apical plane images (20° apart) were displayed. The two mitral leaflet insertion points were manually identified in each plane. The geometry of the mitral annulus was reconstructed from a total of 18 coordinates (x, y, z), and the changes in mitral annular area and mitral annular motion along the apical long axis were calculated. The left ventricular ejection fraction (LVEF) determined by MRI was 41±18%, and 24 patients had LVEF<50%. Mitral annular motion (y) obtained by RT3DE was 11 ± 5 mm and correlated moderately well with LVEF (x) measured by MRI (r = 0.84, y = 0.25x+0.43, p<0.0001). The mitral annular motion < 12 mm was a good threshold for detecting LVEF<50% with 96% sensitivity, 85% specificity, and 91% accuracy.

Conclusion: Mitral annular motion determined by RT3DE correlated moderately well with LVEF; and systolic motion, <12 mm, accurately detected LV dysfunction.

Keywords: Echocardiography; Magnetic resonance image; Mitral valve; Left ventricular function


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Notes
 References
 
Left ventricular (LV) ejection fraction (LVEF) is used widely for evaluating LV contractility.1,2 This parameter can be provided by several invasive or noninvasive methods3–5 based on the geometric assumption. However, the accuracy is limited when the left ventricle appears asymmetric.6–8 Real-time three-dimensional echocardiography (RT3DE) has demonstrated an enhanced ability for assessing the volume of the left ventricle associated with ventricular aneurysm.9–11 However, due to the narrowed sector angle (60°x60°) of the current RT3DE system, it may be impossible for RT3DE to include the entire left ventricle, especially when the heart is dilated.10,11 The endocardial boundary may not be clear enough for tracing because of low image resolution. The dynamic movement of the mitral annulus is an alternative parameter for evaluating LV systolic function without the need to trace the entire endocardial boundary of the LV. Although the systolic velocities of mitral annular motion detected by tissue Doppler echocardiography have been proven to correlate well with LV ejection fraction,12 the Doppler angle may reduce the accuracy of the mitral annular velocity measurements. Several methods that avoid the Doppler angle limitation have been used to reconstruct the three-dimensional shape of the mitral annulus, including the 2D rotational images obtained from transthoracic or the transesophageal echocardiographic images over a cardiac cycle.13–15 Although these methods have yielded promising preliminary results, prolonged acquisition times, imperfect reconstruction techniques, and tedious measurements have restricted their clinical applications. A new computerized method for reconstruction of the mitral annulus with RT3DE, recently developed in our laboratory, offers to overcome these limitations, but clinical application remains unproved.

The aim of this study was, therefore, to validate the accuracy of the mitral annular function determined by our new computerized method using RT3DE for evaluating LV systolic function. In this study, we sought (1) to reconstruct the mitral annular geometry in cardiac patients, (2) to verify the relation between mitral annular motion and LVEF in comparison with magnetic resonance imaging (MRI), and (3) to establish an optimal threshold of mitral annular motion for detection of LV dysfunction.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Notes
 References
 
Patient population
Forty-seven cardiac patients who were referred consecutively to MRI for evaluation of LV systolic function and underwent RT3DE on the same day were enrolled in this study. The echo imaging quality was not screened prior to the study, and patients with arrhythmia were not excluded from the study. The patients' average age was 55 ± 11 years (from 27 to 77 years), and 40 patients were males. Of the 39 from the 47 patients, 11 patients suffered from aortic regurgitation, four had dilated cardiomyopathy, 20 had coronary heart disease, and four had right ventricular dysplasia with normal LV; all of these patients had no significant mitral regurgitation. The remaining eight patients had more than moderate mitral regurgitation (six with coronary heart disease and two with either dilated cardiomyopathy or sarcoidosis). The study was approved by the Institutional Review Board of the Cleveland Clinic Foundation.

Real-time three-dimensional echocardiography
A Volumetric system and a 2.5 MHz hand-held transducer (Volumetrics Medical Imaging Inc., Durham, NC) were used in this study for obtaining 3DE images from apical window transthoracically with a patient in left decubital supine position. Two sinus cardiac cycles' 3DE images were digitally stored on optical disks for off-line analysis, after the highest image quality was achieved. Care was taken to include the entire mitral valvular structure in the real-time pyramidal volumetric data set during the whole cardiac cycle.

Magnetic resonance image
A 1.5-Tesla whole-body scanner (Siemens Vision, Symphony, or Sonata, Erlangen, Germany) with a phased-array coil was employed to acquire MRI images of LV. The detailed technique has been described in previous studies.16,17 In brief, the LV volumes and LVEF were determined with a series of short-axis slices (8–10 mm apart) of LV by Simpson's rule, and served as references. All measurements were performed by an experienced investigator without the knowledge of the RT3DE measurements.

Reconstruction of mitral annulus
With the use of a commercially available software (3D EchoTech, Lafayette, CO), the center of the LV apex and mitral annulus were identified manually to establish a reference/long axis of LV. Around the axis, nine consecutive rotational apical plane images (20° between each plane) were created and read into a custom-made software package programmed in our laboratory in LabView environment (National Instruments, Austin, TX). The coordinates of the two mitral leaflet insertion points were manually identified in each image at end-systolic and end-diastolic phases (Fig. 1). Those coordinates were converted into a Cartesian coordinate system with the z-axis corresponding to the reference axis, the x-axis corresponding to septal and lateral walls, and the y-axis corresponding to the inferior and anterior walls. The end-diastolic and end-systolic mitral annuli were then reconstructed by fitting and interpolating these original 18 coordinates in each of the three spatial axes using Fourier filtration.14 In this way, the reconstructed mitral annulus was not affected by the location of the LV apex. The projected area on the short-axis plane (X–Y plane) of the mitral annulus, its changes during the cardiac cycle (the difference between end-diastolic and end-systolic value, divided by end-diastolic value, multiplying 100), and the longitudinal mitral annular motion (the difference between mean heights of mitral annulus at end-diastolic and end-systolic phases) were automatically calculated from the fitted data. The time for the reconstruction of mitral annulus, which included importing the 3D data to workstation and identifying the coordinates, was less than 10 min in all patients.18


Figure 1
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  		Figure 1 An illustration of real-time 3DE image with nine apical planes (20° apart) at the end-diastolic phase. The common left ventricular long axis is defined as a straight blue line shown in each plane. The mitral annular hinge points in each plane are marked as yellow points. The boundary of the LV is traced as red line in each plane.

 
Inter- and intra-observer variabilities
In order to assess the effect of observational variability on the mitral annular motion measured from the reconstructed mitral annulus, the RT3DE images of 10 randomly selected patients from our patient population were transferred to the same workstation with the same program. The longitudinal mitral annular motion was then measured by two independent observers and finally by the original observer on a different day.

Statistical analysis
All data are presented as the mean value ± SD. To support the accuracy of longitudinal mitral annular motion calculated from reconstructed mitral annulus for evaluation of LV function, linear regression was used to examine the relationship between mitral annular motion, measured by RT3DE, and LVEF, measured by MRI. A ROC curve was used to determine the optical threshold point for detecting LVEF<50%. ANOVA and a post hoc test were used to analyze the difference between patient groups. A p-value<0.05 was considered significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Notes
 References
 
Mitral annular geometry and motion detected by RT3DE
Mitral annular shape
From the projected short-axis view (X–Y plane), the mitral annulus was displayed as an ellipse when viewed from the atrial side with a short-axis to long-axis ratio of 0.8±0.1 both at end-diastole and end-systole. No significant difference was found among the various patient groups (Table 1). In the lateral view (Y–Z plane), the mitral annulus was not in the same plane according to the short-axis view. The difference between the highest point and lowest point of the mitral annulus, which was calculated to assess the non-planarity, was 11.9 ± 4.0 mm at end-diastole and 11.4 ± 3.9 mm at end-systole. Anteroseptal and posterior regions of the mitral annulus elevated superiorly towards left atrium in saddle shapes (Fig. 2).


Figure 2
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  		Figure 2 An example of the reconstructed mitral annulus. The left panel shows the real-time 3DE image and the mitral annulus (pink line). The right panel shows the reconstructed mitral annulus in Cartesian coordinate system (brown line in the cubic center) and on the project views (X–Y plane, X–Z plane and Y–Z plane). AP 3C, apical three chambers; AP 4C, apical four chambers; Ao, aorta.

 


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  		Table 1 Left ventricular and mitral annular function in different patient groups

 
Mitral annular area
The mitral annular area projected to the short-axis view (X–Y plane) was calculated for each patient. The average mitral annular area index (normalized by body surface area) was 6.2 ± 2.0 cm2/m2 at end-diastole and 5.2 ± 1.5 cm2/m2 at end-systole. The mitral annular area indices at both end-diastole and end-systole were significantly larger in patients with dilated cardiomyopathy or mitral regurgitation than those with normal LV or aortic regurgitation (p<0.05, Table 1). The average change in mitral annular area was 15±13% and no significant differences in the changes of mitral annular area among the patient groups were found (p0.05, Table 1).

Mitral annular motion
From end-diastole to end-systole, the mitral annulus moved towards the apex. The average longitudinal mitral annular motion was 11 ± mm. The mitral annular motion significantly decreased in patients with LV dysfunction including dilated cardiomyopathy, coronary artery disease, or mitral regurgitation (Table 1).

Left ventricular function determined by MRI
Left ventricular volumes
The average LV volume indices of all 47 patients were 125 ± 49 ml/m2 at end-diastole and 79 ± 50 ml/m2 at end-systole. Both LV EDV and ESV indices were larger in patients with dilated cardiomyopathy, coronary artery disease, or mitral regurgitation than those with normal LV or aortic regurgitation (p<0.05, Table 1).

Left ventricular ejection fraction
The average LVEF was 41±18% and ranged from 12% to 75% in the 47 patients. Twenty-seven out of the 47 patients had LVEF<50%. Significant differences in LVEF were found between different patient groups (p<0.05); the patients with dilated cardiomyopathy had the lowest LVEF in this patient population (Table 1).

The LV volumes were also measured with a rotational apical nine-plane method by RT3DE18 in 29 patients, who had reasonable image qualities for tracing the endocardial boundary, out of the 47 studied patients (62%). The average LV EDVI, ESVI, and LVEF were 104 ± 32 ml/m2, 63 ± 26 ml/m2, and 41 ± 14%, respectively. Good correlations were found between MRI and RT3DE for LV EDV, ESV, and LVEF. The r-values were 0.95, 0.94 and 0.91, respectively.

Relationship between the geometry of mitral annulus and LV function
Of the 47 patients, the range of mitral annular area was 6.5 cm2–21.7 cm2 at end-diastole and 5.0 cm2–15.2 cm2 at end-systole. Based on both end-diastolic and end-systolic values, the mitral annular area (y) detected by RT3DE correlated moderately well with LV volume (x) measured by MRI (r = 0.71, y = 0.02x+6.43, n = 94, p<0.0001, Fig. 3). These results demonstrate that a more dilated LV is associated with a larger mitral annulus.


Figure 3
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  		Figure 3 The relation between mitral annular size and LV volume. ED, end-diastole; ES, end-systole; MRI, magnetic resonance imaging. The regression line is drawn by combining the values of ED and ES.

 
The range of longitudinal mitral annular motion in the total patient population was 2 mm–23 mm. The positive linear relationship was found between mitral annular motion and LVEF measured by MRI (r = 0.84, y = 0.25x+0.43, p<0.001, Fig. 4). The results indicated a positive relationship between the severity of LV dysfunction and the reduction of the mitral annular motion. However, there was poor correlation between the area change of mitral annulus and LVEF (r = 0.27, n = 47, p>0.05).


Figure 4
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  		Figure 4 The relation between mitral annular motion and LV ejection fraction. ANN, mitral annular; LVEF, left ventricular ejection fraction. The other abbreviations are the same as the above.

 
Accuracy of mitral annular motion for detecting LV dysfunction
Of the 47 patients, 27 patients had LVEF<50%. A ROC curve analysis was used to identify the optimal threshold point of mitral annular motion for detecting LVEF<50%. The area under the ROC curve was 0.966 and the standard error was 0.030. The optimal threshold point of mitral annular motion was <12 mm with 96% sensitivity (95% CI 78.8–99.3), 85% specificity (95% CI 62.1–96.6) and 91% accuracy (Fig. 5).


Figure 5
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  		Figure 5 The ROC curve. The optimal threshold point of mitral annular motion is 12 mm.

 
Inter- and intra-observer variability
There were good agreements between the two independent observers' measurements of the mitral annular motion along the long axis (r = 0.98, mean difference = 0.5 ± 1.5 mm), and between the two measurements made by a single observer (r = 0.99, mean difference = 0.5 ± 0.9 mm).


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Notes
 References
 
In this patient study, a useful clinical tool was established for determining the geometry and motion of mitral annulus. Good correlations between the area of the mitral annulus and LV size, and between longitudinal mitral annular motion and LVEF were demonstrated. The optimal threshold point of the longitudinal mitral annular motion for detecting LVEF<50% was 12 mm with 91% accuracy.

Geometry of mitral annulus
For better understanding of the geometry and function of the mitral annulus, several imaging methodologies have been used in recent decades, including X-ray marker imaging,19,20 sonomicrometer,21,22 MRI,23 and echocardiography.13,15,24–26 The saddle shape of mitral annulus with its septal-anterior and posterior parts elevated to the left atrium was demonstrated in several studies,13,26,27 and the flexibility of the mitral annulus was also confirmed with a 15–26% reduction in mitral annular area from end-diastole to end-systole.13,25,28 The normal mitral annular area and index were 9.5 ± 1.4 cm2 and 3.8 ± 0.7 cm2/m2, respectively.23,28 Similar results for patients with normal LV were also obtained in the current RT3DE study (Table 1). However, larger mitral annular size measured by reconstructed 3D with transesophageal echocardiography was reported previously in our laboratory.13 Such differences in the measurement of the mitral annular size exist because of the lack of a unique definition of mitral annulus. Some investigators may consider the hinge points of the mitral valve at the left atrial side while others may take them well into the LV muscle. In the current study, we select the mitral annular hinge points on the LV side for evaluating the relationship between the longitudinal mitral annular motion and LVEF, therefore, the measurement of mitral annular size might be slightly larger. On the other hand, there is no gold standard for measuring mitral annulus in human beating hearts, making the interpretation of the mitral annular geometry and size more difficult, although this can be done successfully by the implantation of radiopaque markers on the mitral annulus in animal studies.29–32

The accuracy of longitudinal mitral annular motion for evaluation of LV systolic function
During LV systole, the mitral annulus contracts both longitudinally and circumferentially. The magnitude of the mitral annular motion is related to LV contractility. In the prior M-mode echocardiographic studies, the systolic excursion of mitral annulus toward the apex reflected the longitudinal systolic shortening of the LV.33 Two-dimensional echocardiography was also used to evaluate the longitudinal mitral annular motion. In comparison with radionuclide ventriculography, Pai et al. found that the average systolic excursion of the mitral annulus (septal and lateral side in apical four-chamber view) correlated excellently with LVEF.34 However, the longitudinal mitral annular motion may be depressed by age and LV hypertrophy secondary to systemic hypertension or aortic stenosis in the presence of normal LVEF. Wandt et al.35 demonstrated that longitudinal mitral annular motion decreased with age, while circumferential contraction increased; therefore, the mitral annular longitudinal motion may underestimate LVEF in the elderly. Since some elderly patients and patients with a variety of cardiac pathologies such as with/without LV hypertrophy were included in the current study, the longitudinal mitral annular motion correlated only moderately well with LVEF. Therefore, further study is needed to clarify the influence of different cardiac pathologies and old age on the mitral annular motion with RT3DE.

Advantage of analyzing mitral annular function
Mitral annular function has the potential for providing an alternative measure of LV function with the use of RT3DE. Because the limited angle of the 3DE pyramidal volume of the current system is only 60°x60°, it is difficult to include the entire LV of a dilated heart, and it compromises accuracy in measurement of LV volume.10,16,36 The near field of the LV was often out of the 3DE pyramidal volume in dilated hearts; however, the entire mitral annulus was always included in the mid to far fields in both apical and parasternal windows. Also, our software is able to analyze mitral annular motion obtained with a new live 3D system, which is now available in some major institutions.37 Low image resolution of current RT3DE systems is another drawback for clinical applications. Five of 34 (15%) patients in our previous study,16 and 18 patients (38%) in the current study were excluded from the evaluation of LV volumes because of suboptimal imaging quality. Therefore, analyzing mitral annular motion is an alternative to identifying LV function when the endocardium is suboptimal or out of the 3DE pyramidal volume for tracing. The current 3D analysis of the mitral annulus provides not only the longitudinal motion of mitral annulus itself, but also the geometry of mitral annulus, such as the saddle shape of the annulus, the size of both anterior and posterior mitral leaflets, and the angle between the two leaflets,38 all of which could not be demonstrated with traditional 2D and M-mode echo easily.26 Several previous animal studies suggested that enlargement of the annulus mainly in the antero-posterior direction and subsequent annular "circularization" developed after left circumflex artery ligation had important roles to separate edges of two mitral leaflets and caused ischemic mitral regurgitation.32,39 Therefore, analyzing mitral annular geometry may give us the potential to understand the mechanism of ischemic mitral regurgitation.

Limitations
Several previous studies reported that the size of the mitral annulus decreased in systole and reached the minimal area at mid-systole,40 and then increased in diastole and reached the maximal area at the P wave of the EKG.28,31 Only end-diastolic and end-systolic phases in the cardiac cycle were analyzed in our study, therefore, the largest and smallest mitral annulus might have been missed by the current method, resulting in underestimation of area changes of the mitral annulus. The etiology of the mitral regurgitation may affect the mitral annular area with myxomatous degeneration probably being associated with larger areas for a given LVEF. All of these may explain why poor relationship between the area change of mitral annulus and LVEF was found in the present study. An off-center reference axis may be another cause for underestimation of longitudinal mitral annular motion. Good correlation with LVEF may be found when maximal and minimal mitral annular dimensions are detected and when new live 3D with high resolution is used to acquire the images.37 Although the accuracy for prediction of an LVEF less than 50% with the longitudinal mitral annular motion was 91% in the present study, there was a significant spread in annular motion (Fig. 4), and this might limit its clinical use. Low lateral resolution (3–4 mm at 7 cm depth)41 is one of the limitations of the current RT3DE systems. Failure to recognize mitral annular hinge points in apical planes might create measurement errors. Finally, although 39 patients of the 47 patients in this study were considered without obvious mitral valve pathologies, their underline disease might affect the geometry and function of the mitral annulus, therefore, healthy volunteers should be included in the validation study for this new methodology in the future.

In summary, longitudinal mitral annular motion correlated moderately well with LV systolic function in patients with a variety of cardiac pathologies, and the accuracy of systolic motion <12 mm for detecting LVEF<50% was 91%. Further studies are recommended for the effect of age and underline diseases on the potential evaluation of LV systolic function with mitral annular geometry and motion in clinical settings.


   Acknowledgements
 
We thank Mr. David Tollon for his careful editorial assistance.


   Notes
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Notes
References
 
{star} Part of this study was presented at the 51st Annual Scientific Sessions of American College of Cardiology, March 17–20, 2002, Atlanta, Georgia, USA.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Notes
 References
 

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