Real-time three-dimensional (3D) echocardiography and unique software permit mitral annular (MA) tracking throughout systole to assess MA remodeling and function. Whether MA structure and function are altered differently depending on the etiology of mitral regurgitation (MR) is currently not known.
We evaluated dynamic MA characteristics in patients with significant MR secondary to mitral valve prolapse and functional MR and compared them with normal controls. Novel 3D tracking software (based on 3D optical flow combined with block matching) was used to identify 16 circumferential equidistant MA points and to track changes in MA area and apical descent from end-diastole to end-systole. Twenty-eight patients with at least moderate MR and 15 normal controls underwent complete transthoracic two-dimensional and quantitative Doppler studies with 3D full-volume MA imaging from the apical 4-chamber view.
For each group studied, left ventricular size, systolic function, and dynamic MA characteristics were characterized. Patients with functional MR demonstrated end-diastolic MA area enlargement with reduced systolic area change and reduced apical descent (11.1 ± 2.7 cm 2 , 13 ± 5%, and 6 ± 2 mm, respectively) compared with normal controls (9 ± 2 cm 2 , 26 ± 8%, 11 ± 2 mm, respectively) ( P < .05). In comparison, patients with prolapse MR demonstrated the largest end-diastolic MA areas with preserved annular area change and only mild reduction of apical descent (16.1 ± 3.5 cm 2 , 21 ± 6%, and 9 ± 3 mm; P < .05 for area change and apical descent compared with normal). This finding suggests that the pathophysiology of mitral leaflet prolapse may involve significant MA remodeling without deterioration of dynamic MA function.
Patients with MR have significant MA enlargement, irrespective of MR etiology. In contrast to functional MR, patients with MR secondary to leaflet prolapse have the largest annular remodeling—almost 80% increase in area—and yet have preserved annular function and dynamicity. These findings may influence surgical repair technique.
Both experimental and clinical data have demonstrated that the normal mitral annulus is a geometrically complex and dynamic structure that undergoes substantial area change throughout the cardiac cycle. The surgical repair of significant mitral regurgitation (MR) usually involves annular remodeling with a surgical ring. In recent years, several different annular rings (complete or partial, rigid or deformable, flat or saddlelike) have been developed in attempts to optimize postrepair annular function and leaflet stress distribution. However, to date, the dynamic changes of the native mitral annulus in the setting of significant MR have not been well characterized. Three-dimensional (3D) echocardiography has already provided important insight regarding the normal saddlelike mitral annular (MA) conformation. Novel software has been developed to permit tracking of defined 3D structures over time. The intent of this study was to combine real-time 3D echocardiographic imaging and novel 3D MA tracking software to compare dynamic MA characteristics in patients with MR secondary to mitral valve prolapse (P-MR), patients with functional MR (F-MR), and normal controls. We hypothesized that the etiology of MR would have important effects on MA size and function.
The research protocol was approved by the institutional review board, and all participants provided written informed consent. Consecutive patients referred for transthoracic echocardiography that demonstrated at least moderate F-MR or moderate MR on the basis of leaflet prolapse were approached for study participation. At least moderate MR was required for study participation because our aim was to better understand the dynamic function of the mitral annulus in those more likely to undergo surgical valve repair. In addition, the etiology of valve dysfunction is often less certain in patients with less significant regurgitation. Patients were excluded if they had more than mild aortic valve dysfunction or atrial fibrillation. Patients with significant MA or leaflet calcification were also excluded to avoid the limitations imposed by software tracking of calcification-related artifacts. Volunteers for the control group had no significant medical histories and normal echocardiographic results.
Two-Dimensional (2D) Echocardiography
Transthoracic echocardiography (2-4 MHz; iE33 or Sonos 7500; Philips Medical Systems, Andover, MA) was performed on all patients and normal volunteers. Mitral valve pathology was assessed by consensus of two experienced echocardiographers and classified as functional, prolapse, or other. Prolapse was diagnosed from the parasternal long-axis view and required either the anterior or posterior leaflet to travel ≥2 mm past the annular plane during systole. The diagnosis of F-MR required regional or global left ventricular (LV) systolic dysfunction (ejection fraction [EF] < 40%) and normal mitral leaflet appearance. Patients with LV dysfunction on the basis of ischemia were included in this functional group. Left atrial volume was assessed from a single-plane apical imaging window. LV volumes (end-diastole, end-systole) and EF were calculated using Simpson’s method from apical biplane imaging windows. An average of 3 samples was recorded for all 2D, 3D, and Doppler measures. For patients with MR, the effective regurgitant orifice area (EROA) was calculated from pulsed Doppler as EROA = (mitral stroke volume − aortic stroke volume)/MR time-velocity integral. Following patient enrollment, MR severity was also semiquantitated using the integrative approach recommended by the American Society of Echocardiography. To facilitate comparisons between groups, patients with moderate MR were further categorized as mild to moderate (grade 2) or moderate to severe (grade 3) on the basis of quantitative measure of EROA and regurgitant volume. Severe MR (grade 4) was not further categorized. All patients were given MR severity scores of 2, 3, or 4 (as above). By design, patients with mild MR (grade 1) were not enrolled.
All study subjects underwent real-time 3D studies of mitral valve function immediately following complete 2D and Doppler echocardiography. With a breath-hold in expiration, 3D full-volume data were acquired with 4 electrocardiographically triggered sequential volumes, creating a full-volume scan of 90° × 90°, from the apical imaging window. Scan depth and sector density were optimized to encompass the circumference and apical descent of the mitral annulus. The mean 3D frame rate was 17 ± 2 Hz. The acquisition of the 3D data set took approximately 1 minute.
Novel 3D feature-tracking software (TomTec Imaging Systems GmbH, Munich, Germany) was used to identify MA points and to track changes in MA area and apical descent from end-diastole to end-systole. Using a sequence of 8 equidistant radial cut planes, at a defined frame of interest (end-systole), 16 initial tracking points were manually identified and placed along the annular circumference ( Figure 1 ). Because the mitral annulus can be difficult to identify from a still image, beating video loops were first observed, then the annular points tagged on a still end-systolic image. The feature-tracking algorithm follows the first initial tracking points in time by searching the maximum likelihood over its neighborhood in the following frames and then automatically detecting these structures and tracking them throughout the cardiac cycle. The tracking application uses optical flow and region-based matching techniques that are based on the analysis of speckle noise patterns within the 3D data set. With this software, the Cartesian coordinates of 16 equidistant circumferential points along the mitral annulus were tracked throughout the cardiac cycle ( Figure 2 ). Image analysis took up to 6 minutes per study.
Cardiac Event Timing
The 3D full-volume data were captured on the basis of electrocardiographic R wave–triggered stitching together of 4 subvolumes. When exported to the software platform, the electrocardiographic data are lost; however, the first frame depicted corresponds to the R-wave peak (end-diastole). The timing of all other cardiac events was defined on the basis of the position of the aortic and mitral valves. Systole was identified from the opening of the aortic valve, with the period of isovolumic contraction being the period between mitral valve closure and aortic valve opening. End-systole was identified as the frame preceding closure of the aortic valve. Mid-diastole was defined as the midframe with an open mitral valve. The final frame before mitral valve closure was taken as the time point closest to atrial ejection.
Hemodynamic characteristics and summary echocardiographic data are expressed as mean ± SD. Differences between groups were analyzed with one-way analysis of variance, followed by the Holm-Sidak method for multiple pairwise comparisons (SigmaStat version 3.0.1; Systat Software, San Jose, CA). Interobserver variability is expressed as the absolute difference between the two measurements as a percentage of their mean values. All tests were two sided, and P values < .05 were considered statistically significant.
Sixty-five patients were evaluated, of whom 61 had adequate studies for MR quantification. Of 49 patients with at least moderate MR, 21 patients had significant annular or leaflet calcification and were excluded from further analysis. The final study group consisted of a total of 28 patients: 13 patients with F-MR and 15 patients with P-MR. The control group comprised 15 healthy volunteers. Clinical, hemodynamic, and echocardiographic characteristics of the patients with P-MR, those with F-MR, and the normal controls are presented in Table 1 .
|Normal controls||Patients with P-MR||Patients with F-MR|
|Variable||(n = 15)||(n = 15)||(n = 13)|
|Age (yrs)||40 ± 10 (25-56)||62 ± 20 (41-80)||68 ± 11 (54-87)|
|BSA (m 2 )||1.8 ± 0.19 (1.5-2.1)||1.9 ± 0.46 (1.5-2.4)||1.8 ± 0.28 (1.3-1.8)|
|Heart rate (beats/min)||65 ± 10 (50-87)||76 ± 25 (51-101)||82 ± 14 (60-109)|
|LV end-diastolic volume (mL)||133 ± 21 (94-181)||148 ± 62 (78-202) ∗ †||229 ± 68 (138-340) ∗|
|LV end-systolic volume (mL)||51 ± 8 (38-69||56 ± 37 (22-96) †||161 ± 60 (76-265) ∗|
|LV ejection fraction (%)||61 ± 5 (49-73)||63 ± 19 (46-83) †||31 ± 9 (19-45) ∗|
|LA volume (mL)||39 ± 8.5 (18-44)||88 ± 62 (55-176) ∗ †||106 ± 40 (53-201 ∗|
|LA volume index (mL/m 2 )||19 ± 4.5 (13-25)||48 ± 27 (28-120) ∗ †||59 ± 19 (34-90) ∗|
|EROA (cm 2 )||—||0.51 ± 0.19 (0.16-1.09) †||0.21 ± 0.06 (0.11-0.33) ∗|
|Regurgitant volume (mL)||—||61 ± 33 (24-89) †||30 ± 10 (15-45)|
|ASE MR severity grade (range, 1-4)||—||3.6 (2-4) †||2.2 (2-3)|
|Maximum MA displacement (mm)||11 ± 2 (9-15)||9 ± 3 (6-15) ∗ †||6 ± 2 (3-9) ∗|
|Maximum MA area (cm 2 )||9.0 ± 2.0 (5-13)||16.1 ± 3.5 (11-25) ∗ †||11.1 ± 2.7 (8-17) ∗|
|MA area change (%)||26 ± 8 (3-39)||21 ± 6 (13-36) †||13 ± 5 (3-23) ∗|
LV end-diastolic diameter volume was largest in the F-MR group (229 ± 68 mL, P < .05 vs normal) and only mildly increased in the P-MR group (148 ± 62 mL vs normal 133 ± 21 mL, P = NS). LV EF was impaired in the F-MR group (31 ± 9%) and normal in the P-MR group (63 ± 19%) compared with normal controls (61 ± 5%) ( P < .05; Table 1 ). Left atrial volume was severely enlarged in the F-MR group (106 ± 40 mL) and moderately enlarged in the P-MR group (88 ± 62 mL) compared with the control group (39 ± 9 mL) ( P < .05). MR severity was severe in the P-MR group (EROA, 0.51 ± 0.19 cm 2 ; regurgitant volume, 61 ± 33 mL; regurgitant fraction, 66%, American Society of Echocardiography severity score, 3.6) and moderate in the F-MR group (EROA, 0.21 ± 0.06 cm 2 ; regurgitant volume, 30 ±10 mL; regurgitant fraction, 44%; American Society of Echocardiography severity score, 2.2).
Annular tracking was possible for all patient data sets ( Figures 1 and 2 ). The Cartesian coordinates of the entire mitral annulus were tracked throughout the cardiac cycle. The parameters of dynamic MA function reported include 3D MA area and MA displacement toward the LV apex ( Figure 3 ). In the normal control group, the mean largest MA area throughout the cardiac cycle was 9.0 ± 2.0 cm 2 , with the greatest dynamic area change of 26 ± 8%. The largest mitral annulus was observed at end-diastole and the smallest at late systole ( Figure 4 ). In the normal control group, the mean maximal MA descent toward the apex was 11 ± 2 mm ( Table 1 ).