Background
Intraoperative real-time three-dimensional transesophageal echocardiography has been shown useful in the evaluation of the mitral valve (MV) apparatus, and dedicated commercial software allows its quantitative assessment. The aims of this study were to (1) quantify the effects induced by prolapse on MV anatomy in the presence of fibroelastic deficiency (FED) or Barlow’s disease (BD), (2) assess the effect of surgery on the MV apparatus, and (3) investigate the potential role of three-dimensional transesophageal echocardiography in surgical planning.
Methods
Fifty-six patients (29 with FED, 27 with BD) undergoing MV repair and annuloplasty were studied immediately before and after surgery. Also, 18 age-matched patients with normal MV anatomy, undergoing coronary artery bypass, were included as a control group. Three-dimensional transesophageal echocardiographic data sets were acquired and analyzed to quantify several MV annulus and leaflet parameters using dedicated software.
Results
MV prolapse and regurgitation were associated with a markedly enlarged annulus (area, 12.0 ± 3.2 cm 2 in FED and 15.4 ± 3.8 cm 2 in BD) and leaflets compared with controls (area, 7.5 ± 2.1 cm 2 ), while annular height (4.5 ± 1.3 mm in controls, 4.0 ± 1.3 mm in FED, 5.3 ± 1.6 mm in BD) and the mitral aortic angle (136 ± 12° in controls, 141 ± 12° in FED, 137 ± 11° in BD) were similar. Patients with BD showed greater values than those with FED. MV repair and annuloplasty led to a significant undersizing of leaflet and annular areas (4.0 ± 1.1 cm 2 in FED, 4.9 ± 1.3 cm 2 in BD), diameters, and height (2.6 ± 1.1 mm in FED, 3.4 ± 1.4 mm in BD) compared with controls. Coaptation length remained in the normal range (30 ± 5 mm in controls, 24 ± 6 mm in FED, 28 ± 6 mm in BD). Differences between BD and FED were reduced but still present after surgery.
Conclusions
Intraoperative three-dimensional transesophageal echocardiography allows quantitative evaluation of the MV apparatus in the presence of FED or BD and could be useful for immediate assessment of the surgical procedure.
The mitral valve (MV) is a complex three-dimensional (3D) structure whose morphology is related to its function and may change as a consequence of altered physiologic conditions. Degenerative mitral regurgitation (MR), usually related to MV prolapse, is the most common cause of surgical MR in Western countries, representing the 60% to 70% of cases. The two dominant etiologic subsets of this pathologic condition are Barlow’s disease (BD) and fibroelastic deficiency (FED).
The preoperative differentiation between these two etiologies is a crucial aspect for referral, definition of the optimal surgical strategy, and postoperative outcome. In fact, in patients with BD, the prolapse is usually complex, and the best results are likely to be obtained via a full median sternotomy or lateral thoracotomy using several complex surgical techniques to restore valve competency, including leaflet sliding or resection, suture cleft, or annular plication. In particular, leaflet sliding plasty aims to reduce posterior leaflet to the desired height by gathering up excess posterior leaflet tissue in the suture line. This procedure is often necessary in patients with BD to avoid postoperative systolic anterior motion with resultant left ventricular (LV) outflow tract obstruction. In contrast, FED lesions are more localized and often caused by chordal rupture. For these reasons, patients with BD should be at times referred to a reference MV repair surgical center, while FED lesions can be frequently repaired by experienced cardiac surgeons through minimally invasive techniques.
Although two-dimensional (2D) echocardiography is recognized as the reference technique for the preoperative assessment of MV morphology, the accurate assessment of true MV shape has been feasible only in animal models. In fact, in humans, in vivo evaluation has been based on an oversimplified description of MV morphology using 2D main diameters together with a visual assessment of MV shape or using multiple 2D rotational acquisitions, resulting in a time-consuming process followed by offline 3D reconstruction. Real-time 3D (RT3D) transesophageal echocardiography (TEE) could overcome many of the above limitations.
Accordingly, our aim was threefold: (1) to quantitatively describe the morphology of the MV in degenerative MV disease, (2) to describe the effects of MV repair and annuloplasty on the MV apparatus, and (3) to investigate the potential role of RT3D TEE on surgical planning and evaluation of MV repair.
Methods
Patient Population
We studied 56 consecutive patients (44 men; mean age, 59 ± 12 years) with degenerative MV disease and severe MR with indications for MV repair on the basis of complete 2D and RT3D transthoracic echocardiographic examinations. MR was defined as severe in the presence of effective regurgitant orifice area ≥0.4 cm 2 estimated by the proximal isovelocity surface area technique or, alternatively, in the presence of vena contracta width >7 mm, according to recent recommendations. Moreover, MR was considered severe in the presence of chordal rupture associated with flail leaflets. Patients with MV prolapse were retrospectively divided into two subgroups according to the underlying pathology as established by surgical inspection, those with FED ( n = 29) and those with BD ( n = 27), on the basis of the classification of Carpentier et al. FED is characterized by an impaired connective tissue production, leading to leaflet and chordal thinning, and chordal rupture, as the most common cause of regurgitation in these patients. Leaflet redundancy is limited with no billowing, and associated with slight annular dilation and an absence of calcification. The prolapse usually involves a single scallop, frequently P2. In contrast, BD results in a myxomatous-appearing valve, with thickened and redundant leaflets, a highly dilated annulus, and elongated chordae. Leaflet billowing and bileaflet multisegment prolapse are common findings in BD.
In addition, a control group of 18 age-matched patients with normal MV anatomy undergoing coronary artery bypass was also studied.
Exclusion criteria were (1) associated MV stenosis, (2) tricuspid regurgitation greater than mild, (3) aortic valve disease, (4) contraindications to TEE, (5) atrial fibrillation and cardiac arrhythmias, and (6) myocarditis or pericardial or congenital heart disease. An additional exclusion criterion for the control group was the presence of more than mild MR.
Study subjects were enrolled at Centro Cardiologico Monzino (Milan, Italy) or at the University of Chicago Hospitals (Chicago, IL). The protocol was approved by the respective institutional review boards, and informed consent was obtained from all participants.
Protocol
All patients underwent complete 2D transthoracic echocardiographic examinations (S5 probe; Philips Medical Systems, Andover, MA) the day before surgery.
During surgery, standard 2D TEE was used to evaluate the morphology of the MV apparatus and to evaluate for MR, MV stenosis, and systolic anterior motion of the MV. In addition, after endotracheal intubation and before cardiopulmonary bypass, RT3D TEE was performed in all patients and repeated after the completion of MV repair. All patients were examined under deep sedation and in sinus rhythm.
RT3D transesophageal echocardiographic images of the MV were obtained in full-volume mode, in which electrocardiographically triggered wedge-shaped subvolumes were obtained over seven consecutive cardiac cycles, using an iE33 system equipped with a matrix probe (X7-2t; Philips Medical Systems). The volumetric data sets were digitally stored and then transferred to a workstation for offline analysis.
The surgical approach for MV repair varied according to MV morphology and to the surgeon’s discretion. However, in both FED and BD groups, an annuloplasty ring was inserted to stabilize the annulus and the suture line. The surgical repair was considered successful in the absence of significant residual MR (more than mild) and/or stenosis (maximal mean gradient >6 mm Hg) and/or systolic anterior motion of the anterior leaflet.
MV Quantification
Volumetric data sets were analyzed using MVQ software, part of the QLAB suite (Philips Medical Systems). After properly orienting the 3D data set, the software automatically displays four quadrants: two 2D orthogonal-cut long-axis images of the mitral annulus, an MV en face image, and a panel with the rendered 3D data ( Figure 1 ). In this visualization, the operator can separately optimize the position of each of the three cut planes to improve the identification of MV structures. To ensure the best visualization of the prolapse, the late systolic frame, as the frame preceding aortic valve closure, was selected for the analysis. Two couples of opposite reference annular points (anterolateral and posteromedial, anterior and posterior) were selected on the two orthogonal long-axis images. Additionally, the aortic root was manually labeled at the insertion of the posterior cusp into the sinus of Valsalva.
The 3D model of the MV obtained from these initial reference points was subsequently further initialized by placing a couple of annular points in six additional rotational cross-sections of the volumetric data set, thus resulting in a total of 16 points to define the MV annulus.
After positioning the annular points, the leaflet profile was traced and the coaptation points were marked on multiple cut planes orthogonal to the anterolateral-posteromedial direction, with a distance between two subsequent planes equal to 0.25 cm. Finally, the operator subdivided the anterior and posterior leaflets into the three scallops each (A1, A2, A3 and P1, P2, P3). The resulting 3D representation was adjusted to visually match the anatomy as viewed in the 3D and 2D cut-plane views.
From this model, several parameters were calculated ( Figure 2 ): (1) annular geometry: annular area, as the area of the minimal surface spanning the annulus, anteroposterior diameter, anterolateral-posteromedial diameter, annular height, as the distance along the atrial-ventricular direction between the lowest and highest point of the annulus, and the planarity index, defined as the ratio of height to anterolateral-posteromedial diameter, equal to zero for a flat MV and increasing when the MV’s saddle shape was more pronounced; 2) leaflet size: exposed 3D area of the anterior or posterior leaflet, as well as the 3D total exposed leaflet area, as the sum of the two previous measurements; 3) coaptation geometry: the length of the coaptation line projected to approximate leaflet surface, the area of the region where the anterior and posterior leaflets overlap and the mean height of the same region; and 4) the aortic-to-mitral plane angle.
Statistical Analysis
Continuous variables are expressed as mean ± SD and categorical variables as absolute numbers or percentages.
A normal distribution of continuous variables was assessed using the Kolmogorov-Smirnov test. Preoperative and postoperative values were compared using paired Student’s t tests or Wilcoxon’s signed-rank test as appropriate. Analysis of variance for independent measurements and Tukey’s honestly significantly different test for post hoc comparisons were used to assess the difference between the FED, BD, and control groups.
The association between the etiologic subgroups and the adoption of a particular surgical approach was examined using Fisher’s exact tests.
Reproducibility of the 3D morphologic parameters was assessed in a randomly chosen subgroup of 15 patients. Intraobserver variability was assessed using repeated measurements performed by the same observer a month later, while interobserver variability was evaluated by repeating the analysis by a second independent observer, blinded to the results of all prior measurements. Variability was expressed in terms of coefficients of variation between repeated measurements as a percentage of their mean.
Significant determinants of leaflet sliding were evaluated by examining their associations with several intraoperative variables by univariate analysis. Factors with significance on univariate analysis were used as input in multivariate forward stepwise logistic regression to obtain the independent determinants of leaflet sliding.
Statistical analyses were performed using SPSS version 17.0 (SPSS, Inc., Chicago, IL). P values < .05 were considered significant.
Results
The baseline clinical and echocardiographic characteristics of the population (29 with FED, 27 with BD, and 18 controls) included in the study are shown in Table 1 . Age and gender distributions were similar among the groups. As expected, patients with MR had higher New York Heart Association classifications compared with controls but lower than class III in all cases. Both BD and FED groups showed increased LV volumes, left atrial areas, and pulmonary arterial systolic pressure, secondary to the presence of MR, although ejection fractions were similar compared with controls.
| Variable | Controls ( n = 18) | FED ( n = 29) | P | BD ( n = 27) | P |
|---|---|---|---|---|---|
| Clinical | |||||
| Age (y) | 57 ± 4 | 64 ± 12 | .065 | 55 ± 11 | .477 |
| Men | 12 (67%) | 23 (79%) | .493 | 21 (78%) | .499 |
| BSA (m 2 ) | 1.8 ± 0.2 | 1.9 ± 0.3 | .085 | 1.9 ± 0.1 | .108 |
| NYHA class | <.001 | <.001 | |||
| I | 18 (100%) | 12 (41%) | 9 (33%) | ||
| II | 0 (0%) | 17 (59%) | 18 (67%) | ||
| III/IV | 0 (0%) | 0 (0%) | 0 (0%) | ||
| Echocardiographic | |||||
| LVEDV (mL/m 2 ) | 54 ± 8 | 82 ± 25 | <.001 | 79 ± 22 | <.001 |
| LVESV (mL/m 2 ) | 20 ± 7 | 32 ± 14 | <.001 | 27 ± 10 | <.001 |
| LVEF (%) | 62 ± 8 | 61 ± 10 | .814 | 66 ± 8 | .078 |
| LA area (cm 2 /m 2 ) | 12 ± 4 | 17 ± 5 | .001 | 15 ± 4 | <.001 |
| SPAP | 27 ± 5 | 42 ± 16 | <.001 | 34 ± 8 | <.001 |
MR was associated with prolapse or flail of the anterior mitral leaflet in 10 patients (18%), of the posterior leaflet in 41 (73%), and of both in the remaining five (9%).
MV repair was accompanied by annuloplasty in all patients and was performed via median sternotomy in 50 (89%) and by minimally invasive thoracoscopic port access in the remaining six (11%). The variety of surgical procedures applied by the surgeons is listed in Table 2 ; surgical strategies were adopted independently of the MVQ analysis. The mean prosthetic ring sizes were 30 ± 2 mm and 32 ± 3 mm ( P < .01) for FED and BD, respectively.
| FED ( n = 29) | BD ( n = 27) | P | |
|---|---|---|---|
| Posterior leaflet | |||
| Resection | 13 (45%) | 23 (85%) | <.01 |
| Sliding | 8 (28%) | 18 (67%) | <.01 |
| Dreyfuss | 2 (7%) | 2 (7%) | 1.00 |
| Grossi | 2 (7%) | 6 (22%) | .14 |
| Gore-Tex neochord | 4 (14%) | 3 (11%) | 1.00 |
| Suture cleft | 5 (17%) | 1 (4%) | .20 |
| Chordal shortening | 0 (0%) | 1 (4%) | .48 |
| Anterior leaflet | |||
| Resection | 1 (3%) | 0 (0%) | 1.00 |
| Gore-Tex neochord | 3 (10%) | 4 (15%) | .70 |
| Dreyfuss | 1 (3%) | 0 (0%) | 1.00 |
| Chordal shortening | 1 (3%) | 0 (0%) | 1.00 |
| Edge to edge | 1 (3%) | 1 (4%) | 1.00 |
| Postoperative regurgitation | .54 | ||
| None | 13 (45%) | 16 (60%) | |
| Trivial | 15 (52%) | 10 (37%) | |
| Mild | 1 (3%) | 1 (4%) |
None of the 56 patients undergoing MV repair had intraoperative complications, systolic anterior motion, or residual MR greater than mild. As a result, no patients were withdrawn from the study.
The mean time required for the offline image analysis, including manual adjustments when needed, was 7 minutes when performed by an experienced operator.
Examples of the volume rendered RT3D transesophageal echocardiographic data set and the obtained 3D MV representations are shown in Figure 3 , clearly depicting the morphologic abnormalities of the MV apparatus associated with MV propapse, such as annular dilation, flattening, and leaflet redundancy in FED and BD. Also, the RT3D transesophageal echocardiographic data sets relevant to the same patients are illustrated in Videos 1 to 4 ( 
View video clips online).
The preoperative and postoperative values of annular diameter, height, and area for patients with FED, those with BD, and control subjects are shown in Figure 4 . Similarly, Table 3 summarizes the results obtained from the 3D MV quantification regarding leaflet, coaptation, and annular flattening measurements, separately for each study subgroup, immediately before and after MV repair, as well as those relevant to the control group.
| Variable | Controls | FED | BD | ||
|---|---|---|---|---|---|
| Before | After | Before | After | ||
| Planarity index (%) | 12.7 ± 3.4 | 9.3 ± 3.6 ∗ | 10.3 ± 5.3 | 10.5 ± 3.3 ∗ | 11.8 ± 5.0 |
| Leaflet measurements | |||||
| A3DE (cm2) | 8.8 ± 2.4 | 15.0 ± 4.1 ∗ | 6.0 ± 1.7 ∗‡ | 19.4 ± 5.5 ∗† | 7.3 ± 1.9 ∗†‡ |
| A3DE anterior (cm 2 ) | 4.8 ± 1.4 | 7.1 ± 1.8 ∗ | 3.8 ± 1.2 ∗‡ | 8.9 ± 3.2 ∗† | 4.5 ± 1.3 ‡ |
| A3DE posterior (cm 2 ) | 4.0 ± 1.1 | 7.7 ± 2.8 ∗ | 2.2 ± 0.8 ∗‡ | 10.4 ± 2.9 ∗† | 2.8 ± 1.0 ∗‡ |
| Coaptation | |||||
| Area (cm 2 ) | 1.8 ± 0.8 | — | 1.9 ± 0.6 | — | 2.5 ± 0.8 ∗† |
| Height (mm) | 6.3 ± 1.7 | — | 7.7 ± 1.6 ∗ | — | 9.0 ± 2.2 ∗† |
| Length (mm) | 30 ± 5 | — | 24 ± 6 ∗ | — | 28 ± 6 |
| Aortic-to-mitral plane angle (°) | 136 ± 12 | 141 ± 12 | 134 ± 14 | 137 ± 11 | 135 ± 13 |
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