Background
The two-dimensional (2D) proximal isovelocity surface area (PISA) method has important technical limitations for mitral valve orifice area (MVA) assessment in mitral stenosis (MS), mainly the geometric assumptions of PISA shape and the requirement of an angle correction factor. Single-beat real-time three-dimensional (3D) color Doppler imaging allows the direct measurement of PISA without geometric assumptions or the requirement of an angle correction factor. The aim of this study was to validate this method in patients with rheumatic MS.
Methods
Sixty-three consecutive patients with rheumatic MS were included. MVA was assessed using the transthoracic 2D and 3D PISA methods. Planimetry of MVA (2D and 3D) and the pressure half-time method were used as reference methods.
Results
The 3D PISA method had better correlations with the reference methods (with 2D planimetry, r = 0.85, P < .001; with 3D planimetry, r = 0.89, P < .001; and with pressure half-time, r = 0.85, P < .001) than the conventional 2D PISA method (with 2D planimetry, r = 0.63, P < .001; with 3D planimetry, r = 0.66, P < .001; and with pressure half-time, r = 0.68, P < .001). In addition, a consistent significant underestimation of MVA using the conventional 2D PISA method was observed. A high percentage (30%) of patients with nonsevere MS by 3D planimetry were misclassified by the 2D PISA method as having severe MS (effective regurgitant orifice area < 1 cm 2 ). In contrast, the 3D PISA method had 94% agreement with 3D planimetry. Good intra- and interobserver agreement for 3D PISA measurements were observed, with intraclass correlation coefficients of 0.95 and 0.90, respectively.
Conclusions
MVA assessment using PISA by single-beat real-time 3D color Doppler echocardiography is feasible in the clinical setting and more accurate than the conventional 2D PISA method.
Management of mitral stenosis (MS) relies on accurate assessment of the mitral valve orifice area (MVA). Several echocardiographic methods, such as the pressure half-time (PHT) method, planimetry, and the proximal isovelocity surface area (PISA) method, can be used, but all have potential intrinsic limitations, and additional methods are desirable. The PISA method is based on the principles of the continuity equation and the preservation of mass. This method is based on the assumption of hemispheric symmetry of PISA. However, PISA can be variable depending on the shape of the orifice, leading to a discrepancy between MVA calculated with the hemispheric assumption and the actual area. A further limitation of the conventional PISA method is related to the requirement of an angle correction factor (the funnel angle formed by the mitral leaflets). Because it is a difficult and time-consuming technique, the conventional PISA method is the least popular for the calculation of MVA.
Three-dimensional (3D) echocardiography is an imaging technique that can provide the actual geometry of the flow convergence. The recently developed modality of single-beat real-time 3D color Doppler imaging allows direct measurement of PISA without geometric assumptions or the requirement of an angle correction factor, so it should reduce the errors in calculating MVA present in the two-dimensional (2D) method. The aim of this study was to assess the feasibility and accuracy of this novel method in a routine clinical practice in patients with rheumatic MS using as reference methods the MVAs obtained by 2D planimetry, 3D planimetry, and the PHT method.
Methods
Study Population
From January to September 2013, we prospectively considered consecutive patients referred to the echocardiography laboratory at our hospital who met the following inclusion criteria: (1) the presence of at least mild rheumatic MS in the standard 2D evaluation, (2) the presence of a recognizable proximal flow convergence region on the atrial side of the mitral valve in the four-chamber view, and (3) the absence of significant concomitant lesions (more than mild aortic stenosis, aortic regurgitation, or mitral regurgitation) or prior mitral valve intervention. The initial full sample comprised 89 patients. During the recruitment, 18 patients were excluded because of the presence of significant concomitant lesions (eight with mitral regurgitation, seven with aortic regurgitation, and three with aortic stenosis), and eight patients were excluded on the basis of imaging quality (limiting 3D planimetry in eight patients and the 3D PISA method in three patients), resulting in a final sample of 63 patients included. No patient was excluded on the basis of imaging quality for standard 2D imaging. All patients underwent echocardiography for clinical indications and gave written informed consent before undergoing echocardiography, in accordance with a protocol approved by the institutional review board.
2D Echocardiography
Two-dimensional transthoracic echocardiography was performed with the patient in the left lateral decubitus position in expiratory apnea. Conventional evaluation of MS severity with 2D color Doppler echocardiography was performed as previously described. Color flow mapping of the mitral inflow was obtained from the apical window. Typical scanning depth was 12 cm, with a color Doppler sector angle of 30°. These settings provided a color Doppler frame rate of 14 or 15 frames/sec, with a Nyquist limit of 0.9 to 1.0 m/sec. The atrial surface of the mitral leaflets was carefully scanned to recognize the PISA, and its size was magnified to facilitate analysis. The position of the transducer was modified to minimize the angle between the centerline of the PISA and the ultrasound beam. We optimized the appearance of the PISA by shifting the color Doppler aliasing velocity from 23.0 to 45.0 cm/sec (mean, 31.6 ± 7.6 cm/sec). The maximal radius of the proximal flow convergence region was measured in early diastole. A straight line was traced along the centerline of the region from the center of the stenotic orifice as demarcated by the leaflets to the farthest boundary of the PISA. The funnel angle formed by the mitral leaflets and containing the flow convergence region (angle α) was measured in the apical four-chamber view in the same frame of PISA analysis using an offline analysis system. The mean leaflet angle was 104.7°. The maximal velocity of mitral inflow was determined by continuous-wave Doppler. According to reported values of PISA radius, the peak forward mitral flow rate was obtained as (2 × π × PISA radius 2 ) × (angle α/180°) × (aliasing velocity). MVA was then calculated using the continuity equation as the peak forward flow rate divided by peak inflow velocity from the continuous-wave Doppler tracing. The radius, angle, and peak velocity were measured and averaged over five beats for patients in atrial fibrillation. MVA was also obtained by conventional 2D planimetry and the Doppler PHT method (220/PHT), as previously descrived.
3D PISA Method
Without changing flow conditions, 3D Doppler data were acquired immediately after the 2D transthoracic study. We used commercially available software specifically developed for 3D PISA determination (eSie PISA Volume Analysis; Siemens Medical Solutions USA, Inc, Mountain View, CA). Measurements were performed blinded to MVA obtained by the reference methods. A single-beat real-time 3D transthoracic echocardiographic system (Acuson SC2000 Volume Imaging Ultrasound System; Siemens Medical Solutions USA, Inc) with a 2.5-MHz handheld transducer (4Z1c; Siemens Medical Solutions USA, Inc) was used. Three-dimensional full-volume images of the entire left ventricle and 3D color Doppler images of the mitral valve inflow (color four-dimensional mode) were acquired from an apical transthoracic window. High–volume rate acquisition is critical for an accurate quantification of the PISA surface volume. To maximize the volume frame rate of acquisition, depth was optimized. We optimized the aspect of the PISA by reducing the color Doppler aliasing velocity to a value between 24 and 36 cm/sec (mean, 29 ± 4 cm/sec). The full-volume ultrasound images were displayed in three orthogonal planes, as seen in Figure 1 . We were careful to include the entire PISA in the volume data sets. The average 3D color Doppler volume frame rate was 16 Hz. All image data were digitally stored on a hard disk and transferred to a PC-based workstation for offline analysis using the dedicated SC2000 workplace system (Siemens Medical Solutions USA, Inc). In 3D color Doppler images, the frame in which PISA appeared the largest during diastole was chosen to analyze PISA. The software allows the user to select an aliasing velocity and initial seed point for 3D PISA analysis. The software then performs the 3D fully automatic segmentation of the mitral valve and isovelocity surface area computation applying the random walker algorithm, which is well known to behave well with poorly defined boundaries. The voxel-based segmentation result is smoothed using a 3D Gaussian kernel, and an isosurface mesh is successively computed using the marching-cubes algorithm. The intersection with the mitral annulus segmentation is then removed from the mesh. Finally, all mesh vertex locations are transformed from acoustic to Cartesian space for computing the actual 3D PISA. The results are displayed as green overlay on the reference planes as well as in the volume-rendered image ( Figure 1 ). The 3D PISA measurement was used to derive MVA as (3D PISA × V aliasing )/peak inflow velocity.
3D Planimetry of MVA
Three-dimensional transthoracic planimetry of MVA was performed immediately after the 2D study with the aforementioned probe. Three-dimensional full-volume images of the mitral valve were acquired from an apical transthoracic window. The images were acquired during a brief suspension of breathing, and special care was taken to stabilize the probe during data acquisition to avoid any artifacts. All images were digitally stored for offline analysis using the dedicated SC2000 workplace system. Using multiplanar reconstruction of the 3D volume data set, planimetry was performed “en face” at the ideal cross-section of the mitral valve during its greatest diastolic opening, as previously described. The ideal cross-section was defined as the most perpendicular view on the plane with the smallest mitral valve orifice.
Reproducibility
To assess the effect of observer variability and the reproducibility of 2D and 3D PISA methods, a second independent observer analyzed 20 randomly selected cases. Both experienced investigators had previously used the 2D PISA method for several years. On the same 2D and 3D acquisitions, each observer obtained the MVA by 2D PISA and 3D PISA methods as described earlier. Each observer selected the cycle and the frame in which PISA appeared the largest during diastole, and it was chosen to analyze PISA. Intraobserver variability was assessed by comparing the measurements given by the same observer after an interval of >1 week between the two measurements. Both readers were blinded to previous measurements.
Statistical Analysis
Continuous variables are expressed as mean ± SD. Categorical data are presented as absolute numbers or percentages. Correlations between 2D and 3D PISA measurements and those obtained using reference methods were assessed using simple linear regression analysis. Bland-Altman plots were constructed to demonstrate the agreements between methods. Graphed data indicate mean test value ± 2 SDs and measurement bias. Inter- and intraobserver reproducibility were evaluated using intraclass correlation coefficients and coefficients of variation (calculated as the standard deviation of the differences between the two measurements divided by the mean value). Differences were considered statistically significant at P < .05 (two sided). Statistical analysis was performed using SPSS version 15.0 (SPSS, Inc, Chicago, IL) and MedCalc version 9.3 (MedCalc Software, Mariakerke, Belgium).
Results
Patient Data
Clinical and echocardiographic characteristics of 63 patients studied are summarized in Table 1 . The mean age was 68 ± 11 years, and 52 patients (82%) were women. Twenty patients (31.7%) were in sinus rhythm, and 43 (68.3%) were in atrial fibrillation when studied. The mean heart rate was 71 ± 12 beats/min, the mean systolic blood pressure was 114 ± 12 mm Hg, and the mean diastolic blood pressure was 67 ± 7 mm Hg during transthoracic echocardiography. Mitral valve mean gradient averaged 6.8 mm Hg (range, 2.6–17.6 mm Hg).
| Variable | Value |
|---|---|
| Age (y) | 68 ± 11 |
| Men/women | 52/11 |
| Atrial fibrillation | 43 (68.3%) |
| 2D/Doppler echocardiography | |
| End-diastolic diameter (cm) | 4.7 ± 0.6 |
| End-systolic diameter (cm) | 2.9 ± 0.6 |
| End-diastolic volume (mL) (Simpson’s method) | 129.7 ± 43.2 |
| End-systolic volume (mL) (Simpson’s method) | 53.7 ± 3.1 |
| Ejection fraction (%) (Simpson’s method) | 58.6 ± 8.6 |
| Left atrial volume (mL) | 91.2 ± 22.8 |
| PASP (mm Hg) | 42.2 ± 16.1 |
| Mitral valve mean gradient (mm Hg) | 6.8 ± 2.9 |
| Mitral valve peak gradient (mm Hg) | 17.3 ± 6.14 |
| MVA (cm 2 ) | |
| 2D PISA method | 1.01 ± 0.43 |
| 3D PISA method | 1.43 ± 0.37 |
| 2D planimetry | 1.44 ± 0.43 |
| 3D planimetry | 1.39 ± 0.40 |
| PHT method | 1.29 ± 0.26 |
MVA Quantification by the 2D and 3D PISA Methods Compared with Reference Methods
The quality of the PISA zone image was excellent for both 2D and 3D transthoracic echocardiography. The duration of MVA assessment by 3D PISA method was 3 to 4 min. The PISA geometry was hemielliptic rather than hemispheric in the majority of patients. The MVAs determined using the five techniques are reported in Table 1 for comparison. Using the 2D PISA method, the derived MVA was significantly smaller than those obtained using the reference methods (2D planimetry, 3D planimetry, and the PHT method). In contrast, using the 3D PISA method, the resultant MVA was close to those obtained using the reference methods. Correlations between MVA obtained using the 2D and 3D PISA methods and the reference methods (2D planimetry, 3D planimetry, and the PHT method) are shown in Figures 2, 3 and 4 , respectively. Acceptable correlations were observed between 2D PISA–derived MVA and the reference methods (with 2D planimetry, r = 0.63, P < .001; with 3D planimetry, r = 0.66, P < .001; and with PHT, r = 0.68, P < .001). Better correlations were observed between 3D PISA–derived MVA and values obtained using the reference methods (with 2D planimetry, r = 0.85, P < .001; with 3D planimetry, r = 0.89, P < .001; and with the PHT method, r = 0.85, P < .001). Linear regression showed a good correlation with uniform clustering of data around the regression line. Bland-Altman analysis showed better agreement when comparing 3D PISA–determined MVA with values obtained using the reference methods than when comparing the former with 2D PISA–determined MVA. A high percentage of patients (15 of 50 [30%]) with nonsevere MS by 3D planimetry were misclassified by the 2D PISA method as having severe MS (effective regurgitant orifice area < 1 cm 2 ). In contrast, the 3D PISA method had 94% (47 of 50) agreement with 3D planimetry in classifying nonsevere MS. Significant correlations were obtained between 3D PISA–derived MVA and pulmonary artery systolic pressure (PASP; r = 0.39, P = .002) and between 3D planimetry–derived MVA and PASP ( r = 0.31, P = .013). Conversely, no significant correlation was obtained between PHT-derived MVA and PASP ( r = 0.17, P = .19) or between 2D PISA–derived MVA and PASP ( r = 0.01, P = .94).
