Proximal Flow Convergence Method by Three-Dimensional Color Doppler Echocardiography for Mitral Valve Area Assessment in Rheumatic Mitral Stenosis Jose Alberto de Agustin, MD, PhD, Hernan Mejia, MD, Dafne Viliani, MD, Pedro Marcos-Alberca, MD, PhD, FESC, Jose Juan Gomez de Diego, MD, PhD, FESC, Ivan Javier Nu~ nez-Gil, MD, PhD, Carlos Almeria, MD, PhD, Jose Luis Rodrigo, MD, PhD, Maria Luaces, MD, PhD, Miguel Angel Garcia-Fernandez, MD, PhD, Carlos Macaya, MD, PhD, FESC, and Leopoldo Perez de Isla, MD, PhD, FESC, Madrid, Spain
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 cm2). 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. (J Am Soc Echocardiogr 2014;-:---.) Keywords: Proximal isovelocity surface area, Three-dimensional echocardiography, Mitral stenosis
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,1-7 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.6,7 This
From the Instituto Cardiovascular, Unidad de Imagen Cardiaca, Hospital Universitario San Carlos, Madrid, Spain. Reprint requests: Jose Alberto de Agustın, MD, PhD, Instituto Cardiovascular, Unidad de Imagen Cardiaca, Hospital Universitario San Carlos, Profesor Martin Lagos s/n, 28040 Madrid, Spain (E-mail: [email protected]
). 0894-7317/$36.00 Copyright 2014 by the American Society of Echocardiography. http://dx.doi.org/10.1016/j.echo.2014.04.023
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.8 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).6 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 twodimensional (2D) method. The aim of this study was to assess the feasibility and accuracy of this novel method in a routine clinical 1
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practice in patients with rheumatic MS using as reference methods the MVAs obtained by 2D planimetry, 3D planimetry, and the PHT method.
PASP = Pulmonary artery systolic pressure
PHT = Pressure half-time
MS = Mitral stenosis MVA = Mitral valve orifice
From January to September surface area 2013, we prospectively considered consecutive patients 3D = Three-dimensional referred to the echocardiography 2D = Two-dimensional 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 fourchamber 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. PISA = Proximal isovelocity
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.1,2 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 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 a) 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 p PISA radius2) (angle a/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.2,9 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 6 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 PCbased 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,10 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).11 The 3D PISA measurement was used to derive MVA as (3D PISA Valiasing)/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
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Figure 1 Example automatic 3D PISA extraction, visualized as green overlay in 3D color Doppler image (left three reference planes: top, four-chamber view; center, two-chamber view; and bottom, short-axis view) and 3D rendered PISA in the volume-rendered image (right).
diastolic opening, as previously described.12 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 6 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.13 Graphed data indicate mean test value 6 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).
Table 1 Patient characteristics (n = 63) Variable
Age (y) Men/women Atrial fibrillation 2D/Doppler echocardiography End-diastolic diameter (cm) End-systolic diameter (cm) End-diastolic volume (mL) (Simpson’s method) End-systolic volume (mL) (Simpson’s method) Ejection fraction (%) (Simpson’s method) Left atrial volume (mL) PASP (mm Hg) Mitral valve mean gradient (mm Hg) Mitral valve peak gradient (mm Hg) MVA (cm2) 2D PISA method 3D PISA method 2D planimetry 3D planimetry PHT method
68 6 11 52/11 43 (68.3%) 4.7 6 0.6 2.9 6 0.6 129.7 6 43.2 53.7 6 3.1 58.6 6 8.6 91.2 6 22.8 42.2 6 16.1 6.8 6 2.9 17.3 6 6.14 1.01 6 0.43 1.43 6 0.37 1.44 6 0.43 1.39 6 0.40 1.29 6 0.26
Data are expressed as mean 6 SD or as number (percentage).
RESULTS Patient Data Clinical and echocardiographic characteristics of 63 patients studied are summarized in Table 1. The mean age was 68 6 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 6 12 beats/min, the mean systolic blood
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Figure 2 Linear regression plot and Bland-Altman plot showing correlation and agreement between MVA by 2D planimetry and 2D PISA (A,B) and between MVA by 2D planimetry and 3D PISA (C,D). pressure was 114 6 12 mm Hg, and the mean diastolic blood pressure was 67 6 7 mm Hg during transthoracic echocardiography. Mitral valve mean gradient averaged 6.8 mm Hg (range, 2.6–17.6 mm Hg). 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 cm2). 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). Reproducibility Good intra- and interobserver agreement for 3D PISA measures was shown, with intraclass correlation coefficients of 0.95 and 0.90, respectively, and coefficients of variation of 4.9% and 9.6%, respectively. These results were much better than those obtained using the 2D PISA method, with intraclass correlation coefficients of 0.81 and 0.72, respectively, and coefficients of variation of 16.3% and 25.7%, respectively.
DISCUSSION The present study demonstrates that MVA calculation using the 3D PISA method, without relying on hemispheric assumptions or the requirement of an angle correction factor, is feasible in the clinical setting and more accurate than the conventional 2D PISA method. In our study, MVA by the 3D PISA method showed better correlations and agreement with the previously validated reference methods than the value obtained using the conventional 2D PISA method. Our data show that the hemispheric 2D PISA approach results in important underestimation of MVA compared with 2D planimetry,
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Figure 3 Linear regression plot and Bland-Altman plot showing correlation and agreement between MVA by 3D planimetry and 2D PISA (A,B) and between MVA by 3D planimetry and 3D PISA (C,D).
Figure 4 Linear regression plot and Bland-Altman plot showing correlation and agreement between MVA by the PHT method and 2D PISA (A,B) and between MVA by the PHT method and 3D PISA (C,D).
3D planimetry, or PHT. As indicated in previous studies,7,14 the 2D PISA method, using the hemispheric assumption, produces an underestimation of the actual MVA because the shape of the PISA is actually an oblate hemisphere. A high percentage of patients with
nonsevere MS by 3D planimetry (30%) were misclassified by the 2D PISA method as having severe MS (effective regurgitant orifice area < 1 cm2). This is a particularly important range in which surgery may be contemplated. In contrast, 3D PISA had high
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agreement (94%) with 3D planimetry in classifying nonsevere MS. The MVAs determined by the 2D and 3D PISA methods were obtained by application to the continuity equation. In principle, the continuity equation predicts the valve area at the point at which the velocity of the jet is highest. This region is situated immediately distal to, and is generally somewhat smaller than, the anatomic orifice.15 Some underestimation should therefore be expected. However, in previous studies6,16 as well in ours, the method did not show systematic underestimation. In addition, the 3D PISA method was easy to perform, and the time consumed was low. Our results suggest that the 3D PISA method is worthy of application in routine echocardiographic practice. Reliable quantification of MS is required to indicate the correct timing for surgery. Previously, the gold standard method to determine MVA has been invasive evaluation, using the catheter-based data and Gorlin’s equation. However, this method is invasive, can result in complications, and has important limitations, such as using the assumption that a properly confirmed wedge pressure accurately reflects left atrial pressure, the misalignment of the pulmonary capillary wedge and left ventricular pressure tracings, and calibration errors. In addition, significant mitral regurgitation and the presence of an atrial septal defect may confound measurements of transmitral volume flow.17,18 Currently, echocardiography has become the reference method for measuring MVA in many instances. The planimetric method and PHT method are accepted to be good guides for management.1-5 However, both methods have some limitations. The PHT method is unreliable in patients with concomitant aortic or mitral regurgitation and left ventricular compliance disturbances. The main advantage of planimetry is that it provides a relatively hemodynamic-independent assessment of the MVA. Conventional 2D planimetry has several limitations, the most important of which is that there is no controlled sectioning of the mitral funnel orifice. Measurements of the MVA are made in the short-axis view, with no simultaneous independent imaging to verify that the imaging plane corresponds to the smallest and most perpendicular view of the mitral valve orifice. Because of this, this method requires significant experience and operator skill to obtain the correct imaging plane that displays the true mitral valve orifice. In addition, planimetry can be very challenging in the presence of significant leaflet calcification, severe left atrial dilatation, or distortion of the valve anatomy. The introduction of real-time 3D echocardiography provides unique orientations of the cardiac structures not obtainable using routine 2D echocardiography. Using 3D analysis software, it is possible to perform a multiplane reconstruction from the data set and generate a perfectly aligned cross-sectional image of the mitral valve at the leaflet tips, which is selected for MVA measurement by planimetry, and errors due to malpositioning can be obviated. In addition, planimetry using 3D echocardiography is not limited to the parasternal window and allows MVA measurement from an apical window. The utility of 3D transthoracic echocardiography in the evaluation of MS and the accuracy of MVA measurements has been established by multiple studies.12,19,20 The PISA method is a different way of applying the continuity principle to MVA measurement.6,7 According to the PISA method, the flow through a narrow orifice is assumed to form concentric layers of same velocity proximal to the orifice. This method is attractive in MS because the proximal convergence zone can be easily visualized and because the applicability of continuity principle would not be influenced by concomitant aortic regurgitation and mitral regurgitation.1 It has been shown that the PISA method is accurate and reproducible under various clinical conditions (rhythm,
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associated aortic or mitral regurgitation, severity of anatomic lesions, etc).6,16,21,22 Moreover, the PISA method is not limited by valve morphology, such as mitral leaflet calcification, thickening, and distortion, unlike planimetry. Despite these theoretical advantages, in contrast to valvular regurgitation, the PISA method is seldom used in routine practice for the assessment of MS severity. Important problems and pitfalls have been defined in the application of the conventional 2D PISA method for quantitative assessment of MS.7,8 This method is based on the assumption of hemispheric symmetry of the velocity distribution proximal to the stenotic orifice, which may not hold for complex or elliptical orifices. A further limitation is related to the need to accurately define the orifice level on the 2D color Doppler image. This limitation is important because this radial measure is squared to derive the PISA, and minor inaccuracies result in imprecise determination of the MVA. Other important limitation is the requirement of an angle correction factor. As a result of leaflet doming in MS, only a fraction of a hemisphere crosses the orifice, and an angle correction factor must be considered (the funnel angle formed by the mitral leaflets). Usually, a plane-angle correction factor (measured in one dimension only; a/180) is used instead of a solidangle correction factor, which accounts for the 3D shape of the mitral valve.21 Potential variations in leaflet geometry proximal to the orifice may not always be accounted for completely by the simple angle correction used. In addition, this angle cannot be obtained using the machine’s built-in software and requires a manual measurement. For all these reasons, the conventional 2D PISA method is technically demanding and time-consuming. Although some efforts to eliminate the need for angle correction have been made,23,24 these methods have not been popular enough. A new method, which would simplify the PISA method, would be helpful for routine use. Three-dimensional color Doppler echocardiography is expected to overcome the limitations of the 2D PISA method. Three-dimensional imaging has the advantage of avoiding any geometric assumptions and determining the actual PISA. Complete 3D visualization of the convergent flow zone is the ideal solution for accurate calculation of the MVA, without the requirement of an angle correction factor. Automating the assessment of the 3D PISA represents a significant step forward, potentially enabling its point-of-care use in a clinical arena. Automation also should decrease interobserver variability. Experimental in vitro studies have demonstrated that in patients with valve regurgitation, the PISA might be measured using 3D color Doppler echocardiography, even in complex geometric flow fields.25-27 However, this method involved reconstruction of the PISA using multiple parallel slices to calculate the orifice area, limiting its clinical application. Recent advances in 3D echocardiography have enabled high–frame rate acquisition of volumetric color Doppler flow images in a single heart cycle, enabling the direct measurement of PISA without geometric assumptions. This method is relatively easy to perform, is less time consuming than the previously reported 3D-based methodologies, and can be reliably measured with transthoracic approach. Threedimensional PISA analyses should improve accuracy and decrease the interobserver variability that plagues traditional 2D PISA measurements. Recently, our group validated the 3D PISA method using this technology in patients with chronic mitral or tricuspid regurgitation.28,29 To our knowledge, this is the first study demonstrating that this technology can be applied for MVA measurement in patients with rheumatic MS. On the basis of our data, the direct measurement of PISA with 3D Doppler echocardiography is a promising method to circumvent the limitations of the traditional
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methods for MVA measurement. We excluded patients with significant concomitant valvular lesions because we wanted to compare the results with the PHT method, which is the most widely used method and is known for being not valid in the aforementioned circumstances. However, the 3D PISA method should be useful even in patients with associated valvular lesions, because the derivation of the method is based on the mathematical relations and compensates for variations in transvalvular flow. In addition, in our experience the 3D PISA method is easier to perform, more suitable for less experienced echocardiographers, and less dependent on the image quality than transthoracic 3D planimetry of MVA. Study Limitations MVA measurements were not compared with those derived from cardiac catheterization. However, as mentioned above, this method has important limitations17,18 and is no longer considered the gold standard. We used as a reference method 3D planimetry of MVA by the transthoracic approach, which may be limited in patients with poor acoustic windows. Three-dimensional transesophageal planimetry is a more reliable method of accurate MVA assessment, but being an invasive procedure, is not routinely recommended.30,31 The current 3D color Doppler imaging techniques offer images with lower frame rates than conventional 2D echocardiography. In this study, the PISA method was applied using a single diastolic frame, specifically the one with the largest flow convergence region. This approach can be limited by the lower temporal resolution of 3D color Doppler, so the selected convergence region may not necessarily be the absolute largest. In addition, with current technology, orifice velocity and PISA must be measured in different beats. CONCLUSIONS The present study demonstrates that MVA can be simply and accurately measured using the new 3D PISA method without geometric assumptions or the requirement of an angle correction factor. This method is relatively easy to perform and not time consuming. This work demonstrates its potential applicability to the clinical setting, showing feasibility in patients with various degrees of MS. The 3D PISA method has the potential to substitute for the conventional 2D PISA method in measuring MVA in the near future.
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