The two-dimensional (2D) proximal isovelocity surface area (PISA) method has known technical limitations, mainly the geometric assumptions of PISA shape required to calculate effective regurgitant orifice area (EROA). Recently developed single-beat real-time three-dimensional (3D) color Doppler imaging allows the direct measurement of PISA without geometric assumptions and has already been validated for mitral regurgitation assessment. The aim of this study was to apply this novel method in patients with chronic tricuspid regurgitation (TR).
Ninety patients with chronic TR were enrolled. EROA and regurgitant volume (Rvol) were assessed using transthoracic 2D and 3D PISA methods. Quantitative Doppler and 3D transthoracic planimetry of EROA were used as reference methods.
Both EROA and Rvol assessed using the 3D PISA method had better correlations with the reference methods than using conventional 2D PISA, particularly in the assessment of eccentric jets. On the basis of 3D planimetry–derived EROA, 35 patients had severe TR (EROA ≥ 0.4 cm 2 ). Among these 35 patients, 25.7% ( n = 9) were underestimated as having nonsevere TR (EROA ≤ 0.4 cm 2 ) using the 2D PISA method. In contrast, the 3D PISA method had 94.3% agreement (33 of 35) with 3D planimetry in classifying severe TR. Good intraobserver and interobserver agreement for 3D PISA measurements was observed, with intraclass correlation coefficients of 0.92 and 0.88 respectively.
TR quantification 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.
Tricuspid regurgitation (TR) quantification is important because it influences patient outcomes. Although several methods for quantitatively assessing TR exist, determination of severity remains challenging. The effective regurgitant orifice area (EROA) is the central parameter to define valve regurgitation severity because it is less dependent on hemodynamic considerations. The calculation of EROA using the proximal isovelocity surface area (PISA) method has been well validated both with in vitro and in vivo models. Despite its usefulness, pitfalls and limitations of this technique are well recognized. The conventional two-dimensional (2D) PISA method is based on the assumption of hemispheric symmetry of PISA. However, PISA can be variable depending on the instrument settings and the shape of the regurgitant orifice. Three-dimensional (3D) echocardiography is an imaging technique that can provide the actual geometry of the flow convergence without geometric assumptions and should reduce the errors in calculating EROA present in the 2D method. Recently developed single-beat real-time 3D color Doppler imaging has been validated for mitral regurgitation assessment. The aim of this study was to assess the feasibility and accuracy of the 3D PISA method in routine clinical practice in patients with chronic TR, using quantitative Doppler echocardiography and direct planimetry of EROA by 3D color Doppler transthoracic echocardiography as reference methods.
From March to November 2012, we prospectively included consecutive patients referred to the echocardiography laboratory of our hospital who met the following inclusion criteria: (1) presence of TR of at least mild degree, as determined by standard color-flow Doppler imaging, and (2) presence of a recognizable proximal flow convergence region on the ventricular side of the tricuspid valve in the four-chamber view. Exclusion criteria were the presence of a poor acoustic window, a pacemaker, more than one flow convergence region, and concomitant valvular lesions (more than mild pulmonary stenosis, pulmonary insufficiency, or tricuspid stenosis). The initial full sample comprised 135 patients. Of these, 12 were excluded because of the absence of a recognizable proximal flow convergence region, five because of the presence of poor acoustic windows, nine because of pacemakers, four because of the presence of more than one flow convergence region, and 15 because of the presence of significant concomitant valvular lesions (11 tricuspid stenosis, four pulmonary insufficiency), resulting in a final sample of 90 patients. All patients underwent echocardiography because of clinical indications and gave informed consent before undergoing echocardiography.
A standard color Doppler 2D transthoracic echocardiographic (TTE) examination was completed on each patient in the left lateral decubitus position using both apical and parasternal views. Conventional evaluation of TR severity with 2D color Doppler echocardiography was performed as previously described. Typical scanning depth was 12 cm and color Doppler sector angle 30°. These settings provided a color Doppler frame rate of 14 to 15 frames/sec, with a Nyquist limit of 0.9 to 1.0 m/sec. Two-dimensional TTE assessment of regurgitant jet area (RJA), the ratio of RJA to right atrial area (RAA), and vena contracta (VC) width was obtained in the usual manner. RJA within the right atrium was measured by planimetry from the frame with the maximal jet area during systole. The ratio of maximal RJA to RAA was calculated in the same image. The VC was defined as the narrowest neck of the regurgitant flow just distal to the flow convergence region. To recognize the PISA, the ventricular surface of the tricuspid leaflets was carefully scanned and its size 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 24.0 to 42.0 cm/sec (mean, 32.1 ± 4.2 cm/sec). For each cardiac cycle, the frame with the largest flow convergence region was selected as coinciding with maximal regurgitant flow, excluding transients in the first frame after tricuspid valve closure and the last before tricuspid valve opening. The PISA radius was defined as the largest distance (mm) between the aliasing border and the regurgitant orifice measured parallel to the direction of the Doppler beam. The maximal velocity of the regurgitant jet was determined by continuous-wave Doppler. According to reported values of PISA radius, the EROA was calculated using the following formula: EROA = 2 × π × RPISA 2 × V aliasing /V max , where RPISA is PISA radius (cm), V aliasing is the aliasing velocity of PISA (cm/sec), and V max is the maximal velocity of the continuous-wave Doppler TR signal (cm/sec). If the base of the PISA was not a flat surface, angle correction was performed by multiplying the EROA by the ratio of the angle formed by the walls adjacent to the regurgitant orifice and 180°, as previously described. Patients were classified objectively as having severe TR if they had EROAs ≥ 40 mm 2 . Two-dimensional PISA–derived regurgitant volume (Rvol) was calculated as 2D PISA–derived EROA multiplied by the TR time-velocity integral. Quantitative pulsed Doppler assessment of EROA was performed in all patients as previously described. Tricuspid valve inflow was determined from an apical four-chamber view as the product of the tricuspid inflow time-velocity integral and diastolic tricuspid orifice area, divided by cos Θ. Pulmonary forward flow was calculated from the product of systolic pulmonary area and the pulmonary time-velocity integral. The maximal velocity and time-velocity integral were averaged over five beats in patients with atrial fibrillation. In the absence of pulmonary regurgitation or intracardiac shunt flow, tricuspid Rvol was calculated as the difference between tricuspid and pulmonary forward stroke volumes, and EROA was calculated as Rvol divided by the time-velocity integral obtained from continuous-wave Doppler of the TR signal. Regurgitant fraction was calculated as Rvol divided by tricuspid stroke volume and expressed as a percentage. Regurgitant jets were classified as eccentric if they were in close contact with one of the tricuspid valve leaflets behind the regurgitant orifice and remained in close contact with one of the right atrial walls, whereas central jets were initially directed into the center of the right atrium. The mechanism of TR was determined on the basis of analysis of the right ventricle, tricuspid annulus, subvalvular apparatus, and valve leaflets. Organic regurgitation was related to intrinsic abnormalities of the tricuspid valve, and functional regurgitation was characterized by a lack of leaflet coaptation or failure of the valve leaflets to reach the plane of the tricuspid annulus during systole, without evidence of structural abnormalities.
3D PISA Method
Three-dimensional Doppler data were acquired immediately after the 2D TTE study, without changing flow conditions. Software specifically developed for 3D PISA determination (eSie PISA Volume Analysis; Siemens Medical Solutions USA, Inc., Mountain View, CA) was used. Measurements were performed blinded to flow measurements, regurgitant orifice characteristics, and 2D data. A single-beat real-time 3D TTE 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 right ventricle and 3D color Doppler images of TR (color four-dimensional mode) were acquired from an apical transthoracic window. We optimized the aspect of the PISA by reducing the color Doppler aliasing velocity to a value between 22 and 40 cm/sec (mean, 30 ± 6 cm/sec). To maximize the volume frame rate of acquisition, depth was optimized. To minimize the potential effect of low temporal resolution of 3D color Doppler imaging, five nonstitched real-time 3D color Doppler volumes from consecutive cardiac cycles were acquired in each patient, looking for the largest convergence zone that would be analyzed later using the specific software for 3D PISA, without averaging the measurements of different beats. The full volume ultrasound images were displayed in three orthogonal planes, as seen in Figure 1 . We were careful to include the entire PISA of the TR in the volume data sets. The average nonstitched 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 dedicated the SC2000 workplace system (Siemens Medical Solutions USA, Inc.). In 3D color Doppler images of the TR, the frame in which PISA appeared the largest during systole was chosen to analyze PISA. The software performs automated quantification of 3D PISA, visualized as a green overlay on the 3D color Doppler image ( Figure 1 ). After the selection of an appropriate volume, the software allows the user to select an aliasing velocity and initial seed point for 3D PISA analysis. The software then performs the 3D segmentation in the volume data, applying an optimized segmentation algorithm. The segmented mask is used to generate a mesh in 3D space, and PISA is computed and displayed free of any geometric assumptions. The results are displayed on the reference planes as well as in the volume-rendered image. Three-dimensional PISA was used to derive EROA as (3D PISA × V aliasing )/peak TR velocity. Three-dimensional PISA Rvol was calculated as 3D PISA–derived EROA multiplied by the TR time-velocity integral. To assess the effect of observer variability and the reproducibility of the 2D and 3D PISA methods, a second independent blinded observer analyzed 20 randomly selected cases. Both experienced investigators had previously used the 2D PISA method for several years. On the same full-volume acquisition of the PISA, each observer measured the PISA with the described method. Intraobserver variability was assessed by comparing the measurements given by the same observer after an interval of >1 week between the two measurements.
3D Planimetry of EROA
Three-dimensional planimetry of EROA was performed using a commercially available 3D TTE system (Acuson SC2000) with a 2.5-MHz handheld transducer (4Z1c). Three-dimensional full-volume images of the entire right ventricle and 3D color Doppler images of the TR (color four-dimensional mode) 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. Care was taken to include the entire VC in the color Doppler image set. All images were digitally stored for offline analysis using dedicated SC2000 workplace system. Using multiplanar reconstruction of the 3D volume data set, a cross-sectional plane through the VC perpendicular to the jet direction was selected, and the EROA was measured using manual planimetry of the color Doppler flow signal from an en face view, as previously described ( Figure 2 ). Rvol was calculated as 3D planimetry–derived EROA multiplied by the TR time-velocity integral.
Continuous variables are expressed as mean ± SD. Categorical data are presented as absolute numbers and percentages. Correlations between 2D and 3D PISA measurements versus those obtained by reference methods were assessed using simple linear regression analysis. Bland-Altman plots were performed to demonstrate the agreement between methods. Graphed data indicate mean test value ± 2 SDs and measurement bias. Interobserver and intraobserver reproducibility was evaluated using intraclass correlation coefficients. 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).
Clinical and echocardiographic characteristics are summarized in Table 1 . The mean age was 74 ± 12 years, and 37 patients (41%) were men. Seventy-two patients (80%) were in sinus rhythm and 18 were in atrial fibrillation when studied. The mean heart rate was 78 ± 14 beats/min and the mean blood pressure was 124 ± 25 mm Hg during TTE imaging. The etiology of TR was organic in nine patients (rheumatic in five, prolapse in four) and functional in 81 (left heart disease in 60, chronic obstructive pulmonary disease in 21). No patient had undergone previous surgical procedures on the tricuspid valve. The jet was central in 69 patients (77%) and eccentric in 21 patients (23%). Peak Doppler velocity across the regurgitant orifice averaged 294.8 cm/sec (range, 143-463 cm/sec). The mean values of the PISA radius, RJA, RJA/RAA ratio, and VC width are listed in Table 1 .
|Age (y)||74 ± 12|
|Atrial fibrillation||18 (20%)|
|2D and Doppler echocardiography|
|Four-chamber tricuspid annular diameter (diastolic) (cm)||3.6 ± 0.5|
|Right ventricular end-systolic area (cm 2 )||27.4 ± 7|
|Right ventricular end-diastolic area (cm)||17.3 ± 6|
|Right ventricular area change (%)||36.9 ± 9|
|Tricuspid annular plane systolic excursion (cm)||1.7 ± 0.8|
|RAA (cm 2 )||22.5 ± 8|
|Pulmonary artery systolic pressure (mm Hg)||44.5 ± 5|
|Cause of TR|
|Eccentric jet||21 (23%)|
|Four-chamber color Doppler RJA (cm 2 )||4.7 ± 2|
|Ratio of RJA to RAA (%)||21.4 ± 7|
|VC (cm)||0.5 ± 0.3|
TR Quantification by the 2D and 3D PISA Method Compared with Reference Methods
The quality of the PISA zone image was excellent for both 2D and 3D TTE imaging. The entire duration of EROA assessment was 2 to 3 min by the 3D PISA method, 3 to 4 min by the 2D PISA method, 2 to 3 min by 3D planimetry, and 4 to 5 min by quantitative Doppler echocardiography. Three-dimensional PISA measurements were optimal in all patients. PISA geometry was hemielliptic rather than hemispheric in the majority of patients. EROA, Rvol, and regurgitant fraction determined by the four techniques are reported in Table 2 for comparison. Using the 2D PISA method, the derived EROA was significantly smaller than that obtained using the reference methods (3D planimetry and quantitative Doppler echocardiography). In contrast, using the 3D PISA method, the resultant EROA was similar to that obtained using the reference methods. Correlations between EROA obtained using the 2D and 3D PISA methods and that obtained with 3D planimetry and quantitative Doppler echocardiography are shown in Figures 3 and 4 , respectively. Acceptable correlations were observed between 2D PISA–derived EROA and that obtained using the reference methods (3D planimetry, r = 0.89, P < .001; quantitative Doppler echocardiography, r = 0.88, P < .001). However, the regression equation showed a consistent significant underestimation of EROA using the 2D PISA method. Better correlations were observed between 3D PISA–derived EROA and that obtained using the reference methods (3D planimetry, r = 0.97, P < .001; quantitative Doppler echocardiography, r = 0.97, P < .001). Linear regression showed an excellent correlation with uniform clustering of data around the regression line. Bland-Altman analysis showed better agreement when comparing 3D PISA–determined EROA with the reference methods than when comparing the former with 2D PISA–determined EROA. Figure 5 shows the correlation between 2D and 3D PISA–derived Rvol with the obtained by the reference methods. Consistent with previous data, 3D PISA–derived Rvol had better correlations with the reference methods than did the 2D PISA method. The analysis stratified by the type of jet showed that the 3D PISA method was more accurate than the 2D PISA method for both central and eccentric jets ( Figure 6 ). In addition, there was a bias toward increased relative underestimation of actual EROA in eccentric jets using the 2D PISA method. On the basis of 3D planimetry–derived EROA, 35 patients had severe TR (EROA ≥ 0.4 cm 2 ). Among these 35 patients, 25.7% ( n = 9) were underestimated as having nonsevere TR (EROA ≤ 0.4 cm 2 ) using the 2D PISA method. In contrast, the 3D PISA method had 94.3% agreement (33 of 35) with 3D planimetry in classifying severe TR. Good intraobserver and interobserver agreement for 3D PISA measures was shown, with intraclass correlation coefficients of 0.92 and 0.88, respectively, that were better than those obtained using the 2D PISA method (0.87 and 0.79, respectively)