Background
Three-dimensional (3D) color Doppler echocardiography (CDE) provides directly measured vena contracta area (VCA). However, a large comprehensive 3D color Doppler echocardiographic study with sufficiently severe tricuspid regurgitation (TR) to verify its value in determining TR severity in comparison with conventional quantitative and semiquantitative two-dimensional (2D) parameters has not been previously conducted. The aim of this study was to examine the utility and feasibility of directly measured VCA by 3D transthoracic CDE, its correlation with 2D echocardiographic measurements of TR, and its ability to determine severe TR.
Methods
Ninety-two patients with mild or greater TR prospectively underwent 2D and 3D transthoracic echocardiography. Two-dimensional evaluation of TR severity included the ratio of jet area to right atrial area, vena contracta width, and quantification of effective regurgitant orifice area using the flow convergence method. Full-volume breath-hold 3D color data sets of TR were obtained using a real-time 3D echocardiography system. VCA was directly measured by 3D-guided direct planimetry of the color jet. Subgroup analysis included the presence of a pacemaker, eccentricity of the TR jet, ellipticity of the orifice shape, underlying TR mechanism, and baseline rhythm.
Results
Three-dimensional VCA correlated well with effective regurgitant orifice area ( r = 0.62, P < .0001), moderately with vena contracta width ( r = 0.42, P < .0001), and weakly with jet area/right atrial area ratio. Subgroup analysis comparing 3D VCA with 2D effective regurgitant orifice area demonstrated excellent correlation for organic TR ( r = 0.86, P < .0001), regular rhythm ( r = 0.78, P < .0001), and circular orifice ( r = 0.72, P < .0001) but poor correlation in atrial fibrillation rhythm ( r = 0.23, P = .0033). Receiver operating characteristic curve analysis for 3D VCA demonstrated good accuracy for severe TR determination.
Conclusions
Three-dimensional VCA measurement is feasible and obtainable in the majority of patients with mild or greater TR. Three-dimensional VCA measurement is also feasible in patients with atrial fibrillation but performed poorly even with <20% cycle length variation. Three-dimensional VCA has good cutoff accuracy in determining severe TR. This simple, straightforward 3D color Doppler measurement shows promise as an alternative for the quantification of TR.
Accurately grading the severity of tricuspid regurgitation (TR) is important, and moderate or greater TR may be associated with greater morbidity and mortality. It is also established that rectifying the primary insult does not necessarily retard the progression of secondary TR and its attendant consequences. Therefore, surgical repair of severe TR is often recommended to improve perioperative outcomes, functional class, right ventricular (RV) function, and survival. Even with these favorable data and current practice guidelines, tricuspid valve (TV) surgery is underused. This underuse may be attributed to difficulty in stratifying the severity of TR. Furthermore, because TR is highly sensitive to respiratory variation as well as RV volume and systolic function, the quantification of TR is challenging. Current evaluation of TR severity often relies on integrating semiquantitative and quantitative criteria, including measures such as the ratio of TR jet area (JA) to right atrial area (RAA), vena contracta and vena contracta width (VCW), hepatic venous flow by pulsed-wave Doppler, and proximal isovelocity surface area (PISA) radius. Quantification of valvular regurgitation by effective regurgitant orifice area (EROA) has been used in grading the severity of mitral regurgitation (MR) as well as aortic regurgitation and is widely used. Although quantification of TR by EROA has been validated and recommended, this technique is rarely performed in clinical practice because of measurement complexity (need for angle correction) as well as time constraints.
Current generation three-dimensional (3D) transthoracic echocardiography with the latest equipment now allows the direct measurement of vena contracta area (VCA) using multiplanar reconstruction (MPR). This single-parameter technique is relatively simple in comparison with two-dimensionally derived TR EROA. However, the correlation of 3D-derived VCA with quantitative and semiquantitative conventional two-dimensional (2D) echocardiographic parameters in patients with TR and the validation of 3D VCA in determination of severe TR remain incompletely understood.
Methods
Study Design
This was a prospective and descriptive study performed in patients already undergoing transthoracic echocardiography; the institutional review board of Mayo Clinic approved this study protocol. All patients enrolled in this study provided verbal consent, and written authorization was obtained.
Patient Selection
Patients aged ≥ 18 years with mild or greater TR, regardless of the mechanism, were screened in clinical echocardiography laboratory for enrollment after routine 2D echocardiography. Patients with multiple TR jets or tricuspid prosthetic valves were excluded. All patients were referred from outpatient clinics with a stable hemodynamic condition. Atrial fibrillation (AF) was not an exclusion criterion if the ventricular rate was controlled and if there was no significant variation in cardiac cycle length (<20%).
Echocardiographic Examination
The echocardiographic studies were performed using the Philips iE33 ultrasound system (Philips Medical Systems, Bothell, WA). Both 2D and 3D images were obtained using an X5 transthoracic probe (Philips Medical Systems), without the need to change probes. Two-dimensional parameters for TR quantification and 3D pyramidal full-volume acquisition were taken by the same 3D sonographer in each patient. Care was taken for the respiratory variation of TR in both 2D and 3D imaging, and images were acquired during breath-hold for both 2D and 3D imaging. In patients with AF, five measurements were obtained. Two investigators were assigned to measure 2D parameters, including EROA, and 3D measures, including 3D VCA, independently for blinded comparison (S.H.K. and T.-E.C.).
TR Quantification by 2D Echocardiography
Two-dimensional echocardiography for TR quantification, including JA/RAA ratio, VCW, PISA radius, EROA derived from the flow convergence method, and hepatic venous flow pattern using pulsed-wave Doppler, were performed. Parameters for 2D color Doppler echocardiography (CDE) were obtained from the apical four-chamber view for central TR; foreshortened apical four-chamber, short-axis, or RV inflow views were applied to maximize TR jet visualization for eccentric TR. The Nyquist limit was controlled at 45 to 65 cm/sec for JA/RAA ratio and VCW and 25 to 35 cm/sec for PISA radius to optimize visualization of these parameters; this careful setting can help avoid overestimation or underestimation under color Doppler. The septolateral diameter of the tricuspid annulus was measured in the apical four-chamber view. The hepatic venous flow pattern on pulsed-wave Doppler was acquired from the subcostal view. The morphology of the TV was carefully evaluated using 2D images and further reconfirmed under 3D imaging using an en face view after 2D imaging. Patients with any anatomic defects resulting in malcoaptation of the leaflets were categorized into organic TR. TV with intact leaflets and dilated annulus due to pulmonary hypertension or RV or left heart dysfunction were classified as functional TR. The severity of TR was determined by integral criteria of 2D parameters according to recommendations of the American Society of Echocardiography and European Association of Echocardiography.
TR Quantification by 3D Echocardiography
3D Data Set of the TV
A 3D pyramidal full-volume data set was obtained from the apical window under biplane image guidance using four-beat breath-hold acquisition. By adjusting the cropping plane, en face views from both a right atrial and an RV perspective were evaluated to confirm the morphology of the TV. The TV morphology was carefully examined for TR mechanism categorization. TR caused by leaflet abnormality (such as prolapse, Ebstein’s anomaly, postbiopsy trauma, or thickness due to carcinoid syndrome) or pacemaker lead impingement was categorized as organic TR; TR with normal leaflets was categorized as functional TR. The 3D full volume also provided direct planimetry of tricuspid annulus diameters in offline measurement.
3D CDE of TR
The 3D color setting was the same as the 2D color Doppler setting. The Nyquist limit was controlled within 45 to 65 cm/sec for optimal visualization of the TR jet. For central TR, the 3D color Doppler echocardiographic full volume of TR was obtained from the apical window under the guidance of biplane images (two orthogonal planes showing the apical four-chamber view and apical two-chamber view). For eccentric TR, the acquisition of the 3D color Doppler echocardiographic full volume was taken from foreshortened apical four-chamber, short-axis, or RV inflow views to optimize the visualization of the TR jet. Six-beat breath-hold acquisition, sector narrowing, and right atrial depth reduction were used to maximize frame rate. The average frame rate of 3D CDE in our study was 10 ± 1 volumes/sec (median, 10 volumes/sec). With a frame rate of 10 volumes/sec, there were four frames contained in the systolic phase to allow maximal VCA selection. A low frame rate (<8 volumes/sec) might skip the middle systolic phase and lead to overestimation or underestimation.
The protocol for patients in AF was exactly the same as that for patients in regular rhythm. The software of the 3D system automatically improved the quality of full-volume acquisition in patients with slightly irregular heart rates by rejecting greatly different RR intervals from the average heart rate.
Importantly, all 3D imaging was performed just after clinical imaging was completed as part of the routine throughput of a busy echocardiographic lab (>60,000 echocardiographic procedures performed annually). Acquisition time for the 3D data sets was an additional 3 to 5 min.
Planimetry of 3D VCA
The 3D data set was digitally stored and transferred to a workstation, on which the 3D color Doppler echocardiographic data set was measured offline using customized software (3DQ in QLAB 7; Philips Medical System). The software provided multiple simultaneous orthogonal planes in MPR mode, which allowed 3D-guided 2D direct planimetry for 3D VCA ( Figure 1 ). On reviewing the 3D color pyramidal full-volume data sets in MPR mode at the midsystolic phase, the sagittal plane (red plane) and coronal plane (green plane) were carefully adjusted to be parallel to the color jet and moved into the center of TR, then the transverse plane (blue plane) was moved to reach the level of the vena contracta, where direct planimetry of VCA and the long and short axes of VCA was performed. Color suppress was used to help identify the regurgitation orifice.
The default setting for imaging optimization was 75% for color gain, 50% for grayscale gain, and level 6 for baseline in 3DQ software. Changing color gain did not affect the intensity of the color jet in MPR mode. Changing grayscale gain caused amplification or suppression of the color flow jet. Changing baseline led to changes of the aliasing velocity and jet color. Extremely low (<4) or high (>8) baseline caused color bleeding and can lead to VCA overestimation, so excess grayscale gain change and color baseline adjustment should be avoided in any color flow examination.
All measures were repeated for three beats and averaged. The protocol used for patients in AF was similar, but five beats were averaged.
It took 5 min for 3D VCA offline measures in central TR with good 3D image quality and 5 to 10 min for eccentric TR or suboptimal 3D image quality.
Planimetry of Tricuspid Annulus
The septolateral and anteroposterior diameters of the tricuspid annulus were measured by direct 3D-guided 2D planimetry of the tricuspid annular plane using MPR mode. The diameters of tricuspid annulus were obtained from magnified en face end-systolic and end-diastolic phases separately.
Statistical Analysis
Categorical variables were compared using χ 2 tests and are presented as counts and percentages. Continuous variables are presented as mean ± SD. Statistical analysis was performed using two-sample unpaired Student’s t tests for normally distributed data. Three-dimensional VCA and 2D EROA were compared using paired Student’s t tests. Bland-Altman analysis was applied for agreement between EROA and 3D VCA. Correlations between 3D VCA and 2D EROA as well as other 2D echocardiographic parameters for TR grading were analyzed using linear correlation analysis. Receiver operating characteristic (ROC) curve analysis was used to test these two methodologies in the determination of severe TR. Interclass correlation was used for interobserver and intraobserver variation. P values < .05 were considered statistically significant. Statistical analysis was performed using JMP version 9 (SAS Institute Inc, Cary, North Carolina).
Results
Baseline Characteristics
One hundred patients were initially screened, but eight were excluded because of nonevaluable 3D images (low frame rate). Ninety-two patients were successfully enrolled and studied. Patients’ baseline characteristics, 2D echocardiographic parameters, and current medications regarding TR treatment are shown in Table 1 . All patients were screened in stable hemodynamic status under optimal medication control (59.8% of all patients and 73.2% of those with severe TR were using diuretics). Categorizing by underlying TR mechanism, we found there were more eccentric jets in the organic than the functional group (44.4% vs 18.9%, P = .003). The estimated RV systolic pressure was lower in organic compared with functional TR (41.1 ± 13.6 vs 50.1 ± 16.3 mm Hg, P = .021), and the 2D EROA was larger in organic than functional TR (0.7 ± 0.4 vs 0.5 ± 0.3 cm 2 , P = .014), although 3D VCA failed to show this difference across TR mechanism. Three-dimensional and 2D quantitative variables in categorized by severity of TR as assessed by 2D integrative criteria are shown in Table 2 . Severe TR was associated with larger 3D VCA as well as 2D EROA, planimetry of RAA, RV area, and TV annular diameter.
| Variable | All patients ( n = 92) | Organic TR ( n = 18) | Functional TR ( n = 74) | P |
|---|---|---|---|---|
| Age (y) | 71.3 ± 14.8 | 63.2 ± 17.9 | 73.3 ± 13.3 | .034 |
| Men | 42 (46%) | 6 (33.3%) | 36 (48.7%) | .107 |
| AF | 20 (21.7%) | 3 (16.7%) | 17 (23.0%) | .551 |
| Pacemaker | 29 (31.5%) | 5 (27.8%) | 24 (32.4%) | .704 |
| Coronary artery disease | 28 (30.4%) | 4 (22.2%) | 24 (32.4%) | .399 |
| Hypertension | 42 (45.7%) | 6 (33.3%) | 36 (48.6%) | .242 |
| Diabetes mellitus | 12 (13.0%) | 1 (5.6%) | 11 (14.9%) | .293 |
| LV dysfunction | 20 (21.7%) | 0 | 20 (27.0%) | .013 |
| RV dysfunction | 52 (70.3%) | 10 (55.6%) | 42 (56.8%) | .927 |
| Pulmonary hypertension (RVSP > 36 mm Hg) | 69 (75%) | 9 (50.0%) | 60 (81.1%) | .013 |
| Left heart valvular disease | 47 (51.1%) | 7 (38.9%) | 40 (54.1%) | .248 |
| Diuretics | 55 (59.8%) | 9 (16.4%) | 46 (83.6%) | .345 |
| ACE inhibitors/ARBs | 43 (46.7%) | 7 (38.9%) | 36 (48.6%) | .599 |
| Eccentric | 22 (23.9%) | 8 (44.44%) | 14 (18.92%) | .003 |
| Heart rate (beats/min) | 68.6 ± 12.4 | 68.9 ± 11.9 | 68.5 ± 12.7 | .893 |
| Systolic BP (mm Hg) | 117.5 ± 19.1 | 115.8 ± 13.0 | 117.9 ± 20.6 | .576 |
| Diastolic BP (mm Hg) | 67.1 ± 1.0 | 69.6 ± 11.13 | 66.4 ± 9.6 | .257 |
| LV ejection fraction (%) | 56.6 ± 13.9 | 59.8 ± 5.7 | 55.8 ± 15.1 | .077 |
| LA volume index (cc/m 2 ) | 52.7 ± 22.6 | 55.8 ± 28.5 | 51.9 ± 21.0 | .599 |
| Cardiac output index (l/min/m 2 ) | 2.9 ± 0.8 | 3.2 ± 1.0 | 2.9 ± 0.7 | .217 |
| RV pressure gradient (mm Hg) | 48.4 ± 16.1 | 41.1 ± 13.6 | 50.1 ± 16.3 | .021 |
| TAPSE (cm) | 1.9 ± 0.8 | 2.1 ± 1.1 | 1.9 ± 0.8 | .522 |
| Severity of TR | .025 | |||
| Mild | 18 (19.5%) | 1 (5.6%) | 17 (22.9%) | |
| Moderate | 18 (19.5%) | 1 (5.6%) | 17 (22.9%) | |
| Severe | 56 (60.9%) | 16 (88.9%) | 40 (54.2%) | |
| JA/RAA ratio | 0.4 ± 0.1 | 0.4 ± 0.1 | 0.4 ± 0.1 | .805 |
| TR peak velocity (cm/sec) | 308.4 ± 54.2 | 287.6 ± 47.1 | 314.2 ± 54.9 | .080 |
| TR velocity-time integral (cm) | 101.4 ± 24.6 | 88.9 ± 17.8 | 104.4 ± 25.2 | .005 |
| VCW (cm) | 0.6 ± 0.2 | 0.7 ± 0.2 | 0.6 ± 0.2 | .130 |
| PISA radius (cm) | 0.7 ± 0.2 | 0.8 ± 0.2 | 0.7 ± 0.2 | .099 |
| 2D EROA (cm 2 ) | 0.5 ± 0.3 | 0.7 ± 0.4 | 0.5 ± 0.3 | .014 |
| 3D VCA (cm 2 ) | 0.5 ± 0.3 | 0.7 ± 0.6 | 0.6 ± 0.3 | .085 |
| Elliptical 3D VCA | 53 (57.6%) | 13 (72.2%) | 40 (54.1%) | .154 |
| Variable | Nonsevere TR ( n = 36) | Severe TR ( n = 56) | P |
|---|---|---|---|
| 3D parameters | |||
| 3D VCA (cm 2 ) | 0.3 ± 0.1 (0.27–0.34) | 0.6 ± 0.4 (0.52–0.73) | <.0001 |
| 3D TA SL diameter in ED (cm) | 3.8 ± 0.6 (3.61–3.98) | 4.3 ± 0.8 (4.06–4.49) | .0009 |
| 3D TA AP diameter in ED (cm) | 3.6 ± 0.7 (3.37–3.81) | 4.0 ± 0.8 (3.79–4.22) | .0095 |
| 3D TA SL diameter in ES (cm) | 3.2 ± 0.4 (3.02–3.31) | 3.6 ± 0.7 (3.36–3.73) | .0013 |
| 3D TA AP diameter in ES (cm) | 3.1 ± 0.5 (2.93–3.30) | 3.4 ± 0.7 (3.19–3.55) | .0532 |
| 2D parameters | |||
| 2D EROA (cm 2 ) | 0.3 ± 0.1 (0.24–0.29) | 0.7 ± 0.3 (0.59–075) | <.0001 |
| VCW (cm) | 0.5 ± 0.1 (0.41–0.50) | 0.7 ± 0.2 (0.66–0.77) | <.0001 |
| PISA radius (cm) | 0.6 ± 0.1 (0.52–0.59) | 0.8 ± 0.2 (0.76–0.87) | <.0001 |
| JA/RAA | 0.4 ± 0.1 (0.34–0.40) | 0.5 ± 0.1 (0.44–0.52) | <.0001 |
| JA (cm 2 ) | 7.5 ± 2.5 (6.66–8.32) | 13.7 ± 5.6 (12.23–15.23) | <.0001 |
| RAA (cm 2 ) | 21.0 ± 7.1 (18.61–23.44) | 28.9 ± 9.9 (26.25–31.54) | <.0001 |
| RV area in ED (cm2) | 17.6 ± 4.1 (16.20–18.94) | 26.2 ± 10.9 (23.31–29.12) | <.0001 |
| RV area in ES (cm 2 ) | 9.9 ± 2.5 (9.00–10.71) | 15.7 ± 7.8 (13.59–17.76) | <.0001 |
| RV FAC | 0.4 ± 0.1 (0.41–0.47) | 0.4 ± 0.1 (0.37–0.44) | .2236 |
| 2D TA SL diameter in ED (cm) | 4.0 ± 0.4 (3.87–4.16) | 4.5 ± 0.9 (4.25–4.74) | .0008 |
| 2D TA SL diameter in ES (cm) | 3.1 ± 0.4 (2.96–3.24) | 3.6 ± 0.8 (3.38–3.82) | .0002 |
| RV pressure gradient (mm Hg) | 45.3 ± 14.87 (40.25–50.25) | 50.4 ± 16.8 (45.86–54.86) | .1292 |
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