From March 2019 to May 2020, we prospectively reviewed 107 patients at the Cardiac Surgery Department, Zhongshan Hospital who met the following inclusion criteria: (1) presence of TR verified by 2D transthoracic echocardiography(TTE) at the Department of Echocardiography in our hospital , (2) plan of isolated tricuspid valve surgery or mitral valve surgery combined with tricuspid valve surgery in a week, and (3) presence of a recognizable proximal flow convergence region of the tricuspid valve in the four-chamber view. The definition of TR was determined by echocardiographic findings, qualitative parameters and semiquantitative parameters. Exclusion criteria were: (1) absence of a recognizable proximal flow convergence region, (2) pulmonary regurgitation or pulmonary stenosis (mild and more), (3) intracardiac shunt, (4) presence of prosthetic tricuspid valve, (5) poor acoustic window, and (6) less than 18 years of age. According to the etiology, presence of atrial fibrillation and TR jet location based on 2D TTE, we divided patients into primary TR group and secondary TR group, with atrial fibrillation group and without atrial fibrillation group, and centric TR group and eccenric TR group. Especially, the short-axis plane and the long-axis planes are used to determine the presence of organic tricuspid valve changes in primary TR. Organic tricuspid valve changes include rheumatic changes, congenital changes, trauma induced changes, endocarditis induced changes and degeneration. Secondary TR are determined with no structural abnormalities. It includes left-sided heart disease, atrial fibrillation, pulmonary arterial hypertension, right ventricle dysfunction and pace maker. All patients underwent echocardiography examination before the operation. The study was approved by the Medical Ethics Committee of Zhongshan Hospital Affiliated to Fudan University (Lot Number: B2018-117). All patients were enrolled after the signing of the informed consent.
Each patient in the left lateral position underwent a standard 2D TTE examination[11, 15]. In patients with sinus rhythm, 3 consecutive cardiac cycle images were acquired; in patients with atrial fibrillation, atrial flutter, or pre-systolic systole, 6 consecutive cardiac cycle images were acquired[11, 15, 16]. Images were acquired using Siemens Acuson SC2000 Prime (Siemens Medical Solutions USA, Inc., Mountain View, CA) with 4v1c probe and were analyzed on its online workstation (Siemens Medical Solutions USA，Inc.). Velocity-time integral (VTI) of TR and maximum velocity(Vmax) of TR were determined by continuous-wave Doppler (Figure 1A). The PISA was determined with color baseline shifting to 30.0 to 40.0 cm/sec and zoomed with the area of flow convergence. The hemispheric shape of flow convergence was chosen to measure the PISA radius in the frame with peak velocity during systole. 2D comprehensive multi-parameter method was used to differentiate severe TR and non-severe TR.
Each patient in the left lateral position underwent a 3D TTE examination focusing on the tricuspid valve and the right ventricle(RV). In patients with sinus rhythm, 3 consecutive cardiac cycle images were acquired; in patients with atrial fibrillation, atrial flutter, or pre-systolic systole, 6 consecutive cardiac cycle images were acquired[11, 15, 16]. Images were collected using Siemens Acuson SC2000 Prime (Siemens Medical Solutions USA, Inc., Mountain View, CA) with 4Z1c probe and GE Vivid E95 (GE Vingmed Ultrasound, Horten Norway) with 4V probe. Scanning depth, sector angle and line density were optimized to achieve frame rate of 20 to 25 frames/sec. Multi-beat mode was attempted in patients with normal heart rhythm to improve spatial resolution.
On GE Vivid E95, a 3D full-volume data set of the entire RV and the tricuspid valve covering right ventricular outflow tract (RVOT) was acquired using 3D TTE. RV was traced in a 3D data set by dedicated software tools (Figure 2A). The RVOT VTI was determined by pulse-wave Doppler at the position of the pulmonary valve annulus.
On Siemens Acuson SC2000 Prime, we selected the frame with peak velocity during systole, adopted eSie Flow preset and adjusted color baseline from 30.0 to 40.0 cm/sec. We set first point at the valve coaplation, drew arrow in direction of regurgitation and used zoom as needed (Figure 1B).
Images from Siemens Acuson SC2000 Prime were analyzed on-cart. Images from GE Vivid E95 were analyzed offline on TomTec (4D RV-Analysis; TomTec Imaging Systems, Unterschleissheim, Germany) workstation.
On TomTec, 2D PISA EROA was calculated using the following formula: 2*π* r2*Valiasing/Vmax (r is PISA radius, Valiasing is the aliasing velocity of PISA, Vmax is TR Vmax). Stroke volume of RV (SVRV) was calculated by RV EDV subtracted RV ESV (RV EDV was the maximum of right ventricular volume, RV ESV was the minimum of right ventricular volume) (Figure 2B). Stroke volume of RVOT (SVRVOT) was calculated by VTIRVOT * SRVOT (VTIRVOT is RVOT VTI, SRVOT is the area of RVOT calculating by measuring the diameter of the pulmonary annulus and using the circular area formula). Rvol is calculated by subtracting SVRVOT from SVRV. The 3D Rvol EROA was calculated using the following formula: Rvol/VTITR (VTITR is TR VTI).
On Siemens Acuson SC2000 on-cart, Figure 1C showed the full volume ultrasound images displayed in three orthogonal planes. The entire PISA of the TR was included in the volume data sets and visualized as a green overlay on the 3D color Doppler image (Figure 1C). The 3D PISA EROA was calculated by the following formula: (3D PISA x Valiasing)/ peak TR velocity (Valiasing is the aliasing velocity of 3D PISA). The final result was calculated automatically on its online workstation (Figure 1C).
The data analysis was performed using SPSS 20.0 and MedCalc. The normality of continuous variables was tested by Kolmogorov-Smirnov test. Continuous variables were expressed as mean ± standard deviation. Categorical variables were expressed as percentages or frequency. Categorical variables were compared using Chi-square test. Continuous variables were compared using ANOVA test. Post hoc test of continuous variables adopted the Tukey test for normal distribution data and the Games-Howell test for non-normal distributions data, respectively. The correlation between 3D PISA EROA and 2D PISA EROA and the correlation between 3D PISA EROA and 3D Rvol EROA were tested using Spearman test. The differences between their correlation coefficients were tested using Wolfe Test. The data of 3D PISA EROA and 3D Rvol EROA first underwent the normality test again after logarithmic transformation, and then verified their consistency by Bland-Altman analysis. Correlation between 3D PISA EROA and other indicators (etiology, sex, atrial fibrillation, TR jet location, VCW, PISA radius, TR VTI, TR Vmax, hepatic vein systolic reversal and dilated RV with preserved function) was tested using multivariate linear regression analysis. Taking 2D comprehensive multi-parameter method as reference, receiver-operator characteristic curve (ROC) analyses were used to access the ability of 3D PISA EROA to identify severe TR. The value closest to the upper left corner of the receiver operating characteristic curve was defined as Youden index or cut-off value, which had optimal sensitivity and specificity. The sequential logistic regression analysis was used to access the incremental diagnostic value of integrating multiple diagnostic indicators for diagnosing severe TR. 3D Rvol EROA≥0.4cm2 was used to define severe TR. Model 1 was clinical symptoms of right heart failure, such as lower limb edema, jugular vein distension and dyspnea. The positive echocardiographic results referring to the guideline were forced into the Model 1 as Model 2, including abnormal/flail/large coaptation defect tricuspid valve, very large central jet or eccentric wall impinging jet, VCW≥0.7cm, PISA radius >0.9cm, systolic reversal of hepatic vein flow, RV with preserved function and 2D PISA EROA≥0.4cm2. As the Model 3, a 3D PISA EROA≥cut-off value was forced into the Model 2 to access the incremental diagnostic value. To examine the reproducibility of 3D PISA EROA measurements, the same observer and another independent blinded observer remeasured 3D PISA EROA of 20 randomly selected cases 1 month later, respectively. The reproducibility of 3D PISA EROA was tested using intraclass coefficient (ICC). All P values were tested by two-sided test, P<0.05 was considered statistically significant.