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Division of Cardiovascular and Thoracic Surgery, Cliniques Universitaires Saint-Luc, Brussels, BelgiumPôle de Recherche Cardiovasculaire, Institut de Recherche Expérimentale et Clinique, Universitè Catholique de Louvain, Brussels, Belgium
Pôle de Recherche Cardiovasculaire, Institut de Recherche Expérimentale et Clinique, Universitè Catholique de Louvain, Brussels, BelgiumDivision of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Pôle de Recherche Cardiovasculaire, Institut de Recherche Expérimentale et Clinique, Universitè Catholique de Louvain, Brussels, BelgiumDivision of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Division of Cardiovascular and Thoracic Surgery, Cliniques Universitaires Saint-Luc, Brussels, BelgiumPôle de Recherche Cardiovasculaire, Institut de Recherche Expérimentale et Clinique, Universitè Catholique de Louvain, Brussels, Belgium
Pôle de Recherche Cardiovasculaire, Institut de Recherche Expérimentale et Clinique, Universitè Catholique de Louvain, Brussels, BelgiumDivision of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Current guidelines advise using prophylactic tricuspid valve annuloplasty during mitral valve surgery, especially in the presence of annular diameter enlargement. However, several retrospective studies and a prospective randomized study from our department could not confirm that diameter enlargement is predictive of late regurgitation. We examined whether 2- and 3-dimensional echocardiographic and clinical characteristics could identify patients who will develop moderate or severe recurrent tricuspid regurgitation.
Methods
Patients with less than severe functional tricuspid regurgitation (FTR) were randomized not to receive tricuspid annuloplasty, and 11 of 53 of them were excluded from the study because 3-dimensional echocardiographic analysis was not possible. Cox regression was used to estimate the model-based probability of moderate or severe FTR (vena contracta ≥3 mm) or progression of TR and FTR regression using valve dimensions (annulus area, diameter perimeter, nonplanar angle, and sphericity index), dynamics (annulus contraction, annulus displacement, and displacement velocity), and clinical parameters as possible predictors.
Results
At a median follow-up of 3.8 years (range, 3-5.6 years), 17 patients had moderate or severe FTR or progression, and 13 had FTR regression. Our models identified annular displacement velocity as a significant predictor for FTR recurrence and nonplanar angle as a significant predictor for FTR regression.
Conclusions
Annular dynamics, not the dimension, predict recurrence and regression of FTR. Annular contraction should be systematically investigated as a possible surrogate of right ventricle function to prophylactically treat the tricuspid valve.
The tricuspid annulus’s saddle shape and annular displacement predict postoperative functional tricuspid regurgitation, not the simple diameter or area.
In patients treated with mitral valve surgery, 3D echo-derived annular parameters predict postoperative functional tricuspid regurgitation as a surrogate of right ventricle function and thus tricuspid regurgitation derived from subclinical dysfunction of the right ventricle.
See Commentary on page XXX.
Not diameter but annular dynamics predict functional tricuspid regurgitation.
2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American college of cardiology/American Heart Association joint Committee on Clinical practice Guidelines.
recommend performing tricuspid annuloplasty on patients with severe FTR undergoing left-sided valve surgery as a Class I indication. However, it remains uncertain whether patients with milder degrees of FTR should also undergo prophylactic tricuspid surgery.
Mid-term results of a randomized trial of tricuspid annuloplasty for less-than-severe functional tricuspid regurgitation at the time of mitral valve surgery.
studies suggest that such patients do benefit from the addition of tricuspid annuloplasty to left-sided valve surgery, as they display less postoperative tricuspid regurgitation (TR),
Impact of concomitant tricuspid annuloplasty on tricuspid regurgitation, right ventricular function, and pulmonary artery hypertension after repair of mitral valve prolapse.
Tricuspid annuloplasty prevents right ventricular dilatation and progression of tricuspid regurgitation in patients with tricuspid annular dilatation undergoing mitral valve repair.
Accordingly, recent ACC/AHA and European Society of Cardiology guidelines now recommend, as a Class IIa indication, to perform tricuspid valve (TV) annuloplasty on patients undergoing left-sided valve surgery, provided that they exhibit both mild-to-moderate TR and a dilated tricuspid annulus (TA; 21 mm/m2 or 40 mm). These cutoff values were previously found to best discriminate between patients with and without severe TR after left-sided valve surgery.
However, recent studies have questioned the validity of these anatomical criteria, as they have failed to demonstrate any meaningful association between preoperative 2-dimensional (2D) echo tricuspid annular dimensions and either the presence or severity of postoperative TR.
Because the TV has a complex 3-dimensional (3D) and noncircular geometry, 2D echocardiography may not be the most accurate method for TA quantification.
Based on these observations, the aim of the present study was to assess the ability of 3D echocardiography to identify patients who will develop or exhibit persistent moderate or severe FTR after mitral valve surgery.
Methods
Study Population
Between May 2009 and December 2010, 106 patients with less-than-severe FTR (<7-mm vena contracta) were enrolled in a randomized trial to evaluate the effects of TV annuloplasty on the persistence or recurrence of moderate-to-severe postoperative FTR. Patients with primary disease of the TV were excluded. The surgical protocol and techniques have been described previously, and the clinical and echocardiographic results have been reported.
Mid-term results of a randomized trial of tricuspid annuloplasty for less-than-severe functional tricuspid regurgitation at the time of mitral valve surgery.
The study protocol was approved by the institutional review board (Ethical committee, Cliniques Universitaires Saint-Luc, approval number: 03604484, date of approval January 2, 2009), and each patient gave written informed consent before inclusion. This study is a subanalysis of the randomized trial. From the original population, among patients who were not treated by TV annuloplasty (53 patients), 42 had 3D echocardiographic images available and were included in the study population.
Pre- and Postoperative 2D Transthoracic Echocardiography
Standardized pre- and postoperative transthoracic echocardiography examinations were performed according to established guidelines using iE33 Ultrasound Systems (Philips Medical Systems), which were equipped with a 3.5/1.75-MHz phased-array transducer. For offline analysis, images were stored on an XCELERA 2.1 PACS server (Philips Medical Systems). Four-chamber views centered on the RV were used to evaluate RV dimensions and function and to measure the TA dimensions. Magnified 2D color Doppler images centered on the TV were used to measure the vena contracta of the tricuspid regurgitant jet.
Intraoperative 2D and 3D Transesophageal Echocardiography (TEE)
Experienced cardiologists or anesthesiologists performed all TEE examinations after induction of general anesthesia and before cardiopulmonary bypass using an iE-33 ultrasound system equipped with an X7-2t TEE probe (Philips Medical Systems). First, 2D standard and magnified color Doppler images of the TV were acquired at an average frame rate of 55 to 60 Hz. The TA diameter was measured at end-systole and end-diastole from 3 different views: a 4-chamber view, RV inflow–outflow view, and transgastric right ventricle inflow view. 3D echo images of the TA were then acquired during brief periods of breath holding without electrical interference or patient movement over 4 to 8 cardiac cycles. Great care was taken to include the entire TA within the 3D volume.
3D Echo Data Analysis
3D echo datasets were analyzed offline using Image Arena software (Tom-Tec Corporation GmBH) and the 4D mitral valve analysis package. This package was initially designed for the semiautomatic identification and measurements of the mitral annulus and leaflets throughout the entire cardiac cycle. However, we recently demonstrated that it can also be used to assess the dimension and shape of the TA.
For annular measurements, only 6 specific time points were analyzed: early systole: the first frame after closure of the TV; late systole (LS): the last frame before TV opening; midsystole: the midpoint between early systole and late systole; early diastole: the first frame after valve opening; late diastole: the last frame before completing TV closure; and mid-diastole: the midpoint between early diastole and late diastole. For each of the prespecified time points, the software automatically generates the following measurements: (1) the maximal diameter from the septum to the anterior leaflet (SA diameter); (2) the lateral–lateral diameter (the largest diameter perpendicular to the previous); (3) the annulus area (2D and 3D); (4) the annulus perimeter (2D and 3D); (5) the annulus height; (6) the sphericity index of the annulus; (7) the annular displacement and displacement velocity (defined as the longitudinal movement of the annulus centroid and its first derivative); (8) the annular area fraction, defined as the follows: (max annulus area–min annulus area)/(max annulus area); and (9) the nonplanar angle, defined as the angle between the 2 vectors from the 2 hinge points of the annulus in the SA plane to the center of the laterolateral axis (Figure 1).
Figure 1A, Kaplan–Meier curve of moderate-to-severe FTR in function of annular displacement velocity (Displ. Vel.) with 95% confidence intervals. B, Spline function of hazard risk of FTR and its progression in function of annular displacement velocity with 95% confidence intervals. FTR, Functional tricuspid regurgitation.
The primary end point was the presence of more than mild FTR (defined as vena contracta ≥3 mm) in the latest postoperative transthoracic echo available or an increase in FTR severity (increase in vena contracta width of ≥2 mm) from the preoperative transthoracic echo to the last postoperative transthoracic echo available. The secondary end point was the regression of FTR, which was defined as a reduction in the vena contracta width of ≥2 mm between pre- and postoperative echoes. The definition of the vena contacta threshold was derived from the intra-rater and inter-rater reliability analysis of the FTR. Those measurements were are 0.09 ± 0.3 and 0.15 ± 0.4 mm and therefore we chose the 2-mm threshold, taking in consideration the variability of the FTR measurements.
Statistical Analysis
All analyses were conducted with RStudio software (Version 1.0.153; RStudio, Inc). Continuous variables were expressed as the mean ± standard deviation, categorical variables were expressed as counts and percentages, and follow-up times were expressed as the median and range. Continuous variables were compared using a Student t-test or the Mann–Whitney U test. Categorical variables were compared using the χ2 test or Fisher exact test as appropriate. All tests were 2-sided. Kaplan–Meier curves and Cox proportional hazard regression analyses were used to identify the factors independently associated with the primary and secondary end points. Penalized smoothing splines were used to show the association between independent predictors as a continuous variable and the risk of primary and secondary end points and to identify adequate cutoff values. A sensitivity analysis was performed for the primary and secondary outcome after exclusion of the patients who underwent reoperation or died during the follow-up.
Results
Clinical, Hemodynamic, and Echocardiographic Characteristics
The study population was divided into 3 groups. Group 1 consisted of patients exhibiting at least moderate postoperative FTR or presenting with worsening FTR, Group 2 consisted of patients showing TR regression, and Group 3 included patients with stable FTR between pre- and postoperative echoes. Table 1 shows their clinical characteristics. No significant differences were found between groups.
Table 1Clinical, hemodynamic, and echocardiographic characteristics
Parameters
All
TR progression
TR regression
Stable TR
N = 42
N = 17
N = 13
N = 12
Demographic data
Age, y
62 ± 14
60 ± 14
60 ± 13
68 ± 15
Male, n (%)
27 (64)
10 (66)
10 (66)
7 (58)
BSA, m2
1.8 ± 0.2
1.8 ± 0.2
1.9 ± 0.2
1.7 ± 0.3
Risk factor
Arterial hypertension, n
20 (47)
8 (53)
6 (40)
6 (50)
Smoking, n (%)
7 (16)
3 (20)
3 (20)
1 (8)
Diabetes, n (%)
2 (5)
1 (7)
1 (7)
0 (0)
Comorbidities
Stroke, n (%)
2 (5)
0 (0)
1 (7)
1 (8)
COPD, n (%)
3 (7)
0 (0)
1 (7)
2 (17)
PVD, n (%)
1 (2)
1 (7)
0 (0)
0 (0)
Kidney failure, n (%)
1 (3)
0 (0)
0 (0)
1 (8)
Sinus rhythm, n (%)
36 (85)
14 (93)
13 (87)
9 (75)
Symptoms and etiology
NYHA III-IV, n (%)
11 (26)
4 (26)
2 (13)
5 (41)
Degenerative, n (%)
27 (64)
11 (73)
8 (53)
8 (66)
Barlow, n (%)
8 (19)
2 (13)
4 (27)
2 (17)
Rheumatic, n (%)
7 (16)
2 (13)
3 (20)
2 (16)
TR, Tricuspid regurgitation; BSA, body surface area; COPD, chronic obstructive pulmonary disease; PVD, peripheral vascular disease; NYHA, New York Heart Association.
The hemodynamic and echocardiographic characteristics of the 3 groups are shown in Tables 2 and 3. As shown, the 3 groups differed in the severity of preoperative FTR, which was significantly lower in group 3 than the 2 other groups. Group 2 had smaller nonplanar angles, and group 1 displayed lower annular displacement velocity and lower absolute annular displacement. Interestingly, no significance differences in annular dimensions were found between the 3 groups.
The median follow-up was 3.1 years. During follow-up, 3 patients died: one patient from acute pulmonary bleeding, one from progressive pulmonary insufficiency (severe chronic obstructive pulmonary disease), and one from progressive heart failure. The overall 5-year survival rate was 92 ± 4%. During the same period, 3 patients needed mitral reoperation because of recurrent severe mitral regurgitation. The overall 5-year rate of freedom from reoperation was of 89 ± 6%. At the end of follow-up, 94% of the patients were in New York Heart Association class I to II.
Primary End Point
At the end of follow-up, 17 patients displayed more than mild FTR or had experienced progression of FTR. The Cox regression analysis identified LS annular displacement velocity as the sole independent predictor of persistent or progressing FTR (hazard ratio, 0.93; confidence interval, 0.87-0.99, P = .02; Table 4). Using penalized spline function analysis (Figure 2), a cutoff value of 45 mm/s for the annular displacement velocity was found to best predict the primary end point, with sensitivity of 94%, specificity of 50%, overall accuracy of 78%, and area under the receiver operating characteristic curve of 75%. As shown in Figure 3, the 5-year rate of freedom from the primary end point was significantly better in patients with LS annular displacement velocity of more than 45 mm/s.
Figure 2A, Kaplan–Meier curve of FTR regression in function of annulus nonplanar angle with 95% confidence intervals. B, Spline function of hazard risk of FTR regression in function of annulus nonplanar angle with 95% confidence intervals. FTR, Functional tricuspid regurgitation.
Figure 33D echo-derived annular displacement and saddle shape predict TR changes suggesting a possible link between subclinical RV dysfunction and the development of postoperative FTR. 3D, 3-Dimensional; TR, tricuspid regurgitation; RV, right ventricular; FTR, functional tricuspid regurgitation; 4D, 4-dimensional; 2D, 2-dimensional.
At the end of follow-up, 13 patients experienced FTR regression. The Cox regression analysis identified the mid-diastole nonplanar angle as the sole independent predictor of FTR regression (hazard ratio, 0.92; confidence interval, 0.86-0.98, P = .01; Table 5). Using penalized spline function analysis, we found a cutoff value of 165° for the nonplanar angle to best predict FTR regression with sensitivity of 92%, specificity of 68%, overall accuracy of 77%, and area under the receiver operating characteristic curve of 75%. As shown in Figure 4, the 5-year rate of freedom from the secondary end point was significantly better in patients with a nonplanar angle less than 150°.
Table 5Cox analysis for regression of TR
Parameters
Univariate
Multivariate
HR
P value
HR
P value
MD nonplanar angle
0.91
.006
0.91
.006
LS sphericity index
0.03
.05
LS tenting height
0.65
.11
ES annular displacement
0.77
.21
TR, Tricuspid regurgitation; HR, hazard ratio; MD, mid-diastole; LS, late systole; ES, early systole.
Figure 4Postoperative FTR is best predicted by functional parameter of the tricuspid annulus. FTR, Functional tricuspid regurgitation; TA, tricuspid annulus; 2D, 2-dimensional.
The aim of the present study was to assess the ability of 3D echocardiography to identify patients who will develop or exhibit persistent moderate or severe FTR after mitral valve surgery. Our findings can be summarized as follows:
-
Preoperative annular dimensions, including diameter, area, and perimeter, did not differ among patients with stable, progressing, or regressing FTR after mitral valve surgery.
-
Preoperative annular displacement velocity was lower in patients with progressing FTR than in those with stable FTR, and annular displacement velocity was the only parameter able to predict FTR progression over time.
-
The nonplanar angle was smaller in patients with regressing FTR than in those with either stable of progressing FTR and was also the only parameter able to predict FTR regression over time.
The usefulness of TV annuloplasty for patients undergoing mitral surgery remains a matter of debate. Based on the observations made by Dreyfus and colleagues,
ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.
proposed first proposed the threshold recommended by the guidelines to indicate tricuspid surgery in 1989 (ie, SA diameter ≥40 mm). They studied 90 patients undergoing left heart valve surgery and observed that 88% of patients with severe TR exhibited a maximum diastolic SA diameter ≥38 mm or 21 mm/m2. We recently demonstrated
that an SA diameter ≥42 mm predicts severe FTR with a sensitivity of 50% and a specificity of 81%, thus corroborating the cutoff value proposed by the guidelines. In the same study, we also showed that preoperative 3D-echo measurements of annular area/perimeter and tenting height provided a much better prediction of preoperative FTR severity and could thus be the preferred method for assessing annular dilatation.
In the present study, we investigated whether the preoperative 3D echocardiography-derived annular area/perimeter could also predict spontaneous postoperative changes in TR severity. Surprisingly, none of the 3D annular dimensional parameters correlated with changes in postoperative TR. This is in line with the findings of Sordelli and colleagues,
who were also unable to demonstrate any significant correlation between 3D annular dimensions and postoperative TR severity. Nonetheless, our study identified 2 independent parameters associated with postoperative TR dynamics: the tricuspid annular displacement velocity and the annular nonplanar angle.
Annular Displacement
The annular displacement parameter that we measured is analogous to tricuspid annular phase systolic excursion, a well-known index of RV function. The relationship between the RV diameter or function and FTR after TV surgery has been demonstrated before.
Early failure of tricuspid annuloplasty. Should we repair the tricuspid valve at an earlier stage? The role of right ventricle and tricuspid apparatus.
Early failure of tricuspid annuloplasty. Should we repair the tricuspid valve at an earlier stage? The role of right ventricle and tricuspid apparatus.
reported similar results in patients with pulmonary hypertension. In the present study, we did not observe any significant relationship between FTR and RV dimensions or volumes, which was probably attributable to our exclusion of patients with severe FTR. However, we did observe a significant relationship between the velocity of annular displacement and FTR progression, suggesting a possible link between subclinical RV dysfunction and the development of postoperative FTR. Further studies are needed to confirm this hypothesis.
Nonplanar Angle
The nonplanar angle is an index of the saddle shape of the TA. Our study demonstrates that the maintenance of a saddle-shaped TA is needed for FTR to regress after mitral surgery. Previous investigators also reported similar results.
Nonetheless, in each of these studies, development of FTR was also linked to annular dilatation. This was not necessarily the case in our study, because only 8 patients (only in the regression group) exhibited annular dilatation. This could indicate that the flattening of TA precedes the development of TA dilatation and subsequent FTR.
Taken together, these data suggest that the development of FTR after mitral procedure is the result of the complex interplay between the shape, dimension, and function of both the TA and the RV. Our data suggest that subclinical RV dysfunction and reduced saddle shape of the TA are the initial triggers and precede annular dilation and RV remodeling. Accordingly, tricuspid annuloplasty should probably be performed before the onset of annular or RV dilatation in the presence of these triggers. Nonetheless, larger studies are needed to support this approach.
Limitations
Our study has limitations that should be acknowledged. Despite the prospective design, the analysis was retrospective and limited to patients with available 3D images. Therefore, the results need to be confirmed in larger prospective cohorts. Furthermore, we did not have specific analysis software dedicated to the TV, so we used a vendor-independent software that was primarily designed for the mitral valve. This forced us to consider the TV as a 2-commissure structure rather than a 3-commissure structure. This probably affected most of the leaflet measurements and likely explains why none of these came out from the analysis. However, we do not believe that it affected the assessment of the TA dynamics as, visually, TA was always well tracked by the software throughout the cardiac cycle.
Conclusions
Our study identified 3D echo-derived annular displacement and saddle shape as possible early predictors of TR changes after mitral valve surgery. Nevertheless, our findings should be considered more as hypothesis-generating, and further studies are needed to clarify their role in indicating concomitant TA surgery in patients undergoing left heart-valve interventions.
Conflict of Interest Statement
The authors reported no conflicts of interest.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
Supplement Material
Figure E1Intraoperative picture of the tricuspid valve (left panel) with measurements used in the analysis. Right panel shows annular measurements obtained from the echocardiographic analysis.
2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American college of cardiology/American Heart Association joint Committee on Clinical practice Guidelines.
Mid-term results of a randomized trial of tricuspid annuloplasty for less-than-severe functional tricuspid regurgitation at the time of mitral valve surgery.
Impact of concomitant tricuspid annuloplasty on tricuspid regurgitation, right ventricular function, and pulmonary artery hypertension after repair of mitral valve prolapse.
Tricuspid annuloplasty prevents right ventricular dilatation and progression of tricuspid regurgitation in patients with tricuspid annular dilatation undergoing mitral valve repair.
ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.
Early failure of tricuspid annuloplasty. Should we repair the tricuspid valve at an earlier stage? The role of right ventricle and tricuspid apparatus.
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