Objective
Although the functional anatomy of mitral regurgitation has been thoroughly studied and is strongly predictive of postoperative outcome, the functional anatomy of tricuspid regurgitation (TR) in patients with systemic right ventricles has not been described.
Methods
We measured the indices of tricuspid valve deformation, right ventricular remodeling and function, and brain natriuretic peptide (BNP) concentrations in a series of 42 patients (mean age 20.8 ± 3.7 years) with systemic right ventricles after atrial switch for complete transposition of the great arteries.
Results
TR was present in 34 patients. It was associated with predominant annular dilatation in 5 patients (14.7%), valvular prolapse in 14 patients (41.1%), and systolic leaflet tethering in 15 patients (44.1%). Compared with patients with valve prolapse, patients with leaflet tethering had greater end-systolic right ventricular cavity area (21.1 ± 3.6 cm 2 vs 27.3 ± 7.9 cm 2 ; P < .05), lower right ventricular fractional area change (0.40 ± 0.09 vs 0.34 ± 0.09, P < .05), and higher BNP levels (14.6 ± 13.5 pg/mL vs 25 ± 24.3 pg/mL, P < .05). Intermediate values were observed in patients with annular dilatation (23.9 ± 5.6 cm 2 ; 0.37 ± 0.05 pg/mL and 19.0 ± 0.07 pg/mL, respectively).
Conclusion
Three distinct types of TR, caused by predominant annular dilatation, valve prolapse, and valve tethering, were apparent in patients with systemic right ventricles. They were associated with diverse severity of right ventricular dysfunction and BNP activation. Further studies are needed to assess the impact of variable functional anatomy of the systemic tricuspid valve on the outcome of medical and surgical therapies.
Ventricular failure and tricuspid regurgitation (TR) are the key problems in patients with systemic right ventricles. Moderate TR is found in up to 27.5% of patients and severe TR is found in up to 20% of patients with Mustard or Senning procedures for complete transposition of the great arteries. If TR is significant, surgical treatment should be considered. However, the results of tricuspid valve surgery are not encouraging, and current guidelines recommend selective surgical referral. Contrary to the functional anatomy of mitral regurgitation, which has been extensively studied and is strongly predictive of valve repairability and postoperative outcome, functional anatomy of TR in patients with systemic right ventricles has not been examined systematically. Therefore, we prospectively assessed TR and measured the indices of tricuspid valve deformation, right ventricular remodeling and function, and brain natriuretic peptide (BNP) concentrations in a series of patients with systemic right ventricles after the atrial switch procedure.
Materials and Methods
Study Population
The initial group of this prospective study consisted of 47 consecutive adult patients, with complete transposition of the great arteries after the atrial switch procedure, who attended our outpatient adult congenital heart disease unit between 2005 and 2007. Patients in unstable clinical condition because of acute tachyarrhythmias (3 patients), infectious endocarditis (1 patient), and heart failure with severe pulmonary hypertension caused by a significant baffle leak (1 patient) were excluded. Therefore, the final study population comprised 42 patients (mean age 20.8 ± 3.7 years) who had undergone Mustard or Senning procedures.
Echocardiographic Examination
Global and segmental right ventricular remodeling and function
All patients underwent a complete transthoracic echocardiographic study, including two-dimensional, color flow and spectral Doppler, and tissue Doppler imaging, using a GE-Vingmed Vivid 7 system (GE Vingmed Ultrasound, Horten, Norway). Echocardiographic studies were performed by a single operator (P.S.) experienced in congenital heart disease. The right ventricular end-systolic and end-diastolic cavity areas were traced in the apical 4-chamber view, and fractional area change was calculated. Right ventricular systolic function was defined as impaired when fractional area change was less than 0.40. Systolic function of the systemic right ventricle was also assessed by tissue Doppler echocardiography, with the sample volume placed at the right ventricular lateral wall at the level of tricuspid annulus. The right ventricular long axis and short axis at the upper one-third level were measured in end diastole in the apical 4-chamber view, and the right ventricular sphericity index was calculated by the ratio of the long and short axes. The systolic displacement of the interventricular septum (“septal shift”) toward the left ventricle was defined as the distance between the line drawn from the points of attachments of the right ventricular free wall to the left ventricle/interventricular septum and the top of the maximally displaced portion of the interventricular septum ( Figure 1 A).
![](https://i0.wp.com/thoracickey.com/wp-content/uploads/2018/06/gr1-495.jpg?w=960)
Tricuspid deformation
Tricuspid valve anatomy was carefully analyzed in all views available to visualize all 3 leaflets and to classify their motion as normal, excessive, or restrictive. The mechanisms of TR were qualitatively classified, on the basis of Carpentier’s classic functional classification of the types of leaflet motion, as type I with predominant annular dilatation and normal leaflet motion, type II caused by leaflet prolapse or excessive motion, and type III with restricted leaflet motion during systole (corresponding to Carpentier’s type IIIb). In type III, leaflet tethering was classified as symmetric or asymmetric, according to the appearance of the valve ( Figure 1 B). The mechanism of TR was defined as mixed when both excessive and restrictive leaflet motion contributed to the development of TR.
Systolic leaflet deformation was quantified in a standard 4-chamber view. Valvular tethering area was measured by the area enclosed between the annular plane and the tricuspid leaflets (septal and lateral) from the apical 4-chamber view at the time of maximal systolic leaflet closure ( Figure 1 C). The tethering height was measured as the distance between the tricuspid annular plane and the leaflet coaptation point at systole ( Figure 1 C). Tricuspid annular diameter was measured in the apical 4-chamber view at end diastole, as the distance between the points of reflection of the septal and mural endocardium on the anterior and septal tricuspid leaflets, respectively.
Quantification of TR
The study of TR involved a comprehensive evaluation of the tricuspid jet using Doppler color flow with particular attention paid to the origin, appearance, and direction of the regurgitant jet. The latter was classified as central or eccentric. The proximal isovelocity surface area method was used to quantify the effective regurgitant orifice. TR was considered significant when the effective regurgitant orifice area was greater than 0.2 cm 2 . In patients with no or trivial TR assessed by color Doppler, the effective regurgitant orifice was assumed as null.
Brain natriuretic peptide measurements
Venous blood samples were collected from the antecubital vein for the analysis of plasma BNP levels. The specimen collection and preparation were performed with commercially available kits as recommended by the manufacturers. The pre-chilled tubes were immediately placed on ice and centrifuged. The plasma fraction was stored at −70°C for further analysis. BNP concentrations were measured using an immunoradiometric assay (Shionoria BNP kit, CIS Bio International, Saclay, France). The laboratory upper limit of normal values was 18.4 pg/mL.
Statistics
Patients were divided into subgroups according to the functional type of TR. Patients without regurgitation served as controls. One-sample Kolmogorov-Smirnov test was used to evaluate the distribution of data. All variables included in the analyses, except BNP levels, were normally distributed. The results were presented as mean (± standard deviation), percentages, median, and range, where appropriate. Group comparisons were performed with analysis of variance, with Fisher’s least significant difference post hoc test, Student t test (Mann–Whitney U test, when data were not normally distributed), and chi-square test (Fisher’s exact test for subgroups of ≤ 5) as appropriate. The relationships among the effective regurgitant orifice, indices of tricuspid valve deformation, right ventricular geometry and function, and BNP levels were analyzed in the whole population and the subgroups with different functional types of TR. Univariate and multivariate logistic regression analyses were used to establish the association among the indices of tricuspid valve deformation, right ventricular geometry and function, and significant TR in the overall population. For BNP levels, logarithmic values were used for regression analyses. P values less than .05 were considered significant.
Intraobserver variabilities for measurement of annular dimension, tethering height, and tethering area were determined by the analysis of 10 randomly selected studies and analyzed by the linear regression analysis.
All patients gave their informed consent for the participation in the study. The study protocol was approved by the institutional review board and ethics committee. The authors had full access to the data and take responsibility for the integrity of the data. All authors have read the manuscript and agree to it as written.
Results
Overall Patient Characteristics
The overall group characteristics and echocardiographic results are presented in Table 1 . TR was present in 34 patients, with an average effective regurgitant orifice area of 0.22 ± 0.16 cm 2 . The effective regurgitant orifice area exceeded 0.2 cm 2 in 2 of 22 patients with preserved right ventricular systolic function and in 11 of 20 patients with impaired right ventricular systolic function ( P < .002).
Clinical variables | |
Male/female (n/n) | 31/11 |
Age at surgery, y (x ± SD) | 2.8 ± 2.9 |
Age at follow-up, y (x ± SD) | 20.8 ± 3.7 |
Mustard/Senning (n/n) | 14/28 |
NYHA class I/II (n/n) | 27/15 |
Ventricular septal defect, closed (n/%) | 5/11.9 |
Left ventricular outflow tract obstruction (n/%) | 8/19 |
Pacemaker (n/%) | 2/4.8 |
BNP, pg/mL (median/range) | 13.5/3-95 |
Echocardiographic variables | |
Systolic function normal/impaired, n/n | 22/20 |
Peak systolic velocity of tricuspid annulus, cm/sec (x ± SD) | 10.7 ± 3.2 |
Sphericity index (x ± SD) | 1.7 ± 0.2 |
Left ventricular outflow tract obstruction (n/%) | 8/19.0 |
Annular diameter, cm (x ± SD) | 3.6 ± 0.5 |
Effective regurgitant orifice, cm 2 (x ± SD) | 0.22 ± 0.16 |
TR type (I, II, IIIb) (n/n/n) | 5/14/15 |
Regurgitation jet, symmetric/asymmetric (n/n) | 16/18 |
TR type was a significant predictor of elevated BNP levels at univariate logistic regression analysis (odds ratio 3.3; 95% confidence interval, 1.1-9.7; P = .03). It remained significant at multivariate analysis, when age and gender were added to the model (odds ratio 3.1; 95% confidence interval, 1.1-10.2; P = .03). However, it did not remain significant when effective regurgitant orifice area and indices of right ventricular systolic function were included in the multivariate model.
Tricuspid Regurgitation Types
The mechanisms of TR were qualitatively classified into 3 groups: type I, caused by predominant annular dilatation without significant tethering or prolapse ( Figure 2 A and Video 1 ; view video online.) in 5 patients (14.7%) (no female); type II, caused by excessive leaflet motion in 14 patients (41.1%) (3 female) ( Figure 2 B and Video 2 ;
view video online.), including 2 cases with a clearly mixed mechanism: excessive leaflet motion and asymmetric septal leaflet tethering caused by the systolic displacement of the interventricular septum toward the left ventricle ( Video 3 ;
view video online.); and type III, caused by systolic leaflet tethering in 15 patients (44.1%) (6 female) ( Figure 2 C and Video 4 ;
view video online.), including 3 patients in whom leaflet restriction was clearly asymmetric with the tethering of septal tricuspid leaflet by the outward systolic displacement of the interventricular septum ( Figure 2 D and Video 5 ;
view video online.).
Patients with different functional types of TR differed significantly in terms of BNP levels and effective regurgitant orifice area ( Figures 3 and 4 ). The comparison of right ventricular remodeling and tricuspid valve deformation indices in patients with respective regurgitation types and without TR is presented in Table 2 . The tethering height cutoff value of 3 to 5 mm differentiated best between patients with regurgitation type III versus types I and II ( Figure 5 ). There were no statistically significant differences among the respective TR type subgroups with respect to patient gender.
Regurgitation types | ||||
---|---|---|---|---|
Indices of tricuspid valve deformation/RV function and remodeling | No regurgitation (8 patients) (n ± SD) | Type I (5 patients) (n ± SD) | Type II (14 patients) (n ± SD) | Type III (15 patients) (n ± SD) |
Annular diameter (cm) | 3.37 ± 0.30 b d | 4.22 ± 0.47 a c | 3.40 ± 0.27 b d | 3.82 ± 0.60 a c |
Tethering height (cm) | 0.35 ± 0.09 d | 0.08 ± 0.08 d | 0.15 ± 0.23 d | 0.83 ± 0.32 a b c |
Tethering area (cm 2 ) | 0.45 ± 0.20 d | 0.16 ± 0.16 d | 0.21 ± 0.32 d | 1.30 ± 0.70 a b c |
Peak systolic velocity of tricuspid annulus (cm/sec) | 11.9 ± 2.3 d | 10.0 ± 0.7 | 12.3 ± 3.7 d | 8.8 ± 2.5 a c |
RV fractional area change (n/n) | 0.47 ± 0.08 b d | 0.37 ± 0.05 a | 0.40 ± 0.09 d | 0.34 ± 0.09 a c |
RV end-diastolic cavity area (cm 2 ) | 32.5 ± 2.7 d | 37.4 ± 6.6 | 34.7 ± 5.2 | 39.0 ± 9.5 a |
RV end-systolic cavity area (cm 2 ) | 17.9 ± 3.5 d | 23.9 ± 5.6 | 21.1 ± 3.6 d | 27.3 ± 7.9 a c |
Septal shift (cm) | 0.42 ± 0.30 b d | 0.94 ± 0.47 a | 0.76 ± 0.37 | 0.82 ± 0.34 a |
RV sphericity index (n/n) | 1.9 ± 0.2 b d | 1.6 ± 0.1 a | 1.7 ± 0.3 | 1.6 ± 0.2 a |
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