Published online Mar 21, 2022.
https://doi.org/10.22468/cvia.2021.00332
Global and Regional Right Ventricular Function Investigation by 2D Speckle Tracking Echocardiography in Congenital Heart Disease Patients With Pulmonary Arterial Hypertension
,1
and Hoai Thi Thu Nguyen1,2
Abstract
Objective
The aim of our study was to evaluate the global and regional free wall longitudinal strains of the right ventricle (RV) to detect RV dysfunction in congenital heart disease (CHD) patients with pulmonary arterial hypertension (PAH).
Materials and Methods
Seventy CHD patients with PAH and 30 normal controls were enrolled in this study. Patients were placed into three subgroups including patients with pretricuspid shunt Eisenmenger syndrome (ES) (Group A), patients with post-tricuspid shunt ES (Group B), and patients with non-fixed PAH (Group C). The World Health Organization functional classification (WHO FC) was used to functionally classify the study population. RV free wall strain (FWS); regional RV strains of apical, mid, basal FWS; and RV global longitudinal strain (GLS) were measured by 2D speckle tracking echocardiography (STE), while other parameters were measured by conventional echocardiography.
Results
Forty-three patients (61.4%) were classified as WHO FC III or greater. Mean RVFWS and RVGLS were -20.42%±5.9% and -17.62%±5.5%, respectively. All RV strains including regional FWS were lower in patients compared with healthy controls (p<0.001). RV strains exhibited a higher rate of RV dysfunction compared to the conventional parameters. Mean RVGLS and RVFWS in the two ES groups were lower compared to that in Group C (p<0.001). Within regional trains, basal FWS in Group C was higher than in Group A (p<0.001) but similar to that of Group B. RVFWS, RVGLS, and regional FWS significantly correlated with pulmonary arterial systolic pressure and WHO FC.
Conclusion
In CHD with PAH, 2D-STE parameters are potentially more capable of early detection of RV dysfunction than are conventional echo indices.
INTRODUCTION
Congenital heart disease (CHD) with pulmonary arterial hypertension (PAH) is a critical problem in developing countries due to its late diagnosis and lack of appropriate treatments. Patients hospitalized in the adult CHD department for the first time with Eisenmenger conditions are associated with severe complications. Furthermore, the post-surgical patient population with persistent pulmonary hypertension has grown as a result of advanced medical treatments and surgical progress. These patient groups require long-term and frequently lifelong follow-ups. Right ventricle (RV) systolic function was proven to be an independent predictor of adverse outcomes in a large number of cardiovascular diseases [1, 2, 3]. Cardiac magnetic resonance (CMR) is considered the best modality for evaluating RV function due to its ability to identify endocardial contours and take into account the RV outflow tract. However, in daily practice, echocardiography is preferable because of its greater availability and shorter image acquisition time. American Society of Echocardiography (ASE) recommendations provide a list of echocardiographic parameters in assessing RV function [4]. However, in CHD patients, the correlation of these conventional parameters with CMR-derived RV function remains inconclusive [5, 6]. Recently, RV speckle tracking echocardiography (STE) has been proven to be an effective technique in identifying RV dysfunction in different etiologies. A number of studies has shown the role of strain parameters in prognosis because of early detection of RV dysfunction [7, 8, 9]. Nevertheless, the characteristics and advantages of STE-derived parameters in assessing RV dysfunction in CHD patients with PAH especially with Eisenmenger conditions have not been widely investigated. Our study hypothesized that the use of multiple parameters based on STE could be a useful tool for early detection of RV dysfunction in this patient group compared to other echocardiographic parameters.
MATERIALS AND METHODS
Study population
We enrolled consecutively CHD patients with PAH confirmed by right heart catheterization (RHC) between June 2020 and August 2021. All patients agreed to participation in the research with written informed consent, and the study protocol was approved by our Institute’s Research Ethics Committee (No. VN01001/IRB00003121/FWA00004148). Patients presenting with coronary artery disease, cardiomyopathy, significant left valvular disease (moderate to severe aortic or mitral stenosis or regurgitation), and/or poor image quality were excluded. A total of 70 CHD patients with PAH (mean age: 42±16 years; 14 males) was included in our study. The clinical data of the patient population were collected, including symptoms and signs with levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and creatinine. Using the World Health Organization functional classification (WHO FC), all patients in our study were classified as WHO FC II or greater. Therefore, the patients were divided in 3 subgroups: WHO FC class II, WHO FC class III, and WHO FC class IV [10]. WHO FC class I was labeled the control group. After confirmation by RHC, the patients were divided in subgroups of three etiologies. Patients with Eisenmenger syndrome (ES) due to pre-tricuspid shunts including atrial septal defects, partial anomalous pulmonary venous return to the right atrium or vena cava, and partial atrio-ventricular septal defects were labeled as Group A. ES due to post-tricuspid shunt including ventricular septal defects, patent ductus arteriosus, aorto-pulmonary windows, and double outlet right ventricles was labeled Group B. Finally, the non-fixed PAH group due to CHD was labeled as Group C. The control group was composed of 30 age- and gender-matched subjects (mean age: 44±14 years; 8 males) who exhibited normal physical examination findings with no history of cardiopulmonary disease and good echo image quality.
Conventional echocardiography
Two-dimensional (2D) and Doppler echocardiography were performed using the Philips CVX ultrasound system (Koninklijke Philips N.V., Eindhoven, Netherlands) by senior doctors. The ASE recommendations were applied for quantification protocols [4]. Right heart morphological parameters included parasternal long axis RV outflow diameter (PLAX RVOT) and RV end diastolic area (RVA). Conventional RV function parameters included tricuspid annular longitudinal excursion (TAPSE), fractional area change (FAC), and pulsed tissue Doppler S wave (S’). Pulmonary arterial systolic pressure (PASP) was calculated by adding the tricuspid regurgitation (TR) peak gradient to the estimated right atrial pressure (RAP). RAP estimations were scored as 3, 8, or 15 mm Hg based on inferior vena cave (IVC) diameter and this diameter in respiratory variation [4].
2D speckle tracking echocardiography
The RV-focused apical 4-chamber view was used to obtain 2D STE-derived longitudinal RV strain parameters. These parameters were calculated semi-automatically using EPIQ Release 5.0 AutoStrain software (Koninklijke Philips N.V.). After acquiring an RV focused view with good visualization of the RV wall, the AutoStrain RV mode was selected to begin the analysis. With the help of electrocardiogram information, AutoStrain RV went directly to the analysis step. In cases of extremely dilated trabeculated RV, endocardial contour, end diastolic start, and end diastolic end markers can be manually adjusted. In the analysis, the global measurement of right ventricle free wall strain (RVFWS) and RV 4-chamber global logitudinal strain (RVGLS) will be displayed. Regional (segmental) free wall strains including basal free wall strain (BFWS), mid free wall strain (MFWS), and apical free wall strain (AFWS) can be separately displayed as well. RVFWS is automatically calculated based on the average of these three free wall regional strains (Fig. 1). The peak systolic longitudinal strain was a negative percentage value indicating tissue contraction/shortening. As in many other international published studies, when analyzing data, we used the absolute value for convenience.
Fig. 1
The image illustrates the sequential steps to acquire cardiac cycles of a healthy control. RV strain values are automatically calculated in the analysis process. The strain values are displayed as right ventricle free wall longitudinal strain (RVFWSL), right ventricle 4-chamber longitudinal strain (RV4CSL), and basal, mid-, and apical free wall strain.
Data analysis
Statistical analysis was performed with SPSS 19.0 (IBM Corp., Armonk, NY, USA). Categorical variables were presented as numbers and percentages. Categorical variables between the 2 groups were compared using Pearson’s chi-squared test. Continuous variables were presented as means±standard deviations. Continuous variables between the 2 groups were compared by independent sample t-tests for normally distributed data and the Mann-Whitney U test for abnormally distributed data. One-way Anova test for normal distribution data and the Kruskall Wallis H test for abnormal distribution data were used to compare the means of the echocardiographic parameters between the subgroups (A, B, and C). The Pearson correlation coefficients for normally distributed data and Spearman correlation coefficients for abnormally distributed data of FAC, TAPSE, S’, RVA, RVFWS, RVGLS, BFWS, MFWS, and AFWS with PASP were tested in the CHD group. The Spearman rho test was used to identify the correlation coefficient between continuous echocardiographic variables and ordinal variables of WHO FC. A 2-tailed p value <0.05 was considered statistically significant.
RESULTS
Study population
Seventy CHD patients with PAH were included in the study after 4 were excluded due to poor echogenicity. All normal subjects (30 subjects) successfully underwent STE. The baseline characteristics of the CHD patients with PAH are provided in Table 1. The majority of patients (61%) was classified as WHO functional class III or greater, and nearly 60% of the patients with ES were in Groups A and B. Of all patients, 80.0% were female. The major cause of PAH in our study was atrial septal defect (Fig. 2).
Fig. 2
The pie chart demonstrates the distribution of CHD in the study population. ASD, atrial septal defect; VSD, ventricular septal defect; PDA, patient ductus ateriosus; Others, other CHD lesions. CHD, congenital heart disease.
Table 1
Baseline characteristics of CHD in the PAH study population
RV conventional echocardiographic parameters and RV strains
Conventional echocardiographic parameters and strain values of both the patient population and controls are summarized in Table 2. All strain values of the patient groups were significantly lower than those of the control group. Interestingly, when we used the cut-off value recommended by the ASE guidelines, TAPSE, FAC, and S’ means remained in the normal range (Table 3) despite the high mean PASP (78.4±28.6 mm Hg). If 20% of the ASE recommendation was used as the cut-off value, all control strains including regional strains were normal. In the patient group, surprisingly, mean RVFWS and RVBFWS were in the normal range, while RVGLS showed the largest decrease in value. This result reminds us that using a single strain parameter might be not sufficient for evaluating RV function. In order to compare the strain parameters and conventional echocardiographic values in detecting RV dysfunction, we found that RV strains (cutoff value <20%) indicated higher rates of functional abnormality. Impaired RV systolic function was found in 68.1% of patients by RVGLS, 51.4% of patients by RVFWS, 26.9% of patients by TAPSE (<17 mm), 37.3% of patients by FAC (<35%), and 18% of patients by S’ (<9.5 cm/s).
Table 2
Conventional and strain echocardiographic parameters of the congenital heart disease study population
Table 3
Comparison of conventional echocardiographic and strain parameters between CHD with PAH and the cut-off values recommended by American Society of Echocardiography (n=70)
RV regional free wall longitudinal strains
Using RHC, we divided the patient population into 3 subgroups based on aetiology causing PAH. All strains exhibited significant differences among groups (Table 4). Group A had the lowest strain, while Group B had the highest mean PASP. In Group B, only RVGLS and apical FWS showed abnormal mean values when using a 20% cut-off. In comparison with mean basal FWS in Group C, that in Group A showed significant decrease (p<0.001), whereas Group B did not exhibit a difference (p=0.064). Among the 2 ES groups, RVFWS and basal and mid-apical FWSs in Group A were lower than those in Group B (p=0.007 and p=0.006, p=0.006 and p=0.016, respectively). Nonetheless, RVGLS did not exhibit a difference between the 2 groups (p=0.190). In the 2 ES groups, 20% of patients had predominant apical FWS, whereas this pattern was not observed in the control group or Group C.
Table 4
Comparison of conventional echocardiographic parameters and strain parameters between the subgroups by aetiology
RV strains and correlations with WHO FC and PASP
According to the correlation analysis (Figs. 3 and 4), both RVGLS and RVFWS exhibited significant correlations with many conventional parameters. Correlation coefficients (r) between RVGLS and PASP, TAPSE, S’, and FAC were r=-0.505, p<0.001; r=0.508, p<0.001; r=0.307, p=0.016; r=0.625, p<0.001, respectively. The results of RVFWS obtained by the same analysis were r=-0.439, p<0.001; r=0.603, p<0.001; r=0.417, p=0.001; r=0.628, p<0.001, respectively. However, all these correlations were weak to moderate. The strongest correlation was found between RVFWS and FAC. The correlations between echocardiographic parameters, functional capacity, and PASP are summarized in Table 5. When analyzing within patient groups, all variables except S’ had weak to moderate significant correlations with WHO FC. RVGLS and RVFWS showed the strongest r values in correlation with WHO FC, even though FAC showed a slightly higher r in correlation with PASP. When a correlation test was applied for the entire population including the control group labeled as WHO class I, the coefficients of RVGLS and RVFWS were much higher at -0.668 and -0.674, respectively.
Fig. 3
Correlation analysis showing significant weak to moderate correlations of RVFWS with sPAP as evaluated by echocardiography (r=-0.439, p<0.001); with TAPSE (r=0.603, p<0.001); with S’ (r=0.417, p=0.001); and with FAC (r=0.628, p<0.001) in CHD patients with PAH. RVFWS, right ventricle free wall strain; S’, pulsed tissue Doppler S wave; TAPSE, tricuspid annular plane systolic excursion; sPAP, systolic pulmonary arterial pressure; FAC, fractional area change; CHD, congenital heart disease; PAH, pulmonary arterial hypertension.
Fig. 4
Correlation analysis showing significant weak to moderate correlations of RVGLS with sPAP as evaluated by echocardiography (r=-0.505, p<0.001); with TAPSE (r=0.508, p<0.001); with S’ (r=0.307, p=0.016); and with FAC (r=0.625, p<0.001) in CHD patients with PAH. RVGLS, right ventricle four chamber global longitudinal strain; S’, pulsed tissue Doppler S wave; TAPSE, tricuspid annular plane systolic excursion; sPAP, systolic pulmonary arterial pressure; FAC, fractional area change; CHD, congenital heart disease; PAH, pulmonary arterial hypertension.
Table 5
Correlations between PASP, WHO FC, and the echocardiographic parameters of RV function in the CHD population
DISCUSSION
RV longitudinal strains and conventional parameters
The number of studies investigating the predictive role of RV longitudinal strain not only in patients with idiopathic PAH, but also in patients with PH due to different etiologies including pulmonary diseases, connective tissue diseases, and CHD is increasing. STE is a useful tool with high availability for CHD patients who require lifelong follow-up. In developing countries, RV failure of ES patients who frequently visit the adult CHD department is a major concern. We demonstrated the relative preservation of RV function in CHD patients with PAH despite being in ES stages and undergoing poor medical treatment. The majority of our patients was on monotherapy for PAH as a result of economic burden. Fortunately, our research mean age (42±16 years) and patient exercise capacity classified by WHO FC were similar to those of a study conducted in Europe where patients received advanced medical therapy [11]. Our STE-derived strain parameters showed a higher rate of RV function impairment in comparison with TAPSE, S’, and FAC. Our findings were in agreement with previously published studies [11, 12]. This advantage might be due to the self-characteristic of STE imaging that is angle-independent and not influenced by heart translational motion, which is a critical concern with TAPSE and S’ by M-mode measurements. RVFWS has demonstrated a good correlation with RVEF by CMR [13] and has been recommended as a parameter for estimating RV systolic function in ASE guidelines [4].
RV longitudinal strain patterns in different etiologies
The RV wall is anatomically described as having 2 fiber layers. The outer layer fibers are arranged circumferentially and turn toward the cardiac apex, whereas the inner layer fibers are longitudinally arranged from the base to the apex [14]. Therefore, longitudinal deformation is physiologically predominant in normal RV [15]. There is a ‘shift’ from longitudinal function to transverse function of RV in cases of long-term pressure overload. Decreasing longitudinal strain potentially occurs as an early sign of RV dysfunction [12]. This mechanism might help to explain the lowest FWS of Group A among the three subgroups. Group A was characterized by chronic volume overload before transforming to ES, indicating that the RV badly tolerates hypertensive situations. In contrast, Group B was characterized by chronic pressure overload from birth before resulting in fixed pulmonary hypertension in ES. Both ventricles have long periods of training under systemic pressure (in cases of large ventricular septal defects, for example). As a result, decrease of FWS occurs later in life. Once longitudinal strains diminished, both of the ventricle functions significantly deteriorated [12]. Among the 3 regional strains, basal strain contributes most to FWS [11]. Therefore, in the ES group, several studies have demonstrated loss of the gradient of longitudinal strain between the apical and basal segments [11, 12]. While 20% of our ES patients exhibited predominant apical FWS, the patterns as not observed in the control group or Group C. Our prevalence was less than that (44%) in a study by Moceri et al. [11] conducted in Europe. This difference might be explained by the different percentage of pre-tricuspid shunt patients among the ES group (43.9% versus 32.5%). This finding suggests use of RVGLS to identify RV dysfunction in post-tricuspid shunt defects instead of RVFWS due to its late impairment. In contrast, RVFWS is recommended for pre-tricuspid shunt lesions. Moreover, a decreasing gradient between basal and apical strains is an early sign of RV dysfunction.
RV longitudinal strain and its associations with pulmonary arterial pressure and exercise capacity
Both RVGLS and RVFWS had correlations with PASP through echocardiography and with WHO FC in CHD patients with PAH. This result is similar with reports from other studies. Our correlation coefficient (0.44) between RVFWS and PASP is in agreement with that from the research by Li et al. [16] where 66 pulmonary hypertension patients exhibited a significant correlation of RVFWS with mPAP by RHC (r=0.597, p<0.001). However, in our study, RVGLS showed a higher r value. This difference might come from our analysis of a CHD population instead of chronic thromboembolic pulmonary hypertension patients. Wright et al. [17] carried out a perspective study on 187 PAH patients at 2 time points. A highly significant correlation between Δ RVFWS and Δ PASP was discovered. Despite correlations between RV strains and PASP, r values mostly ranged from weak to moderate. Therefore, a multivariate correlation test is required to assess RV function in a more comprehensive way. When using Spearman’s correlation, WHO FC and RV strains in our study also exhibited a significant correlation. This result suggests the potential role of strain value as a predictive factor in prospective studies.
Study limitations
This was a cross-sectional, single-center study recruiting CHD patients with PAH, with more than half of our population having ES. This might have led to a selection bias. The focus of our department on adult CHD enabled us to enroll a great number of patients with ES but limited the collection of other PAH etiologies to specify different patterns of RV dysfunction. Using 2D speckle-tracking to evaluate the RV lateral wall as seen in the four-chamber view might have had an effect on the accuracy of RV function measurement in comparison with CMR. Only two-thirds of our patients underwent RHC during this study, and some data of RHC were collected from previous hospitalizations. Considering the long time interval between RHC and STE, we could not test the correlation between mean PAP by RHC and RV strain. 3D speckle-tracking imaging of the RV compared with CMR will probably be the next step toward early detection of RV impairment.
In conclusion, STE-derived parameters are potentially more capable of detecting RV systolic dysfunction than are conventional echo indices. When assessing RV function, RVGLS is a suggested parameter for post-tricuspid shunt defects, whereas RVFWS and RV basal FWS are recommended for pre-tricuspid shunt lesions. RV longitudinal strains exhibited significant correlations with PASP on echocardiography and with exercise capacity by WHO FC.
Conflicts of Interest:The authors have no potential conflicts of interest to disclose.
Author Contributions:
Conceptualization: Hoai Thi Thu Nguyen.
Data curation: Thuy Thu Pham.
Formal analysis: Thuy Thu Pham.
Investigation: Thuy Thu Pham.
Methodology: Hoai Thi Thu Nguyen.
Project administration: Hoai Thi Thu Nguyen.
Supervision: Hoai Thi Thu Nguyen.
Validation: Hoai Thi Thu Nguyen.
Writing—original draft: Thuy Thu Pham.
Writing—review & editing: Hoai Thi Thu Nguyen.
Acknowledgments
None
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