Noninvasive right ventricular work in patients with atrial septal defects: a proof-of-concept study
Cardiovascular Ultrasound volume 21, Article number: 10 (2023)
Noninvasive right ventricular (RV) myocardial work (RVMW) determined by echocardiography is a novel indicator used to estimate RV systolic function. To date, the feasibility of using RVMW has not been verified in assessing RV function in patients with atrial septal defect (ASD).
Noninvasive RVMW was analysed in 29 ASD patients (median age, 49 years; 21% male) and 29 age- and sex-matched individuals without cardiovascular disease. The ASD patients underwent echocardiography and right heart catheterization (RHC) within 24 h.
The RV global work index (RVGWI), RV global constructive work (RVGCW), and RV global wasted work (RVGWW) were significantly higher in the ASD patients than in the controls, while there was no significant difference in RV global work efficiency (RVGWE). RV global longitudinal strain (RV GLS), RVGWI, RVGCW, and RVGWW demonstrated significant correlations with RHC-derived stroke volume (SV) and SV index. The RVGWI (area under receiver operating characteristic curve [AUC] = 0.895), RVGCW (AUC = 0.922), and RVGWW (AUC = 0.870) could be considered good predictors of ASD and were superior to RV GLS (AUC = 0.656).
The RVGWI, RVGCW, and RVGWW could be used to assess RV systolic function and are correlated with RHC-derived SV and SV index in patients with ASD.
Atrial septal defect (ASD) is a common form of congenital heart disease with an estimated prevalence of 1 in 1000 live births [1, 2]. The rate of right ventricular (RV) dysfunction increases in patients with untreated ASD.
Echocardiography plays a crucial role in the evaluation of RV function . Tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV FAC), tissue Doppler-derived tricuspid lateral annular systolic velocity (RV Sʹ), and three-dimensional RV ejection fraction (3D RV EF) are the commonly used parameters for assessing RV systolic function [3, 4]. However, these parameters are load dependent. As a reliable and superior indicator, RV global longitudinal strain (RV GLS) remains a load-related parameter because of the low ventricular elastance and the thin wall of the right ventricle [5, 6].
Recently, noninvasive RV myocardial work (RVMW) by echocardiography was demonstrated as a novel and reliable indicator to assess RV systolic performance [7, 8]. RVMW integrates RV GLS, pulmonary artery pressure, and cardiac cycle events, which provide more precise information than conventional RV systolic function parameters.
To date, noninvasive RVMW has not been applied to assess RV systolic function in patients with ASD. Therefore, the present study was designed to achieve the following objectives: (i) compare the RVMW between ASD patients and healthy controls; (ii) explore the correlations between the noninvasive RVMW and RV stroke volume (SV) and SV index measured by right heart catheterization (RHC) in ASD patients; and (iii) explore the possibility of using RVMW indices to evaluate myocardial performance among patients with ASD.
A total of 57 ASD patients (> 17 years of age) were prospectively recruited in Xiamen Cardiovascular Hospital between May and August of 2022. The study flow chart is shown in Fig. 1. The exclusion criteria were as follows: RHC not performed within 24 h after echocardiogram, coronary heart disease, cardiac arrhythmias during the echocardiogram, other congenital cardiac diseases, left ventricular (LV) dysfunction or heart failure, severe tricuspid regurgitation (TR) , TR Doppler envelope of poor quality, poor echocardiography images, and pulmonary capillary wedge pressure > 15 mmHg . After exclusion, 29 patients were finally included. An additional 29 age- and sex-matched subjects without cardiovascular diseases were enrolled as the control group. The Ethics Committee approved the study, and informed consent forms were obtained.
Transthoracic echocardiographic images were obtained by a Vivid E95 ultrasound system (GE Vingmed Ultrasound) according to the recommended protocols [11, 12]. Two-dimensional and three-dimensional (3D) echocardiographic images were obtained by M5S and 4 V transducers, respectively. All echocardiographic images were stored over 3–4 consecutive cardiac cycles with the electrocardiogram connected. Datasets were analysed offline using EchoPAC (version 204).
The LV ejection fraction, TAPSE, RV FAC, RV Sʹ, RV basal diameter, and tricuspid annular diameter were measured in line with the current guidelines [3, 4, 13]. The 3D RV volume and RA volume were obtained by the software packages 4D Auto RVQ and 4D Auto LAQ, respectively. RV GLS and RV free wall longitudinal strain (RV FWLS) were assessed by tracing the endocardial border of the interventricular septum and the RV free wall (Fig. 2A) .
Systolic pulmonary artery pressure (SPAP) was estimated as follows: SPAP = 4 × (TR peak velocity)2 + RA pressure (estimated by the inferior vena cava) [3, 14]. The mean RV-RA gradient pressure was obtained by tracking the TR velocity-time integral (Fig. 2B) . Mean pulmonary artery pressure (MPAP) equals the RA pressure plus the mean RV-RA gradient pressure. Diastolic pulmonary artery pressure (DPAP) was computed as follows: DPAP = 1.5 × MPAP − 0.5 × SPAP . RVMW was analysed using the LV myocardial work (LVMW) assessment software package (AFI). Prognostic validation of LVMW was performed in several studies [16,17,18]. The event timings of tricuspid and pulmonic valves were obtained from visualization in the short-axis parasternal views (Fig. 2C). Then, RV GLS, SPAP, and DPAP were synchronized by valve event timings to create a noninvasive RV pressure–strain loop (RV PSL) (Fig. 2A-D). RVMW was calculated by integrating the product of the instantaneous RV pressure over time and the rate of segmental shortening to obtain myocardial work as a function of time during the cardiac cycle.
Four RVMW indices were obtained as follows:
RV global work index (RVGWI): total work, the area of RV PSL from tricuspid valve closure to opening.
RV global constructive work (RVGCW): positive work, myocardial lengthening during isovolumic relaxation and shortening during systole.
RV global wasted work (RVGWW): negative work, myocardial shortening during isovolumic relaxation and lengthening during systole.
RV global work efficiency (RVGWE): the ratio of RVGCW to the sum of RVGCW and RVGWW.
RHC was performed by experienced interventional cardiologists. A 6 F Swan Ganz catheter was inserted through the femoral or internal jugular vein under fluoroscopic guidance. RV systolic and diastolic pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure were acquired at end-expiration. The ratio of pulmonary to systemic blood flow and LV and RV cardiac output were obtained by the Fick formula. RV SV was calculated as RV cardiac output divided by heart rate. The RV SV index and LV and RV cardiac indices were calculated as RV SV and LV and RV cardiac output divided by body surface area, respectively.
Categorical variables were expressed as numbers (percentage). The normality of continuous variables was verified by the Kolmogorov–Smirnov test. Based on the normality of the data, continuous variables were expressed as the mean (SD) or median (interquartile range), appropriately. Differences between the ASD and control groups were compared by the χ2 test, Student’s t test, and Mann‒Whitney U test as appropriate. Relationships between parameters of RV systolic function and invasively derived SV and SV index were investigated by Pearson or Spearman correlation as appropriate. Receiver operating characteristic (ROC) curves were analysed to determine optimal cutoff values to predict ASD and to calculate the area under the ROC curve (AUC), sensitivity, and specificity. Fifteen random subjects with ASD were selected for the calculation of intra-observer and inter-observer variabilities by Bland–Altman analysis and intraclass correlation coefficients. All data were processed using SPSS (version 26.0). A two-sided P value < 0.05 was considered indicative of statistical significance.
Fifty-seven patients with ASD were enrolled in this study (Fig. 1). Forty-seven patients underwent RHC for clinical indications. Twenty-nine patients were included in the final analysis, and the rest of the patients were excluded based on the exclusion criteria. An additional 29 subjects without cardiovascular and pulmonary disease were set as the control group. The clinical characteristics are summarized in Table 1.
All enrolled patients had left-to-right colour Doppler shunts, and the median ASD size was 11.0 (8.0-18.5) mm. Table 2 summarizes the echocardiographic parameters of patients with ASD and controls. TAPSE, RV Sʹ, 3D RV end-diastolic volume, 3D RV end-systolic volume, 3D RV SV, RV basal diameter, tricuspid annular diameter, 3D RA volume, pulmonary artery pressure, and RV GLS were higher in the ASD group. LVEF, RV FAC, 3D RV EF, and RV FWLS were not significantly different between the two groups. Patients with ASD had a higher RVGWI, RVGCW, and RVGWW than the controls (RVGWI: 571.7 ± 203.2 mmHg% vs. 311.2 ± 98.7 mmHg%, P < 0.001; RVGCW: 690.8 ± 254.8 mmHg% vs. 361.5 ± 101.3 mmHg%, P < 0.001; RVGWW: 56.0 [37.5–75.0] mmHg% vs. 22.0 [9.0-37.5] mmHg%, P < 0.001), while RVGWE showed no significant difference between ASD patients and controls.
RHC data of patients with ASD are summarized in Table 3. RV SV (114.7 ± 37.9 mL), RV SV index (71.2 ± 24.0 mL/m2), RV cardiac output (8.9 ± 3.7 L/min), RV cardiac index (5.5 ± 2.4 L/min/m2) were increased in patients with ASD. SPAP calculated by RHC showed no significant difference from SPAP estimated by echocardiography (38.0 [29.0-48.5] mmHg vs. 35.4 [29.1–48.4] mmHg, P = 0.320). The mean Qp/Qs ratio was 1.9 ± 0.8 in the patients with ASD.
Relationship between parameters of RV systolic function and RHC parameters
The correlations between RHC-derived SV and SV index and the echocardiographic parameters of RV systolic function were calculated in the ASD group (Table 4 and Supplementary Fig. 1). Except for RV GLS, which was significantly correlated with RV SV and RV SV index (r = -0.478, P = 0.009 and r = -0.488, P = 0.007, respectively), none of the standard echocardiographic parameters of RV systolic function were significantly correlated with RV SV or the RV SV index. However, RVGWI showed moderate correlations with RV SV and SV index (r = 0.503, P = 0.005 and r = 0.521, P = 0.004, respectively), RVGCW showed weak correlations with RV SV and SV index (r = 0.440, P = 0.017 and r = 0.461, P = 0.012, respectively), and RVGWW showed weak correlations with RV SV and SV index (r = 0.444, P = 0.016 and r = 0.410, P = 0.027, respectively).
ROC analysis was performed to determine whether standard echocardiographic parameters and RVMW indices could identify patients with ASD (Table 5; Fig. 3). The ROC analysis revealed that the optimal TAPSE, RV Sʹ, RV GLS, RVGCW, RVGWI, and RVGWW cutoff points were 20.2 mm (AUC = 0.842), 13.5 cm/s (AUC = 0.713), -19.8% (AUC = 0.656), 376.5 mmHg% (AUC = 0.895), 430.0 mmHg% (AUC = 0.922), and 45.5 mmHg% (AUC = 0.870), respectively.
Intra-observer and inter-observer variabilities in RVMW indices
This study is a proof-of-concept study to identify the feasibility of using noninvasive RVMW in ASD patients. Assessing RVMW may enhance the understanding of the pathophysiology of RV myocardial systolic function in ASD patients.
Changes in RV systolic function parameters in ASD
In our study, RV FAC showed no significant difference between ASD patients and controls, which was consistent with previous research . TAPSE and RV Sʹ were higher in ASD patients than in controls, which was in line with previous studies [20, 21].
In patients with ASD, there was an increased volume load on the right ventricle, which subsequently led to an enlargement of the RV cavity [22, 23]. However, the 3D RV EF in ASD patients was not significantly different from that in controls, which may be due to preserved RV contractility in RV volume overload for long periods . In addition, RV FWLS showed no significant difference between ASD patients and controls, and this result was consistent with the study by Dragulescu et al. . However, the RV GLS was worse in ASD patients than in controls, perhaps because RV dilatation by increased preload led to augmented wall tension of the interventricular septum.
The increased RV preload of ASD patients leads to an increase in the volume of blood in the pulmonary circulation and ultimately increases the afterload . The RVGWI and RVGCW reflected positive myocardial performance and increase as the afterload increases. Moreover, the increase in RVGWW may be related to remodelling of the cardiomyocytes under prolonged load and myocardial dyssynchrony in a state of increased RV afterload . However, there was no significant difference in RVGWE between ASD patients and controls. This demonstrates that RV global myocardial systolic performance could be well preserved under long-term capacity loads as well as pressure loads in ASD patients.
Superiority of RVMW in evaluating RV systolic function
Compared with TAPSE, RV FAC, RV Sʹ, and RV longitudinal strain, RVMW integrates myocardial systolic function, RV pressure and cardiac cycle into the RV PSL. The function of the right ventricle is more susceptible to afterload than that of the left ventricle . In addition, RV dyssynchrony has a substantial impact on RV function [27, 28]. Theoretically, comprehensive evaluations of RV systolic performance could be derived from the four RVMW indices.
Except for RV GLS, none of the standard echocardiographic parameters were significantly correlated with RHC-derived SV or SV index. Conversely, the RVGWI, RVGCW, and RVGWE showed positive correlations with RHC-derived SV and SV index. According to the ROC analysis, the RVGWI, RVGCW, and RVGWE could be considered good predictors of ASD and are superior to load-dependent RV GLS. Although the correlations between the three RVMW indices and RHC-derived RV SV and SV index are weak and moderate, RVMW is the best noninvasive method to evaluate RV systolic function in ASD patients compare to standard RV systolic indices.
Conventional echocardiographic RV systolic function parameters were used to examine RV myocardial contractile performance in ASD patients, but none of these parameters incorporated the effect of pre- or afterload on the right ventricle [19, 21, 29,30,31]. As RV afterload is reflected in RVMW, the latter could expand the echocardiographic assessment of RV function in patients with untreated ASD.
This study is a single-centre study, and the sample size of ASD patients included was small. Noninvasive RVMW was not validated by radionuclide ventriculography or cardiovascular magnetic resonance. Additionally, RVMW was acquired by using a single-provider platform specifically designed for measuring LVMW. The RV GLS was calculated by measuring the strains of the interventricular septum and RV free wall because of the irregular and complicated RV anatomy . Therefore, the RVMW derived by RV PSL is not as accurate as the LVMW derived by the LV pressure-strain loop . Moreover, noninvasive RVMW should be validated by invasive RV PSL in the future.
RVGWI, RVGCW, and RVGWW are feasible indicators that assess RV systolic function and correlate with RHC-derived SV and SV index in patients with ASD. Noninvasive RVMW may predict RV systolic function and correlate with RHC-derived SV and SV index in patients with ASD, with possible prognostic implications. Further studies are required to verify the clinical role of noninvasive RVMW.
Availability of data and materials
The data and material underlying this article will be shared on reasonable request to the corresponding authors.
Atrial septal defect
Tricuspid annular plane systolic excursion
- RV FAC:
RV fractional area change
- RV Sʹ:
tissue Doppler-derived tricuspid lateral annular systolic velocity
- RV EF:
RV ejection fraction
- RV GLS:
RV longitudinal strain
RV myocardial work
Right heart catheterization
Systolic pulmonary artery pressure
Mean pulmonary artery pressure
Diastolic pulmonary artery pressure
LV myocardial work
- RV PSL:
RV pressure–strain loop
RV global work index
RV global constructive work
RV global wasted work
RV global work efficiency
Receiver operating characteristic.
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Ethics approval and consent to participate
The protocol was approved by the Institutional Ethics Committee of Xiamen Cardiovascular Hospital of Xiamen University, and all subjects provided written informed consent before undergoing examinations.
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Correlations of RV GLS, RVGWI, RVGCW, and RVGWWwith RHC-derived stroke volume and stroke volume index. GLS, globallongitudinal strain; RHC, right heart catheterization; RV, right ventricular;RVGCW, RV global constructive work; RVGWE, RV global work efficiency; RVGWI, RVglobal work index; RVGWW, RV global work waste.
The Bland–Altman analysis for assessinginter-observer variability of right ventricular global work index (RVGWI),right ventricular global constructive work (RVGCW), right ventricular global wasted work (RVGWW), and right ventricular globalwork efficiency (RVGWE).
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Wu, J., Huang, X., Chen, W. et al. Noninvasive right ventricular work in patients with atrial septal defects: a proof-of-concept study. Cardiovasc Ultrasound 21, 10 (2023). https://doi.org/10.1186/s12947-023-00306-8