Echocardiographic Z-Score to Predict Pulmonary-Systemic Flow Ratio in Children With Atrial Septal Defect

Abstract

Background: The correlation between pulmonary-to-systemic flow ratio (Qp/Qs) and right heart enlargement in children with atrial septal defect (ASD) remains unclear. This study aimed to (1) assess echocardiographic Z-scores of the right heart, and (2) determine whether they predict Qp/Qs.

Methods and Results: This retrospective study included 175 children (median age 6.8 years; 68 males) with isolated ASD who underwent cardiac catheterization between 2013 and 2020 at 2 centers in Japan. Patients with genetic anomalies or other conditions affecting right heart size were excluded. Echocardiographic parameters were measured, converted to a Z-score, and compared with the catheterization data. In all patients, the Qp/Qs on cardiac catheterization (cQp/Qs) significantly correlated with the Z-scores of the right ventricular end-diastolic diameter of the basal (RVB), mid-cavity (RVM), and longitudinal length (RVL; r=0.54, 0.57, and 0.52, respectively). The average of these 3 parameters (ARV) showed the strongest correlation (r=0.63). Z-scores of the right atrium, tricuspid valve, and pulmonary artery showed weaker correlations. An ARV cut-off of +2.0 best predicted cQp/Qs ≥1.5 (area under the curve 0.85; 95% confidence interval 0.79–0.92; sensitivity 76.8%; specificity 82.4%). Regression-predicted cQp/Qs also significantly correlated with measured cQp/Qs (r=0.63).

Conclusions: ARV may be a useful, non-invasive marker for assessing cQp/Qs and determining the indication for closure in children with ASD.

Central Figure

Various methods have been used to measure the volume of the right ventricle (RV), which has a complex crescent-shaped morphology. While cardiac catheterization has been used to evaluate RV volume in children,¹ it involves invasive procedures such as vascular puncture and general anesthesia, and is now less commonly used. Subsequently, 2-dimensional transthoracic echocardiography (2D-TTE) became a widely used non-invasive alternative.² More recently, cardiac magnetic resonance (CMR) and 3-dimensional (3D) echocardiography have gained popularity for assessing RV volume,^3,4 particularly in conditions involving RV volume overload.

Atrial septal defect (ASD) is a common congenital heart disease that causes RV enlargement due to increased pulmonary overcirculation and requires surgical intervention or catheter-based closure using various devices.^5–9 Closure is indicated when a significant left-to-right shunt is present, typically defined by RV enlargement on TTE and a pulmonary-to-systemic flow ratio (Qp/Qs) ≥1.5, measured by catheterization or CMR.^10–12 While Qp/Qs can be assessed in children and adults, quantitative criteria for RV enlargement by 2D-TTE are only well established in adults.¹³ In children, RV size varies with body size, and no standardized thresholds by 2D-TTE exist. Although pediatric normal RV volumes by CMR and 3D-TTE have been reported,^14–16 a clear definition of RV enlargement is still lacking.

Echocardiographic Z-scores enable normalization of cardiac size to body habitus and are useful for assessing volume overload in congenital heart disease.^17,18 For instance, left ventricular (LV) Z-scores correlate with catheter-derived Qp/Qs (cQp/Qs) and predict volume overload in children with ventricular septal defect or patent ductus arteriosus.¹⁹ Recent studies have also applied Z-score analysis to the right heart system – right atrium (RA), tricuspid valve (TV), main pulmonary artery (MPA), and RV.^17,18,20,21 Although patients with ASD often show an increased right heart system,^22,23 the correlation between the degree of pulmonary overcirculation and right heart Z-scores remains unclear. This study tested the hypothesis that Z-scores of the right heart system correlate with RV volume overload due to pulmonary overcirculation in children with ASD.

Methods

Study Design and Sample Size

This retrospective study was conducted at 2 hospitals (Keio University Hospital, and Tokyo Metropolitan Children’s Medical Center) in Japan. Patients were identified from catheterization records, and demographic, clinical, TTE, catheterization, and surgical data were collected from medical records. To determine the required sample size for correlation analysis between cQp/Qs and echocardiographic Z-scores, we assumed a strong correlation (r=0.5) based on our prior research.¹⁹ The significance level (α) was set at 0.05 and the statistical power at 80%. Using Python (version 3.9.12) and the statsmodels package (version 0.13.5), we estimated the required sample size to be approximately 48 participants under these conditions. However, considering variability in the correlation coefficient, we set the final sample size between 100 and 200.

Inclusion Criteria

Children aged 0–18 years with unrepaired ASD and no other congenital heart disease who underwent cardiac catheterization between 2013 and 2020 at either facility were enrolled. Catheterization was typically performed to determine indications for ASD closure. In contrast, CMR was not routinely used for treatment evaluation in pediatric patients. Transesophageal echocardiography (TEE) was simultaneously performed in patients ≥15 kg with suitable defect morphology. Catheterization was generally performed under general anesthesia or local anesthesia in older children without concurrent TEE. Patients eligible for device closure underwent catheter intervention in the same or a subsequent session, while those requiring surgery had elective repair. Some patients were followed without closure if the indications were not met.

Exclusion Criteria

Patients were excluded if they had: (1) chromosomal abnormalities including trisomy 21, genetic syndromes, or multiple malformations; (2) severe pulmonary hypertension (PH), defined as MPA systolic pressure/LV systolic pressure ≥50% or pulmonary vascular resistance/systemic vascular resistance (PVR/SVR) >1/3 based on guidelines;¹⁰ or (3) the following TTE findings: LV dysfunction (ejection fraction <50%), pulmonary valve stenosis (gradient ≥40 mmHg), or moderate to severe regurgitation of any valve (mitral, aortic, tricuspid, pulmonary), and reduced RV function defined as a Z-score of tricuspid annular plane systolic excursion ≤−2.0,²⁴ as these may affect right heart size independently of cQp/Qs.

Cardiac Catheterization Data

Cardiac catheterization data, blinded to TTE results, included blood oxygen saturation and mean MPA pressure. cQp/Qs was calculated using Fick’s principle, with mixed venous oxygen saturation estimated as the average of superior and inferior vena cava values, accounting for left-to-right shunting due to ASD. PH was defined as a mean MPA pressure ≥20 mmHg. In patients with PH, MPA systolic/LV systolic pressure ratio and PVR/SVR were also recorded.

Transthoracic Echocardiography Data

We used TTE data obtained within 1 week before or after catheterization. A skilled investigator (N.F.S), blinded to the catheterization data, measured the following 2D parameters according to guidelines:²⁴ RA anterior–posterior (RAAP) and lateral–lateral (RALL) diameters, TV anterior–posterior (TVAP) and lateral (TVL) diameters, and TV area (TVA) calculated as (π / 4) × TVL × TVAP; RV basal (RVB), mid-cavity (RVM), and longitudinal (RVL) diameters; and MPA. Measurement views and timing are summarized in the Supplementary Table. Image analysis used software specific to each facility (Centricity Enterprise Web v3.0 at Keio University Hospital; Prime Vita Plus at Tokyo Metropolitan Children’s Medical Center). If a clear image was unavailable, the measurement was omitted. In 4-chamber views with a mid-septal defect, a virtual line was used to define the measurement boundary. RAAP, RALL, RVB, RVM, and RVL were converted to Z-scores using Cantinotti’s formula,²¹ and TVAP, TVL, TVA, and MPA using Lopez’s formula (Supplementary Table).¹⁸ Body surface area was calculated using Haycock’s formula.²⁵ RA and RV areas, which can also be converted to Z-scores,²¹ were not analyzed in this study because planimetric measurements by manual tracing could not be performed on past images at these facilities.

Statistical Analyses

The Shapiro-Wilk test was used to assess normality. Correlation between cQp/Qs and TTE parameters was evaluated using Pearson’s correlation for normally distributed variables and Spearman’s rank correlation otherwise. To assess the age effect, patients were divided into younger and older groups based on the median age, and correlations were analyzed separately. For TTE parameters significantly correlated with cQp/Qs, receiver operating characteristic analysis was conducted to determine thresholds using the Youden Index, with cQp/Qs ≥1.5 as the clinical criterion. Area under the curve (AUC) was calculated using a non-parametric method. Linear regression with curve fitting was used to generate a predictive equation for cQp/Qs from Z-scores. Bland–Altman plots assessed agreement between predicted and cQp/Qs. When proportional bias was visually suspected (i.e., greater variance at higher means), log transformation was applied to stabilize variance and interpret ratios. Inter- and intra-observer variability was evaluated by 2 blinded pediatric cardiologists using repeated RAAP, TVL, and RVL measurements in 20 participants. For each measurement, a pre-selected apical 4-chamber cine loop representing 1 cardiac cycle was provided for each patient. Observers could independently select any frame within the same cardiac cycle for their measurements, following guideline-recommended measurement principles,²⁴ thereby simulating real-world clinical variability. All measurements were performed in a blinded manner, without access to previous measurement values. Intra-observer reproducibility was assessed after a 1-week interval using the same cine loops. Intraclass correlation coefficients (ICCs) were calculated to assess measurement reliability. All statistical analyses were performed using IBM SPSS Statistics (version 27). P<0.05 was considered significant.

Ethics

The institutional review board of each participating facility approved the present study (approval numbers for Keio University Hospital and Tokyo Metropolitan Children’s Medical Center are 20190333 and 2019b-177, respectively). Owing to the retrospective design of this study, the requirement for written informed consent was waived.

Results

Demographics

Between 2013 and 2020, 217 patients with isolated ASD underwent cardiac catheterization at the 2 facilities. Of these, 42 met exclusion criteria, leaving 175 for analysis. No patient was included more than once. All patients were Japanese except for 4. The most common exclusion reason was chromosomal/genetic abnormalities (n=37). Three were excluded for pulmonary valve stenosis (gradient ≥40 mmHg), and 2 others had a mediastinal tumor or right lung hypoplasia. No patients had severe PH, moderate/severe valve regurgitation, reduced RV function, or LVEF < 50%. A participant flow diagram is shown in the Supplementary Figure.

Table 1 summarizes patient characteristics. The median age was 6.8 years (range 0.7–18.5 years), and 61% were female. Most defects were ostium secundum (n=170), with 3 primum, and 1 each of sinus venosus and coronary sinus type. Nineteen (11%) patients had PH (median mPAP 21 mmHg, MPA systolic/LV systolic pressure ratio 0.37, and PVR/SVR 0.06). Regarding treatment, 55% underwent surgical closure, 37% catheter closure, and 8% were managed conservatively based on operator judgment due to small shunt volumes.

Table 1.

Patient Characteristics (n=175)

Variable
Age (years)	6.8±4.1 (0.7–18.5)
Body surface area (m2)	0.77±0.33 (0.37–2.03)
Sex
Male	68 (39)
Female	107 (61)
Type of defect
Ostium secundum	170 (97)
Ostium primum	3 (1.8)
Sinus venosus	1 (0.6)
Coronary sinus	1 (0.6)
Pulmonary hypertension†
No. patients (% of all patients)	19 (11)
mPAP (mmHg)	22.3±2.7 (10–30)
sPAP/LVP	0.37±0.06 (0.28–0.47)
PVR/SVR	0.06±0.06 (0.04–0.31)
Treatment
Catheter closure	97 (55)
Surgical closure	65 (37)
No treatment	13 (8)

Data are expressed as median±SD (range), or n (%). ^†Defined as a pulmonary artery mean pressure of ≥20 mmHg on cardiac catheterization. LVP, left ventricular systolic pressure; mPAP, pulmonary artery mean pressure; PAPVC, partial anomalous pulmonary vein connection; PVR, pulmonary vascular resistance; sPAP, pulmonary artery systolic pressure; SVR, systemic vascular resistance.

Correlation Analysis

Table 2 summarizes the echocardiographic Z-scores and their correlations with cQp/Qs in all patients (n=175), and in those <7 years (n=91) or ≥7 years (n=84), divided by the median age. The median cQp/Qs was 1.9±0.8 (range 0.8–5.1). Because cQp/Qs was not normally distributed, Spearman’s rank correlation was used. Across all ages, Z-scores for RVB, RVM, and RVL significantly correlated with cQp/Qs (r=0.54, 0.57, and 0.52, respectively). Other parameters had weaker correlations. Figure 1 shows these correlations. The average Z-score of RVB, RVM, and RVL (ARV) showed the strongest correlation (r=0.63; Figure 2). In the age-stratified analysis, Z-scores for RAAP, RALL, and TVL correlated more strongly with cQp/Qs in the younger group (<7 years; RAAP: r=0.60; RALL: r=0.65; TVL: r=0.50). Inter-observer ICCs were high for RAAP (0.99), TVL (0.94), and RVL (0.98), despite the use of independently selected frames within the same cardiac cycle according to guideline-based measurement methods. Intra-observer ICCs ranged from 0.95 to 0.99, with all measurements performed in a blinded fashion.

Table 2.

Measured Values and Correlation Analysis (n=175)

	No. valid measurements	Measurement value, median±SD (range)	Correlation coefficient for cQp/Qs, r
			All ages (n=175)	Age <7 years (n=91)	Age ≥7 years (n=84)
RAAP	174	2.6±1.1 (−0.2 to 5.9)	0.47	0.60	0.46
RALL	172	2.3±1.6 (−2.4 to 5.9)	0.48	0.65	0.44
TVAP	168	1.7±1.2 (−1.4 to 5.4)	0.24	0.27	0.24
TVL	174	2.0±1.4 (−1.0 to 7.5)	0.32	0.50	0.28
TVA	167	2.6±1.8 (−0.7 to 11.3)	0.37	0.47	0.30
RVB	163	1.4±1.4 (−3.2 to 5.5)	0.54	0.60	0.57
RVM	162	3.4±1.3 (−0.1 to 7.3)	0.57	0.62	0.57
RVL	164	2.5±1.1 (−1.3 to 4.8)	0.52	0.60	0.48
ARV	160	2.4±1.1 (−1.2 to 5.6)	0.63	0.69	0.64
MPA	164	1.4±1.5 (−2.2 to 7.2)	0.39	0.47	0.35

All echocardiographic measurement values are expressed as a Z-score. ARV, average value of Z-score of right ventricular end diastolic basal diameter, mid-cavity diameter and length; cQp/Qs, pulmonary-systemic flow ratio measured according to Fick’s principle via cardiac catheterization; MPA, main pulmonary artery diameter; RAAP, right atrial anterior-posterior diameter; RALL, right atrial lateral-lateral diameter; RVB, right ventricular end diastolic basal diameter; RVL, right ventricular end diastolic longitudinal length; RVM, right ventricular end diastolic mid-cavity diameter; TVA, tricuspid valve area; TVAP, tricuspid valve anterior-posterior diameter; TVL, tricuspid valve lateral diameter.

Figure 1.

Scatterplot correlation for pulmonary-systemic flow ratio by catheterization vs. echocardiographic Z-score. cQp/Qs, pulmonary-systemic flow ratio by catheterization; MPA, main pulmonary artery diameter; RAAP, right atrial anterior-posterior diameter; RALL, right atrial lateral-lateral diameter; RVB, right ventricular end diastolic basal diameter; RVD, right ventricular end diastolic diameter; RVL, right ventricular end diastolic longitudinal length; RVM, right ventricular end diastolic mid-cavity diameter; TVA, tricuspid valve area; TVAP, tricuspid valve anterior-posterior diameter; TVL, tricuspid valve lateral diameter.

Figure 2.

Correlation between catheter-derived pulmonary-systemic flow ratio (cQp/Qs) and ARV (average Z-score of right ventricular basal, mid-cavity, and longitudinal diameters).

Assessment of cQp/Qs From ARV

In all the patients, receiver operating characteristic analysis revealed an ARV cut-off value of +2.0 to determine whether the cQp/Qs was ≥1.5 (area under the curve 0.85; 95% confidence interval 0.79–0.92; P<0.001; sensitivity 76.8%; specificity 82.4%; Figure 3). The participants’ regression equation to predict the cQp/Qs based on ARV was as follows: 1.324 − (0.001 × ARV) + (0.198 × ARV²) − (0.025 × ARV³) (F=28.6; P<0.001; R²=0.36). The predicted Qp/Qs from this equation had a significant correlation with cQp/Qs (r=0.63; Figure 4), and Bland–Altman analysis using log-transformed values showed a small bias (mean difference±SD, −0.04±0.272), with 95% limits of agreement on the natural log scale ranging from −0.574 to +0.490. This corresponds to a geometric mean ratio of 0.96, with 95% limits of agreement from 0.563 to 1.632 on the original scale (Figure 5).

Figure 3.

Receiver operating characteristic (ROC) analysis for ARV (average Z-score of right ventricular basal, mid-cavity, and longitudinal diameters) to predict pulmonary-systemic flow ratio on cardiac catheterization ≥1.5. AUC, area under the curve; CI, confidence interval; SE, standard error.

Figure 4.

Correlation between predicted and catheter-derived pulmonary-systemic flow ratios (pQp/Qs and cQp/Qs, respectively).

Figure 5.

Log-transformed Bland-Altman plots to assess agreement between echocardiographic prediction and catheter measurement of pulmonary-systemic flow ratio. CI, confidence interval; cQp/Qs, pulmonary-systemic flow ratio by catheterization; LoA, limits of agreement; pQp/Qs, predicted pulmonary-systemic flow ratio by echocardiographic Z-score; SD, standard deviation.

Discussion

To the best of our knowledge, this is the first study to examine the relationship between echocardiographic Z-scores and RV volume overload caused by pulmonary overcirculation in children with ASD. The major findings of this study can be summarized as follows: (1) at all ages, ARV had the highest correlation with cQp/Qs among all parameters; (2) ARV had an accurate cut-off value of +2.0 for determining whether the cQp/Qs was ≥1.5; and (3) the predicted Qp/Qs from the ARV were significantly correlated with cQp/Qs, with small differences.

Relationship Between Right Ventricular Volume and Diameter

Our results demonstrated that the ARV, which averages Z-scores of RVB, RVM, and RVL, better reflects RV volume overload compared with any single directional measurement. This finding suggests that evaluating RV enlargement across multiple axes provides a more accurate estimation of overall RV cavity size. In children with ASD, RV enlargement may occur asymmetrically – some hearts enlarge more longitudinally or in the mid-portion, while others show more lateral or basal dilation.

Figure 6 illustrates this concept. In Figure 6A, a patient with a cQp/Qs of 1.7 had Z-scores of +3.3 for RVM and RVL, and +1.7 for RVB. Although basal enlargement was mild, the ARV was +2.8, reflecting relatively uniform dilation. In Figure 6B, another patient with a similar cQp/Qs (1.6) had Z-scores of +4.3 (RVM), +2.4 (RVL), and +0.5 (RVB). Despite regional variation, the ARV was +2.5, again appropriately indicating volume overload. These examples reinforce the hypothesis that ARV captures partial and uneven enlargement patterns better than unidirectional measures. By averaging multiple axes, ARV provides a more integrated index of RV volume. Notably, these 3 diameters – RVB, RVM, and RVL – are also highlighted in recent ESC recommendations, which support standardized, multidirectional echocardiographic assessment of right heart structures using Z-scores.²⁶ This further underscores the clinical relevance and applicability of the ARV-based approach.

Figure 6.

Examples of right ventricular enlargement in the 4-chamber view. (A) A patient with cQp/Qs of 1.7 had uniformly high Z-scores for RVM and RVL (+3.3) and a mildly elevated RVB (+1.7), resulting in an ARV of +2.8. (B) A patient with cQp/Qs of 1.6 showed marked variability: RVM +4.3, RVL +2.4, RVB +0.5, yielding an ARV of +2.5. These cases illustrate that ARV more reliably reflects RV volume overload than individual measurements. ARV, average value of Z-score of right ventricular end diastolic basal diameter, mid-cavity diameter and length; cQp/Qs, pulmonary-systemic flow ratio by catheterization; RVB, right ventricular end diastolic basal diameter; RVL, right ventricular end diastolic longitudinal length; RVM, right ventricular end diastolic mid-cavity diameter.

Comparison With Other Imaging Modalities

RV volumetry using 3D-TTE or CMR can reflect RV enlargement more accurately than 2D-TTE. However, these imaging techniques for patients were not routinely performed at the institutions that participated in this study. In addition, to the best of our knowledge, the Z-score converting formula for RV volume by such measurement methods is not yet available, and in the case of an enlarged RV, interpretation of the disparity in the measured RV volumes between 3D-TTE and CMR remains a problem.^27,28 Moreover, regarding CMR, the need for sedation in younger children to obtain an accurate image is also a disadvantage. However, echocardiographic 2D measurement can be performed non-invasively in less time than 3D-TTE measurement and CMR; hence, it is a remarkably easy-to-use method for daily clinical use. Therefore, the ARV based on 2D measurements is a simple and superior method for quantitatively evaluating RV enlargement.

Echocardiographic Parameters Less Associated With cQp/Qs Than With ARV

In our study, TV diameter had the weakest correlation with cQp/Qs, although the participants’ Z-score for TV diameter was as high as that of other parameters. This suggests that the TV diameter does not accurately reflect the amount of transit blood flow despite the increase in blood flow. The exact reason for this is unknown; however, it may be difficult to precisely change the volume of blood flow given the stiff fibrous skeleton of the tricuspid annulus. Our study also showed that the Z-score of the MPA was weakly correlated with cQp/Qs, similar to that of the TV diameter. Because the MPA receives blood flow during the systolic phase, its diameter is thought to be affected not only by the amount of blood flow but also by the systolic pressure of the RV and turbulent flow at the level of the pulmonary valve due to pulmonary overcirculation. Therefore, MPA diameter did not reflect the amount of pulmonary blood flow. However, the RV directly receives blood flow during the diastolic phase; hence, cQp/Qs is accurately reflected by RV diameter in patients with ASD. Our study also suggests that the Z-score of the RA diameter shows a high correlation only in the younger age group and may be useful for predicting cQp/Qs in young children. However, the RV diameter, especially ARV, showed a consistently high correlation, regardless of age, suggesting its highest utility for a wide range of ages.

Comparison With Previous Studies Using RV Z-Scores

Our findings extend the prior work by Koestenberger et al., who demonstrated that RV Z-scores could identify ASD-related RV enlargement in children under 8 years of age.²¹ While their study established normal reference values and evaluated structural enlargement as a diagnostic marker, it did not include hemodynamic data such as Qp/Qs. In contrast, our study incorporated catheter-derived Qp/Qs as a reference standard to evaluate whether RV Z-scores can predict hemodynamically significant left-to-right shunting (Qp/Qs >1.5), a clinically actionable threshold. By doing so, we confirmed the utility of RV Z-scores in identifying RV enlargement and demonstrated their potential value in informing treatment decisions. This hemodynamic validation offers a more direct application to real-world clinical decision-making, especially when catheterization is not immediately available.

Clinical Implications

The present findings provide new criteria for non-invasive quantitative assessment of RV enlargement in children with ASD. From our study, we can consider that a significant left-to-right shunt exists when the ARV is ≥+2.0 in a patient with ASD. The ARV is easily obtained from the 3 RV diameters in an apical 4-chamber view without requiring advanced technical expertise. This provides a practical advantage, as RV volumes calculated using 3D-TTE are not always easy to acquire due to poor acoustic windows and the irregular geometry of the RV. Moreover, 3D-TTE tends to underestimate RV volumes compared with CMR.²⁶ In addition, TTE is less invasive and costly compared with cardiac catheterization and CMR imaging, and can also be used in the outpatient setting. This study is based on patient data from 2 different institutions and is considered to have a certain degree of external validity.

Importantly, current clinical guidelines for ASD closure in children emphasize the presence of RV volume overload rather than a fixed Qp/Qs threshold.^10,11 However, standardized echocardiographic definitions of RV dilation in the pediatric population remain lacking. In this context, our study addresses an important clinical gap by proposing an evidence-based cut-off (ARV ≥+2.0), which may serve as a reference point for identifying significant RV dilation. This quantifiable marker may support consistent decision-making regarding ASD closure across diverse clinical settings, particularly when invasive or advanced imaging modalities are not feasible.

Limitations of Using Z-Score

Predicting the pulmonary blood flow based on the Z-score also presents problems, as we excluded some candidate patients from this study. First, a dilated LV, such as LV dysfunction or mitral and aortic valve regurgitation, depresses the RV volume, potentially leading to an underestimation of the Z-score of RV dimensions. Second, the presence of RV dilatation by the amount of tricuspid and pulmonary valve regurgitation may lead to an overestimation of the amount of pulmonary circulation using the Z-score because each increases the RV dimensions. Moreover, significant pulmonary valve stenosis or severe PH, which results in concentric RV hypertrophy via afterload, can affect the size of the RV internal cavity. The impact of these factors on the Z-score of RV diameter was not examined in this study. Furthermore, it is unclear whether predictions based on the Z-score can be applied to patients with a chromosomal or other genetic anomaly who often have congenital heart disease because they were excluded from the present study owing to the lack of normal TTE measurements.

Study Limitations

This study has some limitations. First, this study did not include the following echocardiographic RV measurements: the RV area in the 4-chamber view and the proximal and distal diameters of the RV outflow tract (RVOT), which are also considered to reflect RV enlargement.² Although the RVOT can present <25% of the entire RV volume,²⁹ the formula for converting the RVOT diameter into a Z-score is not yet available. Thus, we could not analyze these parameters in this study. Therefore, our results may not accurately reflect the actual RV volume. In addition, this study did not include patients with moderate PH (mean PA pressure >30 mmHg); thus, the influence of moderate PH on the relationship between QpQs and right heart size could not be assessed. Second, this study did not include CMR, which is widely regarded as the reference standard for assessing RV volume. The absence of CMR data limited our ability to validate echocardiographic measurements and to comprehensively assess total RV volume, similar to the absence of RVOT and RV area measurements described above. Third, this study did not include patients who did not undergo cardiac catheterization, that is, patients who were considered to have no significant shunt due to the small defect size; therefore, our study could not consider all cases of ASD in each facility. Fourth, because most participants were Japanese, it is unclear whether our findings are generalizable to other ethnicities. Although some reports have indicated that racial differences may influence cardiac structural dimensions, particularly in left ventricular size and function,³⁰ another study suggested that the Z-score is relatively unaffected by ethnicity.¹⁶ Fifth, because the present study had a retrospective design with a relatively small number of patients, a prospective study with a larger number of patients is necessary to reconfirm our results. Last, although the correlation between RV dilation and left-to-right shunt in ASD is well known, and our study reaffirmed this physiological relationship, it also provided a practical cut-off (ARV ≥+2.0) that may serve as a reference for defining RV enlargement in children. Given the lack of standardized echocardiographic thresholds in pediatric guidelines, this cut-off may help inform clinical decision-making. However, further studies are needed to validate whether this threshold aligns with real-world treatment strategies, such as ASD closure.

Conclusions

This study provides evidence of a correlation between Z-scores and right heart system volume overload in children with ASD. Using ARV, we can non-invasively and quantitatively assess patients’ RV volume to consider the indication for closure.

Acknowledgments

This work was supported by JSPS KAKENHI grant no. JP 25K19211.

Disclosures

H.Y. is a member of Circulation Reports’ Editorial Team. N.F.S. receives a grant from the Kawano Foundation for Pediatric Medical Research. The other authors declare no conflicts of interest. This work was supported by JSPS KAKENHI grant no. JP 25K19211.

IRB Information

All procedures in this study were in accordance with the ‘Declaration of Helsinki’. The present study was approved by the institutional review board of Keio University Hospital and the institutional review board of Tokyo Metropolitan Children’s Medical Center (approval numbers for each facility are 20190333 and 2019b-177, respectively).

Data Availability

The dataset is available from the corresponding author upon reasonable request.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circrep.CR-25-0119

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