Persistent left superior vena cava causing change in cardiac chamber size: anatomical and hemodynamic changes

Introduction

The incidence of persistent left superior vena cava (PLSVC) during the fetal period is approximately 0.3–0.5% (1), making it a notable congenital anomaly of the venous system. Approximately 90% of fetal PLSVC cases drain into the atrium dextrum (AD) via the coronary sinus (CS), whereas the remaining cases drain into the atrium sinistrum (AS), a configuration that is relatively rare and frequently associated with complex congenital malformations. No significant gender predisposition has been observed for PLSVC. PLSVC often coexists with various cardiovascular malformations, including ventricular septal defects (VSDs) and tetralogy of Fallot (TOF) (2), and has been identified in up to 3–10% of patients with congenital heart disease (CHD) (3). Fetal echocardiography is the preferred diagnostic modality, as it allows accurate visualization of PLSVC anatomy and blood flow dynamics. Prognosis depends on the presence and severity of concurrent cardiac or extracardiac malformations and the chosen treatment approach. PLSVC is commonly detected during prenatal ultrasound or fetal echocardiography, with some fetuses presenting with arrhythmias or tricuspid regurgitation. Most PLSVC cases are isolated, and the prognosis for these fetuses is generally favorable. PLSVC may increase the risk of atrial fibrillation development in adulthood or pose challenges during device implantation. In contrast, when PLSVC is accompanied by other defects, it may pose hemodynamic considerations that warrant a prenatal diagnosis and close postnatal follow-up.

Given that isolated PLSVC could affect cardiac structure, and that most cases drain into the CS causing CS dilation, this condition can potentially influence the hemodynamic load of the fetal cardiac chamber, leading to alterations in fetal hemodynamics. This study aimed to investigate whether isolated PLSVC contributed to changes in cardiac chamber size and fetal hemodynamics, thereby providing an objective theoretical basis for prenatal counseling and clinical management.

To achieve this, we conducted a retrospective analysis of fetal echocardiographic data from a cohort of fetuses diagnosed with isolated PLSVC. Echocardiographic measurements of cardiac chamber size and hemodynamics were compared between fetuses with isolated PLSVC and normal fetuses. By clarifying the specific effects of PLSVC on fetal heart structure and function, we aimed to inform clinical decision-making and improve outcomes in relation to the neonate who may be a prospect for cardiothoracic intervention. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2635/rc).

Methods

This retrospective study analyzed clinical and ultrasonographic data from 166 fetuses diagnosed with isolated PLSVC and 166 normal fetuses via prenatal fetal echocardiography at our hospital between January 2020 and December 2024. The study focused on fetuses with a gestational age (GA) of 21+2 to 34+5 weeks who were prenatally identified with Type I PLSVC. Type I PLSVC, one of the most common fetal vascular anomalies, is characterized by drainage from the CS into the AD (4,5). The study population comprised pregnant women aged between 21 and 40 years. A total of 135,420 prenatal ultrasounds were performed, screening for 166 cases of type I PLSVC and 166 cases of normal fetuses. All cases were singleton pregnancies, and normal fetuses were matched with the isolated PLSVC for GA. All cases were not associated with other intracardiac or extracardiac structural malformations. Data visualization was performed on ultrasound parameters and clinical baseline data for isolated PLSVC and normal fetuses (Table 1). All pregnant women underwent transabdominal fetal echocardiography during the study period. Follow-up after birth indicated that all isolated PLSVC cases had favorable outcomes.

The exclusion criteria included twin pregnancies; fetal non-cardiac structural abnormalities; pregnancy complications, including gestational diabetes and gestational hypertension; non-type I PLSVC; and loss to follow-up. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Gansu Provincial Maternity and Child Care Hospital (No. 2023-GSFY-54). Informed consent was provided by all of the pregnant women.

Images were acquired using an eM6C transducer (2.0–5.0 MHz) on a Voluson E10 ultrasound system (GE Healthcare, Zipf, Austria). Two-dimensional (2D) ultrasonography was employed to detect conventional ultrasound findings and fetal structures. Fetal echocardiography was performed to assess abnormalities in both intracardiac and extracardiac structures. Prenatal ultrasonographic results were independently evaluated by two senior physicians specializing in fetal echocardiography, who examined the imaging characteristics of type I PLSVC. Comprehensive data from 2D fetal echocardiography and high-definition flow (HD-flow) imaging were collected for detailed analysis.

The 2D images revealed a dilated CS in the four-chamber view (Figure 1A) and the PLSVC in the three-vessel-trachea (3VT) view (Figure 1B). By rotating the probe 90 degrees, a long-axis view of the PLSVC was obtained (Figure 1C). HD-Flow imaging in the long-axis view illustrated drainage of the PLSVC into the right atrium (RA) through the dilated CS (Figure 1D).

Figure 1 PLSVC visualized using 2D ultrasonography and HD-flow. (A) 2D ultrasonographic image showing the dilated CS in the four-chamber view. (B) 3-VT section demonstrating the PLSVC located to the left of the pulmonary artery. (C,D) 2D and HD-flow images illustrating the anatomical features of the PLSVC draining into the AD through the dilated CS in long-axis view. 2D, two-dimensional; 3-VT, three-vessel-trachea; AD, atrium dextrum; AS, atrium sinistrum; CS, coronary sinus; DAO, descending aorta; HD-flow, high-definition flow; PA, pulmonary artery; PLSVC, persistent left superior vena cava; RSVC, right superior vena cava; T, trachea; VD, ventriculus dexter; VS, ventricle sinistrum.

AS and AD diameters were measured during ventricular systole in the four-chamber view, from the atrial surface to the atrial side wall (Figure 2A). Thoracic transverse diameter (TTD), ventricle sinistrum (VS), and ventriculus dexter (VD) diameters were measured during ventricular diastole in the four-chamber view (Figure 2B). Aortic diameter (AOD) and pulmonary artery diameter (PAD) were measured during ventricular systole when the aortic or pulmonary valves were fully open in the left and right ventricular outflow tract sections, respectively (Figure 2C,2D). Aortic (AOV) and pulmonary artery velocities (PAV) were assessed by placing the pulsed Doppler sample volume at the respective valves in the left and right ventricular outflow tract sections. The arterial duct diameter (ADD) was measured in the 3VT view. Diameter ratios of VD/VS, AD/AS, and PAD/AOD were calculated.

Figure 2 The measurements of cardiac chamber size presentation: (A) AS and AD diameters were measured during ventricular systole in the four-chamber view. (B) VS and VD diameters were measured during ventricular diastole in the four-chamber view. (C,D) AOD and PAD were measured during ventricular systole in the left and right ventricular outflow tract sections, respectively. AD, atrium dextrum; AOD, aortic diameter; AS, atrium sinistrum; PAD, pulmonary artery diameter; VD, ventriculus dexter; VS, ventricle sinistrum.

Sources of inter-observer variability and its impact on diagnostic accuracy

Observer variability can arise from several factors, including differences in the interpretation of ultrasound images, minor variations in measurement techniques, and divergent understandings of diagnostic criteria. To minimize this variability, the study implemented several strategies. A 2-week standardized training program was conducted for the two primary physicians performing the assessments. In addition to their extensive prior expertise in these procedures, the training covered identification of fetal echocardiographic anatomical structures, standardized measurement procedures, and detailed diagnostic criteria, ensuring full comprehension of the research requirements and consistent operational skills. During data collection, 20% of cases were randomly selected for independent evaluation by both observers. Inter-observer consistency (κ value) was calculated and found to be 0.87, indicating strong agreement and reliable assessment outcomes. Additionally, a communication protocol was established: when significant discrepancies arose, the observers discussed the results jointly to identify causes and reach consensus, thereby improving assessment accuracy.

Statistical analysis

All statistical analyses were performed using the software SPSS 22.0 (IBM Corp., Armonk, NY, USA) and R 4.0.1 (rms package for nomogram construction; R Foundation for Statistical Computing, Vienna, Austria). The analysis methods were as follows.

Variable distribution test and description: the Shapiro-Wilk test assessed the normality of continuous variables including TTD, VS, VD, AS, AD, AOD, PAD, AOV, PAV, and ADD. Normally distributed variables were expressed as mean ± standard deviation, and comparisons between groups were conducted using the independent samples t-test, with Levene’s test applied to assess variance homogeneity. Non-normally distributed variables were expressed as median (interquartile range) and compared using the Wilcoxon signed-rank test. Categorical variables were expressed as count (%) and compared using the χ² test or Fisher’s exact test, depending on expected frequencies.

Predictive model construction and validation: univariate logistic regression was performed for all ultrasound measurement parameters, and variables with P<0.10 were included in the multivariate logistic regression. The multivariate analysis used backward stepwise elimination, retaining variables with P<0.05 in the final model. Multicollinearity was assessed using the variance inflation factor (VIF), with VIF <5 indicating no significant multicollinearity. Model discrimination was evaluated using the area under the curve (AUC) with 95% confidence interval (CI). Calibration was assessed using calibration curves, with the agreement between predicted and observed values judged by the fit to the ideal prediction line. The clinical utility of the model was evaluated using decision curve analysis (DCA).

Bivariate correlation analysis: Pearson correlation analysis was used when both variables conformed to a normal distribution, whereas Spearman rank correlation was applied when either variable deviated from normality. For significant correlations (P<0.05), a linear regression equation (Y = βX + α, where β is the regression coefficient and α is the intercept) was constructed, and the coefficient of determination (R2) was reported to reflect the explanatory power of the independent variable on the dependent variable. All tests were two-tailed, and P<0.05 was considered statistically significant.

Results

A total of 135,420 prenatal ultrasounds were performed, screening for 166 cases of type I PLSVC. The negative controls were normal fetuses of the same GA matched to the isolated PLSVC group. All cases not associated with other intracardiac or extracardiac structural malformations. Two cases had only a LSVC, whereas 164 cases had both right and LSVC. Data visualization was performed on ultrasound parameters and clinical baseline data for isolated PLSVC and normal fetuses (Table 1). Follow-up after birth indicated that all isolated PLSVC cases had favorable outcomes.

Analysis of prenatal ultrasound measurements between isolated PLSVC and normal fetuses showed that the measurements of VD, AD, AOD, PAD, ADD, AOV, and PAV differed significantly between isolated PLSVC and normal fetuses (P<0.05). 3D scatter plots effectively visualized the distinct spatial distribution patterns of vascular parameters in isolated PLSVC versus normal fetuses (Figure 3A-3C). Comparative analysis of vascular ratios demonstrated significant intergroup differences in VD/VS, AD/AS, and PAD/AOD (P<0.05; Table 1). Univariate and multivariate logistic regression analyses were performed on ultrasound measurement parameters. Prior to analysis, multicollinearity among variables was excluded via VIF testing (VIF values ranged from 1.2 to 1.8, all <5). Variables were then screened using backward stepwise elimination (retention criterion: P<0.05). Univariate logistic regression showed that VD, AD, AOD, PAD, and PAV were all associated with isolated PLSVC (specific coefficients and P values are shown in Table 2). Multivariate logistic regression, adjusting for potential confounders such as AOD and PAD, revealed that only VD and AD were independent factors for identifying isolated PLSVC. Receiver operating characteristic (ROC) curve analysis showed that the AUC for combined detection of VD and VS was significantly higher than that of individual indicators, confirming that the combination of VD and VS has high diagnostic value for distinguishing fetuses with isolated PLSVC from normal fetuses.

Figure 3 Three-dimensional scatter plots comparing prenatal measurement parameters between the PLSVC group and controls. (A) Visualization of VS, VD, and AS. (B) Visualization of PAD, TTD, and AV. (C) Comparative visualization of AD, VD, and ADD. (A: control group; B: isolated PLSVC cardiac data group). AD, atrium dextrum; ADD, arterial duct diameter; AS, atrium sinistrum; AV, aortic velocity; PAD, pulmonary artery diameter; PLSVC, persistent left superior vena cava; TTD, thoracic transverse diameter; VD, ventriculus dexter; VS, ventricle sinistrum.

In the control group, fetal VS showed a positive correlation with AS (R²=0.96, P<0.001) (Figure 4A). In the isolated PLSVC group, fetal VD positively correlated with AD (R²=0.96, P<0.001) (Figure 4B), and PAD correlated positively with AOD (R²=0.54, P<0.001) (Figure 4C). AD achieved an AUC of 0.674 (95% CI: 0.621–0.727) with 47.59% sensitivity and 83.03% specificity, whereas AOD yielded an AUC of 0.695 (95% CI: 0.643–0.747) with 50.00% sensitivity and 83.13% specificity (Table 3, Figure 4D). Combined use of AD and AOD enhanced diagnostic accuracy, demonstrating a positive predictive value of 81.2% and a negative predictive value of 75.6%.

Figure 4 Comparative statistical analysis of prenatal measurement parameters between the PLSVC group and controls. (A) Correlation between VS and AS in both groups. (B) Correlation between VD and AD in both groups. (C) Comparative analysis of PAD and AOD. (D) Comparative analysis of AUC, sensitivity, and specificity for cardiac chamber sizes and great artery diameters in diagnosing isolated PLSVC. (A: control group; B: isolated PLSVC cardiac data group). AD, atrium dextrum; ADD, arterial duct diameter; AO, aorta; AOD, aortic diameter; AS, atrium sinistrum; AUC, area under the curve; LPA, left pulmonary artery; PAD, pulmonary artery diameter; PAV, pulmonary artery velocity; PLSVC, persistent left superior vena cava; RPA, right pulmonary artery; VD, ventriculus dexter; VS, ventricle sinistrum.

Discussion

PLSVC is one of the most common abnormalities of the fetus during pregnancy (6-8). In isolated PLSVC, drainage into the RA via the CS leads to abnormal CS dilation, directly increasing AD volume load (9). Although the prognosis of isolated PLSVC is almost always favorable, this study observed that isolated PLSVC was accompanied by changes in fetal cardiac chamber size and hemodynamics. Differences in VD, AD, AOD, PAD, ADD, AOV, and PAV were statistically significant between isolated PLSVC and normal fetuses. The average diameter of the CS positively correlated with the degree of right heart enlargement, suggesting that right heart enlargement in isolated PLSVC fetuses may results from anatomical structural changes. Comparisons of AOV and PAV between isolated PLSVC and normal fetuses also demonstrated statistically significant differences, indicating that hemodynamic changes contributed to right heart enlargement.

In cases with bilateral superior vena cava, blood volume in the right heart system may increase further. The right heart of fetus is already in a high-flow state during pregnancy, and the additional load may exceed its compensatory capacity. Persistent volume overload may induce compensatory dilation of the VD, consistent with the “CS-AD blood flow redistribution” theory in which dilation of the CS opening can affect the function of the foramen ovale (FO) and tricuspid valve, limiting blood flow from the AD to the AS, increasing right heart volume, and reducing left heart volume. In this study, 7.8% (13/166) of isolated PLSVC cases had restricted FO flow with FO diameter <3 mm, resulting in elevated pressure and volume load in the right heart and contributing to fetal right heart enlargement. The dilation of the CS may partially impair the function of the FO, leading to a reduction in its internal diameter. This restricts blood flow from the AD to the AS, thereby increasing the fetal right heart volume. Notably, isolated PLSVC alone can cause right heart enlargement, suggesting that its independent pathogenic role may be underestimated.

Approximately 30–40% of PLSVC cases are associated with other cardiovascular malformations, such as VSD, pulmonary stenosis (PS), TOF, and total anomalous pulmonary venous connection (TAPVC), which can cause right heart enlargement through structural and hemodynamic changes (10-13). In our study, right heart enlargement related to isolated PLSVC primarily manifested as uniform dilation of the AD and VD, whereas ventricular wall motion and valve function were generally preserved. Therefore, when fetal isolated PLSVC is detected, it is essential first to rule out any other cardiovascular malformations that could lead to right heart enlargement. If isolated PLSVC is accompanied by right heart enlargement, attention should be given to tricuspid regurgitation, VD function, and the condition of the FO to comprehensively assess fetal prognosis.

Theoretically, when the fetal right heart enlarges due to changes in left heart pressure and blood volume, the left heart system may relatively decrease in size. In this study, the left heart internal diameters of fetuses with isolated PLSVC were smaller compared to those of controls. This reduction likely resulted from two factors. First, the relative decrease in left heart dimensions in the isolated PLSVC group was considered secondary to increased right heart volume, rather than primary hypoplasia. Enlargement of the CS may restrict FO activity, reducing blood flow from the AD to the AS and consequently decreasing left atrial volume and left heart size. Second, as the CS runs along the left atrioventricular groove, its enlargement protrudes into the AS, occupying space and producing a relatively smaller AS volume. Clinical studies have confirmed that CS enlargement can significantly reduce AS size and potentially impede mitral valve outflow, an anatomical “mass effect” that contributes to smaller left heart and aortic valve dimensions, including AOD (14). Therefore, when isolated PLSVC is detected, assessment of fetal left heart and aortic development is essential. In some cases, differentiation from hypoplastic left heart syndrome (HLHS) or coarctation of the aorta (CoA) is required. Comprehensive evaluation should consider VS size, mitral valve development, and AOD, with Z-score quantitative assessment of the VS and mitral annulus improving diagnostic sensitivity (15). Our case series showed no postnatal evidence of CoA or HLHS, indicating that although isolated PLSVC fetuses may exhibit temporary intrauterine changes in VS and AOD, these alterations resolve spontaneously after birth and closure of the FO. This natural resolution supports effective prenatal counseling for isolated PLSVC cases.

Although fetuses with isolated PLSVC generally have a favorable prognosis, potential risks related to hemodynamic changes from right heart enlargement—especially tricuspid regurgitation and altered right heart function—should be monitored. Prenatal combined fetal echocardiography assessment and close follow-up until the neonatal period are recommended. This study was a single-center retrospective analysis with a limited sample size. Future research should expand the cohort, extend follow-up, and include quantitative hemodynamic analyses to provide deeper mechanistic insights.

Conclusions

Fetal isolated PLSVC with changes in cardiac chamber size may have significant implications for prenatal diagnosis due to hemodynamic alterations caused by CS dilation.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2635/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2635/dss

Funding: This work was supported by the National Natural Science Foundation of China (No. 82560345), and Gansu Provincial Major Science and Technology and the Innovation Project for the Cultivation of Young Talent in the Health Industry (No. GSWSQNPY2024-05).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2635/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Gansu Provincial Maternity and Child Care Hospital (No. 2023-GSFY-54). Informed consent was obtained from all the pregnant women.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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