ACRT Journal

Abbreviations: ASD: Atrial septal defect; CI: Confidence interval; DA: Ductus arteriosus; IAS: Interatrial septum; LA: Left atrium; N-SC: Non-Spontaneous ASD Closure; PFO= Patent foramen ovale; PVR: Pulmonary vascular resistance; RA: Right atrium; RV: Right ventricle; SC: Spontaneous ASD Closure; TTE: Transthoracic Echocardiogram.

Introduction

The transthoracic echocardiogram (TTE) is a widely used imaging diagnostic tool in the clinical management of cardiovascular conditions in the neonatal population, playing a crucial role in clinical decision-making by providing valuable information regarding congenital or acquired conditions. Among the various parameters evaluated through TTE, the analysis of the ASD stands out, as it plays a vital role in fetal circulation by connecting the right atrium (RA) and the left atrium (LA) and allowing shunting from the RA to the rest of the body.

During the fetal period, circulation operates under a different regime than postnatally, wherein the ASD and the ductus arteriosus (DA) work to divert a large portion of pulmonary flow to the rest of the body (systemic output), playing a fundamental role in maintaining cardiac output. After birth, there is a progressive decrease in pulmonary vascular resistance (PVR), and all the flow passing through the lungs also goes through the systemic circulation, which should function without the need for shunts.

While the DA is expected to close spontaneously within the first few hours of life, the ASD generally closes within the first two years. However, in a significant portion of the population (approximately 25 to 30%), the ASD may not close spontaneously, potentially leading to varied clinical repercussions. These clinical repercussions are attributed to the shunting of systemic flow to the pulmonary circulation due to the presence of the communication and the physiological low PVR, resulting in pulmonary over circulation. The magnitude of these repercussions is closely related to factors such as the size of the defect, the patient’s hemodynamic status, PVR, and the compliance of the right ventricle (RV). In certain cases, the persistence of a significant ASD may require therapeutic interventions, either surgical or percutaneous. It is important to note that, although small communications may close spontaneously, studies have shown that even larger ASDs, with diameters of up to 8 mm, have a chance of spontaneous closure [1–4].

In this context, the precise evaluation of ASD using TTE is invaluable not only for providing critical information for clinical decision-making but also for guiding the selection of the most appropriate treatment for each patient. A thorough understanding of these aspects is essential for enhancing clinical outcomes in new-borns with interatrial communication.

Objective

The aim of this study is to determine if the size of the ASD in the neonatal period can predict spontaneous closure.

Methods

Between January 2015 and July 2021, the echocardiograms of 1873 neonates born at the Albert Einstein Hospital, initially diagnosed with ASD or PFO were retrospectively reviewed. Included in the study were 302 patients who had ASD or PFO as their initial diagnosis and who underwent a second TTE in our service more than 3 months after the first examination, with the aim of evaluating spontaneous closure. Collected demographic data included age at the time of examination and birth weight. Patients with complex congenital heart diseases or other comorbidities with cardiovascular impact were excluded from the study.

TEE were conducted by a team of echo cardiographers with more than three years of experience, utilizing Philips CX 50, Philips Affinity 70, and EPIC CVx systems (Philips Medical Systems), equipped with S12 8-MHz or S8 4-MHz transducers. All examinations adhered to standard echocardiographic protocols. The interatrial septum (IAS) analysis was performed from the subcostal position, with measurements of the IAS diameter and ASDs captured at the end of diastole (Figure 1). The septumto-ASD ratio was calculated in each case. These measurements, as well as the atrial septal diameters for ASDs, were remotely assessed by a single, experienced examiner who was blinded to clinical data. In cases of multiple defects, the diameters were aggregated to compute the septum-to-ASD ratio.

Comparisons between continuous variables were conducted using the Mann-Whitney U test. Neonates were categorized into two groups: those with spontaneous ASD closure (SC) and those without (N-SC), based on the outcomes of the follow-up echocardiogram. Standard tests were employed to ascertain the sensitivity and specificity of predictive factors for spontaneous closure, observed three months post-initial TTE. A linear regression model was applied to analyse the ASD diameter and septum-to-ASD ratio, aiming to delineate differences between the groups with a 95% confidence interval (CI). Results were reported as mean ± standard deviation (SD) or percentages, with statistical significance set at p ≤ 0.05.

Results

A total of 1,873 medical records were evaluated. Among these, 302 patients were diagnosed with either ASD or PFO during their initial neonatal TTE and underwent a follow-up examination more than three months later, qualifying them for inclusion in this study.

Of these, 215 were diagnosed with ASD, with 72 (33%) demonstrating spontaneous closure. No statistically significant difference was observed in the mean age at the time of the first examination between the groups; the SC group had an average of 6.25 ± 16.17 days of life (DOL), compared to 4.81 ± 8.74 DOL in the N-EC group (p=0.519). However, a statistically significant difference was noted in the age (days) at the time of the second TTE between the FeE and NFeE groups (466.81 ± 365 vs. 273.91 ± 359; p < 0.001).

The measurement of the ASD (mm) showed no statistical difference between the SC group and N-SC group (17.8 ± 4.94 vs. 17.56 ± 4.28; p=0.666). Echocardiographic parameters that demonstrated statistically significant differences in predicting spontaneous closure were the ASD diameter (mm) at the first TTE (2.89 ± 1.03 vs. 3.58 ± 1.57mm; p < 0.008; OR = 0.69 [0.54-0.88]) and the septum-to-ASD ratio (6.68 ± 2.64 vs. 5.75 ± 2.78; p < 0.005; OR = 1.14 [1.02-1.27]) as can be seen in Table 1. The ROC curve analysis for predicting spontaneous closure using septum/ASD ratio indicated an Optimal Cutoff Point of 4.78, with an area under the curve (AUC) of 0.62, a sensitivity of 80.6%, and a specificity of 45.6% (Figure 2).

Figure 1: two-dimensional echocardiogram in the subcostal view showing ASD. Red line: septum diameter. Dashed line: ASD diameter.

Figure 2: ROC curve for atrial septal defect diameter. Septum-to-ASD ratio vs. spontaneous closure.

Table 1: Comparison of variables measured in the first echocardiogram of patients who did or did not undergo spontaneous closure of the atrial septal defect (ASD) in the second echocardiogram.