Echocardiographic and pathomorphological features in fetuses with ductal‐dependent congenital heart diseases

To individually analyze echocardiographic features in fetuses with ductal‐dependent congenital heart diseases (DDCHD) and to verify the anatomical characteristics corresponding to the echocardiogram scan views.


| INTRODUC TI ON
Therefore, the purpose of this study was to individually analyze the prenatal echocardiographic and anatomical features in fetuses with DDCHD.

| Patient population
We conducted a retrospective cohort study of fetuses at ≥17 weeks gestation that were transferred by subordinate hospitals to the Medical Ultrasound Center at Xinqiao Hospital, Chongqing, between May 1, 2011, and January 31, 2017. Fetuses with suspected DDCHD according to prenatal echocardiography were selected.
The results of postpartum echocardiography or autopsy specimens were compared with prenatal echocardiography. Normal gestational age-matched controls were also evaluated. We did not include fetuses with isolated mild-to-moderate pulmonary or aortic stenosis because there is no ductal dependency. Follow-ups in the antenatal and postpartum periods were performed for live births and included clinical interventions and evaluation of changes in echocardiographic characteristics. This study was performed in accordance with a protocol that was approved by the Xinqiao Hospital Ethics Committee for Clinical Investigations.

| Echocardiographic diagnosis and follow-up
All fetal patients underwent at least one detailed prenatal echocardiogram, and neonates received echocardiographic examinations following birth. Echocardiography was performed using a Philips IE33 unit (Philips Healthcare) with an S8-3 and C5-1 probe. The Pulmonary or aortic atresia (AA) was defined as a lack of blood flow from the RVOT or LVOT into the pulmonary atresia (PA) or aorta (AO), including primary atresia and secondary functional atresia. The flow directions of the foramen ovale (FO), transverse aortic arch, and DA were also recorded. All direct measurements were performed by a single experienced investigator who was blinded to the patient information when measuring these parameters.

| Pathomorphological analyzes
When performing autopsies, the RV was opened along the coronal plane from the apex to the base, and the PA was opened along the long axis of the PA. The left side of the heart was opened according to the path of blood flow. 7 Each investigator was blinded to the patient information when analyzing the pathomorphology.

| Statistical analysis
The data are primarily presented in a descriptive manner and as the medians (range), mean ± SD, and percentages. Statistical analyzes were performed using Student's t test to compare parameters between echocardiographic results and normal reference standards.
The correlation between echocardiographic findings and autopsy results of the diameter ratio of the AAO to the PT was assessed using Pearson's analysis via SAS 9.3 (SAS Institute Inc), and a P-value of<.05 was considered statistically significant.

| Patients and follow-up
During the study period, 13 141 fetuses were referred for enrollment in the study. A total of 108 fetuses with DDCHD in the pulmonary or systemic circulation combined with other complex cardiac malformations were diagnosed by prenatal echocardiography (Figure 1). Gestational ages-matched normal fetuses served as controls. During the follow-up, 76 parents elected to terminate the pregnancy after considering the poor prognosis associated with a fetal heart condition. Through the kind efforts of the dedicated families who signed the donation agreements, 22 formalin-fixed heart specimens from DDCHD fetuses (gestational age 17.7-34.9 weeks) were obtained from the Department of Pathology at Xinqiao Hospital including 10 cases with DDCHD in the pulmonary circulation, and 12 cases with DDCHD in the systemic circulation. Follow-ups in the antenatal and postpartum periods were performed for eight live births. Of these subjects, one boy with HLHS died at 126 days of age, 1 day after selective angiocardiography catheterization during hospitalization. One boy with HLHS died at 89 days of age, 1 week after computed-tomography angiography. A pair of twin brothers with HLHS died (one twin at 18 days of age and the other twin at 135 days of age). One boy with PA and RV dysplasia died at 136 days of age. One girl with severe Ebstein anomaly and functional PA died at 59 days of age. Two infants with PA were alive after cardiac surgery over a median of follow-up period of 6 months. Twenty-four fetuses were lost to follow-up and were not included in statistical analysis.

| Echocardiographic examinations and Pathomorphological findings
Echocardiographic reference parameters of normal fetuses with different gestational weeks were displayed in Table 1   and single ventricular. The overall morphology of DA was displayed in Figure 5.

| Role of the patency of DA during pregnancy and for newborn with DDCHD
The DA is one of the main physiological shunt pathways in the fetal blood circulation. During the fetal period, 90% of the blood in the pulmonary artery enters the descending AO sequentially through the DA, and most of the blood then passes through the umbilical artery

| Prenatal echocardiographic characteristics and hemodynamic changes in DDCHD
Currently, fetal echocardiography is the best way to diagnose DDCHD.
The views of the LVOT, RVOT, three vessels, 3VT, long axis of the pulmonary artery-DA, and long axis of the transverse aortic arch are important in the diagnosis of fetal DDCHD. [11][12][13][14] The contrast of the same segments between the systemic and pulmonary circulation is helpful for detecting abnormalities and avoiding missed diagnoses.

| Ductal-dependent pulmonary circulation
In fetuses with PA and IVS, blood in the right ventricle cannot be injected into the PA and refluxes into the right atrium (RA) through The main PA trunk can manifest as atresia, hypoplasia, or dilatation.
The branches of the pulmonary artery can be poorly developed or normal. In fetuses with PA and ventricular septal defect (VSD), blood in the right ventricle can be injected into the AO through the VSD. Therefore, the sizes of the left and right heart are still symmetric.

| Ductal-dependent systemic circulation
When LVOT obstruction occurs, the LV blood flow is blocked, and the LV pressure overload leads to LV wall thickening or LV dysplasia.
The blood flow from the FO to the right heart increases, the volume of the right heart increases, and the right heart becomes enlarged.
When AA occurs, the AAO is dysplastic, and the blood flow in the aortic arch comes from the DA, which presents as a reversed flow.

| CON CLUS ION
In conclusion, although fetal heart disease complicates only a small percentage of pregnancies, CHD causes more neonatal morbidity and mortality than any other congenital malformation.
Unfortunately, screening approaches for fetal heart disease continue to miss a large percentage of cases. This weakness in fetal screening has important clinical implications because the prenatal detection and diagnosis of CHD may improve the outcome for many of these fetal patients. In fact, the detection of major heart disease prenatally can improve neonatal outcomes by avoiding discharge to home of neonates with DDCHD. Education and training regarding the fetal heart are an important part of this process to ensure that sonographers are taught and can maintain the skills of the fetal heart examination. [15][16][17][18][19] Fortunately, recent advances in screening techniques, an increased ability to change the prenatal natural history of many forms of fetal heart disease,