Case Report: 5 Cases of Variant Hypoplastic Left Heart Syndrome Diagnosed on Prenatal Fetal Ultrasound

Background

Normal postnatal blood flow will enter the right heart and enter the lungs through the pulmonary artery, which then enters the left heart to be pumped through the ascending aorta to the systemic circulation. In the case of hypoplastic left heart syndrome (HLHS), there is an obstruction on the left side of the heart. This is a stenotic condition that blocks left ventricular filling, output, and systemic blood flow. In addition to HLHS, there are other conditions, namely aortic stenosis (AS), bicuspid aortic valve (BAV), and aortic coarctation (CoA). HLHS is a deadly univentricular defect, characterized by an underdeveloped left ventricle (LV) and abnormalities in the ascending aorta [1].

The etiology of HLHS is multifactorial. HLHS is a form of severe congenital heart disease characterized by a failure of the left heart structure to grow normally [2,3]. This syndrome plays a critical role because LV hypoplasia can accompany some types of heart defects or other congenital abnormalities that lead to morbidity and mortality in the first week of life [4,5]. Current evidence suggests that left ventricular hypoplasia is caused by primary defects in ventricular development [6].

There are 2 types of defect, leading to 2 distinct groups based on obstruction of blood flow: the defect of the first group is when there is obstruction of blood flow entering the LV such as mitral valve atresia (MVA) or mitral valve stenosis (MVS). The defect of the second group is a restrictive foramen ovale. This condition of the second group is when there is an obstruction in the outflow from the LV, such as atresia or aortic valve stenosis. Aortic valve stenosis is the most common cause of LV retardation. The pathophysiology of HLHS is evolutionary during fetal life: the LV will decrease in size as the pregnancy progresses, and the defect may not be detected by echo-cardiography until the third trimester. The right ventricle (RV) and right atrium (RA) will often appear dilated from increased volume loading during the prenatal period. Visualization by 4-chamber view (4CV) ultrasound is ideal for comparing the sizes of both ventricles [7].

The main treatment is surgery. Neonates with HLHS are in critical status, require care in the neonatal intensive care unit (NICU), and need to be stabilized prior to surgical intervention. Initial management includes: (1) maintaining an open ductus arteriosus; (2) avoiding massive blood flow to the lungs; and (3) ensuring blood flow from the left atrium (LA) to the RA [7].

Prenatal ultrasound with fetal echocardiography has made it possible to recognize and monitor fetuses with HLHS. This has demonstrated the progressive nature of HLHS and emphasized the significance of aberrant flow patterns in the mechanisms of development of HLHS. This report is of 5 cases of variants of HLHS diagnosed by prenatal fetal ultrasound at the 4CV level.

Case Reports

CASE 1:

A 38-year-old mother had a fetus with a gestational age of 33 weeks at the time of ultrasonography. The results of prenatal ultrasonography at the level of 4CV showed the presence of MVS, tricuspid regurgitation, narrow LV, and wide RV, and in the intraventricular part, there was endocardial fibroelastosis. The LV cavity shrank as a result of the very thickening of the LV wall, making it impossible for the heart to continue pumping blood throughout the body. At the 3 vessels view (TVV) level, it was evident that the diameter of the main pulmonary artery was wider than that of the aorta. This was accompanied by dilation of the cisterna magna (more than 1 cm), indicating abnormalities in the posterior fossa. Neonates born vaginally with this condition do not survive (Figure 1).

CASE 2:

A 41-year-old mother was at 30 weeks of gestation at the time of ultrasound examination. Her fetus had MVA and narrow LV. As a consequence of MVA, blood flow was not visible in this case and the LV was not clearly visualized by ultrasound. The wall of the LV looked thinner when compared to the wall of the LV seen in Case 1. At the TVV level, it was shown that the diameter of the aorta appeared narrower than that of the main pulmonary artery. This disorder was also accompanied by wider cisterna magna, and the neonate did not survive in postpartum (Figure 2).

CASE 3:

A 36-year-old mother underwent ultrasound examination at 29 weeks of gestation. Her fetus was found to have severe MVS, a tiny LV, tricuspid regurgitation, and a small aorta. Uniatrial conditions were described in this case. A limitation in case 3 was that there were only ultrasound results to support the diagnosis of HLHS, so that the presence of other congenital abnormalities was not included in describing the case (Figure 3).

CASE 4:

A 43-year-old mother underwent ultrasound examination at 31 weeks of gestation. The fourth case, at level 4CV had a narrow LV appearance, MVA, ventricular septal defect, nearly united atria, and tricuspid regurgitation. At the TVV level, the size of the aorta was narrower than that of the main pulmonary artery. This condition was also accompanied by other abnormalities. As seen in the other cases, there was a widening of the cisterna magna. This neonate did not survive in the post-partum period (Figure 4).

CASE 5:

A 30-year-old mother underwent ultrasound examination at 26 weeks of gestation. In this fetus, we observed HLHS associated with other abnormalities; namely, congenital diaphragmatic hernia. Seen at the level of 4CV, the size of the LV was narrower than the size of the RV. The mitral valve was stenosed, while the tricuspid valve was in a state of regurgitation. The 2 atria had fused. The stomach in the thoracic cavity was at the same level as the heart. In this fetus, abnormalities in the shape of the cerebellum were also observed, accompanied by dilation of the cisterna magna, indicating a Dandy-Walker malformation or posterior fossa abnormality. The neonate did not survive these conditions (Figure 5).

Discussion

This case series shows that 4CV ultrasonography can determine various forms of HLHS abnormalities, with variations in left ventricular size. The size of the LV determines postpartum prognosis [8]. These 5 cases also showed other associated abnormalities such as the widening of the cisterna magna. All of the cases were referred initially because of visible congenital abnormalities in the third trimester. Most HLHS is diagnosed at 18 to 22 weeks of gestation or even in the first trimester, with a 4-chamber view of the fetal heart [9]. However, other studies have found that HLHS is usually detected in the 3rd trimester; a situation similar to the case presented by Sadineni [10].

On in-depth examination of the heart, especially at the 4-CV level, HLHS abnormalities were found in all cases. As many as 80% were associated with wider cisterna magna or Dandy-Walker malformations with abnormalities in the cerebellum and posterior fossa. In all of these cases, karyotyping was not carried out do to the cost of chromosome examination. The current national insurance system does not cover the cost of such assays.

The maternal age in these reported cases was, for the majority of the mothers, over 35 years (80%). All patients were directed to return to the referrer and were advised to undergo delivery based on obstetric indications. However, it is recommended that vaginal delivery still be preferred because the prognosis is poor, and cesarean section does not improve the prognosis for the fetus.

The morphology of HLHS varies greatly. Fetuses with HLHS at the time of intrauterine development will have ventricles that are small or narrow in size accompanied by a narrow aortic size (stenosis), as seen in Case 1. In the atresial type, the aorta is still partially visible due to retrograde flow from the ductus arteriosus to the aortal arch, but It is ineffective functionally because blood flow from the left ventricle does not occur, as seen in Case 2. The other stream passes through the ductus arteriosus towards the descending aorta during systole, and then on to the systemic blood flow [11]. Subsequently, this mixed blood enters the main pulmonary artery and then enters the left and right pulmonary arteries, as well as reaching the aorta and flowing in the direction of the systemic blood flow, through the ductus arteriosus [12]. Dependence on the presence of the ductus arteriosus makes HLHS belong to the group of congenital heart defects classified as “ductus arteriosus dependent”.

At the time of delivery, the ductus arteriosus will shrink and eventually close. Thus, the baby will not survive if there is no immediate interventions [13]. Interventions include maintaining the presence of the ductus arteriosus by administering prostaglandins that inhibit closure of the ducts [14]. Prostaglandins are often given to infants until gradual surgery can be performed to repair heart abnormalities. The left side of the heart is irreparable, so the goal of postnatally corrected heart surgery is to rebuild parts of the heart and “direct” the blood flow.

Case 1 showed the most common variant of HLHS. This variant has a strongly thickened left ventricular wall, resulting in a reduced size of the left ventricular cavity [15]. This variant is associated with mitral valve stenosis and is usually accompanied by aortic atresia. In some cases, however, the aortic valve can be more stenotic than atresic, but still has a thick-walled left ventricle [12].

In Case 2, the ventricles appeared to be very small, most likely due to mitral atresia. The size of the left ventricle depends largely on the size or degree of damage to the mitral valve [6]. Mitral valve hypoplasia is also related to the presence or absence of a connection between the right ventricle and the left ventricle through the ventricular septal defect as shown in Case 4. The atria in HLHS tend to unite into a uniatrium [16]. This situation can be seen in Cases 3 and 5, in which there was a clear uniatrium. In Case 5, HLHS was combined with another fatal congenital abnormality, a diaphragmatic hernia. This fetus also had cerebellar abnormalities, no visible vermis cerebellar state, and cisterna magna widening. HLHS is the second most common congenital heart disease associated with congenital diaphragmatic hernia. The reported survival rate of neonates with congenital diaphragmatic hernia and HLHS is only 1–5% [17].

The final result in all cases in this study was neonatal death. All of the neonates underwent intensive conservative care after birth. Currently, the hospital can only provide prostaglandins to maintain the temporary opening of the ductus arteriosus or patent ductus arteriosus stent. Meanwhile, the surgical treatment of HLHS entails a highly complex surgery that is costly and has a high mortality rate: the mortality rate during the first stage of the surgery ranges from 25 to 80% [18]. Surgery services for corrective HLHS are not currently available in our institution. Top surgeons in Indonesia have attempted corrective surgery with an unknown success rate.

One limitation of the present study is that no gene or chromosome examination was performed in any of the cases, especially to determine the association with the presence of another congenital disorder: Dandy-Walker malformation. The diagnosis of posterior fossa abnormalities, including the diagnosis of Dandy-Walker malformations, can only be established by ultrasound examination. Another limitation was present in Case 3, in which there were only ultrasound results to support the diagnosis of HLHS, so that the presence of other congenital abnormalities was not included in describing the case.

Conclusions

The degree of HLHS abnormalities varies greatly depending on the morphology of the mitral valve, whether there is stenosis or atresia, and the degree of development of the left ventricle. However, the 4-chamber cardiac view level can detect abnormalities found in the left ventricle.