CHAPTER 7

Hypoplastic Left Heart Syndrome

Definition

Hypoplastic left heart syndrome (HLHS) refers to a spectrum of cardiac abnormalities that includes underdevelopment of the left ventricle, mitral valve, aorta, and aortic valve.1–3

This syndrome is the most severe form of left-sided obstructive lesions, and it is among the most severe forms of congenital heart disease (CHD).4–8 It consists, in varying degrees, of a small left ventricle associated with aortic atresia, a hypoplastic ascending aorta, mitral valve atresia or hypoplasia, and a small left atrium (Fig. 7–1).

Figure 7–1 Diagrammatic representation of the abnormalities associate with HLHS. Note the small left ventricle *(LV),* an atretic or hypoplastic mitral valve, and the very small aorta. *LA,* Left atrium; *PA,* pulmonary artery; *RA,* right atrium; *RV,* right ventricle.

HLHS may be associated with a malaligned atrioventricular canal, although this is much less common than its association with mitral valve atresia or hypoplasia.

Cardiac anomalies resulting in a hypoplastic aorta or coarctation of the aorta with a normally functioning left ventricle are not included in this syndrome.

The terms “aortic atresia” and “HLHS” are often used in reference to the same lesion; however, these two anomalies are not synonymous because a small percentage of patients with aortic atresia have a normal left ventricle.⁹

Embryology

The early developmental changes that result in a hypoplastic left ventricle are not completely understood.¹⁰ Several hypotheses currently exist.⁴

Decreased ventricular size has been achieved in animal models by reducing the blood flow through the foramen ovale.¹¹ The development of the cardiac chambers is dependent on the flow of blood through them. Therefore decreased perfusion of the left atrium and left ventricle may result in hypoplastic chambers, aortic valve atresia, mitral valve atresia, and hypoplasia of the aortic arch.^4,12

Malalignment of the interatrial septum toward the left has also been proposed as a mechanism of interfering with left ventricular filling, resulting in poor development of that chamber.¹³

Another explanation for HLHS is that fusion of the endocardial cushions occurs but fails to produce a valve.12,13

It may also be due to an overgrowth of the ventral atrioventricular cushion, which deprives the ascending aorta of adequate blood flow.¹⁴ The resultant change in flow leads to the development of the structural cardiac anomalies associated with this syndrome.^12,15

Normally, the primitive heart tube in the embryo forms three wall layers, becomes elongated, and bends into a loop—the cardiac loop. Expanded portions of the heart tube form the atrioventricular canal.

Endocardial cushions develop at the superior and inferior ends of the atrioventricular canal; lateral endocardial cushions develop on the right and left edges of the canal. Fusion of the superior and inferior atrioventricular cushions divides the canal into right and left atrioventricular orifices. Each orifice is surrounded by mesenchymal tissue that eventually becomes thinned out by the flow of blood over it, thus forming valves that are attached to the ventricular wall. These valves develop into the mitral and tricuspid valves at approximately 6 or 7 weeks’ gestation.

Part of the interventricular septum and the ventricular muscle develops from this atrioventricular canal; papillary muscles and chordae tendinae arise from the ventricular muscle.¹⁰

In the embryo, the aorta and pulmonary artery develop from the division of a common trunk, and small projections or tubercles form within the lumen. These tubercles grow toward the midline and become thinned out by resorption of excess tissue and hollowed out at the site of attachment with the vessel walls, thus giving rise to the semilunar valves.

A third hypothesis is that the causative factor is a rudimentary left atrium and, consequently, diminished blood flow to the mitral portion of the atrioventricular canal. The left ventricle and aorta or aortic valve thus fail to develop properly because of the decreased blood flow through the lumen.¹⁰

The left ventricle will be small, the aortic valve may be stenotic, and coarctation of the aorta may result.12,16 Aortic stenosis or atresia may be valvular, subvalvular, or supravalvular. Subvalvular and valvular types often occur together.^14,17

The position of the heart in HLHS is usually normal. There are also normal atrioventricular and ventriculoarterial connections. The great vessels are normally oriented to one another. The inferior and superior venae cavae drain normally into the right atrium; however, anomalies of pulmonary venous return frequently occur.

The tricuspid valve is structurally normal; however, the right ventricle is often enlarged and in some cases hypertrophic because of the increase in blood volume and blood pressure caused by the obstructive left side. This increase in volume may lead to tricuspid insufficiency. The pulmonary artery and its branches are usually dilated. The pulmonary valve is normal in the majority of cases.

The ductus arteriosus is patent; however, the foramen ovale may close completely in utero with resultant severe hypoplasia of the left ventricle.¹⁸

The ascending aorta is poorly developed, with normal coronary artery orientation. Coarctation of the aorta is present in the majority of patients with HLHS, and this may result in narrowing of the subclavian artery and left common carotid artery origins. An interrupted aortic arch occurs much less commonly. The aortic valve is either stenotic or atretic in most cases.

An abnormal mitral valve is always present. If the valve is atretic, the left ventricle is severely underdeveloped, appearing as a slitlike cavity. However, if the mitral valve is stenotic but perforate, the left ventricle is somewhat larger with thickened walls.

The ventricular septum is generally intact but may be deviated into a subaortic position.

Conduction disturbances may be present in HLHS because of an interruption in the bundle of His.12,16,19–21

Hemodynamically, blood is unable to pass through the left ventricle and aortic valve and therefore is shunted in a retrograde manner from the left atrium, through the foramen ovale, and back into the right atrium (Fig. 7–2). This results in an increase in the size of the right atrium, right ventricle, and main pulmonary artery.

Figure 7–2 Diagram of the hemodynamics of HLHS, showing blood being supplied to the aorta only through the ductus arteriosus *(D).* Blood flow from the left atrium *(LA)* is shunted in a retrograde fashion to the right atrium *(RA)* as a result of the atretic mitral valve and hypoplastic left ventricle *(LV)*. A, Aorta; *IVC,* inferior vena cava; *PA,* pulmonary artery; *RV,* right ventricle; *SVC,* superior vena cava.

Because of the left heart hypoplasia, the right ventricle supplies both the pulmonary and systemic circulations. The pulmonary veins may be either normal or increased in size. The blood volume and pressure in the right heart are elevated.²² The left atrium, left ventricle, and aorta are all decreased in size. In severe cases of hypoplasia of the ascending aorta, the coronary arteries are perfused in a retrograde manner by the ductus arteriosus.^6,23

HLHS results in cardiac function similar to that seen in univentricular hearts. The increased right ventricular pressure, together with inadequate flow out of the left atrium, results in elevated pulmonary venous pressure and pulmonary congestion.¹⁶

Occurrence Rate

HLHS is the most common cause of death from CHD in the early neonatal period, accounting for 7% to 9% of all structural heart defects and 25% of all cardiac-related deaths.3,24 HLHS comprises 13% of all prenatally diagnosed CHD. There appears to be a male dominance, especially in the presence of atresia of the aortic valve.^{20–22,25,26}

Most cases of HLHS are likely multifactorial. However, multiple studies suggest a genetic basis as the etiology of many cases. Approximately 19% of affected patients with HLHS have a first-degree relative with CHD, reinforcing the case for a genetic link to HLHS.4,27,28 It is thought to have an autosomal recessive inheritance pattern.

The risk of occurrence has been reported to be 2% in siblings of an affected child.24,25,28–30

Sonographic Criteria

HLHS is easily recognized in utero. It should be borne in mind, however, that HLHS is a progressive lesion and may not manifest itself until the late second trimester. Studies show early screening may be advantageous but does not obviate the importance of second-trimester fetal echocardiography.3,31

First trimester nuchal translucency screening has increased early detection of HLHS. Studies suggest a stronger correlation between left-sided obstructive lesions and a thickened nuchal translucency. A measurement greater than 2.5 multiples of the median is associated with an increased risk for CHD, including HLHS and should be an considered an indication for fetal echocardiography.3,32

The majority of patients with HLHS maintain a normal cardiac axis. An apical (Fig. 7–3) or subcostal (Fig. 7–4) four-chamber view of the heart can be used to show the size discrepancy of the ventricles. It is important to identify the morphological features of the right ventricle, including the moderator band and the tricuspid valve, to confirm it is the left ventricle that is hypoplastic. In HLHS, the right ventricle constitutes the cardiac apex, giving rise to the term “apex-forming ventricle” (Fig. 7–5).^21,22,33

Figure 7–3 Apical four-chamber view in a fetus with HLHS showing the decreased size of both the left ventricle *(LV)* and the left atrium *(LA). RA,* Right atrium; *RV,* right ventricle.

A short-axis view of the great vessels (Fig. 7–6), a long-axis view of the aorta (Fig. 7–7), or a three-vessel view (Fig. 7–8) can be used to assess the size of the ascending aorta. An atretic aorta can be difficult to visualize because of its small size. On the other hand, the pulmonary artery is often enlarged. Sonographically, an atretic aorta and aortic valve can appear hyperechoic in addition to being small.