Marc Gewillig, Ingrid Witters, Derize Boshoff

Fetal Cardiology, University Hospital Leuven

Left heart malformations are frequently observed in a fetus. This manuscript will focus on problems relating to the aortic valve and to the aortic arch.

There are many reasons for an aortic valve to be abnormal and dysfunctional. The role of genetic factors is partially known through the recognition of genetic syndromes associated with aortic valve abnormalities and through the description of families with a high incidence of aortic valve disease.

Since echocardiography has become available on a routine basis, it also has become evident that abnormal fetal cardiac flow patterns can contribute to abnormal development of the left heart ¹. Conditions that can cause an abnormal preload to the left heart include: restrictive fetal foramen ovale, any mitral valve disease including persistent left superior caval vein to coronary sinus (which causes a small mitral annulus), and ventricular septal defects especially with left deviation of the outlet septum (causing subaortic stenosis).

Visualization of the aortic valve itself can be difficult in early gestation. The normal aortic leaflets are very thin. In systole, they adhere to the aortic wall and are therefore difficult to demonstrate. In diastole, however, the coaptation point of the valve leaflets can frequently be seen; it is central in the normal aortic valve. Asymmetry and/or stenosis result in abnormal poststenotic dilatation of the ascending aorta. With colour flow Doppler abnormal turbulence in the ascending aorta can be visualized. Colour Doppler is very sensitive in detecting even minor degrees of aortic regurgitation. As the fetus grows, the aortic valve can be visualized more easily.

A mild aortic stenosis is always well tolerated by the fetus and neonate. If isolated, it will not impede fetal growth or cardiac development. However, any aortic valve disease may be associated with more complex heart disease, with possible abnormalities of the mitral valve, the left ventricle or its trabeculations, the subaortic region, the supra aortic region and the aortic arch (Shone complex).

A moderate aortic stenosis will cause more turbulence in the ascending aorta, with blood being ejected through the aortic valve at a higher velocity. The left ventricle will become mildly hypertrophied; however, this condition is usually well tolerated by the fetus and neonate. Only in later life, such valve may become more stenotic during growth, requiring intervention at that stage.

A severe degree of aortic stenosis will cause a significant increase of left ventricular pressure, resulting in moderate to severe left ventricular hypertrophy. This will decrease the compliance of the left ventricle, favouring fetal blood flow to the right heart instead of to the left heart. Such decrease in left heart flow may cause an asymmetric four chamber view with poor development of specifically the terminal end of the aortic arch. Clinically this may result in severe aortic stenosis with coarctation of the aorta.

Critical fetal aortic stenosis will cause an extremely high afterload to the left ventricle, resulting in severe hypertrophy and progressive fibroelastosis of the left heart. This will lead to destruction of the left ventricle with hypocontractility and congestive failure despite the hypertrophy ². LV growth is severely hampered under these conditions with hypoplasia and dysfunction of the left ventricle being evident at birth. The blood returning from the pulmonary veins will no longer be pumped into the aorta by the left ventricle; the left atrial pressure will increase, causing the septum secundum to bulge through the foramen ovale. Usually, the foramen ovale will be incompetent, allowing pulmonary venous return to the right atrium. However, in 5% of the patients the foramen ovale will be competent, giving rise to significant left atrial hypertension and retrograde pulmonary congestion. Over time this may cause an abnormal development of the lungs with occurrence of pulmonary lymphangiectasia. Such lungs are unable to achieve normal oxygenation resulting in fatal outcome shortly after birth.

An even more severe degree of aortic dysfunction is aortic atresia: at some stage the critical stenotic valve closes off completely, rendering the aortic valve atretic, fibrous and membranous. The left heart will stop growing, nearly invariably resulting in the hypoplastic left heart syndrome.

All the varying degrees of aortic valve dysfunction are usually very well tolerated by the fetus. The fetal heart consists of two parallel circuits, the right and left heart, both connected at atrial and at arterial level. Any dysfunction from one half can thus easily be compensated by the other half. Even in aortic atresia, the most severe form of aortic dysfunction, the fetal heart will keep functioning as an adequate pump for the fetal circulation: the complete volume load will be dealt with by the right heart.

Early after birth, two problems may arise: inadequate return of oxygenated blood to the circulation, and systemic hypoperfusion after closure of the duct.

In any severe left heart disease, such as critical aortic stenosis and aortic atresia, the pulmonary venous blood should be allowed to cross the atrial septum to re-enter the circulation, as no adequate forward flow through the left ventricle is possible. However, in 5% of the patients the septum secundum will seal off the foramen ovale, thereby impeding adequate oxygenation. These newborns are likely to die a few minutes after transsection of the umbilical cord.

All other patients will do very well in the labour room. After birth, oxygenated blood will be allowed to re-enter the circulation through the left heart or through the incompetent foramen ovale. In the following hours the arterial duct begins to constrict. Initially the systemic circulation can rely on the right heart. However, after 48 tot 72 hours, -due to the constriction of the duct- the systemic circulation has to be maintained by the left heart. In patients with severe or critical stenosis, and invariably in aortic atresia, rapid heart failure will result in early cardiogenic shock.

Frequently a fetus may present with an asymmetric four chamber view; in this manuscript we will only discuss the small left heart. The left heart may be small because of intrinsic disease (eg severe aortic stenosis), or because of a limited preload (eg small foramen ovale). A small preload will result in limited growth. The most critical structure of the left heart to display insufficient growth is its most distal part: the aortic isthmus. An asymmetric four chamber view due to a small fetal left heart is therefore frequently the most predictive sign for postnatal coarctation. Late onset asymmetry is, however, frequently associated with a normal development of the distal aortic arch; prediction of coarctation therefore remains difficult.

The role of the fetologist or fetal cardiologist is to determine whether the left heart will be able to sustain systemic circulation after closure of the arterial duct. Patients with mild to moderate aortic stenosis or late onset asymmetry will have no cardiac problems in the labour room, or during the first days after birth. In this situation delivery may take place in a maternity without an adjacent neonatal cardiac unit.

In patients with a higher degree of aortic valve- or aortic arch-obstruction, problems may arise in the delivery room or in the first hours to days.

If the atrial septum during fetal scans is competent, without any left to right shunt and without echocardiographic appearance of pulmonary lymphangiectasia, one can predict a catastrophic outcome after delivery, whereby the neonate will not be able to oxygenate himself immediately after birth. Correct prediction of such an event will allow to prepare the situation by counselling parents and the medical team (gynaecologist, midwife, paediatrician). Treatment options can be discussed prior to delivery: therapeutic abstinence versus urgent septectomy.

If the left heart appears to be borderline adequate to provide sufficient systemic circulation, it is recommended to make a full evaluation in the first hours after birth. The cardiologist must attempt to predict the clinical course after ductal closure. If it is obvious that the left heart is inadequate to fulfil its duties, prostaglandins should be started in order to avoid eminent cardiogenic shock.

Recently some fetal interventions have been proposed to improve the neonatal condition: dilation of the fetal aortic valve and dilation of the fetal atrial septum.

Dilation of the fetal aortic valve can be considered in patients with a severe aortic stenosis and evidence of further progression to critical aortic stenosis with evolution towards LV-destruction/hypoplasia. In such patients, balloon dilation of the aortic valve may decrease the gradient, reduce the afterload to the left ventricle and diminish the degree of hypertrophy with an increased forward flow. Such dilation can avoid evolution towards a univentricular heart, and increase the chances for postnatal biventricular repair ³. Such fetal intervention should ideally occur between 22 and 26 weeks. Before this age, the fetal structures are too small; after this age, there is insufficient time for the fetal heart to recover from hypoplasia.

If the atrial septum is severely restrictive, developmental damage may occur to the lungs. This can be avoided by balloon dilation of the atrial septum. It remains, however, doubtful whether a successful dilation of the atrial septum will allow adequate growth of the lungs, good enough for a univentricular Fontan-repair, which invariably requires a perfect lung circulation.

References

1. Hove JR, Koster RW, Forouhar AS, et al. Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature. 2003; 9: 421: 172–177.

2. Danford DA, Cronican P. Hypoplastic left heart syndrome: progression of left ventricular dilation and dysfunction to left ventricular hypoplasia in utero. Am Heart J. 1992; 123: 1712–1713.

3. Tworetzky W, Wilkins-Haug L, Jennings RW, van der Velde ME, Marshall AC, Marx GR, Colan SD, Benson CB, Lock JE, Perry SB. Balloon dilation of severe aortic stenosis in the fetus: potential for prevention of hypoplastic left heart syndrome: candidate selection, technique, and results of successful intervention. Circulation. 2004 ;110(15):2125-31.

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