Progression of fetal heart disease and rationale for fetal intracardiac interventions

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Summary

The outcome of cardiac disease diagnosed before birth is paradoxically worse than that diagnosed postnatally. In part, this is because fetal screening detects cases that are already showing failure of cardiac growth which are usually progressive with secondary damage to the myocardium, lungs and brain. Fetal valvuloplasty has been proposed for cases of critical aortic and pulmonary stenosis or atresia, and atrial septostomy for a restrictive oval foramen associated with aortic stenosis, hypoplastic left heart syndrome and transposition of the great arteries. The rationale for fetal therapy is to restore forward flow and reduce intraventricular pressure, thus improving coronary perfusion and minimizing ischaemic damage. Successful valvuloplasty has reduced systemic venous pressures and reversed fetal hydrops, thus prolonging pregnancy. It has resulted in improved ventricular growth in some cases and spontaneous opening of a closed oval foramen with normalization of pulmonary venous waveforms. These signs suggest better fetal cardiopulmonary development and improved surgical outcomes.

Introduction

By 50 embryonic days, the fetal heart has developed from a cardiac crescent to assume its final morphological form. Left and right sidedness of fetal organs, including the heart, have been determined and defects in signalling, responsible for structural malformations, have left their mark; apart from small septal defects, these are usually irreversible.1, 2 We are unable to image the heart diagnostically until about 12–14 weeks of gestation using modern ultrasound techniques, but we can already appreciate the effect that abnormal fetal flow patterns have begun to play in further remodelling valves, their supporting ventricles and great arteries.3 Significant progression may be defined as secondary damage to the heart and lungs, resulting from abnormalities of growth and flow, so that a biventricular repair is no longer possible after delivery. Disease progression occurs in most conditions, except minor septal defects, but the most aggressive progression of disease is seen in congenital heart defects (CHDs) with aortic or pulmonary stenosis, and often results in hypoplasia of the supporting ventricle, thus precluding its use in the postnatal circulation.

Progression of a cardiac lesion may be monitored most easily using a combination of morphological and physiological parameters. There are a few studies that document the natural history of cardiac growth for specific fetal malformations.4 These provide helpful information on growth of valves and ventricles throughout gestation. Cardiac malformations in the fetus are associated with abnormalities of flow through the atrioventricular valves (usually regurgitation), increased velocities through the semilunar valves, reversal of flow in the arterial and venous ducts and aortic isthmus, and abnormalities of pulmonary venous Doppler. Reversal of flow with atrial contraction in venous duct waveforms is seen in very early gestation as part of normal development. It may be seen later as a result of increased right atrial pressure when atrioventricular regurgitation is severe or the oval foramen is restrictive, but is not usually a sign of fetal hypoxaemia in this setting.5 Serial studies of pulmonary venous Doppler are useful to assess left atrial pressure where there is left heart obstruction. Abnormal waveform patterns, characterized by reversal of flow in late diastole, may be seen in association with hypoplastic left heart syndrome and biphasic reversal with severe mitral regurgitation due to critical aortic stenosis (Fig. 1a).6 Although simple transposition of the great arteries is not usually considered to be a malformation that ‘progresses’, serial evaluation of pulmonary venous and oval foramen flows may detect those who do badly because they develop early pulmonary venous congestion and haemorrhage.7

Section snippets

Associated malformations and counselling

Extracardiac abnormalities and/or aneuploidy are associated with one-third of cases of major congenital heart disease. Patient management should be shared with a fetal medicine specialist, and karyotyping should be offered where appropriate.8 Counselling may be difficult, particularly when the scan is performed in early gestation or there is suboptimal imaging. Some major defects may only become apparent later in gestation, such as diaphragmatic hernia, or may be missed altogether. These may

Secondary cardiopulmonary damage

Chronic elevation of ventricular pressure in the setting of aortic or pulmonary atresia may have already damaged the fetal myocardium by the time of the first evaluation, and a biventricular repair already be unlikely because of poor ventricular function.9, 10 These fetuses may do badly even if fetal intervention is attempted, and have a poor chance of survival without transplantation. Fetuses with both mitral and aortic atresia usually have very severe disease at presentation. Some have a

Fetal therapy

The number of fetuses suitable for intervention is not large. Critical pulmonary and aortic stenosis or atresia will each affect 4–5% of fetuses with CHD.12 While no intervention is currently available or desirable for most defects, antenatal intervention has been performed for aortic valve stenosis/atresia, pulmonary valve stenosis/atresia and defects associated with restriction or closure of the interatrial septum such as simple transposition of the great arteries (TGA) and hypoplastic left

Techniques for fetal valvuloplasty

The techniques for fetal valvuloplasty vary slightly from group to group and are fully described in their publications.13, 29, 30, 31 Most have been performed using percutaneous access under ultrasound guidance in fetuses ranging from 21 to 30 weeks' gestation using the Seldinge technique. Some have performed the procedure under maternal general anaesthetic, and others have used local anaesthesia with maternal sedation. All have given fetal analgesia, usually Fentanyl, either intramuscularly or

Aortic valve stenosis

Several centres have performed aortic valvuloplasty with good technical success and have observed forward flow through the valve and about the arch with continuing growth of the left ventricle throughout pregnancy. Technical difficulties have led to occasional fetal demise in series, and morbidity including bradycardia, pericardial effusion (usually associated with equipment withdrawal) and cerebral haemorrhage have been reported leading to an unsuccessful outcome. The largest reported series

Restrictive/closed oval foramen

Although only a small proportion of fetuses with aortic stenosis, HLHS and simple TGA develop a restrictive communication, it is associated with considerable perinatal mortality and morbidity. The major causes of increased mortality are fetal hydrops and persistent pulmonary hypertension and haemorrhage. Prenatal detection with delivery local to the cardiac centre and early septostomy or septectomy have been shown to improve outcome.7, 13 Abnormal pulmonary venous flow patterns are seen from

Pulmonary atresia/critical pulmonary stenosis

PAIVS presents with a spectrum of morphologies ranging from the small heavily trabeculated hypertrophied right ventricle to a dilated poorly functional ventricle. The tricuspid valve is usually hypoplastic and there is a strong association with tricuspid valve dysplasia. The outlet portion of the right ventricle may have thin membranous atresia that is amenable to fetal intervention in contrast to long segment muscular atresia. The high-pressure right ventricle may also have ventricular to

How might we evaluate future cases?

The creation of an unselected database based on intention to treat is one way to determine whether fetuses with similar morphology and physiology might benefit from a fetal intervention, over and above the natural history of the disease process. The success of such an approach will depend very much on the population and practises of the cardiac centres. In Europe, at least two-thirds of pregnant women whose fetus has a diagnosis of HLHS or PAIVS will choose termination of pregnancy.35, 36 It is

Summary

Progression of fetal heart disease is rapid in cases of aortic and pulmonary stenosis/atresia. A number of babies will die in the newborn period despite good surgery because of the secondary pulmonary damage and myocardial disease caused by these types of severe cardiac pathology. Fetal intervention has seemed encouraging in certain cases, and if it is to be performed, it is likely to be more successful early rather than later in pregnancy. A multidisciplinary team approach is essential to the

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