Left ventricular dysfunction in the fetus: relation to aortic valve anomalies and endocardial fibroelastosis.

OBJECTIVE: To examine the relation between a characteristic form of left ventricular dysfunction in the fetus and abnormalities of the aortic valve and endocardial fibroelastosis of the left ventricle. DESIGN: A retrospective study to examine the correlation between echocardiographic findings in the fetus and postnatal or necropsy findings. SETTING: Tertiary referral centre for fetal echocardiography. PATIENTS: Thirty fetuses showing a characteristic echocardiographic picture of left ventricular dysfunction. MAIN OUTCOME MEASURES: The relation between the prenatal echocardiographic features and the postnatal and necropsy findings. RESULTS: At presentation the size of the left ventricular cavity was normal or enlarged in all cases. The measurements of the orifice of the aortic root and mitral valve were either normal or small for the gestational age. The echocardiographic diagnosis made at presentation was critical aortic stenosis in all cases. At necropsy or postnatal examination the aortic valve was dysplastic and stenotic in 15 cases and the left ventricle had become hypoplastic in one of these. Aortic atresia was present in seven patients, three of whom had a hypoplastic left ventricle. In six patients the aortic valve was bicuspid although not obstructive. One of these patients had hypoplasia of the aortic arch and one had a hypoplastic left ventricle but in the remaining four patients endocardial fibroelastosis of the left ventricle was the only abnormality found. No follow up information was available in two. Of 26 patients for whom there was postmortem information, 24 had evidence of some degree of endocardial fibroelastosis of the left ventricle. Sequential observations showed that five cases developed into the hypoplastic left heart syndrome. CONCLUSIONS: This type of left ventricular dysfunction in the fetus is the result of an overlap of diseases, including primary left ventricular endocardial fibroelastosis, critical aortic stenosis, and the hypoplastic left heart syndrome.

Factors influencing the outcome of congenital heart disease detected prenatally.

The diagnosis of structural heart disease before birth is associated with a poor prognosis. Of 222 continuing pregnancies seen in a 10 year period, there has been a 79% mortality. This is inconsistent with published results and current concepts of the outcome for children with cardiac malformation. Of the 222, death occurred in intrauterine life in 57, 87 died as neonates, and 31 in infancy or childhood. There are 47 survivors of whom only five have survived beyond 4 years. Factors influencing the outcome in these cases were examined further. A high mortality was associated with the presence of extracardiac anomalies in 71 (32%) and prenatal cardiac failure in 28 (13%). As many patients were referred for these reasons, referral methods preferentially select patients with a different range of heart disease from that seen postnatally. In addition, some forms of heart disease progress in severity during fetal life. Those involved in the management and counselling after diagnosis of heart disease in early pregnancy must be aware of the additional prenatal factors influencing prognosis and allow for them in making predictions of outcome.

Tricuspid valve dysplasia or displacement in intrauterine life.

In 450 cases of structural heart disease diagnosed prenatally, 38 fetuses (8.5%) had either a dysplastic or a displaced tricuspid valve. The tricuspid valve was dysplastic in 22 fetuses, all of which had evidence of tricuspid regurgitation resulting in right atrial dilation and increased cardiothoracic ratio. An associated abnormality of the pulmonary valve occurred in 16 fetuses. The remaining 16 fetuses had Ebstein's malformation, 14 with evidence of tricuspid incompetence at presentation and 10 with an associated abnormality of the pulmonary valve. Of the 38 cases, the pregnancy was interrupted in 17, spontaneous intrauterine fetal death occurred in 8, 11 infants died postnatally and 2 infants are still alive; additional abnormalities were found in 8 cases (chromosomal anomalies in 2, ventricular septal defects in 2, corrected transposition in 2, the Chiari malformation in 2, supraventricular tachycardia in 1 case and coarctation of the aorta in 1). Fetuses with severe abnormalities are selected for fetal echocardiography by the four chamber screening program and a high rate of natural loss both in intrauterine life and immediately after birth was observed in the 21 cases in which pregnancy was continued. This would explain the higher incidence of tricuspid valve disease in our prenatal compared with postnatal series. Although increased cardiothoracic ratio and associated lesions of the right ventricular outflow tract contribute to the poor outcome in the cases detected prenatally, the absence of these features does not always indicate a good prognosis because progression of disease can occur with advancing gestational age. No absolute measurement or single echocardiographic feature emerged as a consistent predictive factor of prognosis.

Chromosomal anomalies in fetal congenital heart disease.

A series of 467 cases of congenital heart disease detected in prenatal life were analyzed to identify the forms of cardiac malformation associated with karyotypic defects and to calculate the incidence of chromosomal abnormalities associated with such malformations. Of these, 77 were proved to have chromosomal anomalies although not all were karyotyped. The results were analyzed in two ways. First, the whole series of 77 cases was examined in order to describe the form of congenital heart disease found in association as, although many cases were forms of heart disease known to be associated with chromosomal defects, several were unexpected. In many cases which proved positive, there were other abnormal findings on ultrasound, further suggesting a high likelihood of a chromosomal defect. Some cardiac defects, however, such as atrial isomerism or transposition of the great arteries, were not associated with trisomies. The second part of the study examined in detail the records of 124 cases of congenital heart disease seen in 1989, as these were more completely documented than the previous cases. No chromosomal anomaly was therefore thought to be missed. Of this group, 20 (16%) proved positive. This is a higher rate than would be expected in an unselected population of live births. The difference between prenatal and postnatal life can be accounted for by the increased rate of spontaneous fetal loss in those with chromosomal defects. We conclude that, because of the high rate of chromosomal anomaly, all continuing pregnancies where congenital heart disease has been found in the fetus should be karyotyped unless specific types of heart defect which are rarely associated are confidently defined.

Flecainide in the treatment of fetal tachycardias.

Fourteen mothers were treated with flecainide for fetal atrial tachycardias associated with intrauterine cardiac failure. Twelve of the 14 fetuses responded by conversion to sinus rhythm. One of the 12 fetuses subsequently died in utero. The remaining fetuses suffered no morbidity and were alive and well 3 months to 2 years after delivery. The two fetuses in whom atrial tachycardia did not convert with flecainide were successfully treated with digoxin. These results compare favourably with previous forms of antiarrhythmic treatment. After recent reports of the side effects of flecainide treatment, however, it has been advised that this drug should be confined to high risk patients and those with life threatening arrhythmias. The use of flecainide for fetal arrhythmias should be limited to patients with severe fetal hydrops and supraventricular tachycardias. It should not be the first drug of choice in atrial flutter.

The use of colour Doppler in fetal echocardiography.

Doppler colour flow mapping provides a non-invasive method for studying patterns of blood flow in the cardiovascular system. We undertook a prospective study using this technique in order to document normal and abnormal patterns in the human fetus. A group of 50 consecutive normal fetuses were examined with colour flow mapping. Patterns of flow that could be readily identified in the majority included inflow at the atrioventricular valves, outflow through the arterial valves and flow in the aortic arch and arterial duct. Flow across the oval foramen and in the pulmonary veins was identified in approximately half the patients. Colour Doppler also proved helpful in the detection and definition of cardiac anomalies. A series of 74 cardiac malformations, seen during 1988, were examined with colour flow mapping. The presence or absence of flow across valves could be confirmed, valvar incompetence demonstrated and the direction of blood flow displayed across both normal and abnormal communications. Colour Doppler studies in the human fetus can thus improve the understanding of the characteristics of flow of blood and add to the accuracy of antenatal diagnosis of congenital heart disease.

Prenatal measurement of cardiothoracic ratio in evaluation of heart disease.

The cardiothoracic ratio was measured in 410 normal fetuses and in a group of 73 fetuses with functional or structural heart disease. In normal fetuses it was fairly constant throughout pregnancy, but of those with congenital heart disease it was raised in cases of Ebstein's anomaly, tricuspid dysplasia, atrioventricular septal defect, and complete heart block. In some forms of congenital heart disease, however, it was within the normal range. There was a significant positive correlation between the cardiothoracic ratio and fetal hydrops in the group of 15 fetuses with supraventricular tachycardias. In these fetuses the cardiac size decreased significantly once the fetus reverted to sinus rhythm after the mother had been treated. Measurement of the cardiothoracic ratio is essential in the evaluation of fetal hydrops, as an increased value may point to the diagnosis of an intermittent fetal tachycardia if the fetus is assessed during a period of sinus rhythm. The measurement of this index forms a part of the complete prenatal evaluation of structural heart disease. The degree of cardiomegaly may provide useful information about secondary lung compression or cardiac failure and therefore assist in giving an accurate prognosis for postnatal survival.

The accuracy of fetal echocardiography in the diagnosis of congenital heart disease.

The accuracy of the echocardiographic diagnosis of fetal heart disease in an experienced centre was evaluated by analysing the results achieved during 1987 at the Perinatal Cardiology Unit, Guy's Hospital. In this one year, 978 high-risk patients were referred for fetal echocardiography. Of these, 74 cases were found to have cardiac malformation, 69 of which were predicted from the prenatal study. Of the 69, the autopsy specimen was available for correlative purposes in 41 cases. A postnatal echocardiogram was performed by us in a further 15 cases. The result of autopsy or of a postnatal echocardiogram was obtained from another hospital in 7 cases. Postmortem was refused in 5 cases, while one further case remains alive but has not had a postnatal echocardiogram. Close correlation was achieved between the predicted echocardiographic diagnosis and the anatomical results. Some minor errors in the complete interpretation of a defect were found, particularly in those fetuses in whom image quality was poor, due to early (less than 20 weeks) or late (greater than 34 weeks) gestation or to maternal obesity. Difficulty in echocardiographic interpretation was also experienced in unusual defects. There was one false positive prediction of coarctation of the aorta. One major (total anomalous pulmonary venous drainage) and 5 minor abnormalities (two atrial and three ventricular septal defects) detected after birth were overlooked on the fetal study. Although the echocardiogram in prenatal life is not as accurate as it can be postnatally, with suitable experience a high degree of precision can now be achieved.

Evidence of redistribution of cardiac output in asymmetrical growth retardation.

Thirty-one fetuses with growth retardation were studied by Doppler estimation of the cardiac output from each side of the fetal heart. Asymmetrical growth retardation was diagnosed in 16 fetuses by a head to abdominal circumference ratio above the 95th centile. In the 15 fetuses with symmetrical growth retardation, the distribution of cardiac output was normal. The mean and maximum velocity of blood flow in the pulmonary artery and aorta were similar to values in normal fetuses, and there was a greater calculated output from the right heart than from the left. The right heart flow expressed as a percentage of the combined cardiac output was not statistically significantly different from that in normal fetuses. In contrast, all 16 fetuses with asymmetrical growth retardation had a higher mean and maximum velocity in the aorta than in the pulmonary artery. The calculated volume flow from each side of the heart showed a greater output from the left than the right heart in 15. The right heart flow expressed as a percentage of the combined cardiac output was statistically different from the value in normal fetuses. These findings are consistent with theories of the redistribution of fetal blood flow, where cerebral blood flow is preferentially 'spared'.

Measurements of the dimensions of the aortic and pulmonary pathways in the human fetus: a correlative echocardiographic and morphometric study.

Thirty normal hearts from fetuses aborted at 10-33 weeks' gestation were measured directly and the results were compared with echocardiographic measurements in 20 normal live fetuses of 23-27 weeks' gestation. The diameters of the aorta, aortic isthmus, pulmonary arteries, and arterial duct were measured at standard levels and expressed as a ratio of the diameter of the ascending aorta. The ratios for the isthmus, the duct, and the right pulmonary artery were: 0.63 (0.11), 0.51 (0.13), 0.56 (0.10) respectively for the direct measurement and 0.73 (0.07), 0.7 (0.08), 0.62 (0.06) respectively at echocardiography. These results show that in mid-gestation the isthmus of the human fetus is not as small as that reported in animal models. This indicates that the distribution of the fetal circulation may not be the same either.

Prenatal detection of congenital heart disease: factors affecting obstetric management and survival.

Our recent experience in the diagnosis and management of fetal congenital heart disease is presented. During an 18-month period from January 1985 to June 1986, 1757 fetal echocardiograms were performed on a total of 989 antenatal patients. Cardiac anomalies were accurately predicted in 74 cases, 34 of which were associated with extracardiac or chromosomal anomalies. Twenty-three pregnancies were electively terminated. Currently the survival rate for ongoing pregnancies is 17%. A false negative diagnosis was made in 16 cases, the majority involving minor anomalies with a good prognosis and a survival rate of 81%. Prenatal detection of congenital heart disease places the fetus at high risk for chromosomal and extracardiac anomalies. Congenital heart disease detectable during pregnancy is usually severe and associated with a poor long-term prognosis. Termination of the pregnancy may be a reasonable option if a severe anomaly is detected early in pregnancy.

Coarctation of the aorta in prenatal life: an echocardiographic, anatomical, and functional study.

In a prospective echocardiographic study of over 2000 pregnancies, 24 fetuses were found to have dilatation of the right ventricle and pulmonary artery when these structures were compared with those of the left heart. In 18 of these cases the diagnosis of coarctation or interruption of the aorta was correctly inferred from these findings. On direct echocardiographic examination of the aortic arch, arch hypoplasia or interruption of the aortic arch was recognisable prenatally in 10 of these 18 cases, most readily between 20-30 weeks' gestation. In 11 of 12 cases of aortic arch anomaly studied by Doppler echocardiography, a reduction in blood flow in the ascending aorta was demonstrated. The intracardiac appearances were suggestive of coarctation but the Doppler findings were within normal limits in two further cases which later proved to be normal. A diaphragmatic hernia was found in four fetuses and the intracardiac echocardiography and Doppler findings were the same as those found in fetuses with aortic coarctation. Five cases of coarctation were overlooked on the prenatal echocardiogram but these were found at follow up of the infants. Thus coarctation of the aorta can be diagnosed prenatally, although the condition may be missed or incorrectly predicted by the criteria examined in the present study. Reduced aortic blood flow is a demonstrable feature of aortic arch abnormalities but it is found in other conditions that are not associated with coarctation.

Doppler assessment of umbilical artery blood flow for the prediction of outcome in fetal cardiac abnormality.

In a series of 244 pregnancies referred for fetal echocardiography, the umbilical artery waveform was also studied by pulsed Doppler ultrasound. In 152 normal pregnancies diastolic flow in the umbilical artery was always detectable after 20 weeks gestation. In 4 of 58 normal patients examined before 20 weeks, diastolic flow was absent in some part of the recording. In 34 fetuses with congenital heart disease detected at between 18 and 37 weeks gestation, 10 were found consistently to have associated absent diastolic flow. Five of these fetuses died in utero between 5 and 21 days after the recording; three were aborted and the remaining two died in the neonatal period at 4 and 7 days after the examination. Fetal congenital heart disease with normal umbilical blood flow also had a poor prognosis in general, but the adverse outcome was much less immediate than in fetuses with absent diastolic flow. No correlation was found between the type of congenital heart disease and the characteristics of the umbilical artery waveform. Absent diastolic flow in the umbilical artery indicates a poor short-term prognosis for fetuses with congenital heart disease, particularly after 20 weeks, when fetal death is predictable.

Doppler echocardiographic evaluation of the normal human fetal heart.

Pulsed wave Doppler estimates of blood flow velocity were made across the mitral, tricuspid, aortic, and pulmonary valves in a series of 120 normal fetuses (gestational age 16-36 weeks). In 36 of these the data were obtained in all four sites. The maximum and mean velocities were calculated for each valve and these values were plotted against gestational age. There was little change in these values throughout pregnancy. The orifice dimensions of the valves were measured by cross sectional echocardiography. At all ages the tricuspid orifice was larger than the mitral and the pulmonary orifice was larger than the aortic. The blood flow values for each valve were derived from the product of the mean velocity and the valve orifice dimensions. The output of the right ventricle was usually, but not always, greater than that of the left ventricle. Combined ventricular output increased from approximately 50 ml/min at 18 weeks to 1200 ml/min at term. Despite limitations in the accuracy of the technique these results form a useful basis for the analysis of blood flow in the normal fetus and for the interpretation of abnormal Doppler findings in prenatal life.

Familial recurrence of congenital heart disease in a prospective series of mothers referred for fetal echocardiography.

Fetal echocardiography can ascertain, at an early stage in pregnancy, recurrences of congenital heart disease (CHD) in mothers with a family history of CHD. In 1,021 mothers referred for this reason, 20 recurrences were found; 17 occurred when there had been 1 previously affected child, and 3 when there had been 2 previously affected children. No recurrences were found in the 41 cases in which a parent had CHD. The overall recurrence rate was 1 in 52 with a previously affected child and 1 in 10 with 2 previously affected children. However, certain forms of CHD recurred much more frequently than others. Aortic valve atresia was associated with a recurrence rate of 1 in 28, coarctation of the aorta at a rate of 1 in 15, complex CHD at a rate of 1 in 11 and truncus arteriosus at 1 in 13. These findings are inconsistent with previous family studies; this may be due to more complete ascertainment, particularly of major lesions, possibly overlooked by postnatal family studies because of fetal loss. Alternatively, the availability of prenatal diagnosis may be producing an increase in family size after major CHD. The results support current doubts on the polygenic theory of inheritance for all forms of CHD.

Prenatal screening for congenital heart disease.

Routine ultrasound examination of the fetus is already established in most obstetric units in Britain. A simple method was devised to evaluate one section of the fetal heart systematically. Examination of this section, the four chamber view, may readily be incorporated into routine obstetric screening. Severe cardiac abnormalities detectable in this view occur in two per 1000 pregnancies. For six years the department of paediatric cardiology at Guy's Hospital, London, served as a referral centre for fetal echocardiography. As teaching became more widespread an increasing proportion of cases of cardiac anomaly were referred because the obstetrician suspected abnormality on examination of the four chamber view. Currently 80% of detected abnormalities are referred for this reason. Further extension and organisation of teaching might result in most severe cardiac malformations being detected in early prenatal life.