Fetal Echocardiography: Where are we? Anita Saxena and N. Reeni Soni 1

Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India and 1Section of Pediatric Cardiology, Department of Pediatrics, University of Manitoba, Winnipeg, MB, Canada

A b s t r a c t . This article reviews the indications, technique and benefits of fetal echocardiography. The impact of fetal echocardiography has become evident with better surgical outcome of infants with prenatal diagnosis of congenital heart disease. A major use of this technique has also been shown in the field of fetal arrhythmias. Fetal echocardiography is not only used to diagnose a specific type of arrhythmia, it is also very helpful in assessing the effect of the arrhythmia on the fetus and in guiding transplacental therapy. However it is important to remember that even experienced echocardiographers can make both false positive and false negative diagnosis of congenital heart disease. As fetal cardiac interventions including fetal cardiac surgery loom on the horizon, fetal echocardiography assumes further importance. [Indian J Pediatr 2005; 72 (7) : 603-608] E-mail: anitasaxena @hotmail.com

Key words : Fetal echocardiography; Congenital; Arrhythmia

"The history of mankind for the nine months preceding his birth could, probably, be far more interesting and contain events of greater than all the threescores and ten years that follow it" Samuel Taylor Coleridge Miscellanies, Aesthaticand literary, 1803 Congenital heart disease is present in 0.8% of all live births and is therefore one of the most common congenital malformations. 1 It accounts for half of all deaths from lethal malformations in children. Almost one third to one half of congenital heart defects are severe and lethal unless an i n t e r v e n t i o n is d o n e early. 2 U l t r a s o u n d examination of the heart is an important diagnostic tool in p e d i a t r i c c a r d i o l o g y for d e t e c t i o n of these cardiac malformations. This modality became available in the late 1970s and by 1980 its use was extended to the evaluation of the fetal heart for cardiac anomalies, primarily by cross sectional imaging. 3,4 With advances in technology and wider experience, it is now possible to define the details of fetal cardiac a n a t o m y in the mid second trimester of pregnancy. Ultrasound examination is safe, noninvasive and easy to perform. It is highly sensitive and specific in experienced hands, s-7 Prenatal diagnosis of congenital heart disease results in referral of mothers with affected fetuses to tertiary care centers where all facilities for neonatal cardiac care are available. The diagnosis of a congenital heart disease in a fetus should also p r o m p t evaluation for genetic s y n d r o m e s and associated non cardiac malformations.

Correspondenceand Reprintrequests : Dr Anita Saxena, Professor, Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India 110029. Indian Journal of Pediatrics, Volume 72--July, 2005

Scope of Fetal Echocardiography The primary aim of antenatal screening by ultrasound is to exclude a congenital heart disease (CHD) or to make accurate diagnosis if a malformation is present. However with increasing experience, fetal echocardiography is also contributing to the discipline of perinatal cardiology in many other ways. It is the single most important diagnostic tool for arrhythmia diagnosis in the fetal period. Fetal echocardiography has also helped us to understand the natural history of several congenital heart diseases like hypoplasia of a ventricle, thus broadening our understanding of fetal cardiac development. The most exciting, u p c o m i n g area of fetal cardiac intervention is totally dependent on the technique of fetal echocardiography, which acts as a navigator at every stage.

Optimal Timing of Screening Fetal h e a r t e x a m i n a t i o n is possible b y t r a n s v a g i n a l t r a n s d u c e r s as early as 9 to 10 w e e k s of gestation. Transabdominal good quality echo pictures are generally obtainable by 16 weeks onwards. The usual time for fetal heart screening is at about 18 to 22 weeks since at this stage almost all details of fetal cardiac a n a t o m y are possible to e v a l u a t e , i n c l u d i n g v e n t r i c u l o a r t e r i a l connections. Screening in the mid second trimester of gestation is necessary even if an earlier first trimester scan was normal as some of the congenital heart defects can develop later eg. hypoplasia of a ventricle secondary to inflow or outflow obstruction. Lesions like single ventricle, atrioventricular valve or semilunar valve atresia are easy to see, however, minor defects like small ventricular septal defects are difficult to visualize. Diagnosing s e c u n d u m atrial septal defect is almost impossible as defects of the fossa ovalis are 603

Anita Saxena and N. Reeni Soni

normally present in fetal life. Fetal echocardiography is technically difficult beyond 28 to 30 weeks due to increased shadowing by the ribs.

Indications for fetal echocardiography Ideally all pregnancies should be screened for congenital heart disease at about 18 weeks of gestation. However, this is not always feasible even in developed countries with adequate resources. Therefore screening efforts should be aimed at pregnancies where the risk of congenital heart disease in the fetus is likely to be higher than the general population. Indication can be divided into two major categories: fetal and maternal? It must be pointed out that nearly 90% of heart defects detected in utero occur in otherwise low risk pregnancies. Maternal Indications: These include 1. Family history of congenital heart disease 2. Metabolic disorders like phenylketonuria, diabetes 3. Exposure to teratogens like lithium, anticonvulsants, steroids 4. Exposure to prostaglandin synthetase inhibitors eg. Ibuprofen, salicylic acid, indomethacin 5. Rubella infection 6. A u t o i m m u n e disease eg. Systemic lupus erythematosis, Sjogren's syndrome 7. Familial inherited disorders like Marfan's syndrome, Etlisvan Creveld syndrome, Noonan's syndrome etc 8. In vitro fertilization

Fetal indications: These include 1. Abnormal obstetric ultrasound screen 2. Presence of extracardiac abnormality 3. Chromosomal abnormality 4. Heart beat irregularity 5. Presence of fetal hydrops 6. Multiple gestation and suspicion of twin to twin transfusion syndrome 7. Increased first trimester nuchal translucency Recently an interesting new parameter, increased fetal nuchal translucency in the first trimester has been highly correlated with the presence of congenital and chromosomal anomalies. 9 All normal fetuses have a lucency at the back of the neck at about 10 to 12 weeks of gestation. The diameter of this translucency can be measured and an increased thickness beyond 3 to 4 standard deviations from normal is often associated with chromosomal anomalies. A similar relationship has also been shown with congenital heart disease. 1~ Hence this parameter may be a surrogate marker for early detection of congenital heart disease. It is important to note that this significant finding of increased nuchal thickness resolves in the second trimester and hence a conventional second trimester scan is likely to miss this important finding. The exact mechanism of this abnormality is not clear. There is also data, which indicates a three-fold increase in the prevalence of congenital heart disease in infants conceived via in vitro fertilizaion. 12 604

Who Should Perform Fetal Echocardiography? Certain guidelines have been established by the American Society of Echocardiography in 2004 regarding which physicians should be considered suitable for performing fetal echocardiography? Some of these guidelines are: 1. The physician should be well versed with all modalities of echocardiography including M mode, 2 dimensional, Doppler and color flow mapping. 2. He/she should be able to recognize all types of heart disease, simple and complex, congenital and acquired. 3. He/she should have knowledge of the natural history of congenital heart disease during pregnancy. 4. H e / s h e should know the limitations of fetal echocardiography. 5. He/she must understand the various types of fetal arrhythmia and should know how to diagnose them. 6. He/she should have the understanding of maternalfetal physiology. 7. H e / s h e should have knowledge of upcoming developments including fetal interventions. 8. He/she should have good communication skills and a high level of compassion. Since all the above skills and knowledge are most likely to be present in a well-trained pediatric cardiologist, he or she may be most suitable for performing fetal echocardiography.

Equipment The ultrasound system needed for fetal echocardiography should have capabilities for real time imaging as well as simultaneously acquired M mode and pulse wave and color Doppler interrogation. M mode analysis is useful for measuring cardiac dimensions as well as for reconstructing the fetal electrocardiogram. Color flow mapping predicts the direction of blood flow and identifies areas of turbulence due to obstruction or restriction of flow. Since the fetal heart is very small, especially in early pregnancy and the heart rates are faster, a high resolution along with high frame rates are necessary for optimal visualization. The equipment should also have high focusing power with "Zoom" abilities. Most of the available ultrasound systems have software for fetal screening. Phased array transducers with frequency range of 3 to 10 MHz are generally used. Ideally one should use dual or multi frequency transducers. High frequency transducers give better resolution images. Generally a 5 MHz transducer is suitable for a mid second trimester scan, although color and pulse wave Doppler may be better with a 3.5 MHz transducer. For pregnancies with maternal obesity or polyhydroamnios, one may have to use a 2.25 or 3 MHz transducer which gives better penetration but lesser resolution. Large curvilinear probes are more helpful as the near field of view is wide.

Technique of Prenatal Screening by Ultrasound The success of the technique depends on the skill in Indian Journal of Pediatrics, Volume 72--July, 2005

Fetal Echocardiography: Where are we? getting the optimal echo window. Since the fetal position is not fixed, in fact the position may constantly change during echo examination, it is important to be thoroughly familiar with the cardiac views and their correct analysis. The situs should be determined first and then if apex and stomach bubble are on left side, the situs is solitus. After that one usually begins with a two-dimensional imaging of the cardiac anatomy. A four-chamber view is obtained and it should be analyzed in detail for size, morphology and function of both ventricles, atrioventricular valves, direction of motion of the fossa ovalis flap and presence of any ventricular septal defect. A four chamber view is the most often obtained view, possible in 90% of cases (Fig. 1). H o w e v e r it has a low s e n s i t i v i t y for d e t e c t i o n of congenital heart diseases. 13A four chamber view can detect conditions such as h y p o p l a s i a of a ventricle, atriventricular septal defect (Fig. 2) or atresia of one of the atriventricular valves, but it is likely to miss a subaortic ventricular septal defect, tetralogy of Fallot, transposition

of great arteries, double outlet right ventricle and many o t h e r c o m p l e x defects. H e n c e o u t f l o w v i e w s are necessary.14A cranial sweep images the great artery connection, ductal and the aortic arch (Fig. 3a,b,c). A pulsatile descending aorta is identified slightly anterior

Fig. 3a

Fig 1. Four chamber view in a fetus at 22 weeks of gestation. FO: fossa ovalis, LA: left atrium, LV: left ventricle, RA: right atrium, RV: right ventricle.

Fig 2. Four chamber view in afetus at 20 weeks of gestation showing complete atriventricular septal defect with large atrial and ventricular septal defects and a common atrioventricular valve (CAVV). Indian Journal of Pediatrics, Volume 72--July, 2005

Fig. 3b

Fig. 3r Fig. 3. Outflow views showing left ventricular outflow (a), right ventricular outflow (b), and ductus arteriosus (c). Ao: aorta, DAO: descending aorta, MPA: main pulmonary artery, PDA: patent ductus arteriosus. 605

Anita Saxena and N. Reeni Soni and to left of spine. It is usually possible to rule out a structural cardiac lesion if all these views are seen in detail. Color flow m a p p i n g is i m p o r t a n t and s h o u l d be combined with cross sectional imaging. It is utilized to identify normal p u l m o n a r y venous connection and abnormalities like a ventricular septal defect, atrioventricular valve or semilunar valve regurgitation. It must be remembered that certain abnormalities like small or moderate sized ventricular septal defect m a y not be detected by fetal echocardiography. In a normal fetal heart, the heart should occupy about one third of the fetal thorax. The apex should point towards the left anterior chest wall. The right atrium and right ventricle are approximately equal to the left atrium and the left ventricle respectively. The lateral walls of two ventricles are of equal thickness, although the right ventricle has more trabeculations at the apex. The tricuspid valve is noted to insert more apically than the mitral valve. The great arteries and their outflows crisscross each other and they never run parallel to each other. The flap of fossa ovalis opens in left atrium as there is right to left shunt across the foramen ovale. The shunt is right to left through the ductus arteriosus, as can be seen by color Doppler mapping. Prenatal screening by echocardiography can detect most types of c o n g e n i t a l heart disease, as seen in p o s t n a t a l life. Some of the p r e n a t a l l y d i a g n o s e d c o n g e n i t a l heart defects become more obvious as pregnancy advances eg. hypoplasia of a ventricle (Fig. 4) or development of atrioventricular valve regurgitation (Fig. 5). Hence if an abnormality is detected and the p r e g n a n c y is c o n t i n u e d , repeat u l t r a s o u n d m a y be necessary to assess the fetal heart and fetal well being.

Fig. 4. Four chamber view in a fetus with hypoplastic left ventricle 606

Fig 5. Four chamber view from a fetus with severe tricuspid regurgitation due to dysplastic tricuspid valve.

Echocardiography for Fetal Arrhythmia Fetal echocardiography is very useful in the diagnosis and management of fetal arrhythmia. Fetal ECG can be constructed by combined use of two dimensional imaging and simultaneous M mode recording and matching the atrial and ventricular contractions. The incidence of fetal arrhythmia is 1-2 %, 90% of these are due to isolated atrial or ventricular ectopics, which are largely benign. More serious arrhythmia include supraventricular tachycardia, atrial flutter/fibrillation, ventricular tachycardia and complete heart block. Some of these arrhythmia may be associated with underlying structural heart disease. Supraventricular Tachycardia - The heart rates are fast, usually beyond 180 beats per minute. 15In most cases there is no underlying cardiac lesion, Ebstein's anomaly of the tricuspid valve and rhabdomyomas may be responsible in a small proportion of cases. Supraventricular tachycardia is generally well tolerated for short periods, but if it continues, it can cause myocardial dysfunction, atriventricular valve regurgitation and fetal heart failure seen as hydrops. Echocardiography can detect each of these complications and hence is very useful. The initial treatment of supraventricular tachycardia is with transplacental antiarrhythmic therapy such as digoxin given to mother. Other drugs include verapamil, sotalol and flecainide. If this m o d a l i t y is unsuccessful, direct umbilical vein or fetal intramuscular drug administration can be considered. If there is no response to drugs, a p r e m a t u r e d e l i v e r y m a y have to be p e r f o r m e d . Echocardiography again helps in follow up of these cases to monitor response to therapy. Complete Heart Block: Echocardiography can distinguish complete heart block from sinus bradycardia by showing a normal atrial rate, a slow ventricular rate and presence of atrioventricular dissociation. Complete heart block can be an isolated abnormality, in which case the mother often has a connective tissue disorder like systemic lupus erythematosis, which may be subclinical. In this setting the heart block is caused by circulating antibodies, specially anti Ro and anti La antibody. These antibodies Indian Journal of Pediatrics, Volume 72--July, 20G5

Fetal Echocardiography: Where are we?

cross the placenta and damage the fetal conduction tissue producing complete heart block. The bradycardia is generally well tolerated but a small number of fetuses decompensate producing intrauterine heart failure. Maternal treatment with sympathomimetic drugs such as salbutamol a n d / o r steroids may be beneficial. 1~, Alternatively an elective early delivery with postnatal epicardial pacing can be performed if fetal compromise is evident. In another half of cases with complete heart block, there is an underlying cardiac malformation such as corrected transposition of great arteries, atrioventricular septal defect, heterotaxy syndrome etc. The outcome of these cases depends upon the underlying cardiac defect. 17Generally the mortality is high in this group with intrauterine deaths.

Potential Benefits of Fetal Echocardiography Fetal echocardiography has many benefits; some of these are borne out by prospective studies. A negative scan also has great importance, as it is very reassuring for a family with a previous child affected with congenital heart disease. Diagnosis of a congenital cardiac defect in the fetus is very useful as outlined below: 1. It helps in parental counseling and education allowing the parents to be better prepared psychologically at the time of delivery. If a serious defect is detected, such as hypoplastic left heart syndrome, parents can be given a choice of termination of pregnancy if it still safe for the mother. 2. The baby is delivered in a center well-equipped with neonatal cardiac care. 3. Delivery in a tertiary cardiac center helps in smooth transition from pre to post natal life as periods of hypoxia, acidosis can be avoided by early institution of therapy eg. Prostaglandin infusion for ductus dependent lesions. 4. There are several studies to suggeSt that immediate survival rates are improved when the cardiac defect is diagnosed prenatal. 18-2~ 5. Logically this should result in better long term and neurologic outcome, but data is not yet available. 6. Some of the cardiac defects may be amenable to in utero treatment in the future. Echocardiography will have a major role in guiding this form of therapy. 7. In the case of fetal arrhythmia, fetal echocardiography has proven benefit. Management of arrhythmia in utero can be life saving and if features of hydrops are present, an early delivery can be undertaken if drug therapy is not effective.

Safety of Ultrasound Although theoretical concerns remain, to date there have been no confirmed harmful effects detected. The ultrasound expenditure increases with each modality of ultrasound used. Hence use of ultrasound energy should be as low as possible to obtain a satisfactory Indian Journal of Pediatrics, Volume 72--July, 2005

echocardiography examination, usually at or below 100mW/cm 2.

Fetal Cardiac Interventions This is the most exciting aspect of fetal cardiology for a pediatric cardiologist and echocardiography is indispensable for the development of this specialty. Neonatal corrective surgery has established itself in the belief that neonatal repair may optimize ventricular function and development. However, there are people who say that even neonatal repair may be too late and intrauterine correction of abnormality is ideal. This may be true in conditions where a ventricle becomes hypoplastic secondary to inadequate passage of flow through it eg. hypoplastic right ventricle in pulmonary atresia with intact ventricular septum. Although fetal interventions and surgery for congenital heart disease have been on the horizon for a while, many obstacles must still be overcome. Fetal cardiopulmonary bypass is difficult to achieve and carries the potential for placental dysfunction.21Creation and correction of right ventricular outflow tract obstruction in utero has been performed in animals. Several large perinatal and pediatric centers around the world are now offering in utero catheter based valvuloplasty to mothers who carry fetuses with stenosis of the aortic or pulmonary valves. 22The prerequisites for fetal cardiac interventions are 1. Fetus is at risk of death. 2. The postnatal outcome is expected to be very poor. 3. The intended procedure is to prevent defect or improve outcome. 4 The procedure should not be performed if the damage is already irreversible. 5. The procedure must not put the mother at undue risk. The procedures which are considered for in utero intervention include valvar aortic stenosis/atresia, restrictive atrial septal defect, pulmonary atresia/severe valvar pulmonic stenosis. More than 40 cases of balloon dilatation of semilunar valves have been done worldwide in humans. However despite the technical success, fetal survival has been about 50%. Fortunately all these procedures have been safe for mother. A lot of advancement is still needed in the area of fetal cardiac interventions. CONCLUSIONS

Fetal echocardiography is a very useful tool for the prenatal diagnosis of congenital heart defects. It has proven itself in the diagnosis and management of fetal arrhythmia. The true future of fetal echocardiography lies not in identification and termination of fetuses with congenital heart malformations, but in the exciting new specialty of fetal cardiac interventions, where fetal echocardiography will act as a navigator. The lingering ethical, moral, legal and spiritual dilemmas are lagging behind and will need to be answered in the future. REFERENCES

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Indian Journal of Pediatrics, Volume 72--July, 2005