Fetal Echocardiography : A Window to the Developing Heart M. Regina L. Lantin

Division of Pediatric Cardiology, Department of Pediatrics, University of Texas-Houston Medical School, Memorial Hermann Children's Hospital, Houston, Texas, USA. Abstract. This paper aims to help the reader understand the indications and the underlying physiologic concepts that relate to the findings obtained from a fetal cardiac evaluation. Techniques to obtain the basic fetal echocardiographic views and to identify gross cardiac abnormalities will also be discussed. [Indian J Pedlatr 2002; 69 (6) : 507-511]

Key words : Fetal echocardiography; Fetal circulation; Congenital heart disease.

The practice of fetal echocardiography had its early beginnings in the 70's, when real time ultrasonography equipment became a popular tool in obstetrics. At around the same time, pediatric cardiologists began imaging the neonatal heart. Familiarity and increasing expertise with both techniques led to advances in the field. By the mid 80's, most forms of congenital heart defects detectable in the neonate were described in utero as well? Our present technology has allowed us to use fetal echocardiography as a clinical tool to make an early and accurate assessment of fetal cardiac structure, as well as an aid to diagnose and treat fetal arrhythmias. The applications for fetal echocardiography are many. It is a useful tool in the diagnosis of fetal cardiac structural anomalies and is thus helpful for genetic counselling, and in planning the method of labor, delivery and post-natal care. It is also used for a r r h y t h m i a diagnosis and monitoring of anti-arrhythmic therapy. It may be useful in the assessment of fetal cardiac function and circulation. It may also be used to define the natural history of selected cardiac defects, thus broadening our understanding of fetal cardiac physiology. INDICATIONS Although there has been controversy regarding which patients should be referred for a formal fetal cardiac evaluation, there are certain pregnancy categories that are at high risk for fetal congenital cardiac defects, and therofore are appropriate referrals for a targeted cardiac examination. Maternal risk factors include exposure to known cardiac teratogens such as retinoic acid (conotruncal defects), anti-convulsants (ventricular septal defects, coarctation of the aorta, hypoplastic left heart syndrome), lithium (Ebstein's anomaly and tricuspid Reprint requests : Dr. ReginaM. Lantin,MD, UT-HoustonMedical School, 6431 Fannin, Room 3,126, Houston, TX 77030, USA. Fax : 713-500-5751; E-mail : [email protected] Indian Joumal of Pediatrics, Volume 69--June, 2002

atresia), and alcohol (VSD), to name a few. Poorly controlled maternal diabetes, particularly those with elevated first trimester HgbAlc levels, has been thought to increase the risk for fetal heart defects by three to five times.2 Maternal phenylketonuria, especially those cases with first trimester phenylalanine levels >600 umol/1, is associated with a 14% higher incidence of fetal cardiac anomalies. 3 Maternal collagen vascular disorders that result in transplacental transfer of autoantibodies, place the fetus at risk for complete heart block and cardiomyopathy. Depending on the lesion type, the severity, and the number of affected relatives, the recurrence risk for congenital heart disease based on a positive family history varies from 2-12%, with the highest risk in left heart obstructive lesions? There is a dictum which states that if an anomaly is detected, one must look for a second; if one finds a second, one must search for a third. This is particularly true for congenital heart defects, as they often occur in the context of aneuploidy. Even in the absence of chromosomal abnormalities or genetic s y n d r o m e complexes, certain extra cardiac anomalies such as cleft lip/palate, spina bifida, tracheo-esophageal fistula, duodenal atresia, omphalocoele, diaphragmatic hernia, nuchal edema or a single umbilical artery should make one suspicious for a possible associated cardiac defect. Although a formal fetal cardiac evaluation should be obtained for all the above indications, it is important to remember that nearly 90% of heart defects detected in utero occur in otherwise normal low-risk pregnancies. Therefore, a suspicious level I obstetric screening u l t r a s o u n d is by far the most i m p o r t a n t of all the indications for a formal fetal cardiac evaluation, with a relative yield of as much as 40% in some series. The standard screening 4 chamber view will be abnormal in approximately I in 500 pregnancies, and should detect 60% of major cardiac defects. 5 The evaluation of the great 507

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arteries during the cardiac assessment improves the detection rate of major cardiac anomalies to nearly 90%. Timing The fetal heart is fully septated by 8 weeks of gestation. However, the limitations of our present technology make resolution difficult at this time. A transvaginal study may be p e r f o r m e d prior to 18 weeks, after which the transabdominal approach is preferred. Optimum images are obtained between 24-32 weeks. During the late third trimester, the fetal spine is often in an anterior position. This results in increased shadowing by the ribs, making visualization of all the structures difficult.

Equipment State of the art ultrasound assessment for fetal structural heart defects must include two dimensional real time imaging, as well as simultaneously acquired M-mode and range gated pulse wave and color Doppler interrogation. Two-dimensional (2D) real time imaging permits dynamic analysis of tomographic anatomical planes through the heart and blood vessels. Real time, 2D directed M-mode allows the examiner to view the cardiac structures in real time and then direct the M-mode cursor to the area of interest and obtain an M-mode recording. This is useful for measuring cardiac dimensions as well as for reconstructing the fetal electrocardiogram. The pulse and continuous w a v e Doppler modalities detect obstruction by identifying increases in flow velocity across the cardiac valves. Color flow mapping predicts the direction of blood flow, and identifies areas of turbulence that may be associated with restriction to flow or obstruction. In fetal echocardiography, high resolution ultrasound imaging is essential. The ideal equipment should have high focusing power with "zoom" abilities, variable depth and gain control, and simultaneous M-mode and Doppler modalities, with pulse wave, continuous wave and color flow Doppler. Although to date, echocardiography has not been reported to have harmful effects on the developing fetus, it is prudent to keep ultrasound energy at or below 100mW/cm2. 6 Ideally, one should use a dual frequency or multifrequency transducer that can be changed from 5 to 3.5 MHz rather quickly. The highest frequency transducers generally give the best resolution images. We prefer a 5 MHz transducer with a medium focus for the typical 2nd trimester small to average sized patient. However, the lower frequency 3.5 MHz transducer is preferred for color flow mapping or for pulse and continuous w a v e Doppler interrogation. For third trimester pregnancies, or for those especially challenging patients with an anterior placenta, polyhydramnios, maternal obesity or unfavorable lie, one may use a 3.5 or even a 2.25 MHz transducer, which have a greater depth of penetration, but at the expense of image clarity. In the truly difficult patient, the newer harmonic imaging 508

techniques may prove to be quite valuable. 7 FETAL CIRCULATION PHYSIOLOGY The fetal circulation is influenced by the presence of three shunts: the ductus venosus, the foramen ovale and the ductus arteriosus. Oxygenated b l o o d from the placenta and the umbilical vein bypasses the liver and enters the inferior vena cava (IVC) through the ductus venosus. The orientation of the valve of the IVC (eustachian valve) directs blood flow from the right to the left heart via the patent foramen ovale (PFO). This ensures that the developing brain and heart get first priority on oxygenated placental blood. In turn, cephalic deoxygenated blood enters the superior vena cava and is preferentially directed through the tricuspid valve into the right ventricle. However, because of the presence of a high pulmonary vascular resistance in utero, this deoxygenated blood return bypasses the lungs through the patent ductus arteriosus (PDA), and instead flows into the descending aorta which then perfuses the caudal part of the body. About half of this flow is returned v/a the umbilical arteries to the low resistance placenta for oxygenation. The fetus is highly dependent on the patency and the right to left shunting of blood at the foramen ovale and the ductus arteriosus levels to maintain its unique circulation. Any obstruction to this circuit, either at the level of inflow (the tricuspid and mitral valves) or outflow, (the pulmonary and aortic valves), will result in a redistribution of blood within the cardiac chambers which, in turn, may manifest itself as disproportionate growth of the right and left atria and ventricles. During fetal scanning, gross discrepancies in chamber sizes may thus be readily evident. Based on these nuances in fetal cardiac physiology, one may then expect three key findings in a normal fetal cardiac evaluation: (1) right to left shunting of blood through the PFO, (2) right to left shunting of blood through the PDA, and (3), in most cases, symmetric chamber size. In some fetuses, depending on gestational age, it may be normal to see slight right ventricular predominance. These are important observations, as studies have shown that reversed (left to right) shunting across the PFO or PDA, as identified by both color flow m a p p i n g and Doppler interrogation, suggests the presence of severe left heart and right heart obstruction, respectively.8

TECHNIQUE It is helpful to begin fetal heart scanning with the determination of the fetal lie, as well as right and left sidedness. A reliable method to ascertain fetal laterality has been described. 9 A short axis view of the fetal abdomen is obtained to visualize the spine and the location of the descending aorta and the inferior vena cava relative to it. This will enable the echocardiographer to determine abdominal situs, from which atrial situs and Indian doumal of Pediatdcs, Volume 69--June, 2002

Fetal Echocardiography cardiac position m a y usually be inferred. One m u s t ascertain that the fetal heart and stomach lie on the same side. The conventional 4 chamber view is a good starting point. Obtained b y cutting the thorax horizontally just above the diaphragm, it demonstrates both atria and ventricles, the tricuspid and mitral valves (AV valves), as well as the posterior or inlet portion of the ventricular septum (Fig. 1). In late gestation, the right ventricle (RV) m a y appear to be slightly more prominent than the left ventricle (LV), but in general, both atria and ventricles should be quite similar in size, with symmetric mitral and t r i c u s p i d v a l v e e x c u r s i o n . AV v a l v e h y p o p l a s i a or

Fig. 1. The 4 chamber view in a fetus in cephalic, spine posterior presentation. The atria and ventricles are symmetric in size, with the moderator band that characterizes the morphologic right ventricle (RV)readily evident. Note that the majority of the cardiac mass is located in the left chest. The descending aorta (Desc Ao), is seen in cross-section,posterior to the left atrium (LA).RA-right atrium, LV-left ventricle, PFO-patent foramen ovale.

Fig. 2. The "4 chamber view" in a 23 week old fetus with tricuspid atresia and a hypoplastic right ventricle (RV).Note the gross asymmetry in the ventricular size. A large ventricular septal defect is also visualized.

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diminished or even absent AV valve mobility m a y be seen in the context of hypoplastic ventricles, with mitral or t r i c u s p i d atresia in e v o l u t i o n (Fig. 2). G r o s s discrepancies in ventricular size should also p r o m p t the examiner to evaluate for coarctation of the aorta (CoArct) or total anomalous p u l m o n a r y v e n o u s return, both of which may cause disproportionate RV dominance. No matter what the fetal position is, orientation follows the same rules. The spine is located first, and directly opposite the spine, the anterior chest wall is identified, w i t h the RV just p o s t e r i o r to it. W i t h g o o d e c h o resolution, the coarse trabeculations and the moderator b a n d which characterize the morphologic RV m a y be demonstrated. The tricuspid valve is noted to insert more apically than the mitral valve. The pulsatile descending aorta is identified slightly anterior and to the left of the spine. Anterior to the aorta, the left atrium (LA) is visualized, with its characteristic flap valve of the foramen ovale, a derivative of the septum primuum. At least 2 of the 4 p u l m o n a r y veins m a y be seen to enter the LA in this view. Once the right ventricle and the left atrium have been identified, recognition of the right atrium and left ventricle follows. An imaginary line is then drawn from the spine to the anterior chest wall to divide the chest into two equal halves. Most of the cardiac mass is seen to lie in the left chest, with only the right atrium and a small portion of the left atrium and right ventricle in the right chest. One should also compare the cardiac circumference relative to that of the thorax. The cardio-thoracic ratio should not be greater than 60%. Although the 4 chamber view is usually the easiest to obtain and interpret, one must be aware that it does not pass through a plane that allows recognition of the aorta and pulmonary arteries. It is therefore important to obtain orthogonal views to visualize the right and left outflow tracts in order to define cono-truncal defects. If one were to angle anteriorly toward the fetal right shoulder utilizing the standard 4 chamber view as a reference point, the left ventricular outflow tract (LVOT) view, akin to the post-natal parasternal long axis view, may be obtained (Fig. 3). This demonstrates the left atrioventricular and ventriculo-arterial connections, as well as the c o n t i n u i t y of the a n t e r i o r m u s c u l a r a n d o u t l e t ventricular septum. This view thus permits imaging of a n t e r i o r and o u t l e t v e n t r i c u l a r s e p t a l d e f e c t s , a n d o v e r r i d i n g of the aorta seen in t e t r a l o g y of Fallot or Double outlet right ventricle. With further anterior angulation from this scan plane, the pulmonary artery is seen to arise anteriorly from the right ventricle, running beneath the aortic arch. Slight a n t e r i o r - p o s t e r i o r tilting of the t r a n s d u c e r will d e m o n s t r a t e the v e n t r i c u l o - a r t e r i a l c o n n e c t i o n s . Normally, the great vessels are related in such a way that the p u l m o n a r y artery is anterior and leftward to the posterior and rightward aorta. The crossing, anteriorposterior relationship of the right and left outflow tracts is

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M. Regina L. Lantin a normal finding that cannot be demonstrated in fetuses with transposition of the great arteries. From the LVOT view, slight clockwise rotation allows one to display the entire aortic arch, including the origin of the head and neck vessels (Fig. 4). In this longitudinal section, the arch is seen to arise f r o m the center of the chest. The configuration of the aortic arch m a y be likened to a "candy cane", or a "hook" before it descends in front of the spine. The right pulmonary artery is seen within the c u r v e of the arch. The spine is located posterior to the d e s c e n d i n g aorta. The aortic i s t h m u s , w h i c h is just proximal to the connection of the ductus arteriosus to the descending aorta, is normally the narrowest portion of the aortic arch, because it is that part of the arch that sees the least amount of blood flow. From the aortic arch view, slight angulation towards

Fig. 3. Long axis view of the left ventricular outflow tract. The right ventricle (RV) is anterior, and the ventricular septum is intact. Note the continuity between the anterior mitral leaflet and the aorta, characteristic of the morphologic left ventricle (LV). LA-left atrium, AO-Aorta.

Fig. 4. Long axis view of the aortic arch, which has been likened to a "candy cane". Care must be taken to avoid confusing the true aortic arch with the ductal arch, which has been likened to a "hockey stick" due to the obtuse angle it takes as it originates from the anterior right ventricle. 510

the fetal left shoulder will demonstrate the ductal arch. In contrast to the true aortic arch w h i c h arises from the middle of the chest, the ductal arch has its origin from the m o r e anterior p u l m o n a r y artery, thus f o r m i n g a m o r e obtuse angle likened to a "hockey stick". One m u s t keep this in mind as it is quite easy to mistake the ductal arch for the true aortic arch. The ductus arteriosus has the highest Doppler flow velocity in the fetus, reaching a peak of u p to 1.2 m / s e c at term. There s h o u l d a l w a y s be f o r w a r d f l o w t h r o u g h the d u c t in b o t h s y s t o l e a n d diastole. Flow reversal in the ductus arteriosus should p r o m p t an i n v e s t i g a t i o n for a p o s s i b l e right h e a r t obstructive lesion. The more severe forms of coarctation of the aorta are associated with hypoplasia of the left heart structures, and a correct diagnosis m a y be m a d e in early p r e g n a n c y . H o w e v e r , milder f o r m s of coarctation, w i t h n o other finding other than mild isthmus narrowing slightly more prominent than usual, m a y be associated with a normal i n t r a c a r d i a c a n a t o m y . Studies h a v e s h o w n t h a t no specific echo finding, alone or in combination, can reliably diagnose subtle cases of coarctation prenatally. Longitudinal views of the fetal heart, angled toward the fetal right shoulder, will image the inferior vena cava passing t h r o u g h the d i a p h r a g m into the right atrium, with the superior vena cava originating cephalad (Fig. 5). Many complex congenital cardiac defects, especially in patients with heterotaxy, are associated with interrupted inferior vena cavae. Using any of the above described longitudinal views as a reference point, angling the transducer at right angles to the long axis of the fetal heart, or parallel to the fetal spine, demonstrates a family of short axis views obtained from the cardiac base to the apex. In the short axis view of the great vessels, the central aorta is visualized flanked b y the.right atrium, right ventricle, right v e n t r i c u l a r outflow tract and pulmonary arteries (Fig. 6). Sliding the

Fig. 5. Long axis view through the right side of the fetal thorax, illustrating the integrity of the venous return to the right atrium (RA). SVC-superior vena cava, IVC - inferior vena cava. Indian Journal of Pediatrics, Volume 69--June, 2002

Fetal Echocardiography transducer caudad from this view, a cross section of the two ventricles will be obtained. The left ventricle is the posterior, circular ventricle, flanked b y the more anterior, crescent shaped right ventricle (Fig. 7). The a f o r e m e n t i o n e d technique described in detail above allows the examiner to diagnose the presence of a n o r m a l fetal c a r d i a c a n a t o m y . In a d d i t i o n to 2dimensional imaging, D o p p l e r interrogation and color flow m a p p i n g of all 4 valves and the ventricular septurn will permit the recognition of most forms of congenital heart defects.

Fig. 6. Short axis view of the base of the fetal heart, at the level of the great vessels. The central aorta (AO) is flanked by the right atrium (RA) and right ventricle (RV). The branches of the pulmonary arteries are well visualized.

reconstructed, utilizing mechanical and not electrical e v e n t s as in the c o n v e n t i o n a l e l e c t r o c a r d i o g r a m s . Through this technique, fetal b r a d y or tachyarrhythmias, as well as premature atrial or ventricular contractions and complete heart block m a y be diagnosed. CURRENT ISSUES A N D FUTURE CONSIDERATIONS Fetal echocardiography is truly a very sophisticated and useful tool that permits the diagnosis of cardiovascular a n o m a l i e s p r e n a t a l l y , t h u s e n a b l i n g c a r e - g i v e r s to anticipate the needs of a potentially compromised fetus during its transition to extra-uterine life. However, it is important to remember that even in the best hands, both false positive a n d false negative diagnoses of cardiac defects m a y occur. In fetuses w i t h c o m p l e x cardiac anomalies, it is often difficult to delineate all associated defects. Small ventricular septal defects, m i n o r valve abnormalities, and of course, persistence of the ductus a r t e r i o s u s a n d f o r a m e n ovale p o s t natally cannot be predicted by a fetal scan. Towards the end of the 1990's, the impact of prenatal diagnosis on congenital heart defects b e c a m e evident, with non-surprisingly better surgical outcomes for those infants w h o were diagnosed in utero. I~ With advances in the ability to reliably diagnose congenital cardiac defects prenatally, fetal cardiology became a natural extension of pediatric cardiology. The prospect of fetal cardiac surgery n o w l o o m s in the horizon. A l t h o u g h n e w ethical a n d m o r a l issues will u n d o u b t e d l y be raised, w e can only speculate on the m a g n i t u d e of the impact fetal cardiac s u r g e r y will h a v e on congenital h e a r t disease in the future. REFERENCES

Fig. 7. Short axis view at the level of the cardiac apex, illustrating the anterior right ventricle (RV), flanking the posterior, circular left ventricle (LV). Note the mitral valve leaflets within the LV cavity. FETAL ELECTROPHYSIOLOGY Fetal arrhythmias are evaluated by the combined use of 2 D imaging and simultaneous M-mode recordings. With the aid of a 2 D image, an M m o d e cursor is aligned to record atrial and ventricular wall motion. By matching atrial and ventricular wall contractions with assumed P and QRS complexes, the fetal electrocardiogram can be Indian Journal of Pediatrics, Volume 69---June, 2002

1. Allan LD. Early detection of congenital heart disease in prenatal life. Clin Obstet Gynecol 1983; 10 : 507-514 2. Shields LE, Gan EA, Murphy HF et al. The prognostic value of Hemoglobin Alc in predicting fetal heart disease in diabetic pregnancies. Obstet and Gynecol 1993; 81 : 954-957. 3. Rouse B, Azen C, Kocj R et al. Maternal Phenylketonuria Collaborative Study. Am J Med Genet 1997; 69 : 89-95. 4. Brenner JI, Berg KA, Schneider DS et al. Cardiac malformations in relatives of infants with the hypoplastic left heart syndrome. Am J Dis Child 1989; 143 : 1492-1494. 5. Allan LD, Crawford DC, Chita SK et al. Prenatal Screening for Congenital Heart Disease. Br Med J 1986; 292 : 1717-1719. 6. O'Brien WD Jr. Safety of Ultrasound with selective emphasis for obstetrics. Semin Ultrasound 1984; 5 : 105-120. 7. Thomas JD, Rubin DN et al. Tissue harmonic imaging: Why does it work? J Am Soc Echocardiogr 1998; 11: 803-808. 8. Berning RA, Silverman NH, Villegas M et al. Reversed shunting across the duc~s arteriosus or atrial septum in utero heralds severe congenital heart disease. JAm Coll Cardio11996; 27 : 481-486. 9. Cordes TM, O'Leary PW, Seward JB et al. Distinguishing right from left: a standardized technique for fetal echocardiography, l Am Soc Echocardiogr 1994; 7 : 47-53. 10. Bonnet D, Coltri A, Butera Get al. Detection of transposition of the great arteries in fetuses reduces neonatal mortality and morbidity. Circulation 1999 ; 99: 916-918. 511