Fetal echocardiography—applications and limitations

LNrrasound m Med & Biol Printed in the U.S.A.

Vol.

IO,

No.

6, pp.

747-755,

FETAL

t .C4l

1984

0301-5629/84 $3.00 Pergamon Press Ltd.

ECHOCARDIOGRAPHY-APPLICATIONS AND LIMITATIONS

CHARLES S. KLEINMAN, ELLEN M. WEINSTEIN, NORMAN S. TALNER and JOHN C. HOBBINS Department

of Pediatrics,

Diagnostic

Imaging,

and Obstetrics & Gynecology CT 065 10, U.S.A.

Yale University

School of Medicine

New Haven,

Abstract-Fetal echocardiography has been a useful technique for demonstrating the anatomy of the developing human heart. M-mode echocardiography may be used to provide rhythm diagnosis in the absence of high-fidelity transabdominal fetal electrocardiograms. The information so generated may be applied to plan the management of pregnancy and delivery in a population at “high risk” for structural or functional heart disease and may provide the impetus for developing in utero treatment programs. For this reason, a high degree of sensitivity and specificity must be asked of the technique and of the personnel performing the examination. “Major” malformations which impart marked hemodynamic and structural alterations on the fetal heart may be reliably diagnosed. Diseases which must be identified on the basis of direct recognition of subtle abnormalities of structure, with little impact on fetal flow patterns (e.g. mild semilunar valve stenosis of perimembranous ventricular septal defect) have been more problematic. Before effective screening and treatment programs for the fetal heart can be developed, a cooperative effort between cardiologists and perinatologists is essential in order to gain facility with imaging as well as familiarity with the natural history of these conditions. Key Words: Fetal echocardiography,

Congenital

malformations,

Cardiac

malformations.

many cases, cardiac catheterization and angiography. This redundancy of diagnostic approaches does not exist for fetal cardiac diagnosis. With the exception of non-specific findings of fetal heart rate monitoring and gross changes in amniotic fluid volume (poly- or oligohydramnios), the fetal echocardiogram stands alone as the diagnostic modality central to the diagnosis of fetal cardiac disease. The uniqueness of this information increases the need for a more complete understanding of the strengths and weaknesses of these techniques. It is important to emphasize that these studies often involve, for the echocardiographer and pediatric cardiologist, application of a familiar imaging modality in an unfamiliar arena (the fetus) or, for the obstetrician-perinatologist, the imaging of an unfamiliar organ (the heart) in a familiar setting. At once it should be stated that successful fetal echocardiographic studies can only be expected after the accumulation of a considerable body of experience using a team approach, involving both perinatology and pediatric cardiology. Fetal echocardiographic studies have been performed at our institution on approx. 2000 pregnant women during the past 7 yr. Indications for study have included maternal, fetal, and familial risk factors that have been previously reported (Kleinman et al., 1980) (Kleinman and Santulli, 1983). After an obstetrical ultrasound study has been performed to ascertain fetal size, gestational age, and to detect somatic abnormalities, the fetal position within the uterus and the position of the fetal heart

The combined application of M-mode and two-dimensional echocardiographic imaging for examination of the human fetal heart has at once increased our understanding of developmental cardiovascular physiology, while providing, information that has been central to the development of programs for the evaluation and treatment of fetuses with structural and/ or functional heart disease. The pediatric cardiologist has thus, for the first time, faced the clinical, moral and ethical questions inherent in fetal diagnosis and therapy, including the question of elective termination of pregnancy. It is, therefore, crucial that these techniques be both sensitive and specific and that the personnel involved be aware of the potential pitfalls of the technique. It is the purpose of this report to bring into perspective the strengths and potential weaknesses of fetal echocardiography as a diagnostic and monitoring technique. We will attempt to illustrate these weaknesses using examples from our laboratory as well as examples that have been reported in the literature. STRUCTURAL HEART DISEASE Two-dimensional echocardiography has assumed an important role in the diagnosis of complex congenital heart disease in most clinical pediatric cardiology services. The tomographic images so provided are central to many diagnoses, but the echocardiogram is usually interpreted in the context of information from many sources, including physical examination, electrocardiography, chest roentgenography, and in 747

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with respect to the maternal abdominal wall is ascertained. Utilizing this information a two-dimensional echocardiographic examination is performed from the anterior maternal abdominal wall. Attempts are made to obtain tomographic images from planes similar to those used in post-natal examinations DeVore et ul., 1982; Allan et al., 1980; Gussenhoven and Becker, 1983). Under normal circumstances standard anatomic landmarks such as the fetal spine and its approximation to the normal left atrium and pulmonary veins, flap of the foramen ovale within the left atrium, apical insertion of the septal tricuspid valve leaflet at the crux of the heart compared to the level of insertion of the anterior mitral valve leaflet, septal insertion of tricuspid chorda to the ventricular septum, coarse trabeculation of the right ventricular myocardium, and mitral-to-aortic valve fibrous continuity are used for orientation during the examination and a segmental approach for the analysis of cardiac structure (Gussenhoven and Becker, 1983). Using this approach we have been successful in attaining adequate images (of diagnostic quality) in 94% of patients studied between the 18th and 41st weeks of gestation. The most frequent cause of failure has been maternal obesity, often in conjunction with anterior placental implantation-resulting in displacement of the fetal heart to greater than 10 cm. from the maternal abdominal wall. Interchangeable transducer systems are used utilizing a mechanically swept (ATL MK600), a dynamically-focused phased array (Hewlett-Packard), and a linear array (Toshiba SAL30A) system interfaced with 3.0, 3.5 and 5.0 MHz transducers with short or medium acoustic focal lengths. Increased distance of the fetal heart from the maternal abdominal wall necessitates utilization of lower frequency transducers with increased depth of penetration offset by a decrease in spatial resolution. This must be kept in mind if one is to attempt to diagnose subtle abnormalities of cardiac structure by direct recognition (e.g. semilunar valve stenosis, or small perimembranous interventricular septal defects). Difficulties may also be encountered when attempting to resolve fetal cardiac structure at a cardiac depth that falls beyond the focal length of the transducer system in use. To date, we have prospectively diagnosed 34 cases of congenital heart disease in utero (See Table 1). It is interesting that while natural history studies indicate that ventricular septal defect is, by far, the most common structural cardiac malformation, (Keith et al., 1978) we have diagnosed only one example of ventricular septal defect-and that was a rather large perimembranous defect with posterior extension into the inflow septum, making the defect evident both in

November/December Table

1984, Volume

10, Number

I. Congenital

cardiac malformations by fetal echocardiography

Aortic

coarctation

Atrial

isomerism

Atria1 isomerism Atrioventricular Absent

- Asplenia

- Polysplenia

demonstrated

(2)

syndrome

canal defect

pulmonary

Cardiac

syndrome

6

(2)

- (5)

valve

rhabdomyoma

Conjoined

twins

Double outlet Ebstein’s

right ventricle

malformation

Hypertrophic

cardiomyopathy

Hypoplastic

Pulmonary

of foramen

atresia stenosis

Tetralogy

of Fallot (3)

Transposition

right ventricle

of the Great Arteries

atresia

(2)

septal

Univentricular Unguarded

(2)

wale

- hypoplastic

Pulmonic

Ventricular

(3)

left heart syndrome

In utero closure

Tricuspid

- (2)

defect

heart (2)

tricuspid

orifice

sagittal views of the left ventricular outflow tract as well as in the four-chamber view of the inflow septum. The relative rarity of isolated ventricular septal defect in our experience and the predominance of “complicated” lesions is almost certainly related to preselection of our patients (e.g. a high percentage of cardiac disease was encountered in hydropic fetuses (Kleinman et al., 1982) and to the insensitivity of our techniques for the detection of small to moderate ventricular septal defects. Our experience consists predominantly of “major” defects which result in significant alteration in fetal cardiovascular flow patterns. These flow patterns may themselves impart marked alterations in cardiac structure (Rudolph, 1974) that are readily identifiable using echocardiographic imaging techniques (for example, marked right ventricular enlargement with left ventricular hypoplasia in fetuses with mitral atresia) (Fig. 1). We have encountered difficulties when attempting to identify structural abnormalities that may impart little or no alteration in fetal flow patterns in utero (e.g. ventricular septal defect). More problems have arisen in detecting small or moderate ventricular septal defects than we had anticipated at the onset of our studies. We have recently had the opportunity of detecting aortic coarctation in utero. We have noted

Fetal echocardiography-Applications

and limitations

0 C. S. KLEINMAN

et a/.

749

Fig. I. Hypoplastic left heart syndrome. Two-dimensional scan at mid-ventricular level at 32 weeks gestation. There is a marked disparity in ventricular dimensions, with a dilated right ventricle (RV) and hypoplastic left ventricle (LV).

also that our experience parallels that of previous authors (Allan et al., 1981) in that while the aortic narrowing was detectable upon careful evaluation, that increased right ventricular size was the most dramatic abnormality--calling the examiner’s attention to the “right heart” before attention was drawn to the left ventricular outflow tract and distal aorta. While we have correctly diagnosed structural cardiac disease in 34 patients, we have had occasion to incorrectly diagnose interventricular septal defect in two cases and transposition of the great arteries in one case. In each example in which we had incorrectly diagnosed interventricular septal defect, the interventricular septum was thought to be deficient of tissue in only one examining plane, during only a single examination. In the first case, we believed that the “four chamber” assessment suggested an interventricular septal defect, but on retrospective reevaluation we believe that we were actually orienting the transducer in a plane achieving an oblique view of the aortic outflow tract that is the equivalent to the “five chamber” apical view which shows the four cardiac chambers as well as the aorta in cross section (Fig. 2) (Silverman and Schiller, 1978; Weyman, 1982). The latter was thought to be a septal defect. In the second case the long axis left ventricular outflow tract view suggested aortic override of the interventricular septum with a normal pulmonary root (Fig. 3). The diagnosis of double outlet right ventricle was entertained. Again, this defect was viewed in only one tomographic plane. In neither case was an interventricular septal defect detected postnatally by the physicians caring for the infants. Unfortunately, nei-

ther infant was examined by us echocardiographically after birth in order to determine whether there was anything “unusual” about the plane of the interventricular septum, which could have confounded our imaging techniques. Both Silverman et al. (1982) and Allan et al. (1981) have reported the false positive diagnosis of interventricular septal defect. We have decided that due to the complex shape of the interventricular septum, which defies complete visualization in any single tomographic plane (Gussenhoven and Becker, 1983), we will not make the diagnosis of interventricular septal defect unless the defect is visualized consistently on several examinations and can be visualized in more than one tomographic examining plane. One patient, undergoing study near term due to a history of maternal glucose intolerance, was thought to have a fetus with complete transposition of the great arteries. This diagnosis was based on visualization of the “sweep” of an arching vessel from the right ventricular outflow tract to its continuity with the descending aorta. The arching vessel subsequently proved to be, of course, the ductus arteriosus. This emphasized the importance of identifying both the ductus arteriosus and the aortic arch in fetuses in whom arterial origins are in question. Identification of the great arterial branches from the aortic arch is the most important diagnostic finding and must be insisted upon in order to establish aortic “identity” (Fig. 4). Similarly, we are aware of having “missed” two examples of an interventricular septal defect that subsequently led to neonatal congestive cardiac fail-

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Fig. 2. Four-chamber view of the fetal heart at 26 weeks gestation. Arrow denotes area that could be mistakenly identified as a defect within the atrioventricular septum. This represents an oblique view including a portion of the left ventricular outflow tract (LA, left atrium; RA, right atrium).

me. One case was in a patient followed in our clinic and one was diagnosed by a pediatric cardiologist in a neighboring state. Both children underwent catheterization and angiography and were noted to have multiple small muscular interventricular septal defects. Neither patient has required cardiac surgery

and our patient has had these defects subsequently undergo spontaneous closure. In the case of the patient followed at Yale, we were unable to visualize the trabecular ventricular septal defects on post-natal echocardiographic study. We have falsely diagnosed normality in the case of

Fig. 3. Sagittal (long-axis) scan of left ventricular outflow tract at 30 weeks gestation. In this plane there appears to be a large outflow ventricular septal defect with aortic override. At birth there was no defect found (Ao, aorta).

Fetal echocardiography-Applications

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Fig. 4. Distal portion of aortic arch and continuity with the descending aorta. Curved arrow demonstrates great arterial branch from arch, which distinguishes this structure from the fetal ductus arteriosus.

a child subsequently noted to have tetralogy of Fallot. Retrospectively, we believe that the study that was obtained was technically sub-optimal and should have been interpreted as such. Only a brief view of a “normal” four-chamber view was obtained and on the basis of this finding the study was interpreted as “normal”. We, of course, recommend that judgment be reserved concerning the integrity of the outflow portion of the septum and arterial outflow tracts until these structures are well visualized, preferably from multiple tomographic planes, ideally on more than one occasion. We view this unfortunate experience to have been part of what otherwise was a “painless” learning curve. We have recently encountered the first case in which a neonate we had scanned in utero was diagnosed to have an ostium secundum atria1 septal defect. This fetus had been scanned at 38 weeks gestation, due to an irregular fetal cardiac rhythm. The fetus was diagnosed to have isolated atria1 extrasystoles. These parents were informed, as are all parents whose fetuses are scanned in our laboratory, that atria1 communications at the level of the foramen ovale and patent ductus arteriosus are normal in utero and that persistent patency of these communications cannot be commented upon on the basis of in utero imaging studies.

RHYTHM ANALYSIS

We have recently reported our use of M-mode recording of cardiac motion against time for the analysis of fetal cardiac rhythm disturbances (Kleinman et al., 1983). Several authors have since reported similar experiences (DeVore et al., 1983; Allan et al., 1983). With the increased interest of perinatologists in fetal cardiac rate and rhythm as an index for the assessment of fetal well being, there has been increased awareness of the frequency of cardiac rhythm disturbances. We have analyzed cardiac rhythm disturbances in almost 200 fetuses during the past 5 yr. Most of these fetuses have been found to have isolated extrasystoles (mostly supraventricular, N = 145) with occasional ventricular extrasystoles (N = 9). With rare exception these extrasystoles resolve spontaneously later in gestation or during the first five days of life. We have encountered 18 patients with sustained supraventricular tachyarrhythmias. Fourteen of these patients had supraventricular tachycardia and three had atria1 flutter with varying degrees of atrioventricular block. One patient had atria1 fibrillation in

utero. Of the 14 patients with supraventricular tachycardia, gestational ages varied from 29 to 34 weeks.

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Thirteen of 14 patients had hydrops fetalis at the time of referral. Using fetal echocardiography for diagnosis and monitoring of therapy, successful control of the in utero arrhythmia was achieved in 13 of these 14 cases, utilizing digoxin alone in seven cases, digoxin plus verapamil in four cases, and digoxin plus propranolol in two cases. In the 14th case, postnatal treatment was successful after failure of digoxin plus propranolol to control the arrhythmia. The experience with atria1 flutter was encouraging with two of the three fetuses succumbing with hydrops fetalis. In one case (Fig. 5) the nature of the arrhythmia did not become apparent until the ventricular response was “slowed down” by a combination of digoxin plus verapamil, thus demonstrating the role of echocardiography both for initial diagnosis as well as for monitoring of the response to therapy. The patient with atria1 fibrillation converted to sinus rhythm after administration of maternal digoxin. We have not noted the Wolff-Parkinson-White syndrome postnatally in any of the 14 patients with supraventricular tachycardia or in the two survivors of atria1 flutter or fibrillation. While postnatal studies have demonstrated the feasibility of noting abnormal ventricular wall and/or interventricular septal motion in patients with preexcitation (Feigenbaum, 198 I), we are unaware of any such studies in utero and would be reluctant to suggest that pre-excitation could be diagnosed with any degree of reliability in utero, especially in the absence of a high fidelity simultaneous fetal electrocardiographic signal. It should be noted that while we continue to employ digoxin as the “drug of choice” in the treatment of fetal supraventricular tachycardia (a condition, we view as life-

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threatening, especially in the presence of hydrops fetalis), there are data to suggest that digoxin may have a detrimental effect upon patients with Wolff-Parkinson-White syndrome, by facilitating conduction in the accessory conduction pathway (Sellers et al., 1977). Such reports exist in pediatrics, but have rarely been associated with deterioration of the patient. The use of digoxin in this setting must, however, be approached with care (Gillette and Garson, 1981). We have recently encountered recurrent tachycardia at a rate of 180/200 beats per minute in the fetus of a mother with gestational diabetes mellitus. During tachycardia the fetus’ respiratory rate increased to SO/l00 breaths per minute. Despite the absence of hydrops fetalis, we reasoned that fetal tachypnea was suggestive of fetal distress and that transplacental therapy was in order. The mother received Digoxin therapy without complication. Fetal tachycardia was still noticed on multiple occasions, but tachypnea appeared to resolve. No further medication was added to the regimen. Post-natal electrocardiograms demonstrated that the arrhythmia was unifocal ventricular tachycardia without compromise of the neonate. The digoxin had, indeed, been administered inappropriately. This case demonstrates several points-(a) therapy should be reserved for the compromised (edematous) fetus with sustained tachycardia; (b) therapy of tachycardia is probably not needed for tachycardia below 200 beats per minute; and (c) even with close evaluation of atrioventricular activation sequence the echocardiogram may not provide an adequate means for diagnosis of sustained tachyarrhythmia.

Fig. 5. M-mode echocardiogram at 30 weeks gestation in fetus with tachycardia and severe hydrops fetalis. After administration of digoxin and verapamil had resulted in atrioventricular block, the ventricular response rate slowed (curved arrows) allowing rapid flutter waves to be recognized by their effect on atrioventricular valve motion (vertical arrows).

Fetal echocardiography-Applications

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Fig. 6(A). Cross sectional scan at diaphragmatic level in a 34 week fetus with atria1 isomerism. The descending (DAo) and inferior vena cava (IVC) are side-by-side. The Doppler sample volume is in the IVC.

Pulsed Doppler echocardiography We have recently added range-gated pulsed Doppler echocardiography for the evaluation of the fetal heart. Using a duplex imaging system, it has become possible for us to better define the identity of vascular structures within the fetal cardiovascular system through the identification of characteristic

E :C Cl F

T F

Fig. 6(B). Doppler

E

N

I3

blood flow profiles. This may, for example, enable us to distinguish with a greater degree of confidence the great arteries from great veins (Fig. 6). Pulsed Doppler flow analysis may also enable the examiner to detect atrioventricular or semilunar valve insufficiency. The use of range-gated pulsed Doppler flow analysis for the detection of retrograde ascending aortic flow in

RWG -!

wave form generated

aorta

from inferior vena cava in the fetus whose two-dimensional is seen in Fig. 6(A).

scan

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the hypoplastic ascending aorta of a patient with aortic-mitral atresia and left heart hypoplasia has recently been described (Silverman et al., 1984). The addition of this modality offers a means of improving the sensitivity and specificity of in utero cardiac diagnosis. One must, however, be aware of the relatively high energy levels delivered by many currently available pulsed Doppler systems. These high energy levels are related to the high repetition frequencies involved in Doppler examination. The inclusion of pulsed Doppler analysis as a “routine” screening technique for in utero heart disease should, therefore, be discouraged until the examiner is confident that the power output of his equipment is within approved limits and/or that the potential risks are outweighed by the potential benefits of such examination. In reflecting upon our initial seven year experience in the field, another interesting problem has become apparent. This is totally unrelated to shortcomings of the imaging technique itself but relates rather to the evaluation of fetuses who are in severe distress and who are unlikely to survive to term. Our evaluation of the neonate with congenital heart disease is largely based upon our familiarity with the gradual in utero adaptation that occurs to structural cardiac malformations (Rudolph, 1974). The high rate of spontaneous abortion encountered in our in utero population suggests that we are evaluating, to some extent, a different population of patients than we have in the past. Our previous experience, even with the critically ill neonate in the delivery room or the neonatal intensive care unit, has been with the survivor of a

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natural selection process that had gone on during in gestation. Many of the patients being diagnosed utero (e.g. massive cardiac tumors with virtual absence of functional ventricular cavities, or single atrioventricular connection with a single hypoplastic ventricular cavity) (Fig. 7) have not had adequate circulatory compensation and are in the process of being “selected out.”

CONCLUSION

We have concluded on the basis of a seven year experience, therefore, that the human fetal heart can be effectively imaged during the second and third trimesters utilizing commercially available ultrasound equipment. The information generated in these studies may be put to use in formulating management plans for the conduct of the remainder of pregnancy, delivery and the neonatal period. Because this information may be applied for the formulation of in utero treatment plans (e.g. for treatment of arrhythmias) or for planning premature delivery or even elective termination of pregnancy, it is critical that a high level of confidence be achieved. This can best be attained utilizing a “team approach,” involving the pediatric cardiologist and perinatologist. It is also important that if intervention is to be entertained as a possibility there be an appreciation of the natural history of the conditions being evaluated and treated. It is, therefore, apparent that we may, with commercially available imaging equipment, obtain tomographic images of the fetal heart. The accurate

Fig. 7. Two-dimensional scan in a 32 week fetus with Severe hydrops fetalis. Only a single small ventricular could be identified. The ventricular walls are markedly hypertrophic (PE, pericardial effusion).

cavity (V)

Fetal echocardiography-Applications

interpretation of this information and the effective application of these data for the furthering of our understanding of developmental cardiovascular physiology and for attainment of the ultimate goal of pragmatic application of this information for the development of effective in utero treatment protocols will continue to require a long “learning curve.” Acknowledgemenl-This National Foundation.

work was supported March of Dimes.

by a grant from the

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Gussenhoven E. J. and Becker A. E. (1983) Congenital Heart Disease: Morphologic Echocardiographic Correlations. Churchill Livingstone, Edinburgh. Keith J.-D., Rowe R. b. and Vlad P. (1978) Heart Disease in Infuncv and Childhood. 3rd Edn.. D. 35 I. MacMillan. New York. Kleinman C. S., Hobbins J. C., Jaffe C. C., Lynch D. C. and Tamer N. S. (1980) Echocardiographic studies of the human fetus: Prenatal diagnosis of congenital heart disease and cardiac dysrhythmias 65, 10591067. Kleinman C. S., Donnerstein R. L., DeVore G. R., Jaffe C. C., Lynch D. C., Berkowitz R. L., Talner N. S. and Hobbins J. C. (1982) Fetal echocardiography for evaluation of in utero congestive heart failure. New Engl. J. Med. 306, 568-575. Kleinman C. S., Donnerstein R. L., Jaffe C. C., DeVore G. R., Weinstein E. M., Lynch D. C., Talner N. S., Berkowitz R. L. and Hobbins J. C. (1983) Fetal echocardiography, A tool for evaluation of in utero cardiac arrhythmias and monitoring of in utero therapy: analysis of 71 patients. Am. J. Curdiol. 51, 237-243. Kleinman C. S. and Santulli T. V., Jr. (1983) Ultrasonic evaluation of the fetal human heart. Seminar in Perinatol. 7, 9&101. Rudolph A. M. (1974) Congenital Diseases of the Heart. Yearbook Medical Publishers, Chicago. Sellers T. D., Bashore T. M. and Gallagher J. J. (1977) Digitalis in the pre-excitation syndrome. Analysis during atria1 Circulation 56, 26c-267. fibrillation. Silverman N. H. and Schiller N. B. (1978) Apex echocardiography: a two-dimensional technique for evaluation of congenital heart disease. Circulation 57, 503-5 11. Silverman N. H., Snider A. R., Golbus N. S. and Stanger P. (1982) Perspectives on fetal echocardiography ler Symposium International d’echocardiologie foetale. Milupa, Strasbourg pp. 95111. Silverman N. H., Enderlein M. A. and Golbus M. S. (1984) Am. J. Cardiol. 53, 391-392. pp. Weyman A. E. (1982) Cross-sectional Echocardiography, 122- 123. Lea & Febiger, Philadelphia.