Liat Gindes, MD, Julian Hegesh, MD, Gad Barkai, MD, Jeffrey M. Jacobson, MD, Reuven Achiron, MD

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Isolated Levocardia Prenatal Diagnosis, Clinical Importance, and Literature Review Liat Gindes, MD, Julian Hegesh, MD, Gad Barkai, MD, Jeffrey M. Jacobson, MD, Reuven Achiron, MD

Objective. Isolated levocardia is a rare type of situs inversus in which the heart is in the normal levo position, but the abdominal viscera are in the dextro position. We aim to describe our experience with prenatal diagnosis and management in fetuses with isolated levocardia. Methods. Of all the cases referred to our tertiary ultrasound unit, 3 cases of isolated levocardia were diagnosed. Patients and fetuses were evaluated every 4 weeks until delivery and postnatally. Results. Two of the 3 fetuses had interruption of the inferior vena cava with azygous continuation. However, postnatal evaluation revealed polysplenia in 1 neonate and asplenia in another. Polysplenia was also diagnosed in the third neonate, who had a normal inferior vena cava on antenatal examination. One neonate had a small ventricular septal defect. Conclusions. Fetal isolated levocardia is associated with a good outcome, in which other malformations are excluded. Therefore, we suggest conservative management in such cases. Key words: dextrogastria; levocardia; outcome.

Abbreviations IVC, inferior vena cava; SVC, superior vena cava

Received August 3, 2006, from the Departments of Obstetrics and Gynecology (L.G., G.B., R.A.) and Pediatric Cardiology (J.H.) and Pediatric Unit, Department of Diagnostic Imaging (J.M.J.), Chaim Sheba Medical Center, Tel Hashomer, Israel; affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Revision requested August 23, 2006. Revised manuscript accepted for publication October 9, 2006. Address correspondence to Liat Gindes, MD, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, 52621 Tel Hashomer, Israel. E-mail: [email protected]

I

solated levocardia is a rare type of situs inversus in which the heart is in the normal levo position, but the abdominal viscera are in dextro position. It has been described by Van Praagh et al1 as a distinct entity, not considered a part of situs ambiguous and heterotaxy (asplenia and polysplenia) syndromes. The estimated reported incidence is 1 per 22,000 in the general population and from 0.4% to 1.2% in all patients with congenital heart disease.2,3 It has been extensively reported that children and adults with isolated levocardia have complex cardiac defects, whereas the incidence of this association in fetuses is not known.4 The only information regarding the outcome of patients with this anomaly has been that of case reports on adults and children in whom the diagnosis was made incidentally or after abdominal surgery, particularly for a volvulus or bowel obstruction.3–6 Moreover, according to published data, the outcome is exiguous in children and adults. In only approximately 5% to 13% do patients survive for more than 5 years,2 mainly because of the severity of an associated cardiac abnormality.

© 2007 by the American Institute of Ultrasound in Medicine • J Ultrasound Med 2007; 26:361–365 • 0278-4297/07/$3.50

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Because, as a MEDLINE search revealed, there is no information regarding fetuses with isolated levocardia, prenatal counseling is difficult, and it is impossible to apply treatment and outcome data of adults and neonates to the prenatal period. Therefore, this study was conducted to describe prenatal diagnosis and management in 3 fetuses with isolated levocardia and to review the literature.

Materials and Methods Two patients were referred to our diagnostic ultrasound unit because of suspected dextrocardia or dextrogastria, and 1 patient was sent for a routine sonographic examination to rule out malformations. Sonographic examinations were performed with a 6.5- to 7.5-MHz transvaginal transducer or an abdominal 3.5- to 7-MHz curvilinear transducer (LOGIQ 9 system; GE Healthcare, Milwaukee, WI). Patients and fetuses were evaluated every 4 weeks until delivery. Postnatal imaging studies were performed by a certified pediatric cardiologist and a pediatric radiologist. Late outcome was verified with the patients.

Results Case 1 A 36-year-old woman at 25 weeks’ gestation with spontaneous twins was referred to our diagnostic unit because of suspected dextrocardia in one of the fetuses (Table 1). The woman was a known homozygous carrier of a 5,10-methylene tetrahydrofolate reductase mutation and had positive findings for antinuclear factor, and she was taking a regimen of low-molecular-weight heparin and aspirin. Sonography revealed male and female twins. The female fetus had a leftappearing heart and a right-sided stomach and Table 1. Major Findings in 3 Cases of Prenatal Isolated Levocardia Characteristic

Case 1

Case 2

Case 3

Sex Chromosomal aberration Isomerism in the thorax Spleen IVC present Azygous continuation

Female None None Polysplenia Yes* No

Male None None Asplenia No Yes

Female None None Polysplenia No Yes

*Left side.

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spleen. The gallbladder was located lateral to the umbilical vein in the right side. Fetal echocardiography showed situs solitus of the atria, the ventricles, and the main arteries. The inferior vena cava (IVC) and aorta were both on the left, and the superior mesenteric artery was on the right side. Sonographic evaluation of the male fetus revealed no abnormalities. Amniocentesis showed normal male and female karyotypes. Induction of labor was performed at 37 weeks’ gestation. Two neonates were delivered; birth weights were 2750 g (male) and 2645 g (female), and both had Apgar scores of 9 and 10 at 1 and 5 minutes, respectively. Postnatal sonography in the female neonate revealed a right-sided stomach, a rightsided, bilobular spleen with another small spleen (polysplenia), a left-sided large liver, and a left sided IVC. The kidneys and gallbladder appeared normal. No thoracic isomerism was evident on chest radiography. Cardiac echography revealed a normal heart with no abnormalities. At the latest follow-up, the 6-year-old child was developing well and in good health. Case 2 A 29-year-old woman underwent a routine sonographic examination at 22 weeks’ gestation. Pregnancy was achieved by in vitro fertilization by way of intracytoplasmic sperm injection because of teratospermia. Sonography revealed a male fetus with a left-sided, normal-appearing heart and right-sided stomach (Figure 1). The intrahepatic IVC was not discernible; rather, the azygous vein drained the abdominal venous flow. No cardiac abnormalities were found on a targeted echocardiographic scan. A presumptive diagnosis of IVC interruption with azygous continuation was suggested. Amniocentesis showed a normal male karyotype. At 38 weeks’ gestation, elective cesarean delivery was performed because of a breech presentation. The birth weight was 2950 g, and Apgar scores were 8 and 9 at 1 and 5 minutes. Neonatal cardiac echography revealed levocardia with an absence of the hepatic segment of the IVC and 2 small ventricular septal defects. Computed tomography of the chest showed subpleural and paramediastinal cysts without involvement of the lung parenchyma. Abdominal sonography and computed tomographic angiography revealed asplenia and an absent intrahepatic IVC; the superior J Ultrasound Med 2007; 26:361–365

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mesenteric vein entered the transverse liver, which had a small portal vein. Blood from the abdomen entered the heart via the azygous and hemizygous veins and the superior vena cava (SVC). Nephrolithiasis and undescended testes were also noted. After 7 days, the neonate was discharged in good health. At the 3-year follow-up, the child was developing well, and spontaneous closure of the ventricular septal defects has occurred. Figure 1. A, Case 2: male fetus with a left-sided, normalappearing heart (H). Arrows show the aorta (Ao) and the azygous vein (Azy). Lt indicates left side of the fetus; and Rt, right side of the fetus. B, Case 2: male fetus with a right-sided stomach (St). Arrows show the aorta and the azygous vein.

A

Case 3 A 34-year-old woman was referred to our unit for evaluation of dextrogastria detected during a routine scan at 23 weeks’ gestation. Sonography confirmed dextrogastria with levocardia, and the gallbladder was located in the midline. Hyperechogenicity posterior to the stomach was interpreted as a spleen. There were normal connections of pulmonary and hepatic veins to the fetal heart. The intrahepatic IVC was not identified, and azygous continuation to the SVC was visualized. A female fetus was delivered with a birth weight of 3885 g and Apgar scores of 9 and 10 at 1 and 5 minutes. Abdominal sonography revealed a transverse liver and 2 spleens on the right side and confirmed interruption of the IVC with azygous continuation. Findings from chest radiography and echocardiography were normal. After a long-term follow-up of 2 years, the child was healthy and developing well.

Discussion

B

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The lungs, liver, spleen, stomach, and atria are usually asymmetric organs. The term situs is used to define their position relative to the midline. Levocardia, dextrocardia, and mesocardia are general terms indicating the position of the cardiac apex only and do not give any sign of cardiac structure or body situs. Situs solitus is the normal arrangement of abdominal organs with levocardia and is associated with a less than 1% incidence of congenital heart disease.7 Situs inversus describes the mirror-image location of the heart and abdominal viscera and is almost always associated with dextrocardia. Individuals with this condition have a 3% to 5% incidence of congenital heart disease.7 Heterotaxy is a disorderly arrangement of organs and major blood vessels, which differ from situs solitus and situs inversus.8 Left and right isomerism in this situation refers to the presence of similar atria and lung lobes with corresponding abdominal anomalies. Cardiac malformations are extremely common in rightside isomerism (99%–100%) and very common in left side isomerism (90%).7 Isolated levocardia is an extremely rare condition in which the heart is located in the normal position; however, abdominal viscera are inverted.7 To our knowl363

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edge, no prenatal data are available in the literature. The only descriptions are of children and adults. Isolated levocardia in the neonate or infant may be complicated by bowel obstruction and cardiac anomalies. Duodenal obstruction may be due to peritoneal bands,3 an intraluminal web, or, rarely, an aberrant vessel (usually the superior mesenteric artery) crossing the duodenum.6 A volvulus of the gut is extremely rare. This syndrome may also present with splenic and cardiac defects. Most publications consider this entity a serious disease because it is associated with severe cardiac anomalies. Some minor cardiac defects have also been reported.3,4 Our series is unique in that it describes this entity in utero and provides long-term outcome. In contradiction to the literature, our first case had no cardiac defects, and the patient was healthy at 6 years old. The second case is interesting because asplenia was associated with intrahepatic interruption of the IVC. Interruption of the IVC is usually accompanied by polysplenia syndrome,7 as detected in case 3. We could find only 1 case report describing an adult with a combination of interruption of the IVC and asplenia, with a normal appearance of the lungs and heart.9 Because small accessory spleens are difficult to diagnose in utero, a meticulous abdominal scan of the neonate is indicated. The suggested workup in the prenatal evaluation of isolated levocardia should include determination of the situs, identification of heart anomalies, and detection of the major vessels and abdominal viscera. First, determine the cardiac position and situs. Once the fetal heart is located, we look at the cardiac structure. The complete heart examination includes the 4chamber view, definition of the atrial situs (identification of the venous connections and atrial structures, coronary sinus, septum primum, and septum secundum), the outflow tract, and the great artery view. Second, check the abdominal viscera: the stomach, liver, and gallbladder. When an ambiguous situs is found, careful assessment of the heart is mandatory, combined with a detailed search for syndromes such as polysplenia and asplenia (Ivemark syndrome). Subsequently, the abdominal blood vessels should be examined for interruption of the IVC, 364

which is usually associated with azygous continuation of the blood flow to the SVC. This can be easily diagnosed by 4-chamber views showing the azygous vein situated posterior to the aorta.8 Heterotaxic syndromes do not appear to carry an increased risk of chromosome abnormalities.10 Detection of IVC interruption may be helpful in the postnatal period because the incidence of overwhelming sepsis is increased in congenital asplenia, and a prophylactic lifelong antibiotic should be prescribed for the neonate. Our study confirmed the previous assumption that isolated levocardia is a distinct anomaly from heterotaxy syndrome because no lung isomerism (left or right) could be found. The absence of cardiac and pulmonary vein anomalies emphasizes this theory. Although, according to the literature, the prognosis of isolated levocardia is poor, we can speculate that cases of asymptomatic isolated levocardia were misdiagnosed and not included in the statistical evaluation. We think that with accurate, thorough sonographic examination and in the absence of congenital heart malformations and chromosomal aberrations, the risk for morbidity and mortality decreases, and parents should be counseled appropriately.

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Vijayakumar V, Brandt T. Prolonged survival with isolated levocardia and situs inversus. Cleve Clin J Med 1991; 58: 243–247.

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Ruscazio M, Van Praagh S, Marrass AR, Catani G, Iliceto S, Van Praagh R. Interrupted inferior vena cava in asplenia syndrome and a review of the hereditary patterns of visceral situs abnormalities. Am J Cardiol 1998; 81:111–116.

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Brown DL, Emerson DS, Shulman LP, Doubilet PM, Felker RE, Van Praagh SV. Predicting aneuploidy in fetuses with cardiac anomalies: significance of visceral situs and noncardiac anomalies. J Ultrasound Med 1993; 3:153–161.

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