Address correspondence to: Patricia A. Stewart, PhD, Dept.Ob-Gyn, Academic Hospital Rotterdam-Dijkzigt, Dr. Molewaterplein 40, 3015 GD Rotterdam, Netherlands. Ph: 31-10-463-3632; Fax: 31-10-408-7213

Synonyms: Atrioventricular - ventri­culo­arterial discordance, con­genitally corrected transposition of the great arteries. L-transposition.

Definition: Right heart: morphologic right atrium connected to morphologic left ventricle connected to pulmonary artery. Left heart: morphologic left atrium connected to morphologically right ventricle connected to ascending aorta.

Prevalence: 0.45:10,000 births, less than 1% of congenital heart disease.

Etiology: Multifactorial.

Pathogenesis: Anomalous looping of the primordia of the ventricle associated with lack of spiral rotation of the conotruncal septum².

Associated anomalies: Malposition of the heart and situs inversus are commonly encountered. The aortic valve is separated from the tricuspid valve by a complete infundibulum, and there is fibrous continuity between the pulmonary and mitral valve⁵. A ventricular septal defect is present in more than 50% of cases, with pulmonary stenosis also being present in approximately 50%. In some cases, the pulmonary artery overrides the ventricular septal defect^4,5. Atrioventricular valve abnormalities are frequent and include Ebstein type malformations and straddling of the tricuspid valve^4,5. Conduction system disturbances, principally atrioventricular block, may result from derangement of conduction tissue due to malalignment of the atrial and ventricular septa.

Diagnosis: Sequential analysis of the cardiac connections should allow this diagnosis to be made. The unexpected finding of the moderator band of the right ventricle and a more apically inserted tricuspid valve connected to a left-sided atrium with pulmonary venous connections is the most obvious “marker” on a 4-chamber view. Further sequential analysis of the great vessels will further clarify the discordant connections.

Differential diagnosis: In principle, there is  none; definition of the abnormal atrioventricular and ventriculoarterial connections should confirm the diagnosis.

Prognosis: When no associated anomalies are present, the disorder may be minimally symptomatic (except for some conduction disorders). Otherwise, it depends on the associated anomalies.

Management: Prenatal: If diagnosed before the legal limit for termination of pregnancy, this option may be offered to the parents. In continuing pregnancies, regular monitoring to detect signs of the fetal hydrops is recommended. Development of hydrops in the late third trimester might result in earlier delivery in order to optimize neonatal condition. If hydrops develops before viability/maturity, conservative management only may be provided.

Postnatal: Immediate transfer of the neonate to the pediatric cardiology unit is necessary, in particular to provide a realistic prognosis to the parents. Obviously, further treatment will depend on careful assessment of the anomalies.

MESH Transposition of great vessels BDE 0540 ICD9 745.12 CDC 745.120

Introduction

Inverted ventricles with transposition of the great vessels is a rare cardiac anomaly comprising less than 1% of liveborn congenital heart defects. Although the anomaly may remain undetected due to the “corrected” physiology, many of these hearts have serious associated defects^4,5.

Prenatal diagnosis is condsidered difficult, and as far as we are aware, this is the first report concerning this anomaly. Following the basic rules of sequential echocardiographic analysis clearly allows the diagnosis to be made accurately.

Case reports

Case 1

A 31-year-old G₂P_l Canadian patient was referred to this Department for prenatal diagnosis because of diabetes mellitus. In this unit, it is policy to perform amniotic fluid alpha-fetoprotein analysis to exclude open neural defects at 16 weeks gestation and a detailed fetal scan at 20 weeks to exclude major anomalies in diabetic patients. Following counseling, the parents refused the option of amniocentesis. The fetal survey was performed at 20 weeks and 4 days gestation, and a complex cardiac anomaly was discovered. There was a situs solitus. The four-chamber view showed a large ventricular septal defect and a morphologic right ventricle under the left atrium and a morphologic left ventricle under the right atrium (fig. 1).

Figure 1: Four-chamber view at 20 weeks and 4 days gestation. The right-sided left ventricle (LV) is identified by its smooth walled appearance and the basal insertion mitral valve. The left-sided right ventricle (RV) is identified by its more trabeculated pattern and the apical insertion of the tricuspid valve. LA=Ieft atrium.

Scanning of the great vessels revealed the pulmonary artery connected to the left ventricle and the ascending aorta connected to the right ventricle. Both great vessels appeared normal. A normal sinus rhythm was present.

A diagnosis of atrioventricular-ventriculoarterial discordance with a ventricular septal defect was made. Pulsed Doppler interrogation of all valves was normal, and there was a bi-directional shunt through the ventricular septal defect. No other structural anomalies were found. Chorionic villus sampling was performed thereafter, and a normal 46,XY karyotype was found. The parents elected to continue the pregnancy, and serial ultrasounds were advised. This was refused, as the parents felt that ultrasound was not yet “proven to be 100% safe”. They did, however, agree to one further examination which was performed at 30 weeks gestation. The findings were unchanged. Spontaneous delivery occurred at 32 weeks with a birth weight of 2200g. Postnatal echocardiography confirmed the diagnosis but showed that the anomaly was more complex than had been suspected. The tricuspid valve (left-sided) straddled the ventricular septal defect, and a large portion of the chordae tendinae inserted into the right ventricle. This meant that closure of the ventricular septal defect was impossible.

The only surgical possibility was felt to be a Fontan operation, whereby the pulmonary artery would be connected to the right atrium and the mitral valve (right-sided) would be closed. At an earlier stage a banding of the pulmonary artery would be required to reduce pulmonary blood flow. The parents returned to Canada a few weeks following delivery, and, unfortunately, further follow-up is unavailable to us.

Case 2

A 33-year-old G₂P_l was referred at 30 weeks and 5 days gestation because a fetal bradycardia was detected at routine obstetric care. Fetal biometry was consistent with the gestational age and, except for the heart, no structural anomalies were detected. There was a complete congenital heart block detected on M-mode echocardiography. The atrial rate was 155 beats per minute and the ventricular rate 53 beats per minute. On cross-sectional ultrasound there was a cardiomegaly, cardio-thoracic ratio 0.65. No other evidence of congestive cardiac failure was noted. A complex cardiac anomaly was also present. There was a situs solitus. The 4-chamber view showed a hypoplastic morphologic right ventricle under the left atrium and a morphologic left ventricle under the right atrium (fig.2).

Figure 2: Four-chamber view at 30 weeks and 5 days gestation. The right-sided left ventricle (LV) is identified by its smooth walled appearance and the less apical insertion (horizontal arrows) of the mitral valve. The hypoplastic left-sided right ventricle (RV) has a more trabeculated pattern and more apical insertion (oblique arrows) than that of the tricuspid valve. RA=right atrium. LA=Ieft atrium.

The pulmonary artery was connected to the left ventricle and was mildly dilated (8.4 mm). A narrowed (5.5 mm) ascending aorta was connected to the right ventricle.

A diagnosis of atrioventricular-ventriculoarterial discordance with hypoplastic right ventricle and ascending aorta and complete congenital heart block was made. Doppler investigation revealed a severe tricuspid insufficiency of 4.6 m/sec and normal antegrade profiles across the mitral, aortic and pulmonary valves.

Amniocentesis revealed a normal 46XY chromosome pattern. Weekly ultrasound followed to detect possible signs of increasing cardiac failure and an induced delivery was planned around the 38th week to optimize neonatal care. The patient went into spontaneous labor at 37 weeks and 3 days, and a male infant weighing 2565g was delivered vaginally.

Postnatal evaluation confirmed the antenatal diagnosis with the addition of severe valvular aortic stenosis. Operative intervention was not thought to be feasible, and the neonate suffered circulatory and respiratory collapse 48 hours postpartum as a result of functional aortic atresia. Postmortem confirmed the atrioventricular-ventriculoarterial discordance, hypoplastic right ventricle, and dysplastic tricuspid valve and revealed a stenotic unicuspid aortic valve.

Discussion

To our knowledge, the prenatal diagnosis of atrioventricular-ventriculoarterial discordance has not previously been published. It is considered a difficult prenatal diagnosis to make, especially in the absence of arrhythmias or other immediately obvious morphologic distortions of the four-chamber view.

Definition

In this cardiac anomaly, the morphologic right atrium is connected to morphologic left ventricle which is connected to the pulmonary artery. The morphologic left atrium is connected to the morphologically right ventricle, itself connected to the ascending aorta (fig. 3).

Figure 3: Normal heart (left) and ventricular inversion with transposition of the great vessels on the right. The pulmonary veins return to the left atrium, the aorta arises from the left side of the heart, but morphologically right-ventricle, while the pulmonary artery arises from the right-sided left-ventricle. The vena cavae return to the right atrium. RA: right atrium, RV: right ventricle, LA: left atrium, LV: left ventricle, Ao: aorta, PA: pulmonary artery, IVC: inferior vena cava, SVC: superior vena cava.

Hemodynamically, these anomalies should cancel one another out and, at times, are incidentally discovered at autopsy. However, in most cases other anomalies are also present.

Prevalence

This rare anomaly (0.45:10,000 births) represents less than 1% of congenital heart disease. The first case of congenitally corrected transposition of the great arteries was described by Karl von Rokitansky in 1875¹.

Embryology

The hypothesis of De la Cruz et al² suggests that the in the first stages the  embryonic heart is formed by the primordia of both ventricles (fig 4).

Figure 4: Diagram showing the normal embryology of the heart and abnormal ventricular looping resulting in atrioventricular ventriculo-atrial

discordance. RA: right atrium, RV: right ventricle, LA: left atrium, LV: left ventricle, Ao: aorta, PA: pulmonary artery.

Subsequently, while the primordia of both ventricles form a loop, both the caudal atrial segment and the cephalic conus (the primordia to the outflow tract) develop. Thereafter, the truncus appears. The aorticopulmonary septum, which has a spiral course, divides the truncus into aorta and pulmonary trunk. The conus becomes incorporated into the walls of the ventricle. In a normal relationship, the pulmonary artery is anterior and to the right of the aorta. It has been suggested that anomalous looping of the primordia of the ventricle associated with lack of spiral rotation of the conotruncal septum results in this disorder.

Associated anomalies

The term “corrected” transposition of the great arteries is rather ironic, considering that most of these hearts have associated, often severe pathology. Malposition of the heart and situs inversus are commonly encountered. The aortic valve is separated from the tricuspid valve by a complete infundibulum, and there is fibrous continuity between the pulmonary and mitral valves. A ventricular septal defect is present in more than 50% of cases with pulmonary stenosis also being present in approximately 50 percent. In some cases the pulmonary artery overrides the ventricular septal defect^4-5.

Atrioventricular valve abnormalities are frequent and include Ebstein type malformations and straddling of the tricuspid valve^4,5. Conduction system disturbances, principally atrioventricular block, may result from derangement of conduction tissue due to malalignment of the atrial and ventricular septa.

Diagnosis

If the basic rules of sequential echographic analysis are followed,⁶ it is clear that this serious anomaly can be accurately detected during pregnancy. The moderator band in the left-sided ventricle and more apical insertion of the atrioventricular valve in this ventricle are very specific of this condition.

Of particular interest in these two cases is that in case 1 a normal sinus rhythm was present and that the postnatal prognosis differed vastly from that prenatally. Careful postnatal review of the videotapes of the 2 ultrasound examinations did not alter the prenatally stated findings. This highlights the difficulties of prognosticating complex cardiac anomalies, in this case due to the inability of ultrasound to precisely define chordae tendinae morphology. The valve annulus itself was not seen to be straddling, and a possible explanation for this could be the “distortion” of the anatomy due to its complex anomaly.

In the 2^nd case, the prognosis was guarded prior to delivery as a result of the severe bradycardia, serious clearly detectable structural anomalies, and the hemodynamic effects of the tricuspid valve disease already present prior to birth. However, the functional aortic atresia seen following birth could not have been predicted by ultrasound, as clear antegrade flow was detected through the (narrowed) aortic valve using color, pulsed and continuous wave Doppler⁷. This again clearly demonstrates the difficulty of predicting the prognosis and can of course be explained due to the hemodynamic changes effected by birth.

Differential diagnosis

In principle, there is none as the abnormal atrioventricular and ventriculoarterial connections should allow the diagnosis.

Prognosis

When no associated anomalies are present, the disorder may be minimally symptomatic (except for some conduction disorders). Otherwise, it depends on the associated anomalies.

Management

The management of prenatally detected serious cardiac anomalies remains difficult. If diagnosis is made before the legal limit for termination of pregnancy (24 weeks in the Netherlands), this option should be discussed with the parents. In ongoing pregnancies, counseling with the pediatric cardiologists should be arranged and delivery planned to optimize the immediate care and transfer of the neonate.

References

1. Von Rokitansky K: Die Defekte der Scheidewände des Herzens. Vienna: Wilhelm Braumüller, pp. 83-86, 1875.

2. De la Cruz MV, Arteaga M, Espino-Vela J, et al:

Complete transposition of the great arteries: Types and morphogenesis of ventriculoarterial discordance. Am Heart J 102: 271-281, 1981.

3. Schiebler GL, Edwards JE, Burchell HB, et al: Congenital corrected transposition of the great vessels. A study of 33 cases. Pediatrics 27: 851-888, 1961.

4. Becker AE, Anderson RH: Pathology of congenital heart disease. London: Butterworths, 1981.

5. Bonfils-Roberts EA, Guller B, McGoon DC, et al: Corrected transposition. Surgical treatment of associated anomalies. Ann Thorac Surg, 17:200-209, 1974.

6. Gussenhoven WJ, Becker AE: Congenital heart disease: Morphologic echographic correlations. Edinburgh: Churchill Livingstone, 1983.

7. Stewart PA, Wladimiroff JW: Fetal echocardiography and color Doppler flow mapping. The Rotterdam experience. Ultrasound  Obstet Gynecol 3: 1-8, 1993.