During embryonic life, the venous blood enters the heart through the cardinal veins and sinus venosus. Owing to drainage of venous blood to the right side through the innominate vein, the right sinus horn and anterior cardinal vein ultimately become the superior caval vein, whereas the left sinus horn and anterior cardinal vein are diminished and form the coronary sinus (Fig 1).
Figure 1 Development of the superior caval vein (SVC) in the structurally normal heart, persistent left SVC, and absent right with persistent left SVC.
A persistent left superior caval vein is the most common thoracic venous anomalyReference Choi, Anderson and Macartney 1 – Reference Yuce, Kizilkan, Kus, Davutoglu and Sari 3 and is found when the left anterior cardinal vein fails to close. In 2.4% of foetuses with persistent left superior caval vein,Reference Berg, Knüppel and Geipel 4 the right anterior cardinal vein obliterates (Fig 1). The left superior caval vein is then fed through retrograde flow in the brachiocephalic vein and empties into the coronary sinus. This in turn drains into the right atrium, except in 1–10% of cases where the coronary sinus remains unroofed and communicates with the left atrium,Reference Postema, Rammeloo, van Litsenburg, Rothuis and Hruda 2 , Reference Sheikh and Mazhar 5 – Reference Buirski, Jordan, Joffe and Wilde 7 which in turn leads to arterial desaturation due to the shunting of blood from right to left.Reference Postema, Rammeloo, van Litsenburg, Rothuis and Hruda 2 , Reference Neema, Manikandan and Rathod 6 Absent right and persistent left superior caval vein are found in 0.05–0.07% of the general population and in 0.007–0.14% of hearts with congenital cardiovascular malformations.Reference Sheikh and Mazhar 5 , Reference Buirski, Jordan, Joffe and Wilde 7 – Reference Waikar, Lahie, De Zoysa, Chand and Kamalanesan 10
Foetal echocardiography can in the three-vessel view visualise the absent right superior caval vein with persistent left superior caval vein. In the normal three-vessel view, the pulmonary artery, the aortic arch, and the right superior caval vein form a line from left to right. In cases with absent right and persistent left superior caval vein, the three-vessel view also shows three vessels in a line, but the left superior caval vein is to the left and the aortic arch is to the right (Fig 2). Another marker is the dilated coronary sinus.Reference Postema, Rammeloo, van Litsenburg, Rothuis and Hruda 2 , Reference Sheikh and Mazhar 5 , Reference Waikar, Lahie, De Zoysa, Chand and Kamalanesan 10 – Reference Gologorsky, Macedo, Carvalho, Govindaswamy and Salerno 11 In the four-chamber view, this anomaly can be mistaken for an atrioventricular septal defect or an inlet ventricular septal defect,Reference Barrea, Ovaert, Moniotte, Biard, Steenhaut and Bernard 12 (Fig 3).
Figure 2 Three-vessel view of the absent right superior caval vein in situs solitus. This view can give the false impression of transposition of the great arteries.
Figure 3 Four-chamber view at the level of the large coronary sinus that gives the appearance of atrioventricular septal defects. The AV-valves were structurally normal and there was no ventricular septal defect detected after delivery.
Absent right superior caval vein is associated with additional congenital heart disease in about half the patients.Reference Bartram, Van Praagh, Levine, Hines, Bensky and Van Praagh 9 It is commonly associated with cardiac situs anomaliesReference Buirski, Jordan, Joffe and Wilde 7 , Reference Gologorsky, Macedo, Carvalho, Govindaswamy and Salerno 11 and seems to be associated with atrial septal defects, atrioventricular septal defect and tetralogy of Fallot, as well as arrhythmias.Reference Bartram, Van Praagh, Levine, Hines, Bensky and Van Praagh 9 Furthermore, persistent left superior caval vein is associated with a relative obstruction of the left atrioventricular inflow caused by the dilated coronary sinus,Reference Postema, Rammeloo, van Litsenburg, Rothuis and Hruda 2 , Reference Bartram, Van Praagh, Levine, Hines, Bensky and Van Praagh 9 , Reference Barrea, Ovaert, Moniotte, Biard, Steenhaut and Bernard 12 subsequently resulting in aortic stenosis and coarctation of the aorta.
We wished to study the consequences of absent right superior caval vein in situs solitus as an incidental finding on prenatal ultrasonic malformation screening at the national referral hospital of Denmark. Our aim was to familiarise obstetric sonographers and paediatric cardiologists with the condition as well as its consequences and pitfalls. To our knowledge, although the condition in adults is well-described in the literature, the consequences of diagnosing it prenatally have not been adequately addressed.
Material and methods
This is a retrospective case series study of all foetuses diagnosed with absent right superior caval vein at the national referral hospital, Rigshospitalet, in Denmark from 2009 to 2012. No patients were lost to follow-up. Rigshospitalet conducts standard prenatal ultrasound screening as well as specialised foetal echocardiography. If standard screening at regional hospitals raises suspicion of cardiac malformations, the patient is referred to Rigshospitalet where foetal echocardiography is carried out by trained foetal cardiologists.
All patients diagnosed with absent right superior caval vein during this period were included. The mothers’ obstetric records as well as prenatal ultrasounds were reviewed, and prenatal findings along with obstetric complications were described. Invasive procedures and genetic investigations, if any, were reported.
The newborns’ medical records were reviewed and the method of delivery, gestational age, and complications during delivery were recorded. The neonatal period was described and any symptoms or objective findings were reported. Postnatal ultrasounds were assessed and compared with the prenatal ultrasounds.
Follow-up was carried out at 1–3 months of age. The medical records were reviewed for any contact with the hospital during the following 1–4 years.
Ethical protocol was followed.
Results
Over a period of 4 years, five foetuses were diagnosed with absent right superior caval vein. In three cases, the anomaly was an incidental finding during a standard prenatal ultrasonic screening for malformations at gestational age 19–22 weeks. In cases 2 and 3, the women were referred to foetal echocardiography as the standard screening had raised suspicions of a cardiac anomaly. The atrial arrangement was situs solitus in all five foetuses, all atrioventricular and ventriculoarterial connections were concordant and no extra-cardiac anomalies were detected.
In this study, we describe the prenatal and postnatal findings in the individual cases. Prenatal and postnatal cardiac anomalies in each patient are described in Table 1.
Table 1 Associated cardiac anomalies and outcome in five cases of absent right and persistent left superior caval vein.
ass.= associated; CoA=coarctation of the aorta; dCS=dilated coronary sinus; HAA=hypoplastic aortic arch; HAV=hypoplastic aortic valve; HMV=hypoplastic mitral valve; LA=left atrium; L–R=left to right; PH=pulmonary hypertension; PDA=persistant ductus arteriousus; PFO=persistant foramen ovale; RVH=right ventricular hypertrophy; TI=triscupid insufficiency; VD=ventricular disproportion; VES=ventricular extrasystoles; and VSD=ventricular septal defect
* Re-referred for evalutation at 3 years of age due to irregular heart beat and heart murmur
Case 1
During a standard prenatal ultrasound at gestational age 20+3, the foetus was found to have an absent right and persistent left superior caval vein. Foetal echocardiography performed the same day confirmed the diagnosis.
The flow in the brachiocephalic vein was right to left. The left caval vein emptied into a dilated coronary sinus, but there was no obstruction of inflow to the left ventricle.
The left ventricle and mitral valve were of normal size, but the aortic arch was assessed to be slightly smaller than normal.
Furthermore, the foetus was suspected of having minor muscular ventricular septal defects.
Follow-up foetal echocardiography every 3 weeks due to oligohydramnios for the remainder of the pregnancy showed no change in the condition, and as heart function was found to be normal no further measures were taken.
Amniocentesis was carried out according to the local protocol and the genetic analysis was normal.
The girl was born at full term and was not admitted to the Neonatal Intensive Care Unit for observation after delivery. Postnatal echocardiography at 2 months confirmed the diagnosis of absent right superior caval vein, but no ventricular septal defect could be identified. Ventricles, valves, and aortic arch were of normal size, but the coronary sinus was dilated.
Final follow-up echocardiography was carried out a year later and no development in the condition was found.
During a standard child examination at age 3, an irregular heart rate and heart murmur were found. After tests had been carried out, these were found to be extrasystoles and a Still’s murmur, and no further actions were taken.
Case 2
The diagnosis was made at gestational age 22+5. Although the brachiocephalic vein could not be visualised, it was assumed that the flow would have to be retrograde. No other anomaly was found; however, during follow-up foetal echocardiography at 28 and 34 weeks of gestation, the mitral and aortic valves were found to be considerably smaller than the tricuspid valve and the pulmonic valve (z-scores, respectively, −4.1 and −6.4 versus −0.9 and 0.7). The aortic arch was deemed hypoplastic (z-score unavailable). The left ventricle was evaluated to be smaller than the right ventricle, but its function was normal.
No genetic analysis was carried out.
The boy was born at full term and received full Apgar Scores at 1 and 5 minutes. Postnatal echocardiography after 24 hours revealed absent right and persistent left superior caval vein, a normal aortic arch, an insignificant persistent arterial duct, and a small muscular ventricular septal defect. The right ventricle was slightly dilated with a tricuspid insufficiency gradient of 50 mmHg. Electrocardiogram showed right ventricular hypertrophy. The boy, however, had no respiratory problems, saturated 100% without supplementary oxygen, and was discharged from the Neonatal Intensive Care Unit. Additional echocardiographies showed full regression of pulmonary hypertension and ventricular septal defect at 3 months of age.
Case 3
At gestational age 21+1, the foetus was found to have absent right and persistent left superior caval vein. Flow from right to left was seen in the brachiocephalic vein, draining into the left superior caval vein, which in turn emptied into a dilated coronary sinus. There was no obstruction of the left atrioventricular inflow and no ventricular disproportion or dysfunction was observed.
Follow-up foetal echocardiography at 30 weeks of gestation revealed a subjectively slightly hypoplastic mitral valve, aortic valve, and aortic arch as well as a small left ventricle with normal function.
The foetus also presented with polyhydramnios and macrosomia, and flow measurements and weight scans were carried out every 2 weeks for the remainder of the pregnancy. No gestational diabetes, foetal hydrops, or incompensation were found and therapeutic amniocentesis was carried out once. At this time, genetic analysis was carried out according to local protocol, and the karyotype was found to be normal.
The boy was delivered by caesarean section at gestational age 38+1 because of macrosomia. His Apgar score was 9 at 1 minute and 10 at 5 minutes. Postnatal echocardiography performed the same day confirmed the diagnosis and showed a left ventricle that was slightly smaller than the right, but with normal function. Follow-up echocardiography 4 days later revealed a small atrial septal defect with a left-to-right shunt. He was discharged from the Neonatal Intensive Care Unit after 4 days of observation. Final echocardiography after 2 months did not show an atrial septal defect or a small left ventricle.
Case 4
The diagnosis was suspected during a routine scan at gestational age 20+0, and was confirmed by foetal echocardiography the next day. Retrograde flow was found in the brachiocephalic vein, which emptied into the left caval vein. The caval vein drained into the coronary sinus, which was not found to be dilated.
Discrete hypoplasia of the aortic arch was noted, as the diameter was 50% of that of the pulmonary trunck. The left ventricle was of normal size and function.
At week 26 of gestation, there was some ventricular disproportion, the left ventricle being subjectively smaller than the right, but its function was still normal. At 31 weeks of gestation, the foetus had signs of coarctation of the aorta, and at 39 weeks slight tricuspid insufficiency.
Genetic analysis by amniocentesis offered according to local protocol was normal.
The boy was born at gestational age 41+3, and received normal Apgar scores of 9 and 10 at 1 and 5 minutes, respectively. He received treatment with continuous positive airway pressure for 5 minutes due to grunting. Pulse oximetry was normal.
At the Neonatal Intensive Care Unit, a systolic heart murmur was found. Echocardiography 3 days after birth revealed an insignificant persistent foramen ovale and a possible ventricular septal defect, but no signs of coarctation of the aorta. Neither foramen ovale nor a ventricular septal defect were found during the follow-up echocardiography at 2 months of age, and the child did not have a heart murmur.
Case 5
Case 5 was a twin pregnancy. Twin A was, at gestational age 19+0, found to have absent right and persistent left superior caval vein, which was fed through the braciocephalic vein and emptied into the coronary sinus. Twin B had no heart anomalies. Follow-up foetal echocardiography was carried out at 21 and 28 weeks of gestation, and the condition was stationary with no hypoplasia of the aortic arch, left ventricle, or valves.
Flow measurements and weight scans were carried out every week for the remainder of the pregnancy.
The risk for Down’s syndrome was greater than 1:300 due to an enlarged nuchal fold, wherefore chorionic villus biopsy was secured at 12 weeks of gestation and was found to be normal.
The girl was delivered by acute caesarean section at gestational age 34+3, as the mother developed severe preeclampsia. Apgar score was 8 at 1 minute and 10 at 5 minutes. Shortly after birth, she developed respiratory distress. She received treatment with continuous positive airway pressure and supplementary oxygen and was admitted to the Neonatal Intensive Care Unit. After 6 days, she no longer needed continuous positive airway pressure.
Postnatal echocardiography after 24 hours confirmed the diagnosis of absent right superior caval vein and showed a slightly dilated left atrium with a persistent foramen ovale with a left-to-right shunt. There was also a persistent arterial duct with bi-directional flow.
After 10 days, follow-up echocardiography showed no persistent arterial duct or foramen ovale and the girl was discharged after 4 weeks.
Discussion
We have presented five cases of absent right with persistent left superior caval vein in situs solitus diagnosed prenatally. To our knowledge, this is the largest collection of absent right superior caval vein diagnosed in foetuses. In all cases, the finding proved to be a benign condition with no clinical manifestations or complications. This is in keeping with previous reports of isolated absent right superior caval vein found as an incidental finding at autopsy, during pre-surgical imaging, or during surgical procedures in asymptomatic individuals.Reference Sheikh and Mazhar 5 , Reference Waikar, Lahie, De Zoysa, Chand and Kamalanesan 10 , Reference Luo, Liu, Han, Zhou, Liu and Zhou 13
With the offer of prenatal screening for malformations, more cases of absent right superior caval vein in situs solitus can be diagnosed prenatally, raising questions about the prognosis and implications.
During standard prenatal ultrasonic scan for malformations, the heart is systematically reviewed in the screening for congenital heart defects. This always includes the four-chamber view, but not always the three-vessel view, depending on the experience of the examiner. As mentioned, a dilated coronary sinus can be misinterpreted as an atrioventricular septal defect, and in severe cases it may be misconceived as mitral atresia, as the mitral valve is located anteriorly and may not necessarily be seen in the four-chamber view.Reference Barrea, Ovaert, Moniotte, Biard, Steenhaut and Bernard 12 Furthermore, a dilated coronary sinus may also be caused by increased pressure in the right atrium, abnormal pulmonary or systemic venous return, or a fistulous connection with the coronary arteries. The finding of a dilated coronary sinus should, therefore, always lead to the evaluation of the three-vessel view.Reference Barrea, Ovaert, Moniotte, Biard, Steenhaut and Bernard 12 , Reference Uçar, Paşaoğlu, Ciçekçioğlu, Vural, Kocaoğlu and Aydoğdu 14
Previous studies have reported associated cardiac anomalies in 46–100% of the cases.Reference Choi, Anderson and Macartney 1 , Reference Lenox, Zuberbuhler and Park 8 , Reference Bartram, Van Praagh, Levine, Hines, Bensky and Van Praagh 9 Usually, the associated defect is depicted first, but the absence of the right superior caval vein should prompt a search for additional cardiac malformations, as they will determine the outcome.Reference Barrea, Ovaert, Moniotte, Biard, Steenhaut and Bernard 12 The direction of blood flow is of great importance, and should the left superior caval vein drain directly into the left atrium surgery is needed regardless of the associated anomalies.Reference Luo, Liu, Han, Zhou, Liu and Zhou 13
None of our five patients presented with unroofed coronary sinus or anomalies associated with reduced flow through the left ventricle, such as coarctation of the aorta, aortic stenosis, or hypoplasia of the left ventricle; four patients were suspected of small muscular ventricular septal defects prenatally or postnatally, but follow-up echocardiography found the ventricular septum to be intact. Only one patient had pulmonary hypertension, but full regression was found at 3 months of age. Arrhythmias are associated with absent right superior caval vein, but electrocardiograms were only available in two cases – one showed right hypertrophy due to pulmonary hypertension and the other was diagnosed with extrasystoles at the age of 3 years.
Few studies could be found where the association between absent right superior caval vein and extra-cardiac malformations was investigated, which Barrea et al call to attention.Reference Barrea, Ovaert, Moniotte, Biard, Steenhaut and Bernard 12 In their study of 27 patients with anomalous systemic venous return, 14 (52%) – including one patient with absent right superior caval vein – had associated extra-cardiac anomalies. Bearing this in mind, although none of our patients had any extra-cardiac malformations, vigilant investigation should be undertaken in these patients.
No genetic anomaly was detected in our case series. This is in keeping with the findings of Barrea et al, who did not find any abnormal karyotype in four patients with absent right superior caval vein;Reference Barrea, Ovaert, Moniotte, Biard, Steenhaut and Bernard 12 however, they did find five patients (26%) with persistent left superior caval vein with chromosomal anomalies, which corresponds to the 23% reported by Postema et al.Reference Postema, Rammeloo, van Litsenburg, Rothuis and Hruda 2
Invasive procedures such as central catheters, pacemaker implantation, and cardiac surgery can be challenging if the right superior caval vein is absent.Reference Postema, Rammeloo, van Litsenburg, Rothuis and Hruda 2 , Reference Luo, Liu, Han, Zhou, Liu and Zhou 13 , Reference Alemzadeh-Ansari, Shafiee and Yaminisharif 15 Catheter insertion through the left or right subclavian vein will enter the right atrium unexpectedly through the coronary sinus, necessitating a longer lead, which may not be available at the time of the procedure.Reference Alemzadeh-Ansari, Shafiee and Yaminisharif 15 Positioning the lead in the right atrial appendage is challenging, as the opening into the right atrium from the coronary sinus is very close to the right ventricular inlet, and the procedure requires careful manipulation.Reference Rizkallah, Burgess and Kuriachan 16 Furthermore, when the chosen approach of the procedure is impossible due to the anomaly, the necessary adaptation of the procedure may increase the risk of arrhythmiasReference Gologorsky, Macedo, Carvalho, Govindaswamy and Salerno 11 , Reference Chovanec, Krajina, Hůlek, Mest'an and Renc 17 or other complications such as puncture of the atriumReference Rizkallah, Burgess and Kuriachan 16 or the liver capsule.Reference Chovanec, Krajina, Hůlek, Mest'an and Renc 17 During open-heart surgery, it is important to bear in mind the changed anatomy when selecting perfusion techniques to ensure adequate venous drainage and myocardial protection.Reference Neema, Manikandan and Rathod 6 , Reference Buirski, Jordan, Joffe and Wilde 7 , Reference Gologorsky, Macedo, Carvalho, Govindaswamy and Salerno 11 , Reference Luo, Liu, Han, Zhou, Liu and Zhou 13
With the increased use of central catheters, pacemaker implantation, and cardiac surgery, knowledge of this anomaly is important to prevent future complications and morbidity.
Conclusion
Isolated absent right superior caval vein is frequently a benign condition, but when it is diagnosed prenatally it is important to carry out investigations to detect any associated anomalies, this being intra-cardiac, extra-cardiac, or chromosomal, as this is crucial to guide parental counselling and management appropriately. Furthermore, diagnosis of isolated absent right superior caval vein is important, because knowledge of the anomaly can prevent future problems when invasive procedures are necessary.
Acknowledgements
None.
Financial Support
This research received no specific grant from any funding agency, commercial, or not-for-profit sectors.
Conflicts of Interest
None.
Ethical Standards
This research followed national guidelines for ethical standards.
