Persistent left superior vena cava: clinical importance and differential diagnoses

1Persistent left superior vena cava (PLSVC) may lead to significant clinical symptoms and may affect surgical management.PLSVC may accompany various congenital cardiac diseases as well as heterotaxy spectrum.To be aware of the differential diagnoses of PLSVC is essential for correctly interpreting left-sided mediastinal vascular structures.

2Persistent left superior vena cava (PLSVC) may lead to significant clinical symptoms and may affect surgical management.

3PLSVC may accompany various congenital cardiac diseases as well as heterotaxy spectrum.

4To be aware of the differential diagnoses of PLSVC is essential for correctly interpreting left-sided mediastinal vascular structures.

5Persistent left superior vena cava (PLSVC) is a rare vascular anomaly that begins at the junction of the left subclavian and internal jugular veins, passes through the left side of the mediastinum adjacent to the arcus aorta. It mostly drains into the right atrium via the coronary sinus (CS). Although PLSVC is infrequent among all vascular anomalies, it is the most common thoracic venous anomaly. Mostly, PLSVC is asymptomatic and detected incidentally in diagnostic and therapeutic examinations due to different reasons. However, it can be discovered as a component of the complex cardiac pathologies and may lead to significant problems such as arrhythmia.

6There are different modalities for evaluation of PLSVC, such as perinatal echocardiography, multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), and invasive angiography. The advantages, disadvantages of these modalities, and optimal techniques for imaging of PLSVC are shown in Table 1.

7In this article, we will describe the epidemiology, embryology, and anatomic variations of PLSVC. Possible accompanying cardiac anomalies (CA) and heterotaxy spectrum will be reviewed with the help of MDCT images. The radiological pitfalls with their CT imaging features that may help make the differential diagnosis, and the clinical importance of PLSVC will be highlighted.

8The exact frequency of PLSVC is not known because PLSVC is often asymptomatic and is detected incidentally. There is no significant difference in its prevalence between males and females. The prevalence of PLSVC ranges from 0.2 to 3% in the general healthy population. In patients with congenital heart disease (CHD), its prevalence ranges between 1.3 and 11%. Additionally, the prevalence of PLSVC is thought to be higher in the prenatal period since the accompanying anatomic anomalies, including heart defects, may cause spontaneous abortions and premature deaths.

9The primitive venous system consists of three paired veins: vitelline veins (VV), umbilical veins (UV), cardinal veins (CV). Superior and inferior CVs are essential structures that allow the blood to return from the cranial and caudal parts of the embryo to the primitive heart. They combine to form common CVs (or the duct of Cuvier) draining into the double horned sinus venosus. The caudal part of the right superior CV, together with the common CV, forms the right superior vena cava (RSVC). Generally, the left common CV and the caudal part of the left superior CV will regress. If these veins do not regress, then they will persist as PLSVC. The detailed schematic anatomy of the developmental stages of the primitive venous system is shown in Fig. 1.

10Different hypotheses regarding the development of PLSVC have been proposed. One of these is “low left atrial pressure theory.” According to this theory, in the presence of anomalies, which may cause reduced left atrial pressure and insufficient development of the left atrium, such as atrioventricular septal defect (AVSD), the left atrium will be smaller than expected. Thus, it will not be able to compress the CS and left CVs adequately. As such, the left common CV and caudal part of the left superior CV will not regress, and PLSVC will develop. Some hypotheses suggest the vice versa. According to the “obstructive theory” hypothesis, the presence of PLSVC, which may cause an increase in CS size, could lead to the formation of a left-sided obstructive lesion because of the space restriction.

11PLSVC is responsible for approximately 20% of the total venous blood return from the left arm, left half of the head and neck. The right atrial drainage is seen in 80–90% of cases, while the left atrial drainage accounts for the remaining 10–20%. Generally, it joins into the right atrium through the CS and mostly has no hemodynamic effect. However, CS ostial atresia may accompany PLSVC. In that case, PLSVC becomes the major retrograde drainage pathway for coronary veins unless collateral drainage pathways develop between the coronary sinus and the heart chambers. The left atrial drainage, which is rare, occurs directly via the left atrial appendage or indirectly through the left pulmonary veins or the CS. In some sources, the latter is defined as an unroofed CS or CS atrial septal defect. The association of the atrial septal defect (ASD) and PLSVC draining into the left atrium via unroofed CS is called as Raghib syndrome (Fig. 2a–f).

12Left atrial drainage is a cause of right-to-left shunt and is mostly accompanied by CA. However, it was reported that this condition might also be observed without any cardiac defects.

13It has been reported that the drainage of more than the expected venous blood volume into the right atrium leads to some changes in the heart anatomy. Of those, the most well-known is the enlargement of the CS, which is a helpful clue indicating PLSVC existence. This enlargement may rarely reach the aneurysmatic level (Fig. 2g, h). There are also other anatomical changes reported in the literature, and they are described in Table 2, together with possible underlying mechanisms.

14In up to 90% of the cases, the right superior vena cava (RSVC) accompanies PLSVC, and this situation is known as double SVC (DSVC). If the caudal part of the right superior CV regresses in the intrauterine period, RSVC cannot develop, resulting in the presence of isolated PLSVC (IPLSVC). Mostly, IPLSVC is associated with CA and cardiac situs disorders. However, there are examples of IPLSVC without any accompanying apparent CA in the literature. In cases of DSVC, dimensions of RSVC may be larger or smaller than PLSVC (Fig. 3a–c).

15In 65% of the cases, DSVC runs along each side of the mediastinum without interconnection. However, there could be the left brachiocephalic vein (LBCV) connecting them, which is also called the bridging vein (BV) (Fig. 3d, e).

16To date, many CA associated with PLSVC have been identified and grouped in different ways. Shunt lesions (Figs. 4 and 5), conotruncal malformations (CTMs) (Figs. 6 and 7), left-sided obstructive lesions (LOLs) (Fig. 8), right-sided lesions, and single ventricular anomalies (Fig. 9) constitute the main CA groups. Aortic arch anomalies are also associated with PLSVC (Figs. 10 and 11). The subgroups of these anomalies are listed in Table 3. Besides, a summary of the literature about PLSVC and accompanying CAs is compiled in Table 4. Additionally, heterotaxy forms another disease spectrum associated with PLSVC and will be discussed under a separate title.

17In the literature, there is a wide range of information about the frequency of cardiac anomalies accompanying PLSVC. According to Lendzidan et al., the most common cardiac anomalies accompanying PLSVC are single ventricle, atrioventricular septal defect (AVSD), and tetralogy of Fallot (TOF). Cha et al. reported that the most frequent concomitant anomaly is ASD, whereas, according to Eldin et al., complete atrioventricular septal defect comes the first.

18Moreover, attention has been drawn to the relationship of some specific cardiac anomalies with PLSVC in many publications. In addition to left-sided pathologies such as mitral atresia, cor triatriatum, and hypoplastic left heart, transposition of the great arteries (TGA) and tricuspid atresia are other rarer anomalies that have been reported to be closely related to PLSVC in the literature.

19Different cardiac anomalies come to the fore in different situations such as type of accompanying cardiac anomaly (cyanotic or acyanotic), presence of heterotaxy, and drainage location of PLSVC. Different parameters, such as odds ratio and PLSVC index, are calculated in the literature and used to determine the relationship between PLSVC and cardiac anomaly. In some publications, cardiac anomalies accompanying PLSVC were grouped and evaluated as in Table 3, and in others, they were examined separately.

20Association of PLSVC with aorta-related pathologies such as right-sided arcus aorta (RAA) and coarctation of the aorta (CoA) have also been emphasized in the literature. It was mentioned that the association of PLSVC with RAA is approximately 16%. In another study, CoA was reported to be an independent and powerful factor for the existence of PLSVC. Gustapane et al. underlined the coexistence of PLSVC with coarctation of the aorta (CoA) (21.3%) and suggested that fetuses with PLSVC that are detected in the antenatal period should be followed during pregnancy in terms of CoA development.

21The term heterotaxy comprises situs inversus and situs ambiguus (right/left isomerism) (Fig. 12). DSVC or IPLSVC anomalies may be present in patients with heterotaxy. Meanwhile, in a study, “patients with both IPLSVC and situs inversus” were considered normal because of mirror image and excluded. In contrast, “patients with both isolated RSVC and situs inversus” were regarded as abnormal and accepted as SVC anomaly.

22According to the literature, PLSVC-heterotaxy coexistence is frequently observed, and PLSVC is present in 50–70% of heterotaxy cases. Additionally, it is informed that 45% of patients with PLSVC in the antenatal period have accompanying heterotaxy. In a study, DSVC is detected in nearly half of patients with heterotaxy. Another study reported that 72% of heterotaxy patients with SVC anomaly have DSVC, while the remaining have IPLSVC.

23According to a study, while right atrial isomerism in patients with PLSVC is about 7%, left atrial isomerism is about 9%. In another study, those prevalences are nearly 15% and 30%, respectively. It was stated that the absence of inferior vena cava (IVC) is associated with left atrial isomerism, while the juxtaposition of IVC is observed in right atrial isomerism (Fig. 13).

24Complete atrioventricular septal defect, right ventricular outflow tract obstruction (RVOTO) (pulmonary stenosis and atresia), and double outlet right ventricle (DORV) are found as the most common accompanying anomalies of PLSVC in patients with heterotaxy (Table 4, Fig. 14). The presence of concomitant heterotaxy and atrioventricular septal defect in patients with PLSVC during the antenatal period has been associated with poor prognosis.

25Berg et al. reported that they never saw CS dilatation, which is a well-known sonographic finding supporting the presence of PLSVC, in the heterotaxy group. The absence of CS dilatation has been associated with unroofed CS, which is found in almost all heterotaxy cases. It should be kept in mind that the absence of CS dilatation does not exclude the presence of PLSVC in patients with heterotaxy during the antenatal period, and the possibility of concomitant unroofed CS anomaly is high.

26The clinical significance of PLSVC depends on the drainage site and the accompanying anomalies. PLSVC without CA is generally asymptomatic and is detected as an incidental finding. In the case of PLSVC with right atrial drainage, the CS often expands (Fig. 2g, h). This enlargement may cause compression of the atrioventricular node and His bundle. So, it can lead to cardiac arrhythmias, such as atrial/ventricular fibrillation. The compression of the left atrium and decreased cardiac output may occur due to this enlargement. Moreover, the presence of CS dilatation may complicate mitral valve surgery due to the close anatomic relationship.

27In a recent study by Yun Gi Kim et al., it was demonstrated that PLSVC plays a considerable role in the induction and maintenance of atrial fibrillation (AF) in nearly half of the patients. So, pre-radiofrequency catheter ablation cardiac imaging in AF patients is useful and necessary for not only the evaluation of pulmonary venous anatomy but also for the detection of PLSVC existence. If PLSVC is detected as the trigger or driver of AF, it can be ablated (Fig. 2c).

28It is crucial to know the PLSVC existence in advance in invasive procedures, such as central venous catheter (CVC) insertion (Fig. 2a, b), cardiac resynchronization therapy leads, or pacemaker implantation. It may complicate pacemaker implantation by causing fixation difficulties of the electrode due to the tortuous course. CVC insertion without fluoroscopy may cause angina, hypotension, and heart perforation. Furthermore, there may be constriction or atresia of the CS ostium. In this case, the catheterization will be challenging and may result in serious complications, such as dangerous arrhythmias, cardiogenic shock, and tamponade.

29The presence of CS ostial atresia is also critical in the operations that require PLSVC ligation. In this case, the CS still drains the blood from the coronary veins to the right atrium via the retrograde PLSVC-LBCV-RSVC pathway, instead of the atretic ostium. The ligation of PLSVC will be catastrophic due to the acute interruption of the cardiac venous drainage.

30The left atrial drainage of PLSVC (Fig. 2d–f), sometimes, remains asymptomatic because it does not cause a right-to-left shunt at a significant level. In cases where the shunt is more pronounced, as a result of desaturation, the condition manifests itself with severe cyanosis, syncope, reduced exercise tolerance, and progressive fatigue. Thromboembolic events and even brain abscesses may develop in these patients. In this case, treatment can be done in two ways based on anatomy: PLSVC can be ligated if there is an adequate sized BV, and PLSVC can be re-anastomosed to the CS if the BV is not adequate in size or there is no RSVC.

31The knowledge of PLSVC is fundamental in some cardiac surgeries such as venous rerouting procedures, operations with cavo-pulmonary anastomosis (Glenn, Fontan), and heart transplantation. In heart transplantation surgery, if PLSVC without BV is present in the recipient’s heart, the bicaval anastomosis technique will be performed. It requires separation of the CS of the donor’s heart for the establishment of the recipient’s PLSVC anastomosis to the donor’s right atrium.

32In the case of unknown PLSVC, retrograde cardioplegia, a common practice for cardiac surgeries for myocardial protection, will be ineffective. Clamping of PLSVC may be required for the prevention of retrograde flow. However, cardioplegia may fail even after clamping of PLSVC, due to the steal effect by the hemiazygos venous system linked to PLSVC.

33During cardiopulmonary bypass, not knowing PLSVC existence may result in both surplus blood return through the right atrium and insufficient venous return to the pump. This problem is mostly encountered in pathologies such as pulmonary atresia, tricuspid atresia, TOF, where increased systemic venous pressure gets over the level of left atrial pressure.

34With the help of screening echocardiography, PLSVC can be detected as early as in the prenatal period. It can be used as a marker for cardiac or non-cardiac embryopathy. It may require extensive evaluation to exclude possible developmental anomalies. In cases with CHD, symptoms will be mainly due to these anomalies.

35In the presence of the vessel on the left side of the aorta in the mediastinum, other vascular structures apart from PLSVC should be considered in the differential diagnosis. They are vertical vein, levoatriocardinal vein, left superior intercostal vein, aberrant left brachiocephalic vein, pericardiophrenic vein, and vascular structures secondary to surgery.

36To make the definitive diagnosis, features which should be taken into consideration are as follows: “origin site,” “drainage site,” “orientation of the route between the origin and drainage site according to mediastinal structures,” “the expected direction of the blood flow,” and “characteristics of accompanying cardiac and non-cardiac diseases.” According to the above-mentioned features, a comprehensive summary of the differential diagnoses of PLSVC is depicted in Fig. 15.

37Some masses on the expected course of PLSVC could be confusing at first look due to their location. For making the differential diagnosis, it is essential to follow all of the slices carefully and see the beginning and end of the mass (Fig. 16).

38Moreover, an interesting variant of PLSVC, which has an intra-atrial course within the left atrium, has been identified recently. If this pitfall variant is not known, it may be misunderstood as left atrial cystic mass, may cause patient anxiety, and may lead to unnecessary effort for further investigations.

39The vertical vein (VV) is the vessel that drains the blood from the pulmonary veins into the LBCV in the presence of supracardiac type total or partial APVD (TAPVD or PAPVD) (Fig. 17). It may be left- or right-sided. The left APVD accounts for approximately 18% of all PAPVD and left superior pulmonary veins are affected mostly. The left-sided VV is one of the differential diagnoses of PLSVC. The critical point in the distinction is the caudal continuity of the vessel with atrial chambers. If there is no continuity, it is compatible with the VV. However, PLSVC may have a direct connection with the left pulmonary veins. In this scenario, the pulmonary vein drains into the left atrium after joining PLSVC.

40There are also some auxiliary features to differentiate PLSVC and VV. The expected flow direction is craniocaudal in PLSVC, while it is caudocranial in the VV. In the case of PLSVC, there are two vessels in the anterior aspect of the left main bronchus: one of them is PLSVC, and the other one is the left superior pulmonary vein. Ordinarily, only the left superior pulmonary vein is expected to be at this location. However, in the case of the VV with PAPVD, no vessel is seen in the anterior aspect of the left main bronchus. The size of the LBCV can also be helpful in finding for differentiation. In the case of APVD, the LBCV and RSVC may be of large caliber because the VV transports blood via these venous structures. On the other hand, PLSVC, frequently, is associated with an absent or small-sized LBCV.

41The levoatriocardinal vein (LACV) is the interatrial connection that originates from the left atrium (68%) or pulmonary vein (32%). It drains into one of the systemic venous structures, mostly, into the LBCV (48%) (Figs. 18 and 19).

42The differentiation of LACV from PLSVC with right atrial drainage is straightforward. Because this drainage site is unlikely for the levoatriocardinal vein. Similarly, in cases where PLSVC drains into the left atrium via the unroofed CS, unroofed CS and ASD facilitate the differential diagnosis in favor of PLSVC, since they are unusual for LACV.

43However, PLSVC may drain directly into the left atrium or pulmonary vein. In this situation, the expected origin and drainage site of those two vessels will be the same, and it is necessary to search other features for distinguishment. The anatomical feature that may help distinguish is their relative orientation according to the left pulmonary artery. PLSVC is seen in the anterior aspect of the left pulmonary artery, while the LACV is in the posterior aspect. The evaluation of the flow direction with echocardiography or velocity-encoded cine magnetic resonance imaging is another way to make differential diagnoses. The blood flows in the caudocranial direction in the LACV while it flows craniocaudal direction in the PLSVC. However, the bidirectional flow could be seen in the levoatriocardinal vein.

44Moreover, the caudocranial flow may be observed in PLSVC when there is atresia or stenosis of the CS ostium. Identification of accompanying CA may also help in the differential diagnosis. If LOLs without ASD are present, LACV should be considered in the differential diagnosis, firstly. It is hypothesized that, in the presence of in utero LOLs such as mitral stenosis, collaterals between pulmonary and systemic circulations cannot regress due to increased pressure in the left atrium and remain as LACV in the postnatal period. However, in the presence of complex CA, the diagnosis of PLSVC should be considered mainly.

45LACV could be isolated without any CA, like PLSVC. Nevertheless, the frequency of this probability is very low for LACV compared to PLSVC. Additionally, they may be seen together, and the LACV may drain into PLSVC.

46The pericardiophrenic veins (PCPV) are responsible for pericardial and diaphragmatic venous drainage. They lie along the lateral border of the heart and mediastinum, accompany pericardiophrenic arteries/phrenic nerve and drain into the internal thoracic, superior intercostal, or BCV. Due to the connection with inferior phrenic veins, dilated PCPVs could be observed as a collateral pathway in cases of SVC or IVC occlusion. Besides, they can serve as a collateral route via portosystemic shunting in portal hypertension (Fig. 20).

47In the case of catheters located at the left paramediastinal region, the left PCPV is one of the possible differential diagnoses. In posteroanterior chest X-ray, left PCPV has a lateral course along the left heart border, while PLSVC turns medially near the left atrium. Although they both are located in the middle mediastinum and connected with left brachiocephalic vein cranially, their caudal courses differ in CT imaging. While the caudal end of PLSVC is either the coronary sinus or the left atrium, the left pericardiophrenic vein moves toward the diaphragm lateral to the heart when it is followed from top to bottom.

48The left superior intercostal vein (L-SICV) drains the blood from the second, third, and fourth left intercostal veins into RSVC through the hemiazygos/azygos venous systems. Ordinarily, it can be seen as a small aortic nipple (1.4–5%) on the chest radiograph and is indistinguishable in CT. If its diameter exceeds 4.5 mm, it should be considered as abnormal. In the case of occlusion of SVC at the distal level of the azygos vein, the connection between SVC and IVC becomes possible with the dilation of L-SICV and other collateral vessels (Fig. 21).

49Furthermore, L-SICV may dilate in congenital conditions such as hypoplasia of LBCV, and diseases leading to volume overload such as congestive heart failure. In such cases, L-SICV might be confused with PLSVC. However, knowing their courses and drainage sites will facilitate the diagnosis.

50Aberrant left brachiocephalic vein (ALBV) is a rare anomaly (≈ 1%) and is often associated with CAs, such as TOF, septal defects, and right atrial isomerism. Ordinarily, the LBCV passes through the anterior of the arcus aorta and connects with the right BCV. In the presence of an aberrant course, the LBCV begins with the junction of the left subclavian and jugular veins, moves inferiorly along the left side of the mediastinum, and joins to the right BCV passing behind the ascending aorta or esophagus. Retroesophageal ALBV is a more rare variation (Fig. 22).

51Vascular structures located on the left side of the mediastinum in patients with the history of cardiac surgery performed for complex CA may also be included in the differential list of PLSVC. The differential diagnosis could be made by knowing the performed surgery and demonstrating the drainage site of the vessel. Bicaval Glenn shunt, the left-sided Blalock-Taussig (BT) shunt, and collateral vessels after Fontane surgery are possible differentials (Fig. 23).

52Bicaval Glenn shunt is an anastomosis of both SVCs to pulmonary arteries in the presence of PLSVC. The Glenn shunt allows the direct drainage of venous blood into the pulmonary arteries via bypassing the right heart chambers.

53BT shunt is one of the surgical methods for complex CA. In this procedure, the connection of the subclavian artery and the pulmonary artery is enabled via the graft placement.

54In Fontan surgery, the SVC and IVC are anastomosed to the pulmonary artery. After surgery, collaterals, which may be seen as large vessels on the left side of the mediastinum, may develop and may be confused with PLSVC.

55In conclusion, PLSVC is the most common thoracic venous anomaly known to be mostly asymptomatic. However, contrary to common misconception, it may cause a number of clinically significant symptoms, even in a heart with normal anatomy. Likewise, it may significantly affect the proper approaches to heart transplantations, effective surgical treatments for complex cardiac anomalies, and ablative procedures for cardiac arrhythmias. Thus, it should be recognized correctly and reported explicitly in radiological reports, even when it is an incidental finding. Besides, it is important to be aware of differential diagnoses of PLSVC and their radiological features to correctly interpret the vascular structures on the left side of the mediastinum.