Intrathymic and other anomalous courses of the left brachiocephalic vein in the fetus
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K. Karl (1), E. Sinkovskaya (2), A. Abuhamad (2), R. Chaoui (3) 1) Center for Prenatal Diagnosis, Munich, Germany 2) Division of Maternal-Fetal Medicine of the Department of Obstetrics & Gynecology at Eastern Virginia Medical School, Norfolk, VA, USA 3) Center for Prenatal Diagnosis and Human Genetics, Berlin, Germany Correspondence: PD Dr. med. Katrin Karl Tegernseer Landstraße 64, 81541 München-Germany
email: [email protected] Keywords: Left brachiocephalic vein, Left superior vena cava, Intrathymic vein, Subaortic left brachiocephalic vein, Retrotracheal vein. Summary Objective: The left brachiocephalic vein (LBCV) (innominate vein) connects the left jugular vein to the right superior vena cava. Its course is posterior to the thymus directly anterior and superior to the aortic arch. Pediatric and adult cardiology studies reported on the subaortic or retrotracheal courses of the LBCV or on the presence of double LBCV. We have recently observed in the fetus that the LBCV may have a course across the thymus or be absent in the presence of a left superior vena cava. The aim of this study was to report on the prevalence of isolated intrathymic and absent LBCV in fetuses undergoing second trimester ultrasound screening as well the prevalence of other courses in cardiac anomalies. Methods: In the prospective part of the study, consecutive obstetric ultrasound examinations were evaluated to assess for the presence and course of the LBCV. In the case-control part of the study the databases of two centers were reviewed for cardiac anomalies and the pattern and prevalence of the anomalous courses of the LBCV were reported Results: 1418 consecutive fetuses were examined prospectively. Intrathymic course of the LBCV with a typical bent shape was found in 1.76% (1:57) of cases and the absence of a LBCV in association with a persistent left superior vena cava (LSVC) in 0.28% (1:350) of cases. All fetuses with an isolated intrathymic course or absence of the LBCV had a normal outcome. At 2 centers and over a period of 4.5 years, a total of 1544 fetuses with cardiac malformations were reviewed and anomalous LBCV was noted in 8 cases (0.5%) 6 subaortic, 1 retrotracheal, 1 double LBCV). Conclusion: A course of the LBCV across the thymus is a common condition and appears to be a normal variant in the fetus. The prevalence of a LSVC in a screening population is similar to that of previous reported studies. In cardiac malformations, anomalous courses of the LBCV are occasionally seen.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/uog.15795 This article is protected by copyright. All rights reserved.
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Introduction Recently, the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) recommended the inclusion of the three-vessel-trachea view in the guidelines for fetal cardiac screening [1]. The three-vessel-trachea view (3VT) includes visualization of the great vessels in the upper mediastinum [2] along with the thymus gland [3]. In a slightly cephalad plane to the 3VT view, the left brachiocephalic vein (LBCV) [4] can be seen. The LBCV also called innominate vein connects the left jugular vein to the right superior vena cava and crosses the upper mediastinum in an oblique plane anterior and superior to the aortic arch and posterior to the thymus gland [5-7]. In a previous study we have introduced normal reference ranges for the width of the LBCV during gestation and reported that its abnormal size can be a marker for the presence of supracardiac total anomalous venous drainage or vein of Galen arteriovenous malformation [4]. Furthermore, absence of the LBCV was observed in fetuses with left superior vena cava (LSVC)[4]. We have also noted that the course of the LBCV can occasionally run through the thymus gland, termed intrathymic course [4]. In pediatric and adult cardiology anecdotal reports and small studies are found on other anomalous courses of the LBCV, as double LBCV, subaortic or retrotracheal course. The present study was undertaken to explore the prevalence of isolated intrathymic course and absent LBCV in normal fetuses undergoing second trimester ultrasound screening. Furthermore, we reviewed our databases of cardiac anomalies to report on the prevalence and pattern of the other anomalous courses reported in postnatal studies. Material and methods In the prospective part of the study, ultrasound examinations performed in the second trimester between 18 and 24 weeks’ gestation were considered. Highresolution ultrasound equipment (Voluson E8, Voluson E10, GE Medical Systems, Zipf, Austria) and convex transabdominal transducers (RM-6C, RAB6C and 9L) were used. Pregnancies with fetal cardiac or extracardiac abnormalities were excluded from this part of the study with the exception of fetuses with an isolated LSVC. The prior performance of a first trimester ultrasound examination did not exclude the patient from study participation. Fetal cardiac evaluation was performed by the systematic cross-sectional approach of the fetal chest in gray scale and color Doppler based upon published guidelines [1]. Since our previous study [4], we have included the visualization of the upper mediastinum in a plane cephalad to the 3VT view depicting the LBCV in gray scale and color Doppler (Fig. 1) as part of cardiac screening performed at our ultrasound centers. An intrathymic LBCV course was defined by the presence of thymic tissue between the brachiocephalic arteries and the LBCV as shown in Figure 2. In order to properly assess the frequency of findings, the study was performed on consecutive fetuses. Only singleton pregnancies were included in the study. Pregnancy outcome was reviewed. Patients were informed on the occurrence of an anomalous course and those with LSVC were offered third trimester evaluation and postnatal echocardiography.
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In the retrospective part of the study we reviewed the databases of the last 4.5 years of two large fetal medicine centers for cardiac anomalies and searched for the prevalence and pattern of associated anomalous courses of the LBCV. The intrathymic course was not routinely documented in the databases and was therefore not evaluated.
Results In a period of 13 months (January 2014 to February 2015), 1437 fetuses underwent ultrasound examinations between 18 and 24 weeks´ of gestation. 16 fetuses (1.1%) were excluded due to maternal habitus or fetal positions in utero, which resulted in the inability to obtain adequate views of the upper mediastinum. Three additional fetuses were excluded, two fetuses due to the third trimester detection of muscular ventricular septal defects (VSD) and one fetus due to an unexplained intrauterine death in late gestation. In the remaining 1418 fetuses, an abnormal course or absence of the LBCV was noted in 29 fetuses (2%), including 25 fetuses (1.76 %) with an intrathymic course of the LBCV (Figure 2) and 4 fetuses (0.28%) with an absent LBCV in association with a LSVC and a right superior vena cava (Figure 3). All 29 cases with an abnormal course or absence of the LBCV had an uneventful postnatal outcome without additional anomalies. Between January 2011 and June 2015, 1544 fetuses with cardiac anomalies diagnosed after 15 weeks of gestation were seen in two fetal medicine centers of the authors. An abnormal course was found in 8 fetuses (0.5%). In this group a subaortic course of the LBCV was found in six fetuses, all in combination with a right aortic arch, two isolated and four in combination with pulmonary atresia with VSD. A double LBCV and a retrotracheal LBCV were found in one case each. Discussion The ultrasound assessment of the LBCV was not commonly performed until recently with the increased utilization of the 3VT view and other transverse views of the upper mediastinum in cardiac screening [4,8]. Similar to other abdominal, cardiac and intracerebral veins in the fetus [6,7,9,10], the LBCV shows variations in anatomy and course. Case reports and small series in infants and adults, primarily resulting from angiography and Magnetic Resonance Imaging (MRI), report on the anomalous course of the LBCV including its absence. In these small series, the presence of double LBCV [11,12] and its anomalous courses, either below the aortic arch called retro-aortic or sub-aortic [13-15] or behind the esophagus and trachea [12,16] have been described. To our knowledge a course across the thymus gland was not previously reported and based upon this study, the intrathymic course is a fairly common occurrence with normal neonatal outcome. The brachiocephalic veins are formed within the embryonic cardinal venous system between the 4th and 8th embryonic week. During this period, the anterior and posterior cardinal veins converge into the common cardinal veins and are responsible for the main venous drainage of the fetus. Anastomotic transverse veins are formed between the right and left cardinal veins, with drainage of blood from left to right ultimately resulting in regression of the left-sided veins. The LBVC is formed
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as an anastomotic transverse vein between the anterior cardinal veins with regression of the left anterior cardinal vein. A failure of the LBCV to form results in the persistence of the left anterior cardinal vein, as left persistent superior vena cava draining into the coronary sinus. The embryological background of an abnormal course of the LBCV is not completely understood, but the pattern of venous anomalies suggests that two transverse veins or even a large venous plexus connecting both right and left anterior cardinal veins exist during embryogenesis [13]. With growth of the aorta and pulmonary artery in the upper mediastinum, lower parts of the venous plexus are compressed and the LBCV is formed. In cases of abnormal branching of aortic arch or pulmonary artery as observed in right-sided aortic arch, the upper venous plexus is compressed resulting in an anomalous subaortic course of the LBVC due to sparing of the lower dorsal plexus (see for an overview Chen et al. [13]). The various courses of the LBCV, such as double LBCV, subaortic course, retrotracheal course and others can thus be explained by compression of various parts of the venous plexus. The retrotracheal course could however, be also a remnant of the accessory hemiazygous or superior intercostal vein. Intrathymic LBCV The present study shows that in approximately one out of 60 fetuses examined in mid-trimester, the course of the LBCV is not posterior to but across the thymus, a condition we called the intrathymic course [4]. The unusual bent course of the LBCV in these conditions (Figure 2) may surprise the ultrasound examiner when first encountered, and may result in unnecessary referrals of patients for fetal echocardiography. This study confirms the preliminary observation of the authors [4] that the intrathymic course is a common normal variant with no impact on fetal well-being. In our opinion there are two possible reasons why this variant is not reported in the pediatric and adult literature. The first is the larger size of the thymus in the fetus which becomes smaller after birth due to the physiologic subinvolution of the gland and the second is the fact that most studies on infants and adults are performed with angiography, which primarily focuses on the vascular anatomy of the upper mediastinum rather than on soft tissues. Absent LBCV in LSVC: Typically the LBCV is absent in the majority of fetuses with a LSVC when the right superior vena cava is present (Figure 3). Persistence of LSVC has been reported to occur as an isolated finding in about 0.3%, reported in one study on autopsies [17] and 0.5% of patients undergoing pacemaker implantation[18]. The prevalence in association with cardiac defects is much higher [19,20]. Our study confirms a prenatal prevalence of LSVC in 0.28% (1: 350 fetuses) in combination with an absent LBCV. In cases with LSVC and an absence of the right superior vena cava, a right brachiocephalic vein is observed instead of a LBCV. The presence of a LSVC in a fetus should not be considered as a variant before detailed ultrasound evaluation is achieved including a fetal echocardiogram to rule out associations with other abnormalities [21]. LSVC was reported as an isolated finding in 12.5 % of fetuses in two large series of 136 fetuses in two referral centers [19,20]. Associated abnormalities included chromosomal anomalies in 9%, heterotaxy syndrome in 40% and other cardiac malformations such as conotruncal anomalies, left ventricular outflow tract obstruction, especially aortic coarctation [19,20]. Referral bias in these two series however may have contributed to the low rate of an isolated LSVC [19,20].
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Subaortic or retroaortic course: The subaortic or retroaortic course of the LBCV is the most commonly reported anomalous or aberrant course of the LBCV in the pediatric literature [13,22,23]. This condition was reported typically in cases with a right aortic arch, in tetralogy of Fallot, in pulmonary atresia with VSD and other cardiac defects, often in combination with a right aortic arch. This course can be demonstrated in the fetus as well (Figure 4) and in all six fetuses with a subaortic course the finding was associated either with an isolated right aortic arch or in combination with pulmonary atresia with VSD. Retroesophageal and retrotracheal course: One very unusual course is a course behind the trachea and esophagus, similar to an aberrant right subclavian artery [12]. Such condition is reported as retrotracheal [12] or retroesophageal course [16]. This condition was first recently reported as a case report by Yigit et al. [12]. Ming et al. [16] reported 4 additional such cases. The anomalous LBCV has in such cases a course behind the heart and trachea and drains into the right superior vena cava. We detected this condition only once in a fetus (Fig. 5) presenting with a complex cardiac anomaly. Double LBCV: Few case reports exist in the literature on the presence of a double LBCV either isolated or as part of an additional cardiac anomaly [11,12]. In these cases both veins can be anterior to the aortic arch or one vein can have a course anterior to and the other vein either directly posterior to the arch or posterior to the heart and trachea [11,12,24]. Figure 6 shows the finding in the only fetus we found with this condition in combination with a tetralogy of Fallot (Fig.6). In summary, our findings suggest that the intrathymic course of the LBCV is present in about 1.76% of fetuses (1:57) and the condition has no clinical impact on fetal wellbeing if cardiac anatomy is otherwise normal. Our study was not designed to assess the frequency of the intrathymic course of the LBCV in fetal cardiac defects. In addition we found that in 0.28% of fetuses (1:350), a LSVC can be found with an absence of a LBCV. In addition for the first time ultrasound images of other abnormal courses of the LBCV such as the subaortic/retroaortic, the retrotracheal/retroesophageal and the double LBCV (Figure 3-6) are presented in this paper.
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Figures Figure 1: Schematic drawing A) and corresponding color-Doppler figure B) of a cross section of the upper mediastinum at a level slightly more cranial than the threevessel-trachea view. This plane shows the left brachiocephalic vein (LBCV) behind the thymus with a course from left posterior to right anterior draining into the superior vena cava (SVC). In this plane the aortic arch is not seen, as it is inferior to the LBCV. Note however that the three brachiocephalic arteries (Brach. Aa.) of the aortic arch are seen in cross section posterior to the LBCV. Figure 2: Schematic drawing A) and corresponding color-Doppler figures B) and C) of a cross section of the upper mediastinum in the same plane showed in figure 1, but with a course of the left brachiocephalic vein (LBCV) across the thymus called intrathymic course. The shape of the LBCV is not straight as in figure 1, but more bent. SVC, superior vena cava; Brach.Aa., Brachiocephalic arteries. Figure 3: Schematic drawing A) and corresponding gray-scale figure B) of a cross section of the upper mediastinum at the same level shown in figure 1. In this case there is a left persistent superior vena cava (LSVC) and the left brachiocephalic vein (LBCV) is absent. SVC, superior vena cava; Brach.Aa., Brachiocephalic arteries. Figure 4: Anomalous course of the left brachiocephalic vein (LBCV) below the aortic arch called subaortic/retroaortic LBCV demonstrated in gray-scale A) and in threedimensional color Doppler rendering (B). This fetus shows a right aortic arch (RAA) and a left ductus arteriosus (DA) with the trachea between both arteries. The LBCV, which has normally a course cranial to both great vessels is seen here in a course posterior to the great vessels. The LBCV drains into the superior vena cava (SVC). Figure 5: Anomalous course of the left brachiocephalic vein (LBCV) behind the heart and trachea as a retrotracheal / retroesophageal course. The plane is at the level of the three-vessel-trachea view with aortic arch (AO) and pulmonary artery (PA) visualized with the trachea. The anomalous LBCV has a course behind the trachea with blood flow from left to right draining into the superior vena cava (SVC). The fetus also has a complex cardiac malformation. Figure 6: Double left brachiocephalic veins (LBCV): Gray scale and color Doppler in axial (A and B) and sagittal (C) planes of the chest in a fetus with Tetralogy of Fallot at 23 weeks gestation. Note the presence of double LBCV with both veins (two arrows) having a course anterior to the aortic arch. Color Doppler (B) confirms flow from left (L) to right in both LBCV. In the sagittal plane two vessels are seen anterior to the aorta (Ao). The finding of double LBCV was an incidental finding in this fetus. Sup: Superior.
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atic drawin ng A) and correspond c ding color-Doppler fig gure B) of a cross Figure 1: Schema n of the up pper mediiastinum at a a level slightly more crania al than the e threesection vessel--trachea viiew. This plane p show ws the leftt brachioce ephalic vein (LBCV) behind the thymus with a course frrom left posterior to right r anterior draining g into the superior s vena ccava (SVC C). In this plane the aortic arcch is not seen, s as itt is inferiorr to the LBCV. Note howe ever that th he three brachioceph halic arteries (Brach.. Aa.) of the aortic arch arre seen in cross c section posteriior to the L LBCV.
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atic drawin ng A) and correspond c ding color-D Doppler fig gures B) an nd C) of Figure 2: Schema o the uppe er mediastinum in the same plane showe ed in figure e 1, but a crosss section of with a course of the left brachioce ephalic vein (LBCV) across th he thymuss called intrathyymic coursse. The sh hape of the e LBCV is not straig ght as in fiigure 1, bu ut more bent. SVC, S superrior vena ca ava; Brach h.Aa., Bracchiocephalic arteries
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Figure 3: Schem matic drawing A) and d corresponding gray y-scale figure B) of a cross section n of the up pper media astinum at the same e level sho own in figure 1. In th his case there iss a left perrsistent sup perior vena a cava (LS SVC) and the t left bra achiocepha alic vein (LBCV)) is absentt. SVC, sup perior vena a cava; Bra ach.Aa., Brrachioceph halic arterie es
eft brachioccephalic ve ein (LBCV V) below the aortic Figure 4: Anomalous coursse of the le arch ca alled subaortic/retroa aortic LBC CV demonsstrated in gray-scale e A) and in n threedimenssional color Doppler rendering (B). This ffetus show ws a right aortic arch h (RAA) and a lleft ductus s arteriosuss (DA) with h the trach hea betwee en both arrteries. The e LBCV which h has norma ally a coursse cranial to both grreat vesse els is seen here in a course posterio or to the great vesse els. The LB BCV drains into the su uperior ven na cava (S SVC)
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eft brachioccephalic ve ein (LBCV)) behind th he heart Figure 5: Anomalous coursse of the le achea as a retrotrach heal / retro oesophageal course. The plane e is at the level of and tra the thrree-vessel--trachea vview with aortic arcch (AO) and a pulmo onary arterry (PA) visualizzed with th he trachea. The anomalous LB BCV has a course be ehind the trachea with blo ood flow fro om left to rright drainiing into the e superior vena cava a (SVC). Th he fetus also ha as a complex cardiacc malformation.
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BCV): Grayy scale and d color Doppler in Figure 6: Double left brachiocephalicc veins (LB A and B) and a sagittal (C) plane es of the ch hest in a fe etus with Tetralogy T o Fallot of axial (A at 23 w weeks gesstation. No ote the prresence off double LBCV L with h both vein ns (two arrows) having a course an nterior to the t aortic arch. a Colo or Doppler (B) confirm ms flow eft (L) to rig ght in both LBCV. In the sagitta al plane tw wo vessels are seen anterior from le to the aorta a (Ao).. The findin ng of doub ble LBCV was w an inc cidental fin nding in thiis fetus. Sup: Superior
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K. Karl (1), E. Sinkovskaya (2), A. Abuhamad (2), R. Chaoui (3) 1) Center for Prenatal Diagnosis, Munich, Germany 2) Division of Maternal-Fetal Medicine of the Department of Obstetrics & Gynecology at Eastern Virginia Medical School, Norfolk, VA, USA 3) Center for Prenatal Diagnosis and Human Genetics, Berlin, Germany Correspondence: PD Dr. med. Katrin Karl Tegernseer Landstraße 64, 81541 München-Germany
email: [email protected] Keywords: Left brachiocephalic vein, Left superior vena cava, Intrathymic vein, Subaortic left brachiocephalic vein, Retrotracheal vein. Summary Objective: The left brachiocephalic vein (LBCV) (innominate vein) connects the left jugular vein to the right superior vena cava. Its course is posterior to the thymus directly anterior and superior to the aortic arch. Pediatric and adult cardiology studies reported on the subaortic or retrotracheal courses of the LBCV or on the presence of double LBCV. We have recently observed in the fetus that the LBCV may have a course across the thymus or be absent in the presence of a left superior vena cava. The aim of this study was to report on the prevalence of isolated intrathymic and absent LBCV in fetuses undergoing second trimester ultrasound screening as well the prevalence of other courses in cardiac anomalies. Methods: In the prospective part of the study, consecutive obstetric ultrasound examinations were evaluated to assess for the presence and course of the LBCV. In the case-control part of the study the databases of two centers were reviewed for cardiac anomalies and the pattern and prevalence of the anomalous courses of the LBCV were reported Results: 1418 consecutive fetuses were examined prospectively. Intrathymic course of the LBCV with a typical bent shape was found in 1.76% (1:57) of cases and the absence of a LBCV in association with a persistent left superior vena cava (LSVC) in 0.28% (1:350) of cases. All fetuses with an isolated intrathymic course or absence of the LBCV had a normal outcome. At 2 centers and over a period of 4.5 years, a total of 1544 fetuses with cardiac malformations were reviewed and anomalous LBCV was noted in 8 cases (0.5%) 6 subaortic, 1 retrotracheal, 1 double LBCV). Conclusion: A course of the LBCV across the thymus is a common condition and appears to be a normal variant in the fetus. The prevalence of a LSVC in a screening population is similar to that of previous reported studies. In cardiac malformations, anomalous courses of the LBCV are occasionally seen.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/uog.15795 This article is protected by copyright. All rights reserved.
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Introduction Recently, the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) recommended the inclusion of the three-vessel-trachea view in the guidelines for fetal cardiac screening [1]. The three-vessel-trachea view (3VT) includes visualization of the great vessels in the upper mediastinum [2] along with the thymus gland [3]. In a slightly cephalad plane to the 3VT view, the left brachiocephalic vein (LBCV) [4] can be seen. The LBCV also called innominate vein connects the left jugular vein to the right superior vena cava and crosses the upper mediastinum in an oblique plane anterior and superior to the aortic arch and posterior to the thymus gland [5-7]. In a previous study we have introduced normal reference ranges for the width of the LBCV during gestation and reported that its abnormal size can be a marker for the presence of supracardiac total anomalous venous drainage or vein of Galen arteriovenous malformation [4]. Furthermore, absence of the LBCV was observed in fetuses with left superior vena cava (LSVC)[4]. We have also noted that the course of the LBCV can occasionally run through the thymus gland, termed intrathymic course [4]. In pediatric and adult cardiology anecdotal reports and small studies are found on other anomalous courses of the LBCV, as double LBCV, subaortic or retrotracheal course. The present study was undertaken to explore the prevalence of isolated intrathymic course and absent LBCV in normal fetuses undergoing second trimester ultrasound screening. Furthermore, we reviewed our databases of cardiac anomalies to report on the prevalence and pattern of the other anomalous courses reported in postnatal studies. Material and methods In the prospective part of the study, ultrasound examinations performed in the second trimester between 18 and 24 weeks’ gestation were considered. Highresolution ultrasound equipment (Voluson E8, Voluson E10, GE Medical Systems, Zipf, Austria) and convex transabdominal transducers (RM-6C, RAB6C and 9L) were used. Pregnancies with fetal cardiac or extracardiac abnormalities were excluded from this part of the study with the exception of fetuses with an isolated LSVC. The prior performance of a first trimester ultrasound examination did not exclude the patient from study participation. Fetal cardiac evaluation was performed by the systematic cross-sectional approach of the fetal chest in gray scale and color Doppler based upon published guidelines [1]. Since our previous study [4], we have included the visualization of the upper mediastinum in a plane cephalad to the 3VT view depicting the LBCV in gray scale and color Doppler (Fig. 1) as part of cardiac screening performed at our ultrasound centers. An intrathymic LBCV course was defined by the presence of thymic tissue between the brachiocephalic arteries and the LBCV as shown in Figure 2. In order to properly assess the frequency of findings, the study was performed on consecutive fetuses. Only singleton pregnancies were included in the study. Pregnancy outcome was reviewed. Patients were informed on the occurrence of an anomalous course and those with LSVC were offered third trimester evaluation and postnatal echocardiography.
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In the retrospective part of the study we reviewed the databases of the last 4.5 years of two large fetal medicine centers for cardiac anomalies and searched for the prevalence and pattern of associated anomalous courses of the LBCV. The intrathymic course was not routinely documented in the databases and was therefore not evaluated.
Results In a period of 13 months (January 2014 to February 2015), 1437 fetuses underwent ultrasound examinations between 18 and 24 weeks´ of gestation. 16 fetuses (1.1%) were excluded due to maternal habitus or fetal positions in utero, which resulted in the inability to obtain adequate views of the upper mediastinum. Three additional fetuses were excluded, two fetuses due to the third trimester detection of muscular ventricular septal defects (VSD) and one fetus due to an unexplained intrauterine death in late gestation. In the remaining 1418 fetuses, an abnormal course or absence of the LBCV was noted in 29 fetuses (2%), including 25 fetuses (1.76 %) with an intrathymic course of the LBCV (Figure 2) and 4 fetuses (0.28%) with an absent LBCV in association with a LSVC and a right superior vena cava (Figure 3). All 29 cases with an abnormal course or absence of the LBCV had an uneventful postnatal outcome without additional anomalies. Between January 2011 and June 2015, 1544 fetuses with cardiac anomalies diagnosed after 15 weeks of gestation were seen in two fetal medicine centers of the authors. An abnormal course was found in 8 fetuses (0.5%). In this group a subaortic course of the LBCV was found in six fetuses, all in combination with a right aortic arch, two isolated and four in combination with pulmonary atresia with VSD. A double LBCV and a retrotracheal LBCV were found in one case each. Discussion The ultrasound assessment of the LBCV was not commonly performed until recently with the increased utilization of the 3VT view and other transverse views of the upper mediastinum in cardiac screening [4,8]. Similar to other abdominal, cardiac and intracerebral veins in the fetus [6,7,9,10], the LBCV shows variations in anatomy and course. Case reports and small series in infants and adults, primarily resulting from angiography and Magnetic Resonance Imaging (MRI), report on the anomalous course of the LBCV including its absence. In these small series, the presence of double LBCV [11,12] and its anomalous courses, either below the aortic arch called retro-aortic or sub-aortic [13-15] or behind the esophagus and trachea [12,16] have been described. To our knowledge a course across the thymus gland was not previously reported and based upon this study, the intrathymic course is a fairly common occurrence with normal neonatal outcome. The brachiocephalic veins are formed within the embryonic cardinal venous system between the 4th and 8th embryonic week. During this period, the anterior and posterior cardinal veins converge into the common cardinal veins and are responsible for the main venous drainage of the fetus. Anastomotic transverse veins are formed between the right and left cardinal veins, with drainage of blood from left to right ultimately resulting in regression of the left-sided veins. The LBVC is formed
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as an anastomotic transverse vein between the anterior cardinal veins with regression of the left anterior cardinal vein. A failure of the LBCV to form results in the persistence of the left anterior cardinal vein, as left persistent superior vena cava draining into the coronary sinus. The embryological background of an abnormal course of the LBCV is not completely understood, but the pattern of venous anomalies suggests that two transverse veins or even a large venous plexus connecting both right and left anterior cardinal veins exist during embryogenesis [13]. With growth of the aorta and pulmonary artery in the upper mediastinum, lower parts of the venous plexus are compressed and the LBCV is formed. In cases of abnormal branching of aortic arch or pulmonary artery as observed in right-sided aortic arch, the upper venous plexus is compressed resulting in an anomalous subaortic course of the LBVC due to sparing of the lower dorsal plexus (see for an overview Chen et al. [13]). The various courses of the LBCV, such as double LBCV, subaortic course, retrotracheal course and others can thus be explained by compression of various parts of the venous plexus. The retrotracheal course could however, be also a remnant of the accessory hemiazygous or superior intercostal vein. Intrathymic LBCV The present study shows that in approximately one out of 60 fetuses examined in mid-trimester, the course of the LBCV is not posterior to but across the thymus, a condition we called the intrathymic course [4]. The unusual bent course of the LBCV in these conditions (Figure 2) may surprise the ultrasound examiner when first encountered, and may result in unnecessary referrals of patients for fetal echocardiography. This study confirms the preliminary observation of the authors [4] that the intrathymic course is a common normal variant with no impact on fetal well-being. In our opinion there are two possible reasons why this variant is not reported in the pediatric and adult literature. The first is the larger size of the thymus in the fetus which becomes smaller after birth due to the physiologic subinvolution of the gland and the second is the fact that most studies on infants and adults are performed with angiography, which primarily focuses on the vascular anatomy of the upper mediastinum rather than on soft tissues. Absent LBCV in LSVC: Typically the LBCV is absent in the majority of fetuses with a LSVC when the right superior vena cava is present (Figure 3). Persistence of LSVC has been reported to occur as an isolated finding in about 0.3%, reported in one study on autopsies [17] and 0.5% of patients undergoing pacemaker implantation[18]. The prevalence in association with cardiac defects is much higher [19,20]. Our study confirms a prenatal prevalence of LSVC in 0.28% (1: 350 fetuses) in combination with an absent LBCV. In cases with LSVC and an absence of the right superior vena cava, a right brachiocephalic vein is observed instead of a LBCV. The presence of a LSVC in a fetus should not be considered as a variant before detailed ultrasound evaluation is achieved including a fetal echocardiogram to rule out associations with other abnormalities [21]. LSVC was reported as an isolated finding in 12.5 % of fetuses in two large series of 136 fetuses in two referral centers [19,20]. Associated abnormalities included chromosomal anomalies in 9%, heterotaxy syndrome in 40% and other cardiac malformations such as conotruncal anomalies, left ventricular outflow tract obstruction, especially aortic coarctation [19,20]. Referral bias in these two series however may have contributed to the low rate of an isolated LSVC [19,20].
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Subaortic or retroaortic course: The subaortic or retroaortic course of the LBCV is the most commonly reported anomalous or aberrant course of the LBCV in the pediatric literature [13,22,23]. This condition was reported typically in cases with a right aortic arch, in tetralogy of Fallot, in pulmonary atresia with VSD and other cardiac defects, often in combination with a right aortic arch. This course can be demonstrated in the fetus as well (Figure 4) and in all six fetuses with a subaortic course the finding was associated either with an isolated right aortic arch or in combination with pulmonary atresia with VSD. Retroesophageal and retrotracheal course: One very unusual course is a course behind the trachea and esophagus, similar to an aberrant right subclavian artery [12]. Such condition is reported as retrotracheal [12] or retroesophageal course [16]. This condition was first recently reported as a case report by Yigit et al. [12]. Ming et al. [16] reported 4 additional such cases. The anomalous LBCV has in such cases a course behind the heart and trachea and drains into the right superior vena cava. We detected this condition only once in a fetus (Fig. 5) presenting with a complex cardiac anomaly. Double LBCV: Few case reports exist in the literature on the presence of a double LBCV either isolated or as part of an additional cardiac anomaly [11,12]. In these cases both veins can be anterior to the aortic arch or one vein can have a course anterior to and the other vein either directly posterior to the arch or posterior to the heart and trachea [11,12,24]. Figure 6 shows the finding in the only fetus we found with this condition in combination with a tetralogy of Fallot (Fig.6). In summary, our findings suggest that the intrathymic course of the LBCV is present in about 1.76% of fetuses (1:57) and the condition has no clinical impact on fetal wellbeing if cardiac anatomy is otherwise normal. Our study was not designed to assess the frequency of the intrathymic course of the LBCV in fetal cardiac defects. In addition we found that in 0.28% of fetuses (1:350), a LSVC can be found with an absence of a LBCV. In addition for the first time ultrasound images of other abnormal courses of the LBCV such as the subaortic/retroaortic, the retrotracheal/retroesophageal and the double LBCV (Figure 3-6) are presented in this paper.
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Figures Figure 1: Schematic drawing A) and corresponding color-Doppler figure B) of a cross section of the upper mediastinum at a level slightly more cranial than the threevessel-trachea view. This plane shows the left brachiocephalic vein (LBCV) behind the thymus with a course from left posterior to right anterior draining into the superior vena cava (SVC). In this plane the aortic arch is not seen, as it is inferior to the LBCV. Note however that the three brachiocephalic arteries (Brach. Aa.) of the aortic arch are seen in cross section posterior to the LBCV. Figure 2: Schematic drawing A) and corresponding color-Doppler figures B) and C) of a cross section of the upper mediastinum in the same plane showed in figure 1, but with a course of the left brachiocephalic vein (LBCV) across the thymus called intrathymic course. The shape of the LBCV is not straight as in figure 1, but more bent. SVC, superior vena cava; Brach.Aa., Brachiocephalic arteries. Figure 3: Schematic drawing A) and corresponding gray-scale figure B) of a cross section of the upper mediastinum at the same level shown in figure 1. In this case there is a left persistent superior vena cava (LSVC) and the left brachiocephalic vein (LBCV) is absent. SVC, superior vena cava; Brach.Aa., Brachiocephalic arteries. Figure 4: Anomalous course of the left brachiocephalic vein (LBCV) below the aortic arch called subaortic/retroaortic LBCV demonstrated in gray-scale A) and in threedimensional color Doppler rendering (B). This fetus shows a right aortic arch (RAA) and a left ductus arteriosus (DA) with the trachea between both arteries. The LBCV, which has normally a course cranial to both great vessels is seen here in a course posterior to the great vessels. The LBCV drains into the superior vena cava (SVC). Figure 5: Anomalous course of the left brachiocephalic vein (LBCV) behind the heart and trachea as a retrotracheal / retroesophageal course. The plane is at the level of the three-vessel-trachea view with aortic arch (AO) and pulmonary artery (PA) visualized with the trachea. The anomalous LBCV has a course behind the trachea with blood flow from left to right draining into the superior vena cava (SVC). The fetus also has a complex cardiac malformation. Figure 6: Double left brachiocephalic veins (LBCV): Gray scale and color Doppler in axial (A and B) and sagittal (C) planes of the chest in a fetus with Tetralogy of Fallot at 23 weeks gestation. Note the presence of double LBCV with both veins (two arrows) having a course anterior to the aortic arch. Color Doppler (B) confirms flow from left (L) to right in both LBCV. In the sagittal plane two vessels are seen anterior to the aorta (Ao). The finding of double LBCV was an incidental finding in this fetus. Sup: Superior.
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atic drawin ng A) and correspond c ding color-Doppler fig gure B) of a cross Figure 1: Schema n of the up pper mediiastinum at a a level slightly more crania al than the e threesection vessel--trachea viiew. This plane p show ws the leftt brachioce ephalic vein (LBCV) behind the thymus with a course frrom left posterior to right r anterior draining g into the superior s vena ccava (SVC C). In this plane the aortic arcch is not seen, s as itt is inferiorr to the LBCV. Note howe ever that th he three brachioceph halic arteries (Brach.. Aa.) of the aortic arch arre seen in cross c section posteriior to the L LBCV.
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atic drawin ng A) and correspond c ding color-D Doppler fig gures B) an nd C) of Figure 2: Schema o the uppe er mediastinum in the same plane showe ed in figure e 1, but a crosss section of with a course of the left brachioce ephalic vein (LBCV) across th he thymuss called intrathyymic coursse. The sh hape of the e LBCV is not straig ght as in fiigure 1, bu ut more bent. SVC, S superrior vena ca ava; Brach h.Aa., Bracchiocephalic arteries
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Figure 3: Schem matic drawing A) and d corresponding gray y-scale figure B) of a cross section n of the up pper media astinum at the same e level sho own in figure 1. In th his case there iss a left perrsistent sup perior vena a cava (LS SVC) and the t left bra achiocepha alic vein (LBCV)) is absentt. SVC, sup perior vena a cava; Bra ach.Aa., Brrachioceph halic arterie es
eft brachioccephalic ve ein (LBCV V) below the aortic Figure 4: Anomalous coursse of the le arch ca alled subaortic/retroa aortic LBC CV demonsstrated in gray-scale e A) and in n threedimenssional color Doppler rendering (B). This ffetus show ws a right aortic arch h (RAA) and a lleft ductus s arteriosuss (DA) with h the trach hea betwee en both arrteries. The e LBCV which h has norma ally a coursse cranial to both grreat vesse els is seen here in a course posterio or to the great vesse els. The LB BCV drains into the su uperior ven na cava (S SVC)
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eft brachioccephalic ve ein (LBCV)) behind th he heart Figure 5: Anomalous coursse of the le achea as a retrotrach heal / retro oesophageal course. The plane e is at the level of and tra the thrree-vessel--trachea vview with aortic arcch (AO) and a pulmo onary arterry (PA) visualizzed with th he trachea. The anomalous LB BCV has a course be ehind the trachea with blo ood flow fro om left to rright drainiing into the e superior vena cava a (SVC). Th he fetus also ha as a complex cardiacc malformation.
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BCV): Grayy scale and d color Doppler in Figure 6: Double left brachiocephalicc veins (LB A and B) and a sagittal (C) plane es of the ch hest in a fe etus with Tetralogy T o Fallot of axial (A at 23 w weeks gesstation. No ote the prresence off double LBCV L with h both vein ns (two arrows) having a course an nterior to the t aortic arch. a Colo or Doppler (B) confirm ms flow eft (L) to rig ght in both LBCV. In the sagitta al plane tw wo vessels are seen anterior from le to the aorta a (Ao).. The findin ng of doub ble LBCV was w an inc cidental fin nding in thiis fetus. Sup: Superior
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