Sonographic Determining The Left/Right Axis In The Fetal Heart
Sezgin Dursun Medicenter Tip merkezi Obstetrics and Gynaecology Department Agri,
The current methods for the ultrasonographic assessment of the left/right axis in the fetal heart are reliable and adequate for physicians performing advanced level studies. On the other hand, there is a need for a fast, reliable, and practical method for centers performing level one routine studies. The Sezgin method provides rapid diagnosis of the cardiac malposition for physicians in every level.
The first step in the assessment of the fetal heart is to see whether the heart has a proper alignment and angulation in the thoracic cavity. (1,2) The axis of the heart is approximately 45 (22-75) degrees.(1) Confirming that the axis of the heart points to the left may not be as easy as determining its angle.(1,2) Observing that the heart is in the correct left/right axis is essential for evaluation of the correct position of not only the heart but also of the viscerae.(3) Situs assessment that utilizes abdominal and thoracic organ locations will not work in the presence of situs inversus totalis.(4) Identification of the left/right axis of the heart is also necessary for the detection of heterotaxy syndromes.(3,4)
Although determining the axis of the heart is crucial, it may be not be performed during routine ultrasound studies due to orientation difficulties or time constraints. Also, the variable position of the fetus inside the uterus further increases the difficulties.(4)
We herein suggest the Sezgin method for assessment of the fetal heart axis as a practical method that does not require orientation or mental calculations. This method is not affected by fetal movements or the position of the spine. Also, the angle of the heart can be determined while observing the left/right axis of the heart. The Sezgin method requires less time compared to other methods of determination of the fetal cardiac axis, therefore it may be a good solution for clinics with a high patient load.
Sezgin Method
This method is valid in the standart abdominal ultrasound position, the physician must be seated on the right side of the patient, holding the probe with the right hand. The left side of the probe should be on the left side of the physician’s screen.
The thoracic cavity must be accepted as a watch dial. The spine constitutes the 12 o’clock position. If the head is at the bottom, the axis of the heart must be always 4:30 o’clock (±40 minutes). If the head is at the top, the axis of the heart must always be 7:30 o’clock (±40 minutes) .
In the transverse posture, which is very rare in routine studies, the right side is accepted as the top and the probe is shifted from the right to the left. When the head is located on the right (since it is accepted as the top) the apex of the heart should be again at 7:30 o’clock.
Figure 1 : The cardiac apex shows approximately 7 o’clock. Either the head is at the top, or there is a cardiac malposition.
Figure 2: The apex of the heart shows approximately 4:30 o’clock. Either the head is at the bottom or there is a cardiac malposition.
The motto “seven-up” can be used to facilitate easy recall of the head up position.
References
1) Obstet Gynecol. 1987 Aug;70(2):255-9
Normal fetal heart axis and position.
2) J Am Soc Echocardiogr. 1994 Jan-Feb;7(1):47-53.
Cordes TM1, O’Leary PW, Seward JB, Hagler DJ
3) Obstet Gynecol Surv. 2016 Jan;71(1):33-8. doi: 10.1097/OGX.0000000000000262.
Lambert TE1, Kuller J2, Small M3, Rhee E3, Barker P4.
4)Obstet Gynecol. 2002 Jun;99(6):1129-30.
Bronshtein M1, Gover A, Zimmer EZ.
5) Obstet Gynecol 1998;91:495–9. Right fetal cardiac axis: Clinical significance and assorted findings.. 9 Comstock CH, Smith R, Lee W, Kirk JS
situs inversus with complete transposition
fetus dextrocardia . fetus situs inversus . situs inversus totalis . dextrocardia . fetus position . fetal heart position . prenatal diagnosis of situs inversus .fetus heart position
3 Vessel Tracheal View (See: Information)
Normal Fetal Heart Anatomy
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The section on “Fetal Situs” has been updated.
Page Links: 11-13 Week Scan, Overview Aims, Fetal Heart Assessment: Gray Scale, 2-D Optimization, ‘Videos’, Fetal Viabilty, Fetal Situs, Four Chamber View, Interventricular Septum, Atrial Views, Pulmonary Veins, Left Ventricular Outflow Tract (LVOT), Right Ventricular Outflow Tracts (RVOT), Three Vessel View, Three Vessel Tracheal View (3VT), Inflow Tracts, Aortic Arch, Ductal Arch, Color Doppler, References
Overview Aims
The cardiac screening exam is one of the most important aspects of fetal assessment since congenital heart defects are a major cause of mortality and prenatal detection can improve outcomes. All major specialty organizations, including the American Institute for Ultrasound in Medicine (AIUM), recommend the four-chamber view, the left ventricular outflow tract (LVOT) and the right ventricular outflow tract (RVOT) views.(http://www.aium.org/resources/guidelines/obstetric.pdf) In addition, the transverse view of abdomen, the 3 vessel (3V) view and the 3 vessel tracheal (3VT) views are recommended by the International Society of ultrasound in Obstetrics and Gynecology (ISUOG).1 The aim of the screening exam is to define normality and whether there is deviation from normality, requiring referral for fetal echocardiogram.
Fetal Heart Assessment: Gray Scale
To assess fetal cardiac anatomy, a disciplined approach is necessary and optimization of the 2-D equipment is necessary prior to application of color Doppler. This topic summarizes a step-wise approach to the ultrasound anatomy of the fetal heart.
2-D Optimization
Always follow ALARA principle to use as low as is reasonably achievable to obtain satisfactory images. Use the highest frequency transducer, adjust the overall gain, correct depth, adjust sector width, decrease the compression or dynamic range and adjust the focal zone. Use magnification or “zoom” to increase the frame rate and obtain cine loops and video clips to define anatomic details.The cardiac image should occupy approximately 1/3 to 1/2 of the ultrasound screen. Use a higher megahertz transducer prior to application of color Doppler.
Screening Cardiac Exam
A summary of the key axial views of the heart will be presented as recommended by the ISUOG guidelines1 followed by a more detailed description of fetal cardiac views and their significance.
Above Images Courtesy Jill Beithon RT, RDMS, RDCS, RVT
Fetal Heart (11 -13 Week Scan)
11-13 Week Scan
Prenatal detection of congenital heart defects at the 11-to-13 week scan using a simple protocol.2
In this prospective observational study performed at 11 to 13 weeks among 1084 patients, 35 cases were confirmed to have a congenital heart defect. The most effective approach was color mapping of the 4-chamber and 3-vessel and trachea views. The ideal insonation beam was 45 degrees with the fetal spine at 6 o’clock. The transducer assessed ventricular inflows in color at the level of the 4-chamber view, the 3-vessel view and finally demonstrating the V sign at the level of the 3-vessel trachea view. Using this approach a sensitivity of 88.5% and a specificity of 100% for the detection of CHD at 11 to 13 weeks. In addition, the vascular patterns for many of the defects are presented.
Videos
Above. 4 chamber view with LV (left ventricle) and ascending aorta identified. The color Doppler indicates the aortic blood flow is, as expected, towards (red) the transducer.
Video Player
Above. LVOT (Left ventricular outflow tract). Note LV (left ventricle) with the aorta and aortic valve visible. This represents a key view (circled in red) for defining a VSD (ventricular septal defect).
Video Player
Above. A short axis view demonstrating the RV (right ventricle), the MPA (main pulmonary artery) and the PV (pulmonary valve). In this view, the aorta is seen as the MPA crosses over it.
Above. Slightly oblique transverse view of chest demonstrating the 3 vessel view in appropriate order: the MPA (main pulmonary artery), the aorta, and the SVC (superior vena cava). The trachea is not well seen in this view.
Fetal Viability
Determine fetal viability by either M-mode or by direct visualization of fetal cardiac activity.
Fetal Situs
Situs solitus (also see separate chapter) describes the normal position of fetal organs. The fetal stomach is normally on the left side; the left atrium is nearest to the fetal spine and the cardiac axis points to the left.
To determine fetus situs:
1. Define within the uterus the presentation of the fetus (generally vertex or breech).
2. Determine whether the fetal spine is parallel or transverse to the maternal spine. In sagittal view if the fetal and maternal spine are parallel, the fetus is in longitudinal lie. When the fetal spine is perpendicular to the maternal spine, the fetus is in transverse lie.
3. Determine the position of the fetal left side. The fetal left side will be as follows:
A. With respect to the maternal abdomen, the fetal left side is anterior and near to the ultrasound transducer.
B. With respect to the posterior uterine wall, the fetal left side is posterior and farthest from the transducer.
C. With respect to the right uterine wall, the fetal left side will be on the maternal right.
D. With respect to the left uterine wall, the fetal left side will be on the maternal left.
4. Obtain a transverse view of the abdomen and define the fetal stomach which is positioned in the left side of the abdomen.
5. Obtain a 4-chamber view of the heart by obtaining a transverse view of the thorax. The left atrium and descending aorta are nearest to the spine and the cardiac axis points to the left.
6. Finally, ascertain if the stomach and heart are in their correct respective locations, i.e., stomach is on the left side and the cardiac axis points to the left.
7. Place a transverse image of the fetal abdomen and heart side by side and validate that the left side of the fetal abdomen (stomach near to the spine) is concordant with the left side of the fetal heart (left atrium and descending aorta near to the spine, and cardiac axis points to the left). This is done by displaying a side by side comparison of a transverse view through the fetal stomach and a 4-chamber cardiac view.
Above. For example, the fetus is in breech presentation, the spine and stomach are posterior and the long axis of the fetus is parallel to the long axis of the mother. In this example, the fetal right side would be on the maternal right side. In breech presentation, if the stomach and spine were anterior or “up”, the left side of the fetus would be on the maternal right.
In cephalic presentation with the maternal and fetal axis parallel and the spine and stomach posterior, the fetal left side would be on the mother’s right.
Above. Do a check to make certain that the fetal heart orientation confirms normal situs, situs solitus. The stomach should be on the fetal left side. The fetal spine is closest to the left atrium and the axis of the heart is deviated to the left, while the right ventricle is nearest to the anterior chest.
Situs Inversus in Normal Ultrasound of a Fetal Heart
Situs inversus occurs when fetal organs which normally occupy one side of the fetus are found on the opposite side. For example, the fetal stomach is found on the fetal right side instead of the normal left side. Similarly, when the right atrium is on the left side and the left atrium is on the right, situs inversus is also defined. When the fetal organs are complete mirror images, situs inversus totalis is defined.
Above. Situs inversus. The fetal stomach bubble is seen on the fetal right side.
Above. Situs inversus. The right atrium is found on the fetal left side and the left atrium is on the fetal right side. This is a fetus with a large ventricular septal defect and other malformations.
Fetal Heart Ultrasouns of Four Chamber View
Above. In this schematic. [Image of the heart found in the wikimedia commons. 2009-02-03.] of the fetal 4 chamber heart, the respective chambers are defined as well as the major valve anatomy. Note the direction of the right ventricular outflow tract (RVOT) from right to left and the left ventricular outflow tract (LVOT) initially form left to right. The RVOT crosses over the LVOT.
Above. Apical view. The 4-chamber view is obtained through a true transverse view of the fetal chest. The right ventricle is closest to the anterior chest wall and the left atrium is closest to the fetal spine. The fetal cardiac apex points to the left chest (levocardia). In a line perpendicular from the midline the fetal cardiac axis is 45 degrees (± 16 degrees).
Above. The blue arrows define the path of the ultrasound beam which is directed transversely to the fetal chest. This is achieved by obtaining a longitudinal view of the thoracic spine and turning the transducer 90 degrees, then moving the transducer towards the fetal head or feet until the above image is obtained. Normally both atria are similar size and both ventricles are similar size and the ratio between ventricular size and atria size is 2:1. The heart occupies approximate 1/3 of the chest.
Above. 4 chamber heart. With normal situs; use the left atrium’s relationship to the spine to determine sidedness of the cardiac chambers. The fetus is in supine position and the border of the right ventricle is under the sternum.
Above. The fetus is supine, the left atrium is nearest to the spine and the apex of the heart points to the left. The left ventricle occupies most of the left cardiac border.
Above. 4 chamber normal fetal heart ultrasound. Again the left atrium is identified and the atrial-ventricular valves are defined.
Above. 4 chamber heart. The tricuspid valve is inserted towards the apex of the fetal heart compared to the mitral valve. The moderator band is a thick muscle near the apex of the right ventricle. Note the foramen of ovale which opens towards the left atrium.
Fetal Heart Ultrasound of Interventricular Septum
Above. The interventricular septum is the muscular wall that separates and divides the left and right ventricles. It forms part of the crux of the fetal heart and serves as the insertion of the atrial-ventricular valves.
Above. Long axis view of the interventricular septum is best obtained by a scan plane which is perpendicular to the plane of the septum.
Atrial Views
Above. The fetal heart is right side dominant with the well oxygenated blood coming from the umbilical vein through the liver and shunted through the ductus venosus to the inferior vena cava and right atrium. This view of the right atrium with the inferior and superior vena cava is a longitudinal scan plane parallel to the spine and to the right of the fetal heart.
Above. Long axis view of the fetal heart through the atrial septum with the posterior septum secundum and the anterior septum primum. Just to the right of the septum primum is the septum secundum and the valve of the foramen ovale through which well oxygenated blood flows from right atrium to left atrium.
Above. Axial view through the 4 chamber fetal heart demonstrating the right atrium with the leaflets of the tricuspid valve towards the apex and the foramen of ovale opening from right to left.
Above. Long axis view of the heart with the transducer perpendicular to the interventricular septum demonstrating the right to left shunt of blood of blood through the foramen ovale.
Pulmonary Veins
Above. Two of the 4 fetal pulmonary veins are identified. Two inferior and two superior pulmonary veins drain to the left atrium. Sweeping the transducer in a true 4 chamber view identifies the pulmonary vein.
Above. Color Doppler flow demonstrates two pulmonary veins draining to the left atrium.
Left Ventricular Outflow Tract (LVOT)
Above. The left ventricular outflow tract in the fetal heart is seen by obtaining a long-axis view of the heart. The scan head is angled slightly anteriorly and medially (right) from the aortic root. The right ventricle is anterior to the left ventricle. The normal aorta is about 3 mm. at 20 weeks. The number of cusps of the aorta should be noted; the aortic motion should be crisp and not “floppy”.
Above. Another view of the left outflow tract showing a typical configuration of the fetal heart ascending aorta as it exits from the left ventricle.
Right Ventricular Outflow Tract
Above. The main pulmonary artery arises from right to left ; the pulmonary valve is demonstrated. From the 4 chamber view, rock the transducer towards the left fetal shoulder. Again, first obtain a true transverse view of the fetal thorax with the ventricles appearing longer than the atria before changing the direction of the transducer.
Above. The fetal main pulmonary artery (PA) is seen exiting from the right ventricle. Note the ductus arteriosus exiting from the main pulmonary artery and note the right pulmonary branch. The ascending aorta is seen adjacent to main PA.
Images Courtesy Jill Beithon RT, RDMS, RDCS, RVT
Three Vessel View
The three vessel view is a transverse view of the fetal upper mediastinum. The views demonstrate in cross section or oblique section the main pulmonary artery, ascending aorta and the superior vena cava.3
Above. This schematic demonstrates the approximate level of the 3 vessel view which is a transverse view through the fetal mediastinum. In fetal life the pulmonary artery is larger than the ascending aorta and superior vena cava and the typical “dash and 2 dots” demonstrates this relationship.
img class=”alignright” src=”https://www.obimages.net/wp-content/uploads/2013/08/2.3vv.png” alt=”PA is anterior and is the largest vessel followed” width=”273″ height=”222″ title=”PA is anterior and is the largest vessel followed”/>
Above. 3VV. Note the three vessels identified in a transverse view of the fetal mediastinum. The PA is anterior and is the largest vessel followed in size by the aorta and the superior vena cava (SVC).
Above. The vessels form a classic visual image of a dash and 2 dots with the dash being the pulmonary artery and a part of the ductus arteriosus; adjacent to the “dash” is the ascending aorta; adjacent to the ascending aorta is the superior vena cava.
Above. Another 3 vessel view showing the fetal heart main pulmonary artery, the ductus arteriosus, ascending aorta, and the superior vena cava. The echogenic structure to the left of the pulmonary outflow is the pulmonary valve.
Three Vessel Tracheal View (3VT)
Above Images Courtesy Jill Beithon RT, RDMS, RDCS, RVT
Inflow Tracts
Above. The inflow tracts are the superior vena cava (SVC) bring deoxygenated blood to the right atrium and the inferior vena cava bring mostly oxygenated blood from the inferior vena cava (IVC). The oxygenated blood is delivered to the IVC via the umbilical vein to the ductus venosus and IVC. Again, the views of the inflow tract are best obtained with the transducer longitudinal to the right of the heart and parallel to the fetal spine.
Aortic Arch
Images Courtesy Jane JK Burns, RT, AS, RDMS
Above. The aortic arch arises from the left ventricle. The view is achieved by turning the transducer 90 degrees from a transverse position of the fetal heart to a longitudinal or para- sagittal position in the mid-fetal heart. The aortic arch appears as a “candy cane” shape with the head and neck vessels superiorly. Note the ductus venosus and inferior vena cava.
Above. Another gray scale view of the aortic arch with the para-saggital view also demonstrating the inferior vena cava.
Above. Color Doppler of the aortic arch with a view of the descending aorta and fetal head and neck vessels.
Commentary and Color Images Courtesy Jane JK Burns, RT, AS, RDMS
More Normal Ultrasound Fetal Heart Images
Above. Color power Doppler of the aortic arch with the fetal heart superior vessels demonstrated.
Ductal Arch
The ductus arteriosus brings well oxygenated blood from the main pulmonary artery to the descending aorta, and normally closes after birth. The continuity of this vascular connection during fetal life is the ductal arch which is flat, uniform and slightly larger than the aorta.
Above. The approximate components of the sagittal view of the ductal arch are: right ventricle, main pulmonary artery (PA), ductus arteriosus (DA), descending aorta (DA).4 The shape of the fetal ductal arch is often compared to a “hockey stick”.
Above. An additional view of the ductal arch demonstrating the major vascular components.
Above. The ascending aorta’s relationship to the aortic arch is demonstrated in this view of the ductal arch.
Color Doppler
Commentary and Color Images Courtesy: Jane JK Burns, RT, AS, RDMS
Color Doppler adds blood flow information concerning aspects such as perfusion, atresia, and narrowing. Direction as well as detection of flow is possible such as antegrade, retrograde, bidirectional flow and turbulent, shunting, or stenotic flow. Finally demonstration of small vessels is possible and color Doppler helps with the placement of the cursor for spectral Doppler applications.
Start with a good 2-D image and use a high frequency transducer. Maintain a parallel orientation to the direction of blood flow. The image quality is affected by the size of the color box, the velocity range, wall filter, persistence, color gain and color line density. The setting on the 2-D image may need to be reduced. Color persistence may need to be reduced. Initially, low color gain and high PRF settings should be used and continuously adjusted as needed. (see below)
Color box size: the size of the color box affects the quality and frame rate. A smaller color box gives a higher frame rate and better image.
Velocity scale or PRF (pulse repetition frequency): affects quality of the image. A PRF of 45 to 60 cm/sec. is optimal for great arteries and a range of 10 to 20 cm/sec is optimal for venous structures.
Wall filter: eliminates signal from the motion of vessel walls; select a high filter for the great arteries and a low filter for pulmonary arteries and for veins.
Persistence: allows overlap of information from the prior images; use low settings for a cardiac evaluation.
Color gain: reflects the amount of color on the screen. To eliminate artifacts, start with low color gain and adjust as needed.
Color line density: relates to resolution in the axial and lateral planes. If the color line density is increased, the frame rate is decreased. Compromise to obtain best image quality.
Color Examples
Above. Color Doppler flow demonstrating the ventricles and the interventricular septum and direction of flow with flow towards the transducer red and flow away from the transducer blue.
Above. Color Doppler demonstrating the left ventricular outflow tract. Note the spine in normal situs (situs solitus) orients the direction as to the right side and left side of the fetus. In this instance the apex of the heart is to the left of the spine and the left atrium would be the nearest to the spine.
Above. Another color Doppler view demonstrating an intact fetal interventricular septum.
Above. Color Doppler. Flow away from the transducer demonstrates the portion of the aortic arch and thoracic aorta while flow towards the transducer suggests inflow from the inferior vena cava.
References
Diagnosis and Outcome of Pregnancies with Prenatally Diagnosed Fetal Dextrocardia.
Distinguishing right from left: a standardized technique for fetal echocardiography.
Sonographic definition of the fetal situs.
Abnormalities of Fetal Situs: An Overview and Literature Review.
situs inversus with complete transposition
fetus dextrocardia . fetus situs inversus . situs inversus totalis . dextrocardia . fetus position . fetal heart position . prenatal diagnosis of situs inversus .fetus heart position
Distinguishing right from left: a standardized technique for fetal echocardiography.
Sonographic definition of the fetal situs.
Abnormalities of Fetal Situs: An Overview and Literature Review.
situs inversus with complete transposition
fetus dextrocardia . fetus situs inversus . situs inversus totalis . dextrocardia . fetus position . fetal heart position . prenatal diagnosis of situs inversus .fetus heart position
Distinguishing right from left: a standardized technique for fetal echocardiography.
Sonographic definition of the fetal situs.
Abnormalities of Fetal Situs: An Overview and Literature Review.Prenatal echocardiographic diagnosis of cardiac right/left axis and
malpositions according to standardized Cordes technique
Standart Cordes tekniğine göre kalbin sağ/sol ekseninin ve malpozisyonlarının
prenatal ekokardiyografik tanısı
Original Investigation Özgün Araşt›rma
Address for Correspondence/Yaz›şma Adresi: Dr. Süheyla Özkutlu, Department of Pediatric Cardiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
Phone: +90 312 305 11 57-58 Fax: +90 312 309 02 20 E-mail: suheylaozkutlu@yahoo.com
This work was presented at the Second Annual Congress on Update in Cardiology and Cardiovascular Surgery, 20-24 September 2006, Bodrum/Turkey
Accepted Date/Kabul Tarihi: 01.09.2010 Available Online Date/Çevrimiçi Yayın Tarihi: 08.02.2011
©Telif Hakk› 2011 AVES Yay›nc›l›k Ltd. Şti. – Makale metnine www.anakarder.com web sayfas›ndan ulaş›labilir.
©Copyright 2011 by AVES Yay›nc›l›k Ltd. – Available on-line at www.anakarder.com
doi:10.5152/akd.2011.033
Süheyla Özkutlu, Özlem Mehtap Bostan1, Özgür Deren*, Lütfü Önderoğlu*, Gülsev Kale**, Şafak Güçer**, Diclehan Orhan**
From Departments of Pediatric Cardiology, *Obstetrics and Gynecology and **Pediatric Pathology, Faculty of Medicine, Hacettepe University, Ankara,
1Department of Pediatric Cardiology, Faculty of Medicine, Uludağ University, Bursa, Turkey
ÖZET
Amaç: Bu çalışmada, standart Cordes tekniğine göre fetüsün sağ/sol tarafının, kalbin aksının ve pozisyonunun ayrımı ve bu teknikle kardiyak
malpozisyon tanısı konulan 20 olgunun değerlendirilmesi amaçlandı.
Yöntemler: Çalışmamızda, 1999-2006 yılları arasında prenatal Kardiyoloji ünitesinde fetal ekokardiyografi yapılan 1536 olguyu retrospektif olarak
değerlendirildi. Bu olguların 20’sinde kardiyak malpozisyon saptandı. Kalbin aksı ve pozisyonu Cordes tekniğe göre saptandı. Tüm olgular seri
fetal ekokardiyografik çalışmalar ile doğuma veya intrauterinde ölüm meydana gelene kadar izlendi. İntrauterin ölen olgulara otopsi yapıldı.
Doğumdan sonra fizik muayene ve ekokardiyografik değerlendirme yapıldı, prenatal ve postnatal tanılar karşılaştırıldı.
Bulgular: Fetal ekokardiyografi yapılan 1536 olgunun 144’ ünde konjenital kalp hastalığı saptandı ve bu olguların 20’sine kardiyak malpozisyon
tanısı konuldu. Kardiyak malpozisyonlu olguların 16’sında konjenital kalp hastalığı ve 4’ünde kalp dışı nedenlere bağlı malpozisyon mevcuttu. Altı
olguda izole dekstrokardi, 3 olguda situs inversus totalis, 6 olguda situs ambigus ve 1 olguda izole levokardi ile birlikte situs inversus saptandı.
ABSTRACT
Objective: The aim of this study was to evaluate distinguishing the right / left side of the fetus, cardiac axis and position according to the standardized
Cordes technique in 20 cases with cardiac malposition.
Methods: We studied retrospectively 1536 cases whose fetal echocardiographic examinations were performed between 1999 and 2006 in prenatal
cardiology unit. Among these, cardiac malpositions were determined in 20 cases. The cardiac axis and position were determined according
to the Cordes technique. All cases were followed-up by serial fetal echocardiograms until birth or intrauterine death occurred. In cases of
intrauterine death, an autopsy was performed. After birth, physical and echocardiographic examinations were done and prenatal and postnatal
diagnoses were compared.
Results: Of 1536 fetal echocardiograms performed, 144 revealed congenital heart diseases (9.4%), among these cases 20 were diagnosed with
cardiac malposition. Of cases with cardiac malposition, 16 had congenital heart disease, and four had extracardiac malformation. There were
six cases of isolated dextrocardia, three cases of situs inversus totalis, six cases of situs ambiguous, and one case of situs inversus with isolated
levocardia. Of four cases with extracardiac malformations, two cases had mesoposition, one had dextroposition, and one had extreme
levoposition. In six cases the autopsy findings were the same as that their prenatal echocardiographic findings. When postnatal echocardiographic
results of the remaining cases with cardiac malposition due to congenital heart disease were compared with prenatal diagnoses, the
same echocardiographic findings were verified.
Conclusion: The fetal right/left axis must be determined correctly for the accurate diagnosis of cardiac malpositions. Therefore, we recommend
that Cordes technique provides a simple and reliable determination of the fetal right/left axis and fetal situs.
(Anadolu Kardiyol Derg 2011; 2: 131-6)
Key words: Fetal echocardiography, fetal situs, fetal cardiac malposition, dextrocardia, situs ambiguous, Cordes technique
131
Introduction
Fetal cardiac malpositions are difficult to diagnose in routine
screening ultrasound. Determining the fetal right/left axis is
essential for the diagnosis. Constantly variable fetal position
within the uterus can confuse distinguishing the right/left side of
the fetus. Variability among echocardiographers regarding image
acquisition adds to this confusion. If there is confusion regarding
the right/left axis, then atrial and visceral situs, cardiac position
and cardiac segmental anatomy cannot be evaluated correctly.
There are some recommended techniques and images
required for a standard fetal echocardiogram (1-6).
In this study, the 20 cases among 1536 cases diagnosed as
cardiac malposition using standardized technique recommended
by Cordes et al. (2) for assignment of fetal right / left axis
were evaluated. The accuracy of prenatal diagnosis was compared
with postnatal echocardiographic diagnosis and autopsy
findings.
Methods
Study patients
We studied retrospectively 1536 cases whose fetal echocardiographic
examinations were performed between 1999 and 2006
in prenatal cardiology unit. Among these, cardiac malposition was
determined in 20 cases and these cases performed our study
group. These cases were referred to our center either from the
departments of obstetrics and gynecology of our institution or
from other centers by obstetricians or by pediatric cardiologist.
Some were siblings of our patients with congenital heart defects
and fetuses of mothers with congenital heart defects. Data of 20
cases with cardiac malposition were evaluated in respect to gestational
week, maternal age, maternal and familial medical histories,
previous obstetric history, fetal and postnatal echocardiographic
examinations, and autopsy findings.
Fetal echocardiography
The prenatal and postnatal echocardiographic examinations
were performed using a Trinitron GE Vivid Five performance
echocardiographic scanner with 2.5-5 MHz transducers
(Cardiovascular Ultrasound Systems, General Electric, Horten,
Norway). All echocardiographic examinations were performed
by the same pediatric cardiologist and all studies were recorded
on videotape. The fetal examination included the standard positions
used in fetal heart scanning technique (7). The cardiac axis
and position were determined according to the technique
described by Cordes et al. (2).
Cordes technique
In this technique the fetal head and sagittal plane of fetal
body are then located. The transducer is oriented so that it is
parallel to the fetal sagittal plane, with the fetal head on the right
side of the video screen. When the transducer is aligned parallel
to the fetal cranial-caudal axis this way, the side of the transducer
toward the fetal head can be designated the “top” of the
transducer. The transducer is then rotated clockwise (from the
perspective of the echocardiographer) 90 degrees, to visualize
optimally a transverse image of the fetal thorax. In this transverse
image, the fetus’ left side is on the right of the video
screen, and the fetus’ right side is on the left of the video screen
(Fig. 1) (2).
A systematic approach was used based on segmental anatomy
(8, 9). Viscero-atrial situs was determined as situs solitus,
inversus, or ambiguous. In this study, the type of cardiac malposition
was determined by the cardiac base-apex axis as dextrocardia,
mesocardia and levocardia.
Özkutlu et al.
Prenatal echocardiographic diagnosis of malpositions
Anadolu Kardiyol Derg
2011; 1: 131-6
Kalp dışı nedenlere bağlı malpozisyonlu 4 olgunun 2’sinde mezopozisyon, 1’inde dekstropozisyon ve 1’inde ileri levopozisyon mevcuttu. Altı
olguya yapılan otopsi bulguları prenatal ekokardiyografik bulgular ile benzerdi. Konjenital kalp hastalığına bağlı kardiyak malpozisyonlu diğer
olguların doğum sonrası ekokardiyografik sonuçları prenatal tanılarıyla karşılaştırıldığında aynı sonuçlar elde edildi.
Sonuç: Kardiyak malpozisyonun doğru tanısı için fetüsün sağ/sol aksı doğru saptanmalıdır. Bu nedenle fetal situs ve fetüsün sağ/sol aksının
saptanmasında kolay ve güvenilir bir teknik olan Cordes tekniğini öneriyoruz. (Anadolu Kardiyol Derg 2011; 2: 131-6)
Anahtar kelimeler: Fetal ekokardiyografi, fetal situs, fetal kardiyak malpozisyon, dekstrokardi, situs ambigus, Cordes tekniği
Figure 1. Schematic drawing of fetal trunk as viewed in transverse
plane on video display
With fetal spine used as landmark, right and left sides of fetus can be determined.
Relationship of right and left sides of fetus and spine are constant despite fetal rotation from
face up (bottom), right side up (left), face down (top), and left side up (right)
S – spine, L – left, R – right (modified from Cordes TM, O’Leary PW, Seward BS, Hagler DJ.
Distinguishing right from left: A standardized technique for fetal echocardiography. J Am
Soc Echocardiogr 1994; 7:47-53)
132
Situs solitus was defined as liver on the right side and the
stomach on the left side, with the right inferior caval vein and the
superior caval vein connecting to the systemic right atrium on
the right side. Situs inversus was defined as a mirror-image
configuration so that the liver was on the left side and the stomach
was on the right, with the left inferior caval vein and superior
connecting to the systemic right atrium on the left. Situs
ambiguous was defined as the liver on the midline position and
indeterminate stomach situs, abnormal inferior caval vein connection,
or relations with the descending aorta. Situs ambiguous
was divided into two major subtypes: left atrial isomerism
and right atrial isomerism. These were categorized based on the
following echocardiographic criteria: a diagnosis of left atrial
isomerism was made if there was an interrupted inferior caval
vein with azygous continuation and anterior located descending
aorta according to azygous vein, and a diagnosis of right atrial
isomerism was made if the inferior caval vein and aorta was
both located on the right or left side of the spine in parallel
anteroposterior orientation (8, 9).
In this study, dextrocardia was defined as the location of the
heart in the right hemithorax with the apex pointing to the right.
Dextrocardia was divided into two subgroups: Isolated dextrocardia
and situs inversus. Dextrocardia was defined as isolated
dextrocardia, occurring in conjunction with situs solitus and situs
ambiguous. Mesocardia was defined as location of the heart with
the cardiac base-apex axis directed to the midline of the thorax or
with ventricular apices equally directed to both right and left
sides. Levocardia was defined as the location of the heart in the
left hemithorax with the apex pointing to the left. Levocardia as a
cardiac malposition was also defined as isolated levocardia,
occurring in conjunction with situs inversus and situs ambiguous
(8). In this study, the pathologic displacement of the heart into the
right or left thorax by extracardiac malformations was defined as
dextroposition, mesoposition and levoposition (8).
All cases were followed-up by serial fetal echocardiograms
until birth or intrauterine death occurred. In cases of intrauterine
death, an autopsy was performed. After birth, physical and
echocardiographic examinations were done and prenatal and
postnatal diagnoses were compared.
Statistical analysis
All statistical analyses were performed using the SPSS 15.0
statistical software (Chicago, IL, USA). Quantitative variables are
expressed as mean ± standard deviation, and qualitative variables
are given as frequency and percentage. Reliability of fetal
echocardiography for diagnose of cardiac malpositions was
evaluated by sensitivity and specificity formulas.
Results
Of 1536 fetal echocardiograms performed, 144 revealed congenital
heart diseases (9.4%), among these cases, 20 were
diagnosed with cardiac malposition. Of these cases, 16 had
congenital heart disease, and 4 had extracardiac malformation
(Table 1). All the other cases (124 cases) had situs solitus, levocardia
and left cardiac axis between 60° and 90°. The mean
gestational age and the maternal age at the time of first examination
was 28±5 weeks (range 20-37 weeks) and 30.0±3.6 years
(range 24-35 years), respectively.
The indications for referral for fetal echocardiographic
examination were suspected congenital heart disease, fetal
arrhythmia, and fetal hydrops on routine obstetric ultrasound.
Seven of 20 cases were referred for fetal echocardiography
after a preliminary diagnosis of cardiac malposition. One case,
referred for fetal echocardiography after a preliminary diagnosis
of dextrocardia on obstetric ultrasound and magnetic resonance
imaging examination, had normal cardiac anatomy and
position. Except the cases 10 and 18, maternal and familial
medical histories, and previous obstetric history of all cases
were unremarkable. Case 10 had a sibling with situs inversus
totalis and transposition of the great arteries, and the mother of
the case 18 had congenital heart disease.
Of 20 cases with cardiac malposition, 16 cases had congenital
heart disease, four cases had extracardiac malformation.
There were six cases of isolated dextrocardia, three cases
of situs inversus totalis, and six cases of situs ambiguous, and
one case of situs inversus with levocardia (Fig. 2A-B) (Table 1).
Of six cases with situs ambiguous, five cases had left atrial
isomerism and levocardia (Fig. 3A-B) and one case had right
atrial isomerism and dextrocardia (Fig. 4). Of four cases with
cardiac malposition caused by extracardiac congenital malformation,
two cases had mesoposition due to pleural effusion, one
case had dextroposition due to left-sided congenital diaphragmatic
hernia, and one case had an extreme levoposition due to
cystic adenomatoid malformation in the right lung (Table 1). All
of them had normal cardiac anatomy.
In follow-up, in six cases (case 10, 11, 13, 14, 16, and 19)
pregnancy was terminated (Table 1). The autopsy findings of
these cases were the same as their prenatal echocardiographic
findings. The remaining cases were born and have survived the
neonatal period.
On postnatal echocardiographic examination these cases
had the same echocardiographic findings with prenatal diagnosis.
There were not false negative and false positive results in
the cases with cardiac malposition, in terms of fetal echocardiographic
diagnosis. The sensitivity of the prenatal echocardiographic
examination in diagnosing cardiac malpositions was
calculated as 100% and specificity was 100%.
Discussion
Recently, advances in ultrasound technology and increased
experience in fetal echocardiography have led to increased
sensitivity and specificity of fetal echocardiography in the accuracy
of diagnose of congenital heart disease (10-12). However,
the prenatal diagnosis of cardiac malpositions is difficult.
Özkutlu et al.
Prenatal echocardiographic diagnosis of malpositions
Anadolu Kardiyol Derg
2011; 1: 131-6 133
Therefore, cardiac malpositions are usually diagnosed by postnatal
echocardiographic examination or autopsy. The current
methods to distinguish the right side of the fetus from the left
side on the transabdominal ultrasound examination rely on several
parameters including maternal position, fetal position and
transducer orientation. In present study, visceroatrial situs, cardiac
position and cardiac segmental anatomy were evaluated
according to the technique described by Cordes et al. (2). Since
1998, in our prenatal cardiology unit this technique has been
preferred because it is easily applied, and it reduces confusion
significantly relating to fetal right/left axis. This study using
Cordes technique showed that there was no difference between
the type of cardiac malposition diagnosed prenatally and postnatally
(sensitivity and specificity 100%).
There are a few published studies about malpositions (13-16).
Walmsley et al. (16) retrospectively reviewed the fetal echocardiographic
diagnosis of dextrocardia in large series. In this study, 85
cases of dextrocardia were diagnosed from 5539 fetal echocardiograms
and thirty-three of these cases had been referred for fetal
Figure 2. Prenatal and postnatal echocardiographic images demonstrating isolated levocardia in the fetus with complex cardiac anomaly. A:
With fetal spine used as landmark, the apex of the heart is directed toward the left side of the fetal chest (schematic drawing left side up) B: The
fetal stomach and the aorta are positioned in the right side (schematic drawing left side down)
AVV – atrioventricular valve, S – spine, Ao – Aorta, IVC – inferior vena cava, ST – stomach, A – anterior, P – posterior, L – left, R – right
Figure 3. Four-chamber view in the fetus with left atrial isomerism. A: Two vessels are seen in front of the spine, the larger, more anterior vessel
is the descending aorta, the smaller one the azygous continuation of the inferior vena cava (schematic drawing left side down) B: Two vessels
are seen in the posterior thorax, the more posterior proved to be the azygous continuation of the inferior vena cava
S – spine, Ao – aorta, AzV – azygous vein, A – anterior, P – posterior, L – left, R – right
Figure 4. Dextrocardia and right atrial isomerism in the fetus with
common inlet right ventricle. With fetal spine used as landmark, the
apex (arrow) of the heart is directed toward the right side of the fetal
chest and the abdominal vessels showing the aorta and inferior vena
cava lying antero-posteriorly to each other and directly in front of the
spine (schematic drawing left side down and right side down)
S – spine, Ao – aorta, IVC – inferior vena cava, A – anterior, P – posterior, L – left, R – right
Özkutlu et al.
Prenatal echocardiographic diagnosis of malpositions
Anadolu Kardiyol Derg 134 2011; 1: 131-6
Cases Gestational age Visceroatrial Cardiac apex Cardiac Congenital Extracardiac Outcome
at presentation, situs orientation Axis heart disease anomalies
weeks
Case 1 27 Ambiguous Isolated Left axis AVSD – Alive,
(left atrial isomerism) Levocardia 77° DORV Following-up
PS
hemiazygous vein continuation
Case 2 30 Ambiguous Isolated Left axis AVSD – Alive,
(left atrial isomerism) Levocardia 75° azygous vein continuation – Following-up
Case 3 32 Ambiguous Isolated Left axis Sup.Inf. Alive,
(left atrial isomerism) Levocardia 65° Ventricle Following-up
VSD+ASD
Ventriculo-arterial discordance
azygous vein continuation
Case 4 28 Ambiguous Isolated Left axis DORV – Alive,
(left atrial isomerism) Levocardia 70° Subpulmonic Following-up
VSD
PS
hemiazygous vein continuation
Case 5 30 Inversus Isolated Left axis DIRV – Alive,
Levocardia 80° Pulmonary atresia Following-up
ASD
MAPCA
Case 6 37 Ambiguous Dextrocardia Right axis Common inlet right ventricle – Intrauterine
(right atrial isomerism) 75° Large primum and secundum ASD fetal death
(common atrium), MGA+Hypoplastic and autopsy
pulmonary artery was performed
Case 7 34 Solitus Isolated Right axis DORV – Alive,
Dextrocardia 60° VSD Following-up
Case 8 23 Solitus Isolated Right axis Primum ASD – Alive,
Dextrocardia 60° Common inlet single ventricle Following-up
MGA
Case 9 21 Ambiguous Isolated Left axis VSD – Alive,
(left atrial isomerism) Levocardia 72° Sinus venosus ASD Following-up
azygous vein continuation
Case 10 24 Inversus Dextrocardia Right axis TGA – Pregnancy
68° VSD termination
and autopsy
Case 11 24 Solitus Isolated Right axis Common inlet single ventricle – Pregnancy
Dextrocardia 60° Common atrium termination
and autopsy
Case 12 34 Inversus Dextrocardia Right axis VSD – Alive,
70° Following-up
Case 13 19 Solitus Isolated Right axis Primum ASD – Pregnancy
Dextrocardia 60° Dimunitive RV+Inlet VSD termination
(small)+INCVM+PA and autopsy
Case 14 18 Solitus Isolated Right axis Outlet VSD Gastroschisis Pregnancy
Dextrocardia 60° termination
and autopsy
Case 15 37 Inversus Dextrocardia Right axis Primum ASD – Alive,
58° Common ventricle Following-up
Case 16 24 Solitus Isolated Right axis Primum ASD – Pregnancy
Dextrocardia 30° Common ventricle termination
and autopsy
Case 17 22 Solitus Mesoposition 0° – Pleural effusion Alive,
Following-up
Case 18 33 Solitus Dextroposition Left axis – Diaphragmatic Repair of
45° hernia diaphragmati
c hernia and
alive
Case 19 24 Solitus Extreme Left axis – Cystic Pregnancy
Levoposition 30° adenomatoid termination
malformation and autopsy
Case 20 20 Solitus Mesoposition 0° – Pleural effusion Alive
Following-up
ASD – atrial septal defect, AVSD – atrioventricular septal defect, DIRV – double inlet right ventricle, DORV – double-outlet right ventricle, INCVM – Isolated non-compaction of the ventricular
myocardium, MAPCA – multiple aortopulmonary collateral arteries, MGA – malposition of the great arteries, PA – pulmonary atresia, PS – pulmonary stenosis, RV – right ventricle,
Sup. Inf- Superioinferior, TGA – Transposition of the great arteries, VSD – ventricular septal defect
Table 1. Diagnoses and features of the cases with cardiac malposition
Özkutlu et al.
Prenatal echocardiographic diagnosis of malpositions
Anadolu Kardiyol Derg
2011; 1: 131-6 135
echocardiography after a preliminary diagnosis of dextrocardia
on routine ultrasound examination. In present study, only seven
of 20 cases were referred for fetal echocardiography after diagnosis
of cardiac malposition on routine obstetric ultrasound,
and the cases whose preliminary diagnosis of dextrocardia on
obstetric ultrasound and magnetic resonance imaging had normal
cardiac anatomy and position on pre-postnatal echocardiogram.
These studies have shown that fetal cardiac malpositions
are difficult to diagnose on routine obstetric ultrasound.
Fetal cardiac malposition is caused by either intrinsic congenital
heart diseases or extracardiac malformations. Generally,
intrinsic congenital heart diseases cause abnormal cardiac axis
(17, 18). In addition, extracardiac malformations are often
responsible for the abnormal location of the heart in the thorax
due to mediastinal shift (19). In our study among 20 cases with
cardiac malposition, 16 had congenital heart disease, and four
had extracardiac malformation.
Most of the cases with congenital heart disease had abnormal
cardiac axis. Shipp et al. (20) reported that 44% of fetal heart
defects were associated with left-sided heart greater than 57
degrees. Smith et al. (17) also reported that left-sided heart
greater than 75 degrees correlated with a positive predictive
value of 76% for a heart defect in fetuses. In most of our cases
with levocardia and dextrocardia, cardiac axis was greater than
57 degrees (Table 1).
Of six cases with situs ambiguous, five had left atrial isomerism
and one right atrial isomerism. This study demonstrated
significant predominance of fetuses diagnosed with left atrial
isomerism. Some studies have noted that fetuses with left atrial
isomerism appear to be more common in utero because of an
increased rate of very early death of fetuses with right atrial
isomerism (15). All cases with situs ambiguous had severe complex
congenital heart disease. It was stated that the cardiac
anomalies in right atrial isomerism tend to be more severe than
those in left atrial isomerism (18). This study also indicated that
the prognosis of cases with left atrial isomerism was better than
case with right atrial isomerism.
Of four cases with cardiac malposition due to extracardiac
anomalies, one had congenital diaphragmatic hernia and other
had cystic adenomatoid malformation. Although previous studies
were reported that these anomalies could be associated
with cardiac defects and other anomalies, our cases had normal
cardiac anatomy (18, 21, 22).
Conclusion
The fetal right/left side and axis must be determined correctly
for the accurate diagnosis of cardiac malpositions.
Therefore, we recommend that Cordes technique provides a
simple and reliable determination of the fetal right/left side and
fetal situs.
Conflict of interest: None declared.
References
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Fetal dextrocardia: diagnosis and outcome in two tertiary centres
Abstract
Objective: To evaluate the incidence of fetal dextrocardia, associated cardiac and extracardiac malformations, and outcome.
Design: Retrospective echocardiographic study.
Setting: Two tertiary centres for fetal cardiology.
Patients: 81 consecutive fetuses with a fetal dextrocardia presenting at Guy’s Hospital, London, between 1983 and 2003 and at Hôpital Robert Debré, Paris, between 1988 and 2003. Fetal dextrocardia was defined as a condition in which the major axis of the heart points to the right.
Results: The incidence was 0.22%. There were 38 fetuses (47%) with situs solitus (SS), 24 (30%) with situs ambiguus (SA), and 19 (23%) with situs inversus (SI). Structural cardiac malformations were found in 25 cases (66%) of SS, 23 cases (96%) of SA, and 12 cases (63%) of SI. Extracardiac malformations were identified in 12 cases (31%) of SS, in five cases (21%) of SA, and in two cases (10%) of SI. Of the 81 cases of fetal dextrocardia, there were 27 interrupted pregnancies (15 of 24 SA, 10 of 38 SS, and 2 of 19 SI), six intrauterine deaths (3 of 38 SS, 2 of 24 SA, and 1 of 19 SI), and five neonatal deaths (3 of 24 SA, 1 of 19 SI, and 1 of 38 SS). There were 43 survivors (24 of 38 SS, 15 of 19 SI, and 4 of 24 SA).
Conclusion: The majority of fetuses with dextrocardia referred for fetal echocardiography have associated congenital heart disease. There is a broad spectrum of cardiac malformation and the incidence varies according to the atrial situs. Fetal echocardiography enables detection of complex congenital heart disease so that parents can be appropriately counselled.
Fetal dextrocardia is a condition in which the major axis of the heart (from the base to the apex along the interventricular septum) points to the right. Dextrocardia should be distinguished from dextroposition, in which the heart is shifted into the right chest as a consequence of pathological states involving the diaphragm, lung, pleura, or other adjoining tissues.1 The term dextrocardia describes only the position of the cardiac axis and conveys no information regarding chamber organisation and structural anatomy of the heart.2–7 In the postnatal period a broad spectrum of cardiac malformations is observed associated with dextrocardia, and the incidence varies according to the atrial situs. Complex cardiac heart malformations are found more often with situs solitus and situs ambiguus than with situs inversus.3,4,6,7 Apart from a few case reports and one recent retrospective study, published data regarding fetal dextrocardia are sparse.8,9,10,11,12,13 The purposes of our study was to evaluate the incidence of fetal dextrocardia in our high risk fetal populations and to document the associated cardiac and extracardiac malformations and the fetal outcome.
PATIENTS AND METHODS
The fetal echocardiographic databases of two fetal cardiology units were retrospectively reviewed (Guy’s Hospital, London, from 1983 to 2003 and Hôpital Robert Debré, Paris, from 1988 to 2003) and all patients with fetal dextrocardia were identified. This study group was from a population already preselected for tertiary referral, which may influence the incidence of dextrocardia, as well as associated cardiac malformations and outcome. Fetal dextrocardia was defined as a condition in which the major axis of the heart (base to apex) pointed to the right. The strategy followed for detecting dextrocardia was to determine the left and the right of the fetus based on the position of the spine and head of the fetus (breech, cephalic, transverse) in relation to the maternal abdomen. This technique is learnt from obstetric colleagues in our centres.
From a total of 36 765 mothers referred for fetal echocardiography during the study period, 82 cases of dextrocardia were diagnosed. One fetus was excluded because the examination was not technically adequate to define the details of intracardiac anatomy. All fetuses with fetal dextroposition, in which the heart is shifted into the right chest as a consequence of extracardiac abnormality, were excluded from this study. For the 81 fetuses forming the study group, the findings were confirmed by postnatal echocardiography or necropsy, where possible. The gestational age at the time of examination ranged from 17 to 36 weeks, mean (SD) 23.1 (4.7). The referral reason in the majority of cases was a suspicion of cardiac malformation on obstetrical ultrasound (n = 61), followed by extracardiac fetal abnormalities (n = 9), family history (n = 4), fetal dextrocardia (n = 2), abdominal situs inversus (n = 2), maternal diabetes (n = 2), and nuchal translucency (n = 1). Prenatal records were reviewed in all cases and postnatal clinical records (including necropsy reports and karyotype reports) were reviewed where available. For six babies no follow up information was available. All fetuses had an obstetrical anomaly scan to detect extracardiac malformations. Fetal echocardiograms were recorded with the following equipment: Acuson 128 XP, Advanced Technologies Laboratories Ultramark 4 system, Toshiba SSA 270A, and Hewlett Packard 1000, 2000, and 5500 ultrasound systems. Most of the examinations were performed with a 3.5 or 5 MHz transducer. All two dimensional echocardiograms were recorded on videotapes for offline analysis.
The segmental analysis of cardiac anatomy proposed by Tynan et al14 was used for a comprehensive cardiac assessment. Atrial situs was determined by echocardiography according to the location of the inferior vena cava, location of the descending aorta at the level of the diaphragm, and the site of hepatic venous drainage. Situs ambiguus was classified into right and left isomerism. In right isomerism, the inferior vena cava and abdominal aorta lay on the same side of or directly anterior to the spine, with the inferior vena cava running anterior to the aorta. The hepatic veins connected to the inferior vena cava. In left isomerism, the inferior vena cava was interrupted and another venous channel (azygos or hemiazygos) was seen posterior to the aorta. Through this venous channel the abdominal inferior vena cava drained to a superior cava channel. The hepatic veins drained directly to the atria.15 We followed the echocardiographic criteria described by Hagler et al16 for identification of ventricular morphology.
RESULTS
From a total of 36 765 mothers referred for fetal echocardiography during the study period, 81 cases of fetal dextrocardia were diagnosed, giving an incidence of 0.22%. Fetal dextrocardia was most common with situs solitus in 38 (47%), followed by situs ambiguus in 24 (30%) and then situs inversus in 19 fetuses (23%).
Situs solitus
There were 38 cases of fetal dextrocardia with situs solitus.
Intracardiac abnormalities
Thirty four fetuses had two ventricles: 29 had concordant and five had discordant atrioventricular connections (fig 11).). The remaining four had univentricular hearts, three with absent right atrioventricular valve and one with double inlet. Of the four fetuses with univentricular hearts, three had univentricular hearts of left ventricular type, all with absent right atrioventricular valve, and one had a univentricular heart of indeterminate type.
Of the 29 fetuses with concordant atrioventricular connections, 21 had concordant arterial connections: 13 had normal hearts and eight had an associated cardiac anomaly. In the remaining eight, three had a discordant ventriculoarterial connection, three had a double outlet right ventricle, and two had a single outlet with pulmonary atresia. In the five fetuses with discordant atrioventricular connections, four had discordant arterial connections and one had a single outlet with pulmonary atresia. Of the three fetuses with a univentricular heart with a main chamber of left ventricular type, two had concordant arterial connections and one had a discordant arterial connection. The other fetus with univentricular heart of indeterminate type had a double outlet main chamber.
Chromosomal anomalies
Twelve fetuses had documented normal karyotype. In a further 24 fetuses, although fetal karyotype had not been analysed, the karyotype was presumed to be normal, as these had normal phenotype postnatally or at necropsy. One fetus with a ventricular septal defect had trisomy 13, and one fetus with double outlet right ventricle with pulmonary stenosis had balanced 2–9 translocation.
Extracardiac anomalies
In 31% (n = 12) of fetuses with dextrocardia with situs solitus an extracardiac anomaly was noted (one VATER syndrome (vertebral, anal, tracheal, esophageal, and radial anomalies), two cleft lip or palate, one Pierre Robin sequence, three polymalformations, one exomphalos, one hydrocephalus, one kidney malformation, one pericardial effusion, and one facial dysmorphia).
Outcome
Of 38 cases of fetal dextrocardia with situs solitus, 26% (n = 10) of pregnancies were interrupted, 8% (n = 3) of pregnancies resulted in spontaneous intrauterine death, and 3% (n = 1) of babies died after birth. Twenty four survived, representing 86% of continuing pregnancies.
Situs ambiguus
Twenty four cases of dextrocardia with situs ambiguus were detected during fetal life. In this group right atrial isomerism was detected nearly as often as left isomerism (13 and 11 cases, respectively).
Intracardiac abnormalities
All 13 fetuses with right atrial isomerism had two ventricles, with the morphological right ventricle lying to the right (fig 22).). A common atrioventricular valve was found in all but one fetus. Four had a concordant ventriculoarterial connection, six had a double outlet right ventricle, and three had a single outlet with pulmonary atresia. Severe pulmonary stenosis was found in three. Total anomalous pulmonary venous connection was also a common feature and was found in 13 fetuses.
All 11 fetuses with left atrial isomerism also had two ventricles, with the morphological right ventricle to the right. A common atrioventricular valve was found in nine and two fetuses had two patent atrioventricular valves. Six had a concordant and two a discordant ventriculoarterial connection, two had a double outlet right ventricle, and one had a single outlet with pulmonary atresia.
Chromosomal anomalies
Two fetuses had documented normal karyotype and in 22 cases fetal karyotype had not been analysed.
Extracardiac anomalies
Three fetuses with left atrial isomerism had gut malrotation and one had polymalformations. One case of oesophageal atresia was found with right atrial isomerism.
Outcome
In this group 62% (n = 15) of pregnancies were interrupted, 8% (n = 2) of pregnancies resulted in intrauterine death, 12% (n = 3) of fetuses died after birth, and 17% (n = 4) of the total survived. The survival rate in continuing pregnancy was 44%. The important issue in this type of malformation is the underlying cardiac malformations, although surgical procedures may be more difficult in dextrocardia.
Situs inversus
There were 19 cases of fetal dextrocardia associated with situs inversus.
Intracardiac abnormalities
In this group, 18 fetuses had biventricular connections: 17 had concordant and one had discordant atrioventricular connections (fig 33).). The remaining fetus had a univentricular heart of the left type with an absent right atrioventricular connection.
Of the 17 fetuses with concordant atrioventricular connections, 12 had concordant ventriculoarterial connections, four had double outlet right ventricle, and one had a discordant arterial connection. Of the 12 fetuses with concordant atrioventricular connections, seven had a normal heart and five had associated cardiac anomalies. The fetus with discordant atrioventricular connection had a single outlet with pulmonary atresia. In the fetus with a univentricular heart the arterial connection was discordant.
Chromosomal anomalies
Nine fetuses had a documented normal karyotype and in 10 cases fetal karyotype had not been analysed.
Extracardiac anomalies
Two fetuses with associated ventricular septal defect had extracardiac lesions. One of them had dysplastic kidney and the other the VATER syndrome.
Outcome
Of the 19 cases of fetal dextrocardia with situs inversus, two pregnancies were interrupted, one resulted in intrauterine death, and one resulted in neonatal death. Fifteen survived, representing 88% of continuing pregnancies.
DISCUSSION
Incidence of fetal dextrocardia
The incidence of fetal dextrocardia in our study population is low (0.22%), which is very likely to be related to the referral pattern to our tertiary fetal cardiology units. The referral reason was a suspected cardiac malformation during obstetric ultrasound scanning for most of our patients, with only two patients being referred because of dextrocardia. However, in some of the patients referred for a suspected problem, the dextrocardia had been noted at the time of referral.
The incidence in our series compares with an incidence of 0.84% in a previous study on fetal dextrocardia (Walmsley et al13). In their study Walmsley et al13 reviewed 5539 fetal echocardiograms and diagnosed 85 cases of dextrocardia. Of these, 46 cases were classified as primary dextrocardia and 39 as secondary dextrocardia due to extra cardiac malformations such as diaphragmatic hernia. In our study, we excluded all cases of secondary dextrocardia or dextroposition related to an extracardiac abnormality. This difference in patient selection may account for some of the differences in the two studies. Dextrocardia is a permanent position of the heart in the right chest, in contrast to dextroposition, which is transitory and regresses when the extracardiac malformation is treated.
Congenital heart malformations associated with dextrocardia
Both our study and that of Walmsley et al13 show that a wide spectrum of congenital heart malformations, often complex, is associated with fetal dextrocardia. These findings are consistent with postnatal studies.2–7 We concur that the term “fetal dextrocardia” indicates cardiac position only and does not give any indications of cardiac structure. As in postnatal studies, we did not find any case of hypoplastic left heart, in contrast to Walmsley et al,13 who found two cases. We did not note an absent left ventricular connection in our study and this finding remains unexplained in the postnatal studies.2,7
The role of situs
Situs solitus was the most common type in our study (47%), which is in contrast to the study of Walmsley et al,13 in which situs solitus was least frequent (22%).13 All the fetuses with dextrocardia and situs solitus in the study of Walmsley et al13 had a cardiac malformation compared with 66% in our study. In postnatal series, the incidence of a normal heart varied between 0–9%2–7 The fetuses with a normal heart in our population were mostly referred because of associated extracardiac malformations and not because there was concern about the fetal heart. This may explain the discrepancies between prenatal and postnatal studies.
In our study 37% of fetuses with dextrocardia with situs inversus had structurally normal hearts, compared with 89% in the study of Walmsley et al.13 In those with a cardiac malformation a wide spectrum of congenital heart disease was seen, most of which were complex.2–7 However, the best survival was observed in this group.
Postnatal series have reported situs ambiguus as the least common type of situs with dextrocardia. However, in prenatal series the incidence is higher, being 29% in our series and 39% in the series of Walmsley et al.13 The higher incidence in fetal series may be explained by the possibility that many of the fetuses may not survive, either because of interruption of pregnancy or because of death in utero or during the early neonatal period.
Frequency of extracardiac anomalies
We found extracardiac anomalies in all the three groups of situs. However, only 31% (n = 25) of karyotype results were available. The karyotype was presumed to be normal in liveborn babies with a normal phenotype or in fetuses at necropsy with a normal phenotype. Walmsley et al13 mentioned extracardiac anomalies only in the situs ambiguus group with one case of trisomy 18. Fetal dextrocardia may be associated with extracardiac anomalies in all types of situs.
Limitations
Some limitations to our study need to be addressed. The population was preselected by the nature of the referral pattern to our tertiary centres. Thus, the incidence of fetal dextrocardia (0.22%) in our population is low and may not be representative of the global incidence. This also applies to the incidence of associated cardiac and extracardiac malformation, which is high in our series. Another potential limitation of our study is the method used to determine the right and left sides of the fetus. This is the first crucial step in obstetric sonography and thus also fetal echocardiography. We have learned from our obstetric colleagues in our specialist centres that the positions of the spine and head of the fetus in relation to the maternal abdomen help work out left and right in the fetus. Cordes et al17 developed a standardised technique to help determine right and left in fetal echocardiography. This method, which also uses the fetal head and spine as markers, is an alternative way to establish the left and right of the fetus. This method has the advantage of being recordable, which is beneficial in retrospective studies.
Conclusion
A wide spectrum of cardiac disease can be found associated with fetal dextrocardia, depending on the atrial situs. The majority of our fetal population presented because of suspected congenital heart disease during routine obstetric scanning. This is the likely explanation for the low incidence of dextrocardia in our population and accounts for the high incidence of cardiac malformation in our series. The finding of fetal dextrocardia should prompt a comprehensive assessment of fetal cardiac structures by fetal echocardiography. Parental counselling has to take into account whether there is associated congenital heart disease and how severe it is, as these factors will influence prognosis.
Abbreviations
-
SA, situs ambiguus
-
SI, situs inversus
-
SS, situs solitus
-
VATER, vertebral, anal, tracheal, esophageal, and radial anomalies
Two-dimensional fetal echocardiography: where we are
This article has been cited by other articles in PMC.Abstract
Congenital Heart Disease (CHD) is the most common severe congenital abnormality in the newborn and the cause of over half the deaths from congenital anomalies in childhood. Prenatal diagnosis, possible as early as 15 weeks of gestation, allows physicians and families the greatest number of therapeutic options, and can improve the postnatal outcome. There are several potential indications for performing such examination. Evaluation of the heart in the setting of restricted fetal growth or fetal distress is often recommended. Whenever extracardiac anomalies are detected during fetal ultrasound examination or in presence of chromosomal abnormalities detected with amniocentesis, cardiac assessment is mandatory. The test should also be performed as part of the assessment of fetal arrhythmias. Finally, whenever congenital heart disease is suspected for other reasons, such as maternal exposure to teratogenic substances or a parental history of previous children with congenital lesions, the examination should be considered.
The performance of a fetal echocardiogram requires experience and a systematic approach. Guidelines for training have been formulated, and only qualified individuals should perform this highly specialized examination. A description of the techniques of heart examination is presented below.
Keywords: fetal, echocardiography, congenital, cardiopathyIntroduction
Considerable advances in ultrasound technology and a close collaboration between the specialties of paediatric cardiology and fetal medicine have resulted over the last three decades in the increasing ability to diagnose congenital heart disease before birth.
CHD at present time show an incidence of about 4-13 per 1000 live births (1–3), thus representing one of the most frequently detected congenital malformations (4). They are responsible for about half of the deaths caused by lethal malformations during postnatal age (5). The percent probabilities to recognize CC in prenatal age are quite varying (6), being influenced by several factors such as the experience of the operator, maternal obesity, the type of transducer used, gestational age, the volume of amniotic liquid and the fetal position (7, 8).
Echography proves to be a well established exam overall, non-invasive, simple to carry out, and shows sensitivity and specificity which are strictly dependent on the capacities of the individual operator (9–11). The diagnosis of CHD during prenatal age should never be performed without a careful exploration of other eventual genetic and polymalformative syndromes (that may concern other organs). Importantly, outcomes for specific lesions may differ as extracardiac abnormalities and chromosomal defects may alter the prognosis of otherwise straightforward cardiac lesions such as tetralogy of Fallot.
Timing of fetal echocardiography
The echocardiographic study of the fetal heart is optimally performed between 18 and 22 weeks of gestational age, a time window that enables the evaluation of most details of fetal cardiac anatomy. Some alterations may be identified starting from the first trimester of gestation, occasionally with the aid of the transvaginal probe, particularly when an increased thickness of nuchal translucency is detected during the screening for chromosomal abnormalities (12–15) conducted between the 11th + 6 days and the 14th week of gestation. The use of the color Doppler is of utmost importance in the early echocardiography as it helps in the recognition of the large vessels. The undertaking of fetal heart screening towards mid second trimester can be very useful in addition to a previous fetal echocardiography performed a few weeks earlier, since several cardiac pathologies tend to show a later onset (for example, ventricular hypoplasia due to obstructive process).
If fetal echocardiography examination conducted in the first trimester or during pre-morphologic age (16–18 weeks of gestation) cannot exclude the development of late onset pathologies, the undertaking of such exam around the 28th-30th week of gestation can face some obstacles provided by the fetal position and the rib bones.
Indications for performing the examination
The indications for performing such examination can be divided into two main categories: maternal and fetal (16).
Maternal indications
-
Familiar anamnesis positive for CHD.
-
Metabolic disorders such as Insulin-Dependet Diabetes Mellitus (IDDM), especially if not compensated during pregnancy, and phenylchetonuria, due to fetal exposition during organogenesis to values of maternal phenylalanine > 15mg/dL.
-
Exposition to teratogenic agents such as: steroids, anticonvulsivants, alcohol, lithium, but most of all derivatives of vitamine A (retinoic acid and derivatives).
-
Exposition to inhibitors of prostaglandin synthesis (ibuprofen, salicylic acid, indometacine).
-
Infections from rubella, CMV, Coxackie e Parvovirus B19.
-
Autoimmune diseases such as LES and Sjogren’s syndrome.
-
Hereditary familiar disorders such as, for example, Marfan’s syndrome.
-
Medically Assisted Reproduction (PMA).
Fetal indications
-
Morphostructural exam in another gestation age which suggests the presence of factors possibly indicating CC.
-
The presence of other alterations which refer to other fetal organs and/or structures.
-
Cromosomal abnormalities.
-
Cardiac arrhythmia (persistent tachycardia, persistent bradycardia, persistent irregular fetal heart rate).
-
Fetal hydrops.
-
Monocorial twin pregnancy and suspected TTTS (Twin to Twin Transfusion Syndrome).
-
Increased values of nuchal translucency during the first trimester of gestation (>3.5 mm).
-
Early fetal growth restriction (that appears in the II trimester); in these cases, CC are most frequently associated with aneuploidy or with complex syndromes.
Technical execution of fetal echocardiography
The successful outcome of the procedure depends upon the ability to establish a correct frame for the heart using the appropriate ecographic window. Since the fetal position is not fixed in time, but is rather continuously moving during the echographic examination, it is important to have an optimal knowledge of the cardiac scans and of their characteristics.
The cardiac situs
The first step to be undertaken in the study of fetal heart is certainly the establishment of the “Situs” and, thus, of the position of the heart and of its relationships with the superior abdominal organs. Under physiological conditions, we often refer to “Situs Solitus” if the apex of the heart is oh the left (levocardia), the gastric air bubble are on the left side, the abdominal aorta is posterior and on the left of the spinal chord, the inferior vena cava is anterior and on the right of the spinal chord, the liver on the right.
Whenever the cardiac apex is to facing right then we use the term Destrocardia; the term Destropositionrefers to a heart that is displaced from its normal position due to extracardiac reasons (for example, diaphragmatic hernia, pulmonary congenital cystic adenomatoid malformation, pleuric effusion, etc.).
We use the term “Situs Inversus” when all the thoracic and abdominal organs are positioned in a perfect mirror image reversal of the normal situs solitus (apex and the gastric air bubble are on the right, the abdominal aorta is posterior and on the right of the spinal chord, the inferior vena cava is anterior and on the left of the spinal chord, the liver on the left).
Cardiac axis (Fig. (Fig.1)1)
Besides the position, particular attention needs to be placed also on the cardiac axis, which represents an element that can be easily evaluated even though the projection of 4 chambers cannot be visualized clearly (17). The cardiac axis originates from the axis passing through the interventricular septum and the anteroposterior axis of the abdomen, passing from the breastbone to the spinal chord. The angle defined by these two lines is around 45° (normal range 22°-75°). Deviations towards right or left from this normal range represent signs of cardiac anomalies, that can affect particularly the outflow tracts.
Projection of four cardiac chambers (Fig. (Fig.2)2)
The exam of the fetal heart proceeds further on with the projection of the four cardiac chambers (18, 19) (fivechambers in the case the image comprises also the origin of the ascending aorta).
Under physiological conditions, the heart tends to fill almost a third of the fetal thorax with the right apex heading towards the left anterior thoracic wall.
The atrial chambers appear, under physiological conditions, similar for dimensions. The opening of the oval foramen is towards the left atrium since the blood flux is carried through it, always from right towards left.
The thin, crescent fold of endocardium, known as the septum primum should be identified. The pulmonary veins should be visualized on the posterior wall of the left atrium.
Both the ventricles appear similar in terms of dimensions. Sometimes it is possible to recognize a slight ventricular disproportion as a normal variant. Whenever such disproportion should be more evident then it most probably refers to pathologic conditions such as hypoplastic left heart syndrome and aortic coarctation (20, 21).
The four chambers projection is also needed to identify the landmarks that allow the recognition of the atriums and the ventricles.
Two distinct atrio-ventricular (A-V) valves (the tricuspid on the right and the mitral on the left) should be seen opening separately and freely. The tricuspid valve is normally placed in a more apical position with respect to the mitral valve (normal valve off-set distance). An unusual alignment of the atrioventricular valves can be a key element in the identification of atrial-ventricular septal defects (AVSD).
The interventricular septum should be examined entirely in all of its length. The evaluation of ventricular septal defects (VSD) can be quite difficult when the angle of insonation of the transducer is directed parallel towards the ventricular wall. In such case, a false positive defect can be suspected due to the appearance of an acoustic shadow. Minor septal defects (1-2 mm) can be hard to recognize if the echographic machine is not equipped with a sufficient degree of lateral resolution, especially if the dimension and the position of the fetus are not favourable. In synthesis, the four chamber projection is the most frequently used scan and employed in 90% of cases. However it shows a low sensitivity for the recognition of CHD (22).
Such a scan can be able to identify pathologic conditions such as ventricular hypoplasia, defects of the atrioventricular septum or atresia to one or both A-V valves, nonetheless we must regard as absolutely unsatisfactory its capacity to recognize other pathologic conditions such as: subaortic ventricular defects, Fallot’s tetralogy, transposition of large vessels, double outlet right ventricle and many other complex defects. For this reason it appears clear the need to use other types of scan of the fetal heart that can show the relationship between fetal heart and large vessels.
Projection of the cardiac outflow tracts
The evaluation of the outflow tracts can increase the percent probability to identify cardiac malformations with respect to the diagnosis provided by the four cardiac chamber projection alone (23, 24). Under physiological conditions, the large vessels present approximately the same dimensions, crossing over at their origins when they exit their respective ventricular chambers.
The outflow tracts can usually be obtained by moving the transducer towards the fetal head, starting from the four chamber projection, when the interventricular septum is tangential to the ultrasonic beam.
Another method to evaluate the outflow tracts has also been described for the fetus when the interventricular septum is perpendicular to the ultrasonic beam (25).
This approach requires a four cardiac chamber projection where the probe is rotated in order to visualize the left ventricular outflow tract. Once obtained this position, the transducer is shifted in the cephalic sense in order to observe the outflow tract of the pulmonary artery on a plane which is perpendicular to the aorta. Yoo et al. have further described the “three vessel view” (Fig. (Fig.3)3) to evaluate the pulmonary artery, the ascending aorta and the superior vena cava taking into account their relative dimensions and relationships (26, 27).
Projection of the left ventricular outflow tract
The projection of the left ventricular outflow tract (Fig. (Fig.4)4) confirms the presence of a large vessel that originates from the left ventricle and is needed to ascertain the continuity from the anterior wall of the aorta to the ventricular septum.
The aortic valve moves freely without showing any sign of thickness within its context.
The identification of the aorta should be done along with the evaluation of the aortic arch that provides the origin for three vessels: the right brachiocephalic artery, the left common carotid artery, the left subclavian artery.
The aortic arch then folds down on the left of the spinal chord (Fig. (Fig.5)5) showing a typical “candy-cane” shaped structure, which then becomes the descending aorta that is placed in a slightly more medial position.
The projection of the left ventricular efflux tract can help in the identification of defects arising in the ventricular septum and of anomalies affecting the trunks, that are not recognizable with a simple four cardiac chamber projection.
Projection of the right ventricular outflow tract
The right ventricular efflux tract shows the presence of a large vessel that departs from the morphologically right ventricle. The pulmonary artery, normally, originates from the right ventricle and runs on the left of the more posterior ascending aorta. The former is slightly larger than the aorta during fetal life and crosses the ascending aorta at an angle of about 70° just above its origin.
The valves of the pulmonary artery move freely and should not be thickened. Such a projection can be confirmed when the pulmonary artery at its distal extremity shows a bifurcation of its left and right branches, even though such a bifurcation can usually be observed only in a few fetal positions.
Echocardiography for the evaluation of the fetal heart rate (FHR)
Echocardiography is very useful for the diagnosis and the management of fetal arrhythmia. The fetal ECG can be obtained by combining the use or 2D imaging and the M-mode registration during the atrial and ventricular contractions.
The incidence of fetal arrhythmia is 1-2%, 90% of which are due to isolated atrial or ventricular ectopic beats, and are in most cases of benign origin. More severe types of arrhythmia include:
-
supraventricular tachycardia;
-
atrial fibrillation/flutter;
-
ventricular tachycardia;
-
complete A-V block.
Some of these arrhythmias can be associated with structural cardiopathies.
Supraventricular tachycardia: the cardiac beats show a fast rate, normally around 180 beats per minute (28). In most cases there are no underlying cardiac pathologies. Ebstein’s anomaly of the tricuspid valve and rhabdomyomas can be responsible for a low number of cases.
Supraventricular tachycardia is generally well tolerated for short periods, however if should it be continuous it can cause myocardic disfunction, tricuspid valve reflux and cardiac insufficiency that manifest echographically through the appearance of hydrops. Echocardiography can identify all of these complications.
Complete A-V block: echocardiography allows the definition of a differential diagnosis between complete A-V blockade and sinus bradycardia by showing a normal cardiac rhythm, a slow ventricular rhythm and the presence of an A-V dissociation. The complete A-V block can be an isolated anomaly, in those cases where the moter shows a disorder affecting the connective tissue such as systemic lupus erythematosus, even on a subclinical scale.
In such cases the A-V blockade is caused by circulating antibodies, especially anti-Ro and anti-La antibodies. These antibodies cross the placenta and damage the fetal conduction tissue hence producing a complete cardiac blockade.
Bradycardia is generally well tolerated, even though a small number of fetuses experience an intrauterine cardiac insufficiency.
In the other half of cases of complete cardiac blockade, there is a basic cardiac malformation such as the correct complete transposition of great vessels or left isomerism (29). Death rates are generally quite high in the latter group, revealing a substantial number of deaths during prenatal life.
Benefits of fetal echocardiography
Fetal echocardiography has many benefits; some of these are still under investigation. The diagnosis of CHD during prenatal age is fundamental since it helps the counseling and enables parents to be informed and be prepared psychologically for the moment of birth or, alternatively, offers them the free choice of termination of pregnancy.
The newborn affected by CC should be born in a III level centre, equipped with a Unit of Intensive Neonatal Care, so that in the transition from pre- to post-natal life, the baby does not face periods of hypoxia or acidosis, and can be given immediate care.
References
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Am J Obstet Gynecol. 1994;171:392–399.[PubMed]6. Simpson LL. Screening for congenital heart disease. Obstet Gynecol Clin North Am. 2004;31:51–59.[PubMed]7. DeVore G, Medearis AL, Bear MB, Horenstein J, Platt LD. Fetal echocardiography: factors that influence imaging of the fetal heart during the second trimester of pregnancy. J Ultrasound Med. 1993;12:659–663. [PubMed]8. Sharland GK, Allan LD. Screening for congenital heart disease prenatally. Results of a 2 1/2-year study in the South East Thames Region. Br J Obstet Gynaecol. 1992;99:220–225. [PubMed]9. Carvalho JS, Mavrides E, Shinebourne EA, Campbell S, Thilaganathan B. Improving the effectiveness of routine prenatal screening for major congenital heart defects. Heart. 2002;88:387–391.[PMC free article] [PubMed]10. Forbus GA, Atz AM, Shirali GS. Implications and limitations of an abnormalfetale echocardiogram. Am J Cardiol. 2004;94:688–689. [PubMed]11. Allan LD, Sharland GK, Milburn A, Lockhart SM, Groves AMM, Aderson RH, Cook AC, Fagg NLK. Prospective diagnosis of 1006 consecutive cases of congenital heart disease in the fetus. J Am Coll Cardiol. 1994;23:1452–1458. [PubMed]12. Simpson LL. Screening for congenital heart disease. Obstet Gynecol Clin North Am. 2004;31:51–59.[PubMed]13. DeVore G, Medearis AL, Bear MB, Horenstein J, Platt LD. Fetal echocardiography: factors that influence imaging of the fetal heart during the second trimester of pregnancy. J Ultrasound Med. 1993;12:659–663. [PubMed]14. Hunter S, Heads A, Wyllie J, Robson S. Prenatal diagnosis of congenital heart disease in the northern region of England: benefits of a training programme for obstetric ultrasonographers. Heart. 2000;84:294–298. [PMC free article] [PubMed]15. Lee W. American Institute of Ultrasound in Medicine. Performance of the basic fetal cardiac ultrasound examination. J Ultrasound Med. 1998;17:601–607. [PubMed]16. Rychik J, Ayres N, Cuneo B, Gotteiner N, Hornberger L, Spevak P, Van Der Veld M. American Society of Echocardiography guidelines and standards for performance of the fetal echocardiogram. J Am Soc Echocardiogr. 2004;17:803–810. [PubMed]17. Smith RS, Comstock CH, Kirk JS, Lee W. Ultrasonographic left cardiac axis deviation: a marker for fetal anomalies. Obstet Gynecol. 1995;85:187–191. [PubMed]18. Allan LD, Crawford DC, Chita SK, Tynan MJ. Prenatal screening for congenital heart disease. Br Med J. 1986;292:1717–1719. [PMC free article] [PubMed]19. Copel JA, Pilu G, Green J, Hobbins JC, Kleinman CS. Fetal echocardiographic screening for congenital heart disease: theimportance of the four-chamber view. Am J Obstet Gynecol. 1987;157:648–655.[PubMed]20. Sharland GK, Chan KY, Allan LD. Coarctation of the aorta: difficulties in prenatal diagnosis. Br Heart J. 1994;71:70–75. [PMC free article] [PubMed]21. Kirk JS, Comstock CH, Lee W, Smith RS, Riggs TW, Weinhouse E. Fetal cardiac asymmetry: a marker for congenital heart disease. Obstet Gynecol. 1999;93:189–192. [PubMed]22. Nelson NL, Filly RA, Goldstein RB, Callen PW. The AIUM/ ACR antepartum obstetrical sonographic guidelines: expectations for detection of anomalies. J Ultrasound Med. 1993;4:186–196. [PubMed]23. Bromley B, Estroff JA, Sanders SP, Parad R, Roberts D, Frigoletto FD Jr, Benacerraf BR. Fetal echocardiography: accuracy and limitations in a population at high and low risk for heart defects. Am J Obstet Gynecol. 1992;166:1473–1481. [PubMed]24. Yoo S-J, Lee Y-H, Kim ES, Ryu HM, Kim MY, Choi HK, Cho KS, Kim A. Three-vessel view of the fetal upper mediastinum: an easy means of detecting abnormalities of the ventricular outflow tracts and great arteries during obstetric screening. Ultrasound Obstet Gynecol. 1997;9:173–182. [PubMed]25. Yoo S-J, Lee Y-H, Cho KS. Abnormal three-vessel view on sonography: a clue to the diagnosis of congenital heart d in the fetus. AJR Am J Roentgenol. 1999;172:825–830. [PubMed]26. Kirk JS, Riggs TW, Comstock CH, Lee W, Yang SS, Weinhouse E. Prenatal screening for cardiac anomalies: the value of routine addition of the aortic root to the four-chamber view. Obstet Gynecol. 1994;84:427–431. [PubMed]27. DeVore G. The aortic and pulmonary outflow tract screening examination in the human fetus. J Ultrasound Med. 1992;11:345–348. [PubMed]28. Simpson LL. Fetal supraventricular tachycardias: diagnosis and management. Sem Perinatol. 2000;24:360–372. [PubMed]29. Schmidt KG, Ulmer HE, Silverman NH, Kleinman CS, Copel JA. Perinatal outcome of fetal complete heart block: a multicenter experience. J Am Coll Cardiol. 1991;17:1360–66. [PubMed]Ultrasound Obstet Gynecol 2005; 26: 538–545
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/uog.1934
Fetal echocardiographic evaluation of atrial morphology
and the prediction of laterality in cases of heterotaxy
syndromes
C. BERG*, A. GEIPEL*, T. KOHL*, J. SMRCEK†, U. GERMER‡, A. A. BASCHAT§¶,
M. HANSMANN* and U. GEMBRUCH*
*Department of Obstetrics and Prenatal Medicine, University of Bonn, Bonn, †Division of Prenatal Medicine, University Hospital
Schleswig-Holstein, Campus Lubeck, L ¨ ubeck, ¨ ‡Department of Prenatal Medicine, University of Regensburg, Regensburg,
§Department of Obstetrics and Fetal Medicine, University of Hamburg-Eppendorf, Hamburg, Germany and ¶Center of Advanced Fetal
Care, Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore, MD, USA
KEYWORDS: atrial morphology; echocardiography; fetus; heterotaxy; isomerism; prenatal diagnosis
ABSTRACT
Objective To evaluate whether abnormal atrial morphology,
which is well recognized in autopsy series, is
detectable by fetal echocardiographic examination of the
four-chamber view, and can therefore be utilized to differentiate
left from right isomerism in heterotaxy syndromes.
Methods This study was a retrospective review of 30
cases with prenatally diagnosed heterotaxy syndromes.
Ultrasound video recordings and still images were
reviewed with respect to atrial morphology in the fourchamber
view. In 25 cases the morphology of both atria
was sufficiently well visualized on the recordings to be
evaluated and only these were included in the study.
Results Two types of atrial morphology were distinguished
in our cohort: a sickle-shape with the tip pointing
laterally and apically, and a blunt shape resembling the
usual atrial appearance in the four-chamber view. Nineteen
out of the 25 cases (76%) presented with isomerism
of the atria in the four-chamber view. Thirteen had bilateral
sickle-shaped atrial morphology, all associated with
left isomerism. Six had bilateral blunt-shaped atrial morphology,
all associated with right isomerism. The atria of
the remaining six cases were not isomeric, the right atrium
being sickle-shaped and the left blunt-shaped. Five of the
latter cases were associated with left and one with right
isomerism.
Conclusions The majority of prenatally diagnosed heterotaxy
syndromes seem to present with isomeric atrial
morphology in the four-chamber view. In these cases a
differentiation between left and right isomerism can be
based on the two distinct types of atrial morphology.
This may further enhance the prenatal differentiation of
these syndromes. Copyright 2005 ISUOG. Published
by John Wiley & Sons, Ltd.
INTRODUCTION
Heterotaxy is defined as the abnormal arrangement of
viscera across the left-right axis differing from complete
situs solitus and complete situs inversus1,2. There are
two recognized variants of heterotaxy: left isomerism and
right isomerism. Left isomerism is associated with paired
left-sided viscera, while right-sided viscera may be absent.
In contrast, right isomerism features paired right-sided
viscera, while left-sided viscera may be absent3,4.
Typical findings in left isomerism are bilateral morphological
left atrial appendages (left atrial isomerism), multiple
cardiac anomalies (with a predominance of atrioventricular
septal defect and pulmonary stenosis), congenital
heart block, bilateral morphological left (bilobed) lungs
with hyparterial bronchi, multiple splenules (polysplenia),
intestinal malrotation and interruption of the inferior vena
cava with azygos continuation4–12.
In right isomerism typical findings are bilateral morphological
right atrial appendages (right atrial isomerism),
multiple severe cardiac anomalies (with a predominance of
atrioventricular septal defect, pulmonary atresia, anomalies
of ventriculoarterial connections and anomalous
pulmonary venous return), bilateral morphological right
(trilobed) lungs with eparterial bronchi, an absent spleen
(asplenia) and a malpositioned inferior vena cava, which
may be anterior or juxtaposed to the aorta4,6,7,9–13.
Correspondence to: Dr C. Berg, Abteilung fur Pr ¨ anatale Medizin und Geburtshilfe, Zentrum f ¨ ur Geburtshilfe und Frauenheilkunde, ¨
Rheinische Friedrich-Wilhelms-Universitat, Sigmund-Freud-Str. 25, 53105 ¨ Bonn, Germany (e-mail: Christoph.Berg@ukb.uni-bonn.de)
Accepted: 15 February 2005
Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER
Atrial morphology in heterotaxy syndromes 539
The outcome of fetuses diagnosed with heterotaxy
syndromes depends on the cardiac and visceral anomalies
that are differently distributed between left and right
isomerism. Therefore, the two variants of heterotaxy
syndromes should be accurately discriminated in the
prenatal period in order to allow appropriate counseling
of parents and to plan delivery and neonatal management.
As the cardiac malformations associated with heterotaxy
syndromes show a considerable overlap during the
prenatal period, and since the postnatal diagnostic criteria
include features that are not reliably assessed in utero (e.g.
lung lobulation, bronchial branching pattern and spleen
status), prenatal diagnosis of left and right isomerism has
traditionally relied on the presence of heart block, cardiac
defects, interruption of the inferior vena cava and
juxtaposition of the inferior vena cava and aorta4,9–12.
Autopsy studies have shown that recognition of the
morphology of the isomeric atrial appendages is the
best indication of the existence of the two entities in
heterotaxy syndromes8. In normal hearts the right and
left atrial appendages have different morphologies. The
left atrial appendage is finger-like and has a narrow
base, whereas the right atrial appendage is pyramidal in
shape and its base is rather broad3,8. The right atrial
appendage is usually larger and more anterior than
the left atrial appendage6. In right isomerism there are
two morphologically right atrial appendages, while in
left isomerism there are two morphologically left atrial
appendages.
The appendages can be visualized at fetal echocardiography
in a plane slightly cranial to the four-chamber view
but they are not identified reliably under many conditions
due to their small size and their location outside of the
standard planes3. Assessment of the morphology of the
atrial appendagesin utero has been performed successfully
in few fetuses with heterotaxy syndromes14. However, its
routine use has never been established3.
It has recently been proposed that the morphology of
the atria (not necessarily their appendages) assessed in
the four-chamber view is significantly different between
left and right isomerism and could therefore enhance the
diagnosis of laterality in these syndromes (pers. comm.
J.-C. Fouron, 14th World Congress on Ultrasound in
Obstetrics and Gynecology, Stockholm, 2004).
We therefore retrospectively reviewed all ultrasound
recordings of fetuses with heterotaxy syndromes diagnosed
in our centers for the different types of atrial
morphology, and correlated the results with laterality,
and systemic venous and cardiac malformations.
METHODS
Patients with a prenatal diagnosis of heterotaxy syndrome
between 1998 and 2004 were identified in the perinatal
databases of two tertiary referral centers for prenatal
medicine and fetal echocardiography (Bonn and Lubeck, ¨
Germany). Ultrasound video recordings and still images
of these 30 cases were reviewed with respect to atrial
morphology in the four-chamber view. In 25 cases the
morphology of both atria was sufficiently visualized on
still images of the four-chamber view to be evaluated. In
five cases none or only one of the atria was sufficiently
visualized as the recordings focused mainly on the
principal cardiac defects. These five cases were excluded
from the analysis leaving 25 cases for study. In 15 out
of these 25 cases S-VHS video or digital video recordings
of the examinations were available and were additionally
reviewed. The morphology of the atrial appendages was
not assessed as they are not usually visible on the standard
echocardiographic planes and therefore were rarely and
only incompletely demonstrated in our recordings.
During the study period the anatomical survey and
fetal echocardiography was performed in a standardized
fashion. Fetal echocardiography was carried out by
a segmental approach using standardized anatomical
planes incorporating pulsed wave and color Doppler
imaging15,16. For all ultrasound examinations, 3.5-MHz,
4-MHz, 5-MHz or 7.5-MHz sector or curved array probes
(Acuson Sequoia 512, Siemens, Erlangen, Germany; ATL
HDI 5000, Phillips, Solingen, Germany) were used.
Left isomerism was diagnosed in the presence of a
combination of at least two of the following markers:
azygos continuation of an interrupted inferior vena cava;
structural heart disease with or without heart block;
and viscerocardiac heterotaxy2,4,10,17,18. Viscerocardiac
heterotaxy was defined as any situs different from situs
solitus (levocardia, stomach left, left descending aorta,
gallbladder right and portal sinus right) or situs inversus
(dextrocardia, stomach right, right descending aorta,
portal sinus left and gallbladder left). Right isomerism
was diagnosed in the presence of a combination of at least
two of the following markers: juxtaposition of descending
aorta and inferior vena cava on the same side of the
spine; structural heart disease without heart block; and
viscerocardiac heterotaxy2,4,11.
Postnatal follow-up was available for all patients of the
study population. The prenatal diagnosis was confirmed
in all cases either during cardiac surgery, neonatal imaging
studies or at autopsy. In cases with termination of
pregnancy, autopsy was performed in seven out of nine
cases. Two cases (Cases 2 and 4; Table 1) were included in
the study despite missing autopsy data, as the combination
of abnormal situs, complex cardiac malformation and
heart block allowed a diagnosis of left isomerism with
high probability.
Statistical analysis was performed using the χ2 or
Fisher’s exact test. P < 0.05 was considered significant.
RESULTS
In our study group 18 fetuses had left isomerism and seven
had right isomerism. Left isomerism was significantly
correlated with an interrupted inferior vena cava (P <
0.01) and heart block (P = 0.04), while right isomerism
was significantly correlated with a juxtaposition of
inferior vena cava and aorta (P < 0.01) and totally
anomalous pulmonary venous return (P = 0.03). Other
cardiac anomalies did not correlate with laterality. Details
Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2005; 26: 538–545.
540 Berg et al. Table 1 Laterality, atrial morphology, and prenatal and postnatal findings of 25 fetuses with heterotaxy syndromes Morphology Case Isomerism diagnosis Left atrium Right atrium Sonographic findings Additional postpartum findings Outcome and follow-up 1 Left Sickle Sickle VCH, CAVSD, muscular VSD, interr. IVC, NIHF, CHB, bilateral talipes LPSVC, bilobar right lung, polysplenia, malrotation TOP, autopsy 2 Left Sickle Sickle Situs inv., CAVSD, PS, interr. IVC, NIHF, HB II, echogenic bowel No autopsy TOP 3 Left Sickle Sickle VCH, pericardial effusion, CAVSD, common atrium, PS, interr. IVC, HB II LAI, DORV, PAPVC, LPSVC, polysplenia, malrotation, bilobed right lung TOP, autopsy 4 Left Sickle Sickle Situs inv., pericardial effusion, CAVSD, CHB No autopsy TOP 5 Left Sickle Sickle VCH, d-MGA, DORV, outlet-VSD, PS, interr. IVC, LPSVC Polysplenia, bilobar right lung TOP, autopsy 6 Left Sickle Sickle VCH, VSD, MA, CoA, HLV, interr IVC, sinus bradycardia, SUA CAVSD, biliary atresia, hypoplastic left spleen CD 7 Left Sickle Sickle Situs sol., PS, TAPVC, interr. IVC, CHB No additional findings NND 8 Left Sickle Sickle Situs sol., CAVSD, LPSVC, interr. IVC, sinus bradycardia Polysplenia CD 9 Left Sickle Sickle VCH, CAVSD, DORV, MA, PAPVC, HLV, interr. IVC LPSVC, bilobar right lung, polysplenia, malrotation Alive 10 Left Sickle Sickle VCH, interr. IVC, CAVSD, DORV, PS, LPSVC, CHB, NIHF Common atrium, periventricular leukomalacia NND 11 Left Sickle Sickle VCH, interr. IVC, CAVSD, common atrium, VSD, PA, d-TGA, HRV, pericardial effusion LPSVC, PAPVC, right aortic arch Alive 12 Left Sickle Sickle Situs inv., CAVSD, interr. IVC, LPSVC, SUA Muscular VSD, polysplenia, common atrium, PAPVC Alive 13 Left Sickle Sickle Situs sol., CAVSD, PS, interr. IVC, CHB, LPSVC Alive 14 Left Blunt Sickle VCH, CAVSD, DORV, PS, LPSVC, interr. IVC, NIHF, CHB Polysplenia TOP, autopsy 15 Left Blunt Sickle VCH, common atrioventricular-valve without CAVSD, interr. IVC, gall bladder left, PRUV, sinus bradycardia Polysplenia Alive 16 Left Blunt Sickle Situs sol., CAVSD, commom atrium, CoA, interr. IVC, postaxial hexadactyly No additional findings Alive 17 Left Blunt Sickle VCH, interr. IVC, hyperechogenic large kidneys, postaxial hexadactyly, sinus bradycardia Polysplenia, choledochal cyst Alive 18 Left Blunt Sickle VCH, CAVSD, interr. IVC, NIHF, sinus bradycardia LPSVC, incompletely trilobed right lung, polysplenia TOP, autopsy 19 Right Blunt Blunt Situs inv., VSD, HLV, MA, hypoplastic aortic arch, juxtapos. IVC/aorta, plexus cysts Asplenia TOP, autopsy 20 Right Blunt Blunt Situs inv., CAVSD, common atrium, d-TGA, agenesis of ductus arteriosus, asplenia Trilobed left lung TOP, autopsy 21 Right Blunt Blunt VCH, CAVSD, d-MGA, DORV, juxtapos. IVC/aorta RAI, TAPVC, LPSVC NND 22 Right Blunt Blunt VCH, CAVSD, cc-TGA, PS, TAPVC, juxtapos. IVC/aorta Trilobed left lung, asplenia NND 23 Right Blunt Blunt VCH, CAVSD, d-MGA, DORV, PS, juxtapos. IVC/aorta TAPVC (to the LPSVC), asplenia CD 24 Right Blunt Blunt VCH, pericardial effusion, CAVSD, double inlet single ventricle, PA, PAPVC, juxtapos. IVC/aorta, SUA LPSVC, asplenia Alive 25 Right Blunt Sickle VCH, common atrium, double inlet single ventricle, PA, d-MGA, right aortic arch, LPSVC, TAPVC (liver veins), juxtapos. IVC/aorta Asplenia Alive AA, aortic atresia; AF, atrial frequency; ASD, atrial septal defect; CAVSD, complete atrioventricular septal defect; cc-TGA, congenitally corrected transposition of great arteries; CD, childhood death; CHB, complete heart block; CoA, coarctation of the aorta; CTCR, cardio-thoracic circumference ratio; d-MGA, dextro-malposition of great arteries; d-TGA, transposition of great arteries; DORV, double outlet right ventricle; GA, gestational age; HB II, second degree heart block; HLV, hypoplastic left ventricle; HRV, hypoplastic right ventricle; interr. IVC, interrupted inferior vena cava with azygos vein continuation; IUFD, intrauterine fetal demise; juxtapos. IVC/aorta, juxtaposition of inferior vena cava and aorta; LAI, left atrial isomerism; LPSVC, left persistent superior vena cava; NIHF, non-immune hydrops fetalis; NND, neonatal death; NM, no data available; MA, mitral atresia; MI, mitral insufficiency; PA, pulmonary atresia; PAPVC, partial anomalous pulmonary venous connection; PI, pulmonary insufficiency; PRUV, persistent right umbilical vein; PS, pulmonary stenosis; RAI, right atrial isomerism; Situs inv., situs inversus; Situs sol., situs solitus; SUA, single umbilical artery; TAPVC, total anomalous pulmonary venous connection; TI, tricuspid insufficiency; TOP, termination of pregnancy; VCH, viscerocardiac heterotaxy; VF, ventricular frequency; VES, ventricular extrasystoles; VSD, ventricular septal defect.
Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2005; 26: 538–545.
Atrial morphology in heterotaxy syndromes 541
concerning cardiac and extracardiac anomalies, atrial
morphology, outcome and neonatal management are
given in Table 1.
Two general shapes of the atria in the four-chamber
view were distinguished in our collective: a sickle-shaped
atrium with its base at the interatrial septum and the
tip pointing laterally and apically (Figure 1a), and a
blunt-shaped atrium (Figure 1b) resembling the normal
appearance of both atria in the four-chamber view
(Figure 1c). The review of video recordings added no
further information to the diagnosis of the atrial shapes
when compared to the examination of still images alone.
Only three out of four possible combinations of atrial
shapes could be demonstrated in our cohort: bilateral
sickle-shaped atrial morphology (Figure 2); bilateral
Figure 1 Four-chamber view in (a) left isomerism, (b) right
isomerism, and (c) normal cardiac anatomy. The dotted line
illustrates the shape of the right atrium. While in left isomerism the
atrial morphology has a sickle shape (a), in right isomerism the
atrial shape is blunt and pyramidal (b) and resembles the normal
atrial shape (c).
blunt-shaped atrial morphology (Figure 3); and sickleshaped
right atrium in combination with a blunt-shaped
left atrium (Figure 4).
Nineteen out of the 25 studied cases (76%) presented
with isomerism of the atria in the four-chamber view.
Thirteen had bilateral sickle-shaped atrial morphology,
all associated with left isomerism. Six had bilateral
blunt-shaped atrial morphology, all associated with right
isomerism. The remaining six cases were not isomeric and
had a sickle-shaped right atrium and a blunt-shaped left
atrium. Five of the latter cases were associated with left
isomerism and one with right isomerism.
If only right atrial morphology is considered, sickleshaped
anatomy was associated with left isomerism in
18 out of 19 cases (P < 0.01), and was present in all 17
cases with an interrupted inferior vena cava (P < 0.01).
Blunt-shaped right atrial morphology was associated with
right isomerism in all six cases (P < 0.01) and with five
out of six cases with juxtaposition of the inferior vena
cava and aorta (P < 0.01). Details on the correlation of
atrial morphology with laterality, venous anomalies and
main cardiac anomalies are given in Table 2.
If only left atrial morphology is considered, sickleshaped
anatomy was associated with left isomerism in all
13 cases (P = 0.02) and with interrupted inferior vena
cava in 12 out of 13 cases (P = 0.01). A blunt-shaped left
atrium did not correlate with laterality or specific cardiac
anomalies.
Bilateral sickle-shaped atria were significantly correlated
with the presence of an interrupted inferior vena cava
and heart block (P < 0.01 and P = 0.02, respectively).
Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2005; 26: 538–545.
542 Berg et al.
Figure 2 Bilateral sickle-shaped atrial morphology in a case of left
isomerism (Case 11) showing the right atrium (filled arrow) and left
atrium (open arrow). SP, spine.
Figure 3 Bilateral blunt-shaped atrial morphology in a case of right
isomerism (Case 23) showing the right atrium (filled arrow) and left
atrium (open arrow). SP, spine.
Bilateral blunt-shaped right atria were significantly associated
with the presence of a juxtaposition of the inferior
vena cava and aorta (P < 0.01). Other cardiac anomalies,
including complete atrioventricular septal defect, right
outflow tract obstruction, left outflow tract obstruction,
single ventricle morphology and abnormal pulmonary
venous return, were not significantly correlated to atrial
morphology.
Figure 4 Sickle-shaped right (filled arrow) and blunt-shaped left
(open arrow) atrial morphology in case of left isomerism (Case 16).
SP, spine.
DISCUSSION
The intrauterine course and postnatal outcome are
significantly different for left and right isomerism,
and therefore an accurate prenatal differentiation is
mandatory in order to allow appropriate counseling
of parents and to plan neonatal management. The
greatest attrition in left isomerism occurs in the fetal
period, mainly due to the association with heart
block, leading to intrauterine congestive heart failure
and subsequent demise in a significant proportion of
fetuses17–22. In contrast, neonates with right isomerism
face a significantly higher mortality and postoperative
morbidity due to the more complex type of cardiac
malformations2,4,7,9,17,23–25.
Although morbidity and mortality in the neonatal
period are mainly determined by the cardinal cardiac
defects, the visceral anomalies may also strongly affect
the long-term outcome of these patients. Varying degrees
of malrotation and malfixation of the bowel, preduodenal
portal vein, gastric volvulus, esophageal hiatal hernia
and biliary atresia are predominant in left isomerism,
while children with right isomerism and asplenia who
survive cardiac palliation are at great risk of dying
from sepsis17,25–27. With the improvement in long-term
outcome for these patients with modern cardiac surgery,
the intra-abdominal anomalies have become increasingly
significant28,29. Accurate prenatal diagnosis of these
syndromes prompts a thorough evaluation for digestive
tract or splenic disorders in the neonatal period, with
the use of prophylactic antibiotics and vaccination in
preventing possible non-cardiac complications.
Considering the overlap of cardiac and visceral
anomalies in the two variants of heterotaxy syndromes,
Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2005; 26: 538–545.
Atrial morphology in heterotaxy syndromes 543
Table 2 Correlation of atrial morphology with laterality and cardiac anomalies in 25 cases of heterotaxy syndromes
Left atrium Right atrium Both atria
Diagnosis (n)
Sickle
shape (n)
Blunt
shape (n)
Sickle
shape (n)
Blunt
shape (n)
Bilateral
sickle
shape (n)
Bilateral
blunt
shape (n)
Right sickle,
left blunt
shape (n)
Left isomerism (18) 13* 5 18* 0 13* 0 5
Right isomerism (7) 0 7 1 6* 0 6* 1
Interruption of IVC† (17) 12* 5 17* 0 12* 0 5
Juxtaposition of IVC/aorta (6) 0 6 1 5* 0 5* 1
LPSVC (14) 8 6 11 3 8 3 3
CAVSD (19) 11 8 14 5 11 5 3
TAPVC (6) 2 4 3 3 2 3 1
Single ventricle (4) 3 1 3 1 3 1 0
Right outflow obstruction (12) 7 5 9 3 7 3 2
Left outflow obstruction (4) 2 2 3 1 2 1 1
Heart block (8) 7 1 8 0 7* 0 1
*P < 0.05. CAVSD, complete atrioventricular septal defect; IVC, inferior vena cava †with azygos vein continuation; LPSVC, left persistent
superior vena cava; TAPVC, total anomalous pulmonary venous connection.
prenatal differentiation of left and right isomerism mainly
relies on the presence or absence of heart block and
the anomalies of the inferior vena cava. However, these
sonographic markers are not invariably present and have
been described with a wide variety of prevalence in
previous series4,6,8–11,17, leaving a definitive diagnosis
in certain cases in doubt.
The most reliable tool for the diagnosis of laterality
is the morphology of the atria and their appendages
as it has been demonstrated in some autopsy series6,8.
However, this feature has not been evaluated by fetal
echocardiography in larger prenatal series.
In our study we could demonstrate two types of atrial
morphology in the four-chamber view of fetuses with
heterotaxy syndromes, although the atrial appendages
were not visualized entirely. A possible explanation for
this finding is the anatomy of the junction between the
appendage and the smooth-walled venous component
of the atrium. In the morphologically right appendage
this junction is wide and marked with an extensive
crest with pectinate muscles extending all around the
atrioventricular junction; in the morphologically left
appendage this junction is narrow, has no crest, and
only minimal extension of pectinate muscles around the
atrioventricular junction8,30. This would explain the wide
and blunt shape of the atria in right isomerism as well
as the narrow and sickle shape in left isomerism in our
collective. Another explanation could be the anatomical
distortion of the heart in heterotaxy syndromes, leading
to visualization of parts of the atrial appendages already
in the four-chamber view. This would also explain our
experience that the specific atrial morphologies described
in our series could so far not be reproduced in fetuses with
normal cardiac anatomy where both atria have a similar
round shape in the four-chamber view (Figure 1c).
Our results suggest that in fetuses with heterotaxy
syndromes, a sickle-shaped atrium in the four-chamber
view corresponds to left atrial morphology, while a bluntshaped
atrium corresponds to right atrial morphology.
Therefore, bilateral sickle-shaped atrial morphology
would correspond to left atrial isomerism, while bilateral
blunt-shaped atria would correspond to right atrial
isomerism. These findings were in keeping with the
prenatal and postnatal diagnosis of laterality in the
majority of the cases in our collective. However, the
morphology of the atria at autopsy or cardiac surgery
was sufficiently described in only two cases, preventing
further analyses concerning the correlation between the
sonographic findings and the real atrial anatomy.
In our study the morphology of the atria would have
correctly predicted laterality in the 19 (76%) cases with
isomeric atrial morphology, while the six cases (24%)
with distinct atrial shapes were neither compatible with
right nor with left isomerism.
However, it has to be kept in mind, that all these
cases were previously diagnosed with heterotaxy, based
on other criteria and that the presented study is purely
descriptive and was not performed in a blinded manner.
In fetuses without previously diagnosed heterotaxy
syndromes the different types of atrial anatomy identified
in this study have to be judged with caution. A sickleshaped
right atrium would still be a finding suspicious of
left atrial isomerism, while a blunt-shaped right atrium
would not necessarily identify right atrial isomerism as
the normal right atrial anatomy is also blunt. This applies
even more to the left atrial morphology that showed less
concordance with laterality in our cohort. Furthermore,
our knowledge concerning atrial morphology in the fourchamber
view in normal hearts as well as in different types
of complex cardiac malformations other than heterotaxy
syndromes is fragmentary and needs to be prospectively
evaluated. So far, we were not able to demonstrate the two
distinct types of atrial morphology presented in this study
in normal fetal hearts or cardiac malformations other
than those related to heterotaxy syndromes. Therefore,
a diagnosis of heterotaxy syndrome has to precede
the diagnosis of laterality based on the morphology of
the atria.
Copyright 2005 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2005; 26: 538–545.
544 Berg et al.
It has been hypothesized that the shapes of the atrial
appendages in heterotaxy syndromes are related to the
hemodynamics in utero rather than to a genetically
determined isomerism31. In the normal heart the inferior
vena caval blood stream enters the right atrium from
below and flows in the right atrial appendage, distending
it and forming the triangular and relatively large shape.
The bloodstream through the foramen ovale into the left
atrium flows behind the left atrial appendage through the
mitral valve, not distending it, resulting in the fingerlike
and relatively small shape32. In right isomerism
the inferior vena cava is not interrupted and the atrial
septum is often defective in association with common
atrioventricular canal. Consequently, the entering venous
bloodstream coming from below can flow into both
atrial appendages, distending both and resulting in a
bilateral broad and triangular shape. In left isomerism
the blood flow through the inferior vena cava is typically
interrupted, therefore reducing the systemic venous return
to the right atrium from below, and simultaneously
redirecting the inferior vena cava blood flow via the azygos
vein and the superior vena cava into the right atrium
from above, where it flows behind the atrial appendage
through the atrioventricular valve. Consequently, both
atrial appendages are not distended, resulting in a bilateral
finger-like and relatively small shape31. In fact, there
was a high correlation of interrupted inferior vena cava
and a sickle-shaped right atrium as well as a high
correlation of a patent inferior vena cava with a bluntshaped
right atrium in our collective. However, as there
was only one case without an interrupted inferior vena
cava among our cases with left isomerism (also with a
sickle-shaped right atrium), and no case of interrupted
inferior vena cava occurred among fetuses with right
isomerism, it remains unclear whether atrial morphology
is genetically determined by the type of isomerism or
mechanically modulated by the disturbed hemodynamics
in these hearts. Furthermore, neither the presence of an
atrioventricular septal defect nor other cardiac anomalies
were significantly correlated with atrial morphology,
suggesting that atrial morphology is independent from the
major cardiac malformations in heterotaxy syndromes.
Although our results seem promising, there are several
limitations that have to be considered. A potential bias of
this study is that it included only patients with heterotaxy
syndromes. This is particularly relevant when classifying
an atrium as having a blunt shape, which is similar
to the normal morphology of both atria in the fourchamber
view. Thus, differences between normal and
blunt-shaped atria may be more subtle than between a
normal and a sickle-shaped atrium as demonstrated in
Figure 1. A further bias is certainly the retrospective nonblind
design, incorporating video recordings focussing
on cardiac defects rather than atrial anatomy, as well
as stills that were retrieved at various stages of the
cardiac cycle. However, the atrial morphology may be
better seen during systole, in particular at the end of
systole. Standardizing the stage of the cardiac cycle would
therefore be of potential benefit.
In summary, a significant proportion of fetuses with
heterotaxy syndromes present with isomeric atrial morphology
in the four-chamber view at fetal echocardiography.
In these fetuses the distinct atrial shapes may be
used as a surrogate criterion for the determination of
laterality in addition to the presence or absence of heart
block, interrupted inferior vena cava and juxtaposition of
the inferior vena cava and aorta. The value of this diagnostic
tool in clinical practice has yet to be prospectively
evaluated.
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SUPPLEMENTARY MATERIAL ON THE INTERNET
The following material is available from the Journal homepage:
http://www.interscience.wiley.com/jpages/0960-7692/suppmat (restricted access)
Videoclip S1 Videoclip showing the four-chamber view in a fetus with left isomerism. Bilateral sickle-shaped atria
are demonstrated as well as a complete atrioventricular septal defect and the double vesselPrenatal diagnosis of cardiosplenic syndromes:
a 10-year experience
C. BERG*, A. GEIPEL*, J. SMRCEK†, M. KRAPP†, U. GERMER†, T. KOHL*, U. GEMBRUCH* and
A. A. BASCHAT‡
*Department of Obstetrics and Prenatal Medicine, Rheinische Friedrich-Wilhelms-Universitat, Bonn and ¨ †Division of Prenatal Medicine,
Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Lubeck, L ¨ ubeck, Germany and ¨ ‡Center for
Advanced Fetal Care, Department of Obstetrics, Gynecology & Reproductive Sciences, University of Maryland School of Medicine,
Baltimore, USA
KEYWORDS: asplenia; atrial isomerism; cardiac defects; cardiosplenic syndromes; complete heart block; echocardiography;
fetus; heterotaxy; hydrops fetalis; Ivemark syndrome; polysplenia; prenatal diagnosis
ABSTRACT
Objective To assess the accuracy of fetal echocardiography
in the prenatal diagnosis of cardiosplenic syndromes
and the spectrum of associated anomalies.
Methods This was a retrospective survey of fetuses in
our databases over a period of 10 years with postnatally
confirmed prenatal diagnosis of cardiosplenic syndromes.
Results In 32 of 35 fetuses the prenatal diagnosis
of cardiosplenic syndromes was confirmed postpartum.
Twenty-two fetuses had left isomerism. Their main
prenatal ultrasound features were interrupted inferior
vena cava (n = 21), complete atrioventricular septal defect
(n = 15), viscerocardiac heterotaxy (n = 15), persistent
bradyarrhythmia (n = 12) and fetal hydrops or nuchal
edema (n = 12). Twelve pregnancies were terminated,
two fetuses were stillborn and eight infants survived.
Ten fetuses had right isomerism. Their main sonographic
features were juxtaposition of the descending aorta and
inferior vena cava (n = 7), complete atrioventricular
septal defect (n = 7), left persistent superior vena cava
(n = 6) and viscerocardiac heterotaxy (n = 6). In this
group there was one stillbirth, five infant deaths and
four survivors. The overall survival rate and spectrum
of other cardiac malformations were similar between the
two groups. Prenatal diagnosis of other visceral features
of cardiosplenic syndromes was inconsistent.
Conclusion Cardiosplenic syndromes can be diagnosed
with high accuracy by prenatal sonography. A diagnosis
of left isomerism should be strongly suggested in the
presence of a combination of at least two of the
following: (1) complete atrioventricular septal defect or
other structural heart disease; (2) interruption of inferior
vena cava with azygos continuation; (3) early fetal heart
block; (4) viscerocardiac heterotaxy. Right isomerism
should be suspected in the presence of a combination
of at least two of the following: (1) structural heart
disease, namely complete atrioventricular septal defect;
(2) juxtaposition of inferior vena cava and descending
aorta; (3) viscerocardiac heterotaxy. Copyright 2003
ISUOG. Published by John Wiley & Sons, Ltd.
INTRODUCTION
Heterotaxy is defined as the abnormal arrangement of
viscera across the left–right axis, differing from complete
situs solitus and complete situs inversus1,2. The
term isomerism refers to the symmetrical development of
normally asymmetrical organs or organ systems, which
is the salient feature of heterotaxy syndromes. A constellation
of cardiac, vascular and visceral abnormalities
make up these syndromes. Heterotaxy syndrome, cardiosplenic
syndrome, right and left isomerism and situs
ambiguous are synonyms for these defects. There are
two recognized types; left isomerism (polysplenia syndrome,
bilateral left-sidedness or left atrial isomerism) is
associated with paired left-sided viscera while right-sided
viscera may be absent. Bilateral morphological left atrial
appendages, multiple cardiac anomalies, congenital heart
block, bilateral morphological left (bilobed) lungs with
hyparterial bronchi, multiple splenules, a malpositioned
stomach, a midline liver and an interruption of the inferior
vena cava with azygos continuation are all associated with
left isomerism3–6. In contrast, right isomerism (asplenia
Correspondence to: Dr C. Berg, Department of Obstetrics and Prenatal Medicine, Center for Obstetrics and Gynecology, Rheinische
Friedrich-Wilhelms-Universitat, Sigmund-Freud-Str. 25, ¨ 53105 Bonn, Germany (e-mail: christophberg@hotmail.com)
Accepted: 10 July 2003
Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER
452 Berg et al.
syndrome, Ivemark syndrome, bilateral right-sidedness or
right atrial isomerism) features paired right-sided viscera
while left-sided viscera may be absent. Typical findings are
bilateral morphological right atrial appendages, multiple
cardiac anomalies, bilateral morphological right (trilobed)
lungs with eparterial bronchi, an absent spleen and a
midline liver. A malpositioned inferior vena cava, which
may be anterior or juxtaposed to the aorta, is frequently
seen4,5,7.
The types of cardiac malformations associated with cardiosplenic
syndrome are complex, showing considerable
overlap. In the postnatal period, cases with left isomerism
tend to present with less severe cardiac defects, demonstrating
a normal ventriculoarterial junction in almost
70% of cases3,8. Bilateral superior vena cava, complete
atrioventricular septal defect, common atrium, ventricular
septal defect, partial anomalous pulmonary venous
return and complete heart block are frequent findings in
left isomerism3,9–12. In contrast, right isomerism is associated
with more severe cardiac defects, especially complete
atrioventricular septal defect, total anomalous pulmonary
venous return and dysfunction in ventriculoarterial connections,
mainly transposition or malposition of the great
arteries and double outlet right ventricle2,5,13–15.
In infants, the minimum diagnostic criteria for
cardiosplenic syndromes include the presence of complex
cardiovascular malformations plus at least two of the
following: ipsilateral abdominal aorta and inferior vena
cava or interruption of the inferior vena cava, isomerism
of the atrial appendages, isomerism of the lobes of
the lungs or bronchial branching, splenic anomaly, and
inverted or symmetrical liver, gall bladder or stomach2. A
number of factors make the application of these criteria
to the prenatal diagnosis of these disorders difficult. In
addition, previous prenatal studies have demonstrated
a distribution of left and right isomerism and their
associated anomalies differing significantly from that
found in the postnatal period10,12,15,16.
The aim of this study was to evaluate prenatal findings
in fetuses in whom suspected cardiosplenic syndrome was
confirmed after delivery and to characterize the diagnostic
value of prenatally diagnosed features.
METHODS
Thirty-five patients with a prenatal diagnosis of cardiosplenic
syndrome between 1991 and 2001 were identified
amongst over 25 000 fetal echocardiograms recorded in
the perinatal databases of the two participating centers
(Lubeck, Germany and Baltimore, USA). Both centers ¨
are tertiary referral centers serving a mainly Caucasian
population.
During the study period the anatomical survey and
fetal echocardiography were performed in a standardized
fashion. Fetal echocardiography was carried out in a
segmental approach using standardized anatomical planes
incorporating pulsed-wave and color Doppler imaging17.
The ultrasound machines used for all examinations
included in the study were the Acuson 128 XP/10 ob and
Acuson Sequoia 512 (Acuson, Mountain View, CA, USA)
and the ATL HDI 5000 (Phillips, Solingen, Germany)
with a 3.5-MHz, 4-MHz or 5-MHz sector probe. Cardiac
rhythm was determined using simultaneous M-mode
atrial and ventricular motion recordings. Diagnosis of
azygos continuation of an interrupted inferior vena cava
was based on the presence of the ‘double vessel’ sign in the
thorax18 and demonstration of the absence of the upper
part of the inferior vena cava with color flow Doppler
mapping showing the umbilical venous drainage into the
right atrium in a sagittal view of the fetal abdomen.
All echocardiograms were performed by two principal
investigators (U.G., A.A.B.).
Left isomerism was diagnosed in the presence of
azygos continuation of an interrupted inferior vena
cava and/or fetal heart block, supported by structural
heart disease and viscerocardiac heterotaxy (stomach
visualized contralateral to the cardiac apex). A diagnosis
of right isomerism was made in the presence of a
combination of complete atrioventricular septal defect
and/or viscerocardiac heterotaxy and/or juxtaposition of
inferior vena cava and aorta on the same side of the spine.
A detailed anatomical survey to evaluate extracardiac
anomalies was performed in all cases of prenatally
suspected heterotaxy.
Postnatal follow-up of live births was available for
95% of patients in the general population seen in our two
centers and in 100% of patients included in the study. A
thorough search of our follow-up records demonstrated
no missed cases of cardiosplenic syndrome. Four cases of
our series have been published previously. Three were
diagnosed in the first trimester of pregnancy19. One
was a combination of right isomerism and agenesis of
the corpus callosum20. All terminated pregnancies except
one underwent pathological examination. This case was
excluded from the analysis. In two further cases the
prenatal diagnosis was not confirmed or remained in
doubt after birth; these were also excluded, leaving 32
fetuses in the final analysis.
Statistical analysis was performed using chi-square and
Student’s t-tests. All values given are mean ± SD unless
otherwise indicated.
RESULTS
Of the 32 fetuses with postnatally confirmed prenatal
diagnosis of heterotaxy, left isomerism was diagnosed in
22 fetuses and right isomerism in 10 fetuses. A summary
of the findings in these 32 cases is given in Table 1.
The indications for fetal echocardiography in cases of
left isomerism were suspected congenital heart disease
on routine obstetric ultrasound (n = 9), dysrhythmia
(n = 4), nuchal edema/hydrops (n = 5) and screening for
cardiac anomalies (n = 4). In cases of right isomerism
the indications were suspected congenital heart disease on
routine obstetric ultrasound (n = 5), fetal arrhythmia (n =
1), non-immune hydrops fetalis (n = 1), situs inversus
(n = 1), polycystic right kidney (n = 1) and screening
for cardiac anomalies (n = 1). Karyotyping had been
Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2003; 22: 451–459.
Cardiosplenic syndromes 453
Table 1 Incidence of cardiovascular abnormalities in left and right
isomerism (n = 32)
Cardiovascular abnormality
Left
isomerism
(n = 22)
(n (%))
Right
isomerism
(n = 10)
(n (%))
Levocardia 15 (68) 5 (50)
Dextrocardia 7 (32) 4 (40)
Atrioventricular septal defect 15 (68) 7 (70)
Ventricular septal defect 4 (18) 4 (40)
Atrial septal defect, common
atrium
8 (36) 2 (20)
Cor triatriatum sinister 1 (05) – –
Interrupted inferior vena cava 21 (95) – –
Left persistent superior vena cava 7 (32) 6 (60)
Juxtaposition of descending aorta
and inferior vena cava
– – 7 (70)
Double outlet right ventricle 5 (23) 2 (20)
Truncus arteriosus 2 (09) – –
Corrected transposition of the
great arteries
1 (05) 3 (30)
Partial anomalous pulmonary
venous connection
3 (14) 2 (20)
Total anomalous pulmonary
venous connection
1 (05) 2 (20)
Tetralogy of Fallot 1 (05) – –
Pulmonary stenosis 9 (41) 3 (30)
Pulmonary atresia 1 (05) 2 (20)
Mitral stenosis 1 (05) – –
Tricuspid atresia – – 1 (10)
Coarctation of the aorta 1 (05) 2 (20)
Hypoplastic left ventricle 2 (09) – –
Viscerocardiac heterotaxy 15 (68) 6 (60)
Arrhythmia 12 (55) 1 (10)
performed in 30 cases prior to referral and was normal
in all cases. The mean gestational age at first fetal
echocardiography was 23.3 (± 7.4) weeks and 26.6
(± 4.8) weeks for left and right isomerism, respectively
(P = 0.13).
Fetuses with left isomerism
Of the 22 fetuses with left isomerism 13 were female and
9 were male. Table 2 displays their prenatal sonographic
findings as well as the additional anomalies diagnosed at
autopsy or by neonatal imaging studies. Interruption of
the inferior vena cava with azygos continuation (Figure 1)
was the most consistent finding, and was observed
in 21 fetuses. The remaining case had a combination
of viscerocardiac heterotaxy, complete atrioventricular
septal defect and complete heart block at 12 weeks
of gestation. Additionally an interrupted inferior vena
cava with azygos continuation was demonstrated at
autopsy.
Complete atrioventricular septal defect was demonstrated
in 15 fetuses, isolated atrial septal defect in 3, and
isolated ventricular septal defect in 1 fetus. A combination
of atrial septal defect and ventricular septal defect
was seen in 1 fetus. Only 2 fetuses had an intact atrial
and ventricular septum.
Figure 1 Color Doppler ultrasound image showing interruption of
the inferior vena cava with azygos continuation, demonstrated in a
fetus with left isomerism at 21 weeks of gestation. The blood flow
in the azygos vein is colored red. Fetal ascites is also evident. (AZV,
azygos vein; DAO, descending aorta; DV, ductus venosus; RA,
right atrium; SVC, superior vena cava).
Figure 2 Doppler ultrasound image showing complete heart block
(CHB) demonstrated in a fetus with left isomerism at 21 weeks of
gestation. The occurrence of ventricular systoles (V) as
demonstrated by the blood flow in the descending aorta is
absolutely independent from the atrial systoles (A) as demonstrated
by the blood flow in the azygos vein.
Viscerocardiac heterotaxy was diagnosed in 15 fetuses,
11 with levocardia and a right-sided stomach, and 4
with dextrocardia and a left-sided stomach. Among
the 7 fetuses without viscerocardiac heterotaxy, 4 had
levocardia and a left-sided stomach (situs solitus),
and 3 had dextrocardia and a right-sided stomach
(situs inversus).
Fetal dysrhythmia was detected in 12 fetuses, 10 with
complete heart block (Figure 2) and 2 with second-degree
heart block. Other frequent findings were pulmonary
stenosis (n = 9), left persistent superior vena cava (n = 7)
and double outlet right ventricle (n = 5). There were 12
fetuses with nuchal edema or hydropic changes.
Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2003; 22: 451–459.
454 Berg et al.
Outcome
Twelve patients underwent therapeutic abortion. Eight of
them had a combination of congenital heart block and
nuchal edema or non-immune hydrops. In addition, two
fetuses died in utero at 27 and 34 weeks of gestation,
respectively. Both had non-immune hydrops fetalis, one
in combination with complete heart block. All of the eight
delivered children were alive at the time of writing. None
of the survivors had hydropic changes and only one had
a complete heart block. The cardiac malformations of
all fetuses, their outcome and corrective procedures are
shown in Table 2. Two cases of left isomerism occurred
Table 2 Cardiac malformations and pregnancy outcome in 22 fetuses with left isomerism
Case
Gestational
age at
detection
(weeks)
Cardiac malformations
at prenatal
echocardiography
Additional findings
at prenatal
sonography
Additional postpartum
findings
at autopsy or neonatal
imaging studies Outcome and follow-up
1 12 + 4 CAVSD, ASD, interr. IVC Situs inv., HB II,
nuchal edema,
PAPVC, LAI, polysplenia TOP
2 13 + 5 CAVSD, PA, interr. IVC VCH, HB II, nuchal
edema
Bilobed right lung, spleen
right
TOP
3 14 + 1 VSD, d-MGA, DORV,
LPSVC, right aortic
arch, interr. IVC
VCH, CHB, nuchal
edema,
Polysplenia, agenesis of
corpus callosum
TOP
4 11 + 4 CAVSD, PS VCH, CHB, nuchal
edema
Interr. IVC, right spleen, TOP
5 21 + 1 CAVSD, common atrium,
TAC, PAPVC, right
aortic arch, interr. IVC
Situs inv. Bilobed right lung,
hypoplastic pancreas,
spleen right, malrotation of
gut
TOP
6 24 + 2 CAVSD, TAC, HLV,
interr. IVC
Situs inv. Bilobed right lung,
hypoplastic pancreas,
polysplenia
TOP
7 22 + 1 CAVSD, d-MGA, DORV,
PS, PAPVC, interr. IVC
VCH, CHB, NIHF Bilobed right lung,
hypoplastic pancreas,
polysplenia, incomplete
malrotation of gut,
extrahepatic biliary atresia
TOP
8 22 + 3 CAVSD, PS, interr. IVC VCH CHB, NIHF Polysplenia TOP
9 19 + 4 CAVSD, DORV, PS,
LPSVC, interr. IVC
VCH, CHB, NIHF Polysplenia TOP
10 19 + 2 CAVSD, DORV,
interr. IVC
VCH Polysplenia TOP
11 20 + 6 CAVSD, VSD, LPSVC,
interr. IVC
VCH, CHB, clubbed
feet, NIHF
Bilobed right lung, pancreas
right, polysplenia,
malrotation of gut
TOP
12 24 + 1 CAVSD, common atrium,
PS, interr. IVC
VCH, CHB, NIHF Cleft palate, brachymelia,
microretrognathia, partially
bilobed right lung, aplasia
of pancreas, splenomegaly
TOP
13 22 + 0 CAVSD, VSD, PS,
d-MGA, interr. IVC
Situs sol., pericardial
effusion, nuchal
edema
Bilobed right lung,
polysplenia, malrotation of
gut, lumbosacral spina
bifida
Intrauterine demise at
27 + 0 weeks
14 26 + 4 Tetralogy of Fallot, ASD,
LPSVC, interr. IVC
VCH, CHB, NIHF None Intrauterine demise at
34 + 4 weeks
15 23 + 5 ASD, interr. IVC VCH Total anomalous liver vein
connection, cor triatriatum,
LAI, right spleen
Reconstruction of the atrial
anatomy, clipping of the
ductus arteriosus, follow-up
11 years
16 35 + 2 CoA, LPSVC, MS, HLV,
interr. IVC,
VCH, sinus
bradycardia
Bilobed right lung, LAI Resection of the ductus
arteriosus,
patch-reconstruction of the
aortic arch, closure of the
foramen ovale, follow-up
12 years
17 33 + 2 CAVSD, PS, LPSVC,
interr. IVC
Situs sol, CHB None Pacemaker implantation,
biventricular correction of
AVSD is pending,
follow-up 3 months
Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2003; 22: 451–459.
Cardiosplenic syndromes 455
Table 2 (Continued)
Case
Gestational
age at
detection
(weeks)
Cardiac malformations
at prenatal
echocardiography
Additional findings
at prenatal
sonography
Additional postpartum
findings
at autopsy or neonatal
imaging studies Outcome and follow-up
18 30 + 1 ASD, interr. IVC VCH None Digitalis treatment in the
neonatal period, follow-up
7 years
19 27 + 1 ASD, VSD, l-TGA, PS,
interr. IVC
VCH Spleen left No treatment, follow-up
4 years
20 40 + 4 CAVSD, d-MGA, PS,
DORV, TAPVC,
interr. IVC
VCH Spleen right Surgery pending, follow-up
1 month
21 29 + 1 right aortic arch, LPSVC,
interr. IVC
Situs sol. None No treatment, follow-up
6 months
22 18 + 6 CAVSD, common atrium,
PI, interr. IVC
Situs sol., pericardial
effusion, nuchal
edema
None Surgery pending, follow-up
1 month
ASD, atrial septal defect; CAVSD, complete atrioventricular septal defect; CHB, complete heart block; CoA, coarctation aortae; DORV,
double outlet right ventricle; HB II, second degree heart block; HLV, hypoplastic left ventricle; interr. IVC, interrupted inferior vena cava
with azygos vein continuation; LAI, left atrial isomerism; LPSVC, left persistent superior vena cava; l-TGA, congenitally corrected
transposition of great arteries; d-MGA, dextro-malposition of great arteries; MS, mitral stenosis; NIHF, non-immune hydrops fetalis; PA,
pulmonary atresia; PAPVC, partial anomalous pulmonary venous connection; PS, pulmonary stenosis; PI, pulmonary insufficiency; Situs
inv., situs inversus totalis; Situs sol., situs solitus; TAC, truncus arteriosus communis; TAPVC, total anomalous pulmonary venous
connection; TOP, termination of pregnancy; VCH, viscerocardiac heterotaxy; VSD, ventricular septal defect.
in subsequent pregnancies of a patient with a family
history of congenital heart disease. Other associated
conditions in left isomerism were maternal diabetes
mellitus type 1 (n = 1), consanguineous parents (n = 1),
clubbed feet (n = 1), agenesis of the corpus callosum
(n = 1), extrahepatic biliary atresia (n = 1), cleft palate
(n = 1), brachymelia (n = 1), and lumbosacral spina
bifida (n = 1).
Fetuses with right isomerism
Of the 10 fetuses with right isomerism 8 were male and
2 female (Table 3). There were 7 which had a complete
atrioventricular septal defect and 4 had ventricular septal
defect, 1 of them of the ‘atrioventricular canal type’.
Juxtaposition of the descending aorta and inferior vena
cava (Figure 3) was demonstrated in 5 fetuses. Viscerocardiac
heterotaxy was present in 6 fetuses, 4 with
levocardia and a right-sided stomach, and 2 with dextrocardia
and a left-sided stomach. Among the 4 fetuses
without viscerocardiac heterotaxy, 2 had levocardia and a
left-sided stomach (situs solitus), and 2 had dextrocardia
and a right-sided stomach (situs inversus). Other findings
included left persistent superior vena cava (n = 6), pulmonary
stenosis/atresia (n = 3/2), congenitally corrected
transposition of the great arteries (n = 3), double outlet
right ventricle (n = 2) and fetal hydrops (n = 1). There
was 1 fetus with sinus bradycardia.
Outcome
Due to the advanced gestational age at detection, no
case of right isomerism was terminated. The fetus with
non-immune hydrops fetalis died in utero at 32 weeks of
Figure 3 Gray-scale ultrasound image showing juxtaposition of
descending aorta and inferior vena cava demonstrated in a fetus
with right isomerism at 27 weeks of gestation (DAO, descending
aorta; IVC, inferior vena cava; PS, portal sinus; ST stomach).
gestation. Following 4 neonatal and 1 infant death (at
6 months of age) only 4 children survived. Associated
conditions were maternal diabetes mellitus type 1 (n = 1),
agenesis of the corpus callosum (n = 1), arachnoid cyst
(n = 1), brachymelia (n = 1), and thoracic spina bifida
(n = 1).
When the spectrum of prenatally diagnosed anomalies
was compared, interruption of the inferior vena cava
and fetal arrhythmia were significantly more frequent
in left isomerism, while juxtaposition of the descending
Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2003; 22: 451–459.
456 Berg et al.
Table 3 Cardiac malformations and pregnancy outcome in 10 fetuses with right isomerism
Case
Gestational
age at
detection
(weeks)
Cardiac malformations
at prenatal
echocardiography
Additional findings
at prenatal
sonography
Additional postpartum
findings
at autopsy or neonatal
imaging studies Outcome and follow-up
1 32 + 5 CAVSD, CoA, l-TGA, LPSVC Situs inv., NIHF Multilobar left lung,
asplenia, malrotation
of gut
Intrauterine demise
2 24 + 2 CAVSD, PS, HRV, LPSVC VCH TAPVC, trilobed left
lung, right pancreas,
asplenia
Demise at 6 months, central
thrombosis after central shunt
placement and bi-directional
Glenn shunt
3 23 + 5 CAVSD, l-TGA, PA,
PAPVC, LPSVC,
juxtapos. IVC/aorta
Situs inv. Asplenia No treatment, demise in the
neonatal period
4 28 + 0 CAVSD, d-MGA,
DORV, PS, LPSVC,
juxtapos. IVC/aorta
VCH, short
extremities, agenesis
of corpus callosum,
facial dysmorphy,
duodenal stenosis
Trilobed left lung,
pancreas annulare,
asplenia, malrotation
of gut, incomplete
closure of T3 + T4
No treatment, demise in the
neonatal period
5 24 + 2 VSD, CoA, l-TGA, TA,
juxtapos. IVC/Aorta
Situs sol. Asplenia Demise in the neonatal period
during cardiac surgery
6 23 + 2 CAVSD, PAPVC VCH, arachnoid cyst Asplenia Demise in the neonatal period
after removal of the arachnoid
cyst
7 30 + 6 CAVSD, VSD, PA,
TAPVC, d-MGA, LPSVC,
juxtapos. IVC/aorta
VCH, multicystic right
kidney
Trilobed left lung,
asplenia
Blalock–Taussig shunt,
aortopulmonary anastomosis,
prophylactic antibiotic
therapy, follow-up 5 years
8 35 + 0 VSD, PS, d-MGA, DORV,
juxtapos. IVC/aorta
VCH Asplenia Blalock–Taussig shunt,
prophylactic antibiotic
therapy, follow-up 8 months
9 24 + 4 ASD, VSD,
juxtapos. IVC/aorta
VCH, sinus
bradycardia,
Asplenia Prophylactic antibiotic therapy,
follow-up 1 year
10 19 + 5 CAVSD, common atrium,
LPSVC
Situs sol. Asplenia Reconstruction of the atrial
anatomy, follow-up 1 year
ASD, atrial septal defect; CAVSD, complete atrioventricular septal defect; CoA, coarctation aortae; DORV, double outlet right ventricle;
HRV, hypoplastic right ventricle; juxtapos. IVC/aorta, juxtaposition of inferior vena cava and aorta; LPSVC, left persistent superior vena
cava; l-TGA, congenitally corrected transposition of great arteries; d-MGA, dextro-malposition of great arteries; NIHF, non-immune
hydrops fetalis; PA, pulmonary atresia; PAPVC, partial anomalous pulmonary venous connection; PS, pulmonary stenosis; Situs inv., situs
inversus totalis; Situs sol., situs solitus; TA, tricuspid atresia; TAPVC, total anomalous pulmonary venous connection; VCH, viscerocardiac
heterotaxy; VSD, ventricular septal defect.
aorta and inferior vena cava was more common in right
isomerism (P < 0.05).
In three fetuses the prenatal diagnosis of cardiosplenic
syndrome could not be confirmed after birth (Table 4).
In one of these polysplenia was diagnosed at 12 weeks’
gestation; however, no autopsy was performed after termination
of pregnancy. Another fetus had viscerocardiac
heterotaxy, ventricular septal defect, pulmonary stenosis,
dextro-malposition of the great arteries, double outlet
right ventricle and second-degree heart block. However,
postnatal imaging studies revealed situs inversus totalis
and a normal spleen, so the diagnosis of asplenia syndrome
remained in doubt. The third case had azygos
continuation of interrupted inferior vena cava and pericardial
effusion without associated cardiac malformations
or situs anomalies. Additional prenatal findings were
hemifacial microsomia and hexadactyly. After birth the
presumptive diagnosis of Goltz–Gorlin syndrome, a focal
dermatosis, was made.
DISCUSSION
This study reports the prenatal sonographic findings
in fetuses with cardiosplenic syndromes. The relative
frequency of right and left isomerism and the spectrum
of anomalies is comparable to some of the previously
reported prenatal series10,15 while it significantly differs
from others12,16. The presence of cardinal cardiac defects,
which are readily detectable by fetal echocardiography,
raises several issues regarding prenatal diagnosis and
management.
Formation of the heart begins with a straight midline
tube and involves an orderly sequence of folding and
turning to eventually create the four chambered organ
with aligned inflow and outflow tracts, all of which are
positioned on the left side of the body. Growth of the
endocardial cushions, septation of the conotruncus and
establishment of the connection between the atria and
the venous plexus occurs between 28 and 35 days of
Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2003; 22: 451–459.
Cardiosplenic syndromes 457
Table 4 Cardiac malformations and pregnancy outcome in three unconfirmed cases
Case
Gestational
age at
detection
(weeks)
Cardiac malformations
at prenatal
echocardiography
Additional findings
at prenatal
sonography
Additional postpartum
findings at
autopsy or neonatal
imaging studies Outcome and follow-up
1 12 + 4 VSD, d-MGA, DORV Nuchal edema, HB II,
VCH
No autopsy TOP
2 38 + 1 VSD, d-MGA, DORV, PS HB II, VCH Situs inversus totalis,
normal spleen
Alive after central shunt
placement, VSD-repair
and ASD-repair
3 23 + 5 Interr. IVC Hemifacial microsomia,
hexadactyly
Suspected focal dermatosis Alive
ASD, atrial septal defect; DORV, double outlet right ventricle; HB II, second degree heart block; interr. IVC, interrupted inferior vena cava
with azygos vein continuation; d-MGA, dextro-malposition of great arteries; PS, pulmonary stenosis; TOP, termination of pregnancy; VCH,
viscerocardiac heterotaxy; VSD, ventricular septal defect.
gestation, the same time period as when the spleen arises
from the left side of the mesogastrium. An embryological
insult at this time has therefore been postulated to
be the pathogenic mechanism of laterality defects21–23.
Cardiac manifestations of heterotaxy often result in
complex congenital heart disease because the left and
right chambers may be abnormal or misaligned with the
inflow (caval and pulmonary veins) and outflow (aorta
and pulmonary artery) vessels. In left isomerism this
often leads to discontinuity between the atrioventricular
node and the ventricular conduction tissues, resulting in
complete heart block9.
A common embryological origin for left and right isomerism
has been proposed based on animal models and
human gene locus mapping24–26. Despite this proposed
common mechanism to obtain asymmetry, left and right
isomerism appear as phenotypically distinct entities with
unequal frequency distributions before and after birth. In
the majority of studies left isomerism is more commonly
detected in fetal life, while right isomerism is more common
postnatally10,15. Although this could be due to a
selection bias, more likely it is due to the clinically apparent
disease spectrum of left isomerism. Nuchal edema,
non-immune hydrops fetalis and fetal dysrhythmia, which
are present in a high percentage of cases with left isomerism,
may be detected early in fetal life prompting
referral for detailed cardiac imaging. This is corroborated
in our series by the earlier gestational age at referral and
the four fetuses with first-trimester diagnosis. In our series
fetuses with right isomerism were all detected later than
20 weeks’ gestational age, suggesting that an unknown
percentage may have had an earlier demise and therefore
escaped detection. On the other hand there seems to be a
predominance of right atrial isomerism in the Asian population.
Lin et al. found only four cases of left isomerism
among a series of 29 cases of cardiosplenic syndromes16.
The spectrum of cardiovascular malformations in right
isomerism in our series only partly matches the results of
a previously published fetal autopsy study and the fetal
echocardiography studies6,10,15,16. In fetuses with right
isomerism our prevalence of double outlet right ventricle,
discordance in ventriculoarterial connection, pulmonary
atresia and total anomalous pulmonary venous return
was lower (25%, 25%, 13% and 25%, respectively) than
that described by Ho et al.
6 (50%, 40%, 50% and 40%,
respectively), Atkinson and Drant12 (38%, 50%, 63%
and 50%, respectively) and Lin et al.
16 (88%, 4%, 72%
and 40%, respectively). The largest series of cardiosplenic
syndromes in fetuses published to date demonstrated
double outlet right ventricle in 70% of fetuses with right
isomerism15. However, the 62 cases of left isomerism
and the 37 cases of right isomerism presented in that
study were a subset of fetuses with the prenatal diagnosis
of atrioventricular septal defect. This discrepancy could
therefore be due to the limited number of cases with right
isomerism in our series or to a selection bias in previous
studies.
We found no significant differences in severe lifelimiting
cardiovascular malformations between fetuses
with left or right isomerism. This contrasts with postnatal
studies in which fetuses with right isomerism tend to
present with more severe cardiac malformations4,14,27.
The most plausible explanation is the selection bias
imparted by the high intrauterine lethality of heart defects
found in left isomerism. Particularly, the combinations
of complete atrioventricular canal with complete heart
block carry a high risk for intrauterine heart failure
and/or fetal demise. This constellation was observed in the
majority of patients that presented early enough to elect
pregnancy termination. Consequently, survivors with less
severe disease at birth had better outcomes than did their
counterparts with right isomerism.
In addition to the classic disease spectrum of heterotaxy
that was observed, one of the cases for which the diagnosis
was rejected postnatally may fall into a separate disease
group. In this neonate the diagnosis was revised, as there
was situs inversus totalis and a right-sided spleen. Van
Praagh and Van Praagh found five cases of isolated right
spleen and levocardia among 104 cases of heterotaxy and
classified them as a separate group, distinct from asplenia
and polysplenia28.
In our patients with left isomerism nine of 14 fetuses
that underwent autopsy had polysplenia, three had rightsided
spleen without further morphological description,
Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2003; 22: 451–459.
458 Berg et al.
one had splenomegaly and in one case the splenic situs was
not described. It has been emphasized that none of the
features seen in cardiosplenic syndrome is mandatory5.
Although polysplenia is the most common finding in left
isomerism, asplenia or a normal spleen may be present.
Similarly, in right isomerism the presence of a spleen does
not rule out the diagnosis5,6. The most reliable tool for
the diagnosis is autopsy by a specialized fetal pathologist.
The majority of the associated malformations in our
series (agenesis of the corpus callosum20, spina bifida,
cleft palate) can be considered as midline developmental
field defects, representing coherent and synchronic defects
rather than causally independent malformations.
When the spectrum of possible cardiac and extracardiac
anomalies associated with heterotaxy is considered, it
becomes apparent that postnatal diagnostic criteria are
not as useful in utero. Although, prenatal diagnosis of
right atrial isomerism based upon the configuration of
the atrial appendages has been reported29, the marked
variability in configuration of the atrial appendages makes
prenatal diagnosis based on morphology alone difficult.
In the fetus lung lobulation and bronchial branching
patterns are difficult to assess in the absence of a pleural
effusion. Gray-scale identification of the fetal spleen
is possible from 20 weeks’ gestation, but it may be
difficult in heterotaxy due to the anatomical distortion
that is associated with situs ambiguity in these patients.
Color Doppler mapping of the splenic artery may be
helpful after 26 weeks30. Phoon et al. proposed that a
thorough examination of the viscerocardiac situs may lead
to the prenatal diagnosis of cardiosplenic syndrome10.
However, we found viscerocardiac heterotaxy to be a
very inconsistent finding. Stomach, liver, and gall bladder
may be in the solitus as well as in the inversus position.
In our series, fetuses with polysplenia had viscerocardiac
situs ambiguous, inversus and solitus in 68%, 14% and
18% of cases, respectively. Among those with asplenia,
50% had situs ambiguous and 50% had situs inversus.
In contrast to the viscera, the delineation of cardiovascular
anomalies is more readily achieved and offers
important diagnostic pointers. Discontinuity of the inferior
vena cava represents an excellent marker of left isomerism.
The reported incidence of this anomaly amongst
fetuses with left isomerism ranges between 55% and 85%
in postmortem series and infants, respectively3,4,6,31. In
our series all fetuses had an interrupted inferior vena
cava. A selection bias cannot be completely excluded in
this respect; however, a thorough search of our follow-up
records did not reveal any missed case of left isomerism
without interruption of the inferior vena cava. In contrast,
interruption of the inferior vena cava is rare under
other circumstances. Only a few cases of right isomerism
with interruption of the inferior vena cava have been
described previously31–33. Similarly, interruption of the
inferior vena cava in situs solitus of the chest, as in our
misdiagnosed Case 3 (Table 4), is extremely rare34. Fetal
heart block detected in the first trimester strongly suggests
the presence of congenital heart disease, namely
complete atrioventricular septal defect and/or left atrial
isomerism, as immune-mediated heart block does not
develop before the antibodies start to cross the placenta
in the early second trimester19. In our series juxtaposition
of the descending aorta and inferior vena cava on the same
side of the spine was found in 70% of cases with right
isomerism and represents another important diagnostic
marker. Although described in a fetal autopsy study6 this
marker has not been evaluated by the largest prenatal
series of right isomerism published to date12,15,16.
Among fetuses with structural cardiac anomalies,
abnormal visceral situs is strongly predictive of a
normal karyotype15,35. In our series, most cases were
karyotyped prior to referral, and all proved to be
normal. However there are several reports on the
association of cardiosplenic syndrome and chromosomal
abnormalities, mainly microdeletion of chromosome
22q11, trisomy 18 and trisomy 132,15,16,36,37, suggesting
that fetal karyotyping still needs to be carefully considered
in suspected cardiosplenic syndrome.
Despite the similar overall mortality in cases of left
and right isomerism in our series these syndromes should
be accurately diagnosed in the prenatal period in order
to allow appropriate counseling of parents and to plan
delivery and neonatal management. Death in the first year
of life is common in right isomerism, especially if there
is pulmonary atresia and anomalous pulmonary venous
return, as demonstrated in Cases 2 and 3 (Table 3) in our
series. In contrast, the prognosis of left isomerism may be
quite good in the absence of heart block, as it tends to
present with less severe cardiac anomalies or even with
normal intracardiac anatomy, as in Case 21 (Table 2) in
our series.
Although morbidity and mortality in the neonatal
period are determined mainly by the cardinal cardiac
defects, the visceral anomalies may strongly affect the
long-term outcome of these patients. Varying degrees of
malrotation and malfixation of the bowel, preduodenal
portal vein, gastric volvulus, esophageal hiatal hernia
and biliary atresia are common in both left and right
isomerism, with a predominance in left isomerism.
With the improvement in long-term outlook for these
patients with modern cardiac surgery the intra-abdominal
anomalies have become increasingly significant38,39.
Children with right isomerism and asplenia who
survive cardiac palliation are at great risk of dying
from sepsis40–42. Accurate prenatal diagnosis of these
syndromes will therefore prompt a thorough evaluation
for digestive tract disorders in the neonatal period,
prophylactic antibiotics and vaccination, preventing
possible non-cardiac complications.
Based on our series, we propose that a diagnosis
of left isomerism should be strongly suggested in the
presence of a combination of at least two of the
following: (1) complete atrioventricular septal defect or
other structural heart disease; (2) interruption of inferior
vena cava with azygos continuation; (3) early fetal heart
block; (4) viscerocardiac heterotaxy.
Right isomerism should be suspected in the presence of a
combination of at least two of the following: (1) structural
Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2003; 22: 451–459.
Cardiosplenic syndromes 459
heart disease, namely complete atrioventricular septal
defect; (2) juxtaposition of inferior vena cava and
descending aorta; (3) viscerocardiac heterotaxy.
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First Published July 25, 2016 Review Article
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