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 Lübeck, Lübeck, ‡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

K E Y W O R D S: atrial morphology; echocardiography; fetus; heterotaxy; isomerism; prenatal diagnosis

ABSTRACT This may further enhance the prenatal differentiation of

Objective To evaluate whether abnormal atrial mor-
phology, which is well recognized in autopsy series, is
detectable by fetal echocardiographic examination of the
four-chamber view, and can therefore be utilized to differ-
entiate 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 four-
chamber 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 distin-
guished 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. Nine-
teen out of the 25 cases (76%) presented with isomerism
of the atria in the four-chamber view. Thirteen had bilat-
eral sickle-shaped atrial morphology, all associated with
left isomerism. Six had bilateral blunt-shaped atrial mor-
phology, 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 het-
erotaxy 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.
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 morpho-
logical left atrial appendages (left atrial isomerism), mul-
tiple cardiac anomalies (with a predominance of atrioven-
tricular 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 mor-
phological right atrial appendages (right atrial isomerism),
multiple severe cardiac anomalies (with a predominance of
atrioventricular septal defect, pulmonary atresia, anoma-
lies 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 für Pränatale Medizin und Geburtshilfe, Zentrum für Geburtshilfe und Frauenheilkunde,
Rheinische Friedrich-Wilhelms-Universität, 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
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 hetero-
taxy 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, car-
diac 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 echocardio-
graphy 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 appendages in 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 diag-
nosed 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 Lübeck,
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
Copyright  2005 ISUOG. Published by John Wiley & Sons, Ltd.
539
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
Ultrasound Obstet Gynecol 2005; 26: 538–545.
 Table 1 Laterality, atrial morphology, and prenatal and postnatal findings of 25 fetuses with heterotaxy syndromes
540

Morphology

Isomerism Left Right Outcome and

Case diagnosis atrium atrium Sonographic findings Additional postpartum findings 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, TOP, autopsy
bilobed right lung
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 LPSVC, PAPVC, right aortic arch Alive
effusion
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

Copyright  2005 ISUOG. Published by John Wiley & Sons, Ltd.

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, Polysplenia Alive
PRUV, sinus bradycardia
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 Polysplenia, choledochal cyst Alive
bradycardia
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 Asplenia TOP, autopsy
cysts
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, LPSVC, asplenia Alive
juxtapos. IVC/aorta, SUA
25 Right Blunt Sickle VCH, common atrium, double inlet single ventricle, PA, d-MGA, right aortic arch, Asplenia Alive
LPSVC, TAPVC (liver veins), juxtapos. IVC/aorta

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.

Ultrasound Obstet Gynecol 2005; 26: 538–545.

Berg et al.
Atrial morphology in heterotaxy syndromes
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
Copyright  2005 ISUOG. Published by John Wiley & Sons, Ltd.
541
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 sickle-
shaped 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, sickle-
shaped 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, sickle-
shaped 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 corre-
lated with the presence of an interrupted inferior vena cava
and heart block (P < 0.01 and P = 0.02, respectively).
Ultrasound Obstet Gynecol 2005; 26: 538–545.
542
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 asso-
ciated 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.
Copyright  2005 ISUOG. Published by John Wiley & Sons, Ltd.
Berg et al.
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,
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

Bilateral Bilateral Right sickle,

Sickle Blunt Sickle Blunt sickle blunt left blunt
Diagnosis (n) shape (n) shape (n) shape (n) shape (n) shape (n) shape (n) 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 blunt-
shaped 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 sickle-
shaped 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 four-
chamber 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
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 finger-
like 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 blunt-
shaped 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 four-
chamber 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 non-
blind 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.
Copyright  2005 ISUOG. Published by John Wiley & Sons, Ltd.
Berg et al.
In summary, a significant proportion of fetuses with
heterotaxy syndromes present with isomeric atrial mor-
phology in the four-chamber view at fetal echocardiog-
raphy. 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 diag-
nostic 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 vessel sign with the aorta and
the dilated azygos vein running behind the heart.
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