Eco fe tal tac e ap civ

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Original Paper
Fetal Diagn Ther 2016;39:90–99
DOI: 10.1159/000433430
Accuracy of Fetal Echocardiography
in the Differential Diagnosis between
Truncus Arteriosus and Pulmonary Atresia
with Ventricular Septal Defect
Olga Gómeza, b
Iris Soverala, b
Mar Bennasara, b
Fatima Crispia, b
Narcis Masollera, b
Edda Marimona, b
Joaquim Bartronsc
Eduard Gratacósa, b
Josep M. Martineza, b
a
Fetal Cardiology Unit, BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clinic and
Hospital Sant Joan de Déu), IDIBAPS, University of Barcelona, b
Centre for Biomedical Research on Rare Diseases
(CIBER-ER), and c
Pediatric Cardiology, Hospital Sant Joan de Déu, Barcelona, Spain
respectively. In the PA-VSD group, patent ductus arteriosus
and major aortopulmonary collateral arteries (MAPCAs)
were present in 70 and 50% of the cases, respectively, coex-
isting in 1 of 5 cases. MAPCAs were significantly associated
with a right aortic arch and with a 22q11 microdeletion in
50% of cases. Conclusions: A prenatal distinction between
CAT and PA-VSD can currently be achieved in most cases.
MAPCAs should be actively searched for when PA-VSD is sus-
pected, as they are associated with a higher risk of 22q11
microdeletion and potentially complicate postnatal treat-
ment. © 2015 S. Karger AG, Basel
Introduction
Prenatal detection of conotruncal anomalies has great-
ly improved in the last years [1–4]. Nonetheless, a differ-
entiation between conotruncal anomalies may be diffi-
cult, with a particular potential for confusion between
truncus arteriosus communis (CAT) and pulmonary
atresia with ventricular septal defect (PA-VSD). A dis-
tinction between these two entities in fetal life is of high
Key Words
Congenital heart defect · Truncus arteriosus (communis) ·
Pulmonary atresia with ventricular septal defect · Major
aortopulmonary collateral arteries · Fetal echocardiography
Abstract
Objectives: To report on the accuracy of fetal echocardiog-
raphy in the distinction between truncus arteriosus com-
munis (CAT) and pulmonary atresia with ventricular septal
defect (PA-VSD) and to describe the association with extra-
cardiac and chromosomal anomalies. Methods: This was a
retrospective study on 31 fetuses with a single arterial trunk
overriding a VSD with a nonidentifiable right ventricle out-
flow tract with anterograde flow. Data on the type of cardiac
defect, gestational age, characteristics of the arterial trunk
valve, presence of additional vascular, chromosomal and
extracardiac abnormalities and postnatal outcome were
obtained. Misdiagnosed cases were reevaluated by four-
dimensional spatiotemporal image correlation (4D-STIC)
echocardiography. Results: The overall diagnostic accuracy
was 81% and increased to 93.5% with 4D-STIC. Chromosom-
al and extracardiac anomalies were detected in 40 and 27%,
Received: January 18, 2015
Accepted after revision: May 19, 2015
Published online: June 25, 2015
Olga Gómez
Fetal Cardiology Unit, BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine
Hospital Clinic and Hospital Sant Joan de Déu
C/Sabino de Arana 1, ES–08028 Barcelona (Spain)
E-Mail ogomez @ clinic.ub.es
© 2015 S. Karger AG, Basel
1015–3837/15/0392–0090$39.50/0
www.karger.com/fdt
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Prenatal Diagnosis of CAT and PA-VSD Fetal Diagn Ther 2016;39:90–99
DOI: 10.1159/000433430
91
importance, since both perinatal conduct and postnatal
treatment strategies greatly differ between them.
Both anomalies share the sonographic finding of a sin-
gle arterial trunk overriding a VSD, and differential diag-
nosis should be based on the characteristics of the arterial
trunk valve, identification of the atretic pulmonary valve
and the origin of the common pulmonary trunk and its
branches, as well as on the identification of a patent ductus
arteriosus (DA), which is absent in most of the CAT cases
and in a significant proportion of PA-VSD cases with ma-
jor aortopulmonary collateral arteries (MAPCAs). The
identification of a patent DA is a key criterion for estab-
lishing a correct differential diagnosis and to define peri-
natal management. It is generally accepted that a fetus
with CAT can be delivered locally, whereas PA-VSD is a
ductus-dependent cardiac defect and the affected fetus
should ideally be born in a reference center with a cardiol-
ogy unit where treatment with prostaglandins can be
started immediately after birth [5]. On the other hand, the
correct definition of the origin and characteristics of pul-
monary blood supply is also highly relevant to adequately
predict postnatal outcome, which will mostly depend on
the possibility of reconstructing separated pulmonary and
systemic circulations [6]. It is noteworthy that even if such
a prognostic evaluation can be difficult in the neonatal pe-
riod, in fetal life the challenge is much greater.
Currently, data on the accuracy of fetal echocardiog-
raphy in the correct distinction between various subtypes
of CAT and PA-VSD are scare. Additionally, extracardiac
and chromosomal anomalies, which worsen the progno-
sis,havebeendescribedwithincreasingfrequencyinboth
PA-VSD and CAT. Again, there is also scant information
from fetal series, and further studies are required to better
determine the risk of associated extracardiac and chro-
mosomal anomalies.
The aims of our study were (1) to evaluate the accu-
racy of fetal echocardiography in the differential diagno-
sis between CAT and PA-VSD, as well as in the correct
distinction between the different subtypes in each group,
and (2) to provide clinically useful information regarding
the risk of associated extracardiac and/or chromosomal
anomalies for both entities.
Subjects and Methods
Subjects
Between July 2006 and October 2013, cases were retrospec-
tively selected from a consecutive series of 1,154 fetuses with a
congenital heart defect (CHD) evaluated in our Fetal Cardiology
Unit, which operates as a referral center for pregnancies at risk of
CHD. The study group consisted of 34 fetuses in which the main
echocardiographic finding was a single arterial trunk overriding
a VSD together with a nondemonstrable direct connection from
the right ventricle into the pulmonary arteries. Thus, fetuses af-
fected by tetralogy of Fallot with pulmonary stenosis, as well as
cases with additional cardiac defects, were not included in the
study. From the original cohort of 34 fetuses, 3 were excluded
from the study due to the impossibility of confirming their diag-
nosis (fig. 1). In the remaining 31 cases, the following data were
retrieved from our computerized fetal CHD database: indication
for fetal echocardiography, gestational age (GA) at diagnosis, type
of anomaly (CAT vs. PA-VSD), arterial trunk valve characteris-
tics, grade of arterial trunk overriding, aortic arch location, pres-
ence of other vascular anomalies, extracardiac malformations or
chromosomal anomalies and, finally, pregnancy and neonatal
outcomes.
Echocardiographic Study
Ultrasound studies were performed by fetal medicine special-
ists together with pediatric cardiologists of our Fetal Cardiology
Unit using a Voluson 730 Expert E6 or E8 machine (GE Medical
Systems, Milwaukee, Wis., USA). GA was determined by ultra-
sound measurements of the crown-rump length between weeks 11
and 14 [7] or of the biparietal diameter between weeks 14 and 22
[8]. All fetuses underwent detailed anatomical scanning and fetal
echocardiography following standardized guidelines [9–11]. In 27
cases, four-dimensional spatiotemporal image correlation (4D-
STIC) volumes in gray scale as well as with color Doppler were
obtained as published elsewhere [12].
CAT was defined as a single great artery overriding a VSD
which supplied both the systemic and the pulmonary flow, thus
with at least one of the pulmonary arteries originating in the as-
cending aorta or the transverse arch until the origin of the left sub-
clavian artery. Moreover, different subtypes of CAT were classified
according to the Van Praagh classification [13, 14], as shown in
table 1.
Fig. 1. Flowchart of cases included in the study. * Misdiagnosed
cases.
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Gómez et al.Fetal Diagn Ther 2016;39:90–99
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92
PA-VSD was defined as an overriding aorta which was identi-
fied in addition to a complete obstruction or an absence of com-
munication between the main pulmonary trunk and the right ven-
tricle. Furthermore, such cases were classified according to the pat-
tern of pulmonary arterial flow supply into three subtypes: (1) DA,
defined as a vessel connecting the aortic isthmus with the pulmo-
nary arteries; (2) MAPCAs, defined as vessels connecting the de-
scending aorta – or, less frequently, the aortic branches or coro-
naryarteries–witheitherthelungparenchymaorthedistalbranch
of the pulmonary arteries, or (3) a combination of both (mixed)
(table 1).
Pregnancy and Postnatal Outcome Data
Prenatal study of the karyotype and 22q11.2 microdeletion by
fluorescence in situ hybridization was offered in all cases. When
refused, postnatal genetic study results were collected. The postna-
tal diagnosis was obtained from neonatal echocardiogram, cardiac
catheterization, surgical or autopsy reports. The study protocol
was approved by the local ethics committee, and informed consent
was provided in all cases for the use of the images in clinical stud-
ies. Statistical analysis was performed with SPSS 17.1 for Windows
(SPSS Inc., Chicago, Ill., USA). Statistical significance was consid-
ered when p < 0.05.
Results
A total of 34 cases (14 CAT and 20 PA-VSD) were
prenatally identified during the study period. As previ-
ously mentioned, autopsies were not performed in 2 cas-
es that underwent termination of pregnancy (TOP)
(fig. 1). The first case corresponded to a suspected PA-
VSD diagnosed in a monochorionic twin pregnancy with
a selective TOP of the affected fetus at 22 weeks. The de-
livery occurred 12 weeks later, thus precluding the per-
formance of the autopsy. In the second case, which cor-
responded to a suspected CAT with a 22q11.2 deletion
that underwent TOP at 14 weeks, the parents did not
authorize the necropsy. Both cases were excluded from
analysis. A third case, with a suspected CAT in a fetus
with a congenital diaphragmatic hernia, was also exclud-
ed due to postnatal loss to follow-up, leaving a total of 12
CAT and 19 PA-VSD cases.
The main indication for the echocardiographic study
was suspicion of CHD in routine obstetric ultrasound
scans in 28/31 cases (90.3%); 2 (6.5%) were referred for
increased nuchal translucency, and the last case (3.2%)
was referred after a diagnosis of 22q11.2 deletion in a pa-
tient with a previous affected pregnancy. The reasons for
referral were not different between the CAT and PA-VSD
groups (p = 0.251, Fisher’s exact test).
The median GA at diagnosis was 20.6 weeks (range
15.0–37.3). The diagnosis was made before 16 weeks in 3
cases (9.7%), between 16 and 24 weeks in 25 cases (80.6%)
and after 24 weeks in the remaining 3 cases (9.7%). These
last 3 cases were referred to our center for suspected CHD
at 27.3, 30.5 and 37.3 weeks. The GA at diagnosis was not
significantly different between the CAT and PA-VSD
groups (18.6 vs. 21.5 weeks, p = 0.105, t test).
Overall Accuracy of Conventional Echocardiography
The prenatal sonographic findings, outcome and post-
natal diagnosis are summarized in tables 2 and 3. The
overall diagnostic accuracy of prenatal echocardiography
was 80.6% in our series (25/31 cases were confirmed). As
shown in figure 1, the diagnostic accuracy was similar in
both groups: 80% in the CAT group (8/10 cases) versus
85% in the PA-VSD group (17/20 cases). No other cases
were found to correspond to CAT and PA-VSD among
the 1,154 fetal CHD cases evaluated in our unit during the
8 years of the study. Therefore, the incidence of PA-VSD
and CAT in our series was 1.73% (20 cases) and 0.87% (10
cases), respectively.
Table 1. CAT nomenclature (based on the revised classification proposed by Van Praagh in 1976) and PA-VSD
subtypes according to the source of pulmonary blood flow
CAT nomenclature
Subtype 1: CAT with confluent pulmonary arteries
Subtype 2: CAT with near-confluent pulmonary arteries
Subtype 3: CAT with absence of 1 pulmonary artery
Subtype 4: CAT with interrupted aortic arch or severe coarctation
PA-VSD nomenclature
DA supply: confluent pulmonary arteries which are supplied by the DA
MAPCA supply: complete absence of pulmonary trunk, the lung being supplied directly by multiple MAPCAs
Mixed supply: confluent pulmonary arteries coexisting with MAPCAs
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Table 2. Summary of cases with a prenatal diagnosis of CAT: postnatal diagnosis, additional prenatal findings and outcome
GA,
weeks
CAT type –
prenatal
Postnatal
diagnosis
Aortic
arch
Additional
cardiovascular
anomalies
Extracardiac anomalies Karyotype/
FISH
Outcome
1 21.4 Type 3 Confirmed Left Normal TOP
2 17.5 Type 1 Confirmed Left Alobar holoprosencephaly, arrhinia, proboscis,
microphthalmia, hypotelorism; umbilical
hernia; double renal system
Trisomy 13 TOP
4 21.6 Type 1 Confirmed Left Semilobar holoprosencephaly Trisomy 13 TOP
6 15.6 Type 1 Confirmed Left PLSVC, SUA Ventriculomegaly, posterior fossa anomaly,
hypertelorism, exophthalmos, ectrodactyly
Triploidy TOP
7 19.5 Type 1 Confirmed Left Normal Alive
8 16.5 Type 1 Confirmed Left PLSVC, SUA Cleft lip, hypoplasia of 1st metacarpal bone Normal TOP
9 20.4 Type 1 PA-VSD – DA Left Trisomy 18 TOP
10 19.3 Type 1 PA-VSD – DA Left Normal TOP
11 22.4 Type 3 PA-VSD – mixed Right 22q11 deletion Alive
12 22.2 Type 2 Complex CHD Left ARSA CHARGE syndromea Normal Neonatal death
FISH = Fluorescence in situ hybridization; PLSVC = persistent left superior vena cava; SUA = single umbilical artery; ARSA = aberrant right subclavian
artery. a
Postnatal diagnosis.
Table 3. Summary of cases with a prenatal diagnosis of PA-VSD: postnatal diagnosis, additional prenatal findings and outcome
GA,
weeks
Pulmonary
blood supply
Postnatal
diagnosis
Aortic
arch
Additional
cardiovascular
anomalies
Extracardiac anomalies Karyotype/
FISH
Outcome
13 17.2 Mixed Confirmed Right PLSVC 22q11 deletion TOP
14 22.3 MAPCAs Confirmed Right Normal TOP
15 17.0 DA Confirmed Left 22q11 deletion TOP
16 20.5 DA Confirmed Left 46,XX,add(8)(p23) TOP
17 21.0 DA Confirmed Left Bilateral radial aplasia, multiple finger aplasia;
IUGR
Normal TOP
18 15.0 DA Confirmed Left Horseshoe kidneya Normal TOP
19 18.2 DA Confirmed Left Bilateral cleft lip and cleft anterior palate Normal TOP
20 22.4 DA Confirmed Left Normal TOP
21 21.0 DA Confirmed Left Normal TOP
22 27.3 MAPCAs Confirmed Right 22q11 deletion TOP
23 20.6 Mixed Confirmed Left Normal TOP
24 20.2 MAPCAs Confirmed Left Normal TOP
25 20.6 MAPCAs Confirmed Left 22q11 deletion Alive
26 30.5 DA Confirmed Left PLSVC Normal Alive
27 21.0 DA PA-VSD – mixed Right Normal Alive
28 21.2 MAPCAs Confirmed Left Normal TOP
29 37.3 MAPCAs Confirmed Right Unilateral kidney agenesis 22q11 deletion TOP
30 16.3 DA CAT type 1 Left Normal TOP
31 15.0 DA CAT type 1 Left 22q11 deletion TOP
FISH = Fluorescence in situ hybridization; PLSVC = persistent left superior vena cava; IUGR = intrauterine growth retardation.
a Postnatal diagnosis.
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Accuracy in the Group with a Prenatal Diagnosis of
CAT
In the 8 cases in which CAT was confirmed, CAT sub-
types were accurately defined in all cases: 7 (87.5%) were
corresponding to subtype 1 (table 2) and 1 to subtype 3
(12.5%). There were 4 cases of misdiagnosed CAT (fig. 1;
table 2): 2 cases were prenatally diagnosed as a subtype 1
CAT, but the postnatal assessment showed a PA-VSD
with DA as a source of pulmonary blood supply (cases 9
and 10); a third case, prenatally diagnosed as a subtype 3
CAT, corresponded to a PA-VSD with a mixed source of
pulmonary supply (case 11), and the fourth case, oriented
as a subtype 2 CAT, was diagnosed after autopsy as a com-
plex CHD [aortic atresia with a VSD, descendent aortic
hypoplasia with MAPCAs and an aberrant right subcla-
vianartery(case12)].Thiscasepresentedanormalkaryo-
type and was clinically diagnosed as a CHARGE syn-
drome after birth based on the combination of the CHD
with the following clinical signs: bilateral coloboma with
right microphthalmia and bilateral malformation of the
ears including absence of the semicircular canal. Two cas-
es in the subtype 1 group presented a truncal valve insuf-
ficiency (cases 3 and 5), which represented an incidence
of 20% in the fetuses with confirmed CAT. None of the 4
misdiagnosed cases presented an aortic valve insufficien-
cy. In cases 6 and 12, the truncal root was defined to orig-
inate predominantly from the right ventricle and thus to
override the VSD more than 50%.
Accuracy in the Group with a Prenatal Diagnosis of
PA-VSD
Among the 17 PA-VSD cases with confirmed diagno-
sis, the source of pulmonary blood supply was correctly
identified in all cases except one (fig. 1; table 3). In case
27, despite the presence of a patent DA, the cardiac cath-
eterization performed after birth showed that the right
lung and the left superior lobe were perfused by a right-
sided collateral and the left inferior lobe by a left-sided
collateral. The 2 cases misdiagnosed as PA-VSD (cases 30
and 31) were classified into the group with present DA,
both really corresponding to a CAT subtype 1 after the
autopsy. None of the cases in this group, including the 2
misdiagnosed cases, presented an arterial trunk valve in-
sufficiency. Finally, the aortic root was identified to over-
ride the VSD more than 50% in cases 20 and 24.
Accuracy of 4D-STIC Echocardiography in the
Misdiagnosed Cases
A 4D-STIC evaluation was retrospectively performed
in 5 of the 6 misdiagnosed cases by one experienced op-
Table 4. Summary of the misdiagnosed cases evaluated with 4D-STIC echocardiography
Prenatal diagnosis Confirmed diagnosis
2D echocardiography 4D-STIC echocardiography
9 CAT type 1 PA-VSD – DA PA-VSD – DA
10 CAT type 1 PA-VSD – DA PA-VSD – DA
11 CAT type 3 PA-VSD – MAPCAs PA-VSD – MAPCAs
12 CAT type 2 CAT type 2 Complex CHD
30 PA-VSD – DA – CAT type 1
31 PA-VSD – DA CAT type 1 CAT type 1
Table 5. Distribution of karyotype and fluorescence in situ hybridization results by confirmed CHD
Postnatal
diagnosis
Karyotype Total
normal 22q11– trisomy 13 trisomy 18 other
CAT 6 (60%) 1 (10%) 2 (20%) 0 1 (10%) 10
PA-VSD 12 (60%) 6 (30%) 0 1 (5%) 1 (5%) 20
Total 18 (60%) 7 (23.3%) 2 (6.7%) 1 (3.3%) 2 (6.7%) 30
22q11– = 22q11 microdeletion.
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erator. This operator was not previously involved in the
study, was blinded to the definitive diagnosis and had ac-
cess solely to the 4D-STIC volumes. 2D and color Dopp-
ler cardiac volumes were analyzed using the multiplanar
reconstruction mode. As shown in table 4, the 4D-STIC
diagnosis was correctly performed in 4 of the 5 cases eval-
uated. Only the case with the complex CHD (case 12) was
misdiagnosed with both 2D and 4D-STIC echocardiogra-
phy. Therefore, by incorporating the 4D-STIC evaluation
in our series, the overall accuracy increased to 93.5%.
Chromosomal Anomalies
Karyotypeandfluorescenceinsituhybridizationresults
were available for all patients. Chromosomal anomalies
were detected in 12 of 30 cases (40%): 4/10 cases (40%) in
the confirmed CAT group and 8/20 (40%) in the con-
firmed PA-VSD group (tables 2, 3). The most frequent
chromosomal anomaly was 22q11.2 deletion, representing
58.3 % of all chromosomal abnormalities. As shown in ta-
ble 5, there were 4 cases of aneuploidy (2 cases of trisomy
13 and 1 case of triploidy in the CAT group; 1 case of tri-
somy 18 in the PA-VSD group). Additionally, 1 case of
46,XX,add(8)(p23) was found in a fetus with PA-VSD. The
overall incidence of chromosomal anomalies was similar
among both groups. Interestingly, 22q11.2 deletion was
more common in the PA-VSD group (6/20 cases, 30%)
than in the CAT group (1/10 cases, 10%; p = 0.372, Fisher’s
exact test). Moreover, in the PA-VSD group, the incidence
of 22q11.2 deletion was also higher in the subgroup with
MAPCAs (5/10 cases, 50%) than in the subgroup without
MAPCAs (1/10 cases, 10%; p = 0.141, Fisher’s exact test).
Associated Vascular Anomalies and Extracardiac
Malformations
As illustrated in tables 2 and 3, associated cardiovascu-
lar anomalies, including aortic arch anomalies, were pres-
ent in 9 of 30 cases (30%). A right aortic arch (RAA) was
identified in 6 cases, all in fetuses with a definitive diag-
nosis of PA-VSD, which represented an incidence of 30%
in this group. Moreover, all the cases with an RAA in the
PA-VSD group had MAPCAs, which represented an in-
cidence of 60% in this subgroup as compared to fetuses
withPA-VSDwithoutMAPCAs(6/10vs.0/10,p=0.0114,
Fisher’s exact test). The presence of other associated vas-
cular anomalies, such as a persistent left superior vena
cava, a single umbilical artery or an aberrant right subcla-
vianartery,wasnotsignificantlydifferentbetweengroups
(p = 0.675, Fisher’s exact test) and was not associated with
the occurrence of chromosomal anomalies (p = 0.447,
Fisher’s exact test).
Extracardiac malformations were present in 8/30 cases
(26.6%). All prenatally diagnosed malformations were
confirmed after birth or by autopsy after TOP. One case
of horseshoe kidney (case 18) was diagnosed after the au-
topsy, and it was the only malformation unrecognized
prenatally. The presence of extracardiac malformations
was higher, though not significantly, in the CAT (4/10;
40%) than in the PA-VSD (4/20; 20%) group (p = 0.384,
Fisher’s exact test). Finally, the occurrence of extracardiac
malformations was not associated with the presence of
chromosomal abnormalities, irrespective of their type
(p = 0.704, Fisher’s exact test).
Outcome
Parents opted for TOP in 25 of 31 cases (80.6%), 9 cas-
es of which were prenatally diagnosed as CAT and 16 as
PA-VSD. Among these 25 cases, 13 fetuses had signifi-
cant associated anomalies: 11 fetuses (44% of the TOP
cases) had a chromosomal anomaly, and cases 17 and 19
had an extracardiac anomaly detected prenatally. In the
remaining 12 cases, the TOP decision was solely based on
the diagnosis of the CHD. TOP was performed before 24
weeks in 23/25 cases (92%). There were no in utero deaths
in our series.
Table 6. Outcome of cases continuing with pregnancy
Prenatal
diagnosis
Postnatal
diagnosis
GA at delivery,
weeks
Postnatal outcome Age at last
follow-up,
months
7 CAT type 1 Confirmed 39.5 Biventricular surgery on the 18th day of life 10
11 CAT type 3 PA-VSD – mixed 41 No surgical repair; cardiologic follow-up 18
12 CAT type 2 Complex CHD 41.2 Neonatal death (CHARGE syndrome) –
25 PA-VSD – MAPCAs Confirmed 39 No surgical repair; cardiologic follow-up 12
26 PA-VSD – DA Confirmed 37.5 Biventricular surgery on the 20th day of life 24
27 PA-VSD – DA PA-VSD – mixed 38.5 No surgical repair; cardiologic follow-up 36
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Delivery at term occurred in the 6 cases continuing
with the pregnancy. There was 1 neonatal death (a
CHARGE syndrome baby). Of the 5 neonates who sur-
vived, 2 achieved a complete biventricular repair during
the first month of life with good outcome (CAT type 1,
case 7, and PA-VSD – DA, case 26). With regard to the
remaining neonates, the 3 of them presenting a PA-VSD
with MAPCAs (cases 11, 25 and 27), surgical repair was
considered not indicated in the neonatal period. Addi-
tional details on the postnatal outcome of these cases are
described in table 6.
Discussion
The major findings of our study are as follows: (1) fetal
echocardiography is highly accurate in the differential di-
agnosis between CAT and PA-VSD and in the correct
distinction between the different subtypes in each group,
and (2) if PA-VSD is diagnosed, the presence of MAPCAs
increases the risk of associated anomalies and worsens the
prognosis. This information is of utmost importance in
the perinatal management of such defects.
CAT and PA-VSD represent two rare subgroups of
conotruncal anomalies particularly difficult to differenti-
ate in fetal life [3, 15–17]. Our overall diagnostic accuracy
was 81%, which is inside the range of 77–96% previously
reported [1–4, 18, 19], although the GA at diagnosis was
lower in our series. The accuracy in the CAT group was
80%, with the most common form corresponding to sub-
type 1 (fig. 2). The accuracy in the PA-VSD group was
slightly superior. As shown in figure 1, we failed in the
diagnosis of 2 CAT cases (cases 30 and 31) and 3 PA-VSD
cases (cases 9–11). Four of the 5 misdiagnosed cases were
studied before the 22nd week of gestation, which could be
a factor contributing to the incorrect diagnosis. It is im-
portant to remark that the presence of truncal valve insuf-
ficiency was low in our CAT group (cases 3 and 5); thus,
it was not a helpful tool for improving the differential di-
agnosis in our series. Moreover, in only 1 of the con-
firmed CAT cases (case 6), the common trunk originated
predominantly from the right ventricle, as compared with
2 cases in the PA-VSD group (cases 20 and 24), which
corresponded to 10% of the cases in both groups and
therefore did not help in improving the differential diag-
nosis between CAT and PA-VSD either.
The prenatal identification of a patent DA is one of the
key criteria, not only for establishing a differential diag-
nosis between these two rare CHDs but also for defining
perinatal management. It is well accepted that fetuses
with a ductus-dependent CHD should be delivered in a
center with a cardiology unit and that treatment with
prostaglandins to maintain an optimal pulmonary blood
supply via the DA should be started immediately after
birth [5]. In our series, the DA was confirmed to be absent
in the 9 necropsies from the CAT cases that underwent
TOP as well as in case 7, in which a corrective surgery was
performed on the 18th day of life. The absence of the DA
in all our CAT cases could be explained because 9 of the
10 cases corresponded to subtype 1, which is rarely asso-
ciated with a patent DA. In contrast, the DA was patent
in 70% of the fetuses with a PA-VSD, including 4 cases
with a mixed pulmonary blood supply. It is noteworthy
that there was a relatively high frequency of mixed pul-
monary blood supply in the PA-VSD group, which
reached 20% in our cases, suggesting that the presence of
a b c
Fig. 2. a Normal four-chamber view in a fetus with a type 1 CAT at 22 weeks of gestation. b Five-chamber view
showing the perimembranous ventricular septal defect (white arrow) with the overriding CAT. c A more oblique
view allowing the demonstration that the CAT was supplying both the systemic (→) and pulmonary circulations
(«). RV = Right ventricle; LV = left ventricle.
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MAPCAs accompanying a functional DA might be more
common than previously reported [2, 20, 21]. Moreover,
in the PA-VSD group, the source of pulmonary blood
supply was correctly defined in all cases except in case 27,
which also represents a high level of accuracy for predict-
ing the postnatal outcome and for discussing the different
options of postnatal treatment with parents.
The presence of MAPCAs in the context of PA-VSD is
also a well-recognized prognostic factor. On the one
hand, postnatal management of these cases still repre-
sents a major challenge. Clinical manifestations in these
children can vary widely depending on the presence of
a patent DA and/or native pulmonary arteries as well as
on the distribution of the pulmonary arteries and the
MAPCAs to the pulmonary segments. Recent advances in
the fields of interventional cardiology and cardiovascular
surgery have increasingly allowed more patients to
achieve a biventricular circulation [22], by different ap-
proaches [23–25] that are basically intended to complete
the unifocalization of the supplying MAPCAs, with or
without incorporation of the central pulmonary arteries,
if present, and concomitant or delayed closure of the
VSD. On the other hand, previous studies [2, 26, 27] have
demonstrated that fetuses with a 22q11.2 microdeletion
have more severely hypoplastic central pulmonary arter-
ies and more branching anomalies, which determines a
poorer postnatal outcome. Thus, a directed study in order
to rule out the presence of MAPCAs is another key issue
when evaluating PA-VSD cases in prenatal life. Our data
demonstrate that at least half of the fetuses with a PA-
VSD will present MAPCAs, these being significantly
more frequent in the group with an RAA and most likely
originating from the thoracic aorta (fig. 3). As highlighted
previously, MAPCAs can be present in 1 of 5 PA-VSD
cases with a functional DA. We only failed in the identi-
fication of 2 cases with MAPCAs (cases 11 and 27; detec-
tion rate 80%), and interestingly no false-positive diagno-
ses occurred for a positive predictive value of 100%.
Moreover, the incidence of 22q11.2 deletion was 5 times
more common in the PA-VSD subgroup with MAPCAs,
although this difference was not statistically significant,
most likely because of the small number of cases.
Previous studies have suggested that both sequential
echocardiography [3, 18] and 4D-STIC echocardiogra-
phy [19, 28] can be used to improve the differential diag-
nosis. In our series, 80% of the parents decided not to
continue with the pregnancy, but we retrospectively ana-
lyzed 5 of the 6 misdiagnosed cases by 4D-STIC echo-
cardiography. As shown in table 4, the diagnosis was
correctly performed in 4 of the 5 misdiagnosed cases. Al-
though we did not analyze the rendered images to
evaluate the anatomy of the pulmonary arteries, the nav-
igation through the color Doppler volumes in the multi-
planar mode allowed us to obtain different planes from
conventional 2D echocardiography as well as to review
not only the origin but also the course of the smallest ves-
sels. This was especially helpful in identifying the DA in
2 cases evaluated before 22 weeks of gestation (cases 9 and
19) as well as in defining the origin of a MAPCA in case
11. We acknowledge that these results should be evalu-
ated in the context of a small and targeted retrospective
study, but when carried out by experienced observers,
targeted 4D-STIC echocardiography can obtain results
similar to those gained with sequential 2D echocardiog-
raphy. Therefore, it could be considered a useful tool to
prospectively complement conventional 2D echocar-
diography.
Finally, our series confirms previous data regarding
the poorer prognosis of these two groups of conotruncal
anomalies when diagnosed in fetal life [1, 2, 4]. Chromo-
somal and extracardiac anomalies were detected in 40
and 27% of the cases, respectively. As shown in table 5,
22q11.2 microdeletion was the most common chromo-
somal abnormality, and although the difference did not
a b
Colorversionavailableonline
Fig. 3. a Sagittal view of the aortic arch in a
fetus affected by a PA-VSD at 21 weeks of
gestation. Two MAPCAs are clearly visible
with color Doppler originating in the de-
scending thoracic aorta (arrows). b Ar-
terial flow characteristics in one of the
MAPCAs demonstrated by pulsed Dopp-
ler.
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DOI: 10.1159/000433430
98
reach statistical significance, the incidence was higher in
the PA-VSD group than in the CAT group (30 vs. 10% of
cases). The presence of extracardiac malformations was
identified in 27% of the cases, which is similar to previ-
ously reported incidence rates [1, 2, 4]. All malformations
except a horseshoe kidney (case 18) were prenatally iden-
tified. The occurrence of extracardiac malformations was
not associated with the presence of chromosomal abnor-
malities, and was higher, although not significantly so, in
the CAT group.
There are some limitations of our study. Firstly, our
series is retrospective, and the case sample size is rela-
tively small for drawing strong conclusions. Secondly, the
percentage of TOP is very high, which clearly limits an
evaluation of results related to postnatal outcome. All
parents were extensively counseled by the fetal medicine
specialist and the pediatric cardiologist based on the in-
formation available at diagnosis. The presence of chro-
mosomal and extracardiac abnormalities in more than
half of the TOP cases as well as the early performance of
the prenatal diagnosis, which has less commonly been re-
ported in other series, may partially explain the high rate
of TOP. One of the current challenges is an even better
identification of those cases with the most unfavorable
cardiac anatomy, which may be achievable with the in-
creased resolution of prenatal echocardiography together
with the greater experience in making such a difficult dif-
ferential diagnosis.
In summary, an accurate prenatal differentiation be-
tween CAT and PA-VSD can be achieved in most cases
from an early GA. Future studies are needed to confirm
the utility of 4D-STIC echocardiography as a prospective
complementary tool, especially when sequential echocar-
diography is not possible. The identification of a patent
DA is a key criterion for establishing a differential diag-
nosis and perinatal outcome. The DA was absent in all the
CAT cases of our series. In contrast, in the PA-VSD
group, a patent DA and MAPCAs were present in 70 and
50% of the fetuses, respectively, thus coexisting in 1 of 5
cases. MAPCAs were significantly more common in fe-
tuses with an RAA and were associated with a higher risk
of 22q11.2 microdeletion. According to our results, study
of the descending thoracic aorta to rule out the presence
of MAPCAs should be incorporated into fetal echocar-
diography when evaluating this complex group of cono-
truncal anomalies.
Acknowledgments
This study was partly supported by grants from: the Instituto
de Salud Carlos III (ref. No. PI11/00051, PI12/00801 and
PI12/02230) integrated into the Plan Nacional de I+D+I and co-
financed by ISCIII-Subdirección General de Evaluación and the
Fondo Europeo de Desarrollo Regional (FEDER) ‘Otra manera de
hacer Europa’; Obra Social ‘la Caixa’ (Barcelona, Spain); Fun-
dación Mutua Madrileña grant No. AP116192013; Fundació
Agrupació Mutua, and AGAUR 2014 SGR grant No. 928.
References
1 Volpe P, Paladini D, Marasini M, Buonadon-
na AL, Russo MG, Caruso G, Marzullo A,
Vassallo M, Martinelli P, Gentile M: Com-
mon arterial trunk in the fetus: characteris-
tics, associations, and outcome in a multicen-
tre series of 23 cases. Heart 2003;89:1437–
1441.
2 Vesel S, Rollings S, Jones A, Callaghan N,
Simpson J, Sharland GK: Prenatally diag-
nosed pulmonary atresia with ventricular
septal defect: echocardiography, genetics, as-
sociated anomalies and outcome. Heart 2006;
92:1501–1505.
3 Galindo A, Mendoza A, Arbues J, Grañeras A,
Escribano D, Nieto O: Conotruncal anoma-
lies in fetal life: accuracy of diagnosis, associ-
ated defects and outcome. Eur J Obstet Gyne-
col Reprod Biol 2009;146:55–60.
4 Swanson TM, Selamet Tierney ES, Tworetzky
W, Pigula F, McElhinney DB: Truncus arte-
riosus: diagnostic accuracy, outcomes, and
impact of prenatal diagnosis. Pediatr Cardiol
2009;30:256–261.
5 Yeu BK, Chalmers R, Shekleton P, Grimwade
J, Mennahem S: Fetal cardiac diagnosis and its
influence on the pregnancy and newborn – a
tertiary centre experience. Fetal Diagn Ther
2008;24:241–245.
6 Khoshnood B, De Vigan C, Vodovar V, Gou-
jard J, Lhomme A, Bonnet D, Goffinet F:
Trends in prenatal diagnosis, pregnancy ter-
mination, and perinatal mortality of new-
borns with congenital heart disease in France,
1983–2000: a population-based evaluation.
Pediatrics 2005;115:95–101.
7 Robinson HP, Fleming JE: A critical evalua-
tion of sonar ‘crown-rump length’ measure-
ments. Br J Obstet Gynecol 1975;82:702–710.
8 Mul T, Mongelli M, Gardosi J: A comparative
analysis of second-trimester ultrasound dat-
ing formulae in pregnancies conceived with
artificial reproductive techniques. Ultra-
sound Obstet Gynecol 1996;8:397–402.
9 Yagel S, Cohen SM, Achiron R: Examination
of the fetal heart by five short axis views: a
proposed screening method for comprehen-
sive cardiac evaluation. Ultrasound Obstet
Gynecol 2001;17:367–369.
10 Allan L: Technique of fetal echocardiography.
Pediatr Cardiol 2004;25:223–233.
11 International Society of Ultrasound in Ob-
stetrics and Gynecology: Cardiac screening
examination of the fetus: guidelines for per-
forming the ‘basic’ and ‘extended basic’ car-
diac scan. Ultrasound Obstet Gynecol 2006;
27:107–113.
12 Bennasar M, Martínez JM, Gómez O, Bar-
trons J, Olivella A, Puerto B, Gratacós E: Ac-
curacy of four-dimensional spatiotemporal
image correlation echocardiography in the
prenatal diagnosis of congenital heart defects.
Ultrasound Obstet Gynecol 2010;36:458–464.
13 Van Praagh R, Van Praagh S: The anatomy of
common aorticopulmonary trunk (truncus
arteriosus communis) and its embryologic
implications. A study of 57 necropsy cases.
Am J Cardiol 1965;16:406–425.
Downloadedby:
128.111.121.42-2/14/20181:37:37PM

DOI: 10.1159/000433430
99
14 Van Praagh R: Truncus arteriosus: what is it
really and how should it be classified? Eur J
Cardiothorac Surg 1987;1:65–70.
15 Sivanandam S, Glickstein JS, Printz BF,
Allan LD, Altmann K, Solowiejczyk DE,
Simpson L, Perez-Delboy A, Kleinman CS:
Prenatal diagnosis of conotruncal malfor-
mations: diagnostic accuracy, outcome,
chromosomal abnormalities, and extracar-
diac anomalies. Am J Perinatol 2006;23:
241–245.
16 Rustico MA, Benettoni A, D’Ottavio G, Mai-
eron A, Fischer-Tamaro I, Conoscenti G,
Meir Y, Montesano M, Cattaneo A, Mandru-
zzato G: Fetal heart screening in low-risk
pregnancies. Ultrasound Obstet Gynecol
1995;6:313–319.
17 Grandjean H, Larroque D, Levi S; The Euro-
fetus Study Group: the performance of rou-
tine ultrasonographic screening of pregnan-
cies in the Eurofetus Study. Am J Obstet Gy-
necol 1999;181:446–454.
18 Duke C, Sharland GK, Jones AM, Simpson
JM: Echocardiographic features and outcome
of truncus arteriosus diagnosed during fetal
life. Am J Cardiol 2001;88:1379–1384.
19 Volpe P, Campobasso G, Stanziano A, De
Robertis V, Di Paolo S, Caruso G, Volpe N,
Gentile M: Novel application of 4D sonogra-
phy with B-flow imaging and spatio-temporal
image correlation (STIC) in the assessment of
the anatomy of pulmonary arteries in fetuses
with pulmonary atresia and ventricular septal
defect. Ultrasound Obstet Gynecol 2006;28:
40–46.
20 Seale AN, Ho SY, Shinebourne EA, Carvalho
JS:Prenatalidentificationofthepulmonaryar-
terial supply in tetralogy of Fallot with pulmo-
nary atresia. Cardiol Young 2009;19:185–191.
21 Haworth SG, Macartney FJ: Growth and de-
velopment of pulmonary circulation in pul-
monary atresia with ventricular septal defect
and major aortopulmonary collateral arteries.
Br Heart J 1980;44:14–24.
22 Song SW, Park HK, Park YH, Cho BK: Pul-
monary atresia with ventricular septal defects
and major aortopulmonary collateral arteries.
18-year clinical experience and angiographic
follow-up of major aortopulmonary collateral
arteries. Circ J 2009;73:516–522.
23 Mei J, Ding F, Zhu J, Bao C, Xie X, Zhang Y:
A novel two-stage complete repair method for
pulmonary atresia with ventricular septal de-
fect and major aortopulmonary collateral ar-
teries. Chin Med J (Engl) 2010;123:259–264.
24 Fouilloux V, Bonello B, Kammache I, Fraisse
A, Macé L, Kreitmann B: Management of pa-
tients with pulmonary atresia, ventricular
septal defect, hypoplastic pulmonary arteries
and major aorto-pulmonary collaterals: focus
on the strategy of rehabilitation of native pul-
monary arteries. Arch Cardiovasc Dis 2012;
105:666–675.
25 Watanabe N, Mainwaring RD, Reddy VN,
Palmon M, Hanley FL: Early complete repair
of pulmonary atresia with ventricular septal
defect and major aortopulmonary collaterals.
Ann Thorac Surg 2014;97:909–915, discus-
sion 914–915.
26 Reddy VM, McElhinney DB, Amin Z, Moore
P, Parry AJ, Teitel DF, Hanley FL: Early and
intermediate outcomes after repair of pulmo-
nary atresia with ventricular septal defect and
major aortopulmonary collateral arteries: ex-
perience with 85 patients. Circulation 2000;
101:1826–1832.
27 Chessa M, Butera G, Bonhoeffer P, Iserin L,
Kachaner J, Lyonnet S, Munnich A, Sidi D,
Bonnet D: Relation of genotype 22q11 dele-
tion to phenotype of pulmonary vessels in te-
tralogy of Fallot and pulmonary atresia-ven-
tricular septal defect. Heart 1998;79:186–190.
28 Gotsch F, Romero R, Espinoza J, Kusanovic
JP, Erez O, Hassan S, Yeo L: Prenatal diagno-
sis of truncus arteriosus using multiplanar
display in 4D ultrasonography. J Matern Fetal
Neonatal Med 2010;23:297–307.
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128.111.121.42-2/14/20181:37:37PM

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