Keywords
Congenital heart disease - double-inlet left ventricle - fetal echocardiography -
single ventricle
Double-inlet left ventricle (DILV) is a form of univentricular atrioventricular connection.
It is a rare congenital cardiac anomaly with an incidence of 0.05 to 0.1 per 1000
live births.[1] It accounts for 1% of all congenital cardiac anomalies and is seen in 4% of neonates
with congenital cardiac disease.[2] Double-inlet ventricle exists when the greater part of both atrioventricular (AV)
junctions is supported by a single ventricular chamber.[3] It comprises a heterogeneous group of cardiac anomalies that can involve several
combinations of morphological and functional variation at the level of the AV valves,
ventriculoarterial connection, and systemic or pulmonary outflow obstruction. The
varying arrangements lead to a single functioning ventricular chamber, more commonly
the left ventricle.
The aim of this study was to characterize the in utero presentation of the subtype
of DILV and assess the postnatal outcome.
Methods
This was a retrospective study performed at the University of Minnesota, Minneapolis.
It was approved by the University of Minnesota Institutional Review Board. Eight fetuses
with DILV were identified from the fetal echocardiography database from July 2007
to February 2011. DILV was identified on the basis of a single large morphological
left ventricle containing two AV valves that were separated from the small underdeveloped
right ventricle by the bulboventricular foramen. The reason for referral for fetal
echocardiography was abnormal cardiac structures found during an obstetric ultrasound
examination. Prenatal echocardiography and Doppler interrogation were obtained at
20 to 34 weeks of gestation. Maternal prenatal and postnatal medical records were
reviewed for gestational age (GA) at diagnosis and at delivery, karyotypic abnormalities,
extracardiac anomalies, growth restriction, and fetal and neonatal clinical course.
All fetal and transthoracic echocardiograms were performed at the University of Minnesota
hospital as part of routine clinical care. Examinations included two-dimensional fetal
and transthoracic echocardiography with pulse wave and color Doppler imaging using
variable frequency transducers. The studies were performed using Hewlett-Packard 5500
(Hewlett-Packard, Andover, MA). All prenatal and postnatal echocardiograms were reviewed
retrospectively by a single examiner. Tei index or myocardial performance index was
measured using pulsed-wave Doppler technique on the prenatal and the first postnatal
echocardiographic stored images. The degree of AV valve insufficiency was recorded
prenatally and postnatally. Cardiothoracic ratios were calculated prenatally. Delivery
information including GA at delivery, mode of delivery, birth weight, and Apgar scores
were also reviewed. The number and type of staged surgical palliative procedure were
recorded for each infant with associated morbidity and mortality. Confirmation of
prenatal diagnosis was obtained from postnatal transthoracic echocardiography, angiography,
and subsequent operations.
All data are presented as the mean ± standard deviation with ranges.
Results
Eight patients were prenatally diagnosed with DILV. All eight fetuses were live-born.
The mean GA at diagnosis was 24.7 ± 5 (range 20 to 34) weeks. Three fetuses were referred
in the third trimester. Seven fetuses (87.5%) were referred to the fetal cardiologist
for abnormal cardiac anatomy on obstetric ultrasound. One fetus (12.5%) was referred
for increased nuchal translucency. The mean maternal age was 27.8 ± 3.3 (range 21
to 31) years. No maternal risk factors were present. None of the infants had any major
extracardiac or karyotypic abnormalities. Two fetuses (25%) had one minor anomaly.
One had a single umbilical artery and, the other had increased nuchal translucency.
All eight fetuses were of (S, L, L) form of DILV with anterior and leftward aorta
arising from the outlet chamber and the pulmonary artery (PA) arising from the left
ventricle. From the four-chamber view, both AV valves are seen opening into the large
smooth-walled left ventricle ([Figs. 1A] and [1B]). The outlet hypoplastic right ventricle was L-looped (left side of the larger left
ventricle). Most patients (87.5%) had two AV valves. Anatomic features and clinical
data of the prenatal and postnatal outcomes are presented in [Table 1]. Four fetuses (50%) had pulmonary atresia, of which one fetus had severe subpulmonary
stenosis at 29 weeks that evolved into pulmonary atresia at 34 weeks of GA. Three
had membranous pulmonary atresia. One fetus (12.5%) with no pulmonary outflow obstruction
was diagnosed with a right aortic arch postnatally. One fetus (12.5%) had tricuspid
hypoplasia at 22 weeks, which evolved into tricuspid atresia at 32 weeks of gestation.
This same fetus was diagnosed postnatally with coarctation of the aorta.
Table 1
Data of Patients with DILV
|
Case
|
Fetal Echo (GA wk)
|
CT Ratio
|
Prenatal Diagnosis
|
Postnatal Diagnosis
|
LV Tei
|
AV Valve Insufficiency
|
GA at Delivery (wk)
|
Birth Wt (g)
|
Surgical Outcome
|
Survival
|
|
Prenatal
|
Postnatal
|
Prenatal
|
Postnatal
|
|
1
|
34
|
0.4
|
DILV, L-TGA pulmonary atresia (membranous)
|
DILV, L-TGA, pulmonary atresia (membranous)
|
34 wk: 0.2
|
0.2
|
No
|
No
|
39
|
3370
|
1. central shunt (14 DOL)
|
Male; alive (12 mo)
|
|
|
|
|
|
|
|
|
|
|
|
2. Glenn (6 mo)
|
|
|
2
|
22
|
0.5
|
DILV, L-TGA, tricuspid hypoplasia, no PS, mild right AV valve insufficiency, LV mildly
dilated
|
DILV, L-TGA, tricuspid atresia, coarctation of aortic arch, no PS, mild right AV valve
insufficiency, LV mildly dilated
|
22 wk: 0.68
|
0.33
|
Mild right AV valve
|
Mild right AV valve
|
39
|
3160
|
1. PA banding, coarctation repair (7 DOL)
|
Female; died (17 mo)
|
|
27
|
|
|
|
27 wk: 0.64
|
|
|
|
|
|
2. CHB pacemaker placed at 4.5 mo
|
|
|
32
|
|
|
|
32 wk: 0.62
|
|
|
|
|
|
3. RSV myocarditis resulted in heart failure needing heart transplant (17 mo)
|
|
|
3
|
20
|
0.5
|
DILV, L-TGA, No PS, mild right AV valve insufficiency
|
DILV, L-TGA
|
20 wk: 0.2
|
0.37
|
Mild right AV valve
|
No
|
38
|
3080
|
Glenn and PA banding (6 mo)
|
Male; alive (23 mo)
|
|
24
|
|
|
|
24 wk: 0.2
|
|
|
|
|
|
|
|
|
30
|
|
|
|
30 wk: 0.3
|
|
|
|
|
|
|
|
|
4
|
29
|
0.5
|
DILV, L-TGA, severe PS evolved into pulmonary atresia with retrograde flow in the
PDA
|
DILV, L-TGA, pulmonary atresia
|
29 wk: 0.35
|
0.56
|
No
|
No
|
38
|
3300
|
1. central shunt (4 DOL)
|
Male; alive (32 mo)
|
|
34
|
|
|
|
34 wk: 0.37
|
|
|
|
|
|
2. Glenn (3.3 mo)
|
|
|
|
|
|
|
|
|
|
|
|
|
3. Fontan (2 y)
|
|
|
5
|
25
|
0.5
|
DILV, L-TGA, pulmonary atresia (membranous)
|
DILV, L-TGA, pulmonary atresia (membranous)
|
25 wk: 0.21
|
0.6
|
No
|
No
|
38
|
3520
|
1. central shunt (7 DOL)
|
Male; alive (33 mo)
|
|
|
|
|
|
|
|
|
|
|
|
2. Glenn (6 mo)
|
|
|
|
|
|
|
|
|
|
|
|
|
3. Fontan (2 y)
|
|
|
6
|
20
|
0.3
|
DILV, L-TGA, no PS
|
DILV, L-TGA, no PS, right aortic arch
|
20 wk: 0.3
|
0.56
|
Mild right AV valve
|
Mild right AV valve
|
39
|
3770
|
1. PA banding (7 DOL)
|
Male; alive (41 mo)
|
|
24
|
|
|
|
24 wk: 0.37
|
|
|
|
|
|
2. Glenn (6 mo)
|
|
|
34
|
|
|
|
|
|
|
|
|
|
3. Fontan (2.5 y)
|
|
|
7
|
28
|
0.5
|
DILV, L-TGA, pulmonary atresia (membranous)
|
DILV, L-TGA, pulmonary atresia (membranous)
|
28 wk: 0.33
|
0.47
|
No
|
No
|
40
|
3380
|
Central shunt (5 DOL)
|
Female; alive (2 mo)
|
|
32
|
|
|
|
32 wk: 0.53
|
|
|
|
|
|
|
|
|
8
|
20
|
0.5
|
DILV, L-TGA, CHB, long QT syndrome, hydrops
|
Neonatal death
|
20–24 wk: 2
|
n/a
|
No
|
n/a
|
28
|
1170
|
Neonatal death
|
Male; Neonatal death
|
|
24
|
|
|
|
|
|
|
|
|
|
|
|
AV, atrioventricular; CHB, complete heart block; CT, cardiothoracic ratio; DILV, double-inlet
left ventricle; DOL, day of life; GA, gestational age; L-TGA, L-transposition of the
great arteries; LV, left ventricle; n/a, not applicable; PA, pulmonary artery; PS,
pulmonary stenosis; RSV, respiratory syncytial virus; Wt, weight.
Figure 1 (A) Two-dimensional fetal echocardiogram at 24 weeks of gestation. (B) Two-dimensional
transthoracic echocardiogram at birth. Both images demonstrate double-inlet left ventricle
(two atrioventricular valves empty in a smooth walled left ventricle).
One fetus (12.5%) with no pulmonary outflow obstruction presented with congenital
complete heart block at 20 weeks of gestation. The atrial rate was 120 to 130 beats
per minute and the ventricular rate was 40 to 50 beats per minute. There was a family
history of long QT syndrome among two maternal second-degree relatives, and there
was concern for coexisting fetal long QT syndrome. Fetal magnetocardiography was performed
at a research laboratory, which diagnosed long QT syndrome with QTc interval at 600
to 700 milliseconds. Steroids for fetal lung maturity were administered, and the fetus
was closely monitored by serial echocardiography. Hydrops developed at 24 weeks. There
was continuous deterioration of fetal cardiac function with a Tei index of 2 and nonreassuring
fetal heart status. At 28 weeks, the baby was delivered live-born but died shortly
after birth.
Mild AV valve insufficiency was present in 37.5% of fetuses, but was only present
postnatally in 25% of infants. All fetuses had a normal cardiothoracic ratio, with
a mean of 0.46 ± 0.07 (range 0.3 to 0.5). The mean GA of delivery was 37.3 ± 3.8 (range,
28 to 40) weeks and the mean birth weight was 3093 ± 805 (range 1170 to 3770) g. Apgar
scores for seven neonates at 5 minutes were 8 or more. None of the neonates required
intubation. Prostaglandin infusion was required for maintaining ductal patency in
cases of systemic or pulmonary obstruction.
The outcome of the fetuses with DILV was variable. One fetus with heart block and
long QT syndrome died shortly after birth. Of the remaining seven fetuses, postnatal
follow-up is available for a period ranging from 2 to 41 months. All seven infants
had staged surgical palliation. Four infants with pulmonary outflow obstruction underwent
a central shunt in the first few days of life (range 3 to 14 days), of which, one
infant has had bidirectional Glenn and three have had Fontan completion and all infants
are doing well.
One infant had PA banding with no pulmonary outflow obstruction in the first week
of life. This was followed by bidirectional Glenn and Fontan completion, and the infant
is doing well. One infant had mild pulmonary stenosis requiring PA band and Glenn
at 6 months of age, and the infant is doing well. The infant with associated tricuspid
atresia and coarctation of the aorta underwent PA band and repair of the coarctation
of the aorta. This infant developed complete heart block and required a permanent
pacemaker at 4.5 months of age. At 6 months of age, this infant developed respiratory
syncytial myocarditis resulting in heart failure and was placed on the heart transplant
list. The infant died postoperatively after a heart transplant at 17 months of age.
Overall survival was 75%.
Discussion
DILV can be associated with a variable neonatal outcome depending on the associated
cardiac anomalies. Common morphological patterns seen are a left anteriorly located
ascending aorta from the right ventricle and pulmonary trunk arising right posteriorly
from the dominant left ventricle (74%), obstruction to the aortic arch (12%), and
pulmonary stenosis (40%).[4] DILV has been associated with AV valve abnormalities (mainly AV insufficiency) in
39% of cases.[5] Our study showed findings with (S, L, L) in all fetuses (100%), with pulmonary atresia
in 50% and aortic arch obstruction in 12.5%. Mild AV valve insufficiency was present
in 37.5% prenatally and 25% postnatally.
Prenatal diagnosis was accurate in seven of the eight fetuses. One fetus with coexisting
coarctation of the aorta was diagnosed postnatally. Detection of coarctation of the
aorta is challenging prenatally. It can be a progressive lesion in utero with relative
worsening of the distal arch hypoplasia in later gestation,[6] due to continual decrease in the amount of blood flow traversing the isthmus as
pregnancy advances. Quantitative distal aortic arch hypoplasia and ventricular and
great artery size discrepancy have been observed and may facilitate the diagnosis
during serial echocardiographic evaluation.
In our study, one fetus had a coexistent congenital complete heart block. There was
also a strong maternal family history of long QT syndrome, and this was suspected
in the fetus. The diagnosis was confirmed with fetal magnetocardiography. The ventricular
rate in the fetus was less than 50 beats per minute, which progressed to hydrops,
resulting in preterm delivery and subsequent neonatal death. The presence of a complete
AV block along with complex congenital heart defect has been associated with poor
prognosis. A ventricular rate of less than 60 beats per minute and the presence of
hydrops are associated with a survival rate of 20%.[7] Fetal magnetocardiography is a noninvasive technique to monitor spontaneous electrophysiological
activity of the fetal heart through extremely weak variations of the associated magnetic
fields, located outside the maternal abdomen by superconducting sensor arrays.[8] It can be recorded reliably from the 20th week of gestation and can be used to classify
arrhythmias.[8] It has also been used to diagnose prolonged QT syndrome.[9]
[10] Long QT syndrome is inherited as an autosomal-dominant form with variable presentation.
It is a rare, but potentially life-threatening condition and can lead to ventricular
flutter in utero.[11] In our study, fetal magnetocardiography facilitated the diagnosis of long QT syndrome
allowing appropriate counseling to the family regarding the severity of the complex
heart defect.
Assessment of fetal cardiac function is of critical importance in some high-risk fetuses.
Tei index has been described as an easily measured Doppler-derived index of left or
right ventricular myocardial performance combining systolic and diastolic time intervals.[12] It is a combined index of global myocardial function and is independent of heart
rate and ventricular geometry.[12]
[13] The fetus with heart block, long QT syndrome, and hydrops had significantly elevated
Tei index (2.0) at 24 weeks, and died shortly after delivery at 28 weeks.
Infants with DILV who have no pulmonary outflow obstruction tend to develop congestive
heart failure within the first few months of life due to the increased blood flow
and require PA banding early in the neonatal period. In cases of pulmonary outflow
obstruction, a systemic-to-PA shunt is required to provide adequate blood flow for
oxygenation. The timing of this procedure depends on the degree of the pulmonary stenosis.
Infants with severe obstruction require this palliative surgery earlier compared with
those with moderate restriction who remain well compensated for a longer time. In
neonates with severe systemic outflow obstruction, repair of the same is needed prior
to the closure of the ductus arteriosus, to maintain adequate systemic flow. The neonatal
course depends on the presence of associated malformations, especially of the AV valves
and outflow tract obstruction. The most common approach to the surgical management
is a staged approach that usually culminates in a modified Fontan operation.[14] The initial surgery is aimed to limit the pulmonary blood flow and repair the aortic
arch obstruction if present, as in our series. None of the infants required Norwood
or Damus-Stansel-Kaye operation; however, regular surveillance echocardiography is
being performed to detect any systemic outflow obstruction. Although the initial palliative
surgery with PA banding compares favorably with Norwood results, lower morbidity and
mortality are seen in Clark series.[15] Fontan is the ultimate procedure of choice for patients with DILV. Early mortality
has decreased to 3% and survival is 97 and 88% at 5 and 10 years after surgery, respectively.[16] Vigilant follow-up is needed to monitor the development of systemic outflow obstruction
after the Fontan operation.
Conclusion
Prenatal diagnosis of DILV has increased over the last decade.[17] DILV, L-transposition of the great arteries, and associated evolving outflow obstruction
can be diagnosed prenatally due to an abnormal four-chamber and outflow tract views
with serial fetal echocardiography. Prenatal diagnosis allows delivery to be planned
at a tertiary care facility with optimal postnatal management and early interventions
including administration of prostaglandins and availability of neonatology, cardiology,
and pediatric cardiac surgery. Prenatal diagnosis helps with the opportunity to discuss
and counsel the complex situation with parents and prepare them for the likely course
of their newborn.
The limitations of the study include a small number of patients identified, which
is not unusual due to the rarity of this complex congenital heart defect. The strength
of our study is that all patients were from a single institution, which relates to
uniformity of care including surgical techniques, and pre- and postoperative management.
Acknowledgment
University of Wisconsin-Madison, WI 53706, for performing fetal magnetocardiography.
