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Hypoplastic left heart syndrome
Oliver Stumper
Heart 2010 96: 231-236
doi: 10.1136/hrt.2008.159889
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Education in Heart
CONGENITAL HEART DISEASE
Hypoplastic left heart syndrome
Oliver Stumper
< Additional references are
published online only at http://
heart.bmj.com/content/vol96/
issue3
Correspondence to
Dr Oliver Stumper, Birmingham
Children’s Hospital NHS Trust,
Birmingham, UK;
[email protected]
Hypoplastic left heart syndrome describes a range
of congenital cardiac lesions, which have in
common a small left ventricle which is unable to
support the systemic circulation. Typically the
volume of the small left ventricle is <20 ml/m2
body surface area (BSA).
A number of fetal cardiac anomalies have been
shown to cause this problemdnamely, aortic or
mitral atresia, with or without mitral or aortic valve
stenosis, or an unbalanced atrioventricular septal
defect.1 Despite the heart being basically fully
developed at some 8 weeks of gestation, the growth
of cardiac structures is entirely dependent on
a normal fetal circulation. Thus, it comes as no
surprise that pronounced aortic stenosis, detected in
a fetus at some 18e20 weeks gestation, may progress to present at birth as classical hypoplastic left
heart syndrome (HLHS).2
The common presentation of newborns with
hypoplastic left heart syndrome at birth is cardiovascular collapse and shock. The peripheral pulses
are weak, without major difference between the
brachial and femoral pulses. There is usually a mild
to moderate degree of cyanosis, but no differential
cyanosis. Chest x-ray normally shows cardiomegaly and plethoric lung fields. The ECG documents
right ventricular hypertrophy and reduced left
ventricular forces. If the diagnosis is suspected, the
administration of a prostaglandin infusion at the
rate of 5e20 ng/kg/min normally maintains
patency of the ductus arteriosus, and will prevent
further cardiovascular compromise, progressive
acidosis and death. Assessment by cardiac ultrasound will make the definitive diagnosis, allow for
optimisation of initial treatment and detailed
discussion of the treatment options and outcomes
with the parents.
The initial description of a surgical procedure to
palliate hypoplastic left heart syndrome in
neonates was provided by William Norwood in
1982.3 This allowed neonates to survive into
infancy when more palliative surgery was required.
The evolution of these techniques has progressed
over the past 25 years, and nowadays the Norwood/
Fontan palliation of children with HLHS can
produce very acceptable early and medium term
results.
In the UK, the surgical treatment of a newborn
with HLHS became available only in early 1993.
Results of this initial Norwood procedure and the
subsequent bidirectional cavopulmonary shunt and
Fontan procedure have improved steadily over time,
with 5 year survival now approaching 70%.4e6
Before this, attempts were made to bridge children
Heart 2010;96:231e236. doi:10.1136/hrt.2008.159889
to primary neonatal heart transplantation, either by
medium term prostaglandin infusion or by stenting
the arterial duct, together with banding the
pulmonary arteries. However, results were disappointing in this early phase (1990) and neonatal
primary heart transplantation can no longer be
viewed as a viable option.
GENETICS
HLHS has been reported to occur in approximately
0.016e0.036% of all live births, representing some
2% of all congenital cardiac defects. Boys are twice
as commonly affected as girls. Over the recent years
the molecular basis for left heart obstructive lesions
has been better understood, in part due to their
dominant inheritance despite low penetrance and
variable expression.7 Gene mutations of NKX2.5
and NOTCH1, involved in cardiac development,
have been identified in some cases. Overall these
new insights raise the prospect of improved genetic
counselling in future.
ANTENATAL DIAGNOSIS
The percentage of children with HLHS who are
diagnosed antenatally is increasing, due to the
widespread establishment of adequate ultrasound
screening programmes over the past two decades.
Currently some 60% of fetuses are detected antenatally. Parents are given earlier and more detailed
counselling regarding the treatment options and
the anticipated outcome in their children. Nonetheless, improved antenatal diagnosis has generally
not resulted in an improved outcome postnatally.8
This may be based on the fact that antenatal diagnosis allows more rapid and dedicated initial
management, and allows for survival of neonates
with HLHS and significant comorbidities such as
a highly restrictive atrial septum or other organ
system lesions. Currently about 50% of parents,
following antenatal diagnosis of HLHS in their child
before 20 weeks gestation, decide to electively
terminate the pregnancy.9 The drive to perform
antenatal scans at an earlier gestational age is likely
to decrease the overall sensitivity of the screening
programmes, as it is known that HLHS may develop
late in pregnancy and thus may not be apparent at
a 14 week scan.
Several pilot studies have been conducted into
catheter or surgical interventions in fetuses with
antenatally detected HLHS. In particular, in fetuses
with severe aortic stenosis, the aim was to open up
the aortic valve and promote anterograde flow and
ultimately growth of the left heart structures.
Similarly, the subgroup of fetuses detected with
231
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Education in Heart
a highly restrictive, or, occasionally, intact atrial
septum are sometimes considered for fetal intervention (balloon atrial septostomy). Such procedures are currently experimental and the actual
benefit of such interventions cannot be ascertained
at present.10
INITIAL MANAGEMENT
Neonates with HLHS are normally born at term
and with a normal birth weightda reflection of the
fact that this serious congenital cardiac defect is
well tolerated during fetal development. Postnatally
the ductus arteriosus will close and pulmonary
vascular resistance will drop, resulting in cardiovascular collapse unless treated rapidly. Patency of
the ductus arteriosus must be maintained by prostaglandin infusion (5e20 ng/kg/min). In the past,
attempts were made to address the drop in
pulmonary vascular resistance, and the resulting
pulmonary over-circulation, by low frequency
ventilation, raising the partial pressure of carbon
dioxide (PCO2), using low inspired oxygen concentrations, increasing dead space ventilation, or even
adding CO2 to the inspired gas. Thus, in the past,
early management focused on increasing pulmonary
vascular resistance and thereby limiting pulmonary
blood flow. In contrast, nowadays, the thrust of
preoperative management is towards better
systemic tissue perfusion, using systemic afterload
reducing agents, ino-dilators and addressing
systemic acidosis early and aggressively.11
COUNSELLING
HLHS remains a very severe congenital cardiac
defect, which is not compatible with survival
unless treated. Despite the improvements in cardiological and cardiac surgical management, the
medium term survival remains limited and the
functional status of the survivors is limited
compared to normal. Even though stage I surgery
can now be offered with an early mortality rate of
some 15%, parents have to understand fully the
implications of embarking on long term palliative
care of their newborn child. Survival at 1, 5 and
10 years is some 75%, 70% and 65%, respectively, in
the largest series reported. These figures, however,
do not quote the risk of survival with very poor
functional outcome or gross neurological deficit or
the uncertainty about future limited treatment
options if the systemic right ventricle fails.
Consenting for treatment of children with hypoplastic left heart syndrome must include these
issues, particularly as cardiac transplantation in this
group of patients will never be an easy and widely
available option.
STAGE I NORWOOD PROCEDURE
The original initial surgical palliation comprised
aortic arch reconstruction, atrial septectomy, endto-side anastomosis of the main pulmonary artery
to the, sometimes, diminutive ascending aorta, and
creation of a BlalockeTaussig shunt to the reconstructed central pulmonary arteries.3 The aortic
232
arch reconstruction is almost universally achieved
by opening the underside of the aortic arch longitudinally and by placing a generous patch of
homograft material along the entire length,
extending distally beyond the site of coarctation
(figure 1dstage 1a). Various techniques have been
employed to enlarge the proximal end of this
reconstruction, so as to allow for an increased size of
the native ascending aorta and improved coronary
perfusion. The size of the Gore-Tex tube to create
a BlalockeTaussig shunt has decreased over time, so
as to limit diastolic run-off to the pulmonary
arteries and avoid volume loading of the systemic
right ventricle. The standard shunt size is now
3.5 mm (3 mm in neonates <2.5 kg bodyweight).
This classical Norwood procedure was replaced,
by many centres, by implanting a non-valved tube
from the right ventricle to the left pulmonary artery
(Sano modification12) and later, at Birmingham
Children’s Hospital (BCH), to the right pulmonary
artery, instead of the original modified
BlalockeTaussig shunt (figure 1dstage 1b). These
modifications have led, in many units, to an
improved early survival and improved early postoperative course in the intensive care unit (ICU).13
The main advantage of this modification is improved
coronary and systemic perfusion due to the absence
of diastolic run-off down a BlalockeTaussig shunt.
However, further analysis and comparison of
detailed haemodynamic data and postoperative
variables documented that systemic arterial mean
pressures were comparable and that there were no
significant differences in markers of pulmonary
blood flow or in markers of systemic blood flow
(blood lactate, oxygen extraction ratio), or in the
estimated ratio of pulmonary:systemic blood flow
(Qp:Qs). There were no significant differences in
markers of cerebral blood flow or renal and hepatic
function in the early postoperative period.14
The growth of the branch pulmonary arteries
was found to be improved after creation of a right
ventricle to pulmonary artery conduit instead of
a BlalockeTaussig shunt.15 This is most likely due
to the pulsatile nature of pulmonary blood flow
after this modification. Nonetheless the incidence of
significant branch pulmonary artery stenosis at the
site of conduit insertion was found to be increased,
and surgical reconstruction was cumbersome. The
latter was the major stimulus for placing the right
ventricleepulmonary artery (RV-PA) shunt to the
right of the end-to-side connection of the pulmonary artery with the ascending aorta, as introduced
at BCH in 2004. Any encountered branch pulmonary artery stenosis at the site of insertion of the
non-valved tube is more easily relieved during the
subsequent cavopulmonary shunt and can be roofed
over by the superior caval vein. Despite these
modifications, the 1 year survival that has been
achieved by RV-PA approach is now also achieved
by some centres utilising the classical Norwood
procedure, utilising a BlalockeTaussig shunt. This
has led to the design of a multicentre randomised
trial carried out in the USA to compare these two
approaches.
Heart 2010;96:231e236. doi:10.1136/hrt.2008.159889
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Education in Heart
Pre-op
Stage 1
a
b
c
Stage 2
Stage 3
Figure 1 Hypoplastic left heart syndrome from birth to final palliation. Pre-op: hypoplastic left ventricle and a diminuitive
ascending aorta with duct dependant systemic circulation. Stage 1: a. classical Norwood procedure with a modified
BlalockeTaussig shunt. b. The Sano modification with a right sided RV-PA conduit. c. The hybrid stage 1 palliation with
bilateral pulmonary artery bands and a stent within the systemic ductus arteriosus. Stage 2: the superior vena cava is
anastomosed to the right pulmonary artery to provide the sole source of pulmonary blood flow. Stage 3: the inferior vena
cava and the hepatic veins are rerouted to the pulmonary arteries by means of a Gore-Tex conduitdthe circulation is in
series with a systemic right ventricle.
Heart 2010;96:231e236. doi:10.1136/hrt.2008.159889
233
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Education in Heart
A further important cardiac surgical focus is on
optimising bypass techniques, avoiding circulatory
arrest and maintaining low flow cerebral perfusion
throughout the arch reconstruction, so as to limit
potential neurologic damage during the stage I
procedure and to ensure best possible neurocognitive outcome in the long run. As yet, no
significant differences between these techniques
have been identified.
Significant independent risk factors for early
mortality in almost all reported surgical series
include: low patient weight (<2.5 kg); a diminutive
ascending aorta of <2 mm in size; a restrictive, or
sometimes intact, atrial septum; an unbalanced
atrioventricular septal defect; or associated noncardiac abnormalities or chromosomal defects. In
such cases, a growing number of centres now offer
an alternative to the classical or modified Norwood
stage I palliation. This was introduced mainly by
the Giessen group and was further modified by the
Columbus group, and is now labelled a hybrid stage
1 procedure.16 17 Through a median sternotomy,
bilateral pulmonary artery bands are placed surgically to limit pulmonary blood flow. A stent is
placed across the systemic ductus arteriosus, either
during the same procedure or at a later stage, to
maintain unrestrictive flow from the right ventricle
to the systemic circulation (figure 1dstage 1c).
Restriction at the level of the atrial septum is
addressed either by static or dynamic balloon
septostomy or by stent placement. Despite the
initial learning curve, the immediate results of this
procedure are excellent. However, there remains
a significant interstage mortality and also a notably
increased risk of the so-called comprehensive stage 2
procedure. During this procedure the aortic arch and
pulmonary artery reconstruction have to be
performed, together with the anastomosis of the
ascending aorta with the main pulmonary artery,
the atrial septectomy and the cavopulmonary
shunt. Again, in some pioneering centres, excellent
results with this approach have been achieved.
Medium term results and data on neurocognitive
development and ability scores after these different
strategies are needed, and are eagerly awaited, to
formulate better the optimal management
approach to this relatively common congenital
cardiac lesion.
Several studies have documented that overall
survival at the different stages of the Norwood
palliation is improved in centres with a high
activity compared to those with very small
numbers.18 The array of options currently available
to embark on initial treatment of neonates with
HLHS should not promote a decentralised approach
to this complex problem.
INTERSTAGE MORTALITY
Early on during the experience with the Norwood
palliation in larger series of patients with HLHS it
became apparent that a fair number of hospital
survivors after stage I palliation were discharged
home in a very satisfactory condition, and then
died suddenly at home before undergoing stage II
234
palliation. Retrospective analysis of these cases has
revealed that, in particular, children with a diminutive sized ascending aorta are at risk of sudden
death. This is likely to be related to inadequate
coronary perfusion either at the level of the Damus
connection or due to the small size of the ascending
aorta. Further factors identified included an acute
blockage of the BlalockeTaussig shunt, obstruction
to the pulmonary arteries, development of
obstruction of the reconstructed aortic arch, or
a restriction to the atrial septum. All of these
potential problems can be exasperated by an acute
illness such as diarrhoea and vomiting, severe reflux
with aspiration or a viral infection. Acute interstage
mortality has remained an issue also with the newer
Sano-modification (RV-PA conduit) or a hybrid
stage I procedure. At present there is no significant
difference in 1 year survival after any of these
approaches, despite some apparent differences in
stage I mortality.
Over the years there has been much focus on
reducing interstage mortality, by developing
sophisticated home monitoring programmes and
very frequent cardiological reviews.19 Although
these measures have been shown to have significant
impact, they have not completely eradicated this
problem. Further work in this area is required to
eventually produce better 1 year overall survival
after palliative surgery for HLHS.
STAGE II PROCEDURE
After some 4e6 months of age, children who
underwent stage I palliation (either the classical
Norwood procedure or a modification utilising
a conduit from the right ventricle to the pulmonary
arteries), suffer from severe cyanosis due to very
limited pulmonary blood supply. At the same time
pulmonary vascular resistance has decreased significantly from the initially high levels shortly after
birth. At this stage it is common practice to proceed
to the surgical creation of a bidirectional cavopulmonary shunt with interruption of the original
BlalockeTaussig shunt or the conduit from the right
ventricle to the pulmonary artery. Most centres
continue to perform a cardiac catheterisation
procedure preoperatively, so as to obtain direct
haemodynamic measurements and to address the
relatively common finding of aortic arch
obstruction by balloon angioplasty.
After the cavopulmonary shunt, the systemic
venous return of the upper body half is redirected
to the lungs without the use of an effective
pumping chamber (figure 1dstage 2). As long as the
pulmonary arteries are of good size and there is
a well developed pulmonary capillary bed and no
restriction at the level of the pulmonary venous
drainage or the atrial septum, this procedure
provides a very good functional result. Initial resting
saturations are commonly around 85e90% in air. As
this “shunt” is created without the use of artificial
material there is normally good growth of the
anastomosis during early childhood. However, as
there is a relative decrease in the amount of superior
caval venous return towards later childhood,
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Education in Heart
children will again suffer from pronounced cyanosis
towards 4e5 years of age. This is aggravated by the
fact that common activities, such as running, will
increase the amount of desaturated inferior caval
venous blood to the circulation and will worsen the
cyanosis very rapidly.
Cardiac catheterisation is normally again
performed before embarking on further surgical
management to assess pulmonary artery size,
distribution and pressures, but also to rule out any
recurrent aortic arch obstructions, systemic venous
fistulae or significant systemic collateral arteries to
the pulmonary circulation. All of these lesions can
be addressed by interventional cardiac catheter
techniques with very good results, and reduce the
risk of the subsequent Fontan procedure.
STAGE III SURGERY
At some 3e5 years of age, children with HLHS who
have undergone stage I and II surgery will get
increasingly tired, breathless and cyanosed after
mild to moderate activity. Surgical connection of
the inferior caval venous return to the pulmonary
arteries, without the use of an effective pumping
chamber, will redirect all desaturated blood to the
pulmonary vasculature before returning to the
heart. This is the completion of the Fontan circulation. Today most centres use an extracardiac PTFE
(polytetrafluoroethylene) conduit to achieve this
(figure 1dstage 3). The majority of centres create
a fenestration with the pulmonary venous atrium,
so as to allow for a small right-to-left shunt to limit
the pressure within the Fontan circuit, and to
prevent diastolic dysfunction of the systemic right
ventricle in the early postoperative period due to
a fall in overall cardiac output and ventricular
preload. The early mortality of such a procedure
now approaches zero in appropriately selected
patients with maintained right ventricular function. In children with decreased right ventricular
function and moderate-to-severe tricuspid valve
regurgitation, an attempt at valve repair should be
made first, rather than embarking on Fontan
completion at the same time.
The morbidity after Fontan completion in
patients with HLHS remains high, mostly due to
the common occurrence of prolonged pleural
effusions.
NEURODEVELOPMENTAL OUTCOME
Presently, there are only very few studies available
to assess the cognitive development and the
neurodevelopmental outcome and quality of life of
patients after surgical palliation for HLHS. Initial
work suggests that the outcome measures are
within the normal range, but the overall performance of the entire cohort is lower than that of the
general age matched population. Comparison of
outcome indices should ideally be performed by
matching other groups of patients with cyanotic
congenital heart disease, requiring bypass surgery
during the first weeks of life, such as patients with
complete transposition of the great arteries, or
Heart 2010;96:231e236. doi:10.1136/hrt.2008.159889
those with longstanding cyanosis in early childhood. There is some recent evidence that the cerebral arterial blood supply in infants with HLHS is
reduced compared to normal, which, in itself, could
have an impact on overall neurocognitive
outcome.20
One of the factors identified for reduced cognitive
development is the use of deep hypothermic circulatory arrest during the initial Norwood stage I
palliation. Most centres now use continuous low
flow cerebral perfusion during the stage 1 procedure.
This is likely to reduce the potential for neurological
damage during the early neonatal period. Studies are
being designed to evaluate any differences in
outcome among children who have undergone
a classical Norwood stage I procedure compared to
those who received a Sano modification. In due
course this line of research will also be able to
evaluate any potential differences in outcome in the
growing group of patients who undergo a hybrid
stage 1 procedure, without the use of cardiopulmonary bypass, during their initial palliation.
THE POST-FONTAN STATE
After completion of the Fontan the circulation is in
series, being supported by only one ventricle, which
is of right ventricular morphology. The myocardial
architecture of the right ventricle is significantly
different from the left ventricle, having only two
layers of myocardial fibres and having a substantially different pattern of contraction and shortening. Systemic and pulmonary vascular resistances
represent the combined afterload to this right
ventricle. The right ventricle has to function in the
context of a limited coronary flow reserve, due to
the Damus connection and a generally small
ascending aorta, which merely serves as a conduit
to the coronary arteries themselves. Medium term
survival in patients with either a right or a left
ventricular dependent Fontan circulation is
comparable, but more detailed functional assessments are currently still awaited.
Systemic venous pressures are significantly
elevated after the Fontan procedure, resulting in
a degree of liver dysfunction and chronic gut
oedema. The Fontan circulation is associated with
a pro-coagulable state, suggesting the use of long
term antiplatelet or anticoagulation therapy. As
yet, no prospective trials in this field have been
concluded and there is a wide variability to centre
specific preference of postoperative chronic medication and management protocols. Furthermore,
endothelial function is significantly altered in the
context of non-pulsatile pulmonary blood flow,
leading to an increased pulmonary vascular resistance. Selective pulmonary vasodilators have
shown promising initial results in the management
of some post-Fontan complications, as did de novo
fenestration of the Fontan circuit to establish
a right-to-left shunt and decreasing right atrial
pressure.
Despite the very significant strides in the initial
treatment and palliation of neonates with HLHS,
the medium to long term outcome of children and
235
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6.
7.
8.
9.
10.
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11.
<
12.
increasing numbers of adolescents and adults with
Norwood palliation of HLHS remains uncertain. It
will require the input of a highly dedicated and
trained team of cardiologists, physicians and
surgeons to achieve the best possible outcome and
quality of life.
Competing interests In compliance with EBAC/EACCME guidelines,
all authors participating in Education in Heart have disclosed potential
conflicts of interest that might cause a bias in the article. The author
has no competing interests.
Provenance and peer review Commissioned; not externally peer
reviewed.
13.
14.
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3.
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Heart 2010;96:231e236. doi:10.1136/hrt.2008.159889