CONGENITAL HEART DISEASE
Congenital heart disease
in infancy and childhood
Hannah Bellsham-Revell
Michael Burch
Abstract
Congenital heart disease occurs in approximately 8 per 1000 live
births. The most common lesion at birth is a ventricular septal defect,
but many are small and do not need surgery. Cyanotic heart disease
includes Fallot’s tetralogy and transposition of the great arteries,
which are both amenable to correction in childhood. More compli-
cated cyanotic lesions are treated by separation of the systemic
venous flow by a cavopulmonary connection, often referred to as a
Fontan circulation. Some genetic syndromes (Marfan’s, Noonan’s,
Williams’) are associated with congenital heart disease, as are chro-
mosomal disorders such as Down’s and Turner’s syndromes.
DiGeorge’s syndrome (thymic aplasia, hypoparathyroidism, cono-
truncal cardiac defect) and velocardiofacial syndrome (palatal abnor-
malities, heart defects, dysmorphic features) are associated with
microdeletions within the q11 region of chromosome 22.
Keywords Atrial septal defect; coarctation of the aorta; congenital
heart disease; Fontan; MRCP; paediatric cardiology; tetralogy of Fal-
lot; transposition of the great arteries; ventricular septal defect
Introduction and epidemiology
Neonatal data collection gives an incidence of significant
congenital heart disease of 8 per 1000 live births. This does not
include minor defects, which often present later in childhood or
adult life (e.g. bicuspid aortic valves occur in 1 per 100 of the
population). Congenital heart disease is even more common in
the antenatal period; the discrepancy is explained by the greater
incidence of spontaneous abortions and stillbirths in fetuses with
congenital heart disease and, increasingly, by prenatal diagnosis
and termination of pregnancy.
Specific lesions
The most common congenital heart defects at birth are shown in
Figure 1.
Ventricular septal defects (VSDs)
The physical signs and symptoms depend on the size of the
defect. Assessment is by echocardiography (using three-
dimensional scanning for further definition of complex defects).
Hannah Bellsham-Revell MB BS MRCPCH MD(Res) is a Consultant in
Paediatric Cardiology at Evelina London Children’s Hospital, London,
UK. Competing interests: none declared.
Michael Burch FRCP FRCPCH is a Consultant Cardiologist, Head of
Department of Cardiology and Director of Cardiothoracic
Transplantation and Heart Failure Service at Great Ormond Street
Hospital, London, UK. Competing interests: none declared.
MEDICINE 46:11
Key points
C Congenital heart disease occurs in approximately 8 per 1000
births
C Most congenital heart disease is amenable to correction, but
patients require life-long follow-up and may need further
interventions
C Some congenital heart disease cannot be corrected, but sur-
gical palliation may be possible, albeit with significant
sequelae
C Many genetic syndromes and chromosomal disorders can be
associated with congenital heart diseases
 Small defects are associated with a loud pan-systolic
murmur (reflecting a high-pressure difference between
the left and right ventricle). Up to 60% close spontane-
ously in the first 5 years of life. If they persist, surgical
closure is not usually undertaken.
 Large defects usually present with heart failure in infancy
(failure to thrive, breathlessness, history of poor feeding).
There may be only a soft murmur, because large defects
result in equalization of the ventricular pressures. A dia-
stolic flow murmur can be heard across the mitral valve
when pulmonary blood flow is more than twice systemic
flow. Surgical closure is indicated in children who fail to
respond to medical therapy or who have pulmonary hy-
pertension with a high pulmonary blood flow (i.e. without
pulmonary vascular disease). Transcatheter closure is also
sometimes possible, but membranous defects are usually
closed with surgery because of the risk of early and late
heart block.
Atrial septal defects (ASDs)
ASDs seldom cause symptoms in childhood, but findings on
auscultation include fixed splitting of the second heart sound, an
ejection systolic pulmonary flow murmur and, sometimes, a
diastolic tricuspid flow murmur. The electrocardiogram (ECG)
typically shows right axis deviation and partial right bundle
branch block, although primum defects (see below) can have a
superior (left) axis. Echocardiography demonstrates the intera-
trial septum clearly, and in children with large shunts there can
be evidence of right ventricular volume overload. ASDs occur in
different positions in the atrial septum:
 Ostium secundum defects (about 70% of ASDs in infancy)
result from incomplete development of the septum
secundum, with a defect at the site of the oval fossa. Small
secundum ASDs noted in infancy can close spontaneously,
but there is consensus that larger defects should be closed
in childhood. Transcatheter closure is usually feasible, but
large defects with deficient rims can require surgical
closure.
 Ostium primum or partial atrioventricular septal defects
(about 25% of ASDs) result from failure of the septum
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 CONGENITAL HEART DISEASE

The most common congenital heart defects

Ventricular 32.1%
septal defect 32.5%

Pulmonary 8.6%
stenosis 7.6%

Persistent ductus 8.3%

arteriosus 11.9%

Atrial septal 7.4%

defect 5.9%

Coarctation of 6.7%
the aorta 6.3%

3.8%
Aortic stenosis
5.1%

Fallot’s tetralogy 3.8%

5.9%

Transposition of 2.6%
the great arteries 5.0%

of 56,109 births; the red bars are from a UK study b of 160,480 births. The lesions
listed account for 70–80% of all congenital heart defects.

aMitchell S C et al. Circulation 1971; 43: 323–32.

bDickinson D F et al. Br Heart J 1981; 46: 55–62.

Figure 1

primum to reach the endocardial cushions. There are
usually two atrioventricular valve orifices, but sometimes
a common atrioventricular valve is present. The left-sided
atrioventricular valve has three leaflets, and there can be
regurgitation through the ‘cleft’ or zone of apposition. In
complete atrioventricular septal defect, a ventricular
communication is also present (Figure 2a,b), and typically
there is severe heart failure in infancy. Atrioventricular
septal defects are associated with Down’s syndrome, and
almost all require surgical closure. In patients with a large
‘cleft’, extensive valve repair or replacement can be
required.
 Failure of absorption of the sinus venosus into the right
atrium causes a defect at the superior or inferior portion of
the atrial septum (about 5% of ASDs). In superior defects,
the right upper lobe pulmonary vein usually drains into the
lower part of the superior vena cava. Sinus venosus lesions
all require surgical closure.
Patent ductus arteriosus (PDA)
The ductus arteriosus is a normal fetal structure allowing blood
flow from the pulmonary artery into the aorta (because little
cardiac output passes to the lungs in the prenatal period).
Closure of the duct normally occurs within a few hours of birth;
persistence beyond the neonatal period is abnormal. Physical
findings depend on the size of the lesion: small ducts usually
cause no symptoms but a continuous murmur through systole
and diastole; large ducts cause cardiac failure but there may be
no murmur. High pulmonary flow can cause left atrial and left
ventricular enlargement. A patent duct is easily diagnosed in
children using echocardiography and colour flow Doppler
(Figure 3). The ECG shows an increase in left-sided voltages and
there can be ST and T wave repolarization changes.
Intervention is usually catheter-based, unless the lesion is
very large or the patient is very small, when surgical closure is
preferred. Treatment of small ducts is often recommended
because the risks of intervention are considered less than the risk
of endocarditis. PDA is more common in premature babies, when
medical treatment with a prostaglandin synthesis inhibitor
(indometacin, ibuprofen) can induce duct closure. Paradoxically,
patients with cyanotic congenital heart disease and some left
heart obstructive lesions can be dependent on a patent duct in
the neonatal period; duct patency can be maintained with
prostaglandin.
Pulmonary stenosis
This is usually valvar, but subvalvar, supravalvar or peripheral
pulmonary artery stenoses is occasionally seen. On

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 CONGENITAL HEART DISEASE

Figure 2 Atrioventricular septal defect. (a) Two-dimensional transthoracic echocardiography standard ‘four-chamber’ view showing an atrioven-
tricular septal defect. Asterisks demonstrate the atrial and ventricular components. (b) Two-dimensional transthoracic echocardiography short-axis
view of the common atrioventricular valve. (c) Diagram from the short-axis view. The dotted line represents the position of the interventricular
septum. IBL, inferior bridging leaflet; LA, left atrium; LML, left mural leaflet; LV, left ventricle; RA, right atrium; RASL, right anterior superior leaflet;
RML, right mural leaflet; RV, right ventricle; SBL, superior bridging leaflet.

auscultation, the intensity of the murmur is related to the
gradient between the right ventricle and pulmonary artery.
Critical pulmonary stenosis presents in infants with cyanosis
caused by reduced pulmonary blood flow and right-to-left
shunting across an atrial communication (patent foramen
ovale, ASD). Mild pulmonary stenosis does not usually cause
symptoms in childhood. Percutaneous balloon valvuloplasty is
indicated has not been defined. The dysplastic pulmonary
valve associated with Noonan’s syndrome is often resistant to
balloon dilatation.

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 CONGENITAL HEART DISEASE
Figure 3 Patent ductus arteriosus (PDA) on two-dimensional echocardiography with colour Doppler. The colour flow Doppler signal is seen
entering the pulmonary artery via the duct. LPA, left pulmonary artery; MPA, main pulmonary artery; RPA right pulmonary artery.
Aortic stenosis
Aortic obstruction is principally valvar but can be subvalvar
(often as a discrete membrane) or supravalvar (associated with
Williams’ syndrome). Critical aortic stenosis can present in the
neonatal period with haemodynamic collapse as the duct closes.
Most aortic stenosis is mild, but moderate and severe aortic
stenosis can result in exertional symptoms in childhood,
including syncope and sudden death. Children with significant
aortic stenosis should be discouraged from participating in
competitive sport.
Intervention is usually based on symptoms, ECG changes
and assessment of the peak instantaneous or mean pressure
Figure 4 Coarctation of the aorta. MRI of coarctation of the aorta with
collaterals (Coll). DAo, descending aorta; IMA, internal mammary ar-
teries; LSCA, left subclavian artery.
MEDICINE 46:11
gradient between the left ventricle and ascending aorta.
Percutaneous balloon valvuloplasty is the usual treatment in
childhood, although surgical valvotomy can be performed,
particularly in infancy. If there is significant associated aortic
regurgitation, valve replacement is required. An alternative
surgical technique that avoids anticoagulation is the Ross
operation, in which the aortic valve is replaced with the pa-
tient’s own pulmonary valve, which is itself replaced by a
homograft. Bicuspid aortic valves are commonly seen in clinics
and often show minimal stenosis or regurgitation, but they
seldom cause problems in childhood.
Coarctation of the aorta
Congenital narrowing of the aortic lumen usually occurs just
distal to the left subclavian artery (Figure 4), although it occa-
sionally arises lower in the descending aorta. Severe coarctation
presents in the neonatal period with breathlessness and reduced
femoral pulses when the arterial duct closes. Older children
present with hypertension. Collateral arteries can develop from
the ascending to the descending aorta, manifesting as rib
notching on a chest radiograph.
Treatment for neonatal coarctation is by surgical repair with
an end-to-end anastomosis or sometimes use of the left subcla-
vian artery for arterioplasty. Older children can undergo percu-
taneous balloon dilatation and stenting, but surgery is sometimes
required. Balloon dilatation is the treatment of choice for re-
coarctation. Long-term follow-up with monitoring of hyperten-
sion is essential, as the aortic vessels are often stiffer than those
without coarctation. There can also be further narrowing or
dilatation around the site of previous surgery.1
Fallot’s tetralogy
The features of tetralogy of Fallot (Figure 5a) are:
 malaligned VSD deviated under the pulmonary valve
 aorta overriding the lower part of the ventricular septum
 pulmonary (typically subpulmonary) stenosis
 subsequent right ventricular hypertrophy.
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 CONGENITAL HEART DISEASE

The large VSD results in equalization of ventricular pressures

Tetralogy of Fallot (such that there is no murmur), but there is a significant gradient
a between the right ventricle and the pulmonary artery (associated
with the systolic murmur of pulmonary stenosis at the left sternal
edge).
Symptoms depend on the severity of the pulmonary stenosis. At
one extreme, virtual pulmonary atresia with duct dependency can
present in the neonatal period. In other cases, there are no initial
signs but, as subpulmonary stenosis progresses, cyanosis (from
right-to-left shunting across the septal defect) becomes apparent.
Severe cyanosis (hypercyanotic spells) can also be the result of
dynamic infundibular/subpulmonary muscle spasm, and can be
relieved by increasing systemic resistance using postural ma-
noeuvres (e.g. bringing the knees to the chest) or by administration
of intravenous propranolol or noradrenaline (norepinephrine).
Definitive treatment is complete surgical correction, usually
performed in infancy. Palliation is occasionally required, partic-
ularly in neonates, by creating a shunt between the subclavian and
pulmonary arteries (BlalockeTaussigeThomas shunt) or placing
a stent in the right ventricular outflow tract. Echocardiography is
used preoperatively to assess for coronary artery anomalies,
additional VSDs and pulmonary artery size. Computed tomogra-
phy (CT) or magnetic resonance imaging (MRI) can further define
pulmonary arterial anatomy. The results of surgery are good, and
mortality is very low in most centres (98.8% survival at 1 year in
the UK in 2011e2012).2

Transposition of the great arteries

Transposition of the great arteries In transposition of the great arteries (Figure 5b), the pulmonary
and systemic circulations exist in parallel rather than in series.
b
This is incompatible with life, but most neonates initially survive
because the foramen ovale and, to a lesser extent, the duct allow
mixing of the circulations. Cyanosis is typically severe, but those
with a large ASD or VSD can have minimal cyanosis. Initial
palliation is by percutaneous balloon atrial septostomy followed
by definitive repair using an arterial switch operation, which is
usually performed in the first few weeks of life.

Other complex congenital heart disease

Some complex lesions can be treated by definitive surgery.
 Total anomalous pulmonary venous drainage can be cor-
rected by reconnection of the pulmonary veins to the left
atrium. Although results can be good, there can be anas-
tomotic narrowing and, in some cases, diffuse pulmonary
vein hypoplasia/stenosis.
 With a common arterial trunk, the pulmonary arteries are
reconnected to the right ventricle, usually with a valved
homograft. The truncal valve is seldom normal and in time
usually needs replacement.
Very complex lesions, such as hypoplastic left heart/right
heart, double-inlet ventricle, straddling atrioventricular valves or
severe hypoplasia/atresia of structures, may mean bi-ventricular
repair is impossible. Palliative procedures have enabled more of
these children to live to adulthood, and they need continuing

Figure 5 Blue arrows mark the path of deoxygenated blood through

the heart, red arrows show deoxygenated blood, and purple arrows
mixed oxygenated and deoxygenated blood.

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 CONGENITAL HEART DISEASE

Total cavopulmonary connection (extracardiac) Single-gene defects and congenital heart disease
Noonan’s syndrome
Cardiac lesions
C Hypertrophic cardiomyopathy
C Pulmonary stenosis
C ASD
Other features
C Short stature
C Ptosis
C Squint
C Hypertelorism
C Low-set, posteriorly rotated ears
Marfan’s syndrome
Cardiac lesions
C Aortic root dilatation (and potential aortic dissection)
C Mitral valve prolapse
Other features
C Tall stature
C Long fingers and increased span
C Lax joints
C Scoliosis/kyphoscoliosis and pectus excavatum
C Dural ectasia
C High palate
C Myopia
C Retinal detachment
HolteOram syndrome
Cardiac lesions
C ASD
C Occasional ventricular septal defect
Figure 6 Diagram showing a completed Fontan circulation (in a patient Other features
with hypoplastic left heart syndrome). The inferior caval vein is con- C Upper limb abnormalities vary from minor clinodactyly to severe
nected via a conduit to the pulmonary arteries, which are anasto- reduction deformities
mosed to the superior caval vein. Pulmonary venous blood returns to
the left atrium from the pulmonary veins, and travels through the open Table 1
atrial communication to the systemic ventricle, and then around the
body through the aorta. In this patient, the coronary arteries are sup-
plied through an anastomosis of the native aorta to the reconstructed common because corrective surgery is undertaken early, avoid-
aorta. Blue arrows mark the path of deoxygenated blood through the ing the development of pulmonary vascular disease (from high
heart and red the deoxygenated blood. flow/high pressure in the pulmonary circulation).

specialist care. When pulmonary blood flow is insufficient, initial Genetics

palliation is with a BlalockeTaussigeThomas shunt (see above).
Alternatively, if pulmonary blood flow is increased, this can be
limited by banding of the pulmonary artery. These measures are
often required in the neonatal period, but some children remain
balanced for some years.
After initial palliation, at around 6 months of age, the superior
vena cava is connected to the pulmonary artery (a bi-directional
Glenn shunt). The total cavopulmonary connection (‘Fontan’
circulation; Figure 6) is completed between the ages of 3 and 5
years, when the inferior vena cava is baffled through the atrium
or via an extracardiac conduit into the pulmonary artery. Older
patients may have undergone the original atriopulmonary Fon-
tan, where the right atrium was connected directly to the pul-
monary artery.
Eisenmenger’s syndrome
Eisenmenger’s syndrome (reversal of a previous left-to-right
shunt because of pulmonary vascular disease) is now less
It is now recognized that many cases of non-syndromic
congenital heart disease have a genetic component.3 The risk
of having a child with congenital heart disease increases if the
parents or any siblings have congenital heart disease, and pre-
natal echocardiography is advisable in these cases.
Single-gene defects
Typical autosomal dominant single-gene defects associated with
congenital heart disease are listed in Table 1. Marfan’s syndrome
is causally related to fibrillin deficiency and associated with
mutations of the fibrillin gene on chromosome 15q. HolteOram
and Noonan’s syndromes have been mapped to chromosome
12q, but have considerable heterogeneity. Other autosomal le-
sions include some forms of familial hypertrophic cardiomyop-
athy, myotonic dystrophy and Alpert’s syndrome
(craniosynostosis with syndactyly, deafness, pulmonary stenosis
and/or VSD). In some families, cardiac conditions are inherited

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 CONGENITAL HEART DISEASE
Trisomy 21 (Down’s syndrome)
C Accounts for 5% of congenital heart disease
C Incidence 1/700 live births
C 40% have congenital heart disease
C 40% of these have atrioventricular septal defects
C Other lesions include VSDs (30%), ASDs (10%), Fallot’s tetralogy
(5%), PDA (5%)
Table 2
Lesions associated with 22q11 deletions
C Truncus arteriosus
C Interrupted aortic arch
C Fallot’s tetralogy
C Pulmonary atresia with VSD
C VSD
C Absent pulmonary valve syndrome
C Anomalous origin of the pulmonary artery
C Right aortic arch
C Vascular ring
C Coarctation
Table 3
as autosomal dominant traits. These include ASDs and total
anomalous pulmonary venous drainage (the latter linked to
chromosome 4).
Chromosomal defects
Trisomy 21 (Down’s syndrome; Table 2) is associated with
congenital heart disease. Most cases are caused by non-
disjunction of chromosomes, usually of maternal origin,
although translocation and mosaicism are well recognized. Other
trisomies include Edward’s (trisomy 18) and Patau’s (trisomy 13)
syndromes, both associated with VSDs, although ASDs and PDA
are also seen.
Turner’s syndrome involves deficiency of the X chromosome;
about 50% of cases are 45XO, but mosaicism and other abnor-
malities of the X chromosome are common. The phenotype is
TEST YOURSELF
To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the
end of the issue or online here.
Question 1
An 8-week-old baby was seen for a routine check. At birth, he
had been on the 75th centile for weight but was now on the
second centile. His parents reported that he was getting sweaty
and breathless with feeds.
On clinical examination, his respiratory rate was 60/minute, and
there was mild rib recession. Femoral pulses were easily
palpable, and there was a 3/6 pan-systolic murmur at the lower
left sternal edge. The liver was palpable 3 cm below the costal
margin. Oxygen saturations were 100%.
MEDICINE 46:11
variable, but short stature and gonadal dysgenesis are usually
seen. Cardiac lesions (principally coarctation of the aorta, but
also aortic stenosis) are seen in 10e20% of patients.
Deletions
It has recently been recognized that some cardiac lesions are
associated with microdeletions.
The acronym CATCH 22 (cardiac, abnormal facies, thymic
hypoplasia, cleft palate, hypocalcaemia) is used for lesions
associated with microdeletions within the q11 region of chro-
mosome 22 (e.g. DiGeorge’s syndrome, velocardiofacial syn-
drome). The typical cardiac lesion involves the outflow of the
heart or great arteries (cono-truncal), although other abnormal-
ities are occasionally seen (Table 3).
Williams’ syndrome is caused by deletions within the elastin
gene locus on chromosome 7. The typical cardiac lesion is
supravalvar aortic stenosis, often associated with peripheral
pulmonary artery stenosis. Average IQ is about 50, and the child
tends to be friendly and outgoing. Facial features include broad
lips, anteverted nares and a long philtrum. Supravalvar aortic
stenosis is sometimes familial but not associated with full Wil-
liams’ syndrome. In these cases, there is a deletion within the
elastin gene locus and inheritance is autosomal dominant. A
KEY REFERENCES
1 Rosenthal E. Coarctation of the aorta from fetus to adult: curable
condition or life long disease process? Heart 2005; 91: 1495e502.
2 National Institute for Cardiovascular Outcomes Research, http://
www.ucl.ac.uk/nicor.
3 Wessels MW, Willems P. Genetic factors in non-syndromic
congenital heart malformations. Clin Genet 2010; 78: 103e23.
FURTHER READING
Anderson RH, Baker EJ, Redington A, Rigby ML, Penny D,
Wenovsky G, eds. Paediatric cardiology. 3rd edn. Philadelphia:
Elsevier, 2009.
Lai W, Mertens L. Echocardiography in pediatric and congenital heart
disease. Oxford: Blackwell Publishing, 2009.
Park MK. Pediatric cardiology for practitioners. 5th edn. St Louis:
Mosby, 2007.
What is the most likely diagnosis?
A Aortic stenosis
B Ventricular septal defect
C Pulmonary stenosis
D Atrial septal defect
E Transposition of the great arteries
Question 2
A 5-year-old child with trisomy 21 was brought to the clinic. She
had a median sternotomy scar, and no murmur was audible on
696 Crown Copyright Ó 2018 Published by Elsevier Ltd. All rights reserved.
 CONGENITAL HEART DISEASE

auscultation. Her mother could not remember which heart con- On clinical examination, his blood pressure (right arm) was 140/
dition she had been diagnosed with. 96 mmHg. There was a soft ejection systolic murmur heard be-
tween the scapulae. The femoral pulses were much weaker than
What is the most likely heart condition that she has had? the radial pulses. Oxygen saturations were 100%.
A Patent ductus arteriosus
B Coarctation of the aorta What is the most likely diagnosis?
C Atrioventricular septal defect A Tetralogy of Fallot
D Tetralogy of Fallot B Ventricular septal defect
E Supravalvar pulmonary stenosis C Aortic stenosis
D Patent ductus arteriosus
Question 3 E Coarctation of the aorta
A 4-year-old child presented with persistent headaches.

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