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Congenital heart disease in infancy and childhood
CONGENITAL HEART DISEASE
Large defects usually present with heart failure in infancy (failure to thrive, breathlessness and a history of poor feeding). There may be only a soft murmur, because large defects result in equalization of the ventricular pressures. A diastolic flow murmur can be heard across the mitral valve when pulmonary blood flow is more than twice systemic flow. Surgical closure is indicated in those who fail to respond to medical therapy or who have pulmonary hypertension 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.
Congenital heart disease in infancy and childhood Hannah Bellsham-Revell Michael Burch
Abstract Congenital heart disease occurs in approximately 8/1000 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 complicated 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 are associated with congenital heart disease (Marfan’s, Noonan’s, Williams’), as are chromosomal disorders such as Down’s and Turner’s. DiGeorge’s syndrome (thymic aplasia, hypoparathyroidism and cono-truncal cardiac defect) and velocardiofacial syndrome (palatal abnormalities, heart defects and dysmorphic features) are associated with microdeletions within the q11 region of chromosome 22.
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 ECG typically shows right axis deviation and partial right bundle branch block, though primum defects (see below) may have a superior (left) axis. Echocardiography demonstrates the interatrial septum clearly and in children with large shunts there may 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 may 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 may require surgical closure. Ostium primum or partial atrioventricular septal defects (about 25% of ASDs) result from failure of the septum primum to reach the endocardial cushions. There are normally two atrioventricular valve orifices, but in some cases there is a common atrioventricular valve. The leftsided atrioventricular valve has three leaflets and there may 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 may 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.
Keywords Atrial septal defect; coarctation of the aorta; congenital heart disease; Fontan; paediatric cardiology; tetralogy of Fallot; transposition of the great arteries; ventricular septal defect
Neonatal data collection gives an incidence of significant congenital heart disease of 8/1000 live births. This does not include minor defects, which often present later in childhood or adult life (e.g. bicuspid aortic valves occur in 1/100 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 defect (VSD): the physical signs and symptoms depend on the size of the defect. Assessment is by echocardiography (using 3D for further definition of complex defects). Small defects are associated with a loud pansystolic murmur (reflecting a high-pressure difference between the left and right ventricle). Up to 60% close spontaneously in the first 5 years of life. If they persist, surgical closure is not usually undertaken.
Hannah Bellsham-Revell MBBS MRCPCH MD (Res) is a Specialist Registrar in Paediatric Cardiology at Great Ormond Street Hospital, London, UK. Competing interests: none declared.
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
Michael Burch FRCP FRCPCH is a Consultant Cardiologist, Head of Department of Cardiology and Director of Cardiothoracic Transplantation and Heart Failure Service, Great Ormond Street Hospital, London, UK. Competing interests: none declared.
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CONGENITAL HEART DISEASE
The most common congenital heart defects 32.1%
Ventricular septal defect 8.6%
Pulmonary stenosis
7.6% 8.3%
Persistent ductus arteriosus
11.9%
Atrial septal defect
7.4%
Coarctation of the aorta
6.7%
Aortic stenosis
a
32.5%
5.9%
6.3% 3.8% 5.1%
Fallot’s tetralogy
3.8% 5.9%
Transposition of the great arteries
2.6%
b
5.0%
These figures are taken from two classic studies. The green bars are from a USA study1 of 56,109 births; the red bars are from a UK study2 of 160,480 births. The lesions listed account for 70–80% of all congenital heart defects. Mitchell S C et al. Circulation1971; 43: 323– 32. Dickinson D F et al. Br Heart J 1981; 46: 55– 62.
Figure 1
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 may 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 may 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 (indomethacin or 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.
c SBL LML
RASL
RML
Figure 2 (a) Two-dimensional transthoracic echocardiography standard ‘four chamber’ view showing an atrioventricular septal defect; (b) Twodimensional transthoracic echocardiography short axis view of the common atrioventricular valve (c) Diagram from the short axis view (SBL, superior bridging leaflet; IBL, inferior bridging leaflet, RASL, right anterior superior leaflet; LML, left mural leaflet; RML, right mural leaflet; dotted line represents the position of the interventricular septum).
Pulmonary stenosis: this is usually valvar, but occasionally subvalvar, supravalvar or peripheral pulmonary artery stenoses are seen. On 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 due
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CONGENITAL HEART DISEASE
Figure 3 Patent ductus arteriosus on two-dimensional echocardiography with colour Doppler. Colour flow Doppler is seen entering the pulmonary artery via the duct. MPA, pulmonary artery; LPA, left pulmonary artery; RPA right pulmonary artery; PDA, patent ductus arteriosus.
to reduced pulmonary blood flow and right-to-left shunting across an atrial communication (patent foramen ovale or ASD). Mild pulmonary stenosis does not usually cause symptoms in childhood. Percutaneous balloon valvuloplasty is the treatment of choice for symptomatic patients but the pressure gradient at which intervention is indicated has not been defined. The dysplastic pulmonary valve associated with Noonan’s syndrome is often resistant to balloon dilatation.
arteries may develop from the ascending to the descending aorta and manifest as rib notching on a chest radiograph. Treatment for neonatal coarctation is by surgical repair with an end-to-end anastomosis or sometimes using the left subclavian artery for arterioplasty. Older children can undergo percutaneous balloon dilatation and stenting, but surgery may be required in some cases. Balloon dilatation is the treatment of choice for recoarctation. Long-term follow-up with monitoring of hypertension is essential, as the aortic vessels are often more stiff than those without coarctation. There may also be further narrowing or dilatation around the site of previous surgery.1
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 peak instantaneous or mean pressure gradient between the left ventricle and ascending aorta. Percutaneous balloon valvuloplasty is the usual treatment in childhood, though surgical valvotomy may also 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 patient’s own pulmonary valve, which is itself replaced by a homograft. Bicuspid aortic valves are commonly seen in the clinic and often have minimal stenosis or regurgitation but 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), though it occasionally 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
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Figure 4 Magnetic resonance imaging of coarctation of the aorta with collaterals. DAo, descending aorta; IMA, internal mammary arteries; Coll, collateral vessels; LSCA, left subclavian artery.
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CONGENITAL HEART DISEASE
Fallot’s tetralogy (Figure 5a): the features of tetralogy of Fallot are: malaligned VSD deviated under the pulmonary valve aorta over-riding the lower part of the ventricular septum pulmonary (typically sub-pulmonary) stenosis and subsequent right ventricular hypertrophy. The large VSD results in equalization of ventricular pressures (such that there is no murmur), but there is a significant gradient between the right ventricle and the pulmonary artery (associated with a 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 (resulting from right-to-left shunting across the septal defect) becomes apparent. Severe cyanosis (hypercyanotic spells) may also be due to dynamic infundibular/sub-pulmonary muscle spasm and can be relieved by increasing systemic resistance using postural manoeuvres (e.g. bringing the knees to the chest), or by administration of intravenous propranolol or noradrenaline (norepinephrine). Definitive treatment is by complete surgical correction, usually performed in infancy. Occasionally, palliation is required, particularly in neonates, by creation of a shunt between the subclavian and pulmonary arteries (BlalockeTaussigeThomas shunt) or by placement of 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 tomography (CT) or magnetic resonance imaging (MRI) may 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
Tetralogy of Fallot a
Transposition of the great arteries b
Transposition of the great arteries (Figure 5b): in which the pulmonary and systemic circulations exist in parallel rather than in series. This is incompatible with life, but most neonates survive initially 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 may 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 corrected by reconnection of the pulmonary veins to the left atrium. Although results can be good, there can be anastomotic narrowing and, in some cases, diffuse pulmonary vein hypoplasia/stenosis. 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 will usually need 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 biventricular
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Figure 5 Blue arrows mark the path of deoxygenated blood through the heart, red - deoxygenated blood and purple mixed oxygenated and deoxygenated blood. 653
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CONGENITAL HEART DISEASE
repair is impossible. Palliative procedures have enabled more of these children to live to adulthood, and they will need ongoing specialist care. When pulmonary blood flow is insufficient, initial 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. Following initial palliation, at around 6 months of age, the superior vena cava is connected to the pulmonary artery (a bidirectional Glenn shunt). The total cavopulmonary connection (‘Fontan’ circulation) (Figure 6) is completed between the ages of 3 and 5 when the inferior vena cava is baffled through the atrium or via an extra-cardiac conduit into the pulmonary artery. Older patients may have undergone the original atriopulmonary Fontan, where the right atrium was connected directly to the pulmonary artery.
development of pulmonary vascular disease (as a result of high flow/high pressure in the pulmonary circulation).
Genetics 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 prenatal echocardiography is advisable in these cases. Singleegene defects: typical autosomal dominant single-gene defects associated with congenital heart disease are listed in Table 1. Marfan’s syndrome is causally related to a deficiency of fibrillin and associated with mutations of the fibrillin gene on chromosome 15q. HolteOram and Noonan’s syndromes have been mapped to chromosome 12q, but both have considerable heterogeneity. Other autosomal lesions include some forms of familial hypertrophic cardiomyopathy, myotonic dystrophy and Alpert’s syndrome (craniosynostosis with syndactyly, deafness, pulmonary stenosis and/or VSD). In some families, cardiac conditions are inherited as autosomal dominant traits. These
Eisenmenger’s syndrome (reversal of a previous left-to-right shunt because of pulmonary vascular disease) is now less common because corrective surgery is undertaken early, avoiding the
Total cavopulmonary connection (extracardiac)
Single-gene defects and congenital heart disease Noonan’s syndrome Cardiac lesions C Hypertrophic cardiomyopathy C Pulmonary stenosis C Atrial septal defect 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
Blue arrows mark the path of deoxygenated blood through the heart and red the deoxygenated blood
HolteeOram syndrome Cardiac lesions C Atrial septal defect C Occasional ventricular septal defect Other features C Upper limb abnormalities vary from minor clinodactyly to severe reduction deformity
Figure 6 Diagram showing the completed Fontan circulation (in a patient with hypoplastic left heart syndrome). The inferior caval vein is connected via a conduit to the pulmonary arteries which are anastomosed to the superior caval vein. Pulmonary venous blood returns to the left atrium from the pulmonary veins, travels through the open atrial communication to the systemic ventricle, and then around the body through the aorta. In this patient, the coronary arteries are supplied through an anastomosis of the native aorta to the reconstructed aorta.
Table 1
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CONGENITAL HEART DISEASE
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 chromosome 22 (e.g. DiGeorge’s syndrome, velocardiofacial syndrome). The typical cardiac lesion involves the outflow of the heart or great arteries (cono-truncal) although other abnormalities 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. The 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 Williams’ syndrome. In these cases, there is a deletion within the elastin gene locus and inheritance is autosomal dominant. A
Trisomy 21 (Down’s syndrome) C C C C C
Accounts for 5% of congenital heart disease Incidence 1/700 live births 40% have congenital heart disease 40% of these have atrioventricular septal defects Other lesions include ventricular septal defects (30%), atrial septal defects (10%), Fallot’s tetralogy (5%), patent ductus arteriosus (5%)
Table 2
Lesions associated with 22q11 deletions C C C C C C C C C C
Truncus arteriosus Interrupted aortic arch Fallot’s tetralogy Pulmonary atresia with ventricular septal defect Ventricular septal defect Absent pulmonary valve syndrome Anomalous origin of the pulmonary artery Right aortic arch Vascular ring Coarctation
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, www.nicor. org.uk. 3 Wessels MW, Willems P. Genetic factors in non-syndromic congenital heart malformations. Clin Genet 2010; 78: 103e23.
Table 3
include ASDs and total anomalous pulmonary venous drainage (the latter linked to chromosome 4).
FURTHER READING Allen HD, Driscoll DJ. Moss and Adams’ heart disease in infants, children, and adolescents: including the fetus and young adult (2-volume set). Philidelphia: Lippincott Williams & Wilkins, 2008. Anderson RH, Baker EJ, Redington A, Rigby ML, Penny D, Wenovsky G, eds. Paediatric cardiology. 3rd edn. Philadelphia: Elsevier, 2009. Driscoll DJ. Fundamentals of pediatric cardiology. 1st edn. Philidelphia: Lippincott Williams & Wilkins, 2006. Eidem BW, Cetta F, eds. Echocardiography in pediatric and adult congenital heart disease. 1st edn. Philidelphia: Lippincott Williams & Wilkins, 2009. Lai W, Mertens L. Echocardiography in pediatric and congenital heart disease. 1st edn. Oxford: Blackwell Publishing, 2009. Park MK. Pediatric cardiology for practitioners. 5th edn. St Louis: Mosby, 2007.
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, though translocation and mosaicism are also well recognized. Other trisomies include Edward’s (trisomy 18) and Patau’s (trisomy 13) syndromes, which are both associated with VSDs, but 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 abnormalities of the X chromosome are also common. The phenotype is 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.
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Large defects usually present with heart failure in infancy (failure to thrive, breathlessness and a history of poor feeding). There may be only a soft murmur, because large defects result in equalization of the ventricular pressures. A diastolic flow murmur can be heard across the mitral valve when pulmonary blood flow is more than twice systemic flow. Surgical closure is indicated in those who fail to respond to medical therapy or who have pulmonary hypertension 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.
Congenital heart disease in infancy and childhood Hannah Bellsham-Revell Michael Burch
Abstract Congenital heart disease occurs in approximately 8/1000 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 complicated 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 are associated with congenital heart disease (Marfan’s, Noonan’s, Williams’), as are chromosomal disorders such as Down’s and Turner’s. DiGeorge’s syndrome (thymic aplasia, hypoparathyroidism and cono-truncal cardiac defect) and velocardiofacial syndrome (palatal abnormalities, heart defects and dysmorphic features) are associated with microdeletions within the q11 region of chromosome 22.
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 ECG typically shows right axis deviation and partial right bundle branch block, though primum defects (see below) may have a superior (left) axis. Echocardiography demonstrates the interatrial septum clearly and in children with large shunts there may 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 may 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 may require surgical closure. Ostium primum or partial atrioventricular septal defects (about 25% of ASDs) result from failure of the septum primum to reach the endocardial cushions. There are normally two atrioventricular valve orifices, but in some cases there is a common atrioventricular valve. The leftsided atrioventricular valve has three leaflets and there may 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 may 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.
Keywords Atrial septal defect; coarctation of the aorta; congenital heart disease; Fontan; paediatric cardiology; tetralogy of Fallot; transposition of the great arteries; ventricular septal defect
Neonatal data collection gives an incidence of significant congenital heart disease of 8/1000 live births. This does not include minor defects, which often present later in childhood or adult life (e.g. bicuspid aortic valves occur in 1/100 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 defect (VSD): the physical signs and symptoms depend on the size of the defect. Assessment is by echocardiography (using 3D for further definition of complex defects). Small defects are associated with a loud pansystolic murmur (reflecting a high-pressure difference between the left and right ventricle). Up to 60% close spontaneously in the first 5 years of life. If they persist, surgical closure is not usually undertaken.
Hannah Bellsham-Revell MBBS MRCPCH MD (Res) is a Specialist Registrar in Paediatric Cardiology at Great Ormond Street Hospital, London, UK. Competing interests: none declared.
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
Michael Burch FRCP FRCPCH is a Consultant Cardiologist, Head of Department of Cardiology and Director of Cardiothoracic Transplantation and Heart Failure Service, Great Ormond Street Hospital, London, UK. Competing interests: none declared.
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CONGENITAL HEART DISEASE
The most common congenital heart defects 32.1%
Ventricular septal defect 8.6%
Pulmonary stenosis
7.6% 8.3%
Persistent ductus arteriosus
11.9%
Atrial septal defect
7.4%
Coarctation of the aorta
6.7%
Aortic stenosis
a
32.5%
5.9%
6.3% 3.8% 5.1%
Fallot’s tetralogy
3.8% 5.9%
Transposition of the great arteries
2.6%
b
5.0%
These figures are taken from two classic studies. The green bars are from a USA study1 of 56,109 births; the red bars are from a UK study2 of 160,480 births. The lesions listed account for 70–80% of all congenital heart defects. Mitchell S C et al. Circulation1971; 43: 323– 32. Dickinson D F et al. Br Heart J 1981; 46: 55– 62.
Figure 1
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 may 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 may 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 (indomethacin or 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.
c SBL LML
RASL
RML
Figure 2 (a) Two-dimensional transthoracic echocardiography standard ‘four chamber’ view showing an atrioventricular septal defect; (b) Twodimensional transthoracic echocardiography short axis view of the common atrioventricular valve (c) Diagram from the short axis view (SBL, superior bridging leaflet; IBL, inferior bridging leaflet, RASL, right anterior superior leaflet; LML, left mural leaflet; RML, right mural leaflet; dotted line represents the position of the interventricular septum).
Pulmonary stenosis: this is usually valvar, but occasionally subvalvar, supravalvar or peripheral pulmonary artery stenoses are seen. On 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 due
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Figure 3 Patent ductus arteriosus on two-dimensional echocardiography with colour Doppler. Colour flow Doppler is seen entering the pulmonary artery via the duct. MPA, pulmonary artery; LPA, left pulmonary artery; RPA right pulmonary artery; PDA, patent ductus arteriosus.
to reduced pulmonary blood flow and right-to-left shunting across an atrial communication (patent foramen ovale or ASD). Mild pulmonary stenosis does not usually cause symptoms in childhood. Percutaneous balloon valvuloplasty is the treatment of choice for symptomatic patients but the pressure gradient at which intervention is indicated has not been defined. The dysplastic pulmonary valve associated with Noonan’s syndrome is often resistant to balloon dilatation.
arteries may develop from the ascending to the descending aorta and manifest as rib notching on a chest radiograph. Treatment for neonatal coarctation is by surgical repair with an end-to-end anastomosis or sometimes using the left subclavian artery for arterioplasty. Older children can undergo percutaneous balloon dilatation and stenting, but surgery may be required in some cases. Balloon dilatation is the treatment of choice for recoarctation. Long-term follow-up with monitoring of hypertension is essential, as the aortic vessels are often more stiff than those without coarctation. There may also be further narrowing or dilatation around the site of previous surgery.1
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 peak instantaneous or mean pressure gradient between the left ventricle and ascending aorta. Percutaneous balloon valvuloplasty is the usual treatment in childhood, though surgical valvotomy may also 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 patient’s own pulmonary valve, which is itself replaced by a homograft. Bicuspid aortic valves are commonly seen in the clinic and often have minimal stenosis or regurgitation but 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), though it occasionally 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
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Figure 4 Magnetic resonance imaging of coarctation of the aorta with collaterals. DAo, descending aorta; IMA, internal mammary arteries; Coll, collateral vessels; LSCA, left subclavian artery.
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CONGENITAL HEART DISEASE
Fallot’s tetralogy (Figure 5a): the features of tetralogy of Fallot are: malaligned VSD deviated under the pulmonary valve aorta over-riding the lower part of the ventricular septum pulmonary (typically sub-pulmonary) stenosis and subsequent right ventricular hypertrophy. The large VSD results in equalization of ventricular pressures (such that there is no murmur), but there is a significant gradient between the right ventricle and the pulmonary artery (associated with a 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 (resulting from right-to-left shunting across the septal defect) becomes apparent. Severe cyanosis (hypercyanotic spells) may also be due to dynamic infundibular/sub-pulmonary muscle spasm and can be relieved by increasing systemic resistance using postural manoeuvres (e.g. bringing the knees to the chest), or by administration of intravenous propranolol or noradrenaline (norepinephrine). Definitive treatment is by complete surgical correction, usually performed in infancy. Occasionally, palliation is required, particularly in neonates, by creation of a shunt between the subclavian and pulmonary arteries (BlalockeTaussigeThomas shunt) or by placement of 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 tomography (CT) or magnetic resonance imaging (MRI) may 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
Tetralogy of Fallot a
Transposition of the great arteries b
Transposition of the great arteries (Figure 5b): in which the pulmonary and systemic circulations exist in parallel rather than in series. This is incompatible with life, but most neonates survive initially 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 may 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 corrected by reconnection of the pulmonary veins to the left atrium. Although results can be good, there can be anastomotic narrowing and, in some cases, diffuse pulmonary vein hypoplasia/stenosis. 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 will usually need 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 biventricular
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Figure 5 Blue arrows mark the path of deoxygenated blood through the heart, red - deoxygenated blood and purple mixed oxygenated and deoxygenated blood. 653
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CONGENITAL HEART DISEASE
repair is impossible. Palliative procedures have enabled more of these children to live to adulthood, and they will need ongoing specialist care. When pulmonary blood flow is insufficient, initial 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. Following initial palliation, at around 6 months of age, the superior vena cava is connected to the pulmonary artery (a bidirectional Glenn shunt). The total cavopulmonary connection (‘Fontan’ circulation) (Figure 6) is completed between the ages of 3 and 5 when the inferior vena cava is baffled through the atrium or via an extra-cardiac conduit into the pulmonary artery. Older patients may have undergone the original atriopulmonary Fontan, where the right atrium was connected directly to the pulmonary artery.
development of pulmonary vascular disease (as a result of high flow/high pressure in the pulmonary circulation).
Genetics 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 prenatal echocardiography is advisable in these cases. Singleegene defects: typical autosomal dominant single-gene defects associated with congenital heart disease are listed in Table 1. Marfan’s syndrome is causally related to a deficiency of fibrillin and associated with mutations of the fibrillin gene on chromosome 15q. HolteOram and Noonan’s syndromes have been mapped to chromosome 12q, but both have considerable heterogeneity. Other autosomal lesions include some forms of familial hypertrophic cardiomyopathy, myotonic dystrophy and Alpert’s syndrome (craniosynostosis with syndactyly, deafness, pulmonary stenosis and/or VSD). In some families, cardiac conditions are inherited as autosomal dominant traits. These
Eisenmenger’s syndrome (reversal of a previous left-to-right shunt because of pulmonary vascular disease) is now less common because corrective surgery is undertaken early, avoiding the
Total cavopulmonary connection (extracardiac)
Single-gene defects and congenital heart disease Noonan’s syndrome Cardiac lesions C Hypertrophic cardiomyopathy C Pulmonary stenosis C Atrial septal defect 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
Blue arrows mark the path of deoxygenated blood through the heart and red the deoxygenated blood
HolteeOram syndrome Cardiac lesions C Atrial septal defect C Occasional ventricular septal defect Other features C Upper limb abnormalities vary from minor clinodactyly to severe reduction deformity
Figure 6 Diagram showing the completed Fontan circulation (in a patient with hypoplastic left heart syndrome). The inferior caval vein is connected via a conduit to the pulmonary arteries which are anastomosed to the superior caval vein. Pulmonary venous blood returns to the left atrium from the pulmonary veins, travels through the open atrial communication to the systemic ventricle, and then around the body through the aorta. In this patient, the coronary arteries are supplied through an anastomosis of the native aorta to the reconstructed aorta.
Table 1
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CONGENITAL HEART DISEASE
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 chromosome 22 (e.g. DiGeorge’s syndrome, velocardiofacial syndrome). The typical cardiac lesion involves the outflow of the heart or great arteries (cono-truncal) although other abnormalities 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. The 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 Williams’ syndrome. In these cases, there is a deletion within the elastin gene locus and inheritance is autosomal dominant. A
Trisomy 21 (Down’s syndrome) C C C C C
Accounts for 5% of congenital heart disease Incidence 1/700 live births 40% have congenital heart disease 40% of these have atrioventricular septal defects Other lesions include ventricular septal defects (30%), atrial septal defects (10%), Fallot’s tetralogy (5%), patent ductus arteriosus (5%)
Table 2
Lesions associated with 22q11 deletions C C C C C C C C C C
Truncus arteriosus Interrupted aortic arch Fallot’s tetralogy Pulmonary atresia with ventricular septal defect Ventricular septal defect Absent pulmonary valve syndrome Anomalous origin of the pulmonary artery Right aortic arch Vascular ring Coarctation
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, www.nicor. org.uk. 3 Wessels MW, Willems P. Genetic factors in non-syndromic congenital heart malformations. Clin Genet 2010; 78: 103e23.
Table 3
include ASDs and total anomalous pulmonary venous drainage (the latter linked to chromosome 4).
FURTHER READING Allen HD, Driscoll DJ. Moss and Adams’ heart disease in infants, children, and adolescents: including the fetus and young adult (2-volume set). Philidelphia: Lippincott Williams & Wilkins, 2008. Anderson RH, Baker EJ, Redington A, Rigby ML, Penny D, Wenovsky G, eds. Paediatric cardiology. 3rd edn. Philadelphia: Elsevier, 2009. Driscoll DJ. Fundamentals of pediatric cardiology. 1st edn. Philidelphia: Lippincott Williams & Wilkins, 2006. Eidem BW, Cetta F, eds. Echocardiography in pediatric and adult congenital heart disease. 1st edn. Philidelphia: Lippincott Williams & Wilkins, 2009. Lai W, Mertens L. Echocardiography in pediatric and congenital heart disease. 1st edn. Oxford: Blackwell Publishing, 2009. Park MK. Pediatric cardiology for practitioners. 5th edn. St Louis: Mosby, 2007.
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, though translocation and mosaicism are also well recognized. Other trisomies include Edward’s (trisomy 18) and Patau’s (trisomy 13) syndromes, which are both associated with VSDs, but 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 abnormalities of the X chromosome are also common. The phenotype is 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.
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