Abstract
This chapter, the first of two devoted to congenital heart disease, deals with the commoner forms including ventricular septal defect, atrioventricular septal defect, tetralogy of Fallot and hypoplastic left heart. The pathological features are described in detail and profusely illustrated, including images of the histopathology, where relevant.
4.1 Introduction
Although the term congenital heart disease is used synonymously with structural congenital heart disease, it should be borne in mind that other forms of heart disease lacking structural defects can also develop in utero and be present at birth: cardiomyopathy, rhythm disorders and myocardial infarction. These will be dealt with separately in subsequent chapters. Increasingly, structural heart disease is being identified in utero by ultrasonography and attempts have been made at in utero intervention. This subject is covered at more length in the chapter on heart disease in the fetus. But by no means is all congenital heart disease identified in utero. Presentation may be at any time in childhood, although the more severe forms present in the first days of life. Hypoplastic left heart, transposition and obstructed total anomalous pulmonary venous connection constitute medical emergencies in the neonate. Most forms of congenital heart disease are amenable to surgical correction or palliation. Operative mortality is low and children with simple defects can expect to live as long as their contemporaries [1]. However, children with more complex congenital heart disease are surviving in ever greater numbers into adulthood where they present a particular set of problems.
The majority of cases of congenital heart disease involve anomalous positioning of the cardiac outflow tracts, impaired remodelling of the endocardial cushions into valve leaflets or abnormal remodelling of the aortic arches into great vessels. There are eight common lesions that together account for about 80% of all cases of structural congenital heart disease [2]. They are listed in Table 4.1. The pathology of these defects will now be discussed in detail.
4.2 Ventricular Septal Defect (VSD)
Closure of a VSD is the commonest surgical procedure for congenital heart disease in children in England, accounting for nearly one-quarter of all such operations [3].
As its name implies, a VSD is a defect in the interventricular septum, permitting direct flow of blood between the two ventricular cavities. Its clinical effect depends on its size and the presence of associated lesions. The defects are usually round or oval, and vary in size from a few millimetres to several centimetres [4]. There may be multiple defects. A VSD forms an integral part of many complex cardiac defects such as common arterial trunk, atrioventricular septal defect and tetralogy of Fallot. VSDs may also occur as an isolated lesion and such defects account for about half of the cases reported in surgical series.
Two basic forms are described depending on their relation to the membranous interventricular septum: those involving the membranous septum, the so-called perimembranous VSD (Figure 4.1), and those in which muscle is interposed between the defect and the membranous septum, the so-called muscular VSD (Figure 4.2). Because the septal attachment of the tricuspid valve crosses the membranous septum and the mitral valve attachment on the left side is also related to the membranous septum, a perimembranous defect will, by definition, have fibrous continuity between the tricuspid and mitral valves through the defect (Figure 4.3). Muscular VSDs may occur in any part of the interventricular septum and may be multiple. Because of associated ventricular hypertrophy, those occurring in the lower parts of the septum can be easily missed, even on close inspection of the heart, being hidden among the hypertrophied muscular trabeculations. Perimembranous and muscular VSDs can, and sometimes do, coexist in the same heart. The significance of the distinction of perimembranous and muscular VSDs lies in the intimate and superficial relation of the atrioventricular conduction tissue to the perimembranous VSD and its susceptibility to damage during surgical closure of the defect. It also has implications for its relation to the atrioventricular and arterial valves.
Figure 4.1 Perimembranous VSD. A neonate with trisomy 21 who died shortly after birth. The left ventricle is viewed from the left and the mitral valve has been divided to display the left ventricular outflow tract. There is a large VSD beneath the aortic valve impinging on the membranous septum (which lies between the right and non-coronary cusps of the aortic valve). The right coronary cusp is the cusp viewed en face in this view. Chordal tissue of the tricuspid valve is visible through the defect.
(A) Two-week-old male infant. In the centre of the interventricular septum (viewed from the left side) there is a large oval muscular VSD.
(B) Viewed from the right side, the defect lies inferior to the septomarginal trabeculation at the junction of the inlet and apical parts of the septum.
Figure 4.2 Muscular VSD.
Figure 4.3 Fibrous continuity of mitral and tricuspid valves through a perimembranous VSD. Termination of pregnancy at 22 weeks’ gestation. At post-mortem: situs inversus (atrial, pulmonary, abdominal) with congenitally corrected transposition and VSD with pulmonary stenosis. There are associated bilateral superior caval veins and retro-oesophageal subclavian artery. The right atrium is connected to the left ventricle. There is a large, central, oval perimembranous VSD through which the mitral valve leaflets are seen to be in continuity with the tricuspid valve.
VSDs may lie in the inlet, outlet or apical trabecular part of the ventricular septum when viewed from the right ventricle – the side most often approached by the surgeon at the time of surgical repair (Figure 4.4). It is important to recall that because the left ventricular outflow tract is wedged between the mitral and aortic valves, the inlet, outlet and apical components on the right side do not match exactly those on the left. Indeed, the right ventricular inlet is separated by the interventricular septum largely from the left ventricular outlet, and this can cause difficulty in ascribing a VSD to one of these components. VSDs may also be closely related to the arterial valves. Thus, the defects can be labelled inlet VSD, outlet VSD or subarterial VSD. A large perimembranous VSD extending into more than one component of the septum is termed a confluent VSD. Outlet perimembranous VSDs are usually associated with malalignment of the outlet septum [5]. Malalignment of the outlet septum occurs when the plane of the outlet septum, as seen in the cardiac short axis, is out of alignment with the rest of the muscular ventricular septum. Malalignment of the outlet septum can be present with perimembranous, muscular or doubly committed and juxta-arterial defects [6].
(A) A normal heart viewed from the right side following removal of the parietal walls of the right atrium and right ventricle.
(B) Cartoon of the specimen showing divisions of the septum into inlet (orange), apical trabecular (green) and outlet (yellow) parts. The septomarginal trabeculation forms the boundary between inlet and outlet. The membranous septum is shown in Figure 4.4 B the membranous septum appears to be a yellow circle rather than red. SVC, superior caval vein; TSM, septomarginal trabeculation; TV, tricuspid valve; IVC, inferior caval vein; SVC, supraventricular crest.
A VSD occurring in the right ventricular outflow tract may permit fibrous continuity between the aortic and pulmonary valves. Such defects (which may be either muscular or perimembranous) are said to be doubly committed and juxta-arterial [7].
In the setting of a double outlet ventricle the outflow from the smaller ventricle will be dependent on the size of the VSD, and, if too small, the VSD is said to be restrictive. Small perimembranous VSDs are usually better appreciated by the pathologist from the left ventricular outflow tract; on the right side they may be obscured by the chordal and leaflet tissue of the tricuspid valve.
Unless there is restricted outflow through the pulmonary valve, blood will tend to flow through the VSD from left to right ventricle because of the pressure gradient between the two, and the right ventricle will suffer volume overload. Ventricular septal defects, if small, may close spontaneously by fibrosis (Figure 4.5) [8], but tissue tags associated with VSDs may cause subvalvar obstruction. VSDs are also a site of predilection for infective endocarditis (Figure 4.6).
(A) Four-year-old girl with trisomy 21 known to have had a perimembranous VSD that closed. The opened left ventricular outflow tract shows a mass of opaque fibrous tissue surrounding the membranous septum beneath the aortic valve at the site of the closed defect. Some endocardial fibrosis extends over the septum forming a mirror image of the anterior leaflet of the mitral valve.
(B) A 13-year-old with known muscular VSD with spontaneous closure. A trabecular muscular VSD that has closed by fibrosis. A fibrous scar extends through the full thickness of the septum and is associated with fibrous tissue tags on the right ventricular aspect.
Figure 4.5 Spontaneous closure of a VSD.
(A) Histological section through the interventricular septum in a child with a muscular VSD. The aortic outflow is to the left of the picture with the aortic valve at the top. There is endocardial fibrous thickening around the edges of the defect, and on the right ventricular aspect there are fibrinous vegetations. The blue haze seen extending into the lower right ventricular endocardium is caused by inflammatory cell infiltration.
(B) A four-year-old girl who died of the effects of sepsis associated with bacterial endocarditis around a restrictive perimembranous VSD. There is dense endocardial thickening and puckering around the margins of the small VSD. Vegetations were not seen at post-mortem but they had previously been seen on echocardiography, and there had been a prolonged course of antibiotics.
Figure 4.6 Infective endocarditis VSD.
The principles of closure of VSD are to achieve secure unobstructed separation of the systemic and pulmonary circulations avoiding damage to the conduction system and valves [9]. Small muscular VSDs are usually closed by pledgeted mattress sutures, but larger muscular VSD and perimembranous VSDs are patched with Gore-Tex, Dacron or pericardium. This is usually achieved via an atriotomy incision, but sometimes a ventriculotomy is required. Increasingly, they are being closed by endovascular devices (Figure 4.7) [10].
Examination of the heart with a patched VSD shows the patch usually attached to the right-handed side of the interventricular septum (Figure 4.8). Viewed from the left side this usually results in a recess at the site of the VSD (Figure 4.9). With time the patch and its accompanying pledgeted sutures becomes covered with a thick layer of fibroelastic tissue. It is unusual for the patch to calcify. Histologically a foreign body reaction is present at the margins of the patch with fibrosis in the surrounding myocardium (Figure 4.10). There may be small residual defects that the patch has not completely covered (Figure 4.11) or, rarely, there may be break down of part of the suture line (Figure 4.12). Very rarely, infective endocarditis develops.
Figure 4.8 Patched VSD right side. One-year-old girl with patched perimembranous VSD. The right ventricular outflow tract has been opened and the parietal wall retracted to expose the right side of the interventricular septum. A rounded patch with overlying endocardial fibrosis is visible between the tricuspid and pulmonary valves and abutting the membranous septum. The outlines of some of the sutures are still visible. The operation site is intact.
Figure 4.9 Patched VSD left side. The left ventricular outflow tract is exposed in a heart with a patched perimembranous VSD. The defect is visible as an oval dark area beneath the aortic valve cusps. It is sealed by a patch applied to the right side of the septum leaving a shelf-like residual recess.
Figure 4.10 Patched VSD histology. A histological section through a patched VSD. The patch material is pericardium. It shows dark pink staining because of its content of collagen, but because of pretreatment, it is completely acellular. At the right of the field it is slightly folded back on itself. Adjacent to this, some myocardium is visible. Multiple rounded holes are visible that represent sutures. This material does not cut well and must be removed before sectioning. At the left upper side of the picture there is a felt buttress, and it has elicited a foreign body inflammatory response. There is dense fibrous thickening of the endocardium over both sides of the patch, more so on the lower part of the picture.
Figure 4.11 Residual defect after repair of a VSD. Ten-year-old with patched doubly committed VSD. The defect was patched some years before death. The picture shows the left ventricular outflow tract. The patch is visible as a concave depression beneath the aortic valve. A rounded, small, residual defect is visible at the superior margin of the patch with some irregularity of the endocardium around it.
Figure 4.12 Patched VSD dehiscence. Two-year-old with repair of tetralogy of Fallot. Death during a respiratory illness. The heart is cut in a simulated long axis view. The left ventricle is globular and dilated. Immediately beneath the aortic valve there is a patch. The patch has come away from the tissues at its upper border, and a large defect is now present.
4.3 Atrioventricular Septal Defect (AVSD)
The basic abnormality in this defect is a common atrioventricular junction. This is in contrast to the separate right and left atrioventricular junctions present in the normal heart (Figure 4.13A) [11]. The common junction is guarded by a common valve (Figure 4.13B), but separate valvar orifices may be present. Because of the common junction, the aorta is displaced from its normal position (where it is wedged between the separate left and right atrioventricular junctions) to lie anterior to the common atrioventricular junction (Figure 4.14). The inferior aspect of the interatrial septum is not connected to the ventricular septum and is a free-standing structure, usually with a concave aspect; the upper border of the interventricular septum lies below the level of the atrioventricular junction and also has a concave aspect giving a so-called scooped-out appearance (Figure 4.15). The common valve has five leaflets: superior and inferior bridging leaflets that cross (bridge) the interventricular septum and that have papillary muscle attachments in both ventricles; on the left side there is a mural leaflet that is smaller than its normally occurring counterpart, and on the right, anterior and inferior leaflets (Figure 4.16). In practice, distinguishing the leaflets is not always straightforward. The valvar tissue may be dysplastic and valvar regurgitation is common.
(A) A dissection of the heart to display the normal atrioventricular junctions. Much of the atrial walls and the atrial appendages have been removed. The two atrioventricular valves – the tricuspid on the right of the picture and the mitral on the left – have separate junctions with the ventricular mass. The long axes of the tricuspid and mitral valves are at almost 90 degrees to each other, forming a “V” into the fork of which the aortic valve sits snugly.
(B) A heart with complete AVSD dissected to display the common atrioventricular junction and common atrioventricular valve. The atria have been removed and the heart is viewed from above. The leaflets of the common atrioventricular valve bridge over the septum. The crest of the interventricular septum is visible on the right-hand side of the field, and most of the ventricular cavity visible is that of the left ventricle.
Figure 4.13 Atrioventricular junction in normal heart and AVSD.
Figure 4.14 AVSD with common junction and unwedging of aorta. The base of the heart viewed from above in a case of complete AVSD. The aorta is displaced anteriorly from its usual position between the atrioventricular valves. It now lies almost side by side with the pulmonary trunk.
(A) The right atrium is above, the right ventricle below and the pulmonary valve anterosuperiorly. The arched lower border of the interatrial septum forms the superior margin of the AVSD. The lower margin is formed by the “scooped-out” crest to the atrioventricular septum that lies well below the plane of the atrioventricular junction. Superior (anterior) and inferior(posterior) bridging leaflets cross the crest of the interventricular septum from the right ventricle to the left ventricle.
(B) Viewed from the left side, the lower border of the interatrial septum and crest of the interventricular septum are again clearly visible as are the bridging leaflets. The left ventricular outflow tract is displaced forward anterior to the superior bridging leaflet.
Figure 4.15 AVSD. A heart with complete atrioventricular septal defect dissected to show the septal structures and viewed from the right side (A) and from the left side (B).
Figure 4.16 Bridging leaflets of AVSD. Heart with AVSD cut in a simulated four-chamber view and viewed from anteriorly. The AVSD lies between the lower border of the interatrial septum and the crest of the interventricular septum. The superior bridging leaflet is firmly attached to the crest of the interventricular septum. The superior and inferior bridging leaflets are separate and do not show connecting tissue; the crest of the septum can be seen in the gap between them.
The attachment of the superior bridging leaflet in the right ventricle is variable, ranging from attachment just to the right of the interventricular septum to attachment well within the right ventricle. This variability gives rise to the Rastelli classification of this defect [12]. Where the bridging leaflets float freely, being attached only at the atrioventricular junction and having no attachment to either interatrial or interventricular septum, or to each other, the defect is called a complete AVSD. In complete AVSD there is free communication of blood between both ventricles beneath the AV valve leaflets and between both atria above them (Figure 4.17). Where there is attachment of the bridging leaflet tissue to the crest of the interventricular septum or where a tongue of leaflet tissue joins the two leaflets over the interventricular septum, there is some restriction in the mixing of blood at the ventricular level and the defect is called a partial AVSD (Figure 4.18). Where the bridging leaflets are attached to the crest of the interventricular septum so as to obliterate the interventricular communication, the defect becomes, in effect, an interatrial communication and is the so-called ostium primum atrial septal defect. That the ostium primum defect is, in reality, an atrioventricular septal defect is reflected in the features it shares with other forms of AVSD – the common AV junction (despite separate orifices), the unwedged aorta, the scooped-out interventricular septal crest and the vestige of the fused bridging leaflets in the misnamed “cleft” anterior leaflet of the mitral valve (Figure 4.19A). Cases also exist where the bridging leaflets are attached to the crest of the interatrial septum so as to obliterate the interatrial communication, and leave only an interventricular communication (Figure 4.19B). The defect is recognised as an AVSD by the same features as an ostium primum defect is recognised as an AVSD.
Figure 4.17 Complete AVSD. The heart is viewed from the left side. The inferior bridging leaflet lies posteriorly and the superior bridging leaflet anteriorly. The superior bridging leaflet rides high above the crest of the interventricular septum and does not show attachments to it, thus leaving a wide interventricular communication beneath the valvar tissue. There is a large interatrial communication evident beneath the interatrial septum.
Figure 4.18 Partial AVSD. Heart cut in a simulated four-chamber view. The inferior bridging leaflet is attached by multiple fibrous cords to the crest of the interventricular septum leaving very little interventricular communication beneath the valve.
(A) Ostium primum AVSD. Six-week old-male infant with ostium primum AVSD. The heart has been opened along the lateral aspect of the left atrium and ventricle and splayed to display the left side of the septal structures. There was a secundum atrial septal defect that is obscured by the atrial wall in this picture. The ostium primum defect is the large oval defect towards the middle of the field. In common with AVSD it lies beneath the lower border of the interatrial septum, the crest of the interventricular septum is scooped-out and the left atrioventricular valve displays fused superior and inferior bridging leaflets. The atrioventricular valve leaflets are firmly attached to the interventricular septum, and the only connection between the right and left sides of the heart is above the valve leaflets.
(B) AVSD without interatrial communication. Heart cut in a simulated four-chamber view. There is situs inversus, and the heart is viewed from posteriorly. There is a large secundum ASD. There are separate atrioventricular orifices with the valvar tissue attached to the lower border of the interatrial septum. The interventricular septum is scooped-out with a large interventricular communication with bridging of the valve leaflets.
In AVSD the relative sizes of both ventricles can vary, and there is often disproportion [13], and at the extreme end of this spectrum one can see a double inlet ventricle (Figure 4.20). AVSD can coexist with other forms of congenital heart disease, such as arterial valve obstruction or tetralogy of Fallot (Figure 4.21) [14]. AVSD is an almost universal finding in cases of right atrial isomerism and in about half of the cases of left atrial isomerism. AVSD is the characteristic cardiac defect occurring with trisomy 21. Because of the anterior displacement of the aorta in this defect, if the superior bridging leaflet is attached to the crest of the interventricular septum then the aortic outflow tract is lengthened and narrowed. While of itself not causing significant obstruction, it takes little additional obstruction, for example by valvar tissue tags, to cause clinical symptoms.
(A) AVSD and double inlet left ventricle. Four-chamber view of a heart with complete AVSD. There is disproportion in the size of the ventricles with the interventricular septum displaced to the right and the right ventricle being small. As a consequence, it can be seen that most of the right atrial connection is with the left ventricle rather than the right – double inlet left ventricle.
(B) In this heart the situation is more extreme
Figure 4.21 AVSD and tetralogy of Fallot. This is the same heart as in Figure 4.17 but viewed from the right side. In addition to the AVSD, there is anomalous anterior insertion of the supraventricular crest giving muscular subpulmonary stenosis, the characteristic morphology of tetralogy of Fallot.
Because the structures of the membranous septum are deficient or absent, the atrioventricular conduction tissue is abnormally sited. The AV node, instead of being located in the usual site of the triangle of Koch, is located more inferiorly in the so-called nodal triangle whose borders are the atrioventricular junction, the mouth of the coronary sinus and the postero-inferior leading edge of the atrial septum [15]. The bundle of His is unusually long, and travels on the crest of the interventricular septum before dividing.
Presentation of AVSD is with cardiac failure. It presents in the first few weeks of life rather than the first days of life. Heart failure is exacerbated in the presence of coarctation, patent arterial duct, ventricular disproportion or valvar regurgitation. Cyanosis is usually not evident. The defect is treated by early operation with a one- or two-patch repair, with or without repair of the left side component of the AV valve (Figure 4.22) [16]. The operation accounts for approximately 9% of all cases of congenital heart disease surgery in children [3]. It may be necessary to replace the left-sided atrioventricular valve. In untreated cases, unless there is associated pulmonary stenosis, pulmonary hypertension develops rapidly, and plexiform lesions may be evident within the first year of life [17].
(A) The heart is viewed from the right side following removal of the free walls of the right atrium and ventricle. There is puckering of the attachment of the atrioventricular valve to the atrioventricular junction. Suture lines for patches in the atrium and ventricle on either side of the valve are evident. The right ventricular wall shows mild thickening, and its endocardium is more fibrous than normal. A suture is also visible in the rim of the oval fossa, and a stent is also present in the fossa.
(B) This heart is cut in a simulated four-chamber view. The cut edges of the two patches are visible with overlying fibrosis. It can be appreciated that both patches have been applied from the right side. There is now offsetting of the two atrioventricular valves.
(C) Ostium primum patch viewed from the right atrium. The patch lies just above the atrioventricular valve and is away from the oval fossa.
Examination of a repaired case of AVSD will show patching of the defect and suturing of the two septal components of the left atrioventricular valve. The patches are Dacron or pericardium and are amenable to histological examination. As with simple VSD, there is a foreign body reaction around the edges of the patch and growth of fibroelastic tissue over the right and left sides of it (Figure 4.23).
(A) Two-patch repair of complete AVSD. This section extends from the lower border of the interatrial septum (top right corner) to the crest of the interventricular septum (bottom left) and is stained with EvG. The interatrial component of the patch is of pericardium and is the bright red line extending from the interatrial septum to the atrioventricular valvar tissue. The ventricular component is of Dacron and is considerably smaller, and its upper border shows a fold at its upper margin. Note the considerable deposition of fibroelastic tissue over both patches. The operation was approximately 12 months before death.
(B) Patch repair of primum AVSD. The interatrial septum is above and the interventricular septum below. Note both atrioventricular valves are connected to the crest of the septum. The patch is applied to the right side of the defect. Death occurred shortly after operation, and there is no deposition of fibrous tissue over the patch.
Figure 4.23 Histological section of repaired AVSD.
Very rarely there may be a small defect of the atrioventricular membranous septum without a common atrioventricular junction, the so-called Gerbode defect. In this defect there is a small communication between the left ventricular outflow tract and the right atrium through (Figure 4.24) deficiency of the atrioventricular septum [18]. It may be congenital but may also be acquired following catheter intervention, endocarditis or myocardial infarction.
(A) The membranous septum between the right and non-coronary cusps of the aortic valve is large and bulges to the right with ragged margins .
4.4 Atrial Septal Defect (ASD)
Most abnormal communications between the two atria occur at the site of the oval fossa. In about 10–20% of the general population there is probe patency of the interatrial septum at the anterosuperior part of the oval fossa [19, 20]. It is sometimes referred to as persistent foramen ovale. These individuals have a normal sized flap valve that is attached to the left side of the interatrial septum (Figure 4.25). Because under normal conditions the pressure of blood in the left atrium is higher than that in the right, the flap is pushed against the atrial septum and the potential communication remains closed.
Deficiency of the flap valve of the oval fossa, usually in the anterosuperior aspect of the flap, is responsible for true ASDs (Figure 4.26A). Such defects are, by definition, ASDs of secundum type. Any ASD occurring outwith the oval fossa cannot be of secundum type. Secundum ASD is one of the commonest types of congenital heart disease [21] and accounts for 42% of heart defects in cases of trisomy 21 [22]. The defects may involve, when extreme, the entire oval fossa or merely a tiny part. The defect may be fenestrated with multiple small holes within the flap valve (Figure 4.26B). There may be slight surrounding endocardial fibroelastosis but usually no other consequence.
(A) The interatrial septum is viewed from the right atrium. The oval fossa is visible, and the flap valve is deficient superiorly giving an interatrial communication –ASD of secundum type. Inferiorly the eustachian valve separates the oval fossa from the coronary sinus.
(B) Oval fossa viewed from the right atrium in term neonate with common arterial trunk. The flap valve bulges into the right atrium. It shows multiple rounded fenestrations of variable size.
The other types of ASD, with the exception of the ostium primum defect – which in reality is a form of AVSD (discussed above under AVSD) – are very rare: the coronary sinus defect [23] and the so-called sinus venosus defect [24] (Figure 4.27), which is usually associated with anomalous drainage of the right pulmonary veins through the defect into the right atrium and which accounts for 4–11% of ASDs [25].
Figure 4.27 Sinus venosus ASD. The septal structures of the heart viewed from the right side. A pulmonary artery band is in situ. The interatrial septum shows deficiency posteriorly, and the venous return from the right lung enters the right atrium astride the septum (forceps).
ASD may, of course, occur in combination with any other cardiac defect and in some is essential for the continued wellbeing of the child. For example, in complete transposition of the great arteries with intact ventricular septum, if an ASD is not present, one has to be created artificially to permit mixing of both pulmonary and systemic circulations and ensure survival (Figure 4.28).
Figure 4.28 Atrial septostomy. A ten-year-old with myocarditis who underwent balloon atrial septostomy as part of extracorporeal life support. The left side of the atrial septum shows an irregular orifice with ragged margins.
Symptoms of isolated ASD in childhood are not usual, and even with large defects it is generally not until the third decade that symptoms begin to occur. Similarly, in isolated secundum ASD pulmonary arterial hypertension is very rare in childhood. If pulmonary arterial hypertension is present in a child with isolated ASD then complicating factors such as trisomy 21, where abnormal lung developments and upper airway obstruction may contribute [26], should be sought.
The ASD may close spontaneously, with almost two-thirds showing closure or reduction in size over time, the major factor predicting closure being the initial size [27]. Elective closure either by surgery or transcatheter device is usually undertaken at age 4–6 years (Figure 4.29) [21].
Figure 4.29 Patched secundum ASD. An infant with trisomy 21 who underwent closure of a secundum ASD with autologous pericardial patch at age two months and who died suddenly six months later. A section through the interatrial septum and upper interventricular septum stained with EvG. The patch has been applied from the right atrial aspect (left side of field). Note the thick layer of elastic tissue on both atrial aspects of the patch.
Inherited ASD associated with conduction disturbance and NKX2–5 mutations is associated with an increased risk of sudden death [28].
4.5 Abnormalities of the Arterial Duct
The arterial duct is a muscular artery interposed between the two elastic arteries (aorta and pulmonary trunk) [29]. It runs from the postero-superior aspect of the junction of the pulmonary trunk with the left pulmonary artery, upwards and slightly laterally and inserts into the medial aspect of the aorta just distal to and opposite the left subclavian artery (Figure 1.40). It develops from the embryonic sixth aortic arch.
Variations in anatomy occur normally; some ducts are long and others short. There is also some variation in the angle of entry of the duct into the aorta, and some authors consider this of importance in ductal closure [30]. In the fetus the angle of entry of the duct to the aorta is acute but subsequent post-natal growth of the aorta converts the angle to nearly a right angle (Figure 1.41). In the presence of a right-sided aortic arch the duct usually remains on the left side, taking origin from the left subclavian artery or the innominate artery.
4.5.1 Absence of the Arterial Duct
In tetralogy of Fallot there is absence of the duct in approximately one-fifth of cases (Figure 4.30). Truncus arteriosus usually lacks an arterial duct. Cases of pulmonary atresia with VSD and major aortopulmonary collateral arteries also lack an arterial duct. Bilateral arterial ducts may also occur in some forms of interrupted aortic arch or with isolated left pulmonary artery.
4.5.2 Normal Closure
Having in the normal course of events become redundant at birth, the arterial duct closes by muscular contraction in the first 24 hours of extrauterine life; this is manifest as shortening and thickening of the duct. This approximates the intimal cushions that form in late fetal life, enhancing the closure and causes ischaemia of the muscle of the duct leading to fibrosis of the media. Over the following weeks permanent closure is achieved by mural fibrosis, and the duct is converted into a thick fibrous cord – the ligamentum arteriosum – that frequently calcifies [29]. Closure is usually complete by 3–4 weeks of age.
4.5.3 Premature Closure in Utero
This is rare and may be associated with in utero right heart failure, fetal distress, hydrops or intrauterine death (31, 32). The duct is contracted and may still be probe patent. The presence of thrombosis assists greatly in making the diagnosis. Maternal ingestion of non-steroidal anti-inflammatory drugs is reported in some cases [33].
4.5.4 Persistent Patency of the Duct
The duct remains functionally patent for the first few days of life in most premature infants [34]. Administration of indomethacin – an inhibitor of prostaglandin synthesis – causes closure of the duct in most, but not all, cases, and a closed duct may reopen by poorly understood mechanisms [31]. Persistent patency of the duct is associated with the development of chronic lung disease in premature infants [35].
Persistent patency of the duct occurs in association with various forms of structural heart disease, its patency in some being essential to life. In the hybrid procedure for hypoplastic left heart the arterial duct is stented to maintain its patency (Figure 4.31). Patent duct and peripheral pulmonary artery stenosis are the commonest cardiac manifestation of maternal rubella infection.
Figure 4.31 Stented arterial duct. The child had hypoplastic left heart and underwent a hybrid procedure with banding of the branch pulmonary arteries and stenting of the arterial duct. The opened duct shows the wire stent in situ, partly endothelialised and incorporated into the intima of the vessel.
The duct may be long or short. The pulmonary artery is wide and the aorta distal to the duct may be of larger diameter than the aortic isthmus proximal to the entry of the duct.
In the premature infant treatment is medical, with surgery reserved for those in whom medical treatment is not possible or fails. Surgical closure is either by thoracotomy or video-assisted thorascopic surgery (Figure 4.32). In the non-premature infant catheter closure is the treatment of choice (Figure 4.33) [36]. In the non-premature infant surgical closure is associated with fewer re-interventions as compared to catheter closure, albeit outcomes are similar [37].
Figure 4.32 Ligated arterial duct. A two-week-old child with AVSD and coarctation who underwent coarctation repair and banding of the pulmonary artery. The pulmonary artery band is visible as a broad loop around the pulmonary trunk tied with a green suture. There is blue Prolene suturing evident in the adventitia of the descending aorta. The arterial duct shows a metal clip and abundant black suture material.
A persistently patent arterial duct is at risk of development of infective endocarditis.
4.5.5 Aneurysm of the Duct
Symptomatic aneurysmal dilatation of the arterial duct is a rare occurrence that may be detected antenatally or postnatally. The antenatally detected cases develop in the third trimester and postnatally, most cases are detected in the first two months of life [38]. Most cases are asymptomatic and resolve spontaneously and the true incidence may thus be commoner than reported. Cases have been associated with Marfan’s syndrome, Ehlers–Danlos syndrome, Smith–Lemi–Opitz syndrome, and trisomy 21 and 13 [38]. The size of the aneurysm varies with most cases being in the order of 0.8–2.4 cm in maximum diameter. Histologically, the findings are variable. Absence of intimal cushions in some cases and disorganisation of the medial elastic tissue in others have been reported [38]. A minority of cases may show luminal thrombus (Figure 4.34) and tears in the intima, or infection [39, 40]. Rupture with fatal tamponade may occur. A case of transient vocal cord paralysis by compression of the recurrent laryngeal nerve has been described [41].
4.6 Coarctation of the Aorta
Coarctation is a narrowing of the aorta, usually at the site of insertion of the arterial duct. The narrowing may be discrete or it may be accompanied by tubular hypoplasia of the aorta [42]. The normal aortic isthmus (that segment of the aortic arch between the left subclavian artery and the arterial duct) is normally narrower than the remainder of the aorta and may remain so well into post-natal life [43], particularly in the situation of prematurity and a persistent patent arterial duct. It is important not to mistake this normal appearance for tubular hypoplasia.
The discrete lesion of coarctation is usually evident externally as a notch in the aortic arch wall (Figure 4.35), most prominently on its convex aspect opposite the ductal insertion; internally there is a shelf of tissue protruding into the lumen from the side of aortic wall opposite the site of insertion of the arterial duct. A degree of post-stenotic dilatation may be visible, but in infants it is usually not marked (Figure 4.36).
Figure 4.36 Coarctation of the aorta. The same specimen as in Figure 4.35 opened to show the discrete narrowing of the aortic lumen distal to the ductal insertion. The duct was closed.
Coarctation of the aorta may occur as an isolated lesion, or it may accompany other cardiovascular malformations, most notably VSD and left-sided obstructive lesions [44]. It is particularly common in Turner’s syndrome [45].
Histologically, a sling of ductal tissue extends around the aortic wall causing the narrowing. This is confirmed on phase contrast tomography [46]. Secondary intimal fibrous proliferation further narrows the lumen (Figure 4.37) [47]. Following resection of the affected segment, re-coarctation may occur if sufficient ductal tissue is left in the aortic wall [48].
Figure 4.37 Coarctation of the aorta. Histological section of excised coarctation stained with EvG. The discrete fibroelastic shelf is readily appreciated. There is secondary intimal fibroelastic thickening associated with the narrowed area.
Those with severe coarctation present in the first weeks of life with evidence of cardiac failure. They may present as a dilated cardiomyopathy beyond the first year of life [49].
4.7 Pulmonary Stenosis and Atresia, Including Tetralogy of Fallot
Congenital atresia of the pulmonary valve may occur with an intact interventricular septum or may be coupled with a VSD. The two entities are distinct clinically and have distinct pathological associations. There may be severe stenosis of the pulmonary valve instead of atresia, and, indeed, there is evidence from serial ultrasound scanning in utero that at least some cases of pulmonary atresia develop from pulmonary stenosis [50].
4.7.1 Pulmonary Atresia with Intact Interventricular Septum
This lesion usually occurs as part of more complex malformations. As an isolated lesion, it is uncommon (1–4% cases of congenital heart disease) [51]. It almost always occurs with concordant atrioventricular and ventriculoarterial connections. Pathologically, it is characterised by patency of the oval foramen and of the arterial duct. The right atrium is dilated; the larger the right ventricle, the more dilated the right atrium. The right ventricle is usually small with a hypertrophied wall, but in those cases in which the tricuspid valve is not competent, the right ventricle may be of normal size. The degree of ventricular hypertrophy may be so great as to obliterate the outlet and apical trabecular components of the right ventricle, leaving only an inlet component (Figure 4.38). The tricuspid valve is small, and there is associated Ebstein’s malformation in about 10% of cases. The tricuspid valve may even be absent. In those cases of unguarded tricuspid orifice and Ebstein’s malformation the right ventricle tends to be dilated (Figure 4.39). The pulmonary trunk is small but may be of normal size (it is rarely atretic), and the valve annulus is narrow. The pulmonary valve is imperforate, being convex towards the pulmonary trunk and showing three ridges radiating from a central fibrous button (Figure 4.40). The branch pulmonary arteries are thin-walled. The left ventricle is also hypertrophied. The ascending aorta is wide, and the normal narrowing of the isthmus is absent. The arterial duct is narrow and arises from the descending aorta with an acute inferior angle.
Figure 4.38 Pulmonary atresia with intact septum. The heart has been cut in a simulated four-chamber view. The right ventricle is small, not extending to the apex, but it is thick-walled and the cavity is almost obliterated. The right atrioventricular valve is patent but is much smaller than that on the left side. Thickened coronary arteries are visible over the epicardial surface of the right ventricle.
Figure 4.39 Pulmonary atresia with intact septum and unguarded tricuspid orifice. In this case of pulmonary valvar atresia with intact interventricular septum there is an unguarded tricuspid orifice. The right atrium and right ventricle have been opened to display the cavities. Note the absence of any valvar tissue at the right atrioventricular junction. In contrast with Figure 4.38, the right ventricular cavity is dilated, and the wall is thin.
Figure 4.40 Pulmonary atresia with intact septum. The pulmonary trunk has been transected near the sinotubular junction, and the valve is viewed from above. The valve is small and imperforate and composed of three cusps that are thickened and rigid, and fused centrally to form a fibrous button with three radiations.
A notable feature is the presence of right ventricular-coronary artery sinusoids. These are said to arise from persistence of the normal ventricular-coronary communications in the embryo because of persistently elevated right ventricular pressure. However, there is at least one report of identification of ventricular-coronary artery sinusoids before the onset of pulmonary obstruction [52]. The sinusoids are readily demonstrable on echocardiography but are very difficult to demonstrate convincingly pathologically. They do, however, cause dramatic secondary changes in the affected coronary arteries. These arteries show greatly thickened muscular walls, intimal fibrous and elastic thickening, and adventitial elastic deposition (Figure 4.41A,B) [53]. Sometimes the epicardial coronary arteries may be two to three times their normal external diameter. On occasion, the affected coronary artery loses its communication with the aorta because of the intimal proliferation. The perfusion of the myocardium supplied by such an artery may then be crucially dependent on the elevated right ventricular pressure for retrograde perfusion. Histologically, the hypertrophied right ventricular myocardium shows myocyte disarray (Figure 4.42) [53].
(A) Heart from an infant aged 12 days who died suddenly on day after insertion of a Blalock–Taussig shunt for pulmonary atresia with intact septum. The heart is viewed from the front. The right ventricular apex is visible about halfway down the right border of the heart. There is congestion of the pericardium. The pulmonary trunk is narrow. The left coronary artery shows irregular thickening of its wall as it courses in the anterior interventricular groove.
(B) A histological section of one of the thickened epicardial arteries showing thickening of all three coats – adventitia, media and intima, by concentric laminar fibrous and elastic tissue. In areas it is impossible to recognise the original arterial wall.
Figure 4.41 Pulmonary atresia with intact septum.
Figure 4.42 Pulmonary atresia with intact septum. Histological section of the thickened right ventricular myocardium to demonstrate the florid myocyte disarray that is a common feature of this condition.
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