Even though, as stated by Lev and Eckner, 1 no two cases are exactly the same, it is the characteristic anatomy that permits the instant recognition of the tetralogy of Fallot. As was emphasised by Arthur Louis Etienne Fallot, as long ago as 1888, all cases have an interventricular communication, biventricular origin of the aorta, muscular obstruction within the right ventricular outflow tract, and right ventricular hypertrophy ( Fig. 36-1 ). There is no question but that hearts with this phenotypic morphology had been described long before Fallot emphasised the constellation of lesions that now bears his name. Thus, according to Marquis, 2 the malformation was first described in 1673 by the Danish monk, Nicholas Steno, in an ectopic heart from a fetus. Fallot deserves his eponym, nonetheless, since it was he who first observed that the combination of lesions accounted for the majority of cases of la maladie bleue, or cyanosis, which he encountered at autopsy. Abbott, 3 in her classic Atlas of Congenital Cardiac Disease, emphasised the observations of Fallot, 3 and the eponym has continued to retain favour since her own descriptions of permanent cyanosis. Arguments have continued, however, as to the essence of the malformation, and which variants should be described with the eponym. Thus, when obstruction within the right ventricular outflow tract is minimal, it can be hard to distinguish tetralogy from the variant of ventricular septal defect with aortic overriding known as the Eisenmenger defect, 4 even using anatomic criterions. 5 When obstruction is complete, the condition unequivocally represents the commonest variant of pulmonary atresia with ventricular septal defect, although not all accept that this form should be described as tetralogy with pulmonary atresia. The phenotypic feature that underscores the existence of the tetralogy is anterior and cephalad deviation of the septal insertion of the outlet septum relative to the septomarginal trabeculation, combined with an arrangement of the septoparietal trabeculations that produces an annular obstruction at the mouth of the infundibulum. Within the collection of hearts unified in this fashion, there is ample room for significant individual variation, as emphasised by Lev and Eckner. 1 It is this variation that will be the focus of our anatomic discussions in this chapter, with emphasis placed on the major differences from the normal heart.
INCIDENCE, PREVALENCE, AND AETIOLOGY
Of infants born with congenital heart disease, approximately 3.5% will have tetralogy of Fallot, giving a figure of 0.28 per 1,000, or 1 in 3,600, live births. 6 Males and females are equally affected. According to existing statistics, the frequency increases with age when compared with other forms of cyanotic congenital cardiac malformations. This is largely because, in the past, infants with more lethal cardiac anomalies tended to die, whereas many with tetralogy of Fallot survive beyond infancy even without treatment. This could well change in the current era.
As with so many congenital cardiac anomalies, precise aetiology is unknown. The majority of cases are sporadic. According to Nora and colleagues, 7 the risk of recurrence in siblings is about 3% if there are no other affected first-degree relatives. Rubella in the first trimester of pregnancy has been implicated in a small number of cases, 8 (Courtesy of Dr Benson Wilcox, University of North Carolina, Chapel Hill.) while viruses have been isolated from cases with severe pulmonary arterial hypoplasia. 9 Keeshond dogs were bred to produce a spectrum of inherited malformations of the ventricular outflow tracts, which included anomalies similar to tetralogy of Fallot. 10 The findings indicated a polygenic model of inheritance, in which the genes act additively to produce the spectrum of maldevelopment. The lesion is also known to be linked with abnormal migration of cells from the neural crest. Dosage of rats with bis-diamine, known to inhibit migration from the neural crest, produces the phenotypic features of tetralogy when given at critical periods of development, including cases with pulmonary atresia rather than stenosis. 11,12 In a significant proportion of cases, it is possible to find microdeletions of the q11 region of chromosome 22, such deletions being known to produce Di George syndrome and the velocardiofacial syndrome, also known as the conotruncal anomaly face syndrome. 13 In some series, 14 microdeletion was found in up to a quarter of cases, suggesting that investigation using fluorescent in situ hybridisation should be undertaken in all patients with the phenotypic features of tetralogy.
Almost all those born with tetralogy of Fallot in all its variants can now expect to survive surgical correction, and reach adult life. Female patients may well ask the question ‘Is it safe for me to become pregnant?’, while both women and men will wish to know the risks of their progeny inheriting the condition. It has been known for some time that the incidence of congenital cardiac disease is higher in children born to women with congenitally malformed hearts than in the normal population, 15 albeit that, with respect to tetralogy, no differences are found in the incidence of affected children according to whether it is the mother or father who had the lesion initially. According to some, the risk is approximately one-tenth for the offspring being affected. This risk is as for any congenital cardiac malformation, including minor lesions not requiring intervention. 16 The risk is much higher, at above two-fifths, however, if the affected parent has a sibling with the same or a similar cardiac anomaly. Identification of those patients having microdeletion of chromosome 22q11 could well allow refinement of these calculations for risk of recurrence.
ANATOMY AND MORPHOGENESIS
Phenotypic Features
The phenotypic feature of the lesion is antero-cephalad deviation of the insertion of the muscular outlet septum relative to the limbs of the septomarginal trabeculation, coupled with an arrangement of the septoparietal trabeculations which produces a squeeze at the mouth of the infundibulum 17 ( Fig. 36-2 ). In the normal heart, the muscular outlet septum is an insignificant structure, inserted and buried between the limbs of the prominent septomarginal trabeculation. Indeed, it is so fully incorporated into the septum ( Fig. 36-3 ) that it is not possible to distinguish an anatomically discrete outlet septal component from the dominant part of the supraventricular crest, which is the ventriculo-infundibular fold, itself supporting the free-standing subpulmonary infundibulum ( Fig. 36-4 ). In tetralogy, these components of the supraventricular crest are divorced one from the other, with the right ventricular muscular outlet septum, rather than the ventriculo-infundibular fold, now supporting the narrowed free-standing subpulmonary infundibulum ( Fig. 36-5 ).
Because of the abnormal position of the outlet septum, which is exclusively a right ventricular structure in tetralogy, the interventricular communication is situated between the limbs of the septomarginal trabeculation, whilst the right ventricular origin of the overriding aortic valve is supported by the ventriculo-infundibular fold (see Fig. 36-1 ). These three anatomic features of the tetralogy, therefore, all reflect the abnormal location of the outlet septum. This particular phenotypic combination, nonetheless, cannot be produced in the absence of the squeeze produced together with the septoparietal trabeculations, which are themselves often hypertrophied, particularly in hearts from older patients. The outlet septum, nonetheless, can be markedly deviated in antero-cephalad direction without there being subpulmonary stenosis, despite the presence of hypertrophied septoparietal trabeculations, as in the so-called Eisenmenger complex ( Fig. 36-6 ).
Although the divorce of outlet septum, ventriculo-infundibular fold, and septomarginal trabeculation are the essence of tetralogy when combined with the annular muscular obstruction at the mouth of the subpulmonary infundibulum, and despite the fact that each can be recognised anatomically in its own right, there has been significant previous confusion and controversy in description of the abnormal outflow tracts. This is because each of these three structures, at various times and in various places, had been nominated as a component of the so-called crista. Consequently, when alleged parts of the crista were described in the setting of tetralogy, it was difficult to be sure which of the different structures was being described. Because of these problems, we suggested quite some time ago 18 that the term crista , or its translation as supraventricular crest, be reserved for description of the muscular structure separating the attachments of the leaflets of the tricuspid and pulmonary valves in the normal right ventricular outflow tract ( Fig. 36-7 ). In situations where the muscular structures are separated one from the other, as is the case in tetralogy, we suggested that each structure be accounted for in its own right, using descriptive and mutually exclusive terms ( Fig. 36-8 ). This suggestion has since stood well the test of time. Thus, the outlet septum is any muscular or fibrous structure that interposes between the subpulmonary and subaortic outflow tracts. This septum has septal and parietal insertions, and is contiguous with the sleeve of free-standing subpulmonary infundibular musculature, albeit that the infundibulum itself is absent when the outlet septum is exclusively a fibrous structure. The ventriculo-infundibular fold, being part of the muscular inner heart curvature, is any muscular structure that separates the leaflets of an arterial from an atrioventricular valve. It is the extensive trabeculation reinforcing the septal surface of the morphologically right ventricle that is nominated as the septomarginal trabeculation, or septal band. It has a body, together with anterior-cephalad and postero-caudal limbs, the latter components usually supporting the inferior margin of the interventricular communication, not only in tetralogy, but also in other lesions such as double outlet right ventricle and common arterial trunk. The moderator band arises apically from its body, and crosses to the free ventricular wall. The moderator band is, however, only one of a series of muscle bars which extend to the parietal wall. The others are the septoparietal trabeculations, an integral component of the normal heart, but forming an integral part of the obstruction to the pulmonary pathways seen in tetralogy. Use of these terms makes it a simple matter to describe and differentiate the muscular structures forming the outflow tracts in tetralogy of Fallot ( Fig. 36-9 ).
Variability in the Margins of the Ventricular Septal Defect
The hole between the ventricles is directly beneath the overriding aortic valvar orifice. It can thus be considered an outlet defect. The muscular outlet septum itself, however, is usually well-formed, albeit malaligned relative to the rest of the muscular septum. Indeed, as already discussed, part of the essence of tetralogy is antero-cephalad deviation of the septal insertion of the outlet septum such that it becomes a right ventricular rather than an interventricular structure, this deviation co-existing with the abnormal arrangement of the most distal septomarginal trabeculation (see Figs. 36-2 and 36-9 ). It is the outlet septum, therefore, and its fusion with the antero-cephalad limb of the septomarginal trabeculation, which forms the anterior margins of the defect. The crest of the muscular ventricular septum, reinforced by the limbs of the septomarginal trabeculation, forms the floor of the defect. Because of the septal malalignment, the roof of the defect is formed by the attachments of the leaflets of the overriding aortic valve to the ventriculo-infundibular fold. Indeed, because of the overriding of the aortic orifice, problems exist in defining specifically the nature of the ventricular septal defect. Any one of a host of planes within the cone of space subtended from the valvar leaflets to the crest of the septum can be nominated as a septal defect ( Fig. 36-10 ).
When describing the boundaries of these planes, we concentrate on the margins of the cone as viewed from the right ventricle, 19 since this is the locus along which the surgeon will attach the patch used to repair the malformation so as to reconstitute the ventricular septum (see Fig. 36-10 ). When the ventricular septal defect is defined in this fashion, it is the postero-inferior quadrant that shows most anatomic variability. In about four-fifths of cases, this margin is formed by fibrous continuity between the leaflets of the aortic, mitral and tricuspid valves ( Fig. 36-11 ) .
In this respect, the defect is directly comparable to typical perimembranous defects opening to the outlet of the right ventricle in the absence of subpulmonary obstruction. In our view, it is unnecessary to consider the defect in tetralogy as a separate entity should it co-exist with malalignment of the outlet septum. In that the postero-inferior margin is an area of fibrous continuity between the leaflets of the aortic and tricuspid valves, the defect is unequivocally perimembranous. These anatomic features are reflected in the distribution of the atrioventricular conduction tissues. As in all other hearts with concordant atrioventricular connections, the guides to the location of the atrioventricular node are the landmarks of the triangle of Koch. The penetrating bundle perforates the central fibrous body through the area of valvar continuity ( Fig. 36-12 ). Here, the bundle is frequently overlaid by a remnant of the interventricular membranous septum, which may on occasions become aneurysmal. The septal remnant itself, called the membranous flap, 20 is safe tissue for anchorage of sutures when such stitches are placed with care. 21 It is positioned, however, directly superficial to the penetrating bundle. 22 Sutures placed deeply in this area are liable to produce complete heart block. It is safer, therefore, to place sutures through the leaflet of the tricuspid valve, which usually overlaps the membranous flap in this area of the defect. Having perforated, the nonbranching atrioventricular bundle enters the left ventricular part of the aortic outflow tract, and almost always then veers away from the septal crest, the branching atrioventricular bundle being carried on the left ventricular aspect of the septum and staying remote from the septal crest. In a minority of hearts, nonetheless, the bundle may branch directly astride the septum. Such an arrangement places the bundle at risk should sutures be placed into the crest of the septum ( Fig. 36-13 ). Irrespective of these differences, the right bundle branch penetrates back through the septum, emerging within the postero-caudal limb of the septomarginal trabeculation and then descending within its substance towards the apex.
The second most common pattern, occurring in about one-fifth of cases, is characterised by interruption of the area of fibrous continuity between the aortic and tricuspid valves by a muscular fold. 17,19 When viewed from its right ventricular aspect, therefore, the septal defect has exclusively muscular rims. The fold itself is formed by fusion of the postero-caudal limb of the septomarginal trabeculation with the ventriculo-infundibular fold. An intact membranous septum is found between the muscular fold and the remaining atrioventricular septal structures. Since the atrioventricular conduction axis runs postero-inferior to the membranous septum, the muscular fold, together with the membranous septum itself, separates the conduction tissues from the crest of the ventricular septum ( Fig. 36-14 ). When the muscular fold is of good dimensions, as is usually the case, the entire muscular margins of the defect are suitable for anchorage of sutures, provided that the stitches are not placed too deeply.
There is then yet a third variety of defect, characterised by presence of a fibrous rather than a muscular outlet septum, and absence of the free-standing subpulmonary infundibular sleeve. 17,19 This is the doubly committed and juxta-arterial defect, by far the least common in the Western World, but commoner in the Far East and South America. The defect is both subaortic and subpulmonary as a consequence of failure of formation of the muscular subpulmonary infundibulum. Such defects can also be found with fibrous continuity between the leaflets of the aortic and tricuspid valves, making them perimembranous ( Fig. 36-15 ), but more usually there is a muscular postero-inferior rim, comparable to the muscular structure seen in Figure 36-14 . If present, the muscular structure will protect the atrioventricular conduction axis, but in the heart shown in Figure 36-15 , the conduction axis will be at direct risk in the postero-inferior margin of the defect.
Patients with tetralogy, of course, all possess defects as described above, which open between the outflow tracts. They can also be encountered with additional defects elsewhere in the septum. Inlet defects are particularly important, be they muscular inlet defects, defects associated with straddling and overriding of the tricuspid valve, or the ventricular component of an atrioventricular septal defect associated with common atrioventricular junction. The combination of tetralogy and an atrioventricular septal defect with common atrioventricular junction, in the past, was considered to pose significant additional problems to the surgeon, but these difficulties have now been overcome in most centres of excellence. Almost always in tetralogy, the ventricular septal defect is large, approximating in size the diameter of the aortic root. Rarely, it may be restrictive due to the presence of accessory fibrous tissue tags formed at the margins of the defect. Such tags may be derived in part from the tricuspid valve, or extend from attachment of the tension apparatus of the mitral valve across the left ventricular aspect of the defect.
Narrowing of the Subpulmonary Infundibulum
The subpulmonary stenosis, which is an essential part of tetralogy, is due to the squeeze between the antero-cephalad deviation of the outlet septum and the abnormal arrangement of the distal septoparietal trabeculations, this being the phenotypic feature of the lesion (see Figs. 36-2 and 36-9 ). The antero-cephalad component of the obstruction, therefore, is produced by the septoparietal trabeculations, often additionally hypertrophied, which extend onto the ventricular free wall. These muscular bundles can be removed by the surgeon without fear of causing damage to significant structures. The maximal area of stenosis, when viewed from the apex of the right ventricle, produces an obvious mouth to the subpulmonary infundibulum, the so-called os infundibulum ( Fig. 36-16 ).
Additional stenosis can then be found more proximally within the ventricle, produced either by hypertrophy of the moderator band, which is one of the septoparietal trabeculations, or by prominent apical trabeculations. This gives the arrangement often described as two-chambered right ventricle. The subpulmonary infundibulum itself, distal to the squeeze between outlet septum and septoparietal trabeculations, varies markedly in length. In some instances, when the ventricular septal defect is doubly committed, the infundibulum is no longer an exclusively muscular structure (see Fig. 36-15 ). In other instances, the narrowed infundibular chamber has considerable length (see Fig. 36-16 ). There is a spectrum between these extremes, but measurements of series of hearts from patients with tetralogy, 23 when compared to measurements of normal hearts, show that the infundibulum is longer in the setting of the malformation ( Fig. 36-17 ). In addition to the muscular stenosis, it is also usual to find obstruction at valvar level, with the valve itself often possessing two rather than three leaflets. Further stenotic lesions can then be found within the pulmonary arterial pathways.
Overriding of the Aortic Valve
In the normal heart, although the right aortic sinus of the aortic valve overrides spatially the crest of the muscular ventricular septum, the leaflets of the valve are attached exclusively within the left ventricle. Whenever the ventricular septum is deficient, however, part of the circumference of the aortic valvar orifice of necessity becomes attached to, and supported by, right ventricular structures. 24 Such aortic overriding becomes more obvious when the outlet septum is deviated so as to become exclusively a right ventricular structure, as in tetralogy of Fallot (see Fig. 36-1 ) or the Eisenmenger ventricular septal defect (see Fig. 36-6 ). The precise degree of override, in other words the proportion of the aortic valvar circumference supported by right as opposed to left ventricular structures, can therefore vary between 5% and 100%. This feature has obvious surgical significance. A much larger patch will be required to reconstitute the ventricular septum, and connect the aorta to the left ventricle, when the larger part of its circumference is supported by the right ventricle. Care must be taken to be sure that the patch is not placed so tightly as to obstruct the newly created left ventricular outflow tract.
This feature also has implications for nomenclature, albeit that the importance has been somewhat exaggerated. As has been explained in Chapter 1 , we describe the situation in which more than half of the circumferences of both great arterial valves are connected in the same ventricle as double outlet ventriculo-arterial connection. In the context of tetralogy of Fallot, in which the entirety of the pulmonary valve is supported by the right ventricular subpulmonary infundibulum, if more than half of the leaflets of the aortic valve are hinged from right ventricular structures, we describe the situation as tetralogy of Fallot co-existing with the ventriculo-arterial connection of double outlet ventricle. There is no reason why the two should not co-exist. Double outlet is simply one particular ventriculo-arterial connection. Tetralogy of Fallot is defined on the basis of its phenotypic feature, namely antero-cephalad deviation of the outlet septum combined with hypertrophy of the septoparietal trabeculations. These two features, self-evidently, are not mutually exclusive ( Fig. 36-18 ).
Other Lesions of the Pulmonary Circulation
Although the subpulmonary infundibulum is usually the narrowest part of the pulmonary outflow tract, other lesions are to be found elsewhere in the outflow tracts and the pulmonary arteries. Pulmonary valvar stenosis is a frequent accompaniment. This is sometimes due to domed stenosis, more frequently to stenosis of a bicuspid valve or to stenosis of a valve with three leaflets. The valvar lesion is rarely the major cause of obstruction, albeit that in some young infants it can be the predominant finding. The valve can also become imperforate as an acquired change. So-called absence of the leaflets of the pulmonary valve is another important lesion. Most usually, the valve is represented by an annular array of fibrous rudiments, usually found with dilation of the pulmonary trunk and its branches ( Fig. 36-19 ).
Stenoses within the pulmonary arteries themselves are of major surgical significance, and usually occur at branching sites from the bifurcation outwards. Lack of origin of one pulmonary artery, typically the left, from the pulmonary trunk is by no means infrequent. The isolated pulmonary artery is almost always present, usually being connected by the arterial duct, or ligament, to some part of the system of aortic arches. Rarely, one pulmonary artery may arise directly from the ascending aorta, but then it tends to be the right one which is anomalously connected. Major systemic-to-pulmonary collateral arteries are sometimes present in association with tetralogy and pulmonary stenosis, but in association with normal right and left pulmonary arteries. Such arteries can be the sole source of pulmonary arterial flow when tetralogy co-exists with pulmonary atresia (see Chapter 37 ).
Associated Anomalies
Many other lesions can co-exist with tetralogy. Patency of the oval foramen is common, and a deficiency of the floor of the oval fossa is far from infrequent. In addition to a second inlet muscular ventricular septal defect, straddling of the tricuspid valve, or presence of a common atrioventricular valve, features already emphasised, the most important associated lesion from the stance of the surgeon is probably anomalous origin of the anterior interventricular coronary artery from the right coronary artery. A right aortic arch, though not of functional importance, is also common. When detected, it alerts to the diagnosis of tetralogy. Aortic incompetence is commoner in older patients.
Morphogenesis
The notion that tetralogy of Fallot reflects malseptation of the arterial segment of the developing heart has a long pedigree, and is supported by observations concerning naturally occurring infundibular lesions in Keeshond dogs. 10 These animals show a spectrum of malformations, ranging from absence of the medial papillary muscle, through presence of a ventricular septal defect, to a constellation of anomalies similar to tetralogy. Study of embryos, in which developmental stages of these malformations were observed, showed that the factory for production of the lesions was within the ventricular outflow tracts. Specifically, abnormalities were found in the formation and position of the endocardial cushions which normally fuse to septate the ventricular outlets. These observations have now been confirmed in rats dosed with bis-diamine, 11,12 while the concept of muscularisation of the proximal outflow cushions to form the subpulmonary infundibulum of the normal heart has been confirmed by observations in the developing human heart ( Figs. 36-20 and 36-21 ).
The findings in patients with deletion of chromosome 22q11 also support the existence of malseptation of the outflow tracts in humans, and point to this being due to problems in migration of cells from the neural crest. Based on the anatomic findings, therefore, it can be said with some degree of certainty that there is malseptation of the ventricular outlets and the arterial pole of the heart at the expense of the pulmonary trunk, together with failure of normal incorporation of the aortic outflow tract into the morphologically left ventricle. As discussed, the abnormal attachment of the muscular outlet septum is sufficient to account for the presence of the interventricular communication and the biventricular connection of the aorta, but production of subpulmonary muscular stenosis requires an additional abnormality involving the septoparietal trabeculations. The right ventricular hypertrophy is simply a haemodynamic consequence of the anatomic lesions.
Clinical Diagnosis
The clinical presentation is dominated by the degree of muscular obstruction of the right ventricular outflow tract. 25 This is sometimes modified by associated anomalies, such as persistent patency of the arterial duct, or presence of large systemic-to-pulmonary collateral arteries.
Presentation When Subpulmonary Obstruction Is Severe from Birth
When the obstruction of the right ventricular outflow tract is severe at birth, presentation is in the neonatal period. Persistent cyanosis becomes apparent within the first few hours or days of life. With severe arterial desaturation, a metabolic acidosis develops that is compensated by an increased respiratory rate. The concomitant fall in arterial content of carbon dioxide gives rise to a compensatory respiratory alkalosis. Intercostal or subcostal recession, however, is unusual. Cyanosis, which dominates the clinical picture, increases with crying, feeding, or other activities. At least initially, the baby does not appear unduly distressed. Sometimes the pulmonary circulation is duct-dependent. In this setting, the degree of subpulmonary obstruction is so great that there is inadequate antegrade flow, and virtually all pulmonary blood flow is derived from a left-to-right shunt via the arterial duct. Under such circumstances, spontaneous closure of the duct results in death. Maintenance of ductal patency, usually by infusion of prostaglandin E, is crucial.
Presentation When Subpulmonary Obstruction Is Moderate at Birth
The majority of children with tetralogy of Fallot are acyanotic at birth. Consequently, they often present because a systolic murmur is detected during routine examination. The development of cyanosis is dependent on increasing infundibular stenosis, and not on the degree of aortic override. 26 This is usually noted within the first few weeks of life, but development of cyanosis may rarely be delayed to late childhood. The systolic murmur, present in all patients other than those with very severe stenosis or acquired atresia, originates at the site of subpulmonary obstruction, and not because of flow across the ventricular septal defect. 27 At this stage, infants or children are usually asymptomatic. Later, hypercyanotic spells or squatting on exercise may all occur. With improved medical surveillance, all of these symptoms are now less often encountered than even a decade ago.
Presentation When Subpulmonary Obstruction Is Minimal at Birth
Some infants with tetralogy may uncommonly present at the age of 4 to 6 weeks with features indistinguishable from those of a large ventricular septal defect (see Chapter 28 ). These babies are breathless, feed poorly, gain weight poorly, and are not cyanosed. With increasing right ventricular hypertrophy, the subpulmonary obstruction becomes more marked and, as the shunt is reversed, the patients exhibit the signs and progression as described for the group with moderate obstruction.
Presentation with Absent Pulmonary Valve
When tetralogy is complicated by so-called absence of the leaflets of the pulmonary valve, which are usually present in rudimentary form (see Fig. 36-19 ), the presentation is characteristic yet different from the previously described groups. The majority with this complication present in infancy with respiratory symptoms of inspiratory and expiratory stridor, dyspnoea caused by lobar collapse or, at times, lobar emphysema. These features reflect compression of the bronchial tree by the grossly dilated proximal pulmonary arteries. While bronchial obstruction may lead to lobar collapse, and subsequent infection, partial obstruction may produce a ball-valve effect, resulting in emphysema. Because there is stenosis at the site of the rudimentary leaflets of the pulmonary valve, symptoms directly related to abnormal haemodynamics are unusual.
Squatting
Squatting, along with other postures, may alleviate the degree of cyanosis, dyspnoea or feeling of faintness induced by exercise. The means by which squatting alleviates the symptoms of cyanosis and dyspnoea have caused considerable debate. Irrespective of the precise mechanisms, there is little doubt that squatting causes an abrupt increase in systemic venous return and a rise in systemic vascular resistance. Right-to-left shunting is decreased by an increase in systemic vascular resistance. This means that the volume of blood passing through the right ventricle to the lungs is proportionally increased, with immediate improvement in effective pulmonary flow, and hence arterial saturations of oxygen.
Hypercyanotic Attacks
An important, and often dramatic, feature of patients with tetralogy is the occurrence of unprovoked severe cyanosis, which may lead to reduced cardiac output, and be accompanied by transient loss of consciousness. 28 These episodes, which are most common between 6 months and 2 years of age, 29 are potentially dangerous, as they may lead to cerebral damage or even death. 28 The majority last between 15 and 60 minutes, but an individual spell may be of shorter duration, or can last for several hours. Initial presentation of infants or children may be with a history of episodic loss of consciousness, or convulsions, episodes of going floppy or pale, transient vacant episodes, or episodes of becoming deeply cyanosed followed by loss of consciousness or sleep. Another striking feature of these spells may be episodes of very rapid deep respiration or hyperpnoea, or a high-pitched abnormal cry. The episodes are usually sufficiently dramatic or unusual for parents to volunteer information, but specific questioning concerning their presence should be part of every outpatient assessment. It was Wood (1958) who postulated that the spells resulted from infundibular spasm or shutdown. 28 Many now believe the concept of infundibular spasm, as a primary phenomenon, to be unsupported by the anatomy or physiology of the subpulmonary infundibulum, and suggest that the shutdown is secondary to other primary physiologic influences, such as dehydration, or tachycardia-induced reduction in right ventricular preload, systemic vasodilation in response to fever, or other sympathetic activity. Irrespective of their aetiology, their occurrence should lead to prompt treatment with continuous β-blockade, and referral for surgery or interventional catheterisation as dictated by the institutional protocols.
Physical Examination
The essential abnormal cardiac findings in the neonate with severe tetralogy of Fallot are cyanosis and, on auscultation, a systolic ejection murmur with a single second heart sound. Overt clubbing of fingers and toes is typically not detected until 2 or 3 months of age. The baby may be normally grown, although a higher proportion weighs less than would be expected by chance. Some degree of facial dysmorphism is quite common, and typical features of associated syndromes may be obvious, such as the DiGeorge, Goldenhauer, or Down syndromes. All patients should now undergo chromosomal analysis on presentation, with specific fluorescent in situ hybridisation for 22q11 deletion. Pulses are almost always normal in all limbs, aortic coarctation being exceedingly rare in symptomatic neonates with tetralogy of Fallot. The cardiac impulse may be normal, or the parasternal right ventricular impulse may be increased. The first heart sound is normal, but the second is characteristically single. In contrast to patients having pulmonary stenosis with an intact ventricular septum, pulmonary ejection sounds in the second or third intercostal space, or third and fourth heart sounds, are virtually never found in children with tetralogy. An aortic ejection click may sometimes be heard at the lower left sternal edge or at the apex. The duration of the systolic ejection murmur will vary depending on the degree of infundibular stenosis. The shorter the murmur, the tighter will be the stenosis and, in turn, the greater the cyanosis. Co-existing rudimentary formation of the leaflets of the pulmonary valve is characterised by an additional long loud early diastolic decrescendo murmur from pulmonary regurgitation, which should be easily distinguishable from a continuous murmur. When a loud continuous murmur is heard in the neonatal period, and clinical features are otherwise compatible with the diagnosis of tetralogy, it is more likely to originate from flow through large major systemic-to-pulmonary collateral arteries than the arterial duct. The patient is then likely to have co-existing pulmonary atresia. In these patients, cyanosis may not be so marked, since pulmonary blood flow is more adequately maintained through the collateral arteries.
Children with tetralogy in whom subpulmonary obstruction is minimal or absent at birth exhibit tachypnoea, dyspnoea, and intercostal or subcostal recession. This group has a large left-to-right shunt, with an increased flow of blood to the lungs. A prominent parasternal impulse, and hepatomegaly, may be present. On auscultation, the second sound is split, possibly with an accentuated pulmonary component.
Investigations
While the diagnosis of tetralogy of Fallot is usually made from clinical assessment, confirmation is now provided largely by cross sectional echocardiography. Before describing the typical echocardiographic features, however, we will discuss the plain chest radiograph and the electrocardiogram, as these are usually carried out as part of the general cardiac assessment of a child.
Chest Radiograph
In the acyanotic patient with tetralogy, the plain chest radiograph may be normal. Most patients have the usual arrangement of thoracic and abdominal organs, together with a left-sided heart, but tetralogy may occur with mirror-imaged arrangement, when the heart is usually right-sided. With usual atrial arrangement, up to one-third of patients with tetralogy have a right aortic arch. Of all subjects with a right aortic arch, three-quarters have tetralogy of Fallot with or without pulmonary atresia. The diagnosis is even more likely if there are reduced pulmonary vascular markings. Pulmonary vascular markings will usually be reduced in cyanotic patients, the lung fields being strikingly oligaemic in neonates when subpulmonary obstruction is severe. In contrast, vascular markings will be normal when infundibular stenosis is moderate. When subpulmonary obstruction is minimal, there will be pulmonary plethora, reflecting the left-to-right shunt. The heart is usually of normal size, but the upper right cardiac border may be prominent owing to displacement of the superior caval vein by a right aortic arch. A pulmonary bay, or concavity at the upper left heart border, reflects a small pulmonary trunk ( Fig. 36-22 ). The apex of the heart may be upturned, probably because the hypertrophied right ventricle forms the apex in the postero-anterior projection. Post-operatively, the heart size can be used as a reasonable surrogate of right ventricular dilation, although other methods are clearly more accurate, and appropriate, for detailed assessment.
