Fetus	Adult
Newly oxygenated, but still partially desaturated, blood leaves the placenta and arrives at the right atrium in the inferior vena cava	Blood which is nearly fully saturated with oxygen arrives at the left atrium via the pulmonary veins
Pressure in right atrium is higher than that in the left atrium	Left atrial pressure is higher than that in the right atrium
Right-to-left shunting of blood occurs across the foramen ovale	There is no shunt at atrial level
The right ventricle supplies blood to the systemic circulation	The right ventricle only supplies blood to the pulmonary circulation
The right ventricle output predominantly passes through the ductus arteriosus into the aorta	The right ventricle output passes to the lungs
Resistance to blood flow is low in the placenta and this leads to a low peripheral resistance overall	Peripheral resistance to blood flow is high
Stiff, fluid-filled, lungs have high resistance to flow	Expanded, air-filled lungs, have low resistance to blood flow

Sometimes transition from fetal to adult circulation at birth is incomplete, leading to so-called persistent fetal circulation. An example of a case history is shown in Case 12.1:1.

Case 12.1 Fetal cardiovascular system and congenital heart disease: 1

A blue child

A newborn baby was noted to be cyanosed at 24-hour review. The respiratory rate was slightly increased at 60–70 breaths per minute but there was no respiratory distress. On auscultation there were no murmurs, the chest was clear and femoral arteries were easily palpable. A blood oxygen saturation check showed saturations of 78–82%. The baby was transferred to the special care baby unit (SCBU) and a hyperoxia test (increased inspired oxygen concentration) was performed. Arterial blood gases breathing room air showed pH = 7.37, Po₂ = 3.5 kPa, Pco₂ = 5.0 kPa, [HCO₃] = 19 mmol/L, base excess = −2.3 mmol/L (see Chapter 1). When given 100% O₂ for 5 minutes arterial blood gas data were pH = 7.36, Po₂ = 9.5 kPa, Pco₂ = 5.5 kPa, [HCO₃] = 19 mmol/L, base excess = −2.2 mmol/L. A diagnosis of congenital cyanotic heart disease was made and after discussion with the regional paediatric cardiology unit dinoprostone infusion (a synthetic prostaglandin) was commenced and arrangements were made for transfer to the regional specialist centre.

On arrival echocardiography confirmed the putative diagnosis of transposition of the great arteries (TGA). The child was prepared for immediate balloon septostomy and was taken to the catheter laboratory.

Septostomy involves transvenous insertion of a catheter with a balloon at the end via the right atrium and patent foramen ovale into the left atrium. The balloon is then inflated and pulled back into the right atrium sharply in order to tear the interatrial septum. Care must be taken to avoid damaging the mitral valve or the inferior vena cava/right atrium junction.

The procedure was performed without complications. Post septostomy, oxygen saturations rose to 85–90%. The child was transferred back to the ward and after a few hours normal feeding was instituted.

Questions for consideration include:

1. What do the initial blood gas measurements tell us about the cardiopulmonary problems in this child?

2. What clinical signs help distinguish cardiac problems from a respiratory cause for cyanosis?

3. What is the rationale for the dinoprostone infusion?

4. How does blood flow around the circulation in a case of TGA?

5. How does septostomy affect the oxygen saturation of haemoglobin in this case?

Answers to these questions are discussed in the text of this chapter and in Case 12.1:2.

Interesting facts

Reptilian and amphibian hearts have three chambers with separation of oxygenated and deoxygenated blood by ridges within the ventricles. However the crocodile has a fully septated four chamber heart. In order to allow it to sustain dives for long periods it has a mechanical valve which diverts pulmonary blood flow to the systemic circulation whilst it is submerged.

How does the transition from fetal to adult circulation occur?

Changes at birth

On taking its first breath, the newborn infant instigates several simultaneous changes which will completely alter its circulation. Though most of these changes occur within minutes, they will take weeks to become fully complete.

The precise stimulus for the initiation of air breathing is not well understood. In utero the fetus makes some respiration-like movements but the process of birth drives the true onset of independent breathing. The clamping of the cord isolates the baby from the placenta. The associated increase in blood Pco₂ and decrease in Po₂ appear to be important in triggering the respiratory drive. The first few breaths are crucial, they must open the airways and complete the process of fluid clearance from the lung. Surfactant, a mixture of lipid, phospholipid and protein which lines the alveoli, is key to the reduction in surface tension necessary to allow the small airways to open. Anything which inhibits this fluid clearance can lead to failure to convert from the fetal to the neonatal pattern of circulation.

The first breath opens the airways and allows gas exchange across the alveolar membrane. The lungs expand and blood vessels open. This initiates a drop in the pulmonary vascular resistance (see Figure 12.5). Combined with the sudden rise in peripheral resistance resulting from the loss of the low-resistance placenta, there is a profound alteration in haemodynamics in the newborn infant. The blood leaving the right ventricle is preferentially directed through the now low-resistance lungs and returns to the left atrium. This increase in venous flow into the left atrium raises the left atrial pressure. At the same time there is a fall in right atrial pressure because venous return to this chamber has been reduced following the loss of the placental circulation. As left atrial pressure is now higher than right atrial pressure the foramen ovale, a flap valve, closes. Thus, in the newborn any detectable flow across the atrial septum is predominantly left to right. With the changes in pressures and the establishment of lung ventilation there is a sharp increase in blood oxygen content. This improved tissue oxygenation reduces the acidaemia to which the fetus has been adapted. Rising pH and Pao₂ inhibit the synthesis of prostaglandins in the ductus arteriosus. This leads to closure of the ductus arteriosus separating the pulmonary circulation from the systemic circulation. Though generally the duct has closed within 24 hours of birth, early echocardiography demonstrates that a small left to right ductal shunt persists in a large minority of newborns for some days or even weeks. However this shunt is not usually of clinical significance.

Fig. 12.5 Changes in pulmonary artery pressure, pulmonary blood flow and pulmonary vascular resistance at birth.

Over the first few days of life the process of adjustment proceeds with a continued fall in pulmonary artery pressure. This single physiological process accounts for many of the clinical features of congenital heart disease and cardiovascular problems in children.

Longer term changes in the heart during childhood and adulthood

Typically the pressure in the pulmonary artery will fall from the comparatively high level in the fetus to a normal adult level (25/5, mean = 10 mm Hg) over a period of a few weeks. The lower working pressure in the right ventricle means that during childhood it becomes increasingly dominated by the left ventricle in terms of muscle mass.

Apart from the fall in pulmonary pressure with time there are a number of physiological changes with maturation. Heart rate (HR) and blood pressure (BP) both vary with age and an appropriate normal range must be used in clinical practice. An adult with a heart rate of 120 bpm and a systolic BP of 85 mm Hg might be in the early stages of hypovolaemic shock but these would be perfectly normal values for a 1 year old. It is critically important to know the normal changes in physiological variables when assessing children, as they do not conform to textbook adult values.

Table 12.2 summarizes the normal variation of HR and BP with age. An estimate of the normal systolic BP, for a given age in children, can be made from the formula: systolic BP = 80 + (2 × age in years).

Table 12.2

Heart rate and BP variations with age

Age (yr)	HR (bpm)	Systolic BP (mm Hg)
<1	110–160	70–90
1–2	100–150	80–95
2–5	95–140	80–100
5–12	80–120	90–110
>12	60–100	100–120

The variation in heart rate reflects the relatively small size of the infant heart compared with its body mass and the relatively low compliance (increased stiffness) of the ventricles. The stiff ventricles mean that the stroke volume of the heart responds less dramatically to increasing venous return (preload effects) compared to an adult (see Chapter 4). In order to meet the demand for increased cardiac output the newborn heart rate must rise substantially, even at rest. Thus it is not unusual to see heart rates in newborns varying from 90 bpm when deeply asleep to 160 bpm when only slightly active. In the sick newborn under stress heart rates over 200 bpm may be seen with the heart still in sinus rhythm.

The normal ECG in childhood

Broadly speaking the ECG of the child has the same components as that of the adult, i.e. P waves, QRS complexes and T waves (see Chapter 7). However the relative contribution of the right and left ventricles to the shape of the ECG trace is different in children compared to adults. There is therefore a progressive change in the pattern of the ECG through childhood which reflects the declining contribution of the muscle mass of the right ventricle compared to the left ventricle. The large muscle mass of the newborn right ventricle affects the axis of the QRS complex in the frontal plane. The axis of the frontal QRS vector in the infant may be well past the upper limit of normal for the adult with the normal range being as high as +180°. Again, with time and the involution of the right ventricle, the axis ‘swings’ leftwards until it reaches the normal range for adults −30° to +90° (see Chapter 7). This change over time means that the acceptable axis for children in the frontal plane is very wide ranging. Broadly speaking, the axis should be inferior, i.e. between 0° and 180°. Deviation above the horizontal axis should be considered abnormal in the absence of evidence to the contrary. In the presence of physical evidence to support it a rightwards axis more extreme than usual may be suggestive of a residual load on the right ventricle. Put simply if the QRS vector is positive (i.e. pen deflection is upwards) in lead aVF then the vertical plane axis of the heart is probably normal.

The chest leads are particularly informative. In V₁ the QRS complexes are initially dominantly positive with a dominant R wave reflecting depolarization in the relatively hypertrophied septum. T waves in V₁ may be positive in the first 2 weeks of life but then become negative and remain inverted up until late childhood. The initial solely, or dominantly, positive deflection in V₁ slowly becomes equiphasic and by adulthood will be purely negative in the majority of normal ECGs. Figure 12.2 shows the typical variation.

Fig. 12.2 ECG pattern—variation with age.

Persistence of infantile ECG patterns may reflect a failure in the decline of RV pressures, as for example in the case of significant obstruction to the right ventricular outflow caused by pulmonary stenosis. Other causes of persistence of high pulmonary pressure (pulmonary hypertension) are a large ventricular septal defect (VSD), a patent ductus arterious (PDA) or, more rarely, primary pulmonary hypertension. Atrial septal defects (ASD) rarely cause pulmonary hypertension even though there may be a substantial left to right shunt. The persistence of infantile ECG patterns a month after birth should prompt urgent discussion with a specialist paediatric cardiology centre particularly in the presence of symptoms or signs supporting a diagnosis of congenital heart disease.

Broadly, the normal range for the intervals between successive components of the ECG for children are shorter than for adults and generally the younger the child the shorter the interval. This largely reflects the physical size of the heart, as a wave of electrical activity spreading through a smaller heart has a shorter distance to travel and so takes less time. This generalization applies for everything but the index referred to as the corrected QT interval (QTc). This is defined as the QT interval/square root (preceding R–R interval). Generally this falls with increasing age. Identification of the QTc has become clinically more important with increasing understanding of the role that abnormal repolarization plays in sudden death in young people. This may be evident in prolongation of the QTc above the normal range for an adult on the resting ECG.

Congenital heart disease

Congenital heart disease (CHD) affects around 1% of all children. The degree to which the heart can be distorted yet remain capable of supporting life is remarkable. One of the most frequently asked questions by parents is ‘Why did it happen?’ The frequently given answer is that, for the most part, we do not know.

It seems likely that with the wide variation of pathologies, largely sporadic in nature, a multifactorial aetiology is involved, possibly with a mix of genetic and environmental factors. Maternal factors such as diabetes and periconception infections such as rubella are strongly associated with congenital heart disease. Also congenital heart disease is strongly associated with other apparently unrelated structural defects, suggesting either a common environmental insult or a common genetic defect whose relationship affects tissues in the early embryo such that apparently unrelated organs are affected. Therapeutic and recreational drugs are associated with CHD, though whether the effects are direct or simply association is not clear. For example sodium valproate, an antiepileptic drug, inhibits folate metabolism. Its association with CHD may be by way of its interference with folate metabolism. Individuals using recreational drugs frequently live chaotic lives with poor nutritional status so that they are at risk of conditions associated with vitamin deficiency, which may be the fundamental cause of pathology and not the drugs per se.

Clearly‘genetic programming’ is crucial to certain forms of congenital heart disease. As genetic knowledge advances more and more syndromes are linked with specific genetic lesions. For example, complete atrioventricular septal defect (AVSD) accounts for around 4% of all cardiac defects in the general population. However in children with Down syndrome (trisomy 21) it accounts for around 40% of the heart defects which are relatively common in this condition. About 40% of children with Down’s syndrome have some form of congenital heart disease. Tetralogy of Fallot (see p. 146) and some related cardiac defects (pulmonary atresia with ventricular septal defect, truncus arteriosus, interrupted aortic arch) are associated with deletion in the q11 region of chromosome 22. However not all children with tetralogy of Fallot have the 22q11 deletion and usually those children with this deletion have substantial non-cardiac problems in addition to their cardiac defects. These include cleft palate, speech and learning difficulties, hypocalcaemia and immunological problems. However the q11 region of chromosome 22 contains several hundred genes and research is underway to see if some specific genes account for the cardiac problems associated with the large DNA deletion. One candidate is the TBX-1 (‘TBOX-1’) gene. In mice in which TBX-1 has been blocked or disabled cardiac defects similar to those found in 22q11 deletion syndromes in humans are found.

Conditions such as Marfan’s syndrome and Williams’ syndrome are associated with specific structural cardiovascular anomalies but not generally abnormalities in the connections of the heart. Marfan’s syndrome is now known to be caused by defects in the gene for fibrillin located on chromosome 15q21. Defective protein leads to weakness in the connective tissues including those of the heart causing mitral valve prolapse due to dysfunction of the subvalvar apparatus and, more importantly, aortic root dilatation with risk of dissection which can be fatal if untreated. Preventive treatment is by replacement of the aortic root and ascending aorta with synthetic substitutes. Williams’ syndrome is caused by a deletion of the elastin gene on chromosome 7q11. Typically this is associated with supravalvar aortic stenosis or peripheral pulmonary stenosis. Pulmonary valvar stenosis and atrial or ventricular septal defects are also recognized cardiac anomalies. Outside the heart renal artery stenosis and stenosis of other major fibrous vessels is also documented. Though all these defects may seem to arise logically from a defect of a structural protein, it is far from obvious why this condition should be associated with developmental delay and many other problems. As yet we understand far too little about the subtle interaction of structure and function in the developing embryo.

Not all congenital heart problems can be explained on a genetic basis however, as overall there is only a weak familial link with congenital heart disease. For siblings of an affected child, or children of affected parents, the overall incidence of congenital heart disease is only mildly increased from about 1% to 3–4%. Thus there must be other factors affecting the development of the fetal heart.

A second important element in the pathogenesis of congenital heart disease is how the growth of structures is dependent on the way they function during fetal development. Thus for vascular structures to grow appropriately they must have a blood flow which encourages them to develop correctly. For example, obstruction on the left side of the heart is frequently associated with problems at multiple levels. This may explain the association between stenosis of the aortic valve and coarctation of the aorta (narrowing of the aorta adjacent to the insertion of the ductus arteriosus into the aorta). As described earlier in this chapter, in the fetus only about 10% of the cardiac output traverses the isthmus—that part of the aortic arch between the origin of the left subclavian artery and the insertion of the duct. If stenosis of the aortic valve reduces the output from the left side of the heart—possibly only marginally—then flow across this critical region of blood vessel may be significantly reduced and normal development of the aorta discouraged.

In the condition called Shone’s syndrome obstruction can occur at many levels on the left side of the heart. Mitral stenosis is often accompanied by aortic stenosis, aortic arch hypoplasia and coarctation of the aorta. It is proposed that impaired development of the mitral valve leads to decreased flow into the left ventricle, through the aortic valve and around the aortic arch. This reduced flow results in impaired development of these structures. At its most extreme it may be seen as hypoplastic left heart syndrome (HLHS) in which the left ventricle is completely underdeveloped, the aortic valve is severely stenotic or even atretic and the ascending aorta and aortic arch are hypoplastic. In the classical HLHS the ascending aorta is simply a functional extension of the coronary arteries and the blood supply to the head and neck vessels is completely retrograde around the arch and fed from the ductus arteriosus. The shunt at atrial level is completely reversed in the fetus and the right ventricle must support the whole circulation.

That the development of cardiovascular structures is dependent on the functional demand placed upon them is elegantly demonstrated by the findings from fetal echocardiography. Fetuses with very poorly developed ventricles at 16–20 weeks of gestation may have undergone complete involution by birth with only a tiny or even undetectable ventricular cavity on a postnatal echocardiograph. The two hypotheses for the genesis of congenital heart disease are not of course mutually exclusive. Subtle errors in the genetic code may be amplified by the interaction between development and function in utero. It is probable that a large proportion of congenital heart disease occurs due to disruption of normal development early in pregnancy, which is then amplified by the effect of changes in function.

Presentation of congenital heart disease

Murmurs

Murmurs are extra sounds caused by turbulent flow of blood during the cardiac cycle (see Chapter 8). Murmurs can initially be divided on the basis of cause; innocent or functional murmurs have no underlying structural cause whereas pathological murmurs result from specific abnormalities of cardiac structures.

Innocent murmurs are generally characterized by:

• low intensity (quiet)

• lack of radiation (can only be heard at one point)

• frequently vary with body position or state, e.g. only audible when sitting, when ill or after exercise

• lack of associated symptoms

• normal ECG findings.

Typical examples of innocent murmurs are:

• flow murmur—ejection murmur typically heard in the pulmonary area when the cardiac output is high

• vibratory (Still’s) murmur—systolic murmur with buzzing musical quality localized to left sternal edge

• venous hum—continuous murmur heard at the base of the neck; typically abolished by lying down or pressing on the jugular vein

• carotid bruit—audible in the neck and thought to arise from blood flow into the brachiocephalic artery.

The intensity of a pathological murmur is largely dependent on the size of the hole through which blood must pass and the pressure gradient across the narrowest point. These are the factors which determine the velocity of flow and hence the likelihood of turbulence occurring (see Chapter 8). Thus with stenotic valves where the whole of the cardiac output must pass through the valve the intensity and length of the murmur increase with the degree of stenosis. However, for ventricular septal defects (VSD) the relationship between size and flow is complex as larger defects have a greater flow but a lower pressure gradient. Thus there is a peaked relationship between the intensity of the murmur and the size of the defect with very large defects generating little or no murmur and very small defects usually quieter murmurs because the flow is low despite maximal pressure difference. As the defect becomes vanishingly small the murmur disappears.

The time course of a murmur is very important in assessing its origin. Murmurs arise from jets of blood passing between chambers or vessels. The timing of the start and finish of the pressure gradient which generates the jet helps define its quality. For example, in the case of a VSD there is no pressure gradient during diastole as both ventricles fill. However almost immediately after the start of systole when the pressure in both ventricles has risen to the point where the atrioventricular valves have closed, i.e. immediately after the first heart sound, the pressure in the left ventricle is greater than that in the right. Thus the flow of blood through the VSD commences at the first heart sound and continues through into early diastole when the semilunar valves are heard to shut, i.e. the second heart sound. Thus the typical VSD murmur occurs throughout systole and is described as being pan- or holo-systolic (Fig. 12.3A). This may be compared with the murmur of aortic valve stenosis. Initially the pressure in the left ventricle is lower than in the aorta so there is a period between the first heart sound (closure of the mitral valve) and the opening of the aortic valve in which there is no blood flow out of the ventricle. The pressure in the ventricle rises to a peak during early systole at which time the volume of blood ejected from the ventricle is maximal and so the murmur reaches its maximum intensity. Then there is a period of reduced ejection of blood during which the pressure in the ventricle begins to fall. The intensity of the murmur falls to zero at the time the semilunar valves close. A recording of heart sounds, a phonocardiogram, has a typical diamond-shaped pattern for ejection systolic murmurs (Fig 12.3B).

Fig. 12.3 Audible patterns of typical murmurs. The pairs of vertical double lines represent the timing of the first and second heart sounds.

Continuous murmurs can only occur where there is a persistent pressure difference between two vessels throughout the cardiac cycle. Apart from the innocent venous hum the commonest cause of continuous murmur is a patent ductus arteriosus (PDA). Since the aorta is always at a higher pressure than the pulmonary vasculature, even in diastole, the murmur occurs both in systole and diastole. However, since the pressure difference is greater in systole the quality of the sound varies between systole and diastole. Thus the murmur is continuous with two phases—it is often described as a machinery murmur (Fig. 12.3C). Large arteriovenous malformations are another cause of continuous murmurs.

Diastolic murmurs are often more difficult to hear because the pressure gradients are less than for systolic murmurs. The loudest diastolic murmurs tend to be caused by leakage (incompetence) in the semilunar valves. These typically occur in early diastole and are decrescendo in character. The typical decrescendo intensity profile reflects the fact that extracardiac vascular pressures fall during diastole whilst intraventricular pressures rise during diastole (Fig. 12.3D). Diastolic murmurs may also occur where there is stenosis of the atrioventricular (AV) valves, though these are likely to be difficult to hear. Classically described as ‘rumbling’ in quality the murmur has a low pitch rather different to high pressure murmurs. Increased flow through the AV valves may cause a murmur because of a functional stenosis.

A common mistake is to ascribe the murmur associated with a large atrial septal defect (ASD) to flow across the atrial septum. This would be a diastolic murmur but in fact the typical murmur is a systolic ejection murmur loudest over the pulmonary area and radiating to the back. This is actually generated by flow through the pulmonary valve which is functionally stenosed because of the increased flow rather than the valve being narrow. It may be possible to hear a diastolic murmur across the tricuspid valve which is also secondary to the increased flow through the right side of the heart.

Radiation

The term radiation is used to describe the spatial distribution of a murmur. It specifically applies to the direction in which a murmur is maximally audible away from the site of maximum intensity. Radiation is a key feature in identifying the cause of murmurs. For example innocent murmurs are typically localized without radiation. In order to interpret radiation as a clinical sign it is necessary to understand the normal anatomical relations of the heart.

The heart lies in an oblique orientation to the body, the apex being anterior and lateral with the base being posterior and medial. The aorta arises in parallel with this axis and turns upwards into the neck. The atrioventricular valves (tricuspid and mitral) lie in a plane perpendicular to this axis and slightly offset from each other. The pulmonary artery arises from the anterosuperior surface of the right ventricle but turns directly posterior before bifurcating into left and right pulmonary arteries. The ventricular septum falls in a plane which extends from apex to base but angles from left inferoposterior to right superoanterior. So what does this tell us about the radiation of murmurs?

It is easy to see how the jet of blood caused by aortic stenosis directs sound towards the right shoulder and neck. Pulmonary stenosis tends to be heard loudest over the left infraclavicular area, but because the artery points backwards the murmur can be heard over the left chest posteriorly. Branch pulmonary artery stenosis may be easily audible in the ipsilateral chest. Typically, the murmur of a VSD is loudest over the praecordium at the left sternal edge reflecting the posterior/anterior relation of the left and right ventricles (jet is from posterior to anterior).

Shunts

The normal ex utero circulation places the right and left ventricles in series with the pulmonary and systemic vascular beds between them (Fig. 12.4A). Though both pumps are combined in a single organ, the heart, they could be separate organs. This would make controlling the balanced output of each ventricle more difficult but not impossible. When blood passes from one side of the heart to the other bypassing the relevant end organs this is known as a shunt. Shunts may be intracardiac (e.g. VSD (Fig. 12.4B) or ASD (Fig. 12.4C)) or extracardiac (e.g. PDA (Fig. 12.4D) or arteriovenous malformation (Fig. 12.4E)). The main effect of a shunt is to volume load one or other side of the heart. Persistently high pulmonary blood flows associated with high driving pressure will eventually produce irreversible pulmonary hypertension. In the extreme case, systemic to pulmonary shunts may reverse, producing a flow of desaturated blood from right to left with consequent peripheral desaturation. This is known as Eisenmenger’s syndrome.

Fig. 12.4 Blood circulation and shunts. (A) Schematic diagram of circulation and various shunts. (B) Ventricular septal defect. (C) Atrial septal defect. (D) Patent ductus arteriosus. (E) Systemic arteriovenous malformation.

The presence of a shunt will affect cardiac performance. For example a PDA will generally cause blood to pass from the aorta into the pulmonary circulation which is at lower pressure. This extra blood, the shunt flow (S), is added to the flow already passing through the lungs from the right ventricle. Since the amount of blood returning to the right ventricle is equal to the amount passing through the systemic organs, the cardiac output (CO), the flow through the lungs is CO+S. The venous return to the left side of the heart from the lungs is equal to CO+S and may be considerably greater than the resting systemic requirement. This produces volume loading of the left side of the heart with a dilated left atrium and ventricle and is associated with exercise limitation. Although the left ventricle has the capacity in a normal adult to increase its output to about five times resting levels (see Chapter 4), in the presence of a substantial shunt it may already be preloaded by several times the resting cardiac output at rest. Thus, during exercise, the left ventricle soon reaches its maximum output and the individual becomes exercise limited. In children this is frequently seen as having to stop for a rest before any of their playmates. Babies may become out of breath whilst feeding and have to stop to ‘catch their breath’. In the case of premature infants the volume load on the left heart and high pulmonary blood flow may mean that they are unable to cope without mechanical ventilatory support.

Arteriovenous malformations may occur in either systemic or pulmonary circulation. These abnormal connections have a low resistance to flow and so increase flow through the circuit. This leads to volume loading of both sides of the heart. In extreme cases they may cause high output cardiac failure. The distinction between arteriovenous malformations and shunts connecting opposite sides of the heart is that the latter lead to volume loading of only one side of the heart.

Calculating shunts

Simple shunt ratios may be calculated using the Fick principle. In practice this is based on the fact that uptake of oxygen in the lungs must be equal to oxygen extraction (consumption) in the systemic circulation. A precise estimate of the flow in either the systemic or the pulmonary vascular bed can only be achieved with accurate measurement of absolute oxygen consumption, a measurement fraught with difficulty. However the ratio of the two flows may be calculated on the basis that oxygen uptake = oxygen extraction. If Q_p is the pulmonary blood flow and Q_s the systemic blood flow, then the following holds true if we ignore the small amount of dissolved oxygen (valid for inhaled O₂ concentrations <30%):

where [Hb] represents the concentration of haemoglobin in the blood in g/L and 1.34 is the volume (mL/gHb) of oxygen carried by a gram of haemoglobin when saturated (see Chapter 1). Since, at equilibrium, pulmonary uptake must equal systemic extraction then it follows that:

and therefore

Where the size of a VSD is small the amount of blood passing through it adds little to the workload of the left ventricle and so is of little significance. However left to right shunts in which the pulmonary blood flow is above twice the systemic flow may be sufficient to produce symptoms. As flow becomes relatively greater so do symptoms. Initially, the most telling sign of a large shunt in a baby is breathlessness, particularly when feeding, their most energy demanding activity. The other major energy demand after homeostasis is growth. Feeding behaviour and weight gain are important markers of cardiac function in the infant. Babies with large shunts feed slowly, become more breathless during feeding and often need calorie supplements or mechanical feeding support such as nasogastric feeds. Tissue oedema leads to relative tissue hypoxia because of impaired diffusion of oxygen. This reduces the efficiency with which nutritional calories can be utilized. Pulmonary oedema occurs because the high blood flow and high blood pressure lead to fluid outflow from the pulmonary capillaries at a rate greater than the lung lymphatics can cope with (see Chapter 11). Oedematous lungs are both stiff and less efficient for gas transfer. Thus the work of breathing is greatly increased due to decreased compliance of the lungs. This increase in energy demand also contributes to the poor weight gain.

Cyanosis

The third common presentation of congenital heart disease is cyanosis which may occur in the newborn for several reasons. Peripheral cyanosis, caused by poor perfusion of tissues with blood, must be differentiated from central cyanosis, caused by reduced oxygenation of blood in the central arterial tree (see Chapter 1). Central cyanosis can be viewed as having two major causes, ‘respiratory’, in which the cyanosis is secondary to lung disease with impaired gas transfer, and ‘cardiac’ in which the cyanosis is due to the mixing of partially desaturated (venous) and normally saturated (arterial) blood (see Case 12.1:2).

Case 12.1 Fetal cardiovascular system and congenital heart disease: 2

Causes of cyanosis (see questions posed in Case 12.1, Box 1)

1. It is important to distinguish cardiac from respiratory causes of cyanosis. The hyperoxia test (increasing inspired Po₂) is a classic way to do this, and is often more helpful in the child with some breathing difficulties. The basic principle lies in the distinction between a problem with gas transfer and one of circulation. Cardiac cyanosis is not responsive to increasing the inspired oxygen to any great extent. An increase in arterial Po₂ of only 5.5 kPa in this case is strong evidence in favour of cardiac disease.

2. Clinically respiratory disease is usually associated with increased work of breathing which is described as respiratory distress. Respiratory distress is an overall term for signs such as subcostal recession, tracheal tug, nasal flaring and grunting. Cardiac cyanosis may be effortless—certainly in older children. In general babies are tolerant of cyanosis because of the hypoxaemia present in the fetal environment.

3. Dinoprostone is a synthetic prostaglandin (PGE₂). Prostaglandins are important in the natural closure of the ductus arteriosus. Prostaglandins inhibit closure of the duct. Exogenous prostaglandin is given in many types of congenital heart disease where flow through the duct is critical to maintaining pulmonary blood flow or peripheral perfusion. In the case of TGA it is important to maintain high circulating volume in the pulmonary circuit as this promotes shunting of oxygenated blood back into the systemic circulation across the atrial septum.

4. In the normal circulation deoxygenated blood is carried in the systemic veins to the right atrium. From the right atrium it passes through the tricuspid valve into the right ventricle from which it is pumped across the pulmonary valve into the pulmonary artery and thence to the pulmonary capillary bed. Oxygenated blood returns to the heart in the pulmonary veins to the left atrium. Blood crosses the mitral valve into the left ventricle from whence it is pumped via the aortic valve into the aorta and around the body. Eventually it passes through the systemic capillary bed and is collected in venules which drain into the venous system.

5. In the case of TGA the systemic venous return is to the right atrium and then to the right ventricle. However the right ventricle is connected to the aorta and hence pumps de-oxygenated blood back around the body. The pulmonary venous return is to the left atrium and thence to the left ventricle. However the left ventricle is connected to the pulmonary artery and thus directly back to the lung. Fully oxygenated blood is circulated back to the pulmonary circulation.

6. The function of balloon septostomy is to open up the atrial communication thereby improving mixing of systemic venous return (desaturated) and pulmonary venous return (saturated) and thus increasing the systemic saturation of haemoglobin with oxygen.

The single major distinguishing feature between the pulmonary and cardiac causes of cyanosis is the lack of response to increasing the inhaled oxygen concentration. If cyanosis is due to impaired gas transfer then increasing Po₂ in the inhaled gas mixture and hence increasing the concentration of O₂ within the alveolus should improve the transfer of oxygen into the blood. However in the case of cyanotic heart disease the blood passing through alveolar capillaries is already nearly fully oxygenated and so little change results from increasing the oxygen content of inhaled gas. The cyanosis is due to mixing of this oxygenated sample with blood which has not been exposed to oxygen in the pulmonary vascular bed. The lack of respiratory distress is suggestive of a cardiac cause for cyanosis, as is the presence of a murmur or other physical sign linked with cardiac disease. However these are not 100% predictive as respiratory distress may occur secondary to the effects of heart failure or hypoxia whilst murmurs are frequently not present in cyanotic lesions particularly in the newborn period.

The key to understanding cyanosis is analysis of the routes which saturated and desaturated blood take through the circulation. Cyanosis will occur where desaturated blood is able to enter the systemic circulation. Many different possibilities occur and frequently they are clinically indistinguishable. Cyanosis must occur where there is loss of some part of the standard circuit, e.g. pulmonary or tricuspid atresia, where systemic and pulmonary venous returns must be joined before re-dividing to supply systemic and pulmonary vascular beds. In other cases the mixing may not be obligatory, but functional, resulting from a combination of lack of a divider between the systemic and pulmonary circulations and haemodynamic conditions within the heart. An ASD, normally not a cyanotic lesion, may produce cyanosis if the right heart pressures rise above those of the left such as when an infant cries—producing transient cyanosis as desaturated blood passes from right atrium to left atrium.

Ultimately management of cyanotic heart disease relies on surgical repair. This may be definitive, in which a normal circulation with two separate ventricles is achieved, or palliative in which stable saturations are achieved even though a normal circulation cannot be produced (see Blalock–Taussig shunt and Fontan circulation described on p. 147). Medical therapy may be important in stabilizing the child prior to surgery, e.g. the use of exogenous prostaglandin to maintain ductal patency prior to the insertion of a synthetic shunt to give a stable pulmonary blood flow (see Case 12.1:1).

Change from in utero to ex utero physiology: impact on physical signs

The change from in utero to ex utero physiology also has a profound influence on the presentation of congenital heart disease. Left-to-right shunts may be clinically undetectable at birth because of the high pulmonary pressure. As the right ventricular pressure falls (Fig. 12.5) VSD murmurs will become louder as the degree of left-to-right shunting increases. Parents frequently question the quality of newborn examination when significant defects are missed at the routine examination. However the paediatrician may take comfort in the fact that some murmurs may not be present in the first few days of life. This is a key feature differentiating obstructive lesions such as pulmonary stenosis or aortic stenosis from shunting lesions such as VSDs. In the former, since the cardiac output must pass through these valves at all times, a murmur will be audible from birth whereas the latter will depend upon the relative pressures between right and left ventricles which changes in the first few days of life. Initially, with right and left ventricular pressures equal, shunts from one side of the heart to the other will be minimal and in fact a mild degree of de-saturation may be observed reflecting right-to-left shunting.

The volume of left-to-right shunt with a VSD demonstrates a similar variation over time as the murmur. Initially a newborn baby may tolerate a large VSD because the high pulmonary pressure associated with fetal life restricts the amount of blood passing from the left to the right ventricle and back through the pulmonary circulation. Commonly infants become more breathless over the first few weeks of life as the flow through the shunt increases and the volume load on the left ventricle increases. Babies may develop significant cardiac failure. Unless steps are taken to restrict the pulmonary blood flow then permanent damage may occur in the pulmonary vascular bed with the development of pulmonary hypertension. Clinically this is indicated by an improvement in the heart failure, a worrying sign. For some children the pulmonary vascular resistance never falls and they never show signs of heart failure.

By contrast, the residual presence of prenatal structures may obscure complex underlying lesions. For example it is common in transposition of the great arteries (TGA) for children to present at a few days of age with profound cyanosis or collapse. The underlying lesion in TGA is a complex failure of septation in which the aorta arises from the right ventricle and the pulmonary artery arises from the left ventricle. Thus there are essentially two separate circulations. Venous blood returns from the body to the right atrium, passes into the right ventricle and is pumped out round the body again. Fully saturated oxygenated blood returns from the lungs to the left atrium, passes into the left ventricle and is then pumped back to the lungs via the pulmonary artery. Clearly in a completely separate circulation oxygen would be extracted until the point where tissues would become hypoxic and die. In order to be compatible with life there must be some mixing of oxygenated and deoxygenated blood. This can occur if the foramen ovale remains open and is of a good size and if the ductus arteriosus remains patent. Mixing only occurs at the foramen ovale but the ductus arteriosus is crucial for maintaining left atrial pressure by filling the pulmonary circulation. As in the normal circulation the pulmonary pressure is lower than systemic pressure and so shunting at the duct is always left to right (systemic to pulmonary).

Initially the child may appear well as the duct remains patent and there is a good flow of blood to the lungs. It should be noted that TGA is frequently not associated with a murmur. Clinical cyanosis may be difficult to identify in the first 48 hours of life because of facial congestion following delivery and a relatively high saturation (85–90%). Infants may behave quite normally leading to routine discharge. However as the ductus arteriosus closes over the subsequent few days the child may become increasingly cyanosed and breathless with increasing hypoxia and acidaemia. The child commonly presents to the emergency department in a collapsed or near collapsed state.

A single anatomical abnormality may vary sufficiently to present with completely different clinical pictures. Take for example the anatomical variability of Fallot’s tetralogy. This is the combination of a large subaortic VSD which does not provide any obstruction to flow (not ‘restrictive’), and an overriding of the aorta across the ventricular septum, subpulmonary and pulmonary stenosis and right ventricular hypertrophy. At one end of the spectrum the pulmonary obstruction is mild and the pulmonary blood flow is high—remember the VSD is not restrictive. A murmur of pulmonary stenosis may be noted in the newborn period (the VSD is not restrictive and therefore does not produce a murmur). However saturations will be near normal with predominantly left-to-right shunt across the VSD though some mixing at the ventricular level will occur. As the pulmonary vascular resistance falls the left-to-right shunt may increase and the child may become breathless but systemic blood will remain almost fully saturated with oxygen. By comparison, where the pulmonary obstruction is severe, resistance to blood flow to the lungs is greater than that to the body and so desaturated blood preferentially enters the systemic circulation and the child may present with a murmur and cyanosis in the newborn period.

Early and late management of congenital heart disease

Management of congenital heart disease can be divided into three main categories. Firstly there is medical versus surgical management. Thereafter the surgical management may be considered as curative or palliative, i.e. whether the surgeon is able to produce a normal circulation with two ventricles pumping blood separately or whether the best that can be achieved is stabilization and minimization of exercise restriction with surgical reconstruction which does not achieve a normal circulation.

One of the major success stories in modern neonatal medicine has been the medical management of ductus arteriosus patency. Since the key role of E-series prostaglandins in maintaining ductal patency was identified in 1975, two opposing management strategies have had a major impact on the physician’s ability to stabilize neonates. Prostaglandins act to maintain ductal patency. A synthetic prostaglandin infusion can be used to re-open and maintain ductal patency in conditions such as pulmonary atresia, TGA or hypoplastic left heart syndrome in which the circulation is critically dependent on ductal patency. Many infants with life threatening congenital heart disease can be stabilized with the use of relatively simple and safe prostaglandin therapy until definitive surgical management is arranged. Conversely in the preterm neonate the PDA can be a troublesome problem causing heart failure and high flow pulmonary oedema resulting in dependency on mechanical ventilation. Treatment with indometacin, a non-steroidal anti-inflammatory drug which inhibits production of prostaglandins, induces ductal closure. The use of indometacin has greatly reduced the number of preterm infants requiring surgical ligation of the duct.

In the infant with a high left-to-right shunt the high output cardiac failure may be managed with diuretics in order to offload excess pulmonary fluid. As with adults a combination of loop (furosemide (frusemide)) and potassium sparing (amiloride, spironolactone) diuretics are used to avoid inducing electrolyte imbalance. In some instances angiotensin converting enzyme (ACE) inhibitors are used to try and reduce pulmonary blood flow by lowering systemic vascular resistance and thereby increasing systemic cardiac output at the expense of pulmonary blood flow. The introduction of ACE inhibitors should only be made with extreme caution in infants, as they frequently have inadequate cardiac reserve to meet the increased demand.

It is almost axiomatic that any congenital heart lesion which requires medical management in early life requires definitive surgical intervention. Advances in surgical and anaesthetic techniques, including cardiopulmonary bypass, have allowed the surgical management of more and more complex lesions with low mortality. Average surgical mortality for all congenital heart disease is now around 2%.

Interesting facts

With the huge improvement in the techniques used, average surgical mortality for all congenital heart disease is now around only 2%.

Though the primary aim of surgical intervention is to reconstruct a circulation which is as close to normal as possible with a single operation this is not always feasible. Some hearts cannot be reconstructed with two ventricles whilst the constraints of surgical technique mean that in other conditions for which two ventricle repair is technically feasible the limitations of early repair mean that initial palliation with later definitive repair is the optimum strategy.

The first intervention which may be performed is a balloon septostomy. This palliative, interventional technique involves the passage of a balloon-tipped catheter from the systemic veins via the right atrium and foramen ovale into the left atrium. The balloon is then inflated and forcibly withdrawn from left to right atrium, tearing the atrial septum and improving atrial mixing. First performed by William Rashkind in 1966, this procedure is most frequently used in TGA to improve spillover of saturated blood from the left atrium to the right atrium whence it can then be circulated to the body. It is one of the earliest interventions a newborn is likely to receive and can be life saving, preventing a terminal hypoxic spiral and relieving the dependence on prostaglandin to maintain ductal patency.

Palliative techniques such as Blalock–Taussig (BT) shunts (connection of the subclavian artery to the pulmonary artery, originally directly but now usually with a Gore-Tex tube) allow the maintenance of pulmonary blood flow in circumstances where this may be restricted such as in tetralogy of Fallot or pulmonary atresia. This stabilizes systemic saturation and encourages growth of the pulmonary arteries whilst protecting the lung vasculature from damage by high pressures and flows. The construction of the shunt is such that it provides a significant resistance between the systemic and pulmonary circulations, balancing adequate blood flow against damage to the pulmonary vasculature. Initially performed in 1944, this was one of the first palliative repairs for cyanotic heart diseases though now definitive repair is more common. Other forms of artificial shunt exist from the aorta to the pulmonary artery, though it is technically more difficult to obtain controlled results. More recent practice has involved the introduction of conduits from the right or, more rarely, left ventricle to pulmonary artery, the Sanno procedure. This was originally developed to avoid the problem of a reduction in coronary circulation during diastole which may occur with BT shunts. Since the pulmonary artery pressure is lower than systemic at all points of the cardiac cycle, diastolic steal can occur in which coronary perfusion is compromised by preferential flow into the pulmonary system during diastole. Remember that coronary perfusion occurs primarily during diastole (see Chapter 5).

Case 12.1 Fetal cardiovascular system and congenital heart disease: 3

Corrective surgery

The child described in Case 12.1:1 proceeded to corrective surgery on day 7 of life. This involved switching the pulmonary artery and aorta with coronary transfer and re-implantation using cardiopulmonary bypass to provide a circulation to the rest of the body during surgery. The operation was uneventful and after 3 days of mechanical ventilation the baby was transferred back to the ward on the fourth postoperative day. The postoperative recovery was otherwise uneventful and the infant was discharged on the tenth postoperative day with normal feeding established.

What is the effect of the corrective operation on the circulation?

The arterial switch operation reconnects the appropriate great arteries to the appropriate ventricles, i.e. pulmonary artery to right ventricle and aorta to left ventricle. Apart from suture lines the only residual abnormalities are that the pulmonary valve remains in the aortic position and the aortic valve lies between the right ventricle and the pulmonary artery. The normal crossover relation of the aorta and pulmonary artery are also disrupted with the pulmonary artery generally lying anterior to the aorta.

Where there is unrestricted pulmonary blood flow the aim is to reduce the pressure and flow in the lungs. This may be achieved by pulmonary artery banding, the application of a tight ligature around the pulmonary artery, thereby creating an artificial stenosis. This is used in patients who have large VSDs whose anatomy is not favourable for primary closure. For example multiple muscular VSDs may allow high pulmonary blood flow and be easily identifiable on echocardiogram. However they are often difficult to see once the heart is opened and emptied of blood, particularly as the trabeculations in the right ventricle obscure the orifices. Pulmonary artery banding reduces pulmonary blood flow and the pressure in the pulmonary arterial bed, thereby preventing long term damage to the lung vasculature whilst the child grows. With luck the muscular septum will hypertrophy and close the defects spontaneously, or some form of surgical intervention can be attempted later once the child is larger. Once the VSDs have been closed the band may be removed and the circulation functions normally. Pulmonary artery banding is also used to protect the pulmonary vascular bed in lesions with a single ventricle and unobstructed pulmonary flow. This is particularly important in cases with only one ventricle, as the long-term plan can only be palliative and the quality of palliation is critically dependent on the pressure in the pulmonary arterial tree (see Fontan circulation below). Pulmonary artery banding, whilst an apparently simple procedure, is far from uncomplicated. The operation is a move from one stable state to another – akin to changing canoes in mid-stream. The potential for catastrophic loss of cardiac output is significant.

In some conditions there is inadequate development of one or other of the ventricles and so two ventricle repair is not possible. Traditionally this was palliated with a repair involving either restricting pulmonary blood flow with pulmonary artery banding or augmenting it with some form of shunt, e.g. Blalock–Taussig. This left the child with an inadequate saturation of their blood with oxygen and a permanent left to right shunt and subsequent volume loading of the single ventricle. However in the late 1960s Francis Fontan demonstrated that with favourable pulmonary artery pressure it was possible to make a direct connection of the systemic venous system to the pulmonary artery. The resulting circulation has no active pumping of blood into the lungs (normally the function of the right ventricle) but relies on passive filling augmented by the negative intrathoracic pressure generated by respiration to promote flow into the lungs. Key to the success of this strategy is the similar value of mean central venous pressure (5–7 mm Hg) and mean pulmonary artery pressure (around 10 mm Hg). Whilst not providing as efficient a system as a two ventricle repair, the Fontan circulation provides a long-term palliation well into early adulthood. Beyond this, longer term outlook is poor however, with the likely need for a transplant at around 30 years of age.

Interesting facts

Gore-Tex is a material widely used in waterproof jackets and boots. It is also a material used to repair and replace damaged major blood vessels.

The construction of a Fontan circulation is staged to allow for the changing haemodynamics of the pulmonary vasculature. Initially the pulmonary vasculature needs to be protected and pulmonary blood flow maintained. In situations such as tricuspid atresia and VSD with hypoplastic right ventricle this may require banding of the pulmonary artery to restrict pulmonary blood flow and lessen damage to the pulmonary vascular bed. It is critical to avoid long-term damage to the pulmonary vascular bed as elevated pulmonary artery pressures will prevent completion of the Fontan circulation. Alternatively, where there is inadequate pulmonary blood flow the creation of a shunt to augment the blood flow may be necessary. Between 4 months and 1 year of age, depending on the lesion and progress of the child, the next stage may be completed with connection of the superior vena cava (SVC) to the right pulmonary artery. Usually any arterial shunt is tied off at this time. Then, between 2 and 6 years of age, the venous connections may be completed with connection of the inferior vena cava (IVC) to the pulmonary arteries. Prior to the completion of the venopulmonary connections the blood of the child will be poorly saturated with oxygen. However, after completion of the surgery the systemic blood saturation with oxygen will generally be in the mid to high 90+% range. Various residual shunts, e.g. the venous drainage from the cardiac muscle itself which returns via the coronary sinus to the right atrium, will generally mean that full saturation can never be achieved.