The right ventricle (RV) can be hypoplastic in various settings. It can be small in the presence of deficient ventricular or atrioventricular septation, producing so-called left ventricular dominance. The chamber can also be small and incomplete in the setting of univentricular atrioventricular connections such as double-inlet left ventricle (LV) or tricuspid atresia. The ventricle can be hypoplastic when the ventricular septum is intact and there is critical stenosis of the pulmonary valve. All of these entities are dealt with elsewhere in this book. This chapter is concerned with pulmonary atresia in the setting of an intact ventricular septum ( Fig. 43.1 ) and includes the situation in which the cavity of the RV is dilated, as well as hypoplastic. In two of the final encyclopedic reviews led by Freedom, attention was directed to the huge problems produced by lesions of the coronary arteries or tricuspid valve in this setting, making it one of the most lethal of current congenital cardiac malformations. It was not without reason that Freedom had previously commented, in one of his many perceptive reviews of this lesion, “How can something so small cause so much grief?”
Genetics, Embryogenesis, and Incidence
Pulmonary atresia with intact ventricular septum is a relatively uncommon disease, accounting for about 3% of serious congenital heart disease at birth. It is the third most common type of cyanotic congenital cardiac malformation in neonates, coming after transposition and tetralogy of Fallot with pulmonary atresia. The distribution according to sex was 1.5 males to 1 female in the population-based study carried out in the United Kingdom and Ireland from 1991 through 1999, with figures of 1.3 : 1 in the Swedish-based study. The estimated prevalence at birth from the various epidemiologic studies varies from 4.2 to 8.5 per 100,000 live births.
These data, of course, reflect the prevalence of the disease at birth. The advent of fetal echocardiography has shown that there may be significant spontaneous death during fetal life. In particular, those fetuses with severe tricuspid regurgitation seem to have a poor outcome, often developing hugely dilated atriums, hypoplasia of the lungs, atrial arrhythmias, ascites, and pleural and pericardial effusions. In the collaborative study performed in the United Kingdom and Ireland, only about one-third of those diagnosed during fetal life survived to become live births. The prevalence at birth in mainland Britain is estimated to have fallen by 26% because of fetal diagnosis and selective termination of affected individuals.
Morphogenesis and Etiology
Morphogenesis
As for many types of congenital heart disease, the morphogenesis of the lesion remains unclear. The very presence of an intact ventricular septum strongly implies that development has proceeded normally beyond 8 weeks of gestation, this being the time at which there is normal closure of the embryonic interventricular communication. The pulmonary valve will have been patent at this stage of development. It follows that the developmental insult that produces pulmonary atresia likely occurs subsequent to closure of the interventricular communication. The leading paradigm holds that the primary developmental insult initially produces valvar stenosis, which progresses to atresia. This view is supported by evidence from fetal echocardiography, which has documented cases of progression from pulmonary stenosis to atresia. The insult promoting such initial stenosis, and ultimately fusion, of the valvar leaflets, however, has yet to be identified.
An alternative thesis has been proposed in which, at least in those with fistulous connections, the primary disease may be one of persistence of these communications, or abnormal morphogenesis of the RV, rather than the pulmonary valve itself. Here it is believed that in the presence of high prenatal RV afterload, blood would preferentially pass through the fistulous communications, rather than the pulmonary valve, leading to pulmonary stenosis and atresia.
Etiology
The fundamental etiology of pulmonary atresia has not been elucidated. Both developmental and acquired etiologies have been proposed. The lesion has been observed in siblings, which raises the possibility of a genetic mechanism in some cases. There have also been observations showing the development of the lesion during fetal life in association with twin-twin transfusion. It seems likely, therefore, that the morphologic entity represents a common endpoint for a range of underlying disorders, both hereditary and acquired during fetal life.
Morphology
By definition, the unifying morphologic abnormality is complete obstruction of the outflow from the morphologically right ventricle in the presence of an intact ventricular septum. The cavity of the RV is usually hypoplastic, but it can be grossly dilated when the tricuspid valve is incompetent or its leaflets are absent, giving the “wall-to-wall” heart. This latter lesion, therefore, can be considered a variant of pulmonary atresia with intact ventricular septum, indeed one of its most lethal forms. It is certainly one of the most difficult to treat. This form of the lesion is discussed in this chapter, even though the cavity of the RV is dilated, along with the tricuspid valvar orifice. In this regard, there had been a vogue for considering the right ventricular cavity as either small or large. Recognition of the degree of cavitary hypoplasia produced by mural hypertrophy is now accepted as the best way of assessing the severity of the malformation, while accepting that some individuals have dilation of the RV, and that patients showing the latter features tend to have a very poor prognosis ( Fig. 43.2 ). The lesion is a global condition affecting the entirety of the RV. The extent of morphologic heterogeneity is illustrated by the frequency in which each anatomic feature occurs within the United Kingdom and Ireland population-based study ( Table 43.1 ).
| Morphologic Feature | Type | N (%) |
|---|---|---|
| Type of pulmonary atresia | Membranous | 130/174 (74.7) |
| Muscular | 44/174 (25.3) | |
| Partite state of the RV | Tripartite | 84/143 (58.7) |
| Bipartite | 48/143 (33.6) | |
| Unipartite | 11/143 (7.7) | |
| Coronary arterial abnormalities | RV-to-coronary fistulas | 60/132 (45.5) |
| Coronary arterial stenoses, interruption and ectasia | 10/132 (7.6) | |
| Ebstein malformation | 18/183 (9.8) | |
| Significant RV dilatation | 8/183 (4.4) | |
| Size of tricuspid valve | Median z -score: echocardiogram a | −5.2 (range, −18.3 to 9.4) |
| Median z -score: autopsy b | −1.6 (range, −2.9 to −0.4) | |
| Size of RV inlet | Median z score a | −5.1 (range, −16.0 to 3.5) |
Hypoplastic Ventricular Cavities
In those with small ventricles, the cavitary hypoplasia is due to mural hypertrophy. First, the thickened walls squeeze out the apical trabecular component of the ventricle. Then, with ongoing hypertrophy, the outlet is obliterated. Eventually, therefore, the inlet is the only effective cavity in those with the smallest RVs. If describing this spectrum in terms of “unipartite” and “bipartite” ventricles, it should be remembered that all three ventricular components are present in all cases. The key to appropriate interpretation is recognition that the increasing muscular hypertrophy squeezes out the different parts of the RV cavity. In those with the least severely affected hearts, therefore, all three parts of the ventricular cavity are well formed, with minimal mural hypertrophy ( Fig. 43.3 ).
In these hearts with minimal mural hypertrophy, the outlet component is patent to the undersurface of the imperforate pulmonary valve, which separates the right ventricular cavity from that of the pulmonary trunk (see Fig. 43.3 , right ). With increasing hypertrophy of the walls and obliteration of the apical component of the ventricle, the cavity is effectively formed by the inlet and outlet components. In this situation, the infundibulum still extends to the undersurface of the imperforate valve, but through a very narrow channel. The inlet component also becomes hypoplastic, with the tricuspid valve tethered by short cords to the margins of the obliterated apical component. All three initial parts of the morphologically right ventricle remain identifiable in the hearts with effectively bipartite ventricular cavities. This remains the case when mural hypertrophy has also squeezed out the outlet of the ventricle ( Fig. 43.4 ). Individuals having hearts with the cavity effectively represented by only the grossly hypoplastic ventricular inlet ( Fig. 43.5 ) represent the most severely incapacitated patients with pulmonary atresia and intact ventricular septum.
When the outlet component is also obliterated, it is not possible to trace a patent infundibulum to the ventriculoarterial junction, although evidence of the channel initially present can be seen within the ventricle (see Fig. 43.5 , left ). When examined from the arterial aspect, it can be seen that the pulmonary trunk retains its origin from the RV (see Fig. 43.5 , right ) so that the ventriculoarterial connections remain effectively concordant. The blind-ending pulmonary trunk originates above the triradiating sinuses, with the central dimple indicating that they did, initially, support valvar leaflets. The tricuspid valve is grossly hypoplastic in the hearts in which the cavity of the RV is represented essentially by only the inlet component, but the leaflets themselves are usually minimally malformed. Because of this, the hypertrophied myocardium is able to generate suprasystemic ventricular pressures. Hearts of this type are typically associated with abnormalities of the coronary arteries. In the most severe cases, the proximal portions of both coronary arteries can be obliterated, with the entirety of the coronary arterial tree fed through fistulous communications from the RV. In less severe instances, interruptions are still found in the origin or course of either the right or the left coronary arteries ( Fig. 43.6 ).
A significant portion of the coronary arterial supply in such instances will again be provided by fistulous communications from the RV, underscoring the so-called right ventricular–dependent coronary arterial circulation, which creates major problems in treatment. Therefore fistulous communications are the key to diagnosis of the state of the coronary arterial tree. It is rare to find such communications except when there is gross mural hypertrophy and a poorly formed cavity. This makes recognition of obliteration of the infundibulum an important diagnostic feature when seeking to determine the best options for treatment.
Because the size of the tricuspid valve parallels the diminishing RV cavity, measurement of the valve serves as a reasonably good guide to the volume of the hypoplastic ventricular cavity. The tricuspid valvar apparatus itself shows varying degrees of malformation in most cases. Dysplasia of the leaflets is common but does not correlate with the size of the cavity. Ebstein malformation is the most common abnormality. Ebstein malformation, or severe valvar dysplasia, is a ubiquitous finding in cases with dilated ventricles, but failure of full delamination of the septal leaflets can also be found when the cavity is hypoplastic ( Fig. 43.7 ).
Exaggerated persistence of the valves of the systemic venous sinus is also a frequent finding in hearts with ventricular cavitary hypoplasia. A deficiency of the floor of the oval foramen, or patency of the foramen, is a universal finding. The pulmonary trunk is usually mildly hypoplastic or of normal size ( Fig. 43.8 , left ). On occasion, it may be small, or even no more than a threadlike solid cord (see Fig. 43.8 , right ).
The dimensions of the pulmonary trunk show no correlation with the size of the right ventricular cavity. Even those with a tiny RV can have a pulmonary trunk of near-normal size. Almost always the pulmonary arteries are fed through a persistently patent arterial duct. Should systemic-to-pulmonary arteries be encountered, the suspicion should be raised that initially there was an interventricular communication, but that the hole between the ventricles closed during fetal life.
With Dilated Right Ventricular Cavity
Patients with dilated cavities, along with those having RV-dependent circulations, present the greatest problems in treatment and have the worst prognosis. The dilation of the cavity occurs during fetal life, so when the patients present at birth, the heart fills the entirety of the thoracic cavity, producing the “wall-to-wall” heart ( Fig. 43.9, top ). Significant tricuspid regurgitation is present in most of these cases.
The pulmonary atresia itself is usually produced by an imperforate pulmonary valve, and the pulmonary arteries are typically of good size, being fed through the persistently patent arterial duct. The problem lies with the tricuspid valve, which exhibits either severe Ebstein malformation (see Fig. 43.8 , bottom ), or significant tricuspid valvar dysplasia. The consequence of the gross dilation of the heart is that the lungs become squeezed during fetal life, and do not develop properly hypoplastic lungs. All the component parts are present, but they are unable to expand in appropriate fashion because almost all the space within the thorax is occupied by the heart. The walls of the RV also become excessively thin. Such myocardial thinning, existing as a consequence of ventricular dilation, should not be misinterpreted as representing the Uhl anomaly. The latter lesion is the consequence of congenital absence of the myocardium in the parietal walls of the RV, and is found with normal tricuspid and pulmonary valves.
Segmental Combinations
In typical pulmonary atresia in the setting of an intact ventricular septum, there is usual atrial arrangement, with concordant atrioventricular, and potentially concordant ventriculoarterial connections, with the atretic pulmonary trunk arising from the morphologically right ventricle. In exceedingly rare circumstances, pulmonary atresia can be found in the setting of an intact ventricular septum when the ventriculoarterial connections are discordant. In this setting, because of the discordant connections, the atretic pulmonary trunk arises from the morphologically left rather than right ventricle. Hence left ventricular hypoplasia dominates the picture, typically with the ventricle having a fibroelastotic lining as is the case in hypoplasia of the left heart with usual segmental combinations (see Chapter 69 ). This rare variant of pulmonary atresia with intact ventricular septum can be found either with concordant or discordant atrioventricular connections. As far as we are aware, it has not been found in the setting of isomeric atrial appendages.
Clinical Diagnosis
Prenatal Diagnosis
Fetal echocardiography is now well established, and it has proved to be effective at detecting the lesion. Cases are usually detected because of an abnormal four-chamber view on echocardiography, but prenatal identification of tricuspid regurgitation, and even recognition of coronary arterial abnormalities, is now feasible. On the mainland of the United Kingdom, even by the early 1990s, two-fifths of all cases were diagnosed during fetal life. The proportion at the current time is likely to be even higher. This has changed the natural history of the disease, leading at least in the United Kingdom to selective termination of pregnancy, fetal intervention, and planned delivery.
Postnatal Diagnosis
After birth, infants present with cyanosis in the neonatal period, and/or a “failed” pulse oximetry screening. The arterial duct is the sole source of blood flow to the lungs, although this channel rarely remains widely patent for more than a few days. Very rarely, patients may be found with systemic-to-pulmonary collateral arteries, but usually, as soon as the duct narrows, arterial desaturation increases, and visible cyanosis results. Infants with severe tricuspid regurgitation may also show signs of congestive heart failure and respiratory distress.
Physical Findings
The usual physical findings can be explained by the abnormal morphology. Cyanosis has already been discussed. Pulses and blood pressure are normal because systemic cardiac output is not impaired. The jugular venous pulse is hard to evaluate in newborns, and is not a useful diagnostic sign. Precordial motion is normal because a pure pressure overload of the RV does not usually result in an exaggerated left parasternal lift. The second heart sound at the high left sternal border is soft and single, or is inaudible. The first heart sound is normal, and an ejection sound is not present. Several murmurs may be heard. The most common is a soft high-pitched continuous murmur at the high left sternal border. This murmur originates in the duct, and is usually quite subtle. Occasionally, it may be heard only intermittently, disappearing when the duct narrows and cyanosis deepens, and appearing again as the duct opens and cyanosis lightens. Some infants with pulmonary atresia have a soft high-pitched systolic murmur of tricuspid regurgitation at the low left sternal border. The presence of this murmur correlates strongly with a relatively large RV, but lack of a murmur of tricuspid regurgitation does not rule out an RV of normal size. When there is severe tricuspid regurgitation, there is often a soft, medium-pitched, mid-diastolic murmur at the low left sternal border, representing increased tricuspid flow. Such a murmur is not heard in those with severe tricuspid stenosis alone because there is little or no flow across such a valve in the presence of pulmonary atresia. Some infants with pulmonary atresia have no murmur. In this situation, the only indication of congenital cardiac disease on physical examination is the severe cyanosis.
Investigations
Electrocardiography
The electrocardiogram is usually abnormal, and reflects the abnormal morphology. The frontal plane axis is less rightward than normal, usually between 30 and 90 degrees. Most newborns have an adult precordial pattern, rather than the usual right ventricular hypertrophy ( Fig. 43.10 ). Less commonly, the pattern of right ventricular hypertrophy is present. It must be noted that the electrocardiographic patterns of right ventricular hypertrophy, or of left ventricular predominance, do not reliably predict right ventricular size. ST–T wave changes suggestive of myocardial ischemia are occasionally present and may be related to the abnormal coronary arteries. The tall peaked P waves of right atrial enlargement may be present.
Chest Radiography
There is no characteristic radiographic appearance. The abdominal organs are normally positioned, and the heart is left-sided. The bronchi are normally lateralized, and the aortic arch is left-sided. Pulmonary vascular markings are not increased, but the distinction between normal and decreased markings is difficult at best in the neonatal period, which is when most infants with pulmonary atresia present. The cardiac contour is not distinctive, and there is a wide range of cardiac size, from normal to wall-to-wall ( Fig. 43.11 ). Although the very largest hearts occur when there is severe tricuspid regurgitation, the size of the heart is not a reliable predictor of the size of the right ventricular cavity.
Echocardiography
Cross-sectional echocardiography is the diagnostic investigation of choice. In addition to confirming the diagnosis, it is important to document all the morphologic features systematically, and use the findings to determine the optimal strategy for treatment. In the first instance, the atrial arrangement should be confirmed. The right atrium will often be dilated. Any prominent venous valves should be noted. The oval foramen is usually widely patent before, but not always after, construction of a systemic-to-pulmonary shunt. Next, the morphology of the tricuspid valve should be assessed, documenting any dysplasia or displacement of the leaflets. The degree and velocity of regurgitation should be recorded ( Fig. 43.12 ; ). The diameter of the valvar orifice should be measured, and converted to a z score using published nomograms. The measured orifice may not represent the effective orifice, particularly where there is limited opening due to tethering or raised filling pressures.
The RV should be assessed to determine its overall size and the degree of mural overgrowth ( Fig. 43.13 ). A judgment should be made as to whether the cavity possesses all three of its components, or only one or two ( and ). In our experience, the right ventricular cavity may seem smaller echocardiographically than it appears angiographically, largely because the apical trabecular zone may seem completely obliterated when, in reality, there are intertrabecular spaces. The presence of tiny ventricular septal defects should be noted. An assessment of the patency of the infundibulum should be made ( ), particularly from the subcostal paraoblique view. The atresia may be membranous ( Fig. 43.14 ) or muscular depending on the extent of muscular mural hypertrophy. The presence of any forward or retrograde flow across the pulmonary valve should be assessed to exclude critical pulmonary stenosis or functional atresia. The presence of any fistulous communication to the coronary arteries should be sought ( Fig. 43.15 ; ).
The pulmonary trunk and branches should be measured to ascertain their size, and the source of blood flow to the lungs determined. Normal pulmonary venous return should be confirmed. Structure and function of the left ventricle should be assessed, including regional abnormalities of mural motion.
Following such investigations, it should be possible to decide whether the long-term strategy is for biventricular as opposed to univentricular repair, and to plan the initial intervention.
Cardiac Catheterization and Angiography
In addition to echocardiography, from a diagnostic perspective, cardiac catheterization and angiography may be helpful in the evaluation of an infant with this lesion, particularly to assess the size of the RV and the presence and severity of fistulous communications. The usual approach is via the femoral vein because it can be difficult to enter the RV from the umbilical vein. The latter approach can be used, however, for balloon atrial septostomy if a univentricular repair is planned. Oximetry is not particularly helpful, except to show right-to-left shunting at the atrial level.
A step-up from right atrium to ventricle of more than 6% is said to be indicative of retrograde flow into the RV from coronary arterial fistulous connections. Mean right atrial pressure is usually slightly higher than left atrial pressure, but a large gradient is not expected because the oval foramen is usually large and widely patent. Right ventricular pressure is typically suprasystemic, although right ventricular pressure is low if tricuspid regurgitation is very severe (see Table 43.2 ). If the RV is small, it may be entered only after repeated probing with an end-hole catheter.
| RV Inlet z -Score (Increased Inlet Length) | Ductal Angle (Normal) | Fistulae (Absence) | Type of Atresia (Membranous) | Partite (Tripartite) | Stenoses (Absence) | Tricuspid Regurg. (Increased) | RV Pressure (Lower) | |
|---|---|---|---|---|---|---|---|---|
| TV z -score (increased valve size) | <.0001 R = 0.45 | .0120 | <.0001 | <.0001 | <.0001 | .1763 | .0050 | .0011 R = 0.402 |
| RV inlet z -score (increased inlet length) | .3304 | .0011 | .0131 | <.0001 | .5755 | .0052 | .7459 R = 0.041 | |
| Ductal angle (normal) | .0095 | <.0001 | <.0001 | .0852 | .0743 | .3077 | ||
| Fistulas (absence) | <.0001 | <.0001 | .0055 | .0321 | ||||
| Type of atresia (membranous) | <.0001 | >.9999 | .0140 | .1938 | ||||
| Partite (tripartite) | .8409 | .0022 | .9720 | |||||
| Stenoses (absence) | .2090 | .0008 | ||||||
| Tricuspid regurgitation (increased) | .0143 |
The diagnosis will usually have already been made by echocardiography and can be confirmed by a right ventriculogram. Assessment of right ventricular size is far from simple in often bizarrely shaped RVs ( Fig. 43.16 ). Stenosis or atresia of the infundibulum can be diagnosed. If an imperforate pulmonary valve is present, it may be seen moving to and fro at the top of a patent infundibulum. Tricuspid regurgitation can be approximately quantified because catheter-induced regurgitation is usually mild. Coronary arterial fistulous connections are also well demonstrated by right ventriculography. Stenoses in, or interruption of, both right and left coronary arteries should be sought. If there is doubt about the coronary arterial anatomy or distribution after the right ventriculogram, an injection should be performed in the aortic root. As summarized by Freedom and colleagues in their excellent review, and listed in decreasing order of severity, coronary abnormalities include:
- ▪
Atresia of the aortic orifices of both coronary arteries.
- ▪
Atresia of the aortic orifice of the left coronary artery.
- ▪
Proximal interruption or occlusion of the main stem of the left coronary artery, its anterior interventricular or circumflex branches, or the right coronary artery (see Fig. 43.6 ), combined with fistulous communications from the RV.
- ▪
Important stenosis of the main stem of the left coronary artery, its anterior interventricular or circumflex branches, or the right coronary artery, in combination with fistulous communications from the RV. Less severe abnormalities could also progress with time.
- ▪
Presence of a huge fistulous communication from the RV to a coronary artery (see Figs. 43.6 and 43.12 ). Decompression of the RV in this setting would result in a massive steal, and hence result in coronary arterial insufficiency.
