The heart may be only mildly enlarged, or it may be massively enlarged, with a hugely dilated right atrium occupying much of the right hemithorax. In this latter situation, the lungs may be compressed by the enlarged heart and may exhibit a varying degree of hypoplasia. When the heart is only mildly enlarged, the course of the anterior descending coronary artery in the anterior interventricular sulcus outlines a smaller than normal right ventricle. The right atrium is usually somewhat enlarged, accounting for the cardiomegaly. The right ventricle may be profoundly thinned and this may be apparent even with the heart in situ.

From external inspection of the heart, there may be obvious clues that there are significant abnormalities of the coronary artery circulation. The coronary arteries may be obviously thickened and nodular, and rarely the coronary arteries may be seen connecting with the pulmonary trunk. Severe abnormalities may be readily apparent with epicardial aneurysmal dilation (Fig. 40.1). So-called dimples may be observed on the epicardial surface of the heart, usually, but not exclusively, in association with the subepicardial coronary arteries. Such dimples may be considered the external stigmata of ventriculocoronary connections and may indicate the site of such connections.

Braunlin et al. (20) documented the morphologic bases for pulmonary atresia in this disorder, correlating the type of imperforate pulmonary valve with the character of the right ventricle and its infundibulum. In patients with a well-formed infundibulum the imperforate pulmonary valve exhibits three semilunar cusps with complete fusion of the commissures (Fig. 40.2). The pulmonary valve is primitive in patients with a diminutive right ventricle and a severely narrowed or atretic infundibulum. As described in the
previous section, the muscular nature of the infundibulum has received morphologic, clinical, and angiocardiographic attention, and the nature of those right ventricular muscle bundles contributing to the infundibular atresia has been described.

A peculiar relationship exists between persistent right venous valve, ventriculocoronary connections, and pulmonary atresia with intact ventricular septum. It would be too simplistic, indeed incorrect, to speculate that a persistent venous valve is causal to right heart hypoplasia. The coronary sinus usually terminates in the right atrium. Stenosis and atresia of the coronary sinus ostium have been observed, with decompression through an unroofed coronary sinus–left atrium fenestration.

Because of the obligatory right-to-left shunt at atrial level, with rare exception, there is either a patent foramen ovale or true secundum atrial septal defect. Premature closure of the foramen has been observed in this disorder, usually with fetal death. Rarely, if the interatrial septum is intact or nearly so, alternative pathways for systemic venous return have been recognized, including coronary sinus–left atrial fenestration. The septum primum may assume aneurysmal proportions in patients with a restrictive atrial septal defect, and its herniation through or obstruction of the left ventricular inflow has been observed.

The tricuspid valve is rarely normal in patients with pulmonary atresia and intact ventricular septum. This atrioventricular valve demonstrates the continuum of abnormalities and a functional impact that ranges from extreme stenosis to profound regurgitation (21) (Fig. 40.3). The stenotic valve can demonstrate a hypoplastic obstructive annulus that may be muscularized with a very abnormal valve apparatus consisting of a thickened free valve margin, shortened dysplastic chordae, and papillary muscle abnormalities. The severely regurgitant valve can be characterized by a dilated annulus. In this situation, the valve exhibits both profound displacement with the severest form of Ebstein anomaly and dysplasia. In some severely regurgitant valves, the valve is not displaced, but it is extremely dysplastic. Rarely, the valvar orifice may be virtually unguarded, a situation similar to profound Ebstein anomaly (22). The most severely stenotic and obstructive tricuspid valve is observed in patients with the most hypoplastic of right ventricles. Conversely, patients with a large right ventricle usually have severe tricuspid regurgitation with a valve exhibiting features of Ebstein anomaly and dysplasia. This latter malformation represents a major management challenge with a poor overall prognosis.

Clinicians and pathologists have attempted to characterize the size of the right ventricle in this disorder for decades. Methodologies have included angiocardiographic volumetric analysis, a variety of measurements of the inlet/outlet axis and the convention advocated
by the Congenital Heart Surgeons Study (CHSS); the use of the so-called tricuspid diameter Z-value (5). This reflects the deviation of the valvar diameter from that expected for body surface area and was based on an early pathologic study of the normal quantitative anatomy. Data from the CHSS showed that the Z-value of the tricuspid valve was correlated with the size of the right ventricular cavity (r = 0.68, p <0.0001) and this relationship has been confirmed in more recent studies as well (23). This continues to be referenced to the present day.

Others have advocated a semimorphologic approach to the right ventricle. Although there is no consensus as to whether the morphologically right ventricle is embryologically a bipartite or tripartite structure, there are examples of congenitally malformed hearts that may support the view of the right ventricle as a tripartite structure. Taking this latter approach, the normal right ventricle can be considered to be composed of confluent inlet, apical trabecular, and outlet components. This approach has been used widely in the categorization of patients with pulmonary atresia and intact ventricular septum. Thus, some patients have pulmonary atresia and intact ventricular septum wherein the right ventricle is particularly well formed and all three components are well represented. In others, the right ventricle is extremely underdeveloped and seemingly limited to an inlet only (24) (Figs. 40.3C–E and 40.4). Attempts to characterize the size of the right ventricle are plagued by difficulty in assessing the contribution of muscular hypertrophy of the apical and outlet myocardium (25). This has tremendous impact on clinical management, as it appears that relief of outflow tract obstruction with associated pulmonary insufficiency may result in remodeling with regression of hypertrophy that can result in real or perceived growth of the right ventricle (25,26,27,28,29,30,31,32).

The left atrium usually receives the pulmonary veins in a normal fashion, although one or more pulmonary veins may connect anomalously to the systemic circulation. The left ventricle may
exhibit variable degrees of hypertrophy, especially in patients who survive past infancy. Some years ago, attention was given to a convexity of the outlet portion of the interventricular septum that occurred in those patients with small and extremely hypertensive right ventricles (Fig. 40.5). In this setting, severe left ventricular outflow tract obstruction resulting in death occurring after surgical creation of a cavopulmonary connection has been observed when there is an unfavorable change in the ratio between left ventricular mass and end-diastolic volume (33,34). Aortic valve stenosis has been described in patients with pulmonary atresia and intact ventricular septum, including the neonate with critical aortic stenosis and the somewhat older child with severe aortic valve stenosis (35). With rare exceptions, the aortic arch is left sided.

Confluent pulmonary arteries usually receive flow from a left-sided ductus arteriosus. Rarely, nonconfluent pulmonary arteries are supported by bilateral ductus arteriosus or aortopulmonary collaterals (36). A main pulmonary trunk is almost always present. Unlike the patient with pulmonary atresia with ventricular septal defect, the caliber of the pulmonary arteries in patients with pulmonary atresia and intact ventricular septum is rarely a major determinant of outcome. This may be in part mediated by the observation that the arterial duct tends to close earlier in patients with pulmonary atresia and intact septum than it does in patients with pulmonary atresia and ventricular septal defect (37). More recently transcatheter means of maintaining pulmonary blood flow such as stenting of the arterial duct have necessitated increased awareness of the assessment the neonatal anatomic details of the pulmonary artery at the insertion of the patent ductus arteriosus (38,39,40,41).

The myocardium of patients with pulmonary atresia and intact ventricular septum can demonstrate a wide range of abnormalities. Ischemia, fibrosis, infarction, and myocardial rupture have been observed in these patients (42,43,44,45,46,47) (Fig. 40.6). Other abnormalities include myocardial disarray, the appearance of the so-called spongy myocardium, and ventricular endocardial fibroelastosis. In this regard, an inverse relationship exists between ventricular endocardial fibroelastosis and extensive ventriculocoronary communications. Perhaps this observation is fundamental to the frequent finding of ventriculocoronary connections in pulmonary atresia and intact ventricular septum: dense, “sugar-coated” right ventricular endocardial sclerosis is uncommon. Conversely, dense, sugar-coated left ventricular endocardial sclerosis is common in patients with a hypoplastic left heart syndrome; but a perforate mitral valve, and thus ventriculocoronary connections, is uncommon. The right ventricular myocardium may be particularly thinned in babies with severe tricuspid regurgitation.

It is important to gain an understanding of the status of the coronary circulation in patients with pulmonary atresia and intact ventricular septum prior to proceeding with an interventional algorithm as myocardial ischemia may be related to the presence and extent of these ventriculocoronary connections. An extensive literature has documented the vast array of changes in the coronary arteries among some patients with pulmonary atresia and intact ventricular septum (48,49,50,51,52). Several articles have characterized the histopathologic alterations of the involved coronary arteries. This process is not characterized by inflammation, as once thought, but more appropriately as myointimal hyperplasia with a rich background of glycosaminoglycans. There is a wide spectrum of histopathologic lesions of both the extramural and intramural coronary arteries. These lesions range from mild degrees of intimal and medial thickening in which a continuous internal elastic lamina and normal lumen are present to a loss of normal arterial wall morphology with replacement of
the arterial wall by fibrocellular tissue containing irregular, disorganized elastin strands and severe stenosis or obliteration of the arterial lumen. Some have designated these changes as fibroelastosis of the coronary arteries, but emphasis would be more appropriately focused on myointimal hyperplasia. Staining for glycosaminoglycans shows the prominence of ground substance formation by the activated smooth-muscle cells rather than the reduplicated elastic and collagen characteristic of fibroelastosis (Fig. 40.7). This pathologic process leads to a profound distortion of the normal architecture, resulting in endothelial irregularity, stenosis, or interruption. Such coronary arterial involvement occurs only in patients with ventriculocoronary connections and, by inference, with a hypertensive right ventricle. The pathogenesis of these arterial lesions is likely predicated on the repeated and sustained injury to the coronary arterial intima from high-pressure right ventricular systolic turbulent flow mediated by the presence of the ventriculocoronary connections. Intramural or extramural coronary arteries remote from the ventriculocoronary connections do not demonstrate these arterial lesions, nor do the coronary arteries of hearts without ventriculocoronary connections. These lesions have been found in fetal hearts with pulmonary atresia and intact ventricular septum and in hearts of the immediate newborn. Ventriculocoronary connections do not occur in thin-walled, low-pressure right ventricles.

The coronary abnormalities in patients with pulmonary atresia and intact ventricular septum embrace the same spectrum of abnormalities as those seen in patients with otherwise normal hearts, including abnormalities of origin, epicardial course, and number. A single coronary artery may originate from the aorta or, rarely, from the pulmonary trunk. Several congenital and acquired conditions of the coronary circulation are specific to pulmonary atresia and intact ventricular septum and impact surgical management. These conditions include an absence of a proximal aortocoronary connection between one or both coronary arteries, coronary arterial stenosis or interruption, or a so-called coronary–cameral fistula with a major fistula between right or left coronary artery and the right ventricle. Particularly rare arterial connections such as those from the descending thoracic aorta or the gastric artery to the coronary circulation have been described.

Intrinsic to awareness of ventriculocoronary connections in this disorder and their impact on the myocardium is the concept of a right ventricular–dependent coronary circulation (Table 40.1). In the normal circulation, it is in large part the aortic diastolic pressure that is the driving pressure for coronary flow. Factors that reduce aortic diastolic pressure or shorten diastole will compromise coronary flow. The presence of ventriculocoronary artery connections may promote coronary artery stenosis and interruption, and aortic diastolic pressure may not be sufficient to drive coronary blood flow when obstructive lesions are present within the coronary circulation. It is important to remember that these infants are hemodynamically fragile, tachycardic, and often receiving prostaglandin or palliated with a systemic-to-pulmonary artery shunt to augment pulmonary flow. Notably these therapeutic maneuvers will reduce aortic diastolic pressure therefore coronary flow from the hypertensive right ventricle occurring during systole through the ventriculocoronary connections may be necessary to sustain adequate myocardial perfusion. In a coronary circulation that is wholly or in part right ventricular dependent, it is the blood that gets into the right ventricle at systemic or above-systemic right ventricular systolic pressure that supplies the dependent myocardium in a retrograde fashion. Unfortunately this process can lead to further coronary arterial distortion. The management corollary to this is clear: interference of flow into the right ventricle or a reduction in right ventricular systolic pressure in situations in which the coronary circulation is dependent on the right ventricle may result in myocardial ischemia, infarction, and death.

There is unequivocally a predisposition to ventriculocoronary connections among patients who have the smallest right ventricles. Thus, it is unlikely but not impossible to define such abnormal communications in patients with a normal-sized right ventricle or with a nearly normal right ventricle (53). It is much more likely to observe ventriculocoronary communications in patients whose ventricles have been categorized as unipartite or bipartite. Using the convention of the tricuspid Z-value, data from the CHSS demonstrated a positive correlation with ventriculocoronary connections. A negative tricuspid Z-value correlated with the presence of ventriculocoronary connections. Data from this study support the observation that the smallest tricuspid valves (i.e., the most negative Z-value) are observed in patients with the smallest right ventricles (5). Data
provided by the CHSS indicated that, of the 145 patients for whom this information was available, ventriculocoronary connections were observed in 45%. In 9% of the 145 patients, the coronary circulation was considered wholly right ventricular dependent. Ventriculocoronary connections may involute after successful right ventricular decompression (whether by pulmonary valvotomy or tricuspid valve excision or avulsion). Such involution has been demonstrated in the newborn and in the older patient. After a reduction in right ventricular pressure, there is always the possibility that flow from the coronary artery to the right ventricle might occur or become exaggerated, and this phenomenon has been recognized.

Perhaps of more concern is a determination of the timing of the occurrence of coronary arterial obstructive lesions, coronary artery stenosis, or interruption. Such coronary arterial obstructive lesions can occur in fetal tissues and these lesions have been identified clinically by both angiography and by histopathology in hearts from patients who die in the first few hours and days after birth. Thus, such changes should not be interpreted as a later, acquired postnatal phenomenon (49). Obviously, some changes may be acquired late, but clearly obstructive coronary arterial lesions may be present and identified in the immediate newborn.

Newborns with pulmonary atresia and intact ventricular septum become cyanotic and hypoxemic coincident with functional and anatomic closure of the patent arterial duct. In rare patients in whom the interatrial communication is truly restrictive, the cardiac output may be affected as well by restricting the obligatory right-to-left shunt.

There is no known sex predilection, and there is no identified genetic predisposition, although familial cases have been described as well as an occurrence in monozygotic twins (54). It has been assigned to a single gene theory in at least one instance (55). Infants typically are born at term. Cyanosis is usually apparent within hours of birth and is progressive. Dyspnea is not conspicuous without significant acidosis, reduced cardiac output, or pulmonary hypoplasia but tachypnea may be prominent.

In the absence of profound cardiac enlargement, the left precordium will not bulge. The left ventricle may be enlarged, and at the apex, its impulse may be forceful. The first and second heart sounds are single. A pansystolic murmur often is audible at the left lower sternal border, consistent with tricuspid regurgitation. In infants with severe tricuspid regurgitation, the murmur of tricuspid regurgitation is conspicuous, sometimes associated with a thrill, and a tricuspid diastolic rumble may be audible. A murmur of the arterial duct may be distinguished in the second and the third left intercostal space, especially after prostaglandin has been administered to promote ductal patency. Unless the atrial septum is profoundly restrictive, affecting cardiac output, the caliber of the arterial pulses is normal. The liver is not particularly enlarged unless there is severe tricuspid insufficiency or a restrictive foramen ovale.

The most striking and consistent finding before prostaglandin is administered is hypoxemia refractory to increased inspired oxygen concentration and a mild degree of hypocarbia, reflecting the tachypnea. Significant metabolic acidosis usually indicates progressive hypoxic cellular damage signifying imminent death in the absence of intervention.

The chest radiograph may demonstrate a heart that is only mildly enlarged or one that fills the entire chest cavity. In the former, the pulmonary vascular markings are reduced, which may be confirmed on the lateral radiograph, where hilar pulmonary arterial markings are sparse. In the latter situation, with massive cardiomegaly, it may be difficult to define enough pulmonary parenchyma to evaluate the lung markings. The differential radiographic diagnosis of extreme cardiomegaly in the newborn includes the conditions shown in Table 40.2.