Introduction
Channels permitting shunting between the atrial chambers are important congenital cardiac anomalies because they are relatively common and are more nearly completely correctable than most other cardiac malformations, even more so in the era of catheter intervention. It may be difficult, nonetheless, to diagnose the presence of such communications, and often there is no suspicion of cardiac disease during infancy and early childhood. Moreover, the anatomic arrangement may be more complex than a mere deficiency of the floor of the oval fossa. Anatomic features underscore the specific description of these lesions as interatrial communications rather than the more usual reference to “atrial septal defects.” The subtle differences between true atrial septal defects and interatrial communications are emphasized in the initial section, devoted to morphology. The lack of early symptoms coupled with the added subtlety of the physical findings can delay the diagnosis, sometimes until well into adult life or even until middle or old age. Nonetheless, a clinical diagnosis can still be made on the basis of a meticulous cardiac physical examination. The chest radiograph and electrocardiogram usually support such diagnosis, but echocardiography and Doppler studies are diagnostic in virtually all cases. Therapeutic intervention during childhood, after documentation of an important shunt at atrial level, should now result in a normal life expectancy, free of cardiac morbidity. With the increasing use of transcatheter devices, this can now frequently be achieved without the need for surgery.
Incidence
Interatrial communications account for up to 10% of all congenital cardiac anomalies. Probe patency of the oval foramen, furthermore, is remarkably frequent, being found in up to 33% of hearts examined at autopsy irrespective of age. The suggestion that probe patency may underscore some cases of migraine brought this normal finding to clinical attention, although the suggested association has yet to be proven.
Etiology
There are no known intrauterine events that predispose to deficient atrial septation. Thus most cases occur sporadically, with no family history of congenital cardiac disease. Nonetheless, there is a significant familial incidence when the lesion is associated with certain skeletal abnormalities of the forearm and hand, called Holt-Oram syndrome. This has now been shown to be due to mutations of the Tbx5 gene, a member of the Brachyury family of genes. When observed in families, atrial septal defects are also associated with prolongation of the PR interval.
Morphology and Classification
Normal Atrial Septum
An understanding of the morphology and classification of interatrial communications depends on knowledge of the extent of the normal atrial septum. This, in turn, requires an appreciation of the difference between partitions that separate the atrial cavities, which can be removed without transgressing on the pericardial cavity, as opposed to the removal of folds, which do produce a communication with the extracavitary space ( Fig. 29.1 ).
Thus, when one views the septal surface of the right atrium, it seems at first sight that a large expanse of the atrial walls between the orifices of the superior and inferior caval veins and the attachment of the septal leaflet of the tricuspid valve are potentially interposed between the cavities of the right and left atria ( Fig. 29.2 , left ).
When the heart is sectioned across the oval fossa, its anterior and posterior rims are seen as folds between the atrial walls (see Fig. 29.2 , right ). Sections taken through the atrial chambers in the frontal plane show that the superior rim of the fossa, often considered to represent the septum secundum, is similarly a fold (see Fig. 29.1 ). This fold is the area known to surgeons as the Waterston or Sondergaard groove. Inferiorly, the rim separates the fossa from the orifice of the coronary sinus, with the mouth of the coronary sinus itself separated from the mouth of the inferior caval vein by an additional fold, the sinus septum . The tendon of Todaro, one of the important landmarks of the triangle of Koch, runs through this area to insert into the central fibrous body (see Fig. 29.2 , left ). This anteroinferior muscular buttress, traversed by the tendon, is another true septal structure ( Fig. 29.3 ).
Thus only the floor of the oval fossa and the anteroinferior muscular buttress constitute true interatrial septal structures, which can be removed without exiting the cavities of the heart (see Fig. 29.1 ).
Types of Interatrial Communication
Recognition of the extent of the normal septum underscores the fact that not all interatrial communications are septal deficiencies. Of the channels that permit interatrial shunting, those within the confines of the oval fossa, along with the much rarer deficiencies of the anteroinferior muscular buttress, are true septal defects. The ostium primum defects, along with the sinus venosus defects and those found at the site of the mouth of the coronary sinus, are interatrial communications, but they lie outside the confines of the atrial septum ( Fig. 29.4 ).
Defects Within the Oval Fossa
These lesions, which are true septal defects, are by far the commonest type of interatrial communication. Although most frequently termed secundum defects , this term is justified only because the defect represents persistence of the second interatrial communication to be formed during cardiac development. Should they be found postnatally, it is because of deficiencies of the floor of the fossa, which is derived from the primary atrial septum. If development proceeds normally, the floor of the fossa is usually of sufficient dimension to overlap the infolded superior rim, often described as the septum secundum . The floor and rim, however, do not always fuse with one another, and failure of such fusion produces the probe-patent oval foramen ( Fig. 29.5 ).
Even if the flap valve fails to fuse with the superior interatrial fold, there will be no interatrial shunting as long as the left atrial pressure is higher than right, which is the normal postnatal situation. Nonetheless, probe patency is known to be responsible for paradoxic embolism and can be an important finding in those undertaking deep sea diving. The suggested association with migraine, however, has still to be proven. The simplest true defect within the oval fossa is found when the flap valve is minimally deficient, so that it fails to entirely overlap the left atrial margin of the rim of the fossa. With increasing deficiency of the flap valve or in presence of a perforated valve, the defect becomes larger ( Fig. 29.6 , left ). In extreme cases there may be no floor to the fossa (see Fig. 29.6 , right ).
When the deficiency is marked, the hole can extend toward the mouth of the inferior caval vein, which may straddle the persisting rim to open in part to the left atrium (see Fig. 29.6 , right ). Although these defects may exist in isolation and do not disturb the location of the conduction tissues, they often occur in combination with many other congenital cardiac malformations, as shown at right in Fig. 29.6 .
Vestibular Defect
The heart shown in Fig. 29.7 , in addition to the multiple perforations in the floor of the oval fossa, has an additional defect in the anteroinferior buttress. This lesion is the second type of true atrial septal defect.
Sinus Venosus Defects
The essence of the sinus venosus defects is that they exist outside the confines of the oval fossa. Found most frequently in the mouth of the superior caval vein, they can also be found at the orifice of the inferior caval vein or draining to the midpoint of the systemic venous sinus. In the case of the superior sinus venosus defect, the orifice of the superior caval vein typically overrides a defect, which has the superior rim of the fossa as its floor ( Fig. 29.8 , left ).
In some instances there is no overriding of the orifice of the superior caval vein (see Fig. 29.8 , right ). Despite the normal attachment of the caval vein to the right atrium, the anomalous attachment of the right pulmonary veins still creates the interatrial communication outside the confines of the intact atrial septum. Therefore the phenotypic feature of the lesions is the anomalous attachment of one or more pulmonary veins to a systemic vein, with the pulmonary veins retaining their left atrial connection ( Fig. 29.9 ).
In this setting the superior rim of the fossa becomes a muscular tube enclosing a corridor of extracardiac fat. A probe can be passed from back to front through the tube without encroaching on the atrial cavities (see Fig. 29.8 , left ). The presence of a superior sinus venosus defect does not markedly affect the site of the sinus node, which is found lateral to the superior cavoatrial junction, lying immediately subepicardially within the terminal groove. Thus a patch placed within the atrium to reconnect the caval vein to the right side should not jeopardize the sinus node. Inferior sinus venosus defects are far less common. They too are associated with an anomalous attachment of the right pulmonary veins, but in these cases the anomalous attachment of the right inferior pulmonary vein creates the extracardiac conduit. Closure of such a defect should not jeopardize either the sinus or the atrioventricular node. Inferior sinus venosus defects must, nonetheless, be distinguished from defects within the oval fossa that extend to the mouth of the inferior caval vein (see Fig. 29.6 , right ). If the middle right pulmonary vein is anomalously connected to the right atrium while retaining its left atrial connection, the sinus venosus defect can drain to the middle part of the smooth-walled systemic venous component of the right atrium ( Fig. 29.10 ).
Coronary Sinus Defects
In the absence of the walls that usually separate the sinus from the left atrium, the right atrial orifice of the sinus becomes an interatrial communication ( Fig. 29.11 ).
Most often a persistent left superior caval vein is also connected to the left atrial roof. In some examples of this combination, filigreed remnants of the atrial wall persist between the orifice of the coronary sinus and the termination of the left caval vein in the left atrium. The opening of the coronary sinus is usually large. Its anterior margin encroaches on the triangle of Koch, approximating the area of the atrioventricular node. Therefore care must be taken when the defect is closed. Unless previously diagnosed, a coronary sinus defect may be difficult to recognize as an interatrial communication in the operating room, appearing simply to be the mouth of the coronary sinus itself. Such defects are significant in the setting of hypoplastic left heart syndrome with intact atrial septum, since they provide an overflow for the obstructed left atrial chamber.
Morphogenesis
During normal development, the first sign of atrial septation is the growth of the muscular primary septum from the roof of the atrial component of the primary heart tube. As it grows down to divide the primary atrium, it carries on its leading edge a cap of mesenchymal tissue ( Fig. 29.12 , left ).
The space between the cap and the atrioventricular endocardial cushions, which divide the atrioventricular canal into the eventual mitral and tricuspid valvar orifices, is the primary atrial foramen. Prior to closure of the primary foramen, the pulmonary vein canalizes within the pharyngeal mesenchyme behind the developing heart, opening to the atrial cavity between the ridges formed at the site of the dorsal mesocardium, which is the initial connection between the heart tube and the pharyngeal mesenchyme (see Fig. 29.12 , right ). The fusion of the cap with the endocardial cushions thus obliterates the primary atrial foramen. The site of closure is reinforced by the growth of additional tissues through the right-sided ridge of the two pulmonary ridges, thus producing the vestibular spine ( Fig. 29.13 , left ). By the time the primary foramen has closed, the cranial origin of the primary septum has broken down to form the secondary atrial foramen (see Fig. 29.12 , right , and Fig. 29.13 , left ).
In the final stages of septation, the upper edge of the remaining primary atrial septum is usually overlapped by the infolding of the atrial roof between the superior caval and pulmonary veins. This fold forms the superior rim of the oval fossa, often described as the septum secundum (see Fig. 29.13 , right ).
Failure of septation of the common atrioventricular junction due to lack of growth of the vestibular spine prevents the lower edge of the primary septum from fusing with the ventricular septum. This results in the ostium primum defect, which is an atrioventricular septal defect with a common atrioventricular junction. This lesion is described further in Chapter 32 . Therefore maldevelopment of the primary atrial septum itself, after it has fused with the ventricular septum and the endocardial cushions, results in defects within the oval fossa. This can be due either to deficiency of its superior edge, so that it no longer overlaps the infolded superior rim, or to breakdown of the septum to a greater or lesser degree, resulting in the various types of perforate or fenestrated defects within the fossa (see Fig. 29.5 ). In the most severe defects, the muscular rim also becomes effaced. It is possible to envisage temporary effacement of the rim of the oval fossa, since this is no more than a muscular infolding. Such effacement in the presence of volume load, with subsequent restoration of the fold once the volume load has been corrected, is a likely explanation for spontaneous closure of some defects within the oval fossa during the neonatal period. Sinus venosus defects are explained on the basis of anomalous connection of the right pulmonary veins to a systemic venous channel, with the pulmonary veins retaining their left atrial connections (see Fig. 29.10 ). The coronary sinus defect is explained on the basis of resorption of the dual walls that usually separate the lumen of the coronary sinus itself from the cavity of the left atrium (see Fig. 29.11 ). The rare vestibular defect (see Fig. 29.7 ) is due to improper fusion or muscularization of the components forming the anteroinferior buttress of the atrial septum; this process involves both the vestibular spine and the mesenchymal cap carried on the leading edge of the atrial septum.
Associated Anomalies
Cardiac
Almost any cardiac disease can be associated with an interatrial communication, and for some its presence is crucial to survival (e.g., totally anomalous pulmonary venous connection, absent left and right atrioventricular connections). Partially anomalous connection of the pulmonary veins is a relatively common associated finding in patients with interatrial communications. Indeed, it is the phenotypic feature of the sinus venosus variety. An oval fossa defect commonly occurs in addition to the primum defect when there is an atrioventricular septal defect, with the most extensive instances (leading to almost complete absence of atrial septation) occurring when there is isomerism of the atrial appendages.
Noncardiac
The association of Down syndrome with ostium primum defects is well known. The incidence of Down syndrome has been only 2.9% in those having surgery for defects in the oval fossa. The skeletal anomalies of Holt-Oram syndrome and electrophysiologic abnormalities are examples of noncardiac anomalies, which occur in a few patients. Familial defects are well reported, with transmission rates of 40% to 100%, suggesting autosomal dominant inheritance. Indeed, if more than two family members are affected, genetic evaluation would be warranted and the screening of other family members and first-degree relatives suggested. As with associated cardiac malformations, noncardiac anomalies are relatively rare in patients with an atrial septal defect.
Pathophysiology
The pathophysiology of interatrial communications depends on the underlying and associated diseases, the resulting hemodynamics, and the size of the defect. In isolated oval fossa defects there is usually a substantial left-to-right shunt, resulting in a high ratio of pulmonary-to-systemic flow. Under these circumstances the primary determinants of the amount of shunting are the size of the defect and the relative resistance to inflow, or the compliance of the ventricles. As with a ventricular septal defect, the site of the defect in the atrial septum does not influence the magnitude of flow across it, although relative contributions to the shunt from the individual pulmonary veins may vary depending on the location of the defect.
Effect of Size of the Defect
Most isolated interatrial communications that are recognized clinically are essentially nonrestrictive, and flow across them will depend on very subtle pressure transients between the atria, generated, at least in part, by the function of the ventricles. At birth, right and left ventricular compliance is approximately equal, and there is little shunting across an atrial defect in either direction. Pulmonary vascular resistance and pressure generally undergo their normal dramatic fall over the first days of life in patients with an interatrial communication, and right ventricular hypertrophy regresses. Hypertrophy per se does not worsen compliance, but the normal response to a volume load is for the atrium and ventricle to dilate progressively, and this is the norm no matter what the type of interatrial communication. Progressive dilation may be subclinical for years, and the pulmonary vascular resistance stays low in childhood and early adult life, but patients are susceptible to an increase in resistance if the flow of blood to the lungs remains high for decades. If the right ventricle fails, Eisenmenger syndrome may result, with reversal of the atrial shunt to a predominant right-to-left pattern. A right-to-left atrial shunt may also be promoted by tricuspid stenosis or severe tricuspid valvar regurgitation.
In some cases the interatrial communication may result from incompetence of the valve of the oval foramen rather than from a true deficiency of the atrial septum. This incompetence can lead to considerable left-to-right shunting (even if the defect is small) when there are associated abnormalities that lead to increased left atrial pressure. Mitral stenosis, a dysfunctional left ventricle, aortic stenosis, coarctation of the aorta, systemic hypertension, patency of the arterial duct, and ventricular septal defect are examples, and atrial shunting may improve with treatment of the underlying problem. A small amount of left-to-right shunting is usual in the newborn and young infant and defects less than 6 mm at this age are likely not to be important later in life; however, probe patency of the oval fossa is present in up to one-third of these individuals as adults.
Cardiac Response to the Interatrial Communication
In childhood, the usual hemodynamic characteristics of an uncomplicated interatrial communication are a large net left-to-right shunt and normal pulmonary arterial pressure. Left-to-right flow across the defect is phasic and occurs predominantly in late ventricular systole and early diastole. Numerous studies have documented that most patients with a typical defect within the oval fossa also have a small right-to-left shunt. This small shunt is not detectable by oximetry, so there is no systemic desaturation, but it can be demonstrated by indicator dilution techniques, contrast echocardiography, and Doppler studies.
The contribution of the pulmonary venous return from each lung to the total left-to-right shunt is unequal. In a typical large defect, 80% of the pulmonary venous return from the right lung shunts left to right. This is in contrast to between 20% and 40% of the pulmonary venous return from the left lung. In a sinus venosus defect, the anomalously connected right pulmonary veins provide most of the shunted blood. Interestingly, this preferential shunting from the right lung does not occur to any great extent with an ostium primum interatrial communication.
As discussed, a large left-to-right shunt at the atrial level leads to enlargement of both the right atrium and the right ventricle. The left atrial and left ventricular dimensions are usually normal in childhood, and systemic cardiac output is almost always normal in children. In contrast, left ventricular end-diastolic volume may be less than normal, and systemic cardiac output has been found to be decreased in up to half the patients with an atrial septal defect who are older than 18 years. Numerous studies in adults have shown significant left ventricular dysfunction, which may persist even after surgical correction.
Despite the greatly increased flow of blood to the lungs, pulmonary arterial pressure is rarely elevated in children and pulmonary vascular resistance is low, frequently less than 1 Wood unit. The incidence of pulmonary hypertension in patients younger than 20 years is no more than 5% in most studies but increases to 20% of those aged from 20 to 40 years and is found in half of the patients older than 40 years. However, severe elevation of resistance and the Eisenmenger reaction are unusual and are decreasing in frequency as surveillance techniques improve. The changes in the pulmonary vascular bed at this stage are similar no matter what the cause of pulmonary vascular disease may be, including a predominance of intimal fibrosis and endothelial proliferation, albeit with less medial muscular hypertrophy than is seen in patients with ventricular septal defects. The Eisenmenger reaction is not a uniform response in older age, and such a response is somewhat idiosyncratic. However, a progressive rise in pulmonary artery pressure with worsening cardiopulmonary function is the norm (presumably due to increased shunting as left ventricular compliance worsens with age and right ventricular function worsens as a result), thus providing the rationale for surgery in childhood. Nonetheless, congestive heart failure rarely occurs before the fourth or fifth decade. Rarely an isolated defect may cause congestive heart failure in infancy; early surgery may be indicated in such cases, although a search for other precipitating factors is a crucial part of the evaluation of these infants. Another cardiac consequence of the long-standing left-to-right shunt is the occurrence of atrial arrhythmias, particularly atrial flutter and fibrillation. They presumably result from chronic stretching of the atria and occur most commonly in patients older than 40 years of age. As with the other complications associated with interatrial communications, atrial arrhythmias rarely occur in childhood. Nonetheless, electrophysiologic studies have demonstrated a high incidence of subclinical dysfunction of the sinus node, along with conduction disturbances, in children prior to operative intervention.