Atrial septal defects (ASDs) originate at particular sites in the atrial septum and are named according to their embryonic origin. The most common occurs in the central part of the atrial septum in the region of fossa ovalis (secundum ASD). Others include those in the region of endocardial cushion (primum ASD), in the sinus venosus septum (sinus venosus ASD), and in the region of ostium of coronary sinus (CS) (CS ASD). In this chapter, we also address patent foramen ovale (PFO), which is a normal interatrial communication present in fetal life that may persist in adults. Ostium primum ASD is discussed in Chapter 29 since it is a part of the spectrum of atrioventricular septal defects (AVSD).

ASDs constitute 8% to 10% of congenital heart defects in children. The incidence of ASDs has been estimated to be 56 per 100,000 live births (1). The recent estimates are much higher (100 per 100,000 live births), likely due to increased recognition of ASDs in this era of the common use of echocardiography (2). The female:male ratio for secundum ASDs is 2:1, but for the sinus venosus ASDs it is 1:1 (3,4). Secundum ASDs constitute approximately 75% of ASDs, followed by ostium primum ASD (20%) and sinus venosus ASD (5%) (5). CS ASDs more often are seen in association with heterotaxy syndromes and systemic venous anomalies, and isolated CS ASDs are rare (<1%).

Although most ASDs occur sporadically, familial modes of inheritance have been reported. The risk of congenital heart disease in offspring of a woman with a sporadic ASD is estimated to be 8% to 10% (6). ASDs may be related to mutations in either regulatory genes or their target sarcomeric genes. Heterozygous mutations in the transcription factor NKX2.5/CSX were among the first found in families with autosomal dominant transmission of secundum ASDs (7). Mutations in other transcription factors such as TBX5, GATA4, GATA6, and TBX20 also have been associated with secundum ASDs (7,8,9,10,11). TBX5 mutations also are responsible for Holt–Oram syndrome, which is an autosomal dominant syndrome characterized by secundum ASD, anomalies of the upper extremities, and atrioventricular (AV) conduction delay (12). A locus on chromosome 14q12 with a missense mutation in alpha-myosin heavy chain (MYH6), a structural protein expressed at high levels in the developing atria, has been linked to dominantly inherited ASD (13). Secundum ASDs also have been reported in association with cardiomyopathies that have resulted from mutations in sarcomeric genes (14,15). In ASDs associated with prolonged AV conduction, an autosomal dominant pattern of inheritance has been reported (16). Secundum ASDs also are associated with other syndromes such as Noonan, Down, Klinefelter, Williams, Kabuki, Goldenhar, and Ellis–van Creveld. In addition to genetic factors, maternal diseases and exposure to environmental risk factors may play a role in development of ASDs (17). These factors include pregestational diabetes, phenylketonuria, influenza and exposure to retinoids, nonsteroidal anti-inflammatory drugs, anticonvulsants, thalidomide, smoking, and alcohol (17,18,19).

During embryogenesis, the primitive atrium undergoes a complex septation process (Fig. 28.1) (20). In the fourth week of embryonic life, the septum primum appears as a thin-walled sagittal fold in the middle of the common atrium and grows inferiorly toward the endocardial cushion. The opening between the leading edge of the septum primum and the endocardial cushion is called the ostium primum. Before complete closure of the ostium primum, tissue reabsorption occurs in the superior portion of the septum primum resulting in another opening called the ostium secundum. This occurs during the fifth and sixth week of embryonic life. Concurrently, an anterosuperior infolding of the atrial roof develops to the right of the septum primum, called the septum secundum that is concave shaped with a superior and inferior limb. The inferior limb fuses with the lowermost part of the atrial septum to join the endocardial cushion, thus separating the inferior portions of the two atria. The thick muscular ridge of the superior limb forms an incomplete
partition that overlies the ostium secundum resulting in an opening called the foramen ovale. The septum secundum thus forms the concave-shaped superior margin of the fossa ovalis, called the limbus of fossa ovalis (annulus ovalis) and the septum primum forms the valve of fossa ovalis. During fetal life, inferior vena caval flow from the placenta is deflected toward the foramen ovale by the eustachian valve, and then blood is directed from the right atrium to the left atrium via the foramen ovale. This fetal interatrial communication (the PFO) normally closes after birth as a result of fusion of the septum primum and septum secundum. However, it may persist in 25% to 30% of adults where it is probe patent with a competent valve. In some cases, the valve of fossa ovalis is incompetent, either congenitally or acquired due to elevated right or left atrial pressures allowing interatrial shunting across the foramen.

The atrial septal anatomy and location of various types of ASDs are shown in Figure 28.2. Secundum ASDs occur in the central part
of the atrial septum (fossa ovalis) as a result of deficient valve tissue, ectopic or excessive resorption of septum primum, or deficient growth of septum secundum (Fig. 28.3). Such defects result in an enlarged ostium secundum. These defects usually are single, but rarely can occur as multiple atrial septal fenestrations.

Sinus venosus defects occur outside the margins of the fossa ovalis, in relation to the venous connections of the right atrium (Fig. 28.4). The right horn of sinus venosus incorporates the right superior vena cava (SVC) and inferior vena cava (IVC) into the right atrium. Ectopic or incomplete resorption of the sinus venosus
results in deficiency of the wall that separates the right pulmonary veins from the SVC, IVC, and the right atrium resulting in a sinus venosus ASD (21). Some argue that these should be termed partial anomalous pulmonary venous return to the SVC. The interatrial communication in these defects is, in fact, the orifice of the unroofed right pulmonary vein and is not a true defect in the atrial septum per se (21). Most commonly, the sinus venosus ASDs are related to the SVC where blood from the right upper and/or middle pulmonary veins is directed into SVC or the right atrium. Less frequently, a similar defect can occur inferior to the fossa ovalis in relation to the IVC and the right lower pulmonary venous orifice. This defect often has been termed an IVC-type sinus venosus ASD, although direct involvement of the IVC almost never occurs. Hence, the term sinus venosus defect of right atrial type is preferred (21).

The left horn of the sinus venosus forms the CS. The CS defect (unroofed CS) results from failure of the wall between the left atrium and CS to develop. There may be complete or partial unroofing of the CS resulting in direct communication with the left atrium (Fig. 28.5). Almost always, this anomaly is associated with a left SVC. A rare variation consists of complete absence of the CS rather than unroofing, along with a defect in the expected location of the ostium of CS. In such defects, blood from the left SVC directly enters the left atrium. Kirklin and Barratt-Boyes (5) classified the unroofed CS defects as type I, completely unroofed with LSVC; type II, completely unroofed without LSVC; type III, partially unroofed midportion; and type IV, partially unroofed terminal portion.

Interatrial communications can occur in isolation, but often are associated with other congenital heart defects. The presence of an interatrial communication may be crucial for survival in some such defects such as hypoplastic left heart syndrome, D-transposition of great arteries, tricuspid atresia, and total anomalous pulmonary venous return. Partial anomalous pulmonary venous return is present in almost 90% of patients with sinus venosus ASDs and, more rarely, can occur with secundum ASDs. Although valvular pulmonary stenosis frequently has been associated with ASDs, the increased gradient across the pulmonary valve may be flow related and not necessarily due to an abnormal valve per se. CS ASDs commonly are associated with a persistent left SVC. Aside from congenital heart defects, secundum ASDs also have been reported in association with noncompaction and apical hypertrophic cardiomyopathy (14,15).

During fetal life, the majority of the blood reaching the left atrium comes via the foramen ovale since there is minimal flow to the lungs. After birth, the lungs expand and the pulmonary blood flow increases. The increased pulmonary venous return to the left atrium results in the left atrial pressure exceeding the right atrial pressure causing functional closure of the foramen ovale. Intrauterine physiology is not altered in the presence of an ASD, but unlike the PFO, the ASD does not close with the hemodynamic changes that occur following birth. The physiologic consequences of an ASD depend on the magnitude and duration of the shunt and its interaction with the pulmonary vascular bed. The primary determinant of the magnitude and direction of the shunt is the relative compliance of the
ventricles. During the neonatal transition period as the pulmonary vascular resistance drops and the right ventricular wall becomes thinner and hence more compliant than that of the left ventricle, there is an increase in left-to-right shunting. Catheter-based studies on flow dynamics in ASD provide insight into the circulatory pattern during the various phases of cardiac cycle. Maximum left-to-right shunting occurs during diastole when all four cardiac chambers are in communication. Atrial contraction further augments this shunt. A small right-to-left shunt, predominantly from IVC blood can occur during early diastole or during onset of systole. The magnitude and amount of shunting varies with the respiratory cycle. During inspiration when the intrathoracic pressure is decreased, there is a decrease in the left-to-right shunt across the ASD. Conversely, during expiration, when the intrathoracic pressure is increased, there is an increase in the left-to-right shunt.

Moderate-to-large left-to-right shunts across an ASD result in volume overload and dilation of the right atrium and ventricle (see Fig. 28.3). The tricuspid and pulmonary annuli may dilate and become incompetent. The volume-overloaded right ventricle alters the diastolic configuration of the left ventricle with septal bowing toward the left. Occasionally, the abnormal left ventricular geometry may result in prolapse of the mitral valve or superior systolic motion of the mitral leaflet (23). As a result of the increased flow into the lungs, the pulmonary arteries, capillaries, and the veins are dilated and there can be flow-related pulmonary artery hypertension. Over time this can lead to medial hypertrophy of pulmonary arteries and muscularization of the arterioles resulting in pulmonary vascular obstructive disease (24,25). With severe pulmonary vascular obstructive disease, patients develop Eisenmenger syndrome as the atrial level shunt becomes right-to-left, resulting in cyanosis (see Fig. 28.3).