Isolated atrial septal defects (ASDs) in children: Classification, clinical features, and diagnosis

INTRODUCTION — Atrial septal defects (ASDs) are common, accounting for approximately 10 to 15 percent of congenital heart disease. The clinical consequences of an ASD are related to the anatomic location of the defect, its size, and the presence or absence of other cardiac anomalies.

The classification, clinical features, and diagnosis of isolated ASDs in children will be reviewed here. The management and prognosis of children with isolated ASDs are discussed separately. (See "Isolated atrial septal defects (ASDs) in children: Management and outcome".)

EPIDEMIOLOGY — ASDs account for approximately 10 to 15 percent of congenital heart disease, with a reported birth prevalence of approximately 1 to 2 per 1000 live births [1-4].

The apparent incidence of ASD may be increasing because of increased use of echocardiography in the neonatal period. Many secundum ASDs or incompetent foramen ovales identified on echocardiograms obtained for nonspecific indications in early infancy close spontaneously during later infancy or early childhood. (See 'Natural history' below.)

CLASSIFICATION — ASDs are classified based on their anatomic location, which generally reflects the abnormality of embryogenesis that led to the anomaly (figure 1 and figure 2):

●Primum ASD

●Secundum ASD

●Sinus venosus ASD

●Coronary sinus ASD

Patent foramen ovale (PFO) is also an open communication between the right and left atria; however, a PFO is not considered an ASD, because no septal tissue is missing. (See "Patent foramen ovale".)

Normal development — The septation of the atria begins as early as the fifth week of gestation and involves three structures: septum primum, septum secundum, and the atrioventricular (AV) canal septum, which is made up in part by the superior and inferior endocardial cushion.

The septum primum arises from the superior portion of the common atrium and grows caudally towards the AV canal septum (eg, the endocardial cushions) located between the atria and ventricles. The fusion between the septum primum and the endocardial cushions closes the orifice (ostium primum) separating the right and left atria (figure 2).

A second orifice (the ostium secundum) develops in the septum primum; this orifice is covered by the septum secundum that arises on the right atrial side of the septum primum. The septum secundum grows caudally and covers the ostium secundum forming the fossa ovalis. However, the septum secundum does not completely divide the atria in the fetus; it leaves an oval orifice (the foramen ovale) that is covered (but not sealed) on the left side by the flexible flap of the septum primum (figure 2).

In the fetus, the foramen ovale is held open by the pressure gradient between the right and left atria. Right atrial pressure is higher than that on the left and pushes the flexible septum primum aside, permitting right to left flow of oxygenated blood from the inferior vena cava into the left ventricle. At birth, expansion of the lungs lowers right heart pressures at the same time that systemic vascular resistance rises, causing reversal of the atrial gradient. The septum primum is then held against the septum secundum and the interatrial shunt ceases. (See 'Pathophysiology' below.)

In approximately 70 percent of individuals, the septum primum and septum secundum fuse during infancy or early childhood, creating an intact interatrial septum; the remnant of the foramen ovale in the right atrium is termed the fossa ovalis. However, in a significant minority of the population, the septae do not fuse. If the foramen ovale is completely covered, but not sealed, it is called a PFO, indicating that the foramen can be opened (by a reversal of the interatrial pressure gradient or by an intracardiac catheter).

Primum defects — The primum-type ASD develops if the septum primum does not fuse with the endocardial cushions, leaving a defect at the base of the interatrial septum that is usually large (image 1 and figure 1). This type of defect accounts for 15 to 20 percent of ASDs. Primum ASDs are usually not isolated, typically being associated with AV canal defects that include anomalies of the AV valves and ventricular septal defects. These disorders are discussed separately. (See "Clinical manifestations and diagnosis of atrioventricular (AV) canal defects".)

Secundum defects — Secundum ASDs are typically located within the fossa ovalis (remnant of the foramen ovale in the right atrium). This type of ASD can result from arrested growth of the secundum septum or excessive absorption of the primum septum (figure 1). Multiple defects can be seen if the floor of the fossa ovalis is fenestrated. The defects vary greatly in size, from less than 3 mm to greater than 20 mm. Secundum ASDs typically present as an isolated cardiac defect, though they may be contiguous with other ASDs, such as a sinus venosus defect or a primum defect. Some patients with secundum ASD have functional mitral valve prolapse, perhaps related to a change in the left ventricular geometry associated with right ventricular volume overload [5,6].

Secundum defects account for approximately 70 percent of all ASDs and occur twice as often in females as in males [7-10]. The familial recurrence rate has been estimated to be approximately 7 to 10 percent [11,12]. In a comprehensive literature review, the median reported incidence was 5.64 per 10,000 live births [13]. However, the true incidence of secundum ASD may be substantially higher because many ASDs are commonly undiagnosed in infancy and childhood, and spontaneously resolve. (See 'Spontaneous closure' below.)

Genetic disorders — Most secundum ASDs occur sporadically and are isolated defects. However, in some cases, individuals may have a family history of this defect due to a specific genetic mutation. These genetic disorders are often associated with other congenital cardiac and extracardiac abnormalities [14].

Holt-Oram syndrome is an autosomal dominant disorder characterized by upper limb defects (deformities of the radius, carpal bones, and/or thumbs) and cardiac septal defects, most commonly a secundum ASD [15,16]. Cardiac conduction disturbances, including complete heart block, are also common. Holt-Oram syndrome is genetically heterogeneous; mutations in the TBX5 gene are the most common cause [17]. Other genes that have been linked to familial isolated ASDs include GATA4, MYH6, and NKX2-5 [18-21].

Other congenital syndromes in which a secundum ASD may occur include Noonan syndrome, Treacher Collins syndrome, and the thrombocytopenia-absent radii syndrome. (See "Causes of short stature", section on 'Noonan syndrome' and "Syndromes with craniofacial abnormalities", section on 'Treacher Collins syndrome'.)

Sinus venosus defects — Sinus venosus ASDs are characterized by malposition of the insertion of the superior or inferior vena cava straddling the atrial septum (figure 1) [22]. The interatrial communication is within the mouth of the overriding vein and is outside the area of the fossa ovalis. Sinus venosus defects account for approximately 5 to 10 percent of ASDs.

●Superior sinus venosus defects (sometimes called superior vena caval defects) are located in the atrial septum immediately caudal to the orifice of the superior vena cava. The right upper lobe and middle lobe pulmonary veins often connect to the junction of the superior vena cava and right atrium, resulting in a partial anomalous pulmonary venous connection [23]. (See "Partial anomalous pulmonary venous return", section on 'Sinus venosus defects'.)

●Inferior sinus venosus defects, also known as inferior vena caval defects, are less common. They are located in the atrial septum immediately cranial to the orifice of the inferior vena cava. Inferior sinus venosus defects are often associated with partial anomalous connection of the right pulmonary veins. (See "Partial anomalous pulmonary venous return".)

Coronary sinus defects — In coronary sinus ASDs (unroofed coronary sinus), part or the entire common wall between the coronary sinus and the left atrium is absent. This rarer form accounts for less than 1 percent of all ASDs. Many such patients also have a persistent left superior vena cava.

Patent foramen ovale — PFOs are identified on autopsy in approximately 30 percent of the adult population [24]. The size of a PFO can range from 1 to 10 mm in maximal potential diameter [24]. A PFO is not considered an ASD, because no septal tissue is missing. Interatrial shunting generally does not occur as long as left atrial pressure exceeds right atrial pressure and the flap valve remnant of septum primum of the foramen ovale is competent. However, persistent left-to-right shunting frequently occurs in the first few weeks of life. Mild shunting during the neonatal period is common, particularly in premature infants, and is usually considered a normal finding. (See "Patent foramen ovale".)

Associated cardiovascular defects — ASDs are often associated with other congenital cardiac anomalies. Often the associated defect is clinically more important than the ASD itself. However, in some cases, the ASD may contribute substantially to the physiology of the condition. As examples, an ASD permits mixing between the pulmonary and systemic circulations in complete transposition of the great arteries, while in tricuspid atresia, the entire cardiac output passes across the ASD. (See "D-transposition of the great arteries (D-TGA): Anatomy, clinical features, and diagnosis" and "Tricuspid valve atresia", section on 'Associated cardiac lesions'.)

ATRIAL SEPTAL DEFECT SIZE — For the purpose of the discussion in this topic review, we generally define the size of isolated ASDs as follows:

●Trivial – <3 mm in diameter

●Small – 3 to <6 mm in diameter

●Moderate – 6 to 8 mm in diameter

●Large – >8 mm in diameter

These absolute measurements are not exact and the relative size of the defect (related to overall heart size) may be more clinically relevant. For example, a 6 mm ASD would be insignificant in an adult but would be of moderate size in a newborn.

PATHOPHYSIOLOGY — The pathophysiology of isolated ASDs depends upon the relationship of pulmonary and systemic resistances, the compliance of the right and left ventricles, and the size of the defect.

●Perinatal physiology – In utero, pulmonary arterial blood flow in the fetus is limited by high pulmonary vascular resistance, which results in decreased right ventricular diastolic filling. Instead of traversing the tricuspid valve, much of the blood that flows into the right atrium is shunted across the isolated ASD into the left atrium, similar to the blood flow through the normal patent foramen ovale. At birth, left atrial pressure becomes greater than right atrial pressure, resulting in left-to-right shunting across the defect. Initially, the volume of blood shunted from left to right is small because the right ventricle is still relatively thick-walled and noncompliant. As the right ventricle remodels in response to the decreased pulmonary vascular resistance, its compliance increases and the mean right atrial pressure decreases. As a result, the left-to-right shunting increases in volume. (See "Physiologic transition from intrauterine to extrauterine life", section on 'Transition at delivery'.)

In some neonates, transient right-to-left shunting may also occur during the cardiac and respiratory cycles, resulting in mild cyanosis. In these patients, there is a drop in atrial pressure at the onset of ventricular contraction due to atrial relaxation that is more rapid in the left than the right atrium. During inspiration, the decrease in intrathoracic pressure results in an increase in systemic venous return and a decrease in pulmonary venous return, decreasing left atrial pressure and increasing right atrial pressure, which results in right-to-left shunting.

●Postnatal physiology – The pathophysiology of the different forms of ASDs is similar.

With a small ASD, left atrial pressure is slightly higher than right atrial pressure, resulting in continuous flow of oxygenated blood from the left to the right atrium across the defect (figure 3 and movie 1). The pressure gradient between the two atria and the amount of shunt flow depend upon the size of the defect and the relative distensibility of the right and left sides of the heart. Left-to-right shunting occurs primarily in late ventricular systole and early diastole, with some augmentation during atrial systole. Even when the right and left atrial pressures are equal, as will be seen with a large defect, left-to-right shunting still occurs because of the greater compliance of the right ventricle compared with the left ventricle.

The shunt flow consists of fully oxygenated blood from the left atrium, and constitutes a "useless circuit" of ineffective pulmonary blood flow through the right atrium and ventricle, pulmonary circulation, left atrium and back to the right atrium. Thus, the volume of blood flow in the pulmonary circulation is greater than that in the systemic circulation. The pulmonary flow to systemic flow ratio (Qp/Qs) can be over 3:1 in patients with large defects. (See "Pathophysiology of left-to-right shunts".)

The increased flow leads to right-sided dilatation evident on chest radiograph and echocardiographic imaging. Right ventricular function is also occasionally decreased. The main pulmonary arteries dilate and the pulmonary vascularity is increased. These pulmonary vascular changes may be evident on the chest radiograph, and large vessels in both the lower and upper lobes may be seen. (See 'Chest radiograph findings' below.)

The right-sided volume overload is usually well tolerated for years. Heart failure is unusual before age 30, but the prevalence increases substantially in older uncorrected patients over time. Other complications in older patients include atrial arrhythmias such as flutter and fibrillation, thought to result from chronic stretching of the atrial muscle and, occasionally, pulmonary arteriopathy leading to progressive pulmonary hypertension resulting in right-to left shunting of blood (ie, Eisenmenger syndrome). (See 'Persistent moderate to large ASDs' below and "Clinical manifestations and diagnosis of atrial septal defects in adults", section on 'Clinical manifestations' and "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

NATURAL HISTORY — The natural course of isolated ASDs, most of which are secundum ASDs, varies; small defects often close spontaneously in infancy, whereas moderate and large defects tend to persist and cause symptoms over time.

Spontaneous closure — Spontaneous closure is most likely to occur in patients with small secundum ASDs that are diagnosed during infancy or early childhood [8-10,25,26]. Secundum defects of moderate and large size, types of ASDs other than secundum, and those that are detected later in childhood or adolescence are unlikely to close spontaneously, and some may increase in size over time [10,26].

In a study of 200 children diagnosed at a mean age of five months (range 0.1 months to 13.9 years) who were followed for a mean 3.5 years, spontaneous closure or a decrease in size to ≤3 mm in diameter was observed in 86 percent of patients with ASDs 4 to 5 mm in diameter, 64 percent of patients with ASDs 6 to 7 mm in diameter, 36 percent of patients with ASDs 8 to 10 mm in diameter, and in no patients with ASDs >10 mm [26]. Patients who were <1 year old at the time of diagnosis were more likely to have spontaneous closure compared with older children.

Persistent moderate to large ASDs — In patients with uncorrected moderate to large ASDs, left-to-right shunting may increase with age, leading to volume overload, heart failure, atrial arrhythmia, and/or pulmonary hypertension. Most patients become symptomatic before 40 years of age. Common symptoms include palpitations reflecting atrial arrhythmias (the most frequent presenting symptom), exercise intolerance, dyspnea, and fatigue. Arrhythmias are thought to result from stretching of the atria by the increased shunting. In some patients, exercise intolerance may develop as early as the second decade of life. (See 'Pathophysiology' above and "Clinical manifestations and diagnosis of atrial septal defects in adults".)

The right-sided volume overload associated with an ASD is usually well tolerated for years. Pulmonary vascular disease develops in approximately 10 percent of older patients with isolated ASDs [27], but this complication is rare in childhood and adolescence. In a retrospective study over a 10-year period from two tertiary centers, only 8 of 355 pediatric patients (2 percent) with isolated ASD had severe pulmonary hypertension [28]. These eight infants (six with secundum and two with primum ASD) had elevated pulmonary arterial pressures (PAP) of 50 to 100 percent of systemic pressure and were operated on within the first year of life with subsequent normalization of PAP. These results highlight that elevated pulmonary vascular resistance in infants with ASDs is almost always reversible with correction, unlike the rare complication of fixed pulmonary vascular disease seen in affected adults.

In uncorrected older patients, severe irreversible pulmonary hypertension (Eisenmenger syndrome) may develop and presents with signs of right ventricular failure resulting in right-to-left shunting. Clinical findings include cyanosis, dyspnea with exertion, hepatomegaly, and clubbing of the fingers and toes. These patients are also at risk for paradoxical embolization of clot from the venous system or right atrium via right-to-left shunting into the arterial system. (See "Atrial septal abnormalities (PFO, ASD, and ASA) and risk of cerebral emboli in adults" and "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

CLINICAL FEATURES

Presentation — Most ASDs are small and do not cause symptoms in infancy and childhood. They most commonly come to attention because a murmur is detected on physical examination or as an incidental finding on echocardiogram obtained for other reasons [29,30].

Infants with large ASDs occasionally present with symptoms of heart failure, recurrent respiratory infections, or failure to thrive. Failure to thrive in infants with ASDs may be associated with extracardiac pathology [31,32].

Paradoxical embolization and resultant embolic stroke is a rare complication of ASDs in pediatric patients.

Physical examination — Physical examination findings are dependent on the size of the defect, the degree of shunting, and the pulmonary arterial pressure. Characteristic findings include a midsystolic pulmonary flow or ejection murmur accompanied by a fixed split second heart sound (S₂) (movie 2). In one study of 33 asymptomatic children with ASDs, an ejection systolic murmur and/or fixed split of S₂ was present in >90 percent of patients [33].

●Murmur – The low velocity shunt flow across the ASD produces insufficient turbulence to be audible itself. However, several other murmurs may be heard. (See "Approach to the infant or child with a cardiac murmur", section on 'Auscultation of heart sounds and murmurs'.)

•A midsystolic pulmonary flow or ejection murmur, resulting from the increased blood flow across the pulmonic valve, is classically present with moderate to large left-to-right shunts (movie 2) and may be louder than that attributed to the usual functional murmur. This murmur is loudest over the second intercostal space and is usually not associated with a thrill. The presence of a thrill typically indicates a very large shunt or pulmonic stenosis.

•A murmur of mitral regurgitation may be heard and is due to a cleft mitral valve in ostium primum defects, and mitral valve prolapse in secundum defects. In the latter setting, an apical late or holosystolic murmur of mitral regurgitation radiating to the axilla may be heard (movie 3).

•A middiastolic murmur of low to medium frequency due to high flow across the tricuspid valve may be heard with careful auscultation in patients with a left-to-right shunt greater than 2:1. A low-pitched diastolic murmur of pulmonic regurgitation may result from dilatation of the pulmonary artery.

●Fixed split of S₂ – In contrast to the normal variation in S₂ splitting during the respiratory cycle, patients with ASDs typically have a wide fixed split. The fixed split of S₂ occurs because the atrial defect equalizes the respiratory effect on both right and left ventricular output. The widening of the split is due to prolonged emptying of the enlarged right ventricle which delays pulmonic closure. A relatively wide (though not fixed) S₂ split is common in healthy individuals in the supine position. Therefore S₂ should be evaluated in both the supine and sitting or standing position. (See "Approach to the infant or child with a cardiac murmur", section on 'Heart sounds'.)

●Signs of heart failure – In patients with large ASDs, signs of heart failure (eg, tachypnea, rales, failure to thrive, hepatomegaly) may be seen. (See "Heart failure in children: Etiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)

●Signs of right atrial enlargement – A large left-to-right shunt may result in a precordial bulge due to atrial enlargement. In some patients, atrial enlargement leads to chest deformity with transverse depressions along the sixth and seventh costal cartilages at the site of attachment of the anterior part of the diaphragm, known as Harrison grooves. Patients with large left-to-right shunts also may have a hyperdynamic right ventricular impulse that results in a right ventricular heave. This is most pronounced along the left sternal border and in the subxiphoid area.

●Signs of pulmonary hypertension – Pulmonary hypertension (PH) is unusual in pediatric patients with ASDs but can occur. Patients with PH usually have an accentuated pulmonic component of S₂ (movie 4). Other characteristic findings of PH are discussed separately. (See "Pulmonary hypertension in children: Classification, evaluation, and diagnosis", section on 'Clinical features'.)

Extracardiac features — Children with an ASD may also have manifestations of associated syndromes. As an example, abnormalities of the radius, carpal bones, and/or thumbs occur in Holt-Oram (heart-hand) syndrome. (See 'Genetic disorders' above.)

Electrocardiogram findings — Though not necessary to make the diagnosis of ASD, many patients undergo electrocardiogram (ECG) as part of the initial evaluation for suspected heart disease. The ECG may be normal in a child with an uncomplicated ASD and a small shunt. In patients with a moderate to large degree of shunting, the QRS complex is often slightly prolonged and has a characteristic rSr' or rsR' pattern in V1 (often described as incomplete right bundle branch block) (waveform 1). This pattern is thought to result from enlargement of the right ventricular outflow tract, which is the last portion of the ventricle to depolarize. Alternatively, it may result from stretching of peripheral specialized conduction fibers secondary to right ventricular outflow tract distension. In one study of asymptomatic children with ASD, the incomplete right bundle branch block pattern was noted in 78 percent of patients (26 of 33) [33]. However, in another study of 1363 children who underwent ECG testing, the rSr' pattern was noted in only 36 percent of patients with ASD and was also seen in 20 percent of normal children [34]. Patients with increasing PH tend to lose the rSr' and develop a tall monophasic R wave with a deeply inverted T wave.

The P wave axis is typically normal with secundum ASDs. In comparison, sinus venosus ASDs are often associated with a leftward frontal plane P wave axis (ie, negative in leads III and aVF, and positive in lead aVL) [35]. This leftward shift is caused by an ectopic pacemaker resulting from an ASD located near the sinus node. Right atrial enlargement may be reflected by increased P wave voltage. Sinus node dysfunction may develop in early childhood [36].

The PR interval may be prolonged and increases with increasing age [37]. First degree atrioventricular (AV) block can occur in any type of ASD but is classically present in ostium primum defects in association with complete right bundle branch block and left anterior fascicular block. The rim of the ostium primum defect is in close spatial relationship to the His bundle, accounting for abnormalities of impulse conduction through this area.

The frontal plane QRS axis often ranges from +95° to +135° (right axis deviation) with a clockwise loop. In the previously mentioned series of Japanese school children, 55 percent had right axis deviation [33]. Left axis deviation of the QRS axis with a counterclockwise frontal plane loop can occur with uncomplicated secundum ASD, although it usually suggests the presence of an AV canal defect.

Notching of the peak of the R wave in the inferior leads (a pattern called "crochetage") has been described in patients with an ASD. In a series of 82 children with secundum ASDs and 244 control children with other congenital heart disease or normal echocardiograms, the presence of crochetage in at least one inferior limb lead had a sensitivity of 32 percent and a specificity of 86 percent for ASD [38].

Chest radiograph findings — Though not necessary to make the diagnosis of ASD, many patients have a chest radiograph performed as part of the initial evaluation for suspected heart disease or to evaluate pulmonary symptoms. The chest radiograph appearance in patients with ASD depends on degree of shunting. In patients with small ASDs, the chest radiograph is typically normal. In patients with an isolated secundum ASD with a large left-to-right shunt, chest radiography findings include cardiac enlargement and increased pulmonary vascularity (image 2). The increase in pulmonary vascularity typically extends to the periphery of the lung fields, and the pulmonary trunk and central branches appear dilated. The heart often has a characteristic triangular appearance because the enlarged pulmonary arteries prevent the normal-diameter ascending and transverse aorta from forming the heart border. The right atrium and ventricle are usually enlarged, while the left atrium and left ventricle are normal.

DIAGNOSIS

Prenatal diagnosis — The prenatal detection by echocardiography is dependent on the type of ASD and the skill of the echocardiographer. Postnatal echocardiography is recommended to confirm all ASDs that are suspected prenatally.

●Primum ASD – Prenatal ultrasounds by experienced fetal echocardiographers (Level III Fetal Ultrasound) can usually diagnose primum ASDs in the fetus at 18 to 22 weeks gestation. Advances in technology have enabled some specialized centers to identify primum ASDs in the first trimester, but the accuracy of detection remains low even in these centers.

●Secundum ASD – The more common secundum ASD cannot be reliably detected by fetal echocardiography, since the normal fetus has a sizable patent foramen ovale (PFO), and distinguishing between a small to moderate size secundum ASD and a PFO with right-to-left flow is usually not possible. However, the presence of very large secundum ASD may be suspected on fetal echocardiography but must be confirmed by postnatal echocardiograms.

●Sinus venosus and coronary sinus ASDs – Experienced fetal echocardiographers may be able to detect sinus venosus ASDs and coronary sinus ASDs. However, the sensitivity and specificity of fetal ultrasound for identification of these more unusual types of atrial septal defect is not known.

Postnatal diagnosis — An isolated ASD may be clinically suspected based upon findings on physical examination (midsystolic pulmonary flow or ejection murmur and fixed splitting of the second heart sound (movie 2)) and electrocardiogram (incomplete right bundle branch block (waveform 1)). The diagnosis is confirmed by echocardiography.

Echocardiography — Echocardiography is the test of choice for the diagnosis of ASD. Transthoracic echocardiography (TTE) is usually definitive in diagnosing secundum ASDs (image 3 and movie 1). Shunt volume, shunt ratios, and pulmonary artery pressures can be estimated with Doppler flow echocardiography.

Although TTE is usually adequate to identify the presence of an ASD and determine its overall size, transesophageal echocardiography (TEE) is often necessary to precisely measure ASD margins at the time of catheter closure of secundum ASDs (image 4). TEE is generally superior to TTE in measuring the size and position of ASDs (movie 5), diagnosing sinus venosus defects (image 5), and the assessing for other abnormalities such as anomalous venous connections [39-41]. In addition, TEE more precisely measures ASD margins and, on occasion, may determine that the ASD rims are inadequate for catheter device closure. (See "Isolated atrial septal defects (ASDs) in children: Management and outcome", section on 'Transcutaneous closure'.)

Finally, not all patients have good acoustic windows for adequate TTE visualization. False dropout of the thin fossa ovalis region of the atrial septum can occur even in childhood. Thus, TEE prior to planned surgical or percutaneous closure can provide an additional level of diagnostic assurance and sometimes prevent unnecessary therapeutic procedures.

Magnetic resonance imaging — Magnetic resonance imaging (MRI) can be helpful in selected cases with suspected associated defects such as partial anomalous pulmonary venous connection or in patients in whom there are inconclusive echocardiographic findings. MRI can also provide accurate quantitation of ventricular volumes, and of pulmonary and systemic flow when this information is required [42]. (See "Clinical manifestations and diagnosis of atrial septal defects in adults", section on 'CMR and CT'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of isolated ASDs includes other cardiac conditions that present as an incidental finding of a cardiac murmur in asymptomatic children. Although other physical findings (eg, fixed second heart sound) and electrocardiographic findings of incomplete right bundle branch block suggest ASD, echocardiography conclusively distinguishes these conditions from ASD. (See 'Diagnosis' above.)

●Pulmonic stenosis (see "Pulmonic stenosis in infants and children: Clinical manifestations and diagnosis")

●Innocent or functional murmurs (see "Approach to the infant or child with a cardiac murmur", section on 'Distinguishing pathologic from innocent murmurs')

●Aortic stenosis (see "Valvar aortic stenosis in children")

●Ventricular septal defect (see "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis")

●Patent ductus arteriosus (see "Clinical manifestations and diagnosis of patent ductus arteriosus (PDA) in term infants, children, and adults")

●Mitral stenosis (see "Rheumatic mitral stenosis: Clinical manifestations and diagnosis")

The approach to evaluating a child with a cardiac murmur is discussed in detail separately. (See "Approach to the infant or child with a cardiac murmur".)

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SUMMARY AND RECOMMENDATIONS

●Prevalence – Atrial septal defects (ASD) are common, accounting for approximately 10 to 15 percent of all congenital heart disease. (See 'Epidemiology' above.)

●Classification – ASDs are classified based on their anatomic location, which generally reflects the abnormality of embryogenesis that led to the anomaly (figure 1 and figure 2). (See 'Classification' above.)

•Primum ASDs account for 15 to 20 percent of ASDs. They develop when the septum primum does not fuse with the endocardial cushions. This results in a defect at the base of the interatrial septum that typically is associated with atrioventricular (AV) canal defects (eg, anomalies of the AV valves and ventricular septal defects). (See 'Primum defects' above.)

•Secundum ASDs account for approximately 70 percent of all ASDs and generally present as an isolated defect. They are due to arrested growth of the secundum septum or excessive absorption of the primum septum resulting in an opening in the fossa ovalis. (See 'Secundum defects' above.)

•Less common forms of ASDs include:

-Sinus venosus defects, which are characterized by malposition of the insertion of the superior or inferior vena cava in the atrial septum. (See 'Sinus venosus defects' above.)

-Coronary sinus ASDs, which occur when part or the entire wall between the coronary sinus and the left atrium is absent. (See 'Coronary sinus defects' above.)

•Patent foramen ovale is also a potential open communication between the right and left atria. However, it is not considered an ASD, because no septal tissue is missing. Interatrial shunting cannot occur as long as left atrial pressure exceeds right atrial pressure and the flap valve remnant of septum primum of the foramen ovale is competent. (See 'Patent foramen ovale' above and "Patent foramen ovale".)

●Natural history – The natural course of isolated ASDs varies. Small defects often close spontaneously in infancy, whereas moderate and large defects tend to persist and can cause symptoms over time. (See 'Natural history' above.)

●Presentation – Most patients with ASDs present during a routine health care visit when an incidental heart murmur is detected. Infants with large ASDs occasionally present with symptoms of heart failure (eg, tachypnea and dyspnea), recurrent respiratory infection, or failure to thrive. (See 'Presentation' above.)

●Clinical findings – Characteristic physical findings include a midsystolic pulmonary flow or ejection murmur accompanied by a fixed split second heart sound (S₂) (movie 2). Electrocardiogram may show a QRS pattern suggestive of incomplete right bundle branch block (rSr' or rsR' in V1) (waveform 1). Chest radiography may demonstrate cardiac enlargement (eg, right atrial and ventricular dilation) and increased pulmonary vascularity (image 2). (See 'Physical examination' above and 'Electrocardiogram findings' above and 'Chest radiograph findings' above.)

●Diagnosis – The diagnosis of an isolated ASD is confirmed by echocardiography (image 3 and movie 1). Echocardiography also establishes the specific type of ASD, size of the defect, and detects other cardiac anomalies, if present. (See 'Diagnosis' above.)

Antenatal echocardiography may detect some affected fetuses, especially those with primum ASDs. However, secundum ASDs cannot be reliably detected antenatally. All suspected antenatal cases should be confirmed by postnatal echocardiography. (See 'Prenatal diagnosis' above.)