Authors
Susan E Wiegers, MD, FACC, FASE
Martin G St John Sutton, MBBS, FRCP, FACC, FASE
Section Editors
Thomas P Graham, Jr, MD
Heidi M Connolly, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC


INTRODUCTION — Atrial septal defect (ASD) is the most common congenital lesion in adults after bicuspid aortic valve. Although the defect is often asymptomatic until adulthood, potential complications of an undetected ASD include right ventricular failure, atrial arrhythmias, paradoxical embolization, cerebral abscess, and pulmonary hypertension that can become irreversible and lead to right-to-left shunting (Eisenmenger syndrome).

The pathophysiology, anatomy, natural history, and clinical features of ASDs in adults will be reviewed here. The identification and assessment of ASDs, methods for treatment, and issues related to ASDs in children are discussed separately. (See "Identification and assessment of atrial septal defects in adults" and "Management of atrial septal defects in adults" and "Classification and clinical features of isolated atrial septal defects in children" and "Management and outcome of isolated atrial septal defects in children".)

PATHOPHYSIOLOGY — Isolated communications in the atrial septum have several distinctive anatomic locations. (See 'Embryology' below.) However, the pathophysiology of each lesion is similar. With a small ASD, left atrial pressure is slightly higher than right atrial pressure, resulting in the continuous flow of oxygenated blood from the left to the right atrium across the defect (figure 1 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 occurs with a large defect, left-to-right shunting still occurs because of the greater compliance of the right compared to left ventricle.

The shunt flow constitutes a "useless circuit" through the right atrium, right ventricle, pulmonary circulation, left atrium, and through the defect back to the right atrium. The pulmonary flow to systemic flow ratio can be as high as 8:1 but, in asymptomatic young adults, is more likely to be in the range of 2:1 to 5:1. The increased flow leads to right-sided dilatation evident on chest x-ray and echocardiographic imaging. The main pulmonary arteries dilate and the pulmonary vascularity increases. These changes may be evident on the chest x-ray, and large vessels in both the lower and upper lobes may be seen.

The right-sided volume overload is usually well tolerated for years. Eventual development of pulmonary arteriopathy signals the onset of progressive pulmonary hypertension and its sequela, Eisenmenger syndrome with right ventricular failure and right-to-left shunting of blood. The development of pulmonary hypertension is highly variable and depends not only on the size and duration of the shunt but on unknown individual factors. (See "Evaluation and prognosis of Eisenmenger syndrome".)

EMBRYOLOGY — The septation of the atria begins as early as the fifth week of gestation. The septum primum arises from the superior portion of the common atrium and grows caudally to the endocardial cushions located between the atria and ventricles, eventually closing the orifice (ostium primum) between the atria (figure 2).

A second orifice (the ostium secundum) develops in the septum primum; this orifice is covered by another septum (the septum secundum) that arises on the right atrial side of the septum primum. The septum secundum grows caudally and covers the ostium secundum. However, the septum secundum does not completely divide the atria, but 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; the right atrial pressure is higher than that on the left and pushes the flexible septum primum aside. 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 "Classification and clinical features of isolated atrial septal defects in children", section on 'Perinatal physiology'.)

In approximately 70 percent of individuals, the primum and secundum septa fuse after birth creating an intact interatrial septum. However, in a significant proportion of the population, the septae do not fuse. If the foramen ovale is completely covered but not sealed, it is called a "probe patent" or simply "patent" foramen ovale (PFO), indicating that the foramen can be opened by a reversal of the interatrial pressure gradient or by an intracardiac catheter. Less commonly, an open communication persists between the atria after septation. Such a communication is called an atrial septal defect (ASD).

CLASSIFICATION — The various types of ASDs are classified according to their location and the nature of the embryologic defect:

* Isolated ASDs result from abnormal development of the septa that partition the common atrium of the developing heart into right and left chambers.
* Atrioventricular (AV) septal defects (AVSD, also known as atrioventricular canal or endocardial cushion defects) result primarily from maldevelopment of the partitioning of the AV canal by the endocardial cushions.

Isolated ASDs include PFO, ASD at the fossa ovalis (secundum ASD), a defect superior to the fossa ovalis (superior sinus venosus type ASD, superior vena caval defect), a defect inferior to the fossa ovalis (inferior sinus venosus type ASD, inferior vena caval defect), and coronary sinus defects (figure 3).

Atrioventricular septal defects are by definition not isolated and include complete forms, incomplete forms, and common atrium. Primum ASDs are a type of AVSD and are typically associated with ventricular septal defects and/or AV valve malformations.

Secundum ASD — Defects in the area of the foramen ovalis are classified as secundum type ASD. This type of ASD can result from poor growth of the secundum septum or excessive absorption of the primum septum (figure 3 and movie 2). This defect accounts for 70 to 75 percent of all ASDs and is more common in females. Secundum ASDs may be associated with or continuous with other ASDs, such as a sinus venosus defect or an ostium primum defect.

Mitral valve prolapse is present in up to 70 percent of patients with secundum ASD, perhaps related to a change in the left ventricular geometry associated with right ventricular volume overload. The rare combination of an ASD with mitral stenosis, the result of rheumatic valvulitis, is known as Lutembacher syndrome.

Although most cases of secundum ASD are isolated, some individuals have a family history of this defect with or without other congenital cardiac and extracardiac abnormalities. These syndromes typically present in childhood or adolescence and are discussed elsewhere. (See "Classification and clinical features of isolated atrial septal defects in children", section on 'Genetic disorders'.)

Rarely patients with a secundum ASD have a partial anomalous pulmonary venous connection.

Primum ASD — The primum type ASD develops if the primum septum does not fuse with the endocardial cushions, leaving a defect at the base of the interatrial septum that is usually large (figure 3). This type of defect accounts for 15 to 20 percent of ASDs. It has been suggested that both partial and complete AV canal defects are related to maldevelopment of the ventricular septum rather than a decrease in atrial septal tissue [1].

Primum ASDs are generally not isolated and are nearly always associated with anomalies of the AV valves, particularly a cleft in the anterior mitral valve leaflet, and/or defects of the ventricular septum (called a complete endocardial cushion defect) or common AV canal. Discrete subaortic stenosis may develop following primum ASD repair.

Sinus venosus ASD — Sinus venosus defects account for five to ten percent of ASDs. These defects represent an abnormality in the insertion of the superior or inferior vena cava, which overrides the interatrial septum; the interatrial communication is then formed within the mouth of the overriding vein and is outside the area of the fossa ovalis (figure 3) [2]. A partial anomalous pulmonary venous connection is present in most patients (eg, 112 of 115 patients undergoing surgical repair) [3].

Sinus venosus ASDs are of two types [2]:

* Superior sinus venosus defects (sometimes called superior vena caval defects) are located in the atrial septum immediately below 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 [4].
* Inferior sinus venosus defects, also known as inferior vena caval defects, are less common. They are located in the atrial septum immediately above the orifice of the inferior vena cava. These defects are also often associated with partial anomalous connection of the right pulmonary veins.

Even if the pulmonary veins are in their usual anatomic location, either of the right pulmonary veins may have its flow directed into the right atrium, depending upon the location of the venosus defect. The pulmonary veins may also be completely displaced and insert into either vena cava. The "scimitar sign" describes the opacity on the chest x-ray formed by the insertion of the pulmonary vein into the inferior vena cava. (See 'Chest x-ray' below.)

The triad of partial anomalous pulmonary venous return, hypoplasia or aplasia of a lobe of the right lung (most often), and the presence of thoracic aorta to pulmonary artery collaterals to the small lung is referred to as the "scimitar syndrome." This syndrome may be associated with the development of pulmonary hypertension.

The hemodynamic effect of partial anomalous venous return depends upon the number of malplaced pulmonary veins and the proportion of right ventricular stroke volume that perfuses the lung drained by these veins.

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

Patent foramen ovale — A patent foramen ovale (PFO), which can be detected in approximately 25 to 40 percent of normal adult hearts, is another form of interatrial communication associated with shunting of blood [5-8]. In an autopsy study of 965 normal hearts, the incidence of PFO progressively declined with age from 34 percent during the first three decades to 25 percent during the fourth through the eighth decades to 20 percent during the ninth and tenth decades [5]. However, the size of the PFO tended to increase with age from a mean of 3.4 mm in the first decade to 5.8 mm in the tenth decade. In almost all cases, the PFO was between 1 and 10 mm in size.

The anatomic arrangement of the foramen and its valve permit right-to-left flow in utero, but no flow after birth. If left atrial pressure exceeds right atrial pressure and the flap valve remnant of septum primum of the foramen ovale is competent, interatrial shunting cannot occur.

However, an elevation in right atrial pressure can cause right-to-left interatrial shunting through a PFO. Intermittent increases in right atrial pressure occur in normal individuals during early ventricular systole (movie 3) and with the decreased intrathoracic pressure of inspiration [9]. A persistent, large fetal Eustachian valve can also direct inferior vena caval blood toward the midportion of the atrial septum and potentially into the left atrium and systemic circulation throughout the cardiac cycle.

In addition, transient right-to-left shunting in patients with a PFO can be induced by the straining and release phases of the Valsalva maneuver. During the straining phase, the right atrial pressure rises disproportionately, and during release there is a sudden increase in systemic venous return into the right atrium. In one series of 148 patients with a PFO, 84 (57 percent) had right-to-left shunting at rest, and 136 (92 percent) had right-to-left shunting with straining or coughing [8].

The clinical importance of a PFO lies in its association with paradoxical embolism and cryptogenic stroke [6]. Paradoxical embolization occurs when an embolus arising in the systemic venous system or the right atrium crosses the PFO during right-to-left shunting and enters the systemic arterial circulation. A larger PFO (≥4 mm) or one with a significant right-to-left shunt at rest are risk factors for adverse events [6]. (See "Atrial septal abnormalities (PFO, ASD, and ASA) and risk of cerebral emboli in adults", section on 'Risk of embolic stroke'.)

Left-to-right shunting does not occur with a PFO, provided that the septum primum of the foramen ovale remains competent (ie, fully covers the orifice of the foramen). In some patients, stretch on the margins of the foramen can cause the valve and foramen to become incompetent or patent; this is not truly an ASD since septal tissue is not missing. However, in many clinical studies such patients are for practical purposes considered to have a small ASD.

A PFO may be a familial trait. In a study of 62 patients with an ischemic stroke and 62 matched control siblings, the prevalence of a PFO in female siblings of patients with a PFO was 77 percent compared to 25 percent in female siblings of those without a PFO (odds ratio 9.8); there was no such association in men [10].

ASSOCIATED LESIONS — About 30 percent of patients with ASDs have an additional malformation.

NATURAL HISTORY — The natural history of ASDs has primarily been documented in reports prior to the age of enhanced diagnosis by echocardiography. Selection bias may have been present in these studies since it was the symptomatic patients who were brought to medical attention.

Most children and adolescents with an ASD, particularly an isolated secundum ASD, are asymptomatic even in the presence of large shunts. This was illustrated in a review of 481 patients with a secundum ASD who were seen between 1957 and 1976 who underwent surgical correction before the age of 40; the defect was discovered on routine examination in 202 (42 percent) [11]. In comparison, patients who present in infancy, particularly with heart failure and/or failure to thrive, usually have associated cardiac defects [12]. (See "Classification and clinical features of isolated atrial septal defects in children", section on 'Presentation'.)

Studies in which serial echocardiographic examinations were performed have shown that, among newborns with an ASD, the majority of defects close spontaneously in infancy, with the exception of those larger than 8 mm in diameter [13]. In comparison, spontaneous closure is uncommon in children, since most ASDs that will close spontaneously will have already done so.

The natural history of secundum ASDs in children was illustrated in a series of 104 patients (average age 4.5 years at diagnosis) who had an isolated ASD >3 mm in size; serial echocardiograms were performed at an interval of more than six months between studies [14]. Spontaneous closure of the ASD occurred in only four patients, while ASD diameter increased in 65 percent; 30 percent of patients had a >50 percent increase in diameter and 12 percent had an increase to >20 mm. The only independent factor associated with growth was the initial size of the ASD. (See "Management and outcome of isolated atrial septal defects in children", section on 'Natural history'.)

The increase in left-to-right shunting with age in many patients with uncorrected moderate to large ASDs increases the likelihood of developing symptoms as described in the next section. The increase in ASD size over time also has important implications for treatment, since there is the potential that ASD enlargement will be sufficient to preclude the use of percutaneous transcatheter closure with specific devices. (See "Management of atrial septal defects in adults", section on Percutaneous closure.)

CLINICAL MANIFESTATIONS — It is estimated that most patients with an ASD with significant shunt flow (ie, pulmonary to systemic flow more than 2:1) will be symptomatic and require surgical correction by the age of 40 [11]. However, some patients do not become symptomatic until 60 years of age or older [15,16]. Patients with unexplained right ventricular volume overload should be referred for evaluation of possible obscure ASD, partial anomalous venous connection, or coronary sinoseptal defect [17].

Initial symptoms associated with an ASD may be mild and ignored by the patient. As an example, in one series of 32 patients diagnosed by incidental findings on physical examination, chest x-ray, or echocardiography who were thought to be asymptomatic, exercise tolerance improved after closure of the ASD [18].

Atrial arrhythmias, exercise intolerance, fatigue, dyspnea, and overt heart failure are common manifestations of symptomatic ASDs. In the series cited above of 481 patients with a secundum ASD who were seen between 1957 and 1976 and who underwent surgery before the age of 40, more than one-half had symptoms of dyspnea and fatigue [11].

Atrial arrhythmias — Atrial arrhythmias are a common manifestation of an ASD. In three series with a total of over 600 patients, atrial fibrillation or atrial flutter was present in almost 20 percent overall [16,19,20]. The risk of atrial arrhythmias increases with age and the pulmonary artery pressure [19,20]. In a report of 211 adults, the incidence of atrial fibrillation or atrial flutter prior to surgery was 1 percent for those aged 18 to 40, 30 percent for those aged 40 to 60, and 80 percent in those over the age of 60 [19]. The effect of surgical repair on these arrhythmias is discussed separately. (See "Management of atrial septal defects in adults", section on 'Atrial tachyarrhythmias'.)

Patients with atrial fibrillation are at risk for embolic events, particularly if not appropriately anticoagulated [16,20]. (See "Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation".)

Left ventricular dysfunction — Left ventricular failure is uncommon, but can occur after many years in patients with an uncomplicated ASD. More subtle evidence of left ventricular dysfunction is a frequent finding. In a report of 12 adults with a secundum ASD, the mean cardiac index was significantly reduced compared to an age-matched group of normal subjects (3.6 versus 4.5 L/min per m2) [21].

The cause of this complication is unclear since the primary pathophysiologic change is right ventricular volume overload. Early studies suggested an associated intrinsic left ventricular abnormality. However, it is currently thought that reversible mechanical factors operating primarily on diastolic function are of primary importance [22]. In an echocardiographic study of 34 children (mean age 9 years) undergoing percutaneous device closure of an ASD, left ventricular end-diastolic volume (LVEDV) was diminished prior to the procedure as a result of leftward interventricular septal shift [23]. After ASD closure, LVEDV increased significantly (from 56.4 to 65.3 ml) as septal shift resolved, with a resulting increase in ejection fraction (from 54.9 to 62.1 percent).

Systemic hypertension, if present, can exacerbate the hemodynamic changes due to an ASD. The development of left ventricular hypertrophy is associated with an increase in left ventricular stiffness. These changes tend to increase in left-to-right shunting, possibly resulting in the late development of pulmonary hypertension and right-sided heart failure.

Stroke due to paradoxical embolization — Patients with a PFO or, much less often, an ASD with a right-to-left shunt are at risk for stroke due to paradoxical embolization (stroke, transient ischemic attack, or peripheral emboli) [6,24-27]. Right-to-left shunting occurs in some patients at rest and in others during transient increases in right-sided pressure (eg, with a Valsalva maneuver or coughing) (see 'Patent foramen ovale' above. In addition, right-to-left shunting can be persistent in the presence of pulmonary hypertension (see 'Pulmonary hypertension and Eisenmenger syndrome' below.

The relative frequency of PFO and ASD was evaluated in a series of 103 patients (mean age 52 years) with a presumed paradoxical embolism [26]. A PFO alone was present in 81, an ASD alone in 12, and both a PFO and ASD in 10.

PFO is also common in patients with cryptogenic stroke. In a review of 581 such patients who were under the age of 55, 216 (37 percent) had a PFO, 10 (1.7 percent) had an atrial septal aneurysm, and 51 (9 percent) had both [25]. The patients with PFO were younger and less likely to have traditional risk factors for stroke (hypertension, hypercholesterolemia, smoking) than those without PFO.

Issues related to the causes, diagnosis, and management of paradoxical embolization are discussed in detail separately. Only about 10 to 20 percent of patients have a documented proximal deep vein thrombosis; other potential sources include thrombus forming at the edges of a PFO or in a concurrent atrial septal aneurysm. (See "Atrial septal abnormalities (PFO, ASD, and ASA) and risk of cerebral emboli in adults".)

Migraine headache — Migraine headache occurs with increased frequency in patients with PFO or, much less often, an ASD [25,27]. In a study of 581 young patients with a cryptogenic stroke, 267 (46 percent) had a PFO [25]. These patients were more likely to have a migraine (27 versus 14 percent without a PFO), especially when the PFO was associated with an atrial septal aneurysm (ASA) (adjusted odds ratio 2.71). It has been suggested that the migraines may result in at least some patients from movement across the interatrial defect of vasoactive substances such as serotonin that would normally be inactivated in the lungs. Closure of the defect can lead to a reduction in migraine frequency. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Right-to-left cardiac shunt' and "Acute treatment of migraine in adults", section on Right-to-left cardiac shunt.)

Pulmonary hypertension and Eisenmenger syndrome — The normal pulmonary vasculature accommodates the increased volume of flow in patients with an ASD by recruitment of previously unperfused vessels. As a result, pulmonary artery pressures do not rise significantly unless the volume of pulmonary blood flow exceeds 2.5 times baseline. The development of pulmonary vascular injury is related to the degree and duration of right heart volume overload. (See "Pathogenesis of pulmonary hypertension", section on Congenital heart disease and volume overload.)

Moderate to severe pulmonary hypertension is relatively uncommon in patients with an ASD, being present in less than 10 percent of adults at the time of diagnosis [16,28]. Patients with a sinus venosus defect have higher pulmonary artery pressures and resistances and develop pulmonary hypertension at an earlier age compared to patients with other forms of ASD. In a study of 169 patients, for example, pulmonary hypertension was present in 26 percent of those with a sinus venosus defect compared to 9 percent with an isolated secundum ASD; elevated pulmonary vascular resistance was present in 16 and 4 percent, respectively [29].

The development of severe irreversible pulmonary hypertension or Eisenmenger syndrome (irreversible pulmonary hypertension at near systemic levels and reversal of shunt flow to a predominantly right-to-left direction) is now uncommon because of surgical or percutaneous correction of the defect. However, there may be an appreciable lifetime incidence of severe pulmonary hypertension in unoperated ASDs, with some older estimates being in the range of 50 percent. Although Eisenmenger syndrome is much less common with ASDs than with ventricular septal defects, ASDs have been a common cause of the syndrome because of their greater prevalence [30]. The prognosis is relatively poor once Eisenmenger physiology has been established. (See "Evaluation and prognosis of Eisenmenger syndrome".)

The incidence of pulmonary hypertension and the efficacy of repair of the ASD were evaluated in a report of 179 consecutive adults over the age of 40 [16]. Among these patients, 26 percent had mild to moderate pulmonary hypertension (pulmonary artery systolic pressure 40 to 60 mmHg), 7 percent had severe pulmonary hypertension (pulmonary artery systolic pressure greater than 60 mmHg), and 2 percent had a marked elevation in pulmonary vascular resistance indicative of severe pulmonary vascular obstructive disease [16]. The patients who underwent surgical repair (at a mean age of 56 years) had a higher adjusted 10-year survival when compared to those treated medically (95 versus 84 percent) and a much lower rate of functional deterioration (relative risk 0.21). (See "Management of atrial septal defects in adults".)

Cyanosis — Cyanosis in patients with ASD is usually associated with Eisenmenger syndrome in which there is shunting of unoxygenated blood from the right to the left atrium. In addition, transient reversal of the atrial pressure gradient and transient cyanosis can be induced by some respiratory maneuvers, such as forceful crying, Valsalva, and cough.

In rare instances, right-to-left shunting across the ASD can lead to cyanosis without pulmonary hypertension being present. In these cases, some unusual anatomic feature is responsible for directing unoxygenated blood across the defect to the left atrium in the absence of a reversed pressure gradient. Examples include prominent Eustachian valves, right atrial masses. and distortion of the usual anatomy by a dilated coronary sinus [31].

Pregnancy — Women with an ASD may have problems during pregnancy, including arrhythmias, thromboembolism, and bleeding. However, there is no available evidence to suggest that pregnant patients should be managed differently from nonpregnant patients with respect to the indications for ASD closure [32]. (See "Management of atrial septal defects in adults", section on 'Pregnancy'.)

Scuba diving and altitude exposure — Individuals with small ASDs who are treated medically may be at increased risk for complications when they experience high or low atmospheric pressure as with scuba diving or high-altitude climbing. Scuba diving in patients with an ASD or a PFO has been associated with increased risks of decompression illness and paradoxical emboli, while high-altitude exposure has been associated with risk of increased right-to-left shunting and oxygen desaturation. Among patients with an ASD (or other intracardiac shunt), scuba diving is generally contraindicated, while consultation with a cardiologist specializing in congenital defects is recommended before altitude exposure [6]. (See "Complications of scuba diving" and "High altitude and heart disease", section on 'Congenital heart disease'.)

PHYSICAL FINDINGS — The classic physical findings of an ASD are related to the degree and duration of the defect. The findings involve precordial palpation, heart sounds, and heart murmurs, and include the abnormalities associated with Eisenmenger syndrome.

Precordial palpation — Dilatation of the right atrium and right ventricle may initially be undetectable on physical examination. Eventually, large left-to-right shunts can lead to one or more of the following findings:

* An enlarged and hyperdynamic right ventricle can produce a right ventricular heave that is most pronounced along the left sternal border and in the subxiphoid area. It can also cause chest wall deformity with asymmetry and a left precordial bulge.
* Enlargement of the pulmonary artery may be associated with a palpable pulmonary artery impulse at the left upper sternal border. This may be more pronounced in patients with pulmonary hypertension.

Heart sounds — The characteristic finding in ASDs with large left-to-right shunts and normal pulmonary artery pressure is wide, fixed splitting of the second sound (S2), in contrast to the normal variation in splitting during the respiratory cycle. The second sound should be evaluated when the patient is sitting or standing because splitting may be relatively wide but not fixed in the supine position. (See "Auscultation of heart sounds".)

Fixed splitting is thought to result from altered characteristics of the pulmonary vascular bed associated with increased pulmonary blood flow. In all individuals, the aortic and pulmonic closure sounds (A2 and P2) occur shortly after (but not instantly after) ventricular pressure falls below arterial pressure. The delay between the ventricular pressure drop and valve closure is referred to as the "hangout time," and is the delay due to pressure recoil from the arterial bed.

In the systemic arterial circulation, the hangout time is short because of high aortic impedance and rapid pressure recoil; it does not vary with respiration. In contrast, the pulmonary hangout time is longer, because of the greater compliance of the pulmonary vascular bed, and is prolonged by inspiration, which increases pulmonary capacitance. As a result, P2 normally occurs after A2, and this separation ("splitting") of S2 increases with inspiration.

With an ASD, the capacitance of the pulmonary bed is increased throughout the respiratory cycle without much respiratory variation. The increased and constant capacitance results in an increased and fixed hangout time, with wide splitting between the first and second components of the S2 and little respiratory variation.

The intensities of the pulmonic and aortic components of S2 are equal in most patients with uncomplicated ASDs. Patients with pulmonary hypertension usually have an accentuated pulmonic component of S2. A similar finding is occasionally seen with normal pulmonary pressures, because of the proximity of the dilated pulmonary artery to the chest wall.

The first heart sound (S1), which is heard best at the apex and lower left sternal border, is often split and the second component (tricuspid closure) is intensified in patients with an ASD. An explanation for this increase in intensity is that the large volume of diastolic blood flow from right atrium to right ventricle presses the tricuspid leaflets toward the right ventricular wall and the forceful right ventricular contraction causes the tricuspid leaflets to move abruptly cephalad during systole.

Heart murmurs — The shunt flow across the ASD has too low a velocity and produces too little turbulence to be audible, although it can be demonstrated by intracardiac phonocardiography. However, several other murmurs may be heard. (See "Auscultation of cardiac 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. 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 also be heard 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.
* A diastolic rumble due to the increased flow across the tricuspid valve may be heard by a careful examiner but is usually quite subtle. The rumble is accentuated by inspiration.
* A low-pitched diastolic murmur of pulmonic regurgitation may result from dilatation of the pulmonary artery.

Pulmonary hypertension — Right-to-left shunting due to pulmonary hypertension in the occasional patient with ASD may be associated with the following auscultatory findings:

* A right ventricular fourth heart sound
* A midsystolic ejection click
* A midsystolic pulmonic murmur that is softer and shorter because the ejected stroke volume is less
* No tricuspid flow murmur
* Increased intensity of the pulmonic component of S2, but no fixed splitting
* A pulmonic insufficiency murmur, if present, is high-pitched
* A holosystolic murmur of tricuspid insufficiency may result from right ventricular and atrial enlargement

Eisenmenger syndrome — The development of Eisenmenger physiology is accompanied by signs of right ventricular failure (including elevated jugular venous pressure, hepatic congestion, and pedal edema), cyanosis, and clubbing, in addition to the auscultatory features of pulmonary hypertension described above. (See "Evaluation and prognosis of Eisenmenger syndrome".)

ELECTROCARDIOGRAM — The electrocardiogram (ECG) may be normal with an uncomplicated ASD and small shunt. Most affected individuals have normal sinus rhythm, but atrial arrhythmias often occur beyond the third decade (especially atrial fibrillation but also atrial flutter and supraventricular tachycardia).

P waves are 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) [33]. This leftward shift is caused by an ectopic pacemaker resulting from an ASD located near the sinus node.

First degree 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 +95º to +135º (right axis deviation) with a clockwise loop. 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.

The QRS complex is often slightly prolonged and has a characteristic rSr' or rsR' pattern that is thought to result from disproportionate thickening of the right ventricular outflow tract, which is the last portion of the ventricle to depolarize. This pattern, which is often described as incomplete right bundle branch block, results from hypertrophy rather than a conduction disturbance. Patients with increasing pulmonary hypertension tend to lose the rSr' pattern in V1 and develop a tall monophasic R wave with a deeply inverted T wave.

A notch on the R wave in the inferior leads (a pattern called "crochetage") has also been suggested as a sensitive and specific electrocardiographic sign of ASD. In one report, this finding was present in 73 percent of patients with ASD versus 7.4 percent of normals, 36 percent of ventricular septal defects, and 23 percent of patients with pulmonic stenosis [34]. In patients with ASD, it correlates with the size of the defect and the degree of left-to-right shunt.

CHEST X-RAY — The chest radiograph reflects the dilatation of the right atrium, ventricle, and pulmonary arteries. Left atrial enlargement may be seen if there is associated mitral regurgitation. Shunt vascularity is characterized by enlarged main pulmonary arteries and pulmonary vessels, without redistribution of flow to the apical vessels (picture 1).

In comparison to these classic findings, the radiographic appearance in patients diagnosed at a later age may be atypical. The atypical findings include normal vasculature, evidence of pulmonary venous hypertension, left atrial enlargement, and pulmonary edema [35]. In one study, atypical findings were more common in patients over the age of 50 (30 versus 6 percent in younger subjects) [35].

In patients with a sinus venosus defect, the insertion of the pulmonary vein into the inferior vena cava can be seen as an abnormal density on the chest x-ray called the "scimitar sign" [36]. The scimitar sign is a vertical, gently curved, right-sided paracardiac linear density that increases in width as it approaches the right cardiophrenic angle.

ECHOCARDIOGRAPHY — Echocardiography is the test of choice for the diagnosis of ASD. Transthoracic echocardiography is usually definitive in ostium secundum defects, while transesophageal echocardiography may aid in the sizing of defects, the diagnosis of sinus venosus defects, and the assessment of associated congenital anomalies or other abnormalities such as mitral valve prolapse. Shunt volume, shunt ratios, and pulmonary artery pressures can be measured with Doppler flow echocardiography. These issues are discussed in detail elsewhere. (See "Identification and assessment of atrial septal defects in adults".)


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