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Clinical manifestations and diagnosis of atrial septal defects in adults

Clinical manifestations and diagnosis of atrial septal defects in adults
Literature review current through: Aug 2023.
This topic last updated: May 31, 2022.

INTRODUCTION — Atrial septal defect (ASD) is the most common congenital heart lesion in adults and is often asymptomatic until adulthood. Diagnosis is important, as timely ASD repair improves outcomes. (See "Management of atrial septal defects in adults".)

The anatomy, pathophysiology, natural history, clinical features, diagnosis, and assessment of ASDs in adults will be reviewed here [1,2].

The management of ASDs in adults and issues related to ASDs in children are discussed separately. (See "Management of atrial septal defects in adults" and "Isolated atrial septal defects (ASDs) in children: Classification, clinical features, and diagnosis" and "Isolated atrial septal defects (ASDs) in children: Management and outcome".)

EMBRYOLOGY AND CLASSIFICATION — ASDs result from lack of sufficient tissue to completely septate the atria and are classified according to their location in the atrial septum, as described in the following sections (figure 1 and figure 2). The location of the defect in relation to adjacent cardiac structures defines the anomalies associated with the ASD and impacts the natural history and requirements for repair.

Atrial septation 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 1). 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 1).

Flow through the foramen ovale is essential for fetal circulation. The foramen ovale closes spontaneously within the first two years of life in 70 percent of children. However, in a significant proportion (20 to 30 percent) of the population, the septa do not fuse, leading to a patent foramen ovale, which is discussed separately. (See "Patent foramen ovale".)

Secundum ASD — Secundum ASD accounts for 70 to 75 percent of all ASDs. Secundum ASD is a defect in the septum primum resulting from poor growth of the secundum septum or excessive absorption of the septum (figure 2 and movie 1). Although most secundum ASDs are isolated defects, familial forms exist, some of which are associated with other congenital cardiac and extracardiac abnormalities. The best described genetic disorder associated with secundum ASD is the Holt-Oram syndrome (also known as heart-hand syndrome) which is caused by various mutations, most commonly mutations in the TBX5 gene. Other genes linked to familial isolated secundum ASD include GATA4, MYH6, and NKX2-5. These syndromes typically present in childhood or adolescence and are discussed elsewhere. (See "Isolated atrial septal defects (ASDs) in children: Classification, clinical features, and diagnosis", section on 'Genetic disorders'.)

Secundum ASDs are occasionally associated with partial anomalous pulmonary venous connection and/or pulmonary stenosis. The rare combination of an ASD with rheumatic mitral stenosis is known as Lutembacher syndrome. (See "Rheumatic mitral stenosis: Clinical manifestations and diagnosis" and "Clinical manifestations and diagnosis of rheumatic heart disease".)

Primum ASD — Primum ASD accounts for 15 to 20 percent of ASDs. A primum ASD is a defect in the septum secundum caused by failure of the primum septum to fuse with the endocardial cushions at the base of the interatrial septum (figure 2). This results from maldevelopment/malalignment of the ventricular septum due to malformation of the endocardial cushions rather than a decrease in atrial septal tissue [3]. Primum ASDs are nearly always associated with anomalies of the atrioventricular (AV) valves, particularly a cleft in the anterior mitral valve leaflet, with or without a contiguous defect in the inlet ventricular septum. When the combination of the primum ASD, cleft mitral valve, and an inlet ventricular septal defect are seen, this is called a partial AV septal defect (AVSD). The most severe form of AVSD (or endocardial cushion defect) is the complete AV septal (or canal) defect, in which a primum ASD and inlet ventricular septal defect are present along with a common AV valve. (See "Clinical manifestations and diagnosis of atrioventricular (AV) canal defects", section on 'Classification'.)

Discrete subaortic stenosis as well as elongation (often referred to as a "goose-neck deformity") of the left ventricular outflow tract are often seen in association with endocardial cushion defects. Endocardial cushion defects are often noted in patients with Trisomy 21.

Sinus venosus defect — Sinus venosus defects account for 5 to 10 percent of ASDs and are located in the venoatrial portion of the atrial septum. Sinus venosus 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 2) [4]. Thus, sinus venosus defects are technically not ASDs since the defect is within the sinus venosus septum. An anomalous connection involving one or more pulmonary veins is present in most patients with sinus venosus ASD (eg, 112 of 115 patients undergoing surgical repair) [5]. Sinus venosus defects are of two types [4]:

Superior sinus venosus defects are located 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 or on the superior vena cava, resulting in a partial anomalous pulmonary venous connection [6]. (See "Partial anomalous pulmonary venous return".)

Inferior sinus venosus defects, also known as inferior vena caval defects, are much less common. They are located immediately above the orifice of the inferior vena cava. These defects are also often associated with partial anomalous connection of the right pulmonary veins to the junction of the right atrium and inferior vena cava.

Unroofed coronary sinus — Unroofed coronary sinus (also known as coronary sinus defect) is caused by absence of part or all of the common wall between the coronary sinus and the left atrium. This defect accounts for less than 1 percent of ASDs and is commonly associated with a persistent left superior vena cava.

GENETIC FACTORS — Most ASDs occur sporadically, though familial transmission has also been identified. Gene mutations causing ASDs have been identified among patients with familial or sporadic disease, including mutations of NKX2.5, causing an autosomal dominant syndrome of ASD with or without conduction defect [7]. Genetic syndromes with skeletal abnormalities associated with ASD include a variety of heart-hand syndromes, which also have autosomal dominant transmission. Holt-Oram syndrome (caused by mutations in the TBX5 gene) is the best known of these heart-hand syndromes.

PATHOPHYSIOLOGY — ASDs in adults are associated with left-to-right shunt causing volume overload of the right heart chambers (figure 3 and movie 2A). The severity of the shunt is determined by the size of the defect and atrial and ventricular compliance and pressure. The left-to-right shunting occurs primarily in late ventricular systole and early diastole, with some augmentation during atrial systole. The shunt flow due to an ASD moves from the left to the right atrium, right ventricle (RV), pulmonary circulation, back to the left atrium, and through the defect back to the right atrium. This leads to volume overload of the right heart chambers and pulmonary arteries with possible late development of progressive pulmonary vascular obstructive disease and pulmonary hypertension when the degree of shunting is substantial and, more commonly, in sinus venosus defects and primum ASDs. (See 'Pulmonary hypertension and Eisenmenger syndrome' below and "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

In addition, there is transient right-to-left shunting at the onset of ventricular contraction, particularly under conditions of bradycardia and/or decreased intrathoracic pressure [8]. This explains the possibility of paradoxical embolism in the setting of ASD. Significant right-to-left shunting can develop later in life if severe pulmonary hypertension or tricuspid regurgitation develops.

Left atrial enlargement is also seen in adults with ASDs, particularly in patients older than 50 years, with atrial fibrillation, with diastolic dysfunction with elevated left heart filling pressure, or with a primum defect associated with cleft mitral valve and mitral regurgitation.

NATURAL HISTORY — The natural course of isolated ASDs varies from spontaneous closure in secundum ASDs to asymptomatic right ventricular enlargement and to increasing symptoms with age. Spontaneous closure of ASDs, noted in approximately 40 percent of secundum ASDs, mostly occurs when ASDs are small, usually less than 8 mm in diameter, and in childhood. Secundum ASDs ≥8 mm in diameter and those in adults do not typically close spontaneously. Primum ASDs, sinus venosus defects, and coronary sinus defects do not close spontaneously. (See "Isolated atrial septal defects (ASDs) in children: Classification, clinical features, and diagnosis", section on 'Natural history'.)

Increases in left-to-right shunting with age (due to relative increases in the left versus right ventricular end-diastolic pressures), development of systemic hypertension, and other acquired heart disease leading to increased left ventricular end diastolic and/or left atrial pressure, especially in patients with moderate to large ASDs, increase the likelihood of developing symptoms and complications as described in the next section. (See 'Complications' below.)

CLINICAL MANIFESTATIONS

History — Most ASDs occur sporadically, although familial transmission has been observed in a minority of cases. Because of the possibility of familial occurrence, a careful family history should be taken in patients with ASD.

The right-sided volume overload in isolated ASDs is usually well tolerated for years despite right heart chamber enlargement (seen on echocardiography and chest radiograph). It is estimated that most patients with an ASD and significant shunt flow (ie, pulmonary to systemic blood flow ratio [Qp:Qs] ≥1.5:1) will become symptomatic and require surgical correction or percutaneous repair by the age of 40 years [9]. However, some patients do not report symptoms until later, likely due to some degree of adaptability to their limitations. In addition, initial symptoms might be mild and nonspecific and therefore ignored [10-12]. Exercise intolerance, fatigue, and dyspnea are common clinical manifestations of ASDs in adults; some patients develop overt heart failure.

In a series 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 [9]. These symptoms improve after ASD repair [12].

Physical findings — The classic physical findings of an isolated ASD are related to the size and location of the defect, the size of the shunt at atrial level, and the pulmonary arterial pressure.

A small minority of patients develop signs of central cyanosis (with blueish discoloration of the skin and mucous membranes) due to various causes, as described below. (See 'Cyanosis' below and 'Eisenmenger syndrome' below.)

Precordial palpation — Dilation of the right atrium and RV may initially be undetectable on physical examination. The larger the shunt, the higher the likelihood it will be manifested by one or more of the following findings (see "Examination of the precordial pulsation", section on 'Palpation'):

An enlarged and hyperdynamic RV 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.

Auscultation

General ASD findings

Heart sounds

The characteristic auscultatory finding in ASDs with large left-to-right shunts and normal pulmonary artery pressure is wide, fixed splitting of the second heart 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.

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. (See "Auscultation of heart sounds", section on 'Splitting of S2'.)

The intensities of the pulmonic and aortic components of S2 are equal in most patients with an uncomplicated ASD. 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. (See "Auscultation of heart sounds", section on 'Factors determining the intensity of S2'.)

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 RV 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. (See "Auscultation of heart sounds", section on 'Intensity of S1'.)

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 phonocardiography. However, several other murmurs may be heard. (See "Auscultation of cardiac murmurs in adults".)

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 left intercostal space and is usually not associated with a thrill. The presence of a thrill typically indicates a very large shunt or pulmonic stenosis. (See "Auscultation of cardiac murmurs in adults", section on 'Increased semilunar blood flow'.)

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 may be heard radiating to the axilla. (See "Auscultation of cardiac murmurs in adults", section on 'Mitral regurgitation' and "Auscultation of cardiac murmurs in adults", section on 'Mitral valve prolapse'.)

A diastolic rumble due to the increased flow across the tricuspid valve may also be heard but is usually quite subtle. The rumble is accentuated by inspiration. (See "Auscultation of cardiac murmurs in adults", section on 'Increased flow across the atrioventricular valve'.)

A low-pitched diastolic murmur of pulmonic regurgitation may result from dilation of the pulmonary artery.

A systolic murmur of tricuspid regurgitation can be heard in patients with severe RV enlargement and annular dilation.

With pulmonary hypertension — Right-to-left shunting due to pulmonary hypertension in the occasional patient with an ASD may be associated with the following auscultatory findings (see 'Pulmonary hypertension and Eisenmenger syndrome' below):

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

Increased intensity of the pulmonic component of S2, but no fixed splitting

A pulmonic regurgitation murmur, if present, is high-pitched

A holosystolic murmur of tricuspid regurgitation may result from right ventricular and atrial enlargement

Eisenmenger syndrome — The development of Eisenmenger physiology is accompanied by cyanosis and clubbing in addition to the auscultatory features of pulmonary hypertension described above. As the disease progresses, features of right ventricular failure (including elevated jugular venous pressure, hepatic congestion, tricuspid regurgitation, and pedal edema) are noted. (See 'Pulmonary hypertension and Eisenmenger syndrome' below and "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

Complications — Complications in patients with ASDs include atrial arrhythmias, pulmonary hypertension (including Eisenmenger syndrome), cyanosis, and paradoxical embolism.

Atrial arrhythmias — Atrial arrhythmias (particularly atrial fibrillation, but also atrial flutter and other supraventricular tachycardias) occur commonly with ASDs beyond the third decade. These arrhythmias may cause palpitations and dyspnea and increase the risk of cardioembolic events. In three series with a total of over 600 patients, atrial fibrillation or atrial flutter was present in almost 20 percent overall [11,13,14]. The risk of atrial arrhythmias increases with increasing age and pulmonary artery pressure [13,14]. 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 years [13]. (See 'Electrocardiogram' below.)

Pulmonary hypertension and Eisenmenger syndrome — The normal pulmonary vasculature accommodates the increased volume flow in patients with an ASD by recruitment of previously underperfused 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 "The epidemiology and pathogenesis of pulmonary arterial hypertension (Group 1)", section on 'Congenital heart disease'.)

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 [11,15]. Patients with a sinus venosus defect have higher pulmonary artery pressures and resistances and develop pulmonary hypertension at an earlier age compared with patients with other forms of ASD. The presence of partial anomalous pulmonary venous connection in association with sinus venosus ASD increases the severity of the shunt and may contribute to the increased risk of pulmonary hypertension. In a study of 169 patients, pulmonary hypertension was present in 26 percent of those with a sinus venosus defect compared with 9 percent with an isolated secundum ASD; elevated pulmonary vascular resistance (PVR) was present in 16 and 4 percent, respectively [16]. The differences in pulmonary artery pressures between patients with sinus venosus and secundum ASDs remained when patients were stratified by age.

The development of irreversible pulmonary hypertension or Eisenmenger syndrome with reversal of the shunt and associated cyanosis is now uncommon because of earlier identification and appropriate surgical or percutaneous correction of the defect. The prognosis is poor once Eisenmenger physiology has been established but has improved significantly compared with the 1960s due to advanced therapeutic options. (See "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

The prevalence of pulmonary hypertension and the effect of ASD repair were evaluated in a retrospective study of 179 consecutive adults over the age of 40 years [11]. 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 PVR indicative of severe pulmonary vascular obstructive disease [11]. Multivariate analysis showed that pulmonary artery systolic pressure >40 mmHg, Qp:Qs >2.5:1, and New York Heart Association functional class III or IV were significant risk factors for mortality, while surgical treatment was associated with reduced mortality. However, surgical treatment is appropriate only in patients without severe pulmonary hypertension. Management of patients with ASD with pulmonary hypertension is discussed separately. (See "Surgical and percutaneous closure of atrial septal defects in adults".)

Cyanosis — Cyanosis in patients with ASDs is usually associated with either concomitant pulmonary valve stenosis resulting in elevated right heart pressures, and thus right-to-left shunt, or Eisenmenger syndrome (picture 1). It can be worsened by the presence of significant tricuspid regurgitation and right ventricular dysfunction. (See 'Eisenmenger syndrome' above and "Medical management of cyanotic congenital heart disease in adults" and "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

Cyanosis due to right-to-left shunting across an ASD is uncommon in the absence of pulmonary hypertension or elevated right atrial pressure. Rarely, a prominent Eustachian valve may direct unoxygenated blood from the vena cava across the ASD to the left atrium, leading to the orthodeoxia-platypnea syndrome [17], as discussed separately. (See "Patent foramen ovale", section on 'Platypnea-orthodeoxia syndrome'.)

Paradoxical embolization — Patients with a patent foramen ovale or, much less often, an ASD, are at risk for stroke due to paradoxical embolization (stroke, transient ischemic attack, or peripheral emboli) [18-22]. This issue is discussed in detail separately. (See "Atrial septal abnormalities (PFO, ASD, and ASA) and risk of cerebral emboli in adults".)

Initial tests

Electrocardiogram — An electrocardiogram (ECG) is routinely performed in patients with a suspected ASD. The ECG may be normal with an uncomplicated small ASD. Most individuals with an ASD have normal sinus rhythm, but atrial arrhythmias often occur in adults. (See 'Atrial arrhythmias' above.)

The frontal plane QRS axis often ranges from +95 to +135° (right axis deviation) with a clockwise loop. A northwest (right superior) QRS axis (an axis from -90 to ±180°) usually suggests the presence of an AV canal defect.

P waves are typically normal with secundum ASDs. In comparison, sinus venosus defects are often associated with a leftward frontal plane P-wave axis (ie, negative in leads III and aVF and positive in lead aVL) [23]. 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 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. Patients with increasing severity of pulmonary hypertension tend to lose the rSr' pattern in V1 and develop a tall monophasic R wave with a deeply inverted T wave as right ventricular hypertrophy develops.

A notch on the R wave in the inferior leads (a pattern called "crochetage") has also been suggested as a sensitive and specific ECG sign of secundum ASD (waveform 1). In one report, this finding was present in 73 percent of patients with a secundum ASD versus 7.4 percent of normal subjects, 36 percent of patients with ventricular septal defects, and 23 percent of patients with pulmonic stenosis [24]. Among patients with an ASD, its frequency correlates with the size of the defect and the degree of left-to-right shunt.

Chest radiograph — The chest radiograph with an isolated ASD reflects the dilation of the right atrium, RV, and pulmonary arteries. Left atrial enlargement may be seen if there is associated mitral regurgitation or chronic atrial fibrillation. Shunt vascularity is characterized by enlarged main and branch pulmonary arteries, without redistribution of flow to the apical pulmonary vessels (image 1).

In comparison to these classic findings, the radiographic appearance in patients diagnosed at a later age may be atypical, especially in presence of acquired cardiovascular diseases. The atypical findings include normal vasculature, evidence of pulmonary venous hypertension, left atrial enlargement, and pulmonary edema [25]. In one study, atypical findings were more common in patients over the age of 50 (30 versus 6 percent in younger subjects) [25].

Transthoracic echocardiogram — Transthoracic echocardiography (TTE), often using agitated saline contrast if the defect is not readily apparent, is the primary test for the diagnosis of ASDs. Use of echocardiography and other tests to identify ASDs and associated lesions is discussed below. (See 'Echocardiography' below.)

DIAGNOSIS AND EVALUATION

When to suspect an ASD — Patients with a systolic murmur at the left sternal border associated with fixed splitting of the second heart sounds, unexplained right ventricular volume overload, atrial arrhythmias, or pulmonary hypertension should be referred for evaluation of possible ASD and/or partial anomalous pulmonary venous connection [1]. Diagnosis is important given the potential benefit of timely repair.

Approach to diagnosis and evaluation — The diagnosis and evaluation of an ASD includes demonstration of the presence, location, size, and direction of the shunt, as well as evaluation of any associated cardiac lesions and complications including RV volume overload, pulmonary hypertension, and arrhythmias [1]. The Qp:Qs should be assessed by cardiovascular magnetic resonance (CMR) or cardiac catheterization if the cause of right ventricular volume overload is uncertain. This information is used to determine whether ASD closure is indicated and candidacy for device closure. (See "Management of atrial septal defects in adults".)

Identification of ASD and associated anomalies

Echocardiography

-TTE with Doppler is generally the initial test for diagnosis and evaluation of ASDs, as it identifies most secundum and primum ASDs (movie 2A and movie 2B and movie 1 and movie 3 and movie 4) [1] and may also identify unroofed coronary sinus [26] and some variants of partial anomalous pulmonary venous connection (PAPVC). (See 'Transthoracic echocardiography' below.)

-Contrast echocardiography – If comprehensive TTE is not conclusive for ASD, echocardiography with agitated saline contrast with maneuvers (Valsalva and cough) may be helpful to identify an intracardiac shunt (movie 3). Agitated saline contrast in a left upper extremity vein is also helpful for identifying persistent left superior vena cava (which commonly accompanies unroofed coronary sinus. (See 'Agitated saline contrast' below.)

-Transesophageal echocardiography (TEE) is suggested if TTE is technically suboptimal or fails to show an ASD in a patient with suspected ASD. TEE is more sensitive than TTE in detection of ASDs, enables diagnosis of sinus venosus defects (of superior vena cava or inferior vena type), and aids in the sizing of secundum ASDs (as well as determination of suitability for transcatheter device closure). TEE is also helpful in identification of the most common forms of PAPVC. The TEE procedure should be performed by an experienced examiner or in conjunction with a congenital heart specialist since identification of the ASD and anomalous pulmonary veins can be challenging. (See 'Transesophageal echocardiography' below.)

Cross-sectional imaging – If TTE and TEE results are inconclusive, particularly for identification of sinus venosus defect or unroofed coronary sinus, assessment of anomalous pulmonary venous connection, or for the presence and cause of right ventricular volume overload, CMR or computed tomography (CT) imaging may be helpful. The CT or CMR procedure should be performed by an experienced cardiac imaging specialist since identification of the ASD and anomalous pulmonary veins requires special imaging protocols and can be challenging. (See 'CMR and CT' below.)

Evaluation of RV volume overload – Echocardiography is the primary means of assessment of RV size and function. RV volume overload is suggested by RV enlargement with diastolic flattening of the interventricular septum. The pulmonary arteries may also be dilated. If the echocardiogram is technically suboptimal or indeterminate, RV overload can be assessed using CMR or CT imaging. (See "Echocardiographic assessment of the right heart" and "Clinical utility of cardiovascular magnetic resonance imaging".)

Evaluation of pulmonary artery pressure – Pulmonary pressures should be assessed in all patients with ASDs. RV and pulmonary artery systolic pressures are estimated using Doppler echocardiography by obtaining the peak tricuspid regurgitation continuous-wave Doppler signal, using the modified Bernoulli equation, and adding the estimated right atrial pressure [27]. RV volume overload is suggested by diastolic flattening of the interventricular septum. RV pressure overload is suggested by systolic (or systolic and diastolic) flattening of the interventricular septum. (See 'Associated findings' below and "Echocardiographic assessment of the right heart".)

Indications for invasive cardiac catheterization to assess pulmonary artery pressures include an inconclusive noninvasive evaluation or features of severe pulmonary hypertension and are described below. (See 'Cardiac catheterization' below.)

Estimation of Qp:Qs - Estimation of the pulmonary blood flow to systemic blood flow (Qp:Qs) ratio is helpful in cases in which the cause of right atrial and RV chamber enlargement is uncertain and in cases in which the degree of shunt may help determine whether intervention would be beneficial.

The Qp:Qs ratio can generally be estimated noninvasively using CMR imaging; thus, cardiac catheterization is generally not required to determine the shunt flow ratio. (See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Congenital heart disease'.)

The Qp:Qs estimated by Doppler echocardiography has also been described, but this technique has limited reliability.

When required, a formal "shunt run" at cardiac catheterization measures the oxygen content in the blood at multiple sites, and the Fick equation is then used to calculate the Qp:Qs ratio (figure 4). (See 'Cardiac catheterization' below and "Pulmonary artery catheterization: Interpretation of hemodynamic values and waveforms in adults", section on 'Detection of left-to-right shunts'.)

Arrhythmia evaluation – Since atrial arrhythmias are common in adults with ASDs, these are assessed by electrocardiography. Longer-term monitoring (eg, by ambulatory cardiac monitoring, such as a Holter or longer-duration monitor) may be used to identify intermittent arrhythmias. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Evaluation'.)

Key tests

Echocardiography — Echocardiography is the imaging modality of choice for the diagnosis of ASDs, as it generally identifies and characterizes the ASD as well as associated abnormalities and complications. Since the sensitivity of echocardiography varies with technology, acoustic windows, and operator/patient factors, negative suboptimal or noncomprehensive echocardiograms do not exclude an ASD.

Transthoracic echocardiography — A comprehensive TTE includes two-dimensional imaging as well as color flow, pulsed-wave, and continuous-wave Doppler to determine the presence, size, location, flow characteristics, and hemodynamic effects of the ASD as well as associated lesions (movie 2A).

ASD and associated flow — TTE is usually diagnostic for secundum and primum ASDs when a complete examination (including multiple precordial windows) is performed by a trained sonographer/imager, unless the shunt is very small or images are technically suboptimal. Clues to the presence of a secundum or primum defect include abrupt discontinuity or drop out of the interatrial septum. Hypermobility of the septum, particularly in association with an abrupt discontinuity, is also suggestive of secundum defect. TTE may also detect unroofed coronary sinus defects.

The interatrial septum is often best visualized in the subcostal view in which the ultrasound beam is generally nearly perpendicular to the atrial septum [28]. However, this view is suboptimal in some individuals, particularly in obese subjects. Off-axis apical, parasternal short axis, and other nonstandard views are frequently necessary to interrogate the whole interatrial septum.

The diagnostic sensitivity of two-dimensional echocardiographic imaging using the subcostal approach was evaluated in a review of 154 patients (mean age 31 years) with a documented ASD (105 secundum, 32 primum, and 16 sinus venosus) in whom a satisfactory image of the atrial septum could be obtained by TTE [28]. The defect was successfully visualized in 89 percent of secundum ASDs, 100 percent of primum ASDs, and only 44 percent of sinus venosus ASDs. Contrast echocardiography using peripheral vein injection of agitated saline, when performed, identified all defects missed by two-dimensional TTE.

The interatrial septum may also be visualized in the apical four-chamber view, but this view should generally not be relied upon given the risk of artifactual echo dropout (low signal) as the ultrasound beam may be parallel to the atrial septum in this view.

The size of an ASD on two-dimensional TTE does not correlate well with shunt flow measured at catheterization. ASD size is better assessed with color flow (movie 2A) and pulsed-wave Doppler or three-dimensional TTE or TEE imaging. The addition of color flow Doppler imaging can help identify or confirm the presence of an ASD and indicate the overall direction of the flow across the atrial septum (movie 2A-B). Reducing the Nyquist limit (the upper limit of velocity that can be detected with a given Doppler pulse frequency) may enable detection of the turbulent shunt flow.

There are several limitations to color flow Doppler echocardiography in the diagnosis of ASD:

Ghosting of color across the interatrial septum sometimes gives the false impression of shunt flow (in particular with apical imaging).

An ASD can be missed by TTE when there is associated severe pulmonary hypertension as the latter reduces the shunt flow across the ASD. In this setting, agitated saline injection or TEE should be considered.

Unusual ASD location is another possible cause for missing an ASD; specifically, the sinus venosus and coronary sinus ASDs should be sought when no ASD is readily identified. Sinus venosus defects that are high or low in the septum (figure 2) may not be visualized with routine TTE imaging (only seen in 7 of 16 patients in one report); TTE with agitated saline contrast or TEE can identify nearly all of these patients [28].

Three-dimensional echocardiography (TTE or TEE) can facilitate precise sizing of ASDs and provide information that may be important for treatment (eg, transcatheter closure), such as the shape of the ASD and its relationship to atrial superior and inferior limbic band tissue, the aortic root, and the AV valves [29-31]. (See "Three-dimensional echocardiography".)

Use of agitated saline contrast in select cases is described below. (See 'Agitated saline contrast' below.)

Associated findings — Since initial imaging of the interatrial septum may be inconclusive, other evidence of ASD such as right atrial and ventricular enlargement due to volume overload (ie, diastolic interventricular septal flattening and increased pulmonary artery velocities without anatomic stenosis) and pulmonary artery dilatation should be sought. Continuous-wave Doppler echocardiography is used to estimate the RV and (thus indirectly) pulmonary artery systolic pressures. (See 'Approach to diagnosis and evaluation' above and "Echocardiographic assessment of the right heart", section on 'Pulmonary artery pressure'.)

In addition, associated congenital lesions should be sought:

Primum ASDs are generally accompanied by cleft anterior mitral valve leaflet and, less commonly, tricuspid valve, ventricular septal, and left ventricular outflow tract abnormalities.

Unroofed coronary sinus is commonly accompanied by persistent left superior vena cava.

Partial anomalous pulmonary venous drainage (primarily of the right upper and middle pulmonary veins) frequently accompanies superior sinus venosus defects and less frequently occurs with secundum ASDs [32]. (See "Partial anomalous pulmonary venous return".)

PAPVC with right-sided pulmonary veins connecting into the inferior vena cava (Scimitar) or left-sided pulmonary veins connecting into the innominate vein (the most common type) are better seen by TTE than TEE. Cross-sectional imaging readily demonstrates these congenital anomalies.

TEE is more helpful in identifying PAPVC to the superior vena cava. Partial anomalous pulmonary venous drainage (primarily of the right upper and middle pulmonary veins) frequently accompanies superior sinus venosus defects and less frequently occurs with secundum ASDs [32].

Agitated saline contrast — If comprehensive TTE with two-dimensional and color Doppler imaging is not conclusive for ASD, imaging following agitated saline contrast injection in a peripheral vein at rest and with one or more maneuvers (Valsalva or cough) is helpful to confirm the diagnosis [1]. Agitated saline contrast can be performed with TTE or TEE imaging (movie 3).

Contrast injection can be via any peripheral vein, but a left upper extremity injection site is required to assess persistent left superior vena cava (commonly associated with unroofed coronary sinus). The presence of unroofed coronary sinus with persistent left superior vena cava is identified after intravenous agitated saline injection in the left arm by detection of contrast in the left atrium before or simultaneous to the right atrium.

An adequate contrast injection causes opacification of the right atrium and ventricle. If there is a right-to-left interatrial shunt (transient or net), early appearance of contrast can be seen in the left atrium. (See "Contrast echocardiography: Clinical applications".)

A right-to-left interatrial shunt can be detected by contrast echocardiography in three circumstances:

Patent foramen ovale, with no or net left-to-right shunt, with transient elevation in right atrial pressure above left atrial pressure (generally timed during the end of the T wave) (movie 5). (See "Patent foramen ovale".)

With an uncomplicated ASD with net left-to-right shunt, when flow is temporarily reversed with transient increases in right atrial pressure relative to left atrial pressure (eg, with a Valsalva maneuver or coughing) or briefly during the onset of left ventricular contraction (movie 3 and movie 6).

With an ASD complicated by severe pulmonary hypertension with reversal of shunting across the ASD.

Agitated saline contrast echocardiography may also be used in the detection of a left-to-right shunt. However, negative contrast in the right atrium is an insensitive and nonspecific sign of left-to-right interatrial shunting [33,34] as flow from the contrast-free left atrium produces areas in the right atrium in which contrast is not seen. Care must be taken to distinguish this finding from lack of contrast opacification of the right atrium due to streaming of blood from vena cava inflow.

Transesophageal echocardiography — TEE is superior to TTE for imaging the interatrial septum and pulmonary veins and is often used when a definitive diagnosis is not made by TTE due to indeterminate findings or technically suboptimal images (eg, in patients with chest wall deformities, lung disease, or other causes for poor acoustic windows).

TEE is highly accurate for the diagnosis of all types of septal defects (movie 1) in the hands of an experienced operator. It is particularly helpful for detection of sinus venosus defects, which are often missed with TTE [28]. When performed with color flow Doppler, preferably with agitated saline contrast study, TEE can detect right-to-left shunting when there is transient reversal of flow through the ASD when right-sided pressure is increased (eg, with a Valsalva maneuver) or briefly during the onset of left ventricular contraction (movie 3 and movie 7). TEE is also more sensitive than TTE for the detection of left-to-right shunting as negative right atrial contrast (93 versus 58 percent in one report) [33]. TEE can also detect flow through multiple ASDs (movie 4).

Estimation of ASD size using the diameter of the Doppler color flow jet on TEE or three-dimensional TEE imaging generally correlates well with direct measurement at the time of surgery or balloon measurement at the time of percutaneous device placement [31,35].

TEE is also helpful in identification of PAPVC, especially connection to the superior vena cava. However, other types of PAPVC are better seen on TTE. Anomalous venous connection to the superior or inferior vena cava may be beyond the TTE/TEE imaging plane [36]. In this setting, CMR or CT should be used to define the anatomy of the anomalous venous connections.

CMR and CT — CMR and cardiac CT imaging can identify and characterize ASDs (including sinus venosus defect and unroofed coronary sinus, which might not be well characterized by echocardiography), identify and characterize PAPVC [37-40], and also estimate shunt flow (both by volumetric assessment and by direct flow measurements). Quantification of left-to-right shunting by CMR correlates well with shunt flow calculation based upon cardiac catheterization (invasive oximetry) with a small but not clinically significant overestimation of Qp:Qs by CMR [41]. Since ASDs can be diagnosed and treated based on noninvasive evaluation including CMR, there is only occasionally the need for cardiac catheterization. (See "Clinical utility of cardiovascular magnetic resonance imaging".)

Cardiac catheterization — Invasive cardiac catheterization is rarely required for diagnosis of ASDs since the evaluation can generally be performed using noninvasive means. Determination of the presence of an ASD by catheterization involves sampling of the oxygen content at multiple sites described below; a "step-up" in oxygen saturation is indicative of a left-to-right shunt. (See "Pulmonary artery catheterization: Interpretation of hemodynamic values and waveforms in adults", section on 'Detection of left-to-right shunts'.)

Cineangiography is rarely required to identify an ASD. When performed, optimal direct visualization of left-to-right shunting through an ASD is achieved by an injection of contrast just outside the orifice of the right upper pulmonary vein in the cranially angulated left anterior oblique projection (also known as the four-chamber view). With this view, secundum ASDs are seen in the middle of the atrial septum, and sinus venous and AV canal defects are seen at the superior and inferior aspect of the atrial septum, respectively.

Indications for cardiac catheterization in the evaluation of ASD include the following:

Inconclusive assessment of left-to-right shunt severity (ie, uncertain if hemodynamically significant, which is defined as causing right atrial and/or right ventricular enlargement with a Qp:Qs ≥1.5:1) by noninvasive means (echocardiography and CMR).

If significant pulmonary hypertension is suspected (pulmonary artery systolic pressure ≥50 percent of systemic systolic arterial pressure or pulmonary vascular resistance (PVR) ≥ one-third of systemic vascular resistance, and with no cyanosis at rest or during exercise), cardiac catheterization is indicated to measure pulmonary artery pressures, determine PVR, and assess reversibility with vasodilators, as this is important in determining whether defect closure is indicated [1,2]. (See "Management of atrial septal defects in adults", section on 'ASD closure' and "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis", section on 'Diagnosis and evaluation'.)

Assessment of left ventricular diastolic function, especially in adults with hypertension and other risk factors for elevated left ventricular diastolic pressure.

Device closure of secundum ASD.

When required, a formal "shunt run" at cardiac catheterization measures the oxygen content in the blood at multiple sites, and the Fick equation is then used to calculate the Qp:Qs ratio (figure 4). (See "Pulmonary artery catheterization: Interpretation of hemodynamic values and waveforms in adults", section on 'Detection of left-to-right shunts'.)

The sequence of steps in this determination is as follows:

The "shunt run" is performed, measuring oxygen saturation in the inferior vena cava (IVC), superior vena cava (SVC), right atrium, RV, and pulmonary artery (PA). Accurate catheter position during this procedure is essential. Mixed venous oxygen saturation (MvO2) can then be calculated as follows:

MvO2 = [(3 x SVC oxygen saturation) + (IVC oxygen saturation)] / 4

The SVC oxygen saturation is multiplied by three because SVC flow is approximately three times IVC flow.

Systemic arterial oxygen saturation (SaO2) is measured by arterial blood gas analysis or by pulse oximetry. (See "Pulse oximetry".)

O2 consumption is determined (this assessment should be based upon direct measurement, rather than assumed from available nomograms). This measurement requires substantial patient cooperation. (See "Oxygen delivery and consumption".)

The patient's blood hemoglobin (Hb) concentration is obtained from a complete blood count or blood gas analysis.

The systemic blood flow (Qs) is calculated from the Fick equation (figure 4):

Qs = (O2 consumption) ÷ (13.4 x [Hb] x [SaO2 - MvO2])

The pulmonary blood flow (Qp) is also calculated from the Fick equation (figure 4):

Qp = (O2 consumption) ÷ (13.4 x [Hb] x [pulmonary venous O2 saturation - PA O2 saturation])

This calculation requires a value for the pulmonary venous O2 saturation, which is not usually measured directly (although a catheter can be inserted across the ASD and into the pulmonary veins). If the SaO2 is above 95 percent, it may be used as an approximation of the pulmonary venous measurement.

If the SaO2 is less than 95 percent, a right-to-left shunt may be present and must be excluded by contrast echocardiography or other means. An SaO2 of less than 95 percent not due to a right-to-left shunt (eg, due to chronic lung disease) should be used as the accurate estimate of the pulmonary venous O2 saturation. If a right-to-left shunt is present, an assumed value of 98 percent for the pulmonary venous O2 saturation is used.

If there is no evidence of an associated right-to-left shunt, the volume of the left-to-right shunt is determined from the Qp:Qs. More complex calculations are required to determine shunt volume in the presence of bidirectional shunting.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Congenital heart disease in adults".)

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Atrial septal defects in adults (The Basics)")

SUMMARY AND RECOMMENDATIONS

An atrial septal defect (ASD) is a defect in the atrial septum and is classified by type based upon location including secundum ASD, primum ASD, superior sinus venosus defect, inferior sinus venosus defect, and unroofed coronary sinus (figure 1). (See 'Embryology and classification' above.)

ASDs are associated with left-to-right shunt which causes volume overload of the right heart chambers (figure 3), which is generally tolerated well for years. The development of progressive pulmonary vascular disease and pulmonary hypertension is highly variable and depends not only on the size and duration of the shunt but also the presence of other left-to-right shunts such as partial anomalous pulmonary venous connection. (See 'Pathophysiology' above and 'Pulmonary hypertension and Eisenmenger syndrome' above and "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

Most patients with an ASD and significant shunt flow (ie, pulmonary to systemic flow ≥1.5:1) will be symptomatic (with atrial arrhythmias, exercise intolerance, fatigue, dyspnea, and heart failure) and require closure by the age of 40. However, some patients do not become symptomatic until 60 years of age or older. (See 'History' above.)

The characteristic physical findings with an ASD with large left-to-right shunt and normal pulmonary artery pressures are a right ventricular heave, wide, fixed splitting of the second sound (S2), and pulmonary outflow murmur due to increased volume of flow across the pulmonary valve. (See 'Physical findings' above.)

Patients with a systolic murmur at the left sternal border associated with fixed splitting of the second heart sounds, unexplained right ventricular volume overload, or pulmonary hypertension should be referred for evaluation of possible ASD and/or partial anomalous pulmonary venous connection. (See 'When to suspect an ASD' above.)

The diagnosis and evaluation of an ASD includes demonstration of the presence, location, size, and direction of the shunt as well as evaluation of any associated cardiac lesions and complications including right ventricle (RV) volume overload and pulmonary hypertension. (See 'Approach to diagnosis and evaluation' above.)

Echocardiography is the initial imaging modality of choice for the diagnosis of ASD. Transthoracic echocardiography (TTE) can be definitive for ostium secundum and primum defects. Transesophageal echocardiography (TEE) aids in the diagnosis of sinus venosus defects of superior or inferior type, and the assessment of associated anomalies such as anomalous pulmonary venous connection. TEE is superior to TTE for the sizing and anatomic evaluation of defects for potential device closure. (See 'Echocardiography' above.)

If TTE and TEE results are inconclusive for the presence and cause of right ventricular volume overload, cardiovascular magnetic resonance (CMR) or computed tomography (CT) imaging may be helpful, particularly for identification of sinus venosus defect or assessment of anomalous pulmonary venous connection. (See 'CMR and CT' above and 'Approach to diagnosis and evaluation' above.)

Cardiac catheterization is not generally required for diagnosis and assessment of ASDs but is most commonly performed for assessment of equivocal shunts, severity and reversibility of pulmonary hypertension and left ventricular diastolic dysfunction, and for device closure of secundum ASD. (See 'Approach to diagnosis and evaluation' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledges Martin St. John Sutton, MD (deceased), who contributed to earlier versions of this topic review.

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Topic 1418 Version 26.0

References

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