Pediatric Atrial Septal Defects

Updated: Mar 31, 2017
  • Author: Michael R Carr, MD; Chief Editor: Syamasundar Rao Patnana, MD  more...
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Overview

Background

Congenital heart defects (CHD) are common in children, with an incidence of approximately 8 cases per 1000 live births. These defects can cause an array of problems in the primary care of children. Atrial septal defects (ASDs) are a prevalent form of CHD. An understanding of human embryology is essential for diagnosing these abnormalities, understanding the pathophysiology and in planning long-term treatment.

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Pathophysiology

Cardiac tissues are first detectable on the 18th or 19th day of fetal life. Cardiac development continues for the next several weeks. The atrial septum begins to form during the fourth week of gestation and is complete by the end of 5 weeks' gestation.

Classic model of cardiac development

According to the classic model of cardiac development, the process begins when a thin crescent-shaped membrane (septum primum) begins to form along the dorsal and cranial walls of the atrium. The space between the septum primum and the endocardial cushions (ostium primum) becomes progressively smaller as the septum primum grows toward the endocardial cushions. Before the ostium primum completely closes, small perforations develop in the anterosuperior wall of septum primum and ultimately coalesce to form a second interatrial communication, the ostium secundum. Meanwhile, the leading edge of the septum primum fuses with the endocardial cushions, and the ostium primum disappears.

Near the end of 5 weeks' gestation, the second phase of the process begins when a second crescent-shaped membrane (septum secundum) begins to form within the atrium to the right of the first septum. This membrane also begins to grow toward the endocardial cushions, covering the ostium secundum. However, the septum secundum remains incomplete. The foramen ovale is the opening remaining after the septum secundum completely forms.

The final phase of the process begins when the upper portion of the septum secundum proceeds to degenerate and finally disappears. The fully formed atria now have 2 overlapping but incomplete septae. The upper portion of the septum secundum covers the ostium secundum and creates a one-way valve allowing right-to-left shunting of blood in the fetus.

Van Praagh and Corsini model of cardiac development

Van Praagh and Corsini proposed another model of cardiac development. [1] According to their model, the septum primum (also known as the flap valve of the foramen ovale) grows from the portion of the left venous valve of the sinus venosus that is furthest left. As it extends from the most dorsal aspect of the atrium, the septum primum begins to meet the septum secundum, which is an invagination of the most rostral portion of the primitive atrium. The marginal edges of the septum primum eventually meet the left aspect of the septum secundum.

During embryonic and fetal life, the central portion of the septum primum billows into the left atrium due to the normal right to left shunting at the atrial level. After birth, the remainder of the septum primum adheres to the left aspect of the septum secundum.

Recent identification of an anomaly called deviated superior attachments of septum primum provides evidence in favor of the Van Praagh and Corsini model. Additional detailed morphologic analysis of murine cardiac development is needed to determine which model is correct.

Types of atrial septal defects

Four basic types of atrial septal defects are known. Patients who simultaneously have the first 3 types of atrial septal defect, as described below, are said to have common atrium.

The first type is an ostium secundum defect. The most common yet least serious type of atrial septal defect is an ostium secundum defect. This defect occurs in the area of the fossa ovalis and presumably results from excessive fenestration or resorption of septum primum, underdevelopment of septum secundum, or some combination of the 2 conditions (see images below).

In approximately one half of patients with left atrioventricular (AV) valve underdevelopment (ie, hypoplastic left heart syndrome or Shone complex), the superior attachments of the flap valve of the foramen ovale lie on the left atrial roof, well to the left of the septum secundum. Weinberg et al (1986) called this anomaly "(leftward and posterior) deviation of the superior attachments of septum primum." [2] This deviation is observed extremely rarely in patients with a normal-sized left AV valve. Of importance, the classic model does not explain its existence well. This type can be regarded as a variation of an ostium secundum defect, although it is most rigorously designated as a malalignment-type atrial septal defect.

A second variant of the ostium secundum defect is its association with an aneurysm of the atrial septum. This is thought to be due to redundancy of the valve of the fossa ovalis. It may be associated with mitral valve prolapse or atrial arrhythmias. There is debate regarding its association with thrombus formation and an increased risk for stroke.

Subcostal echocardiographic view of a child with a Subcostal echocardiographic view of a child with a secundum atrial septal defect (ASD). Note the position of the defect in the atrial septum. LA = left atrium; RA = right atrium; SVC = superior vena cava.
Subcostal long-axis view of the same child as in t Subcostal long-axis view of the same child as in the previous image with a secundum atrial septal defect (ASD). LA = left atrium; RA = right atrium; RUPV = right upper pulmonary vein.
Parasternal short axis view of a child with a secu Parasternal short axis view of a child with a secundum atrial septal defect (ASD). AO = aorta; LA = left atrium; RA = right atrium.

The second type is an ostium primum defect. This atrial septal defect presumably results from failure of the endocardial cushions to close the ostium primum. Because endocardial cushions also form the mitral and tricuspid valves, ostium primum defects are virtually always associated with a cleft in the anterior mitral valve leaflet (see the images below).

Apical echocardiographic view of a primum atrial s Apical echocardiographic view of a primum atrial septal defect (ASD). Note the position of the defect when compared with a secundum ASD. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.
Apical echocardiographic view of a primum atrial s Apical echocardiographic view of a primum atrial septal defect (ASD). Note that the atrioventricular valves are at the same level (instead of mild apical displacement of the tricuspid valve), which is seen in the spectrum of atrioventricular canal defects. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.
Apical color Doppler echocardiographic view of a p Apical color Doppler echocardiographic view of a primum atrial septal defect (ASD). Note the flow across the defect from the left atrium to the right atrium (RA), and note the mitral regurgitation (MR) through a cleft in the anterior leaflet of the mitral valve. LV = left ventricle; MV = mitral valve.

The third type is a sinus venosus defect. This atrial septal defect is found in the posterior aspect of the septum near the superior vena cava (where it may coexist with partial anomalous pulmonary venous connection of the right upper pulmonary vein) or the inferior vena cava (where it may coexist with partial anomalous pulmonary venous defect of the right lower pulmonary vein). See the image below.

Subcostal short-axis view of a child with a sinus Subcostal short-axis view of a child with a sinus venosus atrial septal defect (ASD). Note the position of the defect compared with that of a secundum or primum ASD. Also note the anomalous position of the right upper pulmonary vein (RUPV). LA = left atrium; RA = right atrium.

The sinus venosus defects may also be located in the inferior-posterior part of the atrial septum, overriding the inferior vena caval orifice, but these are extremely rare. [3]

The fourth type is a coronary sinus septal defect. This least common type of atrial septal defect is called an unroofed coronary sinus or coronary sinus septal defect. A portion of the roof of the coronary sinus is missing; therefore, blood can be shunted from the left atrium into the coronary sinus and subsequently into the right atrium. This type is often associated with a left superior vena cava.

To complete the discussion of the atrial septal defects, one might add patent foramen ovale (PFO) to the list of atrial septal defects. The PFO is present in nearly one third of healthy infant populations and is likely to be a normal variant. [3] However, the PFO may become important in the presence of structural abnormalities of the heart in that it facilitates intracardiac shunts to permit egress and/or mixing of blood flows. The PFO is also deemed be the seat of paradoxical embolism resulting in stroke/transient ischemic attacks, or in other conditions such as migraine, Caisson disease and platypnea-orthodexia syndrome, particularly in adult subjects. [3]

Left-to-right shunting

Clinical effects of isolated atrial septal defects are usually related to left-to-right shunting. The magnitude of shunt is related to the size of the defect in the septum, to the relative compliance of the left-sided and right-sided cardiac chambers, and indirectly related to the resistance of the pulmonary and systemic circulations. At birth, the right and left ventricles are of equal thickness and similar compliance. In the first few days to weeks after birth, the pulmonary vascular resistance (PVR) remains mildly elevated and has not reached its nadir.

As impedance to pulmonary blood flow decreases and the right ventricle becomes more compliant, blood is able to flow to the pulmonary vascular bed more easily, and the atrial level left-to-right shunt increases.

On occasion, the septal defect is small, with little left-to-right shunting. However, most defects that cause murmurs or symptoms are moderate to large, and the size of the defect does little to limit left-to-right shunting. Approximately 15% of ostium secundum atrial septal defects spontaneously close by age 4 years, and others may decrease in size as to not be hemodynamically significant.

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Etiology

Although many cases of atrial septal defect are sporadic, atrial septal defect clearly has a genetic component and may be associated with genetic syndromes. [4, 5]

Ostium secundum atrial septal defect is typically a part of the Holt-Oram syndrome, which is caused by mutations in the T-box transcription factor TBX5 on chromosome 12q. Most of the mutations are deletions, frameshifts, or premature stop codons. This autosomal dominant and highly penetrant disease also includes absent or hypoplastic radii and first-degree heart block. [6]

Ostium secundum atrial septal defect can also be associated with the following genetic abnormalities: Ellis-van Creveld syndrome, Noonan syndrome, Rubinstein-Taybi syndrome, Kabuki syndrome, Williams syndrome, Goldenhar syndrome, and thrombocytopenia-absent radius syndrome, as well as chromosomal abnormalities (eg, deletions in 1, 4, 4p, 5p, 6, 10p 11, 13, 17, 18, 22) or in trisomy 18 and Klinefelter syndrome. [7] Ellis-van Creveld syndrome can be associated with a common atrium.

Ostium secundum, ostium primum atrial septal defect, or both may occur in trisomy 21 (Down syndrome). For unknown reasons, sinus venosus defects are rare in Down syndrome, making common atrium similarly rare in this population.

An autosomal dominant form of familial atrial septal defects with incomplete penetrance has been detected.

Mutations in NKX2.5, a homeodomain-containing transcription factor, have been associated with atrial septal defects with and without atrioventricular (AV) block and was the first gene identified leading to nonsyndromic atrial septal defect. To date, more than 40 NKX2.5 mutations have been detected. [8] Interestingly, the type and location of the mutation predicts the phenotype, with nonsense mutations, frameshift mutations, and all mutations located in the homeodomain causing AV conduction disease, and missense mutations outside the homeodomain show no AV conduction disease.

Mutations in GATA4, an important regulator of cardiac development, have been associated with atrial septal defects. Interactions between GATA4and NKX2.5 and interactions between GATA4 and TBX5 may be the root of the cardiac defects seen with GATA4 mutations, which establishes a link among these genes. [7, 9]

TBX20, a member of the TBX transcription factor family, is very highly expressed in the embryonic heart and also interacts extensively with NKX2.5GATA4 and TBX5 during cardiac embryogenesis. It has been speculated that it may have a role in defects of the atrial septum. [7]

Interestingly, a missense mutation in myosin heavy chain 6 (MHY6) has also been identified with an autosomal dominant form of atrial septal defect. MHY6 was previously described in late-onset hypertrophic cardiomyopathy. This gene is highly expressed in the developing atria and appears to be influenced by TBX5 and GATA4 mutations, again establishing a link between several genes. In a recent study by Posch et al, 3 novel missense mutations were found in MYH6 and no other mutations were identified in 11 other sarcomeric genes analyzed, leading the authors to conclude that MYH6 was the predominant sarcomeric disease gene for familial atrial septal defect. [7, 10]

The prognostic implications of the involvement of a sarcomeric protein with atrial septal defects has yet to be fully elucidated but suggest that sarcomeric filaments play a role in cardiac morphogenesis and atrial septal development. Further genetic analysis will likely yield other mutations and genetic links associated with familial atrial septal defects.

Atrial septal defects have been linked to maternal disease and exposure to environmental risk factors during pregnancy. Maternal diseases include phenylketonuria, pregestational diabetes, methylenetetrahydrofolate reductase deficiency (MTHFR deficiency), febrile illnesses, and influenza. Environmental risk factors include medications such as anticonvulsants and nonsteroidal anti-inflammatory drugs (NSAIDs) or exposure to organic solvents. Atrial septal defects are also found in children with fetal alcohol syndrome.

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Epidemiology

United States data

Research indicates that congenital heart disease is diagnosed in 0.8% of children in the first year of life. Atrial septal defect is the second most common congenital heart defect in children and adults and occurs in anywhere from 0.67-2.1 per 1000 live births. Secundum atrial septal defects comprise just over 90% of all atrial septal defects, whereas sinus venosus and primum atrial septal defects comprise between 3-4% each. About 15-30% of healthy adults have an unfused foramen ovale in which the valve functions normally but has failed to fuse. In these individuals, a cardiac catheter passed into the right atrium can pass into the left atrium through the foramen ovale (ie, probe-patent foramen ovale).

Sex- and age-related demographics

The female-to-male ratio is approximately 2:1.

Atrial septal defect, a congenital abnormality, is present at birth. However, in most cases, a murmur is not audible until the child is a few months old. Symptoms usually do not occur in individuals with atrial septal defect until late childhood, adolescence, or adulthood.

Secundum type (ie, ostium secundum), sinus venosus, and unroofed coronary sinus defects are sometimes not diagnosed until the third decade of life.

Ostium primum atrial septal defects are usually diagnosed in the first few years of life because of mitral regurgitation murmur or an abnormal ECG.

A common atrium (ie, a combination of sinus venosus, ostium secundum, and ostium primum defects) is usually diagnosed in the first few years of life because systemic venous blood and pulmonary venous blood often partially mix before entering each ventricle; this condition manifests as cyanosis. In addition, a common atrium may be associated with complex CHD, and patients may present relatively early because of other intracardiac abnormalities.

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Prognosis

The prognosis for a child with an atrial septal defect (ASD) is good; the rate of surgical mortality is less than 1%. Many children are candidates for catheter-based device implantation, which also carries a very low procedural morbidity and mortality and avoids the risks associated with a median sternotomy and cardiopulmonary bypass.

Ostium secundum defects may spontaneously close. A wide range of spontaneous closure rates have been reported among different studies, ranging from 4-87%. The likelihood of spontaneous closure appears to be closely related to the initial size of the defect. One study demonstrated a 56% spontaneous closure rate and 30% regression to a diameter of less than 3 mm for defects 4-5 mm in diameter. Conversely, none of the defects more than 10 mm in diameter closed spontaneously, and 77% of those required intervention. The general thought is that spontaneous closure does not occur with ostium primum, sinus venosus, or coronary sinus defects. [11, 12]

Infants weighing less than 10 kg with ostium secundum defects may undergo interventional closure with favorable outcomes and without any additional major risks. [13] Favorable outcomes are likely even in select infants with significant noncardiac comorbid conditions. [13]

Certain patients with ostium primum atrial septal defects and an abnormal mitral valves may require a second operation for mitral valve dysfunction later in their lives.

The repair of sinus venosus atrial septal defects can be more complex and often involves baffling of the right upper pulmonary vein to the left atrium and anastomosis of the superior vena cava to the right atrial appendage. Stenosis of the right upper pulmonary vein baffle or superior vena cava/atrial appendage anastomotic site may require further catheter-based or surgical intervention. [14]

Endocarditis of catheter-placed devices has been reported (but rare) and may necessitate removal of the hardware and surgical repair.

Surgical or catheter-based intervention of atrial septal defects in individuals outside of childhood is generally feasible, even in the face of pulmonary vascular changes and evidence of pulmonary hypertension. This is distinctly different from similar aged individuals with moderate-to-large post-tricuspid shunts (ventricular septal defect, aortopulmonary window, patent ductus arteriosus, or major aortopulmonary collateral vessels), who often have markedly elevated pulmonary vascular resistance and Eisenmenger physiology. However, when compared with earlier timing of intervention, some evidence suggests that patients repaired later in life have higher longer-term morbidity. [15]

Morbidity/mortality

In developed countries, mortality rate of atrial septal defect is low (<1%). Morbidity secondary to atrial septal defect is unusual and typically limited to 3 groups of patients.

Approximately 1% of infants with moderate or large (ie, nonrestrictive) atrial septal defects, but no other left to right shunting lesion (eg, patent ductus arteriosus, ventricular septal defect), have tachypnea and failure to thrive. In these individuals, the pulmonary artery pressure, when measured during catheterization or Doppler echocardiography, is at or near systemic level. In most instances, this is a flow-related phenomena (high flow/low resistance), but in infants predisposed to abnormal pulmonary vasculature, there may be a combination of both elevated flow and resistance. Attempts to exclude mitral or left ventricular diastolic abnormalities as a cause of these hemodynamics must be undertaken, as well as a thorough assessment of pulmonary anatomy and mechanics, as both left-sided cardiac disease and primary pulmonary disease can mimic symptoms of pretricuspid shunting.

Patients in whom atrial septal defects go unrecognized until late childhood may develop arrhythmias (eg, atrial fibrillation, atrial tachycardia) or pulmonary hypertension. Atrial septal defects that initially appear in middle-aged or elderly adults can indicate congestive heart failure (CHF). Symptoms of CHF can also appear in pregnant women with undiagnosed atrial septal defect due to the increased circulating blood volume normally seen in pregnancy.

Patients with atrial septal defects may have an embolic stroke as the initial presentation.

Complications

Atrial septal defect is usually an asymptomatic disease. However, children with atrial septal defects are at increased risk for several complications, such as endocarditis (if associated mitral valve insufficiency is present) and respiratory tract infections, which are less well tolerated in children with atrial septal defects than in children without atrial septal defects. Any individual with an atrial level shunt is at risk for a paradoxical embolus from a venous thrombus, but in children, this is exceedingly rare, unless there is an underlying hypercoagulable state.

Children with clinically significant and untreated atrial septal defects are at risk for various cardiac complications, including congestive heart failure, pulmonary hypertension, and arrhythmias. However, these cardiac complications generally manifest in adulthood.

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Patient Education

Focus patient education on ensuring that the family and caregivers understand potentially serious symptoms so that they seek prompt medical attention when necessary. However, parents also require consistent education regarding long-term prognosis, which is generally quite good, as well as the expected signs and symptoms that can be seen with the defect, which are usually minimal.

Reassurance is often needed due to the stigmata associated with the diagnosis of congenital heart disease (CHD). Some children may be unnecessarily restricted from activity by well-meaning medical personnel or by over-cautious parents.

Education regarding care of an atrial septal defect and its complications should also include input from the cardiologist and cardiac surgeon.

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