Atrial Septal Defect

Updated: May 01, 2017
  • Author: David H Adler, MD, FACC; Chief Editor: Yasmine Subhi Ali, MD, FACC, FACP, MSCI  more...
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Overview

Background

Atrial septal defect (ASD) is one of the more commonly recognized congenital cardiac anomalies presenting in adulthood. ASD is characterized by a defect in the interatrial septum allowing pulmonary venous return from the left atrium to pass directly to the right atrium. Depending on the size of the defect, size of the shunt, and associated anomalies, this can result in a spectrum of disease ranging from no significant cardiac sequelae to right-sided volume overload, pulmonary arterial hypertension, and even atrial arrhythmias.

With the routine use of echocardiography, the detection and, therefore, the incidence of ASD is increased compared to earlier incidence studies using catheterization, surgery, or autopsy for diagnosis. [1]  The subtle physical examination findings and often minimal symptoms during the first 2-3 decades of life contribute to a delay in diagnosis until adulthood, the majority (more than 70%) of which is detected by the fifth decade of life. However, earlier intervention of most types of ASD is recommended.

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Pathophysiology

The magnitude of the left-to-right shunt across the atrial septal defect (ASD) depends on the defect size, the relative compliance of the ventricles, and the relative resistance in both the pulmonary and systemic circulation. With small ASD, left atrial pressure may exceed right atrial pressure by several millimeters of mercury, whereas with large ASD, mean atrial pressures are nearly identical. Shunting across the interatrial septum is usually left-to-right and occurs predominantly in late ventricular systole and early diastole. Likely some augmentation occurs during atrial contraction. Note, however, that a transient and small right-to-left shunt can occur, especially during respiratory periods of decreasing intrathoracic pressure, even in the absence of pulmonary arterial hypertension.

The chronic left-to-right shunt results in increased pulmonary blood flow and diastolic overload of the right ventricle. Resistance in the pulmonary vascular bed is commonly normal in children with ASD, and the volume load is usually well tolerated even though pulmonary blood flow may be more than 2 times systemic blood flow. Altered ventricular compliance with age can result in an increased left-to-right shunt contributing to symptoms. The chronic significant left-to-right shunt can alter the pulmonary vascular resistance leading to pulmonary arterial hypertension, even reversal of shunt and Eisenmenger syndrome.

Because of an increase in plasma volume during pregnancy, shunt volume can increase, leading to symptoms. Pulmonary artery pressure usually remains normal.

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Etiology

Atrial septal defect (ASD) is a congenital cardiac disorder caused by the spontaneous malformation of the interatrial septum. Note the following types of ASD:

  • Ostium secundum ASD: This type of ASD results from incomplete adhesion between the flap valve associated with the foramen ovale and the septum secundum after birth. The patent foramen ovale usually results from abnormal resorption of the septum primum during the formation of the foramen secundum. Resorption in abnormal locations causes a fenestrated or netlike septum primum. Excessive resorption of the septum primum results in a short septum primum that does not close the foramen ovale. An abnormally large foramen ovale can occur as a result of defective development of the septum secundum. The normal septum primum does not close this type of abnormal foramen ovale at birth. A combination of excessive resorption of the septum primum and a large foramen ovale produces a large ostium secundum ASD.
  • Ostium primum ASD: These defects are caused by incomplete fusion of septum primum with the endocardial cushion. The defect lies immediately adjacent to the atrioventricular (AV) valves, either of which may be deformed and incompetent. In most cases, only the anterior or septal leaflet of the mitral valve is displaced, and it is commonly cleft. The tricuspid valve is usually not involved.
  • Sinus venosus ASD: Abnormal fusion between the embryologic sinus venosus and the atrium causes these defects. In most cases, the defect lies superior in the atrial septum near the entry of superior vena cava. Often there is associated anomalous drainage of the right superior pulmonary vein. The relatively uncommon inferior type is associated with partial anomalous drainage of the right inferior pulmonary vein. Anomalous drainage can be into the right atrium, the superior vena cava, or the inferior vena cava.
  • Coronary sinus ASD: The coronary sinus defect is characterized by unroofed coronary sinus and persistent left superior vena cava that drains into the left atrium. A dilated coronary sinus often suggests this defect. This can result is desaturation due to right-to-left shunt into the left atrium. The diagnosis can be made by injecting contrast agent into left upper extremity; coronary sinus opacification precedes right atrial opacification.

Genetics

ASD may occur on a familial basis. Holt-Oram syndrome characterized by an autosomal dominant pattern of inheritance and deformities of the upper limbs (most often, absent or hypoplastic radii) has been attributed to a single gene defect in TBX5. [2] The penetrance is nearly 100% for Holt-Oram syndrome. Approximately 40% of Holt-Oram cases are due to new mutations.

Ellis van Creveld syndrome is an autosomal recessive disorder associated with skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth, and a common atrium, occurring in 60% of affected individuals. [3]

Mutations in the cardiac transcription factor NKX2.5 have been attributed to the syndrome familial ASD associated with progressive atrioventricular block. [4, 5, 6]  This syndrome is an autosomal dominant trait with a high degree of penetrance but no associated skeletal abnormalities.

Variants in the GATA4 gene have also been implicated in ASD. [5, 7] More recently, a novel mutation at the methylation position of GATA4 (c.A899C, p.K300T) has been reported in association with ASD. [7]

Wang et al reported that downregulation of the following genes in ASD may affect heart atrial septum formation, cardiomyocyte proliferation, and cardiac muscle development [5] :

  • Cardiac specific transcriptional factors GATA4 and NKX2-5
  • Extracellular signal molecules VEGFA and BMP10
  • Cardiac sarcomeric proteins MYL2, MYL3, MYH7, TNNT1, and TNNT3

The investigators noted that dysregulation of these genes during heart septum morphogenesis may lead to cell cycle as the dominant pathway among downregulated genes, with the potential for the decreased expression of the proteins included in the cell cycle then disturbing cardiomyocyte growth and differentiation during atrial septum formation. [5]

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Epidemiology

The three major types of atrial septal defect (ASD) account for 10% of all congenital heart disease and as much as 20-40% of congenital heart disease presenting in adulthood. The most common types of ASD include the following:

  • Ostium secundum: The most common type of ASD accounting for 75% of all ASD cases, representing approximately 7% of all congenital cardiac defects and 30-40% of all congenital heart disease in patients older than 40 years.
  • Ostium primum: The second most common type of ASD accounts for 15-20% of all ASDs. Primum ASD is a form of atrioventricular septal defect and is commonly associated with mitral valve abnormalities.
  • Sinus venosus: The least common of the three, sinus venosus (SV) ASD is seen in 5-10% of all ASDs. The defect is located along the superior aspect of the atrial septum. Anomalous connection of the right-sided pulmonary veins is common and should be expected. Alternate imaging is generally required.

Sex- and age-related demographics

ASD occurs with a female-to-male ratio of approximately 2:1.

Patients with ASD can be asymptomatic through infancy and childhood, though the timing of clinical presentation depends on the degree of left-to-right shunt. Symptoms become more common with advancing age. By age 40 years, 90% of untreated patients have symptoms of exertional dyspnea, fatigue, palpitation, sustained arrhythmia, or even evidence of heart failure.

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