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INTRODUCTION
Atrial septal defect (ASD) is an opening in the atrial septum permitting the shunting of blood between
the atria. There are three major types: ostium secundum, ostium premium, and sinus venosus. Ostium
secundum is the most common type (Toyno M, et al., 2008).
An isolated secundum atrial septal defect very seldom causes significant symptoms in pediatric patients,
regardless of defect size (Abid D, et al., 2013).
ASD secondum occurs in 7% of patients with congenital heart disease and is two times more common in
females than males. The defect is most often sporadic but may be familial or have a genetic basis such
as“Holt-Oram syndrome” (Syamasundar p, et al., 2012).
Mitral valve prolapse (MVP) is the most common anomaly of mitral valve, it occurs when one leaflets
excessively billows into the left atrium toward the end of systole. Mitral regurgitation (MR) develops in
some patients with mitral valve prolapse, particularly those with more significant prolapse (Mansoory
MS et al., 2013).
The Incidence of mitral valve prolapse in patients with atrial septal defect (ASD) has been reported to be
high; this incidence is about 35 % (Suchon E et al., 2004).The reasons for this high incidence has not
been completely explained yet. The discussion on the high incidence of MVP in patients with ASD have
focused on two hypotheses, one of these is the anatomical co-existence of ASD and MVP as a result of a
congenital common connective tissue defect. The other hypothesis is the anomaly occurring in the
geometry of the left ventricle due to ASD (Kestelli M et al., 2002).
Atrial septal defect closure leads to normalization of left ventricular geometry and in patients with
evidence of mitral valve prolapse, is associated with a decrease in the degree of prolapse. (Suchon et al.,
2004).
Echocardiography is the most useful method of diagnosing a prolapsed mitral valve. Two- and threedimensional echocardiographies are particularly valuable as they allow visualization of the mitral leaflets
relative to the mitral annulus. This allows measurement of the leaflet thickness and their displacement
relative to the annulus. Thickening of the mitral leaflets >5 mm and leaflet displacement >2 mm
indicates classic mitral valve prolapse (Addetia K, et al., 2013).
Three-dimensional (3D) echocardiography has recently become a practical reality. It is now practicable
to perform 3D echocardiography using transthoracic and transesophageal acoustic windows both in
adults and children. An important aspect of 3D echocardiography is its ability to supply accurate
quantitative data without the use of geometric assumptions (Bartakian S, et al., 2012).
By 3D echocardiography it is possible to visualize the mitral valve en face from either the left
atrium or the left ventricle. In volume rendered images looking down in the left atrium, mitral valve
prolapse is viewed as a convexity or bulge, and often as bright area when compared with the rest of the
mitral leaflet. Looking up in the left ventricle mitral valve prolapse appears as a spoon-like depression. In
patients with mitral valve prolapse and mitral regurgitation a crack due to noncoaptation can be
identified (Gabriel V`, et al., 2005).
AIM OF THE WORK
We aimed through this work to identify the effect of ASD closure on the associated MVP and to evaluate
the role of 3 D echocardiography in the diagnosis and follow up of this condition.
ATRIAL SEPTAL DEFECT
Arial septal defect (ASD) is an abnormal opening in the muscular wall separating the left and right upper
chambers (atria) of the heart permitting the shunting of blood between the atria. ASDs account for 5%
to 10% of all congenital heart diseases , As a group, atrial septal defects are detected in 1 child per 1500
live births and for about 30% of the congenital heart defects diagnosed in adults (Lairakdomrong K, et
al., 2013).
Figure (1): Atrial septal defect (John J, et al., 2011).
Embryology
In the early embryo heart, the atria comprise a common chamber. The septum primum, which is the first
septum to develop, is an incomplete thin-walled partition in which the anteroinferior free edge is above
the atrioventricular canal and becomes lined by tissue derived from the superior and inferior
endocardial cushions. Before the resultant interatrial opening (ostium primum) becomes sealed by
endocardial cushion tissue, programmed cell death in an area near the anterosuperior aspect of the
septum primum creates small cribriform perforations. These perforations coalesce to form a large,
second interatrial communication (ostium secundum) maintaining interatrial blood flow.
At this time, to the right of the first septum, an anterosuperior infolding of the atrial roof occurs and
forms a second septal structure (septum secundum). It expands posteroinferiorly as a thick-walled
muscular ridge to form an incomplete partition that overlies the ostium secundum. As atrial septation is
accomplished, septum secundum forms the limbus of the fossa ovalis and septum primum forms the
valve of the fossa ovalis. The channel for interatrial blood flow through the ostium secundum is known
as the foramen ovale (Hidalgo A, et al., 2008).
Concurrently with atrial septation, the left horn of the sinus venosus forms the coronary sinus, and the
right sinus horn becomes a part of the right atrium. Infolding at the sinoatrial junction forms the right
and left venous valves. Whereas the right venous valve is maintained and forms the rudimentary valves
of the inferior vena cava (Eustachian valve) and the coronary sinus (Thebesian valve), the left venous
valve becomes fused to the superior, posterior, and inferior margins of the fossa ovalis
et al., 2012).
(Briggs LE,
Figure (2) Schematic diagram showing the embryologic sequence of atrial septation. Left, left atrium;
right, right atrium; PFO, patent foramen ovale(Briggs LE, et al., 2012).
Patent Foramen Ovale
The foramen ovale (PFO) represents a normal interatrial communication that is present throughout fetal
life, Functional closure of the foramen ovale occurs postnatally as pressure in the left atrium exceeds
that in the right atrium. As a result, the valve of the fossa ovalis is pressed against the limbus and forms
a competent seal. During the first year of life, fibrous adhesions may develop between the limbus and
valve and thereby produce a permanent anatomic seal and an imperforate atrial septum. In 25% to 30%
of people, however, anatomic closure does not occur, and a potential interatrial channel persists
through which blood or air may shunt whenever pressure in the right atrium exceeds that in the left
atrium (Saremi F, et al., 2008).
If atrial dilation occurs among individuals with a patent foramen ovale, the limbus may become so
stretched that the ostium secundum (valve of the fossa ovalis) may no longer be covered by the limbic
ledge. The result is a valvular incompetent patent foramen ovale that allows interatrial shunting
throughout the cardiac cycle and thus constitutes an acquired ASD (Anderson RH, et al., 2002).
Types of ASDs:
1.
The ostium secundum defect, located in the area of the fossa ovalis, is the most common type of
ASD, accounting for 75% of all cases. Although it usually consists of a single defect, fenestrated defects
have also been reported. Secundum ASDs can be associated with partial anomalous pulmonary venous
return (< 10%) and mitral valve prolapse.
2.
The ostium primum defect accounts for 15% of ASDs, and is located in the lower part of the
interatrial septum. It can be associated with a "cleft" anterior mitral valve leaflet, resulting in mitral
regurgitation.
3.
The sinus venosus defect, which accounts for 10% of ASDs, usually involves the junction of the
superior vena cava. Anomalous pulmonary venous return is a common manifestation. Sinus venousinferior vena cava defects are rare.
4.
Coronary sinus ASDs are also rare and result from direct communication of the coronary sinus
and the left atrium. Persistent left superior vena cava is commonly associated with this condition
(Bradley EA, et al., 2013).
Figure (3): Types of ASD (Saremi F, et al., 2008).
Pathophysiology
In unaffected individuals, the chambers of the left side of the heart make up a higher pressure system
than the chambers of the right side of the heart. This is because the left ventricle has to produce enough
pressure to pump blood throughout the entire body, while the right ventricle only has to produce
enough pressure to pump blood to the lungs.
In the case of a large ASD (>9mm), which may result in a clinically remarkable "left-to-right shunt", blood
will shunt from the left atrium to the right atrium causing excessive interatrial communication (In the
case of hemodynamically significant ASD (QP: Qs > 1.5:1), the patient is often found to be notably
symptomatic and ASD repair may be indicated). This extra blood from the left atrium may cause a
volume overload of both the right atrium and the right ventricle, which if left untreated, can result in
enlargement of the right side of the heart and ultimately heart failure (Suchoń E, et al., 2008).
Any process that increases the pressure in the left ventricle can cause worsening of the left-to-right
shunt. This includes hypertension, which increases the pressure that the left ventricle has to generate in
order to open the aortic valve during ventricular systole, and coronary artery disease which increases
the stiffness of the left ventricle, thereby increasing the filling pressure of the left ventricle during
ventricular diastole. The right ventricle will have to push out more blood than the left ventricle due to
the left-to-right shunt. This constant overload of the right side of the heart will cause an overload of the
entire pulmonary vasculature. Eventually the pulmonary vasculature will develop pulmonary
hypertension to try to divert the extra blood volume away from the lungs (John J, et al., 2011).
The pulmonary hypertension will cause the right ventricle to face increased afterload in addition to the
increased preload that the shunted blood from the left atrium to the right atrium caused. The right
ventricle will be forced to generate higher pressures to try to overcome the pulmonary hypertension.
This may lead to right ventricular failure (dilatation and decreased systolic function of the right ventricle)
or elevations of the right sided pressures to levels greater than the left sided pressures.
When the pressure in the right atrium rises to the level in the left atrium, there will no longer be a
pressure gradient between these heart chambers, and the left-to-right shunt will diminish or cease. If
left uncorrected, the pressure in the right side of the heart will be greater than the left side of the heart.
This will cause the pressure in the right atrium to be higher than the pressure in the left atrium. This will
reverse the pressure gradient across the ASD, and the shunt will reverse; a right-to-left shunt will exist.
This phenomenon is known as Eisenmenger's syndrome. Once right-to-left shunting occurs, a portion of
the oxygen-poor blood will get shunted to the left side of the heart and ejected to the peripheral
vascular system. This will cause signs of cyanosis (Giardini A, et al., 2008).
Small ASDs result in trivial shunting and have no hemodynamic consequences. Larger defects are
associated with substantial shunting, which may lead to volume overload of the right atrium, right
ventricle, and pulmonary arteries. The magnitude of left-to-right shunting depends on the size of the
ASD, the relative compliance of the 2 ventricles, and the pulmonary and systemic vascular resistance. If
left untreated, this may result in pulmonary hypertension, right ventricular failure, decreased right
ventricular compliance, and potentially right-to-left shunting. However, Eisenmenger's syndrome
secondary to ASDs is rare in the adult population (5%) (Faletra FF, et al., 2011).
Epidemiology
As a group, atrial septal defects are detected in 1 child per 1500 live births. PFO are quite common
(appearing in 10 - 20% of adults) but asymptomatic and therefore undiagnosed. ASDs make up 30 to
40% of all congenital heart disease that is seen in adults. The ostium secundum atrial septal defect
accounts for 7% of all congenital heart lesions. This lesion shows a female preponderance, with a male:
female ratio of 1:2 (Liu XK, et al., 2013).
Mortality/Morbidity:
In developed countries, the rate of mortality from ASD is very low (i.e. < 1%). Morbidity secondary to
ASD is unusual and is limited typically to the following 3 groups of patients:
o
Perhaps 1% of infants diagnosed with moderate or large (i.e., nonrestrictive) ASDs but no ductus
arteriosus have tachypnea and fail to thrive. Pulmonary artery pressure, when measured by
catheterization or by Doppler echocardiography, is at or near systemic level in these individuals.
Attempts to exclude mitral or left ventricular diastolic abnormalities as a cause of this hemodynamics
must be undertaken; however, these attempts frequently yield equivocal data.
o
A second group of patients, in whom ASDs go unrecognized until later childhood, may develop
arrhythmias (e.g., atrial fibrillation) or pulmonary hypertension. Initial presentation of ASDs in middleaged and elderly adults can be congestive heart failure (CHF).
o
A third group of patients with ASDs has an embolic stroke as the initial presentation
(Chodchanok V, et al., 2012).
Sex: Female-to-male ratio is approximately 2:1.
Age of presentation:
o
ASD, 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 ASD until
late childhood, adolescence, or adulthood.
o
Secundum type (i.e., ostium secundum), sinus venosus, and unroofed coronary sinus defects
sometimes are not diagnosed until the third decade of life.
o
Ostium primum ASDs usually are diagnosed in the first few years of life because of the presence
of a mitral regurgitation murmur.
Patients with common atrium (i.e., combination of sinus venosus, ostium secundum, and ostium
primum defects) also are diagnosed in the first few years of life because systemic venous blood and
pulmonary venous blood typically mix partially before entering each ventricle, and this manifests as
cyanosis (Chia- Ting su, et al., 2013).
Etiology:
Both hemodynamic and genetic mechanisms for the formation of secundum atrial septal defects have
been proposed. Abnormal formation of the atrial septum could be due to increased flow from the IVC
across the atrial septum during fetal life, causing a deficient valve of the foramen ovale (septum
primum), which then cannot close the foramen ovale at birth. This may be the cause of secundum ASDs
seen in association with other congenital heart defects such as tricuspid atresia, but it has not been
demonstrated as a cause of isolated ASDs in fetal models.
Transcription factors involved in the regulation of atrial septal development in human include sonic
hedgehog (Shh), Gata4, Nkx2-5, and Tbx5; perturbation of these transcription factors leads to the
formation of atrial septal defects (Xie L, et al., 2012).
Mutations in the gene encoding the Tbx5 transcription factor on human chromosome 12q24.1 have
been identified as the cause of both the atrial septal defects and skeletal abnormalities that characterize
the autosomal dominantly inherited Holt-Oram syndrome. Mutations in the gene encoding the Nkx2-5
transcription factor lead to an autosomal dominant disorder characterized by secundum ASDs and
progressive atrioventricular block (Hoffmann AD, et al., 2009).
Emerging research in cardiac development has revealed that pharyngeal mesoderm-derived progenitor
cells in the posterior second heart field give rise to atrial septal structures. Progenitor cells in the murine
posterior second heart field (SHF) that receive Shh signaling migrate from the posterior SHF to form the
primary atrial septum and dorsal mesenchymal protrusion and are necessary for normal septal
development. Gata4, Nkx2-5, and Tbx5 are also expressed in the posterior SHF during atrial septal
progenitor specification, and Tbx5 expression in the murine posterior SHF is necessary for normal septal
development
(Kelly RG, et al., 2012).
Ostium secundum, ostium primum ASD, or both may occur alone or with other lesions as part of other
genetic syndromes, such as trisomy 21 (i.e., Down syndrome). For unknown reasons, sinus venosus
defects are rare in Down syndrome, making common atrium similarly rare in this population (Posch MG,
et al., 2011).
An understanding of the genetic and molecular mechanisms of normal and abnormal atrial septal
development continues to evolve.
Diagnosis
History:
o
Infants and young children with ASDs may be nearly or completely asymptomatic.
o
Most patients with ASDs are diagnosed after a suspicious murmur is detected during a routine
health maintenance examination.
o
Even in symptomatic children with ASDs, clinical manifestations are often subtle and
nonspecific. Some children with ASDs have poor weight gain, remain somewhat small, and may have
exertional dyspnea or frequent upper respiratory tract infections.
o
More severe symptoms, such as arrhythmia, pulmonary artery hypertension, and pulmonary
vascular obstructive disease (PVOD), are rare in children with ASDs. Some infants and young children
with large defects may present with symptoms of CHF, especially if an associated lesion (e.g., patent
ductus arteriosus) or lung disease (e.g., bronchopulmonary dysplasia) is present (Demir B , et al., 2012).
Physical examination
At first glance, many children with ASDs appear completely healthy; however, a careful physical
examination often yields clues to diagnosis. Patients with ASDs may exhibit a prominent right ventricular
cardiac impulse and may have palpable pulmonary artery pulsations. Both are signs of increased blood
flow to the right side of the heart and pulmonary vascular bed.
On auscultation of the individual with ASD, the first heart sound may be normal. Although the second
heart sound may be normal in newborns with ASDs, it becomes widely split and fixed over time as
pressures on the right side of the heart decrease, a midsystolic click may be present, but this murmur
can be difficult to detect in some patients with ASDs. A large shunt increases flow across the tricuspid
valve, and the patient with ASD is likely to have a mid diastolic rumble at the left sternal border. Mitral
valve prolapse occurs with increased frequency in the presence of ASD, probably due to left heart
compression secondary to right heart enlargement. In patients with mitral valve prolapse, an apical
holosystolic or late systolic murmur often is heard radiating to the axilla (Fang F, et al., 2011).
Pulmonary vascular resistance (PVR) may increase through childhood, adolescence, and adulthood,
resulting in pulmonary vascular obstructive disease (PVOD). The rise in PVR and pulmonary artery
pressure results in right ventricular hypertrophy, which in turn reduces right ventricular compliance and
then may reduce the degree of left-to-right shunting, Such patients may be recognized on physical
examination to have a prominent right ventricular impulse but diminution of the previously noted
diastolic tricuspid flow rumble as well as a diminution in the systolic ejection murmur on the pulmonic
area. The wide splitting of the second heart sound may narrow, and the pulmonic component of the
second heart sound may become loud and equal in intensity to that of the aortic component, in all
patients with common atrium, some degree of right-to-left shunting occurs, resulting in cyanosis. Adult
patients with an unrecognized ASD may have worsening of their left-to-right shunt if systemic arterial
hypertension develops, resulting in left ventricular hypertrophy, reduced left ventricular compliance,
and increased left-to-right shunt (Taniguchi M, et al., 2013).
Diagnosis
Electrocardiogram
An electrocardiogram (ECG) typically demonstrates normal sinus rhythm, right axis deviation with a QRS
axis +95– +170 , PR interval prolongation in older children and adults, and rsR’ or RSR’ pattern in rV3,
eV4, and V1 due to right ventricular dilation. Intermittent or persistent tachycardias such as atrial flutter
can be observed with ECG monitoring (Syamasundar p, 2012).