Atrial septal defect

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]; Assistant Editor(s)-In-Chief: Kristin Feeney, B.S. [3]

The embryological development of human fetal heart takes place as early as 4th week of intrauterine life. The normal septal development requires a proper alignment and fusion of the two interatrial septums i.e. septum primum and septum secundum. Failure to do so may lead to the development of atrial septal defects.

The development of the fetal heart takes place as early as the 4th week of gestation. An abnormal septal development at this stage may lead to atrial septal defect.

Normal septal embryogenesis occurs as follows:

• The developing heart has an orifice called ostium primum or primary interatrial foramen between the atrium that serves as an opening between the free edge of the septum primum and the AV cushions.
• A septum primum arises from the superior portion of the common atrium of the developing heart. It serves to subdivide the cavity of the primitive atrium into right and left chambers.
• An endocardial cushion is located between the atria and ventricles, serving to create the infrastructure to the basis of the four-chambered heart formation.
• Septum primum grows downward to the endocardial cushions. This leads to the closing of the orifice (ostium primum) between the atria.
• A second entity, the septum secundum, develops to the right of the septum primum and the opening between the upper and lower limbs of the septum secundum is known as the foramen ovale of the heart and persists until birth. These two septae fuse later in life to complete the formation of the atrial septum.
• In the fetus this orifice allows shunting of blood from right to left side of the heart. This is so because during the fetal life right side heart pressures are more than the systemic pressure. However, there is a reversal of pressure gradient after birth (systemic pressures becomes more than right sided pressure) and this change of pressure causes the septum primum to be held against the septum secundum and closing the interatrial shunt.
• In approximately 30% of population the septum primum and secundum fails to fuse leading to patent foramen ovale (PFO) in the newborn. In this case, elevation of pressure in the pulmonary circulatory system (ie: pulmonary hypertension due to various causes, or transiently during a cough) can cause the foramen ovale to remain open. The patent foramen ovale can be of two types:
  • Completely covered but not completely sealed so that the foramen can be opened with reversal of shunt. This is also sometimes called as a probe patent or patent foramen ovale (PFO)
  • An open communication exists between right and left atrium persists is the true definition of what is known as an atrial septal defect (ASD).

Template:WikiDoc Sources CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]; Assistant Editor(s)-In-Chief: Kristin Feeney, B.S. [3]

The normal septal development requires a proper alignment and fusion of the two interatrial septums i.e. septum primum and septum secundum. Failure to do so may lead to a patent fossa ovalis and the development of atrial septal defects (ASDs). Atrial septal defects are classified into various types based on their location and the nature of the embryological defect. The types of atrial septal defects that can occur are: ostium primum, ostium secundum, sinus venosus, common or single atrium and coronary sinus defects. Patent foramen ovale, commonly associated with atrial septal defects, is a sister condition involving communication between the two atria. Patent foramen ovale is not a true atrial septal defect as flap like tissue that functions usually like a one way valve is present in a PFO.

Atrial septal defects are classified into various types based on their location and the nature of the embryological defect ^[1]. Isolated ASDs occur due to abnormal development of the septal between the right and left atrium of the heart and normally are not associated with other cardiac defects.

Ostium secundum ASD at the fossa ovalis account for 75% of all atrial septal defects.

An ostium primum defect usually occurs due to the failure in fusion of the septum primum with the endocardial cushion. This defect is commonly associated with other cardiac anomalies in the septum such as ventricular septal defect, mitral valve cleft, pulmonary stenosis, subaortic stenosis, left superior vena cava, coarctation and atrioventricular septal defect.

Sinus venosus ASD defects can be of two types depending on their location in comparison to the fossa ovalis. They form 5-10% of all the atrial septal defects.

The defect is superior to fossa ovalis.

The defect is inferior to the fossa ovalis.

Accounting for less than 1% of all atrial septal defects, this rare atrial septal defect occurs at the site of the coronary sinus drainage.

Patent foramen ovale (PFO): A flap like formation where communication exists between the right and left atria. It is commonly associated with atrial septal defects, however, it is not technically considered a true atrial septal defect as no septal tissue is missing. There is not continuous flow across a PFO as there is with an ASD. There is only flow across a PFO when there is an increase in right atrial pressure such as occurs during the valsalva maneuver.

Common (or single) atrium is a failure of development of the embryologic components that contribute to the atrial septal complex. It is frequently associated with heterotaxy syndrome. ^[2]

ASDs are associated with other malformations in 30% of cases of atrial septal defect.

Associated defects include:

• Ostium primum ASDs /Atrioventricular canal defects: Occur due to malformation of the partitioning of the atrioventricular (AV) canal by the endocardial cushions (accounts for 15% to 20% of all atrial septal defects) and is located inferiorly near the crux of heart. It is most commonly associated with other malformations such as cleft in the anterior mitral valve leaflet. AV canal defects can be classified as: complete, incomplete, and common atrium.

• Ostium primum ASD or Ostium secundum ASD: Aneurysmal formations found in some patients and may have multiple small fenestrations.

Template:WikiDoc Sources CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]; Assistant Editor(s)-In-Chief: Kristin Feeney, B.S. [3]

Atrial septal defects are the most common form of congenital heart disease, accounting for 20-40% of all congenital heart disease cases in adults. The Centers for Disease Control and Prevention (CDC) estimated that each year about 1,966 babies in the United States are born with an atrial septal defect.^[1]Atrial septal defects can be classified into : ostium secundum, ostium primum, sinus venosus, coronary sinus ASDs and common or single atrium defects. Collectively, atrial septal defects account for 10% of all congenital heart disease. Infants and adolescent patients may be asymptomatic until later in life. By 40 years of age, approximately 90% of untreated atrial septal defect patients will experience an onset of symptoms.

There are four major types of atrial septal defects, ostium secundum, ostium primum, sinus venosus and coronary sinus type ^[2]

• The ostium secundum defect is the commonest type of atrial septal defect. It constitutes 75% of all types of atrial septal defect. It accounts for 7% of all congenital heart defects and 30-40% of all congenital heart disease in patients aged 40 or older.

• The ostium primum defect is the second most common type of atrial septal defect. It accounts for 15-20% of all atrial septal defects. This particular form of atrial septal defect is also categorized as an atrioventricular septal defect and is associated with mitral valve abnormalities.

• The sinus venosus defect is the third most common form of atrial septal defect. It accounts for 5-10% of all atrial septal defects. It is commonly associated with anomalous connection of the right-sided pulmonary veins and often requires additional imaging tests in diagnosis.

• The coronary sinus ASD is the least common and forms less than 1% of all types of atrial septal defect.

• Another form of inter-atrial communication is patent foramen ovale. A patent foramen ovale is not an atrial septal defect as no septal tissue is missing. (PFOs) are quite common (appearing in 10 – 20% of adults) but are asymptomatic and therefore undiagnosed.

• By 40 years of age, approximately 90% of untreated atrial septal defect patients will experience an onset of symptoms.

• Prior to 40, patients may be entirely asymptomatic and live without complication.

• As a group, atrial septal defects (ASDs) are detected in 1 child per 1500 live births.

• It accounts for 10% of all congenital heart disease.

• ASDs make up 20-40% of all congenital heart disease that is seen in adults and are the most common form of congenital heart defect in adults besides bicuspid aortic valve and mitral valve prolapse.^[3]

• In general, atrial septal defect shows a female preponderance, with a female-to-male ratio of 2:1.^[4]

Template:WikiDoc Sources CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]; Assistant Editor(s)-In-Chief: Kristin Feeney, B.S. [3]

As is common with most congenital heart conditions, the exact cause of atrial septal defect is not known. Research suggests a potential link between genetic conditions such as Down syndrome and the development of an atrial septal defect. Other potential causes include exposure to environmental contaminants such as rubella as well as alcohol consumption. A clinician should encourage families with a history of congenital heart defect to consider genetic counseling to identify potential risks.

Although the cause(s) of atrial septal defects are not known, some factors have been found associated with an increased risk of developing an atrial septal defect:

• Increased familial occurrence: Secundum atrial septal defects have been found to occur with an increased frequency among members of a family. In a study done by Whittemore et al. the risk of having congenital heart disease in a child born to a mother with congenital heart disease has been found to somewhere between 8% to 10%.^[1][2]

• Genetics: In some studies the genes responsible for atrial septal defects have been shown to be located on chromosome 5. Researchers have observed that an autosomal dominant inheritance with mutations occur within the cardiac transcription factor^[3]. These heart defects have been found to be associated with some skeletal abnormalities like Holt-Oram syndrome ^[4]. Additionally, both secundum and primum ASDs have been found to be associated with trisomy 21 (Down syndrome)

• Maternal health: Some general factors in the mother that may increase the risk of congenital heart diseases include

• Genetics
• Age over 40
• Alcoholism ^[5]
• Diabetes
• Prenatal nutrition
• Rubella or other viral illness during pregnancy^[5].

• Associated conditions: The cause of atrial septal defect is not known. Atrial septal defects are often associated with other malformations such as:

• Partially anomalous pulmonary venous return
• Pulmonary valve stenosis
• Mitral stenosis or mitral valve prolapse
• Ventricular septal defects
• Coarctation of the aorta

Template:WikiDoc Sources CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]; Assistant Editor(s)-In-Chief: Kristin Feeney, B.S. [3]

Infants and adolescent patients may be asymptomatic until later in life. By 40 years of age, approximately 90% of untreated atrial septal defect patients will experience an onset of symptoms. Symptom onset and severity is largely dependent upon the size of the defect. Without intervention prior to the development of Eisenmenger’s syndrome, the mortality rate for symptomatic adults is greater than 50%. Possible complications include atrial fibrillation, pulmonary hypertension and stroke.

As many atrial septal defect patients are asymptomatic, it is common to survive into adulthood without any need for intervention. Many atrial septal defects smaller than 8 mm in diameter close spontaneously during infancy. Spontaneous closure is uncommon in children and adults. During adulthood there can be the onset of symptoms and an altered life expectancy. Beyond 40-50 years of age, survival without intervention is under 50% with a mortality rate of about 6% per year. Complications occur later in life and include atrial fibrillation, pulmonary hypertension, and stroke.

In a study involving 128 adult (age range 18 to 67 years) atrial septal defect patients, 75% were found to be symptomatic with mild to moderate non-progressive symptoms. Less than 25% of patients had significant pulmonary artery hypertension. Pulmonary artery involvement can be progressive and can lead to shunt reversal, Eisenmenger’s syndrome and ultimately death. The prognosis following medical and / or surgical treatment of pulmonary hypertension can be poor. Heart failure and atrial arrhythmias were other complications found associated with atrial septal defects, mostly in elderly patients.^[1]

Atrial septal defect is associated with complications such as atrial fibrillation, pulmonary hypertension, heart failure, and stroke.

50-60% of atrial septal defect patients over the age of 40 will develop atrial fibrillation. Late-onset atrial fibrillation is associated with both morbidity and mortality. Anticoagulation may lower the mortality risk. Closing an ASD at this point does not prevent occurrence of atrial fibrillation in these patients. But early closure of ASD lowers the risk of developing atrial fibrillation.

15-20% of atrial septal defect patients develop pulmonary hypertension. Although rare in children and adolescents, pulmonary arterial hypertension is observed in approximately 50% of patients over the age of 40. The development of Eisenmenger’s syndrome can result in reversal of the original left-to-right shunt which may switch to become a right-to-left shunt. Right-to-left shunting can in turn lead to deoxygenation (hypoxemia and cyanosis).

Atrial septal defect is associated with left-to-right shunting which in turn may be associated with right ventricular volume overload. Patients may experience right heart failure as a result of right ventricular volume overload.

Even without surgery, as many as 5-10% of all atrial septal defect patients experience thromboembolic events such as stroke and transient ischemic attack. Paradoxical emboli in atrial septal defect patients is not correlated with defect size and can occur in all ASD patients. Early closure of ASD lowers the risk of developing atrial fibrillation.

The prognosis for most atrial septal defect patients, especially prior to the age of 40, is positive. As atrial septal defect patients age, symptoms and complications may advance and influence quality of life. With surgical intervention, the mortality rate is less than 1% for atrial septal defect patients under 45. Surgical intervention in older populations is equally promising and can result in longer longevity and improvements in quality of life. Left untreated, the prognosis for atrial septal defect patients is significantly less favorable and may lead to earlier death.

• Most atrial septal defect patients live to advance in age.

• If an atrial septal defect is detected and diagnosed early in life, surgery is most successful when performed at 2-4 years of age.

• As atrial septal defect patients age, mortality rates of surgical intervention repair increases linearly with age and pulmonary artery pressure.

• The mortality rate for surgical intervention repair is less than 1% for atrial septal defect patients under the age of 45, with no pulmonary artery pressure issues.

• Repair is normally only performed in youth with clinically significant complications. Surgery is still advised for all patients with uncomplicated ASDs with clinically significant shunting from left-to-right. Patients with normal pulmonary artery pressure have comparable age and sex matched 30-year survival rates until the age of 40.

• Patients with pulmonary artery pressure issues may experience a lower survival rate.

• Life expectancy in surgical therapy older patients, though, is better than that of patients with medical therapy. In a small population of patients over the age of 60, presenting without comorbodities, still benefit from surgical intervention.

• In general, surgical intervention of an ASD is associated with an increase in mortality. However, the age of the patient at the time of surgical closure is the single most important predictor of development of potentially serious life-threatening comorbidities.

• Most types of atrial septal defects, when repaired with surgical intervention, are associated with low mortality and low morbidity risks.

• In children, surgical repair can even result in reduction in the right ventricular size from abnormal to closer to normal. Size reduction is not as common in adults with only 20% of all repairs experiencing changes in dimensions. Patients with tricuspid regurgitation and right ventricular failure may experience lifelong symptoms and may have differed long-term outcomes.

• Complications are more common in older atrial septal defect patients after surgical intervention. It is believed that prognosis is influenced by the long-term effect of volume overload on the chambers of the right side. It is also associated with the volume overload as a result of right atrial enlargement and of pulmonary hypertension. These particular strains on the right chamber of the heart lead to increased risk for atrial arrhythmia and stroke. As many as 22% of late deaths can be attributed to cerebrovascular events. Age at repair as well as preoperative status, such as NYHA class III and IV heart failure, are independent predictors of mortality.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]; Cafer Zorkun, M.D., Ph.D. [3] Ayokunle Olubaniyi, M.B,B.S [4]Assistant Editor(s)-In-Chief: Kristin Feeney, B.S. [5]

Atrial septal defect is associated with complications such as migraine headache with aura, atrial fibrillation, pulmonary hypertension, heart failure, and stroke.

A relationship between migraine with aura and right-to-left shunt or patent foramen ovale has been documented in many studies.^[1] Patent foramen ovale is more common in patients with migraine headache with aura than in the general population. The prevalence of PFO in migraineurs varies between 40 – 60% as compared to 17 – 30% of people in the general population.^[2] In a study, the prevalence of PFO in migraineurs with aura was found to be 47% as compared to 17% among the control subjects. The presence of a large shunt may also increase the odds of having MHA by more than 7-folds.^[3] A recent meta-analysis suggests a 3-fold increase in the risk of patients with PFO developing MHA.^[4] In a similar manner, migraine with aura is more prevalent in the presence of PFO.

Although the exact causal relationship remains unclear, several pathogenetic mechanisms have been explained, namely:

• Co-inheritance – An autosomal dominant inheritance of atrial shunts was linked to the inheritance of MHA.^[5]
• Increased neuronal excitability – Right-to-left shunting of blood exposes neurons to microemboli or vasoactive peptides such as serotonin, which triggers migraine attacks by lowering the neuronal excitability threshold.
• Reduced plasma atrial natriuretic peptide – Atrial natriuretic peptide, which is released by atrial myocytes in response to atrial stretch, is known to play roles in natriuresis, inhibition of platelet aggregation^[6] and lowering of vasoreactivity of vascular smooth muscles to vasoconstrictor substances (i.e., it helps in vasodilation). As a result of increased blood volume observed in atrial shunts, patients with ASD have elevated levels of ANP, which subsequently normalizes following closure in majority of patients.^[7] As a direct result of this, migraine auras may be facilitated due to the lack of vasodilatory and antiplatelet activities in vulnerable patients.

Although there is no direct evidence to link migraines and atrial septal defects, some researchers noted that closure of patent foramen ovale resulted in complete resolution or marked reduction in severity and frequency of migraine episodes.^{[8][9][10][11]} A meta-analysis study involving 1,306 patients who underwent PFO closure reported 46% of cases with complete resolution of migraine symptoms and a significant improvement of migraine in 83% of cases.^[12] Conversely, there were also reported cases of an increased frequency and severity of migraine attacks with prolonged aura symptoms following closure,^[13][14] especially with the closure of secundum ASD.

The MIST (Migraine Intervention with STARFlex Technology) trial which is the only completed randomized trial for PFO closure for migraine headaches was highly critiqued for its failure in reaching its primary and secondary endpoints.^[15] The ongoing PREMIUM and the terminated PRIMA randomized controlled trials promises to investigate the role of PFO closure in migraine patients and address the methodological flaws of the MIST trial.^[16]

Currently, no conclusion can be drawn from all these studies, but available evidence suggests that PFO is not a risk factor for migraine headaches with aura.

Even without surgery, as many as 5-10% of all atrial septal defect patients experience thromboembolic events such as stroke and transient ischemic attack. Paradoxical emboli in atrial septal defect patients is not correlated with shunt size and can occur in all ASD patients. Early closure of ASD lowers the risk of developing atrial fibrillation.

50-60% of atrial septal defect patients over the age of 40 will develop atrial fibrillation. Late-onset atrial fibrillation is associated with bothmorbidity and mortality. Anticoagulation may lower the mortality risk. Closing an ASD at this point does not prevent occurrence of atrial fibrillation in these patients. But early closure of ASD lowers the risk of developing atrial fibrillation.

15-20% of atrial septal defect patients develop pulmonary hypertension. Although rare in children and adolescents, pulmonary arterial hypertension is observed in approximately 50% of patients over the age of 40. The development of Eisenmenger’s syndrome can result in reversal of the original left-to-right shunt which may switch to become a right-to-left shunt. Right-to-left shunting can in turn lead to deoxygenation (hypoxemia and cyanosis).

Atrial septal defect is associated with left-to-right shunting which in turn may be associated with right ventricular volume overload. Patients may experience right heart failure as a result of right ventricular volume overload.

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