An atrial septal defect is a birth defect of the heart in which there is a hole in the wall (septum) that divides the upper chambers (atria) of the heart. A hole can vary in size and may close on its own or may require surgery. An atrial septal defect is one type of congenital heart defect. Congenital means present at birth.

As a baby’s heart develops during pregnancy, there are normally several openings in the wall dividing the upper chambers of the heart (atria). These usually close during pregnancy or shortly after birth.

If one of these openings does not close, a hole is left, and it is called an atrial septal defect. The hole increases the amount of blood that flows through the lungs and over time, it may cause damage to the blood vessels in the lungs. Damage to the blood vessels in the lungs may cause problems in adulthood, such as high blood pressure in the lungs and heart failure. Other problems may include abnormal heartbeat, and increased risk of stroke.

The word septum is derived from the Latin for “something that encloses;” in this case, a septum (plural = septa) refers to a wall or partition that divides the heart into chambers. The septa are physical extensions of the myocardium lined with endocardium. Located between the two atria is the interatrial septum. Normally in an adult heart, the interatrial septum bears an oval-shaped depression known as the fossa ovalis, a remnant of an opening in the fetal heart known as the foramen ovale. The foramen ovale allowed blood in the fetal heart to pass directly from the right atrium to the left atrium, allowing some blood to bypass the pulmonary circuit. Within seconds after birth, a flap of tissue known as the septum primum that previously acted as a valve closes the foramen ovale and establishes the typical cardiac circulation pattern.

Between the two ventricles is a second septum known as the interventricular septum. Unlike the interatrial septum, the interventricular septum is normally intact after its formation during fetal development. It is substantially thicker than the interatrial septum, since the ventricles generate far greater pressure when they contract.

The septum between the atria and ventricles is known as the atrioventricular septum. It is marked by the presence of four openings that allow blood to move from the atria into the ventricles and from the ventricles into the pulmonary trunk and aorta. Located in each of these openings between the atria and ventricles is a valve, a specialized structure that ensures one-way flow of blood. The valves between the atria and ventricles are known generically as atrioventricular valves. The valves at the openings that lead to the pulmonary trunk and aorta are known generically as semilunar valves. The interventricular septum is visible in the figure below. In this figure, the atrioventricular septum has been removed to better show the bicupid and tricuspid valves; the interatrial septum is not visible, since its location is covered by the aorta and pulmonary trunk. Since these openings and valves structurally weaken the atrioventricular septum, the remaining tissue is heavily reinforced with dense connective tissue called the cardiac skeleton, or skeleton of the heart. It includes four rings that surround the openings between the atria and ventricles, and the openings to the pulmonary trunk and aorta, and serve as the point of attachment for the heart valves. The cardiac skeleton also provides an important boundary in the heart electrical conduction system.

Heart: Heart Defects

One very common form of interatrial septum pathology is patent foramen ovale, which occurs when the septum primum does not close at birth, and the fossa ovalis is unable to fuse. The word patent is from the Latin root patens for “open.” It may be benign or asymptomatic, perhaps never being diagnosed, or in extreme cases, it may require surgical repair to close the opening permanently. As much as 20–25 percent of the general population may have a patent foramen ovale, but fortunately, most have the benign, asymptomatic version. Patent foramen ovale is normally detected by auscultation of a heart murmur (an abnormal heart sound) and confirmed by imaging with an echocardiogram. Despite its prevalence in the general population, the causes of patent ovale are unknown, and there are no known risk factors. In nonlife-threatening cases, it is better to monitor the condition than to risk heart surgery to repair and seal the opening.

Coarctation of the aorta is a congenital abnormal narrowing of the aorta that is normally located at the insertion of the ligamentum arteriosum, the remnant of the fetal shunt called the ductus arteriosus. If severe, this condition drastically restricts blood flow through the primary systemic artery, which is life threatening. In some individuals, the condition may be fairly benign and not detected until later in life. Detectable symptoms in an infant include difficulty breathing, poor appetite, trouble feeding, or failure to thrive. In older individuals, symptoms include dizziness, fainting, shortness of breath, chest pain, fatigue, headache, and nosebleeds. Treatment involves surgery to resect (remove) the affected region or angioplasty to open the abnormally narrow passageway. Studies have shown that the earlier the surgery is performed, the better the chance of survival.

A patent ductus arteriosus is a congenital condition in which the ductus arteriosus fails to close. The condition may range from severe to benign. Failure of the ductus arteriosus to close results in blood flowing from the higher pressure aorta into the lower pressure pulmonary trunk. This additional fluid moving toward the lungs increases pulmonary pressure and makes respiration difficult. Symptoms include shortness of breath (dyspnea), tachycardia, enlarged heart, a widened pulse pressure, and poor weight gain in infants. Treatments include surgical closure (ligation), manual closure using platinum coils or specialized mesh inserted via the femoral artery or vein, or nonsteroidal anti-inflammatory drugs to block the synthesis of prostaglandin E2, which maintains the vessel in an open position. If untreated, the condition can result in congestive heart failure.

Septal defects are not uncommon in individuals and may be congenital or caused by various disease processes. Tetralogy of Fallot is a congenital condition that may also occur from exposure to unknown environmental factors; it occurs when there is an opening in the interventricular septum caused by blockage of the pulmonary trunk, normally at the pulmonary semilunar valve. This allows blood that is relatively low in oxygen from the right ventricle to flow into the left ventricle and mix with the blood that is relatively high in oxygen. Symptoms include a distinct heart murmur, low blood oxygen percent saturation, dyspnea or difficulty in breathing, polycythemia, broadening (clubbing) of the fingers and toes, and in children, difficulty in feeding or failure to grow and develop. It is the most common cause of cyanosis following birth. The term “tetralogy” is derived from the four components of the condition, although only three may be present in an individual patient: pulmonary infundibular stenosis (rigidity of the pulmonary valve), overriding aorta (the aorta is shifted above both ventricles), ventricular septal defect (opening), and right ventricular hypertrophy (enlargement of the right ventricle). Other heart defects may also accompany this condition, which is typically confirmed by echocardiography imaging. Tetralogy of Fallot occurs in approximately 400 out of one million live births. Normal treatment involves extensive surgical repair, including the use of stents to redirect blood flow and replacement of valves and patches to repair the septal defect, but the condition has a relatively high mortality. Survival rates are currently 75 percent during the first year of life; 60 percent by 4 years of age; 30 percent by 10 years; and 5 percent by 40 years.

In the case of severe septal defects, including both tetralogy of Fallot and patent foramen ovale, failure of the heart to develop properly can lead to a condition commonly known as a “blue baby.” Regardless of normal skin pigmentation, individuals with this condition have an insufficient supply of oxygenated blood, which leads to cyanosis, a blue or purple coloration of the skin, especially when active.

Septal defects are commonly first detected through auscultation, listening to the chest using a stethoscope. In this case, instead of hearing normal heart sounds attributed to the flow of blood and closing of heart valves, unusual heart sounds may be detected. This is often followed by medical imaging to confirm or rule out a diagnosis. In many cases, treatment may not be needed. Some common congenital heart defects are illustrated in Figure.

Figure. Congenital Heart Defects (a) A patent foramen ovale defect is an abnormal opening in the interatrial septum, or more commonly, a failure of the foramen ovale to close. (b) Coarctation of the aorta is an abnormal narrowing of the aorta. (c) A patent ductus arteriosus is the failure of the ductus arteriosus to close. (d) Tetralogy of Fallot includes an abnormal opening in the interventricular septum.

The heart folds quickly like origami and now starts beating. This begins with the formation of two tubes and beats spontaneously by week 4 of development.

Developing rapidly and early, the heart is the first organ to function in the embryo, and it takes up most of the room in the fetus's midsection in the first few weeks of its life. During its initial stages of development, the fetal heart actually resembles those of other animals. In its tubelike, two-chambered phase, the fetal heart resembles that of a fish. In its three-chambered phase, the heart looks like that of a frog. As the atria and then the ventricles start to separate, the human heart resembles that of a turtle, which has a partial septum in its ventricle. The final, four-chambered design is common to mammals and birds. The four chambers allow low-pressure circulation to the lungs and high pressure circulation to the rest of the body.

Development of the Heart

The human heart is the first functional organ to develop. It begins beating and pumping blood around day 21 or 22, a mere three weeks after fertilization. This emphasizes the critical nature of the heart in distributing blood through the vessels and the vital exchange of nutrients, oxygen, and wastes both to and from the developing baby. The critical early development of the heart is reflected by the prominent heart bulge that appears on the anterior surface of the embryo.

The heart forms from an embryonic tissue called mesoderm around 18 to 19 days after fertilization. Mesoderm is one of the three primary germ layers that differentiates early in development that collectively gives rise to all subsequent tissues and organs. The heart begins to develop near the head of the embryo in a region known as the cardiogenic area. Following chemical signals called factors from the underlying endoderm (another of the three primary germ layers), the cardiogenic area begins to form two strands called the cardiogenic cords (Figure 19.36). As the cardiogenic cords develop, a lumen rapidly develops within them. At this point, they are referred to as endocardial tubes. The two tubes migrate together and fuse to form a single primitive heart tube. The primitive heart tube quickly forms five distinct regions. From head to tail, these include the truncus arteriosus, bulbus cordis, primitive ventricle, primitive atrium, and the sinus venosus. Initially, all venous blood flows into the sinus venosus, and contractions propel the blood from tail to head, or from the sinus venosus to the truncus arteriosus. This is a very different pattern from that of an adult.

Development of the Human Heart This diagram outlines the embryological development of the human heart during the first eight weeks and the subsequent formation of the four heart chambers.

The five regions of the primitive heart tube develop into recognizable structures in a fully developed heart. The truncus arteriosus will eventually divide and give rise to the ascending aorta and pulmonary trunk. The bulbus cordis develops into the right ventricle. The primitive ventricle forms the left ventricle. The primitive atrium becomes the anterior portions of both the right and left atria, and the two auricles. The sinus venosus develops into the posterior portion of the right atrium, the SA node, and the coronary sinus.

As the primitive heart tube elongates, it begins to fold within the pericardium, eventually forming an S shape, which places the chambers and major vessels into an alignment similar to the adult heart. This process occurs between days 23 and 28. The remainder of the heart development pattern includes development of septa and valves, and remodeling of the actual chambers. Partitioning of the atria and ventricles by the interatrial septum, interventricular septum, and atrioventricular septum is complete by the end of the fifth week, although the fetal blood shunts remain until birth or shortly after. The atrioventricular valves form between weeks five and eight, and the semilunar valves form between weeks five and nine.

During prenatal development, the fetal circulatory system is integrated with the placenta via the umbilical cord so that the fetus receives both oxygen and nutrients from the placenta. However, after childbirth, the umbilical cord is severed, and the newborn’s circulatory system must be reconfigured. When the heart first forms in the embryo, it exists as two parallel tubes derived from mesoderm and lined with endothelium, which then fuse together. As the embryo develops into a fetus, the tube-shaped heart folds and further differentiates into the four chambers present in a mature heart. Unlike a mature cardiovascular system, however, the fetal cardiovascular system also includes circulatory shortcuts, or shunts. A shunt is an anatomical (or sometimes surgical) diversion that allows blood flow to bypass immature organs such as the lungs and liver until childbirth.

The placenta provides the fetus with necessary oxygen and nutrients via the umbilical vein. (Remember that veins carry blood toward the heart. In this case, the blood flowing to the fetal heart is oxygenated because it comes from the placenta. The respiratory system is immature and cannot yet oxygenate blood on its own.) From the umbilical vein, the oxygenated blood flows toward the inferior vena cava, all but bypassing the immature liver, via the ductus venosus shunt (image). The liver receives just a trickle of blood, which is all that it needs in its immature, semifunctional state. Blood flows from the inferior vena cava to the right atrium, mixing with fetal venous blood along the way.

Although the fetal liver is semifunctional, the fetal lungs are nonfunctional. The fetal circulation therefore bypasses the lungs by shifting some of the blood through the foramen ovale, a shunt that directly connects the right and left atria and avoids the pulmonary trunk altogether. Most of the rest of the blood is pumped to the right ventricle, and from there, into the pulmonary trunk, which splits into pulmonary arteries. However, a shunt within the pulmonary artery, the ductus arteriosus, diverts a portion of this blood into the aorta. This ensures that only a small volume of oxygenated blood passes through the immature pulmonary circuit, which has only minor metabolic requirements. Blood vessels of uninflated lungs have high resistance to flow, a condition that encourages blood to flow to the aorta, which presents much lower resistance. The oxygenated blood moves through the foramen ovale into the left atrium, where it mixes with the now deoxygenated blood returning from the pulmonary circuit. This blood then moves into the left ventricle, where it is pumped into the aorta. Some of this blood moves through the coronary arteries into the myocardium, and some moves through the carotid arteries to the brain.

The descending aorta carries partially oxygenated and partially deoxygenated blood into the lower regions of the body. It eventually passes into the umbilical arteries through branches of the internal iliac arteries. The deoxygenated blood collects waste as it circulates through the fetal body and returns to the umbilical cord. Thus, the two umbilical arteries carry blood low in oxygen and high in carbon dioxide and fetal wastes. This blood is filtered through the placenta, where wastes diffuse into the maternal circulation. Oxygen and nutrients from the mother diffuse into the placenta and from there into the fetal blood, and the process repeats.

Developing rapidly and early, the heart is the first organ to function in the embryo, and it takes up most of the room in the fetus's midsection in the first few weeks of its life. During its initial stages of development, the fetal heart actually resembles those of other animals. In its tubelike, two-chambered phase, the fetal heart resembles that of a fish. In its three-chambered phase, the heart looks like that of a frog. As the atria and then the ventricles start to separate, the human heart resembles that of a turtle, which has a partial septum in its ventricle. The final, four-chambered design is common to mammals and birds. The four chambers allow low-pressure circulation to the lungs and high pressure circulation to the rest of the body.

In a 2019 study using data from birth defects tracking systems across the United States, researchers estimated that each year about 2,118 babies in the United States are born with Atrial Septal Defect. In other words, about 1 in every 1,859 babies born in the United States each year are born with Atrial Septal Defect.

The causes of heart defects such as atrial septal defect among most babies are unknown. Some babies have heart defects because of changes in their genes or chromosomes. These types of heart defects also are thought to be caused by a combination of genes and other risk factors, such as things the mother comes in contact with in the environment or what the mother eats or drinks or the medicines the mother uses.

An atrial septal defect may be diagnosed during pregnancy or after the baby is born. In many cases, it may not be diagnosed until adulthood.

During Pregnancy

During pregnancy, there are screening tests (prenatal tests) to check for birth defects and other conditions. An atrial septal defect might be seen during an ultrasound (which creates pictures of the body), but it depends on the size of the hole and its location. If an atrial septal defect is suspected, a specialist will need to confirm the diagnosis.

After the Baby is Born

An atrial septal defect is present at birth, but many babies do not have any signs or symptoms. Signs and symptoms of a large or untreated atrial septal defect may include the following:

• Frequent respiratory or lung infections
• Difficulty breathing
• Tiring when feeding (infants)
• Shortness of breath when being active or exercising
• Skipped heartbeats or a sense of feeling the heartbeat
• A heart murmur, or a whooshing sound that can be heard with a stethoscope
• Swelling of legs, feet, or stomach area
• Stroke

It is possible that an atrial septal defect might not be diagnosed until adulthood. One of the most common ways an atrial septal defect is found is by detecting a murmur when listening to a person’s heart with a stethoscope. If a murmur is heard or other signs or symptoms are present, the health care provider might request one or more tests to confirm the diagnosis. The most common test is an echocardiogram which is an ultrasound of the heart.

Treatment for an atrial septal defect depends on the age of diagnosis, the number of or seriousness of symptoms, size of the hole, and presence of other conditions. Sometimes surgery is needed to repair the hole. Sometimes medications are prescribed to help treat symptoms. There are no known medications that can repair the hole.

If a child is diagnosed with an atrial septal defect, the health care provider may want to monitor it for a while to see if the hole closes on its own. During this period of time, the health care provider might treat symptoms with medicine. A health care provider may recommend the atrial septal defect be closed for a child with a large atrial septal defect, even if there are few symptoms, to prevent problems later in life. Closure may also be recommended for an adult who has many or severe symptoms. Closure of the hole may be done during cardiac catheterization or open-heart surgery. After these procedures, follow-up care will depend on the size of the defect, person’s age, and whether the person has other birth defects.

Introduction

Patent foramen ovale (PFO), is part of a group of entities known as atrial septal defects, is a remnant of normal fetal anatomy. More than half of infants will have PFO at six months of age. Although it's doesn't have a major clinical effect in neonates, it may persist into adulthood. The majority of adult patients with a PFO are asymptomatic; however, in some adults, PFO may result in an inter-atrial, right-to-left shunting of deoxygenated blood and potential for shunting venous thromboembolism to the arterial circulation. These changes explain the pathophysiologic determinant of several conditions associated with PFO, including cryptogenic (having no other identifiable cause) stroke, decompression sickness, migraine, platypnea-orthodeoxia syndrome, and acute limb ischemia secondary to emboli.

Epidemiology

Data in 1988 revealed that 30% to 40% of young patients who had a Cryptogenic stoke had a PFO. This percentage compared to 25% in the general population. Since that time, the largest target population studied has been patients of all ages with cryptogenic stroke, in whom the frequency of finding a PFO is often double that of the general population. In adults with PFO, an optimal secondary prevention strategy is not well defined. Patients with PFO and atrial septal aneurysm who have experienced strokes seem to be at higher risk for recurrent stroke (as high as 15% per year), and secondary preventive strategies are necessary. In another study, 50% of patients with cryptogenic stroke were found to have right-to-left shunting compared to 15% of the controls. Approximately 2/3rds of divers with undeserved (following safe dive profiles) decompression illness are found to have a PFO.

Pathophysiology

PFO is a flap-like opening between the atrial septum secundum and primum at the fossa ovalis. In utero, it serves as a conduit for blood to the systemic circulation. Once the pulmonary circulation increases after birth, the functional PFO starts to close. Anatomical closure of the PFO usually occurs at about 12 months. PFO primarily increases the risk of stroke from a paradoxical embolism. The risk for a cryptogenic stroke in patients with PFO increases with the larger defects and the presence of interatrial aneurysm (perhaps because of increased in situ thrombus formation in the aneurysmal tissue or because PFOs associated with an interatrial septal aneurysm tend to be larger). Despite prior reports concerning paradoxical embolism through a PFO, this phenomenon's magnitude as a risk factor for stroke remains undefined because deep venous thrombosis is infrequently detected in such patients. In one study, pelvic vein thrombi were found more frequently in young patients with cryptogenic stroke than in those with a known cause of stroke. This finding may provide the source of venous thrombi, mainly when a source of venous thromboembolism (VTE) is not initially identified.

History and Physical

The majority of patients with PFO are asymptomatic. However, some may present with severe clinical symptoms like migraines-like headaches, symptoms, and signs for ischemic brain stroker or a transient ischemic event to any of the vital organs ( brain, limb, kidneys, intestine, etc..). Less common clinical presentations include paradoxical embolism, acute myocardial infarction, systemic embolism, and dyspnea at rest.The physical exam is usually unremarkable. A faint systolic murmur due to turbulence of the flow across the foramen may be heard on auscultation.

Evaluation

The most common circumstance prompting the search for PFO is a cryptogenic stroke ( Stroke with no identifiable contributor after extensive workup). PFO also represents a common incidental finding on routine echocardiogram performed for another reason, especially in the neonatal period. A PFO is usually detected by transthoracic echocardiography, transesophageal echocardiogram (TEE), or transcranial Doppler. TEE is the most sensitive test, mainly when performed with contrast media injected during a cough or Valsalva maneuver. However, technical difficulties and the need for sedation make TEE less favorable in the neonatal and pediatric population. Evaluation for PFO in neonates with congenital heart disease should include a detailed description of the presence of PFO, size, flow restriction, and pressure gradient. Patients with cryptogenic strokes should also be evaluated for the existence of venous thromboembolism (VTE). Divers with more than one episode of undeserved decompression illness should undergo evaluation for a right to left shunt. A 2015 diving medicine consensus panel recommended contrasted provocative transthoracic echocardiography for this evaluation because it has a lower complication rate than TEE and is unlikely to miss a clinically significant PFO. Patients with cryptogenic strokes should also be evaluated for venous thromboembolism (VTE) to assess the associated tendency for thromboembolism associated with PFO that influence morbidity and mortality.

Treatment / Management

In neonates and the pediatric population, PFO doesn't require treatment of followup. PFO is vital in some congenital heart conditions that are dependent on blood shunting at the atrial level.

In adults, treatment for PFO is mainly indicated in a patient with cryptogenic strokes. Different approaches have been suggested, including:

• Medical therapy mainly includes antithrombotic medications ( aspirin), especially in those with stroke due to embolism. Anticoagulant is indicated if the stroke is associated with vein thrombosis.

• Percutaneous device closure: Multiple studies and trials shown the percutaneous device close of PFO is superior to medical therapy in reducing the risk for recurrence in patients less than 60 years old. The FDA has approved the Cardioseal Septal occlusion system and the amp later PFO occluder for percutaneous closure. The procedure is done under fluoroscopic guidance and requires hospital admission. Aspirin or warfarin is required for a minimum of 6 months.

• Surgical approach to close PFO is pursued in the following conditions:

  • PFO that is larger than 25 mm

  • Failure of the PFO to close by percutaneous method

  • The inadequate rim at the edge-this can make it difficult for percutaneous closure

Surgical approach results in complete closure and avoiding the need for long term anticoagulant. However, surgery does require open-heart surgery and the usual risks of the procedure.

Differential Diagnosis

As mentioned earlier, PFO is a common finding in newborns and adults; the major differential diagnosis includes other congenital heart diseases like:

• Atrial septal defect ( In contrast with PFO, there is an actual defect in the septum, and usually fixed split-second heart sound is heard on examination)

• Ventricular septal defect ( Membrenous or muscular, usually associated with pansystolic murmur)

• Patent ductus arteriosus (another shunt that exists in fetal life as part of the fetal circulation, it may remain patents in newborns, and very few may stay patent into childhood. It usually associated with continuous machinery murmur)

Prognosis

In neonates and children, the prognosis of PFO is excellent, and PFO usually closes in most of them. For those children and adults who require surgical closure due to thromboembolism riks, the prognosis is favorable. Surgical outcomes have been well established. Percutaneous closure is promising, but complications are not uncommon. Embolism, dislodgment, and failure to close the PFO have all been reported. Besides, the percutaneous procedure may be associated with damage to the blood vessels, stroke, thrombus formation, and infective endocarditis.

Complications

The usual complications of antiplatelet and anticoagulant therapies include bleeding and intracerebral hemorrhage. Intraprocedural complications utilizing device closure include perforation resulting in tamponade, air embolism, device embolization, and stroke. However, these are all rare events in experienced hands, with rates of less than 1%. Subsequent atrial arrhythmias may occur in 3% to 5% but are transient. Although the rate of development of atrial fibrillation has been 5% to 6% with some devices, it is usually associated with thrombus formation. Late cardiac perforation has been reported with some devices but appears to be rare. In comparison, atrial fibrillation was more common among closure patients than anticoagulated patients in secondary preventive strategies.

Enhancing Healthcare Team Outcomes

PFO is a common finding in newborns. It is present in 25% of the general adult population and has been identified as the major contributing factor in cryptogenic stroke in 50% of affected young adults. Identifying PFO, particularly in young cryptogenic stroke patients, is accomplished via TEE with contrast media. Treatment is aimed at preventing a secondary event primarily with antiplatelet or anticoagulation therapy or atrial septal device closure. The risk associated with either treatment is low overall, and the superiority of one therapy over the other is still contested. Accepted device closure treatment is for large PFOs and patients with PFOs who have already had a recurrent neurological event. Any identified venous thromboembolic event involving PFO should be treated with anticoagulation.

The management of patent foramen ovale is made by an interprofessional team that consists of a pediatrician, cardiologist, interventional radiologist, and a cardiac surgeon. The decision to treat depends on the presence of symptoms, size, and presence of complications. Today, in high-risk patients, percutaneous methods of closure have evolved. Patients should be educated on their treatment options and possible complications of each treatment.