Definition and Morphology
An atrial septal defect (ASD) is a direct communication between the cavities of the atrial chambers that permits shunting of blood. In the normal heart the true atrial septum is within the boundaries of the oval fossa; the majority of the remaining tissue separating the atrial chambers is composed of an infolding of the atrial wall.
The morphology of the various types of interatrial communication has been known since the early description by Rokitansky and forms the basis for that classification ( Box 29.1 ; Fig. 29.1 ). Defects within the oval fossa are known as secundum defects, in spite of the fact that the oval fossa is the primum septum. They may extend outside the true limits of the oval fossa when there is a deficiency of infolding of the atrial wall. Such extension may be directed posteroinferiorly to the mouth of the inferior vena cava (IVC), superiorly to the mouth of the superior vena cava (SVC), inferiorly to the atrioventricular (AV) junctions, or posteriorly to the mouth of the coronary sinus (CS). With posterolateral extension to the atrial wall, the defect will encroach toward the entry of the right pulmonary veins (PVs) into the left atrium (LA). Therefore it is not unusual for large secundum defects to extend beyond the limits of the oval fossa. In contrast, the most frequent interatrial communication is found when the so-called flap valve of the oval fossa fails to fuse with the rim, sometimes allowing left-to-right shunting but more frequently giving rise to a probe patent foramen ovale, which can permit only right-to-left shunting when the right atrial pressure is higher than that of the left. When the flap valve fails to overlap, a small deficiency will also allow left-to-right shunting. Although in most instances there is a single defect, it is not unusual to find additional fenestrations; occasionally, multiple small fenestrations occur ( Fig. 29.2 ), often associated with an aneurysm of the oval fossa.
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Secundum (oval fossa)
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Primum (partial atrioventricular septal defect)
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Superior sinus venosus
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Inferior sinus venosus
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Coronary sinus
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Confluent or common atrium
A superior sinus venosus defect occurs when there is a deficiency of infolding of the atrial wall in the environs of the SVC. It is found within the mouth of the SVC, which has a biatrial connection, overriding the rim of the oval fossa so as to produce what is effectively an extracardiac but interatrial communication. Most frequently, the PVs from part of the right lung are also involved, connecting anomalously to the SVC near its junction with the atria. Occasionally the anomalous pulmonary venous connection is to the more proximal part of the SVC and therefore more remote from the RA. A defect found similarly in the mouth of the IVC, which has a biatrial connection, is known as an inferior sinus venosus defect. It is much rarer than the superior type, often associated with right-to-left shunting and cyanosis and sometimes difficult to distinguish from an oval fossa defect, which extends posteroinferiorly to the mouth of the IVC. The rarest type is a deficiency of the wall between the CS and the LA, producing an interatrial communication through the mouth of the CS—a so-called CS defect. In its most extreme form, a left SVC connects to the roof of the LA, the entire wall of the CS is lacking, and the mouth of the CS forms a large communication. A primum defect is part of an AV septal defect with a common AV junction and is roofed superiorly by the inferior border of the oval fossa and inferiorly by the superior and inferior bridging leaflets, forming two AV valves. Primum defects have a trileaflet left AV valve, which impacts on long-term outcome and is discussed in Chapter 31 .
Large interatrial communications may represent a confluence of one type of defect with another. When an ASD is the primary diagnosis, associated malformations occur in approximately 30% of cases. These include pulmonary valve stenosis, partial anomalous pulmonary venous connection, congenital mitral stenosis, mitral valve prolapse, ventricular septal defect (VSD), patent ductus arteriosus, and coarctation of the aorta (AO). Defects within the oval fossa are essential for survival in tricuspid atresia, mitral atresia, hypoplastic left heart syndrome, pulmonary atresia with intact ventricular septum, and total anomalous pulmonary venous connection.
Genetics and Epidemiology
There is a well-recognized association of secundum and primum defects with Down syndrome. Ostium primum ASD may be associated with DiGeorge syndrome and Ellis-van Creveld syndrome. Adults with AV septal defects have an approximate 10% risk of recurrence in their offspring. Secundum defects may be associated with skeletal abnormalities of the forearm and hand, which have been shown to result from mutations of TBX5, a member of the brachyury family of genes. The familial forms of secundum ASD have been associated with GATA4 and NKX2.5 mutations. In these forms, prolonged AV conduction times are common. In 250 consecutive patients undergoing closure of a secundum ASD at the Royal Brompton Hospital, London, there was a family history in one or more close relatives in 2%.
Apart from a bicuspid aortic valve, an ASD is the most common congenital heart malformation to be encountered, with a frequency of 10% to 17%. Approximately 60% are found in females. Secundum defects are the most common (60%), with primum defects accounting for 20% and superior sinus venosus defects 15%. The other types are rare.
Although many individuals with an ASD are diagnosed and treated during childhood, a significant number present with symptoms for the first time in adult life. Of all the cases of ASD treated at the Royal Brompton Hospital, London, in the past 3 years, more than 50% presented in adult life.
Early Presentation and Management
Although the occasional infant presents with breathlessness and even heart failure, and a few children have recurrent chest infections or breathlessness on exertion, the majority are symptom free and present with a heart murmur. In the current era, many children are referred to a pediatric cardiologist for spurious reasons and are found to have an ASD on echocardiography. A few children present with cyanosis because of pulmonary stenosis, Ebstein anomaly, or pulmonary vascular disease (uncommon).
Although it has been argued that routine closure is not of proven benefit to every individual, there is a consensus that when a defect gives rise to right ventricular dilation, it should be closed. Such holes usually measure 10 mm or more in diameter and occupy at least one-third of the length of the atrial septum in echocardiographic four-chamber sections. The hospital mortality rate after operation should be less than 1%, with correspondingly low complication rates. The long-term outcome after surgical repair during childhood is excellent, with a reduced incidence of late arrhythmia, heart failure, stroke, pulmonary hypertension, or cardiovascular death.
Transcatheter Closure
The era of transcatheter closure of secundum defects is now well established. It is important to emphasize that defects only within the oval fossa are suitable for transcatheter device closure, and there should be a 4- to 5-mm rim between the hole and the AV valves or the entry of the systemic and PVs. Three-dimensional (3D) echocardiography can be used to demonstrate the shape and borders of an oval fossa defect. The most reliable imaging modalities for delivery of a device are a combination of fluoroscopy with transesophageal or intravascular ultrasonography.
A number of different closure devices have been used or are currently available, and modifications to these together with introduction of new systems have resulted in significant changes in practice over the past years. Details of the technique for transcatheter closure of suitable interatrial communications are discussed in Chapter 10 . In brief, the morphology of the defect is important when selecting which device to use for closure. Oval fossa defects with a stretched diameter of up to 20 mm may be closed with any of the available systems. Larger defects that are also suitable with a stretched diameter of up to 40 mm should always be closed with a self-centering device. The most frequently used are the nitinol-based devices, Amplatzer septal occluder (AGA Medical, Golden Valley, Minnesota) ( Fig. 29.3 ), Occlutech (Occlutech, Jena, Germany), and Ceraflex (Lifetech).
Smaller defects, as well as multiple fenestrations in the oval fossa, can be closed with a device in which the left and right atrial discs are connected by a thin connecting stem, such as the Gore Helex septal occluder. A septal aneurysm need not be a contraindication to transcatheter closure, but the left atrial disc should cover most of the septum. In general, for all patients, device diameter should never exceed that of the atrial septum.
Inevitably some newer devices are undergoing clinical trials, whereas others have been found wanting after encouraging early investigations and outcomes. It is the original Amplatzer occluder that remains the gold standard against which any new device must be compared. HeartStitch (Sutura Inc., Fountain Valley, California) is a concept in transcatheter patent foramen ovale closure that leaves less material in the atria, with the possible benefit of a reduced risk of thrombus formation, device migration, and erosion.
When an expert neurologist considers that a patient suffers from neurologic symptoms that can be explained on the basis of paradoxic emboli resulting from right-to-left shunting across a patent foramen ovale or small ASD, transcatheter closure can be achieved with conventional devices designed for ASD or those designed specifically for very small defects.
Late Outcome
Survival and Functional Status
The precise natural history of an individual born with an ASD is somewhat unclear, although there is little doubt that in the majority of patients, life expectancy is reduced. In 1970 Campbell reported an early mortality rate during infancy of 1%, increasing to 15% in the third decade of life due to pulmonary hypertension and congestive heart failure, and an actuarial survival rate at 60 years of only 15%. This study clearly exaggerates the poor outcome of isolated ASD. We are now aware that a number of patients with sizeable interatrial communications remain remarkably well and symptom free through early adulthood. However, they are at risk of premature death due to progressive right ventricular dilation with diminished coronary reserve, right-sided heart failure, recurrent pneumonia and pulmonary hypertension, atrial flutter and fibrillation, and paradoxic embolus and stroke.
Most patients are symptom free during the first and second decades of life. Then an increasing number develop effort intolerance in subsequent decades, although patients are often unaware of any symptoms until closure of the defect results in improved exercise performance. Spontaneous closure of a secundum ASD can occur during the first 2 years of life, and our own observations have confirmed that in some patients the defect increases in size in late childhood and early adolescence with somatic growth. The degree of left-to-right shunting may also increase with time, related to decreasing left ventricular compliance and increasing systemic arterial resistance occurring during the fifth to seventh decades. An increasing left-to-right shunt will also tend to give rise to mitral and tricuspid valve regurgitation in later life. As a result of the various later complications, New York Heart Association (NYHA) functional class typically declines from I to II in the first 3 to 5 decades of life to class III to IV in subsequent decades. Kuijpers et al. also reported better survival in women than men.
Most patients who have undergone early closure of a defect remain well with an excellent outlook and a normal survival (when repair is undertaken before 25 years of age). Older age at repair is a risk factor for premature late death, which becomes progressively more powerful with increasing age at operation.
Late Complications
Although pulmonary hypertension is found with increasing frequency with advancing age, a pulmonary vascular resistance greater than 6 U is relatively rare ( Box 29.2 ). However, advanced pulmonary hypertension is not expected early in the course of an ASD. Right ventricular volume overload and increased end-diastolic dimensions are well tolerated for many years, but eventually, diminished right ventricular ejection fraction, hypokinesia, and right ventricular failure tend to occur, usually after the fifth or sixth decade. As outlined earlier, an additional aggravating factor at this time is the increasing left-to-right shunt. There appears to be an interaction between the volume-overloaded right ventricle and the left ventricle. In the latter, diastolic dimensions are reduced and, with increasing age, ejection fraction does not increase with maximal exercise. Important mitral regurgitation is found in a few adult patients, although tricuspid insufficiency is more common, particularly when heart failure begins to develop. By the age of 40 years, more than 20% will have developed atrial fibrillation, but by 60 years of age the number will have increased to approximately 60%. Systemic arterial hypertension is surprisingly common and difficult to explain. A rare but concerning and serious late complication following transcatheter closure is cardiac erosion, which is more likely with very large defects and oversized devices.
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Premature death
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Exercise intolerance
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Right-sided heart failure
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Left ventricular dysfunction
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Tricuspid and mitral valve regurgitation
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Atrial fibrillation or flutter
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Sinus node dysfunction
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Paradoxic thromboembolism
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Endocarditis (rare)
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Pulmonary hypertension or pulmonary vascular disease (uncommon)
Outpatient Assessment
Operated Patients
Patients operated on or repaired during the first or second decades for a secundum or superior sinus venosus defect can usually be considered to have a normal heart, so follow-up is not needed. The vast majority are symptom free with no abnormal physical signs and with normal chest radiography and echocardiography findings. Such patients are often discharged 1 to 2 years after operation because late problems are extremely rare. Occasionally, residual ASDs are encountered after either surgical or catheter closure. Unless responsible for a significant left-to-right shunt, they do not require additional intervention. Progressive pulmonary vascular disease is occasionally encountered after late repair; such patients warrant lifelong follow-up. A complication specific to superior sinus venosus defects is stenosis of the SVC at its junction with the RA. This merits specific attention with echocardiography before the patient is discharged from follow-up.
There is a consensus for periodic, infrequent follow-up of patients operated on after the second decade of life because of the greater risk of chronic right and even left ventricular dysfunction, late atrial arrhythmias, and premature late death. A careful history of lifestyle and symptoms should be an integral part of the review, together with chest radiography, electrocardiography, and cross-sectional echocardiography to assess the AV valves and ventricular function, with Holter monitoring if appropriate.
There is still no consensus as to the follow-up required for patients undergoing transcatheter device closure of a secundum defect. Most publications about immediate, intermediate, and long-term follow-up describe the procedure as safe and efficient with low morbidity and mortality. When compared with surgical repair in developed countries, hospital stay is shorter and the cost is reduced. Immediate and early complications are rare (less than 1%) but can include mitral regurgitation, obstruction of one PV, retroperitoneal hematoma, atrial arrhythmias, embolization of the device, cardiac perforation, and even death. Cardiac perforation is fortunately very rare (fewer than 30 cases reported in the literature) but is associated with significant morbidity and mortality. It can occur immediately or up to 2 years after the procedure. The pathophysiology is not fully understood, but it seems to be related to the forces transmitted by the device to the vulnerable anterosuperior wall of the atria and the AO.
Another significant midterm complication is newly developed or deteriorating aortic valve regurgitation. Schoen et al. reported new or worsened aortic regurgitation (usually mild) in up to 10% of patients at 12 months. Although this potential complication should be taken into account when decisions about transcatheter closure are undertaken, the experience of these authors is not universal. Our experience is that this complication is extremely rare even when larger devices are used. Small residual defects are infrequent but more likely with devices without a self-centering mechanism.
Late complications, such as thrombus on the device, thromboembolic events (including stroke and coronary artery embolism), complete heart block, and infective endocarditis, have been reported occasionally (up to 8 years after the procedure). Because the exact risk of late complications in this group is unknown, our current policy is to review patients annually or every 2 years but with the exception of defects closed with smaller devices. In these patients follow-up is often discontinued after 2 years.
Unoperated Patients
The majority of new patients with an ASD seen in the outpatient clinic will have presented with breathlessness on exertion, which in some cases may have been attributed erroneously to asthma. Palpitations due to atrial arrhythmias might also be the presenting symptom, whereas other modes of presentation include cardiac enlargement on a routine chest radiograph, a heart murmur detected during pregnancy or routine physical examination, and occasionally cyanosis or symptoms of a paradoxic embolus.
A comprehensive outpatient diagnostic workup should determine the following:
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The type, number, and size of ASD
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The hemodynamic significance of the defect
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The presence and degree of right atrial and ventricular dilation and function
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Shunt size depicted from Doppler measurement of pulmonary and aortic flow volumes (in reality rarely performed).
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Pulmonary arterial pressure—derived from tricuspid valve regurgitation Doppler
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The presence of associated anomalies that need to be addressed
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Whether there is a history of sustained arrhythmia that required intervention. The management of the atrial arrhythmia should ideally be performed before the ASD closure, whereas the antegrade access to the LA is still available across the ASD.
History and Clinical Examination
The history and clinical examination includes a search for the following:
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Right ventricular left parasternal impulse
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Wide and fixed splitting of the second heart sound—cardinal physical sign of an ASD (not always present)
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Pulmonary ejection systolic murmur at the upper left sternal edge
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Tricuspid mid-diastolic murmur at the lower left sternal edge, which might radiate toward the cardiac apex
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An accentuated pulmonary component of the second heart sound, suggesting raised pulmonary arterial pressure
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Cyanosis—this is uncommon and more likely with a large defect or virtually common atrium, an inferior sinus venosus defect, a large CS defect, pulmonary vascular disease, or associated pulmonary stenosis, right ventricular dysfunction, or Ebstein anomaly.
Pulse Oximetry
On pulse oximetry normal oxygen saturation is expected.
Electrocardiography
Electrocardiography may show the following:
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Right-axis deviation
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Incomplete right bundle branch block pattern
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Evidence of right ventricular hypertrophy
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Lengthened PR interval
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Abnormal P-wave axis (outside the normal range of 0 to 60 degrees) would suggest a superior sinus venosus ASD
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Extreme right- or left-axis deviation (so-called superior QRS axis) would suggest a primum ASD.
Chest Radiography
Chest radiography in adults with significant ASDs reveals the following:
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Cardiac enlargement with retrosternal filling in the lateral view
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Right atrial dilation
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Prominent central pulmonary arteries and pulmonary vascular markings
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When severe pulmonary hypertension complicates a large ASD, the heart size is large, in contrast to usually a normal heart size in a patient with a pulmonary hypertensive large VSD.
Echocardiography
The diagnosis is usually confirmed by cross-sectional transthoracic echocardiography, using a combination of subcostal, parasternal, and apical four-chamber sections with color flow Doppler interrogation.
Secundum defects are found within the oval fossa and appear in the middle of the atrial septum. However, a superior sinus venosus defect is overridden by the SVC and right upper PV ( Fig. 29.4 ), an inferior sinus venosus defect is overridden by the IVC, and a CS defect is seen posterior to the AV valves ( Fig. 29.5 ).
