AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

An ostium secundum atrial septal defect is an abnormally large opening in the atrial septum at the site of the foramen ovale and the ostium secundum.

Embryology

In the early embryo heart, the atria comprise a common chamber. As the atria enlarge, the septum primum forms and grows toward the developing atrioventricular canal area, which is later divided by the superior and inferior endocardial cushions. These cushions fuse and bend with their convexity toward the atria, thereby approaching the down-growing septum primum. This process continually narrows the passageway between the atria, which is then defined as the ostium primum.¹

The ostium primum completely closes; however, before this occurs, a central perforation appears in septum primum, allowing continuous unrestricted flow from the right atrium to the left atrium. This perforation, the second opening in the septum primum, is called ostium secundum. As the atria expand to either side of the truncus arteriosus, a fold is produced within the atria just to the right of septum primum. This passively formed fold is septum secundum. The leading edge of septum secundum is concave in shape and is called the foramen ovale. It comes to overlay the ostium secundum but does not interfere with blood flow from right to left through ostium secundum. After birth, with onset of pulmonary blood flow and elevation of left atrial pressure, the septum primum is pushed against the septum secundum, effectively closing the ostium secundum.

Fusion of the septum primum and the septum secundum closes the foramen ovale. Complete closure occurs in most individuals. In 25-30% of normal adult hearts, however, a probe can be passed from the right atrium to the left atrium via the foramen ovale and ostium secundum. This patent foramen ovale allows a tiny left-to-right shunt that can be detected by sensitive techniques, such as color Doppler echocardiography, in 15-20% of adults.

Anatomy

A secundum atrial septal defect is usually bordered by the edge of the fossa ovalis and the exposed circumference of ostium secundum. The shape of the defect varies from circular to oval. Less often, strands of tissue cross the defect creating a fenestrated appearance that suggests multiple defects. Rarely, a defect can extend posteriorly and inferiorly, approaching the site of inferior vena cava entrance into the right atrium.²

Pathophysiology

A secundum atrial septal defect can result from inadequate formation of the septum secundum so that it does not completely cover the ostium secundum. More often, the ostium secundum is excessively large because of increased resorption so that septum secundum cannot cover it.

Natural history

Although heart failure from secundum atrial septal defect rarely occurs in children, this complication can often occur in adults. Adults also demonstrate a propensity for atrial dysrhythmias, including atrial flutter and fibrillation, presumably caused by chronic right atrial dilation. These complications may not be reversible if closure is delayed. Data indicate that closure in persons older than 40 years does not reduce the risk of atrial dysrhythmia. Spontaneous closure of a small secundum atrial septal defect does occur and is usually documented when the initial diagnosis is made early in infancy.^{3, 4} A moderate atrial septal defect may also decrease significantly in size or even close when the defect is diagnosed early in life.⁵  However, defects diagnosed later in childhood seldom decrease in size and many significantly increase in size.⁶
 
The foramen ovale mechanism remains patent in at least 15% of adults (echocardiography can identify clinically insignificant shunts with this frequency). Some of these individuals could be classified as having a small secundum atrial septal defect. The presence of this phenomenon has been identified as a potential risk factor for stroke due to embolization into the systemic arterial circulation.

Although unusual, obstructive pulmonary vascular disease may occur in adults with an atrial septal defect.⁷

Frequency

International

Isolated secundum atrial septal defects account for approximately 7% of congenital cardiac defects. Congenital heart defects of significance occur in approximately 8 per 1000 live births. Therefore, 5-6 cases of secundum atrial septal defect occur per 10,000 live births. This number refers only to defects that are large enough to come to clinical attention. Many small defects that remain undetected occur in addition to numerous cases of patent foramen ovale, as mentioned above.

Mortality/Morbidity

An isolated secundum atrial septal defect very seldom causes significant symptoms in pediatric patients, regardless of defect size.

• Rarely, an infant may develop congestive heart failure in the presence of a secundum atrial septal defect. Whether the defect alone is responsible for causing heart failure is not well established, although it certainly adds to the patient's hemodynamic difficulties. Failure to thrive caused only by a secundum atrial septal defect is, similarly, a rare occurrence.
• Bacterial endocarditis is not a risk with this lesion and the American Heart Association does not advise use of antibiotic prophylaxis.
• No data indicate that an uncomplicated secundum atrial septal defect can cause pulmonary vascular disease in pediatric patients.
• A patient with primary pulmonary hypertension may demonstrate a secundum atrial septal defect, but no cause-and-effect relationship can be established.
• Patients with a significant secundum atrial septal defect who live at an altitude higher than 4000 feet may incur a small risk of developing pulmonary vascular disease.
• Death from an isolated secundum atrial septal defect does not occur in pediatric patients.

Race

No significant racial influences have been identified.

Sex

Secundum atrial septal defect occurs more commonly in females than males, with a female-to-male ratio of 2:1.

Age

Secundum atrial septal defect is a congenital abnormality and, therefore, is present at birth. It may be diagnosed at any age, including early infancy, although the characteristic findings on physical examination often escape detection until the patient reaches a few years of age. An acquired defect occurs only iatrogenically.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Patients with ostium secundum atrial septal defects rarely have symptoms resulting directly from the defect. Decreased exercise tolerance in relation to peers may occur in older children and young adults. Some reports suggest that children with secundum atrial septal defects are smaller than other children; if so, this is an association. A cause-and-effect relationship has not been established.

Physical

Patients are acyanotic and may have a slender build. Respirations are normal except in the young infant, in whom mild tachypnea may occur.

The jugular venous pulse demonstrates equal a and v waves when the defect is large enough to allow equilibration of right and left atrial pressure. A right ventricular lift occurs along the lower left sternal edge, and a mild precordial bulge may be present in the same location, both caused by right ventricular dilation. A pulmonary artery systolic impulse may be felt at the upper left sternal edge. The normal left ventricular apical impulse may be absent because the left ventricle is displaced posteriorly because of the dilated anterior right ventricle. The first heart sound may be split. This is not a particularly helpful observation except that it should not be confused with the presence of a pulmonary ejection sound.

A systolic ejection murmur is found over the pulmonary trunk in the second left intercostal space. This murmur peaks in mid systole and is never more than grade 2-3/6. If a thrill is palpated in this location, the patient likely has pulmonic valve stenosis. The murmur radiates well over both lung fields. This murmur, by itself, is indistinguishable from an innocent pulmonic flow murmur. Significance of the systolic murmur depends upon identification of an abnormal second heart sound (S₂) and a diastolic murmur. The S₂ is widely split, and respiratory variation in the splitting interval cannot be identified.

Indeed, with a large shunt caused by a secundum atrial septal defect, the splitting interval does not vary at all with respiration; it is fixed. Wide fixed splitting of S₂ typically occurs with a large atrial shunt caused by an atrial septal defect. Identifying by auscultation alone that S₂ splitting is fixed, as opposed to very wide but with some respiratory variation (eg, with right bundle branch block), may be difficult. Diagnosis of an atrial septal defect by auscultation requires identification of the characteristic diastolic murmur.

A medium frequency mid diastolic murmur at the lower left sternal edge occurs with rapid ventricular filling of the right ventricle after the tricuspid valve opens. The murmur is never more than grade 1-2/6, and identifying it usually takes effort. If the shunt is large enough to cause wide, seemingly fixed, splitting of S₂, this murmur should be audible.

Causes

Isolated secundum atrial septal defect occasionally demonstrates familial inheritance in an autosomal dominant pattern, particularly when associated with prolonged atrioventricular conduction (ie, prolonged PR interval on ECG). Familial secundum atrial septal defect also occurs in Holt-Oram Syndrome.

Even when not associated with an identifiable inheritance pattern, the incidence of secundum atrial septal defect is 2-3 times higher in first-degree relatives than in the general population.⁸ A PTPN11 gene mutation has been identified in patients with Noonan syndrome in whom heart defects occur in 85%.⁹ The most prevalent defects are secundum atrial septal defect and pulmonary valve stenosis; these defects were significantly associated with this gene mutation. Evidence suggests that increased folic acid intake in the general population by fortification of grain products can produce a 20% reduction in occurrence of atrial septal defects.¹⁰

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Pulmonic valve stenosis
Peripheral pulmonic stenosis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• No specific laboratory blood tests are necessary in the evaluation of patients with an ostium secundum atrial septal defect.
• A small degree of right-to-left shunt may occur with a large atrial septal defect. This may be detected by observing a mild decrease in cutaneous oxygen saturation to 93-95%. Although this may increase hemoglobin and hematocrit minimally, it is insufficient to cause clinical cyanosis.

Imaging Studies

• Routine chest radiography is not essential in the evaluation of a child with a suspected secundum atrial septal defect. They demonstrate increased pulmonary arterial vascularity with a prominent pulmonic trunk, right atrial enlargement, no evidence of left atrial enlargement, and right ventricular dilation.
• Echocardiography is essential in the evaluation of a child with a suspected atrial septal defect. The right atrium and right ventricle are dilated; paradoxical motion of the ventricular septum is usually present.
• • Two-dimensional imaging from the subcostal position best reveals the defect in the atrial septum. The diameter of the defect can be measured, multiple defects can be identified, and associated anomalies can be evaluated. Some investigators use 3-dimensional echocardiography to provide an accurate assessment of the exact shape of the defect because this can be important in device closure of atrial septal defects.
  • Color Doppler studies provide direct, simulated visualization of flow from the left atrium to the right atrium. This flow is not turbulent when the defect is large enough to be clinically apparent because its size eliminates the pressure difference between the atria.
  • Complete echocardiographic examination must also identify normality of the coronary sinus, normal entrance of the pulmonary veins, an intact primum portion of the atrial septum, and normal mitral valve function. Left ventricular contractility may appear abnormal due to the dilated right ventricle. This corrects rapidly after atrial septal defect closure.^{11, 12, 13}
  • Transesophageal echocardiography may be necessary in some patients because of large body size or other impediments to adequate transthoracic visualization. Transesophageal echocardiography is also used during interventional catheterization to close a secundum atrial septal defect by guiding device placement.
• MRI is not indicated in the evaluation of a child with a suspected secundum atrial septal defect and does not add significantly to echocardiography findings.

Other Tests

• An ECG demonstrates sinus rhythm, often with evidence of right atrial enlargement manifested by tall, peaked P waves (usually best seen in leads II and V₂) and prolongation of the PR interval. The QRS axis is slightly directed to the right (+100º), and the precordial leads reveal right ventricular enlargement of the so-called volume overload type that is characterized by an rSR' pattern in leads V₃R and V₁ with normal T waves.
• The QRS duration may be mildly prolonged because of right ventricular dilation. This mimics the finding in right ventricular conduction delay.
• A significant proportion (20-40%) of children with secundum atrial septal defect may not have abnormal ECG findings.¹⁴
• Uncommonly, a patient with a secundum atrial septal defect may demonstrate a superior QRS axis with right ventricular enlargement, mimicking findings observed in the ECG of a patient with an ostium primum atrial septal defect (see Atrial Septal Defect, Ostium Primum).

Procedures

• Cardiac catheterization is not indicated in the routine evaluation of a child with a suspected secundum atrial septal defect. If concerns about pulmonary hypertension are noted, the pulmonary artery pressure and the reactivity of the pulmonary vascular resistance to vasodilators can be measured at cardiac catheterization.
• Additional tests and procedures are necessary only in evaluation of other components of the patient's status, as indicated by complete history and physical examination.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Small-to-moderate–sized ostium secundum atrial septal defects diagnosed in the infant demonstrate significant likelihood of either spontaneous closure or reduction in size to the point that medical intervention no longer is indicated. Such patients should be followed until age 3-4 years before considering either device use or surgical closure.^{5, 15}

Surgical Care

• Minimally invasive cardiac surgery techniques allow closure without the use of blood or blood products in appropriately sized patients.^{16, 17}
• • The skin incision is short because complete vertical division of the sternum is not necessary.
  • If the defect is moderate in size and oval in shape, direct suture closure may be appropriate. Larger or rounder defects require patch closure. The patch can be fashioned from the patient's pericardium or made from Dacron.
  • Results of surgery are excellent; a 100% closure rate should be achieved. Risk of mortality does not exceed that of general anesthesia.^{18, 19}
  • Inpatient hospital stay now averages 2-3 days. Perform postoperative echocardiography to confirm closure.
  • Postoperative care includes bacterial endocarditis precautions for 6 months if a patch was placed.
• Catheter intervention may be indicated.
• • Transcatheter device closure of secundum atrial septal defect now represents a standard of care for this abnormality.²⁰ Experience at centers throughout the world is extensive; the success rate has been high, and the risk of complications has been low.^{21, 22, 23} Indication for closure in the pediatric age range is a shunt of sufficient size to be clinically apparent. The reason for closure is to prevent development of complications (eg, atrial dysrhythmia, right heart dysfunction) that may appear in the adult. Small defects in children that are detectable only by echocardiography do not require closure.
  • In adult patients who experience a suspected thrombotic stroke and who manifest a patent foramen ovale (15-20% of all adults demonstrate a patent foramen ovale on echocardiography), concern arises that the stroke may have been caused by a paradoxical embolus.²⁴ In these patients, device closure of the communication is often recommended and accomplished. Studies remain controversial regarding the appropriateness of this treatment.
  • Transcatheter device occlusion of a secundum atrial septal defect should be accomplished only by physicians properly trained and experienced in the procedure. Proper sizing of the defect and anatomic evaluation to assure reliable seating of the device is essential.
  • The device is placed in the atrial septum via a catheter introduced into a femoral vein. Most operators advise monitoring the procedure with transesophageal echocardiography. Multiple studies indicate a high degree of success, with complete closure rates only slightly less than those obtained by surgery.
  • Studies comparing device closure with surgery establish that hospital stay is shorter in patients undergoing device closure. Total costs of the 2 techniques do not significantly differ, apparently because of the cost of the device.²⁵
  • Complications of device occlusion include hemorrhage, vascular disruption, pain, nausea and vomiting, and arterial or venous obstruction from thrombosis or spasm. Other complications include rupture of blood vessel, tachyarrhythmias, bradyarrhythmias, and vascular occlusion. Embolization of the device during placement rarely occurs but can result in emergency surgery for removal. The most common complication is incomplete closure of the defect.²⁶

Consultations

Patients should be evaluated by a pediatric cardiologist. Patients with defects considered appropriate for transcatheter device closure should be evaluated by an interventional pediatric cardiologist experienced in the procedure. If surgery is contemplated, the patient should be evaluated by a cardiovascular surgeon experienced in surgery of congenital heart defects. Ideally, decisions regarding therapy should result from simultaneous evaluation of patient data at a group meeting that includes all of these physicians.

Diet

No special diet is required.

Activity

No activity restrictions are required except for a few weeks following either device closure or heart surgery.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Drug therapy is not currently a component of the standard of care for this condition. No specific medications are indicated for patients with a secundum atrial septal defect. Bacterial endocarditis prophylaxis is required for the first 6 months following device closure or surgical closure with a patch (see Endocarditis, Bacterial for further information). Preoperatively, antibiotic prophylaxis is not required in an isolated ostium secundum atrial septal defect. For information regarding antibiotics used for endocarditis prophylaxis, see Antibiotic Prophylactic Regimens for Endocarditis.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• No further inpatient care is required in patients with ostium secundum atrial septal defect.

Further Outpatient Care

• If the immediate postoperative echocardiography confirms complete closure, a follow-up visit one year following closure is adequate to evaluate possible long-term complications (rare). Patients who undergo closure of a large defect late in childhood (when >8 y) should be advised to continue infrequent cardiology evaluations with electrocardiographic studies approximately every 5 years to monitor for the possible occurrence of a dysrhythmia.²⁷
• Patients who undergo device closure of a secundum atrial septal defect should continue cardiology evaluations until long-term published studies establish the absence of late complications.

In/Out Patient Meds

• No medications are required, except bacterial endocarditis prophylaxis for 6 months following either device or patch closure.

Transfer

• Evaluation and treatment should be carried out at a center specializing in congenital heart disease.

Complications

• Surgical damage to the sinoatrial node occurs rarely when experienced individuals accomplish closure. Short and long-term postoperative rhythm disturbances can occur, however, particularly when closure of a large defect is delayed beyond early childhood (ie, >8 y).
• Late complications of device closure can include rhythm disturbance, perforation of the heart, fracture of the supporting structures of the device, and residual shunts. Long-term late complications remain unknown

Prognosis

• The surgical mortality rate should be less than 0.1%. If defects are closed in children younger than 8 years, the prognosis is excellent, with rare short-term or long-term cardiac abnormalities.
• Patients with incomplete closure or closure at older age remain at risk for development of cardiac rhythm disturbances. Whether closure of a secundum atrial septal defect in a person older than 40 years alters the patient's risk of either cardiac disability or limitation of life remains controversial.²⁸

Patient Education

• No patient restrictions are indicated. Families and patients should have some familiarity with symptoms of cardiac dysrhythmias.
• Genetic counseling is advised for all patients and their families, especially if other family members are affected.
• When a child with a secundum atrial septal defect reaches maturity education regarding the significance of the defect is advisable.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure of the primary care physician to identify abnormal cardiac physical examination findings can create a problem.
• Surgical or catheter mishaps may raise concerns, especially if the operator is inexperienced in treating congenital heart defects.

Special Concerns

• Pregnancy does not involve an altered risk after successful closure of a secundum atrial septal defect, even with a persistent residual small shunt. Women with an unoperated and uncomplicated defect generally tolerate pregnancy well.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Gessner IH. Atrial septal defect. In: Surgery of Congenital Heart Disease: Pediatric Care Consortium 1984-1995. Armonk, NY: Futura Publishing Co.; 1998:31-44.
2. Vick GW, Titus JL. Defects of the atrial septum, including the atrioventricular canal. In: Garson A, Bricker JT, Fisher, DJ, Neish, SR eds. The Science and Practice of Pediatric Cardiology. Vol 2. Baltimore, MD: Lippincott Williams & Wilkins; 1998.
3. Azhari N, Shihata MS, Al-Fatani A. Spontaneous closure of atrial septal defects within the oval fossa. Cardiol Young. Apr 2004;14(2):148-55. [Medline].
4. Saxena A, Divekar A, Soni NR. Natural history of secundum atrial septal defect revisited in the era of transcatheter closure. Indian Heart J. Jan-Feb 2005;57(1):35-8. [Medline].
5. Hanslik A, Pospisil U, Salzer-Muhar U, Greber-Platzer S, Male C. Predictors of spontaneous closure of isolated secundum atrial septal defect in children: a longitudinal study. Pediatrics. Oct 2006;118(4):1560-5. [Medline]. [Full Text].
6. McMahon CJ, Feltes TF, Fraley JK, et al. Natural history of growth of secundum atrial septal defects and implications for transcatheter closure. Heart. Mar 2002;87(3):256-9. [Medline].
7. Sachweh JS, Daebritz SH, Hermanns B, et al. Hypertensive pulmonary vascular disease in adults with secundum or sinus venosus atrial septal defect. Ann Thorac Surg. Jan 2006;81(1):207-13. [Medline].
8. Caputo S, Capozzi G, Russo MG, et al. Familial recurrence of congenital heart disease in patients with ostium secundum atrial septal defect. Eur Heart J. Oct 2005;26(20):2179-84. [Medline].
9. Sznajer Y, Keren B, Baumann C, et al. The spectrum of cardiac anomalies in Noonan syndrome as a result of mutations in the PTPN11 gene. Pediatrics. Jun 2007;119(6):e1325-31. [Medline]. [Full Text].
10. Godwin KA, Sibbald B, Bedard T, Kuzeljevic B, Lowry RB, Arbour L. Changes in frequencies of select congenital anomalies since the onset of folic acid fortification in a Canadian birth defect registry. Can J Public Health. Jul-Aug 2008;99(4):271-5. [Medline].
11. Wu ET, Akagi T, Taniguchi M, et al. Differences in right and left ventricular remodeling after transcatheter closure of atrial septal defect among adults. Catheter Cardiovasc Interv. May 1 2007;69(6):866-71. [Medline].
12. Walker RE, Moran AM, Gauvreau K, Colan SD. Evidence of adverse ventricular interdependence in patients with atrial septal defects. Am J Cardiol. Jun 1 2004;93(11):1374-7, A6. [Medline].
13. Giardini A, Donti A, Formigari R, et al. Determinants of cardiopulmonary functional improvement after transcatheter atrial septal defect closure in asymptomatic adults. J Am Coll Cardiol. May 19 2004;43(10):1886-91. [Medline].
14. Arrington CB, Tani LY, Minich LL, Bradley DJ. An assessment of the electrocardiogram as a screening test for large atrial septal defects in children. J Electrocardiol. Nov-Dec 2007;40(6):484-8. [Medline].
15. Brassard M, Fouron JC, van Doesburg NH, Mercier LA, De Guise P. Outcome of children with atrial septal defect considered too small for surgical closure. Am J Cardiol. Jun 1 1999;83(11):1552-5. [Medline].
16. Doll N, Walther T, Falk V, et al. Secundum ASD closure using a right lateral minithoracotomy: five-year experience in 122 patients. Ann Thorac Surg. May 2003;75(5):1527-30; discussion 1530-1. [Medline].
17. Argenziano M, Oz MC, Kohmoto T, et al. Totally endoscopic atrial septal defect repair with robotic assistance. Circulation. Sep 9 2003;108 Suppl 1:II191-4. [Medline]. [Full Text].
18. Shah D, Azhar M, Oakley CM, et al. Natural history of secundum atrial septal defect in adults after medical or surgical treatment: a historical prospective study. Br Heart J. Mar 1994;71(3):224-7; discussion 228. [Medline].
19. Bolz D, Lacina T, Buser P, et al. Long-term outcome after surgical closure of atrial septal defect in childhood with extensive assessment including MRI measurement of the ventricles. Pediatr Cardiol. Sep-Oct 2005;26(5):614-21. [Medline].
20. Lock JE, Cockerham JT, Keane JF, et al. Transcatheter umbrella closure of congenital heart defects. Circulation. Mar 1987;75(3):593-9. [Medline].
21. Jones TK, Latson LA, Zahn E, et al. Results of the U.S. multicenter pivotal study of the HELEX septal occluder for percutaneous closure of secundum atrial septal defects. J Am Coll Cardiol. Jun 5 2007;49(22):2215-21. [Medline].
22. Patel A, Lopez K, Banerjee A, Joseph A, Cao QL, Hijazi ZM. Transcatheter closure of atrial septal defects in adults > or =40 years of age: immediate and follow-up results. J Interv Cardiol. Feb 2007;20(1):82-8. [Medline].
23. Post MC, Suttorp MJ, Jaarsma W, Plokker HW. Comparison of outcome and complications using different types of devices for percutaneous closure of a secundum atrial septal defect in adults: a single-center experience. Catheter Cardiovasc Interv. Mar 2006;67(3):438-43. [Medline].
24. Handke M, Harloff A, Olschewski M, Hetzel A, Geibel A. Patent foramen ovale and cryptogenic stroke in older patients. N Engl J Med. Nov 29 2007;357(22):2262-8. [Medline].
25. Vida VL, Barnoya J, O'Connell M, et al. Surgical versus percutaneous occlusion of ostium secundum atrial septal defects: results and cost-effective considerations in a low-income country. J Am Coll Cardiol. Jan 17 2006;47(2):326-31. [Medline].
26. Butera G, Carminati M, Chessa M, et al. Percutaneous versus surgical closure of secundum atrial septal defect: comparison of early results and complications. Am Heart J. Jan 2006;151(1):228-34. [Medline].
27. Giardini A, Donti A, Specchia S, Formigari R, Oppido G, Picchio FM. Long-term impact of transcatheter atrial septal defect closure in adults on cardiac function and exercise capacity. Int J Cardiol. Feb 29 2008;124(2):179-82. [Medline].
28. Brochu MC, Baril JF, Dore A, et al. Improvement in exercise capacity in asymptomatic and mildly symptomatic adults after atrial septal defect percutaneous closure. Circulation. Oct 1 2002;106(14):1821-6. [Medline]. [Full Text].

Article Last Updated: Nov 10, 2008