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Pediatrics: Cardiac Disease and Critical Care Medicine > Cardiology
Atrial Septal Defect, Patent Foramen Ovale
Article Last Updated: Aug 21, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Barry A Love, MD, Assistant Professor, Department of Medicine, Division of Cardiology, Assistant Professor, Division Pediatric Cardiology, Pediatrics and Medicine, Division of Pediatric Cardiology, Mount Sinai School of Medicine
Coauthor(s):
Michael A Portman, MD, Research Director, Department of Pediatrics, Division of Cardiology, Associate Professor, Childrens' Hospital
Editors: Paul M Seib, MD, Associate Professor of Pediatrics, University of Arkansas for Medical Sciences; Medical Director, Cardiac Catheterization Laboratory, Co-Medical Director, Cardiovascular Intensive Care Unit, Arkansas Children's Hospital; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Alvin J Chin, MD, Professor of Pediatrics, Division of Cardiology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine; Gilbert Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College; Steven R Neish, MD, SM, Director of Pediatric Cardiology Fellowship Program, Department of Pediatrics, Baylor College of Medicine
Author and Editor Disclosure
Synonyms and related keywords:
atrial septal defect, patent foramen ovale, ASD PFO, interatrial communication, congenital heart defect, left-to-right shunting, right-to-left shunting, incompetent valve of the fossa ovalis, right atrial enlargement, left atrial enlargement, paradoxical embolism
Background
The foramen ovale is a normal cardiac structure found in all newborns and can be best described as a "door" between the right and left atria.
The foramen ovale is essential for proper fetal circulation, directing oxygenated, nutrient-rich blood from the placenta, preferentially to the developing fetal brain. During fetal life, the "door" is open, and blood passes from the right to left atrium. However, with separation from the placenta and with the first few breaths, the left atrium fills with blood returning from the lungs and closes the "door."
During the first years of life, the foramen ovale seals shut and becomes a true wall that separates the right and left atria. However, in a significant proportion of people, the foramen ovale does not seal shut and remains a potential trapdoor between the 2 atria. A patent foramen ovale (PFO) is defined as a foramen ovale that does not seal.
All newborns are expected to have a patent foramen ovale. The time frame over which most seal shut is variable. However, adult autopsy studies have shown that 25-30% of individuals have a small patent foramen ovale, even at an older age.
Although it is a normal structure, a foramen ovale has several special circumstances under which it may be implicated in disease.
Pathophysiology
The foramen ovale is an interatrial communication that permits blood from the inferior vena cava to freely enter the left atrium in utero. Anatomically, a thick muscular ridge, the limbus of the fossa ovalis, borders the foramen ovale. A thin tissue flap on the left atrial side of the septum, which represents an embryological remnant of the septum primum, forms the valve of the fossa ovalis. At birth, the left atrial pressure exceeds the right atrial pressure and forces the valve against the limbus, thus achieving physiological closure. During the first weeks of life, Doppler echocardiographic studies in healthy newborns can often demonstrate incompetence of the valve that allows some degree of left-to-right shunting. Shunting generally resolves by age 1 year as the foramen ovale closes.
Persistent left atrial enlargement associated with specific cardiac lesions, such as mitral valve stenosis, mitral valve regurgitation, patent ductus arteriosus, or ventricular septal defect, can dilate the foramen. Atrial left-to-right shunting can continue as a result.
Right-to-left shunting can occur through a patent foramen ovale, especially in conditions associated with elevated right atrial pressure such as tricuspid valve stenosis or right ventricular hypoplasia with decreased right ventricle compliance. Patients with persistent or transient elevation of right atrial pressure can experience a paradoxical embolus through a patent foramen ovale. Some congenital heart lesions depend on the foramen ovale for obligatory left-to-right (mitral atresia) or right-to-left (tricuspid atresia, total anomalous pulmonary venous return) shunting to maintain adequate cardiac output.
Frequency
International
Several echocardiography and postmortem studies indicate that the foramen remains competent in 30% of patients with otherwise normal cardiac anatomy.
Mortality/Morbidity
- The vast majority of patients with a patent foramen ovale experience no symptoms throughout life.
- Morbidity, although rare, is predominantly due to paradoxical embolism. Cerebrovascular ischemic events can be attributed to paradoxical embolism through a patent foramen ovale. This usually occurs in patients without other risk factors, although deep venous thrombosis and hypercoagulable states may significantly increase this risk.
- Recently, migraine headaches, especially with aura, have been found to be associated with the presence of a patent foramen ovale. Up to 50% of patients with migraine headaches can be found to have a patent foramen ovale, compared with a 15-30% prevalence in the normal population. The reason for this correlation is not established. Paradoxical embolization of small clots is a possible etiology. Eight percent of patients with migraine headaches have been shown to have evidence of asymptomatic strokes on brain MRI. Another possible etiology is the transit of vasoactive substances from the venous circulation to the arterial circulation without being modified by the lungs, which then causes cerebral hyperreactivity.
Race
Based on transesophageal echocardiography (TEE) findings in the setting of cryptogenic stroke in adults, African American patients have been shown to be about half as likely to have patent foramen ovale as white patients.
Age
The foramen ovale is a potential opening in virtually all newborns. The foramen ovale seals shut over the first months of life in most infants. However, it remains as a trapdoor and has the potential to be opened in 15-30% of adults.
History
- The trivial amount of left-to-right shunting through a patent foramen ovale generally produces no symptoms.
- Patients with right-to-left shunting can experience transient or persistent periods of cyanosis. This can be exacerbated by acute increases in pulmonary vascular resistance, such as those that occur during breath holding, crying, or the Valsalva maneuver. Persistent cyanosis due to right-to-left shunting may also occur during the neonatal period until pulmonary vascular resistance falls.
- Premature closure of the foramen ovale in-utero may lead to underdevelopment of the left-sided structure of the heart and hypoplastic left-sided heart syndrome. About 10% of patients with hypoplastic left-sided heart syndrome have an intact or nearly intact atrial septum in-utero.
- Paradoxical emboli through a patent foramen ovale can cause a constellation of neurologic symptoms, such as stroke or transient ischemic attacks. Paradoxical embolization more often produces symptoms when the embolization occurs in the posterior cerebral circulation.
- Migraine headaches are associated with a patent foramen ovale. The exact mechanism is not yet clear.
- Rarely, the clinical constellation of orthodeoxia-platypnea may be seen as a result of a patent foramen ovale. Orthodeoxia is desaturation with upright posture, while platypnea is dyspnea with upright posture.
- In patients with a patent foramen ovale and certain conditions such as pneumonectomy, the flow from the inferior vena cava may be preferentially directed through the patent foramen ovale in the upright position, producing right-to-left shunt and cyanosis. This occurs in the absence of pulmonary hypertension and with relatively low or normal right and left atrial pressures. Transcatheter patent foramen ovale closure eliminates the right-to-left shunt and restores normal arterial oxygen saturation.
Physical
- No physical findings clearly indicate a patent foramen ovale without an associated congenital heart defect; however, the presence of a patent foramen ovale with right-to-left shunting should be considered in an infant with generalized cyanosis.
- Right-to-left atrial level shunting results in symmetric central cyanosis rather than differential cyanosis.
Atrial Septal Defect, Coronary Sinus
Atrial Septal Defect, Ostium Primum
Atrial Septal Defect, Ostium Secundum
Atrial Septal Defect, Sinus Venosus
Partial Anomalous Pulmonary Venous Connection
Total Anomalous Pulmonary Venous Connection
Other Problems to be Considered
Other causes of cerebral ischemic events
Other causes of right-to-left shunting (eg, left superior vena cava [SVC] to the left atrium, right SVC to left atrium, pulmonary arteriovenous malformation)
Lab Studies
- No laboratory tests are specific for patent foramen ovale.
- In patients with a cryptogenic stroke and a patent foramen ovale, a complete hypercoagulable workup is indicated to rule out a hypercoagulable state. If a hypercoagulable condition is found, specific treatment of this condition, usually with anticoagulation, is indicated. Closure of the patent foramen ovale may be indicated in patients with a hypercoagulable state, although surgical closure should be considered, as the risk of thrombosis on transcatheter occlusion devices may be increased in the presence of a hypercoagulable state.
- A hypercoagulable workup typically consists of the following tests:
- CBC count (for platelet count)
- Prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR)
- Factor V Leiden assessment
- Prothrombin gene mutation
- Protein C and protein S assessment (Note that proteins C and S are vitamin K–dependent factors and should not be measured while the patient is taking warfarin [Coumadin]).
- Antithrombin III assessment
- Homocysteine assessment
Imaging Studies
- Echocardiography
- Transthoracic 2-dimensional echocardiography can generally reveal a gap in the midinteratrial septum consistent with a patent foramen ovale in infants and small children. In older children and adults, transthoracic echocardiography does not visualize the atrial septum as well. Subcostal views are particularly proficient in imaging the atrial septum.
- TEE should be performed in patients with suspected shunting and poor transthoracic acoustic windows. In patients with cryptogenic stroke, TEE is mandatory to identify the presence of a patent foramen ovale and to identify a concomitant atrial septal aneurysm. An atrial septal aneurysm is a hypermobility of the septum primum tissue that forms the left atrial wall of the atrial septum. An excursion of more than 1 cm is diagnostic for an atrial septal aneurysm and confers an increased risk for a subsequent neurologic event.
- Bubble-contrast echocardiography
- Bubble-contrast echocardiography is mandatory to diagnose a patent foramen ovale and to demonstrate a potential right-to-left shunt. A bubble-contrast study is performed by inserting a peripheral intravenous line and agitating 8 mL of saline with 1 mL of the patient's blood and 1 mL of air. The air is agitated into the solution and the bubble contrast is injected. The atrial septum and left atrium are visualized during the injections. In the presence of a patent foramen ovale, bubbles can be seen crossing the atrial septum and entering the left atrium.
- The bubble-contrast injection should be performed at rest and with a Valsalva maneuver. The Valsalva maneuver transiently increases right atrial pressure above left atrial pressure, encouraging potential right-to-left shunting.
- TEE is usually the best echocardiographic imaging tool to use with a bubble-contrast injection, although it can be performed using transthoracic echocardiography. The sensitivity of transthoracic echocardiography with bubble-contrast injection is poor compared with transesophageal imaging.
- Transcranial Doppler with bubble-contrast injection is a useful screening tool for right-to-left shunting via a patent foramen ovale. An ultrasound probe is placed on the head, and the ultrasound beam is used to sample the middle cerebral arteries. A bubble-contrast injection is performed at rest and with the Valsalva maneuver. Any right-to-left shunt is revealed by the appearance of bubble artifacts on the transcranial Doppler signal. The number of bubble counts correlates with the potential for right-to-left shunting. Modern transcranial Doppler with bubble-contrast injection is as sensitive as transesophageal echocardiography with bubble-contrast injection in identifying a patent foramen ovale.
Procedures
- Transcatheter closure of a patent foramen ovale is controversial. In the setting of cryptogenic stroke and a patent foramen ovale, nonrandomized data shows that transcatheter patent foramen ovale closure is at least as effective as medical therapy (aspirin or warfarin) in preventing recurrent strokes. In the United States, 2 closure devices, the Amplatzer PFO Occluder (AGA Medical Company; Golden Valley, Minn) and the CardioSeal device (NMT) Medical; Boston, Mass), are available under a special humanitarian device exemption (HDE) for patent foramen ovale closure. The HDE requires that patients have had more than one stroke or transient ischemic attack while receiving warfarin to qualify for patent foramen ovale closure.
- Ongoing randomized controlled trials are comparing medical therapy (warfarin or aspirin) with transcatheter device closure of patent foramen ovale in the prevention of stroke. Patients who have had one stroke with a patent foramen ovale may qualify for these trials. One of the difficulties in comparing therapies for secondary prevention of stroke in patients with a patent foramen ovale is the relatively low recurrence rate. In patients with stroke and a patent foramen ovale, the recurrence risk appears to be 1-3% per year. In patients with atrial septal aneurysm, the risk is somewhat higher, about 5% per year. Even so, this relatively low recurrence risk means that randomized trials need to enroll large numbers of patients and observe them for many years to establish a benefit (or at least noninferiority) to medical therapy.
- Outside the United States, at least 2 devices are used commonly for patent foramen ovale closure, the Amplatzer PFO Occluder and the StarFlex PFO occluder (NMT Medical; Boston, Mass). Other devices, such as the Premiere PFO Closure System (St Jude Medical; St Paul, Minn), are under investigation.
- In the United States, off-label use of transcatheter closure devices is common in situations in which patients have a patent foramen ovale and have had a single stroke and do not wish to enter a randomized trial. Although the American Academy of Neurology has discouraged this type of an approach and encourages participation in randomized controlled trials, evidence of nonrandomized trials is sufficient for many to proceed with this approach. The Amplatzer Septal Occluder (AGA Medical Company; Golden Valley, Minn), approved for closure of atrial septal defects, and the CardioSeal device, approved for closure of muscular ventricular septal defects, are both used off-label for transcatheter patent foramen ovale closure in the United States.
Medical Care
A small left-to-right shunt associated with a patent foramen ovale should not require treatment. In patients who have experienced a stroke or transient ischemic attack, treatment with aspirin or warfarin appears to decrease the risk of a subsequent event. Two trials showed that warfarin was no better than aspirin in preventing subsequent strokes; however, if medical therapy rather than transcatheter patent foramen ovale closure is chosen, many neurologists feel that warfarin is a better choice because of controversy related to the patient population.
Surgical Care
- Closure of a patent foramen ovale is indicated if right-to-left shunting is identified as a previous or potential source of paradoxical embolism. Closure should be undertaken in patients with a patent foramen ovale and history of stroke only after an extensive evaluation excludes other causes of the stroke or sources of emboli. Closure may also be indicated in patients who have recurrent symptoms of stroke while receiving warfarin. Patent foramen ovale closure may be indicated in preparation for neurosurgical procedures in the sitting position, which carry a high risk of paradoxical air embolism. Closure may also be indicated in divers, for whom a patent foramen ovale represents an increased risk for decompression illness.
- In patients with orthodeoxia-platypnea secondary to a patent foramen ovale, patent foramen ovale closure is curative and normalizes the arterial oxygen saturation.
- Surgical closure of a foramen ovale has largely been supplanted by the availability of safe and effective transcatheter closure methods. The safety and effectiveness of surgical foramen ovale closure has not been systematically compared with medical therapy or transcatheter device closure.
Consultations
Consultation with a pediatric cardiologist for evaluation of associated congenital heart defects and assessment of degree of left-to-right or right-to-left shunting may be indicated. Consultation with a neurologist in patients with suspected stroke is indicated.
Activity
Activity is not restricted. However, scuba diving at depths greater than 35 ft increases the risk of decompression illness. Patent foramen ovale closure is therefore recommended for divers who descend to depths greater than 35 ft.
Drug Category: Anticoagulants
These agents are used to prevent recurrent or ongoing thromboembolic occlusion. Systemic anticoagulation may be indicated for patients with patent foramen ovale and history of stroke or those at a significantly increased risk for paradoxical embolus.
| Drug Name | Warfarin (Coumadin) |
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| Description | Interferes with hepatic synthesis of vitamin K-dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor dose to maintain an INR in the range of 2-3. |
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| Adult Dose | 5-15 mg/d PO qd for 2-5 d; adjust dose according to desired INR |
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| Pediatric Dose | Administer weight-based dose of 0.05-0.34 mg/kg/d PO qd; adjust dose according to desired INR |
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| Contraindications | Documented hypersensitivity; severe liver or kidney disease; open wounds or GI ulcers |
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| Interactions | Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, and sucralfate
Medications that may increase anticoagulant effects of warfarin include oral antibiotics, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen and sulindac |
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| Pregnancy | X - Contraindicated in pregnancy
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| Precautions | Do not switch brands after achieving therapeutic response; caution in active tuberculosis or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis |
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Drug Category: Antiplatelets
Aspirin, at doses of 3-5 mg/kg daily, acts as an antiplatelet agent and appears to reduce the risk of recurrent stroke in patients with cryptogenic stroke and patent foramen ovale.
| Drug Name | Aspirin (Anacin, Bayer) |
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| Description | Stronger inhibitor of both prostaglandin synthesis and platelet aggregation than other salicylic acid derivatives. Acetyl group is responsible for inactivation of cyclooxygenase via acetylation. Hydrolyzed rapidly in plasma, and elimination follows zero-order pharmacokinetics.
Irreversibly inhibits platelet aggregation by inhibiting platelet cyclooxygenase. This, in turn, inhibits conversion of arachidonic acid to PGI2 (potent vasodilator and inhibitor of platelet activation) and thromboxane A2 (potent vasoconstrictor and platelet aggregate). Platelet inhibition lasts for the life of the cell (approximately 10 d). May be used in low doses to inhibit platelet aggregation and to improve complications of venous stases and thrombosis. Indicated to prevent recurrent ischemic stroke. |
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| Adult Dose | 81 mg or 325 mg PO qd |
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| Pediatric Dose | 3-5 mg/kg PO qd |
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| Contraindications | Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; because of the association of aspirin with Reye syndrome, do not use in children ( <16 y) with viral infections |
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| Interactions | Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses > 2 g/d may potentiate glucose lowering effect of sulfonylurea drugs |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks.
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| Precautions | May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia or history of blood coagulation defects or those taking anticoagulants |
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Further Inpatient Care
- Inpatient observation in the neonate with cyanosis due to atrial right-to-left shunting may be required until the underlying cause is defined.
Further Outpatient Care
- Outpatient follow-up is indicated for patients with cyanosis due to right-to-left shunting at the patent foramen ovale to check for evidence of resolution of shunting as changes in pulmonary vascular resistance occur. Follow-up echocardiography is recommended after surgical closure or placement of a transcatheter device to confirm persistent closure.
Transfer
- Transfer of patients with patent foramen ovale is likely to be indicated only for surgical closure or transcatheter device closure of the patent foramen ovale in patients with problematic right-to-left shunting.
Complications
- Symptomatic desaturation due to right-to-left shunting at the patent foramen ovale or paradoxical embolus with stroke or other systemic embolization may occur as described above.
Prognosis
- In general, the prognosis is excellent but may depend on underlying problems or associated defects. For instance, the neonate with right-to-left patent foramen ovale shunting resulting in cyanosis may have complete resolution of right-to-left shunting as pulmonary vascular resistance falls. Alternatively, associated congenital heart defects (eg, Ebstein malformation of the tricuspid valve) may continue to exhibit right-to-left shunting, especially with exercise, as these patients grow. Also, some patients with stroke thought to be caused by paradoxical embolus may continue to have cryptogenic stroke even after surgical or transcatheter device closure of a patent foramen ovale.
- Healthy patients who have a patent foramen ovale discovered incidentally do not require any special treatment or follow-up. Patients with a patent foramen ovale who have not had prior stroke or transient ischemic attack are not at measurably increased risk for these events.
Medical/Legal Pitfalls
- Failure to recognize a patent foramen ovale as a source of paradoxical embolism
- Failure to evaluate a patient for patent foramen ovale prior to a sitting neurosurgical procedure
Special Concerns
- Pregnancy: Patients with a patent foramen ovale who have not had a prior stroke or transient ischemic attack do not appear to be at any elevated risk during pregnancy. Normal pregnancy and delivery can be safely advised.
| Media file 1:
This 2-dimensional echocardiogram in an infant (subcostal long-axis view) shows a patent foramen ovale. Right atrium (RA) and left atrium (LA). |
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| Media file 2:
Color Doppler of the patent foramen ovale (PFO) seen in image 1. A small amount of left-to-right flow is present. This left-to-right flow pattern is typical for PFO seen in newborn infants. |
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| Media file 3:
Transesophageal echocardiogram showing the atrial septum. The "flap" of the septum primum is seen. LA (left atrium) RA (right atrium). The diagnosis of patent foramen ovale cannot be made until right-to-left bubble contrast is demonstrated (see Image 4). |
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| Media file 4:
Bubble-contrast injection during Valsalva maneuver. The "flap" of the foramen ovale is opened and bubbles are seen crossing from the right atrium to the left atrium (arrow). |
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Media type: Image
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| Media file 5:
Transesophageal echocardiogram showing a 25-mm Amplatzer patent foramen ovale (PFO) occluder in place across the PFO shown in Images 3 and 4. |
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| Media file 6:
Transesophageal echocardiogram of a patent foramen ovale (PFO) closed with 25-mm Amplatzer PFO occluder. Bubble-contrast study with Valsalva post–device placement shows no residual right-to-left bubble passage. |
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| Media file 7:
Transcranial Doppler (TCD) study with bubble-contrast study. A Doppler probe is used to interrogate the right middle cerebral artery.Frame 1 shows a normal study. Note the absence of bubble artifact of Doppler signal in the middle cerebral artery.Frame 2 shows strongly positive (5/5) bubble transit seen in a patient with a patent foramen ovale (PFO) during Valsalva maneuver.TCD is a useful screening tool for PFO because of its ease-of-use and ability to easily quantify the amount of potential right-to-left shunt. One of the pitfalls is the inability to differentiate between other sources of right-to-left shunt, such as pulmonary arteriovenous malformation and a PFO. |
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| Media file 8:
Transesophageal echocardiogram of bubble contrast study showing right-to-left passage of bubble-contrast with a Valsalva maneuver. RA = Right atrium. LA = Left atrium. Arrow shows bubble passage to LA. |
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| Media file 9:
Transesophageal echocardiogram showing a 10-mm Amplatzer Septal Occluder in place across a patent foramen ovale. |
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Atrial Septal Defect, Patent Foramen Ovale excerpt Article Last Updated: Aug 21, 2006
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