Pediatric Patent Foramen Ovale Atrial Septal Defects 

Updated: Sep 16, 2019
Author: Barry A Love, MD; Chief Editor: Syamasundar Rao Patnana, MD 

Overview

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 two atria. A patent foramen ovale (PFO) is defined as a foramen ovale that does not seal. See the images below.

This 2-dimensional echocardiogram in an infant (su This 2-dimensional echocardiogram in an infant (subcostal long-axis view) shows a patent foramen ovale. Right atrium (RA) and left atrium (LA).
Color Doppler of the patent foramen ovale (PFO) se Color Doppler of the patent foramen ovale (PFO) seen in the previous image. A small amount of left-to-right flow is present. This left-to-right flow pattern is typical for PFO seen in newborn infants.

All newborns are expected to have a patent foramen ovale. The time frame over which most seal shut varies. However, adult autopsy studies have shown that 20-34% of adults from the third to ninth decades of life have at least a small patent foramen ovale.[1]

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 seals shut.[2, 3, 4, 5]

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 render the foramen ovale "incompetent." 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 atresia, 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.

Epidemiology

International data

Several echocardiography and postmortem studies indicate that the foramen remains competent in 30% of patients with otherwise normal cardiac anatomy.

 

Presentation

History

The trivial amount of left-to-right shunting through a patent foramen ovale (PFO) 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.[6, 7] 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.[8] Orthodeoxia is desaturation with upright posture, whereas platypnea is dyspnea with upright posture. This occurs even in the absence of pulmonary hypertension and with relatively low or normal right and left atrial pressures and is sometimes seen following pneumonectomy. Transcatheter patent foramen ovale closure eliminates the right-to-left shunt and restores normal arterial oxygen saturation.[9]

Physical Examination

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.

 

DDx

Diagnostic Considerations

Important considerations

Do not fail to recognize a patent foramen ovale as a source of paradoxical embolism.

Evaluate a patient for patent foramen ovale prior to a sitting neurosurgical procedure.

Special concerns

Pregnant 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 for developing such episodes during pregnancy. Normal pregnancy and delivery can be safely advised.

Other problems to be considered

Also consider the following when evaluating patients with suspected patent foramen ovale atrial septal defects:

  • 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)

Differential Diagnoses

 

Workup

Laboratory Studies

No laboratory tests are specific for patent foramen ovale (PFO).

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 with antiplatelet therapy or anticoagulation may be indicated. Consultation with a hematologist should be considered for patients in whom a hypercoagulable state is suspected. Closure of the patent foramen ovale may be indicated in patients with a hypercoagulable state, although one needs to be aware that surgical closure should be considered because 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

Transthoracic 2-dimensional echocardiography

Transthoracic 2-dimensional echocardiography can generally image the atrial septum and show the flap of the foramen ovale in infants and small children. Color Doppler flow across the atrial septum proves the presence of the foramen ovale. A foramen ovale may be differentiated from an atrial septal defect by the overlap of septal tissue. In older children and adults, transthoracic echocardiography does not visualize the atrial septum as well.

Transesophageal echocardiography

Transesophageal echocardiography (TEE) is preferred in patients where the atrial septum is inadequately visualized by transthoracic echocardiography. Older children and adults fall into this category. In addition to the patent foramen ovale, redundancy of septum primum can also be seen. When the redundancy of the septum moves more than 1 cm, it is called an atrial septal aneurysm. In the presence of a patent foramen ovale in patients who have had a prior stroke, atrial septal aneurysm confers an increased risk for a subsequent neurologic event.[10]

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.

Transesophageal echocardiogram showing the atrial Transesophageal echocardiogram showing the atrial septum. The "flap" of the septum primum is seen. The diagnosis of patent foramen ovale (PFO) cannot be made until right-to-left bubble contrast is demonstrated. LA = Left atrium; RA = Right 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.

Bubble-contrast injection during Valsalva maneuver 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).

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.

Khan et al reviewed the relationship of a patent foramen ovale (PFO) with stroke and evaluated associated comorbidities. They performed an electronic database literature search of PubMed, Cochrane, and EMBASE from January 2000 to December 2014, and they used 65 reports for the comprehensive review. They found that the concurrent use of transthoracic echocardiography with color Doppler and a bubble contrast study is excellent for visualization of the atrial septum and PFO and for identification of a right-to-left shunt.[11]

Transcranial Doppler imaging with bubble-contrast injection

Transcranial Doppler imaging with bubble-contrast injection is a useful screening tool for right-to-left shunting via a patent foramen ovale (see image and video below). 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 TEE with bubble-contrast injection in identifying a patent foramen ovale.[12]

Transcranial Doppler (TCD) study with bubble-contr Transcranial Doppler (TCD) study with bubble-contrast study. A Doppler probe is used to interrogate the right middle cerebral artery. Frame 1 shows normal findings. 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.
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.
 

Treatment

Approach Considerations

Zier et al conducted a comprehensive literature review of contemporary studies, focusing on randomized trials and meta-analyses that compare medical therapy and device closure of patent foramen ovale (PFO) for the treatment of PFO-associated clinical syndromes. It can be difficult to determine the extent to which the PFO is a causative factor in the disease process in many PFO-associated conditions. As a result, the investigators recommend that before implicating the PFO and proceeding with closure, healthcare providers perform a comprehensive diagnostic evaluation to exclude other obvious etiologies of PFO-associated conditions.[13]

Medical Care

Inpatient observation in the neonate with cyanosis due to atrial right-to-left shunting may be required until the underlying cause is defined.

A small left-to-right shunt associated with a patent foramen ovale (PFO) does 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; however, no evidence in adults suggests that warfarin is superior to aspirin.[14]

Outpatient follow-up is indicated for patients with cyanosis due to right-to-left shunting at the patent foramen ovale (PFO) to check for evidence of resolution of shunting as changes in pulmonary vascular resistance occur. 

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.

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.

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.[15]

Surgical Care

In most instances, no therapy is needed for a patent foramen ovale. The simple presence of a patent foramen ovale in an infant, child, or adult is a normal finding. Asymptomatic patients do not require medication and should not be considered for patent foramen ovale closure.

Residual atrial septal defects or patent foramen ovale following prior cardiac surgery for complex congenital heart disease, including Fontan fenestrations, should be closed to treat systemic hypoxemia and to prevent potential paradoxical embolism.[16]

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 performed 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.[17] Closure may also be indicated in divers, for whom a patent foramen ovale represents an increased risk for decompression illness.[15]

Transcatheter closure of a patent foramen ovale is controversial. In the setting of cryptogenic stroke and a patent foramen ovale, nonrandomized data show that transcatheter closure is effective in preventing recurrent strokes.[18]

In the United States, two closure devices, the Amplatzer PFO Occluder (Abbott Cardiac Arrhythmias and Heart Failure, Plymouth, MN)

and the CardioSEAL device (NMT Medical; Boston, MA), were available under a special humanitarian device exemption (HDE) for patent foramen ovale closure; however, the HDE was withdrawn in 2006 because the number of device uses exceeded the 4000/year allowed by the US Food and Drug Administration under the HDE rules. Currently, Amplatzer PFO Occluder (Abbott Cardiac Arrhythmias and Heart Failure, Plymouth, MN) is approved for patent foramen ovale closure in the United States. Outside the United States, several closure devices are available including the Amplatzer PFO Occluder, the StarFlex PFO Occluder (NMT Medical; Boston, MA), the CardioSEAL device, and the Gore Helex Occluders (Gore Medical, Flagstaff, AZ). Transcatheter suture closure[19] and radiofrequency closure[20] are investigational; to date, the results have been disappointing.

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.[10] In patients with atrial septal aneurysm, the risk is somewhat higher at about 5% per year.[10] 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.

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,[21] evidence of nonrandomized trials is sufficient for many to proceed with this approach. The Amplatzer Septal Occluder (AGA Medical Company; Golden Valley, MN), approved for closure of atrial septal defects (see video below), 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.

Transesophageal echocardiogram showing a 10-mm Amplatzer Septal Occluder in place across a patent foramen ovale.

In patients with orthodeoxia-platypnea secondary to a patent foramen ovale, patent foramen ovale closure is curative and normalizes the arterial oxygen saturation.[9]  

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.

Follow-up echocardiography is recommended after surgical closure or placement of a transcatheter device to confirm persistent closure.

 

Medication

Anticoagulants

Class Summary

These agents are used to prevent recurrent or ongoing thromboembolic occlusion. Systemic anticoagulation may be indicated for patients with patent foramen ovale (PFO) and history of stroke or those at a significantly increased risk for paradoxical embolus.

Warfarin (Coumadin)

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.

Antiplatelets

Class Summary

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.

Aspirin (Anacin, Bayer)

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.