Patent Foramen Ovale 

Updated: Dec 17, 2017
Author: Sandy N Shah, DO, MBA, FACC, FACP, FACOI; Chief Editor: Yasmine S Ali, MD, FACC, FACP, MSCI 

Overview

Practice Essentials

Patent foramen ovale (PFO) is a flaplike opening between the atrial septa primum and secundum at the location of the fossa ovalis (see the image below) that persists after age 1 year. With increasing evidence being found that PFO is the culprit in paradoxical embolic events, the relative importance of the anomaly is being reevaluated.

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

Signs and symptoms

Most patients with isolated PFO are asymptomatic. When they do occur, signs and symptoms can include the following:

  • History of stroke or transient ischemic event of undefined etiology

  • Migraine or migraine-like symptoms - Whether symptoms are due to transient ischemic attacks or paradoxical embolism is not clear

  • Neurologic decompression sickness - Seen with PFO in a small percent of scuba divers

Other, less common clinical manifestations of PFO include the following:

  • Acute myocardial infarction[1, 2]

  • Systemic embolism, such as renal infarction[3]

  • Fat embolism[4]

  • Paradoxical embolism caused by right atrial tumors that increase right atrial pressure[2]

  • Left-sided valve disease in carcinoid syndrome[5]

See Clinical Presentation for more detail.

Diagnosis

The following types of echocardiography can be used in the detection of PFO:

  • Color flow Doppler imaging - A small "flame" of color signal may be seen in the middle region of the atrial septum

  • Contrast echocardiography - Usually required to detect a small PFO

  • Two-dimensional transesophageal echocardiography (2-D TEE) with contrast - Provides superior visualization of the atrial septum

  • Three-dimensional transesophageal echocardiography (3-D TEE) - Provides direct visualization of the entire PFO anatomy and surrounding structures[6]

  • Transmitral Doppler (TMD) echocardiography - In current practice, the role of TMD is uncertain due to limited experience with this modality[7]

  • Transcranial Doppler (TCD) - An alternative to TEE; however, although it can detect a right-to-left shunt, it cannot show the shunt’s location[8]

See Workup for more detail.

Management

Most patients with a patent foramen ovale (PFO) as an isolated finding receive no special treatment. No consensus exists on the treatment of PFO in patients with transient ischemic attack or stroke.

When PFO is associated with an otherwise unexplained neurologic event,[9] traditional treatment has been antiplatelet (ie, aspirin) therapy alone in low-risk patients or such therapy combined with the use of warfarin in high-risk individuals, to prevent cryptogenic stroke.

Surgery

Surgical closure of PFO with double continuous suture has resulted in elimination of residual shunt across the PFO.

Indications for surgical closure include the following:

  • PFO of more than 25 mm in size

  • Inadequate rim of tissue around the defect

  • Percutaneous device failure

Percutaneous closure

Percutaneous closure of PFO during cardiac catheterization is another, less-invasive therapeutic option. Indications for its use include the following:

  • Recurrent cryptogenic stroke due to presumed paradoxical embolism (resulting from PFO failure of conventional drug therapy)

  • Contraindications to anticoagulant treatment

  • Alternative to medical therapy or surgical closure - Cryptogenic transient ischemic attack due to presumed paradoxical embolism through a PFO

  • Presumed paradoxical peripheral or coronary embolism through a PFO

  • Cryptogenic stroke, transient ischemic attack, or peripheral or coronary embolism due to presumed paradoxical embolism (through a PFO that is associated with a hypercoagulability state)

See Treatment and Medication for more detail.

Background

Patent foramen ovale (PFO) is an anatomical interatrial communication with potential for right-to-left shunt. Foramen ovale has been known since the time of Galen. In 1564, Leonardi Botali, an Italian surgeon, was the first to describe the presence of foramen ovale at birth. However, the function of foramen ovale in utero was not known at that time. In 1877, Cohnheim described paradoxical embolism in relation to PFO.

See also the Medscape Drugs & Disease articles Atrial Septal Defect and Pediatric Atrial Septal Defects.

Pathophysiology

Patent foramen ovale (PFO) is a flaplike opening between the atrial septa primum and secundum at the location of the fossa ovalis that persists after age 1 year. In utero, the foramen ovale serves as a physiologic conduit for right-to-left shunting. Once the pulmonary circulation is established after birth, left atrial pressure increases, allowing functional closure of the foramen ovale. This is followed by anatomical closure of the septum primum and septum secundum by the age of 1 year.

The Mayo Clinic autopsy study revealed that the size of a PFO increases from a mean of 3.4 mm in the first decade to 5.8 mm in the 10th decade of life, as the valve of fossa ovalis stretches with age.[10]

With increasing evidence that PFO is the culprit in paradoxical embolic events, the relative importance of the anomaly is being reevaluated. James Lock, MD, postulated that PFO anatomy results in a cul-de-sac between the septa primum and secundum, predisposing individuals to hemostasis and clot formation. Any conditions that increase right atrial pressure more than left atrial pressure can induce paradoxical flow and may result in an embolic event.

This reasoning has greatly altered the previous conception of PFO and is changing current management of the condition.

Epidemiology

United States statistics

Patent foramen ovale (PFO) is detected in 10-15% of the population by contrast transthoracic echocardiography. Autopsy studies show a 27% prevalence of probe-patent foramen ovale.[10]  This difference is probably due to the ability to directly visualize PFO on autopsy study, while contrast echocardiography relies on detection of secondary physiologic phenomena.

Sex- and age-related demographics

The prevalence and size of probe-patent PFO is similar in males and females.

The prevalence of PFO declines progressively with age—34% up to age 30 years, 25% for age 30-80 years, and 20% older than 80 years.

 

Presentation

History and Physical Examination

Most patients with isolated patent foramen ovale (PFO) are asymptomatic. Patients may have a history of stroke or transient ischemic event of undefined etiology.[11]

Some present with migraine or migrainelike symptoms. Whether symptoms are due to transient ischemic attacks or paradoxical embolism is not clear.

Neurologic decompression sickness is seen with PFO in a small percent of scuba divers. Risk of nitrogen gas embolism across PFO increases in scuba divers. In unexperienced divers, PFO can worsen hypoxemia at great depth leading to death.

Other less common clinical manifestations of PFO include the following:

  • Acute myocardial infarction[1, 2]

  • Systemic embolism, such as renal infarction[3]

  • Fat embolism[4]

  • Right atrial tumors increase right atrial pressure, which can cause paradoxical embolism[2]

  • Left-sided valve disease in carcinoid syndrome[5]

No abnormal cardiac clinical findings are associated with isolated PFO.

 

DDx

Diagnostic Considerations

Other considerations in patient with suspected patent foramen ovale (PFO) include the following:

  • Obstructive sleep apnea

  • Cardiac surgery

  • Hypoxemia increases in PFO due to transient elevation of right atrial pressure with an increase in right-to-left shunt resulting in systemic arterial desaturation.

  • In off-pump coronary artery bypass surgery, PFO increases the risk of postoperative atrial fibrillation and hypoxemia.

PFO is often associated with other cardiac anomalies, such as the following:

  • Atrial septal aneurysm: A redundant and mobile interatrial tissue in fossa ovalis that has phasic excursion of 10-15 mm during cardiorespiratory cycle.

  • Eustachian valve: Eustachian valve is located at junction of inferior vena cava and right atrium.

  • Chiari network: A fenestrated mobile structure consists of a network of threads and fibers in the right atrium that originate from the region of the Eustachian and thebesian valve at the orifice of inferior vena cava with attachments to upper wall of right atrium or atrial septum.

  • In a study by Schneider, 1436 consecutive patients were referred for TEE. A Chiari network was found in 29 subjects (2%), 24 (83%) had PFO, and 7 (24%) had an atrial septal aneurysm.[12]

  • Atrial septal defect: In a study of 103 patients by Khositseth who were referred for transcatheter closure for a paradoxical embolism, PFO was present in 81 subjects , ASD in 12 subjects, and both PFO and ASD in 10 subjects.[13]

  • Ebstein anomaly: In a study by Attenhofer of 106 patients, 79% had either persistent or previously closed PFO or atrial septal defect.[14]

 

Workup

Approach Considerations

No specific laboratory tests are necessary to diagnose patent foramen ovale (PFO), and no specific electrocardiographic findings are noted in affected patients

Imaging Studies

Echocardiography

In some instances, patent foramen ovale (PFO) is detectable with color flow Doppler imaging. A small "flame" of color signal may be seen in the middle region of the atrial septum.

Contrast echocardiography is usually required to detect small PFO. After obtaining optimal visualization of the atrial septum on transthoracic or transesophageal echocardiography, a bolus of agitated saline is injected into an antecubital vein. Subsequently, microbubbles appear in the right atrium. The study is positive for PFO if the microbubbles appear in the left atrium within 3 cardiac cycles of their appearance in the right atrium. Valsalva maneuver increases right atrial pressure and facilitates right-to-left shunting.

Two-dimensional transesophageal echocardiography (2D TEE) with contrast provides superior visualization of the atrial septum and therefore is preferred to transthoracic contrast echocardiography for detecting PFO. When clinically indicated, 2D TEE with contrast is strongly recommended for patients whose findings on transthoracic echocardiography are negative.

A 3-dimensional transesophageal echocardiography (3D TEE) provides direct visualization of the entire PFO anatomy and surrounding structures. It allows more accurate diagnosis of PFO by direct visualization of the bubbles crossing fossa ovalis.[6]

A small study evaluated transmitral Doppler (TMD) echocardiography with agitated saline contrast in 44 patients. The sensitivity and specificity of TMD were 100% and 96% when compared with TEE. Greater than 10 bubbles on a single beat of resting-contrast TMD correlated with a maximum resting TEE PFO opening diameter greater than 2 mm with 78% sensitivity and 100% specificity. In current practice, role of TMD is uncertain due to limited experience.[7]

Transcranial Doppler (TCD) is an alternative to TEE. TCD is a noninvasive test that can be easily performed at the bedside. However, it can only detect right-to-left shunt, not the location of the shunt.[8]

TCD and TEE are comparable for detection of right-to-left shunts. However, TEE is a better test because it provides anatomic information about the site and size of shunt. It also helps to detect presence of other causes of stroke such as intracardiac mass, atrial septal aneurysm, infective endocarditis, and aortic atherosclerosis.[15]

In an evaluation of 2680 patients with cryptogenic stroke, researchers found that strokes with certain radiologic characteristics were more likely to be associated with PFO. In the study, the investigators determined that strokes that were small, deep, or not apparent on radiologic imaging were less likely to be associated with PFO than were large, superficial, or radiologically apparent strokes. An association was also found between PFO and strokes that had no relation to previous radiologic infarcts.[16]

 

Treatment

Medical Care

Most patients with a patent foramen ovale (PFO) as an isolated finding receive no special treatment. No consensus exists on treatment of PFO in patients with transient ischemic attack (TIA) or stroke.

When PFO is associated with an otherwise unexplained neurologic event, traditional treatment has been antiplatelet (ie, aspirin) therapy alone in low-risk patients or combined with warfarin in high-risk individuals to prevent cryptogenic stroke.[9, 17] With administration of warfarin, the international normalized ratio (INR) is maintained at 2-3. Consultation with a neurologist is mandatory to direct this treatment.

The recurrence rate of stroke or TIA has been reported to be as high as 3.4-3.9% per year.

In patients with atrial septal aneurysm and PFO, the risk of first recurrent stroke within 2 years has been reported to be as high as 9%, whereas the rate of subsequent stroke or TIA recurrence within 2 years increases to 22%.

In a study that evaluated the antiplatelet effects of clopidogrel and aspirin in 140 patients who underwent interventional PFO/atrial septal defect (ASD) closure, Polzin et al reported a 71% incidence of high on-treatment platelet reactivity (HTPR) to clopidogrel but only a 4% HTPR for aspirin.[18] Of the 12 complications noted, 9 were bleeding events (including 3 major bleeding events) and the remaining 3 were TIAs. The investigators noted that despite the high incidence of HTPR to clopidogrel in this patient population, there were no reports of stroke or thrombus formation on the occluder.[18]

 

Surgical Care

Surgical closure

Surgical closure of patent foramen ovale (PFO) with double continuous suture has resulted in elimination of residual shunt across the PFO.

Indications include the following:

  • PFO more than 25 mm in size

  • Inadequate rim of tissue around the defect

  • Percutaneous device failure

Advantages include the following:

  • Permanent closure of the defect

  • Prevents future paradoxical emboli

  • No long-term anticoagulation and its risks

Disadvantages include the following:

  • General anesthesia

  • Open-heart surgery

  • Hospital stay for a few days

  • The usual risks of cardiac surgery

Percutaneous care

Percutaneous closure of PFO during cardiac catheterization is an emerging therapeutic option.

Indications

  • Recurrent cryptogenic stroke due to presumed paradoxical embolism through PFO failure of conventional drug therapy

  • Contraindications to anticoagulant treatment

  • Alternative to medical therapy or surgical closure - Cryptogenic transient ischemic attack (TIA) due to presumed paradoxical embolism through a PFO

  • Presumed paradoxical peripheral or coronary embolism through PFO

  • Cryptogenic stroke, TIA, or peripheral or coronary embolism due to presumed paradoxical embolism through a PFO that is associated with hypercoagulability state, [19] such as (1) divers with a PFO who are at risk of clinical events that are related to paradoxical embolism through a PFO during decompression, (2) those with systemic deoxygenation due to right-to-left shunting through a PFO in the absence of severe pulmonary hypertension (eg, platypnea orthodeoxia, right ventricular infarction), (3) those with migraine headache accompanied by aura, and (4) those with posttraumatic fat embolism syndrome with cerebral embolism by way of PFO.

Long-term follow-up (40.2 ± 11.0 y) in 301 patients who underwent percutaneous PFO closure following cryptogenic stroke or TIA demonstrated the procedure to be safe and effective, with a low incidence of procedural complications and recurrent neurovascular events.[19]

The Federal Drug Administration (FDA) has approved 2 percutaneous devices for PFO closure. The CardioSEAL Septal Occlusion System is a double umbrella-shaped permanent implant. It is made up of metal framework to which polyester fabric is attached. The CardioSEAL implant is available in sizes 17 mm, 23 mm, 28 mm, and 33 mm.

The Amplatzer PFO Occluder is a self-expanding wire mesh with double discs. It contains inner polyester fabric patches that, along with the wire mesh, cause the formation and accumulation of a blood clot, which seals the opening. After the device is in place, tissue will grow over it, and the device then becomes a part of the atrial septum.

The procedure requires a hospital stay of 24-48 hours and prophylactic aspirin or warfarin for 6 months following the procedure. After more than 5 years of follow-up observation, the results are promising.

Although hypertrophy and lipomatosis of the interatrial septum have been considered contraindications for transcatheter PFO closures, a study by Rigatelli et al suggests that this is not always the case.[20] The authors investigated outcomes in 10 patients with PFO who, owing to multiple recurrent stroke events (9 patients) or to the need for a posterior cerebral operation (1 patient), underwent transcatheter PFO closure, despite the presence of hypertrophy or lipomatosis of the rim of the fossa ovalis.

Following intracardiac echocardiography assessment and measurements, a 25-mm Amplatzer device was implanted in 2 patients in the Rigatelli study, and a 25-mm Premere Occlusion System device was implanted in 8 patients. On mean follow-up (36.6 months), 2 patients were found to have a small residual shunt. During this period, however, none of the patients experienced stroke recurrence, aortic erosion, or device thrombosis. The investigators concluded that in patients with hypertrophy or lipomatosis of the fossa ovalis rim, safe and effective PFO closure may be attainable, at least in the absence of severe atrial septal aneurysm, if rim thickness is carefully evaluated with intracardiac echocardiography, and if soft and asymmetrical opening devices are used.

Midterm results of interventional closure of patent foramen ovale with the third-generation Occlutech Figulla Flex II Occluder in patients who suffered from cryptogenic stroke, TIA, or paradoxical peripheral embolism appear to show the device and its delivery system to be safe.[21] Of 57 patients who had suffered from a thromboembolic event of unknown cause and underwent transcatheter PFO closure with the device, over 94% had sufficient closure without residual right-to-left shunt at 6 months follow-up and 3 patients had only minimal residual shunt. There were no major periprocedural or inpatient complications, nor any thrombotic formations related to the device, although one patient each had atrial fibrillation or a recurrent cerebral ischemic event (TIA).[21]

In a single-center study of 201 patients who underwent transcatheter  closure of interatrial communications (IAC) using the Cera and the CeraFlex Occluder, occlusion was successful in 183 patients (94.3%), with no reports of death, embolization, or major complications.[22] Although immediate postimplantation occurrence of small residual shunts was noted in 8 patients, these resolved after 3 months. 

Complications

Complications of catheter-based closure of patent foramen ovale (PFO), such as embolism of device, device entrapment within the Chiari network, frame fracture, vessel damage, or perforation of atrial wall, may require further surgery. Other possible complications include air embolism during device delivery, thrombus formation around the device, and infective endocarditis.

 

Medication

Medication Summary

Most patients with a patent foramen ovale as an isolated finding receive no particular treatment.

Anticoagulants

Class Summary

Antiplatelet therapy and anticoagulation with warfarin can be indicated to prevent recurrent systemic thromboembolism.

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 to 3.