Percutaneous device closure for patent foramen ovale

Sam Firoozi and Stephen J Brecker
St Georges Hospital, London

Address for correspondence:
Dr Stephen Brecker MD, FRCP, FACC, FESC
Department of Cardiology, St George's Hospital,
Blackshaw Road, London, SW17 0QT, UK
Tel: +44-(0)20-8725-3556 Fax: +44-(0)20-8725-0211
Email: sbrecker@sgul.ac.uk

Abstract
The patent foramen ovale (PFO) is a very common anatomical variant of the interatrial septum and is associated with a number of paradoxical embolism syndromes including cryptogenic stroke, decompression illness in divers and migraine with visual aura. There is a particularly strong association between cryptogenic stroke and PFO in young individuals and the association is particularly strong in the presence of both a PFO and an atrial septal aneurysm.

Catheter closure of a PFO was introduced in the early 1990s and has developed considerably as a safe and effective treatment, such that surgical closure of a PFO is a near obsolete procedure. With new techniques in imaging, such as intra-cardiac echocardiography, a large proportion of percutaneous PFO closure procedures are carried out as day cases under local anaesthesia.

Perhaps the most challenging aspect in the management of patients with PFO remains the selection of target populations for percutaneous device closure. At present, this is mainly restricted to secondary prevention in young adults with cryptogenic stroke deemed to be at high risk. Ongoing and future randomised controlled trials will help to improve the definition of the role of this procedure.

Background and embryology
Patent foramen ovale (PFO) is an anatomical variant of the interatrial septum which until relatively recently was believed to be of no clinical importance. The PFO provides a communication between the right and left atria. The septum remains patent before birth and closes early in life. This is due to a drop in the rightsided pressures caused by a decrease in pulmonary vascular resistance and an elevation in left atrial pressure due to an increase in pulmonary venous return. Complete anatomical closure is achieved by the age of 2 years in 75% of the population but patency occurs in the other 25% - this is reflected in autopsy series demonstrating an overall prevalence of 27%. The residual communication is a slit-like oblique tunnel. The mechanism why the PFO fails to close remains unknown but is likely to be related to multifactorial inheritance. The prevalence decreases with age (35% and 20% in age groups less than 35 years and greater than 80 years respectively).[1] This may either represent selective mortality of patients with a PFO or late spontaneous closure.

The PFO is the subject of increasing clinical interest as a congenital cardiac lesion and is associated with a number of clinical syndromes including paradoxical embolism (ischaemic stroke, myocardial infarction, peripheral embolism), migraine with visual aura and decompression illness in divers. Although the exact mechanism by which a PFO predisposes to these phenomena remains a subject of debate, it is thought to involve the passage of emboli from the right to the left atrium through the PFO.

PFO anatomy and associations
The size of a PFO can range from pinhole to 20 mm or more. Some studies suggest PFO size increases with each decade of life, perhaps reflecting size-based selection, in which the larger PFOs remain open while smaller defects close. Larger PFO size increases the risk of paradoxical embolism. The heterogeneity of PFO size and anatomy are pertinent to interventional device closure selection.

Atrial septal aneurysms
A common association of the PFO is an atrial septal aneurysm (ASA), where part of the atrial septum exhibits aneurysmal dilatation and protrudes into either atrium due to exaggerated septal excursion. ASA is more common in individuals with a PFO and ASA is frequently associated with a PFO. There appears to be a strong association between the risk of cryptogenic stroke in the younger population and the combination of a PFO and an ASA.[2,3]

Chiari networks
These are a remnant of the right valve of the sinus venosus and their role is poorly understood. There is an association between Chiari networks and PFO and ASA. Large right-to-left shunting is seen more commonly in individuals with Chiari networks and they are associated with patients with cryptogenic stroke and may facilitate paradoxical embolism.

PFO and its clinical significance in cryptogenic stroke
There is considerable evidence supporting an association between a PFO and ischaemic stroke, particularly in those with cryptogenic stroke. The association is particularly strong in the presence of both a PFO and an ASA in young patients. Paradoxical embolism through the PFO is postulated to be the primary mechanism and certain findings support this hypothesis:

• These include right-to-left shunting demonstrated with normal atrial pressures in Valsalva manoeuvres, during coughing, during mechanical ventilation and with increased right atrial pressures.[4,5] Stroke patients have higher rates of PFO patency at rest without any induction manoeuvres.[6]
• Deep vein thrombosis is detected only in a small percentage of patients with cryptogenic stroke, but this prevalence is definitely higher when compared to controls with stroke of determined origin or no stroke.[7]
• Size of the PFO and the amount of shunting had a direct correlation with the prevalence of cryptogenic stroke as opposed to stroke with determined causes or normal controls.[8,9]

Other postulated mechanisms for stroke include in-situ thrombus formation due to stasis of blood in the PFO canal.

Although these findings are consistent with a causal relationship, they do not prove it. Non-randomised studies of PFO closure do suggest a reduction in recurrent stroke risk, which would support a causal role for PFO in stroke pathogenesis. However, these data are open to selection bias and only randomised trials comparing closure with medical therapy will clarify whether PFO closure really can prevent stroke.

PFO and its clinical significance in migraine
Studies have shown an association between PFO with migraine with visual aura and retrospective analyses in patients where a PFO was closed have shown a significant improvement and resolution of migraine symptoms.[10-13] PFO may have played a key role in the transport of small paradoxical emboli to the vertebrobasilar system and was associated with increased levels of vasoactive chemicals reaching the cerebral circulation through bypass of the pulmonary circulation. In 2006, the MIST study (Migraine Intervention with STARFlex Technology trial) reported a 42% incidence of a 50% reduction in headache days when comparing patients with device closure before and after PFO closure.[14,15]

PFO and diving/decompression illness
The mechanism postulated in decompression illness in divers involves formation of nitrogen bubbles in the venous circulation, which bypass the lungs by traversing a PFO. The possibility of a link between neurological decompression illness and PFO was suggested in the late 1980s[16,17]. Studies have confirmed an increased prevalence of a PFO at rest among divers reporting decompression illness compared to controls. Other studies have confirmed a relationship between particular types of decompression illness and PFO size as well as atrial septal mobility.[18]

PFO detection
The initial screening is carried out using transthoracic echocardiography (TTE) with colour Doppler and agitated saline contrast and with the use of the Valsalva manoeuvre. The apical 4-chamber view and the subcostal views are best suited to the visualisation of contrast in the right heart (Figure 1). The presence of contrast bubbles in the left atrium within 3 cardiac cycles indicates an intracardiac shunt whereas contrast appearance in the left heart after 3 cardiac cycles is suggestive of an intrapulmonary shunt[19]. Transoesophageal echocardiography (TOE) is advised for all borderline cases and in cases where clinical suspicion remains high despite a normal TTE result (Figure 2). Mild shunting corresponds to less than 5 bubbles, moderate shunting to 5 to 25 bubbles, while greater than 25 bubbles corresponds to a large shunt. A TOE examination is also indicated to characterise the precise nature of the shunt (i.e. atrial septal defect versus PFO) in positive cases.


PFO closure in cryptogenic stroke
Due to the lack of large randomised trials comparing medical therapy with surgical and percutaneous closure, the treatment of patients with PFO and cryptogenic stroke remains controversial. Studies have shown aspirin to be effective in treating patients with isolated PFO and cryptogenic stroke but with a high recurrence rate in patients with PFO and ASA[2]. Other studies comparing aspirin versus warfarin therapy in patients with PFO and cryptogenic stroke have reported mixed findings. These studies are generally affected by limitations such as inadequate sample size, inadequate follow-up and a lack of homogeneity among control groups making comparisons between studies difficult. Other studies have suggested that anticoagulation with warfarin may be more effective than antiplatelet agents such as aspirin, as secondary stroke prevention in patients with PFO and ASA. A meta-analysis of the limited data available published in 2001 reported a reduced risk with warfarin therapy.[20] However, most of the data available are from uncontrolled and non-randomised studies. The only randomised study is from the Patent Foramen Ovale in Cryptogenic Stroke (PICSS) study cohort of the larger WARSS (Warfarin-Aspirin Recurrent Stroke) study which was double blind. Among patients with any stroke subtype and PFO, there was no difference in the recurrent stroke rate between treatment with warfarin or aspirin. In the cryptogenic cohort with PFO, there was a marked trend towards a reduction in recurrent stroke rate among warfarin-treated patients but this did not meet statistical significance[21]. Data from further randomised trials will be required to resolve this question.

The most convincing evidence for causality of PFO in stroke would be if PFO closure abolished the risk of stroke recurrence. Currently there are no randomised trial data available but such trials are in progress and will take a number of years to report their results. The only data currently available are from uncontrolled non-randomised studies, which are prone to selection and reporting bias and extreme caution should be taken when interpreting their results.

Catheter closure of PFO was first reported in 1992 and since then devices specifically designed for PFO closure have been developed and the procedure has become widely available. Increasing numbers of uncontrolled series have been reported with successful procedural outcomes, low complication rates and low event recurrence rates at follow-up.

Percutaneous PFO closure technique
The procedure can be carried out under either general or local anaesthesia depending on the modality of intra-procedural echocardiographic imaging. In cases where TOE imaging is planned, the procedure is carried out under general anaesthesia, whereas in cases where intracardiac echocardiography (ICE) is planned, the patient is conscious and the procedure is carried out under local anaesthesia. Because of the size of the catheters used to deliver devices and the need for anticoagulation with heparin and treatment with antiplatelet drugs, a key tip is that operators should go to significant lengths to avoid femoral access site complications.

Clean entry into the femoral vein, with the possible requirement of multiple sheaths, is important and post-procedure femoral access site management is as important as with other interventional procedures. A multipurpose catheter is then passed through the PFO. This is usually undertaken quite easily by orientating the catheter to the left and applying some clockwise posterior torque whilst drawing the catheter down the septum and "probing". The catheter should be passed into the right upper pulmonary vein and an angiogram can be performed profiling the atrial septum using a 4-chamber view (left anterior oblique with cranial angulation).

The catheter should be monitored both on fluoroscopy and with ultrasound guidance (TOE or ICE) to determine the site of passage across the septum. The catheter should then be advanced into the left upper pulmonary vein and an exchange length 0.035 inch guide wire can be passed into the left upper pulmonary vein. With the guide wire in place, the next step will be placement of the delivery catheter over the wire. A number of PFO occluder devices have been developed and used in clinical practice including the Amplatzer®, CardioSEAL®, STARFlex®, Helex®, Premere™, Intrasept™ and Coherex FlatStent™.

Typical deployment of an Amplatzer septal occluder
In the typical deployment of an Amplatzer septal occluder (Figure 3), an appropriately sized delivery sheath should be selected, flushed, de-aired and advanced over the wire across the atrial septum. Once in position, the guide wire and dilator should be withdrawn. This should be done slowly with the hub of the catheter positioned as low as possible or in a bowl of saline. These methods will avoid air being sucked into the system. The device should be mounted onto the loading cable, and this is performed by aligning the screw on the loading cable to the hub on the device.

Figure 3. Amplatzer® PFO occluder device. Images copyright AGA Medical Corporation.

Once the attachment has been tested and confirmed as secure, the device should be turned back one quarter turn to ease the device release. The device is then pulled into the short loading sheath and the entire system should be thoroughly flushed several times. The loading sheath, together with the device and loading cable, can then be taken to the patient and the loader pushed through the haemostatic valve on the delivery sheath. The O-ring securing the loading cable is loosened and the device is pushed through the short loading sheath into the long delivery sheath and up into the catheter under fluoroscopy.

The device is visualised at the distal tip of the sheath. At this point, the distal end of the delivery sheath should be sitting freely within the left atrium. The left atrial disc is then pushed out under fluoroscopic and echocardiographic guidance. Once the left atrial disc has conformed, the whole system can be pulled back against the interatrial septum. While maintaining tension, the delivery sheath is then withdrawn which releases the right atrial disc. The device can then be pushed gently to secure its position and it should then be sitting in a satisfactory position occluding the atrial septal defect with secure rims.

Figure 4. Fluoroscopy image demonstrating a deployed Amplatzer® PFO occluder device. Image is courtesy of Dr Stephen Brecker.

The position of the device should be checked using both fluoroscopy (Figure 4) and echocardiography (TOE or ICE). With ultrasound imaging, colour flow should ensure that there is no flow adjacent to the device or through any separate defect. Some flow into the device can be expected as the device will allow blood into it and through it until it is fully endothelialised. The stability of the device should be tested by gentle pulling and pushing of the loading cable. The cable should be pushed gently but firmly enough to see it form a small curve within the right atrium while it should be pulled gently but firmly enough just to separate the discs. Once the operator is satisfied with the position, the deployment of the device can be released by applying anti-clockwise rotations to the loading cable. It is necessary to turn and then to pinch the cable in order for the torque to be transmitted to the tip. After release, there is very often a degree of movement of the device as it correctly aligns to the septum. This movement indicates that there was a degree of tension on the loading cable.

Patient selection for percutaneous PFO closure
Perhaps the most challenging aspect in managing patients with PFO is the identification of a target population where percutaneous closure would be most beneficial. At present, this is mainly restricted to secondary stroke prevention in young adults with cryptogenic stroke, especially those with high risk anatomy (i.e. PFO and ASA).

Other indications would include:

• Divers with a history of decompression illness who wish to continue to dive (e.g. professional divers).
• Patients with previous major peripheral arterial embolisation.
• Patients with severe recurrent and frequent migraine with visual aura, on a compassionate or clinical trial basis.

Future role for the procedure
Multiple novel and exciting technologies are emerging for treating PFO percutaneously promising rapid, safe and effective PFO treatment. Large ongoing randomised controlled trials will help confirm cause and effect relationships between PFO and clinical conditions such as stroke, migraine and headache and also help confirm the benefit of this procedure in specific patient populations.


References

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01-2009 BUY1163892/JB3484/CMC 17th edition

 

Source: C2I2, Volume VI, Issue 2, 2008

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