The foramen ovale is vital for fetal circulation, when blood returning to the right atrium is shunted through to the left atrium. Postnatally the foramen ovale closes spontaneously in most people, but patent foramen ovale (PFO) occurs in about 25% of the population.1
Most people with PFO are asymptomatic. But an atrial septal aneurysm may open the PFO with every heartbeat, thereby increasing the possibility for thrombus to pass from the venous to arterial system, which can cause stroke.2
STROKES IN THE U.S.5
400,000 CRYPTOGENIC STROKES
AND TRANSIENT ISCHEMIC ATTACKS (TIAs)
IN WESTERN EUROPE ALONE4
Nearly 50% of patients with
cryptogenic stroke have a PFO2
Moreover, patients with PFO and a prior cryptogenic ischemic stroke are at risk for recurrent stroke6—a 20.4% rate of a recurrent embolic event at 2 years7
The dilemma of whether to percutaneously close PFOs in selected patients in order to reduce the risk of recurrent embolism has been a matter of ongoing debate for more than a decade.
But now the long-term data from the RESPECT trial,8 as well as data from the CLOSE and REDUCE trials,9,10 have clariﬁed the issue. These studies have revealed that with attentive patient selection, transcatheter PFO closure signiﬁcantly reduces the risk of recurrent stroke compared with medical therapy in patients with cryptogenic stroke—with no increased risk of serious adverse events or inﬂuence on major bleeding.2
American Heart Association/American Stroke Association – Guideline for the Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack11 - 2021
Recommendation: In patients 18 to 60 years of age with a non-lacunar ischemic stroke of undetermined cause, despite a thorough evaluation and a PFO with high-risk anatomic features, it is reasonable to choose closure with a transcatheter device and long-term antiplatelet therapy over antiplatelet therapy alone for preventing recurrent stroke. (Recommendation level 2b, level of evidence B-R).
American Academy of Neurology – Practice Advisory Patent Foramen Ovale and Secondary Stroke Prevention12 – 2020
Recommendation: In patients younger than 60 years with a PFO and an embolic-appearing infarct and no other mechanism of stroke identified, clinicians may recommend closure following a discussion of potential benefits (reduction of stroke recurrence) and risks (procedural complication and atrial fibrillation) (Level C).
Asian-Pacific Consensus Statement13 - 2020
With most of the evidence on PFO closure being obtained from Caucasian patients, a consensus statement was developed by Asian-Pacific clinical experts, accounting for the specific stroke and bleeding characteristics of Asian-Pacific patients and the specific Asian-Pacific context.
Key aspects of this consensus statement include:
- Regarding indications for PFO closure, follow international/global guidelines.
- Ensure that patients with recent embolic stroke of undetermined source (ESUS) are screened for PFO, using imaging modalities that are readily available in the hospital and on which the staff is best trained and most experienced (e.g. TTE, contrast TCD, TEE, ICE). Contrast TCD is widely available in the Asian-Pacific region and may be used as a first screening tool, followed by confirmation using TEE or TTE with bubble contrast.
- ESUS patients with significant PFO should undergo PFO closure as early as possible.
It was emphasized that clinical evidence for the above aspects should be collected among Asian-Pacific patients.
Japanese Guidance Document14 – 2019
The Japan Stroke Society, The Japanese Circulation Society and Japanese Association of Cardiovascular Intervention and Therapeutics came together to review the evidence on PFO closure and recommend the following when it comes to selecting the appropriate patient for PFO closure:
Indication criteria for percutaneous closure of PFO for the purpose of stroke recurrence prevention:
- Indispensable condition: Implementation of the intervention will be considered in case of satisfaction of all items described below:
- Patients who meet the diagnosis criteria for PFO related cryptogenic stroke
- Patients in whom antithrombotic therapy can be conducted during a certain period after percutaneous closure implementation
- Patients with <60 years of age in principle
- Female patients who are not pregnant or do not want to become pregnant within a year
- Recommendation condition: Implementation of the intervention will be recommended in case of satisfaction of all aforementioned items and any items described below:
- The presence of high risk PFO in terms of function/anatomy such as:
- Large volume of shunt
- Concomitant atrial septal aneurysm (ASA)
- Concomitant Eustachian valve (EV)
- Concomitant Chiari network
- Right-left shunt found at rest (without Valsalva maneuver)
- Onset of the aforementioned type of cryptogenic stroke during appropriately conducted antithrombotic therapy.
- The presence of high risk PFO in terms of function/anatomy such as:
German Guidelines – Cryptogenic Stroke and Patent Foramen Ovale15 – 2018
Interventional PFO closure should be performed in patients aged 16 to 60 years (after extensive neurological and cardiological diagnostic work-up) with a history of cryptogenic ischaemic stroke and patent foramen ovale, with moderate or extensive right-to-left shunt. Recommendation level A, Evidence level I.
BMJ Rapid Recommendation16 – 2018
Among patients younger than age 60 who have had a cryptogenic ischemic stroke thought to be secondary to PFO (due to absence of other etiologies):
- Strong recommendation—among patients in whom anticoagulation is contraindicated or declined—to provide PFO closure + antiplatelet therapy, vs antiplatelet therapy alone
- Weak recommendation—among patients who are open to all options—to provide PFO closure + antiplatelet therapy vs anticoagulant therapy
- Weak recommendation—among patients in whom closure is contraindicated or declined—to provide anticoagulant therapy vs antiplatelet therapy
European Position Paper17 – 2018
Among patients age 18-65 who have had a cryptogenic ischemic stroke cryptogenic stroke, TIA, or systemic embolism thought to be secondary to PFO due to absence of other etiologies:
- Recommend percutaneous PFO closure
Canadian Guidelines18 – 2017
For carefully-selected patients with a recent ischemic stroke or TIA attributed to a PFO, PFO device closure plus long-term antiplatelet therapy is recommended over long-term antithrombotic therapy alone, provided all the following criteria are met: [Evidence Level A]:
- Age 18–60 years;
- The diagnosis of the index stroke event is confirmed by imaging as a nonlacunar embolic ischemic stroke or a TIA with positive neuroimaging or cortical symptoms;
- The patient has been evaluated by a neurologist or clinician with stroke expertise, and the PFO is felt to be the most likely cause for the index stroke event following a thorough etiological evaluation to exclude alternate etiologies.
There are challenges in determining causation and treatment for cryptogenic stroke. Yet nearly half of patients with cryptogenic stroke have PFO.2 Neurologists and other referring physicians, who represent the primary point of care for recurrent stroke prevention, may consider these factors in treatment planning:
IS THE STROKE CRYPTOGENIC?
Rule out known causes
Is the patient eligible for alternative therapy?
Consider age and medical history
Is there a possibility of PFO?
Determine the likelihood of paradoxical embolism
A cardiologist can then determine if the patient has a PFO and can help determine treatment options.
Characteristics that are strongly associated with a causal role of PFO in cryptogenic stroke are:17
- Atrial septal aneurysm and/or a moderate-to-severe shunt
- Atrial septal hypermobility
- PFO size
The presence of other risk factors does not exclude PFO as the causative factor, but PFO is more likely when patients are young and lack other risk factors. Determining whether a patient’s stroke is related to a PFO should involve a multidisciplinary team including a neurologist, a cardiologist, and other health professionals trained in the care of patients with stroke.2
It is important to identify whether atrial fibrillation is present, since recurrences of left circulation embolism are often due to LAA thrombosis. In certain patients at high risk for atrial fibrillation, insertable cardiac monitor use for 6 months can reasonably rule out LAA involvement before proceeding with PFO closure.16
The RESPECT trial was conducted at 69 centers across the U.S. and Canada. Alone among PFO closure studies, RESPECT included patients on anticoagulation therapy, providing a real-world cross section of patients. This trial has the most extensive follow-up data among all PFO closure studies; it spanned 13 years overall with 5,810 patient years of safety follow-up. The RESPECT trial also revealed low rates of serious atrial fibrillation with the closure device, consistent with medical therapy.
Practitioners are anticipating updated guidelines about device closure and medical therapy for cryptogenic stroke caused by PFO. From the perspective of Mojadidi et al., the relative safety and simplicity of percutaneous PFO closure and the proven protection against stroke open an avenue of further indications for PFO closure.2
The information provided is not intended for medical diagnosis or treatment as a substitute for professional advice. Consult with a physician or qualified healthcare provider for appropriate medical advices.
MAT-2005253 v3.0 | Item approved for U.S. use only
- Homma S, Sacco R. Patent foramen ovale and stroke. Circulation. 2005;112:1063-1072. doi: 10.1161/CIRCULATIONAHA.104.524371.
- Mojadidi MK, Zaman MO, Elgendy IY, et. al. Cryptogenic stroke and patent foramen ovale. J Am Coll Cardiol. 2018;71(9):1035-1043. doi: 10.1016/j.jacc.2017.12.059.
- Shah R, Nayyar M, Jovin IS, et. al. Device closure versus medical therapy alone for patent foramen ovale in patients with cryptogenic stroke. Ann Intern Med. 2018;168:335-342. doi:10.7326/M17-2679.
- Li L, Yiin GS, Geraghty OC, et. al. Incidence, outcome, risk factors, and long-term prognosis of cryptogenic transient ischaemic attack and ischaemic stroke: a population-based study. Lancet Neurol. 2015;14:903–913. doi.org/10.1016/S1474-4422(15)00132-5.
- American Heart Association/American Stroke Association. Understanding Diagnosis and Treatment of Cryptogenic Stroke. 2015.
- Kernan WN, Ovbiagele B, Black HR, et. al. AHA/ASA guidelines for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke. 2014;45:2160-2236.
- Homma S, Sacco RL, Di Tullio MR, et. al. Effect of medical treatment in stroke patients with patent foramen ovale: Patent foramen ovale In Cryptogenic Stroke Study (PICSS). Circulation. 2002;105:2625-2631. doi: 10.1161/01.CIR.0000017498.88393.44.
- Saver JL, Carroll JD, Thaler DE, et.al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. 2017;377:1022-1032. doi: 10.1056/NEJMoa1610057.
- Mas J-L, Derumeaux G, Guillon B, et.al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377:1011-1021 and supplementary appendix. doi: 10.1056/NEJMoa1705915.
- Søndergaard L, Kasner SE, Rhodes JF, et. al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017;377:1033-1042. doi: 10.1056/NEJMoa1707404.
- Kleindorfer, D. et al, 2021 Guideline for the Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack. A Guideline from the American Heart Association/American Stroke Association. Stroke. 2021;52:00–00. DOI: 10.1161/STR.0000000000000375.
- Messé SR, Gronseth GS, Kent DM, et al. Practice Advisory Update: Patent Foramen Ovale and Secondary Stroke Prevention. Neurology® 2020;94:1-10.
- Diener HC, Akagi T, Durongpisitkul K, et al. Closure of the patent foramen ovale in patients with embolic stroke of undetermined source: A clinical expert opinion and consensus statement for the Asian-Pacific region. Int J Stroke. 2020;0(0):1–8.
- The Japan Stroke Society, The Japanese Circulation Society, and Japanese Association of Cardiovascular Intervention and Therapeutics Guidance on Percutaneous Closure of Patent Foramen Ovale (PFO) in Cryptogenic Stroke Patients pfo-council.jp/publications/
- Diener et al. Neurological Research and Practice doi.org/10.1186/s42466-019-0008-2
- Kuijpers T, Spencer FA, Siemieniuk RAC, et. al. Patent foramen ovale closure, antiplatelet therapy or anticoagulation therapy alone for management of cryptogenic stroke? A clinical practice guideline. BMJ. 2018;362:k2515. doi: 10.1136/bmj.k2515.
- Pristipino C, Sievert H, D’Ascenzo F, et. al. European position paper on the management of patients with patent foramen ovale. EuroIntervention. 2018. doi: 10.4244/EIJ-D-18-00622.
- Wein T, Lindsay MP, Côté R, et. al. Canadian Stroke Best Practice Recommendations: Secondary Prevention of Stroke, Sixth Edition Practice Guidelines, Update 2017. International Journal of Stroke, 2017. DOI: 10.1177/1747493017743062
AMPLATZER™ PFO OCCLUDER
INDICATION FOR USE
The AMPLATZER™ PFO Occluder is indicated for percutaneous transcatheter closure of a patent foramen ovale (PFO) to reduce the risk of recurrent ischemic stroke in patients, predominantly between the ages of 18 and 60 years, who have had a cryptogenic stroke due to a presumed paradoxical embolism, as determined by a neurologist and cardiologist following an evaluation to exclude known causes of ischemic stroke.
- Patients with intra-cardiac mass, vegetation, tumor or thrombus at the intended site of implant, or documented evidence of venous thrombus in the vessels through which access to the PFO is gained.
- Patients whose vasculature, through which access to the PFO is gained, is inadequate to accommodate the appropriate sheath size.
- Patients with anatomy in which the AMPLATZER™ PFO device size required would interfere with other intracardiac or intravascular structures, such as valves or pulmonary veins.
- Patients with other source of right-to-left shunts, including an atrial septal defect and/or fenestrated septum.
- Patients with active endocarditis or other untreated infections.
- Patients who are at increased risk for venous thromboembolic events should be managed with thromboembolic risk reduction regimen after the PFO Closure following standard of care.
- Do not use this device if the sterile package is open or damaged.
- Prepare for situations that require percutaneous or surgical removal of this device. This includes availability of a surgeon.
- Embolized devices must be removed as they may disrupt critical cardiac functions. Do not remove an embolized occluder through intracardiac structures unless the occluder is fully recaptured inside a catheter or sheath.
- Patients who are allergic to nickel can have an allergic reaction to this device.
- This device should be used only by physicians who are trained in standard transcatheter techniques.
- Transient hemodynamic compromise may be encountered during device placement, which may require fluid replacement or other medications as determined by the physician.
- Do not release the device from the delivery cable if the device does not conform to its original configuration, or if the device position is unstable or if the device interferes with any adjacent cardiac structure (such as Superior Vena Cava (SVC), Pulmonary Vein (PV), Mitral Valve (MV), Coronary Sinus (CS), aorta (AO)). If the device interferes with an adjacent cardiac structure, recapture the device and redeploy. If still unsatisfactory, recapture the device and either replace with a new device or refer the patient for alternative treatment.
- Ensure there is sufficient distance from the PFO to the aortic root or SVC (typically defined as 9 mm or greater as measured by echo). See Figure 6. and Figure 7.
- The safety and effectiveness of the AMPLATZER™ PFO Occluder has not been established in patients (with):
- Age less than 18 years or greater than 60 years because enrollment in the pivotal study (the RESPECT trial) was limited to patients 18 to 60 years old
- A hypercoagulable state including those with a positive test for a anticardiolipin antibody (IgG or IgM), Lupus anticoagulant, beta-2 glycoprotein-1 antibodies, or persistently elevated fasting plasma homocysteine despite medical therapy
- Unable to take antiplatelet therapy
- Atherosclerosis or other arteriopathy of the intracranial and extracranial vessels associated with a ≥50% luminal stenosis
- Acute or recent (within 6 months) myocardial infarction or unstable angina
- Left ventricular aneurysm or akinesis
- Mitral valve stenosis or severe mitral regurgitation irrespective of etiology
- Aortic valve stenosis (mean gradient greater than 40 mmHg) or severe aortic valve regurgitation
- Mitral or aortic valve vegetation or prosthesis
- Aortic arch plaques protruding greater than 4 mm into the aortic lumen
- Left ventricular dilated cardiomyopathy with left ventricular ejection fraction (LVEF) less than 35%
- Chronic, persistent, or paroxysmal atrial fibrillation or atrial flutter
- Uncontrolled hypertension or uncontrolled diabetes mellitus
- Diagnosis of lacunar infarct probably due to intrinsic small vessel as qualifying stroke event
- Arterial dissection as cause of stroke
- Index stroke of poor outcome (modified Rankin score greater than 3)
- Pregnancy at the time of implant
- Multi-organ failure
- Use on or before the last day of the expiration month that is printed on the product packaging label.
- This device was sterilized with ethylene oxide and is for single use only. Do not reuse or re-sterilize this device. Attempts to re-sterilize this device can cause a malfunction, insufficient sterilization, or harm to the patient.
- The AMPLATZER™ PFO Occluder device consists of a nickel-titanium alloy, which is generally considered safe. However, in vitro testing has demonstrated that nickel is released from this device for a minimum of 60 days. Patients who are allergic to nickel may have an allergic reaction to this device, especially those with a history of metal allergies. Certain allergic reactions can be serious; patients should be instructed to notify their physicians immediately if they suspect they are experiencing an allergic reaction such as difficulty breathing or inflammation of the face or throat. Some patients may also develop an allergy to nickel if this device is implanted.
- Store in a dry place.
- Pregnancy – Minimize radiation exposure to the fetus and the mother.
- Nursing mothers – There has been no quantitative assessment for the presence of leachables in breast milk.
Potential adverse events that may occur during or after a procedure using this device may include, but are not limited to: Air embolus; Allergic drug reaction; Allergic dye reaction; Allergic metal reaction: Nitinol (nickel, titanium), platinum/iridium, stainless steel (chromium, iron, manganese, molybdenum, nickel); Anesthesia reactions; Apnea; Arrhythmia; Bacterial endocarditis; Bleeding ; Brachial plexus injury; Cardiac perforation; Cardiac tamponade; Cardiac thrombus; Chest pain; Device embolization; Device erosion; Deep vein thrombosis; Death; Endocarditis; Esophagus injury; Fever; Headache/migraine; Hypertension/hypotension; Myocardial infarction; Pacemaker placement secondary to PFO device closure; Palpitations; Pericardial effusion; Pericardial tamponade; Pericarditis; Peripheral embolism; Pleural effusion; Pulmonary embolism; Reintervention for residual shunt/device removal; Sepsis; Stroke; Transient ischemic attack; Thrombus; Valvular regurgitation; Vascular access site injury; Vessel perforation