About PFO
Patent Foramen Ovale (PFO)
Patent foramen ovale (PFO) is a small opening in the wall of the heart that separates the two upper chambers or atria. It is due to a persistence of the fetal circulation where a flap-like opening does not close as it normally should after birth. It is very common to have a PFO and is found in approximately 20% of the adult population. This flap-like valve enables shunting (abnormal mixture of blood between the right and left sides of the heart), which is often dynamic and of variable degree.
PFO has been associated with a variety of clinical syndromes afflicting hundreds of thousands of people in the United States alone and is to be equally common in Europe and other regions of the world. These clinical syndromes include cryptogenic stroke, migraine headache, hypoxemia (low blood oxygen), decompression illness in divers, high altitude sickness, and sleep apnea. Standard of care for these clinical syndromes may vary but generally have focused on medications.
Open heart surgery to close PFO has been largely replaced by the development of catheter based therapies. PFO closure for these clinical syndromes has been an area of active clinical investigation. Multicenter randomized trials to evaluate treatment strategies include catheter closure of PFO versus sham closure with medical management for migraine sufferers. Other trials have compared closure of PFO versus medical therapy to reduce clot formation to prevent recurrent stroke in stroke victims. Most clinical trials have struggled to finish due to slow enrollment. There has also been concern that the patients with the most severe clinical syndromes and abnormal PFO anatomy and physiology have been underrepresented due to patient and provider unwillingness to accept randomization in FDA supervised clinical trials.
PFO closure has been advocated based on clinical evidence of effectiveness and safety from single center reports as well as an acceptance of a causative link between the presence of a PFO and several clinical syndromes. Specifically cryptogenic stroke and transient ischemic attacks (TIA) are felt to often be the result of presumed paradoxical embolism and hypoxemia from right to left atrial shunting. The causative link with migraines is under study. The causative link to hypoxemia is suggested by larger amounts of low oxygen content blood flowing thru the PFO from the right to left atrium.
The absence of FDA approval for any implantable PFO closure device or alternative strategies for catheter-based PFO closure has resulted in the off-label use of several devices approved for the closely related but distinct congenital heart defect, secundum atrial septal defect. CE Mark approval has been obtained for a number of PFO closure devices in Europe. Estimates of the number of PFO closures currently being performed in clinical practice using both approved devices in Europe and off-label devices in the United States are in the thousands to tens of thousands worldwide. The results from ongoing, properly controlled clinical trials of catheter PFO closure for a variety of clinical syndromes are anxiously awaited in order to guide and inform clinical practice.
Definition of Terms
- Fetal circulation: The blood circulation in the fetus before birth. A normal part of the fetal circulation in all people is an open, i.e. patent, foramen ovale allowing blood to bypass the non-functioning lungs.
- Circulation: the movement of blood through the vessels of the body that is induced by the pumping action of the heart and serves to distribute nutrients and oxygen to and remove waste products from all parts of the body
- Merriam-Webster’s Medical Dictionary. Merriam-Webster, Inc. http://dictionary.reference.com/browse/circulation (accessed: May 11, 2010).
- Shunting: diversion of blood flow thru an abnormal opening or pathway
- Clinical syndrome: A constellation of symptoms, physical exam findings, and medical test results that characterize a disease or disorder.
- Cryptogenic Stroke: Stroke of undetermined cause.
- Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Adams HP Jr; Bendixen BH; Kappelle LJ; Biller J; Love BB; Gordon DL; Marsh EE 3rd. Stroke 1993 Jan;24(1):35-41.
- Hypoxemia: Insufficient or abnormally low oxygenation of blood
- Decompression illness: symptoms and physical findings upon ascending from a deep underwater dive that are caused by nitrogen bubbles forming in the blood and tissues
- High altitude sickness: a general term including different disorders occurring at high altitude. Acute mountain sickness, high-altitude pulmonary edema, and high-altitude cerebral edema are the three major clinical syndromes.
- Sleep apnea: a medical condition including repeated abnormal pauses in breathing. Obstructive sleep apnea i(OSA) includes the occurrence of obstruction of the airway to the lungs.
- Catheter based therapies: Catheters, thin flexible tubes, are inserted in the body and used for delivering therapies such as medications, electrical energy, or implanting medical devices, like a PFO closure device.
- Multicenter randomized trials: A type of scientific study to determine the relative merits of two or more different treatments. Patients are assigned randomly (by chance alone) to one of the treatments. The study is performed at multiple different medical sites.
- Sham procedure: A procedure is performed that closely resembles the true procedure but the main element of the real procedure is omitted. For a PFO closure procedure, a sham procedure can involve anesthetizing the patient, making a nick over the vein in the neck, but not actually implanting a PFO device. The goal is to have the patient blinded, i.e. not knowing whether or not they have received the device.
- Transient ischemic attack: A neurological event with the signs and symptoms of a stroke but only transient in duration and without permanent brain damage.
- Paradoxical embolism: The passage of a clot from its origin in the venous system to a location in the arterial system often resulting in obstruction of the artery.
- Off-label use: The use of a medication or medical device for an unapproved indication. The regulations of the Food and Drug Administration (FDA) permit physicians to use medications and devices for other than their intended indication. “If physicians use a product for an indication not in the approved labeling, they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product’s use and effects. Use of a marketed product in this manner when the intent is the “practice of medicine” does not require the submission of an Investigational New Drug Application (IND), Investigational Device Exemption (IDE) or review by an Institutional Review Board (IRB).”
- Secundum atrial septal defect: A type of heart defect, i.e. lack of cardiac tissue, in the wall separating the left and right upper heart chambers, the atria.
- CE Mark approval: “The CE marking (also known as CE mark) is a mandatory conformity mark on many products placed on the single market in the European Economic Area (EEA). The CE marking certifies that a product has met EU consumer safety, health or environmental requirements. CE stands for Conformité Européenne, “European conformity” in French.”
