1	PATIENT INFORMATION PATENT FORAMEN OVALE (PFO) NEUROVASCULAR STROKE PREVENTION PROGRAM SHERMAN G SORENSEN MD, DIRECTOR
2	STROKE AND PFO Stroke is the third leading cause of death in the United States. One million people suffer from stroke each year. Stroke is the major cause of disability in the United States. There are 5 million survivors of stroke in this country. Stroke is not rare in young people under 50 years of age accounting for 5% of all strokes. Until recently, 40% of all strokes were of unknown cause. We now know that most of these unexplained strokes may be caused by a PFO (Patent Foramen Ovale).
3	WHAT IS A PFO? PATENT FORAMEN OVALE During formation of the heart in the fetus, two pieces of the wall grow to overlap each other to divide the upper chambers (atria) of the heart into right and left chambers. Before birth, the lower divider acts as a flap or tunnel which allows blood to flow from the right side of the heart to the left side. This blood flow contains oxygen from the mother’s placenta.
4	WHAT IS A PFO? After birth, right-to-left blood flow is no longer needed. The two dividers of the right and left atria fuse to form a solid wall (septum). The septum is fused in 90% of people by 18 months of age. However, the dividers which form the septum do not fuse in 10% of people leaving a flap or tunnel which may open and close as right heart pressure changes. This opening (flap or tunnel) is the Patent Foramen Ovale or PFO
5	WHY PFO CAUSE STROKE In the normal adult heart, the right and left sides are completely separated. Blood from the body enters the right atrium and flows to the lungs. Filtered blood from the lungs carries oxygen and is pumped to the brain and organs of the body.
6	WHY PFO CAUSE STROKE With a PFO present, blood from the body can bypass the lungs and travel to the left side of the heart. In the normal heart (no PFO), a blood clot from the body would be stopped in the lungs. But if a clot crosses the PFO, it can go to the brain causing a stroke.
7	WHY PFO CAUSE STROKE Where do blood clots come from to cause stroke in patients with a PFO? Blood clots may form in the veins in the legs, break lose, and travel with blood flow to the heart. These clots may pass through the PFO causing a stroke.
8	WHY PFO CAUSE STROKE Or, blood trapped within the PFO flap or tunnel for a period of time may clot. When increased pressure in the right heart opens the flap of the PFO, the clot may dislodge and travel to the left side of the heart and then to the brain.
9	HOW ARE PFO DIAGNOSED? TRANSTHORACIC ECHO Heart disorders are the most common cause of stroke. TransThoracic Echocardiography ( or TTE) is a noninvasive, ultrasound test which evaluates heart structures. Microscopic bubbles injected into a vein show a PFO when they cross to the left side. TTE is about 60% reliable in finding a PFO.
10	HOW ARE PFO DIAGNOSED? TRANSESOPHAGEAL ECHO Although surface echo (or TTE) can define most heart structures, the atrial septum ( the site of the PFO) is hard to see. Trans-Esophageal Echo (or TEE) uses a special ultrasound probe which is placed in the esophagus after giving sedation. The atrial septum and PFO can be clearly seen by this technique.
11	HOW ARE PFO DIAGNOSED? TRANSCRANIAL DOPPLER TransCranial Doppler (or TCD) is a new, non-invasive test for diagnosing the presence of a PFO. TCD is more sensitive than TTE or TEE for finding a PFO, but does not show heart anatomy. TCD+TTE may render TEE unnecessary. When microscopic bubbles are injected by IV into a vein in a normal heart, the lungs reduce their passage to the left side of the heart. When a PFO is present, TCD detects bubbles which pass through the PFO and travel to the arteries in the brain. TCD, unlike TTE/TEE, is quantitative. The abnormal flow of blood through the PFO (detected by TCD) is called “shunting”. Shunting is one of the hallmarks of the PFO.
12	WHAT IS KNOWN ABOUT PFO AND STROKE PFO occurs in 10-15% of all adults PFO is diagnosed in 50-70% of patients with stroke of unknown cause. After a first stroke due to PFO, ½ of patients still have moderate to severe disability after 1 year. After a first stroke due to PFO, second strokes occur at a rate of 2%-9% each year. (depending on risk) After several strokes from PFO, repeat strokes occur at a rate of 6%-20% each year. The risk of repeat stroke due to PFO is increased in patients with leg clots, migraine headache, atrial septal aneurysm (seen by echo), and large PFO shunting (seen by TCD).
13	NOT ALL PFO ARE THE SAME RISK AND AMOUNT OF PFO FLOW While blood flow from the right atrium to the left atrium is the hallmark of a PFO, it is the AMOUNT of flow (or shunt) that is associated with the risk of recurrent stroke; the greater the flow: the greater the risk. Bubbles injected by an IV appear in the right atrium and are detected by echo when they appear in the left atrium. (A small number of bubbles may pass through the lungs normally). Tiny PFO communications are low risk for stroke and do not need treatment. Large PFO are much more likely to result in stroke, migraine, decompression illness in divers, and low oxygen levels in the blood. Mistakenly thinking that all PFO are the same is one of the reasons doctors may disagree on PFO treatment.
14	NOT ALL PFO ARE THE SAME ATRIAL SEPTAL ANEURYSM AND INCREASED STROKE RISK In ½ of patients with high flow PFO, the septum primum (lower divider) is redundant and floppy due to excessive tissue. This floppy divider is called an atrial septal “aneurysm” (ASA). It is not at all like a true arterial aneurysm and cannot burst. In patients with both ASA + PFO, the chance of repeat stroke is increased four fold (even on blood thinning medications). The presence of an ASA in a PFO stroke patient means that the YEARLY stroke risk is 4%. (Risk > 1.5% / year is considered very high).
15	DEFINING PFO STROKE RISK
16	WHAT ARE MY TREATMENT OPTIONS? No specific treatment Aspirin/Plavix to reduce clotting Coumadin to reduce clotting Open heart surgery to close the PFO Trans-catheter closure of the PFO
17	PFO TREATMENT OPTIONS ASPIRIN/ PLAVIX/ COUMADIN RISKS -Continued lifelong risk of stroke ranging from 2-9% each year -Bleeding due to medication effect aspirin:1.4% per year coumadin:2.2% per year -Inconvenience of frequent blood tests (coumadin) BENEFITS -No procedure related problems -Possible reduction in stroke risk Reduction of stroke due to PFO by medicines remains unproven
18	PFO TREATMENT OPTIONS OPEN HEART SURGERY RISKS -Serious complications (5%): death, stroke, nerve injury, lung injury, infection, transfusion, anesthesia, re-operation , chest scar -5-7 day hospital stay/ 4-6 week recovery period BENEFITS -Reduction of stroke risk -Good complete closure rate: 90% at our hospital -Established procedure
19	PFO TREATMENT OPTIONS CATHETER CLOSURE OF PFO RISKS -Serious complications (0.2%): death, stroke, infection, bleeding, blood vessel injury, anesthesia, device movement or dislodgement (1:400), incomplete closure (1-5%) clot forming on device (30/10,000 cases) BENEFITS -Stroke reduction to less than 1% -No scar; minimal pain -Out-patient procedure -Return to full activity in 2 days
20	AVAILABLE DEVICES FOR CATHETER SEPTAL DEFECT CLOSURE These 2 central pin (umbrella) devices are available for PFO closure under 2 regulated circumstances: INVESTIGATIONAL REGISTRIES: You must sustain 2 strokes while on blood thinning drugs (i.e. failing medicines) to be eligible. If you are interested or need more information, contact NMT Medical® or AGA Medical®. RANDOMIZED CLINICAL TRIALS: You must sustain a stroke to be eligible for closure. Treatment is randomly assigned. ½ of patients receive a device. The rest are treated with medicines. If you are interested in either option, you should contact either NMT Medical® or AGA Medical®.
21	AVAILABLE DEVICES FOR CATHETER SEPTAL DEFECT CLOSURE The Amplatzer SO device is approved for septal defect closure. It has been used “off-label” for PFO closure and in a recent survey (TCT 2005), 90% of centers reported use of this device for PFO closure. Two other devices for atrial septal defect closure are marketed. Use of devices or medications “off-label” is common, legal, and accepted in medical practice. Indeed, in many circumstances “off-label” treatments are mandatory. “Off-label” use occurs because research and experience and patient need move beyond original intended use of a therapy. Patients should understand these issues, risks, and all options before considering “off-label” treatments.
22	HOW DO SEPTAL DEFECT CLOSURE DEVICES WORK? These devices consist of two back-to-back umbrellas (Starflex®) or discs (Amplatzer® PFO and Amplatzer® Cribriform) which are connected centrally by a thin pin. The devices are “spring loaded” to open to their original shape after being folded into a catheter or tube for placement in the body.
23	HOW DO SEPTAL DEFECT DEVICES WORK? The Amplatzer® SO device is similar to the other 2 devices and is inserted in the same way. It is available in 17 sizes rather than 3. However, this closure device has a thicker middle section which fills the atrial septal defect space better than the thin pin connectors of the other devices. Use of this device for a PFO septal defect would be an “off-label” use since it was originally intended and tested for atrial septal defect closure. The largest world experience is with this device (>100,000 devices implanted). For large PFO defects, completeness of closure is better with the SO device compared with the PFO device (Amplatzer®).
24	HOW CLOSURE DEVICES WORK? The closure device is delivered to the heart through a small catheter or tube. The ICE (echo) catheter is placed in the same vein. These catheters are introduced into the body through a major vein in the groin. After the procedure, the catheters are removed and sutures are not needed.
25	HOW DO CLOSURE DEVICES WORK? Intra-Cardiac Echo (or ICE) and fluoroscopy ( low level xrays) are used to safely and accurately place the devices in the heart. The ICE catheter is placed in the same vein as the device delivery catheter. The ICE pictures assure safe device placement, testing for absolute device stability, and completeness of closure. The discs or umbrellas on each side of the atrial septum (divider) hold onto the tissue and “pinch” the PFO closed. The SO device “pinches + fills” the septal defect. Device stability and completeness of closure are confirmed by the ICE images immediately during the procedure.
26	HOW CLOSURE DEVICES WORK
27	HOW SEPTAL OCCLUDERS HEAL Within 3-6 months, the normal lining cells of the heart grow over the device, completely covering the artificial materials. The occluder device becomes part of the atrial septum and blood flows normally and clots cannot form or pass through the septum.
28	SEPTAL DEFECT CLOSURE SAFETY AND EFFICACY EXPERIENCE We have performed over 1600 implants: CardioSEAL(261), Amplatzer PFO (750) and Amplatzer SO (650=ASD+PFO); over 2000 TCD studies; over 950 ICE procedures. SAFETY Our very low procedural and device complication results have been published and can be seen on our RESEARCH page. EFFICACY Primary efficacy, the correction of PFO flow, is best quantified by our TCD studies: 95% of patients have complete resolution; 4% have residual shunt which is reduced; 1% have no improvement in amount of shunt.
29	WHAT HAPPENS AFTER CATHETER CLOSURE? ACTIVITY: Return to normal activity in 2 days MEDICATION: Aspirin 6 months Plavix 3 months TESTING: TCD 3 months TTE 3 months Other testing may be required RESTRICTIONS: No dental care for 6 months No contact sports for 1 month No heavy lifting for 1 month
30	WHY OUR PROGRAM MAY BE RIGHT FOR YOU Our rigorous Program requirements assure that you are informed and receive the safest and most effective treatment. Over 25 neurology specialists choose our Program Different devices and more than one technique for different patient anatomy and physiology assure better results More than one hospital system to meet insurance needs A dedicated, specialized team of echo, nursing, catheterization laboratory, and physician members One of the most experienced centers in this country and abroad with excellent results over many years An active research and education program involving new device applications and better testing for stroke prevention