Atrial Fibrillation
 RESOURCES FOR PATIENTS

    The annual international Boston A-Fib Symposium is one of the most important conferences on A-Fib in the world. It brings together researchers and doctors who share the latest information.  But if you haven't read and understood most of A-Fib.com, it may be difficult reading.

    Each Symposium features an Overview, followed by summaries of individual presentations listed by Doctor and Topic.

BOSTON A-FIB SYMPOSIUM, January 17-19, 2008 "Atrial Fibrillation: Mechanisms and New Directions in Therapy"
OVERVIEW-HIGHLIGHTS

    The 13th annual Boston A-Fib Symposium may mark the emergence of the Robotics Era in the treatment of A-Fib. Much attention was focused on the competing robotic ablation systems by Hansen and Stereotaxis. These systems are already changing the way doctors perform ablations, and will likely provide significant benefits to A-Fib patients.

Catheter Ablation Outside the Heart
    In what may be a major medical breakthrough, two doctors announced that they had combined Endocardial ablation (ablating inside the heart) with Epicardial ablation (outside the heart) to more effectively ablate sources of A-Fib which are hard to reach.

Significantly Decreasing the Risk of Stroke
    Clinical trials are underway of the Watchman device for closing off the Left Atrial Appendage, which may well be another major medical breakthrough. In a simple, very low risk procedure performed in as little as twenty minutes, the Watchman device is inserted via a catheter into the Left Atrial appendage to close it off. This simple procedure reduces the risk of stroke by as much as 95%. (The risk of A-Fib stroke risk is reduced to that of someone with a normal heart).
    (The Watchman device may also help people with other risks of stroke.) (See Reddy, Novel Catheter Approaches to Thrombo-Prophylaxis.)

Eight-step Ablation Procedure for Treating Chronic A-Fib with a 93% Success Rate
    The Italian Milan group announced an eight step ablation procedure for treating Chronic (all-the-time) A-Fib which is 93% successful. This is a significant improvement in the success rate for ablating Chronic A-Fib. (See also 95% success rate in curing Persistent A-Fib reported by the French Bordeaux group at the 2007 Boston A-Fib Symposium.) (Other centers like Massachusetts General are using similar procedures and are achieving similar success rates for curing Chronic A-Fib.)

Atrio-Esophageal Fistula
    Though no cases of Atrio-Esophageal Fistula were reported since last year's Boston A-Fib Symposium, there was still a  great deal of concern over this rare complication (where the ablation catheter unintentionally burns a hole through the back of the heart and into the esophagus).
    Some centers use an esophageal temperature probe and stop ablating if the esophageal temperature rises 0.2 degrees.  But research indicates that even this small increase in esophageal temperature may cause ulceration in the esophagus. This ulceration, however, is easily cured by administering Proton Pump Inhibitors (to limit gastric acid) and other meds. (Examples of Proton Pump Inhibitors are: Nexium, Prilosec, Prevacid, and Protonix.)
    (Doctors commented that they would now routinely use Proton Pump Inhibitors after Pulmonary Vein Ablation procedures to help prevent Atrio-Esophageal Fistula.)

Electrophysiologists and Surgeons Present Consensus Statement on Treating A-Fib
    In an inspiring example of collaboration and cooperative concern for A-Fib patients, EPs and Surgeons together developed a consensus statement on A-Fib ablation that is detailed, practical, far reaching, and addresses head-on many of the major issues of A-Fib ablation. (This document may have major implications for A-Fib patients not only from its content, but also because it demonstrates how effectively EPs and surgeons are now working together to cure A-Fib.)

Catheter Ablation Far Superior to Current Antiarrhythmic Meds in Treating A-Fib
    Data from several research studies demonstrated that catheter ablation is significantly better at restoring and maintaining sinus rhythm than current antiarrhythmic (AA) drugs (one study showed a 64% difference).
    These studies also compared complication rates for both treatment approaches. One-time complications for catheter ablation were relatively low, compared to the side effects and long time complication risk of antiarrhythmic drugs. In addition, the research showed that A-Fib patients on AA drugs run an additional risk of getting worse and developing Cardiomyopathy.

Live Satellite Demos of both Catheter and Surgical Ablation
     This Symposium featured two live catheter ablations: one from the Un. of Austin using the Hansen robotics system, and the other from Massachusetts General using the Phillips ultrasound 3-D imaging which produces a real time 3-D image during the ablation. Also, for the first time at a Boston A-Fib Symposium, there was a live satellite surgical ablation case (from the Medical College of Virginia).
 

Danger of "Silent" A-Fib Strokes
    Several disturbing studies indicated that A-Fib patients, without any apparent neurological symptoms, often had silent cerebral strokes (15%-26%) which showed up on computer tomography (CT) images of the brain. A-Fib patients with "silent" strokes are at much greater risk of a subsequent stroke. (If you've had A-Fib for a while, you might want to discuss with your doctor getting a computer tomography (CT) scan of your brain to see if you've had any "silent" strokes or TIAs [Transient Ischemic Attacks].) (See Camm: Oral Anticoagulation: A Critical Review of the Data But be aware of the possible long term dangers of too much exposure to radiation through CTs, X-rays, etc.)

Aspirin may not be Effective in Preventing A-Fib Stroke    Several studies were presented which cast doubt on the effectiveness of aspirin as an anticoagulant to prevent A-Fib stroke. According to Dr. John Camm of St. George's Medical School, London, England, "there is little if any efficacy of aspirin...The evidence for aspirin (to prevent clotting) is marginal and at best modest." (See Camm: Oral Anticoagulation: A Critical Review of the Data)

French Bordeaux Group Honored
    Ten years ago in 1998 the French Bordeaux group published their groundbreaking article demonstrating how A-Fib is initiated by ectopic beats in the Pulmonary Veins. This article helped develop catheter ablation as it is performed today. Many patients have been cured of A-Fib thanks to their pioneering research. In recognition of their work, Drs. Michel Haïssaguerre and Pierre Jaïs from  the French Bordeaux group were presented with a Chelsea clock from Boston with the inscription: "In recognition of your pioneering contribution to the science of catheter ablation and to the care of patients with cardiac arrhythmias."
    (The author was surprised to find out that he was the first US patient to be cured of A-Fib by the French Bordeaux group back in 1998.)

PRESENTATIONS

Dr. John Camm of St. George’s Medical School, London, England, UK was part of a 3-person panel and discussion on Stroke Prophylaxis (Prevention) in the A-Fib Patient. His presentation was on "Oral Anticoagulation: A Critical Review of the Data."

    One of the most difficult challenges for A-Fib patients and doctors is to prevent A-Fib stroke. Oral anticoagulation with dose-adjusted warfarin remains the mainstream therapy for the prevention of A-Fib stroke.
    So many people have A-Fib today (2.3 million in the US alone) that it’s considered an world-wide epidemic, affecting 1%-1.5% of people in developed countries.¹¹⁴ Someone with A-Fib has a five times greater risk of stroke, and the A-Fib stroke is usually more severe, with a greater risk of death, permanent disability, and increased health care cost. An A-Fib stroke is twice as likely to be fatal. Nearly three-quarters of stroke victims with A-Fib require daily health care assistance, compared to about one-third with sinus rhythm, and are more likely to remain handicapped. (Poor stroke outcome may be due to a reduction in cerebral blood flow caused by A-Fib.)
    In A-Fib the atria don’t contract properly, which results in increased atrial pressure, atrial stretch, and dilation often leading to blood stagnation and clot formation. Atrial stretch also produces chemical changes in the atria (increased natriuretic peptide and decreased vasopressin) which can produce increased blood concentrations (often resembling a gelatinous, Jell-O-like substance), and increased platelet activity.
    The left atrium and particularly the Left Atrial Appendage (LAA) produce 70-90% of A-Fib clots. The LAA is a long, closed-end pouch which acts as a decompression chamber in volume overload where blood can easily stagnate. It has many cavities, resembling a piece of coral. Even when A-Fib patients are effectively anticoagulated, 14% of patients are still found with clots. However, approximately 4 weeks of warfarin therapy dissolves these clots in 75% of cases.
    According to Dr. Camm, patients today are generally being successfully managed with warfarin therapy to prevent thrombis (clotting), though there is room for improvement.

THE "CHADS2" RISK MODEL
    Doctors today use a risk-based approach to stroke prevention. Each individual's stroke risk is calculated to identify those who are at higher risk, and who may benefit most from anticoagulant (warfarin) therapy. The CHADS2 is currently the recommended risk model to determine anticoagulant use.
    CHADS2 refers to risk factors for stroke. If you have one of the risk factors, you have a risk score of 1. However, if you’ve had a stroke already, that counts as a risk score of 2 ("S2"):

    Someone with a risk factor of 1 not receiving any anticoagulant therapy would have 1.9%-2.8% chance of having a stroke within a year, whereas someone with a score of 6 would have an 18.2% chance of having a stroke. Aspirin is recommended for A-Fib patients who have a low to intermediate risk of stroke, but aspirin only provides modest protection.¹¹⁵.
    Dr. Camm pointed out that the CHADS2 risk score model doesn’t take into account other less predictive risk factors such as female gender, coronary artery disease, age 65-74, and thyrotoxicosis (overactive thyroid). (Editor's Note: A-Fib by itself, such as Lone A-Fib with no other risk factors, is not part of the CHADS2 risk model for stroke. The chances of low-risk or intermediate-risk A-Fib patients getting an A-Fib stroke, according to the Center for Shared Decision Making, are:
    Under age 65 with no history of hypertension, stroke, arterial embolism, left ventricular dysfunction, or TIA:
        Chance of stroke in two years 2 out of 100
        Taking daily coated aspirin 1.5 out of 100
        Taking daily warfarin 1 out of 100)
    Age 65-75 with no history of hypertension, stroke, arterial embolism, left ventricular dysfunction, or TIA:
        Chance of stroke in two years 4 out of 100
        Taking daily coated aspirin 3 out of 100
        Taking daily warfarin 2 out of 100¹¹⁷

ASPIRIN VS. WARFARIN EFFECTIVENESS
    Dr. Camm cited seven recent studies which together showed a 22% overall risk reduction effectiveness of aspirin in preventing A-Fib stroke. However, the range of these studies varied from 2% to 39% and was not consistent. "The evidence for aspirin thrombus prophylaxis (preventing clot formation) is marginal and at best modest."
    However, studies comparing warfarin to both a placebo and to aspirin demonstrated compelling, convincing evidence of the effectiveness of warfarin. "There can be no doubt that warfarin is superior to aspirin." Warfarin had a 64% relative risk reduction in preventing A-Fib stroke vs. a questionable 22% for aspirin. "There is little if any efficacy for aspirin."

WARFARIN UNDERUSED
    Both the young (under 55) and the elderly tend to under use warfarin. The difficulty of maintaining the proper INR (International Normalized Ratio) is a factor. But also 40% of those at high risk of stroke, particularly the elderly, aren’t receiving warfarin therapy, often because of an assumed inherent risk of hemorrhagic stroke. (The risk of a hemorrhagic [bleeding] stroke increases when the INR level goes above 4. An ideal INR level is between 2-3, Below 2 one runs more of a risk of an A-Fib ischemic stroke.)
    Even young Paroxysmal (Intermittent) A-Fib patients with a high risk of stroke aren’t being properly anticoagulated. But studies show that there is no difference in A-Fib stroke risk between Persistent and Paroxysmal A-Fib. Warfarin therapy should depend on one’s CHADS2 score, not on what type of A-Fib one has.

SILENT CEREBRAL STROKE
    Dr. Camm cited several disturbing studies which showed that A-Fib patients, without any apparent neurological symptoms, often had silent cerebral strokes (15%-26%) which showed up on computer tomography images of the brain. A-Fib patients with these "silent" strokes are at much greater risk of a subsequent stroke. (If you've had A-Fib for a while, you might want to discuss with your doctor getting a computer tomography (CT) scan of your brain to see if you've had any "silent" strokes or TIAs [Transient Ischemic Attacks]. But be aware of the possible long term dangers of too much exposure to radiation through CTs, X-rays, etc.)

GENETIC WARFARIN THERAPY
    Using genotypes to help determine warfarin dosage reduces the number of times an A-Fib patient is out of INR range, and the number of times INR has to be calculated. But it doesn’t seem to make a significant difference in keeping patients in the approved INR range. See FDA APPROVES GENETIC TESTING LABELING FOR COUMADIN

CONCLUSION
    The prevention of A-Fib by improved medications, and/or by Pulmonary Vein Ablation procedures (which have a 75%-85% success rate) may reduce the prevalence of stroke by almost one-quarter in the general population, particularly in the elderly. (In this author’s opinion, one of the major advantages of a successful Pulmonary Vein Ablation procedure is the reduction of A-Fib stroke risk. Studies indicate that a successful catheter ablation does lower the risk of an A-Fib stroke without having to take warfarin.¹¹⁶ But see also the danger of stroke from "silent" A-Fib attacks after catheter ablation.)

The second presenter on the 3-person stroke prevention panel was Dr. Albert Waldo of University Hospitals of Cleveland, OH who talked about "Novel Medical Approaches to Thrombo-Prophylaxis"

    Though warfarin (brand name Coumadin) is very effective and reduces the risk of A-Fib-related stroke by about 70%, doctors are very aware of its problems and wish there were better options for patients.
    (Warfarin is what is called a Vitamin K Antagonist (VKA). A technical description of how VKAs work is the following: "they prevent the y-carboxylation of the vitamin K-dependent coagulation factor prothrombin and Factors VII, IX, and X."¹¹⁵ In layman’s terms warfarin works by affecting several steps in the anticoagulation pathway to prevent clotting.)

WARFARIN PROBLEMS

1. Narrow therapeutic window. Insufficient anticoagulation (INR less than 2) may result in stroke. Over-anticoagulation (INR over 4) increases the risk of bleeding.
2. Late onset and offset. A patient has to be taking warfarin for a while for it to reach a therapeutic level.
3. Unpredictable dose response. Genetic and other factors may influence how individuals react to warfarin.
4. Drug-drug interactions. Certain drugs (and some supplements) interfere with warfarin.
5. Drug-food interactions. People taking warfarin must limit foods containing vitamin K (like broccoli or some leafy vegetables)
6. Problematic monitoring. It’s very difficult for both doctors and patients to monitor INR levels. Patients may be required to visit a doctor’s office weekly in order to be adequately monitored.
7. Slow reversibility. It’s difficult to reverse, for example, a too high INR level.

    Dr. Waldo pointed out that this was only a partial list of the problems with warfarin.

FUTURE ALTERNATIVES TO WARFARIN
    Dr. Waldo discussed ongoing research and clinical trials of alternatives to warfarin.
    One of the most promising seems to be dabigatran, a direct thrombin inhibitor (affecting the last stage in the anticoagulation pathway). (A more technical description of how dabigatran works is: "In the final step of the coagulation pathway, thrombin converts fibrinogen to fibrin. Dabigatran binds directly to thrombin, blocking its interaction within substrates and thereby preventing fibrin formation, thrombin-mediated activation of Factors V, VIII, XI, and XIII, and thrombin-induced platelet aggregation.¹¹⁵)
    Dabigatran is in Phase III clinical trials with 15,000 patients. (Phase III is usually the last phase before FDA approval.) Results are expected in 2010.
    So far dabigatran seems to be as effective and safe as warfarin. It’s administered as a pill and doesn’t require frequent monitoring. It starts working right away and has a wide therapeutic window. Its effects are reliably predictable. It doesn’t seem to have many food and drug interactions, and can be administered in fixed doses. (The other direct thrombin inhibitor formerly in clinical trails, ximelagatran, was rejected by the FDA because of liver toxicity and heart problems. Dabigatran doesn’t seem to have those problems.)

    Other possible future alternatives to warfarin are Factor Xa Inhibitors which work further up the anticoagulation pathway. They may cause fewer side effects, because they affect mainly coagulation and not other functions like thrombin. There are many different Factor Xa medicines in development, but they are not as far along in clinical trials as dabigatran.

Dr. Vivek Reddy of Massachusetts General in Boston, MA was the third speaker of the 3-person panel on Stroke Prophylaxis in the A-Fib Patient. His topic was "Novel Catheter Approaches to Thrombo-Prophylaxis (Prevention)."   

    (Editor's Note: Dr. Reddy's presentation raised an important question: what if the threat of A-Fib stroke could be easily eliminated without having to take warfarin or other meds? This may be possible in the near future because of the Watchman device.)
    Dr. Vivek Reddy described ongoing clinical trials of the Watchman device which closes off the Left Atrial Appendage (LAA) where most A-Fib clots originate. (The Watchman device is produced by Atritech, Inc., Plymouth, MN; http://www.atritech.net. Graphics courtesy of WATCHMAN®)

HOW THE WATCHMAN DEVICE WORKS

    Once a patient's Left Atrial Appendage is measured, a wide-sheathed catheter with a spline is used to insert the Watchman device which has a self-expanding Nitinol (a special metal) open-ended circular frame. The atrial surface of this frame is covered with a thin, permeable 160 μm (micron) pore filter made of polyester material (Polyethylene Terephthalate known as Dacron or PET). This filter allows blood to pass through while stopping clots. Little hooks or anchors called fixation barbs at the middle of the device make sure it is attached firmly to the LAA wall. The Watchman device comes in multiple sizes from 21mm to 33mm to accommodate the different sizes of LAAs.
     Before the catheter is removed (which fixes the Watchman device in place), contrast agents are used to make sure the Watchman device is stable and entirely closes off the LAA opening. Over time heart tissue grows over the polyester (PET) material so that it completely closes off the LAA with smooth heart tissue similar to other heart surfaces.
    Some doctors are inserting the Watchman device in as little as 20 minutes. It is a low risk procedure with no surgery or ablation involved.
    Patients on Coumadin continue to take it for six weeks after the Watchman device is inserted. They are then examined using a TEE (Transesophageal Echogram) to make sure there is complete closure of the LAA. At that time they are taken off of Coumadin.

    You can see a video of how the Watchman device is deployed at:

http://www.atritech.net/media/deviceanimation.aspx

CLOSING OFF THE LAA AND A-FIB STROKE
    The theory behind the Watchman device is that most A-Fib clots are found in the Left Atrial Appendage (LAA). Dr. Reddy cited a study where 98% of A-Fib strokes came from the LAA.
    Studies of the early Maze operations (in which the Left Atrial Appendage was routinely cut out and sewn shut) showed a major decrease in A-Fib strokes. After 11 1/2 years of following 265 patients, only one had a stroke. However, there was no way to determine if this stroke risk reduction was due to the elimination of A-Fib or to the excision of the LAA.
    Dr. Reddy cited studies of current Mini-Maze operations which show a high percentage of incomplete closure of the LAA. Even though surgeons have direct vision of the LAA and can over-sew or re-staple, sutures have a less than 50% success rate, while staples have a success rate of around 72%. In addition, 20% of patients in these studies later had strokes.
    Instead of sewing or using staples, surgeons are also researching the use of a fabric coated band which is placed as close to the base of the LAA as possible. This band draws shut and closes off the LAA in 16 weeks.

PRELIMINARY DATA ON THE WATCHMAN DEVICE
    Preliminary non-randomized data from the Watchman device clinical trials has been very positive. Following some patients for up to 5 years, there have been no strokes, cardiovascular deaths, or systemic embolisms (there were concerns about possible air bubbles forming in the heart due to the large catheter sheath used to insert the Watchman device).
    Of the people who applied to participate in the Watchman clinical trials, 80% were accepted. Patients had to have a CHADS2 score of at least 1. Also, patients with Vagal A-Fib were excluded (Dr. Reddy reported that some researchers suspect that Vagal A-Fib patients tend to have less clots originating in the LAA). (An acceptance rate of 80% for a clinical trial indicates that the Watchman device, if and/or when it receives FDA approval, will be available for many, if not most A-Fib patients.)
    The Watchman device clinical trial is entitled "PROTECT-AF." (The full title is: Watchman Left Atrial Appendage System for Embolic PROTECTion in Patients with Atrial Fibrillation.) It is a multi-center, prospective, randomized-controlled trial at 60 medical centers across the US comparing the Watchman device to drug therapy using warfarin (brand name Coumadin). It attempts to answer the question, "Can the Watchman device replace warfarin treatment in A-Fib patients?" (In the future a subset of these clinical trials will include patients who can not take Coumadin.)
    It will also directly measure how important the Left Atrial Appendage is to the development of A-Fib stroke.
    This clinical trial also examines if there are potential detrimental effects of closing off the Left Atrial Appendage.

EDITOR'S COMMENTS
    Though some heart pumping dynamics and other functions of the LAA may be lost when the Watchman device closes off the LAA, this seems a small price to pay to be freed from the threat of an A-Fib stroke.

FUTURE USE OF THE WATCHMAN DEVICE
    If the Watchman device works as well as preliminary data indicate and if the FDA approves it, how will it be used? Will it be a stand-alone procedure, or will it be routinely inserted as part of an A-Fib ablation procedure? (The following opinions are speculative and depend on the results of the ongoing clinical trials.)

The Watchman device as a stand-alone procedure
     
    Since A-Fib is so damaging to the heart and to one's overall health, most A-Fib patients probably won't be satisfied with just having their Left Atrial Appendage closed off by the Watchman device, even though this would virtually eliminate the threat of an A-Fib stroke.
    People with other risks of stroke than A-Fib may opt for insertion of the Watchman device to prevent stroke.
    If insertion of the Watchman device becomes routine and easy to do, someone newly diagnosed with A-Fib with a moderate to high risk of stroke may have the Watchman device insertion procedure right away, while waiting for a  catheter ablation to cure their A-Fib.
    Asymptomatic A-Fib patients at risk of stroke but who don't want to take warfarin may be prime candidates for the Watchman device.
    Young people and athletes with A-Fib who do not have a high risk of stroke may not want the Watchman device, because of the potential damage to their heart's dynamics from losing the Left Atrial Appendage.

The Watchman device as part of a catheter ablation procedure
    If the Watchman device works as intended, it may become part of most catheter ablation procedures. If the catheter ablation procedure were unsuccessful or in case of silent A-Fib attacks after ablation, the patient would still be protected from A-Fib stroke by the closing off of the Left Atrial Appendage. 

(More to follow.)

Dr. John Camm of St. George’s Medical School, London, England, UK was part of a 3-person panel and discussion on Stroke Prophylaxis (Prevention) in the A-Fib Patient. His presentation was on "Oral Anticoagulation: A Critical Review of the Data."

    One of the most difficult challenges for A-Fib patients and doctors is to prevent A-Fib stroke. Oral anticoagulation with dose-adjusted warfarin remains the mainstream therapy for the prevention of A-Fib stroke.
    So many people have A-Fib today (2.3 million in the US alone) that it’s considered an world-wide epidemic, affecting 1%-1.5% of people in developed countries.¹¹⁴ Someone with A-Fib has a five times greater risk of stroke, and the A-Fib stroke is usually more severe, with a greater risk of death, permanent disability, and increased health care cost. An A-Fib stroke is twice as likely to be fatal. Nearly three-quarters of stroke victims with A-Fib require daily health care assistance, compared to about one-third with sinus rhythm, and are more likely to remain handicapped. (Poor stroke outcome may be due to a reduction in cerebral blood flow caused by A-Fib.)
    In A-Fib the atria don’t contract properly, which results in increased atrial pressure, atrial stretch, and dilation often leading to blood stagnation and clot formation. Atrial stretch also produces chemical changes in the atria (increased natriuretic peptide and decreased vasopressin) which can produce increased blood concentrations (often resembling a gelatinous, Jell-O-like substance), and increased platelet activity.
    The left atrium and particularly the Left Atrial Appendage (LAA) produce 70-90% of A-Fib clots. The LAA is a long, closed-end pouch which acts as a decompression chamber in volume overload where blood can easily stagnate. It has many cavities, resembling a piece of coral. Even when A-Fib patients are effectively anticoagulated, 14% of patients are still found with clots. However, approximately 4 weeks of warfarin therapy dissolves these clots in 75% of cases.
    According to Dr. Camm, patients today are generally being successfully managed with warfarin therapy to prevent thrombis (clotting), though there is room for improvement.

THE "CHADS2" RISK MODEL
    Doctors today use a risk-based approach to stroke prevention. Each individual's stroke risk is calculated to identify those who are at higher risk, and who may benefit most from anticoagulant (warfarin) therapy. The CHADS2 is currently the recommended risk model to determine anticoagulant use.
    CHADS2 refers to risk factors for stroke. If you have one of the risk factors, you have a risk score of 1. However, if you’ve had a stroke already, that counts as a risk score of 2 ("S2"):

    Someone with a risk factor of 1 not receiving any anticoagulant therapy would have 1.9%-2.8% chance of having a stroke within a year, whereas someone with a score of 6 would have an 18.2% chance of having a stroke. Aspirin is recommended for A-Fib patients who have a low to intermediate risk of stroke, but aspirin only provides modest protection.¹¹⁵.
    Dr. Camm pointed out that the CHADS2 risk score model doesn’t take into account other less predictive risk factors such as female gender, coronary artery disease, age 65-74, and thyrotoxicosis (overactive thyroid). (Editor's Note: A-Fib by itself, such as Lone A-Fib with no other risk factors, is not part of the CHADS2 risk model for stroke. The chances of low-risk or intermediate-risk A-Fib patients getting an A-Fib stroke, according to the Center for Shared Decision Making, are:
    Under age 65 with no history of hypertension, stroke, arterial embolism, left ventricular dysfunction, or TIA:
        Chance of stroke in two years 2 out of 100
        Taking daily coated aspirin 1.5 out of 100
        Taking daily warfarin 1 out of 100)
    Age 65-75 with no history of hypertension, stroke, arterial embolism, left ventricular dysfunction, or TIA:
        Chance of stroke in two years 4 out of 100
        Taking daily coated aspirin 3 out of 100
        Taking daily warfarin 2 out of 100¹¹⁷

ASPIRIN VS. WARFARIN EFFECTIVENESS
    Dr. Camm cited seven recent studies which together showed a 22% overall risk reduction effectiveness of aspirin in preventing A-Fib stroke. However, the range of these studies varied from 2% to 39% and was not consistent. "The evidence for aspirin thrombus prophylaxis (preventing clot formation) is marginal and at best modest."
    However, studies comparing warfarin to both a placebo and to aspirin demonstrated compelling, convincing evidence of the effectiveness of warfarin. "There can be no doubt that warfarin is superior to aspirin." Warfarin had a 64% relative risk reduction in preventing A-Fib stroke vs. a questionable 22% for aspirin. "There is little if any efficacy for aspirin."

WARFARIN UNDERUSED
    Both the young (under 55) and the elderly tend to under use warfarin. The difficulty of maintaining the proper INR (International Normalized Ratio) is a factor. But also 40% of those at high risk of stroke, particularly the elderly, aren’t receiving warfarin therapy, often because of an assumed inherent risk of hemorrhagic stroke. (The risk of a hemorrhagic [bleeding] stroke increases when the INR level goes above 4. An ideal INR level is between 2-3, Below 2 one runs more of a risk of an A-Fib ischemic stroke.)
    Even young Paroxysmal (Intermittent) A-Fib patients with a high risk of stroke aren’t being properly anticoagulated. But studies show that there is no difference in A-Fib stroke risk between Persistent and Paroxysmal A-Fib. Warfarin therapy should depend on one’s CHADS2 score, not on what type of A-Fib one has.

SILENT CEREBRAL STROKE
    Dr. Camm cited several disturbing studies which showed that A-Fib patients, without any apparent neurological symptoms, often had silent cerebral strokes (15%-26%) which showed up on computer tomography images of the brain. A-Fib patients with these "silent" strokes are at much greater risk of a subsequent stroke. (If you've had A-Fib for a while, you might want to discuss with your doctor getting a computer tomography (CT) scan of your brain to see if you've had any "silent" strokes or TIAs [Transient Ischemic Attacks]. But be aware of the possible long term dangers of too much exposure to radiation through CTs, X-rays, etc.)

GENETIC WARFARIN THERAPY
    Using genotypes to help determine warfarin dosage reduces the number of times an A-Fib patient is out of INR range, and the number of times INR has to be calculated. But it doesn’t seem to make a significant difference in keeping patients in the approved INR range. See FDA APPROVES GENETIC TESTING LABELING FOR COUMADIN

CONCLUSION
    The prevention of A-Fib by improved medications, and/or by Pulmonary Vein Ablation procedures (which have a 75%-85% success rate) may reduce the prevalence of stroke by almost one-quarter in the general population, particularly in the elderly. (In this author’s opinion, one of the major advantages of a successful Pulmonary Vein Ablation procedure is the reduction of A-Fib stroke risk. Studies indicate that a successful catheter ablation does lower the risk of an A-Fib stroke without having to take warfarin.¹¹⁶ But see also the danger of stroke from "silent" A-Fib attacks after catheter ablation.)

The second presenter on the 3-person stroke prevention panel was Dr. Albert Waldo of University Hospitals of Cleveland, OH who talked about "Novel Medical Approaches to Thrombo-Prophylaxis"

    Though warfarin (brand name Coumadin) is very effective and reduces the risk of A-Fib-related stroke by about 70%, doctors are very aware of its problems and wish there were better options for patients.
    (Warfarin is what is called a Vitamin K Antagonist (VKA). A technical description of how VKAs work is the following: "they prevent the y-carboxylation of the vitamin K-dependent coagulation factor prothrombin and Factors VII, IX, and X."¹¹⁵ In layman’s terms warfarin works by affecting several steps in the anticoagulation pathway to prevent clotting.)

WARFARIN PROBLEMS

1. Narrow therapeutic window. Insufficient anticoagulation (INR less than 2) may result in stroke. Over-anticoagulation (INR over 4) increases the risk of bleeding.
2. Late onset and offset. A patient has to be taking warfarin for a while for it to reach a therapeutic level.
3. Unpredictable dose response. Genetic and other factors may influence how individuals react to warfarin.
4. Drug-drug interactions. Certain drugs (and some supplements) interfere with warfarin.
5. Drug-food interactions. People taking warfarin must limit foods containing vitamin K (like broccoli or some leafy vegetables)
6. Problematic monitoring. It’s very difficult for both doctors and patients to monitor INR levels. Patients may be required to visit a doctor’s office weekly in order to be adequately monitored.
7. Slow reversibility. It’s difficult to reverse, for example, a too high INR level.

    Dr. Waldo pointed out that this was only a partial list of the problems with warfarin.

FUTURE ALTERNATIVES TO WARFARIN
    Dr. Waldo discussed ongoing research and clinical trials of alternatives to warfarin.
    One of the most promising seems to be dabigatran, a direct thrombin inhibitor (affecting the last stage in the anticoagulation pathway). (A more technical description of how dabigatran works is: "In the final step of the coagulation pathway, thrombin converts fibrinogen to fibrin. Dabigatran binds directly to thrombin, blocking its interaction within substrates and thereby preventing fibrin formation, thrombin-mediated activation of Factors V, VIII, XI, and XIII, and thrombin-induced platelet aggregation.¹¹⁵)
    Dabigatran is in Phase III clinical trials with 15,000 patients. (Phase III is usually the last phase before FDA approval.) Results are expected in 2010.
    So far dabigatran seems to be as effective and safe as warfarin. It’s administered as a pill and doesn’t require frequent monitoring. It starts working right away and has a wide therapeutic window. Its effects are reliably predictable. It doesn’t seem to have many food and drug interactions, and can be administered in fixed doses. (The other direct thrombin inhibitor formerly in clinical trails, ximelagatran, was rejected by the FDA because of liver toxicity and heart problems. Dabigatran doesn’t seem to have those problems.)

    Other possible future alternatives to warfarin are Factor Xa Inhibitors which work further up the anticoagulation pathway. They may cause fewer side effects, because they affect mainly coagulation and not other functions like thrombin. There are many different Factor Xa medicines in development, but they are not as far along in clinical trials as dabigatran.

Dr. Vivek Reddy of Massachusetts General in Boston, MA was the third speaker of the 3-person panel on Stroke Prophylaxis in the A-Fib Patient. His topic was "Novel Catheter Approaches to Thrombo-Prophylaxis (Prevention)."   

    (Editor's Note: Dr. Reddy's presentation raised an important question: what if the threat of A-Fib stroke could be easily eliminated without having to take warfarin or other meds? This may be possible in the near future because of the Watchman device.)
    Dr. Vivek Reddy described ongoing clinical trials of the Watchman device which closes off the Left Atrial Appendage (LAA) where most A-Fib clots originate. (The Watchman device is produced by Atritech, Inc., Plymouth, MN; http://www.atritech.net. Graphics courtesy of WATCHMAN®)

HOW THE WATCHMAN DEVICE WORKS

    Once a patient's Left Atrial Appendage is measured, a wide-sheathed catheter with a spline is used to insert the Watchman device which has a self-expanding Nitinol (a special metal) open-ended circular frame. The atrial surface of this frame is covered with a thin, permeable 160 μm (micron) pore filter made of polyester material (Polyethylene Terephthalate known as Dacron or PET). This filter allows blood to pass through while stopping clots. Little hooks or anchors called fixation barbs at the middle of the device make sure it is attached firmly to the LAA wall. The Watchman device comes in multiple sizes from 21mm to 33mm to accommodate the different sizes of LAAs.
     Before the catheter is removed (which fixes the Watchman device in place), contrast agents are used to make sure the Watchman device is stable and entirely closes off the LAA opening. Over time heart tissue grows over the polyester (PET) material so that it completely closes off the LAA with smooth heart tissue similar to other heart surfaces.
    Some doctors are inserting the Watchman device in as little as 20 minutes. It is a low risk procedure with no surgery or ablation involved.
    Patients on Coumadin continue to take it for six weeks after the Watchman device is inserted. They are then examined using a TEE (Transesophageal Echogram) to make sure there is complete closure of the LAA. At that time they are taken off of Coumadin.

    You can see a video of how the Watchman device is deployed at:

http://www.atritech.net/media/deviceanimation.aspx

CLOSING OFF THE LAA AND A-FIB STROKE
    The theory behind the Watchman device is that most A-Fib clots are found in the Left Atrial Appendage (LAA). Dr. Reddy cited a study where 98% of A-Fib strokes came from the LAA.
    Studies of the early Maze operations (in which the Left Atrial Appendage was routinely cut out and sewn shut) showed a major decrease in A-Fib strokes. After 11 1/2 years of following 265 patients, only one had a stroke. However, there was no way to determine if this stroke risk reduction was due to the elimination of A-Fib or to the excision of the LAA.
    Dr. Reddy cited studies of current Mini-Maze operations which show a high percentage of incomplete closure of the LAA. Even though surgeons have direct vision of the LAA and can over-sew or re-staple, sutures have a less than 50% success rate, while staples have a success rate of around 72%. In addition, 20% of patients in these studies later had strokes.
    Instead of sewing or using staples, surgeons are also researching the use of a fabric coated band which is placed as close to the base of the LAA as possible. This band draws shut and closes off the LAA in 16 weeks.

PRELIMINARY DATA ON THE WATCHMAN DEVICE
    Preliminary non-randomized data from the Watchman device clinical trials has been very positive. Following some patients for up to 5 years, there have been no strokes, cardiovascular deaths, or systemic embolisms (there were concerns about possible air bubbles forming in the heart due to the large catheter sheath used to insert the Watchman device).
    Of the people who applied to participate in the Watchman clinical trials, 80% were accepted. Patients had to have a CHADS2 score of at least 1. Also, patients with Vagal A-Fib were excluded (Dr. Reddy reported that some researchers suspect that Vagal A-Fib patients tend to have less clots originating in the LAA). (An acceptance rate of 80% for a clinical trial indicates that the Watchman device, if and/or when it receives FDA approval, will be available for many, if not most A-Fib patients.)
    The Watchman device clinical trial is entitled "PROTECT-AF." (The full title is: Watchman Left Atrial Appendage System for Embolic PROTECTion in Patients with Atrial Fibrillation.) It is a multi-center, prospective, randomized-controlled trial at 60 medical centers across the US comparing the Watchman device to drug therapy using warfarin (brand name Coumadin). It attempts to answer the question, "Can the Watchman device replace warfarin treatment in A-Fib patients?" (In the future a subset of these clinical trials will include patients who can not take Coumadin.)
    It will also directly measure how important the Left Atrial Appendage is to the development of A-Fib stroke.
    This clinical trial also examines if there are potential detrimental effects of closing off the Left Atrial Appendage.

EDITOR'S COMMENTS
    Though some heart pumping dynamics and other functions of the LAA may be lost when the Watchman device closes off the LAA, this seems a small price to pay to be freed from the threat of an A-Fib stroke.

FUTURE USE OF THE WATCHMAN DEVICE
    If the Watchman device works as well as preliminary data indicate and if the FDA approves it, how will it be used? Will it be a stand-alone procedure, or will it be routinely inserted as part of an A-Fib ablation procedure? (The following opinions are speculative and depend on the results of the ongoing clinical trials.)

The Watchman device as a stand-alone procedure
     
    Since A-Fib is so damaging to the heart and to one's overall health, most A-Fib patients probably won't be satisfied with just having their Left Atrial Appendage closed off by the Watchman device, even though this would virtually eliminate the threat of an A-Fib stroke.
    People with other risks of stroke than A-Fib may opt for insertion of the Watchman device to prevent stroke.
    If insertion of the Watchman device becomes routine and easy to do, someone newly diagnosed with A-Fib with a moderate to high risk of stroke may have the Watchman device insertion procedure right away, while waiting for a  catheter ablation to cure their A-Fib.
    Asymptomatic A-Fib patients at risk of stroke but who don't want to take warfarin may be prime candidates for the Watchman device.
    Young people and athletes with A-Fib who do not have a high risk of stroke may not want the Watchman device, because of the potential damage to their heart's dynamics from losing the Left Atrial Appendage.

The Watchman device as part of a catheter ablation procedure
    If the Watchman device works as intended, it may become part of most catheter ablation procedures. If the catheter ablation procedure were unsuccessful or in case of silent A-Fib attacks after ablation, the patient would still be protected from A-Fib stroke by the closing off of the Left Atrial Appendage. 

(More to follow.)