Atrial Fibrillation Study Research Paper
Atrial fibrillation (AF), not to be confused with atrial flutter, is the term used to describe an irregular or abnormal heart rate.1 While AF and atrial flutter are similar,2 AF has more serious health implications such as an increased risk of having a stroke or a blood clot (thrombosis).
Many patients with atrial fibrillation are not on optimal therapy, according to a recent study that found one-third of patients are not prescribed the gold standard for blood thinners.Atrial Fibrillation Study Research Paper
To diagnose atrial fibrillation, your doctor may review your signs and symptoms, review your medical history, and conduct a physical examination. Your doctor may order several tests to diagnose your condition, including:
Electrocardiogram (ECG). An ECG uses small sensors (electrodes) attached to your chest and arms to sense and record electrical signals as they travel through your heart. This test is a primary tool for diagnosing atrial fibrillation.
Holter monitor. This portable ECG device is carried in your pocket or worn on a belt or shoulder strap. It records your heart’s activity for 24 hours or longer, which provides your doctor with a prolonged look at your heart rhythms.
Event recorder. This portable ECG device is intended to monitor your heart activity over a few weeks to a few months. When you experience symptoms of a fast heart rate, you push a button, and an ECG strip of the preceding few minutes and following few minutes is recorded. This permits your doctor to determine your heart rhythm at the time of your symptoms.
Echocardiogram. This test uses sound waves to create moving pictures of your heart. Usually, a wandlike device (transducer) is held on your chest. Sometimes, a flexible tube with the transducer is guided down your throat through to your esophagus. Your doctor may use an echocardiogram to diagnose structural heart disease or blood clots in the heart.
Blood tests. These help your doctor rule out thyroid problems or other substances in your blood that may lead to atrial fibrillation.
Stress test. Also called exercise testing, stress testing involves running tests on your heart while you’re exercising.
Chest X-ray. X-ray images help your doctor see the condition of your lungs and heart. Your doctor can also use an X-ray to diagnose conditions other than atrial fibrillation that may explain your signs and symptoms.Atrial Fibrillation Study Research Paper
The atrial fibrillation treatment that is most appropriate for you will depend on how long you’ve had atrial fibrillation, how bothersome your symptoms are and the underlying cause of your atrial fibrillation. Generally, the treatment goals for atrial fibrillation are
Reset the rhythm or control the rate
Prevent blood clots, which may decrease the risk of a stroke
The strategy you and your doctor choose depends on many factors, including whether you have other problems with your heart and if you’re able to take medications that can control your heart rhythm. In some cases, you may need a more invasive treatment, such as medical procedures using catheters or surgery.
In some people, a specific event or an underlying condition, such as a thyroid disorder, may trigger atrial fibrillation. Treating the condition causing atrial fibrillation may help relieve your heart rhythm problems. If your symptoms are bothersome or if this is your first episode of atrial fibrillation, your doctor may attempt to reset the rhythm.
Resetting your heart’s rhythm
Ideally, to treat atrial fibrillation, the heart rate and rhythm are reset to normal. To correct your condition, doctors may be able to reset your heart to its regular rhythm (sinus rhythm) using a procedure called cardioversion, depending on the underlying cause of atrial fibrillation and how long you’ve had it.
Cardioversion can be done in two ways:
Electrical cardioversion. In this brief procedure, an electrical shock is delivered to your heart through paddles or patches placed on your chest. The shock stops your heart’s electrical activity for a short moment. The goal is to reset your heart’s normal rhythm.
You will be given a sedative before the procedure, so you shouldn’t feel the electric shock. You may also receive medications to help restore a normal heartbeat (anti-arrhythmics) before the procedure.
Cardioversion with drugs. This form of cardioversion uses medications called anti-arrhythmics to help restore normal sinus rhythm. Depending on your heart condition, you may receive medications through an IV or by mouth to help return your heart to normal rhythm.
This is often done in the hospital with continuous monitoring of your heart rate. If your heart rhythm returns to normal, your doctor often will prescribe the same anti-arrhythmic medication or a similar one to try to prevent more spells of atrial fibrillation.
Before cardioversion, you may be given warfarin or another blood-thinning medication for several weeks to reduce the risk of blood clots and strokes. If your episode of atrial fibrillation lasted more than 48 hours, you may need to take this type of medication for at least a month after the procedure to prevent blood clots in the heart.
Maintaining a normal heart rhythm
After electrical cardioversion, your doctor may prescribe anti-arrhythmic medications to help prevent future episodes of atrial fibrillation. Medications may include:Atrial Fibrillation Study Research Paper
Although these drugs may help maintain a normal heart rhythm, they can cause side effects, including:
Rarely, they may cause ventricular arrhythmias — life-threatening rhythm disturbances originating in the heart’s lower chambers. These medications may be needed indefinitely. Even with medications, there is a chance of another episode of atrial fibrillation.
Heart rate control
You may be prescribed medications to control how fast your heart beats and restore it to a normal rate.
Digoxin. This medication may control the heart rate at rest, but not as well during activity. Most people need additional or alternative medications, such as calcium channel blockers or beta blockers.
Beta blockers. These medications can help to slow the heart rate at rest and during activity. They may cause side effects such as low blood pressure (hypotension).
Calcium channel blockers. These medicines also can control your heart rate, but may need to be avoided if you have heart failure or low blood pressure.
Catheter and surgical procedures
A heart during catheter ablation
Catheter ablation to isolate the pulmonary veins to treat atrial fibrillation
A heart during AV node ablation
AV node ablation
Sometimes medications or cardioversion to control atrial fibrillation doesn’t work. In those cases, your doctor may recommend a procedure to destroy the area of heart tissue that’s causing the erratic electrical signals and restore your heart to a normal rhythm. These options can include:
Catheter ablation. During this procedure, a doctor inserts long, thin tubes (catheters) into your groin and guides them through blood vessels to your heart. The catheter’s tip produces radiofrequency energy, extreme cold (cryotherapy) or heat to destroy areas of heart tissue that are causing rapid and irregular heartbeats. Scar tissue forms, which helps signaling return to normal. Cardiac ablation may correct the arrhythmia without the need for medications or implantable devices.
Your doctor may recommend this procedure if you have atrial fibrillation and an otherwise normal heart and medication has not improved your symptoms. It may also be helpful for heart failure patients who have an implanted device and cannot take or tolerate anti-arrhythmic medications.
Maze procedure. There are several variations of the maze procedure. The doctor may use a scalpel, radiofrequency or extreme cold (cryotherapy) to create a pattern of scar tissue that interferes with stray electrical impulses that cause atrial fibrillation.
The maze procedures have a high success rate, but atrial fibrillation may come back. If this happens, you may need another cardiac ablation or other heart treatment.Atrial Fibrillation Study Research Paper
Because the surgical maze procedure (using a scalpel) requires open-heart surgery, it’s generally reserved for people who don’t get better with other treatments or when it can be done during a necessary heart surgery, such as coronary artery bypass surgery or heart valve repair.
Atrioventricular (AV) node ablation. If medications or other forms of catheter ablation don’t work or cause side effects, or if you’re not a good candidate for these therapies, AV node ablation may be an option. The procedure involves using a catheter to deliver radiofrequency energy to the pathway (AV node) connecting the upper and lower heart chambers.
The procedure destroys a small area of heart tissue, preventing abnormal signaling. However, the upper chambers of the heart (atria) will still quiver. You’ll need a pacemaker to be implanted to keep the lower chambers (ventricles) beating properly. You’ll need to take blood thinners after this procedure to reduce the risk of a stroke due to atrial fibrillation.
Published in the Journal of the American College of Cardiology, this study looked at blood thinner use among patients with atrial fibrillation. Atrial fibrillation (or AFib) is the most common type of irregular heart rhythm, affecting up to 6 million people in the United States.
Since atrial fibrillation increases risk of stroke, blood thinners are recommended to prevent clots and reduce risk for heart events. Current guidelines recommend prescription blood thinners like warfarin for AFib patients at moderate to high risk of stroke, rather than aspirin alone. But how well are we meeting guidelines in the real world?
To learn more, researchers analyzed data from the American College of Cardiology’s PINNACLE Registry, which tracks heart patients to improve care and treatment. More than 505,000 AFib patients were included in the analysis, all of whom enrolled in the registry between 2008 and 2012 and took some form of blood thinner as part of therapy. Patients also had moderate to high risk for stroke based on risk factors like age and blood pressure.
Stress can contribute to heart rhythm disorders (arrhythmias) such as atrial fibrillation. Some studies suggest that stress and mental health issues may cause your atrial fibrillation symptoms to worsen. High levels of stress may also be linked to other health problems. Coping with your stress is important for your health.Atrial Fibrillation Study Research Paper
Manage your stress
Finding ways to manage your stress may help improve your health and manage your condition.
Some stress management ideas include:
Support from family and friends
Regular physical activity
A healthy diet
A positive attitude
If these stress management techniques aren’t helping, talk to your doctor.
Depression and anxiety
There is a complex relationship between atrial fibrillation and anxiety and depression.
Some research shows that people with atrial fibrillation may be more affected by depression and anxiety.
Having depression or anxiety may negatively affect your quality of life and the severity of your atrial fibrillation symptoms.
At present, researchers don’t know whether people with anxiety or depression are more likely to develop atrial fibrillation or whether having atrial fibrillation increases the risk of anxiety and depression.
More research is needed to fully understand the complex relationship between atrial fibrillation and these mental health conditions.
If you have symptoms of depression or anxiety — such as persistent feelings of sadness or worry, difficulty concentrating, and loss of interest in most activities — talk with your doctor. He or she may recommend you see a specialist trained in mental health conditions (psychologist or psychiatrist) for diagnosis and treatment.
Based on current guidelines, prescription blood thinners should have been recommended for all patients included in this study, rather than aspirin alone. However, only 60–62% of patients were treated with warfarin or non-vitamin K antagonist drugs, while the remaining 38–40% took aspirin only.
After analysis, researchers found that patients with high blood pressure, high cholesterol and heart disease were more likely to take aspirin only than those without. In contrast, patients taking prescription blood thinners were more likely to be male, overweight or obese and have a history of stroke or heart failure.
Based on findings, it’s clear that treatment recommendations are not being consistently applied to patients with atrial fibrillation. Among patients eligible for prescription blood thinners, one-third of patients do not receive optimal therapy. This gap in care is especially prominent among patients with AFib and heart disease, who are at particularly high risk for heart events.Atrial Fibrillation Study Research Paper
To address this issue, experts highlight the need to increase appropriate prescription of prescription blood thinners in patients with atrial fibrillation. Authors also encourage future research to better understand the factors that drive sub-optimal therapy in AFib patients.
In atrial fibrillation, the upper chamber of the heart beats irregularly,” said Patrick Ellinor, a cardiologist at Massachusetts General Hospital, a professor of medicine at Harvard Medical School, and an associate member of the Broad Institute of MIT and Harvard who helped lead the new study. “The electrical chaos in this chamber is similar to what happens after you throw a handful of pebbles into a pond and waves crash into each other randomly.”
The American College of Cardiology, American Heart Association and Heart Rhythm Society in January released a new guideline on atrial fibrillation. Reflecting the latest research, it updates the guideline published in 2014. Here’s what you should know about the recommendations, and what they mean for people living with atrial fibrillation.
About Atrial Fibrillation
Atrial fibrillation, also called AFib, is the most common type of abnormal heart rhythm and affects more than 3 million adults in the United States. It occurs when your heart beats too slowly, too quickly or in an irregular way. Atrial fibrillation can cause poor blood flow to the rest of your body. If you have AFib, you may feel:
Shortness of breath
Atrial Fibrillation also can make it more likely for you to develop blood clots, have a stroke, heart failure or other problems. You are at greater risk of having a stroke because when your heartbeat is out of sync, blood can pool in parts of your heart and form clots. Those blood clots can travel to the brain, which causes a stroke. Strokes related to AFib tend to be more severe and deadly.
The good news is that finding out you have AFib and treating it early on can improve your quality of life and help you live longer.Atrial Fibrillation Study Research Paper
Infographic: Atrial Fibrillation
(Click to view)
Diagnosis and Treatment
AFib can be found with several tests, such as a stress test, electrocardiogram or echocardiogram. These tests help monitor your heart’s activity and detect any abnormal heart rhythms that may occur.
If you have AFib, treatment will depend on how severe your symptoms are and what the underlying cause is. Your treatment may include any combination of lifestyle changes, medication or procedures. The main goals are to stop abnormal heart rhythms and make it less likely for you to have a stroke.
2018 Guideline Updates
The latest guideline updates specific sections of the 2014 recommendations. Updates are based on new data as well as new guidance from the U.S. Food and Drug Administration.
An important change is that, in general, new blood thinners now are recommended over warfarin, the longtime standard choice of blood thinner. The newer options, often called NOACs (non-vitamin K oral anticoagulants), are easier to take than warfarin. They require less monitoring and often have fewer drug interactions. NOACs are as safe and effective as warfarin — if not more — studies show.
However, these recommendations do not apply to patients who have a mechanical heart valve or severe mitral stenosis. If you have mitral stenosis, the valve on the left side of your heart cannot open as wide and so lets less blood through.
Infographic: Atrial Fibrillation,
Stroke and Blood Thinners
(Click to view)
Newly Approved Treatments
Two treatments have been added to the list of options to help people with atrial fibrillation. A new medicine called edoxaban has been cleared to prevent blood clots and stroke in patients with AFib. Edoxoban is also a NOAC (non-vitamin K oral anticoagulant).
Also, a new device called the Watchman device has been approved to help prevent stroke in patients at high risk who have problems with using blood thinners for the long term. The device is placed in a part of the heart to prevent blood clots from moving from the heart to the rest of the body.Atrial Fibrillation Study Research Paper
Keep in mind that a number of factors help determine which treatment is best for you, such as your risk of stroke and your current treatments. You and your care team will talk about the options.
MORE: For help understanding your options, visit CardioSmart.org/AFibDecisionAids
A number of lifestyle factors make it more likely for you to have AFib, such as having obesity or drinking too much alcohol. If you have sleep apnea, high blood pressure or diabetes, your chance of developing AFib also may be greater. Controlling or avoiding these conditions can help lower your chance of developing atrial fibrillation.
New studies suggest that addressing weight, sleep apnea and alcohol use also can help patients with AFib control their condition. In fact, research shows that if you are overweight or obese, the number of pounds you lose can affect how much your symptoms improve. The more weight you lose, the fewer symptoms of atrial fibrillation you may have.
To get the heart pumping normally again, cardiologists may try to shock the heart back into a normal rhythm, but that doesn’t work for all patients. In some cases, more invasive procedures are done to attempt to control the heart’s rhythm. Most who are diagnosed with AF will take blood thinners for their entire lives to reduce the risk for stroke, a treatment that addresses a potential complication of the disease rather than its cause and increases the risk of dangerous bleeding.
With the goal of opening the door to new AF treatments, Ellinor and fellow researchers at the Broad several years ago set out to uncover AF’s genetic roots via the institute’s partnership with Bayer aimed at leveraging insights from human genetics to help create new cardiovascular therapies. While AF is more common in the elderly, inherited genetic risk factors that lead even some young people to develop the condition could be the key to novel therapies. Working with colleagues around the globe to gather existing genetic data and generate new data from more than half a million people representing four ethnic groups, including more than 65,000 with AF, the team identified dozens of new genetic risk factors for the condition. Of the nearly 100 genetic regions associated with risk of developing AF, 67 were never before linked to the disease.
Further analyses of the samples revealed that many of these genes exhibit different levels of expression between healthy patients and those with AF; some of these genes are associated with the development of cardiac tissue, its electrophysiological capabilities, and the structural and contractile properties of cardiac muscle.Atrial Fibrillation Study Research Paper
“Our results provide a more complete picture of the genomic basis of atrial fibrillation,” said Carolina Roselli, a computational biologist in the Broad’s Cardiovascular Disease Initiative who led the study’s data analysis. “I am very excited for our team to take these findings into the lab to learn more about the molecular mechanisms responsible for the disease.”
While insights from this study may help to generate new AF treatments, Ellinor stressed that they have much work to do before patients see new drugs in the clinic. “The findings give us a really good foundation for what we ought to be studying in the lab,” he said. “It’s a much broader portfolio of genes and pathways to focus on that we just haven’t had in the past, and we’re excited about the future possibilities
Atrial fibrillation (AF) poses a major global public health challenge because it is increasing in prevalence and is associated with an increased risk of stroke, dementia, heart failure, and death.1–3 In response to the many challenges posed by AF, the American Heart Association (AHA) convened a conference in Washington, DC, on June 12–13, 2010, that included patients, nurses, physicians, and healthcare policy makers and regulators. In addition, basic, translational, population, outcomes, and clinical scientists participated (Appendix). The 22 presentations and 6 panel discussions were organized into 4 sessions: (1) Mechanisms of AF: Basic and Translational Science and Genetics; (2) Epidemiology, Outcomes, Cost, AF, and Stroke Prevention; (3) Meeting the Clinical Challenges in AF; and (4) Redefining the Therapeutic Goals of AF (Appendix). The focus of the present report is to provide an overview of the key concepts presented and the core recommendations made by the summit participants.Atrial Fibrillation Study Research Paper
Atrial fibrillation (often called “A-fib” or AF) is the most common type of abnormal heartbeat. In a normal heartbeat, the four chambers of the heart work in a steady, rhythmic way. With atrial fibrillation, disorganized electrical signals cause the upper two chambers of the heart (the atria) to quiver, contracting in a very fast (often more than 300 beats per minute) and irregular way (fibrillating)—hence the name. In turn, that rapid and irregular upper chamber beating causes the lower chamber to beat more rapidly than normal, also in an irregular way. In some patients the atrial fibrillation causes the lower chamber to beat faster than 100 to 175 beats per minute (bpm). A normal heartbeat, in contrast, is very regular and beats at about 60 bpm at rest.
“It’s best to consider atrial fibrillation as a medical condition rather than a disease,” says Johns Hopkins cardiologist Hugh Calkins, M.D. “The more patients learn about this condition, the better equipped they are to be active partners in management.”
Atrial fibrillation can be a dangerous condition because it dramatically increases the risk of stroke, by as much as fivefold. Most strokes that are caused by atrial fibrillation result in permanent disability or death.
About 15 percent to 20 percent of all strokes are due to A-fib. What happens is this: Like a sponge that doesn’t get completely wrung out or emptied, the heart of a person with A-fib is unable to move blood fully from chamber to chamber, raising the risk of clotting. A clot can then be pumped to the brain, causing a type of stroke called embolic stroke.
Inefficient pumping can also cause another, but less common, condition called heart failure. In this case, the heart beats inefficiently, causing blood to back up in the heart and resulting in fluid in the lungs, says Calkins.
In addition to heart failure, atrial fibrillation has been linked to dementia. This may be related to multiple small strokes that affect the memory centers of the brain.
About 2.7 million Americans have been diagnosed with atrial fibrillation. Even more have the condition but aren’t aware of symptoms.
Not all cases of atrial fibrillation can be prevented. By taking steps to avoid coronary artery disease or high blood pressure, however, you can help avoid developing A-fib due to these causes. The basics include not smoking, following a heart-healthy Mediterranean-style diet (high in plant-based foods, fruits and vegetables, and low in saturated fats), being physically active and keeping to a normal weight (as indicated on a body-mass index chart).Atrial Fibrillation Study Research Paper
Atrial fibrillation is a progressive condition that tends to worsen over time. It’s important to know that atrial fibrillation sometimes causes no symptoms at all. The condition may be diagnosed after complaints of symptoms lead to an examination and tests, or it may be discovered during testing for other heart conditions. Your doctor will try to pinpoint what’s causing it.
Tests used to diagnose atrial fibrillation include:
Electrocardiogram (ECG or EKG): This test, which evaluates the heart’s electrical activity, can usually confirm the condition.
Holter monitor : This portable monitor tracks the heart’s electrical activity over 24 to 48 hours. It’s useful because some people are not in atrial fibrillation all the time. While wearing the monitor, you go about your normal activities. Some monitors can be worn for longer (an event monitor is usually work for four weeks) — they start tracking when irregular activity in the heart is detected .
Stress test : A “treadmill test” (so called because it’s typically done using one) checks the heart when it has to pump hard and faster during exercise.
Echocardiogram (transthoracic echocardiogram): This test uses sound waves to create a moving picture of the heart and evaluate the size of the atria and the overall heart function.
Transesophageal echocardiogram : Because it’s easier to see the atria of the heart through the esophagus (the canal that connects the mouth, throat and stomach), this sound wave test is administered through the throat. “It’s useful in detecting if a blood clot has formed in the atrium prior to a cardioversion procedure,” Calkins says.
Chest X-ray : An X-ray is used to see complications of A-fib in the heart and lungs.
Blood tests : The results may be used to evaluate heart markers, like cholesterol, as well as thyroid and electrolyte levels.
“With the latest medical options, including new blood-thinning medications and catheter ablation [radiofrequency energy sent to the heart via thin wires guided through blood vessels] of atrial fibrillation, AF patients are getting the best treatments ever,” Calkins says.
How atrial fibrillation is treated depends on the underlying cause, and on the frequency and severity of symptoms. In general, your doctor aims to:
Reduce your risk of stroke. Most people need a type of blood-thinner medication (such as warfarin, apixaban, rivaroxaban or dabigatran) to reduce the risk of clotting. With warfarin, frequent blood checks are needed to monitor effectiveness and dose, but this is not required for the newer blood thinners, says Calkins. Medication decisions are based on assessment of your stroke risk. Most patients with AF who are over age 65 require a blood thinner, Calkins says.Atrial Fibrillation Study Research Paper
New Treatment Option. If you are unable to take a blood thinner because of risk of bleeding or falls, your doctor may recommend a procedure to occlude your left atrial appendage. Find out more about these options here .
Manage “rate control.” That’s the rate at which the lower chambers of the heart are beating. Medications that do this include beta-blockers.
Restore a normal heart rhythm. If symptoms persist despite having a controlled heart rate, efforts to restore and maintain the heart’s rhythm are often undertaken. One way normal rhythm can be restored is with a procedure called electrical cardioversion. Anti-arrhythmic medications can also be used. If these options are ineffective, catheter ablation can be performed. This procedure is used to eliminate atrial fibrillation by cauterizing certain areas in the heart that cause atrial fibrillation, says Calkins. Your doctor can explain this procedure to you in more detail.
Treat any underlying disorder, such as a thyroid problem or high blood pressure. For heart problems, lifestyle changes that improve weight and blood markers—a heart-healthy diet, being more active and losing weight if needed—can help. Medications may be given to manage certain conditions. In some cases, surgery is needed to repair damaged arteries (if there’s coronary artery disease) or heart valves (if there’s rheumatic heart disease).
Living With Atrial Fibrillation
Having A-fib and not knowing when quivering episodes will start may cause you stress. But by carefully managing your condition, you’ll feel better physically and mentally. Many people with this disorder lead normal, active lives.
“The main concern in patients with AF is stroke,” Calkins says. “It’s important that you meet with your physician and determine if your stroke risk warrants treatment with a blood-thinning medication. This is the single most important aspect of AF management.”
Be sure to follow medication guidelines carefully. When you take a blood-thinner called warfarin, you need to have your blood checked monthly to evaluate effectiveness. Don’t double up on a dose if you miss one—consult your doctor. With all blood thinners, you can bleed more easily, so let your doctor know if you notice any unusual bruising or bleeding. Your doctor may also advise dietary changes when taking blood thinners, such as avoiding intermittent larger servings of dark leafy greens: It is much better to eat a consistent amount of green leafy vegetables on a near daily basis.Atrial Fibrillation Study Research Paper
Keep a symptom record. In a notebook, write down when you experience quivering episodes and how long they last, as well as any other symptoms. Bring this information to doctor visits. One way to check if you’re having palpitations is putting two fingers on the artery on the underside of your wrist to feel your pulse. You may be able to detect palpitations if the beating is faster or more irregular than usual, such as skipping beats.
Learn your “triggers.” Keeping a record may also help you identify causes that set off an irregular heartbeat. Common triggers for people with A-fib include stress, drinking alcohol or caffeine, doing certain exercises and consuming foods that contain the flavor enhancer monosodium glutamate (MSG). Being aware of these triggers can help you avoid them.
Johns Hopkins researchers have added much to the understanding of what causes atrial fibrillation and how to manage it. Among their accomplishments:
They defined the guidelines indicating which symptoms call for the use of catheter and surgical ablation of atrial fibrillation, based on the type of AF, the patient’s symptoms and the response to anti-arrhythmic drug therapy. These guidelines help doctors deliver the best, most up-to-date treatments. Calkins was the lead author of the Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation, published by the Heart Rhythm Society.
Johns Hopkins clinicians also helped to define the indications, techniques and outcomes of atrial fibrillation ablation, in the above expert consensus statement.
They learned that people with a history of sudden drops in blood pressure are at increased risk for later A-fib. A Johns Hopkins-led study found that those who experience orthostatic hypotension—a sudden drop in blood pressure when going from lying down to standing—have a 40 percent increase in their risk of developing atrial fibrillation over the next two decades, an important possible early warning sign.Atrial Fibrillation Study Research Paper
Atrial fibrillation (AF) is the most common arrhythmia and accounts for one-third of hospitalizations for rhythm disorders in the United States . The prevalence of AF averages 1% and increases with age, such that 10% of the population over the age of 80 has AF, and approximately 70% of cases of AF are in patients between 65 and 85 years of age . With the aging of the population, the number of patients with AF is expected to increase 150% by 2050, with more than 50% of AF patients being over the age of 80 [3–8]. This increasing burden of AF will lead to a higher incidence of stroke, as patients with AF have a five- to sevenfold greater risk of stroke than the general population [9–11]. Strokes secondary to AF have a worse prognosis than in patients without AF [12, 13]. Moreover, AF is an independent risk factor for mortality as seen in the Framingham population with an adjusted odds ratio of 1.5 in men and 1.9 in women . Vitamin K antagonists (e.g., warfarin), direct thrombin inhibitors (dabigatran), and factor Xa inhibitors (rivaroxaban and apixaban) are all oral anticoagulants that have been FDA approved for the prevention of stroke in AF. Edoxaban is another factor Xa inhibitor that is likely to be FDA approved in the coming months. In this paper, we will not cover the edoxaban experience in the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial in detail given that the primary results have just recently been published.
There has been an explosion of data emanating from these trial databases and from registries over the past 5 years which is redefining much of the knowledge around antithrombotic therapy for AF. This paper will summarize the clinical research experience with anticoagulation in patients with AF at Duke Clinical Research Institute and related work by others.
2. Risk Stratification Using Biomarkers
The CHADS2 and CHA2DS2-VASc scores are the primary tools currently used to calculate risk of stroke in patients with AF for the purpose of deciding who has sufficient risk to warrant oral anticoagulation. Although these risk stratification tools are easy to use, they only have a modest discriminating value for individual patients. For example, the CHA2DS2-VASc score has a C-statistic of 0.55–0.64, where 1.0 would represent the perfect ability to correctly rank risk and 0.5 would indicate correct classification only half the time or random chance . Given only a modest ability to discriminate the risk of stroke given available predictive factors, it is important to continue to search for new predictors of risk. There is increasing evidence to support risk stratification with the use of biomarkers for myocardial injury, cardiovascular hemodynamic stress, renal dysfunction, coagulation, and inflammation. Blood biomarkers for these conditions have an independent association with clinical events in AF and may improve risk stratification . Much of this work has been led by investigators at Uppsala Clinical Research Institute and some of it in collaboration with investigators at Duke.Atrial Fibrillation Study Research Paper
While the mechanism of cardiac troponin elevation in patients with AF is not entirely understood, detecting an elevated level of cardiac troponin has been associated with an increased risk of stroke or systemic embolism and of cardiovascular death. This was first reported in a large data set in the Randomized Evaluation of Long-term Anticoagulant Therapy (RE-LY) biomarker study and subsequently confirmed in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) biomarker study [17, 18], with these two trials including a total of 21,081 patients in the biomarker substudies. While RE-LY and ARISTOTLE used troponins I and T, respectively, both studies confirmed that having an elevated troponin level (troponin I > 0.04 ug/L and high sensitive troponin T > 13 ng/L, based on the 99th percentile upper reference limit for healthy subjects) was associated with increased rates of thromboembolic events and cardiovascular death. This relationship was independent of clinical characteristics and other biomarkers, which suggests that troponin measurements may improve the accuracy of risk stratification in AF.
In states of cardiovascular hemodynamic stress, the neurohormone B-type natriuretic peptide (BNP) is secreted from myocytes and BNP or its inactive N-terminal fragment (NT-proBNP) can be detected in the serum. In AF it is hypothesized that elevated levels of natriuretic peptide may be from diastolic dysfunction, leading to increased atrial stress, risk for thrombus formation, and chance of subsequent thromboembolic events. This hypothesis is a plausible mechanism for the association between rising levels of NT-proBNP and increased risk of thromboembolic events and cardiovascular mortality in the RE-LY biomarker study . In this study, the addition of NT-proBNP to clinical risk assessment tools improved the discrimination performance. The results of the RE-LY study were confirmed in the ARISTOTLE biomarker study, showing improvement in risk stratification for overall stroke, as well as for ischemic and for hemorrhagic subtypes, with the addition of NT-proBNP to clinical risk assessment tools . These studies identify the opportunity to use natriuretic peptides as prognostic markers in AF.Atrial Fibrillation Study Research Paper
Reduced renal function can be measured by calculations of glomerular filtration rates (GFR), based on creatinine, or by cystatin C, which is a small protein that is freely filtered by the glomerulus. Patients in ARISTOTLE showed an inverse association between GFR and rates of stroke and bleeding . In the same population, rising cystatin C levels were independently associated with increased rates of stroke or systemic embolism, mortality, and major bleeding. When added to current risk tools, cystatin C improved risk stratification. Similar findings with cystatin C were identified in the RE-LY biomarker study . While cystatin C had improved risk stratification for stroke, GFR was a better predictor of bleeding, so both markers have the potential to improve risk prediction in patients with AF.
D-dimer, a marker of coagulation in AF, may also be a clinically useful predictor of risk. A significant association between baseline D-dimer levels and risk of stroke, cardiovascular death, and major bleeding was seen in the RE-LY biomarker study and confirmed in the larger ARISTOTLE data set [17, 18].
Inflammation may be involved in the development and the perpetuation of AF, and markers of inflammation may have prognostic significance . Markers of inflammation that have been studied in AF include interleukin-6 (IL-6) and C-reactive protein (CRP). Initially, a small study reported an association between IL-6 and a composite outcome of stroke and death . A larger study subsequently found an association between CRP and all-cause mortality, in addition to a composite endpoint of TIA/stroke, systemic embolism, acute coronary syndrome, acute heart failure, and cardiac death . Finally, the RE-LY biomarker study showed an independent association between IL-6 and stroke or systemic embolism, while CRP levels were associated with cardiovascular mortality after multivariate adjustments . These studies indicate that there may be potential to use markers of inflammation in risk stratification for AF, but further investigation will need to be done prior to inclusion as a routine marker.Atrial Fibrillation Study Research Paper
3. Anticoagulation with Warfarin in High-Risk Patients
Patients with AF and acute myocardial infarction (AMI) are at high risk of death and major cardiovascular outcomes. In the Duke Databank for Cardiovascular Disease, patients with AMI and AF, who underwent cardiac catheterization during their AMI hospitalization between 1995 and 2007, tended to be older, have increased comorbidities, and have higher one-year mortality (24). Given the increase in comorbidities, this population had a higher stroke risk based on CHADS2 and CHA2DS2-VASc scores, as well as increased bleeding risk based on the ATRIA bleeding score. The identified population had a low rate of warfarin use with less than 25% of patients discharged on warfarin, and the rate of warfarin use was not correlated with stroke or with bleeding risk (Figure 1). The rate of warfarin use remained low over time, despite reductions in clopidogrel use from 6 to 12 months after discharge. These findings suggest that providers are using factors other than clinical risk stratification tools to guide anticoagulation decisions in high-risk patients. Providers may also be hesitant to prescribe triple therapy (therapy with aspirin, clopidogrel, and warfarin) because of bleeding risk . It is important to note that the current guidelines on anticoagulation in the setting of stent placement were not available at the time these patients were followed.
Mechanisms of AF: Basic and Translational Science and Genetics
Attempts to develop safe and effective pharmacological therapy for AF have focused on atrium-selective drugs that take advantage of electrophysiological differences between the atrium and ventricle.4–7 Heterogeneous abbreviation of the effective refractory period within the atrium provides the electric substrate for development of AF. The reduced effective refractory period results from abbreviation of the atrial action potential duration, which is caused by a decrease in the calcium channel current (ICa) and an increase in the potassium channel current (IK1) and the constitutively active acetylcholine-sensitive current (CA IKACh).4–7 Maintenance of AF is facilitated by structural remodeling and additional abbreviation of the effective refractory period. The principal goal of pharmacological therapy is therefore to augment the effective refractory period.Atrial Fibrillation Study Research Paper
Distinctions in the ion channel currents between the atrium and ventricle open the possibility for development of atrium-specific and -selective drugs for rhythm control of AF, which might avoid ventricular proarrhythmic effects. Atrium-specific targets include IKur, IKACh, and the constitutively active IKACh, the most investigated of which is inhibition of IKur.7 Recent experimental studies have identified atrium-selective INa blockers that can effectively suppress AF while exerting little or no effect in the ventricles.5,6 Combinations of antiarrhythmic medications, such as amiodarone and ranolazine or dronedarone and ranolazine, are a promising avenue of investigation.8,9 In animal models, such combinations produce potent synergistic effects that result in atrium-selective depression of sodium channel–dependent parameters and effective suppression of AF. Although synergism between atrium-selective drug combinations holds great promise, future work will be required to determine the safety and efficacy of such drug combinations in patients.
Multiple lines of evidence from basic, translational, and human studies suggest that atrial fibrosis plays an important role in the maintenance of AF.10–13 Understanding of the mechanisms of atrial fibrogenesis will provide better targets for antifibrotic treatment of AF. There is a lack of detailed information about the biological and electrophysiological properties of fibroblasts and myofibroblasts under normal and AF conditions. Insights into signaling pathways suggest that atrial fibroblasts can be effective therapeutic targets for prevention of fibrosis.14–16 Multiple agents with antifibrotic properties have demonstrated effects on reducing atrial fibrosis in animal models, but clinical evidence supporting their efficacy in AF prevention is currently lacking. Identification of fibroblast-specific genes will help to develop a fibroblast-specific knockout or transgenic mouse model.Atrial Fibrillation Study Research Paper
Endothelin 1, a potent vasoconstrictor and mitogen involved in blood pressure regulation, may merit further investigation in AF because it modulates calcium cycling in cardiac myocytes and promotes fibroblast proliferation.17 Because of the differential distribution of downstream signaling elements, endothelin 1 has a greater impact on atrial than on ventricular calcium cycling and contractility.17 Interestingly, atrial endothelin 1 levels are elevated in the left atrium of patients with structural heart disease and persistent AF.17
Late gadolinium enhancement by cardiac magnetic resonance imaging is a highly specific and sensitive method for detecting scar in the ventricular myocardium.18,19 Furthermore, it has been demonstrated recently that the same gadolinium-based extracellular contrast agents can be used for the quantification of extracellular remodeling and the detection of diffuse interstitial fibrosis.20,21 Development of methods for direct assessment of myocardial collagen burden using extracellular collagen-binding contrast agents might allow imaging to characterize the presence and severity of atrial fibrosis noninvasively.
Over the past 5 years, family history has been established as a risk factor for AF.22 Familial forms of AF have been described, and mutations have been identified in ion channel proteins and signaling molecules; however, these genes are rare causes of AF.23–26 Genome-wide association studies have revealed genetic risk factors for AF unanticipated by prior knowledge. In one case, the genetic variants are adjacent to a transcription factor that specifies left atrial and pulmonary vein development. How variants at this and other loci lead to AF remains unclear. Future efforts should be focused on the identification of new genetic loci, determination of the mechanism by which polymorphisms are associated with the initiation or promotion of AF, and exploration of the relation between genetic data and clinical outcomes for AF. Systems biology approaches can provide important insights by addressing the complex interactions between risk factors and disease and thus may facilitate our understanding of novel AF mechanisms.Atrial Fibrillation Study Research Paper
The resting heart rate of someone without AF is usually between 60 and 100 beats per minute1 but this number is usually over 100 beats per minute in AF.
It is usually the result of an underlying condition such as hypertension (high blood pressure) or having an overactive thyroid3 but may develop for no known reason. In this circumstance, the person is said to have ‘lone atrial fibrillation’.3 AF can affect people at any age but is rare in children and is more common in the elderly population. Atrial Fibrillation Study Research Paper