Atrial Fibrillation
What is Atrial Fibrillation?
Atrial fibrillation is an electrical disorder affecting the upper chambers of the heart, called the atria. In this condition, electrical signals in the upper chambers circulate rapidly. Rather than taking a specific path within these chambers, the electrical signal swirls around at a rate of many hundreds of beats per minute. An analogy of a sandstorm or a windstorm may be used. The impulse in the upper chamber can travel from the upper chamber to the lower chamber by a connector called the AV node, like a staircase connecting the top to the bottom floors of the building.
A consequence of these rapid electrical signals is that the upper chambers do not contract in an organized fashion. Therefore, rather than pumping out blood with considerable force, as during normal rhythm, the blood empties from the atria to the ventricles passively on its own. This decreased pumping function may result in the patient having less energy or cause a limitation of exertion (see section on symptoms associated with atrial fibrillation). In addition, the lack of coordinated contraction of the upper chambers can lead to less forceful blood flow and therefore some stagnation or pooling of blood within the heart, within the upper chambers. This may lead to an increased risk of blood clots or stroke (see section on anticoagulation and prevention of blood clots and stroke).
SYMPTOMS ASSOCIATED WITH ATRIAL FIBRILLATION
There is a wide range of symptoms in patients who have atrial fibrillation. Some patients are truly asymptomatic, without any noticeable limitations. In contrast, there are patients who appear to be much more symptomatic and become quite limited. Some patients recognize that they are in atrial fibrillation because they feel the irregularity of the heart beat or an increased heart rate. For others, they are aware they are in atrial fibrillation because of symptoms of decreased energy and increased fatigue. There may be a sense of ill-being which is much more subtle, and may not be as easy to initially detect. Some patients and their families note that there is greater irritability during episodes of atrial fibrillation.
For some patients, during exertion they notice that they have less stamina, although they are able to conduct most of their regular activities. Exertional limitation may have the manifestation of being associated with shortness of breath. This also may be relatively subtle, and only noted with extreme exertion such as carrying objects up stairs.
Some patients are most aware of the sensation they get, particularly with the heart beat extending into their upper chest and into their neck. For others, they notice the irregular beating in their head, or in the temple region. Often it is possible to sense the atrial fibrillation more in different positions. Some patients note that the atrial fibrillation is more noticeable when they are lying on their side, particularly on the left side. Thus, some patients are more aware of atrial fibrillation at rest, and others are more aware with exertion.
Since many of the treatment goals relate to the relief or improvement of symptoms, physicians spend a great deal of time inquiring about how patients feel.
TRIGGERS OF ATRIAL FIBRILLATION
Emotional triggers
Physical exhaustion
Surgery or medical procedures
Dehydration
Sleep
Hormonal influences
Caffeine
Alcohol
Exercise
Emotional triggers. There are a number of triggers of atrial fibrillation that have been described. The first section is regarding emotional triggers. Emotional triggers of various types have been described as being frequently seen as causes of atrial fibrillation. In these cases, atrial fibrillation may occur on extreme emotional stress. This also may be combined with other forms of stress such as physical stress or dehydration.
Physical exhaustion
Physical exhaustion is a common cause trigger of atrial fibrillation. There are a number of different circumstances in which this may occur. This may occur due to a long period of lack of sleep and overwork. For example, there may be an executive working on a deal and staying up several nights in a row or a student may be pulling a number of “all-nighters”. There are also is commonly physical exhaustion associated with travel. In many of these cases of physical exhaustion are related to a disturbance of sleep pattern, so it may be just not getting enough sleep, as well as an upset of the diurnal variation. This may be compounded with emotional stress, such as loss of a loved one, acute illness, or recent job disturbance. Physical exhaustion can also be that of physical exertion itself. It may occur after a particularly strenuous form of activity. Sometimes it even occurs in cool-down after a major sporting event.
Surgery or medical procedures
Patients undergoing surgery or medical procedures seem to have an increased likelihood of developing atrial fibrillation. Almost any type of surgery seems to be associated with an increase in the likelihood of developing atrial fibrillation. Atrial fibrillation may even prior to surgery with the administration of sedatives or anesthetic agents, may occur during the surgery, or after the surgery. Heart surgery is associated with a significantly increased risk of developing atrial fibrillation, in many series up to 20-30%. Medical procedures such as endoscopy (looking down into the esophagus or stomach with a camera) or colonoscopy (looking into the intestine or colon with a camera) are also more commonly associated with atrial fibrillation. Even the colonic “washout” preparation for colonoscopy may precipitate atrial fibrillation. Surgery and medical procedures may alter the autonomic nervous system, stimulating to different degrees the sympathetic and parasympathetic nervous systems. Endoscopy and colonoscopy are associated with a particular degree of parasympathetic activation.
Dehydration
Dehydration has been frequently reported as a trigger of atrial fibrillation. It commonly is associated with a change in sleeping and waking patterns, and this may be compounded by alteration in sleep as well as physical exhaustion. It frequently occurs with travel, where one is outside of one’s usual eating habits. One may be missing meals and therefore missing fluids, which can tend towards dehydration. Dehydration is common during the summer months particularly during times in increased physical exertion. Dehydration may also accompany flu-like illnesses with vomiting and diarrhea.
Sleep
Many individuals develop atrial fibrillation upon rest, but particularly develop it as they go to sleep or during sleep, and awaken with the episodes. Many people have theorized that this is related to an alteration of the balance of the autonomic nervous system which controls the body’s functions, including sleep. The autonomic nervous system incorporates a balance between sympathetic nervous system, which is involved with “fight-or- flight reaction”, and the parasympathetic nervous system, which is involved in rest and relaxation. During sleep, parasympathetic activity predominates over sympathetic activity. People have theorized that the influence of the parasympathetic system on the heart may be a particular trigger for many individuals.
Hormonal influences
It is well established that various arrhythmias may be affected by one’s hormonal fluctuations. Women in particular have noted changes at the time of their menstrual cycle. While this has been documented for a number of arrhythmias, it has not been completely evaluated for atrial fibrillation. Another major time is with the onset of menopause; during which there may be an increase in atrial fibrillation. Postmenopausal woman appear to have an increase in frequency of atrial fibrillation. There are some data relating hormonal therapy to atrial fibrillation but the data are inconclusive.
Caffeine
Caffeine is an important trigger in some individuals, but not necessarily in others. It has been clearly documented that some individuals have an increased frequency of atrial fibrillation, with excessive caffeine intake. This may include ingestion of coffee, tea, and chocolate.
Alcohol
Alcohol appears to increase the likelihood of atrial fibrillation in some individuals. This may occur with excessive alcohol, and for some individuals appears to occur with minimal alcohol. Some people with atrial fibrillation, for example, can note that even less than a glass of wine or other alcohol consumption can result in an increased frequency of atrial fibrillation. It is not well known whether there is a difference in the type of alcoholic beverage in triggering atrial fibrillation. There is evidence that alcohol creates changes in the heart muscle itself. The use of alcohol in addition to many other factors such as sleep deprivation and physical exhaustion may further increase one’s risk. Sudden intake of a moderately high dose of alcohol, often called binge drinking, may increase the likelihood of atrial fibrillation. This is often termed “Holiday Heart Syndrome”.
Exercise
Atrial fibrillation is less commonly induced by exercise; however, there are individuals in whom exercise appears to be the predominant trigger of atrial fibrillation.
Termination of atrial fibrillation. In general, most patients do not have an identifiable mechanism or method of terminating atrial fibrillation. Many individuals will note that they will rest and relax and their ventricular rate will decrease as expected. However, they will remain in atrial fibrillation. The exception may be patients for whom exercise may serve as means of termination, but this is not particularly well studied.
RATE CONTROL IN ATRIAL FIBRILLATION
In the treatment of atrial fibrillation, the control of the heart rate is very important. The heart rate in atrial fibrillation is determined by the number of impulses that goes from the upper chambers, the atria, through to the lower chambers, the ventricles.
These electrical impulses travel from the upper chamber to the lower chamber through the AV node. This is like a staircase that connects the top floor of the building to the bottom floor of the building. The AV node acts as an effective filter in blocking most of the beats that go from the top chamber to the bottom chamber.
There are a number of reasons to control the heart rate during atrial fibrillation. In many patients, controlling the heart rate markedly improves their symptoms. These symptoms may include shortness of breath, dizziness, a racing heart sensation, a pounding sensation as if their heart is going to jump out of their chest, or fatigue. Determining the rate during atrial fibrillation therefore is an important first step in treating atrial fibrillation. By assessing the heart rate in atrial fibrillation, one can determine whether it is necessary for medications to be used to control the heart rate further.
There are a number of different forms of electrocardiographic monitoring or recording that can be used to determine whether the heart rate control in atrial fibrillation is adequate. This may include a standard routine echocardiogram (ECG, EKG) that may be performed in a doctor’s office, in the hospital, or in an emergency department. Alternately, the EKG recordings may be obtained using a longer term monitor. These monitors may include a 24-hour recording using a device that the patient carries with him or herself. This is often called a Holter monitor. Other forms of monitoring include a longer term monitor that lasts several weeks. This form of monitor is able to capture the heart rate over a more extended period of time.
The appropriate heart rate for the patient will depend on the patient’s heart condition, their needs at a particular period of time, and their overall medical and cardiac status. Therefore it is not possible to select a particular heart rate for all individuals. As a rule of thumb, however, it is a common target that we will try to achieve a heart rate of approximately 60 to 80 beats per minute while at rest. In some cases, we will need to achieve a lower heart rate such as 50 beats per minute, or possibly a higher heart rate between 80 and 90 beats per minute. For example, in some cases, patients may be treated for various kinds of heart conditions such as artery problems with the heart, the heart rate may need to be slower. On the other hand, some individuals in the time of acute illness may need to have a faster heart rate such as 80 beats per minute.
During any exertion, even mild exertion, many patients with atrial fibrillation have an exaggerated heart rate increase. For example, instead of their heart rate going from 60 or 80 to 100 beats per minute with a mild walk, their heart rate might jump up to 120, 130 or 140 beats per minute. The goal of treatment therefore may also be to prevent this increase, or to prevent a large increase in heart rate with exertion.
Methods of controlling the heart rate, and slowing it, include medications that have specific effects on the AV node, the staircase that we have described between the upper and lower heart chambers. The groups of medications used to control the rate fit into three categories. These categories include beta-blockers, calcium channel blockers, and digoxin.
Beta blockers and calcium channel blockers are used for other conditions, such as high blood pressure. Beta blockers in particular may also be used in certain heart conditions which may be described as heart failure. Examples of beta blockers include metoprolol, atenolol, and carvedilol. A list of a variety of beta blockers listed in table #1. Beta blockers should be used with caution in patients with asthma. Both beta blockers and calcium channel blockers may also slow the heart rate in normal rhythm, and therefore need to be used with caution in order to prevent the heart rate from being too slow.
Some patients with atrial fibrillation have a tendency to have slow rates in normal rhythm and relatively rapid rates in atrial fibrillation. This is because the heart’s own pacemaker, the sinus node, is responsible for the rate in normal rhythm, and the sinus node may have a tendency to be slow. On the other hand, the heart rate in atrial fibrillation is largely dependent upon the properties of the AV node, which is the connector between the upper and lower chambers. In these same individuals, it is possible that the AV nodal function may be quite intact, and therefore lead to a relatively rapid rate. Some patients require a pacemaker to be implanted, so that their heart rate, particularly in normal rhythm, does not get too slow, when medications are used to decrease the rate during atrial fibrillation.
Digoxin is a medication that also may be used to control the heart rate in atrial fibrillation. There are some medications that elevate the digoxin level. The digoxin level may be assessed with a simple blood test, and can be used to determine if the dose is appropriate, in addition to following and assessing the patient’s heart rate. Medications such as amiodarone may increase the digoxin level. Digoxin is removed from the body by the kidneys, and therefore patients with kidney impairment or decreased kidney function will generally need a lower digoxin dose. Significantly elevated digoxin levels may lead to symptoms such as nausea, vomiting and yellow vision. In addition, there may be other beats, such as ventricular premature beats, or other fast rhythms that can occur as a result of a high digoxin level.
Assessing rate control is usually performed by examining the heart rate at rest with an electrocardiogram, the longer term monitoring as discussed above, and the assessment of symptoms. If patients continue to have a significant palpitation, or other symptoms, and their heart rate remains elevated, additional medications are often prescribed.
In very selected patients, it may be extremely difficult to control the heart rate. This can lead to severe symptoms that require repeated visits to the emergency department. For such patients, it may be necessary to consider alternatives to medications. A specific form of catheter ablation is called AV junction ablation. The goal of this procedure is to eliminate conduction through the AV node or adjacent structures. Therefore, there are no heart beats that get from the top chamber to the bottom chamber. The patient is therefore reliant upon a permanent pacemaker to maintain their heart rate in the ventricles. Such as strategy does not prevent atrial fibrillation, but simply controls the rate, specifically the ventricular rate, in the patient. Nevertheless, many patients have a significant improvement in their symptoms if they have had excessive heart rates previously on medication alone.
The treatment of catheter ablation of the AV node or junction is irreversible, and therefore should be only performed where it is certain that a return to conduction is not desired. This is usually when all previous medication strategies have been excluded. In addition, it has been determined that the patient is not an appropriate candidate for catheter ablation of atrial fibrillation itself.
Most patients following AV junction ablation have improved symptoms. There is a modest portion of patients that have worse symptoms after an AV junction ablation. This may be because the heart rate now is particularly well controlled, and slower than what the patient has become accustomed to. This can be overcome simply by programming the pacemaker rate to a higher rate, and only gradually decreasing the ventricular rate. In other situations, the patient may be symptomatic because the ventricular pacing leads to an abnormal pattern of conduction within the lower heart chambers, the ventricles. In these individuals, they may feel particularly fatigued or short of breath because of this lack of coordination. Such individuals may be candidates for a type of pacemaker system which uses an additional lead which serves to pace the left ventricle in addition to the right ventricle. This treatment is quite frequently used in patients who have decreased heart function and a limitation of their functional ability.
ANTIARRHYTMIC AGENTS
There are several groups of antiarrhythmic agents. One group includes flecainide and propafenone. These two agents are sometimes called Class I. These agents are often selected in patients with no significant heart disease or heart abnormalities, including artery narrowing of the heart, called the coronary arteries. Patients with a prior history of heart attack or other abnormalities of pumping function of the heart, called cardiomyopathy, are usually excluded from treatment with flecainide or propafenone. The reason for this exclusion is that some studies have shown that there may be an increased risk of deaths with these agents and serious ventricular or lower heart chamber rhythm abnormalities, such as ventricular tachycardia.
Flecainide and propafenone are generally well-tolerated, without what we would call end-organ toxicity. The adverse effects are not felt to accumulate over time. Flecainide and propafenone are sometimes associated with mild central nervous system adverse effects, including tingling around the mouth and sometimes mental slowing or a sensation of being in a cloud. They also may cause some degree of tremors. Most patients seem to tolerate these medications well. Propafenone and flecainide may be increased in dose if at the initial dose the desired effect is not obtained. Some physicians will check a flecainide level, in order to assess in what part of the therapeutic range the patient is at the current dose.
Flecainide and propafenone are particularly known to organize atrial fibrillation into another rhythm called atrial flutter, which most commonly has a single path or circuit. Atrial flutter has a different electrocardiographic appearance and therefore the diagnosis may be made by ECG. In uncommon situations, it is possible that patients may develop faster heart rates in atrial flutter than in atrial fibrillation. This is because with the organization the rate of the atrium is slower than that in atrial fibrillation. Therefore fewer impulses try to get through the AV node to the lower heart chambers.
In atrial fibrillation, because there are so many impulses trying to get down the AV node, the impulses tend to cause the conduction to be slowed through the AV node. The analogy that may be used may be a group of people trying to leave a room. If there are fewer people trying to leave the room at the same time, they may be able to get through more rapidly than if there are many people trying to get through. Therefore the slower atrial rate in atrial flutter can sometimes lead to faster ventricular rate. In some cases this can cause an extremely rapid heart rate that can cause the patient to be dizzy or even pass out. This typically warrants discontinuation of the medication or strategies to treat the atrial flutter. Sometimes an extremely rapid rate can occur and can be often mistaken for ventricular tachycardia.
Another category of medication includes that of sotalol and dofetilide. Sotalol and dofetilide are also free of significant end-organ toxicity. However, there are rare incidents of ventricular arrhythmias that require that patient be hospitalized for initiation of these medications. The purpose of hospitalization is to monitor the patient's electrocardiogram or any changes that would likely increase the risk of serious ventricular arrhythmias. Sotalol acts both to treat the atrial fibrillation itself and try to maintain normal rhythm, as well as controlling the overall ventricular rate in atrial fibrillation. Sotalol's beta-blocking effect probably accounts for a lot of its ability to control rate. Appropriate caution, however, should be used if the patient's heart rate already is starting on the slow side prior to initiation of sotalol. Dofetilide does not have a beta blocker component and does not affect the heart rate in most situations. It still however may be effective in treating atrial fibrillation.
Dofetilide has a number of drug interactions which must be considered. Patients on these drugs cannot be started on dofetilide because of concern that the level of dofetilide in the body will significantly increase the risk of these serious ventricular arrhythmias. Table 3 is a list of medications that have interactions with dofetilide that are most prominent and serve as a contraindication, as well as those that likely require intensive monitoring or adjustment in dose. Hydrochlorothiazide, verapamil, cimetidine and megestrol are a few of the c agents that should not be used with dofetilide. Patients should not be taking sotalol or dofetilide if they are on other medications that may prolong the QT interval and may increase the risk of ventricular tachycardia.
Amiodarone is considered by most physicians to be the most potent medication to control atrial fibrillation. It, however, has a large number of side effects. These are largely dose related and therefore patients at the lowest doses tend to have relatively few side effects. However, they are significant and merit close follow-up. Thyroid dysfunction is particularly common and increases with age for patients on amiodarone. Most commonly underactive thyroid or hypothyroidism is observed. However, not infrequently hyperthyroidism or overactive thyroid may also result from amiodarone therapy. In the situation of underactive thyroid, thyroid replacement may be necessary. In the case of overactive thyroid, medication to block the effects of thyroid hormone or surgery might be necessary. Observing for the development of amiodarone related thyroid dysfunction can be performed by obtaining thyroid function tests which are widely available blood tests. TSH is the most commonly blood test, but other blood tests, such as free T3 or free T4, may be used.
The most serious side effect of amiodarone is its potential for lung toxicity. This effect is considered fairly specific and is called pulmonary fibrosis or fibrosis of the lung. Only a small percentage of patients develop this, but it is potentially life-threatening. Patients with amiodarone related lung abnormalities can usually be identified early prior to development of symptoms if testing such as pulmonary function tests with diffusing capacity are used. A pulmonary function test involves a machine in which one blows into a tube. A specific test, called diffusing capacity, is generally thought to be the most sensitive in terms of detecting early changes that might represent pulmonary fibrosis. However, in many circumstances these abnormalities are probably not related to amiodarone therapy and fortunately reverse themselves.
There are a number of medications used to treat atrial fibrillation. In this section, we will discuss medications, specifically trying to keep the heart rhythm in normal rhythm, rather than in atrial fibrillation. There are a variety of medications that can be used to treat atrial fibrillation. The goal of these treatments is to keep atrial fibrillation from recurring or in some cases to convert atrial fibrillation.
Let us consider the first situation, in which we want to convert atrial fibrillation with medications. First let us consider the situation where we want to convert the rhythm rather urgently. This may occur when the patient's blood pressure is particularly low. There may be symptoms of chest pain, dizziness or shortness of breath. Either intravenous or oral medication may be selected. Intravenous medication would be delivered typically in the hospital or Emergency Department setting and would include medications such as ibutilide or other intravenous medications.
These medications are statistically more likely to convert the rhythm if it has only been present for a relatively short time, such as less than 24 or 48 hours. As the duration of the atrial fibrillation increases, it still may be possible to stop the atrial fibrillation with these intravenous medications, but the percent decreases.
The ibutilide may be given relatively rapidly, but has the potential to result in possibly serious or life-threatening rhythm problems called ventricular tachycardia, a fast heart rhythm of the lower chambers. This is related to a specific property of ibutilide and is related to its ability to prolong the interval recorded on the electrocardiogram called the QT interval. Patients thus need to be monitored even after they have received ibutilide for these arrhythmias, typically for several hours.
Other intravenous medications include intravenous amiodarone or intravenous procainamide. These medications typically involve an initial dosage given, often called a bolus, and may be followed by a continuous infusion, which is the medication being given intravenously over a more extended period of time. Intravenous amiodarone is used in a variety of in-hospital settings, as well as in the Emergency Department. Intravenous amiodarone likely represents the most commonly used of these intravenous agents, to control atrial fibrillation.
Oral medications may also be used to convert atrial fibrillation. There are a number of studies that show the effectiveness of giving a dose of medication in converting atrial fibrillation. As for intravenous medications, oral medications are most likely to work if they are given within 24 to 48 hours of the arrhythmia onset. A number of studies have shown that a dose of oral medication that is higher than what would be used if given on a regular basis is likely to convert the rhythm of atrial fibrillation back to normal rhythm. However, because the dose is considerably higher than that which has been used on a regular basis, there is some caution regarding potential serious side effects. As a result, many physicians require at least the first time that the medication is given at this increased dose to be performed while a physician monitors the patient, typically in an Emergency Department situation. If the atrial fibrillation does not convert with this initial dose of the medication, it is still possible they will occur after the medication has been given for a longer period of time.
In addition to converting atrial fibrillation, it can be used to prevent its occurrence again. Even if the medication has not been effective in converting the atrial fibrillation initially, it is still possible that the medication may be effective in preventing it from occurring. In many cases, atrial fibrillation may not be prevented 100% of the time, but may be decreased in its frequency. Therefore medications may improve the patient's quality of life significantly without eliminating all episodes of atrial fibrillation. We therefore consider frequently the goals of atrial fibrillation therapy to not be 100% elimination of atrial fibrillation, but to decrease its frequency and often also its severity.
We are able to provide a list of various medications used to prevent atrial fibrillation, decrease its recurrence or to convert atrial fibrillation.
PREVENTING STROKE IN ATRIAL FIBRILLATION
Atrial fibrillation is known to be associated with an increased risk of a stroke. There are a number of risk factors that particularly increase this risk of stroke. The scoring system to assess the risk of stroke is called CHADS2. The risk factors included in this score include high blood pressure, or hypertension, diabetes mellitus, congestive heart failure, age 75 or greater, or prior stroke. For each of the first four risk factors, one point is given, and there are two points given for a stroke or transient ischemic attack (TIA).
The most recent guideline for prevention of stroke in atrial fibrillation utilizes this scoring system. High blood pressure, or hypertension, is included as a score even if the patient’s blood pressure is currently normal with treatment. Similarly, diabetes, whether treated with medications or with insulin, is included in this risk factor. There is no specific distinction made with respect to diet-regulated high blood pressure or diabetes. The risk factor of prior stroke is not defined to be necessarily due to atrial fibrillation, but includes any previous cause of stroke. Congestive heart failure is usually diagnosed with the occurrence of symptoms of fluid overload, or shortness of breath. While age of 75 is used, there is general recognition that the risk of stroke increases per decade, particularly 65 years of age or greater, but the risk is considerably higher at 75 years of age or greater.
It is known that patients with no risk factors—none of these risk factors—are at a low risk of stroke. Depending on the patient’s age, the risk of stroke still is higher than others without atrial fibrillation. With one risk factor, the risk of stroke rises significantly above that of a patient without any risk factors. However, the risk of stroke with two or more points markedly increases that risk.
The use of medications to prevent stroke in atrial fibrillation has evolved somewhat over time. The mainstays of treatment still, however, include warfarin, known by its trade name, Coumadin, or aspirin, and are still the two most commonly used agents. Warfarin and aspirin act differently in the way in which they prevent blood clots. Warfarin needs to be adjusted according to the results of a blood test. The accepted blood test is based on the International Normalized Ratio, or INR. This is a standard across laboratories worldwide, which assures the ability to compare laboratory results.
The value of INR depends partly on the patient’s history and prior stroke, particularly, if the patient has had a previous stroke on anticoagulation. The most commonly used range for atrial fibrillation is 2.0 to 3.0 of the INR. The INR has been known to fluctuate to a great degree over time, modified by vitamin K injections as well as factors that affect its metabolism. Warfarin is affected by vitamin K injection. Vitamin K is present in many green leafy vegetables and therefore taking any meal, for example, of spinach, would reduce the INR significantly.
There are a number of factors that affect metabolism of warfarin by the liver. One of the most common effects on the liver is alcohol ingestion. Alcohol affects metabolism of warfarin, and can markedly affect the INR.
There are a number of precautions that patients should take when they are on warfarin. Close follow-up of the INR is important, since the risk of bleeding goes up significantly as the INR increased above 3.0 or 3.5. Bleeding risks can be divided into spontaneous or related to trauma or intervention. Sometimes bleeding appears to be truly spontaneous. This may include internal bleeding, such as bleeding from a stomach ulcer, or from the intestine. Usually when this occurs without an excessively high INR, there usually is an underlying abnormality in the gastrointestinal tract. On the other hand, bleeding at extremely high INR levels may not as clearly represent an underlying abnormality. This is particularly true for bleeding in the urine, which may occur on warfarin and does not as frequently represent underlying cause. In most cases, however, physicians will investigate as to whether there is an underlying abnormality that may lead to an increased risk of bleeding on warfarin.
Perhaps the greatest risk of bleeding with warfarin is with trauma. Even a relatively innocent bump of one’s knee or elbow can lead to significant bleeding, and sometimes bleeding into the joints. One of the most serious forms of bleeding is bleeding in the brain, called intracranial hemorrhage. This can occur spontaneously, but is particularly of concern if there is any head trauma such as due to a fall or otherwise hitting one’s head. Some cases of such bleeding, which may result in a condition called a subdural hematoma, may not be clearly identified initially. It may present as decreased mental function or overall decreased mental status, as well as a prolonged headache, particularly in a patient without a history of headaches. As a result, many physicians will obtain a CT scan of the head if there has been head trauma in a patient on warfarin, even though the symptoms may be fairly minimal.
Warfarin is available both as a generic or as the trade name, Coumadin. There may be some variation from preparation to preparation on its effects on the INR.
Some people on Warfarin prefer to check their INR values themselves. There are currently services available which allow one to obtain a home-based system, called a Point of Care System, that allows the patient with a pinprick to measure their INR without needing to go to a laboratory. Some physicians suggest that a comparative value be used, that a patient have an INR obtained through a laboratory at the same time that the Point of Care System is used. Some patients find this to be a convenience.
Aspirin also may be used to prevent stroke in atrial fibrillation. There are a number of studies which describe aspirin’s role, and have demonstrated its utility. The exact dose of aspirin that is used varies from study to study, including 81 to 325 mg a day. There is no evidence that a dose higher than 325 mg a day is necessary. Many physicians recommend taking the enteric, or stomach-coated preparation of aspirin, to decrease the likelihood of irritation of the stomach called gastritis, which may lead to internal bleeding. Aspirin, unlike warfarin, acts on the platelets. The effect on the platelets lasts approximately one week, if taken as expected.
Plavix, or clopidogrel, has been used in a number of settings, such as after a heart artery stent. However, it is not routinely used to reduce stroke in atrial fibrillation.
Some patients, however, may have an indication to be on Plavix, such as a heart stent, but also may be recommended to be on warfarin. Being on multiple agents that affect different parts of the blood clotting process will increase the risk of stroke. However, many patients are on such combinations, and it is worthwhile to ask one’s physician directly whether multiple agents should be used.
The use of non-anticoagulant medications while on aspirin or warfarin can also be problematic. For example, the use of nonsteroidal anti-inflammatory agents such as Advil and Indocin, seems also to potentiate or increase the likelihood of bleeding on warfarin or aspirin.
New agents to prevent the risk of stroke in atrial fibrillation are actively being developed and tested. Dabigatran has been approved as an anticoagulant. Its role in reducing stroke in atrial fibrillation has also been demonstrated. It is as effective as warfarin, but does not require the blood tests such as the INR to be obtained. Instead, a fixed dose is prescribed for each patient. Dabigatran also does not have any significant interactions with food or other medications. Medications that cause bleeding, however, will still need to be used with caution. Dabigatran is taken twice daily.
Patients often inquire what would need to be done if in fact they developed an acute bleeding problem that results in an emergency while being on an anticoagulant. In most cases, it is possible to reverse the effects.
TREATMENT OF ATRIAL FIBRILLATION:
CATHETER ABLATION
Catheter ablation is an alternative treatment to drug therapy for the treatment of atrial fibrillation. The term catheter ablation refers to “catheters,” which are small plastic tubes that are inserted into the heart through the blood vessels, and “ablation,” which refers to the process of treating the arrhythmia that involves killing islands of cells responsible for the heart rhythm problem. Catheter ablation for a number of arrhythmias has been a relatively common treatment choice for approximately twenty years. However, the treatment of atrial fibrillation with catheter ablation has been much more recent, and has become particularly common in the last several years.
During catheter ablation, the specific regions of the upper chambers, the atria, felt to be responsible for atrial fibrillation, are targeted. In most patients, it is felt that vessel structures called pulmonary veins are important in triggering atrial fibrillation. The pulmonary veins are tubes which connect the lungs to the left upper chamber, the left atrium. The pulmonary veins themselves are not the site of atrial fibrillation, but are instead the triggers. One may use the analogy that the pulmonary veins are like a match which is used to light a fire, with the fire being located in the fireplace, which are the atria. Atrial fibrillation continues once it is initiated and the electrical signals travel throughout the atria. Frequently there are additional areas outside the pulmonary veins that are also responsible for the atrial fibrillation and these too may be targeted.
During the ablation procedure for atrial fibrillation, it is common to assess whether the electrical signals in the pulmonary veins have been eliminated. To do this, one usually records from a catheter called a halo or loop catheter, which has ten or more very small recording sites which are called electrodes. By using this catheter, one can determine whether the electrical signals have been adequately eliminated. Though the goal is to eliminate electrical signals in the pulmonary veins, ablation is performed outside the pulmonary veins in a region called the antrum, which refers to the atrial tissue outside the pulmonary veins. Blood flow therefore is not impeded in coming from the lungs, through the pulmonary veins, to the left atrium.
In some cases, catheter ablation may consist also of delivering the energy along a line. The ablation delivery lines are called an ablation line. These lines may extend along the top or roof of the left atrium and therefore are called the roof lines. Another commonly used ablation line is from one of the pulmonary veins, often the left inferior pulmonary vein, to part of the heart called the mitral annulus, which is a ring-like structure from where the mitral valve connecting the left atrium and left ventricle resides. The use of these lines is somewhat variable, based on physician practice, but more dependent upon the persistence of the atrial fibrillation. Patients with longer-standing atrial fibrillation are more likely to receive such ablation lines, because it is felt that a more diffuse region of the heart is responsible for the atrial fibrillation.
CATHETER ABLATION: THE PROCEDURE
Steps taken to perform ablation for atrial fibrillation begin with inserting plastic tubes that are somewhat like IVs, or intravenous lines. These are somewhat larger, approximately 2 to 3 mm in diameter. They are inserted typically in an area called the femoral region at the groin crease site. In addition, sometimes access is obtained in the vein on the side of the neck, or less commonly the vein under the clavicle in the upper chest near the collar bone. By inserting the intravenous lines called introducer sheaths, one is able to get safe and ready access to the blood vessels of the heart. From these sites, one accesses rapidly the relatively large blood vessels that travel to the heart.
Entry is usually performed into the veins, and these lead to the right upper chamber called the right atrium. From within the right atrium, the tubes or catheters—called electrode catheters as they have electrical recording elements—are positioned at various areas and may be positioned at sites within the atrium and most commonly in a structure called the coronary sinus, which is where the large veins of the heart exist, draining blood from the left ventricle or lower pumping chamber.
After these recording catheters have been positioned, one typically performs the trans-septal catheterization. Trans-septal catheterization permits one to get access to the left atrium from the right atrium. Trans-septal catheterization involves using a needle a fraction of a millimeter in diameter that is used to puncture across the wall between the right atrium and left atrium called the atrial septum. The site of puncture needs to be precisely performed in a thin area of the atrial septum. Some physicians use an ultrasound catheter, which is placed in the right atrium, in order to image the site of trans-septal puncture in the atrial septum. Use of intracardiac echocardiography is an aid to make the procedure safer and more rapid. Intracardiac ultrasound or echocardiography also can be used to image the catheters once they are placed in the left atrium.
Following the trans-septal puncture catheterization, the physician advances the electrode catheters from the right atrium to the left atrium. Most commonly, or in many cases a second trans-septal catheterization is performed, to allow a second catheter to be advanced to the left atrium. The two trans-septal catheterizations are used to place a small catheter which has multiple electrode poles (halo or loop catheter) and the catheter used for ablation, called the ablation catheter.
To minimize the risk of stroke or blood clot formation during a catheter ablation procedure, medications are used to reduce the likelihood of blood clotting. Most commonly, measurement of the degree of blood clotting is monitored during the procedure.
A number of measurements or assessments may be made to determine whether the ablation procedure is complete and most likely to be successful. In many cases in which the atrial fibrillation is paroxysmal, meaning that it comes and goes on its own, an adrenaline like medication called isoproterenol is used to try to stimulate the atrial fibrillation. If atrial fibrillation is produced, then the additional areas are assessed. In addition, if there is evidence of electrical signal coming from the pulmonary veins that enter the atria, a phenomenon called reconnection, additional ablation at those sites is performed.
The current technology used for most catheter ablations involves either radiofrequency ( radio waves) or cryoablation (or freezing) of these regions. Radiofrequency energy has been approved for other heart rhythm problems for many years, but only recently has been approved for use for atrial fibrillation. Ablation catheters with a metal tip called an ablation tip electrode is used to deliver the energy to the heart. In the case of radiofrequency or radio waves, the energy travels through the electrodes into the tissue. The energy travels into the neighboring several millimeters of depth. It is heating of the tissue that causes the cellular death of the regional cells. This phenomenon of cell death may occur relatively quickly or may occur as a result of healing. Catheter cryoablation may also be performed using a catheter with a single electrode tip. Instead of heating the tissue, the heart tissue is brought to a very low temperature resulting in freezing of the tissue locally.
In addition to radiofrequency ablation catheters that have a single tip electrode, new designs are currently being introduced and are in various stages of clinical investigation in the United States. In Europe and many other parts of the world, some of these tools have been used for several years in a large number of patients.
Most of the new technologies share in common the same general approach of using a balloon which sits outside the pulmonary veins. It is felt to be quite an attractive strategy because the balloon can be fairly easily positioned just outside the pulmonary veins. After one performs trans-septal catheterization, the balloon catheters are then advanced and oriented in a way that the front end of the balloon sits just outside the opening of the pulmonary veins. The cryoablation balloon has been used most extensively, and relies on the ability to use the end most frequently. The cryoablation balloon becomes extremely cold and freezes any tissue it comes in contact with. It is particularly important that adequate occlusion of the pulmonary vein be performed, so that effective freezing occurs. This requires the assessment of a significant decrease in blood flow around the pulmonary veins. A laser balloon is in clinical investigation in the United States and is available in Europe. The laser balloon has an endoscope which permits visualization of lesion formation as well as positioning of the laser energy in specific regions of the pulmonary veins. Balloon technologies are currently limited to treatment of the pulmonary veins.
A new non-balloon technology is a radiofrequency energy array which is a series of electrodes used to deliver radiofrequency energy, both in the pulmonary veins as well as at certain regions of the atria.
Conventional single point radiofrequency ablation may also be performed with the aid of control devices. One such system (Stereotaxis) utilizes a large fixed magnet to control precisely the tip of the radiofrequency ablation catheter within the heart. Another system is a catheter robotics system (Hansen Medical) that precisely controls the catheter using a computerized steerable sheath. Both these techniques may allow more precise control during catheter ablation but clinical trials comparing these methods to conventional techniques have not been completed.
Surgical techniques have been developed to treat atrial fibrillation. Most surgical techniques that are used in patients not undergoing other forms of heart surgery usually employ a small thoracotomy (incision in the chest) or use small holes or ports in the chest and use a video camera (thoracoscope). Surgical ablation approaches the heart from the outside (epicrdial approach). This is in contrast to catheter ablation which approaches the heart from the inside using catheters (endocardial). For patients with long-standing persistent atrial fibrillation and dilated atria, surgical techniques may not be sufficient to achieve an improved single procedure success. The epicardial surgical and catheter ablation approaches are both limited by the inability to achieve ablation through the full thickness of the atrial tissue at all sites. This is felt to be a major determinant of the recurrences after the first procedure. A hybrid combined epicardial and endocardial ablation strategy is being used in selective cases tbecause it may improve the single procedure results by approaching the ablation from both sides of the heart tissue during a single procedure.
RISKS OF CATHETER ABLATION, SUCCESS, AND RECURRENCE
There are serious potential risks of catheter ablation of atrial fibrillation including stroke, heart attack, death, damage and puncture of the heart or lungs, damage to the esophagus which is rare but life-threatening, paralysis of the diaphragm or narrowing of the pulmonary veins that may lead to breathing difficulties. The incidence of these serious potential risks is about 3-4 %. In addition there is a risk of damage to the artery, nerves, and veins requiring surgery or transfusions, bleeding and bruising, blood clots, and infection. There is a cancer risk based on the radiation receiving during the procedure.
Some patients require a cardioversion (electrical shock to the chest) and may experience a burn to the chest at the site of the cardioversion. A proportion of the patients may continue to have atrial fibrillation after the catheter ablation. Some of the patients are significantly improved symptomatically despite recurrence of atrial fibrillation and repeat ablation is not necessary. A proportion of patients have repeat ablation. This proportion of patients with recurrences is highest in patients with long-standing persistent atrial fibrillation (atrial fibrillation constantly for more than a number of years) or enlarged atria. The success rate and recurrence rate will depend on these factors as well as the increased success with advances in the technologies and techniques. Patients with paroxysmal atrial fibrillation, likely depending on the technology used, have the highest single procedure success, approaching 70-80%, with increased success after more than one procedure. In patients with persistent atrial fibrillation and enlarged atria, the single process success may be 50%.
Some patients may be more symptomatic than prior to the ablation.
SELECTING TREATMENT STRATEGIES
Treatment strategies are generally focused on improving the patient’s symptoms. In general, control of the heart rate in atrial fibrillation is the first objective. In other words, if the patient’s rate is felt to be too rapid, one would use medication to control that rate. If the patient remains symptomatic from the point of view of symptoms such as fatigue, shortness of breath, dizziness or lightheadedness, despite improved control of the heart rate, one may consider trying to prevent atrial fibrillation from occurring. This may be done with medication or in some cases with catheter ablation.
For most patients, the decision is made based on symptoms and how interested the patient is in preventing these symptoms. This intervention, whether it consists of medications or catheter ablation, may involve some side effects and potential risk. The patient is usually significantly involved in this decision. For patients with atrial fibrillation that have minimal symptoms with or without the need for medication to control the rate, the need for maintaining normal rhythm is much less.
Are there circumstances in which the patient can be asymptomatic, that is, without any symptoms such as chest pain, dizziness or fatigue and still one might want to prevent atrial fibrillation or restore sinus rhythm? In selected cases, probably representing a minority of patients, one is uncertain whether the patient has symptoms related to atrial fibrillation. This is potentially more common in patients who are in atrial fibrillation continuously, since they may to some extent adjust to the atrial fibrillation. It is possible that some patients have adapted so well that they are not aware of these symptoms. For example, a patient may answer that, yes, it is true that there is more fatigue than a year ago, but this is often attributed to increased age or some other medical problems. When asked whether the patient can exert as much as previously, sometimes the answer is, “I am mainly limited by my hips or knees.”
The options in such situations are to continue to observe the patient for worsening of symptoms or clear symptoms. The alternative would be to try to maintain normal rhythm on a somewhat temporary basis, to see whether the patient has fewer symptoms in sinus rhythm. This approach gives the patient the option then, once one has restored sinus rhythm for a period. In some cases, the patient will continue to say there is no difference in how they feel. In such cases, one may decide to not pursue maintaining sinus rhythm. On the other hand, if the patient is surprised and in fact remarks that they have more energy, then strategies to restore normal rhythm may be pursued.
In some cases, there may be evidence of decreased heart function. There may be clear causes of decreased heart function, but in other cases there may not be. Examples of apparent reasons for decreased heart function might be a known heart attack or myocardial infarction. There also may have been decreased heart function prior to the onset of atrial fibrillation, without any subsequent change in the degree of dysfunction. In such cases, atrial fibrillation would not be likely to play such a large role in impairing heart function. On the other hand, if the heart function has been previously normal, then was only noted to be abnormal on discovery of atrial fibrillation, it is possible that restoration of normal rhythm may result in improved heart function.
One known mechanism of how atrial fibrillation impairs heart function is the effect of heart rate on the heart function. It is well described that excessive ventricular rate in atrial fibrillation may significantly impair left ventricular function. Sometimes this is called a tachycardia myopathy, indicating tachycardia, meaning fast heart rate, and myopathy, meaning an abnormality of the heart muscle itself. This phenomenon is felt to be due to the direct effects of the rapid rate on the heart tissue. In most situations, there is normalization or near normalization of the heart function in such circumstances. However, there may be a combination of effects and the heart function may not recover.
The ability to restore left ventricular function back to normal is extremely important, since left ventricular dysfunction can be a major cause of future need for hospitalizations or fluid retention or what is called heart failure. It also may lead to decreased overall survival. Restoration of normal rhythm, even the absence of apparent symptoms, in the setting of unexplained dysfunction of the heart, may be very important to the overall patient condition.
There has been the hypothesis that simple restoration of sinus rhythm improves the overall outcome independent of symptoms. There were a number of studies, including several extremely large studies in patients with atrial fibrillation, which examined the role of maintaining normal rhythm, the so-called rhythm control approach. The largest study was called the AFFIRM study, which randomized patients to control of their rhythm, medications designed to restore normal rhythm and medications that simply control the rate during atrial fibrillation. This study and other similar studies did not show any benefit of the rhythm control strategy and even shows a slight trend toward harm. These patients were mainly 70 years of age or older and these results may not be applicable to younger patients. In this study, only 50% of patients in the rhythm control arm had anticoagulation with warfarin, where nearly all the patients in the rate control arm were on warfarin. There is a higher ischemic stroke risk in the rhythm control arm, despite the fact that on the majority of visits they were in normal rhythm.
Therefore many physicians have concluded that it is insufficient to determine that a patient with atrial fibrillation is in normal rhythm; one must consider the patient still to have a risk of blood clots and stroke and therefore patients should be treated with anticoagulation appropriately.
At present most physicians and current national guidelines indicate that patients should continue on anticoagulation based on their CHADS2 score. Thus, even if the patient remains in sinus rhythm on an antiarrhythmic agent or after catheter ablation, current recommendations are that anticoagulation should be continued if the CHADS2 score is 2 or more.
The option for catheter ablation of atrial fibrillation has been increasing promising with improved results and greater data and experience. In addition use of new tools will likely lead to simpler and more effective procedures. For the patient with symptoms catheter ablation is a reasonable option, particularly after one or more antiarrhythmic agents are not successfully in adequately controlling atrial fibrillation.
Once the decision has been to proceed to catheter ablation, the selection of approach and technology allows one to tailor the approach to the patient. Most patients with paroxysmal atrial fibrillation may be treated with the new balloon technology or conventional radiofrequency ablation tools with our without robotic assistance. Patients with persistent atrial fibrillation may be treated with new balloon technology with robotic assistance during radiofrequency with the goal of improving precision and contact with the tissue. Patients with prior catheter ablation and recurrence of atrial fibrillation or with long-standing persistent atrial fibrillation or with enlarged atria the hybrid endocardial-epicardial approach may be an option.