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Atrial Fibrillation

Atrial Fibrillation (AF) is the most prevalent cardiac dysrhythmia in the United States and a substantial cause of morbidity and mortality.1  Even though AF is commonly diagnosed by clinicians; the most appropriate treatment course remains elusive.  The main controversy is between controlling the rate versus the rhythm.  The ventricular rate is the number of cardiac cycles (systole and diastole) in one minute, normally 60 to 100 beats per minute (bpm) in an adult; it can be determined on an electrocardiogram (ecg) by measuring the distance between R waves.2  The rate is typically pharmacologically controlled by beta or calcium channel blockers.  A normal sinus rhythm demonstrates an electrical impulse generated by the sinoatrial node or "pacemaker" of the heart and maintains a consistent R-R interval on the ecg.2  AF is associated with an "irregularly irregular" rhythm due to the erratic atrial depolarization and the resulting variable ventricular response.2  AF is expressed on an ecg as a wavy baseline with an atrial rate of 400 to 600 bpm "without identifiable P waves."2  The rhythm found in AF is controlled with electrocardioversion or antiarrhythmic drugs, such as flecainide, quinidine, and amiodarone.1 

Over the last decade there have been advancements in the understanding of the pathophysiology of AF which has aided further exploration of the appropriate treatment through several key studies.  For example, the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study concluded that there was no significant difference between the two treatment strategies.3  However, the rhythm control group was associated with slightly more adverse drug effects and hospitalizations than the rate control group studied.3  Other related key studies include the Pharmacological Intervention in AF (PIAF), Rate Control versus Electrical Cardioversion for Persistent AF (RACE), Canadian Registry of AF cohort (CARAF), How to Treat Chronic AF (HOT CAFE) and Strategies of Treatment of AF (STAF). 

The objective of this paper is to do a literature review of the pertinent published works related to the treatment of AF and outline the conclusions obtained.  The review will include the key studies completed in the last decade featuring AF patients comparing rate versus rhythm control.  This author will explore possible subsets of AF patients for which a certain treatment is more efficacious, as well as, the cost effectiveness of the treatment.  Although practitioners have long considered rhythm control to be the most effective treatment for AF, this paper will show that rate control is equal in efficacy and should be an acceptable first-line therapeutic option.

Review of Literature

Pathophysiology

AF occurs due to a focal mechanism or multiple reentry atrial circuits.  As early as 1896 Englemann "proposed that AF could be the result of a single atrial focus activating the atria with a rapid rate."4  The typical depolarization rate of the atria is between 400 and 600 beats per minute.2  As a result of the rapid rate the atrial muscles fibrillate leading to an erratic baseline on ecg "without an identifiable P wave."2  Due to the irregular atrial depolarization and the corresponding irregular ventricular response the rhythm of AF is referred to as "irregularly irregular."2  Jais later showed that "ablation of a single focus, most typically from one of the pulmonary veins, could stop AF."4  During the last century, it was shown that the variable rhythm of AF can be the result of multiple reentry circuits instead of rapidly firing foci.  Reentry "is not a disorder of impulse formation but rather a disorder of impulse propagation, it occurs when an impulse travels around an abnormal circuit repetitively."5  By performing several experiments on animals and humans, Allessie et al. "confirmed multiple wavelet reentry as the cause of AF by multipolar mapping."4   Multiple reentry as the cause of AF was further supported by the demonstration by Kumagai et al. that pathways in certain anatomic locations helped maintain AF.4   More important in AF than anatomic reentry is functional reentry in which "variations in the electrophysiologic properties of contiguous tissues, not anatomic obstacles, may serve as the boundaries" of the circuit.5  There have been several functional reentry models proposed including the leading circle, spiral wave and multiple wavelets.5 

Since 1960 the multiple wavelet theory has been the most accepted and it is explained as a "critical number of wavelets, which travel throughout the atria, colliding, combining or dividing and thereby spawning daughter wavelets that perpetuate the process."5  Any condition that alters the structure of the atria or decreases the wavelength "permit multiple wavelets and promote AF."5  Atrial remodeling is the concept that changes in the atrium promote and maintain AF, "these changes include a shortening of the refractory period of the atrium and atrial dilation...which may be caused by increased left atrial pressure."1  There are three characteristic parts of the atrial remodeling process: electrical, contractile, and structural remodeling.5  Electrical remodeling is completed in the first 24 to 48 hours after onset of AF and is due to "tachycardia induced intracellular calcium overload, a downregulation of the L-type calcium channels and a subsequent reduction of sarcolemmal calcium influx."5  Since elevated intracellular calcium can lead to toxicity homeostatic mechanisms reduce the influx of calcium that contributes to the normal duration of the action potential.5  The end result is a "shortening of the atrial refractory period and a reduction of the wavelength which increases the vulnerability of AF."5  Further consequences of electrical remodeling include "myocyte calcium overload, atrial automaticity, dispersion of conduction, and increased sensitivity to catecholamines."3  Contractile remodeling similar to electrical remodeling is related to calcium conduction.  For example, "myofilament sliding, the cellular action responsible for muscle contraction, is intimately dependent upon intracellular calcium concentrations" and when the calcium influx is altered so are the function of the myocytes.5  As a result dilation of the atria may occur in several days to weeks.4  Structural remodeling is due to several chronic processes including "increased wall stress, a change in the distribution of connexin 40, myolysis with sacromeres replaced by glycogen, and a disruption of the sarcoplasmic reticulum" that leads to "increased fibrosis" of the atria.4  The electrical, contractile and structural remodeling of the atria helps to stabilize and sustain the arrhythmia thereby leading to chronic form of AF, which is summarized by the concept "AF begets AF."6  Another consequence of atrial remodeling is that the "longer AF lasts the more difficult it is to convert to sinus rhythm" and therefore harder to treat effectively.3

Etiology and Epidemiology

AF can present clinically as either a primary or a secondary arrhythmia.  Primary AF is referred to as "lone atrial fibrillation" because it presents without an underlying cardiac disease associated.1  Idiopathic or lone AF is "often found in less than 10% of total AF cases."7  More commonly AF presents secondarily due to a metabolic or cardiac condition.1  Metabolic conditions that predispose someone to developing AF are often associated with "increased sympathetic activity."1  These noncardiac conditions include: thyrotoxicosis, pheochromocytoma, pulmonary embolus, hypoxia, anemia, fever, emotional stress, anxiety, stroke, subarachnoid bleed and the ingestion of alcohol, cocaine, caffeine or other stimulants.6  The Framingham Heart Study which began in 1948 concluded that "low serum thyrotropin concentration (< 0.01 mU/L) in patients age 60 and older was associated with a three-fold increase in the development of AF in the subsequent decade."6 

According to the Framingham study the most common precursor of AF is "hypertensive heart disease" associated with cardiomegaly or left ventricular hypertrophy.1  Other cardiac conditions that are associated with the development of AF include: valvular heart disease, coronary artery disease, cardiomyopathy, pericarditis, cardiac surgery, congenital heart disease, and sick sinus syndrome.6  The strong association between cardiac conditions and the development of AF "suggests that myocardial damage precedes and may be a causative factor for AF."1  The heart of a person with AF due to a cardiac condition is often found to have "atrial dilatation and patchy areas of fibrosis that can even include the SA node," however, when AF is due to metabolic conditions the pathological changes, such as atrial fibrosis, do not occur which provides a discernible difference between the two types of causes.1  

Risk factors for AF development have been identified as "increasing age, heart failure, smoking, diabetes, hypertension, male sex, left ventricular hypertrophy, myocardial infarction and valvular heart disease."8  Most of the aforementioned cardiac and metabolic conditions are more common in the elderly thereby explaining the increased prevalence of AF with age, "nearly doubling in each decade over age 50."6  AF occurs in the United States at a rate of "2.2 million cases per year" in which "fewer than 1% of individuals in their fifties, up to 11% of 80 year olds suffer from this arrhythmia."8   AF is more common in whites than blacks and in men rather than women.6  Males have a "1.5 times greater risk of developing AF versus their female counterparts, however, women have a greater mortality risk (1.9 times increased risk) than men (1.5 times increased risk)."1  AF is commonly associated with myocardial infarction and heart failure and AF "accounts for over 5% of hospital admissions for cardiovascular diseases."9  Approximately 10 to 15% of acute myocardial infarction patients have a comorbidity of new onset AF in addition.1  Furthermore, AF has "been reported to occur in 15 to 30% of heart failure patients."3  Prasun and Kocheril state that "studies indicate that individuals with AF may have twice the mortality rate compared to individuals in sinus rhythm."3       

Clinical Manifestations

The clinical presentation of AF varies greatly from asymptomatic individuals to those suffering from hemodynamic collapse or heart failure.8  The most common presenting symptoms are "palpitations, fatigue and dyspnea on exertion."6  The Canadian Registry of Atrial Fibrillation (CARAF) which followed 899 patients found 21% to be asymptomatic and of the symptomatic individuals "palpitations occurred in 50%, chest pain and fatigue in more than 25% and dizziness, presyncope or syncope in about 25%."8  The symptoms associated with hemodynamic instability are "lightheadedness, angina, congestive heart failure, or rarely syncope" which results from a decrease in stroke volume due to "dependence of left ventricular filling on late diastolic atrial contraction and/or a rapid ventricular response."6  Decreasing stroke volume helps to promote and advance congestive heart failure which provides an explanation for the common combination of heart failure and AF where "each condition is possibly initiating and perpetuating the other."1  The worst complication of AF is stroke which is often a result of thromboembolism due to "clotting in the relatively static blood pool of the fibrillating atrium, particularly in the left atrial appendage."8  The presence of AF increases an individuals' risk of stroke "about 5 times and is the single factor most commonly associated with stroke in those over 75 years of age."8   

AF can be classified into five categories based on the presentation these include first onset, recurrent, paroxysmal, persistent and permanent, of which the latter three are chronic conditions.1  The first episode of AF can be symptomatic or asymptomatic, self-limited or persistent.8  Recurrent AF is defined as "2 or more episodes of AF lasting > 30 seconds."8  Paroxysmal AF is "characterized by recurrent, self-limiting episodes, which tend to break spontaneously within 48 hours."1  Paroxysmal AF can be vagonotic which is "predominantly nocturnal episodic AF" or adrenergic mediated which is related to exercise.10  Adrenergic mediated paroxysmal AF is found equally in both sexes and related to underlying heart diseases whereas vagonotic AF is found mostly in males without heart disease.10  AF is described as persistent if the "arrhythmia is continuous but conversion to sinus rhythm by means of treatment, either pharmacological or electrical, is possible."1  Persistent AF is typically a result of "an acute cardiac insult" such as "acute myocardial infarction, cardiac surgery or pulmonary embolism."10  In contrast if the arrhythmia is "refractory to conversion to sinus rhythm or the conversion is rapidly reversed" it is classified as permanent AF and is typically present for greater than one year.1

Treatment

There are three key goals involved in the treatment of AF: controlling the ventricular rate, restoring the normal sinus rhythm and preventing thromboembolism.1  Acute management of AF "does not depend upon the absolute heart rate, but rather upon the individual patient's response to the ventricular rate."6  Even though "50% of all patients with new onset AF will convert to sinus rhythm spontaneously within 24 to 48 hours" it is important to closely monitor for cardiovascular compromise.1  The patient that presents with hemodynamic instability, heart failure or angina needs to undergo immediate cardioversion.6  More stable patients at presentation can undergo rate control pharmacologically "with drugs that slow AV nodal conduction, such as, beta blockers, calcium channel antagonists, and digoxin."6  Beta blockers such as atenolol and metoprolol and calcium channel blockers such as verapamil and diltiazem administered intravenously or orally are "most effective since they are rapid-acting and well tolerated."6  A large multi-center study calculated the average therapeutic response time following an infusion of diltiazem as 45 minutes.1  Digoxin is used first-line in patients with heart failure due to left ventricular dysfunction because it does not "depress left ventricular contractility" however it should be used sparingly in patients with renal failure, "thyrotoxicosis, fever, or profound anemia."6  Unfortunately digoxin takes longer than beta blockers and calcium channel blockers to effectively control AF, it has been shown to take "an average of 9.5 hours" and furthermore it "does not seem to be suitable for the treatment of paroxysmal AF."11  Regardless of these limitations digoxin still remains vital in the acute treatment of patients that have left ventricular dysfunction.11  Once the patient becomes asymptomatic and the rate is adequately controlled the management of their arrhythmia in the extended setting needs to be approached.

The goals of long term management differ from acute treatment of AF.  The main goal during the acute setting is to stabilize the patient which often occurs in the hospital setting.11  However, long term therapy "attempts to overcome a series of cardiac changes that tend to develop during chronic AF" and it must be "carefully adapted to patients' individual characteristics in order to grant rate control during all their daily activities."11  Furthermore, adequate long term treatment must "confer a satisfactory quality of life" for the patient and can often be managed in the outpatient setting.11 
 There have been several recent recommendations on the appropriate strategies for the long term management of AF.  The American Academy of Family Physicians and the American College of Physicians presented a collaborative effort in 2003 which outlined six recommendations for the management of AF.12 

• Recommendation 1: "rate control with chronic anticoagulation is the recommended strategy for the majority of patients."12
• Recommendation 2: "patients with AF should receive chronic anticoagulation with adjusted-dose warfarin."12
• Recommendation 3: "atenolol, metoprolol, diltiazem, and verapamil" have been shown to be effective in controlling the ventricular rate of AF patients during exercise and at rest.12
• Recommendation 4: "for those patients who elect to undergo acute cardioversion to achieve sinus rhythm in AF, both direct-current cardioversion and pharmacological conversion are appropriate options."12
• Recommendation 5: "both transesophageal echocardiography with short-term prior anticoagulation followed by early acute cardioversion with postcardioversion anticoagulation versus delayed cardioversion with pre and post anticoagulation are appropriate."12
• Recommendation 6: "most patients converted to sinus rhythm from AF should not be placed on rhythm maintenance therapy since the risks outweigh the benefits."12

These six recommendations were derived after the outcomes of several clinical trials on AF were reviewed.  The importance of anticoagulation with both rhythm and rate control treatment strategies for AF is accepted and is not the focus of this paper.  The clinical trials that led to the remaining recommendations are presented next.

Results

Rhythm control is the traditional approach to chronic AF management; however, recently several clinical trials have concluded that rate control is equally efficacious.  Reasons that the restoration of the normal sinus rhythm are important include that it "allows for an improvement in hemodynamics, alleviation of symptoms, restoration of AV synchrony, physiological control of heart rate, prevention of dilatation of the atria and left ventricular dysfunction, and it eliminates the risk of thromboembolism."1  Once the sinus rhythm is restored the goal via electrical or pharmacological cardioversion is then to prevent recurrence of AF typically via the use of antiarrhythmic drugs, such as, ibutilide, dofetilide, sotalol and amiodarone.13  Antiarrhythmics are found to have a success rate of 40 to 60%.1  The use of antiarrhythmics is associated with serious adverse effects including proarrhythmia and increasing mortality.14  One effect is the promotion of lethal arrhythmias, such as, torsades de pointes "which occurs in 2% to 4% of patients and is more likely in women, the elderly, and patients with left ventricular dysfunction."13  The chronic use of oral antiarrhythmics is the most concerning for proarrhythmia which "can also take the form of recurrent ventricular tachyarrhythmias refractory to cardioversion and acceleration of the ventricular response to AF."14  Amiodarone, a Class III antiarrhythmic that has properties of all four drug classes, is the least likely to produce ventricular arrhythmias that has shown superior efficacy and is equally tolerated as other antiarrhythmics.9  However, amiodarone has been associated with "significant noncardiac toxicity."15  The noncardiac adverse effects of amiodarone range from "photosensitivity of the skin to thyroid, liver and pulmonary dysfunction."10  Due to the safety concerns and ineffectiveness of antiarrhythmics as a whole there was a search for a more advantageous treatment of AF which lead to the generation of several clinical trials comparing rhythm control to controlling the rate of AF. 

The largest trial, AFFIRM, which enrolled 4060 patients compared rate control with digoxin, beta blockers or calcium channel antagonists to rhythm control using primarily amiodarone or sotalol.16  The patients enrolled were at least 65 years old or with stroke risk factors, such as, hypertension or coronary artery disease (CAD).16  The study defined adequate rate control as a "ventricular rate of 80 beats per minute at rest and 110 beats per minute during a six minute walk."16  Several key conclusions were derived from AFFIRM including there were more noncardiovascular deaths with rhythm control and that there was no difference between the quality of life of the patients between the two groups.16  Other results concluded were that rate control showed an "almost significant trend toward a decrease in the rate of occurrence of the primary end point (all cause mortality)," however, there was no difference in the "incidence of cardiac death, arrhythmic death or deaths due to ischemic or hemorrhagic stroke" found between the two groups.16  Several subgroups of the rate control arm, "those without heart failure, those with CAD, and those greater than 65 years of age" had a statistically significant decrease in mortality and none showed an increase.16  The rate control group was associated with fewer hospitalizations at the five year follow-up and a lower risk of ischemic strokes.16  The latter was explained because the individuals in the rhythm control group often received no anticoagulation with warfarin or it was suboptimal with international normalized ratios (INR) less than two.6  Seventy percent of the strokes that occurred in the rhythm control group were a result of the poor anticoagulation received.12  "The presence of sinus rhythm was associated with a significant reduction in mortality;" however, the use of antiarrhythmics was associated with an increase in mortality related to "noncardiovascular causes" such as pulmonary and cancer-related deaths.16  The use of antiarrhythmic drugs is associated with proarrhythmia; therefore the benefit of sinus rhythm restoration seems to be negated by the numerous adverse effects.15 

The PIAF trial followed 252 individuals, ages 18 to 75, with symptomatic persistent AF and attempted pharmacological cardioversion with diltiazem for rate control and amiodarone to control the rhythm.17  Symptom improvement was the main outcome of the study and was defined as "an elimination of palpitations, a reduction in the frequency of episodes of dyspnea, or a reduction in the frequency of dizzy spells" which are the three main symptoms of AF.17  The results were similar to the AFFIRM trial in that there was no difference in quality of life or symptom improvement between the two therapeutic groups; however, the rhythm control group had more hospitalizations.17  The rhythm control group was found to have better exercise tolerance, as well.17  Furthermore, amiodarone the main antiarrhythmic used in the PIAF trial only restored sinus rhythm in 23% of patients and 25% of patients discontinued use due to side effects.17  

The RACE trial featured 522 patients, average age of 68, with recurrent persistent AF that required one or two cardioversions within the past two years.16  Rhythm control was initially treated by sotalol and rate control with the same drugs used in the AFFIRM trial.16  After 2.3 years the primary findings were that more patients remained in sinus rhythm in the rhythm control group and that there was no significant difference in quality of life within the two groups.16  However, improvement in quality of life was found in patients that had symptoms at the start of the study, AF lasting a short duration, and sinus rhythm maintenance on follow-up.16  Women and patients with hypertension in the rhythm control group had a higher incidence of the primary endpoints which "was a composite of cardiovascular death, admission for heart failure, thromboembolic event, severe bleeding, pacemaker implantation, or severe side effects from antiarrhythmic drugs."16 

The CARAF cohort had 899 patients and monitored the use of five antiarrhythmics commonly prescribed in Canada even though there were clear contraindications, precautions and warnings known in numerous of the patients enrolled.18  There were between 36 to 54% of patients that had such limitations; however, no correlation was made between the prescription of antiarrhythmics in contraindicated situations and an increase of adverse events.18  It was concluded that this finding was due to the "retrospective assessment of adverse events as well as the limited sample size" or possibly that "practicing physicians appropriately weigh contraindications and warnings against other unmeasured factors."18  The main outcome of the cohort is that there is "the need for new agents that are more friendly to use in the treatment of AF."18  Furthermore, the lack of correlation is currently being analyzed further in the CARAF II.18 

A set of 205 patients, ages 50 to 75, with persistent AF was featured in the HOT CAFE Polish trial that evaluated the long term outcome of rate versus rhythm control.19  The main results were that there were "no significant differences in major end points between the rate control group and the rhythm control group" whereas the New York Heart Association functional class improved in both groups.19  Similar to prior discussed studies the mean exercise tolerance was better in the rhythm control group and that group had greater hospitalizations.19  It was concluded that with the "currently available pharmacological therapy, there is no distinct advantage associated with the rhythm control strategy."19  Furthermore, rate control was shown to have several advantages including "obviation of antiarrhythmic drug therapy and its potential side effects" and being initiated in the outpatient setting "whereas antiarrhythmic drug prophylaxis must often be initiated at a hospital."19  It was concluded that rate control was an acceptable first-line option for persistent AF.19

The STAF trial involved 200 patients with persistent AF that all received cardioversion prior to pharmacological control via rhythm or rate methods.16  Consistent findings were concluded in that there was no difference in the primary or secondary end points and the rhythm control group had a greater number of hospitalizations with lengthier stays.16  However, at the end of three years only 23% of patients in the rhythm control group remained in sinus rhythm compared to 63% found in the AFFIRM trial.16 

Discussion 

Upon consideration of the results derived in the clinical trials discussed there are several conclusions that can be drawn.  The first is that there were limitations to the larger trials including an average patient age around 70 years old.16  Half of the patients were symptomatic only once a month and while antiarrhythmic use causes an increase in mortality the maintenance of sinus rhythm is associated with a decrease in mortality.16  These limitations make it difficult to extrapolate the findings to clinically treat younger or very elderly (>80 years old) patients and those with more symptomatic episodes of AF.16  However, the preferred approach in treating the majority of patients with recurrent AF is now rate control.  Rate control is accepted as adequate first-line therapy because the trial data showed "a strong trend toward a reduction in all-cause mortality with rate control" when a meta-analysis was conducted.16  The proarrhythmic adverse effects associated with antiarrhythmic use are eliminated with rate control therapy.16  The recurrence of AF after conversion to normal sinus rhythm in patients treated with antiarrhythmics was clinically detectable in 20 to 60% within one year of initiation.16  One study conducted by Marshall et al. showed rate control to be a "cost-effective approach to the management of AF compared with maintenance of sinus rhythm in patients with AF similar to those enrolled in AFFIRM."20  It was concluded that rate control "costs $5077 less per person than rhythm control" primarily due to the utilization of less resources, such as, "hospital days, pacemaker procedures, cardioversions, and short-stay and emergency department visits."20  Additionally, the mean survival rate was found to be lower for the rhythm control group than compared to the rate control group.20  Prior to the conduction of these clinical trials one disadvantage of rate control was the requirement of permanent anticoagulation; however, it was shown that an increased number of strokes occurred when anticoagulation was stopped in the rhythm control groups suggesting that anticoagulation should be continued long term with both therapy groups.15  Although rate control has been shown to be equally efficacious to rhythm control and an acceptable first-line therapeutic regimen, there are a few situations in which rhythm control is still recommended.  Rhythm control should be used if the patient has a persistence of symptoms despite adequate rate control, an inability to obtain rate control adequately and patient preference.16  Therefore, practitioners must continue to use clinical judgment on an individual patient basis to determine the best treatment for the long term management of AF.  The therapy in which the benefits outweigh the risks should be chosen for the individual whether that is the traditionally used rhythm control or the newly acceptable rate control.  Furthermore, due to the great variability among the individuals that have AF, no single therapeutic option can be unequivocally stated as the more superior and effective for each person.   

The main goal of this paper is to present a clearer understanding of the most advantageous clinical management of AF hopefully leading to a reduction in the morbidity and mortality associated with the condition in the future.  Further exploration in the management of AF should begin with a more precise understanding of the pathophysiology of AF thereby leading to more effective treatment and eventually a potential cure.  Also, it has been proposed that genetic screening be attempted in the future to look for individuals that are most likely to acquire long QT syndrome, torsades de pointes and other proarrhythmia states associated with taking antiarrhythmics.14  The advancement of nonpharmacological approaches to treat AF should continue to be developed and be utilized when an adequate trial of medication fails.  Unless future research proves otherwise, rate control should be considered an acceptable first-line therapy for the treatment of AF.

References
1. Josephson L, McMullen M. Atrial fibrillation beyond irregularly irregular. Dimensions of Critical Care Nursing. 2002; 21(5):180-189.
2. Aehlert B. ECGs made easy, Second Edition. St. Louis: Mosby; 2002.
3. Prasun M, Kocheril A. Treating atrial fibrillation: rhythm control or rate control. Journal of Cardiovascular Nursing. 2003; 18(5):369-373.
4. Tieleman R. The pathophysiology of maintenance of atrial fibrillation. PACE. 2003; 26:1569-1571.
5. Veenhuyzen G, Simpson C, Abdollah H. Atrial fibrillation. CMAJ. 2004; 171(7):755-760.
6. Mehta N, Greenspon A. Atrial fibrillation: rhythm versus rate control. Geriatrics. 2003; 58(4):39-44.
7. Stewart S. Epidemiology and economic impact of atrial fibrillation. Journal of Cardiovascular Nursing. 2004; 19(2):94-102.
8. Khairy P, Nattel S. New insights into the mechanisms and management of atrial fibrillation. CMAJ. 2002; 167: 1012-1020.
9. Nattel S, Khairy P, Roy D, et al. New approaches to atrial fibrillation management. Drugs. 2002; 62(16):2377-2397.
10. Channer K.  Current management of symptomatic atrial fibrillation. Drugs. 2001; 61(10):1425-1437.
11. Boriani G, Biffi M, Diemberger I, Martignani C, Branzi A. Rate control in atrial fibrillation. Drugs. 2003; 63(14):1489-1509.
12. Snow V, Weiss K, LeFevre M, et al. Management of newly detected atrial fibrillation: A clinical practice guideline from the AAFP and the ACP. Annals of Internal Medicine. 2003; 139(12): 1009-1018.
13. Kowey P, Yan G, Dimino T, Kocovic D. Overview of the management of atrial fibrillation: What is the current state of the art? Journal of Cardiovascular Electrophysiology.  2003; 14(12):275-280.
14. Guerra p, Talajic M, Roy D, Dubuc M, Thibault B, Nattel S. Is there a future for antiarrhythmic drug therapy? Drugs. 1998; 56(5):767-781.
15. Denus S, Sanoski C, Carlsson J, Opolski G, Spinler S. Rate vs. rhythm control in patients with atrial fibrillation: A meta-analysis. Archives of Internal Medicine. 2005; 165:258-262.
16. Podrid P, Manning W. Rhythm control versus rate control in atrial fibrillation.  UpToDate. 2005. Available at: www.uptodate.com. Accessed July 5, 2005. 
17. Hohnloser S, Kuck K, Lilienthal J. Rhythm or rate control in atrial fibrillation-Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomized trial. The Lancet. 2000; 356:1789-1794.
18. Humphries K, Kerr C, Steinbuch M, Dorian P. Limitations to antiarrhythmic drug use in patients with atrial fibrillation. CMAJ. 2004; 171(7):741-745.
19. Opolski G, Torbicki A, Kosior D, et al. Rate control vs. rhythm control in patients with nonvalvular persistent atrial fibrillation. CHEST. 2004; 126(2):476-486.
20. Marshall D, Levy A, Vidaillet H. Cost-effectiveness of rhythm versus rate control in atrial fibrillation. Annals of Internal Medicine. 2004; 141(9):653-661.

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