Asian Annals
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kasliwal, R. R
Right arrow Articles by Bhatia, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kasliwal, R. R
Right arrow Articles by Bhatia, A.
Related Collections
Right arrow Cardiac - pharmacology
Asian Cardiovasc Thorac Ann 2003;11:364-374
© 2003 Asia Publishing EXchange Ltd

REVIEW PAPER

Pharmacotherapy of Atrial Fibrillation

Ravi R Kasliwal, MD, Mukesh Singh, MD, Gagan Manohar, MD, Naveen Aggarwal, MD, Atul Bhatia, MD

Department of Cardiology, Escorts Heart Institute and Research Centre, New Delhi, India

For reprint information contact: Ravi R Kasliwal, MD Tel: 91 11 2682 5000 Fax: 91 11 2682 5013 email: rrkasliwal{at}hotmail.com Department of Cardiology, Escorts Heart Institute and Research Centre, Okhla Road, New Delhi 110 025, India.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 CAUSES OF ATRIAL FIBRILLATION
 CLASSIFICATION OF ATRIAL...
 MANAGEMENT STRATEGIES
 CONCLUSION
 REFERENCES
 
Atrial fibrillation is the most common sustained arrhythmia of clinical significance. Its prevalence rises with age. It is a significant cause of thromboembolic phenomena. We describe briefly the etiology and classification of atrial fibrillation, the risk factors for thromboembolism and stroke associated with it, the indications for hospitalization, and the therapeutic goal. We discuss in depth the management strategies for such patients and compare the impact of rate versus rhythm control in reducing morbidity and mortality attributed to arrhythmia, in light of past and present trials. A brief overview of the drugs used in the management of atrial fibrillation, their pharmacology and dosage, their effects and use in rhythm versus rate control with important side effects are also included. Finally, the prevention and treatment of thromboembolism in patients with atrial fibrillation, an important aspect of therapy, is revisited in light of recent advances.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
CAUSES OF ATRIAL FIBRILLATION
 CLASSIFICATION OF ATRIAL...
 MANAGEMENT STRATEGIES
 CONCLUSION
 REFERENCES
 
Atrial fibrillation (AF) is the most common sustained arrhythmia of clinical significance.1–3 It is characterized by chaotic, rapid, discontinuous atrial depolarizations, resulting in rapid oscillations that are recorded as irregularly formed F waves, in contrast to uniform P waves of sinus rhythm or other distinct supraventricular rhythms. According to the Framingham Heart Study,4 AF has a prevalence of 4% in the adult population. The rate increases with age, from less than 0.05% in people 25 to 35 years of age to more than 5% in those over 69 years of age.5

There is a strong likelihood that the incidence of AF may be substantially underestimated6 because of underdetection in asymptomatic patients and undersampling in patients with paroxysmal AF. AF was detected incidentally in 30% of the patients enrolled in the Cardiovascular Health Study5 and approximately 45% of the patients in the Stroke Prevention in Atrial Fibrillation Study III7 when electrocardiography was performed for unrelated reasons. In patients with symptomatic paroxysmal AF, there is a 12:1 ratio of asymptomatic versus symptomatic episodes.8


   CAUSES OF ATRIAL FIBRILLATION
TOP
 ABSTRACT
 INTRODUCTION
 CAUSES OF ATRIAL FIBRILLATION
CLASSIFICATION OF ATRIAL...
 MANAGEMENT STRATEGIES
 CONCLUSION
 REFERENCES
 
AF is a multifactorial disorder, the underlying cause of which cannot be determined with certainty in most patients. A given individual may have more than 1 abnormality that could predispose to the development of AF.9 There are both cardiac and noncardiac causes. Cardiac causes include hypertension, rheumatic heart disease (RHD), ischemic heart disease, cardiomyopathy, pericarditis, sinus node malfunction, and degeneration of the atrial myocardium. Noncardiac causes include thyrotoxicosis, cardiac surgery, alcoholism, pulmonary infection, pulmonary embolism, and lung carcinoma.10–14

AF may be chronic, which is most often associated with an underlying heart disease, or intermittent (paroxysmal), which may be observed in patients with apparently normal hearts.10,14

RHEUMATIC VERSUS NONRHEUMATIC ATRIAL FIBRILLATION
In a study by Szekely,15 it was observed that patients with RHD and AF were 7 times more likely to develop thromboembolism than patients in sinus rhythm. Similar observations were reported by Fleming and Bailey16 in a nonrandomized study. Subsequent studies confirmed that patients with rheumatic mitral valve disease as well as AF were at significantly higher risk of developing atrial thrombi than those in sinus rhythm.13

For many years, AF in association with rheumatic mitral valve disease was acknowledged as the primary cause of atrial thrombi and subsequent stroke. Small case studies concluded that AF in the absence of RHD was not an important cause of stroke.12 However, in 1972, Fisher17 reported that most patients with AF who suffered stroke did not have RHD. In 1979, he examined 100 cases of AF-associated stroke and found that less than 20% of the patients had RHD while over 80% had only coronary disease.18 Beginning in the late 1970s and into the mid-1980s, large epidemiological studies19–22 confirmed Fisher’s suspicion that AF in the absence of RHD (nonrheumatic AF or nonvalvular AF) is a significant cause of stroke. The findings of these studies are summarized in Table 1Go.


View this table:
[in this window]
[in a new window]
  		Table 1. Studies Assessing the Relative Risk of Stroke in Patients With and Without Atrial Fibrillation
 
The risk factors of stroke in patients with AF include increasing age, RHD, left ventricular (LV) dysfunction or congestive heart failure (CHF), enlarged left atrium (LA), previous myocardial infarction, hypertension, and a history of thromboembolic events.

LONE (PRIMARY) ATRIAL FIBRILLATION
By definition, lone AF occurs in the absence of structural heart disease, as determined by physical examination, electrocardiography, chest radiography, and echocardiography. Lone AF may be an isolated event or it may recur on an intermittent basis; it is rarely chronic. It is significantly more prevalent in men than in women.23,24 It may be triggered by hypoglycemia, surgery, chronic infections, alcohol abuse (especially binge drinking), nicotine, and caffeine.25–29 Serious electrolyte disturbances, such as between potassium and sodium and between calcium and magnesium, are other potent triggers.25,28,30

A fourfold increase in stroke was found in lone AF.31 The risk of stroke in lone AF is governed largely by the presence and the extent of additional risk factors. Most of these high-risk patients are above 60 years of age. In the Stroke Prevention in Atrial Fibrillation Study I, patients of lone AF who were younger than 65 years had a stroke rate of 1% per year compared with 4.3% in patients over 65 years of age.32

ATRIAL FIBRILLATION OF PULMONARY VENOUS ORIGIN
Spontaneous AF of pulmonary venous origin was recently highlighted by Haïssaguerre and colleagues.33 They studied 45 patients with frequent episodes of AF (with a mean duration of 344 ± 326 minutes per 24 hours) refractory to drug therapy. The spontaneous initiation of AF was mapped with multielectrode catheters designed to record the earliest electrical activity preceding the onset of AF and associated atrial ectopic beats. A single point of origin of atrial ectopic beats was identified in 29 patients, 2 points of origin were identified in 9 patients, and 3 or 4 points in 7 patients, for a total of 69 ectopic foci. Three foci were in the right atrium, 1 in the posterior LA, and 65 (94%) in the pulmonary veins (31 in the left superior, 17 in the right superior, 11 in the left inferior, and 6 in the right inferior pulmonary vein). The earliest activation was found to have occurred 2 to 4 cm inside the veins.

The investigators found that AF was initiated by a sudden burst of rapid depolarizations (340 min-1). A local depolarization could also be recognized during sinus rhythm and could be abolished by radiofrequency ablation. During a follow-up period of 8 ± 6 months after ablation, 28 patients (62%) had no recurrence of AF.

Thus, the investigators concluded that the pulmonary veins are an important source of ectopic beats, initiating frequent paroxysms of AF, and these foci respond to treatment with radiofrequency ablation.


   CLASSIFICATION OF ATRIAL FIBRILLATION
TOP
 ABSTRACT
 INTRODUCTION
 CAUSES OF ATRIAL FIBRILLATION
 CLASSIFICATION OF ATRIAL...
MANAGEMENT STRATEGIES
 CONCLUSION
 REFERENCES
 
AF may be categorized as paroxysmal, persistent, or permanent. Paroxysmal AF is AF that terminates spontaneously on at least 1 occasion; persistent AF does not terminate spontaneously; while permanent AF is resistant to pharmacological or electrical cardioversion. This 3P classification allows adequate division along the lines of clinical objectives of management. It can assist the planning of management strategies by defining treatment objectives, although many patients change from one category to another and thus therapy must be individualized.


   MANAGEMENT STRATEGIES
TOP
 ABSTRACT
 INTRODUCTION
 CAUSES OF ATRIAL FIBRILLATION
 CLASSIFICATION OF ATRIAL...
 MANAGEMENT STRATEGIES
CONCLUSION
 REFERENCES
 
There are 2 approaches to the treatment of AF. Traditionally, the initial treatment of AF has been aimed at controlling ventricular rates using atrioventricular (AV) nodal blocking drugs and then allowing spontaneous conversion to sinus rhythm.34–36 However, it has been shown that restoration of sinus rhythm by early cardioversion results in early alleviation of symptoms and may lower the incidence of thromboembolism, thus eliminating the need for long-term use of AV nodal blocking drugs and possibly allowing earlier discharge from the hospital.37

The advantages of rate control are that it is generally safe, well tolerated, and inexpensive. Its drawbacks are that there may be incomplete symptom resolution, bradycardia, the need for lifelong anticoagulation, and cardiomyopathy if the rate is poorly controlled. In contrast, rhythm control relieves symptoms and improves hemodynamics, may reduce thromboembolic risk, and may allow discontinuation of anticoagulation. However, it carries the risk of proarrhythmia, may cause adverse extracardiac effects, is ineffective on frequency, and is expensive.

A randomized multicenter comparison of these 2 treatment strategies in patients with AF at a high risk of stroke or death was undertaken in the recently concluded Atrial Fibrillation Follow-up Investigation of Rhythm Management study.38 The primary end point was overall mortality. A total of 4,060 patients (mean age, 69.7 ± 9.0 years) were enrolled in the study, 70.8% of whom had a history of hypertension and 38.2% had coronary artery disease (CAD). Of 3,311 patients who had echocardiography, 64.7% were shown to have an enlarged LA and 26.0% had LV dysfunction. There were 356 deaths among the patients assigned to rhythm control therapy and 310 deaths among those assigned to rate control therapy (mortality at 5 years, 23.8% and 21.3%, respectively; hazard ratio, 1.15 with 95% confidence interval of 0.99 to 1.34; p > 0.05). More patients in the rhythm control group than in the rate control group were hospitalized, and there were also more adverse drug effects in the former group. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio (INR) was subtherapeutic. The study concluded that the rhythm control strategy offers no survival advantage over the rate control strategy; additionally, rate control offers potential advantages, such as a lower risk of adverse drug effects. It recommended that anticoagulation be continued in these high-risk patients.

The indications for hospitalization of patients with AF and their management are outlined in Table 2Go. The major objectives of therapy in patients with AF are ventricular rate control, cardioversion of AF and subsequent maintenance of sinus rhythm, prevention of thrombo-embolism, and treatment of the underlying cause.


View this table:
[in this window]
[in a new window]
  		Table 2. Indications for Hospitalization of Patients With Atrial Fibrillation
 
VENTRICULAR RATE CONTROL
The consequences of tachycardia in untreated AF vary depending on the underlying heart disease. In addition to the loss of atrial contribution to ventricular filling that occurs with AF, an uncontrolled ventricular response results in decreased diastolic filling time and increased myocardial oxygen demand, either or both of which may have serious clinical consequences. Decreased diastolic filling time may cause significant elevation of left atrial pressure, particularly in patients with restricted ventricular filling, such as those with mitral stenosis or hypertrophic cardiomyopathy.39 In patients with CAD, the combination of shortened diastole and increased oxygen demand may precipitate myocardial ischemia.

Patients with untreated AF may present with a wide range of ventricular responses, but the usual mean ventricular rate in resting untreated patients is between 110 and 160 beats•min-1. Rates lower than 80 beats•min-1 suggest intrinsic AV nodal disease (although high vagal tone may occasionally be responsible), whereas rates above 150 beats•min-1 may indicate a high catecholamine state, such as thyrotoxicosis, fever, dehydration, acute blood loss, or CHF.40

It is probably not possible to be specific about an optimal resting or exercise heart rate in AF because interpatient variability is great, partly due to the presence and the type of underlying disease. Nevertheless, it is clinically appropriate to aim for a resting heart rate under 90 beats•min-1 and to assess carefully and treat patients for objective evidence of symptoms related to exertional tachycardia.40

When a patient is in AF, one of the first goals of therapy should be control of ventricular rate. This can be accomplished using calcium channel blockers such as diltiazem or verapamil, beta-blockers such as metoprolol or esmolol, or digoxin. Various drugs used to control ventricular rate are listed in Table 3Go.


View this table:
[in this window]
[in a new window]
  		Table 3. Drugs for Ventricular Rate Control
 
Intravenous calcium channel blockers and beta-blockers have the advantage of rapid onset of action (see Table 3Go). Digoxin, which is perhaps the oldest form of therapy for AF, has an onset of action between 30 minutes and 2 hours, with peak effect in 2 to 6 hours. Its effects are primarily mediated through the autonomic nervous system.41 At therapeutic doses, vagal tone is enhanced by actions on the central and peripheral parasympathetic nervous systems. Digoxin is therefore not as effective in ventricular rate control when catecholamine levels are elevated. In addition, its effectiveness varies with the individual patient’s autonomic tone.

CARDIOVERSION OF ATRIAL FIBRILLATION
Mortality from cardiovascular disorders is almost doubled in patients with AF compared to an age-matched population without AF.42,43 Patients with AF are also at a higher risk of cerebrovascular embolism. Furthermore, because of the loss of atrial contractility, AF is hemodynamically less effective than sinus rhythm in providing optimal cardiac output.44 Consequently, patients with AF and structural heart disease complain more frequently of palpitations, dyspnea, and syncope than individuals with sinus rhythm. Therefore, attempts to achieve and maintain sinus rhythm are warranted to provide relief of symptoms, prevention of embolism, and avoidance of tachycardic cardiomyopathy, thus reducing mortality and improving the quality of life in patients with AF.

Cardioversion is often performed electively to restore sinus rhythm in patients with persistent AF. The need for cardioversion can be immediate, however, when the arrhythmia is the main factor responsible for acute heart failure, hypotension, or worsening angina pectoris in a patient with CAD.45 The rate of spontaneous cardioversion to sinus rhythm within the first 24 hours is 30% to 50%, depending upon the duration of AF, and can be raised to 70% to 80% by pharmacological cardioversion and to 80% to 90% by electrical cardioversion.37,46,47

External direct current cardioversion is the most effective means of cardioverting AF to sinus rhythm. The risk of proarrhythmia during cardioversion is very low. Unfortunately, electrical cardioversion is painful and requires the use of conscious sedation. Pharmacological cardioversion of recent-onset AF carries the advantage of being simpler, more convenient, and free of the need for sedation.37,47 Various drugs used for pharmacological cardioversion37,48–51 are described in Table 4Go.


View this table:
[in this window]
[in a new window]
  		Table 4. Antiarrhythmic Drugs for Maintenance Therapy in Atrial Fibrillation
 
Pharmacological cardioversion appears to be most effective when initiated within 7 days after the onset of AF.50,52,53 Most such patients have paroxysmal AF, a first-documented episode of AF, or an unknown pattern of AF at the time of treatment.

The need for anticoagulation depends on the duration of AF. If the duration is less than 48 hours, anticoagulation is not mandatory before or after cardioversion. If AF has lasted for more than 48 hours, 3 weeks of anticoagulation at therapeutic INR range before cardioversion is recommended. Alternatively, anticoagulation (heparin and/or warfarin) is initiated followed by transesophageal echocardiography (TEE) to check for atrial thrombi; if the result is negative, cardioversion is attempted. Anticoagulation at therapeutic INR should continue for 4 weeks postcardioversion.

MAINTENANCE OF SINUS RHYTHM
Whether paroxysmal or persistent, AF is a chronic disorder and recurrence is likely at some point in most patients.54 The risk factors for frequent recurrence of paroxysmal AF (> 1 episode/month) include female sex and underlying heart disease,55 while those for persistent AF are age above 55 years, heart failure, hypertension, and AF lasting more than 3 months.56 Prophylactic treatment with antiarrhythmic drugs is therefore often necessary. The goal of maintenance therapy is suppression of symptoms and sometimes prevention of tachycardia-induced cardiomyopathy due to AF. It is not yet known if maintenance of sinus rhythm prevents thromboembolism, heart failure, or death.57

Before starting antiarrhythmic drug therapy, reversible cardiovascular and noncardiovascular precipitants of AF should be addressed. Prophylactic drug treatment is seldom indicated in the case of a first-detected episode of AF and can also be avoided in patients with infrequent and well-tolerated paroxysmal AF.

The commonly used drugs for maintaining sinus rhythm after cardioversion of AF include various classes of antiarrhythmic agents. Class IA antiarrhythmics include quinidine, procainamide, and disopyramide. All patients treated with this class of drugs should be concomitantly administered AV nodal blocking agents. Some patients demonstrate slowing in atrial rate and increase in AV conduction with rapid ventricular rates when treated with class IA agents alone. With all class IA agents, QRS and QTc prolongation are the main electrocardiographic manifestations.

Quinidine should not be used in patients with a prolonged baseline QTc interval (> 460 msec); prior thrombocytopenic purpura during quinidine administration; or complete heart block, unless a ventricular pacemaker is present. The drug slows digoxin elimination and simultaneously reduces its volume of distribution, leading to a higher serum digoxin level. It also potentiates the anticoagulant effect of warfarin. Renal or hepatic dysfunction slows the elimination of the parent drug and/or its metabolites, while CHF causes a reduction in the apparent volume of distribution; any of these conditions can result in quinidine toxicity if its dosage is not appropriately reduced. Periodic blood count and liver and kidney function tests during long-term therapy are recommended.

Procainamide administered intravenously is useful for acute conversion and can subsequently be converted to an oral dose. It is a negative inotropic agent and a vasodilator, and care must be taken in administering this drug to patients with reduced LV function. Contraindications include history of complete heart block, unless a ventricular pacemaker is present; lupus erythematosus; and long QTc at baseline (> 460 msec). The level of its active metabolite, N-acetylprocainamide (itself a class III antiarrhythmic), rises in patients taking cimetidine, ranitidine, beta-blockers, amiodarone, trimethoprim, and quinidine. Procainamide may enhance the effects of skeletal muscle relaxants, quinidine, lidocaine, and neuromuscular blockers. Ofloxacin inhibits tubular secretion of procainamide and may increase its bioavailability. Procainamide taken concurrently with sparfloxacin may increase the risk of cardiotoxicity. Agranulocytosis may occur, so weekly complete blood count is recommended for the first 3 months and at regular intervals thereafter. Renal insufficiency may lead to plasma accumulation of procainamide and its active metabolite.

Disopyramide is not commonly used to treat AF because of its adverse anticholinergic effects and its strong negative inotropic effects, which may precipitate CHF and cardiogenic shock in patients with reduced LV function. Dose adjustment is necessary in patients with liver or renal disease and in elderly persons, as anticholinergic effects can cause urinary retention and blurred vision.

Another group of antiarrhythmics, class IC agents, is indicated for use in patients with AF and supraventricular tachycardia without structural heart disease. These agents generally are not used in patients with concomitant LV dysfunction and/or CAD, given that the Cardiac Arrhythmia Suppression Trials I and II showed increased mortality.58 The applicability of the trial results to other populations (e.g., those without recent myocardial infarction) is uncertain.

The class IC agent propafenone shortens the upstroke velocity (phase 0) of a monophasic action potential. It reduces the fast inward current carried by sodium ions in the Purkinje fibers and, to a lesser extent, in myocardial fibers. It may raise the diastolic excitability threshold and prolong effective refractory period. It reduces spontaneous automaticity and depresses triggered activity. It should be used in conjunction with AV nodal blocking agents when given to patients in AF because conversion to atrial flutter with 1:1 conduction (producing fast ventricular rates) has been noted. Contraindications include documented hypersensitivity, second- or third-degree AV block, right bundle branch block associated with left hemiblock (bifascicular block) or trifascicular block, and concurrent use with ritonavir or amprenavir. It is highly metabolized in the liver and a considerable percentage of its metabolites (18% to 35%) is excreted in the urine. Thus, patients with impaired liver or renal function need careful monitoring for excessive pharmacological effects.

Currently, class III antiarrhythmic agents sotalol and dofetilide are approved by the US Food and Drug Administration for use in treating atrial arrhythmias; however, another class III agent amiodarone also is widely employed in the maintenance of sinus rhythm in patients with AF. Sotalol is an antiarrhythmic with beta-blocking effects. It has been shown to be effective in the maintenance of sinus rhythm, even in patients with underlying structural heart disease. Adult dosage is 80 mg orally twice a day initially, with the therapeutic goal of 120 to 160 mg twice a day. Contraindications include prolonged QTc at baseline (generally > 500 msec), reactive airway disease, renal failure, and electrolyte abnormalities. Class IA and class III agents can enhance potassium channel blocking effect, so they should not be given concomitantly. The risk factors for sotalol-induced torsade de pointes (which has an incidence of 1.5% to 2%) include impaired renal function; hypokalemia; female sex; slow heart rates; daily dosage above 320 mg; history of CHF, ventricular tachycardia, or ventricular fibrillation; and QTc exceeding 500 to 525 msec.

Dofetilide has no effect on cardiac output, cardiac index, stroke volume index, or systemic vascular resistance in patients with ventricular tachycardia, mild to moderate CHF, angina, and either normal or reduced LV function. There is no evidence of negative inotropic effect. The usual dosage is 125 to 500 µg twice daily, and it must be started in inpatient-monitored setting for 3 days by a certified clinician. The dosage is determined by creatinine clearance and QTc response to initial doses. Contraindications include documented hypersensitivity, creatinine clearance below 20 mL•min-1, and QTc above 440 msec at baseline and exceeding 500 msec after the second dose. It should not be used in conjunction with trimethoprim, either alone or in combination with sulfamethoxazole, verapamil, ketoconazole, cimetidine, megestrol, phenothiazines, tricyclic antidepressants, or prochlorperazine.

Amiodarone has antiarrhythmic effects that overlap all the 4 Vaughn-Williams antiarrhythmic classes. It has a low risk of proarrhythmia, and any proarrhythmic reactions generally are delayed. It can be used in patients with structural heart disease. Most clinicians are comfortable with inpatient or outpatient loading with 400 mg orally thrice daily for 1 week because of its low proarrhythmic effect, followed by weekly reduction aiming at the lowest dosage with the desired therapeutic benefit (the usual maintenance dose for AF is 200 mg/day). Contraindications include documented hypersensitivity, complete AV block, intraventricular conduction defects, and use of ritonavir or sparfloxacin. Amiodarone increases the effects and blood levels of theophylline, methotrexate, digoxin, cyclosporine, beta-blockers, and anticoagulants. The cardiotoxicity of amiodarone is increased by ritonavir and sparfloxacin. Co-administration with calcium channel blockers may cause an additive effect and may further decrease myocardial contractility. It is associated with a 3% to 7% incidence of pulmonary toxicity that is dose-related but is rare with doses below 400 mg/day. Baseline thyroid, liver, and pulmonary functions should be tested, followed by thyroid and liver function tests at 6-monthly intervals and yearly chest radiography to look for evidence of pulmonary fibrosis.

A recent study comparing the efficacy of propafenone, sotalol, and amiodarone concluded that amiodarone is more effective than the other 2 drugs in the prevention of recurrence of AF.59 The newer class III drug dofetilide was found to be effective in converting AF, preventing its recurrence, and reducing the risk of hospitalization for worsening heart failure in patients with CHF and LV dysfunction. The drug had a neutral effect on mortality.60

The patient’s cardiac disease has to be taken into account when deciding on the choice of antiarrhythmic agent, as indicated in Table 5Go.


View this table:
[in this window]
[in a new window]
  		Table 5. Choice of Antiarrhythmic Agents for Maintaining Sinus Rhythm in Patients With Atrial Fibrillation and Concomitant Cardiac Diseases
 
An important issue of antiarrhythmic treatment concerns monitoring, which varies with the drug used and with patient characteristics. For class IC antiarrhythmics, QRS widening should not exceed 150% of pretreatment duration. For class IA and III agents, the QTc interval in sinus rhythm should not exceed 520 msec. Exercise testing can be helpful for detecting QRS widening that occurs only at rapid heart rates. During follow-up, serum magnesium, potassium, urea, and creatinine levels should be monitored carefully. Noninvasive tests should be performed to evaluate LV function, especially if there is suspicion of CHF developing during treatment. Patients should be alerted to the potential significance of such symptoms as syncope, angina pectoris, or dyspnea and warned about the use of noncardiac drugs that can prolong QT interval. In addition, antiarrhythmics may cause arrhythmia during treatment. Table 6Go shows the various arrhythmias that can occur during treatment with these drugs.


View this table:
[in this window]
[in a new window]
  		Table 6. Arrhythmias Caused by Antiarrhythmic Drugs During Treatment of Atrial Fibrillation
 
MANAGEMENT OF LONE ATRIAL FIBRILLATION
Although there is no clear consensus on the use of antiarrhythmic drugs in the treatment of lone AF, many experts believe that their use should be limited to cases where symptoms are severe and persistent.61,62 Management of patients with acute attacks of lone AF is based on the same principles as mentioned earlier.

Digoxin has long been the drug of choice for preventing lone AF.26 However, it is now clear that it does not do so and in fact does more harm than good.46,63–66 Digoxin does not prevent intermittent AF, and its prolonged use may actually convert the intermittent form to the chronic form.26,27,46,66 Recent studies concluded that almost 50% of all patients prescribed digoxin should not be taking it at all and can safely be weaned from it.67,68 Thus, digoxin is not recommended for the prevention of intermittent lone AF attacks,27,66,67 while other antiarrhythmic drugs such as quinidine, amiodarone, propranolol, sotalol, and flecainide may be effective.

PREVENTION OF THROMBOEMBOLISM
AF is an independent risk factor for stroke. The risk is four- to fivefold higher in patients with AF than in the unaffected population.13,14,19,69 While the risk of stroke is not due solely to AF, AF substantially increases the risk of stroke in the presence of other cardiovascular disorders. The attributable risk of stroke from AF is estimated to be 1.5% in the age group of 50 to 59 years and approaches up to 30% in the age group of 80 to 89 years.70,71 Patients with paroxysmal AF have an annualized stroke rate (3.2%) similar to that in patients with chronic AF (3.3%).44 Several trials have documented a reduction in the risk of thromboembolism with the use of anticoagulant and antiplatelet agents compared to placebo.6,7,18,42,72,73

In hemodynamically compromised patients, AF must be treated emergently with synchronized electrical cardioversion. However, cardioversion carries a risk of thromboembolism unless anticoagulation prophylaxis is initiated before the procedure, and this risk appears to be greatest when the arrhythmia has been present for more than 48 hours. There are no controlled studies available to suggest recommendations regarding anticoagulation in these patients. A nonrandomized trial in 437 subjects concluded that the incidence of an embolic event was 0.8% in the group receiving anticoagulant therapy compared with 5.3% in the group not receiving anticoagulation.74 These results are impressive because the number of patients with CHF, hypertension, and RHD was higher in the anticoagulated group.

To reduce the risk of thromboembolism when AF is present for more than 48 hours, TEE is done to detect any thrombi in the LA or its appendage. If there is no evidence of clots, cardioversion can be performed safely followed by warfarin administration for at least a month. For stable outpatients with atrial thrombi, anticoagulation with warfarin (to maintain INR at 2.0 to 3.0) for 3 weeks prior to and 4 weeks after cardioversion is recommended.63 The current recommendations for the prevention of thromboembolism in patients with AF45 are outlined in Table 7Go.


View this table:
[in this window]
[in a new window]
  		Table 7. Recommendations for Antithrombotic Therapy in Patients With Atrial Fibrillation Based on Thromboembolic Risk Stratification
 
The pharmacological management of AF according to the 3P classification is summarized in Figure 1Go.





View larger version (59K):
[in this window]
[in a new window]
  		Figure 1. Pharmacological management of patients with (A) newly discovered atrial fibrillation, (B) recurrent paroxysmal atrial fibrillation, and (C) recurrent persistent or permanent atrial fibrillation.

 

   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 CAUSES OF ATRIAL FIBRILLATION
 CLASSIFICATION OF ATRIAL...
 MANAGEMENT STRATEGIES
 CONCLUSION
REFERENCES
 
Despite better understanding of the management of arrhythmia, its prevalence is substantially underestimated, possibly due to underdetection and undersampling. Among other causes, nonrheumatic, nonvalvular AF remains a significant risk factor for stroke. The pulmonary venous openings into the LA remain an important source of ectopic beats, initiating frequent paroxysms of AF. The foci respond to radiofrequency ablation.

Management strategies include rate and rhythm control. Recent studies concluded that rhythm control does not offer greater survival benefit over the rate control strategy, although long-term anticoagulation is required in the latter. Newer drugs are available for maintenance of sinus rhythm. The risk of adverse drug reactions necessitates follow-up monitoring as well as clinical assessments for adverse effects.

TEE has an important role in deciding on cardioversion in acute AF. The risk of thromboembolism in paroxysmal and chronic AF is similar. Trials have documented reduction in the incidence of thromboembolism with the use of anticoagulant and antiplatelet drugs. Synchronized direct current cardioversion remains the treatment of choice in hemodynamically compromised patients.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 CAUSES OF ATRIAL FIBRILLATION
 CLASSIFICATION OF ATRIAL...
 MANAGEMENT STRATEGIES
 CONCLUSION
 REFERENCES
 

  1. Murgatroyd FD, Camm AJ. Atrial arrhythmias. Lancet 1993;341:1317–22.[Medline]

  2. Cuddy TE, Connolly SJ. Auricular fibrillation and flutter [French]. Can J Cardiol 1996;12(Suppl A):6A–9A.

  3. Tavel ME. Atrial fibrillation. Problems in management. Chest 1996;110:1089–91.[Free Full Text]

  4. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: the Framingham Study. N Engl J Med 1982;306:1018–22.[Abstract]

  5. Furberg CD, Psaty BM, Manolio TA, Gardin JM, Smith VE, Rautaharju PM. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol 1994;74:236–41.[Medline]

  6. Chugh SS, Blackshear JL, Shen WK, Hammill SC, Gersh BJ. Epidemiology and natural history of atrial fibrillation: clinical implications. J Am Coll Cardiol 2001;37:371–8.[Abstract/Free Full Text]

  7. Blackshear JL, Kopecky SL, Litin SC, Safford RE, Hammill SC. Management of atrial fibrillation in adults: prevention of thromboembolism and symptomatic treatment. Mayo Clin Proc 1996;71:150–60.[Abstract]

  8. Page RL, Wilkinson WE, Clair WK, McCarthy EA, Pritchett EL. Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia. Circulation 1994;89:224–7.[Abstract/Free Full Text]

  9. Meijler FL, Wittkampf FHM. Role of the atrioventricular node in atrial fibrillation. In: Falk RH, Podrid PJ, editors. Atrial fibrillation: mechanisms and management. 2nd ed. Philadelphia: Lippincott-Raven, 1997.

  10. Braunwald E. Heart disease: a textbook of cardiovascular medicine. 3rd ed. Philadelphia: Saunders, 1988.

  11. Lip GYH. ABC of atrial fibrillation. London: BMJ Publishing, 1996.

  12. Benjamin EJ, Wolf PA, Kannel WB. The epidemiology of atrial fibrillation. In: Falk RH, Podrid PJ, editors. Atrial fibrillation: mechanisms and management. 2nd ed. Philadelphia: Lippincott-Raven, 1997.

  13. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22:983–8.[Abstract/Free Full Text]

  14. Hart RG, Halperin JL. Atrial fibrillation and stroke. Revisiting the dilemmas. Stroke 1994;25:1337–41.[Medline]

  15. Szekely P. Systemic embolism and anticoagulant prophylaxis in rheumatic heart disease. Br Med J 1964;1:1209–12.

  16. Fleming HA, Bailey SM. Mitral valve disease, systemic embolism and anticoagulants. Postgrad Med J 1971;47:599–604.[Abstract/Free Full Text]

  17. Fisher CM. Treatment of chronic atrial fibrillation. Lancet 1972;1:1284.

  18. Fisher CM. Reducing risks of cerebral embolism. Geriatrics 1979;34:59–61,65–6.[Medline]

  19. Wolf PA, Dawber TR, Thomas HE Jr, Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham Study. Neurology 1978;28:973–7.[Abstract/Free Full Text]

  20. Tanaka H, Hayashi M, Date C, Imai K, Asada M, Shoji H, et al. Epidemiologic studies of stroke in Shibata, a Japanese provincial city: preliminary report on risk factors for cerebral infarction. Stroke 1985;16:773–80.[Abstract/Free Full Text]

  21. Onundarson PT, Thorgeirsson G, Jonmundsson E, Sigfusson N, Hardarson T. Chronic atrial fibrillation — epidemiologic features and 14 year follow-up: a case control study. Eur Heart J 1987;8:521–7.[Abstract/Free Full Text]

  22. Flegel KM, Shipley MJ, Rose G. Risk of stroke in non-rheumatic atrial fibrillation. Lancet 1987;1:526–9.[Medline]

  23. Davidson E, Rotenberg Z, Weinberger I, Fuchs J, Agmon J. Diagnosis and characteristics of lone atrial fibrillation. Chest 1989;95:1048–50.[Abstract/Free Full Text]

  24. Rostagno C, Bacci F, Martelli M, Naldoni A, Bertini G, Gensini G. Clinical course of lone atrial fibrillation since first symptomatic arrhythmic episode. Am J Cardiol 1995;76:837–9.[Medline]

  25. Mandel WJ, editor. Cardiac arrhythmias: their mechanisms, diagnosis, and management. 2nd ed. Philadelphia: Lippincott, 1987.

  26. Cheitlin, MD, Sokolow M, McIlroy MB. Clinical cardiology. 6th ed. Norwalk, CT: Appleton & Lange, 1993:527–34.

  27. Havranek EP. The management of atrial fibrillation: current perspectives. Am Fam Physician 1994;50:959–68.[Medline]

  28. Aboaf AP, Wolf PS. Paroxysmal atrial fibrillation. A common but neglected entity. Arch Intern Med 1996;156:362–7.[Abstract/Free Full Text]

  29. Kopecky SL, Gersh BJ, McGoon MD, Whisnant JP, Holmes DR Jr, Ilstrup DM, et al. The natural history of lone atrial fibrillation. A population-based study over three decades. N Engl J Med 1987;317:669–74.[Abstract]

  30. Alpert MA, Kazi W, Mukerji V. Management of atrial fibrillation. Compr Ther 1996;22:501–8.[Medline]

  31. Brand FN, Abbott RD, Kannel WB, Wolf PA. Characteristics and prognosis of lone atrial fibrillation. 30-year follow-up in the Framingham Study. JAMA 1985;254:3449–53.[Abstract/Free Full Text]

  32. Stroke Prevention in Atrial Fibrillation Investigators. Risk factors for thromboembolism during aspirin therapy in patients with atrial fibrillation: the Stroke Prevention in Atrial Fibrillation Study. J Stroke Cerebrovasc Dis 1995;5:147–57.

  33. Haïssaguerre M, Jaïs P, Shah DC, Takahashi A, Hocini M, Quiniou G, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659–66.[Abstract/Free Full Text]

  34. Shettigar UR, Toole JG, Appunn DO. Combined use of esmolol and digoxin in the acute treatment of atrial fibrillation or flutter. Am Heart J 1993;126:368–74.[Medline]

  35. Schreck DM, Rivera AR, Tricarico VJ. Emergency management of atrial fibrillation and flutter: intravenous diltiazem versus intravenous digoxin. Ann Emerg Med 1997;29:135–40.[Medline]

  36. Digitalis in Acute Atrial Fibrillation (DAAF) Trial Group. Intravenous digoxin in acute atrial fibrillation. Results of a randomized, placebo-controlled multicentre trial in 239 patients. Eur Heart J 1997;18:649–54.[Abstract/Free Full Text]

  37. Gallik D, Altamirano J, Singh BN. Restoring sinus rhythm in patients with atrial flutter and fibrillation: pharmacologic or electrical cardioversion? J Cardiovasc Pharmacol Ther 1997;2:135–44.

  38. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825–33.[Abstract/Free Full Text]

  39. Robinson K, Frenneaux MP, Stockins B, Karatasakis G, Poloniecki JD, McKenna WJ. Atrial fibrillation in hypertrophic cardiomyopathy: a longitudinal study. J Am Coll Cardiol 1990;15:1279–85.[Abstract]

  40. Falk RH. Pharmacologic control of heart rate in atrial fibrillation. Cardiol Clin 1996;14:521–36.[Medline]

  41. Watanabe AM. Digitalis and the autonomic nervous system. J Am Coll Cardiol 1985;5(Suppl A):35A–42A.

  42. Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med 1990;323:1505–11.[Abstract]

  43. Stroke Prevention in Atrial Fibrillation Study Group. Preliminary report of the Stroke Prevention in Atrial Fibrillation Study. N Engl J Med 1990;322:863–8.[Abstract]

  44. Alpert JS, Petersen P, Godtfredsen J. Atrial fibrillation: natural history, complications, and management. Annu Rev Med 1988;39:41–52.[Medline]

  45. Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary. Circulation 2001;104:2118–50.[Free Full Text]

  46. Golzari H, Cebul RD, Bahler RC. Atrial fibrillation: restoration and maintenance of sinus rhythm and indications for anticoagulation therapy. Ann Intern Med 1996;125:311–23.[Abstract/Free Full Text]

  47. Costeas C, Kassotis J, Blitzer M, Reiffel JA. Rhythm management in atrial fibrillation — with a primary emphasis on pharmacological therapy: Part 2. Pacing Clin Electrophysiol 1998;21:742–52.[Medline]

  48. Biffi M, Boriani G, Bronzetti G, Capucci A, Branzi A, Magnani B. Electrophysiological effects of flecainide and propafenone on atrial fibrillation cycle and relation with arrhythmia termination. Heart 1999;82:176–82.[Abstract/Free Full Text]

  49. Kingma JH, Suttorp MJ. Acute pharmacologic conversion of atrial fibrillation and flutter: the role of flecainide, propafenone, and verapamil. Am J Cardiol 1992;70:56A–60A.[Medline]

  50. Suttorp MJ, Kingma JH, Jessurun ER, Lie-A-Huen L, van Hemel NM, Lie KI. The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. J Am Coll Cardiol 1990;16:1722–7.[Abstract]

  51. Weiner P, Ganam R, Ganem R, Zidan F, Rabner M. Clinical course of recent-onset atrial fibrillation treated with oral propafenone. Chest 1994;105:1013–6.[Abstract/Free Full Text]

  52. Borgeat A, Goy JJ, Maendly R, Kaufmann U, Grbic M, Sigwart U. Flecainide versus quinidine for conversion of atrial fibrillation to sinus rhythm. Am J Cardiol 1986;58:496–8.[Medline]

  53. Platia EV, Michelson EL, Porterfield JK, Das G. Esmolol versus verapamil in the acute treatment of atrial fibrillation or atrial flutter. Am J Cardiol 1989;63:925–9.[Medline]

  54. Van Gelder IC, Crijns HJ, Tieleman RG, Brugemann J, De Kam PJ, Gosselink AT, et al. Chronic atrial fibrillation. Success of serial cardioversion therapy and safety of oral anticoagulation. Arch Intern Med 1996;156:2585–92.[Abstract/Free Full Text]

  55. Suttorp MJ, Kingma JH, Koomen EM, van’t Hof A, Tijssen JG, Lie KI. Recurrence of paroxysmal atrial fibrillation or flutter after successful cardioversion in patients with normal left ventricular function. Am J Cardiol 1993;71:710–3.[Medline]

  56. Planning and Steering Committees of the AFFIRM study for the NHLBI AFFIRM investigators. Atrial fibrillation follow-up investigation of rhythm management — the AFFIRM study design. Am J Cardiol 1997;79:1198–202.[Medline]

  57. Hohnloser SH, Kuck KH. Atrial fibrillation — maintaining sinus rhythm versus ventricular rate control: the PIAF trial. Pharmacological Intervention in Atrial Fibrillation. J Cardiovasc Electrophysiol 1998;9(Suppl):121–6.

  58. Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med 1992;327:227–33.[Abstract]

  59. Roy D, Talajic M, Dorian P, Connolly S, Eisenberg MJ, Green M, et al. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med 2000;342:913–20.[Abstract/Free Full Text]

  60. Torp-Pedersen C, Møller M, Bloch-Thomsen PE, Køber L, Sandøe E, Egstrup K, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med 1999;341:857–65.[Abstract/Free Full Text]

  61. Roden DM. Risks and benefits of antiarrhythmic therapy. N Engl J Med 1994;331:785–91.[Free Full Text]

  62. Coumel P, Thomas O, Leenhardt A. Drug therapy for prevention of atrial fibrillation. Am J Cardiol 1996;77:3A–9A.[Medline]

  63. Prystowsky EN, Benson DW Jr, Fuster V, Hart RG, Kay GN, Myerburg RJ, et al. Management of patients with atrial fibrillation. A statement for healthcare professionals from the Subcommittee on Electrocardiography and Electrophysiology, American Heart Association. Circulation 1996;93:1262–77.[Free Full Text]

  64. Baer M, Goldschlager N. Atrial fibrillation: an update on new management strategies. Geriatrics 1995;50:22–9.

  65. Pritchett EL. Management of atrial fibrillation. N Engl J Med 1992;326:1264–71.[Medline]

  66. Falk RH. Proarrhythmia in patients treated for atrial fibrillation or flutter. Ann Intern Med 1992;117:141–50.

  67. Aronow WS. Prevalence of appropriate and inappropriate indications for use of digoxin in older patients at the time of admission to a nursing home. J Am Geriatr Soc 1996;44:588–90.[Medline]

  68. Fair JF. Supervised withdrawal of long-term digoxin therapy. Fam Pract 1990;7:56–9.[Abstract/Free Full Text]

  69. Cairns JA, Connolly SJ. Nonrheumatic atrial fibrillation. Risk of stroke and role of antithrombotic therapy. Circulation 1991;84:469–81.[Free Full Text]

  70. Stroke Prevention in Atrial Fibrillation Investigators. Predictors of thromboembolism in atrial fibrillation: I. Clinical features of patients at risk. Ann Intern Med 1992;116:1–5.

  71. Stroke Prevention in Atrial Fibrillation Investigators. Predictors of thromboembolism in atrial fibrillation: II. Echocardiographic features of patients at risk. Ann Intern Med 1992;116:6–12.

  72. Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK Study. Lancet 1989;1:175–9.[Medline]

  73. Connolly SJ, Laupacis A, Gent M, Roberts RS, Cairns JA, Joyner C. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol 1991;18:349–55.[Abstract]

  74. Bjerkelund CJ, Orning OM. The efficacy of anticoagulant therapy in preventing embolism related to D.C. electrical conversion of atrial fibrillation. Am J Cardiol 1969;23:208–16.[Medline]




This article has been cited by other articles:


Home page
 PsychosomaticsHome page
S. J. Finch and L. T. van Zyl
Cardioversion of Persistent Atrial Arrhythmia After Treatment With Venlafaxine in Successful Management of Major Depression and Posttraumatic Stress Disorder
Psychosomatics, December 1, 2006; 47(6): 533 - 536.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kasliwal, R. R
Right arrow Articles by Bhatia, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kasliwal, R. R
Right arrow Articles by Bhatia, A.
Related Collections
Right arrow Cardiac - pharmacology

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS