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Table of Contents

Published May 29, 2002

Thomas J.
Dresing, MD

Department of
Cardiovascular
Medicine

Robert A.
Schweikert, MD

Department of
Cardiovascular Medicine

Print Chapter

Definition

Prevalence

Pathophysiology

Signs and
Symptoms

Diagnosis

Therapy

Outcomes

References

AF may be classified on the basis of the frequency of episodes and the ability of an episode to convert back to sinus rhythm. One method of classification is outlined in guidelines published by the American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC), with the collaboration of the North American Society of Pacing and Electrophysiology (NASPE).¹ According to these guidelines, if a patient has two or more episodes, AF is considered to be recurrent. Recurrent AF may be paroxysmal or persistent. If the AF terminates spontaneously it is designated as paroxysmal, and if the AF is sustained it is designated as persistent. In the latter case, termination of the arrhythmia with electrical or pharmacologic cardioversion does not change its designation. Persistent AF may present either as the first manifestation of the arrhythmia or as the culmination of recurrent episodes of paroxysmal AF. The category of persistent AF also includes permanent AF, which refers to long-standing (generally > 1 year) AF for which cardioversion was not indicated or attempted.

New insights about the factors involved in the initiation and continuation of AF has led some investigators to propose a revised model of this complex arrhythmia. For many years, the focus had been on the substrate within the atria that supports the maintenance of AF. The "multiple wavelet" model suggested that AF is sustained by multiple simultaneous wavelets wandering throughout the atria.² Therefore, therapy was aimed at making these wavelets less likely to sustain and propagate. Such treatments included antiarrhythmic medications and surgical interruption of the atrial tissue.

More recently, it has been recognized that the initiation of AF in most cases is due to premature atrial contractions caused by triggering beats that arise from the pulmonary veins near the junction with the left atrium.³ These triggers may also fire repetitively and contribute to the maintenance of AF, essentially becoming "drivers" of AF. These findings led to a revised model of AF that incorporates the interaction of these triggers for initiation and the substrate for maintenance (Figure 1).

AF may have hemodynamic consequences. It may decrease the cardiac output by as much as 20%, increase pulmonary capillary wedge pressure, and increase atrial pressures. These effects are due to tachycardia, loss of atrial contribution to left ventricular (LV) filling, increased valvular regurgitation, and the irregular ventricular response. Some investigators have suggested that the irregularity of the R-R intervals contributes more to the hemodynamic changes than does the mere presence of tachycardia.⁴

The clinician must realize that an irregular pulse detected by physical examination or an irregular ventricular rhythm seen by electrocardiography (ECG) is not always AF. It is necessary to consider and exclude other types of irregular rhythm disturbances, including atrial or ventricular ectopy, atrial tachycardia or flutter with variable AV conduction, multifocal atrial tachycardia, and chaotic atrial rhythm or wandering atrial pacemaker (Figures 2 and 3). Conversely, a regular pulse or rhythm does not exclude AF. For example, AF can present with a regular ventricular response in the presence of AV block or with a ventricular paced rhythm.

An ECG is essential for proper diagnosis. ECG findings in AF include the absence of P waves, the presence of chaotic atrial activity and fibrillatory waves (f waves), and an atrial rate in the range of 300 to 700 beats per minute (bpm). In the absence of drug therapy, a patient with normal AV conduction will have an "irregularly irregular" ventricular rhythm and will often have a ventricular rate in the range of 120 to 180 bpm (Figure 4). The baseline on the ECG strip often is undulating, and occasionally has coarse, irregular activity. This activity may resemble atrial flutter, but it is not as uniform from wave to wave as atrial flutter.

The diagnosis may be difficult when the atrial activity is of very low amplitude. During the immediate recovery period following cardiac surgery, temporary epicardial pacing wires provide a means of recording atrial electrograms. Likewise, an esophageal lead may provide more accurate atrial recordings than a surface electrocardiogram or rhythm strip. Rarely the diagnosis can only be made by means of intracardiac recordings obtained during an electrophysiologic study.

AF has particular importance in the setting of acute myocardial infarction (MI) and WPW syndrome. The first Global Utilization of Streptokinase and t-PA [tissue plasminogen activator] for Occluded Coronary Arteries (GUSTO-I) trial showed that patients with AF in the setting of acute MI had a higher incidence of both stroke and death at 30 days than did patients who were in sinus rhythm.⁵ Thus, the presence of AF in patients with MI is an ominous sign. Patients with WPW syndrome are particularly vulnerable to ventricular fibrillation and sudden death due to the development of AF, which may result in extremely rapid conduction over the accessory pathway (Figure 5). Prompt direct-current electrical cardioversion is of utmost importance for these patients. Treatment with AV node-blocking medications such as verapamil or digitalis may facilitate rapid conduction over the accessory pathway and result in ventricular fibrillation. When intravenous (IV) pharmacologic therapy is required, the drug of choice is procainamide. Amiodarone also may be an option.

The management of AF is directed at three basic goals: (1) control of the ventricular response, (2) minimization of thromboembolic risk, and (3) restoration and maintenance of sinus rhythm. The ACC/AHA/ESC guidelines provide a more detailed review of the management of AF.¹

Control of the Ventricular Response:

The ventricular response is controlled by drugs that slow conduction through the AV node (Table 1). If these medications are ineffective and if measures to suppress and/or cure AF have failed, a catheter ablation of the AV node and pacemaker implantation may be necessary for some patients.

Minimization of Thromboembolic Risk:

AF carries a considerable risk for thromboembolism. The Framingham study showed that during a follow up period of 30 years, the annual risk of stroke among AF patients was 4.2%; patients with nonvalvular AF had a greater than fivefold higher risk of stroke.⁶ In the Framingham study, even patients with lone AF had a much higher incidence of stroke than did controls over a period of almost 30 years.⁷ The annual risk of stroke may be even higher (7% to 10%) in patients with AF who have one or more of the following risk factors: age greater than 65 years, diabetes mellitus, hypertension, CHF, previous stroke or transient ischemic attack.

A number of trials have studied the reduction of stroke risk in patients with AF, including some that compared the relative benefits and risks of warfarin and aspirin. Overall, warfarin has been shown to reduce the annual average relative risk of stroke by 68%, while the reduction with aspirin has ranged between 0% and 44% (mean: approximately 20%).⁸ Findings of left atrial enlargement and reduced LV systolic function on echocardiography indicate an increase in thromboembolic risk. Younger patients with no other risk factors have a low risk of stroke and aspirin may be an acceptable alternative to warfarin. Patients older than 65 years with or without other risk factors have a greater risk of stroke and should be anticoagulated with warfarin if not contraindicated. The goal of warfarin therapy is an international normalized ratio (INR) of between 2.0 and 3.0. Older patients who are poor candidates for warfarin should be considered for aspirin therapy.

Patients who have been in AF for more than 48 hours are at risk for having formed an atrial thrombus, and these patients should be systemically anticoagulated whenever possible. This can be accomplished with oral warfarin or more quickly with IV heparin. For patients who have been in AF for more than 48 hours and are not adequately anticoagulated, electrical or pharmacological cardioversion should be delayed until appropriate measures are taken to reduce the thromboembolic risk.

There are two approaches to the reduction of thromboembolic risk for patients being considered for cardioversion of AF of greater than 48 hours duration. The conventional approach is to administer warfarin to achieve an INR value between 2.0 and 3.0 for at least 3 to 4 weeks prior to electrical or pharmacologic cardioversion. The second approach is the transesophageal echocardiography (TEE)-guided method. In some cases, cardioversion cannot be postponed for 3 or 4 weeks; in other cases, the patient and/or clinician may prefer an expedited approach to achieving sinus rhythm. In such situations, once a therapeutic level of anticoagulation is achieved with either warfarin or IV heparin, a TEE may be performed to rule out the presence of an intracardiac thrombus. If no thrombus is seen, cardioversion may be performed.

Warfarin should be continued after cardioversion until sinus rhythm has been maintained for at least 4 weeks in order to allow for the recovery of the atrial transport mechanism. If the cardioversion was performed using the TEE-guided approach with IV heparin as the method of anticoagulation, it is advisable to continue IV heparin until a therapeutic INR is achieved with warfarin. The decision to initiate and continue anticoagulation for AF of less than 48 hours' duration should be based on the presence of other risk factors for thromboembolism.

TEE can detect the presence of a thrombus in the left atrium, particularly in the left atrial appendage, which is poorly seen on transthoracic echocardiography. The TEE-guided approach has been validated in several small multicenter trials as well as in a large randomized multicenter trial known as the Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) trial.⁹

Restoration and Maintenance of
Sinus Rhythm:

Patients presenting with an initial episode of paroxysmal AF may not require ventricular rate-controlling or antiarrhythmic drug therapy, particularly if the episode is associated with a physiological stress as described above. Clinical observation may be an option in some patients, with the decision to treat based upon the development of recurrent episodes of AF. Likewise, a patient with an initial episode of persistent AF may be treated with appropriate anticoagulation as described above and if necessary a ventricular rate-controlling medication. At the appropriate time electrical or pharmacologic cardioversion can then be attempted without antiarrhythmic drug therapy. If recurrent AF occurs, then antiarrhythmic drug therapy may be considered.

Patients with symptomatic AF require treatment. If symptoms persist despite adequate ventricular rate control then suppression of paroxysmal AF or cardioversion of persistent AF is necessary. However, the management of patients with AF and minimal or no symptoms is controversial as it is unclear whether such patients benefit from the restoration of sinus rhythm. The possible benefits of achieving and maintaining sinus rhythm include reduction of long-term thromboembolic stroke risk, avoidance of the potential development of atrial cardiomyopathy from ongoing AF, and better quality of life. On the other hand, this approach often requires the use of antiarrhythmic drugs that may have important and potentially life threatening side effects. There is some evidence that these patients may only require treatment with control of the ventricular response and reduction of the thromboembolic risk with anticoagulation. Some nonrandomized trials have shown an increase in mortality among patients who were on long-term antiarrhythmic therapy for AF, presumably from the proarrhythmic effects of the drugs. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial is a large multicenter randomized study that compared restoration of sinus rhythm to ventricular rate control in patients with AF and minimal or no symptoms.¹⁰ This trial recently completed its follow up and preliminary reports suggest that there is no advantage in restoration of sinus rhythm compared with ventricular rate control in such patients. The results have not been reported in the medical literature, and the patients in this study were older (average age of 69 years) and able to tolerate AF.

In general, treatment of persistent AF with anticoagulation and ventricular rate control alone may be appropriate for selected older patients with minimal or no symptoms; however, younger patients may have more benefit from restoration and maintenance of sinus rhythm.

Restoration of sinus rhythm may be achieved with either pharmacological or electrical cardioversion. It is important to remember that electrical and pharmacologic cardioversion are no different with regard to the risk of thromboembolic stroke. Therefore, the requirements for anticoagulation outlined earlier apply to either method of cardioversion.

Direct-current Electrical Cardioversion
Of the two types of cardioversion, electrical is more effective. In the past, direct-current electrical cardioversion with a monophasic waveform was acutely successful in approximately 80% of cases. Since the introduction of the biphasic waveform defibrillator, the success rate has increased to approximately 94%.¹¹

Direct-current cardioversion should be administered with the patient under sedation, with cardiac and hemodynamic monitoring, and in the presence of personnel skilled in airway management. The administration of an antiarrhythmic drug may promote more successful direct-current cardioversion and maintenance of sinus rhythm. Similarly, it is reasonable to add an antiarrhythmic drug for any patient who fails direct-current cardioversion, and to consider a repeat attempt after the drug has been administered.

Pharmacologic Cardioversion
Rates of successful immediate cardioversion by pharmacologic means have ranged from 40% to 90%; the higher rates were observed in patients whose AF was of shorter duration.¹² However, pharmacologic cardioversion is often chosen as the first line of therapy due to its ease of administration and because there is no need to sedate the patient. Any patient who fails pharmacologic cardioversion should be considered for direct-current cardioversion.

The only IV agents approved in the United States for immediate pharmacologic cardioversion of AF are procainamide, amiodarone, and ibutilide (Table 2).

A number of oral agents may be used for maintenance of sinus rhythm for patients with AF (Table 3).

Quinidine was once widely prescribed for AF, but its use has decreased in recent years. In fact, all the class IA antiarrhythmic drugs—quinidine, procainamide, and disopyramide—have become less popular for the long-term treatment of AF. Other antiarrhythmic drugs—such as the class IC agents flecainide and propafenone—have more favorable side-effect profiles. However, the use of these medications does have some degree of risk. The Cardiac Arrhythmia Suppression Trial (CAST) showed that flecainide and encainide were associated with an increase in mortality when used for the suppression of ventricular arrhythmias in post-MI patients with ventricular dysfunction.¹³ As a result, there is much concern about the use of the class IC antiarrhythmics in patients who have any type of underlying coronary artery or structural heart disease, and in such patients other antiarrhythmic drugs may be better initial choices. Flecainide and propafenone are well-tolerated and are appropriate first-line options for the treatment of AF in patients who do not have heart disease.

Sotalol is a class III antiarrhythmic that has beta-blocking properties and is well tolerated. However, like other class III agents, it causes QT prolongation and may result in ventricular proarrhythmia such as torsades de pointes. Dofetilide, another class III agent, is the most recently approved antiarrhythmic for the treatment of AF. Its efficacy is similar to that of other agents in its class, and the incidence of proarrhythmia with this drug is acceptably low. Dofetilide has also been shown to be safe in patients with cardiomyopathy, CHF, and ischemic heart disease.^14,15

Amiodarone generally is reserved for patients whose AF is refractory to other antiarrhythmic drugs and for those in whom the other available agents are contraindicated. Amiodarone has potential time- and dose-dependent organ toxicities that affect the liver, thyroid, lungs and less frequently the eyes. It is recommended that baseline studies be performed prior to initiating this drug. These tests include an ophthalmologic examination, pulmonary spirometry and diffusion capacity test, and blood tests to assess liver and thyroid function. The blood tests should be repeated at regular intervals-approximately every 6 months-and the ophthalmologic examination should be administered yearly.

Implantable Devices
Implantable devices are being used with increasing frequency in patients with AF. These devices have several purposes, including bradycardia pacing support, ventricular response regularization, and AF suppression and/or termination. The ACC and AHA have published guidelines for the use of implantable pacemakers and antitachycardia devices.¹⁶

Pacemakers may be implanted simply for pacing support in patients with bradycardia. Sinus node dysfunction—often referred to as bradycardia-tachycardia syndrome—is not uncommon in patients with AF. Because this condition can be exacerbated by medications used to control AF, the presence of a pacemaker allows for more aggressive use of rate-controlling and/or antiarrhythmic medications. Yet a word of caution is necessary: pauses that occur with conversion to sinus rhythm, some that last as long as several seconds, are quite common; in the absence of symptoms, these pauses are not an indication for a permanent pacemaker.

Pacemakers are implanted in conjunction with catheter ablation of the AV node. This type of ablation is often reserved for patients with permanent or paroxysmal AF that is refractory to medical or curative therapy. The potential benefits of this type of approach extend beyond simply controlling ventricular response, as there is evidence that regularization of the ventricular rhythm confers hemodynamic or symptomatic benefits as well. Even so, such patients may still require systemic anticoagulation due to the ongoing presence of AF.

Several features of pacemaker systems may be useful for patients with AF. A pacemaker that has the capability to automatically change from a dual-chamber to single-chamber pacing mode at the onset of an episode of AF—commonly referred to as mode-switching—is essential for avoiding the rapid heart rates that might otherwise occur when the pacemaker responds to the sensing of atrial activity. Another feature available in some of the newer pacemakers is an algorithm of overdrive pacing that results in suppression of episodes of AF. This algorithm has been reported to effective, with one study showing a 25% decrease in the number of symptomatic AF episodes and a 63% reduction in the need for cardioversion during short-term follow up.¹⁷ Another pacemaker algorithm provides ventricular pacing during AF that results in a more regular ventricular response, and this has been reported to confer symptomatic benefit. Rapid atrial pacing is also being studied because it might be effective in terminating AF.

Implantable atrial defibrillators have been approved, but they have not been widely accepted by patients or physicians. Patients with ventricular arrhythmias and implantable cardioverter defibrillators may have a high incidence of atrial arrhythmias, which has led to the development of implantable devices that offer treatment for both atrial and ventricular arrhythmias, including antitachycardia pacing and defibrillation.

Catheter Ablation
Percutaneous catheter ablation has several applications for the restoration of sinus rhythm in patients with AF. The most exciting of these is pulmonary vein isolation, commonly referred to as focal AF ablation. The latter term is misleading, however, which will become apparent in the subsequent discussion. Other applications of the catheter ablation technique include the so-called linear AF ablation and ablation of atrial flutter.

Linear AF ablation was an attempt to achieve the same effect as the surgical Maze procedure but with a percutaneous, catheter-based approach. However, the results thus far have been disappointing due to modest effectiveness and prolonged procedural and fluoroscopy exposure times. This method has not gained widespread acceptance and is still experimental.

Catheter ablation may be useful for patients with AF that is effectively suppressed with an antiarrhythmic drug but who have developed typical atrial flutter. The antiarrhythmic drug may facilitate the atrial flutter, a condition commonly referred to as drug flutter. Catheter ablation of the right atrial flutter circuit is safe and effective, and with continued antiarrhythmic drug therapy may be effective for the maintenance of sinus rhythm for such patients.

Percutaneous catheter ablation of triggers from the pulmonary veins (focal AF ablation) is a promising approach to curative treatment of AF. Some centers have reported long-term cure rates of 50% to 70%. However, efficacy and complication rates are dependent on operator experience. The high volume of experience at our institution with the use of circular mapping techniques has resulted in a low complication rate and a cure rate of more than 80% among patients who undergo a first procedure. During focal AF ablation, the arrhythmogenic focus is mapped to a particular pulmonary vein and then isolated by using radiofrequency energy to create a line of block at the ostium of that vein. The technique requires at least one and generally two trans-septal punctures for left atrial instrumentation as well as systemic anticoagulation during the procedure. The procedure carries a small risk of stroke and a risk of symptomatic pulmonary vein stenosis in 3% to 5% of cases. The risk of pulmonary vein stenosis has been reduced primarily through use of a circular mapping catheter and intracardiac echocardiography to ensure placement of radiofrequency lesions at the pulmonary vein ostium (Figure 6). The procedure is generally reserved for patients with symptomatic AF that is refractory to at least two antiarrhythmic drugs. However, in some patients, particularly young patients without heart disease, the procedure may be considered as first-line therapy.

Illustration of the pulmonary veins arising from the left atrium. A circular mapping catheter and an ablation catheter are situated at the ostium of the pulmonary vein at its junction with the left atrium.

Figure 6

Newer technologies under clinical investigation might someday enhance the efficacy and safety of catheter ablation. One such development is a catheter-based system that delivers circumferential lesions at the pulmonary vein ostium via ultrasonic energy¹⁸ or cryothermy. With continued improvements in efficacy and safety, catheter ablation may become first-line therapy for most patients with AF.

Surgical Approaches
The maze surgical procedure for treatment of AF has substantially evolved from its initial form. In general, it involves the delivery of a series of incisions or lesions to the atria via radiofrequency, cryothermy, or microwave energy. These lesions are carefully placed to compartmentalize the atrial tissue in order to channel atrial activity and prevent the re-entry required for the maintenance of AF. The maze procedure also involves the isolation of the pulmonary veins, which has assumed greater importance now that pulmonary vein triggers have become more widely recognized. Reported AF cure rates with this procedure are high—perhaps greater than 90% at some experienced centers.^19,20 However, this approach is invasive and requires a thoracotomy and general anesthesia. The incidence of perioperative complications has been low, and there is a potential need for a permanent pacemaker postoperatively in about 7% to 10% of cases. This may occur as a result of the procedure itself or underlying sinus node dysfunction. The invasiveness of this approach makes it a less desirable option for patients with AF alone, but it might be attractive for patients who are undergoing cardiac surgery for another indication (eg, valve replacement or coronary bypass surgery). The development of minimally invasive surgical techniques, such as "keyhole" incisions or thoracoscopy, may make the surgical maze procedure more attractive for patients who do not otherwise require surgery. Finally, investigations are ongoing in the use of alternative energy sources (eg, laser and ultrasound) for creating the lesions.

AF is often considered a "nuisance arrhythmia" because it is not immediately life-threatening. However, it is associated with morbidity and mortality. Follow up data from the Framingham Heart Study²¹ and the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial²² have shown that AF is an independent predictor of increased mortality. It is not clear whether this higher risk is a reflection of the proarrhythmic complications of antiarrhythmic therapy, a failure to comply with prescribed medical therapy, or the presence of other factors such as stroke or worsening CHF. Whatever the reason, the higher risk underscores the importance of identifying and treating patients with this arrhythmia.

Return to Medicine Index

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