Robert A. Schweikert
Atrial fibrillation (AF) occurs when the electrical impulses in the atria degenerate from their usual organized rhythm into a rapid chaotic pattern. This disruption results in an irregular and often rapid heartbeat that is classically described as “irregularly irregular” and occurs because of the unpredictable conduction of these disordered impulses across the atrioventricular (AV) node.
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 has been outlined in guidelines published by the American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC), with the collaboration of the Heart Rhythm Society (HRS).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 paroxysmal and if the AF is sustained, it is designated persistent. In the latter case, termination of the arrhythmia with electrical or pharmacologic cardioversion does not change its designation. The category of persistent AF also includes permanent AF, which refers to long-standing AF (generally >1 year), for which cardioversion was not indicated or attempted.
AF is the most common sustained tachyarrhythmia encountered by clinicians. It occurs in approximately 0.4% to 1.0% of the general population and affects more than 2 million Americans annually. Its prevalence increases with age, and it has been diagnosed at some point in up to 10% of the population older than 80 years. With the projected growth of the older adult population, the prevalence of AF will certainly increase.
AF may be associated with physiologic stresses such as surgical procedures, pulmonary embolism, chronic lung diseases, hyperthyroidism, and alcohol ingestion. Disease states commonly associated with AF include hypertension, valvular heart disease, congestive heart failure (CHF), coronary artery disease, Wolff-Parkinson-White (WPW) syndrome, pericarditis, and cardiomyopathy. When no identifiable risk factor for AF is present, the condition is classified as lone AF.
New insights about the factors involved in the initiation and continuation of AF have led some investigators to propose a revised model of this complex arrhythmia. For many years, the focus had been on the substrate in the atria that supports the maintenance of AF. The multiple wavelet model has suggested that AF is sustained by multiple simultaneous wavelets wandering throughout the atria. 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 occurs because of premature atrial contractions triggered by beats that arise from the pulmonary veins, usually near the junction with the left atrium. These triggers may also fire repetitively and contribute to the maintenance of AF, essentially becoming drivers of AF.
AF may have hemodynamic consequences. It can decrease cardiac output by as much as 20%, increase pulmonary capillary wedge pressure, and increase atrial pressures. These effects are caused by tachycardia, loss of atrial contribution to left ventricular (LV) filling, increased valvular regurgitation, and irregular ventricular response. Some investigators have suggested that the irregularity of the R-R intervals contributes more to the hemodynamic changes than the mere presence of tachycardia.
AF is associated with important morbidity and even mortality. AF can produce bothersome symptoms that affect quality of life, but patients with AF also have a substantial risk of thromboembolic stroke, as discussed later. It is less apparent, however, that AF is also associated with increased mortality, although the reason for this is unclear. Several studies have demonstrated an association of AF with reduced overall survival.2, 3
Signs and symptoms
The clinical manifestation of AF is variable. Often, the symptoms are attributable to the rapid ventricular response. However, even when the ventricular response is controlled, symptoms can occur from loss of AV synchrony. This is particularly important for patients with LV dysfunction. Some patients are completely asymptomatic, even those with rapid heart rates. More often, however, patients report nonspecific symptoms such as fatigue, dyspnea, dizziness, and diaphoresis. Palpitations are a common feature. Occasionally, patients present with extreme manifestations of hemodynamic compromise, such as chest pain, pulmonary edema, or syncope. AF is present in 10% to 40% of patients with a new thromboembolic stroke.
The clinician must realize that an irregular pulse detected by physical examination or an irregular ventricular rhythm seen on the electrocardiogram (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 atrial flutter (Fig. 1) with variable AV conduction, multifocal atrial tachycardia (Fig. 2), and chaotic atrial rhythm, or wandering atrial pacemaker. Conversely, a regular pulse or rhythm does not exclude AF. For example, AF can manifest with a regular ventricular response in the presence of AV block or with a ventricular paced rhythm.
An ECG is essential for proper diagnosis. Electrocardiographic findings in AF include the absence of P waves, the presence of chaotic atrial activity and fibrillary waves (f waves), and an atrial rate in the range of 300 to 700 beats/min. In the absence of drug therapy, a patient with normal AV conduction has an irregularly irregular ventricular rhythm and often has a ventricular rate in the range of 120 to 180 beats/min. The baseline on the ECG strip often is undulating and occasionally has coarse irregular activity (Fig. 3). This activity may resemble atrial flutter, but it is not as uniform from wave to wave as atrial flutter.
Most patients presenting with AF are not in critical condition. However, in some cases, the presence of AF or the way it is treated may be life threatening. It should be emphasized that for any unstable patient presenting with AF—for example, a patient with chest pain, pulmonary edema, or hypotension—the recommended therapy is rapid electrical cardioversion.
AF has particular importance in the setting of the WPW syndrome. Patients with WPW syndrome may be vulnerable to ventricular fibrillation and sudden death because of the development of AF, which can result in extremely rapid conduction over the accessory pathway (Fig. 4). Prompt electrical cardioversion is of utmost importance for these patients. Treatment with AV node–blocking medications such as verapamil or digoxin can 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 or amiodarone.
The management of AF is directed at three basic goals: control of the ventricular rate, minimization of thromboembolism risk (particularly stroke), and restoration and maintenance of sinus rhythm. The first two management goals are essential for most patients, but the third management goal may not be necessary in every patient (see later). The ACC/AHA/ESC guidelines provide a more detailed review of the management of AF.1
Control of the Ventricular Rate
The ventricular rate during AF may be rapid and therefore require control. This usually is accomplished with medications that slow conduction through the AV node (Table 1). If these medications are ineffective or their effectiveness is prohibited by the development of excessive bradycardia, then other measures may need to be considered. One option suitable for some patients is catheter ablation of the AV node and pacemaker implantation. A meta-analysis of 21 uncontrolled studies of the ablate-and-pace approach4 has shown demonstrated improvements in a number of clinical parameters, including symptoms, quality of life, exercise function, and cardiac performance. However, this approach usually results in pacemaker dependence. These patients may be exposed to the risks and complications of the implanted hardware. Pacemaker implantation without AV nodal ablation should be considered if the problem is simply excessive bradycardia that prohibits the effectiveness of rate-controlling medication. Strategies for suppression or cure of AF should be considered for appropriate patients before pursuing ablation of the AV node.
Table 1: Atrial Fibrillation Medications that Slow Conduction Through the Atrioventricular Node
|Drug||Advantages||Disadvantages||Usual Dosage||Onset of Action||Elimination Half-Life|
|Propranolol||Rapid onset of effect, short durations of effect for IV forms; heart rate control at rest and with activity; oral forms available with varying durations of effect||May worsen heart failure in decompensated patient; may exacerbate reactive airway diseases; may cause fatigue, depression; abrupt withdrawal may cause rebound tachycardia, hypertension||
|Esmolol (IV only)||IV: 500 µg/kg over 1 min, then maintenance dose of 25-300 µg/kg/min; titrate by 25-50 µg/kg/min q5-10min to achieve goal||IV: onset of action within 5 min||N/A|
|Nadolol (oral only)||Oral: 40-80 mg daily initially; increase to 240-320 mg daily as needed to achieve goal; can be given once daily||Oral: onset of action within 1-2 hr||14-24 hr|
|Calcium Channel Blockers|
|Diltiazem||Same as for beta blockers||May worsen heart failure in decompensated patient; may cause fatigue; abrupt withdrawal may cause rebound tachycardia, hypertension||
|Verapamil||Same as for beta blockers||May worsen heart failure in decompensated patient; may cause fatigue; abrupt withdrawal may cause rebound tachycardia, hypertension||
|Digoxin||Can be used in patients with heart failure||Slow onset of action; poor control of heart rate with activity; narrow therapeutic margin; long duration of effect||IV loading dose of up to 1.0 mg in first 24 hr, with bolus of 0.25-0.5 mg IV push; then remainder in divided doses 16-8hr; maintenance oral dose, 0.125-0.25 mg qd||
Minimization of Thromboembolism and Stroke Risk
AF carries a considerable risk for thromboembolism and stroke. The Framingham study has shown that during a follow-up period of 30 years, the annual risk of stroke among AF patients is 4.2%; patients with nonvalvular AF had a more than fivefold higher risk of stroke. In the Framingham study, even patients with lone AF had a much higher incidence of stroke than controls over a period of almost 30 years.5 The annual risk of stroke may be even higher (7%-10%) in patients with AF who have one or more of the following risk factors: age older than 65 years, diabetes mellitus, hypertension, CHF, coronary artery disease, previous stroke, or transient ischemic attack. Findings of left atrial enlargement and reduced LV systolic function on echocardiography indicate an increase in thromboembolic risk.
Antithrombotic therapy for AF generally has consisted of the oral vitamin K antagonist warfarin or of the antiplatelet agent aspirin. 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%, whereas the reduction with aspirin ranges from 0% to 44% (mean, approximately 20%). The combination of warfarin with aspirin increases the bleeding risk. Studies involving low-dose aspirin and clopidogrel in combination are under way to evaluate their potential efficacy when used as alternatives to warfarin.
Practice guidelines have been published regarding the recommended form of antithrombotic therapy for patients with AF.1 In general, younger patients with no other risk factors have a low risk of stroke; therefore, 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 receive anticoagulation with warfarin, if it is not contraindicated. The goal of warfarin therapy for preventing stroke and thromboembolism from AF generally is an international normalized ratio (INR) between 2.0 and 3.0. Some older patients may be considered poor candidates for warfarin therapy because of excessive risk for bleeding complications, and these patients should be considered for aspirin therapy.
For patients who have been in AF for more than 48 hours and are not adequately anticoagulated, electrical or pharmacologic cardioversion should be delayed until appropriate measures are taken to reduce the thromboembolic risk. There are two approaches for patients being considered for cardioversion of AF longer 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 before 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, clinician, or both may prefer an expedited approach to achieving sinus rhythm. In such cases, once a therapeutic level of anticoagulation has been achieved with warfarin or IV heparin, TEE may be performed to rule out the presence of an intracardiac thrombus. If no thrombus is seen, cardioversion may be performed. 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.6
Warfarin should be continued after cardioversion until sinus rhythm has been maintained for at least 4 weeks to allow the atrial transport mechanism to recover. 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 shorter than 48 hours’ duration should be based on the presence of other risk factors for thromboembolism.
Because of the relatively narrow therapeutic and safety window for warfarin, and the numerous potential drug and food interactions with this medication, there has been substantial interest in the development of an alternative antithrombotic medication. Studies are in progress with oral platelet inhibitors such as clopidogrel and factor Xa inhibitors such as idraparinux. Several studies have been completed regarding the use of ximelagatran, an oral direct thrombin inhibitor with few drug and dietary interactions that does not require anticoagulation monitoring. Ximelagatran has been shown to be not inferior to warfarin, with similar bleeding risks. However, an undefined risk of hepatotoxicity, among other factors, has led the U.S. Food and Drug Administration (FDA) to discontinue grant approval in 2006 for this medication until further study has been completed. At present, a suitable substitute for warfarin for patients requiring more than aspirin therapy has yet to be demonstrated.
Nonpharmacologic methods of stroke prevention for patients with AF are also being studied. Percutaneous left atrial appendage occlusion has shown early clinical promise, but further study is required.
Restoration and Maintenance of Sinus Rhythm
The restoration and maintenance of sinus rhythm have obvious importance for patients with bothersome symptoms. However, this goal for patients with asymptomatic or minimally symptomatic AF has been controversial for many years There are now data from several clinical trials that may provide guidance for certain patients. Unfortunately, the important limitations of these trials have been often overlooked.
The potential benefits of sinus rhythm include reduction of long-term thromboembolism or stroke risk, avoidance of the development of atrial cardiomyopathy from ongoing AF, and improved quality of life. However, this approach often requires the use of antiarrhythmic drugs that may have important and even life-threatening side effects. Some nonrandomized trials have reported an increase in mortality among patients who were on long-term antiarrhythmic therapy for AF, presumably from the proarrhythmic effects of the drugs. In addition, several randomized studies have compared the treatment strategies of ventricular rate control or rhythm control with restoration and maintenance of sinus rhythm, albeit in older patients (mean age, 65-70 years) with minimal or no symptoms during AF.
The largest study, the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, was a large multicenter randomized study that compared these two treatment strategies for patients with AF.7 Both treatment strategies used appropriate anticoagulation according to established guidelines. This study has demonstrated that a rhythm-control strategy is no better than a ventricular rate control strategy with regard to quality of life, incidence of stroke, or mortality at a follow-up of about 5 years.
A meta-analysis of five randomized, controlled trials of rate control versus rhythm control strategy included more than 5000 patients and demonstrated that a rate-control strategy is not inferior to a rhythm-control strategy for the patients studied.8 Comparisons of ablation therapies for maintenance of sinus rhythm versus conservative therapies are lacking. A randomized pilot study has shown a reduction of AF recurrence and hospitalization and a greater improvement in quality of life for patients who underwent catheter ablation compared with those who underwent antiarrhythmic drug therapy.9 These results are encouraging, but larger studies with longer durations of follow-up are needed.
In some cases, the best treatment approach is relatively clear. Patients presenting with an initial episode of paroxysmal AF might not require ventricular rate-controlling or antiarrhythmic drug therapy, particularly if the episode is associated with a treatable or removable physiologic stress, as described earlier. Clinical observation may be an option in some patients, with the decision to treat based on the development of recurrent episodes of AF. Similarly, a patient with an initial episode of persistent AF may be treated with appropriate anticoagulation (see earlier) 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 and restoration and maintenance of sinus rhythm is still desired, antiarrhythmic drug therapy may be considered.
Patients with symptomatic AF after adequate ventricular rate control has been achieved should be considered for a treatment approach that restores sinus rhythm. Such treatment strategies are discussed below. Acutely, restoration of sinus rhythm may be achieved with either pharmacologic 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 cardioversion 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 almost 95%. Direct-current cardioversion should be administered with the patient under deep 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.
Rates of successful immediate cardioversion by pharmacologic means have ranged from 40% to 90%, with success more likely in patients with AF of shorter duration. However, pharmacologic cardioversion is often chosen as the first line of therapy because of 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). Oral administration of antiarrhythmic medication may also be used for pharmacologic cardioversion. The pill-in-the-pocket treatment may be useful for select outpatients for terminating recent-onset episodes of AF. This approach has the potential to reduce emergency department visits and hospitalizations.
Table 2: Agents for Immediate Pharmacologic Cardioversion of Atrial Fibrillation
|Drug||Advantages||Disadvantages||Guidelines for Dosing||Comments|
|Procainamide, N-acetyl procainamide (NAPA)||Rapid administration may cause hypotension; up to 10% of congestive heart failure patients experience worsened heart failure||10-15 mg/kg given IV up to 50 mg/min, then maintenance drip at 2-4 mg/min||Elimination half-life-2-5 hr for procainamide, 6-8 hr for NAPA; blood levels of both procainamide and NAPA need to be followed to prevent toxicity, especially in the setting of renal or hepatic insufficiency, or both||Can achieve therapeutic levels quickly|
|Amiodarone||Can be used in patients with severe left ventricular dysfunction||Long-term use associated with many side effects-visual disturbances, tremors and other neurologic sequelae, hepatitis, pulmonary fibrosis, photosensitivity, skin discoloration, thyroid abnormalities, cardiac conduction disturbances||150-300 mg given over 10-120 min, depending on tolerance of blood pressure; maintenance infusion (very expensive) at 0.5-1 mg/min||Half-life is extremely long (up to 120 days)|
|Ibutilide||Few extracardiac side effects; ease of use||Incidence of torsades de pointes higher than with procainamide or amiodarone||1-mg IV bolus; can repeat after 10 min if no effect||Avoid use in patients with baseline prolongation of QT interval|
Antiarrhythmic Drug Therapy for Maintenance of Sinus Rhythm
A number of oral agents may be used for long-term 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) has shown that flecainide and encainide are associated with an increase in mortality when used for the suppression of ventricular arrhythmias in post-MI patients with ventricular dysfunction.10 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; in these patients, other antiarrhythmic drugs may be better initial choices. Flecainide and propafenone are usually well tolerated and are appropriate first-line options for the treatment of AF in patients without structural heart disease, particularly cardiomyopathy, including hypertrophic cardiomyopathy (HCM). There is a new sustained-release formulation of propafenone that offers the advantage of twice-daily dosing rather than thrice-daily dosing, as for the immediate-release formulation.
Table 3: Oral Medications for Long-Term Maintenance of Sinus Rhythm for Patients With Atrial Fibrillation
|Drug||Advantages||Disadvantages||Guidelines for Dosing||Comments|
|Quinidine||Low cost; less negative inotropic effects||Low toxic-to-therapeutic ratio; interacts with many drugs, including digoxin, warfarin, verapamil; high incidence of side effects (particularly GI intolerance, neurologic side effects, hematologic suppressive effects)||
|Procainamide, N-acetyl procainamide (NAPA)||Useful in patients with pre-excitation and AF; prolongs refractory period of accessory pathway||Low toxic-to-therapeutic ratio; high incidence of GI, hematologic, immunologic (lupus-like syndrome) side effects; interacts with many medications||
|Flecainide||Generally well tolerated||
||50-150 mg/dose q12hr||
|Propafenone (immediate- release, sustained-release)||Generally well tolerated; twice-daily dosing; sustained-release form results in more stable blood levels than immediate-release formulation||
||Single-dose therapy with up to 600-mg doses shown to have high efficacy (−75%) for converting acute episodes of AF to SR; cannot be used for acute cardioversion (pill-in-the-pocket)|
|Disopyramide||May be useful in hypertrophic cardiomyopathy because of its negative inotropic side effects||Anticholinergic effects (e.g., constipation, urinary retention)||150 mg/dose q6hr, 300 mg/dose q12hr for controlled-release preparation (give two thirds of usual dose for adults weighing <50 kg)|
|Moricizine||Few drug-drug interactions||Should not be used in patients with coronary or structural heart disease||200-300 mg/dose q8hr||Has properties of Classes IA, IB, and IC drugs; shown to increase mortality when used for treatment and suppression of ventricular arrhythmias in patients after MI|
|Amiodarone||Can be used in patients with coronary or structural heart disease||
||Oral loading with 400-600 mg/day for 2-4 wk, then 200 mg/day||
|Sotalol||Can be used in patients with coronary structural heart disease; beta- blocking properties allow single-agent therapy for almost all arrhythmias||Causes QTc prolongation; use limited by side effects related to beta-blocking properties (e.g., exacerbation of reactive airway disease, depression, negative inotropy)||80-160 mg/dose q12hr||Inpatient telemetry recommended for initiation of therapy|
|Dofetilide||Generally well tolerated; few extracardiac effects; can be used in patients with coronary or structural heart disease||Causes QTc prolongation||125-500 µg/dose q12hr||Inpatient telemetry mandated for initiation of therapy; ECG must be checked within 2-3 hr of administration for evidence of QTc prolongation >15% above baseline or >500 msec (550 msec for patients with intraventricular conduction delay)|
|Azimilide*||Few drug-drug interactions or side effects known to date||Causes QTc prolongation||125 mg/dose bid × 3 days, then 125 mg/day||Preliminary experience indicates efficacy similar to amiodarone; acceptable incidence of side effects|
*Not available for use in the United States.
AF, atrial fibrillation; AV, atrioventricular; ECG, electrocardiogram; GI, gastrointestinal; LFT, liver function test; MI, myocardial infarction; SR, sinus rhythm; TFT, thyroid function test.
Sotalol is a Class III antiarrhythmic that has beta-blocking properties and is generally well tolerated. Patients may have difficulty tolerating the beta blocker side effects, such as fatigue, and there is a potential risk of excessive bradycardia. As with other Class III antiarrhythmic agents, sotalol 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 drug 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. Importantly, dofetilide has also been shown to be safe for patients with cardiomyopathy, CHF, and ischemic heart disease. Therefore, dofetilide may be considered as an alternative treatment option to amiodarone for these patients.
Amiodarone, although an effective antiarrhythmic agent, generally is reserved for patients with AF for whom other antiarrhythmic drugs have been contraindicated, ineffective, or poorly tolerated. This is primarily because amiodarone has potential time- and dose-dependent organ toxicities that can affect the liver, thyroid, and lungs and, less frequently, the eyes. It is recommended that baseline studies be performed before initiating this drug. These tests include an ophthalmologic examination, pulmonary spirometry and diffusion capacity tests, 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 performed yearly. There is divergence of opinion with regard to routine performance of pulmonary function testing and chest radiography for asymptomatic patients taking amiodarone.
Several new antiarrhythmic medications are under investigation. Particularly promising is the potential for the development of atrium-specific and ion channel-specific antiarrhythmic medications.
Implantable devices are being used with increasing frequency for patients with AF. Certainly, there is a substantial incidence of sinus node and AV node dysfunction in the AF population. These devices have several purposes, including bradycardia pacing support, ventricular response regularization, and AF suppression or termination. The ACC, AHA, and HRS have published guidelines for the use of implantable pacemakers and antitachycardia devices.11 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 may allow more aggressive use of rate-controlling or antiarrhythmic medications, or both. However, a few points should be kept in mind. Pauses that occur with conversion to sinus rhythm, some that last as long as several seconds, are common; in the absence of symptoms, these pauses are not an indication for a permanent pacemaker. Even with symptomatic postconversion pauses, a curative approach for the appropriate patient should be considered before implanting a pacemaker.
Pacemakers are also implanted in conjunction with catheter ablation of the AV node. This type of ablation is the ultimate method of ventricular rate control and is often reserved for patients with permanent or paroxysmal AF refractory to medical or curative therapy. The potential benefits of this type of approach extend beyond simply controlling ventricular response, because there is evidence that regularization of the ventricular rhythm also confers hemodynamic or symptomatic benefits. This approach has been shown to be effective and leads to improved quality of life for some patients (see earlier discussion). Even so, this approach does not address the fibrillating atria, and such patients may still require systemic anticoagulation for thromboembolism and stroke prevention.
Several features of pacemaker systems may be useful for patients with AF. A pacemaker that has the capability to change automatically 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 rate that might otherwise occur when the pacemaker responds to the sensing of the rapid atrial activity. Other AF suppression algorithms have shown mixed results with regard to effectiveness. Overall, these features have been shown to have modest efficacy at best. Implantable atrial defibrillators have been developed, either as a stand-alone device or in combination with a ventricular defibrillator. However, the atrial defibrillator has not been widely accepted by patients or physicians. In general, patients have difficulty tolerating even the low-energy internal cardioversion shocks without the deep sedation provided during conventional external cardioversion.
The past few years have witnessed a revolution in catheter-based curative strategies for AF. This development is a direct result of the new insights into the critical role of the pulmonary veins as the site of origin for the triggers and drivers of AF. Before these more recent developments, catheter ablation for various forms of atrial arrhythmias, particularly AF, had only limited applications. The best results in terms of success and safety appear to have occurred with catheter ablation of typical right atrial flutter and, to a somewhat lesser degree, atypical atrial flutter and focal atrial tachycardia.
With the recognition of the pulmonary veins as the source of the critical triggering beats of AF in most patients, catheter ablation techniques have shifted to target this substrate. Catheter-based AF ablation techniques have subsequently evolved into several different variations of a pulmonary vein isolation procedure targeting the pulmonary vein–left atrial junction, some of which are purely anatomic approaches and others of which are a combination of anatomic and electrophysiologic mapping approaches. This has led to improved efficacy rates, ranging from about 50% to as high as 90%, and a lower incidence of complications, notably pulmonary vein stenosis. Several experienced centers have reported high rates of successful cure of AF without the need for antiarrhythmic drug therapy.12
In spite of the much-improved efficacy and safety of AF catheter ablation, the procedure is still not the first-line treatment for AF. This approach is generally reserved for patients with symptomatic AF refractory to at least two antiarrhythmic drugs. The ideal candidate is a young patient with paroxysmal lone AF, but older patients and those with structural heart disease are not necessarily excluded and may be good candidates for consideration in experienced centers.
The maze surgical procedure for the treatment of AF has substantially evolved from its initial form. In general, it involves a series of incisions or lesions in the atria. These are carefully placed to compartmentalize the atrial tissue to channel atrial activity and prevent the re-entry required for the maintenance of AF. Nonincisional lesions may be placed using radiofrequency, cryothermy, or microwave energy. Reported AF cure rates with the classic Cox maze procedure are high, perhaps more than 90% at some experienced centers.13, 14 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 postoperative pacemaker in as many as 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 undergoing cardiac surgery for another indication (e.g., valve replacement or coronary bypass surgery).
Surgical approaches have continued to become less invasive, because surgeons are increasingly aware that the invasiveness of the Cox maze procedure is a major obstacle to patient (and referring physician) acceptance, no matter how effective the procedure is. Several centers, such as our own, have been using minimally invasive incisions and even thoracoscopic approaches with robotic equipment.
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 Study2 and the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial3 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, worsening CHF, or unknown factors that were not recognized. Furthermore, subgroup analysis of on-treatment patients (versus the trial's overall intention to treat patients) has demonstrated improved survival associated with sinus rhythm in the AFFIRM study.15 This underscores the importance of completing further studies, including randomized studies of the various treatment options for AF.
The prevalence of AF, already at epidemic proportions, is expected to continue to increase as the population ages and more patients with heart disease live longer. This is especially true for the heart-failure population. The rapid growth of curative approaches to AF, as with catheter-based and surgical ablation procedures, is promising and has already relieved many patients of the burden of AF and the side effects and toxicities of antiarrhythmic medications. However, these approaches are invasive and inherently destructive, with a small but important risk of serious complications. Additional refinements to invasive curative treatment approaches are anticipated, but there remains a desperate need for another solution to management of this arrhythmia.
The most beneficial development might be the effective prevention of AF. Research into the underlying molecular and genetic causes of AF may lead to novel methods of treatment targeting specific ion channel, molecular, or genetic defects. The prevention and optimal management of the medical disorders associated with AF, such as heart disease and hypertension, would have an obvious impact. The choice of treatment of such conditions may make a difference. Studies with drugs such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and the beta blocker carvedilol have shown promise as adjunctive therapies for preventing the development of atrial fibrillation.
Further developments in the understanding of atrial fibrillation will lead to advances in optimal therapy and, hopefully, a reduction in the incidence of this ubiquitous arrhythmia.
- Atrial fibrillation is the most common sustained tachyarrhythmia.
- Therapy for atrial fibrillation is centered around three goals: minimize stroke risk, control ventricular rate, and control the atrial rhythm.
- Any unstable patient presenting with atrial fibrillation should undergo immediate electrical cardioversion.
- Patients who fail pharmacologic conversion to sinus rhythm should be considered for electrical cardioversion, because the success rates for the latter are significantly better. Select patients may safely be treated with long-term anticoagulation and ventricular rate control alone.
- Ablation of atrial fibrillation triggers should be considered for symptomatic patients refractory to standard therapeutic measures.
- Fuster V, Rydén LE, Cannom DS, et al: American College of Cardiology/American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; European Heart Rhythm Association; Heart Rhythm Society: ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006, 114: e257-e354.
- Benjamin EJ, Wolf PA, D’Agostino RB, et al: Impact of atrial fibrillation on the risk of death: The Framingham Heart Study. Circulation. 1998, 98: 946-952.
- Wyse DG, Love JC, Yao Q, et al: Atrial fibrillation: A risk factor for increased mortality—an AVID registry analysis. J Interv Card Electrophysiol. 2001, 5: 267-273.
- Wood MA, Brown-Mahoney C, Kay GN, Ellenbogen KA. Clinical outcomes after ablation and pacing therapy for atrial fibrillation: a meta-analysis. Circulation. 2000, 101: 1138-1144.
- 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: 3449-3453.
- Klein AL, Murray RD, Grimm RA. Role of transesophageal echocardiography-guided cardioversion of patients with atrial fibrillation. J Am Coll Cardiol. 2001, 37: 691-704.
- Wyse DG, Waldo AL, DiMarco JP, et al: A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002, 347: 1825-1833.
- de Denus S, Sanoski CA, Carlsson J, et al: Rate vs rhythm control in patients with atrial fibrillation: A meta-analysis. Arch Intern Med. 2005, 165: 258-262.
- Wazni OM, Marrouche NF, Martin DO, et al: Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: A randomized trial. JAMA. 2005, 293: 2634-2640.
- Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: Effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989, 321: 406-412.
- Gregoratos G, Abrams J, Epstein AE, et al: ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices—summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). J Am Coll Cardiol. 2002, 40: 1703-1719.
- Oral H, Knight BP, Tada H, et al: Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation. 2002, 105: 1077-1081.
- McCarthy PM, Gillinov AM, Castle L, et al: The Cox-Maze procedure: The Cleveland Clinic experience. Semin Thorac Cardiovasc Surg. 2000, 12: 25-29.
- Schaff HV, Dearani JA, Daly RC, et al: Cox-Maze procedure for atrial fibrillation: Mayo Clinic experience. Semin Thorac Cardiovasc Surg. Jan 2000, 12: 30-37.
- Corley SD, Epstein AE, DiMarco JP, et al: Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation. 2004, 109: 1509-1513.
- Benjamin EJ, Wolf PA, D’Agostino RB, et al: Impact of atrial fibrillation on the risk of death: The Framingham Heart Study. Circulation. Sep 8 1998, 98: (10): 946-952.
- Brand FN, Abbott RD, Kannel WB, Wolf PA. Characteristics and prognosis of lone atrial fibrillation. 30-year follow-up in the Framingham Study. JAMA. Dec 27 1985, 254: (24): 3449-3453.
- Fuster V, Ryden Rydén LE, Cannom DS, et al: American College of Cardiology/American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; European Heart Rhythm Association; Heart Rhythm Society: ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. Aug 15 2006, 114: (7): e257-e354.
- Gregoratos G, Abrams J, Epstein AE, et al: ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices-summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). J Am Coll Cardiol. Nov 6 2002, 40: (9): 1703-1719.
- Klein AL, Murray RD, Grimm RA. Role of transesophageal echocardiography-guided cardioversion of patients with atrial fibrillation. J Am Coll Cardiol. Mar 1 2001, 37: (3): 691-704.
- McCarthy PM, Gillinov AM, Castle L, Chung M, Cosgrove D 3rd., et al: The Cox-Maze procedure: The Cleveland Clinic experience. Semin Thorac Cardiovasc Surg. Jan 2000, 12: (1): 25-29.
- Oral H, Knight BP, Tada H, et al: Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation. Mar 5 2002, 105: (9): 1077-1081.
- Wood MA, Brown-Mahoney C, Kay GN, Ellenbogen KA. Clinical outcomes after ablation and pacing therapy for atrial fibrillation: A meta-analysis. Circulation. Mar 14 2000, 101: (10): 1138-1144.
- Wyse DG, Love JC, Yao Q, et al: Atrial fibrillation: A risk factor for increased mortality—an AVID registry analysis. J Interv Card Electrophysiol. Sep 2001, 5: (3): 267-273.
- Wyse DG, Waldo AL, DiMarco JP, et al: A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. Dec 5 2002, 347: (23): 1825-1833.