Atrial Fibrillation: Current Management
January 24, 2000 28 minutes read
Atrial Fibrillation: Current Management
Authors: Patrick Donovan, MD, Cardiology Fellow, University of Kentucky Medical Center, Lexington, KY; Santosh Menon, MD, Assistant Professor, CHF/Heart Transplant Section, Cardiovascular Division, University of Kentucky Medical Center, Lexington, KY; and Gery Tomassoni, MD, Director of the Electrophysiology Lab, Lexington Cardiology Consultants, Central Baptist Hospital, Lexington, KY.
Peer Reviewer: Nicholas Kerin, MD, Professor of Medicine, Wayne State Medical School, Farmington Hills, MI.
Editor’s Note—Atrial fibrillation (AF) is the most common tachyarrhythmia encountered in medicine today. It is present in nearly 1% of all Americans. Although there are numerous etiologies of AF affecting both the young and old, it typically occurs in older patients both in the presence and absence of structural heart disease. Symptoms can range from none to severe incapacitation. Patients with AF are known to have a higher morbidity and mortality, more adverse hemodynamic consequences, and are at increased risk for embolic events when compared to the normal population. Multiple mechanisms have been proposed for AF, although it is unlikely that a single mechanism is present. Many therapeutic options exist, including both pharmacological and non-pharmacological approaches. This article focuses on the present controversies and the current strategies in the management of AF, in particular, rate control, conversion to and maintenance of sinus rhythm, and the prevention of thromboembolism.
Definition and Classification
Electrocardiographically, AF is characterized by disorganized electrical activity with irregularity of both rate and rhythm.1 There are baseline irregular undulations of varying amplitude and morphology, called f waves, associated with the absence of surface P waves.2
There are many methods of classification of AF that are based upon the presence or absence of structural heart disease—the ventricular rate, electrophysiological properties, and, most recently, the temporal pattern or time course for the development of AF.3 This last classification is generally regarded as the most useful clinically. AF is categorized as either recent (new onset) or chronic. Chronic AF is divided into permanent or recurrent. Recurrent AF can be further subdivided into paroxysmal or persistent. Paroxysmal AF is generally classified as episodes of AF that terminate spontaneously. Persistent AF is mostly continuous until some measure is taken to terminate it. AF is permanent when it has resisted all attempts to restore sinus rhythm or when the physician or patient decides that no such attempt should be made.3
Epidemiology
AF is the most common arrhythmia seen in clinical practice.4 Based on the most recent census data, Feinberg et al estimated there are 2.2 million people in the United States with AF, with a median age of 75.5 The incidence of AF is equally distributed among men and women. Additionally, both the incidence and prevalence increase dramatically with age. For those between the ages of 50-59, the incidence is 0.5%, but for octogenarians (age > 80), the incidence of AF is nearly 9%.6 The incidence of thromboembolism also increases with age. For patients aged 80-90, nearly one-third of strokes that occur are related to AF; this is in comparison to only 6% in the 50- to 60-year-old population.7 The risk for embolic stroke in patients with AF greater than 48 hours in duration is fivefold higher than the general population, with an even higher risk (17-fold risk) in patients with rheumatic heart disease, hypertension, dilated cardiomyopathy, dilated left atrium, and a history of previous embolic stroke. Total mortality, including cardiovascular mortality, is nearly twice as high for AF patients compared to patients with normal sinus rhythm.6 Finally, AF is a costly medical problem resulting in significant prolongation of hospital stay, and was responsible for approximately one-third of all arrhythmia-related hospitalizations in 1990.8
Etiology
AF has a multitude of causes that can be categorized according to the presence or absence of structural heart disease (see Table 1). Patients with cardiovascular disease have a three- to fivefold increased risk of AF.9 The cardiac conditions most commonly associated with AF are hypertension, atherosclerotic cardiovascular disease, rheumatic heart disease, mitral valve disease, and cardiomyopathies. Hypertension and coronary artery disease are the most frequent risk factors and account for approximately 65% of the AF cases. Thus, in the majority of cases, AF is associated with an underlying cardiac disease state. However, noncardiac causes can also be important etiologies of AF. The most common noncardiac conditions associated with AF are pulmonary diseases (including COPD), systemic illnesses, and thyrotoxicosis.10 In patients with thyrotoxicosis, nearly 20% have AF.11 Acute alcohol intoxication can precipitate AF even in the presence of a structurally normal heart.12 Therefore, it is important to identify the cause of AF since the treatment of the underlying disease process may result in the termination of the arrhythmia. This is apparent in the treatment of patients with Wolf-Parkinson-White syndrome (WPW syndrome) and atrial fibrillation. Radiofrequency catheter ablation of the accessory pathway can result in the elimination and cure of AF.
| Table 1. Causes of Atrial Fibrillation |
| Structural Heart Disease |
| Hypertension |
| Ischemic heart disease |
| Valvular heart disease |
| Rheumatic: mitral stenosis |
| Nonrheumatic: aortic stenosis, mitral regurgitation |
| Pericarditis |
| Cardiac tumors |
| Sick sinus syndrome |
| Cardiomyopathies |
| Congenital heart disease |
| Wolf-Parkinson-White syndrome |
| Absence of Structural Heart Disease |
| Pulmonary diseases |
| COPD |
| Pneumonia |
| Pulmonary embolus |
| Metabolic disorders |
| Thyrotoxicosis |
| Electrolyte imbalance |
| Acute ethanol intoxication |
| Methylxanthine derivatives |
| Theophylline |
| Caffeine |
| Systemic illness |
| Sepsis |
| Malignancy |
| Lone atrial fibrillation |
| Source: Adapted from Mittal, Lerman. Current strategies for managing atrial fibrillation. Intern Medicine 1998;19:23-28. |
Pathophysiology
Although multiple mechanisms of AF have been proposed, the exact mechanism is unknown. In 1962, Moe developed a theory regarding the mechanism of AF known as the multiple wavelet hypothesis.13 Moe surmised that AF resulted when a propagating wavefront of electrical activation fractionated into multiple individual reentrant wavelets that traveled randomly through the atrium. The maintenance of AF, in turn, depended on the presence of a critical number of these wavelets. Subsequently, Cox et al demonstrated the presence of larger reentrant circuits during AF in humans, which eventually led to the development of the surgical MAZE procedure in an attempt to cure AF.14 Recently, focal activations arising from a discrete source have been proposed as an additional mechanism of AF.15 It appears that certain anatomical structures, such as the left atrial pulmonary veins, may be important sources of ectopic beats that can initiate paroxysms of AF in patients without structural heart disease. Radiofrequency catheter ablation at these discrete sites may reduce the recurrence of the arrhythmia.15
Unfortunately, it is unlikely that a single mechanism is responsible for the initiation and maintenance of AF in most patients. It is more likely that certain mechanisms play a more important role in certain types of AF as well as in different patient populations. Despite the uncertainty surrounding the many types of mechanisms, the demonstration of an electrophysiological process called electrical remodeling16 may have important clinical implications. During AF, time-dependent alterations in electrophysiological properties occur that can lead to the perpetuation and maintenance of AF.16 This includes a shortening of atrial refractoriness and a reduction in atrial conduction velocity. Interestingly, the electrophysiological changes may be completely reversible if early intervention is performed. Thus, early and permanent restoration of sinus rhythm may decrease and/or prevent subsequent recurrences of AF.
Clinical Features
Patients in AF can present in a variety of ways. Frequently, patients with AF are asymptomatic. The arrhythmia may be found during a routine physical examination by either the presence of an irregular pulse or an abnormal electrocardiogram.17 On the opposite end of the spectrum, AF may be associated with a multitude of complaints, with palpitations being the most common presenting symptom.18 More profound symptoms include dizziness, dyspnea, chest pain, syncope, fatigue, or confusion.9 Many of these symptoms are due to a decrease in the cardiac output because of lack of atrial contribution. The chaotic contractions of AF may result in a 20-30% reduction in cardiac output and stroke volume in structurally normal hearts; this may be even more pronounced in patients with heart disease.19
The most common physical sign of AF is the presence of an irregular pulse. Other physical exam findings include a pulse deficit, absent "a" wave in the jugular venous pulse, and a variable intensity of the first heart sound.
Persistent rapid ventricular rates can lead to left ventricular (LV) dysfunction and signs and symptoms of congestive heart failure (CHF). A complete history and physical examination should be performed with special attention to both cardiac and pulmonary auscultation looking for a secondary cause of the AF. At times, treating the underlying cause may help convert patients with AF to normal sinus rhythm.10-12
Diagnostic Studies
All patients with suspected AF on physical exam should have an electrocardiogram (ECG). If the patient is in sinus rhythm, it is important to look for the presence of a delta wave, suggesting WPW syndrome.
Laboratory studies should include chemistries, CBC, PT/PTT, and a thyroid evaluation including a TSH and free thyroxine level.11 A chest x-ray may help in uncovering the etiology of AF, such as COPD, pneumonia, CHF, or cardiomegaly. Ambulatory 24-hour (Holter) ECG monitoring can be performed to determine both the frequency and duration of AF as well as to correlate patient symptoms with the arrhythmia. It may also help in assessing whether adequate rate control is present in these patients.9 The echocardiogram is an invaluable diagnostic tool in patients with AF. It provides information on cardiac dimensions, particularly left atrial size, LV systolic function, presence and severity of valvular disease, and the presence of LV hypertrophy.11 All these assessments are valuable in the diagnosis and management of patients with AF.
Initial Management
Several questions need to be addressed prior to initiating therapy for AF. What is the cause of AF and can treating the cause terminate the arrhythmia? What is the duration of AF? How quickly does sinus rhythm need to be restored? What are the goals of therapy (i.e., cardioversion or rate control)?
The duration issue is best classified as AF occurring less than 48 hours or more than 48 hours. If the duration of AF is less than 48 hours, the initial goals are either cardioversion or ventricular rate control and observation (see Figure 1). The decision is dependent upon many issues, including the etiology of AF and the therapeutic intent. If the patient is not hemodynamically compromised and the AF is of new onset, an initial period of observation using both medications for rate control and anticoagulation with heparin is performed. This initial approach most likely reflects previously reported high spontaneous conversion rates.20 If AF persists despite rate control, restoration of sinus rhythm is the usual goal if the patient is symptomatic during AF, requires AV synchrony for improved hemodynamic profile (i.e., patients with LV dysfunction), or wants to avoid lifelong anticoagulation. It must also be recognized that weakness and fatigue could be the only symptoms associated with AF and in many cases represent a sufficient reason to pursue restoration of sinus rhythm. Sinus rhythm can be achieved with either external cardioversion and/or pharmacological agents. The decision of starting antiarrhythmic therapy to maintain sinus rhythm would depend on the frequency of episodes and the hemodynamic profile during AF. It should be noted, however, that there is little information available demonstrating the benefits of maintaining sinus rhythm regarding cost, adverse effects, and mortality. The AFFIRM, PIAF, and RACE trials will soon provide the much-needed information regarding these issues.21
If the duration of AF is unknown or more than 48 hours, then rate control and anticoagulation therapy should be pursued first (see Figure 2). If the decision is to achieve sinus rhythm, then the patient should be anticoagulated for 3-4 weeks with warfarin prior to cardioversion. Either electrical and/or pharmacological cardioversion can be performed safely after therapeutic anticoagulation for 3-4 weeks. Anticoagulation should be maintained for at least an additional four weeks after cardioversion but in general depends upon the anticipated natural course of the AF and the chance of recurrence in a given patient. A different approach would be to evaluate for the presence of an intracardiac thrombus with a transesophageal echocardiography (TEE).22 With this approach, if the TEE demonstrates a clot, the patient is anticoagulated for three weeks before a scheduled cardioversion. If no left atrial thrombus or other echocardiographic risk factors (see next paragraph) are identified by TEE, heparin is started and the patient is cardioverted. Following successful cardioversion, the patient is placed on warfarin for an additional three to four weeks. Again, the decision of starting antiarrhythmic therapy to maintain sinus rhythm would depend on the frequency of episodes and the hemodynamic profile during AF. Those patients who have frequent episodes of AF and are symptomatic during those periods may benefit from a course of antiarrhythmic therapy.
The role of TEE in the management of AF is controversial. TEE is more sensitive and specific (92% and 98%, respectively) than a transthoracic echocardiogram in evaluating for the presence of a thrombus in the left atrial appendage or any indications of increased propensity for clot formation. Unfortunately, prospective studies have yet to define in which patients a TEE is more beneficial than a transthoracic echo.9,22 It is well established, however, that thrombus in the left atrium, left atrial smoke (red cell and platelet aggregations used as a marker for increased risk of thromboembolism), and reduced flow in the left atrial appendage are predictive of increased risk of embolic stroke in AF.11 The cost-effectiveness of routine TEE in patients with AF, however, remains unknown. The role of cost-effectiveness vs. earlier and safer cardioversion by TEE23,24 must be taken into consideration. Finally, the risk of stroke is not completely eliminated by a negative transesophageal echocardiogram.
Treatment
Antithrombotic therapy. In valvular or rheumatic AF, it has been long established that antithrombotic therapy with warfarin reduces the incidence of cerebrovascular accidents.7 Based on recent studies, it is now also known that anticoagulation (compared to placebo) in patients with nonvalvular AF reduces the incidence of embolic strokes.25-30 In studies comparing warfarin to aspirin, warfarin was found to be more efficacious in reducing the incidence of stroke in patients with AF unless the stroke was considered to be nonembolic in nature, in which case aspirin was as efficacious as warfarin.31
In deciding on anticoagulation, it is important to first determine which patient population would benefit from stroke reduction compared to the higher risk of bleeding complications. A general consensus on anticoagulation in patients with AF does exist, but tailored therapy for individual patients is recommended. Although controversy still exists over certain anticoagulation issues and recommendations are constantly changing, Laupacis and colleagues in the Fourth ACCP Consensus Conference on Antithrombotic Therapy have listed the current guidelines.32 Oral anticoagulation therapy with warfarin with a goal of an INR between 2.0-3.0 should be considered in all AF patients with rheumatic heart disease younger than 75 years old. In patients without rheumatic heart disease who are younger than 75 years of age, warfarin therapy should be initiated if certain risk factors are present, including previous transient ischemic attack or stroke, hypertension, heart failure, diabetes, clinical coronary artery disease, mitral stenosis, prosthetic heart valves, or thyrotoxicosis. In patients younger than 65 and without these risk factors (lone AF), aspirin alone may be appropriate for stroke prevention. Patients between the ages of 65 and 75 with none of these risk factors could be treated with either warfarin or aspirin, depending on patient/physician preference after weighing the risks and benefits of both therapeutic options. In patients older than 75 with AF, oral anticoagulation with warfarin is recommended32 although medical literature documenting clear benefits is limited. Finally, in any patients with major contraindications to warfarin (intracranial hemorrhage, unstable gait, falls, syncope, or poor compliance), a daily aspirin may be a reasonable alternative.
Anticoagulation not only plays an important role in the prevention of stroke in patients with AF but is also important when considering the timing of cardioversion. Most studies show that patients with AF duration greater than 48 hours should be anticoagulated with a therapeutic INR of 2.0-3.0 before an elective cardioversion. Laupacis et al recommend adequate anticoagulation for three weeks prior to elective cardioversion in patients with AF longer than 48 hours and for an additional four weeks after successful cardioversion.32 There is no specific recommendation for anticoagulation in AF lasting less than 48 hours. Most practitioners avoid anticoagulation therapy in such cases; however, there are no reliable data to support this practice.32
Rate control. Conversion to and maintenance of sinus rhythm may not be possible in some patients, including those with left ventricular dysfunction. Patients with AF of greater than one year duration or a left atrial size greater than 50 mm may have difficulty in converting to and maintaining sinus rhythm.9 In these patients, rate control rather than conversion to sinus rhythm may be as beneficial in terms of controlling symptoms and optimizing hemodynamics.
Although no general consensus exists, a controlled ventricular rate in AF has been identified by Rawles as less than 90 bpm at rest.53 This represents the heart rate at which cardioregulatory reflexes can be adjusted to minimize the deleterious effects of AF on the cardiac output.33 The pharmacological agents primarily used for rate control are digoxin, beta blockers, and calcium channel blockers.
Digoxin, which has been in clinical use for more than 200 years, has served as a rate-controlling agent because it has the advantages of low cost as well as ease of administration either intravenously or orally (once a day). Unfortunately, it also has numerous drug interactions, an unpredictable dose response curve, and a potentially lethal toxicity.34 Digoxin works by slowing AV node conduction and increasing AV node refractoriness. Its main effect is on the autonomic nervous system, as it increases vagal tone in the atria, which in turn slows down the ventricular rate.35 This effect on vagal tone, however, can easily be overcome by high catecholamine states, such as in the postoperative patient, patients with shock, and during exercise.34 In addition, there is no evidence of an antiarrhythmic effect with digoxin,36 with randomized studies showing it to be ineffective in terminating AF.37 Also, digoxin does not prevent the recurrence of atrial fibrillation. Its use, therefore, is limited to patients with systolic dysfunction9 or in combination with another rate-controlling agent.
Beta-blockers act by blocking the action of catecholamines.8 In addition, both AV nodal and sinoatrial nodal conduction is slowed. Like digoxin, beta-blockers are not directly responsible for the conversion of AF to sinus rhythm, but they may potentiate the effect of class I antiarrhythmics.8 Unlike digoxin, beta-blockers can work well to limit the ventricular response to exercise in patients with AF.34 In patients with AF caused by thyrotoxicosis, beta-blockers are considered the treatment of choice.9 The most commonly used beta-blockers are metoprolol and atenolol. For acute rate control where rapid drug onset and short half-life are important, intravenous esmolol is available. Esmolol is a beta-1 selective blocking agent; its usefulness in acute situations is limited by its short half-life of approximately 2-5 minutes, thus requiring continuous intravenous infusion. Dosing includes a loading dose at 0.5 mg/kg over 2-5 minutes followed by a maintenance dose at 0.1 mg/kg/min. The maintenance drip can be titrated up by 0.05 mg/kg/min every 15-20 minutes to the desired heart rate. The usual maximal dose is 0.2 mg/kg/min.
Finally, calcium channel blockers, by altering the kinetics of the slow inward current,38 can slow AV node conduction and be used as rate-controlling agents. Like beta-blockers, intravenous forms are available with a rapid onset of action.34 Both Verapamil and Diltiazem have shown the ability to control the ventricular rate in AF.39 There is little evidence that either agent can convert AF,9 and trials have not demonstrated the superiority of Verapamil compared to placebo in the prevention of paroxysmal AF.34 Ellenbogen et al found that more than 90% of patients in acute AF responded with adequate rate control when given boluses of intravenous Diltiazem in an acute care environment.40 Dosing of IV Diltiazem usually includes an initial bolus dose of 0.25 mg/kg over two minutes followed by a second bolus at 0.35 mg/kg 15 minutes later if the response is inadequate. A maintenance drip at 10-15 mg/h is then started. Calcium channel blockers are the first line for rate control therapy in patients who cannot tolerate beta blockers, such as those with asthma or COPD.
Antiarrhythmics. Restoration of sinus rhythm is the optimal goal, as it may relieve symptoms and improve cardiac output at rest and with exertion.35 Following the conversion to sinus, hemodynamic performance can continue to improve over several weeks.41
The medications available for acute conversion of AF and maintenance of sinus rhythm are the Ia, Ic, and III antiarrhythmics in the Vaughn Williams classification.9 Table 2 shows the common antiarrhythmics used in the treatment of AF with their action, dosage, and more common adverse reactions.
Class Ia. These medications act by blocking the fast sodium channel, reducing the upstroke velocity of phase O of the action potential, and reducing the impulse conduction through the myocardium.9 The class includes Quinidine, Procainamide, and Disopyramide.
The use of Quinidine dates prior to the introduction of electrical cardioversion.7 It can be used to convert as well as to maintain sinus. In a meta-analysis, Coplan and colleagues reported that Quinidine was effective in maintaining sinus compared to controls, but the Quinidine group had higher all-cause mortality.42 By prolonging the QT interval, Quinidine predisposes to torsade de pointes.
Procainamide can also be used for both acute conversion and maintenance. It is, however, not as effective as the other Ia agents9 but can be given intravenously. Like Quinidine, it can result in life-threatening arrhythmias including torsade de pointes.43
Disopyramide has negative inotropic properties and should be avoided in patients with LV dysfunction. Torsade de pointes can occur with its use, but less frequently than with Quinidine.44 Disopyramide is no longer a commonly used drug in the treatment of AF due to poor efficacy and frequent side effects. Due to its vagolytic effects, its use is generally restricted to vagally induced AF. It may also be used in patients with AF and hypertrophic cardiomyopathy.
Class Ic. This class of medications acts by slowing the upstroke of phase O of the action potential and prolonging intraventricular conduction.9 There is no effect on the QT interval, but QRS widening can be seen on ECG. The most prescribed members of the class are Flecainide and Propafenone.
Flecainide, given as an oral bolus of 300 mg, can result in acute conversion to sinus rhythm in nearly 75% of patients with AF of less than 24 hours duration.45 Due to its negative inotropic action, Flecainide has to be used cautiously in patients with .46 In addition, it should not be used in patients with structural heart disease due to a high risk of proarrhythmia. It should be reserved for patients with normal LV function and refractory AF.10 Flecainide can be effectively used for sinus maintenance as well.
Propafenone may have fewer side effects and better tolerability than the Ia agents.46 It is available only in an oral form in the United States and can also be given as a single bolus dose (600 mg) for AF of less than 24 hours.45 Proarrhythmia can occur but is reported less frequently than with the other Ic medications.47 The use of Propafenone is advocated in patients who are hypertensive and have a structurally normal heart with AF.18 Like Flecainide, Propafenone should also be avoided in patients with structural heart disease due to its potential proarrhythmic effect in this patient population.
Class III. The medications in this class act by blocking outward potassium currents, resulting in a prolonged repolarization phase of the action potential and increased myocardial refractoriness.9 Included in this class are Amiodarone, Sotalol, Ibutilide, and the investigational drugs Dofetilide and Azimilide.
Amiodarone has sodium, calcium, and beta-blocking effects. It has a large volume of distribution and, as such, requires a significant loading dose. There are many potential side effects associated with its use, affecting the ophthalmologic, pulmonary, gastrointestinal, and endocrinological systems. In treating AF, a lower maintenance dose of 200 mg daily is generally used compared to the 400-mg daily dose for the treatment of ventricular tachycardia. Amiodarone has a low proarrhythmia profile.48 It has been shown to be safe and efficacious in patients with AF and CHF.49 Amiodarone can be used safely for both acute conversions (IV) and for oral maintenance therapy for AF.10
Sotalol has type III plus a beta-blocking effect and, like amiodarone, it is effective against both supraventricular and ventricular arrhythmias.10 A recent European trial found Sotalol less effective than a combination of Quinidine and digoxin for acute conversion.50 It is probably most effective for sinus maintenance in patients with AF and coronary artery disease or LV hypertrophy.18 Due to its significant beta-blocker effect, sotalol should be avoided in patients with severe LV dysfunction and those with severe COPD.
Ibutilide, administered intravenously, is effective for the conversion of recent onset AF10 and also for atrial flutter.51 The Ibutilide Repeat Dose Study investigators reported an 8.3% incidence of polymorphic ventricular tachycardia during or soon after the infusion, of which three patients required immediate cardioversion.51 For this reason, the use of Ibutilide should involve continuous ECG monitoring during its infusion and for at least four hours after its completion. Premedication with intravenous magnesium may reduce the occurrence of proarrhythmia.
Dofetilide is an investigational class III oral agent. A recent multicenter placebo-controlled trial showed its efficacy in acute conversion of AF.52 This same study reported a 3% incidence of torsade that occurred during the first three days of treatment in patients with AF and .
Tables 3 and 4 list a generalization of the efficacy, cost, and safety profiles for the antiarrhythmics used in the acute conversion of atrial fibrillation and in the maintenance of sinus rhythm. The results from the tables represent a cumulative review of multiple prospective and retrospective studies. As depicted in Table 4, the one-year efficacy in maintaining sinus rhythm decreases to approximately 50% for most antiarrhythmics. Therefore, since the overall long-term efficacy of these drugs is similar, the choice of an antiarrhythmic agent should be individualized to a specific patient, depending upon multiple factors including cost, efficacy, and the side effect profile.
It is important to realize that when patients have a recurrence of AF on an antiarrhythmic agent, the medication should not immediately be considered a failure. Due to the inherent recurrent nature of AF, the definition of successful maintenance of sinus rhythm on antiarrhythmic therapy has evolved. The fact that a patient has one or two recurrences during the year does not mean that the antiarrhythmic agent is ineffective. On such an occasion, a change in the dosage of the medication and/or an electrical cardioversion should be used with the maintenance of the same antiarrhythmic agent post-cardioversion.
Nonpharmacologic Strategies. Due to drug intolerance, possible proarrhythmic effects, and disappointing long-term efficacy of the antiarrhythmic agents, nonpharmacological therapies have begun to play a more important role in the management of AF. These treatments include external and internal cardioversion, cardiac pacing and defibrillation, radiofrequency catheter ablation, and surgery.
Electrical Cardioversion
First introduced by Lown et al in 1962,53 this method has proved to be both rapid and highly effective, with success rates greater than 80%.7 The electrical impulse is synchronized to the QRS complex to avoid the vulnerable period of the cardiac cycle.9 Studies have shown that the success rate is dependent on left atrial size, duration of AF, presence of mitral stenosis, and the patient’s age.46,54 The amount of energy required for CV is typically related to the duration of the AF.53 Factors such as transthoracic impedance and electrode size and placement can also affect the success of the procedure.4 If external CV at 360J fails, then a second attempt following the administration of Ibutilide (1 mg IV over 10 minutes) can improve the overall success rate55,56 by lowering the defibrillation threshold. Newer biphasic waveform defibrillators will soon be available, which may lower the energy requirements and increase the success rates of external CV.
If external CV is unsuccessful, then internal CV may be an option. This method was first introduced in 1988 by Levy and associates57 and consists of using defibrillating catheters in the right atrium and coronary sinus and a sensing catheter in the right ventricle. Thus, intravascular access is required. At experienced research centers, internal CV is as safe as external CV, with a success rate approaching 100%.58 The need for special equipment unfortunately limits this investigational therapy to a few centers.
Cardiac Pacing
AF is commonly associated with conduction system disease of the heart, particularly in the elderly.9 In patients with tachy-brady syndrome and paroxysmal AF, atrial-based pacing has been shown to reduce AF episodes, stroke events, left atrial dilatation, and mortality.59,60 Although investigational, dual-site atrial pacing from the high right atrium and coronary sinus has also shown promise in reducing the recurrence of AF.61
Radiofrequency Catheter Ablation/Atrial Defibrillators
The delivery of radiofrequency current through a catheter tip advanced to the atrium via femoral vein access has been demonstrated to be both highly effective and safe in the treatment of arrhythmias. For AF refractory to drug therapy, AV node ablation with permanent pacemaker implantation can relieve symptoms associated with palpitations and may improve both exercise and cardiac performance.62 Following ablation, a single-chamber ventricular pacemaker is usually implanted in patients with chronic AF while implantation of a dual-chamber pacemaker is performed in patients with paroxysmal AF. Radiofrequency ablation resulting in long linear atrial lesions63 and catheter ablation of PACs15 are two additional catheter-based techniques currently being investigated for the treatment of drug refractory AF.
A surgical technique, the "Maze" procedure, has also been used for patients who cannot be medically managed. In this method, the right and left atria are divided by multiple surgical incisions, thereby interrupting potential reentrant circuits.14 Cox et al have reported a "cure" in 98% of patients with medically refractory AF.64 This procedure, however, carries a significant morbidity and mortality and is being done at only a few centers worldwide.
Implantable atrial defibrillators are also being evaluated for the AF patient. In a small group of patients, the defibrillator appeared to be safe and achieved sinus rhythm in 96% of patients.65 However, the cost and tolerability of the application of the device remain important issues.
AF and CHF
AF is fairly common in patients with CHF, with an 8.5-fold increased risk of AF in men and a 14-fold increase in women.66 AF in these patients can cause worsening of CHF, pulmonary edema, and ventricular arrhythmias. It is an indicator of advanced LV dysfunction and possibly an indicator of increased mortality. Antiarrhythmics, for the control and conversion of AF, are the usual initial therapy. Certain Ia agents, such as Quinidine and Procainamide, can be effective in maintaining sinus rhythm. Disopyramide, which has a potent negative inotropic action, should be avoided in patients with CHF. Class Ic agents, including Propafenone and Flecainide, generally are not used in patients with CHF and AF due to their proarrhythmic and worsening CHF effect. Amiodarone typically is used most often in this patient population with a low proarrhythmic profile and a high efficacy rate in maintaining sinus rhythm after cardioversion.
In patients who are difficult to convert to or maintain in sinus rhythm, controlling the ventricular rate in AF may be appropriate. To accomplish rate control, drugs such as digoxin, low-dose calcium channel blockers (including Verapamil), and beta blockers may be effective. Rate control improves hemodynamics, including cardiac output, and reduces symptoms in many CHF patients.
Patients with AF and CHF are also at increased risk for intracardiac thrombus formation and embolic phenomenon. This increased risk is further compounded by the presence of mitral regurgitation, a common valvular condition seen in patients with CHF. Anticoagulation is recommended in these patients unless there is an obvious contraindication.
Conclusion
AF is already a common diagnosis in both the inpatient and outpatient settings. Currently, 11% of the U.S. population is between the ages of 65 and 85 years; 70% of patients with AF are between the ages of 65 and 85 years. As the general population ages, this diagnosis will most likely become more frequent. AF has a multitude of causes and symptoms, yet the pathophysiology is poorly understood. Patients with AF are susceptible to thromboembolism and benefit from anticoagulation therapy. Current management principles include rate control, acute cardioversion (either electrically or pharmacologically), and maintenance of sinus rhythm. Antiarrhythmic medications are still the first-line therapy for maintenance of sinus rhythm but presently have limited efficacy and potentially life-threatening side effects. Newer pacer, defibrillator, and catheter-based techniques offer promise to the patient with AF.
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Physician CME Questions
++++
In a patient with AF and CHF, which of the following antiarrhythmics has been shown to be safe and efficacious for acute conversion to sinus rhythm?
a. Sotalol
b. Flecainide
c. Amiodarone
d. Disopyramide
Which of the following agents is least effective in terminating acute AF?
a. Procainamide
b. Propafenone
c. Ibutilide
d. Amiodarone
e. Digoxin
Which of the following is a false statement regarding antithrombotic therapy in the patient with AF?
a. Patients with AF of more than 48 hours have an increased risk of embolic events.
b. Warfarin has been shown to reduce the incidence of embolic stroke in AF patients.
c. Oral anticoagulation with warfarin in patients with AF should have a goal INR of 2.0-3.0.
d. All patients with AF should be treated with oral anticoagulation therapy with warfarin.
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