Atrial Fibrillation: Current Understanding and Management
Authors: Manoucher Manoucheri, MD, FACP, Department of Internal Medicine and Department of Emergency Medicine, Faculty Member, Family Practice Residency Program, Florida Hospital, Orlando, FL.
David Nakamura, MD, Family Practitioner, Orlando, FL.
Peer Reviewer: Saleem Ahmad, MD, Director, Electrophysiology Laboratory, Kettering Medical Center, Dayton, OH.
Editor's Note-Atrial fibrillation is an arrhythmia commonly encountered in the primary care setting. If left untreated, the patient has a high risk of morbidity and mortality. Clinical goals should be aimed at control of symptoms and reduction of thromboembolic complications. An understanding of the epidemiology, pathophysiology, clinical presentation, and complications are essential in appropriate treatment of this common arrhythmia. The best treatment option is restoration and maintenance of sinus rhythm. If this cannot be accomplished, then chronic rate control and anticoagulation is the alternative. This review presents a discussion of the prevalence and epidemiology of atrial fibrillation, its pathophysiologic basis, clinical presentation, and its thromboembolic complications. The authors present the current medical and surgical treatment methods. These include immediate and long-term treatment options such as electrical or pharmacologic cardioversion, use of medications for rate control, appropriate use of antiarrhythmics, and the rationale for the use of anticoagulation. In addition, the various non-pharmacologic techniques are described for treatment of refractory symptomatic atrial fibrillation. In today's managed care setting, primary care physicians see increasing numbers of patients with this arrhythmia, and they should be able to competently manage such patients.
Epidemiology and Prevalence
Atrial fibrillation (AF) is the most common of all sustained arrhythmias. Chronic AF affects approximately 1.8 million Americans.1 In the Framingham Heart Study, during 22 years of follow-up, atrial fibrillation developed in approximately 2% of men and women.2 It is the second most common cardiac arrhythmia after premature ventricular beats.3 The prevalence increases with age and has a male predominance: 0.2-0.3% in persons 25-35 years old vs. 5-9% in those older than 62 years of age.1,4,5 The prevalence in healthy elderly persons older than age 70 is approximately 11% and rises to 17% by age 84.6 In the Manitoba follow-up study of male air crew recruits, 7.5% developed atrial fibrillation, with the incidence rising with age from less than 0.5 per 1000 person-years before the age 50 to 9.7 per 1000 person-years after age 70.7 Patsy et al reported an incidence of 19.2 per 1000 person-years in patients 65 or older, with males being at greater risk of developing AF in a three-year follow-up study.8
Etiology
The common clinical conditions associated with sustained atrial fibrillation are shown in Table 1. The majority of causes are related to cardiovascular problems.
Coronary artery disease is responsible for 8% of atrial fibrillations in men, and it doubles the risk of atrial fibrillation in this group.9 It is an uncommon presenting feature of acute myocardial infarction. However, it occurs in 6-20% of the cases of acute myocardial infarction, is a marker of more extensive infarct,9 and may portend a decreased long-term survival.10 Rheumatic heart disease increases the risk of atrial fibrillation eight-fold in men and 27- fold in women.9 Hypertensive heart disease is responsible for 14% of causes and increases the risk of atrial fibrillation four-fold in general.9 Increased left atrial size is an important risk for developing AF.8 Atrial fibrillation is a common occurrence in the course of management of the patients post coronary by-pass graft surgery. It occurs in 5-40% of patients and is more common in the elderly age group. One-third of those over age 70 develop this arrhythmia postoperatively, with near doubling of risk for each successive decade past age 40.11 In addition to age, other postoperative risks include previous AF, LV dysfunction, angina pectoris, and non-cardiac illness.12-14 Duration of surgery and method of cardioplegia have also been implicated.15-17 Pulmonary disease is also a common cause of AF. In one series, in patients with atrial fibrillation on presentation, 2-3% had underlying lung disease.18,19 Three percent of the patients with acute pulmonary embolism develop AF.20 Both acute binge drinking and chronic alcohol ingestion predispose to atrial fibrillation.9 Hyperthyroidism is another common cause of atrial fibrillation, and its incidence with overt hyperthyroidism is approximately 10-20%, with a higher prevalence in the older patients.9 In a study of hospitalized elderly patients with hyperthyroidism, 60% had atrial fibrillation.21 In this study, the diagnosis of hyperthyroidism was not suspected in 62% of patients. In the elderly, hyperthyroidism may be masked and not suspected. Other causes of atrial fibrillation include infections (i.e., pneumonia), toxins, anesthetic agents, and metabolic derangements (hypokalemia, hypercalcemia, hypoxemia, and hypomagnesemia).
Table 1. Causes of Atrial Fibrillation
|
CARDIAC · coronary artery disease · myocardial infarction · congestive heart failure · atrial infarction · mitral regurgitation secondary to papillary dysfunction · rheumatic heart disease · hypertension · pericarditis · cardiomyopathy · coronary bypass graft surgery · mitral valve prolapse · atrial myxoma · sinus node dysfunction · concealed pre-excitation (WPW syndrome) · congenital heart disease (e.g., atrial septal defect in adults) NON-CARDIAC · pulmonary embolism · COPD · alcohol · hyperthyroidism · pheochromocytoma LONE ATRIAL FIBRILLATION |
The term "lone atrial fibrillation" is used when no underlying cause is found for the arrhythmia. In one study, 16.6% of men and 6% of women were found to have lone atrial fibrillation without any obvious underlying etiology.22 The incidence may be as high as 30%.23 However, when extensively evaluated, a subset of patients with lone AF may have abnormal atrial histology compatible with myocarditis, noninflammatory localized cardiomyopathy, or patchy fibrosis.24
Pathophysiology
As already noted, many different factors contribute to this form of arrhythmia, and AF should not be considered a disease but, rather, a manifestation of various cardiac and non-cardiac conditions. There still remain many questions about the mechanisms of AF and the pathologic substrate common to all these clinical entities. The currently accepted theory for the mechanism of AF involves random waves or "wavelets" of intra-atrial reentry, with multiple macro-reentrant circuits moving from one area of atrium to another (Moe's multiple wavelet hypothesis).25 This causes disorganized atrial depolarization without effective atrial contraction and produces the characteristic EKG abnormality seen with an undulating baseline, no discernible P waves, and an irregular ventricular response. Atrial fibrillation may result in a 20-30% reduction in cardiac output in normal individuals and a greater decrease in those with heart disease.26
Production of AF is tied to autonomic nervous system activity. Diseased atrial muscle has increased sensitivity to adrenergic stimulation, whereas, in normal atrial muscle, the vagal influences predominate.27 Therefore, either the sympathetic (in diseased heart) or the parasympathetic stimulation (in normal heart) may induce AF.27 Chronic atrial fibrillation is often preceded by episodes of paroxysmal AF.28 The transition from paroxysmal to chronic AF may be due to further progression of the underlying etiologic processes or a change brought about in the myocardium by AF favoring its irreversibility.29,30 The hypothesis that "atrial fibrillation begets atrial fibrillation" was tested by Wijffels et al in chronically instrumented goats.29,30 This experimental study showed that even during the first days of AF, marked physiologic changes occurred in the atria which favored induction and maintenance of AF. After three weeks, when the goats were disconnected from the automatic fibrillation pacemaker, most of them remained in AF. The underlying mechanism for this "electrical remodeling" favoring perpetuation of AF seems to be a fibrillation-induced shortening of effective atrial refractory period.31 Sustained AF in goats leads to structural changes in the atrial myocytes similar to those seen in ventricular myocytes from chronic hibernating myocardium.32 Direct data supporting electrical remodeling in human in situ myocardium is still sparse, but, in one study using action potential recordings, quantitative decreases in atrial action potential duration were noted with AF.33 The atrial myocardium of patients with chronic atrial fibrillation is also abnormal in its histologic features in addition to its electrophysiologic derangements. This "tachycardia-induced atrial myopathy" and the associated electrical remodeling may be the cause or consequence of chronic AF.34 Regardless, the clinical consequence of this abnormal substrate is maintenance and perpetuation of AF. This phenomenon has significant implications in treatment of this arrhythmia which will be discussed later in this review.
Clinical Presentation
AF may present as an asymptomatic arrhythmia or with palpitations, dizziness, chest pain, and, rarely, syncope. Patients with underlying heart disease may experience significant hemodynamic compromise due to chaotic and ineffective atrial contractions resulting in a decrease in left ventricular filling with subsequent drop in cardiac output. This may result in hypotension and could cause angina due to a combination of increased myocardial oxygen demand and reduced coronary filling in diastole.35 Physical findings include absence of an a wave and an irregularly irregular heart rate. A pulse deficit may also be noted with faster ventricular rates; that is, the auscultated apical rate exceeds the palpable peripheral rate. This is due to failure of many ventricular contractions to open the aortic valve or to transmit an arterial pressure wave through to the peripheral artery.36 On electrocardiogram, AF can be suspected by absence of a discernible p wave, undulating baseline, and an irregular ventricular rate. When there is no underlying atrioventricular conduction abnormality, the ventricular response may be rapid, usually between 100 and 160 beats per minute. In patients with Wolff-Parkinson-White (WPW) syndrome, the rate can exceed 300 beats/minute due to presence of an accessory pathway. In such cases, the rhythm may degenerate into ventricular fibrillation.
Complications of Atrial Fibrillation
AF is associated with three potential complications: hemodynamic compromise, arrhythmogenesis, and, most significantly, thromboembolism. Hemodynamic compromise has been alluded to earlier in this review. The potential for development of life-threatening arrhythmias in patients with WPW syndrome is well recognized. In addition, drugs traditionally used for treatment of AF have potential to provoke a new arrhythmia (proarrhythmia). Patients with AF may be at a greater risk for proarrhythmia because of the association of AF with underlying heart disease. The Cardiac Arrhythmia Suppression Trial (CAST I and II) of the early 1990s noted that antiarrhythmic drugs have the potential to exacerbate rather than suppress arrhythmias.37 Torsades des pointes (QRS axis wraps around the isoelectric baseline), also known as polymorphic ventricular tachycardia, is perhaps the most widely recognized proarrythmia associated with treatment of atrial fibrillation, especially with class1A antiarrythmic drugs (quinidine or procainamide) and sotolol.38 Hence, the therapeutic advantages of these agents should be weighed against their potential arrythmogenic complications when these agents are used for chronic treatment of atrial fibrillation.
Table 2. Drugs Used for Ventricular Rate Control
Drug |
Loading dose |
Maintenance dose |
Side effects |
Digoxin |
0.25-0.5 mg IV/PO then 0.25 mg IV every six hours (1.0-1.5 mg in first 24-48 hours) |
0.125-0.375 mg PO daily |
Nausea, anorexia, blurred or yellow vision, accelerated junctional rhythm, AV block, ventricular arrhythmias |
Esmolol |
500 mcg/kg IV over one minute |
50 mcg/kg IV for four minutes. Repeat loading dose if needed and increase maintenance dose by 20-50 mcg/kg/min every 5-10 minutes |
Bronchospasm, heart failure, hypotension |
Propranolol |
1 mg IV every five minutes to a total of 5 mg |
10-80 mg PO 3-4 times a day |
Bronchospasm, heart failure, hypotension |
Metoprolol |
5 mg IV every five minutes to a total of 15 mg |
25-100 mg PO twice a day |
Bronchospasm, heart failure |
Diltiazem |
0.25 mg/kg over two minutes. Repeat if needed after 15 minutes as 0.35 mg/kg over two minutes |
5-15 mg/h IV or 30-90 mg PO four times a day |
Hypotension, heart failure, bradycardia |
Verapamil |
2.5-10 mg IV over two minutes |
0.005 mg/kg/min or 5-10 mg IV every 30-60 minutes |
Hypotension, heart failure, bradycardia, increased serum, digoxin level |
Thromboembolism and stroke are by far the most significant complications of AF. Previously, AF was thought to predispose to embolism only in presence of rheumatic mitral stenosis. In the absence of valvular heart disease, the importance of AF was not fully appreciated. Since the cardiovascular precursors that predispose to AF also predispose to stroke, it had been asserted that the incidence of stroke from AF resulted from the influence of associated vascular conditions rather than from the arrhythmia itself.39 However, the evidence derived from autopsy, clinical, and epidemiological data has strongly linked non-rheumatic AF to stroke.40,41 According to the Framingham study, AF increases the risk of stroke five-fold, with a distinct clustering of events around the onset of AF.42 In addition, the contribution of AF to stroke was also at least as powerful as that of other cardiovascular precursors.42 Patients less than 65 years of age who do not have diabetes, a history of hypertension, a previous TIA or stroke, or heart failure have an annual risk of stroke of about 1% per year. Unfortunately, patients older than age 65, or younger ones with any of the four risk factors have an annual risk of stroke of 4% per year.43 In addition, patients with AF and previous stroke have a higher probability of recurrent thromboembolic events,44 and they experience greater severity of stroke than others with non-AF related ischemic strokes.45 The negative influence of AF on the mortality of patients with stroke is well known. In the Framingham Study cohort of patients with ischemic stroke, AF-associated stroke was nearly twice as likely to be fatal as non-AF stroke, with the survivors experiencing more recurrences and greater functional deficits.46 In the Italian Stroke Study, the one-month case fatality rate in the AF group was 27%, while in the group without AF it was 14%; the six-month case fatality rates were 40% and 20%, respectively.47 Analysis of the FINMONICA stroke registry (stroke in Finnish population) during 1982 through 1992 also revealed a higher mortality rate in AF group both at 28 days and one year after the stroke.48 Cardiac causes of death were more common in the AF group at the acute stage. Persistent AF is an independent risk factor for death after the first cerebral infarction.49 Higher mortality rates, longer hospital stays, lower discharge rate to home, and worse neurological and functional outcomes were also noted in The Copenhagen Stroke Study.50 The increased mortality has also been demonstrated recently in patients with minor strokes in the setting of AF.51
Treatment
The objectives of treating AF are to control or eliminate hemodynamic symptoms and to prevent thromboembolic complications. Treatment encompasses three areas: ventricular rate control, conversion to and maintenance of sinus rhythm, and anticoagulation. Treatment can further be divided into short-term and long-term goals. (See Figure 1.) The immediate goal in treatment of AF is reduction and control of ventricular rate. Hemodynamically unstable patients should undergo immediate direct-current cardioversion rather than attempts at rate control. In stable patients, however, rate control should be the primary short-term goal.52 In long-term treatment of AF, two alternative approaches are possible: restoration and maintenance of sinus rhythm, or chronic rate control and anticoagulation to prevent thromboembolism.
Table 3. Antiarrhythmic Drugs for Atrial Fibrillation
| DRUG | DOSE |
Class Ia |
|
· disopyramide |
100-150 mg qid or CR (sustained release) 200-300 mg bid |
· procainamide |
50 mg/kg/d divided bid or qid (sustained released) |
· quinidine gluconate |
324 mg bid/tid |
· quinidine sulfate |
300-600 mg bid/tid |
Class Ic |
|
· flecainide |
50-100 mg bid |
· propafenone |
150 mg tid; or single oral dose of 600 mg for pharmacoconversion84 |
Class II |
|
· sotolol |
80 mg bid |
Class III |
|
· amiodarone |
oral dosage varies; IV loading dose of 5 mg/kg, infusion rate titrated to ventricular response over 10-40 minutes85 |
· ibutilade |
0.01 mg/kg IV over 10 minutes for pharmacoconversion |
Pharmacologic Therapy for Rate Control
The same drugs are used for both immediate and long-term rate control: digoxin, beta-blockers, and calcium antagonists. (See Table 2.) The choice of agent used depends on clinical considerations and the clinician's preferences. At times, more than one agent may be used to achieve the desired effect. Digoxin increases vagal tone and thus slows AV nodal conduction. It remains the most widely used agent for rate control in AF.53 A major benefit of this drug is its positive inotropic effect, which is beneficial for a large number of patients with AF who also have left ventricular dysfunction. It may also prevent recurrent AF in patients with heart failure, owing to its effectiveness in enhancing left ventricular performance and reducing left atrial pressure.35 Digoxin has its limitations, however. It is ineffective and should not be used in situations in which vagal tone is already low, such as in exercise, thyrotoxicosis, paroxysmal AF of recent onset, or hyperadrenergic states.52 It is often used postoperatively to control the heart rate, though its benefits may be limited in the presence of excess catecholamines.54 It has a slow onset of action even when given intravenously and may require several loading doses to achieve desired rate control. In addition, it is no more effective than placebo in restoring sinus rhythm in patients with AF of recent onset.55 Beta-blockers oppose the enhancing effect of adrenergic stimulation on the AV nodal transmission and are thus of greatest value in settings of high sympathetic stimulation (i.e., hyperthyroidism and hyperadrenergic states). They may be used prophylactically in patients undergoing cardiothoracic surgery with demonstrated protective effect.56 Various beta-blockers have been used to lower heart rate quickly. Esmolol, given as a continuous intravenous infusion, can be titrated to achieve a specific target heart rate. Its short half-life and rapid clearance from circulation give it an advantage if bradycardia or hypotension develop.57 Beta-blockers should not be used in patients with congestive heart failure, bradycardia, or reactive airway disease.
Calcium channel antagonists such as diltiazem and verapamil have been used to control ventricular rate in AF. Intravenous verapamil can quickly lower the rate, but its effect is transient. Its negative inotropic property can precipitate hypotension and worsen the underlying left ventricular failure. Diltiazem, on the other hand, has relatively mild negative inotropic effect, as compared to verapamil, and is well tolerated during short-term continuous infusions.58 Digoxin, beta-blockers, and calcium antagonists can be used for long-term rate control if sinus rhythm can not be restored.
Table 4. Anticoagulation Trials in Nonrheumatic Atrial Fibrillation
AFASAK |
BAATAF |
CAFA |
SPAF I |
SPINAF |
SAPF II | |
£ 75 yrs > 75 yrs | ||||||
Target INR |
2.8-4.2 |
1.5-2.7 |
2.0-3.0 |
2.0-4.5 |
1.4-2.8 |
2.0-4.5 |
Aspirin |
75 mg |
No* |
No |
325 mg |
No |
325 mg |
% Risk reduction |
58% |
86% |
37% |
67% |
79% |
32% 25% |
Benefit of aspirin |
No |
No |
N/A |
Yes§ |
N/A |
N/A |
*controls allowed to take aspirin
§ 42% risk reduction when compared to placebo in warfarin-ineligible patients
AFASAK = Atrial Fibrillation, Aspirin, Anticoagulation Study from Copenhagen;86 BAATAF = Boston Area Anticoagulation Trial for Atrial Fibrillation;87 CAFA = Canadian Atrial Fibrillation Anticoagulation ;88 SPAF = Stroke Prevention in Atrial Fibrillation trial;89,91 SPINAF = Stroke Prevention in Nonrheumatic Atrial Fibrillation study;90 INR= International Normalized Ratio; N/A = non-applicable because aspirin not compared to placebo.
Restoration and Maintenance of Sinus Rhythm
If atrial fibrillation is of recent onset, spontaneous reversal to sinus rhythm generally occurs in 12-24 hours in patients receiving placebo or drugs that slow AV nodal conduction.59 However, for atrial fibrillation of longer duration, and when more rapid rhythm conversion is desired, electrical or pharmacologic cardioversion is appropriate. In general, if medical therapy fails to convert AF in 24-48 hours, electrical cardioversion can be carried out safely without prior anticoagulation using 100-360 Ws of energy. The success of cardioversion is influenced by several clinical factors: duration of arrhythmia, underlying disease, left atrial diameter, and patient's age.58 If AF has been present for 72 hours or more, anticogulation with an INR range of 2-3 should be given at least three weeks prior to and continued for four weeks following cardioversion; this applies to both electrical and pharmacologic cardioversion.36 This anticoagulation recommendation is provided by the American College of Chest Physicians.60 It is based on high prevalence of embolic events in patients undergoing cardioversion, with an event rate of up to 5.6%61 due to dislodgement of pre-existing clot or of formation of new one in stunned atria following successful cardioversion, as their mechanical function may take 4-6 weeks to return.62 Prior to cardioversion, risk stratification with transesophageal echocardiography (TEE) may be useful,63 feasible, and safe,64 but the absence of a left atrial thrombus on TEE does not necessarily ensure that the patient will not have an embolus at or after cardioversion.65 Pending results of the ACUTE (Assessment of Cardioversion Using Transesophageal Echocardiography) trial, routine performance of TEE prior to cardioversion is not recommended at this time.
Pharmacologic cardioversion of AF can be accomplished using classes IA, IC, or III agents. (See Table 3.) The two drugs with most clinical experience in this setting are IA agents quinidine and procainamide. Because it can be given intravenously, procainamide is preferred when the need for cardioversion is semiurgent.66 Conversion success with intravenous procainamide is high when duration of arrhythmia is short (91% for< 2 days; 33% for > 2 days).67 Quinidine enhances conduction through the AV node; hence, pretreatment with digoxin is recommended. Class IC drugs flecainide and propafenone and class III drug amiodarone have success rates of greater than 60%.68 With the possible exception of amiodarone, these drugs should be avoided in patients with significant ventricular dysfunction due to risk of proarrhythmia. In April 1996, a new class III agent, ibutilide, was approved by the FDA. This drug is effective, acts quickly, is well tolerated,69,70 and is touted by some as the first-line agent for pharmacologic cardioversion.59 There are, however, minimal data from randomized clinical trials that show superiority of one agent over the other. Therefore, selection of an antiarrhythmic agent should be individualized, weighing risks and benefits of treatment associated with attempt at maintenance of sinus rhythm.71 Patients with long-standing AF, large left atrial size, or those with multiple drug failures will have the highest rate of recurrence of AF, and concomitant use of AV nodal slowing agents and anticoagulation is recommended.71 The merits and problems of rate control vs. maintenance of sinus rhythm is currently under investigation by AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management), a large, randomized study sponsored by the National Heart, Lung, and Blood Institute.72 Nonpharmacological approaches to refractory AF include endocardial catheter ablation, pacing, and surgery. Radiofrequency ablation of the AV node to create complete heart block, followed by permanent pacemaker placement is one such option.73 In patients with paroxysmal AF not controlled by drugs, this procedure has shown to control symptoms and improve quality of life.74 Endocardial radiofrequency ablation is also performed either in a discrete focus75 or in a multiple linear fashion76 to treat refractory AF. However, it is still investigational, an evolving technology, and cannot be routinely recommended.77 Several surgical approaches have been used to treat patients with AF. The left atrial isolation technique, the "corridor" operation, isolates atrial tissue and AV nodes from the remaining right and left atria.78 The procedure is designed to allow normal conduction from the sinus node via the AV node despite concomitant atrial fibrillation in the isolated segment of atria. The benefits of this procedure appear to be transient, with recurrence of arrythmias.79 In the "maze" operation, successor to the "corridor" surgery, the atria are divided by multiple surgical incisions, thus interrupting potential reentrant circuits and providing a path or a "maze" to channel sinus impulses through the AV node.80
Anticoagulation
The most feared complication of AF is systemic embolization. Anticoagulation with warfarin is highly effective in reducing the incidence of ischemic stroke in this patient population. Five randomized clinical trials using INR ranges of approximately 1.4-4.2 show a significant risk reduction in stroke. (See Table 4.) A meta-analysis of these trials identified four independent clinical features by multivariate analysis that identified patients at high risk for stroke.81 These include a history of transient ischemic attack or stroke, hypertension, diabetes mellitus, and advancing age. Patients with any of these risk factors had an annual stroke risk of 4%. Those with a history of coronary artery disease, and congestive heart failure had a stroke rate three times greater than those with no risk factors. Based on these findings, long-term oral anticoagulant therapy with an INR range of 2-3 is strongly recommended for all patients older than 65 with non valvular AF, and for patients younger than 65 who have the following risk factors: a previous transient ischemic attack or stroke, hypertension, heart failure, diabetes mellitus, or coronary artery disease.60 (See Figure 2.) In patients who decline warfarin or are poor candidates for anticoagulation, aspirin should be offered. For those younger than 65 with no risk factors, aspirin or no antithrombotics may be suggested. In patients between 65-75 years of age without any risk factors, the treatment should be individualized. In those older than 75, warfarin is recommended, although there is an increased risk of bleeding. Some physicians tend to aim at a lower INR range in the elderly to minimize the risk of bleeding.82 However, careful monitoring rather than a compromise in established INR range is recommended to reduce the bleeding risk and prevent thromboembolism. The benefits of anticoagulation in the "very old," those older than 80 years, should be weighed against the high risk of bleeding, with a careful case-by-case selection for warfarin or aspirin in patients at high risk of thromboembolism.83
Conclusion
Nonvalvular atrial fibrillation is a prevalent arrhythmia in the general population, especially in the elderly, with the incidence rising with advancing age. The primary goal in treatment of acute atrial fibrillation is restoration of sinus rhythm as soon as possible if spontaneous conversion does not occur within the first 48 hours. Early cardioversion is important, since "AF begets AF" due to electrical and histological changes that develop in the atrial myocardium with prolonged AF. These changes perpetuate and maintain AF and thus reduce the success rate of cardioversion. Unfortunately, in patients with underlying heart disease such as dilated left atrium or congestive heart failure, the cardioversion success rate is low. In addition, the maintenance of sinus rhythm in these patients often requires membrane-active antiarrhythmics with potential increase in morbidity and mortality. With refractory, symptomatic AF, nonpharmacologic methods may be considered. These include radiofrequency ablation of AV node with permanent pacemaker placement or surgical interventions such as the "maze" procedure. However, only a select number of patients have indications for such procedures. For the large majority of patients with sustained AF, rate control with AV node-active drugs and long-term anticoagulation is the best option. Anticoagulation with warfarin is proven to be effective in prevention of stroke and should be given to at-risk patients. Careful monitoring of anticoagulation with a target range of 2-3 should minimize the risk of bleeding in older patients. Aspirin is a viable alternative when anticoagulation would pose a significant bleeding risk.
References
1. Kannel WB, Wolf PA. Epidemiology of atrial fibrillation. In: Falk RH, Podrid PT, eds. Atrial fibrillation: Mechanism and Management. New York : Raven Press,1992:81-92.
2. Kannel WB, et al. Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med 1982;1018-1022.
3. Kannel WB, et al: Coronary heart disease and atrial fibrillation: the Framingham study. Am Heart J 1983;106:389-396.
4. Furberg CD, et al. Prevalence of atrial fibrillation in elderly subjects(the Cardiovascular Health Study).Am J Cardiol 1994;74:236-241.
5. Cobbe S. Incidence of risks associated with atrial fibrillation. Pacing Clin Electrophysiol 1994;17:1005-1010.
6. Martin A, et al. Five year follow-up of 101 elderly subjects by means of long-term ambulatory cardiac monitoring. Eur Heart J 1984;5:592-596.
7. Krahn AD, et al. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up study. Am J Med 1995;98:476-484.
8. Patsy BM, et al. Incidence of and risk factors for atrial fibrillation in older adults. Circulation 1997;96:2455-2461.
9. Reardon M, Camm AJ. Atrial fibrillation in the elderly. Clin Cardiol 1995;19:765-775.
10. Sakata K, et al. Clinical and prognostic significance of atrial fibrillation in acute myocardial infarction. Am J Cardiol 1997;80:1522-1527.
11. Ommen SR, Odell JA, Stanton MS. Atrial fibrillation after cardiothoracic surgery. N Engl J Med 1997;336:1429-1434.
12. Hashimoto K, Ilstrup DM, Schaff HV. Influence of clinical and hemodynamic variables on the risk of supraventricular tachycardia after coronary artery bypass surgery. J Thorasc Cardioovasc Surg 1991;101:56-65.
13. Leitch JW, et al. The importance of age as a predictor of atrial fibrillation and flutter after coronary artery bypass grafting. J Thorasc Cardiovasc Surg 1990;100:338-342.
14. Creswell LL, et al. Hazards of postoperative arrhythmias. Ann Thorac Surg 1993;56:539-549.
15. The Warm Heart Investigators. Randomized trial of normothermic versus hypothermic coronary bypass surgery. Lancet 1994;343:559-563.
16. Fontan F, et al. Modifying myocardial management in cardiac surgery: A randomized trial. Eur J Cardiothorac Surg 1992; 6:127-136.
17. Butler J, et al. Atrial fibrillation after coronary artery bypass grafting: a comparison of cardioplegia versus intermittent aortic cross-clamping. Eur J Cardiothorac Surg 1993;7:23-25.
18. Hrowsaiva K, Sekiguiki M, Kasinuki H. Natural history of atrial fibrillation. Heart Vessel(suppl) 1987;2:14-23.
19. Schlofmitz RA, Hirsch BE, Meyer BR. New onset atrial fibrillation. Is there a need for emergency hospitalization? J Gen Intern Med 1986;1:139-142.
20. Urokinase Pulmonary Embolism Trial: clinical and electrocardiografic observations. Circulation 1973;47 (suppl 11):60-65.
21. Martin FI, Deam DR. Hyperthyroidism in elderly hospitalizes patients. Clinical features and treatment outcomes. Med J Aust 1996;164:200-203.
22. Brand FN, et al. Characteristics and prognosis of lone atrial fibrillation: 30-year follow-up in the Framingham Study. J Am Med Assoc 1985;254:3445-3453.
23. Levy S. Factors predisposing to the development of atrial fibrillation. Pacing Clin Electrophysiol 1997;20:2670-2674.
24. Frustaci A, et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 1997;96: 1180-1184.
25. Moe GK. On multiple wavelet hypothesis of atrial fibrillation. Arch Int Pharmacodyn Ther 1962;140:183-188.
26. Alpert JS, Peterson, P, Godtfredsen J. Atrial fibrillation: Natural history, complications, and management. Ann Rev Med 1988;39:41-52.
27. Coumel P, Thomas O, Leenhardt A. Drug therapy for prevention of atrial fibrillation. Am J Cardiol 1996;77 (Suppl):3A-9A.
28. Godtfredsen J. Atrial fibrillation. Etiology, course, and prognosis. A follow-up study of 1,212 cases. Dr Med thesis, Univ. Copenhagen, Munksgaard, 1975.
29. Wijffels MCEF, et al. Atrial fibrillation begets atrial fibrillation. In: Olsson SB, Allessie MA, Campbell RWF, eds. Atrial Fibrillation-Mechanisms and Therapeutic Strategies. Armonk, New York: Futura Publishing,1994;195-201.
30. Wijffels MCEF, et al. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation 1995;92:1954-1968.
31. Maurits A, et al. Electrophysiologic mechanisms of perpetuation of atrial fibrillation. Am J Cardiol 1996;77:10A-23A.
32. Ausma J, et al. Structural changes of atrial myocardium due to sustained atrial fibrillation in the goat. Circulation 1997;96: 3157-3163
33. Franz MR, et al. Electrical remodeling of the human atrium: Similar effects in patients with chronic atrial fibrillation and flutter. J Am Coll Cardiol 1997;30:1785-1792.
34. Gallagher MM, Obel OA, Camm CA. Tachycardia-induced atrial myopathy: An important mechanism in the pathophysiology of atrial fibrillation? J Cardiovasc Electrophysiol 1997;8:1065-1074.
35. Repique LJ, Shah SN, Marais GE. Atrial fibrillation 1992: Management strategies in flux. Chest 1992;101:1095-1103.
36. Zipes DP. Specific Arrhythmias: Diagnosis and Treatment. In: Braunwald E (ed): Heart Disease-A Textbook of Cardiovascular Medicine, 5th ed. Philadelphia: 1997:640-704.
37. Echt DS, et al, and the CAST Investigators: mortality and morbidity in patients receiving encanide, flecanide, or placebo: Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324:781-788.
38. Capucci A, Villani GQ, Aschieri D. Risk of complications of atrial fibrillation. Pacing Clin Electrophysiol 1997;20: 2684-2691.
39. Chesebro JH, Fuster V, Halperin JL. Atrial fibrillation-Risk marker for stroke [ editorial]. N Engl J Med 1990;323: 1556-1558.
40. Fisher CM. Embolism in atrial fibrillation. In: Kulbertus HE. Olsson SB, Schlepper M, eds. Atrial fibrillation: Held in Kiruna, Sweden and Proceedings of a Symposium, June 24-27, 1981. Molndal, Sweden: Hassle; 1982:192-210.
41. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: The Framingham study. Stroke 1991;22:983-988.
42. Wolf PA, et al. Duration of AF and imminence of stroke: The Framingham study. Stroke 1983;14:664-667.
43. Laupacis A, Cuddy TE. Prognosis of individuals with atrial fibrillation. Can J Cardiol 1996;12 (Suppl A):14A-16A.
44. Aronow WS, Ahn C, Gutstein H. Prevalence of atrial fibrillation with prior and new thromboembolic stroke in older patients. J Am Geriatr Soc 1996;44:521-523.
45. Novello P, et al. Ischemic stroke and atrial fibrillation. A clinical study. Ital J Neurol Sci 1993t;14:571-576.
46. Lin HJ, et al. Stroke severity in AF. The Framingham Study. Stroke 1996;27(10):1760-1764.
47. Candelise L, Pinardi G, Morabito A. Mortality in acute stroke with atrial fibrillation. The Italian Acute Stroke Study Group. Stroke 1991;22(1):164-164
48. Kaarisalo MM, et al. Atrial fibrillation and stroke. Mortality and causes of death after the first acute ischemic stroke. Stroke 1997;28(2):311-315.
49. Petty GW, et al. Survival and recurrence after first cerebral infarction: A population-based study in Rochester, Minnesota, 1975 through 1989. Neurology 1998;50:208-216.
50. Jorgensen HS, et al. Acute stroke with atrial fibrillation. Copenhagen Stroke Study. Stroke 1996;27(10):1765-1769.
51. Prencipe M, et al. Long-term prognosis after a minor stroke: 10-year mortality and major stroke recurrence rates in a hospital-based cohort. Stroke 1998;29:126-132.
52. Nattel S. Newer developments in the management of atrial fibrillation. Am Heart J 1995;130:1094-1106.
53. Sarter BH, Marchlinski FE. Redefining the role of digoxin in the treatment of atrial fibrillation. Am J Cardiol 1992;69:71G-81G.
54. Coumel P. Autonomic arrhythmogenic factors in paroxysmal atrial fibrillation. In: Olsson SB, Allessie MA, Campbell RWF, eds. Atrial Fibrillation: Mechanism and Therapeutic Strategies. Armonk, NY: Futura Publishing; 1994:171-185.
55. Falk RH, Knowlton AA, Bernard SA. Digoxin for converting recent onset atrial fibrillation to sinus rhythm: A randomized, double-blinded trial. Ann Intern Med 1987;106:503-506.
56. Kowey PR, et al. Meta-analysis of the effectiveness of prophylactic drug therapy in preventing supraventricular arrhythmia early after coronary artery bypass grafting. Am J Cardiol 1992;69:963-965.
57. Pritchett ELC. Management of atrial fibrillation. N Engl J Med 1992;326:1264-1271.
58. Ukani ZA, Ezekowitz MD. Contemporary management of atrial fibrillation. Med Clin N Am 1995;79:1135-1153.
59. Anderson JL. Acute treatment of atrial fibrillation. Am J Cardiol 1996;78:17-21.
60. Laupacis A, et al. Antithrombotic therapy in atrial fibrillation. Chest 1995;108 (suppl):352S-359S.
61. Leung DY, Grimm RA, Klein AL. Transesophageal echocardiography-guided approach to cardioversion of atrial fibrillation. Prog Cardiovasc Dis 1996;39:21-32.
62. Manning WJ, et al. Pulsed Doppler evaluation of atrial mechanical function after electrical cardioversion of atrial fibrillation. J Am Coll Cardiol 1989;59:572-577.
63. Leung DY, et al. Prognostic implications of left atrial spontaneous echo contrast in nonvalvular atrial fibrillation. J Am Coll Cardiol 1994;24:755-762.
64. Klein AL, et al. Cardioversion guided by transesophageal echocardiography: The ACUTE Pilot Study. A randomized, controlled trial. Ann Intern Med 1997;126:200-209.
65. Black IW, et al. Exclusion of atrial thrombus by transesophageal echocardiography does not preclude embolism after cardioversion of atrial fibrillation. A multicenter study. Circulation 1994;89:2509-2513.
66. Stettin GD. Treatment of nonvalvular atrial fibrillation. West J Med 1995;162:331-339.
67. Fenster P, et al. Conversion of atrial fibrillation to sinus rhythm by acute intravenous procainamide. Am Heart J 1983;106: 501-504.
68. Sopher SM, Camm AJ. Atrial fibrillation: Maintenance of sinus rhythm versus rate control. Am J Cardiol 1996;77:24A-37A.
69. Ellenbogen KA, et al. Efficacy of intravenous ibutilide for acute termination of atrial fibrillation and atrial flutter: A dose response study. J Am Coll Cardiol 1996;78:42-45.
70. Stambler BS, et al. Conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators. Circulation 1996; 94:1613-1621.
71. Prystowsky EN, et al. Management of patients with atrial fibrillation: A statement for healthcare professionals from the Subcommittee on Electrocardiography and Electrophysiology, American Heart Association.
72. AFFIRM. The Planning and Steering Committee of the AFFIRM study for the NHLBI AFFIRM investigators. Am J Cardiol 1997;79:1189-1202.
73. Morady F, et al. A prospective randomized comparison of direct current and radiofrequency ablation of the atrioventricular junction. J Am Coll Cardiol 1993;21:102-109.
74. Brignole M, et al. Assessment of atrioventricular junction ablation and DDDR mode-switching pacemaker versus pharmacological treatment in patients with severely symptomatic paroxysmal atrial fibrillation: A randomized controlled study. Circulation 1997;96:2617-2624.
75. Jais P, et al. A focal source of atrial fibrillation by discrete radiofrequency ablation. Circulation 1997;95:572-576.
76. Haissaguerre M, et al. Right and left atrial radiofrequency catheter therapy of paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 1996;7:1132-1144.
77. Haissaguerre M, et al. Role of catheter ablation for atrial fibrillation. Curr Opin Cardiol 1997;12:18-23.
78. Leitch JW, et al. Sinus node atrioventricular node isolation: Long-term result for the "corridor" operation for atrial fibrillation. J Am Coll Cardiol 1991;17:970-975.
79. van Hemel NM, et al. Long-term follow-up of corridor operation for lone atrial fibrillation: Evidence for progression of disease? J Cardiovasc Electrophysiol 1997;8:967-973.
80. Cox JL. The surgical treatment of atrial fibrillation, IV: surgical technique. J Thorac Cardiovasc Surg 1991;101:584-592.
81. Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: Analysis of pooled data from five randomized trials. Arch Intern Med 1994;154:1449-1457.
82. McCrory DC, et al. Physician attitudes about anticoagulation for nonvalvular atrial fibrillation in the elderly. Arch Intern Med 1995;155:277-281.
83. Ackerman RJ. Anticoagulant therapy in patients aged 80 years or more with atrial fibrillation. An editorial. Arch Fam Med 1997;6:105-110.
84. Hughes C, Sunderji R, Gin K. Oral propafenone for rapid conversion of recent onset atrial fibrillation-A review. Can J Cardiol 1997;13:839-842.
85. The treatment of atrial fibrillation: Pharmacologic and nonpharmacologic strategies. Curr Probl Cardiol 1997;February:44-107.
86. Petersen P, et al. Placebo-controlled, randomized trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: The Copenhagen AFASAK study. Lancet 1989;I:175-179.
87. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators: The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med 1990;323:1505-1511.
88. Connolly S, Laupacis A, Gent M. Canadian atrial fibrillation anticoagulation study. J Am Coll Cardiol 1991;18:349-355.
89. The Stroke Prevention in Atrial Fibrillation Investigators: The stroke prevention in atrial fibrillation study: final results. Circulation 1991;84:527-539.
90. Ezekowitz MD, et al. Subclinical cerebral infarction in patients with chronic nonvalvular atrial fibrillation. Circulation 1989;80 (Suppl II):404.
91. Stroke Prevention in Atrial Fibrillation Investigators: Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet 1994;343:687-691.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content