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Author: Jonathan Glauser, MD, FACEP, Staff, Department of Emergency Medicine, Cleveland Clinic Foundation, Faculty, Residency Training Program in Emergency Medicine, MetroHealth Medical Center, Assistant Clinical Professor of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH.
Peer Reviewer: William J. Brady, MD, FACEP, Associate Professor of Emergency Medicine, Department of Emergency Medicine; Associate Professor of Internal Medicine, Department of Internal Medicine; Program Director, Emergency Medicine Residency, Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, VA.
Atrial fibrillation (AF) is the most common, symptomatic sustained tachyarrhythmia that emergency physicians are faced with. Although most physicians consider AF to be a fairly routine and simple problem, its pathophysiology, potential complications, and management are complex and challenging. For older patients, management of AF requires assessing the underlying substrate; choosing the most appropriate pharmacologic agents; considering anticoagulation; and making appropriate disposition and referral decisions.1
Specific management strategies for AF include ventricular rate control coupled with anticoagulation vs. restoration and maintenance of normal sinus rhythm. Rate control is usually achieved pharmacologically with agents that block conduction through the atrioventricular node. Rhythm control may be achieved by electrical or pharmacologic conversion followed by pharmacolgic therapies to maintain sinus rhythm. Part I of this series covered strategies for rate control, emphasizing drug selection and dosages. This issue will offer an in-depth discussion of anticoagulation and restoration of sinus rhythm, with an emphasis on pharmacologic management. In addition, management of AF in special situations (myocardial infarction, Wolff-Parkinson-White [WPW] syndrome, thyrotoxicosis) and indications for hospitalization will be reviewed.
— The Editor
Anticoagulation is warranted if the patient is not certain of the time of onset of AF. Research suggests that thrombi can form within hours of AF onset. Furthermore, even after conversion to sinus rhythm, cardioversion may result in atrial stunning. Therefore, the patient may still develop interatrial clots, necessitating the use of coumadin for 4-12 weeks post-conversion; however, anticoagulation may be discontinued if the restored sinus rhythm persists for 2-4 weeks. In the past, thromboembolism after cardioversion has been attributed to dislodgement of preformed atrial thrombi during the resumption of atrial contraction. However, it appears that thromboembolism after cardioversion more often may be the consequence of the effects of cardioversion on atrial function.2
A stroke risk reduction of approximately 70% has been demonstrated in patients with nonrheumatic AF who are on oral anticoagulation.3 Six major trials have demonstrated that the risk reduction associated with oral anticoagulation for stroke far outweigh the slight increase in annual risk of major hemorrhage: Atrial Fibrillation, Aspirin, Anticoagulation Study (AFASAK) from Copenhagen, Denmark; Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF); Stroke Prevention in Atrial Fibrillation (SPAF) I, II, III;4,5 Stroke Prevention in Non-rheumatic Atrial Fibrillation (SPINAF); Canadian Atrial Fibrillation Anticoagulation (CAFA); and European Atrial Fibrillation Trial (EAFT).6
Risk factors for stroke in AF include hypertension, diabetes, previous transient ischemic attack (TIA), systemic embolism or stroke, advancing age (1.4% for each decade), congestive heart failure (CHF), and global left ventricular dysfunction.7-9 Patients with structural heart disease, such as valvular heart disease or coronary artery disease, represent a high-risk group for thromboembolism.10 Echocardiographic evidence of atrial or ventricular enlargement may pose a risk of embolization,11 as well as represent a group of patients unlikely to remain in sinus rhythm after cardioversion. Pooled data from the first five of those studies listed previously (AFASAK, BAATF, SPAF I, SPINAF, CAFA) showed an annual risk reduction of 85% in AF patients older than 75 years with at least one risk factor, and a 51% risk reduction in AF patients older than 75 years with no risk factors. It is suggested that treating 1000 AF patients for one year will prevent approximately 30 strokes and seven deaths, at the cost of seven major bleeding episodes.
The risk of stroke rises when patients have international normalized ratios (INRs) of less than 2.0, whereas INR values of greater than 3.0 result in an increase in intracerebral hemorrhages.3 No anticoagulation seems warranted in younger AF patients (< 60 years) without any clinical or echocardiographic risk factors. However, most patients with AF are older than 65 years of age and have such risk factors. Patients older than age 75 who had at least one risk factor had an annual stroke risk of 8.1%.12 The decrease in prevalence of embolic events in anticoagulated AF patients has been known for decades.13
Advancing age is considered an independent risk factor for both intracerebral hemorrhage and subdural hemorrhage by some,4,14 perhaps explaining why many elderly AF patients are under-anticoagulated despite strong evidence that warfarin therapy can prevent stroke. An analysis by the EAFT investigators indicated that warfarin was less effective in preventing stroke in patients older than 75 years.15 It is apparent that the prevalence of AF continues to increase with age, as does the contribution of AF to stroke. Theoretically, very old (age > 80) patients may have even more to gain from warfarin therapy than patients younger than 80 years16,17 because 36.2% of strokes in those ages 80-89 years have been shown to be AF related.18 Yet one study found that only 32% of elderly AF patients who were residing in nursing homes and were eligible for warfarin therapy were receiving the medication.19
Clearly, for many physicians the risks of bleeding often prevail over the risk of stroke in elderly AF patients. Others have disputed the correlation between advancing age and hemorrhage, and posited that it is more critical to ensure that patients’ INRs are reliably followed and maintained in the 2-3 range.20 Anticoagulation services have been shown to improve rates of thromboembolism, reduce hemorrhagic complications, and relieve the individual practitioner of the logistic burdens of frequent monitoring and dosage changes.21
Transesophageal echocardiography (TEE) is more accurate than transthoracic echocardiography (TTE) for the detection of left atrial (LA) thrombus.22 TEE has a reported sensitivity of 83-100% for the detection of LA thrombus when compared with operative findings as the reference standard.23,24 It has been utilized in determining the need for and duration of anticoagulation before cardioversion in patients with AF.25 It may demonstrate LA appendage thrombus and appendage dysfunction. As an indication of atrial stasis, swirling patterns in the LA appendage and LA fractional shortening may be observed. Spontaneous echodensities indicative of stasis, or "smoke," are described.26 M-mode can assess left ventricle (LV) size and wall thickness.
In one study of 206 patients with AF, TEE was used for thrombus screening prior to cardioversion. In this group of patients screened with TEE, none of the patients developed a systemic embolus.25 This same study also demonstrated that greater than five weeks of anticoagulation was required before LA thrombi either resolved or became immobile. Two other reports also noted no thromboembolic complications after pharmacologic or electric cardioversion of AF after short-term or no anticoagulation prophylaxis in patients with no atrial thrombus by TEE.27,28 However, others have reported stroke or TIA in 5.6-6.7% of AF patients after cardioversion, despite having no thrombus detectable by TEE.2,29 It is clear that thromboembolic complications may occur after cardioversion despite negative findings on preconversion TEE. Whether this is due to atrial stunning and subsequent hemodynamic stasis with thrombus formation following the procedure has not been ascertained. Since normal atrial contraction after cardioversion may take up to three months, prophylactic anticoagulation has been advocated for a variable period after cardioversion for AF.2
For patients who cannot tolerate warfarin, aspirin has been proposed as an alternative therapy for stroke prevention. Pooled data from three randomized trials utilizing 75-325 mg/day of aspirin indicate that the relative risk reduction for stroke in AF patients treated only with aspirin is approximately 21%, but with a 95% confidence interval of 0-38%.12 A small effect of aspirin in AF patients is indicated.
In 1998, the American College of Chest Physicians and the American Geriatrics Society developed a set of practice guidelines for the medical management of patients with AF.30,31 These guidelines, in agreement with the National Stroke Association’s Stroke Prevention Advisory Board from 1999, recommend that:7
As with any other pharmacologic intervention in the elderly, older patients are more likely to be frail and prone to falling. They also may have comorbidities and levels of functional impairment (higher falls risk) that constitute contraindications to the use of warfarin. In addition, the elderly are more likely to use multiple medications, which can increase the likelihood of adverse drug interactions with warfarin. For patients older than age 75, the preferred target INR may be the lower end of the therapeutic range of 2.0-3.0.
AF of Less Than 48 Hours Duration. If the patient requires emergency cardioversion, consider heparinization prior to cardioversion28 and then coumadization for four weeks. When the patient requires elective cardioversion, consider giving heparin (the likelihood of emboli in AF of < 48 hours duration is low). Physicians may consider using TEE to search for inter-atrial thrombus, followed by anticoagulation with coumadin for 4-6 weeks post-cardioversion. (See Table 1.) Clinicians also may consider giving oral antiarrhythmics.
Table 1. Anticoagulation Guidelines in Atrial Fibrillation
|If AF > 48 hours duration, consider warfarin if:|
|•||Poor LV function|
|•||Rheumatic heart disease or prosthetic heart valve|
|•||Prior thromboembolism, TIA, or stroke|
|•||Hypertension or DM|
|•||Any patient > 65 years with no contraindications (i.e., risk of falls)|
|•||If none of the above risk factors are present and patient is < 65 years, treat with aspirin, 325 mg/day.|
|If AF < 48 hours duration and cardioversion:|
|•||Consider TEE to rule out thrombus or "smoke" prior to cardioversion.|
|If contraindications to warfarin, use aspirin 325 mg/day.|
|Anticoagulate with warfarin for 3-4 weeks post-cardio version (electrical or chemical). If AF of unknown duration, anticoagulate for 3-4 weeks prior to cardioversion.|
AF of Greater Than 48 Hours Duration. Three to four weeks of anticoagulation with coumadin is required before attempting cardioversion (target INR of 2.0-3.074). Use TEE to search for interatrial thrombus or "smoke"33 if present, continue anticoagulation for 3-4 weeks before cardioversion. Also anticoagulate with coumadin for four weeks post-cardioversion.26
It should be noted that these recommendations for anticoagulation are for stroke prophylaxis. Other embolic complications which may ensue after AF include mesenteric ischemia or limb ischemia (which may require surgical intervention).
There are many reasons for restoring sinus rhythm. These include:
Methods for Restoring Sinus Rhythm. In general, the likelihood of maintaining the patient in sinus rhythm should be considered prior to any type of attempted cardioversion. Chronic AF (> 12 months), severe LV dysfunction, mitral valve disease, rheumatic heart disease, sinus node dysfunction, and advanced age have been listed as markers of reduced likelihood of achieving or maintaining sinus rhythm.
The major risk of cardioversion is thromboembolism, with a 5% risk of stroke in the absence of anticoagulation.13 Multiple drug failures, continued presence of acute precipitating factors, and left atrial enlargement greater than 5 cm are markers that diminish the likelihood of successful conversion. These markers are relative and are not absolute contraindications to cardioversion.36
Electrical Cardioversion. Synchronized electrical cardioversion should be performed in unstable AF patients (hypotension with end organ dysfunction or acute pulmonary edema) as is clinically warranted. The possibility that AF has been present chronically must be entertained, since cardioversion entails a risk of systemic embolization. Treating physicians also should recall that, in general, a rapid ventricular rate does not lead to hypotension, although this tachyarrhythmia may lead to impaired ventricular filling from decreased diastolic filling time, as occurs in mitral stenosis. Nonetheless, the hypotensive AF patient should be evaluated for intravascular volume depletion, including dehydration or blood loss. Drug-induced arterial dilatation, cardiac tamponade, cardiogenic shock, pulmonary embolism, and septic shock are other considerations.
In persistent AF, direct current (DC) cardioversion is effective for achieving sinus rhythm in 70-90% of patients.37 It usually requires 50-350 J. In a study of 64 elderly patients, the rates of electrical cardioversion and long-term maintenance of sinus rhythm were similar to those of younger individuals.38 In two other reports, electrical cardioversion was successful in 67-69% of elderly and 71-76% of younger patients, respectively, and multivariate analysis revealed that only duration of AF was associated with failure to establish sinus rhythm.11,39 The rate of successful maintenance of sinus rhythm was significantly lower in elderly patients, however. Therefore, it has been suggested that electrical cardioversion should be avoided in AF patients older than age 70 who have an AF duration that exceeds 36 months and who have adequate exercise tolerance. Some drugs, such as ibutilide and digoxin, may reduce defibrillation thresholds, and their use has been proposed to facilitate defibrillation.33
Systemic embolization is a well-documented complication of electric or pharmacologic cardioversion in patients with AF, and is reported in 0.6-5.6% of patients undergoing cardioversion.29 For this reason, a period of 3-4 weeks of anticoagulation prophylaxis has been recommended before cardioversion of AF of more than 48 hours duration.40,41
Electrical cardioversion of paroxysmal AF has been performed successfully in the emergency department (ED), with an 89% success rate.41 Patients successfully converted to sinus rhythm safely may be discharged home. A nonfasting patient and those who may experience difficulty with sedation can be factors in the ED.
Internal cardioversion utilizes high energy (200-400 J) delivered between a right atrial (RA) cavity and a surface patch, or lower energy (2-20 J) delivered between RA and coronary sinus electrodes. It may be more effective than external cardioversion for restoring sinus rhythm in patients with persistent AF.42 Implantable atrial defibrillators theoretically should be desirable in the hope that early conversion may prevent chronicity and morbidity due to AF, but defibrillation thresholds must be low enough to minimize discomfort. As well, they must have an accurate detection algorithm and have safety demonstrated by prospective studies.33
Pharmacologic cardioversion employs Class IA, IC, and Class III antiarrhythmics. (See Table 2.) These drugs prolong the refractory period of the reentrant wave fronts and impair conduction through the atrial tissue. The result is a reduced number of existing and new wave fronts. These agents also suppress automaticity, which has been implicated in some patients in the development of AF. By prolonging the refractory period or impairing conduction in the atria, they can reduce the number of propagating wavefronts, terminating and preventing the recurrence of AF. Each class will be considered in turn. Their overall success rate may approach 70% in restoring sinus rhythm. Ibutilide and procainamide have been cited as the most frequently used intravenous agents.33
Table 2. Vaughn Williams Classification of Drugs Used in Atrial Fibrillation
|IA||Quinidine, procainamide, disopyramide|
|II||Propranolol, metoprolol, esmolol, atenolol|
|III||Sotalol, amiodarone, ibutilide, dofetilide|
|Mechanisms of Action|
|IA||Decreases conduction velocity (QRS widening), causes pro longation of the action potential (QT prolongation).|
|IC||Markedly decreases conduction velocity.|
|II||Beta-adrenergic blockade, lowers sinus rate.|
|III||Prolongs action potential duration.|
|IV||Blocks calcium (slow) channel|
Class IA Antiarrhythmics. Class IA agents slow conduction through the atria, AV node and His-Purkinje system directly, and decrease conduction in accessory pathways. Both quinidine and procainamide have peripheral vasodilatatory actions. Quinidine rarely is used because IV administration causes hypotension, and oral loading takes longer to convert AF. The oral dose is 200-400 mg 3-4 times per day (e.g., quinidine gluconate 330 mg every three hours up to a total of 990 mg). Side effects associated with quinidine are frequent and include gastrointestinal complaints, proarrhythmia (torsades de pointes), atrioventricular (AV) block, atrial flutter with 1:1 conduction, and sinus node suppression. Use of quinidine has been associated with increased mortality in certain populations.43,44
Historically, procainamide has been the most common drug chosen for AF conversion. Conversion to normal sinus rhythm (NSR) occurs in approximately one-half of patients with AF, and restoration of NSR occurs even more frequently if AF has lasted for less than one day.45,46 The loading dose of procainamide is 10-15 mg/kg IV given as 100 mg q 5 minutes, or up to 500-1000 mg over 10 minutes. The infusion should be stopped if the QRS or QTc intervals exceed 130% of baseline or if systolic BP decreases by greater than 20%. This may be followed by a maintenance regimen of 2-5 mg/min IV infusion or 500-1000 mg q 8 hours orally.
Precautions. Proarrhythmic effects include torsades de pointes. Since a vagolytic effect may increase ventricular rate, many physicians give AV blockers first. Procainamide can induce hypotension and atrial flutter with 1:1 conduction.
Class IC Antiarrhythmics. Class IC agents markedly slow depolarization and conduction and are associated with significant antidysrhythmic properties.
Flecainide is only available in oral form in the United States. It has been used intravenously overseas, and has been effective in preventing recurrences of paroxysmal AF (68% event free after 4-8 weeks).46,47 It may be optimal in facilitating conversion of AF patients with no structural heart disease.33,48,49
After rate control is achieved, 300 mg as a single oral loading dose is suggested. This regimen of flecainide 75-90% effective in converting AF to sinus rhythm within eight hours.49,50 Maintenance dose is 50-100 mg bid or tid PO. Flecainide has been given intravenously as well, 1.5-2 mg/kg up to 150 mg, with a 57% conversion rate after one hour.51
Side effects of paresthesias, visual disturbances, vertigo, fatigue, dyspnea, hypotension can occur but are unusual. Adverse cardiac events, such as conduction disturbances, worsening of CHF, or development of malignant arrhythmias (e.g., ventricular tachycardia) are more common in patients with pre-existing structural heart disease. Exclusion criteria for use have included complete bundle-branch block (BBB), sick sinus syndrome, symptoms of CHF, or New York Heart Association functional class greater than 2, among others.
Propafenone is only available in the oral form in the United States. It is most effective when used for paroxysmal AF. Overall success rate for conversion to sinus rhythm from AF of recent onset is 57-91% within eight hours.52-54 The suggested oral loading dose for propafenone is a 150-600 mg single dose,11 with a maintenance dose of 450-900 mg given in three divided doses. Approximately 40-50% of AF patients who receive propafenone remain free of paroxysmal AF. Adverse effects include GI distress, a regular tachycardia with prolonged QRS and 1:1 AV conduction, ventricular tachycardia, and sinus node dysfunction. Propafenone has been used effectively to convert AF to sinus rhythm when given intravenously 2 mg/kg over 10 minutes and followed by slow infusion at 0.007 mg/kg/min. In one study of 98 patients with AF of less than seven days duration, NSR was restored in 91%.54
Precautions. Data from the Cardiac Arrhythmia Suppression Trial indicate that Class IC antiarrhythmic agents should not be administered to patients with severe underlying cardiac disease or when the QRS duration exceeds 120 msec.55
Class III Antiarrhythmics. Class III agents prolong the refractory period and action potential duration and have antifibrillatory properties.
Sotalol is not available in this country intravenously. It is less effective for converting AF than Class I agents, but more effective in maintaining sinus rhythm after conversion. Patients may have fewer symptoms with recurrent AF because of its beta-blocking activity. Sotalol has been used with digoxin for this reason to lower peak exercise heart rate, as well as for paroxysmal AF. The IV loading dose is 1.0-1.5 mg/kg over 10 minutes; it reduces ventricular rate in 10 minutes. The maintenance oral dose is 80-320 mg PO daily.11 Sotalol has been associated with QT prolongation, polymorphic ventricular tachycardia (1.4%), and torsades de pointes. It should be used with caution in patients with CHF, renal insufficiency, and with pre-existing prolonged QT interval.
Amiodarone is available orally and intravenously. It prolongs refractoriness of atrial muscle and of the AV node. It also has beta-blocking and calcium channel blocking actions. Intravenous amiodarone is more effective for converting AF to NSR and controlling heart rate than digoxin, but central venous access is required for administration. IV administration may cause hypotension, AV block, and ventricular arrhythmias. Amiodarone is extremely effective for rate control even in patients with high catecholamine levels, as occurs with CHF.47 Conversion success rates of 25-81% have been reported,49,56 with an overall success rate of 71% when used for AF of less than 48 hours duration.57
In the acute setting, IV dosing of amiodarone is preferable to oral administration because of an extended loading period and a large side effect profile with PO dosing. IV dosage is 5-7 mg/kg diluted in 100 cc of normal saline (NS) infused over 10-40 minutes. A second loading dose may be given if there is no response to the first dose. Maintenance IV dose is 600-1200 mg over 24 hours titrated to ventricular response. It may be used in conjunction with digoxin for rate control. It may be used as first-line therapy in elderly patients with heart failure11 and in paroxysmal AF to reduce the frequency of episodes and reduce the ventricular rate during episodes of AF. It was not as effective for conversion of AF (34%) as IV flecainide in one report.47
Precautions. Side effects include hypotension and flushing within minutes of administration, bradyarrhythmias, AV block, pulmonary fibrosis, liver, and thyroid toxicity. It may cause thrombophlebitis in smaller veins and is more effective if LA size is less than 4.5 cm.
Ibutilide is specifically approved for conversion of recent onset AF to NSR. It is available in IV form only, and it has a rapid onset and a short half-life of 60 minutes. Its mechanism of action is via delayed inactivation of the slow sodium channel, as well as by potassium channel blockade. Ibutilide converts 35-47% of recent onset AF.33,58 No effectiveness has been determined with arrhythmias of more than 90 days duration. Seventy percent of conversions occur within 60 minutes and one-half of these occur during infusion.58
The suggested loading dose of ibutilide is 0.01 mg/kg IV, up to 1.0 mg over 10 minutes; a second IV dose may be given after 10 minutes. No maintenance dose is given.
Precautions. Ibutilide may cause AV block and QT prolongation, and should not be given concomitantly with other drugs that prolong the QT interval. In 586 patients treated with ibutilide, sustained torsade de pointes occurred in approximately 2%, and nonsustained ventricular tachycardia was seen in another 7.6%.59 Torsade de pointes usually occurs before conversion to NSR, and is more common if there is pre-existing left ventricular dysfunction. Patients should have serum magnesium checked prior to use, and should not have underlying bradycardia, hypotension, or CHF.
Dofetilide is a new compound developed mainly for maintenance of sinus rhythm after its restoration. Analysis of the Diamond Investigators of Arrhythmia and Mortality on Dofetilide (DIAMOND) trial showed dofetilide was effective for maintaining sinus rhythm in patients with depressed left ventricular function without increased mortality when compared with placebo.60 Of patients in the DIAMOND study, 3.3% developed torsade de pointes, most often within the first three days of therapy. (See Table 3.)
Table 3. Patients at Risk for Antiarrhythmic Drug Proarrhythmia (Torsade de Pointes Markers)
|•||QTc ³ 460 msec|
|•||Advanced structural heart disease|
In the Symptomatic Atrial Fibrillation Investigation and Randomized Evaluation of Dofetilide (SAFIRE-D) study, 500 mcg twice daily for three days was used to achieve a conversion rate of 32% compared to 1% with placebo.61 Dofetilide is contraindicated if the patient’s QTc interval is greater than 440 msec or the creatinine clearance is less than 20 mL/min. Currently used exclusively by cardiologists, it was effective in converting 15% of AF patients to sinus rhythm in one report.62 Patients started on this agent must be admitted to a monitored setting for at least three days. The ideal patient for IV cardioversion with this agent is one with new-onset AF, a low likelihood of immediate recurrence, no torsade de pointes risk markers, and no need for maintenance therapy.33
Precautions. Any agents associated with potassium channel blockade can produce torsades de pointes and, therefore, should be administered only after hypokalemia, hypomagnesemia, and bradycardia have been addressed. In general, all Class I and III drugs have been shown to be more effective than placebo in maintaining sinus rhythm, and are effective in maintaining sinus rhythm for 6-12 months in approximately 50% of cases.63
The following guidelines have been proposed for determining optimal antiarrhythmic therapy in the management of AF, depending on the mechanism of the dysrhythmia and any underlying disease:64
If history suggests:
If patient is hypertensive
If ischemic heart disease is present:
"Lone" Atrial Fibrillation. "Lone" AF occurs when the patient presents with AF that develops without underlying structural heart disease or other precipitating illness. Patients presenting to the hospital may be considered for electrical cardioversion or a Class III agent such as ibutilide, since anesthesia is avoided. If the patient is a reliable historian and the time of onset is certain, observation may be an option since approximately 50% of these patients will convert spontaneously;65 if the patient does not convert spontaneously, they still will be within the 48-hour "window" for electrical or pharmacologic conversion. In general, patients should not be discharged on an antiarrhythmic drug after their first episode of AF unless high risk markers for recurrence are present or unless recurrence would pose a greater risk than antiarrhythmic therapy, as in syncope in a patient with hypertrophic cardiomyopathy.63 For recurrent AF, the decision to be made is whether to control the rate or to convert. Patients with structurally normal hearts may be considered for single-dose therapy with a Class IC drug such as flecainide or propafenone orally for cardioversion after rate control.
Atrial Fibrillation in Myocardial Infarction. AF occurs in 6-23% of acute myocardial infarctions (AMIs),66,67 AF often occurs within the first week following the infarction and most commonly affects elderly patients and/or those with large infarcts. This may be related to pericarditis, hypokalemia, hypoxia, increased catecholamine release, or to a hemodynamic burden on the atrium secondary to compromised left ventricular myocardium. There is small increase in short-term and long-term mortality when AF complicates AMI (relative risk of 1.18).68 Patients with inferior AMIs may have a slow ventricular response and may not require any specific intervention.
American Heart Association recommendations for management of AF in AMI include the following:26
In terms of suppression of the arrhythmia after MI, sotolol and amiodarone have been proposed as safe agents.63,72
Atrial Fibrillation in Congestive Heart Failure. If the degree of heart failure is mild to moderate, rate control with diltiazem or digitalis may suffice. In severe CHF, AF may be problematic because the heart rate may be difficult to control safely. Diltiazem is a potentially negative inotrope73 and digitalis is slow-acting. DC cardioversion carries the risk of ventricular stunning, hypotension, or bradyarrhythmias. The arrhythmia may recur after successful cardioversion.69 Amiodarone has little negative inotropy, may control the ventricular response, and is relatively well tolerated.74-76 Class IC agents should not be used.
Atrial Fibrillation in Wolff-Parkinson-White Syndrome (WPW). Ventricular pre-excitation occurs when a sinus impulse bypasses the AV node partially or completely and activates the ventricle through the anomalous pathway. Activation of the ventricles may occur via the AV node, by the accessory pathway, or by both pathways simultaneously. While supraventricular tachycardia with AV nodal reentry (AVNR) and narrow complex tachycardia is more common, AVNR may degenerate into AF. If the AV node is bypassed and the accessory pathway utilized, the accessory pathway may allow 1:1 conduction of atrial impulses to the ventricle. Therefore, the ventricular rate can accelerate to the atrial rate, approaching 300 beats/min with a rapid, wide, and irregular pattern. The rapid ventricular rate can degenerate to ventricular fibrillation (VF) and death.77,78
The treatment of choice in unstable patients or in those with a rapid ventricular response (> 250 beats/min) is electrical cardioversion.
If antiarrhythmic drugs are chosen because the patient is hemodynamically stable, procainamide in 100 mg boluses every five minutes up to 1 g slows conduction through the bypass tract and may chemically convert the rhythm to sinus.
Propafenone, a Class IC agent, and amiodarone, a Class III agent, are drugs used to slow the ventricular rate by selectively blocking the AV node. Digoxin and calcium channel blockers may accelerate conduction through the bypass tract, leading to dramatic increases in rate and hemodynamic compromise. Some advocate adding beta-blockers with AV nodal suppression.
After stabilization or conversion, the patient should be considered for possible radiofrequency ablation or surgical ablation of the anomalous tract.79
Atrial Fibrillation in Thyrotoxicosis. AF is the most common arrhythmia in thyrotoxicosis, occurring in 9-22% patients with this disorder. The incidence of AF increases with age. Patients may have pronounced palpitations due to increased blood volume, shortened circulation time, and decreased systemic vascular resistance. Thyroid hormone acts as a positive chronotrope, with increased cardiac output and stroke volume. The rapid ventricular rate and circulatory overload may precipitate CHF. There is an increased clearance of clotting factors, and a smaller dose of coumadin may be required to prevent embolization.
Beta-blockers represent the initial drugs of choice to control ventricular rate and symptoms. If CHF is present, esmolol may be more desirable than propranolol because of its short duration of effect if the drug must be discontinued. Stable patients with AF may be treated with oral beta-blockers. Standard treatment for CHF includes diuretics and preload and afterload reduction. Digitalis may be ineffective.
AF converts spontaneously to NSR in 62% of patients treated for thyrotoxicosis, though less frequently in patients with heart disease/dilated cardiomyopathy or long-standing AF. Elective cardioversion can be performed after the patient has been euthyroid for 8-10 weeks and anticoagulated. There is a high recurrence rate with DC cardioversion. Class 1A antiarrhythmics may be effective in maintaining NSR.
AF commonly follows coronary artery bypass graft surgery, although new-onset AF in this setting usually is transient. When AF reverts or is converted to sinus rhythm in this setting, it is unlikely to recur. No benefit and, perhaps, increased risk have been reported for antiarrhythmic agents. Standard treatment should consist of observation or control of ventricular response with an appropriate agent until AF relapses to sinus rhythm. Withdrawal of beta-blockers prior to surgery has been shown to increase the risk of developing AF,80 and it is common to consider prophylactic perioperative use of beta-blockers. Beta-blockers also have been reported to be the drugs most effective in treating AF after coronary artery bypass surgery.81 Heart rhythm should be monitored, especially if a Class I agent is administered.82
Non-Pharmacologic Modalities for Management of Atrial Fibrillation. Prophylactic atrial pacing is utilized in patients with paroxysmal AF or electrophysiologic evidence of interatrial conduction delay. Its chief benefit is found in patients whose AF is initiated by increased vagal tone, multiple atrial ectopic beats, or sick sinus syndrome. Patients without sinus disease but with severe sinus bradycardia and high vagal tone prior to onset of AF also are candidates.
Implantable atrial defibrillators utilize right atrial and coronary sinus leads. Dual chamber AV systems have been considered superior to single-chamber ventricular demand pacemakers.83 Success rates for defibrillating AF have been cited at 96%.84 In paroxysmal AF, typically 0.5-5.0 J are needed. For chronic AF, more than 5.0 J may be necessary.
The key concept for implantable defibrillators is that by preventing the atria from remaining in AF, remodeling in the atria is prevented. Single chamber and dual chamber defibrillators are being investigated.26 Newer pacing methods, such as biatrial pacing, also are being studied, as well as appropriate detection of AF for delivering shocks. Patients may feel chest pain, and shocks may be frequent. Microscopic hemorrhage or thrombosis at the site of the defibrillation has not yet been determined to be clinically significant.
There have been two surgical techniques described for definitive treatment of AF, the maze and the corridor procedures.
Maze Procedure. This is a surgical procedure that has been used to restore sinus rhythm and prevent recurrent episodes of AF. Since there is a critical atrial tissue mass necessary to sustain AF, when multiple incisions are performed in both atria and bilateral appendectomies, a series of deadends for wavelets is created. Sinus impulses are made to channel through a path, or "maze," to reach the AV node. AF cannot be maintained, and the atria revert to normal sinus rhythm. First described in 1991, it has been modified several times.85
Since this requires open heart surgery, it is reserved for drug refractory AF or for failed AV node ablation therapy. The operation has a 3% surgical mortality, and patients may require a pacemaker. Its success has been reported to be in the 84-98% range, with 71-91% of patients not requiring pharmacologic treatment following this operation.86
Corridor Procedure. This procedure creates a sleeve of right atrial tissue or "corridor" connecting the sinus node to the AV node.87 It allows impulse conduction from the sinoatrial (SA) node directly to the AV node and protects the AV node from a rapid fibrillatory rate.88 Unfortunately, while it restores sinus node control of the ventricles, the loss of atrial transport and of AV synchrony entails a continued risk of thrombus. Because of this and more effective pharmacologic and surgical therapies, this procedure has fallen out of favor.63
Catheter Ablation. First described in 1994, radio frequency energy can be used to ablate or to modify the AV node.89 Complete atrioventricular block usually can be produced via radio frequency current delivered to the right side of the heart; if not, a left ventricular approach almost always will be successful. Patients will require a permanent pacemaker after AV node ablation.
AV node modification is performed by delivering radio frequency energy in the right atrial posterior septum or mid-septum. The goal of atrioventricular node modification is to control the ventricular rate without creating high-grade AV block. Twenty-five percent of patients end up requiring a permanent pacemaker after AV node modification.90,91 The atria continue to fibrillate, and loss of AV synchrony may pose a risk of intra-atrial thrombus. There is still a need, therefore, for anticoagulation.26
A catheter version of the maze procedure has been performed by creating several linear lesions in the left or right atrium. The goal is similar to the maze procedure, that is, to compartmentalize the atrium by creating transmural linear lesions in the atrial myocardium that will block the wave fronts. When enough atrial tissue is compartmentalized, AF cannot be maintained. A problem with the procedure is that RA ablation alone does not eliminate AF; interatrial tachycardias may develop after ablation of tissue. Radiofrequency causes heat in atria, potentially leading to atrial charring and thrombus formation.
Medically justified admissions for AF have been evaluated retrospectively,92 and it was determined that 98% of patients with AF whose admissions were medically justified could have been identified in the ED. These patients had electrolyte abnormalities, CHF, chest pain suggestive of myocardial ischemia, hypotension, or noncardiac diseases that necessitated admission. (See Table 4.) A case can be made, however, that all new-onset AF should be converted to normal sinus rhythm as soon as possible. Patients who are cardioverted in the ED to sinus rhythm need not be hospitalized any longer than it takes to recover from their procedural sedation. However, if Class IA antidysrhythmic agents are used, the patient should be observed for 72 hours for torsade de pointes associated with QT prolongation.93
|Table 4. Indications for Hospitalizing Patients with Atrial Fibrillation|
|•||Suspicion of ischemic heart disease/acute coronary syndrome|
|•||Management of congestive heart failure|
|•||Any noncardiac disease that mandates admission:|
|•||Any patient started on a Class IA antidysrhythmic agent|
|•||Hypotension, hemodynamic instability, heart rate > 140 beats/min|
|•||High risk of thrombus formation: prosthetic mitral valve|
|•||Suitability for chemical or electrical cardioversion|
Other indications for hospitalizing patients who are in AF include those with decompensated CHF, myocardial contusion, infective endocarditis, hypotension, syncope, or other medical reasons for hospitalization independent of the AF. Recently, recommendations for hospitalization for AF have been reviewed from an HMO perspective.94 Hospitalization was deemed necessary if the patient was hemodynamically unstable or symptomatic from ischemia or from CHF. Patients who represent an unusual anticoagulation or embolic risk are also recommended for immediate hospitalization. Examples would include patients with recent history of gastrointestinal bleeding and patients with prosthetic mitral valves and new-onset AF, respectively.95
On the other hand, outpatient management is preferred if patients are deemed to have permanent AF with no consideration for conversion, whose therapy, therefore, will consist of rate control and anticoagulation. Patients with recurrent paroxysmal AF whose episodes have reverted spontaneously to sinus rhythm, or if AF is chronic (> 1 week), who are already on anticoagulation, usually can be managed as outpatients.
A "gray zone" may include patients who are asymptomatic, but whose AF is of unknown duration or of recent onset. Patients with heart rates of greater than 140 beats/min for example, would not, in general, be discharged from the hospital.94
AF management is not straightforward; it is a complex disorder. Treatment strategies vary by patient, and optimal therapy for each patient in AF has not been defined. Selection of any agent to control rate vs. rhythm conversion and maintenance will depend upon its side effect profile, the clinical urgency, and the patient’s hemodynamic status. For patients with infrequent and non-life-threatening episodes, intermittent cardioversion will have less adverse impact on their daily lives and less adverse risk than would daily antiarrhythmic therapy. Antiarrhythmic drugs may prevent recurrent AF, but most are only modestly effective, and none are uniformly safe. Only selected patients require restoration and maintenance of normal sinus rhythm. Elderly patients who remain in AF are at significant risk for embolic stroke and require anticoagulation unless there are medical or social contraindications for warfarin therapy. The decision to admit will depend upon the presence of cardiovascular instability, the presence of comorbidities, and the patient’s suitability for chemical or electrical cardioversion.
1. Vlay SC. Managing atrial fibrillation in older patients. Cardiol Rev 2000;17:13-24.
2. Fatkin D, Kuchar DL, Thorburn CW, et al. Transesophageal echocardiography before and during direct current cardioversion of atrial fibrillation: Evidence for "atrial stunning" as a mechanism of thromboembolic complications. J Am Coll Cardiol 1994;23:307-316.
4. 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.
5. SPAF-III. Stroke Prevention in Atrial Fibrillation Investigators. Adjusted dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomized clinical trial. Lancet 1996;348:633-638.
6. Turazza FM, Franzosi MG. Is anticoagulation therapy underused in elderly patients with atrial fibrillation? Drugs & Aging 1997;10: 174-184.
7. Gorelick PB, Sacco RL, Smith DB, et al. Prevention of a first stroke. A review of guidelines and a multidisciplinary consensus statement from the National Stroke Association. JAMA 1999;281: 1112-1120.
8. McCormick D, Gurwitz JH, Goldberg RJ, et al. Long-term anticoagulation for atrial fibrillation in elderly patients: Efficacy, risk, and current patterns of use. J Thrombo Thrombol 1997;7: 157-163.
9. Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Arch Intern Med 1994;154:1449-1457.
10. Asinger RW, Hart PG, Helgason CM, et al. Predictors of thromboembolism in atrial fibrillation: I. Clinical features of patients at risk. Ann Intern Med 1992;116:1-5.
11. VanGelder IC, Brugemann J, Crijus HJ. Pharmacologic management of arrhythmias in the elderly. Drugs & Aging 1997;11: 96-110.
3. Kottkamp H, Hindricks G, Breithardt G. Role of anticoagulant therapy in atrial fibrillation. J Cardiovasc Electrophysiol 1998;9 (8 Suppl):S86-S96.
12. Atrial Fibrillation Investigators. The efficacy of aspirin in patients with atrial fibrillation: Analysis of pooled data from three randomized trials. Arch Intern Med 1997;157:1237-1240.
13. Bjerkelund CJ, Orning OM. The efficacy of anticoagulant therapy in preventing embolism related to DC electrical cardioversion of atrial fibrillation. Am J Cardiol 1969;23:208-216.
14. Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994;120:897-902.
15. Van Latum JC, Koudstaal PJ, Venables GS, et al. Predictors of major vascular events in patients with a transient ischemic attack or minor ischemic stroke and with nonrheumatic atrial fibrillation: European Atrial Fibrillation Trial (EAFT) study group. Stroke 1995;26:801-806.
16. Lancaster T. Anticoagulation in patients with atrial fibrillation: Atrial fibrillation associated with aging. BMJ 1993;307:1494.
17. Ackermann RJ. Anticoagulant therapy in patients aged 80 years or more with atrial fibrillation. More caution is needed. Arch Fam Med 1997;6:105-110.
18. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: A major contributor to stroke in the elderly. The Framingham Study. Arch Intern Med 1987;147:1561-1564.
19. Gurwitz JH, Monette J, Rochon PA, et al. Atrial fibrillation and stroke prevention with warfarin in the long-term care setting. Arch Intern Med 1997;157:978-984.
20. Fihn SD, McDonell M, Martin D, et al. Risk factors for complications of chronic anticoagulation. Ann Intern Med 1993;118:511-520.
21. Ansell JE, Bottaro ML, Thomas OV, et al. Consensus guidelines for coordinated outpatient oral anticoagulation therapy management. Ann Pharmacother 1997;31:604-615.
22. Pearson AC, Labovitz AJ, Tatineni S, et al. Superiority of transesophageal echocardiography in detecting cardiac source of embolism in patients with cerebral ischemia of uncertain etiology. J Am Coll Cardiol 1991;17:66-72.
23. Acar J, Cormier B, Grimberg D, et al. Diagnosis of left atrial thrombi in mitral stenosis—usefulness of ultrasound techniques compared with other methods. Eur Heart J 1991;12(Suppl B): 70-76.
24. Lin SL, Hsu TL, Liou JY, et al. Usefulness of transesophageal echocardiography for the detection of left atrial thrombi in patients with rheumatic heart disease. Echocardiography 1992;9:161-168.
25. Stoddard MF, Dawkins PR, Prince CR, et al. Transesophageal echocardiographic guidance of cardioversion in patients with atrial fibrillation. Am Heart J 1995;129:1204-1215.
26. Prystowsky EN. Management of atrial fibrillation: Therapeutic options and clinical decisions. Am J Cardiol 2000;85(10A): 3D-11D.
27. Orsinelli DA, Pearson AC. Usefulness of transesophageal echocardiography to screen for left atrial thrombus before elective cardioversion for atrial fibrillation. Am J Cardiol 1993;72:1337-1339.
28. Manning WJ, Silverman DI, Gordon SPF, et al. Cardioversion from atrial fibrillation without prolonged anticoagulation with use of transesophageal echocardiography to exclude the presence of atrial thrombi. N Engl J Med 1993;328:750-755.
29. Arnold AZ, Mick MJ, Mazurek RP, et al. Role of prophylactic anticoagulation for direct current cardioversion in patients with atrial fibrillation or atrial flutter. J Am Coll Cardiol 1992;19: 851-855.
30. Laupacis A, Alleers G, Dalen J, et al. Antithrombotic therapy in atrial fibrillation. Chest 1998;114:579S-589S.
31. American Geriatrics Society Clinical Practice Committee. The use of oral anticoagulants (warfarin) in older people. J Am Geriatr Soc 1996;44:1112-1113.
32. Kopecky SL, Gersch BJ, McGoon MD, et al. The natural history of lone atrial fibrillation. N Engl J Med 1987;317: 669-674.
33. Costeas C, Kassotis J, Blitzer M, et al. Rhythm management in atrial fibrillation—with a primary emphasis on pharmacological therapy: Part 2. PACE 1998;21:742-752.
34. Petersen P, Kastrup J, Videback R, et al. Cerebral blood flow before and after cardioversion of atrial fibrillation. J Cereb Blood Flow Metab 1989;9:422-425.
35. Waktare JEP, Camm AJ. Acute treatment of atrial fibrillation: Why and when to maintain sinus rhythm. Am J Cardiol 1998; 81(5A):3C-15C.
36. Blitzer M, Costeas C, Kassotis J, et al. Rhythm management in atrial fibrillation—with a primary emphasis on pharmacologic therapy. PACE 1998;21:590-602.
37. Lown B, Amarasingham R, Norman J. New method for terminating cardiac arrhythmias: Use of synchronized capacitor discharge. JAMA 1962;182:548-555.
38. Bjork V, Karesoja M, Hirvonen P. Elective cardioversion in the elderly. In: Olsson SB, Allessie MA, Campbell RWF, Eds. Atrial Fibrillation: Mechanisms and Therapeutic Strategies. Armonk, NY: Futura; 1994:343.
39. Carlsson J, Tebbe V, Rox J, et al for the ALKK-Study group. Cardioversion of atrial fibrillation in the elderly. Am J Cardiol 1996; 78:1380-1384.
40. Weigner MJ, Caufield TA, Danias PG, et al. Risk for clinical thromboembolism associated with conversion to sinus rhythm in patients with atrial fibrillation lasting less than 48-hours. Ann Intern Med 1997;126:615-620.
41. Michael JA, Stiell IG, Agarwal S, et al. Conversion of paroxysmal atrial fibrillation in the emergency department. Ann Emerg Med 1999;33:379-387.
42. Levy S, LaCombe P, Cointe R, et al. High energy transcatheter cardioversion of chronic atrial fibrillation. J Am Coll Cardiol 1988;12:514-518.
43. Coplen SE, Autman EM, Berlin JA, et al. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion: A meta-analysis of randomized control trials. Circulation 1990;82:1106-1116.
44. Flaker GC, Blackshear JL, McBride R, et al. Antiarrhythmic drug therapy and cardiac mortality on atrial fibrillation: The Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol 1992;20:527-532.
45. Halperin JL, Hart RG. Atrial fibrillation and stroke: New ideas, persisting dilemmas. Stroke 1988;19:937-941.
46. Madrid AH, Moro C, Marin-Huerta E, et al. Comparison of flecainide and procainamide in cardioversion of atrial fibrillation. Europ Heart J 1993;14:1127-1131.
47. Donovan KD, Dobb GJ, Coombs LJ, et al. Reversion of recent-onset atrial fibrillation to sinus rhythm by intravenous flecainide. Am J Cardiol 1991;67:137-141.
48. Suttorp MJ, Kingma JH, Jessurun EP, et al. The value of Class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. J Am Coll Cardiol 1990;16: 1722-1727.
49. Capucci A, Lenzi T, Boriani G. et al. Effectiveness of loading oral flecainide for converting recent onset atrial fibrillation to sinus rhythm in patients without organic heart disease or with only systemic hypertension. Am J Cardiol 1992;70:69-72.
50. Boriani G, Capucci A, Botte GC, et al. Different pharmacologic treatment for converting recent-onset atrial fibrillation: Evaluation of 377 patients. J Am Coll Cardiol 1996;27:80A.
51. Donovan KD, Power BM, Hockings BEF, et al. Intravenous flecainide versus amiodarone for recent-onset atrial fibrillation. Am J Cardiol 1995;75:693-697.
52. Bianconi L, Boccademo R, Papalardo A, et al. Effectiveness of intravenous propafenone for conversion of atrial fibrillation and flutter of recent onset. Am J Cardiol 1989;64:335-338.
53. Botto GL, Bonini W, Broffoni T, et al. Conversion of recent onset atrial fibrillation with single loading oral dose of propafenone: Is in-hospital admission absolutely necessary? PACE 1996;19: 1939-1943.
54. Bellandi F, Dabizzi RP, DiNatale M, et al. Intravenous propafenone: Efficacy and safety in the conversion to sinus rhythm of recent onset atrial fibrillation. Cardiovasc Drugs Ther 1996;10:153-157.
55. The 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.
56. Noc M, Stajer D, Horvat M. Intravenous amiodarone versus verapamil for acute cardioversion of paroxysmal atrial fibrillation to sinus rhythm. Am J Cardiol 1990;65:679-680.
57. Strasberg B. Intravenous amiodarone for conversion of atrial fibrillation to sinus rhythm. Am J Cardiol 1991;67:325.
58. Stambler BS, Wood MA, Ellenbogen KA. The Ibutilide Repeat Dose Study Investigators. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Circulation 1996;94:1613-1621.
59. Kowey PR, Vander Lugt JT, Luderer JR. Safety and risk/benefit analysis of ibutilide for acute conversion of atrial fibrillation and flutter. Am J Cardiol 1996;78:46-52.
60. Hohnloser SH, Li YG, Bender B, et al. Pharmacological management of atrial fibrillation: an update. J Cardiovasc Pharmacol Therapeut 2000;5:11-16.
61. McClellan KJ, Markham A. Dofetilide: A review of its use in atrial fibrillation and atrial flutter. Drugs 1999;58:1043-1059.
62. Falk RH, Pollak A, Singh SN, et al. Intravenous dofetilide, a Class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. J Am Coll Cardiol 1997;29:385-390.
63. Kassotis J, Costeas C, Blitzer M, et al. Rhythm management in atrial fibrillation—with a primary emphasis on pharmacologic therapy: Part 3. PACE 1998;21:1133-1142.
64. Reiffel JA. Selecting an antiarrhythmic agent for atrial fibrillation should be a patient-specific, data-driven decision. Am J Cardiol 1998;82(8A):72N-81N.
65. Falk RH, Knowlton AA, Bernard SA, et al. Digoxin for converting recent onset atrial fibrillation to sinus rhythm. A randomized double-blinded study. Ann Intern Med 1987;106:503-506.
66. Madas JE, Patel DC, Singh B. Atrial fibrillation in acute myocardial infarction: A prospective study based on data from a consecutive series of patients admitted to the coronary care unit. Clin Cardiol 1996;19:180-186.
67. Hildebrandt P, Jenson G, Kober L, et al. Myocardial infarction 1979-1988 in Denmark: Secular trends in age-related incidence, in-hospital mortality and complications. European Heart J 1998;19: 287-292.
68. Goldberg RJ, Seeley D, Becker RC. Impact of atrial fibrillation on 67the in-hospital and long-term survival of patients with acute myocardial infarction: A community-wide perspective. Am Heart J 1990;119:996-1001.
69. Cowan JC, Gardiner P, Reid DS, et al. A comparison of amiodarone and digoxin in the treatment of atrial fibrillation complicating suspected acute myocardial infarction. J Cardiovasc Pharmacol 1986;8:252-256.
70. Garcia-Rubira JC, Romero D, Gardia JT, et al. Transient myocardial injury after elective electrical cardioversion. Int J Cardiol 1994;46:283-285.
71. Xiong C, Sonnhag, Nylander E, et al. Atrial and ventricular function after cardioversion of atrial fibrillation. Brit Heart J 1995;74: 254-260.
72. Julian DG, Prescott RJ, Jackson FS, et al. Controlled trial of sotalol for one year after myocardial infarction. Lancet 1982;1:1142-1147.
73. Goldenberg IF, Lewis WR, Dias VC, et al. Intravenous diltiazem in the treatment of patients with atrial fibrillation of flutter and moderate to severe congestive heart failure. Am J Cardiol 1994;74: 884-889.
74. Hou ZY, Chang MS, Chen CY, et al. Acute treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of intravenous amiodarone: A randomized digoxin controlled study. Heart J 1995;16:521-528.
75. Kumar A. Intravenous amiodarone therapy of atrial fibrillation and flutter in critically ill patients with a severely depressed left ventricular function. South Med J 1996;89:779-785.
76. Lie KI, Van Gelder IC. Therapy of recent onset atrial fibrillation and flutter in hemodynamically compromised patients: Chemical cardioversion or control of the ventricular rate? Eur Heart J 1995; 16:433-434.
77. Dreifus LS, Haiat R, Watanabe Y, et al. Ventricular fibrillation: A possible mechanism of death in patients with Wolff White Parkinson Syndrome. Circulation 1971;43:520.
78. Klein GJ, Bashore TM, Sellers TD, et al. Ventricular fibrillation in the Wolff-Parkinson-White syndrome. N Engl J Med 1979;301: 1080-1085.
79. Jackman WM, et al. Catheter ablation of accessory atrioventricular pathways (WPW syndrome) by radio frequency current. N Engl J Med 1991;324:1605-1611.
80. Salazar C, Frishman W, Friedman S, et al. Beta-blockade therapy for supraventricular tachyarrhythmias after coronary surgery: A propranolol withdrawal syndrome? Angiology 1979;30:816-819.
81. Olshansky B. Management of atrial fibrillation after coronary artery bypass graft. Am J Cardiol 1996;78(Suppl 8A):27-34.
82. Humphries JO. Unexpected instant death following successful coronary artery bypass graft surgery: Atrial fibrillation, quinidine, procainamide, et cetera, and instant death. Clin Cardiol 1998;21: 711-718.
83. Feuer JM, Shandling AH, Messenger JC. Influence of cardiac pacing mode on the long-term development of atrial fibrillation. Am J Cardiol 1989;64:1376-1379.
84. Wellens HJJ, Lau CP, Luderitz B, et al. Atrioverter: An implantable device for the treatment of atrial fibrillation. Circulation 1998;98:1651-1656.
85. Cox JL, Boineau J, Schuessler R, et al. Successful surgical treatment of atrial fibrillation: Review and clinical update. JAMA 1991;266:1976-1980.
86. Cox JL, Canavan TE, Schuessler RB, et al. The surgical treatment of atrial fibrillation II. Intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial flutter and atrial fibrillation. J Thorac Cardiovasc Surg 1991;101:406-426.
87. Defauw JJ, Guiraudon GM, van Hemel NM, et al. Surgical therapy of paroxysmal atrial fibrillation with the corridor operation. Ann Thorac Surg 1992;53:564-571.
88. Guiraudon GM. Surgical treatment of atrial fibrillation. Herz 1993;18:51-59.
89. Haissaguerre M, Gencel L, Fischer B, et al. Successful catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol 1994;5: 1045-1052.
90. Morady F. Radio-frequency ablation as treatment for cardiac arrhythmias. N Engl J Med 1999;340:534-544.
91. Williamson BD, Man KC, Daoud E, et al. Radiofrequency catheter modification of atrioventricular conduction to control the ventricular rate during atrial fibrillation. N Engl J Med 1994;331:910-917.
92. Mulcahy B, Coates WC, Heneman PL, et al. New-onset atrial fibrillation: When is admission medically justified? Acad Emerg Med 1996;3:114-119.
93. Phibbs BP. Atrial fibrillation and hospital admission. (letter to the editor). Acad Emerg Med 1996;3:820.
94. Pratt CM. Impact of managed care on the treatment of atrial fibrillation. Am J Cardiol 1998;81(5A):30C-34C.
95. Pritchett EL. Management of atrial fibrillation. N Engl J Med 1992;326:1264-1271.