AUTHOR INFORMATION

Section 1 of 12

Authored by Jeffrey Lazar, MD, MPH, Chief Resident, Section of Emergency Medicine, Yale New Haven Hospital

Coauthored by Alan D Clark, MD, Director, St Johns.com/Healthy People Magazine, Former Department Chairman, St. John's Emergency Trauma Center, St John's Regional Health Center, Springfield, Missouri

Edited by William Lober, MD, Associate Professor, Department of Medical Education, Division of Biomedical and Health Informatics, University of Washington School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Gary Setnik, MD, Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine, Harvard Medical School; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School

Author's Email:	Jeffrey Lazar, MD, MPH
Editor's Email:	William Lober, MD

eMedicine Journal, March 5 2007, VOLUME 8, Number 3

INTRODUCTION

Section 2 of 12

Background: Atrial fibrillation (AF), the most commonly encountered arrhythmia in clinical practice, is defined by the absence of coordinated atrial systole. AF results from multiple reentrant electrical wavelets that move randomly around the atria.

P waves are replaced by irregular, chaotic fibrillatory waves, often with a concomitant irregular ventricular tachycardia. The rate at which the atrial electrical impulses are transmitted to the ventricle is determined by a number of factors including relative refractory period within the atrioventricular (AV) node, hydration status, and presence or absence of pharmacologic agents used to control the rate. When ventricular rate increases to tachycardic levels, a situation of atrial fibrillation with rapid ventricular response (AF with RVR) ensues. This in turn can lead to decompensation in the form of either myocardial ischemia or creation of congestive heart failure (CHF).

AF may increase mortality up to 2-fold, primarily due to embolic stroke. This risk exists as the lack of coordinated atrial contraction leads to unusual fluid flow states through the atrium that are permissive for formation of thrombus that is then at risk to embolize. This risk is theoretically particularly present upon return to normal sinus rhythm when coordinated atrial contraction can entrain a thrombus into flow. The risk of embolism associated with cardioversion is stated to be as high as 2%. Thus, part of the challenge for emergency physicians is the question of managing rate versus rhythm in the ED and the issue of when cardioversion through any mechanism should be attempted.

The incidence of atrial fibrillation increases significantly with advancing age.

Managing AF in the ED, for the most part, involves a straightforward approach. Generally accepted guidelines and protocols for managing AF are of great value in the decision-making process (see Images 1-6).

The cardiologist's approach to AF is well covered in Dr Rosenthal's article, Atrial Fibrillation. Emergency physicians are more concerned with the acute life threat and appropriate ED treatment of patients with AF; however, readers who are interested in topics such as catheter ablation and clinical electrophysiology of AF are referred to Dr Rosenthal's article.

Pathophysiology: Multiple reentrant waveforms within the atria bombard the AV node, which becomes relatively refractive to conduction due to the frequency of upstream electrical activity.

Three mechanisms that have been shown to play a role in the initiation and maintenance of AF include the following:

• Enhanced automaticity in the left atrium extending to proximal 5-6 mc portions of the pulmonary veins

• Electrical remodeling of the atria with resultant shortening of the atrial refractory period increases the duration and stability of AF, well-described by the phrase "atrial fibrillation begets atrial fibrillation"

• In chronic AF, areas of functional conduction block further divide and maintain a persistently chaotic electrical state.

Inflammation is believed to play an as-of-yet undefined role in the pathogenesis of AF.

AF occurs in 3 distinct clinical circumstances:

• As a primary arrhythmia in the absence of identifiable structural heart disease

• As a secondary arrhythmia in the absence of structural heart disease but in the presence of a systemic abnormality that predisposes the individual to the arrhythmia

• As a secondary arrhythmia associated with cardiac disease that affects the atria

While differing classification schemes exist, AF is commonly broken down into acute versus chronic AF, with chronic AF then being subcategorized into one of the following:

• Paroxysmal - Duration less than 7 days, with spontaneous termination

• Persistent - Duration greater than 7 days and would last indefinitely unless cardioverted

• Permanent - Duration greater than 7 days, with restoration to sinus rhythm not possible

• Lone AF has been used to describe AF in individuals without structural or cardiac or pulmonary disease, with low risk for thromboembolism. It has traditionally been applied to patients younger than 60 years.

The 3 primary ways AF affects hemodynamic function include the following:

• Loss of atrial kick (synchronized atrial mechanical activity)

• Irregularity of ventricular response

• Inappropriately rapid heart rate

Frequency:

• In the US: Approximately 2.5 million Americans, or close to 1% of the total population, currently have atrial fibrillation.

  Atrial fibrillation can be considered a disease of aging, and with the projected increase in the elderly population in America, the prevalence is expected to more than double by the year 2050.

Mortality/Morbidity:

• The rate of ischemic stroke among patients with nonrheumatic AF averages 5% a year, which is somewhere between 2-7 times the rate of stroke in patients without AF. The risk of stroke is not due solely to AF; it increases substantially in the presence of other cardiovascular disease.
  

• The attributable risk of stroke from AF is estimated to be 1.5% for those aged 50-59 years, and it approaches 30% for those aged 80-89 years.
  

• The total mortality rate is approximately doubled in patients with AF compared with patients in normal sinus rhythm and is linked with the severity of underlying heart disease.

• AF complicates acute myocardial infarction (AMI) in 5-10% of cases. The causes of AF in AMI are thought to be due to any number of factors, such as atrial infarction, atrial ischemic injury, atrial distension, or, perhaps, pericarditis. According to Rathore et al, patients who developed new-onset AF during the course of myocardial infarction (MI) were at higher risk than patients who presented with chronic AF. Patients with AMI and AF tend to be older, be less healthy, and have poorer outcomes during hospitalization and after discharge than individuals without AF. AF is independently associated with an increased mortality rate.

Race:

• Atrial fibrillation appears to be more common in whites than in blacks.

• Blacks have less than half the age-adjusted risk of developing AF than is seen in whites.

Sex: Incidence is significantly higher in men than in women in all age groups.

Age: The prevalence of atrial fibrillation increases almost exponentially with age.

AF is uncommon in childhood except after cardiac surgery.

• The prevalence of AF among persons younger than 55 years is 0.1%.

• The prevalence of AF among persons 60 years or older is 3.8%.

• The prevalence of AF among persons 80 years or older is 10%.

CLINICAL

Section 3 of 12

History: In addition to eliciting symptoms listed below, history taking of any patient presenting with suspected AF should include questions relevant to temporality, precipitating factors (including hydration status, recent infections, alcohol use), history of pharmacologic or electric interventions and responses, and presence of heart disease. Occasionally, a patient may have clear and strong belief about the onset of symptoms that may be helpful in determining a course of action.

• Palpitations

• Fatigue or poor exercise tolerance

• Dyspnea

• Chest pain (true angina)

• Presyncope or syncope

• Generalized weakness

Physical:

• Pertinent physical findings are limited to the cardiovascular system or, if embolization has occurred, the brain and/or peripheral vasculature. These include the following:

• Irregular pulse, with or without tachycardia, is typically described as the irregularly irregular rhythm.

• Hypotension and poor perfusion caused by decrease in atrial filling pressures and decrease in stroke volume are common findings. This may be either rate related or because of the lack of normal atrial kick.

• Congestive heart failure, if present, may be indicated by rales, jugular venous distension, peripheral edema, and a gallop, which may be difficult to auscultate due to rapid rate.

• Signs of embolization, including transient ischemic attack (TIA), stroke, and peripheral arterial embolization (eg, cold, pulseless extremities), may be identified.

Causes: Risk factors for atrial fibrillation include age, male sex, long-standing hypertension, valvular heart disease, left ventricular hypertrophy, coronary artery disease (with or without depressed left ventricular function), diabetes mellitus, smoking, and any form of carditis.

Causes of atrial fibrillation can be divided into cardiovascular versus noncardiovascular causes.

• Important cardiovascular causes include the following:

• Long-standing hypertension

• Ischemic heart disease

• CHF

• Any form of carditis

• Cardiomyopathy

• Infiltrative heart disease of any type

• Sick sinus syndrome

• Noncardiovascular causes of atrial fibrillation include the following:

• Hyperthyroidism

• Low levels of potassium, magnesium, or calcium

• Pheochromocytoma

• Sympathomimetic drugs, alcohol, electrocution

• Noncardiovascular respiratory causes include the following:

• Pulmonary embolism

• Pneumonia

• Lung cancer

• Idiopathic: Lone AF is idiopathic and defined as the absence of any known etiologic factors plus normal ventricular function by echocardiography. Most patients with lone AF are younger than 65 years, although age is not used to define lone AF.

• Hypothermia

DIFFERENTIALS

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Multifocal Atrial Tachycardia
Wolff-Parkinson-White Syndrome

Other Problems to be Considered:

Narrow complex tachyarrhythmias
Wide complex tachyarrhythmias

WORKUP

Section 5 of 12

Lab Studies:

• CBC (looking for anemia, infection)

• Electrolytes and BUN/creatinine levels (looking for electrolyte disturbances or renal failure)

• Cardiac enzymes - CK and/or troponin level (to investigate myocardial infarction as a primary or secondary event)

• Thyroid function studies (looking for thyrotoxicosis, a rare, but not-to-be-missed, precipitant) may be sent from the ED, but results are not usually available to assist in decision-making.

• Digoxin level when appropriate (to look for subtherapeutic levels and/or toxicity). It is generally considered safe to administer digoxin to a patient with AF on digoxin for rate control without waiting for a level to return from the laboratory when the patient presents with AF with RVR.

• Toxicology testing

Imaging Studies:

• Chest radiography findings are usually normal. Look for radiographic evidence of CHF as well as signs of lung or vascular pathology (PE, pneumonia).

• Echocardiography may be used to evaluate for valvular heart disease, left and right atrial size, LV size and function, LVH, and pericardial disease.

• Transthoracic echocardiography has low sensitivity in detecting LA thrombus, and transesophageal echocardiography (TEE) is the required modality in this case.

Other Tests:

• ECG: Absent P waves, replaced by irregular, chaotic fibrillatory F waves, in the setting of irregular QRS complexes (see Image 1). Look for aberrantly conducted beats after long-short R-R cycles (ie, Ashman phenomenon). Other features to be looked for on the ECG include LVH, preexcitation, bundle-branch blocks, acute or prior MI, and intervals (R-R, QRS, QT).

• Holter monitoring or event monitoring may be considered for those discharged from the ED (eg, in cases of paroxysmal AF not evident upon presentation).

• Exercise testing might also be used in the outpatient setting to determine adequacy of rate-control, to reproduce exercise-induced EF, and to exclude ischemic pathology.

Procedures:

• Emergent electrocardioversion is indicated for an unstable patient with AF. This is not commonly required. Instability is generally considered to be present when any of the following are present and when no cause other than the AF is contributing:

• Symptomatic hypotension

• Altered mental status or loss of consciousness

• Acute coronary syndrome with active myocardial ischemia evident either by symptoms (angina) or ECG, or acute myocardial infarction

• Hypoxia

• Presence or absence of CHF will contribute to the bedside assessment of stability.

TREATMENT

Section 6 of 12

Prehospital Care:

• Care of hemodynamically unstable patients is guided by ACLS protocols, including direct current (DC) cardioversion.

• Symptomatic patients may benefit from intravenous (IV) rate-controlling agents, either calcium-channel blockers or beta-adrenergic blockers.

Emergency Department Care: The immediate role of the emergency medicine physician is to ascertain and ensure hemodynamic stability. Once this is done, the approach to atrial fibrillation is facilitated by generally accepted protocols.

• Urgently assess need for interventions, including the following:
  • Airway and oxygenation (pulse oximetry); O₂ supplementation as needed

  • Blood pressure support (often difficult until rate is controlled)

  • A patient with hemodynamic instability, mental status changes, preexcitation, or angina will require urgent synchronized DC cardioversion.
    • Obtain emergent laboratory and imaging studies (ECG, chest radiography).

    • Once the patient has been determined to be hemodynamically stable, often the first step to control ventricular tachycardia is the administration of a rate-controlling agent (as discussed elsewhere in this article, most typically a beta-blocker or a calcium-channel blocker). In a small percentage of cases, the patient may revert to sinus in response to a slowing down of the rate.

    • If the patient persists in AF, anticoagulation should be initiated with either intravenous or subcutaneous heparin. The treatment branch then divides patients into duration of AF. Patients with duration of less than or equal to 48 hours (and without significant LV dysfunction, mitral valve disease, or prior embolism) may undergo immediate pharmacologic or DC cardioversion. AF of duration of greater than 48 hours, or unknown duration, or high risk of embolization can either undergo TEE-guided DC cardioversion or be anticoagulated for 3 weeks, followed by DC cardioversion. Multiple studies have shown the safety/efficacy of TEE-facilitated early cardioversion versus conventional therapy. Although patients who have been on anticoagulation already for at least 3 weeks can be cardioverted without TEE, if any complicating factor (eg, valvular disease, LV dysfunction) is present, TEE should be considered.

• Methods of cardioversion: Cardioversion may be achieved by means of drugs or electrical shocks. Electrical cardioversion is more effective than pharmacologic cardioversion, though it requires sedation/anesthesia.
  • Electrical cardioversion
    • Direct-current cardioversion involves an electrical shock synchronized with the intrinsic activity of the heart to ensure that electrical stimulation does not occur during the vulnerable phase of the cardiac cycle. The success rate of DC cardioversion is 75-93%, with efficacy positively correlating to energy setting (360>200>100 J), and negatively correlating with duration of AF and left atrial size.

    • Paddle positions include anterior-lateral (ventricular apex and right infraclavicular) and anterior-posterior (sternum and left scapular), with at least one study suggesting increased efficacy with the anterior-posterior method.

    • Cardioversion of patients with implanted pacemakers and defibrillator devices is safe when appropriate precautions are taken. Risks of electrical cardioversion include embolic events and cardiac arrhythmias. Transient ST-segment elevations can be present after cardioversion, as well as a bump in cardiac enzyme levels without apparent myocardial damage.

    • The relapse rate after initial successful cardioversion is high: 25%-50% at 1 month and 70%-90% at 1 year.

    • While successful cardioversion in AF of duration greater than 48 hours will require 6-12 weeks of anticoagulation due to atrial stunning, no clear consensus exists for anticoagulation after cardioversion for AF of less than 48 hours. One approach is to divide these patients into low-risk (treat with aspirin) and higher-risk (traditional anticoagulation).

• Pharmacologic cardioversion
  • Pharmacologic cardioversion appears to be most effective when initiated within 7 days after the onset of AF. Please see Medication for discussion of specific drugs.

  • The risk factors for pharmacologic cardioversion include bradyarrhythmia, QT prolongation, and ventricular arrhythmias.

• Disposition: A number of studies have looked at whether low-risk patients with new-onset AF can be treated and discharged from an emergency department setting.

• A study by Michael et al looked at 289 patients seen during an 18-month period in an emergency department setting. Sixty-two percent (180) underwent attempted chemical cardioversion with a 50% success rate, and 28% (80) had attempted electrical cardioversion with a 89% success rate. Ninety-three percent of electrical cardioversions were performed by emergency physicians. They concluded that cardioversion and immediate discharge of patients who present to the ED with acute atrial fibrillation appears to be both safe and effective.

• Reasons for hospitalization would include but not be limited to the following:
  • Presence of comorbidities

  • For workup or treatment of underlying etiology of AF, including evaluation for ACS or myocardial infarction

  • For elderly patients

  • For patients with underlying heart disease

  • Patients at risk of complications from AF therapies

Consultations:

• Patients with AF who are treated in the ED generally require consultation with a cardiologist. Those with new-onset AF and those with associated symptoms related to rate are generally admitted to rule out MI and to evaluate for possible elective cardioversion.

• A patient's cardiologist plays a vital role in determining the most appropriate long-term strategy for a patient with AF and provides crucial follow-up.

• A cardiologist may become involved emergently if complicating factors are present or if the patient is experiencing ongoing cardiac ischemia or infarction not treatable with rate reduction measures and standard chest pain protocols. A patient with AMI and new-onset AF who is stable may benefit from simple rate-control measures (eg, intravenous beta-blockers, intravenous magnesium sulfate 2 g over 10 min) while being prepared for the catheterization laboratory and intravenous nitrates, heparin, and aspirin are begun.

MEDICATION

Section 7 of 12

Pharmacologic agents in AF fall into 1 of 2 classes: rate-controlling drugs and rhythm restoring/rhythm maintenance drugs (though some overlap exists with some drugs, such as amiodarone, exhibiting both qualities).

Rate-controlling drugs

In patients without ventricular preexcitation, rate is controlled most effectively with intravenous verapamil, diltiazem, or beta-adrenergic blockers. Beta-blockers are especially effective in the presence of thyrotoxicosis and increased sympathetic tone or in patients with myocardial ischemia/AMI. The non-hydropyridine calcium channel blockers may be chosen in patients lacking any history of heart failure and in patients with reactive airway disease.

Anecdotally, intravenous diltiazem has become many emergency medicine physician's first-line rate-controlling drug in patients without a history of heart failure.

Digoxin is ineffective in controlling ventricular rate during acute episodes.

In patients with acute or chronic heart failure, digoxin or amiodarone should be used. (Amiodarone does not currently have FDA approval for this intervention.)

Antiarrhythmic drugs

Antiarrhythmic drugs that can terminate AF include procainamide, disopyramide, propafenone, sotalol, flecainide, amiodarone, and ibutilide.

The efficacy of antiarrhythmic drugs has been linked to the duration of AF.

The American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) Guidelines make the following recommendations regarding pharmacologic conversion of AF:

• Conversion of AF less than or equal to 7 days
  • Agents with proven efficacy include dofetilide, flecainide, ibutilide, propafenone, and to a lesser-degree, amiodarone and quinidine.

  • Less effective or incompletely studied agents in this scenario include procainamide, digoxin, and sotalol.

• Conversion of AF lasting greater than 7 days
  • Agents with proven efficacy include dofetilide, amiodarone, ibutilide, flecainide, propafenone, and quinidine.

  • Less effective or incompletely studied agents in this scenario include procainamide, sotalol, and digoxin.

• Conversion of AF lasting greater 90 days - Oral propafenone, amiodarone, and dofetilide have been shown to be effective at converting chronic AF to normal sinus rhythm (NSR).

A newer agent and recently approved class III antiarrhythmic is dofetilide. Another drug, azimilide, has been studied in the recent Azimilide Post-Infarct Survival Evaluation (ALIVE) trial, a post–heart attack survival study. Additional data from ALIVE further support the ongoing development of azimilide as a treatment for supraventricular arrhythmias. Fewer patients in sinus rhythm at baseline developed AF/atrial flutter during the trial on azimilide compared with placebo.

Another newer drug is dronedarone, a deiodinated derivative of amiodarone that has no organ toxicity. Its use extends to atrial and ventricular arrhythmias. At present, dronedarone is an experimental agent that has multiple actions (all 4 Von Williams class effects). Unlike amiodarone, it does not have the iodine moiety. The lack of iodination may offer a better adverse-effect profile. Dronedarone has been shown to (1) have antiadrenergic effects, (2) prolong atrial and ventricular refractory periods, and (3) prolong atrioventricular node conduction and the paced QRS complex.

In animal models, dronedarone has been shown to decrease ischemia-induced ventricular arrhythmias. The clinical effects of dronedarone are now being examined in patients with AF and in patients with internal cardioverter-defibrillators (ICDs). 

When considering drug therapy for AF, remember the treatment caveat: "Electrical cardioversion is the preferred modality in the patient whose condition is unstable."

Drug Category: Calcium channel blockers -- These agents are more effective than digoxin when given orally for long-term rate control and should be the initial DOC. They reduce rate of AV nodal conduction and control ventricular response. Formulations administered IV are discussed as they apply to the control of severe symptoms related to a rapid ventricular rate in an emergent situation.

Drug Name	Diltiazem (Cardizem) -- DOC for rate control in many cases. During depolarization, inhibits calcium ion from entering slow channels or voltage-sensitive areas of vascular smooth muscle and myocardium.
Adult Dose	Initial dose: 0.25 mg/kg IV over 2 min as a bolus; may repeat at 0.35 mg/kg if inadequate rate reduction after 15 min; in patients weighing 80 kg, these 2 doses are 20 and 25 mg, respectively Maintenance dose: 5-10 mg/h (up to 15 mg/h) IV for up to 24 h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, severe CHF, sick sinus syndrome, second- or third-degree AV block, hypotension (<90 mm Hg systolic)
Interactions	May increase carbamazepine, digoxin, cyclosporine, theophylline levels; when administered with amiodarone, may cause bradycardia and decrease in cardiac output; when given with beta-blockers may increase cardiac depression; cimetidine may increase levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in impaired renal or hepatic function; may increase LFT levels, and hepatic injury may occur

Drug Name	Verapamil (Calan, Isoptin, Verelan) -- Can diminish PVCs associated with perfusion therapy and decrease risk of ventricular fibrillation and ventricular tachycardia. During depolarization, inhibits calcium ion from entering slow channels or voltage-sensitive areas of vascular smooth muscle and myocardium.
Adult Dose	Initial dose: 2.5-5 mg IV bolus; may repeat, total dose not to exceed 15 mg; reduces ventricular rate within 5 min and can be followed by maintenance infusion Maintenance dose: 0.05-0.2 mg/min IV infusion
Pediatric Dose	0-1 years: 0.1-0.2 mg/kg IV bolus over >2 min under continuous ECG monitoring; usual single-dose range 0.75-2 mg 1-15 years: 0.1-0.3 mg/kg IV bolus over >2 min; usual single-dose range 2-5 mg; not to exceed 5 mg
Contraindications	Documented hypersensitivity, severe CHF, sick sinus syndrome, second- or third-degree AV block, hypotension (<90 mm Hg systolic)
Interactions	May increase carbamazepine, digoxin, theophylline, and cyclosporine levels; coadministration with amiodarone can cause bradycardia and decrease in cardiac output; when administered concurrently with beta-blockers may increase cardiac depression; cimetidine may increase levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hepatocellular injury may occur; transient elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have occurred (elevations have been transient and may disappear with continued verapamil treatment); monitor liver functions periodically

Drug Category: Beta-blockers -- These agents slow the sinus rate and decrease AV nodal conduction. Beta-blockers now have more of a secondary role in AF rate control. Carefully monitor blood pressure.

Drug Name	Metoprolol (Lopressor) -- Selective beta 1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG.
Adult Dose	5-15 mg IV over 5-15 min (5-mg increments)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, uncompensated CHF, bradycardia, asthma, cardiogenic shock, AV conduction abnormalities
Interactions	Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly decreasing pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG

Drug Name	Esmolol (Brevibloc) -- Ideal for use in patients at risk of complications from beta-blockade, especially those with mild-to-moderate LV dysfunction and peripheral vascular disease. Has a short half-life of 8 min, thus easily titratable to desired effect. In addition, therapy may be stopped quickly if needed.
Adult Dose	Loading dose: 500 mcg/kg/min (0.5 mg/kg/min) IV infusion over 1 min; followed by a 4-min maintenance infusion of 50 mcg/kg/min (0.05 mg/kg/min); if adequate therapeutic effect observed over 5 min of drug administration, maintain maintenance infusion dosage with periodic adjustments prn; if adequate therapeutic effect not observed, repeat same loading dose over 1 min followed by increased maintenance infusion rate of 100 mcg/kg/min (0.1 mg/kg/min) A quick calculation method is to take patient's body weight in kg and divide by 2 (eg, 70 kg/2 = 35 mg); this is the loading dose; multiply this dose by 0.1 (0.1 x 35 = 3.5 mg) to obtain the mg/kg/min drip rate
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, uncompensated CHF, bradycardia, cardiogenic shock, AV conduction abnormalities
Interactions	Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly decreasing pharmacologic effect; cardiotoxicity may increase when administered concurrently with sparfloxacin, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, or contraceptives; toxicity increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, or catecholamine-depleting agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm, may worsen when medication withdrawn abruptly; withdraw drug slowly and monitor patient closely

Drug Category: Class IA antiarrhythmics -- These agents are used only for chemical conversion. They alter the electrophysiologic mechanisms responsible for arrhythmia.

Drug Name	Procainamide (Pronestyl) -- Class IA antiarrhythmic used for PVCs. Increases refractory period of atria and ventricles. Myocardiac excitability reduced by increase in threshold for excitation and inhibition of ectopic pacemaker activity. IV form is treatment of choice if conduction is over an accessory pathway. May establish pharmacologic conversion to sinus rhythm.
Adult Dose	Up to 17 mg/kg IV drip at rate of 20-30 mg/min under continuous cardiac monitoring; stop infusion if QRS widening or hypotension occurs
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; complete heart block or second- or third-degree heart block, if a pacemaker is not in place; torsade de pointes; systemic lupus erythematosus
Interactions	Can expect increased levels of procainamide metabolite NAPA in patients taking cimetidine, ranitidine, beta-blockers, amiodarone, trimethoprim, and quinidine; may increase effect of skeletal muscle relaxants, quinidine, lidocaine, and neuromuscular blockers; ofloxacin inhibits tubular secretion of procainamide and may increase bioavailability; when taken concurrently with sparfloxacin, may increase risk of cardiotoxicity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Fatal blood dyscrasias reported with therapeutic doses; close monitoring recommended during first 3 mo of therapy May result in lupus erythematosus–like syndrome in about 20-30% of patients; plasma concentration of procainamide and active metabolite, NAPA, may be increased in renal failure; high or toxic concentrations may induce AV block or abnormal automaticity; caution in complete AV block, digitalis intoxication, organic heart disease, renal disease, and hepatic insufficiency

Drug Name	Quinidine (Cardioquin, Quinora) -- Primarily an oral formulation that recently has been studied in sequential combination with verapamil versus digoxin for patients with stable, rate-controlled, acute-onset paroxysmal AF. After controlling rate with IV verapamil, 200 mg of oral quinidine was given q2h until conversion to NSR occurred, 1 g of quinidine was administered, or an adverse effect occurred. Approximately 84% of verapamil-quinidine group converted to NSR within 6 h, whereas 45% of digoxin-quinidine group converted to NSR within 6 h. This suggests that digoxin is relatively inferior in this group of patients. Moreover, Shreck et al found no advantage to adding digoxin to diltiazem for rate control. Quinidine prolongs effective refractory period and increases conduction time. Also has indirect anticholinergic effects and decreases vagal tone, which facilitates conduction in AV nodal junction.
Adult Dose	200 mg PO q2-3h for 5-8 doses; followed by subsequent daily increases until sinus rhythm restored or side effects occur; not to exceed total daily dose of 3-4 g in any regimen; prior to administration, control ventricular rate and CHF (if present) with digoxin
Pediatric Dose	30 mg/kg/d PO in 5 divided doses
Contraindications	Documented hypersensitivity, complete AV block or intraventricular conduction defects, concurrent ritonavir or sparfloxacin
Interactions	Phenytoin, rifampin, and phenobarbital may decrease concentrations; toxicity increased when taken with ritonavir, sparfloxacin, beta-blockers, amiodarone, verapamil, cimetidine, alkalinizing agents, or nondepolarizing or depolarizing muscle relaxants; may enhance effect of anticoagulants
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in G-6-PD deficiency and patients with a tendency to develop granulocytopenia; avoid use in myocardial depression, hepatic or renal insufficiency, and myasthenia gravis

Drug Category: Class IC antiarrhythmics -- These agents are used only in patients with structurally normal hearts (ie, absence of coronary artery disease or cardiomyopathy).

Drug Name	Propafenone (Rythmol) -- Shortens upstroke velocity (Phase 0) of monophasic action potential. Reduces fast inward current carried by sodium ions in Purkinje fibers and, to a lesser extent, myocardial fibers. May increase diastolic excitability threshold and prolong effective refractory period prolonged. Reduces spontaneous automaticity and depresses triggered activity. Indicated for the treatment of documented life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Appears to be effective in the treatment of supraventricular tachycardias including AF and atrial flutter. Not recommended in less severe ventricular arrhythmias, even if symptomatic. Use in conjunction with AV nodal blocking agents when given to patients in AF because conversion to AFL with 1:1 conduction (producing fast ventricular rates) has been noted.
Adult Dose	150 mg PO q8h; increase up to a total dose of 900 mg/d prn
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; preexisting second- or third-degree AV block, right bundle-branch block associated with left hemi-block (bifascicular block or trifascicular block), unless a pacemaker is present to sustain the cardiac rhythm if complete heart block occurs; concurrent use of ritonavir or amprenavir; recent MI
Interactions	Rifampin may decrease plasma levels; quinidine may increase pharmacologic effects; propafenone may increase plasma levels of beta-blockers, cyclosporine, warfarin, and digoxin; CYP2D6 inhibitors (ritonavir, cimetidine, amiodarone) may increase serum levels and cardiotoxicity of propafenone
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in preexisting sinus node dysfunction, history of congestive heart failure, sick-sinus syndrome, post-MI, or myocardial dysfunction; reserve use only for life-threatening arrhythmias because of deaths associated with proarrhythmic effects of Class IC antiarrhythmics; adjust dose in renal or hepatic impairment

Drug Name	Flecainide (Tambocor) -- Blocks sodium channels, producing dose-related decrease in intracardiac conduction in all parts of the heart. Increases electrical stimulation of threshold of ventricle, HIS-Purkinje system. Shortens Phase 2 and 3 repolarization, resulting in a decreased action potential duration and effective refractory period. Indicated for the treatment of paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms and paroxysmal supraventricular tachycardias (PSVT), including atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, and other supraventricular tachycardias of unspecified mechanism associated with disabling symptoms in patients without structural heart disease. Indicated also for prevention of documented life-threatening ventricular arrhythmias, such as, sustained ventricular tachycardia. Not recommended in less severe ventricular arrhythmias even if patients are symptomatic. Use in conjunction with AV nodal blocking agents when given to patients in AF because conversion to AFL with 1:1 conduction (producing fast ventricular rates) can occur.
Adult Dose	50 mg PO q12h; increase by 50 mg bid q4d until efficacy achieved
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; preexisting second- or third-degree AV block, right bundle-branch block associated with left hemi-block (bifascicular block or trifascicular block), unless a pacemaker is present to sustain the cardiac rhythm if complete heart block occurs; concurrent use of ritonavir or amprenavir; recent MI
Interactions	May increase toxicity of digoxin; beta-adrenergic blockers, verapamil, and disopyramide may have additive inotropic effects when administered with flecainide; CYP2D6 inhibitors (ritonavir, cimetidine, amiodarone) may increase serum levels and cardiotoxicity of flecainide; amiodarone may increase plasma levels of flecainide
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in preexisting sinus node dysfunction, history of congestive heart failure, sick-sinus syndrome, post-MI, or myocardial dysfunction; reserve use only for life-threatening arrhythmias because of deaths associated with proarrhythmic effects of Class IC antiarrhythmics; adjust dose in renal or hepatic impairment

Drug Category: Class III antiarrhythmics -- These drugs may effectively establish a chemical conversion to sinus rhythm.

Drug Name	Sotalol (Betapace) -- Class III antiarrhythmic agent that blocks K+ channels, prolongs action potential duration (APD), and lengthens QT interval. Noncardiac selective beta-adrenergic blocker. The D-isomer has less than 1/50 beta-blocking activity of the L-isomer. Sotalol possesses 30% of beta-blocking activity of propranolol.
Adult Dose	80 mg PO bid initial dose; may gradually titrate up to 240-360 mg/d; allow 2-3 d between dosing increments; not to exceed 640 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity, sinus bradycardia, second- and third-degree AV block
Interactions	Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly decreasing pharmacologic effect; cardiotoxicity may increase when administered concurrently with sparfloxacin, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, and contraceptives; toxicity increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Beta-adrenergic blockade may decrease signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor patient closely; caution in hypokalemia, peripheral vascular disease, hypomagnesemia, CHF

Drug Name	Amiodarone (Cordarone) -- May inhibit AV conduction and sinus node function, prolongs action potential and refractory period in myocardium, and inhibits adrenergic stimulation. Prior to administration, control ventricular rate and CHF (if present) with digoxin or calcium channel blockers. Blocks sodium channels and has high affinity for inactive channels. In addition, blocks potassium channels and weakly blocks calcium channels. Also blocks alpha- and beta-adrenergic receptors noncompetitively.
Adult Dose	5 mg/kg IV over 30 min; followed by 1200 mg over 24 h
Pediatric Dose	Loading dose: 6.3 mg/kg IV
Contraindications	Documented hypersensitivity, complete AV block, intraventricular conduction defects; concurrent ritonavir or sparfloxacin
Interactions	Increases effect and blood levels of theophylline, quinidine, procainamide, phenytoin, methotrexate, flecainide, digoxin, cyclosporine, beta-blockers, and anticoagulants; cardiotoxicity increased by ritonavir, sparfloxacin, and disopyramide; coadministration with calcium channel blockers may cause additive effect and decrease myocardial contractility further; cimetidine may increase levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Adverse effects include pulmonary toxicity and fibrosis which can be life-threatening Caution in thyroid or liver disease

Drug Name	Ibutilide (Corvert) -- Class III antiarrhythmic agent which may work by increasing action potential duration, thereby changing atrial cycle length variability; however, this mechanism remains controversial. Mean time to conversion 30 min. Two thirds of patients who converted were in sinus rhythm at 24 h. Ventricular arrhythmias occurred in 9.6% of patients and were mostly PVCs. The incidence of torsade de pointes was <2%.
Adult Dose	Body weight <60 kg: 0.1 mL/kg (0.01 mg/kg) IV over 10 min Body weight >60 kg: 1 mg (1 vial) IV over 10 min If arrhythmia does not terminate within 10 min of end of initial infusion, may give second 10-min infusion of equal strength
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Increases toxicity of quinidine and procainamide; concurrent administration with tricyclic antidepressants, phenothiazines, or astemizole (recalled from US market) may prolong QT interval; increases toxicity of concurrent digoxin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal or hepatic impairment

Drug Name	Dofetilide (Tikosyn) -- Prototype of a "pure" class III agent. Blocks delayed rectifier current (IKr) and prolongs action potential duration; indeed, even at higher magnitudes, has no effect upon other depolarizing potassium currents (IKs and IKl). Terminates induced re-entrant tachyarrhythmias (AF/flutter and ventricular tachycardia) and prevents their re-induction. At clinically prescribed concentrations, has no effect on sodium channels, which are associated with class I effects. Furthermore, no effect noted on alpha-receptors or adrenergic beta-receptors. Indicated for maintenance of NSR in patients with AF/atrial flutter of > 1 wk duration who have been converted to NSR. Also indicated for conversion of AF and atrial flutter to NSR. Has not been effective for patients with paroxysmal AF. Torsade de pointes is only arrhythmia showing dose-response relationship. Incidence with supraventricular arrhythmia is 0.8%. Most torsade de pointes episodes occur within first 3 d of therapy. If patients do not convert to NSR within 24 h of initiation of therapy, electrical cardioversion should be considered. Has no effect on cardiac output, cardiac index, stroke volume index, or systemic vascular resistance. Does not affect blood pressure. Must be initiated with continuous ECG monitoring, which should continue for at least 12 h after conversion. Dose must be individualized according to CrCl and QTc (use QT interval if heart rate <60/min). No information on use of this drug for heart rates <50/min. Patients with AF should be anticoagulated according to established practice. Anticoagulation should be continued after cardioversion as per usual practice.
Adult Dose	Step 1. Determine QTc using average of 5-10 beats; if QTc >440 ms (500 ms in those with ventricular conduction abnormalities), dofetilide is contraindicated Step 2. Calculate CrCl prior to administration, using formulas: CrCl (male) = (140-age) x body weight (kg) over 72 x serum creatinine (mg/dL) CrCl (female) = (140-age) x body weight (kg) x 0.85 over 72 x serum creatinine (mg/dL) Step 3. Determine starting dose as follows: CrCl >60 mL/min: 500 mcg PO bid CrCl 40-60 mL/min: 250 mcg PO bid CrCl 20-40 mL/min: 125 mcg PO bid CrCl <20 mL/min: Contraindicated Step 4. Administer dofetilide and begin continuous ECG monitoring Step 5. 2-3 h after administration of first dose, determine QTc; if QTc has increased by >15% compared to baseline or if the QTc is >500 ms (550 ms in those with ventricular conduction abnormalities), adjust subsequent doses as follows: Starting dose 500 mcg PO bid, adjust to 250 mcg bid Starting dose 250 mcg PO bid, adjust to 125 mcg bid Starting dose 125 mcg PO bid, adjust to 125 mcg qd Step 6. Continuously monitor for minimum of 3 d or for minimum of 12 h after conversion to NSR, whichever is greater
Pediatric Dose	<18 years: Not established
Contraindications	Congenital or acquired long QT syndromes, baseline QT interval or QTc > 440 ms (500 ms in patients with ventricular conduction abnormalities), severe renal impairment (CrCl < 20 mL/min), concomitant use of verapamil, cimetidine, trimethoprim, ketoconazole, or other drugs known to increase plasma levels of dofetilide, inhibit renal cation transport, or prolong QT interval
Interactions	See contraindications above; drugs known to increase plasma levels of dofetilide include verapamil, cimetidine, trimethoprim, and ketoconazole; known inhibitors of renal cation transport include prochlorperazine, megestrol; drugs that prolong QT interval include, but are not limited to, phenothiazines, cisapride, bepridil, tricyclic antidepressants, and certain oral macrolide antibiotics Hold class I or class III antiarrhythmic agents for at least 3 half-lives prior to dosing (terminal half-life is 10 h) Does not affect pharmacokinetics of digoxin, but concomitant use of these two drugs has been associated with higher incidence of torsade de pointes; warfarin pharmacodynamics not altered by this medication
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal impairment (CrCl guides dosing); caution in hepatic impairment (has not been studied in patients with severe hepatic impairment); caution in cardiac conduction problems—no effect on AV node conduction in patients with first-degree heart block (second- and third-degree not studied); has been used safely in conjunction with pacemakers

Drug Category: Cardiac glycosides -- These drugs slow AV nodal conduction primarily by increasing vagal tone. They are used primarily in the setting of AF with CHF.

Drug Name	Digitalis, digoxin (Lanoxin) -- Use of digoxin for acute rate control of AF in ED controversial. May be considered in patients with CHF secondary to impaired systolic ventricular function. However, more effective medications now available. According to literature, digoxin shown to actually increase duration of episodes of paroxysmal AF, a result consistent with its action in decreasing atrial refractory period. Therapeutic concentrations of digoxin also do not prevent a rapid ventricular rate from developing in persons with paroxysmal AF. Therefore, digoxin should be avoided in persons with sinus rhythm with a history of paroxysmal AF.
Adult Dose	Previously undigitalized patients: 400-600 mcg (0.4-0.6 mg) IV single initial dose usually produces detectable effect in 5-30 min; effect becomes maximal in 1-4 h
Pediatric Dose	2-5 years: 25-35 mcg/kg IV 5-10 years: 15-20 mcg/kg IV >10 years: 8-12 mcg/kg IV
Contraindications	Documented hypersensitivity, beriberi heart disease, idiopathic hypertrophic subaortic stenosis, constrictive pericarditis, carotid sinus syndrome
Interactions	Medications that may increase digoxin levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil Medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hypokalemia may reduce positive inotropic effect; IV calcium may produce arrhythmias in digitalized patients; hypercalcemia predisposes patient to digitalis toxicity, and hypocalcemia can make digoxin ineffective until serum calcium levels are normal; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete AV block may progress to complete block when treated with digoxin; use caution in hypothyroidism, hypoxia, and acute myocarditis

FOLLOW-UP

Section 8 of 12

Further Inpatient Care:

• Preventing complications of AF

• Cardioversion (either electrical or chemical) carries a significant risk of embolization. Anticoagulants usually are administered to patients with AF lasting more than 48 hours. They are administered 3 weeks before to 4 weeks after cardioversion. Stunning of the atria may occur for several weeks following cardioversion, and the atrial chambers are at increased risk of developing thrombi. For this reason, antiarrhythmic agents that restore sinus rhythm should be withheld until anticoagulation has been achieved.

• Stroke recurrence rate is high for patients with AF; therefore, long-term warfarin therapy is recommended. Aspirin offers only modest protection against stroke for patients with AF. The effect is less consistent than that of oral anticoagulation. However, for patients who cannot tolerate warfarin, aspirin is a suitable alternative. See In/Out Patient Meds.

Further Outpatient Care:

• Long-term management of AF has most commonly centered around 1 of 2 strategies: rhythm control versus rate control. The discussion surrounding these strategies has been dominated by the following questions: Is AF best managed by rhythm control?, Is AF best managed by rate control?, How is sinus rhythm best maintained?, What is the best means of preventing thromboembolism? While these questions are arguably the purview of cardiologists, it behooves the emergency medicine physician to have a basic knowledge of recent developments in this area.

• Five significant randomized clinical trials have taken place in the past few years and include the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), Paroxysmal Atrial Fibrillation (PAF 2), Pharmacological Intervention in Atrial Fibrillation (PIAF), Rate Control Versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE), and Strategies of Treatment of Atrial Fibrillation (STAF). A review of these studies yielded the following conclusions in regards to rate versus rhythm control:

• AFFIRM and RACE both failed to demonstrate a clear benefit with rhythm control strategy.

• All 5 studies failed to show any significant difference in all-cause or cardiovascular mortality between the two strategies.

• With respect to stroke, no difference was noted between the two strategies. Warfarin lowers the risk of stroke in both strategies.

• With respect to quality of life and functional status, all 5 trials failed to show any differences between rate control and rhythm control.

• In 2003, the American Academy of Family Physicians and the American College of Physicians issued clinical practice guidelines on the management of newly detected atrial fibrillation, with the following recommendations:

• Recommendation 1: Rate control with chronic anticoagulation is the recommended strategy for the majority of patients with atrial fibrillation. Rhythm control is appropriate when based on other special considerations, such as patient symptoms, exercise tolerance, and patient preference. Grade: 2A.

• Recommendation 2: Patients with atrial fibrillation should receive chronic anticoagulation with adjusted-dose warfarin, unless they are at low risk of stroke or have a specific contraindication (eg, thrombocytopenia, recent trauma or surgery, alcoholism) to the use of warfarin.

• Recommendation 3: For patients with atrial fibrillation, the following drugs are recommended for their demonstrated efficacy in rate control during exercise and while at rest: atenolol, metoprolol, diltiazem, and verapamil (drugs listed alphabetically by class). Digoxin is only effective for rate control at rest and therefore should only be used as a second-line agent for rate control in atrial fibrillation.

• Recommendation 4: For patients who elect to undergo acute cardioversion to achieve sinus rhythm in atrial fibrillation, both DC cardioversion and pharmacologic conversion are appropriate options.

• Recommendation 5: Both transesophageal echocardiography with short-term prior anticoagulation followed by early acute cardioversion (in the absence of intracardiac thrombus) with postcardioversion anticoagulation versus delayed cardioversion with preanticoagulation and postanticoagulation are appropriate management strategies for patients who elect to undergo cardioversion.

• Recommendation 6: Most patients converted to sinus rhythm from atrial fibrillation should not be placed on rhythm maintenance therapy since the risks outweigh the benefits.

• As stated previously, stratification of patients with AF into those at high and low risk for thromboembolism is a crucial determinant of optimal antithrombotic prophylaxis. Brass et al found that anticoagulation is underused in elderly patients with stroke and AF, even among ideal candidates.

In/Out Patient Meds:

• Medications for rate control in inpatient and outpatient setting

• Inpatient medication consists of a 24-hour diltiazem drip and/or digoxin loading dose and maintenance therapy; however, digoxin therapy is falling out of favor rapidly as a method of rate control.

• Outpatient management consists of rate control with oral diltiazem, digoxin, or quinidine in addition to prevention of thromboembolic complications (see Stratification by embolic risk).

• Farshi et al compared several standardized drug regimens for 24-hour ventricular rate control (digoxin, diltiazem-CD, atenolol, digoxin plus diltiazem-CD, digoxin plus atenolol). Digoxin plus atenolol produced the most effective rate control due to a synergistic effect on the AV node.

• Because of its vagolytic effect and resultant rapid ventricular response, quinidine should not be given without prior administration of agents that slow AV nodal conduction.

• Occasionally, treatment of patients with tachycardia-bradycardia syndrome worsens sinus node function, resulting in symptomatic bradyarrhythmias that require pacemaker support. For this reason, the author reduces the initial dose of intravenous diltiazem for rate control in the elderly (eg, unknown sick sinus syndrome) or for those on any other AV node-blocking drug, using half to one quarter of the loading dose of IV diltiazem (usually about 5-10 mg in the average adult) and titrating at equal increments every 15 minutes up to the standard mg/kg loading dose. This has proven a very effective method of preventing "bradycardic overshoot."

• Using this method, the author has had no adverse bradycardic events from diltiazem.

• A permanent pacemaker should be implanted in persons who have AF and cerebral symptoms that are not drug induced, such as dizziness or syncope associated with ventricular pauses longer than 3 seconds.

• Many antiarrhythmic agents, especially flecainide and propafenone, can slow the atrial rate, which allows greater impulse conduction through the AV node, resulting in a faster ventricular rate. In fact, many episodes of wide QRS tachycardia in patients who have AF and are treated with flecainide or propafenone appear to be secondary to atrial flutter with 1:1 AV node conduction associated with QRS widening.
  • The resultant arrhythmia is often misdiagnosed as ventricular tachycardia. This situation can be prevented or treated by the addition of agents that slow AV node conduction (eg, digitalis, alpha-adrenergic blockers, calcium channel blockers).

  • The Atrial Fibrillation Follow-up Investigation in Rhythm Management (AFFIRM) study randomized 4060 elderly patients (mean age 68 +/- 9 y) to either rate control or rhythm control and assessed them for total mortality at a mean follow-up of 3.5 years. After this interval, the rate-control group trended toward lower mortality rates (306 vs 356, P=.058). Stroke events were nearly equal in both treatment groups; most occurred when patients ceased intake of warfarin (or levels were subtherapeutic). Therefore, in both groups, the need to continue antiplatelet therapy in patients with stroke risk factors (regardless of the rhythm therapy) was emphasized. Additionally, the AFFIRM trial found that significantly fewer hospitalizations were required in the rate-control group, even in the elderly patient population, indicating that further savings could be achieved by using a rate-control strategy.

  • In the Rate Control vs Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) trial, the investigators used the composite primary end point of rate of death or severe cardiovascular incident. This end point occurred in fewer patients randomized to rate control (n = 256; 17.2%) vs rhythm control (n = 266; 22.6%). When subsets of these end points were analyzed (eg, cardiovascular death, CHF, hemorrhage) they found no statistical difference between the 2 groups. Of importance, the study found that the rate of adverse events was greater in the rhythm-control vs the rate-control group, and this was also true for patients with hypertension (30.8% event rate with rhythm control vs 17.3% with rate-control).

• Inpatient and outpatient prevention of embolic problems is best achieved with vitamin K antagonists (eg, warfarin), which are highly effective in reducing risk of ischemic stroke in patients with AF.

• High-risk patients who can safely receive anticoagulation should be treated with warfarin. For high-risk AF patients younger than 75 years, an INR range of 2-3 is safe and effective. For those older than 75 years, close surveillance of INR levels is recommended because of the apparently greater likelihood of bleeding complications. Feinberg noted that patients with AF have a stroke risk of 4.5% per year. Anticoagulation reduces this to around 1.5% per year, a 70% relative risk reduction.

• The presence of additional risk factors, such as a recent stroke or TIA, hypertension (particularly systolic hypertension), CHF, or diabetes mellitus, greatly increases stroke risk. Patients with any of these risk factors have a stroke risk of 8% per year. In contrast, patients who are younger than 75 years and have none of these risk factors have a low risk for stroke (around 1% per year) when treated with aspirin.

• The value of other antiplatelet agents has not been assessed in patients with AF.

• Inpatients with new-onset AF frequently are placed on intravenous heparin initially before chemical or electrical conversion.

• Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III and V trials were trials performed in Europe (SPORTIF III) and in North America (SPORTIF V). Both were noninferiority trials. By definition, noninferiority trials intend to show that an experimental treatment (ximelagatran) does not produce worse results than those of a known active control (warfarin) by a specified margin (2% per year).

• SPORTIF III was reported in the Lancet in November 2003. It was a phase 3, multicenter, randomized, controlled clinical trial that compared warfarin to ximelagatran in the treatment of 3410 patients with AF and one or more stroke factors. The primary endpoint was stroke or systemic embolism. The primary event rate by intention to treat was 2.3% per year for warfarin and 1.6% for ximelagatran (absolute risk reduction, 0.7%; relative risk reduction, 29%). Rates of disabling or fatal stroke, mortality, and major bleeding were similar, but the rate of combined minor and major hemorrhages was 29.8% per year for warfarin and 25.8% for ximelagatran (relative risk reduction, 14%; P = .007). Raised serum alanine transferase levels were more commonly observed in the ximelagatran group.

• SPORTIF V was reported in the American Heart Journal in September 2003 and at the American Heart Association Scientific Sessions in November 2003. This study included a double-blind treatment allocation with 3922 patients. Again, the primary endpoints were strokes and systemic embolic events with a noninferiority treatment objective compared to warfarin. The study commenced in July 2000 and enrollment ended in December 2001. Data analysis was extensive and included safety monitoring. The primary event rate by intention to treat was 1.2% per year for warfarin and 1.6% for ximelagatran. The ximelagatran rate was identical in the two studies, whereas the rate for warfarin in SPORTIF V was half that noted in SPORTIF III. The reasons for this difference in the warfarin groups continue to be evaluated.

• In both studies, the rates of intracranial and/or other major bleeding events were insignificant. However, when the event rates for major and minor bleeding are combined, ximelagatran was significantly better than warfarin (P <.001 and P <.007, respectively). Elevated alanine transaminase (ALT) levels were noted not only in SPORTIF III and V but also in all previously conducted long-term ximelagatran trials. These elevations are transient and return to normal whether or not the drug is discontinued. It appears that the ALT elevation is limited to the first 6 months of treatment with ximelagatran.

Transfer:

• Transfer to a referral center if the patient has complications, including the following:

• Bradycardia caused by sick sinus syndrome that requires pacemaker therapy

• Unresponsive rate control despite adequate medical therapy. After electrical cardioversion, referral for electrophysiologic ablation may be appropriate. These patients generally are transferred from one inpatient facility to another.

• Embolic complications requiring surgical therapy (arterial embolization) or CVA requiring neurointensive care

Complications:

• Stroke (AF-associated stroke is particularly a problem for patients older than 75 years (see Image 2).

• Arterial embolization

• CHF

• Severe bradycardia

• Rate-related myocardial ischemia

Prognosis:

• As discussed earlier, the rate of ischemic stroke among patients with nonrheumatic AF averages 5% year, which is somewhere between 2-7 times the rate of stroke in patients without AF.

• The total mortality rate is approximately doubled in patients with AF compared with patients in normal sinus rhythm and is linked with the severity of underlying heart disease.

Patient Education:

• In cases of intermittent AF, educating the patient on rapid access to 911 services is beneficial.

• Long-term education should be the responsibility of the primary care provider but certainly knowledge about stroke risk and prevention should be initially imparted by the emergency to the AF patient.

• For excellent patient education resources, visit eMedicine’s Heart Center. Also, see eMedicine’s patient education article Atrial Fibrillation.

MISCELLANEOUS

Section 9 of 12

Medical/Legal Pitfalls:

• Watch for development of severe bradycardia during treatment. This may cause severe hypotension and death if not carefully monitored.

• Rarely, AF may be due to pulmonary embolism, pericardial disease/effusion or carbon monoxide intoxication. Keep these rare events in mind when dealing with the unusual case that does not respond to standard therapy.

• Managed care has recently pushed for discharging stable patients with lone AF for follow-up within 24-48 hours. In these patients, carefully document normal ventricular function (using echocardiography, if possible) and obtain baseline thyroid studies. Be certain that a qualified internist or cardiologist will follow-up with the patient within this time frame. Once established in the ED, oral medication for rate control may be quite appropriate in these cases.

• Most patients with lone or paroxysmal AF will self-convert. Episodes of paroxysmal AF may last from a few seconds to several weeks. Spontaneous conversion of paroxysmal AF to sinus rhythm occurs in 68% of persons presenting with AF of fewer than 72 hours duration.

• Beware of AF in Wolfe-Parkinson-White syndrome. In young patients with this disorder, which appears as rapid wide-complex AF with a rate of more than 200 beats per minute, the use of calcium channel blockers may induce ventricular fibrillation.

Special Concerns:

• For more information on this topic, please consult the following Internet site and resource text.

• American Heart Association

• Management of Patients with Atrial Fibrillation: A Statement for Healthcare Professionals from the Subcommittee on Electrocardiography and Electrophysiology. American Heart Association. Circulation. 1996: 1262-1277.

• Special thanks to Jeffrey Mann, MD, for providing the images at the end of this article, which outline the current AHA recommendations.

TEST QUESTIONS

Section 10 of 12

CME Question 1: New-onset atrial fibrillation (AF) in a patient whose evaluation is negative for a cause is commonly known as which of the following?

A: Uncontrolled AF
B: Holiday heart
C: Lone AF
D: Paroxysmal AF
E: None of the above

The correct answer is C: Lone atrial fibrillation is defined as AF in the absence of any known etiological factors plus normal ventricular function by echocardiography.

CME Question 2: Ibutilide (Corvert) is a class III antiarrhythmic agent. Which of the following statements concerning this drug is true?

A: The mean time of conversion to sinus rhythm is 5 minutes.
B: The incidence of torsade de pointes approaches 30%.
C: Ibutilide may work by increasing the atrial cycle length variability (atrial repolarization).
D: The drug slows conduction in the AV node.
E: All of the above

The correct answer is C: Ibutilide, a newer class III antiarrhythmic agent, may work by increasing the action potential duration, thereby changing atrial cycle length variability.

Pearl Question 1 (T/F): In patients with atrial fibrillation, the chest radiographic findings are usually normal.

The correct answer is True: Chest radiographic findings are usually normal; however, in subacute cases, radiographic evidence of pulmonary edema may be observed.

Pearl Question 2 (T/F): Thyrotoxicosis, pulmonary embolus, and pericardial disease should all be considered in the patient with new-onset atrial fibrillation (AF).

The correct answer is True: Thyrotoxicosis, pulmonary embolus, and pericardial disease should be considered in cases of new-onset AF. Other precipitating factors include coronary artery disease, long-standing hypertension, valvular disease, and diabetes mellitus.

Pearl Question 3 (T/F): In a young patient with rapid wide-complex atrial fibrillation (AF) and a heart rate of 220 beats per minute, the use of calcium channel blockers may induce ventricular fibrillation.

The correct answer is True: The patient described has Wolff-Parkinson-White (WPW) syndrome, which appears as a rapid wide-complex AF with a heart rate of at least 200 beats per minute. Ventricular fibrillation may develop when patients are treated with calcium channel blockers.

Pearl Question 4 (T/F): A 64-year-old patient with atrial fibrillation, no hypertension, and no history of stroke or comorbid conditions is best treated with 1 aspirin tablet a day to prevent embolic disease.

The correct answer is True: Embolic disease can be prevented with the use of aspirin in patients who have atrial fibrillation and no hypertension or history of stroke or other comorbid conditions.

PICTURES

Section 11 of 12

Caption: Picture 1. ECG of controlled-rate atrial fibrillation.
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Caption: Picture 2. Recommendations for antithrombotic therapy based on embolic risk stratification. Image courtesy of Jeffrey Mann, MD.
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Caption: Picture 3. Algorithm for newly discovered atrial fibrillation based on American Heart Association (AHA) guidelines. Adapted from "ACC/AHA/ESC Algorithm for Newly Discovered AF," by Jeffrey Mann, MD.
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Caption: Picture 4. Management of hemodynamically stable atrial fibrillation (based on American Heart Association (AHA) guidelines. Adapted from "ED Management of New-Onset AF Based on the Duration of AF," by Jeffrey Mann, MD.
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Caption: Picture 5. Management of recurrent paroxysmal atrial fibrillation based on American Heart Association (AHA) guidelines. Adapted from "ACC/AHA/ESC Algorithm for Recurrent Persistent AF," by Jeffrey Mann, MD.
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Caption: Picture 6. Management of recurrent persistent atrial fibrillation based on American Heart Association (AHA) guidelines. Adapted from "ACC/AHA/ESC Algorithm for Recurrent Persistent AF," by Jeffrey Mann, MD.
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BIBLIOGRAPHY

Section 12 of 12

• Abdel Latif A, Messinger-Rapport BJ: Should nursing home residents with atrial fibrillation be anticoagulated?. Cleve Clin J Med 2004 Jan; 71(1): 40-4[Medline].
• AFFIRM Investigators: Baseline characteristics of patients with atrial fibrillation: the AFFIRM Study. Am Heart J 2002 Jun; 143(6): 991-1001[Medline].
• Aronow WS: Management of the older person with atrial fibrillation. J Am Geriatr Soc 1999 Jun; 47(6): 740-8[Medline].
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