Browse
Topics & Collections
Search for a specific
disease or term
—  or  —
Learn more about ACP Smart Medicine

Dynamed

X
This content was provided by DynaMed (dynamed.ebscohost.com). For more information click here.
Last Updated: 4/8/2014  

Atrial Fibrillation

Prevention
  • Use an ACE inhibitor or ARB for primary prevention of AF in patients with hypertension-related LVH, a reduced ejection fraction, or HF.

  • Use statins to prevent AF in patients with ischemic heart disease.

Diagnosis
  • Diagnose AF with resting ECG demonstrating absent P waves and an irregular ventricular response.

  • Obtain continuous ambulatory cardiac monitoring or cardiac event monitoring for patients with intermittent symptoms.

  • Selectively obtain additional laboratory data to determine AF etiology; for most patients this includes hemoglobin, serum electrolytes, TSH, pulse oximetry, and echocardiography.

Therapy
  • Use β-blockers or calcium-channel blockers as first-line agents to control heart rate.

  • Use a risk stratification tool, such as CHADS2 or CHA2DS2-VASc to determine the long-term thromboembolic risk.

  • Treat patients at lowest risk for thromboembolism with antiplatelet therapy or no therapy.

  • Treat patients at increased risk for thromboembolism with warfarin, a direct thrombin inhibitor, or a factor Xa inhibitor.

  • Consider elective cardioversion for patients whose symptoms are not controlled with a rate-control strategy.

  • Note that catheter-based ablation of the AV node with placement of a ventricular pacer is an option for patients poorly controlled with or intolerant of drug therapy.

  • Perform emergent electrical cardioversion in patients with AF who are hemodynamically unstable.

Use statins to prevent AF in high-risk patients. 
  • Consider statin use for primary prevention of AF in patients with ischemic heart disease.

  • Consider statin use for primary prevention of AF in patients undergoing cardiac surgical procedures, including coronary artery bypass grafting and valvular interventions.

  • Do not use statins for the primary prevention of AF in patients without heart disease or without other indications for statin treatment.

Evidence
  • The 2014 ACCF/AHA/HRS guideline for the management of patients with AF stated that statins are not beneficial for the prevention of AF in patients without cardiovascular disease but that statins may be reasonable for the prevention of AF after coronary artery surgery (1).

  • A 2013 systematic review of statins for the prevention of AF included 32 studies with 71,000 patients. Overall, compared with control therapy, statin therapy reduced AF, with an OR of 0.69 (CI, 0.57 to 0.83), although there was heterogeneity in the pooled analysis. In specific clinical situations, statin therapy prevented AF in the postoperative setting (OR, 0.37 [CI, 0.28 to 0.51]) and in secondary prevention (OR, 0.57 [CI, 0.36 to 0.91]), but did not prevent new-onset AF (OR, 1.00 [CI, 0.86 to 1.15]) (2).

Rationale
  • Statins have an anti-inflammatory effect that is believed to suppress inflammatory mediators that may play a role in triggering the onset of AF.

Use ACE inhibitors or ARBs to decrease the risk for development of AF in high-risk patients. 
  • Consider use of an ACE inhibitor or ARB for primary prevention of AF in patients with hypertension, particularly those with hypertension-related LVH.

  • Do not use an ACE inhibitor or ARBs for the primary prevention of AF in patients without hypertension, HF, or another indication for treatment with these medications.

Evidence
  • A 2010 systematic review of the prevention of AF through inhibition of the renin-angiotensin system included 23 randomized trials with 87,000 patients. Overall, renin-angiotensin inhibition reduced rates of AF (OR, 0.67 [CI, 0.57 to 0.78]), with similar results for ACE inhibitors and ARBs, although there was heterogeneity in the analysis. Renin-angiotensin inhibition reduced rates of AF in patients with HF (OR, 0.52 [CI, 0.31 to 0.87]), but not in patients with hypertension or MI. For secondary prevention, renin-angiotensin inhibition decreased AF after electrical or chemical cardioversion (OR, 0.55 [CI, 0.34 to 0.89]) and in patients with paroxysmal AF (OR, 0.37 [CI, 0.27 to 0.49]) (3).

  • The LIFE trial was a randomized trial comparing losartan with atenolol in 9193 patients with hypertension and LVH. After a mean follow-up time of 4.8 years, the rate of AF was lower in the losartan group (6.8 vs. 10.1 cases/1000 person-years) (4).

  • The CHARM trial was a randomized trial comparing candesartan with placebo in 7600 patients with symptomatic HF. Among patients without baseline AF, the candesartan group had a lower rate of AF than the placebo group (5.55% vs. 6.74%; P=0.048) (5).

Rationale
  • Both ACE inhibitors and ARBs inhibit the fibrotic and arrhythmogenic activity of angiotensin and decrease the risk for new-onset AF.

Treat high-risk patients undergoing cardiac surgery with preoperative β-blockers or amiodarone to reduce the incidence of postoperative AF. 
  • In patients who are undergoing cardiac surgery and are at high risk for postoperative AF, treat with one of the following:

    • β-blockers

    • Sotalol

    • Amiodarone

Evidence
  • A 2013 Cochrane review of interventions to prevent postoperative AF in patients undergoing heart surgery included 118 studies. Compared with control, β-blockers (OR, 0.33 [CI, 0.26 to 0.43]), sotalol (OR, 0.34 [CI, 26 to 43]), amiodarone (OR, 0.43 [CI, 0.34 to 0.54]), atrial pacing (OR, 0.47 [CI, 0.36 to 0.61]), magnesium (OR, 0.55 [CI, 0.41 to 0.73]), and posterior pericardotomy (OR, 0.35 [CI, 0.18 to 0.67]) all reduced the rate of postoperative AF (6).

  • The PAPABEAR trial was a randomized trial comparing a 13-day perioperative course of oral amiodarone with placebo in patients undergoing coronary artery bypass grafting or valve surgery. The amiodarone group had lower rates of postoperative tachyarrhythmias (mostly AF) (16.1% vs. 29.5%; P<0.001); the difference was seen in all patient subgroups. More patients in the amiodarone group had adverse effects (11.4% vs. 5.3%; P=0.008), mostly from bradycardia and QT prolongation. Perioperative complications did not differ between the groups (7).

  • A prospective study evaluated rates of AF in 1254 patients in sinus rhythm undergoing cardiac surgery. AF occurred in 13.6% of patients. In the multivariate analysis, risk factors for AF included preoperative LVH (OR, 2.37), intraoperative (OR, 2.05) or postoperative (OR, 1.62) inotrope use, and bicaval cannulation (OR, 1.83). Protective factors included age older than 50 years (OR, 0.51) and smoking (OR, 0.63) (8).

Rationale
  • The incidence of atrial arrhythmias, including AF, after open-heart surgery is between 20% and 50%.

  • Amiodarone, β-blockers, sotalol, magnesium, and nonmedical therapies decrease the rate of developing postoperative AF.

Use the history and physical exam to assess for clinical symptoms consistent with a diagnosis of AF and cardiovascular risk factors associated with AF. 
  • Characterize the presenting symptoms and assess their consistency with a diagnosis of AF.

  • Ask about

    • Palpitation or irregular heartbeats

    • Syncope or lightheadedness, dyspnea, angina, indigestion or other chest discomfort

    • Association with exercise, emotional stress, polyuria or daytime onset (adrenergically mediated AF)

    • Association with rest, eating, alcohol ingestion, or nocturnal onset (vagally mediated AF)

  • Determine the onset of the first symptomatic attack or the date of discovery of AF.

  • Document the frequency, duration, precipitating factors, and modes of termination of the symptoms.

  • Discuss the response to any drugs that have been administered.

  • Understand that the risk for developing AF increases with age, doubling with each decade of life.

  • Document cardiac conditions associated with AF:

    • Hypertension

    • Structural heart disease associated with atrial enlargement (e.g., valvular heart disease, hypertrophic cardiomyopathy, congenital heart disease)

    • Coronary artery disease

    • Heart failure

    • Pericardial disease

    • Recent cardiac procedures (cardiac surgery, catheter-based procedures)

  • Determine the presence of a characteristic irregular cardiac rhythm and other cardiac abnormalities.

  • See table Causes of AF.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF noted that AF often occurs in patients with underlying hypertension or structural heart disease, or both (1).

  • A 2012 systematic review of AF in patients with acute MI included 24 studies. Patients with AF were at increased risk for mortality compared with those in sinus rhythm (OR, 2.00 [CI, 1.93 to 2.08]), and the risk was higher in those with new AF than in those with previous AF (9).

  • The prospective Framingham Heart Study assessed risk factors for AF in a cohort of patients aged 55 to 94 years. In the multivariate model, male sex (OR, 1.5), age (OR, 2.1 in men and 2.2 in women for every decade of age), diabetes (OR, 1.4 in men and 1.6 in women), HF (OR, 4.5 in men and 5.9 in women), and valvular disease (OR, 1.8 in men and 3.4 in women) were associated with AF. In men (OR, 1.4) but not women, history of MI was associated with AF (10).

  • A prospective study evaluated rates of AF in 1254 patients in sinus rhythm undergoing cardiac surgery. AF occurred in 13.6% of patients. In the multivariate analysis, risk factors for AF included preoperative LVH (OR, 2.37), intraoperative (OR, 2.05) or postoperative (OR, 1.62) inotrope use, and bicaval cannulation (OR, 1.83). Protective factors included age older than 50 years (OR, 0.51) and smoking (OR, 0.63) (8).

  • A population-based longitudinal study of risk factors for cardiovascular disease included 5201 men and women aged 65 and older. At the baseline examination, the prevalence of AF was 4.8% in women and 6.2% in men. In the multivariate analysis, AF was associated with older age (OR 1.03 for every 7 years), HF (OR, 2.67), valvular heart disease (OR, 3.27), and stroke (OR, 1.57) (11).

Rationale
  • AF may be triggered by either cardiac or noncardiac disorders.

  • Atrial abnormalities, such as inflammation or fibrosis, provide a substrate for the arrhythmia.

  • The onset of AF is often triggered by acute or chronic increases in atrial wall tension, changes in autonomic tone, ectopic atrial foci, or other factors, such as pericarditis or myocarditis.

Comments
  • Paroxysmal supraventricular tachycardia reentry, atrial flutter, atrial tachycardia, and even ventricular tachycardia may degenerate into AF (12; 13; 14; 15).

  • A retrospective, population-based cohort study evaluated the impact of AF on prognosis in patients with severe sepsis. Among hospitalized patients, new AF was more common among patients with severe sepsis (5.9%) than among those without severe sepsis (0.65%) (OR, 6.82 [CI, 6.54 to 7.11]). Compared with patients with severe sepsis and no AF, those with AF were at increased risk for in-hospital stroke (OR, 2.70 [CI, 2.05 to 3.57]) and in-hospital mortality (OR, 1.07 [CI, 1.04 to 1.11]) (16).

Use the history and physical examination to assess for symptoms and signs of noncardiac conditions associated with AF. 
  • Document a history of noncardiac conditions associated with AF:

    • Hyperthyroidism

    • Pulmonary diseases and their treatment and sequelae, such as

      • COPD, pulmonary infection, pulmonary hypertension, or sleep apnea

      • Adrenergic stimulation due to inhaled or oral β-adrenergic agonists

      • Acid-base abnormalities or hypokalemia promoted by respiratory alkalosis

    • Hypoxia of any cause

    • Diabetes

    • Obesity

    • Previous embolic events

    • Sleep deprivation

    • Use of alcohol

    • Use of caffeine, adrenergic stimulants, and drugs, such as cocaine and amphetamines

    • Situations leading to increased adrenergic stimulation, such as with pain or in a surgical postprocedure period

  • Focus the physical examination on assessing for these conditions.

  • See table Causes of AF.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF recommended asking patients with possible AF about symptom pattern and predisposing conditions (1).

  • A 2011 systematic review of the relationship between alcohol consumption and AF included 14 studies. The risk for AF was higher in patients at the highest level of alcohol intake compared with the lowest level (OR, 1.5 [CI, 1.3 to 1.7]) (17).

  • A prospective cohort study evaluated the relationship between subclinical hyperthyroidism and AF in 2007 men and women aged 60 and older who were followed for 10 years. The incidence of AF was higher among patients with subclinical hyperthyroidism (28%) compared with those with normal thyroid function (11%), with an adjusted RR of 3.1 (CI, 1.7 to 5.5) (18).

  • A cross-sectional study evaluated thyroid function in 40 consecutive patients with isolated AF. Overall, 12.5% had occult thyrotoxicosis (19).

  • A prospective cohort study evaluated the association between subclinical hyperthyroidism and AF in 1426 patients with normal TSH levels who were followed for a median of 8 years. There were 105 patients who developed AF (7.4%). In the multivariate analysis, TSH level was associated with developing AF (adjusted HR, 1.94 [CI, 1.13 to 3.34] for the lowest compared with the highest TSH quartile). There was a similar trend for free T4 but it was not significant (20).

  • A study used prospective cohort data from the Framingham study to evaluate the association between obesity and the risk for AF in 5282 men and women without AF. After a mean follow-up time of 13.7 years, 10% of participants (and 9.8% of women) developed AF. AF was associated with obesity in both men (adjusted HR, 1.52 [CI, 1.09 to 2.13]) and women (adjusted HR, 1.46 [CI, 1.03 to 2.07]) (21).

Rationale
  • Details of underlying diseases affect management of AF.

Comments
  • The mechanisms by which alcohol exposure and intoxication precipitate AF is unclear but may be mediated by increases in circulating catecholamines, changes in conduction velocity or refractory periods in the myocardium, and variations in vagal tone (22; 23; 24).

  • Cardioversion is often unsuccessful in patients with thyrotoxicosis before restoration of a euthyroid state (25).

Obtain an ECG and diagnose AF when there are absent P-waves and an irregular ventricular response. 
  • Obtain a resting ECG to verify AF and check for

    • P-waves in all leads; look for P-waves within deformed T-waves or ST-segments if they appear to be absent

    • LVH

    • P-wave duration and morphology or fibrillatory waves

    • Pre-excitation (delta waves)

    • Bundle-branch block

    • Previous MI

    • Other atrial arrhythmias

  • Obtain a long rhythm strip (with multiple lead combinations) to evaluate irregular rhythms.

  • Diagnose AF when there are absent P-waves and an irregular ventricular response.

  • Understand that computer-generated ECG interpretations may be inaccurate.

  • Recognize that

    • P-wave amplitude can be decreased in patients with COPD or electrolyte imbalance

    • The following rhythms can be confused with AF:

      • Marked sinus arrhythmia

      • Premature atrial or ventricular contractions or fusion beats

      • Sick sinus syndrome with junctional escape beats

      • Coarse AF resembling atrial flutter

      • Slow atrial flutter with variable block

      • Multifocal atrial tachycardia in patients with COPD

      • Irregular ventricular tachycardia

      • Digitalis-toxic rhythms, such as atrial tachycardia with block or irregular junctional tachycardia

      • Wandering atrial pacemaker

      • Pre-excited supraventricular tachycardia

  • In patients with intermittent symptoms, consider continuous ambulatory cardiac monitoring or cardiac event monitoring.

    • In patients with daily paroxysmal symptoms, consider 24- or 48-hour continuous ambulatory ECG monitoring

    • Continuous monitoring for 24 to 48 hours may be beneficial even in patients who are asymptomatic during that period because it may reveal an abnormal underlying rhythm or episodes of asymptomatic dysrhythmia

    • In patients with less frequent symptoms, consider cardiac event monitoring:

      • Event monitors are typically worn for weeks at a time, and rhythm data may be transmitted transtelephonically

      • Some monitors continuously record the cardiac rhythm for analysis after a symptomatic event, recording the preceding and event rhythm, although these usually require chest leads

      • Other monitor types record only after triggering by the patient in response to symptoms and record only the postevent rhythm, although they may not require chest leads

  • See table Differential Diagnosis of Arrhythmias Often Confused with AF.

  • See figure Atrial Fibrillation.

  • See figure Atrial Fibrillation Associated with Bypass Pathway.

  • See figure Atrial Fibrillation with Regularized Ventricular Response.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF recommended ECG to make the diagnosis of AF, and noted that ECG signs of AF include replacement of P-waves by oscillatory waves, with an irregular, often rapid, ventricular response. The guideline recommended Holter monitoring or event recording if the diagnosis of AF is unclear (1).

  • A cross-sectional study evaluated the frequency of asymptomatic arrhythmias in 22 patients with symptomatic paroxysmal AF and symptomatic supraventricular tachycardia who underwent 24-hour continuous ambulatory ECG monitoring. Among patients with paroxysmal AF, there were more asymptomatic events than symptomatic events (mean 62.5 per 100 days/patient vs. 5.2 per 100 days/patient; P<0.01) (26).

Rationale
  • Symptoms alone are not diagnostic of AF as many arrhythmias and other medical conditions can mimic AF. Furthermore, many patients with AF are asymptomatic.

  • Diagnosis of AF requires ECG documentation of the arrhythmia.

Comments
  • Symptoms may be due to rapid ventricular rate, the irregular ventricular response to AF, or loss of the atrial contribution to ventricular filling (27).

Obtain pulse oximetry and laboratory testing for TSH levels and renal and liver function in all patients suspected of or likely to have AF. 
Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF recommended blood testing including thyroid, renal, and hepatic tests for patients diagnosed with AF (1).

  • A cross-sectional study performed testing for TSH level in 726 patients with newly diagnosed AF. A TSH level <0.1 mU/L was found in 0.7% of patients, and a TSH level below the normal range but ≥0.1 mU/L was found in 4.7% (28).

Rationale
  • Selected studies may help confirm the diagnosis of AF, determine its etiology, and optimize management.

Comments
  • Cardioversion is often unsuccessful in patients with thyrotoxicosis before restoration of a euthyroid state, and the ventricular response rate can be difficult to control (25).

Obtain a transthoracic echocardiogram in most patients with newly discovered AF, with additional testing as needed. 
  • Obtain a transthoracic echocardiogram if there is no known structural cardiac disease or no recent study for other indications. Look for

    • Left and right atrial size

    • Left ventricular size and function

    • Peak right ventricular pressure (for pulmonary hypertension)

    • LVH

    • Left atrial thrombus (although sensitivity is low)

    • Pericardial abnormalities

  • Consider other studies as part of the evaluation of a patient with AF:

    • TEE if transthoracic images are inadequate to assess for clinically relevant structural heart disease, or before planned early cardioversion to exclude left atrial appendage thrombus

    • Chest radiography for an underlying pulmonary process, if suspected

    • Stress testing to assess exercise-induced symptoms or for suspected ischemia

    • Electrophysiologic tests to evaluate tachycardia of unclear origin

    • Imaging for diagnosis of pulmonary embolism, if suspected based on the clinical circumstances

    • Evaluation for obstructive sleep apnea or nocturnal hypoxia, if suspected

  • See table Laboratory Studies for Patients with New-Onset or Suspected AF.

  • See table Causes of AF.

  • See table Differential Diagnosis of Arrhythmias Often Confused with AF.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF recommended a transthoracic ECG in all patients with AF to assess a variety of factors, plus additional tests in some patients, including a TEE to assess LV thrombus, exercise testing to reproduce exercise-induced AF or to evaluate ischemia, event monitors in patients with intermittent symptoms, and electrophysiologic studies if the diagnosis of a wide-complex tachycardia is unclear (1).

Rationale
  • Selected studies may help confirm the diagnosis of AF, determine its etiology, and optimize management.

Characterize AF as paroxysmal, persistent, or permanent. 
  • Use clinical measures and ECG data to characterize a patient's AF syndrome:

    • Paroxysmal: episodes of AF that typically last less than 24 hours and terminate spontaneously

    • Persistent: continuous AF that persists longer than 1 week

    • Long-standing persistent: continuous AF that persists longer than 12 months

    • Permanent: continuous AF that has usually persisted longer than 1 year, when the patient and physician have decided to accept continuation of AF

  • Classify patients based on their most frequent presentation, noting that

    • A given patient may progress from one category to another (i.e., paroxysmal to persistent to permanent)

    • Termination of AF with drug therapy or direct-current cardioversion does not change the initial designation

    • Descriptions of AF syndromes do not apply to patients with a reversible cause of the arrhythmia

  • Note that atrial flutter commonly accompanies AF and that patients may transition between atrial flutter and AF. In some cases it is difficult to distinguish AF from flutter on the ECG (sometimes referred to as AF/flutter).

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF discussed classification systems for primary AF and recommended that AF be classified as paroxysmal, persistent, long-standing persistent, or permanent (1).

  • A retrospective cohort study evaluated prognosis in 46 patients initially diagnosed with lone AF. The mean duration of follow-up was 27 years and the mean age at diagnosis was 46 years. Half of patients had a cardiovascular or cerebrovascular event, including 15% who had strokes. The rate of mortality was lower than the expected population-based rate and the rate of stroke was the same as the expected rate (29).

Rationale
  • Classification of AF may help understand the clinical course and management options.

Comments
  • The term “lone AF” generally refers to patients younger than age 60 without comorbid cardiopulmonary conditions, including hypertension.

Consider consultation with appropriate specialists when the diagnosis of AF is unclear or the arrhythmia occurs in a patient with significant underlying heart disease. 
  • Consult a cardiologist if

    • There is confusion about the diagnosis of the arrhythmia.

    • There are significant cardiac factors underlying the arrhythmia that may benefit from cardiologist input.

Evidence
  • Consensus.

Rationale
  • Accurate diagnosis of the arrhythmia and its cause are essential for effective management.

Consider consultation with appropriate subspecialists for assistance in diagnosing and managing noncardiac disease that may underlie AF. 
  • Consider consulting an endocrinologist to help in the diagnosis of hyperthyroidism in patients with AF.

  • Consider consulting a pulmonologist to help in the diagnosis of severe pulmonary disease in patients with AF.

Evidence
  • Consensus.

Rationale
  • Treatment of patients with underlying noncardiac disorders with AF is essential in the management of the arrhythmia.

Consult a cardiologist when the patient does not respond to initial therapy. 
  • Consider consulting a cardiologist for

    • Failure to adequately control the ventricular rate during paroxysmal AF or when a single AV-nodal blocking agent in usual dosage fails to control the rate

    • Selection of the initial method of cardioversion or optimal antiarrhythmic agent

    • Decisions on duration of antiarrhythmic or anticoagulant therapy

    • Suspected side effects of antiarrhythmic therapy

    • Recurrent AF requiring a change in therapy

    • AF complicating acute MI, in which case the best strategy may be acute reperfusion

    • Evaluation of underlying tachycardias thought to cause AF and requiring ablation

    • Wolff-Parkinson-White or other pre-excitation syndrome associated with AF, in which case ablation may be useful

    • Consideration of non-drug therapy:

      • Catheter ablation of atrial flutter

      • Pacemaker therapy to prevent AF recurrence

      • AV-node ablation and pacemaker implantation for rate control of AF

      • Catheter ablation of AF

      • Surgical ablation of AF

Evidence
  • Consensus.

Rationale
  • Management of AF is complicated, involving both drug and non-drug treatments with narrow risk-to-benefit ratios and sometimes specialized invasive procedures.

Comments
  • For complex or symptomatic patients with AF, especially those with LV dysfunction or when considering specific types of non-drug therapy, consider consultation with a subspecialist in electrophysiology.

Consult a cardiologist when specialized procedures are required. 
  • Consider cardiology consultation

    • Electrical or pharmacologic cardioversion

    • TEE

    • Non-drug interventions

      • AV-node ablation and pacemaker insertion for rate control of AF

      • Catheter-based ablation of AF

      • Pacemaker therapy to prevent recurrent AF

Evidence
  • A 2006 ACC/AHA clinical competence statement on invasive electrophysiology studies, catheter ablation, and cardioversion specified the education, training, and skills needed to perform cardiac procedures and discussed assessment of competence (30).

Rationale
  • All invasive non-drug therapies for AF involve inherent risk and require special training and experience.

Hospitalize patients with AF when diagnosis and management require close monitoring for optimal patient safety. 
  • Hospitalize patients with AF in the following situations:

    • When the underlying arrhythmia is potentially associated with hemodynamic instability

    • When AF is associated with another condition warranting hospitalization (acute stroke, TIA, MI, pulmonary embolism, sepsis, etc.)

    • When AF is associated with altered mental status, angina, decompensated HF, or hypotension

    • For telemetry monitoring during initiation of certain antiarrhythmic drugs for prevention of recurrent AF

    • When patients require specialized procedures, such as cardiac catheterization, electrophysiological studies, catheter ablation, pacemakers or implantable defibrillators, or surgery to abolish arrhythmogenic foci

Evidence
  • Consensus.

Rationale
  • The goal of hospitalizing high-risk patients with AF is to provide rapid relief of symptoms, ensure optimal management of underlying disorders, and prevent subsequent additional morbidity and mortality.

Comments
  • AF is especially deleterious when cardiac output is dependent on the atrial contribution to ventricular filling or a preserved diastolic filling interval, as in hypertensive heart disease, hypertrophic cardiomyopathy (31), or conditions associated with ventricular hypertrophy, such as aortic stenosis.

  • AF, particularly with poor ventricular rate control, is an important cause of “occult” HF (32).

Control the ventricular rate in all patients with AF using β-blockers and/or nondihydropyridine calcium-channel blockers as first-line agents for most patients.  
  • Control the ventricular rate in patients with AF:

    • Use a β-blocking agent, such as metoprolol, bisoprolol, or atenolol, or a nondihydropyridine calcium-channel blocker, such as diltiazem or verapamil, as first-line therapy

    • Target ventricular rates between 60 and 80 bpm at rest and between 90 and 115 bpm during moderate exercise

    • Use intravenous therapy in the hospital in patients who are extremely symptomatic or hemodynamically unstable and oral therapy in stable patients

  • Do not use digitalis as a single agent for rate control in ambulatory patients with AF, although digitalis can be combined with other agents for rate control, particularly for patients with LV dysfunction or sedentary lifestyles.

  • In patients with AF associated with pre-excitation (Wolff-Parkinson-White),

    • Do not use calcium-channel blockers, β-blocking agents, or cardiac glycosides

    • Consider class I or class III antiarrhythmic drugs in hemodynamically stable patients

    • Use direct-current cardioversion in unstable patients and catheter-based ablation for immediate cardioversion

  • Recognize that rate control may be more difficult to achieve in patients with HF; those patients may require AV nodal ablation and permanent pacemaker implantation.

  • See table Drugs for Rate Control in AF.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF recommended targeting a resting heart rate of <80 bpm for most patients but stated that a lenient rate control strategy (target HR <110 bpm) is also reasonable. The guideline recommended using a β-blocker or non-dihydropyridone calcium-channel blocker to control heart rate in most patients and using intravenous formulations of those drugs in the acute setting. The guideline recommended intravenous amiodarone to control heart rate in critically ill patients with HF and no accessory pathway, or if other interventions are unsuccessful. The guideline noted that digoxin should not be first-line therapy but can be combined with other therapies to control resting heart rate (1).

  • A 2000 systematic review of drugs to control ventricular rate in patients with AF included 45 studies evaluating 17 different drugs. Compared with placebo, diltiazem and verapamil reduced heart rate with preserved or improved exercise tolerance. Seven of 12 comparisons found that β-blockers controlled resting heart rate and nadolol and atenolol appeared to have the best efficacy. Digoxin controlled heart rate at rest in 7 of 8 studies but did not control heart rate with exercise in any studies (33).

  • A 2010 randomized trial evaluated strict (heart rate <80 bpm at rest and <110 bpm with exercise) compared with lenient (heart rate <110 bpm) rate control in 614 patients with AF. There was no difference between the groups in rates of the primary outcome of cardiovascular death, HF hospitalization, stroke, systemic embolism, bleeding, or life-threatening arrhythmia over 2 years, but the achieved mean heart rates in both groups were below 100 bpm and differed by only 10 bpm (34; 35).

  • A randomized trial compared esmolol with diltiazem (both intravenous) in 64 patients with postoperative supraventricular tachycardias, 80% of whom had AF. After 12 hours, rates of conversion to sinus rhythm were 85% in the esmolol group and 62% in the diltiazem group (P=0.116). Mean ventricular rates were similar in both groups, and rates of intensive care unit length of stay and in-hospital mortality did not differ significantly (36).

  • A case series described 10 patients with severe LV dysfunction and rapid AF. With control of ventricular rate (and restoration of sinus rhythm in half), ejection fraction returned to normal or near-normal in all patients (32).

  • A 2004 narrative review discussed drugs for control of heart rate in AF (37).

Rationale
  • Controlling the ventricular rate in patients with AF reduces symptoms and promotes hemodynamic stability.

  • Although digoxin may be useful as an adjunct to β-blockers or calcium-channel blockers, it is slower in onset, potentially more toxic, and less effective in controlling the ventricular rate during exercise.

  • In AF associated with pre-excitation syndromes (such as Wolff-Parkinson-White syndrome), conduction over the AV bypass tract will not slow in response to AV-blocking agents and may accelerate in some cases, requiring different agents for rate control.

  • A tachycardia-related cardiomyopathy can develop if rapidly conducted AF is allowed to persist.

Comments
  • New-onset AF often occurs in conjunction with acute illness and consequent increase in levels of circulating catecholamines; in this situation, digoxin is not as efficacious and digoxin-toxic ventricular arrhythmias may occur (38; 39).

  • Although tight control of heart rate was not superior to lenient control, it may improve symptoms in some patients.

Use a risk stratification tool, such as CHADS2 or CHA2DS2-VASc, to determine the long-term thromboembolic risk. 
  • Estimate the long-term thromboembolic risk and determine the need for systemic anticoagulation using a risk stratification tool, such as CHADS2 or CHA2DS2-VASc, the presence of underlying heart disease, and the presence or absence of certain comorbid conditions.

  • Note that when considering the thromboembolic risk,

    • Factors associated with highest risk are previous thromboembolism, rheumatic mitral stenosis, and mechanical prosthetic heart valves

    • Moderate risk factors include age 75 years or older, hypertension, HF, impaired LV systolic function, and diabetes mellitus

    • Less validated risk factors are age 65 to 74 years, female sex, and CAD

  • Be aware that

    • CHADS2 assigns 1 point each to

      • Congestive heart failure history

      • Hypertension

      • Age 75 years or older

      • Diabetes

    • CHADS2 assigns 2 points for

      • Previous stroke

      • Other systemic thromboembolic event

    • Points are totaled to generate an overall score; patients with 0 points are considered to be at low risk for stroke and those with 2 or more points are considered to be at high risk

    • The CHA2DS2-VASc differs from CHADS2 in assigning an additional point for age older than 75 years and adds a point each for female sex and the presence of vascular disease. CHA2DS2-VASc classifies fewer patients as low risk (score of 0)

  • See Published Risk-Stratification Schemes for Primary Prevention of Thromboembolism in Patients With Nonvalvular Atrial Fibrillation.

  • See table Drugs for Antithrombotic Therapy in AF.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF recommended using the CHA2DS2-VASc score to assess the risk for stroke in patients with AF (1).

  • A 2008 review compared the predictive performance of 12 clinical instruments to assess risk for thromboembolism in AF based on clinical features (40).

  • A 2001 study validated the CHADS2 risk-assessment instrument as a predictor of stroke risk in patients with AF. The study compared the performance of CHADS2 and older risk-assessment instruments in a cohort of 1733 Medicare beneficiaries with nonvalvular AF who were not prescribed warfarin. Over 2121 patient-years of follow-up, the CHADS2 instrument predicted stroke more accurately (c-statistic, 0.82) than older classification schemes (c-statistic, 0.68 to 0.74). Stroke risks were 1.9 events per 100 person-years (CI, 1.2 to 3.0) for patients with 0 points, 2.8 events per 100 person-years (CI, 2.0 to 3.8) for patients with 1 point, 4.0 events per 100 person-years (CI, 3.1 to 5.1) for patients with 2 points, 5.9 events per 100 person-years (CI, 4.6 to 7.3) for patients with 3 points, and 18.2 events per 100 person-years (CI, 10.5 to 27.4) in patients with the maximum 6 points (41).

  • A retrospective cohort study validated the accuracy of the CHA2DS2-VASc score and compared it with the CHADS2 score in 74,000 patients with AF from a national database in Denmark. Patients classified as low-risk (score of 0) with CHA2DS2-VASc and CHADS2 had stroke rates of 0.78 per 100 person-years (CI, 0.58 to 1.04) and 1.67 per 100 person-years (CI, 1.47 to 1.89), respectively. Patients classified as intermediate-risk (score of 1) with CHA2DS2-VASc and CHADS2 had stroke rates of 2.01 per 100 person-years (CI, 1.70 to 2.36) and 4.75 per 100 person-years (CI, 4.45 to 5.07), respectively (42).

  • A pooled analysis of patients from 5 randomized trials assessed risk factors for stroke in patients with AF. In the multivariate analysis, significant risk factors for stroke included previous stroke or TIA (RR, 2.5), hypertension (RR, 1.6), diabetes (RR, 1.7), HF (RR, 1.4), and age (43).

Rationale
  • In addition to the established risk factors for thromboembolism, specific features of AF and underlying disease modulate risk for thromboembolism.

  • Patients with reversible causes of AF and those with structurally normal hearts are less likely to have persistent or recurrent episodes and may be at lower risk for thromboembolism; however, the rate of stroke in patients with nonvalvular AF and additional risk factors exceeds that of hemorrhage from long-term anticoagulation.

Comments
  • The annual risk for thromboembolism is 5% in patients with nonvalvular AF if all patients are considered together, and the risk for stroke is higher in patients older than 75 years (43).

  • Nearly one-third of patients with AF are at low risk and may be treated with aspirin alone. Another third are at high risk and require anticoagulation, and the other third are at moderate risk, warranting therapy guided by patient preferences, access to high-quality anticoagulation monitoring, and other factors (44).

  • Patients with atrial flutter may be at a greater risk for thromboembolism than previously thought.

  • The SPAF-1 trial showed a 42% reduction in ischemic stroke and systemic embolism with aspirin, at a dose of 325 mg daily compared with placebo, but warfarin therapy reduced the incidence of primary events by 67% (45). SPAF II directly compared aspirin at this dose with warfarin in patients younger and older than 75. Primary endpoints occurred in 1.9% of the aspirin and 1.3% of the warfarin-treated patients in the younger group and in 4.8% and 3.6%, respectively, of in the older group, neither of which was statistically significant (SPAF Atrial Fibrillation Investigators, 1994). SPAF III compared standard-dose warfarin to aspirin plus “low intensity” warfarin (INR, 1.2 to 1.5) in patients with at least one risk factor, but the trial was stopped prematurely because of the excess rates of ischemic stroke and systemic embolism in the combination therapy group (7.9%) vs. the standard-dose warfarin groups (1.9%), with similar rates of major bleeding.

Provide long-term oral antithrombotic therapy for all patients with AF using aspirin, warfarin, a direct thrombin inhibitor, or a factor Xa inhibitor. 
  • For patients without risk factors or with a CHADS2 or CHA2DS2-Vasc score of 0,

    • Treat with aspirin

    • Use a dose of 81 to 325 mg daily

    • Note that among patients with aspirin allergy or intolerance, other antiplatelet agents, such as the thienopyridine drugs, may be considered but have not been studied as single agents for this indication

    • Consider not providing any antithrombotic therapy for patients with lone AF

  • For patients with moderate or severe risk factors for stroke, or with a CHADS2 or CHA2DS2-Vasc score of 2 or more,

    • Begin treatment at the time of initial diagnosis

    • Select among warfarin, direct thrombin inhibitors, and factor Xa inhibitors

    • If using warfarin, target an INR of 2 to 3 so as not to load the drug at the onset of therapy

  • For patients with a CHADS2 or CHA2DS2-Vasc score of 1, consider aspirin or anticoagulation with warfarin or other agents, using anticoagulation in patients who are not at increased risk for bleeding.

  • See Published Risk-Stratification Schemes for Primary Prevention of Thromboembolism in Patients With Nonvalvular Atrial Fibrillation.

  • See table Drugs for Antithrombotic Therapy in AF.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF recommended anticoagulation for patients with AF and prior stroke, prior TIA, or a CHA2DS2-VASc score ≥2. The guideline recommended the following options for anticoagulation: warfarin (with goal INR 2 to 3), dabigatran, rivaroxaban, or apixaban. The guideline also recommended anticoagulation for atrial flutter (1).

  • A 2013 guideline from the European Heart Rhythm Association provided detailed advice for the management of newer anticoagulant therapy in patients with AF (46).

  • A 2014 guideline from the American Academy of Neurology on the prevention of stroke in nonvalvular atrial fibrillation recommended informing patients that antithrombotic medication can reduce the risk of stroke and discussing the balance of potential benefits and harms. The guideline recommended using a risk-stratification algorithm to identify patients who need antithrombotic medication, and recommended choosing among warfarin, dabigatran, rivaroxaban, apixaban, and triflusal for patients at higher risk, noting that aspirin or even no therapy may be appropriate for patients at the lowest risk (47).

  • A 2007 Cochrane review of anticoagulants vs. antiplatelet medication for primary prevention of thrombotic events in patients with nonvalvular AF included 8 randomized trials comparing warfarin with aspirin, with a mean follow-up time of 1.9 years. Warfarin was associated with a lower risk for stroke (OR, 0.68 [CI, 0.54 to 0.85]) and ischemic stroke (OR, 0.53 [CI, 0.41 to 0.68]) and a higher risk for intracranial hemorrhage (OR, 1.98 [CI, 1.20 to 3.28]) (48).

  • A 2007 systematic review of antithrombotic and antiplatelet therapy for AF included 29 studies with 28,000 participants. Compared with placebo, warfarin (RR, 0.36 [CI, 0.26 to 0.51]; adjusted RR, 2.7%/year) and aspirin (RR, 0.78 [CI, 0.60 to 0.98]; adjusted RR, 0.7%/year) reduced stroke. Warfarin was superior to aspirin, with an RR of 0.62 (CI, 0,48 to 0.82). The risk for intracranial hemorrhage was approximately twice as high with warfarin as with aspirin (49).

  • A 2006 systematic review of aspirin, warfarin, and ximelagatran for the prevention of stroke in patients with nonvalvular AF included 13 trials with 14,000 participants. Warfarin reduced the risk for stroke or embolism compared with aspirin (RR, 0.59 [CI, 0.40 to 0.86]) and placebo (RR, 0.33 [CI, 0.24 to 0.45]), but the risk for bleeding was lower with aspirin (RR, 0.58) or placebo (RR, 0.45). Ximelagatran was equivalent to warfarin for stroke prevention (RR, 1.04 [CI, 0.77 to 1.40]), with a lower risk for major bleeding (RR, 0.74 [CI, 0.56 to 0.96]). Warfarin reduced mortality compared with placebo (RR, 0.69 [CI, 0.53 to 0.89]) but not compared with other therapies (50).

  • A 2009 systematic review of the quality of warfarin therapy in patients with AF included 8 studies. Overall, patients on warfarin were in the therapeutic range a mean of 55% (CI, 51% to 58%) of the time, with patients cared for in the community spending less time in the therapeutic range than those cared for in anticoagulation clinics (51).

  • The RE-LY trial was a randomized noninferiority trial comparing dabigatran with warfarin in patients with AF. After a median follow-up time of 2 years, rates of stroke or systolic embolism were 1.69% per year in the warfarin group, 1.53% in the dabigatran 110-mg group (RR compared with warfarin, 0.91 [CI, 0.74 to 1.11]) and 1.11% in the dabigatran 150-mg group (RR, 0.66 [CI, 0.53 to 0.82]). Overall, dabigatran met criteria noninferiority. Rates of major bleeding were lower in the 110-mg dabigatran group (2.71% per year) than in the warfarin group (3.36% per year) but similar to warfarin in the 150-mg dabigatran group (3.11% per year) (52).

  • The ARISTOTLE trial was a randomized noninferiority trial comparing apixaban with warfarin in patients with AF and at least 1 additional risk factor for stroke. The primary outcome was stroke or systemic embolism. After a mean follow-up time of 1.8 years, fewer patients in the apixaban group had stroke or embolism (1.27%/year vs. 1.60%/year; HR, 0.79 [CI, 0,66 to 0.95]), with less major bleeding (2.13%/year vs. 3.09%/year; HR, 0.69 [CI, 0.60 to 0.80]) and lower all-cause mortality (HR, 0.89 [CI, 0.80 to 0.99]) (53).

  • The ROCKET AF trial was a randomized noninferiority trial comparing rivaroxaban with warfarin in patients with AF at higher stroke risk (mean CHADS2 score, 3.5). Rivaroxaban was noninferior to warfarin for prevention of stroke/systemic embolism (HR, 0.88 [CI, 0.74 to 1.03]), with no significant difference in the risk for major bleeding (HR, 1.03 [CI, 0.96 to 1.11]) (54).

  • The AVERROES trial compared apixaban with aspirin in patients with AF who were at increased risk for stroke and for whom vitamin K antagonist therapy was not suitable. The study was stopped early, when the rate of stroke or systolic embolism was found to be lower in the apixaban group (1.8%) than in the aspirin group (4.0%, P<0.001), with similar rates of major bleeding (1.6% vs. 1.4%) (55).

  • A retrospective cohort study determined the risk for stroke in 59 patients with atrial flutter. After a mean follow-up time of 10 years, the rate of stroke was 32%, although nearly one-third of patients who had stroke had developed AF before the event. After adjustment for age and sex, patients with atrial flutter had a higher risk for stroke than those with AF (HR, 2.6 [CI, 1.2 to 5.3]) (56).

  • A retrospective, population-based cohort study evaluated the risk for bleeding in 100 patients with stroke and AF treated with warfarin. Major bleeding occurred in 41% of patients; risk factors included a history of hemorrhage before anticoagulation (57).

Rationale
  • In addition to the established risk factors for thromboembolism, specific features of AF and underlying disease modulate risk for thromboembolism.

  • Patients with reversible causes of AF and those with structurally normal hearts are less likely to have persistent or recurrent episodes and may be at lower risk for thromboembolism; however, the rate of stroke in patients with nonvalvular AF and additional risk factors exceeds that of hemorrhage from long-term anticoagulation.

  • Patients with atrial flutter may be at a greater risk for thromboembolism than previously thought.

  • Risk for thromboembolism may be lower in some patients within the first 48 hours of onset of AF.

  • There is less risk for bleeding complications with aspirin than warfarin, but it is less efficacious in decreasing thromboembolic risk.

Comments
  • Nearly one-third of patients with AF are at low risk and may be treated with aspirin alone. Another third are at high risk and require anticoagulation, and the other third are at moderate risk, warranting therapy guided by patient preferences, access to high-quality anticoagulation monitoring, and other factors (44).

  • Concurrent use of aspirin with another platelet inhibitor, such as clopidogrel, is more efficacious for prevention of thromboembolism than aspirin alone but is associated with a significantly greater risk for bleeding.

  • Concurrent use of aspirin or other platelet inhibitors with an anticoagulant (warfarin, dabigatran, or rivaroxaban) is associated with a significantly increased risk for bleeding and no appreciable benefit, except in patients with AF who sustain an acute coronary syndrome or have undergone coronary artery stenting.

  • In patients anticoagulated for AF with a clear indication for antiplatelet therapy (such as following coronary stent placement), concurrent therapy is appropriate for the duration of that indication but is associated with a relatively high risk for bleeding.

  • The risk for stroke remains elevated after cardioversion for up to 2 to 3 weeks (58; 59).

Assess the risks and benefits of a long-term rate-control vs. rhythm-control strategy in a patient with persistent or permanent AF. 
  • Determine whether rate control or rhythm control is the better long-term management strategy:

    • Consider a rhythm-control approach in younger individuals and those with symptoms not ameliorated by a rate-control strategy

    • Consider a rate-control approach in patients with multiple comorbidities or a longer duration of AF

    • Discuss risks, benefits, and expected outcomes of cardioversion and attempts to maintain sinus rhythm with the patient to individualize decisions about whether to pursue a rate- or rhythm-control strategy

  • In patients in whom rhythm control is chosen,

    • Consult a cardiologist with expertise in the management of antiarrhythmic therapy

    • Assess thromboembolic risk and treat appropriately, assuming the patient will remain at risk

    • Consider the need to continue rate-controlling medications in case AF should recur

    • With the exception of amiodarone, initiate antiarrhythmic therapy in a monitored inpatient setting because of the risk for bradycardia or ventricular proarrhythmic toxicity

  • Consider as-needed treatment with an antiarrhythmic agent (“pill-in-the-pocket”) management with propafenone or flecainide for certain patients with AF, such as recurrent, symptomatic paroxysmal episodes in low-risk patients.

  • See table Antiarrhythmics for AF.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF stated that both rate-control and rhythm-control strategies are reasonable, and stated that rhythm control might be preferable in younger patients, particularly those with lone AF, and that rate control might be a reasonable initial approach in older patients with comorbid conditions. The guideline stated that dofetilide, flecainide, propafenone, amiodarone, and intravenous ibutilide are reasonable drugs to use for cardioversion in hospital settings and that propafenone or flecainide are reasonable to use outside the hospital once it has been shown to be safe in a particular patient in a monitored setting (1).

  • A 2005 systematic review of rate control compared with rhythm control for patients with persistent or recurrent AF included 5 studies with 5239 participants. Mortality did not differ between the rate-control and rhythm-control groups, although there was a trend in favor of rate control (13.0% vs. 14.6%; OR, 0.87 [CI, 0.74 to 1.02]) (60).

  • A multicenter, randomized trial compared rhythm control with rate control in 1376 patients with AF and HF. After a mean follow-up time of 3 years, rates of cardiovascular death did not differ between the groups (27% in the rhythm-control group vs. 25% in the rate-control group; P=0.59). Rates of stroke and worsening HF were also similar in both groups (61).

  • A secondary analysis of a randomized trial compared rates of thromboembolism and bleeding in patients with paroxysmal AF and sustained AF who were enrolled in a randomized trial comparing anticoagulation with combined antiplatelet therapy with aspirin and clopidogrel for AF. Patients with paroxysmal AF had fewer comorbidities and lower mean CHADS2 scores (1.79 vs. 2.04) than those with sustained AF. The risk for thromboembolism was similar in the paroxysmal AF and sustained AF groups (2.0% per year vs. 2.2% per year; P=0.76) (62).

  • The ANDROMEDA trial was a randomized trial comparing dronedarone with placebo in patients with recently decompensated HF and depressed LV function. The study was stopped early due to increased mortality in the dronaderone group (63).

  • The PALLAS trial was a randomized trial comparing dronedarone with placebo in patients with permanent AF at high risk for major vascular events. The study was stopped early due to higher rates of HF, stroke, and death from cardiovascular causes in the dronaderone group (64).

Rationale
  • Several large trials have shown no clear benefit to a rhythm-control strategy compared with a rate-control approach on mortality or stroke rates and quality of life in an older patient population (older than 60 years).

  • Antiarrhythmic therapy may be useful to maintain sinus rhythm when the benefits outweigh risks.

  • Restoring sinus rhythm eliminates symptoms due to an irregular heartbeat and lack of atrial contribution to ventricular filling; however, some symptoms can be effectively eliminated by rate control.

  • The likelihood of converting to and maintaining sinus rhythm decreases with increasing duration of AF, but some patients with longstanding AF remain in sinus rhythm after cardioversion.

  • Patients in whom AF has been present for more than 2 years have a lower chance of remaining in sinus rhythm and, if not severely symptomatic, may be better left in AF with therapy aimed at controlling ventricular rate and preventing thromboembolism.

Consider electrical cardioversion in selected stable patients with AF in whom rhythm control is selected. 
  • Although rate control and long-term anticoagulation may be appropriate for a majority of older patients with new-onset AF, consider cardioversion for selected patients:

    • Those who remain symptomatic despite adequate rate control

    • Younger patients with structurally normal hearts and a first episode of AF

    • Those with AF secondary to another medical disorder that has been corrected without spontaneous resumption of sinus rhythm

  • Discuss with the patient risks, benefits, and expected outcomes of cardioversion.

  • Note that

    • Cardioversion may be performed pharmacologically or electrically

    • Electrical cardioversion requires general anesthesia but more rapidly restores sinus rhythm, decreases the time of required monitoring, and may be effective in patients with longer-term AF compared with pharmacologic cardioversion

  • In patients in whom elective cardioversion is considered,

    • Consider treatment with antiarrhythmic drugs before electrical cardioversion, especially if previous cardioversion was followed by early recurrence of AF

    • Establish and continue measures to control heart rate, unless bradycardia develops when sinus rhythm is present

    • For those with a known onset of AF within 48 hours of presentation and low or intermediate risk for thromboembolism, start anticoagulation at the time of diagnosis and continue anticoagulation for at least 4 weeks after cardioversion

    • For those with an onset of AF beginning more than 48 hours previously, or when the onset of the arrhythmia is unknown, administer anticoagulation for at least 3 weeks before and at least 4 weeks after cardioversion

    • Alternatively, for those with onset of AF more than 48 hours previously or when the onset of the arrhythmia is unknown, perform TEE to exclude thrombus in the left atrium or appendage, and if none is identified, carry out cardioversion after anticoagulation and continue anticoagulation for at least 4 weeks after TEE-guided cardioversion

  • Base decisions on anticoagulation beyond 4 weeks after cardioversion on the patient's long-term risk for thromboembolism.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF recommended electrical cardioversion for the restoration of sinus rhythm (1).

  • A 2005 Cochrane review of electrical cardioversion compared with rate control in patients with AF included 3 randomized trials with 927 participants. Mortality was similar with both strategies (OR, 0.83 [CI, 0.48 to 1.43]) with a trend toward more strokes in the cardioversion group (OR, 1.9 [CI, 0.99 to 3.64]) (65).

  • A randomized trial compared TEE-guided therapy with usual care in 1222 patients with AF of more than 2 days' duration. Embolic events did not differ between the groups (0.8% in the TEE group vs. 0.5% in the control group; P=0.50); rates of hemorrhagic events were lower in the TEE group (2.9% vs. 5.5%; P=0.03). At 8 weeks, the groups had similar proportions of patients in sinus rhythm (66).

  • A post-hoc analysis of the RE-LY trial data demonstrated that the incidence of stroke, systemic embolism, and death were similar in the dabigatran-treated and warfarin-treated patients who underwent cardioversion or AF ablation (67).

Rationale
  • Although it requires general anesthesia, electrical cardioversion requires a shorter time to restore sinus rhythm, poses a lower risk for ventricular proarrhythmia, and requires less prolonged telemetry monitoring than chemical cardioversion.

Comments
  • Unfractionated heparin has been studied for anticoagulating patients for cardioversion after TEE, but oral anticoagulants, particularly dabigatran, are likely to be efficacious as well.

  • Antiarrhythmic therapy before electrical cardioversion may not improve the efficacy of cardioversion; however, the defibrillation threshold may be lowered with sotalol or ibutilide.

  • Patients with AF for less than 48 hours are the easiest to cardiovert and most likely to remain in sinus rhythm (68; 69).

  • TEE detects left atrial thrombus, spontaneous echocontrast, reduced left atrial appendage flow velocity, and complex atherosclerotic plaque in the aorta, all of which are associated with risk for thromboembolism (70).

Consider chemical cardioversion in selected patients with AF, generally using flecainide, propafenone, dofetilide, or ibutilide to restore sinus rhythm. 
  • Although rate control and long-term anticoagulation are recommended for most patients with AF, consider cardioversion in the following selected patients:

    • Those who remain symptomatic despite adequate rate control

    • Younger patients with structurally normal hearts and a first episode of AF

    • Those with AF secondary to another medical disorder that has been corrected without spontaneous return to sinus rhythm

  • Discuss with the patient risks, benefits, and expected outcomes of cardioversion.

  • Note that pharmacological cardioversion obviates the need for anesthesia but is less effective and exposes the patient to potential drug toxicity.

  • If pharmacological cardioversion is chosen,

    • Perform pharmacologic cardioversion in a monitored setting to assess rate control, bradycardia, ventricular proarrhythmic toxicity, and other adverse drug effects

    • Institute measures to control heart rate increases associated with AF and continue them through elective cardioversion

    • Consider consulting a cardiologist with expertise in antiarrhythmic therapy when choosing an antiarrhythmic agent

    • Once treatment is initiated, monitor the patient for QT prolongation (QTc >550 ms or more than 130% of baseline QT interval) and for ventricular arrhythmias, especially when class Ic and class III agents are used

  • When choosing a specific drug,

    • Note that the choice of the medication for cardioversion may be influenced by the decision to pursue a long-term rhythm-control strategy

    • Use flecainide (Vaughan Williams class Ic), propafenone (class Ic), dofetilide (class III), and ibutilide (class III) for pharmacologic cardioversion in most patients, particularly in patients with AF of short duration (<1 week)

    • Note that class Ic antiarrhythmic drugs for restoration and maintenance of sinus rhythm are contraindicated in patients with AF who have ischemic heart disease or LV dysfunction

    • Consider intravenous amiodarone (class III) for pharmacologic cardioversion of AF in patients with structural heart disease when rapid restoration of sinus rhythm is not required

  • Note that a single oral bolus of flecainide (class Ic) or propafenone (class Ic) (“pill in the pocket”) can be administered to terminate AF outside the hospital once treatment has proved safe in the hospital for selected patients who do not have significant structural or conduction system disease.

  • See table Antiarrhythmics for AF.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF stated that both rate-control and rhythm-control strategies are reasonable, and stated that rhythm control might be preferable in younger patients, particularly those with lone AF, and that rate control might be a reasonable initial approach in older patients with comorbid conditions. The guideline stated that dofetilide, flecainide, propafenone, amiodarone, and intravenous ibutilide are reasonable drugs to use for cardioversion in hospital settings and that propafenone or flecainide are reasonable to use outside the hospital once it has been shown to be safe in a particular patient in a monitored setting (1).

  • A 2005 Cochrane review of pharmacologic cardioversion compared with rate control for patients with AF included 2 randomized trials. There was no difference in mortality between the groups (RR, 1.14 [CI, 1.00 to 1.31]), but the rhythm-control group had higher rates of hospitalization and adverse events (71).

  • A 2003 systematic review of amiodarone compared with placebo and class Ic drugs for conversion of AF to sinus rhythm included 13 studies. At 24 hours, amiodarone resulted in higher rates of sinus rhythm than placebo (RR, 1.44; P<0.001) and similar rates of sinus rhythm as class Ic drugs (RR, 0.95; P=0.50) (72).

  • A randomized trial compared dofetilide with placebo in 96 patients with AF or atrial flutter. The rate of conversion to sinus rhythm was higher in the dofetilide group (30.3% vs. 3.3%; P<0.006); 3% of patients in the dofetilide group had torsade de pointes (73).

  • A randomized trial compared flecainide, amiodarone, and placebo in 98 patients with recent-onset AF. Within 2 hours, conversion to sinus rhythm occurred in 59% of patients in the flecainide group, 34% in the amiodarone group, and 22% in the placebo group (P value for flecainide vs. placebo= 0.005). After 8 hours, rates of sinus rhythm did not differ among the treatment groups (74).

  • A randomized trial compared ibutilide with placebo in 266 patients with sustained AF or atrial flutter. The rate of reversion to sinus rhythm was higher in the ibutilide group (47% vs. 2%; P<0.0001) (75).

  • A retrospective cohort study described outcomes in 417 consecutive patients admitted to a hospital for chemical cardioversion of AF. Overall, 13.4% of drug trials were complicated by adverse cardiac events, including bradycardia in 7.9%, QT prolongation in 1.5%, and ventricular arrhythmias in 1.3% (76).

  • A cohort study evaluated the safety and efficacy of a rhythm-control strategy using intermittent doses of flecainide or propafenone to terminate the arrhythmia at the time of onset (“pill in the pocket”) in 210 low-risk patients with recurrent episodes of AF. After a mean follow-up time of 15 months, 79% of patients had at least one episode of arrhythmia, of which 92% were treated within a mean of 36 minutes after symptom onset. Treatment successfully restored sinus rhythm in 94% of episodes; adverse events occurred in 7% of patients, including 1 patient with rapid atrial flutter (77).

  • A 2003 narrative review discussed the relative efficacies of drugs for converting and maintaining sinus rhythm in AF (78).

Rationale
  • In contrast to electrical cardioversion, pharmacological cardioversion obviates the need for anesthesia but is less effective and exposes the patient to potentially toxic drugs.

  • Adverse effects of antiarrhythmic drugs include ventricular proarrhythmia, pulmonary toxicity, thyroid disease, and hepatotoxicity.

Comments
  • Be aware that quinidine (class Ia) and procainamide (class Ia), commonly used in the past, are no longer preferred for cardioversion because of lower efficacy compared with other agents and greater potential for side effects.

  • Care must be taken in selecting an antiarrhythmic for cardioversion in specific patient populations, including those with ischemic heart disease, HF, and structural heart disease, because of potential complications in these populations.

  • Ibutilide is typically used in electrophysiology laboratories because of potential adverse electrophysiologic effects (79; 80).

  • ACE inhibitors or angiotensin-II receptor blockers may decrease the incidence of AF and risk for recurrent AF after cardioversion (81; 82).

Provide medication to maintain sinus rhythm after cardioversion. 
  • If rhythm control is attempted, choose an antiarrhythmic drug for maintenance of sinus rhythm after considering the patient's comorbidities:

    • In patients with structurally normal hearts, consider flecainide (class Ic), propafenone (class Ic), amiodarone (class III), dronedarone (class III), sotalol (class III), or dofetilide (class III) as treatment options

    • For patients with underlying structural heart disease, consider amiodarone (class III), sotalol (class III), or dofetilide (class III)

    • In patients with HF, do not use flecainide (class Ic), propafenone (class Ic), dronedarone (class III), or sotalol (class III)

    • In patients with ischemic heart disease, do not use flecainide (class Ic) or propafenone (class Ic)

  • Consider treatment with ACE inhibitors to maintain sinus rhythm in patients with other potential indications for the drugs.

  • See table Antiarrhythmics for AF.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF stated that both rate-control and rhythm-control strategies are reasonable. After electrical or chemical cardioversion, the guideline recommended amiodarone, dronaderone, dofetilide, flecainide, propafenone, or sotalol to maintain sinus rhythm and recommended using amiodarone only after consideration of its potential harms (1).

  • A 2012 Cochrane review of antiarrhythmics to maintain sinus rhythm compared with control (rate control, placebo, or no therapy) after cardioversion in patients with AF included 56 studies with over 20,000 participants. Class Ia drugs (quinidine and disopyramide) (OR, 2.39 [CI, 1.03 to 5.59]; NNH, 109) and sotalol (OR, 2.47 [CI, 1.02 to 5.05]); NNH, 166) increased mortality compared with control; other drugs did not significantly impact mortality. Class Ic drugs (flecainide, propafonone) (OR, 0.36 [CI, 0.28 to 0.45]), class III drugs (amiodarone, dronaderone) (OR, 0.46 [CI, 0.42 to 0.51]), and metoprolol (OR, 0.62 [CI, 0.44 to 0.88]) reduced recurrence of AF. All drugs had more withdrawals due to adverse events than control, and all but amiodarone, dronaderone, and propafenone increased other arrhythmias (83).

  • A 2005 systematic review of ACE inhibitors and angiotensin-II receptor blockers to prevent AF included 11 studies with 56,000 participants. Both drug classes decreased overall rates of AF (RR, 72%). In patients who underwent cardioversion for AF, ACE inhibitors and angiotensin-II receptor blockers reduced recurrence of AF with a relative risk reduction of 48% (CI, 21% to 65%) (84).

Rationale
  • Medication can help maintain sinus rhythm in patients who undergo cardioversion.

Comments
  • Recurrence of AF is likely even when effective antiarrhythmic drugs are used. Only about 50% of patients treated with antiarrhythmic drugs remain free of recurrent AF at 6 months; efficacy may be better with amiodarone than with other therapies. By 4 years, the rates of arrhythmia-free survival are less than 10% without vs. 30% with antiarrhythmic drug therapy. In preventing recurrent episodes of AF, sotalol or amiodarone offer the advantage of providing rate control because they depress AV nodal conduction (85; 74).

Consider catheter ablation in patients with AF who remain symptomatic or have other AF complications despite cardioversion and drug therapy. 
  • Consider catheter-based ablation of the AV node and implantation of a ventricular pacemaker when drug therapy does not adequately control the ventricular rate.

  • Consider radiofrequency catheter ablation to maintain sinus rhythm in patients with significantly symptomatic AF.

  • For patients undergoing cardiac surgery for other conditions, consider the “maze” procedure, in which multiple atrial incisions electrically isolate conduction pathways and reduce the effective size of the left atrium to prevent AF.

  • Note that permanent pacemaker placement may be necessary in patients with the sick sinus syndrome (tachycardia-bradycardia syndrome) accompanying AF.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF stated that catheter ablation is a reasonable option for preventing recurrent AF in patients with symptomatic persistent or intermittent AF who do not tolerate antiarrhythmic medication (1).

  • A 2012 HRS/EHRA/ECAS guideline on catheter and surgical ablation of AF recommended catheter ablation in patients with persistent AF refractory to at least one antiarrhythmic medication and stated that the use of catheter ablation as a first-line therapy is reasonable (86).

  • A 2012 Cochrane review of catheter ablation for AF included 32 studies with 3560 participants. Included studies were generally small and quality was poor. Compared with medical therapy, ablation reduced AF recurrence (RR, 0.27 [CI, 0.18 to 0.41]), but pooling of studies was done in spite of heterogeneity. There was no mortality difference between ablation and control (RR, 0.50 [CI, 0.04 to 5.65]) (87).

  • A 2009 systematic review of catheter ablation compared with medical therapy for AF included 108 studies. Patients in the ablation group were more likely to maintain sinus rhythm (OR, 3.46 [CI, 1.97 to 6.09]) based on moderate-quality evidence. There was poor-quality evidence suggesting better quality of life in the ablation group (88).

  • A randomized trial compared AV-nodal ablation and pacing with medical therapy in 66 patients with HF and chronic AF. After 1 year, among patients who completed the study, those in the ablation group had fewer palpitations and less exertional dyspnea (89).

  • A randomized trial compared AV-nodal ablation with pacing with medical therapy in 56 patients with continued rapid AF despite drug therapy. Overall symptoms (41% difference, P=<0.01), palpitations (58% difference, P=0.0001), and dyspnea (37% difference, P<0.05) were all better in the ablation arm (90).

  • A randomized trial compared radiofrequency ablation to antiarrhythmic drugs in 70 patients with symptomatic AF who had never taken antiarrhythmic medication. After 1 year, the ablation group had a lower likelihood of AF recurrence (13% vs. 63%; P<0.001) and fewer hospitalizations (9% vs. 54%; P<0.001). There were no thromboembolic events in either group (91).

  • A randomized trial compared pulmonary vein isolation to AV-nodal ablation with pacing in 81 patients with drug-resistant AF, symptomatic HF, and decreased LV function. At 6 months, patients with the pulmonary vein isolation had better quality of life, a longer 6-minute walk distance, and a higher ejection fraction (35% vs. 28%; P<0.001) (92).

  • A 2000 narrative review of the surgical “maze” procedure in carefully selected patients cited efficacy of 99% in preventing recurrent AF. Other experience has shown a mortality rate with this operation ranging from 1 to 3% (93).

Rationale
  • These invasive approaches are useful in selected patients with symptomatic AF who have not responded to pharmacological therapy.

Comments
  • Radiofrequency catheter ablation isolates and disrupts electrical activity at the base of the pulmonary vein.

  • Catheter ablation has been most robustly validated in patients who have failed treatment with an antiarrhythmic drug, have normal or mildly dilated left atria, normal or mildly reduced LV function and no severe pulmonary disease but may benefit other patients as well.

  • Pacemaker therapy can be useful to allow for full medical treatment of AF that occurs in the patients with sick sinus syndrome when bradyarrhythmias would otherwise preclude antiarrhythmic or β-blocker medication.

  • The effect of atrial-based pacing (vs. ventricular-only pacing) on AF is controversial; data from a multicenter, randomized trial in patients with AV block suggest that single-chamber pacing does not alter the incidence of AF compared with dual-chamber pacing (94).

  • Anecdotal evidence suggests that DDD pacing prevents AF in some patients with sick sinus syndrome. Randomized trials of atrial pacing (AAI and DDD vs. ventricular pacing) demonstrated benefit in avoiding AF. Although less well tested, atrial pacing may help some patients who already have AF (95; 96).

Perform emergent electrical cardioversion in patients with AF who are hemodynamically unstable. 
  • Admit hemodynamically unstable patients with AF to a monitored acute care setting for emergent treatment of the arrhythmia.

  • Begin anticoagulation as soon as possible in patients undergoing emergent cardioversion and continue for at least 4 weeks after cardioversion; base decisions regarding longer-term antithrombotic therapy on assessment of overall risk when patients are stable.

Evidence
  • The 2014 ACCF/AHA/HRS guideline on the management of AF recommended electrical cardioversion for patients with AF and hemodynamic instability or myocardial ischemia. The guideline recommended that stable patients with AF of unknown duration or duration >48 hours receive anticoagulation for 3 weeks before cardioversion and for 4 weeks after, and that those who are unstable and require urgent cardioversion receive heparin, followed by 4 weeks of anticoagulation after cardioversion (1).

  • A 1995 systematic review of the effect of TEE to risk-assess patients before cardioversion for AF included 25 studies that either used TEE (without anticoagulation for patients in whom thrombus was not detected) or performed cardioversion with anticoagulation. Patients who received TEE had higher rates of embolic events than those who were anticoagulated (1.34% vs. 0.33%; P=0.04), and TEE patients had similar rates of embolism as those who were not anticoagulated (97).

  • A cross-sectional study measured levels of cardiac biomarkers in 72 patients who underwent electrical cardioversion. Ten percent of patients had creatine kinase-MB levels meeting criteria for myocardial injury, myoglobin was elevated in 56% of patients, and levels of troponins were infrequently elevated (98).

  • A 1998 narrative review suggested that TEE may be helpful in defining underlying structural heart disease and assessing risk for thromboembolic complications of urgent cardioversion (99).

Rationale
  • AF with a very rapid ventricular response or loss of the atrial contribution to ventricular filling may cause severe hemodynamic disturbances in patients with underlying structural heart disease.

Comments
  • Cardioversion is especially useful when cardiac output is dependent on the atrial contribution to ventricular filling or preserved diastolic interval, as in patients with hypertensive heart disease, hypertrophic cardiomyopathy (31), or other conditions associated with ventricular hypertrophy, such as aortic stenosis.

  • Electrical cardioversion is typically performed under general anesthesia using short-acting agents and mask-assisted ventilation. An external defibrillator, set to R-wave-synchronous mode, is used to deliver direct-current energy through pads or handheld electrodes placed on the chest wall. The delivered energy is set to 100 to 400 J for monophasic defibrillators and less for biphasic defibrillators.

Provide patients with adequate information to allow them to participate in the decisions regarding management of AF. 
  • Address the following issues in advising patients about AF:

    • That AF is a chronic disease that may require lifelong management

    • Reasonable expectations regarding the results of therapy, e.g., that drug therapy is usually intended to reduce the frequency of AF episodes but may not eliminate all episodes

    • Symptoms that should be reported promptly, including rapid palpitation, lightheadedness, presyncope or syncope, worsening effort intolerance (signifying recurrent AF with inadequate rate control), bruising (signifying excessive anticoagulation), or focal neurological symptoms suggesting stroke

    • Differences between rate-control and rhythm-control strategies for AF

    • Intent of each prescribed medication, e.g., anticoagulation for stroke prevention does not alter symptoms or frequency of AF

    • Importance of adherence to the medical regimen because of the extremely narrow risk-benefit ratios for drugs prescribed for AF, especially warfarin

  • Make patients aware of specific risks of individual antiarrhythmic and rate-control medications.

  • Consider using a validated decision aid to facilitate informed decision making.

Evidence
  • A randomized trial compared a patient decision aid regarding anticoagulation with usual care in 109 patients with AF. The decision aid group had less decisional conflict but were less likely to choose warfarin (100).

  • A study found that highly motivated participants in the SPAF-II trial who were provided with additional information about stroke risk and participated in the decisions about antithrombotic therapy were more knowledgeable and had more realistic expectations than the usual care group; however, satisfaction with care and adherence to assigned therapy did not differ between the two groups (101).

Rationale
  • The onset of AF increases risk for death (in large part related to stroke), medications used to treat AF may have dangerous side effects if not appropriately monitored, and patient participation in management can mitigate risk.

Comments
  • The onset of AF is marked by a two-fold increase in death, even when stratified for comorbid disease states (102).

Assess symptoms and efficacy of therapy in patients treated for AF. 
  • Assess the adequacy and tolerance of rate-control therapy:

    • Inquire about potential medication side effects of drugs used for rate control

    • Ask about palpitation, lightheadedness, and dyspnea

    • Ask about dizziness with standing, presyncope, or syncope

    • Assess blood pressure, orthostatic changes, and the heart rate both at rest and during or after exertion

    • Seek to maintain heart rate within the physiologic range (generally 60 to 100 bpm)

    • Because drugs used for rate control may affect blood pressure, evaluate for symptomatic or orthostatic hypotension

    • Consider ambulatory cardiac rhythm monitoring to assess for tachycardia or bradycardia associated with therapy

  • Evaluate for therapeutic effect and potential complications of antiplatelet or anticoagulant medication:

    • Monitor for evidence of bleeding or other potential complications of therapy

    • For patients receiving warfarin, maintain the INR between 2 and 3, and monitor for bleeding

    • In patients treated with oral direct thrombin inhibitor or factor Xa inhibitor drugs, monitor adherence and assess for bleeding

  • In patients receiving antiarrhythmic therapy, assess for adequacy of treatment and side effects:

    • Evaluate for recurrent AF or need for intermittent therapy to suppress symptomatic episodes

    • Consider ambulatory rhythm monitoring when control is not clear

    • Reassess treatment, possibly with cardiologist input, when antiarrhythmic therapy has failed or produces unacceptable side effects

    • Continue rate-control therapy as needed and antithrombotic medication in patients receiving antiarrhythmic drug therapy

  • Assess for side effects of all treatments.

Evidence
  • A 2009 systematic review of the quality of warfarin therapy in patients with AF included 8 studies. Overall, patients on warfarin were in the therapeutic range a mean of 55% (CI, 51% to 58%) of the time, with patients cared for in the community spending less time in the therapeutic range than those cared for in anticoagulation clinics (51).

  • A retrospective chart review of 660 patients with AF managed by generalists found that 34.7% of eligible patients received warfarin. Among patients receiving warfarin, INR values were outside the target range half the time (103).

  • Ambulatory rhythm monitoring facilitates detection of asymptomatic AF and assessment of the adequacy of rate control (104).

  • Several studies have used ambulatory and transtelephonic cardiac rhythm monitoring to detect asymptomatic episodes of AF in ambulatory patients (26; 105; 106).

Rationale
  • The efficacy, benefit, and risks of restoring and maintaining sinus rhythm must be weighed against those of controlling the rate and assuring safe, therapeutic anticoagulation.

Comments
  • Once prescribed based on risk stratification, antithrombotic therapy is typically continued indefinitely in patients with AF.

  • No trial has proven that reducing the frequency and duration of episodes of AF reduces the risk for thromboembolism. In the AFFIRM study, the incidence of stroke was higher in the rhythm-control group, likely because warfarin therapy was stopped or the INR was subtherapeutic in asymptomatic patients thought to have adequate rhythm control. This finding points out the high frequency of recurrent asymptomatic AF and reinforces the importance of sustained anticoagulation of patients at risk (107).

  • Prolongation of the QT interval predisposes to torsades de pointes; QRS prolongation from class Ic agents may precede ventricular arrhythmias (108).

Table Grahic Jump Location
 Laboratory Studies for Patients with New-Onset or Suspected AF

Swipe to view table

TestNotes
Electrocardiogram and rhythm stripAssess for:
AF or other arrhythmias that resemble AF
Tachycardia (adrenergic excess, pulmonary embolism) ST-T wave and PR-segment abnormalities consistent with pericarditis
ST-T wave changes associated with acute MI or ischemia
QRS changes resembling Wolff-Parkinson-White syndrome or preexcitation
Evidence of underlying conduction system disease
Underlying atrial mechanism in patients with permanent pacemakers
Continuous ambulatory electrographic monitoringMay help evaluate paroxysmal or poorly defined symptoms consistent with AF
Cardiac event monitoringMay be useful in assessing symptoms occurring infrequently or those associated with other clinical symptoms, such as presyncope or syncope
Transthoracic echocardiographyPart of the initial evaluation of a patient with AF to assess chamber size, myocardial mass, ventricular function; presence/severity of valvular disease; pulmonary hypertension; atrial or ventricular septal defects; and acute or constrictive pericardial disease
Transesophageal echocardiographyProvides more detailed information on valvular function, septal defects, and atrial abnormalities and is the procedure of choice for evaluating for left atrial appendage thrombus before cardioversion
Sensitive TSH levelHigh sensitivity and specificity for hyperthyroidism. May be the only indication of thyrotoxicosis, particularly in the elderly
Serum electrolytes, BUN, and creatinineHypokalemia or other electrolyte imbalance can stimulate premature atrial contractions and potentiate AF
Digoxin level for patients receiving therapyElevated serum digoxin levels may cause heart block or arrhythmias (e.g., paroxysmal atrial or junctional tachycardia with block). Digitalis toxicity should be corrected before cardioversion to avoid ventricular arrhythmias. In practice, serum digoxin levels should be drawn no earlier than 12 to 24 hours after an oral dose to avoid falsely elevated readings
Complete blood countLeukocytosis may signify infection, and anemia may signify occult blood loss, which could accelerate during anticoagulation. Either infection or anemia could increase sympathetic tone
Chest x-rayEvaluate heart size, hyperinflation (COPD), infiltrates consistent with pulmonary edema or pneumonia, pleural effusion or cephalization consistent with HF, assess for patterns suggesting mitral stenosis, pulmonary hypertension, or congenital heart disease
Pulse oximetry/arterial blood gas analysisExclude hypoxemia or acute or chronic pulmonary thromboembolism as causes of AF in patients with pulmonary disorders or dyspnea. Consider exercise desaturation study to assess for exercise-related hypoxia if room air arterial oxygen saturation is normal
Pulmonary embolism protocol CT scanEvaluate for acute or chronic pulmonary thromboembolism or as part of work-up for pulmonary hypertension
Evaluation for nocturnal hypoxia, obstructive sleep apnea, or other sleep-disordered breathingPolysomnography or nocturnal oxygen saturation monitoring may be helpful to assess for hypoxia and other conditions that predispose to AF
Serum alcohol level or serum and urine toxicology screenEvaluate patients for alcohol or drug use, which may be an underlying cause of the arrhythmia
Fecal occult blood testingPerform before initiating heparin or warfarin to minimize bleeding risk, particularly in the elderly

AF = atrial fibrillation; BUN = blood urea nitrogen; COPD = chronic obstructive pulmonary disease; CT = computed tomography; HF = heart failure; MI = myocardial infarction; TSH = thyroid-stimulating hormone.

Table Grahic Jump Location
 Differential Diagnosis of Arrhythmias Often Confused with AF

Swipe to view table

DiseaseCharacteristics
AFAbsent P-waves, irregular ventricular response. Other abnormalities may be present
False designation of AF by computer ECG interpretationP-waves present, but misinterpreted by computer.
Look carefully in all leads for P-waves. Low amplitude P-waves (e.g., in hyperkalemia) or poor data quality can lead to incorrect diagnosis
Marked sinus arrhythmiaIrregularly irregular ventricular response, but P-waves obscured by rapid rate and preceding T-waves
Examine ST segments carefully for presence of P-waves; often they will deform T-waves
Frequent premature atrial or ventricular contractionsIrregularly irregular ventricular response, but P-waves present, premature beats may obscure P-waves
Identify P-waves in multiple leads for clarity of rhythm determination
Sick sinus syndrome with junctional escape beatsP-waves are present, but bradycardia permits junctional escape beats to occur, and simulates AF.
Look for P-waves associated with QRS complexes despite bradycardia
Coarse AFResembles aflutter, but ventricular response is not a consistent multiple of an atrial rate.
Tracing in lead V1 can resemble flutter waves, but no consistent P-waves seen in other leads, unlike true aflutter
Slow aflutter with variable AV blockCharacteristics of aflutter, but atrial rate slower than 300 beats/min and ventricular rate not divisor of 300.
Atrial rate slowed due to conduction system disease or antiarrhythmic drugs
Multifocal atrial tachycardiaIrregularly irregular ventricular response, but multiple (>3) morphologies of P-waves seen.
Characteristically seen in patients with COPD or with increased β-adrenergic stimulation (usually in context of treating bronchospasm)
Ventricular tachycardiaVT can be irregular.
Look for AV dissociation and fusion beats, QRS complexes >0.14 sec, which would favor VT
Digoxin toxicity-associated arrhythmiasParoxysmal atrial tachycardia with block, junctional tachycardia with Wenckebach characteristics.
Irregularly irregular rhythms rarely found in other disease states

AF = atrial fibrillation; AV = atrioventricular; COPD = chronic obstructive pulmonary disease; ECG = electrocardiography; VT = ventricular tachycardia.

Table Grahic Jump Location
 Drugs for Rate Control in AF

Swipe to view table

Drug or Drug ClassDosingSide EffectsPrecautionsClinical Use
FirstLineIconβ-blockersBradycardia, hypotension, AV block, bronchospasm (particularly if nonselective), CNS side effects, diarrhea, nauseaAvoid with Wolff-Parkinson-White syndrome. Caution with CKD, HF, hepatic disease, hyperthyroidism, depressionFirst-line agents for rate control
Esmolol (Brevibloc)500 mcg/kg·min IV loading dose over 1 min. Then 50 mcg/kg·min infusion for 4 min. May repeat q5min, and gradually increase infusion up to 200 mcg/kg·minInjection-site reactionsβ1 selective. Extremely short acting
blackboxiconMetoprolol (Lopressor)IV: 5 mg IV over 1-2 min, every 5 min prn, for up to 3 doses total. Oral (regular-release): 25-100 mg bidblackboxicon (oral): Abrupt withdrawal not advisedβ1 selective
blackboxiconNadolol (Corgard)20-120 mg qdblackboxicon Abrupt withdrawal not advisedNonselective. Longest half-life in class
blackboxiconPropranolol (Inderal)IV: 1-3 mg IV (1 mg/min). Second dose if needed after 2-3 min. Then, q4-6h prn. Oral (immediate-release): Initially 10-30 mg tid-qid, up to 80-240 mg total daily dose, dosed tid-qidblackboxicon (oral): Abrupt withdrawal not advisedNonselective
FirstLineIconNon-dihydropyridine calcium-channel blockersBradycardia, hypotension, AV block, edema, asystole, CNS side effectsAvoid with Wolff-Parkinson-White syndrome, advanced aortic stenosis. Caution with HF, hepatic disease, reflux esophagitis. In elderly, start with low doseFirst-line agents for rate control
Diltiazem (Cardizem)IV: 0.25 mg/kg IV over 2 min. After 15 min, may give 0.35 mg/kg IV over 2 min. Then, 5-15 mg/h infusion for maximum of 24 h. Oral (regular-release): 120-360 mg total daily dose, dosed tid-qidGI side effects
Verapamil (Calan)IV: 5-10 mg IV over 2 min. In 30 min, may give 10 mg IV. Oral (regular-release): 120-360 mg total daily dose, dosed tid-qidConstipation, allergic-type reactionsCaution with CKD, neuromuscular disease
Cardiac glycoside
Digoxin (Lanoxin)IV or tablet loading dose: Total of 10-15 mcg/kg, split into 3 divided doses q6-8h, with the first dose equal to half the total. IV maintenance dose: 125-350 mcg IV total daily dose, (depending on CrCl), dosed qd-bid. Tablet maintenance dose: 125-500 mcg qd, depending on CrClArrhythmias, bradycardia, AV block, GI side effects, CNS side effects, visual disturbancesAvoid with Wolff-Parkinson-White syndrome, ventricular fibrillation. Narrow therapeutic index and many drug interactions. Decrease dose in CKD. Caution with elderlyDo not use as a single agent for rate control

FirstLineIcon = first-line agent; blackboxicon = black box warning; AF = atrial fibrillation; AV = atrioventricular; bid = twice daily; CKD = chronic kidney disease; CNS = central nervous system; CrCl = creatinine clearance; CYP = cytochrome P450 GI = gastrointestinal; HF = heart failure; IV = intravenous; PO = oral; prn = as needed; q12h = every 12 hours; q4-6h = every 4-6 hours; qd = once daily; qid = four times daily; tid = three times daily.

ACP Smart Medicine provides key prescribing information for practitioners but is not intended to be a source of comprehensive drug information.

Table Grahic Jump Location
 Causes of AF

Swipe to view table

DiseaseCharacteristicsNotes
HyperthyroidismNot uncommonly associated with new onset AF. In the elderly, may present with few symptoms or signs (apathetic hyperthyroidism)Can be overlooked on initial or subsequent episodes of AF. Consider especially in patients with difficult to control ventricular rates
HypoxiaCan be subtle and may only be detected on exertionAn exercise desaturation study may be necessary to unmask
Ischemia/infarctionAF associated with ischemic mitral regurgitation (only present or worsening with ischemia) may be difficult to detect. Atrial ischemia or increases in LV end-diastolic (and left atrial) pressure during an MI may lead to AFUp to 15% of patients with an acute MI may develop AF
Structural heart disease (e.g., cardiomyopathies, CAD, valvular diseases, hypertension, congenital heart disease)Elevated LV end-diastolic pressure or associated mitral regurgitation can stimulate AF, as can elevated right atrial pressure due to atrial septal defect or pulmonary hypertensionAuscultation or echocardiography aid in diagnosis
Tachycardia-induced tachycardiaEspecially in younger children, consider other atrial tachycardias as stimuli for AF. In older patients, ventricular tachycardia can be the inciting rhythmMonitor rhythm strips or Holter or event monitors to assess type of arrhythmia present

AF = atrial fibrillation; CAD = coronary artery disease; LV = left ventricular; MI = myocardial infarction.

Table Grahic Jump Location
 Drugs for Antithrombotic Therapy in AF

Swipe to view table

Drug or Drug ClassDosingSide EffectsPrecautionsClinical Use
blackboxiconLow molecular weight heparinsBleeding, thrombocytopenia, elevated hepatic enzymes, injection-site reactions, allergic reactionsblackboxicon Spinal or epidural hematomas with neuraxial anesthesia or spinal puncture. Avoid with history of HIT, pork allergy. Monitor thrombocytopeniaInitial anticoagulation, then transition to warfarin
blackboxiconDalteparin (Fragmin)200 IU/kg SC qd or 100 IU/kg SC q12
blackboxiconEnoxaparin (Lovenox)1 mg/kg SC q12h or 1.5 mg/kg SC qdAnemia, fever, edema, nausea
blackboxiconTinzaparin (Innohep)175 IU/kg SC qdCaution with sulfite sensitivity
Factor Xa inhibitor
blackboxiconRivaroxaban (Xarelto)20 mg PO qd with PM mealBleeding, thrombocytopenia, elevated hepatic enzymes Muscle cramps, extremity pain, hypersensitivity reactionsblackboxicon Spinal or epidural hematomas with neuraxial anesthesia or spinal puncture. Stroke risk following discontinuation in AF patients. Avoid with CrCl<30, moderate hepatic disease. Caution with mild hepatic disease, elderly, CrCl 30-50Limited long-term efficacy or safety data
blackboxicon Apixaban (Eliquis)5 mg PO bid
2.5 mg bid with ≥2 of the following: age ≥80 years, weight ≤60 kg, creatinine ≥1.5 mg/dL
Bleedingblackboxicon Do not discontinue without adequate anticoagulation. Avoid with severe hepatic disease, strong dual inhibitors or inducers of CYP3A4 and P-glycoprotein. Caution with moderate hepatic diseaseLimited long-term efficacy or safety data.
Limited experience with the reduced dose of 2.5 mg bid.
Not recommended with prosthetic heart valves
Direct thrombin inhibitor
Dabigatran (Pradaxa)150 mg PO qdBleeding, GI side effectsDecrease dose if CrCl 15-30. Caution with P-glycoprotein inhibitionThe ecarin clotting time is a better test than aPTT. Alternative to long-term warfarin
Unfractionated heparin75 IU/kg IV bolus, then 1250 IU/h IV. Target aPTT 1.5-2Bleeding, thrombocytopenia, elevated hepatic enzymesAvoid with history of HIT, bovine or pork allergy. Monitor plateletsFor initiation of anticoagulation in the hospital
blackboxiconWarfarin(Coumadin)Initially, 5 mg PO qd. Adjust dose according to INR. Target INR 2-3. Continue heparin or LMWH until INR achieved for 2 days. Treat for 3 weeks before and at least 4 weeks after cardioversionBleeding, systemic cholesterol microembolization, uncommon skin necrosisblackboxicon Major or fatal bleeding. Avoid in pregnancy. Caution with idiopathic thrombocytopenic purpura, HIT, hepatic disease, protein C or S deficiency. Many drug interactionsUsed for long-term therapy. Monitor INR regularly
Platelet inhibitor
Aspirin81 mg qdGI side effects, hypersensitivity reactions, minor bleedingAvoid with severe hepatic disease or severe CKD. Caution with asthma, GI diseaseFor patients with very low risk for stroke or those with very high bleeding risk

FirstLineIcon = first-line agent; blackboxicon = black box warning; AF = atrial fibrillation; aPTT = activated partial thromboplastin time; bid = twice daily; CKD = chronic kidney disease; CrCl = creatinine clearance; CYP = cytochrome P450; GI = gastrointestinal; HF = heart failure; HIT = heparin-induced thrombocytopenia; INR = international normalized ratio; IV = intravenous; LMWH = low molecular weight heparin; LVD = left ventricular dysfunction; MI = myocardial infarction; PM = evening; PO = oral; prn = as needed; q12h = every 12 hours; q4-6h = every 4-6 hours; qd = once daily; qid = four times daily; SC = subcutaneous; tid = three times daily.

ACP Smart Medicine provides key prescribing information for practitioners but is not intended to be a source of comprehensive drug information.

Table Grahic Jump Location
 Antiarrhythmics for AF

Swipe to view table

Drug or Drug ClassDosingSide EffectsPrecautionsClinical Use
Class IaArrhythmias, QT prolongation and TdP, AV block, hypotensionCaution with HF
blackboxiconDisopyramide (Norpace, Norpace CR)Immediate-release: 200 mg q4-6h. Maximum total daily dose 800 mg. Extended-release: 200-400 mg q12hAnticholinergic effects, GI side effects, hypoglycemiablackboxicon Increased mortality. Avoid with myasthenia gravis, glaucoma, urinary retention. Decrease dose with CKD, elderly
blackboxiconProcainamideIV loading dose: 15-17 mg/kg IV infusion, infused at 20-30 mg/min. Or, 100 mg IV q5min slow IV push, up to 1000 mg maximum. IV maintenance: 1-4 mg/min (about 50 mg/kg/day) continuous IV infusion.Fever, hepatic injuryblackboxicon Positive ANA titer, proarrhythmic effects, hematological disorders. Avoid with peripheral neuropathy. Decrease dose with CKD, hepatic disease, reduced cardiac outputRarely used
blackboxiconQuinidineOral immediate-release: 200-300 mg q6-8h, maximum 600 mg q6h. Extended- release: 300 or 324 mg to 600 or 648 mg q8-12h. IM: 600 mg IM, then 400 mg IM q2h prn. IV: 800 mg IV in 50 mL D5W, at 1 mL/minGI side effects, syncope, visual impairment, hematologic effects, hypersensitivityblackboxicon Increased mortality. Avoid with myasthenia gravis. Decrease dose with hepatic disease, CrCl<10, elderlyRarely used
Class IcArrhythmias, QT prolongation and TdP, HF, AV block, bradycardia, dizziness, visual impairmentAvoid with structural heart disease, HF. Decrease dose with hepatic disease
blackboxicon Flecainide (Tambocor)50 mg q12h. May increase by 50 mg every 4 days. Maximum 300 mg total daily doseNausea, vomitingblackboxicon Increased mortality, ventricular proarrhythmic, hematological disorders, pulmonary fibrosis. Caution with CrCl<35
blackboxiconPropafenone (Rythmol, Rythmol SRImmediate-release: 150-300 mg q8h. Extended-release: 225 mg q12h. May increase every 5 days to maximum of 425 mg q12hGI side effects, metallic taste, dyspneablackboxicon Increased mortality. Avoid with bronchospastic disorders. Caution with CKD
Class IIIQT prolongation and TdP
blackboxiconAmiodarone (Cordarone, Pacerone, Nexterone)For cardioversion or maintenance of NSR: oral loading: 1.2-1.8 g total daily dose, given in divided doses, until 10 g total is given. Or, 600-800 mg total daily dose, dosed qd-bid, until a total of 10 g is given. Oral maintenance: 200-400 qd. IV loading: 5-7 mg/kg over 30-60 min, then 1.2-1.8 g/d continuous infusion, until a total of 10 g is given. For rate control: IV: 150 mg IV over 10 min, then 0.5-1 mg/min continuous infusion. Oral: 800 mg qd for 1 wk, then 600 mg qd for 1 wk, then 400 mg qd for 4-6 wks, then 200 mg qdHypotension, bradycardia, GI side effects, hematologic disorders, peripheral neuropathy, hypo- or hyperthyroidism, dermatologic reactions, including photosensitivity and blue-gray skin (long-term use), visual impairmentblackboxicon (oral): Pulmonary toxicity, hepatotoxicity, proarrhythmic. Only use for life-threatening arrhythmias. Avoid grapefruit juice. Avoid with iodine hypersensitivity, pregnancy. Decrease dose with hepatic disease, elderly. Caution with HF, LVD. Many drug interactions
blackboxiconDofetilide (Tikosyn)CrCl>60: 500 mcg bid. CrCl 40-60: 250 mcg bid. CrCl 20-39: 125 mcg bidHeadache, chest pain, dizzinessblackboxicon Cardiac monitoring required, caution with CKD, dofetilide training required. Avoid if CrCl<20.
blackboxiconDronedarone (Multaq)400 mg bid with AM and PM mealsBradycardia, GI side effects, dermatologic reactions, hepatotoxicityblackboxicon Avoid with decompensated HF or permanent AF. Avoid with severe hepatic disease (no data), pregnancy, strong CYP3A inhibitors. Caution with Asians
blackboxiconIbutilide (Corvert)For cardioversion: (adults >60 kg): 1 mg IV over 10 minutes. May repeat once prn. Adults <60 kg: 0.01 mg/kg IV over 10 minutes. May repeat once prnNausea, vomiting, headacheblackboxicon Fatal arrhythmias
blackboxiconSotalol (Betapace AF)Oral: Adults with CrCl>60: 80 mg bid. May increase every 3 days, up to 160 mg bid. Adults with CrCl 40-60: 80 mg qd. May increase every 5-6 days, up to 160 mg qd. IV: Adults with CrCl>60: 75 mg IV over 5 h bid. May increase every 3 days, up to 150 mg IV over 5 h bid. Adults with CrCl 40-60: 75 mg IV over 5 h qd. May increase every 5-6 days, up to 150 mg IV over 5 h qdBradycardia, hypotension, fatigue, dyspnea, hypoglycemiablackboxicon (IV): Life-threatening proarrhythmias. (oral): Cardiac monitoring required, caution with CKD. Only Betapace AF has the appropriate patient package insert (not Betapace). Clinical response, CrCl, heart rate and QTc must be evaluated before initiating or dose. Use IV only if oral not tolerated. Avoid with CrCl<40, bronchospastic disease, HF

FirstLineIcon = first-line agent; blackboxicon = black box warning; AF = atrial fibrillation; AM = morning; aPTT = activated partial thromboplastin time; AV = atrioventricular; bid = twice daily; CKD = chronic kidney disease; CNS = central nervous system; CrCl = creatinine clearance; CYP = cytochrome P450; GI = gastrointestinal; HF = heart failure; IM = intramuscular; INR = international normalized ratio; IV = intravenous; LVD = left ventricular dysfunction; MI = myocardial infarction; NSR = normal sinus rhythm; PM = evening; PO = oral; prn = as needed; q12h = every 12 hours; q4-6h = every 4-6 hours; qd = once daily; qid = four times daily; SC = subcutaneous; TdP = torsade de pointes; tid = three times daily.

ACP Smart Medicine provides key prescribing information for practitioners but is not intended to be a source of comprehensive drug information.

  • Atrial Fibrillation This electrocardiogram demonstrates atrial fibrillation. No clear P-waves are seen and the ventricular response is irregular.
  • Atrial Fibrillation Associated with Bypass Pathway The electrocardiogram demonstrates a rapid, irregular, wide-complex tachycardia with slight variations in the QRS morphology. No P-waves are evident and a delta-wave is best seen in leads V2 through V5. This is most consistent with atrial fibrillation with a bypass pathway, also known as preexcited atrial fibrillation or atrial fibrillation with accelerated conduction.
  • Atrial Fibrillation with Regularized Ventricular Response Electrocardiogram demonstrates course atrial fibrillation with a regularized ventricular response in addition to a premature ventricular contraction. These findings indicate a complete heart block with a junctional or ventricular escape rhythm, one of the rhythms that can be seen with digitalis toxicity.
January CT, Wann LS, Alpert JS, Calkins H, Cleveland JC, Cigarroa JE, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014 04 01 [Epub ahead of print]. (PMID: 24685669)
 
Fauchier L, Clementy N, Babuty D. Statin therapy and atrial fibrillation: systematic review and updated meta-analysis of published randomized controlled trials. Curr Opin Cardiol. 2013;28:7-18. (PMID: 23160338)
 
Schneider MP, Hua TA, Böhm M, Wachtell K, Kjeldsen SE, Schmieder RE. Prevention of atrial fibrillation by Renin-Angiotensin system inhibition a meta-analysis. J Am Coll Cardiol. 2010;55:2299-307. (PMID: 20488299)
 
Wachtell K, Lehto M, Gerdts E, Olsen MH, Hornestam B, Dahlöf B, et al. Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study. J Am Coll Cardiol. 2005;45:712-9. (PMID: 15734615)
 
Ducharme A, Swedberg K, Pfeffer MA, Cohen-Solal A, Granger CB, Maggioni AP, et al.; CHARM Investigators. Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. Am Heart J. 2006;152:86-92. (PMID: 16838426)
 
Arsenault KA, Yusuf AM, Crystal E, Healey JS, Morillo CA, Nair GM, et al. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev. 2013;(1):CD003611. (PMID: 23440790)
 
Mitchell LB, Exner DV, Wyse DG, Connolly CJ, Prystai GD, Bayes AJ, et al. Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve Replacement, or Repair: PAPABEAR: a randomized controlled trial. JAMA. 2005;294:3093-100. (PMID: 16380589)
 
Hashemzadeh K, Dehdilani M, Dehdilani M. Postoperative Atrial Fibrillation following Open Cardiac Surgery: Predisposing Factors and Complications. J Cardiovasc Thorac Res. 2013;5:101-7. (PMID: 24252985)
 
Angeli F, Reboldi G, Garofoli M, Ramundo E, Poltronieri C, Mazzotta G, et al. Atrial fibrillation and mortality in patients with acute myocardial infarction: a systematic overview and meta-analysis. Curr Cardiol Rep. 2012;14:601-10. (PMID: 22821004)
 
Benjamin EJ, Levy D, Vaziri SM, D’Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA. 1994;271:840-4. (PMID: 8114238)
 
Furberg CD, Psaty BM, Manolio TA, Gardin JM, Smith VE, Rautaharju PM. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol. 1994;74:236-41. (PMID: 8037127)
 
Prystowsky EN. Tachycardia-induced tachycardia: a mechanism of initiation of atrial fibrillation. In: DiMarco JP, Prystowsky EN, eds. Atrial Arrhythmias: State of the Art. Armonk, NY: Futura; 1995:81-95.
 
Hurwitz JL, German LD, Packer DL, Wharton JM, McCarthy EA, Wilkinson WE, et al. Occurrence of atrial fibrillation in patients with paroxysmal supraventricular tachycardia due to atrioventricular nodal reentry. Pacing Clin Electrophysiol. 1990;13:705-10. (PMID: 1695348)
 
Sung RJ, Castellanos A, Mallon SM, Bloom MG, Gelband H, Myerburg RJ. Mechanisms of spontaneous alternation between reciprocating tachycardia and atrial flutter-fibrillation in the Wolff-Parkinson-White syndrome. Circulation. 1977;56:409-16. (PMID: 884796)
 
Palma EC, Ferrick KJ, Gross JN, Kim SG, Fisher JD. Transition from atrioventricular node reentry tachycardia to atrial fibrillation begins in the pulmonary veins. Circulation. 2000;102:937. (PMID: 10952966)
 
Walkey AJ, Wiener RS, Ghobrial JM, Curtis LH, Benjamin EJ. Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis. JAMA. 2011;306:2248-54. (PMID: 22081378)
 
Kodama S, Saito K, Tanaka S, Horikawa C, Saito A, Heianza Y, et al. Alcohol consumption and risk of atrial fibrillation: a meta-analysis. J Am Coll Cardiol. 2011;57:427-36. (PMID: 21251583)
 
Sawin CT, Geller A, Wolf PA, Belanger AJ, Baker E, Bacharach P, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med. 1994;331:1249-52. (PMID: 7935681)
 
Ciaccheri M, Cecchi F, Arcangeli C, Dolara A, Zuppiroli A, Pieroni C. Occult thyrotoxicosis in patients with chronic and paroxysmal isolated atrial fibrillation. Clin Cardiol. 1984;7:413-6. (PMID: 6744697)
 
Heeringa J, Hoogendoorn EH, van der Deure WM, Hofman A, Peeters RP, Hop WC, et al. High-normal thyroid function and risk of atrial fibrillation: the Rotterdam study. Arch Intern Med. 2008;168:2219-24. (PMID: 19001198)
 
Wang TJ, Parise H, Levy D, D’Agostino RB, Wolf PA, Vasan RS, et al. Obesity and the risk of new-onset atrial fibrillation. JAMA. 2004;292:2471-7. (PMID: 15562125)
 
Coumel P. Autonomic influences in atrial tachyarrhythmias. J Cardiovasc Electrophysiol. 1996;7:999-1007. (PMID: 8894942)
 
Koskinen P, Kupari M, Leinonen H, Luomanmäki K. Alcohol and new onset atrial fibrillation: a case-control study of a current series. Br Heart J. 1987;57:468-73. (PMID: 3593617)
 
Mäki T, Toivonen L, Koskinen P, Näveri H, Härkönen M, Leinonen H. Effect of ethanol drinking, hangover, and exercise on adrenergic activity and heart rate variability in patients with a history of alcohol-induced atrial fibrillation. Am J Cardiol. 1998;82:317-22. (PMID: 9708660)
 
Predictors of thromboembolism in atrial fibrillation: I. Clinical features of patients at risk. The Stroke Prevention in Atrial Fibrillation Investigators. Ann Intern Med. 1992;116:1-5. [Full Text] (PMID: 1727091)
 
Page RL, Wilkinson WE, Clair WK, McCarthy EA, Pritchett EL. Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia. Circulation. 1994;89:224-7. (PMID: 8281651)
 
Naito M, David D, Michelson EL, Schaffenburg M, Dreifus LS. The hemodynamic consequences of cardiac arrhythmias: evaluation of the relative roles of abnormal atrioventricular sequencing, irregularity of ventricular rhythm and atrial fibrillation in a canine model. Am Heart J. 1983;106:284-91. (PMID: 6869209)
 
Krahn AD, Klein GJ, Kerr CR, Boone J, Sheldon R, Green M, et al. How useful is thyroid function testing in patients with recent-onset atrial fibrillation? The Canadian Registry of Atrial Fibrillation Investigators. Arch Intern Med. 1996;156:2221-4. (PMID: 8885821)
 
Osranek M, Bursi F, Bailey KR, Grossardt BR, Brown RD, Kopecky SL, et al. Left atrial volume predicts cardiovascular events in patients originally diagnosed with lone atrial fibrillation: three-decade follow-up. Eur Heart J. 2005;26:2556-61. (PMID: 16141257)
 
Tracy CM, Akhtar M, DiMarco JP, Packer DL, Weitz HH, Creager MA, et al.; Heart Rhythm Society. American College of Cardiology/American Heart Association 2006 update of the clinical competence statement on invasive electrophysiologystudies,catheterablation,andcardioversion: a report of the American College of Cardiology/American Heart Association/American College of Physicians Task Force on Clinical Competence and Training developed in collaboration with the Heart Rhythm Society. J Am Coll Cardiol. 2006;48:1503-17. (PMID: 17010821)
 
Maron BJ, Fananapazir L. Sudden cardiac death in hypertrophic cardiomyopathy. Circulation. 1992;85:I57-63. (PMID: 1728506)
 
Grogan M, Smith HC, Gersh BJ, Wood DL. Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy. Am J Cardiol. 1992;69:1570-3. (PMID: 1598871)
 
Segal JB, McNamara RL, Miller MR, Kim N, Goodman SN, Powe NR, et al. The evidence regarding the drugs used for ventricular rate control. J Fam Pract. 2000;49:47-59. (PMID: 10678340)
 
Van Gelder IC, Groenveld HF, Crijns HJ, Tuininga YS, Tijssen JG, Alings AM, et al.; RACE II Investigators. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010;362:1363-73. (PMID: 20231232)
 
Nieuwlaat R, Connolly SJ. ACP Journal Club. Lenient rate control is as effective as strict rate control for preventing cardiovascular events in AF. Ann Intern Med. 2010;153:JC2-4. [Full Text] (PMID: 20713783)
 
Balser JR, Martinez EA, Winters BD, Perdue PW, Clarke AW, Huang W, et al. Beta-adrenergic blockade accelerates conversion of postoperative supraventricular tachyarrhythmias. Anesthesiology. 1998;89:1052-9. (PMID: 9821992)
 
Tamariz LJ, Bass EB. Pharmacological rate control of atrial fibrillation. Cardiol Clin. 2004;22:35-45. (PMID: 14994846)
 
Rawles JM, Metcalfe MJ, Jennings K. Time of occurrence, duration, and ventricular rate of paroxysmal atrial fibrillation: the effect of digoxin. Br Heart J. 1990;63:225-7. (PMID: 2337493)
 
Beasley R, Smith DA, McHaffie DJ. Exercise heart rates at different serum digoxin concentrations in patients with atrial fibrillation. Br Med J (Clin Res Ed). 1985;290:9-11. (PMID: 3917348)
 
Stroke Risk in Atrial Fibrillation Working Group. Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation. Stroke. 2008;39:1901-10. (PMID: 18420954)
 
Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285:2864-70. (PMID: 11401607)
 
Olesen JB, Lip GY, Hansen ML, Hansen PR, Tolstrup JS, Lindhardsen J, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ. 2011;342:d124. (PMID: 21282258)
 
Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med. 1994;154:1449-57. (PMID: 8018000)
 
Hart RG, Halperin JL, Pearce LA, Anderson DC, Kronmal RA, McBride R, et al.; Stroke Prevention in Atrial Fibrillation Investigators. Lessons from the Stroke Prevention in Atrial Fibrillation trials. Ann Intern Med. 2003;138:831-8. [Full Text] (PMID: 12755555)
 
Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation. 1991;84:527-39. (PMID: 1860198)
 
Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al.; European Heart Rhythm Association. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013;15:625-51. (PMID: 23625942)
 
Culebras A, Messé SR, Chaturvedi S, Kase CS, Gronseth G. Summary of evidence-based guideline update: Prevention of stroke in nonvalvular atrial fibrillation: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014;82:716-24. (PMID: 24566225)
 
Aguilar MI, Hart R, Pearce LA. Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks. Cochrane Database Syst Rev. 2007;(3):CD006186. (PMID: 17636831)
 
Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857-67. [Full Text] (PMID: 17577005)
 
Lip GY, Edwards SJ. Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis. Thromb Res. 2006;118:321-33. (PMID: 16198396)
 
Baker WL, Cios DA, Sander SD, Coleman CI. Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States. J Manag Care Pharm. 2009;15:244-52. (PMID: 19326955)
 
Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al.; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51. (PMID: 19717844)
 
Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al.; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-92. (PMID: 21870978)
 
Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al.; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883-91. (PMID: 21830957)
 
Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, et al.; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806-17. (PMID: 21309657)
 
Halligan SC, Gersh BJ, Brown RD, Rosales AG, Munger TM, Shen WK, et al. The natural history of lone atrial flutter. Ann Intern Med. 2004;140:265-8. [Full Text] (PMID: 14970149)
 
Seet RC, Rabinstein AA, Christianson TJ, Petty GW, Brown RD. Bleeding complications associated with warfarin treatment in ischemic stroke patients with atrial fibrillation: a population-based cohort study. J Stroke Cerebrovasc Dis. 2013;22:561-9. (PMID: 23499334)
 
Berger M, Schweitzer P. Timing of thromboembolic events after electrical cardioversion of atrial fibrillation or flutter: a retrospective analysis. Am J Cardiol. 1998;82:1545-7, A8. (PMID: 9874066)
 
Fatkin D, Kuchar DL, Thorburn CW, Feneley MP. 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;23:307-16. (PMID: 8294679)
 
de Denus S, Sanoski CA, Carlsson J, Opolski G, Spinler SA. Rate vs rhythm control in patients with atrial fibrillation: a meta-analysis. Arch Intern Med. 2005;165:258-62. (PMID: 15710787)
 
Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, et al.; Atrial Fibrillation and Congestive Heart Failure Investigators. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008;358:2667-77. (PMID: 18565859)
 
Hohnloser SH, Pajitnev D, Pogue J, Healey JS, Pfeffer MA, Yusuf S, et al.; ACTIVE W Investigators. Incidence of stroke in paroxysmal versus sustained atrial fibrillation in patients taking oral anticoagulation or combined antiplatelet therapy: an ACTIVE W Substudy. J Am Coll Cardiol. 2007;50:2156-61. (PMID: 18036454)
 
Køber L, Torp-Pedersen C, McMurray JJ, Gøtzsche O, Lévy S, Crijns H, et al.; Dronedarone Study Group. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008;358:2678-87. (PMID: 18565860)
 
Connolly SJ, Camm AJ, Halperin JL, Joyner C, Alings M, Amerena J, et al.; PALLAS Investigators. Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med. 2011;365:2268-76. (PMID: 22082198)
 
Mead GE, Elder AT, Flapan AD, Kelman A. Electrical cardioversion for atrial fibrillation and flutter. Cochrane Database Syst Rev. 2005;(3):CD002903. (PMID: 16034878)
 
Klein AL, Grimm RA, Murray RD, Apperson-Hansen C, Asinger RW, Black IW, et al.; Assessment of Cardioversion Using Transesophageal Echocardiography Investigators. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med. 2001;344:1411-20. (PMID: 11346805)
 
Nagarakanti R, Ezekowitz MD, Oldgren J, Yang S, Chernick M, Aikens TH, et al. Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion. Circulation. 2011;123:131-6. (PMID: 21200007)
 
Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 1995;92:1954-68. (PMID: 7671380)
 
Borgeat A, Goy JJ, Maendly R, Kaufmann U, Grbic M, Sigwart U. Flecainide versus quinidine for conversion of atrial fibrillation to sinus rhythm. Am J Cardiol. 1986;58:496-8. (PMID: 3529911)
 
Stöllberger C, Chnupa P, Kronik G, Brainin M, Finsterer J, Schneider B, et al. Transesophageal echocardiography to assess embolic risk in patients with atrial fibrillation. ELAT Study Group. Embolism in Left Atrial Thrombi. Ann Intern Med. 1998;128:630-8. [Full Text] (PMID: 9537936)
 
Cordina J, Mead G. Pharmacological cardioversion for atrial fibrillation and flutter. Cochrane Database Syst Rev. 2005;(2):CD003713. (PMID: 15846675)
 
Chevalier P, Durand-Dubief A, Burri H, Cucherat M, Kirkorian G, Touboul P. Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis. J Am Coll Cardiol. 2003;41:255-62. (PMID: 12535819)
 
Nørgaard BL, Wachtell K, Christensen PD, Madsen B, Johansen JB, Christiansen EH, et al. Efficacy and safety of intravenously administered dofetilide in acute termination of atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled trial. Danish Dofetilide in Atrial Fibrillation and Flutter Study Group. Am Heart J. 1999;137:1062-9. (PMID: 10347332)
 
Donovan KD, Power BM, Hockings BE, Dobb GJ, Lee KY. Intravenous flecainide versus amiodarone for recent-onset atrial fibrillation. Am J Cardiol. 1995;75:693-7. (PMID: 7900662)
 
Stambler BS, Wood MA, Ellenbogen KA, Perry KT, Wakefield LK, VanderLugt JT. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators. Circulation. 1996;94:1613-21. (PMID: 8840852)
 
Maisel WH, Kuntz KM, Reimold SC, Lee TH, Antman EM, Friedman PL, et al. Risk of initiating antiarrhythmic drug therapy for atrial fibrillation in patients admitted to a university hospital. Ann Intern Med. 1997;127:281-4. [Full Text] (PMID: 9265427)
 
Alboni P, Botto GL, Baldi N, Luzi M, Russo V, Gianfranchi L, et al. Outpatient treatment of recent-onset atrial fibrillation with the “pill-in-the-pocket” approach. N Engl J Med. 2004;351:2384-91. (PMID: 15575054)
 
Naccarelli GV, Wolbrette DL, Khan M, Bhatta L, Hynes J, Samii S, et al. Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation: comparative efficacy and results of trials. Am J Cardiol. 2003;91:15D-26D. (PMID: 12670638)
 
Murray KT. Ibutilide. Circulation. 1998;97:493-7. (PMID: 9490245)
 
Volgman AS, Carberry PA, Stambler B, Lewis WR, Dunn GH, Perry KT, et al. Conversion efficacy and safety of intravenous ibutilide compared with intravenous procainamide in patients with atrial flutter or fibrillation. J Am Coll Cardiol. 1998;31:1414-9. (PMID: 9581743)
 
Madrid AH, Bueno MG, Rebollo JM, Marin I, Pena G, Bernal E, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Circulation. 2002;106:331-6. (PMID: 12119249)
 
Vermes E, Tardif JC, Bourassa MG, Racine N, Levesque S, White M, et al. Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction: insight from the Studies Of Left Ventricular Dysfunction (SOLVD) trials. Circulation. 2003;107:2926-31. (PMID: 12771010)
 
Lafuente-Lafuente C, Longas-Tejero MA, Bergmann JF, Belmin J. Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation. Cochrane Database Syst Rev. 2012;:CD005049. (PMID: 22592700)
 
Healey JS, Baranchuk A, Crystal E, Morillo CA, Garfinkle M, Yusuf S, et al. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. J Am Coll Cardiol. 2005;45:1832-9. (PMID: 15936615)
 
Juul-Möller S, Edvardsson N, Rehnqvist-Ahlberg N. Sotalol versus quinidine for the maintenance of sinus rhythm after direct current conversion of atrial fibrillation. Circulation. 1990;82:1932-9. (PMID: 2242519)
 
Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, et al.; Heart Rhythm Society Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Heart Rhythm. 2012;9:632-696.e21. (PMID: 22386883)
 
Chen HS, Wen JM, Wu SN, Liu JP. Catheter ablation for paroxysmal and persistent atrial fibrillation. Cochrane Database Syst Rev. 2012;:CD007101. (PMID: 22513945)
 
Terasawa T, Balk EM, Chung M, Garlitski AC, Alsheikh-Ali AA, Lau J, et al. Systematic review: comparative effectiveness of radiofrequency catheter ablation for atrial fibrillation. Ann Intern Med. 2009;151:191-202. [Full Text] (PMID: 19581635)
 
Brignole M, Menozzi C, Gianfranchi L, Musso G, Mureddu R, Bottoni N, et al. Assessment of atrioventricular junction ablation and VVIR pacemaker versus pharmacological treatment in patients with heart failure and chronic atrial fibrillation: a randomized, controlled study. Circulation. 1998;98:953-60. (PMID: 9737514)
 
Marshall HJ, Harris ZI, Griffith MJ, Holder RL, Gammage MD. Prospective randomized study of ablation and pacing versus medical therapy for paroxysmal atrial fibrillation: effects of pacing mode and mode-switch algorithm. Circulation. 1999;99:1587-92. (PMID: 10096935)
 
Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, Saliba W, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA. 2005;293:2634-40. (PMID: 15928285)
 
Khan MN, Jaïs P, Cummings J, Di Biase L, Sanders P, Martin DO, et al.; PABA-CHF Investigators. Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N Engl J Med. 2008;359:1778-85. (PMID: 18946063)
 
Cox JL, Ad N, Palazzo T, Fitzpatrick S, Suyderhoud JP, DeGroot KW, et al. Current status of the Maze procedure for the treatment of atrial fibrillation. Semin Thorac Cardiovasc Surg. 2000;12:15-9. (PMID: 10746917)
 
Toff WD, Camm AJ, Skehan JD; United Kingdom Pacing and Cardiovascular Events Trial Investigators. Single-chamber versus dual-chamber pacing for high-grade atrioventricular block. N Engl J Med. 2005;353:145-55. (PMID: 16014884)
 
Andersen HR, Nielsen JC, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T, et al. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet. 1997;350:1210-6. (PMID: 9652562)
 
Connolly SJ, Kerr CR, Gent M, Roberts RS, Yusuf S, Gillis AM, et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med. 2000;342:1385-91. (PMID: 10805823)
 
Moreyra E, Finkelhor RS, Cebul RD. Limitations of transesophageal echocardiography in the risk assessment of patients before nonanticoagulated cardioversion from atrial fibrillation and flutter: an analysis of pooled trials. Am Heart J. 1995;129:71-5. (PMID: 7817928)
 
Lund M, French JK, Johnson RN, Williams BF, White HD. Serum troponins T and I after elective cardioversion. Eur Heart J. 2000;21:245-53. (PMID: 10639307)
 
Silverman DI, Manning WJ. Role of echocardiography in patients undergoing elective cardioversion of atrial fibrillation. Circulation. 1998;98:479-86. (PMID: 9714099)
 
Thomson RG, Eccles MP, Steen IN, Greenaway J, Stobbart L, Murtagh MJ, et al. A patient decision aid to support shared decision-making on anti-thrombotic treatment of patients with atrial fibrillation: randomised controlled trial. Qual Saf Health Care. 2007;16:216-23. (PMID: 17545350)
 
Man-Son-Hing M, Laupacis A, O’Connor AM, Biggs J, Drake E, Yetisir E, et al. A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: a randomized controlled trial. JAMA. 1999;282:737-43. (PMID: 10463708)
 
Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98:946-52. (PMID: 9737513)
 
Samsa GP, Matchar DB, Goldstein LB, Bonito AJ, Lux LJ, Witter DM, et al. Quality of anticoagulation management among patients with atrial fibrillation: results of a review of medical records from 2 communities. Arch Intern Med. 2000;160:967-73. (PMID: 10761962)
 
Atwood JE, Myers J, Sandhu S, Lachterman B, Friis R, Oshita A, et al. Optimal sampling interval to estimate heart rate at rest and during exercise in atrial fibrillation. Am J Cardiol. 1989;63:45-8. (PMID: 2909159)
 
Pritchett EL, DaTorre SD, Platt ML, McCarville SE, Hougham AJ. Flecainide acetate treatment of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation: dose-response studies. The Flecainide Supraventricular Tachycardia Study Group. J Am Coll Cardiol. 1991;17:297-303. (PMID: 1899432)
 
Fauchier L, Pierre B, de Labriolle A, Grimard C, Zannad N, Babuty D. Antiarrhythmic effect of statin therapy and atrial fibrillation a meta-analysis of randomized controlled trials. J Am Coll Cardiol. 2008;51:828-35. (PMID: 2513143)
 
Wyse DG, AFFIRM Investigators. Survival in patients presenting with atrial fibrillation: the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Program and Abstracts of the American College of Cardiology 51st Annual Meeting, March 17-20, 2002, Atlanta, Georgia. Abstract 405-1.
 
Pritchett EL, Wilkinson WE. Mortality in patients treated with flecainide and encainide for supraventricular arrhythmias. Am J Cardiol. 1991;67:976-80. (PMID: 1902055)
 
ACCF

American College of Cardiology Foundation

ACE

angiotensin-converting enzyme

ACP

American College of Physicians

AF

atrial fibrillation

AHA

American Heart Association

aPTT

activated partial thromboplastin time

ARB

angiotensin-receptor blocker

AV

atrioventricular

bid

twice daily

bpm

beats per minute

BUN

blood urea nitrogen

CABG

coronary artery bypass graft

CAD

coronary artery disease

CBC

complete blood count

CI

confidence interval

CNS

central nervous system

COPD

chronic obstructive pulmonary disease

CT

computed tomography

ECG

electrocardiography, electrocardiogram

EHRA

European Heart Rhythm Association

ESC

European Cardiac Society

HF

heart failure

HIT

heparin-induced thrombocytopenia

HR

hazard ratio

HRS

Heart Rhythm Society

INR

international normalized ratio

iv

intravenous

LV

left ventricle

LVH

left ventricular hypertrophy

MI

myocardial infarction

NNH

number needed to treat for harm

NSR

normal sinus rhythm

OR

odds ratio

RR

relative risk

TEE

transesophageal echocardiogram

TIA

transient ischemic attack

TSH

thyroid-stimulating hormone

VT

ventricular tachycardia


Guidelines

American College of Cardiology/American Heart Association/Heart Rhythm Society: 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation

2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society

American College of Cardiology/American Heart Association 2006 update of the clinical competence statement on invasive electrophysiologystudies,catheterablation,andcardioversion: a report of the American College of Cardiology/American Heart Association/American College of Physicians Task Force on Clinical Competence and Training developed in collaboration with the Heart Rhythm Society

European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation

American Academy of Neurology: Summary of evidence-based guideline update: Prevention of stroke in nonvalvular atrial fibrillation

Systematic Reviews

Alcohol consumption and risk of atrial fibrillation: a meta-analysis

Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis

Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation (Cochrane review)

Atrial fibrillation and mortality in patients with acute myocardial infarction: a systematic overview and meta-analysis.

Catheter ablation for paroxysmal and persistent atrial fibrillation (Cochrane review)

Electrical cardioversion for atrial fibrillation and flutter (Cochrane review)

Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery (Cochrane review)

Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation

Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States

Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks (Cochrane review)

Pharmacological cardioversion for atrial fibrillation and flutter (Cochrane review)

Prevention of atrial fibrillation by Renin-Angiotensin system inhibition a meta-analysis

Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis

Rate vs rhythm control in patients with atrial fibrillation: a meta-analysis

Statin therapy and atrial fibrillation: systematic review and updated meta-analysis of published randomized controlled trials

Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis

Systematic review: comparative effectiveness of radiofrequency catheter ablation for atrial fibrillation

The evidence regarding the drugs used for ventricular rate control

DOI: 10.7326/d027
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.
Authors and Disclosures:
Victor A. Ferrari, MD has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. David Callans, MD, FACC has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. Susan Wiegers, MD has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. Jonathan L. Halperin, MD, FACP, FACC, FACP, FAHA, MSVM has received consulting fees from AstraZeneca, Bayer AG HealthCare, Biotronik, Boehringer Ingelheim, Boston Scientific, Daiicho Sankyo, Janssen, Johnson & Johnson, Medtronic, Ortho-McNeil-Janssen Pharmaceuticals, Pfizer, Sanofi-Aventis. Noah Moss, MD has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations.

The following editors of ACP Smart Medicine have nothing to disclose: Deborah Korenstein, MD, FACP, Editor in Chief; Richard B. Lynn, MD, FACP, Editor; and Davoren Chick, MD, FACP, Editor.

Related Content
Annals of Internal Medicine