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Apr.15.2022

Atrial Fibrillation

Synopsis

Key Points

  • Atrial fibrillation is a common form of supraventricular tachyarrhythmia characterized on ECG by low-amplitude baseline oscillations (fibrillatory or f waves from the fibrillating atria) and an irregularly irregular ventricular rhythm. Often associated with hypertension, valvular heart disease, heart failure, or obstructive sleep apnea r1
  • Some patients are asymptomatic or note only a vague sense of fatigue or decreased exercise tolerance. Others note palpitations, lightheadedness, and dyspnea at rest or on exertion. Less commonly, a patient may come to medical attention with a complication of atrial fibrillation (eg, acute embolic stroke, tachycardia-mediated ventricular dysfunction) r1
  • Atrial fibrillation is episodic in nature in many patients and is termed paroxysmal when episodes terminate within 7 days of onset, persistent when episodes are continuous for more than 7 days, and long-standing persistent when episodes have been continuous for longer than 12 months r2
  • Diagnosis is suspected based on history and a compatible physical examination (irregularly irregular pulse, usually with tachycardia) and is confirmed with ECG r2
  • Management of atrial fibrillation is organized around 2 goals:
    • Anticoagulation to prevent embolic stroke in those at increased risk
    • Symptom management, by either a rate control or a rhythm control strategy. Lifestyle changes with weight reduction have been shown to be beneficial in reducing arrhythmia burden r3
  • Anticoagulation recommendations vary, based on stroke risk
    • For patients with nonvalvular atrial fibrillation, use the CHA₂DS₂-VASc score to determine stroke risk. Men with a score of 2 or greater and women with a score of 3 or greater are at elevated risk and should be anticoagulated, usually with a non–vitamin K oral anticoagulant r4
    • Patients with valvular atrial fibrillation, regardless of CHA₂DS₂-VASc score, are considered high risk and should be given warfarin for anticoagulation r4
    • In the acute setting, when contemplating cardioversion, also consider duration of atrial fibrillation in determining stroke risk and need for anticoagulation. When the duration of atrial fibrillation is clearly no longer than 48 hours, stroke risk is presumed to be lower and anticoagulation before cardioversion is often omitted r5r6
  • For symptom management, a rate control strategy is noninferior compared with rhythm control for the prevention of cardiovascular morbidity and mortality. Rate control modalities include atrioventricular-nodal blocking drugs (β-blockers or nondihydropyridine calcium channel blockers for most patients), and atrioventricular-node ablation with implantation of a permanent pacemaker r2r7r8
  • A rhythm control strategy is often elected by younger patients and when rate control is ineffective or not tolerated. Initial cardioversion may be electrical or pharmacologic. Maintenance antiarrhythmic drugs are modestly effective and must be carefully selected. Catheter ablation (pulmonary vein isolation) is indicated in drug-refractory patients r1r2
  • Complications of atrial fibrillation include embolic stroke, tachycardia-mediated ventricular dysfunction and heart failure, and increased risk for cognitive decline and dementia. Patients with atrial fibrillation have increased mortality risk
  • Atrial fibrillation tends to progress from paroxysmal to persistent over time and may eventually become irreversible. In general, outcomes for specific therapies are better for paroxysmal atrial fibrillation than for persistent atrial fibrillation

Urgent Action

  • Patients with hemodynamic compromise that occurs secondary to atrial fibrillation require urgent electrocardioversion r4
    • Requires procedural sedation whenever possible r9
    • Place external electrode pads in an anteroposterior position across the chest wall (superior to anterolateral placement in some but not all studies) r2
    • Deliver a shock with 150 to 200 J on a biphasic machine or 200 to 300 J on a monophasic machine. May need to select lower energy for small patients or higher energy for large patients r9
    • With atrial fibrillation lasting more than 48 hours or of unknown duration, start anticoagulation as soon as possible and continue for at least 4 weeks r4

Pitfalls

  • Anticoagulation reduces ischemic stroke risk by approximately 60%r10 and must be considered based on CHA₂DS₂-VASc score, irrespective of whether the atrial fibrillation pattern is paroxysmal, persistent, or permanent r2
  • In addition to stroke risk, consider bleeding risk before beginning anticoagulation, as this may, in some cases, temper the decision to anticoagulate. A simple guide is the HAS-BLED score. A high-risk score mandates correcting or minimizing modifiable risk factors and planning closer follow-up of the patient r11
  • Hemodynamic instability is uncommonly a direct result of atrial fibrillation and mandates a rapid search for underlying reversible conditions (eg, sepsis, gastrointestinal bleeding) that are contributing to the instability
  • Electrocardioversion of atrial fibrillation and subsequent maintenance of sinus rhythm are more likely to be successful when atrial fibrillation duration is less than 6 monthsr12. Pharmacologic cardioversion is most likely to be effective when initiated within 7 days after onset of an episode r2r12
  • Consider presence or absence of structural heart disease, coronary artery disease, and potential to prolong the QT interval when choosing the specific maintenance antiarrhythmic drug. Cardiology consultation is recommended

Terminology

Clinical Clarification

  • Atrial fibrillation is a common form of supraventricular tachyarrhythmia (1 in 4 lifetime riskr13) with rapid and disorganized atrial activation resulting in ineffective atrial contraction
  • Characterized on ECG by low-amplitude baseline oscillations (fibrillatory or f waves from the fibrillating atria) and an irregularly irregular ventricular rhythm r1

Classification

  • By duration of atrial fibrillation episodes
    • Paroxysmal r2
      • Terminates within 7 days of onset, spontaneously or with intervention
      • Accounts for 20% of atrial fibrillation diagnoses r14
    • Persistent r2
      • Continuous for more than 7 days
      • Often progresses from paroxysmal episodes to persistent episodes over a variable time period
      • Both paroxysmal and persistent episodes may occur in the same patient
      • Accounts for 30% of atrial fibrillation diagnoses r14
    • Long-standing persistent r2
      • Continuous for more than 12 months
      • Accounts for 40% to 50% of atrial fibrillation diagnoses (percentages include those cases designated as permanent) r14
    • Permanent r2
      • Terminology used when the patient and clinician make a joint decision to stop further attempts to restore and/or maintain sinus rhythm
        • Represents a therapeutic attitude as opposed to an inherent pathophysiologic attribute
        • This attitude may change as symptoms, efficacy of therapeutic interventions, and patient and clinician preferences evolve
  • By underlying cause
    • Valvular
      • American Heart Association guidelines use the following definition: atrial fibrillation in the setting of moderate to severe mitral stenosis (potentially requiring surgical intervention) or in the presence of a mechanical heart valve r4
    • Nonvalvular
      • American Heart Association guidelines use the following definition: atrial fibrillation in the absence of moderate to severe mitral stenosis or a mechanical heart valve r4
      • Does not imply the absence of other valvular heart disease
  • A new descriptor, subclinical atrial fibrillation, has recently come into use based on widespread use of cardiac implantable electronic devices that detect asymptomatic atrial fibrillation in a substantial proportion of patients r15

Diagnosis

Clinical Presentation

History

  • Symptoms include:
    • Palpitations c1
    • Shortness of breath at rest and/or with exertion c2c3
    • Exercise intolerance c4
    • Light-headedness c5
    • Syncope is uncommon but can occur as a result of rapid ventricular rate or a long pause on termination of atrial fibrillation in a patient with sick sinus syndrome c6
    • Polyuria can result from increased release of atrial natriuretic peptide c7
  • Patients found to have atrial fibrillation may describe themselves as asymptomatic (25%); this is more common in persistent atrial fibrillation and in older adult patients r1c8
    • May not recognize their irregular heartbeat and deny palpitations
    • Careful questioning may reveal fatigue or effort/exercise intolerance
    • Can be difficult to attribute these symptoms to atrial fibrillation versus other comorbid conditions
  • Patients may come to medical attention with a complication of atrial fibrillation
    • Acute onset of neurologic symptoms consistent with embolic stroke c9
    • Insidious onset of heart failure symptoms due to tachycardia-mediated ventricular dysfunction
  • Consider reversible conditions, both chronic and acute, as a trigger for atrial fibrillation
    • Especially in younger patients, consider hyperthyroidism, binge drinking (sometimes referred to as holiday heart), ingestion of an intoxicant, and alcohol withdrawal
    • Patients with established atrial fibrillation and a previously controlled ventricular response may present with a rapid ventricular response and hemodynamic instability due to an acute state (eg, pneumonia, sepsis, gastrointestinal bleeding, myocardial infarction, pulmonary embolus). New-onset atrial fibrillation may also occur during such precipitating events
  • History typically includes 1 or more risk factors for atrial fibrillation
    • Common general cardiovascular risk factors (eg, hypertension, obesity, diabetes) c10c11c12
    • Established structural cardiovascular disease (eg, valvular disease, left ventricular hypertrophy, heart failure, ischemic heart disease) c13c14c15c16
    • Sleep apnea c17

Physical examination

  • Irregularly irregular pulse c18
  • Tachycardia c19
    • With intact atrioventricular conduction and no accessory pathway, ventricular rate is typically 100 to 160 beats per minute r1
    • Higher heart rate suggests the possibility of an accessory pathway or thyrotoxicosis
  • Irregular jugular venous pulsations c20
  • Peripheral pulses may be decreased or absent owing to low stroke volumes c21
    • Pulse deficit can be noted (peripheral pulse not as rapid as apical pulse)
  • Variable intensity of first heart sound (S₁) c22
  • Absence of a fourth heart sound (S₄) that had previously been heard during sinus rhythm c23
  • Consider physical findings that suggest an underlying triggering condition (eg, fever suggesting infection; tremor; brisk, deep tendon reflexes; enlarged thyroid; ophthalmopathy suggesting thyroid disease) c24c25c26c27c28

Causes and Risk Factors

Causes

  • Atrial fibrillation occurs when structural and/or electrophysiologic abnormalities alter the atrial architecture and promote abnormal impulse formation and/or propagation r2
    • Altered architecture is usually due to hypertrophy, dilation, ischemia, fibrosis, and/or inflammation c29c30c31c32c33
    • Abnormal impulse formation is most commonly from rapidly firing foci at the atriopulmonary vein junctions c34
    • Atrial fibrillation is propagated and maintained by a variety of mechanisms

Risk factors and/or associations

Age
  • Risk increases with age c35c36
    • At age 55 years, 37% lifetime risk
    • As compared with those aged 50 to 59 years, risk increases by a significant factor with each decade r16
      • Ages 60 to 69 years: about 5-fold
      • Ages 70 to 79 years: about 7-fold
      • Ages 80 to 89 years: about 9-fold
Sex
  • Incidence is higher in men, probably owing to sex-related differences in distribution of risk factors r17c37
Genetics
  • Heritable condition: having an affected family member is associated with a 40% increased risk r2c38
  • First-degree relative with atrial fibrillation onset before age 66 years (premature atrial fibrillation) doubles risk of atrial fibrillation r18c39
  • At least 30 associated genetic loci have been identified in genome-wide association studies r19
Ethnicity/race
  • White populations have higher lifetime risk r17c40
    • Black participants in the ARIC studyr20 had 41% lower age-adjusted and sex-adjusted risk of atrial fibrillation compared with White participants
      • However, outcomes (eg, stroke, heart failure, death) in Black participants were 1.5- to 2-fold worse r21
    • Overall atrial fibrillation incidence was significantly lower among Hispanic, Black, and Chinese participants compared with White participants in the MESA studyr22
Other risk factors/associations
  • Hypertension, especially with left ventricular hypertrophy c41c42
    • Most common modifiable risk factor; increases risk by 40% to 50% r23
  • Obstructive sleep apnea c43
    • Highly prevalent condition associated with 4-fold increased risk of atrial fibrillation r24
  • Heart failure c44
    • Confers a 2- to 4-fold increased risk of developing atrial fibrillation r17
    • For patients with heart failure, risk increases with worsening diastolic dysfunction r17
    • For patients with heart failure with reduced ejection fraction, prevalence increases with worsening New York Heart Association class (4.2% for class I; about 50% for class IV) r25
    • Risk association of heart failure and atrial fibrillation is bidirectional; atrial fibrillation confers increased risk of heart failure r17
  • Structural heart disease c45
    • Mitral valve disease c46
    • Cardiomyopathy, both dilated and hypertrophic c47c48
    • Severe pulmonary hypertension c49
  • Atrial ischemia, caused by: c50
    • Coronary artery disease
    • Infiltrative myocardial disease, including amyloidosis, sarcoidosis, and hemochromatosis
  • Obesity r2c51
    • Independently associated with a 49% increased risk of atrial fibrillation r26
    • Dose-response relationship; risk increases with each 1-unit increase in BMI r16
  • Diabetes mellitus c52
    • Relative risk with diabetes is approximately 1.3 r27
    • Relative risk with prediabetes is approximately 1.2 r27
    • Risk increases with both duration of diabetes and worsening of glycemic control r17
    • Patients with diabetes may have less awareness of atrial fibrillation symptoms r28
  • Smoking c53c54
    • Increased risk for both current (relative risk, 1.33) and past (relative risk, 1.09) smoking with a dose-response pattern r29
  • High-endurance training c55
    • Higher risk has been observed only with exercise doses that far exceed recommendations of the Physical Activity Guidelines Advisory Committee Reportr30 (150 minutes per week of moderate-intensity or 75 minutes per week of vigorous-intensity aerobic exercise) r3
      • Meta-analysis showed a significantly high risk of atrial fibrillation associated with athletic endurance activities; however, samples were small and controls not appropriately age-matched in all studies r31
  • Temporary/treatable trigger conditions
    • Patients with these associated factors at the time of diagnosis may have resolution of atrial fibrillation when the factors are reversed/treated; however, most data do not support the idea that atrial fibrillation is permanently cured at that time. Atrial fibrillation may recur r2
    • Such triggers may also precipitate a paroxysm of atrial fibrillation in a patient with previously diagnosed atrial fibrillation who had been maintained in sinus rhythm
    • These conditions include:
      • Thyrotoxicosis (both overt and subclinical) c56
      • Pneumonia c57
      • Pulmonary embolism c58
      • Acute electrolyte abnormalities, particularly hyponatremia and hypokalemia r32r33c59c60c61
      • Alcohol binge drinking c62
      • Alcohol withdrawal c63
      • Cardiothoracic surgery c64
      • Acute ischemic and inflammatory cardiac conditions (eg, acute coronary syndrome, myocarditis, pericarditis) c65c66c67
    • Wolff-Parkinson-White syndrome can also precipitate atrial fibrillation c68

Diagnostic Procedures

Primary diagnostic tools

  • Suspect based on history and physical examination; requires ECG documentation to confirm r2
    • May require prolonged monitoring (eg, telemetry, Holter monitor, event recorder) for confirmation if suspected but not seen on initial ECG or rhythm strip
  • Initial evaluation is to identify a potentially reversible cause, identify underlying cardiac dysfunction or structural abnormality, and assess risk of thromboembolism
    • Echocardiography r2
      • 2-dimensional transthoracic echocardiogram (obtain with new-onset atrial fibrillation; can usually be obtained on a nonurgent outpatient basis)
      • Transesophageal echocardiography is not routine, but it should be considered to identify a left atrial thrombus in specific circumstances (eg, when elective cardioversion is planned for a non-anticoagulated patient who has been in atrial fibrillation for 48 hours or more, without waiting 3 weeks as per guideline recommendations) r4
    • Chest radiograph if underlying acute pulmonary disease (eg, pneumonia) or heart failure is suspected
    • Laboratory assessment
      • Obtain CBC and measurements of thyroid function, serum electrolyte level, and renal and hepatic function

Laboratory

  • Thyroid function tests r2
    • Indicated in all patients with new-onset atrial fibrillation to rule out hyperthyroidism and thyrotoxicosis as a reversible trigger of atrial fibrillation
    • TSH level is the most sensitive test for detecting any degree of hyperthyroidism (overt or subclinical)
    • Free T₄ level and total T₃ are performed to confirm thyrotoxicosis in patients with suppressed TSH level
    • Combination of clearly suppressed TSH level and elevated peripheral hormone level (free T₄ level and/or total T₃) confirms suspected hyperthyroidism
    • Combination of a low TSH and peripheral hormone level within reference range suggests subclinical hyperthyroidism
  • Serum electrolyte levels and renal and hepatic function tests r2
    • Indicated in all patients to identify reversible acute or chronic metabolic abnormality that may cause or exacerbate atrial fibrillation, and to identify abnormalities that could affect pharmacotherapy selection
    • Measure levels of the following:
      • Electrolytes
      • BUN and creatinine
      • ALT and AST
    • CBC
      • Obtain in all patients to evaluate for potential underlying cause (eg, anemia, elevated WBC count suggestive of infection)

Imaging

  • Transthoracic echocardiography r2
    • Indicated as part of initial evaluation but can generally be performed on scheduled outpatient basis
    • Useful to assess atrial size, underlying structural heart disease, and cardiac function
    • Although left atrial thrombus may be identified, sensitivity is poor
  • Transesophageal echocardiography r2
    • Indicated to evaluate for intracardiac thrombus when cardioversion is planned in the absence of an appropriate duration of anticoagulation
    • Other candidates for precardioversion transesophageal echocardiography include symptomatic patients and patients with congestive heart failure with hemodynamic compromise r34
  • Chest radiography r2
    • Indicated only for patients with symptoms or signs suggestive of congestive heart failure or pulmonary disease

Functional testing

  • ECG r2c69
    • Characteristic ECG findings include:
      • Irregular R-R intervals (when atrioventricular conduction is present)
      • Absence of distinct repeating P waves
      • Irregular atrial activity
    • Ventricular rate (untreated) is typically 100 to 160 beats per minute r1
  • Ambulatory monitoring r2
    • Can establish diagnosis when detection of arrhythmia is elusive on routine ECG (ie, paroxysmal atrial fibrillation)
    • In patients with known atrial fibrillation, useful in evaluating if ventricular response (rate control) is satisfactory
    • Diagnostic yield correlates with duration of monitoring and depends on accuracy of patient's symptom reporting r35
      • Holter monitor c70
        • Best for patients who experience symptoms every day
        • Ambulatory 24- to 48-hour Holter recording is used to capture evidence of frequent but transient paroxysms of atrial fibrillation
        • Portable device is attached to patient with ECG wires and electrodes and a continuous ECG tracing is made
      • Event or loop recorders
        • Indicated in patients with less frequent arrhythmias as an alternative to Holter monitoring c71
        • Patient-activated ECG event recorders can help assess the relationship of arrhythmia to symptoms
          • Patient wears device (usually on wrist) and activates device (pushes button) to record when symptomatic
          • Will not record event if patient delays activating the device
        • Auto-triggered event recorders may detect asymptomatic episodes
        • External loop recorders are similar to event recorders; worn on the chest
          • Has a continuous looping memory recording; can retrieve recording of ECG even if patient does not activate the device until several minutes after a symptomatic event
        • 2 weeks of ECG monitoring may provide best diagnostic yield r35c72

Differential Diagnosis

Most common

  • The following present with tachycardia and are differentiated from atrial fibrillation with an ECG, rhythm strip, or other monitoring system:
    • Multifocal atrial tachycardia c73d1
      • More common in patients older than 50 years
      • Hypoxia is usually a trigger (typically associated with heart failure, pulmonary disease, pulmonary embolism, and pneumonia)
      • Atrial rate is more than 100 beats per minute
      • ECG findings include:
        • Each QRS complex is preceded by a P wave but irregular PR and P-P intervals occur (which may lead to confusion with atrial fibrillation)
        • P waves have at least 3 distinct wave morphologies in the same ECG lead
        • An isoelectric baseline occurs between P waves
      • Often precedes atrial fibrillation
    • Atrial flutter c74
      • Common with advancing age and with underlying structural heart disease
      • Regular atrial depolarizations at a rate of 250 to 300 beats per minute
      • ECG shows sawtooth pattern of F (flutter) waves, especially in leads II, III, aVF, or V₁
      • Atrioventricular conduction classically results in a defined ventricular rate
        • 2:1 conduction with atrial rate of 300 beats per minute results in a ventricular rate of 150 beats per minute (most common)
        • Atrioventricular conduction may also be 3:1 or 4:1
        • 1:1 is rare unless preexcitation is present
      • Patients with long duration (years) of atrial flutter will often progress to atrial fibrillation
    • Atrial tachycardia c75
      • Most commonly seen with structural cardiac disease
      • Regular atrial rhythm having a constant rate of 100 beats per minute or greater
      • Usually paroxysmal rather than incessant; patient may be dyspneic or have chest pressure
      • P-wave morphology and axis are typically abnormal, as impulse originates outside sinus node (waves may be normal if impulse originates very close to sinus node)
      • Presence of a positive or biphasic P wave in lead aVL indicates a right atrial focus, and a positive P wave in lead V₁ indicates a left atrial focus
      • Atrioventricular conduction may be 1:1, 2:1, or higher depending on atrial rate (atrial tachycardia with block)
    • Atrioventricular-nodal reentry tachycardia c76d2
      • Reentry circuit is in atrioventricular node
      • QRS complexes at rates of 140 to 250 beats per minute with a regular rhythm and of supraventricular origin
      • In typical (slow-fast) variant, RP interval is shorter than PR interval; P waves are usually not seen because they are buried in QRS complex
        • In atypical (slow-slow) variant, P wave is inscribed after QRS complex
        • In atypical (fast-slow) variant, RP interval is longer than PR interval; retrograde P wave is visible before QRS complex (long RP variant)
      • Most atrioventricular-nodal reentry tachycardias are narrow-complex tachycardias, with QRS duration of less than 120 milliseconds, unless there is aberrant conduction
    • Wolff-Parkinson-White syndrome c77d3
      • Congenital condition involving abnormal electrical conduction via an accessory pathway between the atria and the ventricles that causes ventricular preexcitation
      • During normal sinus rhythm, has a short PR interval and a widened QRS with an initial delta wave
      • Wolff-Parkinson-White syndrome results in a predisposition to atrioventricular reentry tachycardia, atrial fibrillation, and atrial flutter
      • In patients with Wolff-Parkinson-White syndrome, ventricular rate during atrial fibrillation can exceed 250 beats per minute owing to conduction over the accessory pathway r1

Treatment

Goals

  • Stabilize the patient, which may require IV atrioventricular-nodal blocking agents or urgent cardioversion in some cases
  • Identify and treat reversible causes
  • Prevent embolic stroke with anticoagulation when indicated by risk stratification
  • Relieve atrial fibrillation symptoms and improve quality of life r2
    • If rate-control management is elected, maintain heart rate that reduces symptoms, enables exercise, and prevents cardiovascular complications r2r36
    • If rhythm control strategy is elected, use pharmacologic or nonpharmacologic methods to restore and maintain sinus rhythm for improved quality of life

Disposition

Patients who are symptomatic (ie, palpitations, chest pain, shortness of breath, diaphoresis, dizziness) require urgent evaluation in an emergency care setting r37

Patients who are hemodynamically unstable require urgent treatment in an emergency care setting, often with IV nodal blocking medication and, sometimes, urgent cardioversion

Patients who are hemodynamically stable with minimal or no symptoms may be managed as outpatients

Admission criteria

Patients with new-onset atrial fibrillation who undergo elective electrocardioversion in the emergency department are sometimes admitted for monitoring; regional practices vary, and younger, healthier patients are often discharged home afterward if they are stable

Initiation (or dose escalation) of dofetilide for rhythm control requires inpatient evaluation in an ECG-monitored bed; some experts prefer a monitored admission for initiation of sotalol r38

Patients with uncontrolled comorbid conditions that precipitate or exacerbate atrial fibrillation (ie, COPD exacerbation, sepsis, heart failure, trauma) often require hospital admission r39

Patients who are highly symptomatic despite adequate treatment may require hospital admission r40

Criteria for ICU admission
  • Unstable hemodynamics
  • Refractory atrial fibrillation with hemodynamic compromise
  • Atrial fibrillation associated with congestive heart failure or acute coronary syndrome

Recommendations for specialist referral

  • Consultation with a cardiologist is beneficial for all patients, although management by a primary care physician or hospitalist is reasonable for some patients being treated with a rate-control strategy
  • Consultation and follow-up with a cardiologist is recommended when a patient remains symptomatic or has decreased quality of life, and when specific interventions are considered
    • Cardioversion (either electrical or pharmacologic)
    • Maintenance antiarrhythmic drug therapy
    • Invasive procedures: catheter ablation and atrioventricular-nodal ablation (electrophysiologist); left atrial appendage occlusion (electrophysiologist or interventional cardiologist)

Treatment Options

Treatment of atrial fibrillation is organized around 2 main issues:

  • Anticoagulation to prevent embolic stroke if indicated based on risk stratification
  • Symptom control with either a rate-control or a rhythm-control approach

Anticoagulation decisions are based on risk stratification

  • Anticoagulation reduces ischemic stroke risk by approximately 60%r10 and must be considered irrespective of whether the atrial fibrillation pattern is paroxysmal, persistent, or permanent r2
    • For patients with nonvalvular atrial fibrillation, determine eligibility for anticoagulation using the CHA₂DS₂-VASc stroke clinical risk score
      • If CHA₂DS₂-VASc score is 2 or greater in men or 3 or greater in women, anticoagulation is recommended r4
      • If CHA₂DS₂-VASc score is 0 in men or 1 in women, it is reasonable to omit anticoagulant therapy r4
      • Based on limited data, anticoagulation therapy may be considered for patients with a midrange score (1 in men; 2 in women) based on individual risk-benefit shared decision making r4
      • Reassess CHA₂DS₂-VASc score at least annually in patients with atrial fibrillation who were at initial low risk of stroke and prescribe anticoagulation once CHA₂DS₂‐VASc score increases r41
      • CHA₂DS₂-VASc stroke risk score.Add these points to determine the CHA₂DS₂-VASc stroke risk score, with score ranging from 0 through 9. Note that women cannot have a score of 0.Data from January CT et al: 2019 AHA/ACC/HRS focused update of the 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 Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 74(1):104-32, 2019; and January CT 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. Circulation. 130(23):e199-267, 2014.
        Component of CHA₂DS₂-VASc scorePoints assigned
        Congestive heart failure1
        Hypertension1
        Age 75 years or older2
        Diabetes mellitus1
        Prior stroke (or transient ischemic attack)2
        Vascular disease (eg, myocardial infarction, peripheral vascular disease)1
        Age 65 to 74 years1
        Sex category (female)1
    • In addition to stroke risk, consider bleeding risk before initiating anticoagulation as this may temper the decision to anticoagulate. HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly [older than 65 years], Drugs/alcohol concomitantly) is a validated tool that predicts 1-year risk of major bleeding for patients on therapeutic anticoagulation for atrial fibrillation r11
      • Bleeding risk is increased with elevated systolic blood pressure, severe renal disease, severe hepatic disease, history of stroke, history of bleeding, presence of a labile INR, age older than 65 years, concomitant antiplatelet therapy or NSAIDs, and excessive alcohol intake r42
      • High (3 points or higher) HAS-BLED score generally correlates with both bleeding risk and higher stroke risk; therefore, high HAS-BLED score should not automatically result in decision not to anticoagulate r11
        • Instead, in many patients, a high-risk score mandates correcting or minimizing modifiable risk factors and planning closer follow-up of the patient
      • HAS-BLED score.HAS-BLED score of 3 or greater is considered high risk.Data from Lip GY: Implications of the CHA(2)DS(2)-VASc and HAS-BLED scores for thromboprophylaxis in atrial fibrillation. Am J Med. 124(2):111-4, 2011;  and Lip GYH et al: Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest. 154(5):1121-201, 2018.
        Components of HAS-BLED scorePoints assigned
        Hypertension (systolic blood pressure over 160 mm Hg)1
        Abnormal renal and liver function1  point each
        Stroke1
        Bleeding (previous bleeding or predisposition to it)1
        Labile INRs1
        Elderly1
        Drugs (concomitant aspirin or NSAIDs) or alcohol (excess consumption)1 point each
        Add points for total score (maximum 9 points)
        Association of HAS-BLED score with bleeding risk per 100 person-years
        HAS-BLED score of 0 to 11.02 to 1.13
        HAS-BLED score of 21.88
        HAS-BLED score of 3 or greater3.74 or greater
    • With new-onset atrial fibrillation, when cardioversion (electrical or pharmacologic) is contemplated in a non-anticoagulated patient, both the duration of atrial fibrillation at presentation and the CHA₂DS₂-VASc score guide anticoagulation decisions
      • With atrial fibrillation duration less than 48 hours:
        • Patients with new-onset atrial fibrillation of less than 48 hours' duration are less likely to have embolic complications after cardioversion than those with longer duration of atrial fibrillation. However, recent large observational studies suggest that anticoagulation might improve outcomes in these patients and have led to controversy in management r5
          • Finnish CardioVersion, a series of 6 observational studies representing over 10,000 patients with atrial fibrillation who underwent chemical or electrical cardioversion, found a non-negligible risk of embolic events in patients with atrial fibrillation duration of 12 to 48 hours versus duration less than 12 hours (1.1% versus 0.33%) r43r44r45r46r47r48
          • The Finnish CardioVersion studies also found that anticoagulation before cardioversion reduced the risk conferred by atrial fibrillation duration in the first 48 hours of onset
          • There is controversy regarding current recommendations for use of anticoagulation before and after cardioversion in patients presenting with atrial fibrillation duration less than 48 hours
          • In cases of hemodynamic instability, where urgent cardioversion is indicated, cardioversion is often administered without anticoagulation r6
          • The 2019 American College of Cardiology/American Heart Association guidelines recommend consideration of pre-cardioversion anticoagulation or no anticoagulation in men with CHA₂DS₂-VASc of 0 and women with scores less than or equal to 1, with no post-cardioversion anticoagulation r2
          • American College of Cardiology/American Heart Association guidelines recommend anticoagulation before cardioversion when the CHA₂DS₂-VASc score is 2 or greater in men or 3 or greater in women, followed by ongoing oral anticoagulation r4
          • The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society comprehensive guidelines recommend a more aggressive anticoagulation strategy as follows: r38
            • For patients with atrial fibrillation duration less than 12 hours with no recent history of transient ischemic attack or stroke
              • Anticoagulate as soon as possible before cardioversion and continue for 4 weeks after cardioversion
            • For patients with atrial fibrillation duration of 12 to 48 hours with CHA₂DS₂-VASc of 0 to 1
              • Anticoagulate as soon as possible before cardioversion and continue for 4 weeks after cardioversion
            • For patients with atrial fibrillation duration of 12 to 48 hours with CHA₂DS₂-VASc of 2 or greater
              • Anticoagulate for 3 weeks or perform transesophageal echocardiography to exclude left atrial thrombus before cardioversion and continue anticoagulation after cardioversion
      • With atrial fibrillation duration of 48 hours or longer (or of unknown duration):
        • Guidelines recommend anticoagulation for at least 3 weeks before and at least 4 weeks after cardioversion, regardless of the CHA₂DS₂-VASc score r4
        • For patients who have not been anticoagulated for the preceding 3 weeks but for whom earlier cardioversion is desired, consider evaluating with transesophageal echocardiography as an alternative to precardioversion anticoagulation r4
          • If no left atrial thrombus is identified, can initiate anticoagulation and proceed to cardioversion
          • If left atrial thrombus is identified, begin anticoagulation and postpone cardioversion for 3 to 4 weeks to allow for stabilization of the thrombus
          • Maintain anticoagulation after cardioversion for at least 4 weeks r4
          • Randomized controlled trial (1222 patients) showed no difference between 3-week anticoagulation strategy and a transesophageal echocardiogram–guided strategy in terms of embolic events or mortality r49
    • Continue long-term anticoagulation for all patients at elevated risk of embolic stroke
      • Patients with nonvalvular atrial fibrillation
        • Anticoagulate if CHA₂DS₂-VASc score is 2 or greater in men or 3 or greater in women r4
          • Non–vitamin K oral anticoagulants are recommended (over warfarin) by most international guidelines r4r11r50
          • Non–vitamin K oral anticoagulants have several advantages as compared with vitamin K antagonists:
            • Reduced risk of embolic stroke, hemorrhagic stroke, and major bleeding, even in very elderly patientsr52r51
            • More convenient; no requirement for routine laboratory monitoring
            • Fewer dietary and drug interactions r51
          • Apixaban, rivaroxaban, dabigatran, and edoxaban are approved for this indication. No prospective head-to-head clinical trial data are available
          • Based on observational data, apixaban may be safer and more effective than rivaroxaban for treating nonvalvular atrial fibrillation r53
            • Retrospective study compared patients with newly prescribed apixaban to patients with newly prescribed rivaroxaban (about 39,000 patients in each group)
            • Use of apixaban was associated with:
              • Lower rate of ischemic stroke/systemic embolism, corresponding to a hazard ratio of 0.82
              • Lower rate of gastrointestinal bleeding or intracranial hemorrhage, corresponding to a hazard ratio of 0.58
            • Higher rates of gastrointestinal bleeding have been observed in patients taking rivaroxaban (3.2 per 100 patient-years) compared with apixaban (2.5 per 100 patient years) and dabigatran (1.9 per 100 patient years) r54
      • Patients with valvular heart disease and atrial fibrillation
        • Recommendations for formulation of anticoagulation differ based on whether the patient has rheumatic mitral stenosis or other forms of valvular heart disease
        • For patients with rheumatic mitral stenosis or a mechanical valve, risk of embolic complications is high; warfarin anticoagulation is indicated for all patients regardless of CHA₂DS₂-VASc score r4
          • Non–vitamin K oral anticoagulants are not appropriate treatment owing to lack of data for this indication r2
        • 2020 American College of Cardiology/American Heart Association guidelines recommend that non–vitamin K oral anticoagulant or warfarin may be considered for patients with atrial fibrillation with native valvular heart disease (not rheumatic mitral stenosis) or those who received a bioprosthetic valve more than 3 months earlier, based on the CHA₂DS₂-VASc score r55
    • Percutaneous occlusion is a nonpharmacologic option for stroke prevention in selected patients
      • Approximately 90% of thrombi in patients with nonvalvular atrial fibrillation and 57% of thrombi in those with valvular atrial fibrillation originate in the left atrial appendage r56
      • Closure of left atrial appendage with the Watchman device provides an alternative for patients who are not good candidates for long-term anticoagulation (eg, propensity for bleeding, drug intolerance, drug nonadherence) r4r57
      • Meta-analysis of 2 randomized controlled trials (PROTECT AFr59 and PREVAILr60 trials) and 2 nonrandomized registries found that for appropriate candidates, left atrial appendage closure resulted in: r58
        • Similar benefit in all-cause stroke compared to warfarin but with different stroke pathophysiology between groups: more hemorrhagic strokes occurred with warfarin; more ischemic strokes occurred with the device
        • Decreased rates of cardiovascular/unexplained death and nonprocedural bleeding with the device compared to warfarin

Symptom management (control of rate and rhythm)

  • Select either a rate control or rhythm control strategy; strategy may change over time
    • When initiated early (within 1 year of onset), rhythm control treatment was associated with a lower risk of adverse cardiovascular outcomes compared with rate control treatment r61r62
  • Rate control r2
    • Rate control is as effective as rhythm control for preventing cardiovascular morbidity and mortality in large randomized controlled trials r7r8
      • May be preferable for asymptomatic patients with a structurally and functionally normal heart and when risks of restoring sinus rhythm outweigh benefits r63
      • Can be the initial strategy in patients with new-onset atrial fibrillation with a plan for cardioversion to sinus rhythm after 3 weeks of anticoagulation, if atrioventricular-nodal blocking drugs are ineffective or not tolerated r9
    • Use an atrioventricular-nodal blocking drug as initial therapy r2
      • Options include:
        • β-blockers
          • In the acute setting where rapid control of ventricular rate is desired, metoprolol, propranolol, or esmolol can be given by IV r2
          • Oral atenolol, metoprolol, nadolol, and propranolol are effective for ongoing ventricular rate control, and have the most data to support their use r2
            • Rate control achieved in 70% of patients given a β-blocker as first drug in AFFIRM trial
          • Use with caution in patients with decompensated heart failure
        • Nondihydropyridine calcium channel blockers
          • Both verapamil and diltiazem are effective r2
          • In the acute setting where rapid control of ventricular rate is desired, either can be given by IV
          • Rate control achieved in 54% of patients treated with oral calcium channel blockers as first drug in AFFIRMr64 trial
          • Use with caution in patients with heart failure or sinus node dysfunction r2
        • Cardiac glycosides (ie, Digoxin)
          • In the acute setting, not optimal for rapid control of ventricular response due to slow onset of action and delayed peak plasma concentration
          • For long-term rate control, not typically used as a first line drug; ineffective at controlling the ventricular response during exercise r63
          • May be useful in the following situations:
            • Can be used in the setting of heart failure (no negative inotropic effects); however, may increase risk of deathr65 in this population r2
            • Can be combined with a β-blocker and/or a nondihydropyridine calcium channel blocker when ventricular rate control is insufficient r2
            • May be useful in sedentary or bed-bound patients for whom lack of rate control during exercise is not an important factor
        • Amiodarone
          • Sometimes used as second line therapy for chronic atrial fibrillation when other therapies are unsuccessful or contraindicated r2
            • Although primarily used as an antiarrhythmic (rather than as a rate control agent), amiodarone exerts sympatholytic and calcium-antagonistic properties that can depress atrioventricular-nodal conduction
            • Toxicities and drug interactions limit long-term use of amiodarone for control of ventricular rate
        • Goal of rate control is lenient (defined as less than 110 beats per minute at rest) for most patients r66
          • As effective as strict rate control (less than 80 beats per minute at rest) in preventing cardiovascular events including heart failure hospitalizations, stroke, arrhythmias, and cardiovascular death according to results found in RACE II trial r66
          • Stricter rate control is important when an elevated ventricular rate is contributing to ventricular dysfunction (known as tachycardia-mediated cardiomyopathy)
        • Do not use atrioventricular-nodal blocking drugs in patients with known or suspected Wolff-Parkinson-White syndrome; preferential ventricular excitation through accessory pathway and extremely rapid ventricular rates can occur, resulting in hemodynamic collapse
          • For these patients, aim to revert to sinus rhythm with an antiarrhythmic drug, specifically procainamide or ibutilide if hemodynamics are stable; or use electrocardioversion
        • Rapid ventricular rate control using IV medications.
          DrugDose
          β-blockers
          Metoprolol2.5 to 5  mg IV bolus over 1 to 2 minutes; may repeat every 5 minutes up to 3 doses
          Esmolol500 mcg/kg IV bolus over 1 minute, followed by an infusion of 50 mcg/kg/minute for 4 minutes 
          If tachycardia is not controlled, may repeat loading dose and/or increase infusion to 100 mcg/kg/minute for 4 minutes
          Thereafter, repeat loading dose and increase infusion by 50 mcg/kg/minute increments every 4 minutes up to 200 mcg/kg/minute as required
          Propranolol1 mg IV over 1 minute, up to 3 doses at 2-minute intervals
          Nondihydropyridine calcium channel blockers
          Verapamil5 to 10 mg (0.075-0.15 mg/kg) IV over at least 2 minutes 
          If no adequate response after 30 minutes, may give an additional 10 mg (0.15 mg/kg) IV followed by a 0.005 mg/kg/minute continuous IV infusion
          Diltiazem0.25 mg/kg IV bolus over 2 minutes 
          After 15 minutes, 0.35 mg/kg IV over 2 minutes may be given. Individualize as needed.  Begin continuous infusion of 5 to 10 mg/hour after bolus.  Max: 15 mg/hour
          Other agents
          DigoxinNot recommended for rapid ventricular rate control; onset of action is more than 1 hour with peak effect delayed 6 hoursr2
    • Nonpharmacologic rate control with atrioventricular node ablation and permanent pacemaker implantation can be a good option for some patients r2
      • Reasonable when pharmacologic management is inadequate and rhythm control is not achievable. Most appropriate for: r2
        • Older adult patients (because the procedure mandates lifelong pacemaker dependency)
        • Patients with tachycardia-mediated cardiomyopathy with ventricular rate refractory to medical therapy
        • Patients who remain symptomatic on pharmacologic rate control
  • Rhythm control (restoration and maintenance of sinus rhythm)
    • Considerations when choosing this strategy: r2
      • Pharmacologic cardioversion, electrical cardioversion, or an ablative procedure can restore sinus rhythm
      • Rhythm control with maintenance of sinus rhythm confers improvements in symptoms and quality of life, above that achieved with rate control alone, for some patients
      • Early restoration of sinus rhythm may be preferable in younger patients as atrial fibrillation may become less reversible, and eventually irreversible, over time r2
      • Adequate rate control therapy must also continue even if rhythm control is initially successful because atrial fibrillation suppression may not be completely maintained (efficacy of antiarrhythmic drugs is modest and ablation procedures are not always permanently effective) r2
    • Choice of rhythm control method depends on a variety of factors including urgency of the need to restore sinus rhythm, duration of atrial fibrillation, success with previous efforts at rhythm control, and individual preference
      • Emergent electrical cardioversion is indicated when there is hemodynamic instability and in the setting of acute coronary syndrome with worsening ischemia that does not immediately respond to IV atrioventricular-nodal blocking drugs r2
        • Hemodynamic instability is uncommonly a direct result of atrial fibrillation and mandates a rapid search for underlying reversible conditions (eg, sepsis, gastrointestinal bleeding) that are contributing to the instability
      • For new-onset atrial fibrillation in a stable patient presenting to an emergency department
        • Consider nonemergent (but during initial encounter) cardioversion with appropriate anticoagulation precautions
          • It is safe to cardiovert in the any of the following: r40
            • Patients who have been adequately anticoagulated for at least 3 weeks
            • Patients with onset of atrial fibrillation within 12 hours and no history of stroke, transient ischemic attack, or valvular heart disease
            • Patients with onset of atrial fibrillation within 12 to 48 hours and no history of stroke, transient ischemic attack, or valvular heart disease, and negative finding for thrombus on transesophageal echocardiography or fewer than 2 of the following CHADS-65 criteria:
              • Age 65 years or older
              • Diabetes
              • Hypertension
              • Heart failure
        • Electrical cardioversion is increasingly attempted on initial emergency department visit, often with discharge home versus stay in observation bed or overnight monitored admission
          • Consider especially in younger patients, as opposed to an initial trial of only rate control strategy r9
          • After successful cardioversion, can withhold the start of long-term antiarrhythmic drug treatment until warranted by recurrence of atrial fibrillation r2r63
          • 75% of patients will have a recurrence within 1 year r63
        • Pharmacologic cardioversion is rarely attempted in emergency departments in the United States r9
          • Pharmacologic cardioversion is most effective when initiated within 7 days of onset of an episode
          • Can use oral flecainide or propafenone if absence of structural heart disease has been confirmed; however, length of time for drug effect (at least 4-6 hours) means that emergency department use is impractical r9
      • For patients with infrequent paroxysmal atrial fibrillation
        • Consider outpatient, pill-in-the-pocket pharmacologic cardioversion on an as-needed basis to restore sinus rhythm
          • This strategy involves self-administering propafenone or flecainide and a dose of β-blocker or nondihydropyridine calcium channel blocker r2
            • Patient takes β-blocker or calcium channel blocker 30 minutes before administering the antiarrhythmic agent to prevent a rapid ventricular response in case conversion to atrial flutter were to occur
            • Patient then takes a single dose of flecainide (200-300 mg) or propafenone (450-600 mg)
          • Monitor patient during initial self-administration to establish safety, then monitor (telemetry for at least 6 hours, blood pressure checks, and 12-lead ECG monitoring) before discharge. Patients can be discharged with prescriptions to use on an as-needed basis at home r67
          • Good choice for younger patients and those with a low burden of disease
      • For patients with frequent paroxysmal atrial fibrillation or persistent atrial fibrillation
        • Can attempt either electrical or pharmacologic cardioversion to restore sinus rhythm; ablation procedures are an option when antiarrhythmic drugs are ineffective or not tolerated
          • Electrocardioversion of atrial fibrillation and subsequent maintenance of sinus rhythm are more likely to be successful when atrial fibrillation duration is less than 6 months r12
            • Reasonable to perform repeated electrocardioversion in patients with persistent atrial fibrillation provided that sinus rhythm can be maintained for a clinically meaningful period between procedures r2
          • Can attempt pharmacologic cardioversion with a variety of antiarrhythmic drugs if no contraindications are present r2
            • Pharmacologic cardioversion is most likely to be effective when initiated within 7 days after the onset of an episode r2
            • Options include flecainide, propafenone, dofetilide, and IV ibutilide; oral amiodarone is also an option
            • IV vernakalant is another option (available in Canada and Europe but not in the United States)
          • Once restored, maintain sinus rhythm with an appropriate oral antiarrhythmic drug to decrease likelihood of recurrence
            • Consider presence or absence of structural heart disease, coronary artery disease, and potential to prolong the QT interval when choosing the specific antiarrhythmic drug. Cardiology consultation is recommended
            • Specific drug considerations
              • Overall, efficacy of antiarrhythmic drugs is only modest, with a recurrence rate of 43% to 67%, based on a 2019 Cochrane review r1r68
              • Sotalol, dofetilide, amiodarone, and dronedarone cause drug-induced QT-interval prolongation, and sotalol specifically has been linked to increased risk of death compared to placebo, based on data from 5 randomized controlled trials (RR, 2.23; 95% CI, 1.03-4.81) r68
              • Amiodarone is not only the most effective drug for maintaining sinus rhythm but also the drug associated with the highest toxicity and treatment withdrawal; do not use as first line treatment except in patients with heart failure r2
              • Without structural heart disease, first line antiarrhythmic drugs include dofetilide, sotalol, dronedarone, flecainide, and propafenone r63
              • First line antiarrhythmic drug for patients with heart failure is dofetilide or amiodarone r2r63
              • Do not use dronedarone to treat atrial fibrillation in patients with New York Heart Association class III and IV heart failure or patients who have had an episode of decompensated heart failure in the past 4 weeks
              • First line drug for patients with coronary artery disease is dofetilide, dronedarone, or sotalol.r63 Flecainide (and propafenone, by inference) increases mortality in this population r2
          • Consider ablative therapies to achieve rhythm control
            • Catheter-delivered radiofrequency or cryoablation is used to isolate arrhythmogenic impulses originating from the area of the pulmonary vein ostia (known as pulmonary vein isolation or pulmonary vein antrum isolation)
            • Indications for catheter ablation (according to an international expert consensus statement) include: r69
              • Patients who remain symptomatic despite antiarrhythmic drugs
              • Patients intolerant of antiarrhythmic drugs
              • Patients with either symptomatic paroxysmal atrial fibrillation or symptomatic persistent atrial fibrillation (reasonable as first line therapy before trial of an antiarrhythmic drug)
              • Patients with paroxysmal atrial fibrillation who have symptomatic pauses, so-called brady-tachy syndrome (reasonable as first line therapy)
              • High-level competitive athletes with paroxysmal or persistent atrial fibrillation (reasonable as first line therapy) r70
              • Reasonable in selected patients with heart failure r71
              • Patients with atrial fibrillation–mediated tachycardia-induced cardiomyopathy r11
            • Considered first line therapy in patients with concomitant atrial fibrillation and heart failure with reduced ejection fraction r72
          • Outcomes of catheter ablation versus medical therapy
            • CABANA trial showed that for a broad population of symptomatic patients, catheter ablation, compared with medical therapy, led to clinically important and significant improvements in quality of life at 12 months r73
              • No significant reductions in specific end points of death, disabling stroke, serious bleeding, or cardiac arrest; however, treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers r74
            • In a randomized controlled trial comparing several common techniques for ablation, about 75% of patients, overall, were asymptomatic 1 year after catheter ablation when monitored using an implanted loop recorder r75
              • Although at least 1 documented recurrence of an atrial tachyarrhythmia within 12 months occurred in 53% of patients, the burden of atrial fibrillation (percentage of time in atrial fibrillation) was reduced by about 99%
            • Randomized trial results published in 2021 reported:
              • Cryoballoon ablation as initial therapy was superior to drug therapy for prevention of atrial arrhythmia recurrence in patients with paroxysmal atrial fibrillation r76
              • In patients receiving initial treatment for symptomatic paroxysmal atrial fibrillation, there was a significantly lower rate of atrial fibrillation recurrence with catheter cryoballoon ablation than with antiarrhythmic drug therapy r77
          • Cautions with ablative therapy
            • Ablative procedures do not eliminate need for anticoagulation
            • Antiarrhythmic drug treatment for 3 months after ablation can reduce risk of recurrent atrial fibrillation r78
          • Surgical ablation is an option for patients undergoing cardiac surgery for other reasons, but it is rarely performed as a stand-alone procedure r78

Drug therapy

  • Anticoagulants r2r79r80r81d4
    • Vitamin K antagonist
      • Warfarin r82r83r84c78
        • Warfarin Sodium Oral tablet; Adults: A target INR of 2.5 (range: 2 to 3) is recommended. For eligible patients, novel oral anticoagulants (i.e., apixaban, dabigatran, edoxaban, rivaroxaban) are preferred over warfarin therapy.
    • Factor Xa inhibitors
      • Apixaban r85c79
        • Apixaban Oral tablet; Adults: 5 mg PO twice daily. Reduce the dose to 2.5 mg PO twice daily in patients with any 2 of the following characteristics: age 80 years and older; body weight 60 kg or less; or serum creatinine 1.5 mg/dL or greater. Also, decrease to 2.5 mg PO twice daily if patients are taking a drug that is a strong inhibitor of both CYP3A4 and P-glycoprotein (P-gp).
      • Rivaroxaban c80
        • Rivaroxaban Oral tablet; Adults: 20 mg PO once daily with evening meal.
      • Edoxaban c81
        • Edoxaban Oral tablet; Adults: 60 mg PO once daily. Do not use in patients with CrCl more than 95 mL/minute due to increased risk of ischemic stroke compared to warfarin.
    • Direct thrombin inhibitors
      • Dabigatran c82
        • Dabigatran etexilate Oral capsule; Adults: 150 mg PO twice daily.
  • Rate control agents
    • β-blockers
      • Metoprolol r86c83
        • IV
          • Metoprolol Tartrate Solution for injection; Adults: 2.5 to 5 mg IV bolus over 1 to 2 minutes; may repeat every 5 minutes to a max of 3 doses.
        • Immediate-release oral
          • Metoprolol Tartrate Oral tablet; Adults: 25 to 100 mg PO twice daily.
        • Extended-release oral
          • Metoprolol Succinate Oral tablet, extended-release; Adults: 50 to 400 mg PO daily.
      • Esmolol c84
        • Esmolol Hydrochloride Solution for injection; Adults: 50 mcg/kg/minute continuous IV infusion, initially. Titrate by 50 mcg/kg/minute every 4 minutes until goal heart rate is attained. Usual dose: 25 to 200 mcg/kg/minute. Max: 300 mcg/kg/minute. May give 500 mcg/kg IV over 1 minute at initiation and before each infusion rate increase up to 3 doses.
      • Propranolol c85
        • IV
          • Propranolol Hydrochloride Solution for injection; Adults: 1 mg IV; may repeat dose every 2 minutes up to 3 mg.
        • Oral
          • Propranolol Hydrochloride Oral tablet; Adults: 10 to 40 mg PO 3 or 4 times daily.
      • Atenolol c86
        • Atenolol Oral tablet; Adults: 25 to 100 mg PO daily.
      • Nadolol c87
        • Nadolol Oral tablet; Adults: 10 to 240 mg PO daily.
    • Calcium channel blockers
      • Diltiazem c88
        • Do not use when associated with Wolff-Parkinson-White or Lown-Ganong-Levine syndrome
        • IV
          • Diltiazem Hydrochloride Solution for injection; Adults: 0.25 mg/kg IV bolus over 2 minutes. After 15 minutes, 0.35 mg/kg IV over 2 minutes may be given. Individualize as needed. Begin 10 mg/hour continuous IV infusion immediately after IV bolus. Some patients respond to lower doses (e.g., 5 mg/hour). Max: 15 mg/hour.
        • Immediate-release oral
          • Diltiazem Hydrochloride Oral tablet; Adults: Initially, 30 to 60 mg PO 4 times per day. Increase up to 360 mg/day in 3 to 4 divided doses. Individual patients may respond to higher doses up to 480 mg/day.
        • Extended-release oral
          • Diltiazem Hydrochloride Oral tablet, extended-release; Adults: 120 to 360 mg PO once daily.
      • Verapamil r2c89
        • Do not use when associated with Wolff-Parkinson-White or Lown-Ganong-Levine syndrome
        • IV
          • Verapamil Hydrochloride Solution for injection; Adults: 5 to 10 mg (0.075 to 0.15 mg/kg) IV over at least 2 minutes. If no adequate response after 30 minutes, may give an additional 10 mg (0.15 mg/kg) IV followed by a 0.005 mg/kg/minute continuous IV infusion. An optimal interval for subsequent doses has not been determined and should be individualized for each patient.
        • Immediate-release oral
          • Verapamil Hydrochloride Oral tablet; Adults: 240 to 320 mg/day PO, given in 3 to 4 divided doses.
        • Extended-release oral
          • Verapamil Hydrochloride Oral tablet, extended-release; Adults: 180 to 480 mg PO once daily.
    • Cardiac glycosides
      • Digoxin (loading dose) c90
        • Do not use when associated with Wolff-Parkinson-White or Lown-Ganong-Levine syndrome
        • Digoxin Oral tablet; Adults, Adolescents, and Children older than 10 years: Total dose of 10 to 15 mcg/kg PO given in 3 divided doses, with first dose equaling 50% of total loading dose. Then give 25% of total loading dose at 6 to 8 hour intervals for 2 doses; carefully assess response before each dose.
      • Digoxin (maintenance dose)
        • Digoxin Oral tablet; Adults, Adolescents, and Children older than 10 years: Initially, 3.4 to 5.1 mcg/kg/day PO given once daily. Usual daily maintenance dose requirements for the treatment of congestive heart failure are based on corrected CrCl (mL/minute per 70 kg or mL/minute/1.73m2) and lean body weight (LBW). Doses are rounded to the nearest whole/half tablet. According to the Beers Criteria, digoxin should be avoided as first-line therapy for atrial fibrillation or heart failure; if use is necessary, the drug should not be prescribed in daily doses greater than 0.125 mg.
  • Antiarrhythmic agents for cardioversion
    • Flecainide c91
      • Flecainide Acetate Oral tablet; Adults: 200 to 300 mg PO as single dose. For termination of atrial fibrillation out of hospital, use in combination with beta blocker or nondihydropyridine calcium channel blocker given 30 minutes or more before flecainide.
    • Propafenone c92
      • Propafenone Hydrochloride Oral tablet; Adults: 450 to 600 mg PO as single dose. For termination of atrial fibrillation out of hospital, use in combination with beta blocker or nondihydropyridine calcium channel blocker given 30 minutes or more before propafenone.
    • Ibutilide c93
      • Can lead to torsades de pointes; must be administered under ECG monitoring until QTc interval is back to baseline (at least 4 hours)
      • Discontinue if marked prolongation of QT or QTc develops
      • If any arrhythmic activity is noted, longer monitoring is required. Patients with abnormal hepatic function should be monitored for more than the 4-hour period
      • Ibutilide Fumarate Solution for injection; Adults weighing less than 60 kg: 0.01 mg/kg/dose IV over 10 minutes; may repeat 10 minutes after end of initial infusion if arrhythmia is not terminated.
      • Ibutilide Fumarate Solution for injection; Adults weighing 60 kg or more: 1 mg IV over 10 minutes; may repeat 10 minutes after end of initial infusion if arrhythmia is not terminated.
    • Dofetilide r2c94
      • Dofetilide Oral capsule; Adults: Individualize dosage based on renal function and QTc in a monitored facility. NOTE: Initiation of dofetilide treatment requires continual telemetry monitoring in a hospitalized setting for 3 days. Before initiating dofetilide therapy, previous antiarrhythmic therapy should be withdrawn under careful monitoring for a minimum of 3 half-lives. If the patient previously received amiodarone, do not initiate dofetilide therapy until amiodarone serum concentrations are < 0.3 mcg/mL (or until amiodarone has been withdrawn for 3 months or more).
      • Steps for initiation: r87
        • Place patient on telemetry and ensure serum potassium is within reference range before initiating therapy. Potassium should be maintained in reference range throughout dofetilide therapy
        • Obtain baseline QTc (for heart rate 60 beats per minute or higher) or QT (for heart rate less than 60 beats per minute). Note: no data on usage when heart rate is less than 50 beats per minute
          • If QTc/QT is higher than 440 milliseconds, do not use dofetilide
          • If QTc/QT is 440 milliseconds or less, proceed
        • Calculate estimated creatinine clearance using the Cockcroft-Gault equation and dose based on creatinine clearance
          • Initial dofetilide dosing based on creatinine clearance (calculated via Cockcroft-Gault equation).Data from Pfizer Inc: Tikosyn--Dofetilide Capsules [Prescribing Information]. National Library of Medicine Daily Med website. Updated October 9, 2020. Accessed March 29, 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=02438044-d6a3-49e9-a1ac-3aad21ef2c8c.
            Creatinine clearance (mL/minute)Dose
            More than 60500 mcg twice daily
            40 to 60250 mcg twice daily
            20 to 40125 mcg twice daily
            Less than 20Usage contraindicated
        • Check QTc/QT 2 to 3 hours after first dose and adjust dose if necessary based on change in QTc/QT
          • If QTc/QT increase is 15% or less of baseline, continue current dose
          • If QTc/QT increase is more than 15% of baseline or more than 500 milliseconds, decrease dose according to table below
            • Dofetilide dose adjustment after first dose.Data from Pfizer Inc: Tikosyn--Dofetilide Capsules [Prescribing Information]. National Library of Medicine Daily Med website. Updated October 9, 2020. Accessed March 29, 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=02438044-d6a3-49e9-a1ac-3aad21ef2c8c.
              If the starting dose based on creatinine clearance is:Then the adjusted dose (for QTc or QT prolongation) is:
              500 mcg twice daily250 mcg twice daily
              250 mcg twice daily125 mcg twice daily
              125 mcg twice daily125 mcg once daily
        • If at any time after the second dose of dofetilide the QTc/QT increases to higher than 500 milliseconds, dofetilide should be discontinued
    • Amiodarone c95
      • IV
        • Amiodarone Hydrochloride Solution for injection; Adults: 150 mg IV over 10 minutes, followed by 1 mg/minute continuous IV infusion for 6 hours then 0.5 mg/minute continuous IV infusion for 18 hours. After 24 hours, change to PO or consider decreasing rate to 0.25 mg/minute.
      • Oral
        • Amiodarone Hydrochloride Oral tablet; Adults: 400 to 800 mg/day PO in divided doses for 2 to 4 weeks to a total load of up to 10 g then 100 to 200 mg PO once daily.
    • Procainamide (for patients with known or suspected Wolff-Parkinson-White syndrome) c96
      • Loading dose
        • Procainamide Hydrochloride Solution for injection; Adults: 15 to 17 mg/kg as an IV infusion, infused at a rate of 20 to 30 mg/minute. Alternatively, 100 mg IV every 5 minutes given by slow IV push up to 1,000 mg.
      • Maintenance dose
        • Procainamide Hydrochloride Solution for injection; Adults: Initially, 1 to 4 mg/minute continuous IV infusion. The usual initial maintenance dose is 50 mg/kg/day. Adjust dosage based on renal function, clinical goals, and serum drug level monitoring.
  • Antiarrhythmic agents for maintaining sinus rhythm
    • All have a variety of significant precautions and contraindications; consult cardiologist for selection of safe and effective drug based on individual factors
    • Flecainide c97
      • Flecainide Acetate Oral tablet; Adults: Initially, 50 mg PO every 12 hours. Increase dose by increments of 50 mg PO twice daily every 4 days as needed. Max: 300 mg/day.
    • Propafenone c98
      • Immediate-release
        • Propafenone Hydrochloride Oral tablet; Adults: Initially, 150 mg PO every 8 hours. Increase dosage after intervals of 3 to 4 days or more to 225 mg PO every 8 hours, and if necessary, to 300 mg PO every 8 hours.
      • Extended-release
        • Propafenone Hydrochloride Oral capsule, extended-release; Adults: Initially, 225 mg PO every 12 hours. Increase dosage at intervals of 5 days or more to 325 mg PO every 12 hours, and if necessary, to 425 mg PO every 12 hours.
    • Dofetilide r2
      • Dofetilide Oral capsule; Adults: Individualize dosage based on renal function and QTc, which should be re-evaluated every 3 months.
      • Continue dosage at discharge as from initial dosage titration, see dofetilide dosing initiation
    • Dronedarone r2c99
      • Do not use in patients with New York Heart Association class III and IV heart failure or patients who have had an episode of decompensated heart failure in the past 4 weeks r2
      • Contraindicated in patients with permanent atrial fibrillation in whom normal sinus rhythm will not or cannot be restored; dronedarone doubles the risk of death and heart failure events in patients with permanent atrial fibrillation
      • Dronedarone Oral tablet; Adults: 400 mg PO twice daily.
    • Sotalol r2c100
      • Contraindicated in patients with systolic heart failure or significant left ventricular hypertrophy, sinus bradycardia (less than 50 beats per minute), sick sinus syndrome, second- or third-degree atrioventricular block without pacemaker, congenital or acquired long QT syndrome, cardiogenic shock, serum potassium less than 4 mEq/L or baseline QT interval greater than 450 milliseconds r63
      • Initiate or reinitiate oral sotalol in a facility that can provide continuous ECG monitoring and cardiac resuscitation and by personnel who are trained in the management of serious ventricular arrhythmias. Hospitalize patients initiated or reinitiated on sotalol for at least 3 days or until steady-state concentrations are achieved. Normalize serum potassium and magnesium concentrations before initiating. Monitor the QTc interval every 2 to 4 hours after each dose
      • Renal dose adjustments
        • Estimated creatinine clearance at least 60 mL/minute: no dose adjustment necessary
        • Estimated creatinine clearance 40 to 59 mL/minute: extend dosing interval to every 24 hours. Dose may be titrated after at least 5 doses
        • Estimated creatinine clearance less than 40 mL/minute: use is contraindicated
      • Sotalol Hydrochloride Oral tablet; Adults: 80 mg PO twice daily, initially. May increase dose by 80 mg/day every 3 days if the QTc interval is less than 500 milliseconds. Usual dose: 120 mg PO twice daily.
    • Amiodarone
      • Amiodarone Hydrochloride Oral tablet; Adults: 400 to 800 mg/day PO in divided doses for 2 to 4 weeks to a total load of up to 10 g then 100 to 200 mg PO once daily.

Nondrug and supportive care

Modify lifestyle and manage cardiovascular risk factors to decrease the burden of atrial fibrillation (secondary prevention) r3

  • Counsel obese and overweight patients to lose weight c101
    • Target weight loss is 10% or more of body weight r3
      • Based on prospective studies, this degree of weight loss results in:
        • 6-fold arrhythmia-free likelihood compared with those who lost less than 3% or gained weight r88
        • Progression to persistent atrial fibrillation in only 3% r89
        • 88% reversed from persistent to paroxysmal or no atrial fibrillation r89
      • Retrospective study of morbidly obese patients found that bariatric surgery is associated with reduced risk of new atrial fibrillation and a lower atrial fibrillation recurrence after ablation r90
  • Encourage physical activity c102
    • Regular aerobic exercise is effective in reducing atrial fibrillation burden and improving atrial fibrillation–related symptoms and quality of life r3
      • Encourage 150 minutes per week of moderate-intensity exercise r3
      • Effects of high-intensity interval training on atrial fibrillation and atrial remodeling are uncertain r3
      • Extreme endurance exercise far exceeding that recommended by physical activity guidelines has been associated with increased risk of incident atrial fibrillation r31
      • Athletes with short-lived, well-tolerated atrial fibrillation and no structural heart disease may participate in regular sporting activities r70
  • Counsel patients to quit smoking c103d5
    • Recommended as part of general cardiovascular risk factor reduction. No evidence regarding reduction in atrial fibrillation burden attributable specifically to smoking cessation r3
    • Includes behavioral and pharmacologic approaches, which may be used in combination
    • Pharmacologic therapy includes nicotine replacement and the smoking cessation aids bupropion and varenicline
  • Counsel patients who regularly consume moderate or high levels of alcohol to reduce their intake r3c104
    • Abstinence from alcohol in patients with atrial fibrillation who consume 10 drinks per week or more was associated with improved rhythm control compared with control in a randomized controlled trial r91
Procedures
Electrocardioversion r2r92c105
General explanation
  • Delivery of an electric shock synchronized with the QRS complex to restore sinus rhythm
  • Requires procedural sedation whenever possible (eg, propofol, midazolam, fentanyl, etomidate) r9
  • External electrode pads are placed in an anteroposterior position across the chest wall (superior to anterolateral placement in some, but not all studies) r2
  • Deliver a shock with 150 to 200 J on a biphasic machine or 200 to 300 J on a monophasic machine. May need to select lower energy for small patients or higher energy for large patients r9
  • If first attempt is unsuccessful, repeated attempt is made after clinician switches to alternative electrode placement, applies pressure over electrodes (especially for obese patients), increases energy, or administers an antiarrhythmic medication r2
  • With atrial fibrillation lasting more than 48 hours or of unknown duration that requires immediate cardioversion for hemodynamic instability, start anticoagulation as soon as possible and continue for at least 4 weeks r4
  • For elective cardioversion, anticoagulate for 3 weeks before procedure and continue for at least 4 weeks afterwards r4
Indication
  • Selected patients with atrial fibrillation for whom a rhythm control strategy is elected
  • Patients with hemodynamic instability and/or ongoing cardiac ischemia who do not respond immediately to IV atrioventricular-nodal blocking agents
Contraindications
  • Presence of left atrial thrombus

Comorbidities

  • Heart failure c106
    • Heart failure and atrial fibrillation have a bidirectional association, share many of the same risk factors, and frequently complicate each other
    • Heart failure with atrial fibrillation is associated with worse outcomes, including increase in stroke severity and all-cause mortality. Women have worse outcomes than men r93
    • Best treatment strategies for patients with heart failure and atrial fibrillation are unclear r94
      • Rate control is typically accomplished with β-blockers in patients with heart failure
        • Nondihydropyridine calcium channel blockers are contraindicated in patients with left ventricular systolic dysfunction but are reasonable when systolic function is preserved r2
        • Digoxin can also be considered but has been associated with an increased mortality risk in patients with atrial fibrillation r65
      • The AF-CHF trialr95 showed that pharmacologic rhythm control is not superior to a rate control strategy for preventing cardiac death, but it should be considered for patients who remain symptomatic with rate control alone
        • Pharmacologic rhythm control options are limited to amiodarone and dofetilide in heart failure with reduced ejection fraction r2
      • Catheter ablation may be superior to both pharmacologic rate and rhythm control in patients with both heart failure and atrial fibrillation
        • CASTLE-AF trial showed that, for patients with heart failure with reduced ejection fraction, catheter ablation was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure r96
        • Catheter ablation appears to be similarly effective (freedom from recurrent atrial arrhythmia; improvements in New York Heart Association functional class; symptom severity) in both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction r97
        • For the overall population, results from the CABANAr74r73 trial do not show improved survival with catheter ablation; detailed analysis of the heart failure subgroup in the trial is ongoing and will add additional information r94
  • Hyperthyroidism c107
    • Prevalence of atrial fibrillation is 13.8% in patients with overt hyperthyroidism compared with 2.3% in patients with normal thyroid function r98
    • Several associated factors increase the risk of atrial fibrillation in patients with hyperthyroidism: male sex, increasing age, ischemic heart disease, congestive heart failure, and heart valve disease r99
    • Atrial fibrillation itself is initially managed with a rate control strategy using a β-blocker (first line) or a dihydropyridine calcium channel blocker (second line) r2
    • Restoration of euthyroidism is an important element of managing atrial fibrillation in these patients
      • Referral to an endocrinologist for evaluation of the underlying cause and treatment of the condition (which may be complex) is recommended
    • Cardioversion and maintenance of sinus rhythm typically fail unless a euthyroid state has been achieved r2
  • Chronic obstructive pulmonary disease c108
    • Atrial fibrillation is common; must be distinguished from multifocal atrial tachycardia, which is also common but is unlikely to respond to electrical cardioversion r2
    • Can be precipitated by β-adrenergic agonists and theophylline
    • First line therapy is to correct hypoxia and any underlying acid-base abnormality as cardioversion and maintenance with antiarrhythmic drugs may be ineffective otherwise r2
    • Rate control can be achieved with nondihydropyridine calcium channel blockers r2
      • Digoxin can be added if rate control is not sufficient
      • Do not use non–β-1-selective blockers in the presence of bronchospasm but consider them for patients who do not have bronchospasm
      • Atrioventricular nodal ablation/permanent pacemaker insertion is an option for patients refractory to drug therapy
  • Hypertension c109
    • Hypertension is a common comorbidity
    • Control blood pressure
      • Blood pressure treatment targets vary by different professional guidelines
      • Joint National Committee guidelines r100recommend blood pressure target of less than 140/90 and less than 150/90 mm Hg for those younger than 60 and older than 60 years, respectively, whereas 2019 American College of Cardiology/American Heart Association guidelinesr101 on primary prevention of cardiovascular disease recommend target blood pressure of less than 130/80 mm Hg in most cases
      • Lower targets (130/80 mm Hg or lower) are recommended by some organizations for patients with specific comorbidities (diabetes and/or chronic kidney disease)r103r102
      • Mineralocorticoid receptor antagonist treatment significantly reduced recurrent (as well as new-onset) atrial fibrillation in a meta-analysis of clinical trials and observational studies r104
  • Diabetes c110
    • Optimize glycemic control in patients with diabetes
    • Well-controlled glycemia may reduce recurrent atrial fibrillation burden, especially after ablation
      • Glycemic goals are not different for patients with atrial fibrillation as compared with other patients
  • Obstructive sleep apnea c111
    • Take a sleep symptom–oriented clinical history, and/or use a questionnaire to identify those at higher risk for obstructive sleep apnea (eg, Epworth Sleepiness Scaler105; STOP-Bang questionnairer106)
    • Refer for further testing if indicated (ie, polysomnography; home sleep study)
    • Treat with CPAP if indicated
      • A meta-analysis found an inverse relationship between CPAP therapy and atrial fibrillation recurrence r107
      • Use of CPAP decreases likelihood of progression to permanent atrial fibrillation r108

Special populations

  • Women
    • Women with atrial fibrillation are more symptomatic, have poorer quality of life, and have worse major adverse outcomes than men
      • In a meta-analysis of cohort studies, women with atrial fibrillation, as compared to men with atrial fibrillation, had a 12% increased overall mortality risk, as well as increased cardiovascular mortality r109
      • Atrial fibrillation is a strong risk factor for stroke in women
        • Overall, woman have about twice the risk of stroke compared with men r109
        • Cardioembolic stroke is more disabling in women than in men
        • When treated with warfarin, women had higher risk of stroke compared with men, but this difference did not exist when treated with a non–vitamin K oral anticoagulant. Non–vitamin K oral anticoagulant treatment also resulted in less frequent major bleeding r51
    • Therapeutic considerations
      • Treatment with non–vitamin K oral anticoagulants is recommended for women whose CHA₂DS₂-VASc score is 3 or greater and can be considered for women with a CHA₂DS₂-VASc score of 2 r4
        • When treated with warfarin, women have been found to be in therapeutic range less often than men; even when time in therapeutic range was comparable, women had a higher risk of stroke r110
        • When treated with non–vitamin K oral anticoagulants, the sex disparity in outcomes for stroke disappears
      • Avoid unnecessary use of digoxin for rate control; it has been associated with excess risk for invasive breast cancer as well as increased overall mortality r111
      • Rate control may be a preferred strategy rather than rhythm control in women
        • In a randomized trial (522 participants; about 40% women), women treated with antiarrhythmic drugs had a higher incidence of adverse outcomes (eg, cardiovascular death, heart failure, thromboembolic complications, bleeding, need for pacemaker, drug adverse effects) than women treated with a rate control strategy r7
          • Carefully monitor electrolyte levels, QT interval, and adverse effects when women are treated with antiarrhythmic drugs
  • Pregnant patients
    • Atrial fibrillation can be diagnosed during pregnancy in patients with structural heart disease and hypertension, but it can sometimes occur without these comorbidities
    • Manage pregnant patients with atrial fibrillation as high-risk patients in close collaboration with a cardiologist, obstetrician, and neonatologist r112
    • Direct current cardioversion is safe in all stages of pregnancy and appropriate for pregnant patients who are hemodynamically unstable owing to atrial fibrillation r112
    • Anticoagulation is recommended in pregnant patients with atrial fibrillation who are at risk for stroke according to CHA₂DS₂-VASc score r112
      • Non–vitamin K oral anticoagulants are contraindicated during pregnancy
      • Vitamin K antagonists cross the placenta and are contraindicated in pregnancy:
        • Teratogenic in the first trimester
        • Risk of fetal bleeding if given in the weeks leading up to delivery
        • Sometimes used in during pregnancy in patients with mechanical heart valves if the benefit is judged to outweigh the risk
      • Low-molecular-weight heparin is a safe choice r113
      • Additional information and specific recommendations are available from the American College of Chest Physiciansr113 and the European Society of Cardiologyr114
    • Oral β-blockers are first line for rate controlr115. All commonly used antiarrhythmic drugs cross the placenta. Consultation with a cardiologist and obstetrician is advised

Monitoring

  • Monitoring anticoagulation
    • Patients taking warfarin: measure INR at least weekly during initial therapy and at least monthly once anticoagulation is stable. Goal INR is 2.0 to 3.0 r4
    • Patients taking non–vitamin K oral anticoagulants do not usually require monitoring of coagulation r4r116
      • Routine coagulation tests (prothrombin time and activated partial thromboplastin time) do not provide an accurate assessment of their anticoagulant effects
      • Commercial assays to measure non–vitamin K oral anticoagulant serum concentration are available, but results are not well correlated with outcomes. Use these assays only for specific indications, including: r4
        • Measurement of drug concentrations in patients undergoing urgent surgical procedures
        • Detection of potentially toxic drug concentrations in patients with chronic kidney disease or those undergoing dialysis
        • Detection of potential drug–drug interactions to guide dose adjustment
        • Evaluation of drug absorption in severely obese patients (BMI greater than 35 kg/m² or weight above 120 kg)
        • Assessment of patient adherence
    • Patients who are at high risk of bleeding (ie, high HAS-BLED score) require closer follow-up
  • Monitoring rate and rhythm
    • Ambulatory rhythm monitoring (eg, Holter monitor, event recorders) and exercise testing can be useful to judge the adequacy of rate control r2
    • Monitor for adverse effects of antiarrhythmic drugs with periodic measurement of QT interval and electrolyte levels

Complications and Prognosis

Complications

  • Thromboembolism c112
    • Embolic stroke c113
      • 5-fold increased risk of stroke with nonvalvular atrial fibrillation r23r117
      • 20-fold increased risk of stroke with atrial fibrillation associated with mitral stenosis r117
      • Stroke associated with atrial fibrillation is associated with greater disability and higher mortality than stroke not associated with atrial fibrillation, and recurrence is more likely r118
      • Anticoagulation, if eligible by CHA₂DS₂-VASc score, and control of other stroke risk factors (eg, hypertension, dyslipidemia) can greatly reduce stroke risk r2
    • Peripheral thromboembolism risk is a rare complication but most events are subclinical c114
      • Managed with surgical embolectomy
  • Heart failure c115d6
    • Heart failure and atrial fibrillation have a bidirectional association, share many of the same risk factors, and frequently complicate each other
    • Atrial fibrillation can lead to or exacerbate both heart failure with reduced ejection fraction (ie, tachycardia-mediated ventricular dysfunction) and heart failure with preserved ejection fraction
  • Cognitive impairment and dementia (vascular dementia or Alzheimer disease) r119c116c117d7
    • Atrial fibrillation is a risk factor for cognitive dementia, independent of clinical stroke. Strongest association was for younger participants with the longest duration of atrial fibrillation in prospective, population-based study r120
    • Mechanism is likely multifactorial, including nonapparent strokes, cerebral microinfarcts, and reduced cerebral blood flow
    • Indirect evidence that effective anticoagulation in atrial fibrillation reduces the risk of cognitive impairment and dementia r121
    • Observational study of effect of catheter ablation (versus no ablation) on a variety of outcomes showed a significantly lower risk of dementia (both Alzheimer and non-Alzheimer) in patients who underwent ablation r122

Prognosis

  • Atrial fibrillation tends to progress from paroxysmal to persistent over time and may eventually become irreversible
  • In general, outcomes for specific therapies are better for paroxysmal atrial fibrillation than for persistent atrial fibrillation r2
  • Prognosis is affected by any underlying structural heart disease
  • Atrial fibrillation has many associated adverse outcomes, including stroke, heart failure, cognitive impairment, Alzheimer disease, and 2-fold increased mortality risk. The extent to which these outcomes can be mitigated by restoring of sinus rhythm is uncertain r74r119r123
  • There is higher relative risk of cardiovascular and all-cause mortality, stroke, and heart failure in women than men r109

Screening and Prevention

Screening

Screening tests

  • US Preventive Services Task Force concluded that currently evidence is insufficient to assess the balance of benefits and harms of screening for atrial fibrillation with ECG r124
  • American College of Cardiology/American Heart Association/Heart Rhythm Society guideline gives no formal recommendation for screening r2
  • European Society of Cardiology guidelines recommend the following: r11
    • Opportunistic screening for atrial fibrillation is recommended by pulse taking or ECG rhythm strip in patients older than 65 years c118c119
      • A large, randomized controlled trial of systematic ECG screening for atrial fibrillation in a population of older adults showed only a small overall benefit compared with standard of care; further study is underway r125
    • Opportunistic screening is also recommended in hypertensive patients and should be considered in patients with obstructive sleep apnea c120c121c122c123
    • In patients with transient ischemic attack or ischemic stroke, screening for atrial fibrillation is recommended by short-term ECG recording followed by continuous ECG monitoring for at least 72 hours

Prevention

  • Manage/treat known atrial fibrillation risk factors
    • Identify and treat hypertension, prediabetes, and diabetes c124c125c126
    • Recommend normal weight maintenance and weight loss if obese or overweight c127c128c129
      • For obese patients, bariatric surgery has been associated with reduced risk of new atrial fibrillation compared to medical management of obesity r126
    • Advise smoking cessation c130d5
    • Advise limiting alcohol consumption and avoiding binge drinking c131
    • In patients with hyperthyroidism, restore and maintain euthyroid state c132c133
  • May consider ACE inhibitor or angiotensin receptor blocker for primary prevention of new-onset atrial fibrillation in patients with heart failure with reduced left ventricular ejection fraction or in those with hypertension r2
  • Statin therapy may be reasonable for primary prevention of new-onset atrial fibrillation after coronary artery surgery r2
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