Atrial Fibrillation

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 compatible findings on 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. Males with a score of 2 or higher and females with a score of 3 or higher are at elevated risk and should receive anticoagulation therapy, usually with a direct 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 to 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 selected 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 for patients with drug-refractory atrial fibrillation ^r2r9
• 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 patients with paroxysmal atrial fibrillation than for those with persistent atrial fibrillation

Urgent Action

• Patients with hemodynamic compromise that occurs secondary to atrial fibrillation require urgent electrocardioversion ^r4
  • Use procedural sedation whenever possible ^r10
  • 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 ^r10
  • With atrial fibrillation that has lasted 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%^r11 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 start anticoagulation therapy. 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 ^r12
• 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 months^r13. Pharmacologic cardioversion is most likely to be effective when initiated within 7 days of onset of an episode ^r2r13
• 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. Consultation with a cardiologist is recommended

Clinical Clarification

• Atrial fibrillation is a common form of supraventricular tachyarrhythmia (1 in 4 lifetime risk^r14) 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 ^r15
  • Persistent ^r2
    • Continuous for more than 7 days
    • Often progresses from paroxysmal episodes to persistent episodes over a variable period
    • Both paroxysmal and persistent episodes may occur in the same patient
    • Accounts for 30% of atrial fibrillation diagnoses ^r15
  • 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) ^r15
  • 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 ^r16
• American Heart Association recently introduced another new descriptor, acute atrial fibrillation, to describe atrial fibrillation detected in an acute care setting or during an acute illness; this new terminology is intended to replace the term secondary atrial fibrillation used in older literature ^r17

Clinical Presentation

Causes and Risk Factors

Diagnostic Procedures

Differential Diagnosis

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 ^r2r38
  • 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 have symptoms (ie, palpitations, chest pain, shortness of breath, diaphoresis, dizziness) require urgent evaluation in an emergency care setting ^r39

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

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%^r11 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 males or 3 or greater in females, anticoagulation is recommended ^r4
    • If CHA₂DS₂-VASc score is 0 in males or 1 in females, 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 males; 2 in females) based on individual risk-benefit shared decision-making ^r4
    • Reassess CHA₂DS₂-VASc score at least annually for patients with atrial fibrillation who were initially at low risk for stroke and prescribe anticoagulation once CHA₂DS₂‐VASc score increases ^r43

    • 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 score	Points assigned
      Congestive heart failure	1
      Hypertension	1
      Age 75 years or older	2
      Diabetes mellitus	1
      Prior stroke (or transient ischemic attack)	2
      Vascular disease (eg, myocardial infarction, peripheral vascular disease)	1
      Age 65 to 74 years	1
      Sex category (female)	1

  • In addition to stroke risk, consider bleeding risk before initiating anticoagulation, as this may temper the decision to start anticoagulation therapy. 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 ^r12r44
    • Bleeding risk is increased with elevated systolic blood pressure, severe kidney disease, severe liver disease, history of stroke, history of bleeding, presence of a labile INR, age older than 65 years, concomitant antiplatelet or NSAID therapy, and excessive alcohol intake ^r45
    • 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 start anticoagulation therapy ^r12
      • Instead, for many patients, a high-risk score mandates correcting or minimizing modifiable risk factors and planning closer follow-up

    • 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 score	Points assigned
      Hypertension (systolic blood pressure over 160 mm Hg)	1
      Abnormal renal and liver function	1  point each
      Stroke	1
      Bleeding (previous bleeding or predisposition to it)	1
      Labile INRs	1
      Elderly	1
      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 1	1.02 to 1.13
      HAS-BLED score of 2	1.88
      HAS-BLED score of 3 or greater	3.74 or greater

  • With new-onset atrial fibrillation, when cardioversion (electrical or pharmacologic) is contemplated for a patient not on anticoagulation therapy, 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 for these patients and have led to controversy in management ^r6
        • Finnish CardioVersion, a series of 6 observational studies representing more than 10,000 patients with atrial fibrillation who underwent chemical or electrical cardioversion, found a non-negligible risk of embolic events among patients with atrial fibrillation duration of 12 to 48 hours versus duration of less than 12 hours (1.1% versus 0.33%) ^{r46r47r48r49r50r51}
        • The Finnish CardioVersion studies also found that anticoagulation before cardioversion reduced the risk conferred by atrial fibrillation duration within the first 48 hours of onset
        • There is controversy regarding current recommendations for use of anticoagulation before and after cardioversion for patients presenting with atrial fibrillation duration of less than 48 hours
        • In cases of hemodynamic instability, when urgent cardioversion is indicated, cardioversion is often administered without anticoagulation ^r5
        • The 2019 American College of Cardiology/American Heart Association guidelines recommend consideration of precardioversion anticoagulation or no anticoagulation for males with CHA₂DS₂-VASc score of 0 and females with scores of 1 or lower, with no postcardioversion anticoagulation ^r2
        • American College of Cardiology/American Heart Association guidelines recommend anticoagulation before cardioversion when the CHA₂DS₂-VASc score is 2 or higher for males or 3 or higher for females, 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: ^r40
          • For patients with atrial fibrillation duration less than 12 hours with no recent history of transient ischemic attack or stroke
            • Start anticoagulation therapy 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
            • Start anticoagulation therapy 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
            • Maintain anticoagulation therapy 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 on anticoagulation therapy 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 echocardiography–guided strategy in terms of embolic events or mortality ^r52
  • Continue long-term anticoagulation for all patients at elevated risk for embolic stroke
    • Patients with nonvalvular atrial fibrillation
      • Start anticoagulation therapy if CHA₂DS₂-VASc score is 2 or higher for males or 3 or higher for females ^r4
        • Direct oral anticoagulants are recommended (over warfarin) by most international guidelines ^r4r12r53r54
        • Direct oral anticoagulants have several advantages compared with vitamin K antagonists: ^r55
          • Reduced risk of embolic stroke, hemorrhagic stroke, and major bleeding, even for older adults of advanced age^r57r56
          • More convenient; no requirement for routine laboratory monitoring
          • Fewer dietary and drug interactions ^r56
        • 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 ^r58
          • 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 among 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) ^r59
        • For patients with end-stage renal disease or those undergoing dialysis, warfarin and apixaban are reasonable options for anticoagulation ^r54
    • Patients with valvular heart disease and atrial fibrillation
      • Recommendations for choice of anticoagulant 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 ^r4r54
          • Direct oral anticoagulants are not appropriate treatment owing to lack of favorable data for this indication ^r2
          • A large randomized controlled trial comparing rivaroxaban with warfarin therapy for patients with rheumatic heart disease–associated atrial fibrillation found that warfarin therapy led to a lower rate of a composite of cardiovascular events or death compared with rivaroxaban therapy; no significant difference in rate of major bleeding was noted ^r60
        • 2020 American College of Cardiology/American Heart Association guidelines recommend that direct oral anticoagulants or warfarin 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 ^r61
  • 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 ^r62
    • 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) ^r4r63
    • Meta-analysis of 2 randomized controlled trials (PROTECT AF^r65 and PREVAIL^r66 trials) and 2 nonrandomized registries published in 2015 found that for appropriate candidates, left atrial appendage closure resulted in: ^r64
      • Similar benefit in terms of all-cause stroke compared with 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 with warfarin
    • Meta-analysis published in 2022 similarly found that left atrial appendage closure was associated with lower all-cause mortality; cardiovascular mortality; hemorrhagic stroke; major bleeding; and the composite of stroke, systemic embolism, and cardiovascular death compared with oral anticoagulation; but risk of all-cause stroke, ischemic stroke, and systemic embolism was similar between groups ^r67

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 for patients at high risk for cardiovascular complications and may be preferred for this group ^r68r69
  • In general, depending on individual patient factors, either strategy is reasonable ^r2r4
• 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 patients without symptoms who have a structurally and functionally normal heart and when risks of restoring sinus rhythm outweigh benefits ^r70
    • Can be the initial strategy for 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 ^r10
  • Use an atrioventricular-nodal blocking drug as initial therapy ^r2
    • NOTE: Do not use atrioventricular-nodal blocking drugs for 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
    • Options include:
      • β-Blockers
        • In the acute setting where rapid control of ventricular rate is desired, metoprolol, propranolol, or esmolol can be given intravenously ^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 was achieved in 70% of patients given a β-blocker as first drug in the AFFIRM trial
        • Use with caution for 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 intravenously
        • Rate control was achieved in 54% of patients treated with oral calcium channel blockers as first drug in AFFIRM^r71 trial
        • Use with caution for 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 ^r70
        • May be useful in the following situations:
          • Setting of heart failure (no negative inotropic effects); however, may increase risk of death^r72 in this population ^r2
          • In combination with a β-blocker and/or a non-dihydropyridine calcium channel blocker when ventricular rate control is insufficient ^r2
          • For 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 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 ^r73
        • 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 ^r73
        • More strict rate control is important when an elevated ventricular rate is contributing to ventricular dysfunction (known as tachycardia-mediated cardiomyopathy)

      • Rapid ventricular rate control using IV medications.

        Drug	Dose
        β-blockers
        Metoprolol	2.5 to 5 mg IV every 5 minutes up to 3 doses
        Esmolol	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	1 mg IV every 2 minutes as needed for up to 3 doses
        Nondihydropyridine calcium channel blockers
        Verapamil	0.075 to 0.15 mg/kg (Usual dose: 5 to 10 mg) IV bolus May administer an additional 0.15 mg/kg (Usual dose: 10 mg) IV bolus 30 minutes after initial bolus if no response, followed by 0.005 mg/kg/minute continuous IV infusion
        Diltiazem	0.25 mg/kg (Usual dose: 15 to 20 mg) IV bolus, followed by 5 to 10 mg/hour continuous IV infusion, initially Titrate by 5 mg/hour as needed. Max: 15 mg/hour May administer an additional 0.35 mg/kg (Usual dose: 20 to 25 mg) IV bolus 15 minutes after initial bolus if needed
        Other agents
        Digoxin	Not 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 those achieved with rate control alone, for some patients
    • Early restoration of sinus rhythm may be preferable for 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
    • Antiarrhythmic agents have a variety of significant precautions and contraindications; consult cardiologist for selection of safe and effective drug based on individual factors
  • 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
        • Cardioversion is safe for any of the following individuals: ^r42
          • Patients who have had adequate anticoagulation 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 for younger patients, as opposed to an initial trial of only rate control strategy ^r10
        • After successful cardioversion, can withhold the start of long-term antiarrhythmic drug treatment until warranted by recurrence of atrial fibrillation ^r2r70
        • 75% of patients will have a recurrence within 1 year ^r70
      • Pharmacologic cardioversion is rarely attempted in emergency departments in the United States ^r10
        • 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 ^r10
    • 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 taking the antiarrhythmic agent to prevent a rapid ventricular response in case conversion to atrial flutter could 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 ^r74
        • 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 ^r13
          • 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; multiple pharmacologic agent options exist ^r2
          • Amiodarone ^r75
            • May cause pulmonary toxicity; obtain baseline chest x-ray and pulmonary function testing prior to initiation
          • Flecainide ^r76
            • Contraindicated for patients with preexisting second- or third-degree AV block or right bundle branch block associated with left hemiblock
            • Requires adjustment for renal dysfunction
          • Dofetilide ^r77
            • Begin use of telemetry for monitoring patient and ensure serum potassium is within reference range before initiating therapy. Potassium should be maintained in reference range throughout dofetilide therapy
            • Calculate estimated creatinine clearance using the Cockcroft-Gault equation and determine 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 60	500 mcg twice daily
                40 to 60	250 mcg twice daily
                20 to 40	125 mcg twice daily
                Less than 20	Usage contraindicated

            • Obtain baseline QTc (for heart rate 60 beats per minute or higher) or QT (for heart rate less than 60 beats per minute). If QTc/QT is higher than 440 milliseconds, do not use dofetilide. Note: no data on use when heart rate is less than 50 beats per minute
            • 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% of baseline or less, continue current dose; if more than 15% of baseline or more than 500 milliseconds, decrease 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 daily	250 mcg twice daily
                250 mcg twice daily	125 mcg twice daily
                125 mcg twice daily	125 mcg once daily

            • If at any time after the second dose of dofetilide, the QTc/QT increases to higher than 500 milliseconds, discontinue dofetilide
          • Ibutiliide ^r78
            • Can lead to torsades de pointes; must be administered during 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 liver function should be monitored for longer than 4 hours
          • Propafenone ^r79
            • Considered proarrhythmic for patients with structural heart disease; use with caution
          • IV vernakalant is another option (available in Canada and Europe but not in the United States)
        • Once sinus rhythm is restored, maintain it with an appropriate oral antiarrhythmic drug to decrease likelihood of recurrence
          • Overall, efficacy of antiarrhythmic drugs is only modest, with a recurrence rate of 43% to 67%, based on a 2019 Cochrane review ^r1r80
          • Consider presence or absence of structural heart disease, coronary artery disease, and potential to prolong the QT interval when choosing the specific antiarrhythmic drug; consultation with a cardiologist is recommended
          • Sotalol, dofetilide, amiodarone, and dronedarone cause drug-induced QT-interval prolongation, and sotalol has been specifically linked to increased risk of death compared with placebo, based on data from 5 randomized controlled trials (relative risk, 2.23; 95% confidence interval, 1.03-4.81) ^r80
          • 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 for patients with heart failure ^r2
          • First line antiarrhythmic drug for patients with heart failure is dofetilide or amiodarone ^r2r70
          • First line drug for patients with coronary artery disease is dofetilide, dronedarone, or sotalol.^r70 Flecainide (and propafenone, by inference) increases mortality in this population ^r2
          • Without structural heart disease, first line antiarrhythmic drugs include dofetilide, sotalol, dronedarone, flecainide, and propafenone ^r70
          • Dronedarone
            • Do not use for 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 for 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 for patients with permanent atrial fibrillation
          • Sotalol ^r70
            • Initiate or re-initiate oral sotalol in a facility that can provide continuous ECG monitoring and cardiac resuscitation by personnel who are trained in the management of serious ventricular arrhythmias. Hospitalize patients for whom sotalol has been initiated or re-initiated 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
            • Contraindicated for 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
            • Renal dose adjustments are required for creatinine clearance less than 60 mL/minute, and use is contraindicated for patients with creatinine clearance less than 40 mL/minute
        • 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)
          • Candidates for catheter ablation (according to an international expert consensus statement) include: ^r81
            • 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) ^r82
            • Selected patients with heart failure (reasonable option) ^r83
            • Patients with atrial fibrillation–mediated tachycardia-induced cardiomyopathy ^r12
          • Considered first line therapy for patients with concomitant atrial fibrillation and heart failure with reduced ejection fraction ^r84
        • Outcomes of catheter ablation versus medical therapy
          • CABANA trial showed that for a broad population of patients with symptoms, catheter ablation, compared with medical therapy, led to clinically important and significant improvements in quality of life at 12 months ^r85
            • 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 ^r86
          • 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 ^r87
            • 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 controlled 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 ^r88
            • 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 ^r89
          • Evidence suggests that catheter ablation as first line therapy for symptomatic paroxysmal atrial fibrillation results in lower rate of tachyarrhythmia recurrence compared with conventional antiarrhythmic drug therapy, with a similar adverse event profile ^r90r91
          • Mixed data on whether catheter ablation versus medical therapy impacts cognitive outcomes for patients with atrial fibrillation ^r92
        • 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 and associated hospitalizations ^r93r94
        • Surgical ablation is an option for patients undergoing cardiac surgery for other reasons, but it is rarely performed as a stand-alone procedure ^r94

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 to 3 for most patients ^r4
  • Patients taking direct oral anticoagulants do not usually require monitoring of coagulation ^r4r137
    • Routine coagulation tests (prothrombin time and activated partial thromboplastin time) do not provide an accurate assessment of anticoagulant effects
    • Commercial assays to measure direct 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 patients who are severely obese (BMI greater than 35 kg/m² or weight above 120 kg)
      • Assessment of patient adherence
  • Patients who are at high risk for 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
  • Many agents require modification for decreased renal function; monitor at baseline and periodically

Complications

• Thromboembolism ^c112
  • Embolic stroke ^c113
    • 5-fold increased risk of stroke with nonvalvular atrial fibrillation ^r25r138
    • 20-fold increased risk of stroke with atrial fibrillation associated with mitral stenosis ^r138
    • 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 ^r139
    • 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) ^{r140c116c117d7}
  • 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 ^r141
  • 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 ^r142
  • 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 types) among patients who underwent ablation ^r143

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 sinus rhythm is uncertain ^r86r140r144
• There is higher relative risk of cardiovascular and all-cause mortality, stroke, and heart failure in females than males ^r130

Screening

Prevention

• Manage/treat known atrial fibrillation risk factors
  • Identify and treat hypertension, prediabetes, and diabetes ^c124c125c126
  • Recommend normal weight maintenance and weight loss if patient has obesity or overweight ^c127c128c129
    • For patients with obesity, bariatric surgery has been associated with reduced risk of new atrial fibrillation compared with medical management of obesity ^r149
  • Advise smoking cessation ^c130d5
  • Advise patients to limit alcohol consumption and avoid binge drinking ^c131
  • For 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