- The diagnosis of atrial fibrillation (AF) in a patient is based on the patient’s clinical history and physical examination and is confirmed by electrocardiogram (ECG), ambulatory rhythm monitoring (e.g., telemetry, Holter monitor, event recorders), implanted loop recorders, pacemakers or defibrillators, or, in rare cases, by electrophysiological study. The clinical evaluations, including additional studies that may be required, are summarized in Table 3.
- The initial evaluation of a patient with suspected or proven AF involves characterizing the pattern of the arrhythmia (paroxysmal, persistent, longstanding persistent, or permanent), determining its cause, defining associated cardiac and extracardiac disease, and assessing thromboembolic risk.
- AF is a supraventricular tachyarrhythmia with uncoordinated atrial activation and consequently ineffective atrial contraction.
- AF incidence increases with advancing age.
- Rate control (principally with beta-blockers and/or non-dihydropyridine calcium channel blockers) versus rhythm control (cardioversion, antiarrhythmic drugs, AF ablation) strategies may be considered in treating patients with AF.
- Hemodynamic consequences of AF can result from a variable combination of suboptimal ventricular rate control (either too rapid or too slow), loss of coordinated atrial contraction, beat-to-beat variability in ventricular filling, and sympathetic activation.
- Consequences for individual patients vary, ranging from no symptoms to fatigue, palpitations, dyspnea, hypotension, syncope, or HF. The most common symptom of AF is fatigue.
- The appearance of AF is often associated with exacerbation of underlying heart disease, either because AF is a cause or consequence of deterioration, or because it contributes directly to deterioration.
- AF confers an increased risk of stroke and/or peripheral thromboembolism owing to the formation of atrial thrombi, usually in the left atrial appendage (LAA).
- Treatment strategies to reduce the risk of thromboembolism may include anticoagulation with warfarin or newer anticoagulants, and are guided using the CHA2DS2-VASc score.
- The purpose of this document is to update the “2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation” (S1.3-1) (2014 AF Guideline) in areas for which new evidence has emerged since its publication.
- The scope of this focused update of the 2014 AF Guideline includes revisions to the section on anticoagulation (because of the approval of new medications and thromboembolism protection devices), revisions to the section on catheter ablation of AF, revisions to the section on the management of AF complicating acute coronary syndrome (ACS), and new sections on device detection of AF and weight loss.
Table 1. Definitions
|Longstanding persistent AF|
Table 2. Clinical Evaluation
|ECG documentation is recommended to establish the diagnosis of AF.||I||C|
Table 3. Initial Clinical Evaluation in Patients With AF
|History and physical examination, to define|
|ECG, to identify|
|TTE, to identify|
|Blood tests of thyroid, renal, and hepatic function|
|6-min walk test|
|Holter or event monitoring|
|Chest radiograph, to evaluate|
Table 4. Risk-Based Antithrombotic Therapy
|NEW: NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) are recommended over warfarin in NOAC-eligible patients with AF (except with moderate-to-severe mitral stenosis or a mechanical heart valve).||I||A|
|MODIFIED: In patients with AF, anticoagulant therapy should be individualized on the basis of shared decision-making after discussion of the absolute risks and relative risks of stroke and bleeding, as well as the patient’s values and preferences.||I||C|
|MODIFIED: Selection of anticoagulant therapy should be based on the risk of thromboembolism, irrespective of whether the AF pattern is paroxysmal, persistent, or permanent.||I||B|
|MODIFIED: In patients with AF (except with moderate-to-severe mitral stenosis or a mechanical heart valve), the CHA2DS2-VASc score is recommended for assessment of stroke risk.||I||B|
|MODIFIED: For patients with AF who have mechanical heart valves, warfarin is recommended.||I||B|
|MODIFIED: For patients with AF and an elevated CHA2DS2-VASc score of 2 or greater in men or 3 or greater in women, oral anticoagulants are recommended. Options include:|
|MODIFIED: Among patients treated with warfarin, the international normalized ratio (INR) should be determined at least weekly during initiation of anticoagulant therapy and at least monthly when anticoagulation (INR in range) is stable.||I||A|
|MODIFIED: For patients with AF (except with moderate-to-severe mitral stenosis or a mechanical heart valve) who are unable to maintain a therapeutic INR level with warfarin, use of a NOAC is recommended.||I||C-EO|
|MODIFIED: Reevaluation of the need for and choice of anticoagulant therapy at periodic intervals is recommended to reassess stroke and bleeding risks.||I||C|
|MODIFIED: Renal function and hepatic function should be evaluated before initiation of a NOAC and should be reevaluated at least annually.||I||B-NR|
|MODIFIED: For patients with atrial flutter, anticoagulant therapy is recommended according to the same risk profile used for AF.||I||C|
|MODIFIED: For patients with AF (except with moderate-to-severe mitral stenosis or a mechanical heart valve) and a CHA2DS2-VASc score of 0 in men or 1 in women, it is reasonable to omit anticoagulant therapy.||IIa||B|
|MODIFIED: For patients with AF who have a CHA2DS2-VASc score of ≥2 in men or ≥3 in women and who have end-stage chronic kidney disease (CKD; creatinine clearance [CrCl] <15 mL/min) or are on dialysis, it might be reasonable to prescribe warfarin (INR 2.0 to 3.0) or apixaban for oral anticoagulation.||IIb||B-NR|
|MODIFIED: For patients with AF (except with moderate-to-severe mitral stenosis or a mechanical heart valve) and a CHA2DS2-VASc score of 1 in men and 2 in women, prescribing an oral anticoagulant to reduce thromboembolic stroke risk may be considered.||IIb||C-LD|
|MODIFIED: For patients with AF (except with moderate-to-severe mitral stenosis or a mechanical heart valve) and moderate-to-severe CKD (serum creatinine ≥1.5 mg/dL [apixaban], CrCl 15 to 30 mL/min [dabigatran], CrCl <50 mL/min [rivaroxaban], or CrCl 15 to 50 mL/min [edoxaban]) with an elevated CHA2DS2-VASc score, treatment with reduced doses of direct thrombin or factor Xa inhibitors may be considered (e.g., dabigatran, rivaroxaban, apixaban, or edoxaban).||IIb||B-R|
|In patients with AF undergoing percutaneous coronary intervention, bare-metal stents may be considered to minimize the required duration of dual antiplatelet therapy. Anticoagulation may be interrupted at the time of the procedure to reduce the risk of bleeding at the site of peripheral arterial puncture.||IIb||C|
|Following coronary revascularization (percutaneous or surgical) in patients with AF and a CHA2DS2-VASc score ≥2, it may be reasonable to use clopidogrel (75 mg QD) concurrently with oral anticoagulants but without aspirin.||IIb||B|
|MODIFIED: In patients with AF and end-stage CKD or on dialysis, the direct thrombin inhibitor dabigatran or the factor Xa inhibitors rivaroxaban or edoxaban are NOT recommended because of the lack of evidence from clinical trials that benefit exceeds risk.||III: No Benefit||C-EO|
|MODIFIED: The direct thrombin inhibitor dabigatran should NOT be used in patients with AF and a mechanical heart valve.||III: Harm||B-R|
Table 5. Recommendations for Interruption and Bridging Anticoagulation
|Bridging therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) is recommended for patients with AF and a mechanical heart valve undergoing procedures that require interruption of warfarin. Decisions regarding bridging therapy should balance the risks of stroke and bleeding.||I||C|
|MODIFIED: For patients with AF without mechanical heart valves who require interruption of warfarin for procedures, decisions about bridging therapy (UFH or LMWH) should balance the risks of stroke and bleeding and the duration of time a patient will not be anticoagulated.||I||B-R|
|NEW: Idarucizumab is recommended for the reversal of dabigatran in the event of life-threatening bleeding or an urgent procedure.||I||B-NR|
|NEW: Andexanet alfa can be useful for the reversal of rivaroxaban and apixaban in the event of life-threatening or uncontrolled bleeding.||IIa||B-NR|
Table 6. Cardiac Surgery/Percutaneous Approaches— LAA Occlusion/Excision
|NEW: Percutaneous LAA occlusion may be considered in patients with AF at increased risk of stroke who have contraindications to long-term anticoagulation.||IIb||B-NR|
|MODIFIED: Surgical occlusion of the LAA may be considered in patients with AF undergoing cardiac surgery, as a component of an overall heart team approach to the management of AF.||IIb||B-NR|
Table 7. Comparison of the CHADS2 and CHA2DS2-VASc Risk Stratification Scores for Subjects With Nonvalvular AF
|Definition and Scores for CHADS2 and CHA2DS2-VASc||Stroke Risk Stratification With the CHADS2 and CHA2DS2-VASc Scores|
|Score||Adjusted Stroke Rate (% per y)|
|Age ≥75 y||1||2||4.0|
|Stroke/TIA/thromboembolic events (TE)||2||4||8.5|
|Age ≥75 y||2||2||2.2|
|Vascular disease (prior MI, PAD, or aortic plaque)||1||5||6.7|
|Age 65–74 y||1||6||9.8|
|Sex category (i.e., female sex)||1||7||9.6|
b Adjusted stroke rate scores are based on data from Lip and colleagues. Actual rates of stroke in contemporary cohorts might vary from these estimates.
Table 8. Dose Selection of Oral Anticoagulant Options for Patients with Nonvalvular AF and CKD (Based on Prescribing Information for the United States)a
|Normal/Mild Impairment||Dose adjusted for INR 2.0-3.0||150 mg BID (CrCl >30 mL/min)||20 mg QD with the evening meal (CrCl >50 mL/min)||5.0 or 2.5 mg BIDc|
|Moderate Impairment||Dose adjusted for INR 2.0-3.0||150 mg BID (CrCl >30 mL/min)||15 mg QD with the evening meal (CrCl 30-50 mL/min)||5.0 or 2.5 mg BIDc|
|Severe Impairment||Dose adjusted for INR 2.0-3.0d||75 mg BIDe (CrCl 15-30 mL/min)||15 mg QD with the evening meal (CrCl 15-30 mL/min)||No recommendationf|
|End-Stage CKD Not on Dialysis||Dose adjusted for INR 2.0-3.0d||Not recommendedf (CrCl <15 mL/min)||Not recommendedf (CrCl <15 mL/min)||No recommendationf|
|End-Stage CKD on Dialysis||Dose adjusted for INR 2.0-3.0d||Not recommendedf (CrCl <15 mL/min)||Not recommendedf (CrCl <15 mL/min)||No recommendationf,g|
b The concomitant use of P-glycoprotein inducers or inhibitors with dabigatran, or the concomitant use of dual P-glycoprotein and strong CYP3A4 inducers or inhibitors with either rivaroxaban or apixaban, particularly in the setting of CKD, may require dosing adjustment or avoidance of concomitant drug use (see the FDA drug label at http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202155s002lbl.pdf ).
c Use apixaban 2.5 mg BID if any 2 patient characteristics present: Cr ≥ 1.5 mg/dL, ≥80 years of age, body weight ≤60 kg. Apixaban is not recommended in patients with severe hepatic impairment.
d Dose-adjusted warfarin has been used, but observational data regarding safety and efficacy are conflicting.
e Modeling studies suggest that dabigatran 75 mg BID might be safe for patients with CrCl 15-30 mL/min, but this has not been validated in a prospective cohort. Some countries outside the United States use 110 mg BID.
f No published studies support a dose for this level of renal function.
g In patients with end-stage CKD on stable hemodialysis, prescribing information indicates the use of apixaban 5 mg BID with dose reduction to 2.5 mg BID if the patient is either ≥80 years of age or body weight ≤60 kg.
Table 9. Rate Control
|Control of the ventricular rate using a beta blocker or nondihydropyridine calcium channel antagonist is recommended for patients with paroxysmal, persistent, or permanent AF.||I||B|
|IV administration of a beta blocker or nondihydropyridine calcium channel blocker is recommended to slow ventricular heart rate in the acute setting in patients without pre-excitation. In hemodynamically unstable patients, electrical cardioversion is indicated.||I||B|
|In patients who experience AF-related symptoms during activity, the adequacy of heart rate control should be assessed during exertion, adjusting pharmacological treatment as necessary to keep the ventricular rate within the physiological range.||I||C|
|A heart rate control (resting heart rate <80 bpm) strategy is reasonable for symptomatic management of AF.||IIa||B|
|IV amiodarone can be useful for rate control in critically ill patients without pre-excitation.||IIa||B|
|AV nodal ablation with permanent ventricular pacing is reasonable to control heart rate when pharmacological therapy is inadequate and rhythm control is not achievable.||IIa||B|
|Lenient rate control strategy (resting heart rate <110 bpm) may be reasonable as long as patients remain asymptomatic and LV systolic function is preserved.||IIb||B|
|Oral amiodarone may be useful for ventricular rate control when other measures are unsuccessful or contraindicated.||IIb||C|
|AV nodal ablation with permanent ventricular pacing should NOT be performed to improve rate control without prior attempts to achieve rate control with medications.||III: Harm||C|
|Nondihydropyridine calcium channel antagonists should NOT be used in patients with decompensated HF as these may lead to further hemodynamic compromise.||III: Harm||C|
|In patients with pre-excitation and AF, digoxin, nondihydropyridine calcium channel antagonists, or intravenous amiodarone should NOT be administered as they may increase the ventricular response and may result in ventricular fibrillation.||III: Harm||B|
|Dronedarone should NOT be used to control the ventricular rate in patients with permanent AF as it increases the risk of the combined endpoint of stroke, MI, systemic embolism, or cardiovascular death.||III: Harm||B|
Table 10. Common Medication Dosage for Rate Control of AF
|Intravenous Administration||Usual Oral|
|Metoprolol tartrate||2.5-5.0 mg IV bolus over 2 min; up to 3 doses||25-100 mg BID|
|N/A||50-400 mg QD|
|Atenolol||N/A||25-100 mg QD|
|Esmolol||500 mcg/kg IV bolus over 1 min, then 50-300 mcg/kg/min IV||N/A|
|Propranolol||1 mg IV over 1 min, up to 3 doses at 2-min intervals||10-40 mg TID or QID|
|Nadolol||N/A||10-240 mg QD|
|Carvedilol||N/A||3.125-25 mg BID|
|Bisoprolol||N/A||2.5-10 mg QD|
|Nondihydropyridine calcium channel antagonists|
|Verapamil||0.075-0.15 mg/kg IV bolus over 2 min, may give an additional 10.0 mg after 30 min if no response, then 0.005 mg/kg/min infusion||180-480 mg QD (ER)|
|Diltiazem||0.25 mg/kg IV bolus over 2 min, then 5-15 mg/h||120-360 mg QD (ER)|
|Digoxin||0.25 mg IV with repeat dosing to a maximum of 1.5 mg over 24 h||0.125-0.25 mg QD|
|Amiodaronea||300 mg IV over 1 h, then 10-50 mg/h over 24 h||100-200 mg QD|
Table 11. Electrical and Pharmacological Cardioversion of AF and Atrial Flutter
|Prevention of Thromboembolism|
|MODIFIED: For patients with AF or atrial flutter of ≥48 hours’ duration, or when the duration of AF is unknown, anticoagulation with warfarin (INR 2.0 to 3.0), a factor Xa inhibitor, or direct thrombin inhibitor is recommended for ≥3 weeks before and ≥4 weeks after cardioversion, regardless of the CHA2DS2-VASc score or the method (electrical or pharmacological) used to restore sinus rhythm.||I||B-R|
|For patients with AF or atrial flutter of >48 hours duration or unknown duration that requires immediate cardioversion for hemodynamic instability, anticoagulation should be initiated as soon as possible and cont'd for ≥4 weeks after cardioversion unless contraindicated.||I||C|
|MODIFIED: After cardioversion for AF of any duration, the decision about long-term anticoagulation therapy should be based on the thromboembolic risk profile and bleeding risk profile.||I||C-EO|
|MODIFIED: For patients with AF or atrial flutter of <48 hours’ duration with a CHA2DS2-VASc score of ≥2 in men and ≥3 in women, administration of heparin, a factor Xa inhibitor, or a direct thrombin inhibitor is reasonable as soon as possible before cardioversion, followed by long-term anticoagulation therapy.||IIa||B-NR|
|For patients with AF or atrial flutter of ≥48 hours duration or of unknown duration who have not been anticoagulated for the preceding 3 weeks, it is reasonable to perform TEE before cardioversion and proceed with cardioversion if no LA thrombus is identified, including in the LAA, provided that anticoagulation is achieved before TEE and maintained after cardioversion for ≥4 weeks.||IIa||B|
|For patients with AF or atrial flutter of ≥48 hour duration or when duration of AF is unknown, anticoagulation with dabigatran, rivaroxaban, or apixaban is reasonable for ≥3 weeks before and 4 weeks after cardioversion.||IIa||C|
|MODIFIED: For patients with AF or atrial flutter of less than 48 hours’ duration with a CHA2DS2-VASc score of 0 in men or 1 in women, administration of heparin, a factor Xa inhibitor, or a direct thrombin inhibitor, versus no anticoagulant therapy, may be considered before cardioversion, without the need for postcardioversion oral anticoagulation.||IIb||B-NR|
|In pursuing a rhythm-control strategy, cardioversion is recommended for patients with AF or atrial flutter as a method to restore sinus rhythm. If cardioversion is unsuccessful, repeated attempts at direct-current cardioversion may be made after adjusting the location of the electrodes, applying pressure over the electrodes or following administration of an antiarrhythmic medication.||I||B|
|Cardioversion is recommended when a RVR to AF or atrial flutter does not respond promptly to pharmacological therapies and contributes to ongoing myocardial ischemia, hypotension, or HF.||I||C|
|Cardioversion is recommended for patients with AF or atrial flutter and pre-excitation when tachycardia is associated with hemodynamic instability.||I||C|
|It is reasonable to perform repeated cardioversions in patients with persistent AF, provided that sinus rhythm can be maintained for a clinically meaningful period between cardioversion procedures. Severity of AF symptoms and patient preference should be considered when embarking on a strategy requiring serial cardioversion procedures.||IIa||C|
|Flecainide, dofetilide, propafenone, and intravenous ibutilide are useful for pharmacological cardioversion of AF or atrial flutter, provided contraindications to the selected drug are absent.||I||A|
|Administration of oral amiodarone is a reasonable option for pharmacological cardioversion of AF.||IIa||A|
|Propafenone or flecainide (“pill-in-the-pocket”) in addition to a beta blocker or nondihydropyridine calcium channel antagonist is reasonable to terminate AF outside the hospital once this treatment has been observed to be safe in a monitored setting for selected patients.||IIa||B|
|Dofetilide therapy should NOT be initiated out of hospital because of the risk of excessive QT prolongation that can cause torsades de pointes.||III: Harm||B|
Table 12. Recommended Drug Doses for Pharmacological Cardioversion of AF
|Drug||Route of Administration||Dosage||Potential Adverse Effects|
|Amiodaronea||Oral||600-800 mg QD in divided doses to a total load of ≤10 g, then 200 mg QD as maintenance||Phlebitis (IV), hypotension, bradycardia, QT prolongation, torsades de pointes (rare), GI upset, constipation, increased INR|
|IV||150 mg over 10 min, then 1 mg/min for 6 h, then 0.5 mg/min for 18 h or change to oral dosing|
|QT prolongation, torsades de pointes; adjust dose for renal function, body size, and age|
|Flecainide||Oral||200-300 mg × 1b||Hypotension, atrial flutter with 1:1 AV conduction, ventricular proarrhythmia; avoid in patients with CAD and significant structural heart disease|
|Ibutilide||IV||1 mg over 10 min; may repeat 1 mg once if necessary (weight <60 kg use 0.01 mg/kg)||QT prolongation, torsades de pointes, hypotension|
|Propafenone||Oral||450-600 mg × 1b||Hypotension, atrial flutter with 1:1 AV conduction, ventricular proarrhythmia; avoid in patients with CAD and significant structural heart disease|
b Recommended given in conjunction with a beta blocker or nondihydropyridine calcium channel antagonist administered ≥30 minutes before administering the Vaughan Williams Class IC agent.
Table 13. Antiarrhythmic Drugs to Maintain Sinus Rhythm
|Before initiating antiarrhythmic drug therapy, treatment of precipitating or reversible causes of AF is recommended.||I||C|
|The following antiarrhythmic drugs are recommended in patients with AF to maintain sinus rhythm, depending on underlying heart disease and comorbidities:||I||A|
|The risks of the antiarrhythmic drug, including proarrhythmia, should be considered before initiating therapy with each drug.||I||C|
|Because of its potential toxicities, amiodarone should only be used after consideration of risks and when other agents have failed or are contraindicated.||I||C|
|A rhythm-control strategy with pharmacological therapy can be useful in patients with AF for the treatment of tachycardia-induced cardiomyopathy.||IIa||C|
|It may be reasonable to continue current antiarrhythmic drug therapy in the setting of infrequent, well-tolerated recurrences of AF when the drug has reduced the frequency or symptoms of AF.||IIb||C|
|Antiarrhythmic drugs for rhythm control should NOT be continued when AF becomes permanent,||III: Harm||C|
|Dronedarone should NOT be used for treatment of AF in patients with NYHA class III and IV HF or patients who have had an episode of decompensated HF in the past 4 weeks.||III: Harm||B|
Table 14. Upstream Therapy
|An ACE inhibitor or ARB is reasonable for primary prevention of new-onset AF in patients with HF with reduced LVEF.||IIa||B|
|Therapy with an ACE inhibitor or ARB may be considered for primary prevention of new-onset AF in the setting of hypertension.||IIb||B|
|Statin therapy may be reasonable for primary prevention of new-onset AF after coronary artery surgery.||IIb||A|
|Therapy with an ACE inhibitor, ARB, or statin is NOT beneficial for primary prevention of AF in patients without cardiovascular disease.||III: No Benefit||B|
Table 15. Dosage and Safety Considerations for Maintenance of Sinus Rhythm in AF
|Drug||Usual Doses||Exclude/Use With Caution||Major Pharmacokinetic Drug Interactions|
|Vaughan Williams Class IA|
|Vaughan Williams Class IC|
|Vaughan Williams Class III|
Table 16. AF Catheter Ablation to Maintain Sinus Rhythm
|AF catheter ablation is useful for symptomatic paroxysmal AF refractory or intolerant to at least 1 class I or III antiarrhythmic medication when a rhythm-control strategy is desired.||I||A|
|Before consideration of AF catheter ablation, assessment of the procedural risks and outcomes relevant to the individual patient is recommended.||I||C|
|AF catheter ablation is reasonable for some patients with symptomatic persistent AF refractory or intolerant to at least 1 class I or III antiarrhythmic medication.||IIa||A|