Atrial Fibrillation Guidelines Pocket Guide & App

Atrial Fibrillation GUIDELINES Pocket Guide

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American College of Cardiology Foundation

American Heart Association

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Key Points

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 also confers an increased risk of stroke and/or peripheral thromboembolism owing to the formation of atrial thrombi, usually in the 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.

Diagnosis and Treatment

The diagnosis of AF in a patient is based on the patient’s clinical history and physical examination and is confirmed by 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.

Table 1. Definitions

Paroxysmal AF

AF that terminates spontaneously or with intervention within 7 d of onset.
Episodes may recur with variable frequency.

Persistent AF

Continuous AF that is sustained >7 d.

Longstanding persistent AF

Continuous AF of >12 mo duration.

Permanent AF

Permanent AF is used when there has been a joint decision by the patient and clinician to cease further attempts to restore and/or maintain sinus rhythm.
Acceptance of AF represents a therapeutic attitude on the part of the patient and clinician rather than an inherent pathophysiological attribute of the AF.
Acceptance of AF may change as symptoms, the efficacy of therapeutic interventions, and patient and clinician preferences evolve.

Nonvalvular AF

AF in the absence of rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair.

Figure 1. Atrial Tachycardias

Figure 2. Mechanisms of AF

Table 2. Clinical Evaluation

Recommendation	COR	LOE
ECG documentation is recommended to establish the diagnosis of AF.	I	C

Table 3. Initial Clinical Evaluation in Patients With AF

HAS-BLED Score Calculator
HEMORR₂HAGES Score Calculator

Minimum Evaluation

History and physical examination, to define

Presence and nature of symptoms associated with AF
Clinical type of AF (paroxysmal, persistent, or permanent)
Onset of the first symptomatic attack or date of discovery of AF
Frequency, duration, precipitating factors, and modes of initiation or termination of AF
Response to any pharmacological agents that have been administered
Presence of any underlying heart disease or reversible conditions (e.g., hyperthyroidism or alcohol consumption)

ECG, to identify

Rhythm (verify AF)
LVH
P-wave duration and morphology or fibrillatory waves
Pre-excitation
Bundle-branch block
Prior MI
Other atrial arrhythmias
To measure and follow the R-R, QRS, and QT intervals in conjunction with antiarrhythmic drug therapy

TTE, to identify

VHD
LA and RA size
LV and RV size and function
Peak RV pressure (pulmonary hypertension)
LV hypertrophy
LA thrombus (low sensitivity)
Pericardial disease

Blood tests of thyroid, renal, and hepatic function

For a first episode of AF
When the ventricular rate is difficult to control

Additional Testing (1 or several tests may be necessary)

6-min walk test

If the adequacy of rate control is in question

Exercise testing

If the adequacy of rate control is in question
To exclude ischemia before treatment of selected patients with a type IC^a antiarrhythmic drug

Holter or event monitoring

If diagnosis of the type of arrhythmia is in question
As a means of evaluating rate control

TEE

To identify LA thrombus (in the LAA)
To guide cardioversion

Electrophysiological study

To clarify the mechanism of wide–QRS-complex tachycardia
To identify a predisposing arrhythmia such as atrial flutter or paroxysmal supraventricular tachycardia
To seek sites for curative AF ablation or AV conduction block/modification

Chest radiograph, to evaluate

Lung parenchyma, when clinical findings suggest an abnormality
Pulmonary vasculature, when clinical findings suggest an abnormality

^a Type IC refers to the Vaughan Williams classification of antiarrhythmic drugs.

Table 4. Risk-Based Antithrombotic Therapy

Recommendations	COR	LOE
In patients with AF, antithrombotic therapy should be individualized based on shared decision making after discussion of the absolute and relative risks of stroke and bleeding, and the patient’s values and preferences.	I	C
Selection of antithrombotic therapy should be based on the risk of thromboembolism irrespective of whether the AF pattern is paroxysmal, persistent, or permanent.	I	B
In patients with nonvalvular AF, the CHA₂DS₂-VASc score is recommended for assessment of stroke risk.	I	B
For patients with AF who have mechanical heart valves, warfarin is recommended, and the target INR intensity (2.0-3.0 or 2.5-3.5) should be based on the type and location of the prosthesis.	I	B

For patients with nonvalvular AF with prior stroke, TIA, or a CHA₂DS₂-VASc score ≥2, oral anticoagulants are recommended. Options include:

Recommendations	COR	LOE
Warfarin (INR 2.0-3.0)	I	A
Dabigatran, rivaroxaban, or apixaban.	I	B
Among patients treated with warfarin, the INR should be determined at least weekly during initiation of antithrombotic therapy and at least monthly when anticoagulation (INR in range) is stable.	I	A
For patients with nonvalvular AF unable to maintain a therapeutic INR level with warfarin, use of a direct thrombin or factor Xa inhibitor (dabigatran, rivaroxaban, or apixaban) is recommended.	I	C
Re-evaluation of the need for and choice of antithrombotic therapy at periodic intervals is recommended to reassess stroke and bleeding risks.	I	C
Bridging therapy with UFH or 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
For patients with AF without mechanical heart valves who require interruption of warfarin or new anticoagulants for procedures, decisions about bridging therapy (LMWH or UFH) should balance the risks of stroke and bleeding and the duration of time a patient will not be anticoagulated.	I	C
Renal function should be evaluated before initiation of direct thrombin or factor Xa inhibitors and should be re-evaluated when clinically indicated and at least annually.	I	B
For patients with atrial flutter, antithrombotic therapy is recommended according to the same risk profile used for AF.	I	C
For patients with nonvalvular AF and a CHA₂DS₂-VASc score of 0, it is reasonable to omit antithrombotic therapy.	IIa	B
For patients with nonvalvular AF with a CHA₂DS₂-VASc score of ≥2 and who have endstage CKD (CrCl <15 mL/min) or are on hemodialysis, it is reasonable to prescribe warfarin (INR 2.0-3.0) for oral anticoagulation.	IIa	B
For patients with nonvalvular AF and a CHA₂DS₂-VASc score of 1, no antithrombotic therapy or treatment with an oral anticoagulant or aspirin may be considered.	IIb	C
For patients with nonvalvular AF and moderate-to-severe CKD with CHA₂DS₂-VASc scores of ≥2, treatment with reduced doses of direct thrombin or factor Xa inhibitors may be considered (e.g., dabigatran, rivaroxaban, or apixaban), but safety and efficacy have not been established.	IIb	C
In patients with AF undergoing percutaneous coronary intervention,^a 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
The direct thrombin inhibitor dabigatran and the factor Xa inhibitor rivaroxaban are *NOT* recommended in patients with AF and end-stage CKD or on dialysis because of the lack of evidence from clinical trials regarding the balance of risks and benefits.	III: No Benefit	C
The direct thrombin inhibitor dabigatran should *NOT* be used in patients with AF and a mechanical heart valve.	III: Harm	B

^a See the 2011 percutaneous coronary intervention guideline for type of stent and duration of dual antiplatelet therapy recommendations. (Levine GN, et al. J Am Coll Cardiol. 2011;58:e44-122.)

Table 5. Cardiac Surgery—LAA Occlusion/Excision

Recommendation	COR	LOE
Surgical excision of the LAA may be considered in patients undergoing cardiac surgery.	IIb	C

Table 6. Risk Stratification Scores for Subjects With Nonvalvular AF

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CHA2DS2-VASc
Congestive HF	1
Hypertension	1
Age ≥75 y	2
Diabetes mellitus	1
Stroke/TIA/thromboembolic events	2
Vascular disease (prior MI, PAD, or aortic plaque)	1
Age 65-74 y	1
Sex category (i.e., female sex)	1
	Maximum Score: 9

Table 7. Dose Selection of Oral Anticoagulant Options for Patients with Nonvalvular AF and CKD (Based on Prescribing Information for the United States)a

Renal Function	Warfarin	Dabigatran^b	Rivaroxaban^b	Apixaban^b
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 BID^c
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 BID^c
Severe Impairment	Dose adjusted for INR 2.0-3.0^d	75 mg BID^e (CrCl 15-30 mL/min)	15 mg QD with the evening meal (CrCl 15-30 mL/min)	No recommendation^f
End-Stage CKD Not on Dialysis	Dose adjusted for INR 2.0-3.0^d	Not recommended^f (CrCl <15 mL/min)	Not recommended^f (CrCl <15 mL/min)	No recommendation^f
End-Stage CKD on Dialysis	Dose adjusted for INR 2.0-3.0^d	Not recommended^f (CrCl <15 mL/min)	Not recommended^f (CrCl <15 mL/min)	No recommendation^f,g

^a Renal function should be evaluated prior to initiation of direct thrombin or factor Xa inhibitors and should be reevaluated when clinically indicated and at least annually. CrCl should be measured using the Crockoft-Gault method.
^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 8. Rate Control

Recommendations	COR	LOE
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

Figure 3. Approach to Selecting Drug Therapy for Ventricular Rate Controla

Table 9. Common Medication Dosage for Rate Control of AF

Beta Blockers

	Intravenous Administration	Usual Oral Maintenance Dose
Metoprolol tartrate	2.5-5.0 mg IV bolus over 2 min; up to 3 doses	25-100 mg BID
Metoprolol XL (succinate)	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

	Intravenous Administration	Usual Oral Maintenance Dose
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)

Digitalis glycosides

	Intravenous Administration	Usual Oral Maintenance Dose
Digoxin	0.25 mg IV with repeat dosing to a maximum of 1.5 mg over 24 h	0.125-0.25 mg QD

Others

	Intravenous Administration	Usual Oral Maintenance Dose
Amiodarone^a	300 mg IV over 1 h, then 10-50 mg/h over 24 h	100-200 mg QD

^a Multiple dosing schemes exist for the use of amiodarone.

Table 10. Electrical and Pharmacological Cardioversion of AF and Atrial Flutter

Prevention of Thromboembolism

Recommendations	COR	LOE
For patients with AF or atrial flutter of ≥48-hours' duration, or when the duration of AF is unknown, anticoagulation with warfarin (INR 2.0-3.0) is recommended for ≥3 weeks prior to and 4 weeks after cardioversion, regardless of the CHA2DS2-VASc score and the method (electrical or pharmacological) used to restore sinus rhythm.	I	B
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
For patients with AF or atrial flutter of <48-hour duration and with high risk of stroke, intravenous heparin or LMWH, or administration of a factor Xa or direct thrombin inhibitor, is recommended as soon as possible before or immediately after cardioversion, followed by long-term anticoagulation therapy.	I	C
Following cardioversion for AF of any duration, the decision about long-term anticoagulation therapy should be based on the thromboembolic risk profile.	I	C
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
For patients with AF or atrial flutter of <48-hours duration who are at low thromboembolic risk, anticoagulation (intravenous heparin, LMWH, or a new oral anticoagulant) or no antithrombotic therapy may be considered for cardioversion, without the need for postcardioversion oral anticoagulation.	IIb	C

Direct-Current Cardioversion

Recommendations	COR	LOE
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

Pharmacological Cardioversion

Recommendations	COR	LOE
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

Figure 4. Strategies for Rhythm Control in Patients With Paroxysmala and Persistent AFb

Table 11. Recommended Drug Doses for Pharmacological Cardioversion of AF

Drug	Route of Administration	Dosage	Potential Adverse Effects
Amiodarone^a	Oral IV	600-800 mg QD in divided doses to a total load of ≤10 g, then 200 mg QD as maintenance 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	Phlebitis (IV), hypotension, bradycardia, QT prolongation, torsades de pointes (rare), GI upset, constipation, increased INR
Dofetilide	Oral	CrCl (mL/min) >60 40-60 20-40 <20 Dose (mcg BID) 500 250 125 Not recommended	QT prolongation, torsades de pointes; adjust dose for renal function, body size, and age
Flecainide	Oral	200-300 mg × 1^b	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 × 1^b	Hypotension, atrial flutter with 1:1 AV conduction, ventricular proarrhythmia; avoid in patients with CAD and significant structural heart disease

^a Multiple dosing schemes exist for the use of amiodarone.
^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 12. Antiarrhythmic Drugs to Maintain Sinus Rhythm

Recommendations	COR	LOE
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: Amiodarone Dofetilide Dronedarone Flecainide Propafenone Sotalol	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 cont'd when AF becomes permanent,	III: Harm	C
including dronedarone.	III: Harm	B
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 13. Upstream Therapy

Recommendations	COR	LOE
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 14. Dosage and Safety Considerations for Maintenance of Sinus Rhythm in AF

Vaughan Williams Class IA

Drug	Usual Doses	Exclude/Use With Caution	Major Pharmacokinetic Drug Interactions
Disopyramide	Immediate release: 100-200 mg once every 6 h Extended release: 200-400 mg once every 12 h	HF Prolonged QT interval Prostatism, glaucoma Avoid other QT interval-prolonging drugs	Metabolized by CYP3A4: caution with inhibitors (e.g., verapamil, diltiazem, ketoconazole, macrolide antibiotics, protease inhibitors, grapefruit juice) and inducers (e.g., rifampin, phenobarbital, phenytoin)
Quinidine	324-648 mg every 8 h	Prolonged QT interval Diarrhea	Inhibits CYP2D6: ↑concentrations of tricyclic antidepressants, metoprolol, antipsychotics; ↓efficacy of codeine Inhibits P-glycoprotein: ↑digoxin concentration

Drug

Usual Doses

Exclude/Use With Caution

Major Pharmacokinetic Drug Interactions

Disopyramide

Immediate release:

100-200 mg once every 6 h

Extended release:

200-400 mg once every 12 h

HF
Prolonged QT interval
Prostatism, glaucoma
Avoid other QT interval-prolonging drugs

Metabolized by CYP3A4:
caution with inhibitors (e.g., verapamil, diltiazem, ketoconazole, macrolide antibiotics, protease inhibitors, grapefruit juice) and inducers (e.g., rifampin, phenobarbital, phenytoin)

Quinidine

324-648 mg every 8 h

Prolonged QT interval
Diarrhea

Inhibits CYP2D6:
↑concentrations of tricyclic antidepressants, metoprolol, antipsychotics; ↓efficacy of codeine
Inhibits P-glycoprotein:
↑digoxin concentration

Vaughan Williams Class IC

Drug	Usual Doses	Exclude/Use With Caution	Major Pharmacokinetic Drug Interactions
Flecainide	50-200 mg once every 12 h	Sinus or AV node dysfunction HF CAD Atrial flutter Infranodal conduction disease Brugada syndrome Renal or liver disease	Metabolized by CYP2D6 (inhibitors include quinidine, fluoxetine, tricyclics; also genetically absent in 7%-10% of population) and renal excretion (dual impairment can ↑↑plasma concentration)
Propafenone	Immediate release: 150-300 mg once every 8 h Extended release: 225-425 mg once every 12 h	Sinus or AV node dysfunction HF CAD Atrial flutter Infranodal conduction disease Brugada syndrome Liver disease Asthma	Metabolized by CYP2D6 (inhibitors include quinidine, fluoxetine, tricyclics; also genetically absent in 7%-10% of population)—poor metabolizers have ↑beta blockade Inhibits P-glycoprotein: ↑digoxin concentration Inhibits CYP2C9: ↑warfarin concentration (↑INR 25%)

Drug

Usual Doses

Exclude/Use With Caution

Major Pharmacokinetic Drug Interactions

Flecainide

50-200 mg once every 12 h

Sinus or AV node dysfunction
HF
CAD
Atrial flutter
Infranodal conduction disease
Brugada syndrome
Renal or liver disease

Metabolized by CYP2D6 (inhibitors include quinidine, fluoxetine, tricyclics; also genetically absent in 7%-10% of population) and renal excretion (dual impairment can ↑↑plasma concentration)

Propafenone

Immediate release:

150-300 mg once every 8 h

Extended release:

225-425 mg once every 12 h

Sinus or AV node dysfunction
HF
CAD
Atrial flutter
Infranodal conduction disease
Brugada syndrome
Liver disease
Asthma

Metabolized by CYP2D6 (inhibitors include quinidine, fluoxetine, tricyclics; also genetically absent in 7%-10% of population)—poor metabolizers have ↑beta blockade
Inhibits P-glycoprotein: ↑digoxin concentration
Inhibits CYP2C9: ↑warfarin concentration (↑INR 25%)

Vaughan Williams Class III

Drug	Usual Doses	Exclude/Use With Caution	Major Pharmacokinetic Drug Interactions
Amiodarone	Oral: 400-600 mg QD in divided doses for 2-4 wk; maintenance typically 100- 200 mg QD 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; after 24 h, consider decreasing dose to 0.25 mg/min	Sinus or AV node dysfunction Infranodal conduction disease Lung disease Prolonged QT interval	Inhibits most CYPs to cause drug interaction: ↑concentrations of warfarin (↑INR 0%-200%), statins, many other drugs Inhibits P-glycoprotein: ↑digoxin concentration
Dofetilide	125-500 mcg once every 12 h	Prolonged QT interval Renal disease Hypokalemia Hypomagnesemia Diuretic therapy Avoid other QT interval-prolonging drugs	Primary renal elimination involving glomerular filtration and active tubular secretion: verapamil, HCTZ, cimetidine, ketoconazole, trimethoprim, prochlorperazine, and megestrol are contraindicated; discontinue amiodarone ≥3 mo before initiation
Dronedarone	400 mg once every 12 h	Bradycardia HF Long-standing persistent AF/flutter Liver disease Prolonged QT interval	Metabolized by CYP3A: caution with inhibitors (e.g., verapamil, diltiazem, ketoconazole, macrolide antibiotics, protease inhibitors, grapefruit juice) and inducers (e.g., rifampin, phenobarbital, phenytoin) Inhibits CYP3A, CYP2D6, P-glycoprotein: ↑concentrations of some statins, sirolimus, tacrolimus, beta blockers, digoxin
Sotalol	40-160 mg once every 12 h	Prolonged QT interval Renal disease Hypokalemia Hypomagnesemia Diuretic therapy Avoid other QT interval-prolonging drugs Sinus or AV nodal dysfunction HF Asthma	None (renal excretion)

Table 15. AF Catheter Ablation to Maintain Sinus Rhythm

Recommendations	COR	LOE
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
In patients with recurrent symptomatic paroxysmal AF, catheter ablation is a reasonable initial rhythm-control strategy before therapeutic trials of antiarrhythmic drug therapy, after weighing the risks and outcomes of drug and ablation therapy.	IIa	B
AF catheter ablation may be considered for symptomatic long-standing (>12 months) persistent AF refractory or intolerant to at least 1 class I or III antiarrhythmic medication when a rhythm-control strategy is desired.	IIb	B
AF catheter ablation may be considered before initiation of antiarrhythmic drug therapy with a class I or III antiarrhythmic medication for symptomatic persistent AF when a rhythm-control strategy is desired.	IIb	C
AF catheter ablation should *NOT* be performed in patients who cannot be treated with anticoagulant therapy during and following the procedure.	III: Harm	C
AF catheter ablation to restore sinus rhythm should *NOT* be performed with the sole intent of obviating the need for anticoagulation.	III: Harm	C

Table 16. Complications of Radiofrequency Catheter Ablation for AF

Complication	Symptoms/Signs	Treatment
Air embolism	Acute ischemia, cardiac arrest, AV block, hypotension	Supplemental oxygen, fluids, CPR, or pacing if indicated
Atrial-esophageal fistula	Usually 1-4 wk after ablation, dysphagia, unexplained fever, chills, sepsis, neurological events (septic emboli)	CT or MRI of esophagus, avoiding endoscopy, immediate surgical correction
Cardiac tamponade/perforation	Abrupt or gradual fall in blood pressure	Pericardiocentesis, emergent surgical drainage if pericardiocentesis fails
Phrenic nerve injury resulting in diaphragmatic paralysis	Shortness of breath, elevated hemidiaphragm	None, usually resolves spontaneously
Iatrogenic atrial flutter	Tachycardia	Cardioversion, antiarrhythmic drugs, or repeat ablation
Gastric motility disorder	Nausea, vomiting, bloating, abdominal pain	Depends on severity of symptoms
Mitral valve injury requiring surgery	Entrapment of catheter	Advance sheath with gentle catheter retraction, surgical removal
MI	Chest pain, ST changes, hypotension	Standard therapy
Pericarditis	Chest pain, typical quality	NSAIDs, colchicine, steroids
Pulmonary vein stenosis	Shortness of breath, cough, hemoptysis	PV dilation/stent or no therapy
Radiation injury	Pain and reddening at radiation site, can present late	Treat as burn injury
Stroke or TIA	Neurological deficit	Consider lysis therapy
Death	N/A	N/A

Vascular access complication

Complication	Symptoms/Signs	Treatment
Femoral pseudoaneurysm	Pain or pulsatile mass at groin	Observation, compression, thrombin injection, possible surgery
Arteriovenous fistula	Pain, bruit at groin site	Observation, compression, possible surgery
Hematoma	Pain, swelling	Compression
Death	N/A	NA

Pacemakers and Implantable Cardioverter-Defibrillators in the Management of AF

The primary role of pacemakers in the treatment of patients with AF is for treatment of symptomatic bradycardia. Permanent pacing is not indicated for the prevention of AF in patients without other indications for pacemaker implantation.

Athletes

Paroxysmal or persistent AF is common in athletes and may be autonomically mediated or triggered by other supraventricular tachycardias. Contributing conditions such as hypertension and CAD should be considered, particularly for older athletes, and a transthoracic echocardiogram is helpful to evaluate for structural heart disease. Evaluation of the rate of ventricular response during an episode of AF is warranted and may require ambulatory ECG monitoring and/or exercise testing to a level of exertion similar to that of the intended sport. Other therapies such as radiofrequency catheter ablation or a “pill-in-the-pocket” approach can be considered in athletes.

Elderly

It is critical to consider the implications of comorbidities to ensure that the patient’s overall goals of care are factored into management decisions.

Table 17. Surgical Maze Procedures

Recommendations	COR	LOE
An AF surgical ablation procedure is reasonable for selected patients with AF undergoing cardiac surgery for other indications.	IIa	C
A stand-alone AF surgical ablation procedure may be reasonable for selected patients with highly symptomatic AF not well managed with other approaches.	IIb	B

Table 18. Hypertrophic Cardiomyopathy

Recommendations	COR	LOE
Anticoagulation is indicated in patients with HCM with AF independent of the CHA2DS2-VASc score.	I	B
Antiarrhythmic medications can be useful to prevent recurrent AF in patients with HCM. Amiodarone or disopyramide combined with a beta blocker or nondihydropyridine calcium channel antagonists are reasonable therapies.	IIa	C
AF catheter ablation can be beneficial in patients with HCM in whom a rhythm-control strategy is desired when antiarrhythmic drugs fail or are not tolerated.	IIa	B
Sotalol, dofetilide, and dronedarone may be considered for a rhythm-control strategy in patients with HCM.	IIb	C

Table 19. AF Complicating ACS

Recommendations	COR	LOE
Urgent direct-current cardioversion of new-onset AF in the setting of ACS is recommended for patients with hemodynamic compromise, ongoing ischemia, or inadequate rate control.	I	C
Intravenous beta blockers are recommended to slow a RVR to AF in patients with ACS who do not display HF, hemodynamic instability, or bronchospasm.	I	C
For patients with ACS and AF with a CHA2DS2-VASc score of ≥2, anticoagulation with warfarin is recommended unless contraindicated.	I	C
Administration of amiodarone or digoxin may be considered to slow a RVR in patients with ACS and AF associated with severe LV dysfunction and HF or hemodynamic instability.	IIb	C
Administration of nondihydropyridine calcium antagonists might be considered to slow a RVR in patients with ACS and AF only in the absence of significant HF or hemodynamic instability.	IIb	C

Table 20. Hyperthyroidism

Recommendations	COR	LOE
Beta blockers are recommended to control ventricular rate in patients with AF complicating thyrotoxicosis unless contraindicated.	I	C
In circumstances in which a beta blocker cannot be used, a nondihydropyridine calcium channel antagonist is recommended to control the ventricular rate.	I	C

Table 21. Pulmonary Disease

Recommendations	COR	LOE
A nondihydropyridine calcium channel antagonist is recommended to control the ventricular rate in patients with AF and chronic obstructive pulmonary disease.	I	C
Direct-current cardioversion should be attempted in patients with pulmonary disease who become hemodynamically unstable as a consequence of new onset AF.	I	C

Table 22. WPW and Pre-Excitation Syndromes

Recommendations	COR	LOE
Prompt direct-current cardioversion is recommended for patients with AF, WPW, and RVR who are hemodynamically compromised.	I	C
Intravenous procainamide or ibutilide to restore sinus rhythm or slow the ventricular rate is recommended for patients with pre-excited AF and RVR who are not hemodynamically compromised.	I	C
Catheter ablation of the accessory pathway is recommended in symptomatic patients with pre-excited AF, especially if the accessory pathway has a short refractory period that allows rapid antegrade conduction.	I	C
Administration of intravenous amiodarone, adenosine, digoxin (oral or intravenous), or nondihydropyridine calcium channel antagonists (oral or intravenous) in patients with WPW syndrome who have pre-excited AF is potentially harmful because these drugs accelerate the ventricular rate.	III: Harm	B

Table 23. Heart Failure

Recommendations	COR	LOE
Control of resting heart rate using either a beta blocker or a nondihydropyridine calcium channel antagonist is recommended for patients with persistent or permanent AF and compensated HFpEF.	I	B
In the absence of pre-excitation, intravenous beta-blocker administration (or a nondihydropyridine calcium channel antagonist in patients with HFpEF) is recommended to slow the ventricular response to AF in the acute setting, with caution needed in patients with overt congestion, hypotension, or HF with reduced LVEF.	I	B
In the absence of pre-excitation, intravenous digoxin or amiodarone is recommended to control heart rate acutely in patients with HF.	I	B
Assessment of heart rate control during exercise and adjustment of pharmacological treatment to keep the rate in the physiological range is useful in symptomatic patients during activity.	I	C
Digoxin is effective to control resting heart rate in patients with HF with reduced EF.	I	C
A combination of digoxin and a beta blocker (or a nondihydropyridine calcium channel antagonist for patients with HFpEF) is reasonable to control resting and exercise heart rate in patients with AF.	IIa	B
It is reasonable to perform AV node ablation with ventricular pacing to control heart rate when pharmacological therapy is insufficient or not tolerated.	IIa	B
Intravenous amiodarone can be useful to control the heart rate in patients with AF when other measures are unsuccessful or contraindicated.	IIa	C
For patients with AF and RVR causing or suspected of causing tachycardia-induced cardiomyopathy, it is reasonable to achieve rate control by either AV nodal blockade or a rhythm-control strategy.	IIa	B
For patients with chronic HF who remain symptomatic from AF despite a rate-control strategy, it is reasonable to use a rhythm-control strategy.	IIa	C
Oral amiodarone may be considered when resting and exercise heart rate cannot be adequately controlled using a beta blocker (or a nondihydropyridine calcium channel antagonist in patients with HFpEF) or digoxin, alone or in combination.	IIb	C
AV node ablation may be considered when the rate cannot be controlled and tachycardia-mediated cardiomyopathy is suspected.	IIb	C
AV node ablation should *NOT* be performed without a pharmacological trial to achieve ventricular rate control.	III: Harm	C
For rate control, intravenous nondihydropyridine calcium channel antagonists, intravenous beta blockers, and dronedarone should *NOT* be administered to patients with decompensated HF.	III: Harm	C

Table 24. Familial (Genetic) AF

Recommendation	COR	LOE
For patients with AF and multigenerational family members with AF, referral to a tertiary care center for genetic counseling and testing may be considered.	IIb	C

Table 25. Postoperative Cardiac and Thoracic Surgery

Recommendations	COR	LOE
Treating patients who develop AF after cardiac surgery with a beta blocker is recommended unless contraindicated.	I	A
A nondihydropyridine calcium channel blocker is recommended when a beta blocker is inadequate to achieve rate control in patients with postoperative AF.	I	B
Preoperative administration of amiodarone reduces the incidence of AF in patients undergoing cardiac surgery and is reasonable as prophylactic therapy for patients at high risk for postoperative AF.	IIa	A
It is reasonable to restore sinus rhythm pharmacologically with ibutilide or direct-current cardioversion in patients who develop postoperative AF, as advised for nonsurgical patients.	IIa	B
It is reasonable to administer antiarrhythmic medications in an attempt to maintain sinus rhythm in patients with recurrent or refractory postoperative AF, as advised for other patients who develop AF.	IIa	B
It is reasonable to administer antithrombotic medication in patients who develop postoperative AF, as advised for nonsurgical patients.	IIa	B
It is reasonable to manage well-tolerated, new-onset postoperative AF with rate control and anticoagulation with cardioversion if AF does not revert spontaneously to sinus rhythm during follow-up.	IIa	C
Prophylactic administration of sotalol may be considered for patients at risk of developing AF following cardiac surgery.	IIb	B
Administration of colchicine may be considered for patients postoperatively to reduce AF after cardiac surgery.	IIb	B

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Key Points

Diagnosis and Treatment

Table 1. Definitions

Paroxysmal AF

Persistent AF

Longstanding persistent AF

Permanent AF

Nonvalvular AF

Figure 1. Atrial Tachycardias

Figure 2. Mechanisms of AF

Table 2. Clinical Evaluation

Table 3. Initial Clinical Evaluation in Patients With AF

Minimum Evaluation

Additional Testing (1 or several tests may be necessary)

Table 4. Risk-Based Antithrombotic Therapy

For patients with nonvalvular AF with prior stroke, TIA, or a CHA2DS2-VASc score ≥2, oral anticoagulants are recommended. Options include:

Table 5. Cardiac Surgery—LAA Occlusion/Excision

Table 6. Risk Stratification Scores for Subjects With Nonvalvular AF

Table 7. Dose Selection of Oral Anticoagulant Options for Patients with Nonvalvular AF and CKD (Based on Prescribing Information for the United States)a

Table 8. Rate Control

Figure 3. Approach to Selecting Drug Therapy for Ventricular Rate Controla

Table 9. Common Medication Dosage for Rate Control of AF

Beta Blockers

Nondihydropyridine calcium channel antagonists

Digitalis glycosides

Others

Table 10. Electrical and Pharmacological Cardioversion of AF and Atrial Flutter

Prevention of Thromboembolism

Direct-Current Cardioversion

Pharmacological Cardioversion

Figure 4. Strategies for Rhythm Control in Patients With Paroxysmala and Persistent AFb

Table 11. Recommended Drug Doses for Pharmacological Cardioversion of AF

Table 12. Antiarrhythmic Drugs to Maintain Sinus Rhythm

Table 13. Upstream Therapy

Table 14. Dosage and Safety Considerations for Maintenance of Sinus Rhythm in AF

Vaughan Williams Class IA

Vaughan Williams Class IC

Vaughan Williams Class III

Table 15. AF Catheter Ablation to Maintain Sinus Rhythm

Table 16. Complications of Radiofrequency Catheter Ablation for AF

Vascular access complication

Pacemakers and Implantable Cardioverter-Defibrillators in the Management of AF

Athletes

Elderly

Table 17. Surgical Maze Procedures

Table 18. Hypertrophic Cardiomyopathy

Table 19. AF Complicating ACS

Table 20. Hyperthyroidism

Table 21. Pulmonary Disease

Table 22. WPW and Pre-Excitation Syndromes

Table 23. Heart Failure

Table 24. Familial (Genetic) AF

Table 25. Postoperative Cardiac and Thoracic Surgery

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For patients with nonvalvular AF with prior stroke, TIA, or a CHA₂DS₂-VASc score ≥2, oral anticoagulants are recommended. Options include: