Approach

The main elements in the management of atrial fibrillation (AF) are:

  • Ventricular rate control

  • Restoration and maintenance of sinus rhythm

  • Prevention of stroke and thromboembolic events

  • Lifestyle and risk factor modification

The goal of treatment is to alleviate symptoms, improve quality of life, and prevent tachycardia-induced cardiomyopathy and thromboembolic events. Treatment involves correction of the abnormal rate/rhythm, along with anticoagulation.

Factors in the patient's presentation and diagnostic assessment that guide appropriate treatment include the following:

  • Whether the patient is hemodynamically stable or unstable

  • If hemodynamically stable, whether the patient is symptomatic or asymptomatic

  • The presence of associated heart failure (HF) or other comorbidities

  • The presence of a thrombus on transesophageal echocardiography (TEE)

  • If a thrombus is absent on TEE, whether the patient has a high or low thromboembolic risk.

The European Society of Cardiology (ESC) recommends following the integrated Atrial fibrillation Better Care (ABC) pathway for holistic management of any patient with AF:[2][98]

  • A: Anticoagulation/avoid stroke

  • B: Better symptom management (rate/rhythm control)

  • C: Cardiovascular and comorbidity optimization (including lifestyle changes)

Need for hospital admission

Patients with comorbidity may require hospital admission. In particular, admission to the hospital is indicated for:

  • Patients with underlying heart disease who have hemodynamic consequences or symptoms of angina, heart failure, or syncope or who are at risk for a complication resulting from therapy of the arrhythmia.

  • Patients with associated or precipitant medical conditions that require further treatment, such as heart failure, pulmonary problems (e.g., pneumonia, pulmonary embolism), hypertension, or hyperthyroidism.

Hospital admission should also be considered on an individual case basis for older patients.

Hemodynamically unstable AF

Patients with established AF may present acutely with hemodynamic instability. This may occur following a change in clinical situation; for example, exacerbation of heart failure, myocardial ischemia, hypoxia, metabolic abnormalities, etc. AF with a rapid ventricular rate causing ongoing chest pain, hypotension, shortness of breath, dizziness, or syncope requires immediate direct current (DC) cardioversion.[3] This is performed under adequate short-acting general anesthesia and involves delivery of an electrical shock synchronized with the intrinsic activity of the heart by sensing the R wave of the ECG (i.e., synchronized). Most currently used external defibrillators utilize biphasic energy, and as low as 100 J may be used as the starting level for the successful termination of AF. However, energy from 200 J to a maximum of 400 J may be used, depending on body size and the presence of other comorbid conditions. 

Hemodynamically stable AF

In hemodynamically stable patients, in addition to review of lifestyle and risk factors and assessment of stroke risk, a clinical decision on initial management needs to be made as to whether to follow a primarily rate-control or rhythm-control strategy. A rate-control strategy aims to control the ventricular rate, but with no commitment to restore or maintain sinus rhythm. A rhythm-control strategy attempts to restore and maintain sinus rhythm using approaches including pharmacologic therapy, electrical cardioversion, and catheter or surgical ablation. The treatment strategy depends on the severity and duration of the symptoms and is individualized for each patient.[1][2]

Decisions on anticoagulation and rate-control versus rhythm-control strategy should be made with the patient, following discussion of options.

Lifestyle and risk factor modification

US guidelines recommend that all patients with AF receive comprehensive guideline-directed lifestyle and risk factor modification, which includes maintenance of ideal weight and weight loss if overweight or obese, having a physically active lifestyle, reducing unhealthy alcohol consumption, stopping smoking, controlling diabetes, and controlling blood pressure/hypertension.[1]

Prevention of stroke and thromboembolism: anticoagulation

The patient's risk of stroke and thromboembolic events should be assessed using a validated clinical risk score, such as the CHA₂DS₂-VASc tool.[1][2][78]​ Guidelines from the American College of Cardiology/American Heart Association/American Association of Colleges of Pharmacy/Heart Rhythm Society (ACC/AHA/ACCP/HRS) recommend that the risk is evaluated annually.[1] The CHA₂DS₂-VASc tool, a modified version of the CHADS₂ tool, is the most validated risk score and is generally preferred.[1][2][78]​ CHA₂DS₂-VASc allocates 1 point each for chronic heart failure, hypertension, age 65-74 years, diabetes mellitus, vascular disease, and female sex, and 2 points each for a history of stroke or transient ischemic attack, or age 75 years and older.[99] [ Atrial Fibrillation CHA(2)DS(2)-VASc Score for Stroke Risk Opens in new window ] ​ The ACC/AHA/ACCP/HRS and ESC guidelines recommend the use of oral anticoagulants for patients with AF and a CHA₂DS₂-VASc score of ≥2 in men or ≥3 in women (which corresponds to annual thromboembolic risk of ≥2%).[1][2]​ With a score of ≥1 in men or ≥2 in women (which corresponds to annual thromboembolic risk of ≥1% to <2%), the use of oral anticoagulants to prevent thromboembolic stroke can be considered; additional factors that may modify stroke risk, such as hypertension control, can be taken into account.[1][2]​ Use of oral anticoagulants in patients with a nonsex-related CHA₂DS₂-VASc score of 1 is particularly important to consider in patients over the age of 65 years.[3] 

Newer stroke risk scores that have been validated include GARFIELD-AF GARFIELD-AF Risk Calculator Opens in new window​​​​ ​​and ATRIA ATRIA Stroke Risk Score Opens in new window​​​​​ 

Use of any anticoagulation strategy needs to be balanced with the risk of bleeding, particularly intracranial bleeding.[100] Scoring systems such as ORBIT, HAS-BLED, HEMORR₂HAGES, and the newer direct oral anticoagulants (DOAC) score can help to quantify this risk and assess how the bleeding risk can be minimized.[101] MdCalc. HEMORR₂HAGES Score for Major Bleeding Risk Opens in new window [ ORBIT Bleeding Risk Score Opens in new window ] [ HAS-BLED Bleeding Risk Score Opens in new window ] ​​​​​​​ When used in combination with a stroke risk score such as CHA₂DS₂-VASc, bleeding risk tools provide a means to balance the benefits and risks of anticoagulation with patients. Bleeding risk scores should not be used to exclude people from receiving anticoagulant treatment.[1][2][102]

In patients with cardiac implantable electronic devices (CIEDs) such as the permanent pacemakers and defibrillators, AF may be detected as atrial high rate episodes (AHREs). AHREs can be silent, (i.e., not causing or correlating with symptoms [subclinical AF]) and vary in duration. Anticoagulation therapy for prevention of thromboembolism and stroke based on subclinical AF has not shown to be convincingly useful; use of DOACs in the ARTESIA and NOAH-AF trials was associated with increased risk of major bleeding.[103][104]​​ In patients who have longer duration AHREs, are at higher risk of stroke (e.g., measured by CHA₂DS₂-VASc), and have symptomatic AF, anticoagulation may be of benefit.[1][2][105]

Oral anticoagulation drugs for stroke prevention are warfarin or a DOAC such as dabigatran, rivaroxaban, apixaban, or edoxaban. All patients should preferably be started on a DOAC, unless they are not eligible (e.g., presence of moderate to severe mitral valve stenosis or mechanical prosthetic valves) or DOACs are not available.[1][2][78]​​​​ Unlike warfarin, DOACs are nonvitamin K-dependent. While dabigatran is an oral direct thrombin inhibitor, rivaroxaban, apixaban, and edoxaban inhibit factor Xa directly. All DOACs have consistently shown safety and efficacy compared with warfarin in large, randomized clinical trials for stroke prevention in patients with nonvalvular AF.[3][106]

  • Dabigatran was compared with warfarin in patients with AF at increased risk of stroke in the RE-LY trial that included 18,113 patients and had a median follow-up of 2 years.[107] Compared with warfarin, dabigatran at a lower dose showed noninferiority and, at higher doses, it showed superiority regarding rates of stroke and systemic embolism (warfarin 1.69%/year, lower dose dabigatran 1.53%/year, and higher dose dabigatran 1.11%/year for a primary end point of stroke and systemic embolism). Adverse bleeding event rates were lower with a lower dose and similar with a higher dose of dabigatran compared with warfarin. Although there was significantly higher rates of major gastrointestinal bleeding with higher dose of dabigatran, intracranial bleeding was significantly lower with both doses of dabigatran compared with warfarin.[107]

  • Rivaroxaban, apixaban, and edoxaban were compared with warfarin for stroke prevention in patients with nonvalvular AF in the ROCKET AF (14,264 patients and a median follow-up of 1.9 years), ARISTOTLE (18,201 patients and a median follow-up of 1.8 years), and ENGAGE AF (21,105 patients and a median follow-up of 2.8 years) trials, respectively. The primary end point of stroke and/or systemic embolism end points were 1.7% per year with rivaroxaban compared with 2.2% per year with warfarin in the ROCKET AF, 1.27% per year with apixaban compared with 1.6% per year with warfarin in ARISTOTLE, and 1.61% per year with a lower dose and 1.18% per year a higher dose edoxaban compared with 1.50% per year with warfarin in ENGAGE AF trials, respectively.[108][109][110][111]

These trials, together with results of meta-analyses, have shown that DOACs are noninferior to warfarin for stroke prevention in patients with nonvalvular AF, and may be associated with a reduced risk of fatal bleeding.[106][112][113][114][115][116]​​​​​​ [ Cochrane Clinical Answers logo ] ​ It is, therefore, reasonable to use a DOAC as a first-line agent or subsequent replacement for warfarin in patients with AF. DOACs are generally safe in older patients; however, dabigatran may be associated with an increased risk of gastrointestinal bleeding compared with warfarin.[117]​

If DOACs are used in patients with renal impairment, they should be used with caution. Some DOACs may require a dose adjustment and others are not recommended, depending on the degree of renal impairment and the indication for use. Consult a drug information source for specific guidance on use in patients with renal impairment. Regular monitoring, including complete blood count, renal function, and liver function, is recommended. DOACs should not be in combination with heparin (including low molecular weight heparin [LMWH]), heparin derivatives, or warfarin.

The efficacy and safety of anticoagulation with warfarin is highly dependent on the quality of anticoagulation control as reflected by the average time in therapeutic range (TTR) of INR 2 to 3. The SAMe-TT₂R₂ scoring system (based on sex, age, medical history, treatment interactions, tobacco use, and race) is a tool that may help identify anticoagulation-naive patients who are less likely to maintain TTR >70% and who should, therefore, be managed with DOACs instead of warfarin.[118][119] SAMe-TT₂R₂ score Opens in new window​​​

The ACC/AHA/ACCP/HRS, ESC, and NICE (UK) guidelines do not recommend aspirin as an alternative to anticoagulation for stroke prevention in patients with AF.[1][2][78]​​

Adults with AF who are prescribed anticoagulation should discuss the options with their healthcare professional at least once per year.[1][78]​​

Anticoagulation treatment in AF may reduce the risk of cognitive decline and dementia.[120] One meta-analysis found that use of oral anticoagulants was associated with a significant reduction in cognitive impairment in patients with AF, and that DOACs had a more protective effect compared with warfarin.[121] Currently, no unique score system is available for the risk stratification of patients with AF and dementia. Many physicians tend to use CHA₂DS₂-VASc scores as surrogate or extended methodology for dementia risk-stratification. Some investigators have used components of some commonly performed blood tests independently and integrated with CHA₂DS₂-VASc scores to risk stratify dementia. However, much work is still needed in developing simple, easy, and widely applicable risk-stratifying systems for AF-related dementia.[122]

Recommendations for anticoagulation in patients with concomitant conditions are available and should be consulted.[1][2]​​​ See “Considerations for management of specific comorbidities” below for specific examples.​​

Prevention of stroke and thromboembolism: left atrial appendage occlusion and exclusion

Percutaneous left atrial appendage occlusion (LAAO) may be considered as an alternative for stroke prevention when there are absolute contraindications to use of anticoagulants, or the risk of bleeding outweighs the benefits.[1][2][78][123]​​[124]​ 

LAAO devices such as the WATCHMAN™ and the Amplatzer™ Cardiac Plug device may be implanted percutaneously via transeptal catheterization. The WATCHMAN™ device has a polyethylene membrane that covers a self-expanding nitinol cage with barbs to anchor the device in the left atrial appendage (LAA). In the PROTECT AF trial, the primary efficacy event rate (a composite end point of stroke, cardiovascular death, and systemic embolism) of the WATCHMAN™ device was considered noninferior to that of warfarin.[125] There was a higher rate of adverse safety events in the intervention group than in the control group, due mainly to periprocedural complications. The Amplatzer™ Cardiac Plug consists of a small proximal disk, a central polyester patch, and a larger distal disk with hooks to anchor the device in the LAA. It does not require anticoagulation and a European trial found a 96% success rate for deployment/implantation but with a 7% incidence of serious complications.[126]​ Another nonpharmacologic approach to isolate and occlude LAA is to tie off the LAA using the LARIAT device, which is an epicardial snare.[127] The WATCHMAN FLX™ device is a next-generation LAA closure device that has a greater number of struts and dual-row J-shaped anchors to maximize device stability. A prospective, nonrandomized, multicenter study (PINNACLE FLX) found the WATCHMAN FLX™ to be associated with a low incidence of adverse events and a high incidence of anatomic closure.[128]

Concomitant surgical LAA exclusion may be considered (in addition to continued anticoagulation) in patients with a CHA2DS2-VASc score ≥2 or equivalent stroke risk who are undergoing cardiac surgery (e.g., coronary artery bypass graft or valve surgery).[1] The safety and efficacy of concomitant surgical LAAO in patients with AF undergoing cardiac surgery for another indication was evaluated in a multicenter, randomized trial (Left Atrial Appendage Occlusion Study [LAAOS III]). Participants had a mean age of 71 years and a mean CHA₂DS₂-VASc score of 4.2 and most continued to receive ongoing antithrombotic therapy. The risk of ischemic stroke or systemic embolism was lower in the group who had concomitant LAAO performed during the surgery than the group who didn’t at a mean follow-up of 3.8 years.[129]

In a decision-analytic Markov model designed to simulate a virtual clinical trial of stroke prevention strategies (DOACs and LAAO), it was shown that the clinical benefit of LAAO over DOACs depends on patients' baseline risks for stroke and bleeding. Although LAAOs were favorable among patients with the highest bleeding risk (higher HAS-BLED scores), that benefit became less certain at higher stroke risk (higher CHA₂DS₂-VASc scores).[130][131]

Rate-control strategy

Pharmacologic rate control:

  • A rate-control strategy may be preferred over rhythm control in older patients who have a longer history of AF and fewer symptoms.[1][2]​ Older patients (>70 years) are more prone to drug interactions and proarrhythmic effects of antiarrhythmic drugs, such as exacerbation of underlying sinus node dysfunction.[132][133][134][135]​ Additionally, rate control is also generally preferred in patients who have a larger left atrium, less left ventricular (LV) dysfunction, less atrioventricular regurgitation, and an easily controlled heart rate. Aggressive rate control with pharmacologic agents may result in significant depression of the left ventricular systolic function. In some patients who have slow resting heart rates, drug therapy could be hazardous. A lenient rate-control strategy (resting heart rate <110 bpm) may be reasonable as long as patients remain asymptomatic and left ventricular systolic function is preserved. The ACC/AHA/ACCP/HRS and European Society of Cardiology guidelines support lenient rate control (resting heart rate of <100 to <110 bpm) for target rate control therapy, but this should be guided by underlying patient symptoms.[1][2]

  • Patients with paroxysmal/persistent AF with rapid ventricular response requiring acute rate control are treated with either beta-blocker, a nondihydropyridine calcium-channel blocker (diltiazem or verapamil, if ejection fraction [EF] >40%), digoxin, or amiodarone.[1][2]

    • In terms of choosing a single drug or combination of these drugs, consider any comorbid conditions, the presence or absence of heart failure, and left ventricular ejection fraction (LVEF).

    • When LV function is preserved, a beta-blocker or nondihydropyridine calcium-channel blocker is preferred. The beta-blockers atenolol, metoprolol, nadolol, propranolol, and bisoprolol may be used orally. In patients with HF, carvedilol is effective in rate control, and in combination with digoxin may improve LV function. Nondihydropyridine calcium-channel blockers must not be used in the presence of HF with reduced EF (≤40%) owing to their negative inotropic effect.

    • Digoxin is not considered a first-line agent for the purpose of rate control, but it can be useful (either alone or in combination) when beta-blockers and nondihydropyridine calcium-channel blockers are ineffective or contraindicated. One study explored whether digoxin use was independently associated with increased mortality in patients with AF. Compared with propensity score-matched control participants, the risk of death (adjusted hazard ratio [HR]: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxin users. In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations of at least 1.2 nanograms/mL.[136]

    • Amiodarone may be considered for acute rate control in patients who are critically ill or in decompensated heart failure when beta-blockers and nondihydropyridine calcium-channel blockers are ineffective or contraindicated.[1][2]

  • Beta-blockers and nondihydropyridine calcium-channel blockers (if EF >40%) may also be used for long-term rate control, with digoxin considered either alone or in combination if other options are not tolerated or contraindicated.[1][2]

  • Beta-blockers, diltiazem, verapamil, and digoxin may be used in conjunction with drugs typically used for heart failure, such as diuretics and ACE inhibitors. It should be remembered that a rapid rate itself could contribute to heart failure symptoms, and continuing or increasing beta-blockers may be appropriate rather than contraindicated in these patients as long as other medications such as diuretics are adjusted accordingly.

Atrioventricular node ablation (AVNA) and pacing:

  • AVNA and pacemaker implantation may be considered for rate control when rapid ventricular response is refractory to pharmacologic rate control and attempt at rhythm control has either been unsuccessful, or the patient is not eligible for rhythm control.[1][2]

  • This "ablate and pace" strategy involves ablation of the AV junction and implantation of a permanent ventricular pacemaker therapy. Atrial lead implantation in those with paroxysmal AF, a coronary sinus lead in those with ventricular dyssynchrony, and even a defibrillator lead in those at risk of sudden cardiac death from ventricular arrhythmias may be necessary. The ablate and pace strategy provides an improvement in symptoms, better rate control, and reduces adverse events of uncontrolled heart rate on left ventricular function (tachycardia-induced cardiomyopathy), especially in patients in whom rate control with multiple pharmacologic agents proves difficult.[137][138][139][140]​​ 

Rhythm-control strategy

A rhythm control strategy aims to restore and maintain sinus rhythm using approaches including pharmacologic therapy, electrical cardioversion, and catheter or surgical ablation.[1]​ A rhythm control strategy may be preferred over rate control in younger patients who have a shorter history of AF and a higher symptom burden.[1][2][141]​​ Additionally, rhythm control may be preferred in patients who have a smaller left atrium, greater left ventricular dysfunction, greater atrioventricular regurgitation, and a less easily controlled heart rate.[1]

In the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET4), patients diagnosed with AF within the last 12 months were randomized to receive either early rhythm control therapy or usual care. Patients in the early rhythm control group received antiarrhythmic drugs or catheter ablation, as well as cardioversion of persistent AF, early after randomization. Patients receiving usual care were initially treated with rate-control therapy without rhythm-control therapy and only received rhythm-control therapy for uncontrolled symptoms. The trial was stopped early (at 5 years follow-up) for efficacy. The primary outcome, a composite of death from cardiovascular causes, stroke, hospitalization for heart failure, or acute coronary syndrome, occurred in 249 patients in the early rhythm control group (3.9/100 person-years) and in 316 patients in the usual care group (5.0/100 person-years).[142] Prespecified subanalysis found that the primary cardiovascular outcomes continued to be reduced with early rhythm control in patients with a high comorbidity burden (CHA2DS2-VASc score ≥4), but not in those with fewer comorbidities.[143]​ A population-based cohort study in Korea found that a benefit of early rhythm control among low-risk patients who would not have been eligible for EAST-AFNET4 (CHA2DS2-VASc score 0 to 1).[144]​ One meta-analysis (which included EAST-AFNET4) found that early initiation of rhythm control therapy was associated with improved outcomes (a composite of death, ischemic or hemorrhagic stroke, hospitalization with HF, or acute coronary syndrome) in patients who had been diagnosed with AF within 1 year.[145]​ A follow-up study of EAST-AFNET4 suggested that the efficacy of early rhythm control is mediated by the presence of sinus rhythm at 12 months.[146] 

Compared with a rate-control strategy, restoring the sinus rhythm reduces the possibility of embolic stroke due to clot formation in the left atrium. Long-term anticoagulation for stroke prevention may not be necessary in the rhythm-control group. However, one should be cautious in assuming that rhythm control is always effective. Recurrences are common, and asymptomatic AF is frequent when patients have been followed after AF ablations clinically and with cardiac implantable electronic devices. Even though there may be electrical sinus rhythm, mechanical function may not be adequate, and stasis and the other causes of thrombus formation may still exist. The decision to continue with anticoagulation and type used should take into account the risks of the therapy and the risk for stroke. Attention to rate control, even when in sinus rhythm, is also necessary.

Cardioversion

DC cardioversion is indicated to restore sinus rhythm in patients with hemodynamic instability from AF. Either DC cardioversion or pharmacologic cardioversion can be considered in hemodynamically stable patients.[1] DC cardioversion is quicker and more effective than pharmacologic cardioversion and is generally preferred, but it requires sedation.

Both DC and pharmacologic cardioversion are associated with increased risk of thromboembolic events, and risk must be minimized before going ahead.[147][148]

  • If cardioversion is indicated for an episode of AF ≥48 hours or of unknown duration, it must be performed only after a minimum of 3 weeks on oral anticoagulation (DOAC or warfarin), or after imaging to rule out presence of intracardiac thrombus (e.g., if patient has had previous LAAO and is not receiving anticoagulation).[1]

  • If the duration of AF is <48 hours, cardioversion is generally thought to have a low risk of thromboembolic events with anticoagulation afterward; however, imaging to rule out the presence of an intracardiac thrombus may be considered before cardioversion, particularly in those who have not received a minimum of 3 weeks on oral anticoagulation and those at higher thromboembolic risk.[1] The benefit of pericardioversion anticoagulation or imaging in patients with a low risk of thromboembolism and AF duration <12 hours is uncertain.[1] AF that is asymptomatic before the immediate event is common, making a determination of the duration uncertain.

  • Guidelines recommend that therapeutic anticoagulation is started before cardioversion and continued for at least 4 weeks afterward.[1]

  • If intracardiac thrombus is identified on imaging and cardioversion is delayed, anticoagulation is given for a minimum of 3-6 weeks and imaging repeated before cardioversion is considered again.[1]

In patients with hemodynamically stable persistent AF with preserved left ventricular function and no evidence of metabolic and electrolyte disturbances, pharmacologic cardioversion may be attempted with administration of intravenous ibutilide under close telemetry monitoring.[1] Ibutilide prolongs repolarization of the atrial tissue by enhancing the slow inward depolarizing sodium current in the plateau phase of repolarization. For cardioversion of acute AF and atrial flutter to sinus rhythm, ibutilide is very efficacious; the conversion rate of persistent lasting for more than 30 days is approximately 48%.[149]​ Because the half-life of ibutilide is 3-6 hours, prolonged observation period is recommended in patients who have received ibutilide.[150][151] Intravenous amiodarone is also an option for pharmacologic cardioversion (including patients with HF), but time to cardioversion is longer than with ibutilide.[1][2]​ Intravenous procainamide, if available, may be considered for pharmacologic cardioversion (in patients who do not have HF with reduced EF) when other intravenous agents are contraindicated.[1]

Pretreatment with antiarrhythmic drugs may be considered in some patients to facilitate the success of DC cardioversion and reduce risk of AF recurrence.[150][151]

If pharmacologic conversion is attempted and is unsuccessful, DC conversion should be considered rather than switching to an alternative antiarrhythmic agent.[1]

Selected outpatients who have recurrent AF may self-administer a single oral dose of flecainide or propafenone (known as the "pill-in-the-pocket" approach).[1][2] An atrioventricular node-blocking agent (beta-blocker or nondihydropyridine calcium-channel blocker) should be administered concomitantly, to prevent atrial flutter with 1:1 conduction. Safety and efficacy of this approach in selected patients should be established first in a monitored hospital setting.[1][2]

Pharmacologic maintenance of sinus rhythm

Long-term use of antiarrhythmic drugs is considered for maintenance of sinus rhythm after cardioversion in patients in whom catheter ablation is not suitable or not preferred. Pharmacologic maintenance of sinus rhythm can also be considered while awaiting ablation. Adverse effects associated with use of antiarrhythmics include bradycardia or worsening of underlying sinus node dysfunction, or AV block. There is a risk of other arrhythmias developing with the use of these antiarrhythmics for AF. Choice of antiarrhythmic agent is therefore primarily guided by safety, considering cardiac comorbidities and other risk factors for proarrhythmic events.[1][2] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ]

  • In patients with normal LV function, no previous myocardial infarction (MI), and no significant structural heart disease, dofetilide, dronedarone, flecainide, or propafenone are recommended.[1][2] Amiodarone is an alternative option in these patients, but it is associated with a range of adverse effects and drug interactions, so it is recommended only when other antiarrhythmics are ineffective or contraindicated. Sotalol may also be considered in this group.[1]

  • ​Although (like sotalol, propafenone, and flecainide) dronedarone is less effective than amiodarone for the maintenance of sinus rhythm, it has fewer adverse effects.[152][153][154][155]​​ Dronedarone is indicated to reduce the risk of hospitalization in patients with paroxysmal or persistent AF and associated cardiovascular risk factors (i.e., age >70 years, hypertension, diabetes mellitus, prior cerebrovascular accident, left atrial diameter ≥50 mm, or left ventricular ejection fraction <40%), who are in sinus rhythm, or who will be cardioverted. It is contraindicated in patients with AF who cannot, or will not, be converted into normal sinus rhythm (i.e., permanent AF) as a safety review showed that dronedarone doubles the risk of serious cardiovascular events including stroke, systolic and diastolic heart failure, and death in patients with permanent AF.[156]

  • In patients with significant structural heart disease, including heart failure with reduced EF (≤40%), or with history of myocardial infarction, options are amiodarone or dofetilide.[1][2]​ Dronedarone may be considered in patients who do not have New York Heart Association (NYHA) class III-IV heart failure or decompensation in the last 4 weeks.[154]​ Sotalol should not be used in patients with HFrEF.[1][2]

  • The ESC guidelines include specific recommendations for patients with coronary artery disease (CAD), heart failure with preserved EF (EF >40%), or significant valvular disease: these include amiodarone and dronedarone, with sotalol as an alternative.[2]​ Class Ic agents (e.g., flecainide, propafenone) have a higher mortality in patients with CAD and are contraindicated in patients with CAD and cardiac dysfunction.[1]

  • There are also certain specific adverse effects that are more associated with certain antiarrhythmic agents. For example, with class Ic agents (i.e., propafenone or flecainide), conversion of AF to atrial flutter can occur with a faster ventricular response. This is due to slowing of the atrial cycle length allowing faster AV nodal conduction. Indeed, patients can present with a wide complex tachycardia simulating ventricular tachycardia due to rate-dependent conduction slowing in the ventricular myocardium or a bundle-branch block pattern. Therefore, patients eligible for the use of class Ic antiarrhythmics (i.e., propafenone or flecainide) should always be taking an AV nodal blocking drug (e.g., beta-blocker, diltiazem, or verapamil) before initiating treatment.

  • Dofetilide and sotalol may cause QT prolongation and torsades de pointes. These agents should be initiated within the hospital cautiously under close telemetry monitoring, and dosing should be modified based on creatinine clearance.

  • It is important to monitor liver enzymes when patients are treated with dronedarone and amiodarone. For the latter, patients should also have at least 6-month assessment of thyroid function and annual assessment of pulmonary function tests, including diffusing lung capacity for carbon monoxide.[1]

  • Overall, antiarrhythmic drugs should be used very cautiously especially in patients with abnormal left ventricular (LV) function and heart failure, as there is evidence showing that antiarrhythmic drugs increase adverse events. Some antiarrhythmic agents such as sotalol may increase mortality.[157]

Catheter ablation

Catheter ablation is used to prevent AF progression and improve symptoms in selected patients with paroxysmal or persistent AF.[1][2][158]​​​​ It may be used as a first-line option in some patients and in other patients is used when antiarrhythmic drugs have been ineffective, not tolerated, or are contraindicated.[1][2][158]​​​ [ Cochrane Clinical Answers logo ] ​​​ Isolation of the pulmonary vein is generally recommended as the target of ablation, unless another specific AF trigger is identified.[1][2][158]​​​​ Catheter ablation using either radiofrequency or cryo energy to create pulmonary vein isolation (PVI) results in similar outcomes.[158][159][160]​​​​​​ Additional complex atrial substrate modification ablation strategies (e.g., linear ablations to isolate the roof and the posterior wall of the left atrium, ablation of complex fractionated atrial electrograms, focal source, or rotors) may be considered, but the benefit of this versus PVI alone is not confirmed.[1][2][158]​​​

Randomized controlled trials have demonstrated the superiority of catheter ablation over drug therapy for rhythm control in select patients. The RAAFT (Radiofrequency Ablation versus antiarrhythmic drug for Atrial Fibrillation Treatment) II trial and the MANTRA-PAF (Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) trial have shown better outcomes for freedom from any AF or symptomatic AF, and improvement in quality of life with ablation.[161][162]​ In the EARLY-AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) trial, at 3 years of follow-up, compared with initial use of antiarrhythmic drugs, initial treatment of paroxysmal AF with cryoballoon catheter ablation was associated with a lower incidence of persistent AF and recurrent atrial tachyarrhythmia.[163] The Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial, found that, compared with medical therapy, catheter ablation led to improvements in quality of life, but did not significantly reduce a composite end point of death, disabling stroke, serious bleeding, or cardiac arrest.[164][165]​ One subgroup analysis of patients with AF and heart failure symptoms at baseline found that catheter ablation led to improvements in survival, nonrecurrence of AF, and quality of life compared with drug therapy.[166]​ Another randomized trial (CASTLE-AF) showed that the primary end point, composite of all-cause mortality and unplanned hospitalization for worsening heart failure, significantly improved with catheter ablation. In patients with heart failure, catheter ablation for AF was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy (hazard ratio, 0.62; 95% CI 0.43 to 0.87; P=0.007). These findings indicate that catheter ablation should be considered sooner in patients with AF and LV dysfunction.[3][167]​ Meta-analyses and randomized controlled trials comparing catheter ablation with conventional treatment in patients with AF and heart failure with reduced ejection fraction have found that catheter ablation decreases mortality, AF recurrence, and hospitalizations, and improves LV function, functional capacity, and quality of life, without an increase in complications.[167][168][169]​​​​[170]​​[171][172][173]​​ 

Patients with AF and HF are selected for catheter ablation in a shared decision-making process.[174][175]​ In patients with HF and reduced EF (EF ≤40%) factors that should be taken into account include LV dysfunction, functional class, comorbid conditions, hemodynamic stability, ventricular scar burden, duration of AF, and degree of adverse atrial remodeling. Patients more likely to benefit generally are younger and have less severe disease.[174][175]

Patients with persistent AF who are in AF at the time of ablation should have a TEE performed to screen for thrombus. The presence of a left atrial thrombus is a contraindication to catheter ablation of AF.

Risk of thromboembolic events is increased following catheter ablation and all patients should receive uninterrupted oral anticoagulation before, during, and after ablation.[1][158]​​ Following ablation therapy, anticoagulation is continued for at least 3 months, or longer depending on underlying risk factors (such as stroke risk). Rate-lowering medications and antiarrhythmics may also be continued, but this will depend on various patient factors, and the decision is individualized. If symptomatic AF recurs after catheter ablation, a repeat procedure often results in a better success rate. Surgical ablation is another option but does not necessarily have to follow a failed percutaneous catheter ablation.

Surgical ablation

Surgical ablation (open surgery, rather than using catheter techniques) is most often reserved for those who are having cardiac surgery for other reasons, such as bypass or valve surgery (e.g., mitral-valve surgery). Surgical ablation may also be used in patients with left atrial thrombus, or it may be chosen by certain patients who do not prefer the catheter approach, in which case a minimally invasive surgical approach is often used.[158][176]​​​​​ The Cox maze procedure is the conventional surgical approach. Multiple, precisely placed incisions are made in both atria, with the aim of isolating and terminating the abnormal electrical impulses' routes. The Cox maze IV procedure uses a modified approach.[177][178]​​ Alternative methods of creating lesions in the atria by ablation rather than incision have also been developed (e.g., radiofrequency, microwave, cryotherapy, and ultrasound).

Hybrid convergent ablation, which combines minimally invasive surgical (epicardial) and catheter (endocardial) ablation, may be considered for patients with symptomatic, persistent AF refractory to antiarrhythmic drug therapy.[1][2][179]​ 

Considerations for management of specific comorbidities

Heart failure (HF)

  • AF and HF may cause or exacerbate each other and the relationship is complex.[2]​ There are specific considerations for rate control and rhythm control strategies in patients with AF and HF, which are covered above and also summarized here. All patients with AF and HF should receive guideline-directed HF therapy.

  • Rate control:[1][2]

    • The optimal target heart rate in patients with AF and HF is unclear; stricter rate control may be considered in patients with suspected AF-induced cardiomyopathy or refractory HF symptoms undergoing pharmacologic rate-control therapy.[1][2]

    • In patients with AF and HF with preserved EF (HFpEF; EF >40%), a beta-blocker or nondihydropyridine calcium-channel blocker is preferred for rate control.

    • Nondihydropyridine calcium-channel blockers must not be used in patients with HF with reduced EF (HFrEF; EF ≤40%) owing to their negative inotropic effect.

    • Digoxin is an alternative option for rate control in patients with AF and either HFpEF or HFrEF.

    • Amiodarone may be considered for acute rate control in patients with decompensated HF when beta-blockers and nondihydropyridine calcium-channel blockers are ineffective or contraindicated.

    • Beta-blockers, diltiazem, verapamil, and digoxin may be used where indicated in conjunction with drugs typically used for HF, such as diuretics and ACE inhibitors.

    • In patients with HF, carvedilol is effective in rate control, and in combination with digoxin may improve LV function.[180]

    • It should be remembered that a rapid rate itself could contribute to heart failure symptoms, and continuing or increasing beta-blockers may be appropriate rather than contraindicated in these patients as long as other medications such as diuretics are adjusted accordingly.

    • AVNA and pacing may be an option in selected patients with HF where rhythm control or pharmacologic rate control has failed.[1][2]

  • Rhythm control:

    • The US guidelines recommend an early and aggressive approach to AF rhythm control in patients who present with a new diagnosis of HFrEF and AF.[1]

    • DC cardioversion is generally preferred over pharmacologic cardioversion in patients with (and without) HF, but is not always an option.

    • Antiarrhythmic drugs should be used very cautiously especially in patients with abnormal LV function and HF, as there is evidence that antiarrhythmic drugs increase adverse events. Some antiarrhythmic agents, such as sotalol, may increase mortality.[157]

    • Ibutilide may be used for pharmacologic cardioversion in patients with HFpEF (EF >40%), but should be avoided in patients with HFrEF (EF ≤40%). Intravenous amiodarone is an option for both those with HFpEF and HFrEF (but time to cardioversion is longer than with ibutilide).[1][2]​ Intravenous procainamide, if available, may be considered for pharmacologic cardioversion in those with HFpEF when other intravenous agents are contraindicated; it should be avoided in those with HFrEF.[1]

    • The "pill-in-the-pocket" approach, self-administering a single oral dose of flecainide or propafenone, may be an option in selected outpatients who have recurrent AF and preserved EF. It is not an option for those with HFrEF.[1][2]

    • Patients with AF and HF are selected for catheter ablation in a shared decision-making process.[174][175]​​ Patients more likely to benefit from catheter ablation are generally younger, have an earlier stage of HF, and have less severe disease.[174][175]​ In patients with HFrEF (EF ≤40%) factors that should be taken into account include LV dysfunction, functional class, comorbid conditions, hemodynamic stability, ventricular scar burden, duration of AF, and degree of adverse atrial remodeling.

    • Catheter ablation has been shown to improve outcomes compared with pharmacologic therapy/conventional treatment in patients with HF and AF.[166][167]​ See Catheter ablation section above for more details.

    • In patients with AF and significant structural heart disease, including HFrEF, options for long-term maintenance of sinus rhythm are amiodarone or dofetilide.[1][2]​ Dronedarone may be considered in patients who do not have New York Heart Association (NYHA) class III-IV HF or decompensation in the last 4 weeks.[154]​ Sotalol should not be used in patients with HFrEF.[1][2]

    • The ESC guidelines recommend amiodarone and dronedarone for long-term maintenance of sinus rhythm in patients with HFpEF, with sotalol as an alternative.[2]​ For patients with HFpEF and AF, the use of flecainide or propafenone is reasonable for long-term maintenance of sinus rhythm provided no previous MI, or known or suspected significant structural heart disease, or ventricular scar or fibrosis is present.[1]

Obesity

  • Weight loss in patients with comorbid obesity is recommended (as part of comprehensive lifestyle and risk factor modification program) to reduce AF incidence, progression, recurrence, and symptoms.[1][2]

  • The US guidelines recommend an ideal target weight of at least 10% weight loss in those with AF.[1]

  • When considering anticoagulation, DOACs may be used over warfarin in those with class III obesity (BMI ≥40 kg/m²). Given concerns about drug absorption, warfarin may be preferred in those who have undergone bariatric surgery.[1]

  • See Obesity in adults.

Diabetes

  • Control of comorbid diabetes is important for risk factor modification at all stages of AF.[1][2]​ Additionally, optimal glycemic control before AF catheter ablation has been associated with reduced risk of AF recurrence after ablation.[1][2]

  • When considering anticoagulation, DOACs have been associated with reduced vascular mortality compared with warfarin in those with AF and diabetes.[1][2]

  • ​See Overview of diabetes.

Hypertension

  • Control of comorbid hypertension is important for risk factor modification at all stages of AF. Optimal BP control is recommended to reduce recurrence of AF and risk of AF-related cardiovascular events, such as stroke and bleeding.[1][2]

  • See Essential hypertension.

Valvular heart disease (VHD)

  • The risk of stroke and thromboembolism is increased in patients with AF and VHD. The US guidelines recommend that patients with AF and significant (moderate or greater) mitral stenosis or a mechanical heart valve should receive long-term anticoagulation regardless of CHA₂DS₂-VASc score.[1]​ Warfarin is recommended over DOACs in these patients.[1][2]

  • In patients with AF and other comorbid VHD (i.e., not moderate-to-severe mitral stenosis or a mechanical heart valve), DOACs may be used over warfarin in those who are candidates for anticoagulation.[1][2]

  • The ESC guidelines recommend amiodarone and dronedarone for long-term maintenance of sinus rhythm in patients with AF and significant valvular disease, with sotalol as an alternative.[2]

  • Concomitant surgical ablation carried out during mitral-valve surgery has been shown to reduce the risk of recurrent AF.[1][2][181][182]

Chronic kidney disease (CKD)

  • AF and CKD are common comorbidities; however, there are limited data on management of AF in patients with CKD. The US guidelines note that doses of antiarrhythmic drugs are adjusted based on pharmacokinetic data and clinical experience, and that amiodarone is the only antiarrhythmic drug that does not require dose adjustment in patients with CKD or those receiving dialysis.[1]​ The guidelines also note that if performing catheter ablation in patients with CKD, particular attention must be paid to fluid balance when using irrigated radiofrequency catheters.[1]

  • Renal function must be considered when selecting an anticoagulant regimen:

    • Some DOACs may require a dose adjustment and others are not recommended, depending on the degree of renal impairment and the indication for use. Consult a drug information source for specific guidance on use in patients with renal impairment.

    • In patients with AF and mild or moderate renal impairment who do not have valve disease, the use of DOACs has been found to be associated with a reduced risk of stroke or systemic embolism and a reduced risk of major bleeding compared with warfarin, which suggests a favorable risk profile of these agents in patients with mild to moderate renal disease.[183]

    • The US guidelines specifically advise that patients with stage 3 CKD may receive either a DOAC (preferred) or warfarin; patients with stage 4 CKD may reasonably receive either warfarin or a DOAC; and patients with end-stage CKD (CrCl <15 mL/min) or who are on dialysis may reasonably receive warfarin or apixaban.[1]​​ In Europe, DOACs are not approved for patients with CrCl ≤15 mL/min or on dialysis.[2]

  • See Chronic kidney disease.

Liver dysfunction

  • In patients with AF and liver disease, choice of anticoagulation may be guided by liver function.

    • In those with mild or moderate liver disease (Child-Pugh score A or B), DOACs may be used over warfarin; however, rivaroxaban should not be used in moderate liver disease (Child-Pugh B).[1][2]

    • There are no data on use of DOACs in patients with severe liver disease (Child-Pugh class C). In Europe, DOACs are contraindicated in these patients.[1][2]​ Warfarin may be used in patients with Child-Pugh class C liver disease; in high-risk patients (recent major bleeding, active coagulopathy, severe thrombocytopenia, or high-risk varices not amenable to intervention) decision to use is individualized.[184]

Wolff-Parkinson-White (WPW) syndrome

  • In patients with AF and WPW syndrome, rapid conduction of atrial electrical activity to the ventricles via an accessory pathway (preexcitation) may cause fast ventricular rates, with an increased risk of ventricular fibrillation and sudden death.[1][2]

    • Hemodynamically stable patients with preexcited AF may be treated with pharmacologic cardioversion with ibutilide or procainamide (if available). AV nodal blocking agents (e.g., verapamil, diltiazem, amiodarone, digoxin, adenosine, beta-blockers) are contraindicated in preexcited AF.

    • Hemodynamically unstable patients with preexcited AF should be treated with DC cardioversion.

  • See Wolff-Parkinson-White syndrome.

Hypertrophic cardiomyopathy (HCM)

  • Patients with HCM and AF have an increased risk of stroke and thromboembolism and should receive long-term anticoagulation regardless of CHA₂DS₂-VASc score.[1]​ The US guidelines on HCM recommend DOACs as the preferred option in patients with HCM and AF, and warfarin as the second-line alternative.[185]

  • A rhythm control strategy may be preferred in patients with HCM; choice of rhythm control is individualized and cardioversion or antiarrhythmic drugs may be used. Catheter ablation may also be considered, but is less effective in those with HCM compared with those without. Surgical ablation may also be considered as a potential rhythm management option in patients undergoing surgical myectomy.[185]

Pulmonary disease

  • In patients with AF and COPD, cardioselective beta-blockers may be used for rate control (other rate control agents may also be used, but beta-blockers do not need to be avoided). In patients with reactive airway disease, such as asthma, beta-blockers should be avoided.[1]

  • The US guidelines advise that in those with AF and pulmonary hypertension with pulmonary vascular disease, a rhythm-control strategy may improve functional status and potentially prolong survival.[1]

Chronic coronary disease (CCD)

  • For maintenance of sinus rhythm in patients with AF and CAD, the ESC guidelines recommend amiodarone and dronedarone, with sotalol as an alternative.[2]​ Class Ic agents (e.g., flecainide, propafenone) have a higher mortality in patients with CAD and are contraindicated in patients with CAD and cardiac dysfunction.[1]

Sleep-disordered breathing (SDB)

  • Patients with AF should have their risk factors for SDB considered, and screening, diagnosis, and management of SDB provided where indicated.[43]​ Although polysomnography is the gold standard for diagnosing SDB, home sleep apnea testing shows promise in diagnosing OSA in most patients with AF.[43]

  • Treatment of obstructive sleep apnea with continuous positive airway pressure may reduce AF burden and risk of recurrence; however, more evidence is needed to confirm this.[1][2]

Cancer

  • Patients with AF and cancer should be managed by a multidisciplinary team. Treatments for AF may be less effective if it is caused directly by the cancer therapy.[59]

  • Drug-drug interactions can occur between cancer therapies and AF therapies (antiarrhythmics, rate control agents, and anticoagulants).

    • When using antiarrhythmic agents, risk of QT interval prolongation should be considered as patients with cancer are already at an increased risk.[1]

    • Beta-blockers are preferred for rate control in patients with cancer and AF, particularly if the cancer therapies have potential cardiovascular risk; diltiazem and verapamil should be avoided due to associations with negative inotropic effects and drug-drug interactions.[59]

  • When choosing an anticoagulant in patients with cancer and AF, the cancer type, status, and prognosis, as well as the patient’s bleeding/thromboembolic risk should all be considered. DOACs are recommended as first-line in patients without a high bleeding risk, severe renal dysfunction, or significant drug-drug interactions. LMWH can be considered in patients who have active cancer and AF if DOACs are not suitable.[59]

Adult congenital heart disease (ACHD)

  • The US guidelines advise that adults with moderate or complex CHD may tolerate AF poorly and rhythm control is generally preferred over rate control. Choice of antiarrhythmic must be individualized.[1]​ Ablation may be an option in patients with AF and simple CHD.

  • Electrophysiologic procedures should be performed by those with expertize in ACHD and in collaboration with an ACHD cardiologist.[1]

  • Some patients with moderate or complex CHD (e.g., Fontan circulation, cyanosis) are at higher risk for thromboembolic events and anticoagulation may be indicated regardless of usual AF risk score.[1][2]

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