Atrial Fibrillation (AF)

How to Cite This Chapter: Acosta Velez JG, Amit G, Hernández Ruiz EA, Trusz-Gluza M, Leśniak W. Atrial Fibrillation (AF). McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed October 04, 2022.
Last Updated: February 20, 2022
Last Reviewed: February 20, 2022
Chapter Information

Definition, Etiology, PathogenesisTop

Atrial fibrillation (AF) is the most common supraventricular tachyarrhythmia (prevalence in adults, 1%-2%). It is characterized by fast (350-700 beats/min) and irregular atrial activation, which results in the loss of hemodynamic effectiveness of atrial contractions and a concomitant irregular ventricular rhythm. Ventricular rate depends on the electrophysiologic features of the atrioventricular (AV) node, autonomic function, and effects of drugs; it may be normal (resting heart rates, 60-100 beats/min), fast (tachyarrhythmia), or slow (bradyarrhythmia).

AF classification: fig. 3.4-1. In patients with episodes of AF that may be classified as different categories, consider the predominant type of AF.

Risk factors: The main risk factors for developing AF include hypertension, overweight, untreated sleep apnea, and alcohol intake. A variety of other cardiac and extracardiac conditions can also increase the risk of developing AF, including valvular heart disease (primarily mitral valve disease), heart failure irrespective of its cause, cardiomyopathies, diabetes (and other cardiac risk factors), thyrotoxicosis, pulmonary diseases, and chronic kidney disease. However, AF can also be observed in individuals without structural heart disease.

Clinical Features and Natural HistoryTop

Symptoms may include palpitations, weakness, poor exercise tolerance, syncope, or dizziness. Patients may also be asymptomatic.

The European Heart Rhythm Association (EHRA) score used for the classification of AF-related symptoms:

1) EHRA class I: Asymptomatic.

2) EHRA class II: Mild symptoms not affecting normal daily activity.

3) EHRA class III: Severe symptoms affecting daily activity.

4) EHRA class IV: Disabling symptoms.

Signs include grossly irregular heart rate, irregular pulse, and pulse deficit (not every ventricular contraction, especially if occurring shortly after the previous one, may be sufficiently strong to transmit an arterial pulse wave through the peripheral artery).

A detailed history and analysis of the available medical records are important. Paroxysmal AF is self-limiting and resolves within 7 days. Persistent AF does not resolve spontaneously, lasts >7 days, or both. Long-standing persistent AF refers to uninterrupted AF lasting >1 year. Permanent AF refers to situations where efforts to restore sinus rhythm have either failed or been forgone. These categories are not mutually exclusive and it is common for patients with one type of AF to exhibit overlapping features of another type.


Diagnostic Tests

1. Electrocardiography (ECG): A grossly irregular rhythm, P waves absent or not clearly identifiable, fibrillatory waves (fig. 3.4-2).

2. Holter ECG monitoring: Long-term monitoring (24 hours to 14 days) may be useful in the identification of episodes of paroxysmal AF.

3. Echocardiography: This is useful in the identification of structural heart disease and assessing left ventricular function and left atrium size. The larger the left atrium, the less likely it is to achieve a stable sinus rhythm.

4. New technologies can also aid in the diagnosis of AF (watches with optical sensors, mobile cardiac monitoring devices).

Differential Diagnosis

Supraventricular tachycardia: see fig. 3.4-2.


Classification of antiarrhythmic drugs: see table 3.4-1.

Antiarrhythmic agents: see table 3.4-2.

Acute Management

The management of paroxysmal AF depends on episode duration, symptoms, and hemodynamic status:

1) AF <48 hours:

a) In patients with symptomatic AF lasting <48 hours, an acute rhythm control strategy should be favored in order to avoid left atrial remodeling due to persistent AF.

b) If a rhythm control strategy is chosen, cardioversion may be achieved either pharmacologically or electrically. In patients with no structural heart disease and no contraindications, consider oral flecainide 300 mg plus an oral dose of an AV nodal blocker, like a beta-blocker, diltiazem, or verapamil; or propafenone 600 mg as a single dose (no need to add an AV nodal blocker). In all other cases consider IV amiodarone but remember that conversion to sinus rhythm usually takes longer (8-12 hours).Evidence 1Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to heterogeneity of the studied populations. Cordina J, Mead G. Pharmacologic cardioversion for atrial fibrillation and flutter. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD003713. Review. Update in: Cochrane Database Syst Rev. 2017 Nov 15;11:CD003713. PubMed PMID: 15846675. Mead GE, Elder AT, Flapan AD, Kelman A. Electrical cardioversion for atrial fibrillation and flutter. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD002903. Review. Update in: Cochrane Database Syst Rev. 2017 Nov 15;11:CD002903. PubMed PMID: 16034878. In patients with significant hemodynamic disturbances or severe chest pain caused by rapid AF, perform urgent electrical cardioversion.

c) Elderly patients with comorbidities and mild symptoms may benefit from a rate control strategy. For rate control, consider beta-blockers, diltiazem, or verapamil. Digoxin is usually not considered in monotherapy but combined with any of the other medications.

2) AF >48 hours:

a) When considering either electrical or pharmacologic cardioversion of AF, patients should receive adequate anticoagulation treatment to prevent thromboembolic complications. The risk of thromboembolism is the same whether conversion is achieved electrically or pharmacologically (see Complications, below).

b) In case of an AF episode lasting >48 hours, as an alternative to adequate anticoagulation (duration ≥3 weeks), transesophageal echocardiography may be performed to exclude a left atrial appendage thrombus, which would be a contraindication to cardioversion.

Long-Term Management

General Considerations

1. Paroxysmal AF:

1) Eliminate risk factors that may have triggered the arrhythmia, such as alcohol, sleep apnea, or uncontrolled hypertension.

2) If episodes are infrequent and short-lasting, follow up with no antiarrhythmics or consider rate-control medications. If episodes are more frequent but still <1 episode per week, patients with no structural heart disease may be treated with the “pill-in-the-pocket” approach: a single dose of propafenone 600 mg (450 mg in patients <70 kg) or flecainide 300 mg plus an AV nodal blocker (eg, metoprolol, bisoprolol, diltiazem, or verapamil),Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of data and indirectness of the population and outcomes measured. Saborido CM, Hockenhull J, Bagust A, Boland A, Dickson R, Todd D. Systematic review and cost-effectiveness evaluation of 'pill-in-the-pocket' strategy for paroxysmal atrial fibrillation compared to episodic in-hospital treatment or continuous antiarrhythmic drug therapy. Health Technol Assess. 2010 Jun;14(31):iii-iv, 1-75. doi: 10.3310/hta14310. Review. PubMed PMID: 20569652. provided the efficacy and safety of the drug have been previously confirmed in a hospital setting. There is no need to add a nodal blocker on top of propafenone.

3) Patients with frequent episodes should receive daily medications according to their profile. In young patients with no heart disease, flecainide or propafenone is preferred for a rhythm control strategy. In patients with coronary artery disease, amiodarone or dronedarone are options and sotalol may be considered. In patients with left ventricular dysfunction or contraindications for other antiarrhythmics, amiodarone should be considered.

2. In patients with persistent AF, choose a management strategy:

1) Rhythm-control strategy: Restore sinus rhythm either electrically or pharmacologically and attempt to maintain sinus rhythm with antiarrhythmic agents, ablation, or both.

2) Rate-control strategy: Do not attempt to restore sinus rhythm but ensure optimal control of the ventricular rate during AF using an exercise test or Holter monitor to maintain an average 24-hour heart rate of <110 beats/min and no symptoms. Rate control can be achieved with one or more of beta-blockers, diltiazem, verapamil, and digoxin, or with ablation of the AV node (and pacemaker implantation).

3) Asymptomatic patients with persistent AF: Recent studies (EAST-AFNET 4 trial) have revealed that rhythm control is associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with recently (within 1 year) diagnosed AF.Evidence 1Kirchhof P, Camm AJ, Goette A, et al; EAST-AFNET 4 Trial Investigators. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl J Med. 2020 Oct 1;383(14):1305-1316. doi: 10.1056/NEJMoa2019422. Epub 2020 Aug 29. PMID: 32865375. If the left atrium is severely dilated, rhythm control is less likely to succeed.

3. Permanent AF: The goal of treatment is ventricular rate control. The target is to maintain a heart rate <110 beats/min. If left ventricular dysfunction is present, the target for rate control should be more stringent.


Drug selection: table 3.4-1.

Invasive Treatment

1. Catheter ablation: Most AF episodes are thought to originate in the pulmonary veins. The current method for AF ablation focuses on the isolation of the pulmonary veins using radiofrequency or cryoablation. It is recommended in patients with symptomatic paroxysmal AF in whom treatment with ≥1 class I or class III antiarrhythmic agents has been unsuccessful and in patients who prefer to avoid medication. Catheter ablation has shown superior efficacy in maintaining sinus rhythm when compared with antiarrhythmic drugs.Evidence 3Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to heterogeneity of the studied populations. Cheng X, Li X, He Y, et al. Catheter ablation versus anti-arrhythmic drug therapy for the management of a trial fibrillation: a meta-analysis. J Interv Card Electrophysiol. 2014 Dec;41(3):267-72. doi: 10.1007/s10840-014-9945-4. Epub 2014 Dec 4. Review. PubMed PMID: 25465209.

2. Surgical ablation: An option in patients undergoing cardiac surgery, commonly with mitral valve disease, who have persistent AF.

3. Catheter ablation of the AV junction with pacemaker implantation: This may be considered as a last resource in patients with paroxysmal or permanent AF who remain symptomatic despite other treatment strategies. This is a final rate-control strategy.


The most significant complications of AF include thromboembolic events, mainly ischemic stroke. They are associated with the formation of a thrombus in the left atrium (most commonly in the left atrial appendage).

1. Long-term prevention of thromboembolism: In every patient with AF assess the risk of thromboembolic complications using the CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, aortic plaque], age 65-74 years, sex category [female]). Long-term anticoagulation is recommended in patients with a CHA2DS2-VASc score ≥1 except if the single risk factor is female sex (table 3.4-2) or if there is a high risk of intracranial bleeding (table 3.4-3). Recommended prophylaxis: fig. 3.4-3.

2. Prophylactic antithrombotic treatment in patients treated with cardioversion:

1) Patients with AF lasting ≥48 hours or of unknown duration: Before attempting to restore sinus rhythm (electrical or pharmacologic cardioversion), use a vitamin K antagonist (VKA) for ≥3 weeks before cardioversion and 4 weeks after the procedure (maintain an international normalized ratio [INR] of 2.0 to 3.0; note that in some patients longer anticoagulation may be indicated; consider risk factors for thromboembolic complications). Dabigatran, rivaroxaban, or apixaban may be used instead of VKAs. If a left atrial appendage thrombus has been excluded with transesophageal echocardiography, it would be safe to proceed with cardioversion before completing 3 weeks of anticoagulation. In any case, 4 weeks of anticoagulation are needed after cardioversion.

If urgent cardioversion is required in patients with AF lasting ≥48 hours or of unknown duration, exclude the presence of a thrombus using transesophageal echocardiography, if available. Before cardioversion administer IV unfractionated heparin (or subcutaneous low-molecular-weight heparin). After cardioversion use an oral anticoagulant for ≥4 weeks, depending on the risk factors for thromboembolism (CHA2DS2-VASc score; see above).

2) In patients with AF of documented duration <48 hours, pharmacologic or electrical cardioversion may be performed immediately after the administration of heparin. Oral anticoagulation should be started immediately for ≥4 weeks, depending on the risk factors for thromboembolism (CHA2DS2-VASc score; see above).

3. Prevention of thromboembolism in patients with AF after percutaneous coronary intervention (PCI): This field is rapidly changing and no uniform strong recommendations are relevant in all patients. More recently, dual therapy with modified direct oral anticoagulant (DOAC) doses (in the range of 25%-75% of the full anticoagulation dose) plus clopidogrel have been reported to be noninferior to triple therapy with a VKA with respect to the risk of thromboembolic events, with fewer bleeding events than in the case of triple therapy. In patients after PCI in the context of an acute coronary syndrome, the benefit of triple therapy seems limited to the first 30 days, and then aspirin can be safely discontinued while maintaining clopidrogel plus a DOAC. Prasugrel and ticagrelor should be avoided in conjunction with DOACs.

Tables and FiguresTop

Figure 3.4-1. Classification of atrial fibrillation. Based on the European Society of Cardiology guidelines.

Figure 3.4-2. Atrial fibrillation and atrial flutter. A, polymorphic F waves replacing P waves during atrial fibrillation. B, monomorphic biphasic F waves replacing P waves during atrial flutter.

Table 3.4-1. Selection of antiarrhythmic treatment in patients with AF requiring long-term rhythm control to mitigate symptoms

Concomitant cardiac disease

Treatment methoda

No significant structural heart disease

1) Pharmacotherapy:

– Recommended agents: dronedarone, flecainide, propafenone

– Agents that may be considered: sotalolb

2) Percutaneous ablationc

CAD, significant valvular heart disease, HFpEF

1) Pharmacotherapy:

– Recommended agents: amiodarone, dronedarone

– Agents that may be considered: sotalolb

2) Percutaneous ablationc


1) Pharmacotherapy: amiodarone

2) Percutaneous ablationc,d

a The choice between pharmacotherapy and percutaneous ablation depends on the type of treatment (first-line vs second-line), type of AF (paroxysmal vs persistent), and the patient’s decision.

b Patients treated with sotalol should be monitored for proarrhythmia (assess for QT prolongation with periodical ECG; our pattern is baseline 1 week after starting treatment and every 6 months afterwards).

c Pulmonary vein isolation with radiofrequency or cryoballoon ablation. 

d Ablation as first-line treatment is usually reserved for patients with HF secondary to tachycardia-induced cardiomyopathy.

Adapted from the 2020 European Society of Cardiology (ESC) guidelines.

AF, atrial fibrillation; CAD, coronary artery disease; ECG, electrocardiography; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction.

Table 3.4-2. Assessment of the risk of stroke in patients with atrial fibrillation not associated with valvular heart disease

Risk factor




Congestive heart failure or left ventricular dysfunctiona






Age ≥75 years



Diabetes mellitus



History of stroke, transient ischemic attack, or thromboembolisma



Vascular diseaseb


Age 65-74 years


Female sex


a Left ventricular dysfunction and other thromboembolic event are included only in the CHA2DS2-VASc score.

b History of myocardial infarction, peripheral artery disease, or atherosclerotic plaque in aorta.

Table 3.4-3. HAS-BLED bleedinga risk score in patients with atrial fibrillation

Clinical characteristic




Abnormal renalc and liver functiond

1 or 2





Labile INRsf


Elderly (age >65 years)


Drugsg or alcohol

1 or 2


Score ≥3 points: High risk

a Severe bleeding, that is, intracranial, requiring hospitalization, associated with >2 g/dL decrease in hemoglobin levels, or requiring transfusion.

b Systolic blood pressure >160 mm Hg.

c Chronic dialysis or renal transplant or serum creatinine >200 micromol/L.

d Chronic liver disease (eg, cirrhosis) or biochemical evidence of significant liver derangement (eg, bilirubin >2 × ULN + ALT/AST/alkaline phosphatase >3 × ULN).

e History of bleeding, predisposition to bleeding, or both (eg, bleeding diathesis, anemia).

f Unstable/high INR or INR frequently (eg, >40% of test results) outside the therapeutic range.

g Concomitant treatment with antiplatelet agents or NSAIDs.

ALT, alanine aminotransferase; AST, aspartate aminotransferase; INR, international normalized ratio; NSAID, nonsteroidal anti-inflammatory drug; ULN, upper limit of normal.

Figure 3.4-3. Algorithm for prevention of thromboembolism in patients with atrial fibrillation. Adapted from the 2020 European Society of Cardiology guidelines.

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