Atrial fibrillation
- NOTOC**
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Anahita Deylamsalehi, M.D.[2]; Laith Adnan Allaham, M.D.[3]; Sem A.O.F. Rikken, M.D.[4]; Nehal Eid, M.D.[5] Synonyms and keywords: AF; afib; lone fibrillation
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Atrial Fibrillation Microchapters | |
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Special Groups | |
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Diagnosis | |
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Treatment | |
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Cardioversion | |
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Anticoagulation | |
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Surgery | |
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Case Studies | |
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Atrial fibrillation On the Web | |
Overview
Atrial fibrillation (AF or AFib) is a supraventricular tachyarrhythmia characterized by uncoordinated atrial electrical activation with consequent deterioration of atrial mechanical function.[1] On the electrocardiogram (ECG), AF is characterized by the replacement of consistent P waves by rapid oscillations or fibrillatory waves that vary in amplitude, shape, and timing, associated with an irregular, frequently rapid ventricular response when atrioventricular (AV) conduction is intact.[2]
AF is the most common sustained cardiac arrhythmia, affecting an estimated 59.0 million individuals globally as of 2023.[3] In the United States, AF affects up to 1 in 3 people in their lifetime.[4] AF is associated with significantly increased risks of stroke, heart failure, myocardial infarction, dementia, chronic kidney disease, and mortality.[4]
Historical Perspective
The clinical recognition of AF dates to the description of a "peculiar pulse irregularity" in the 19th century.[5] Key milestones include:
1906 — Einthoven published the first human ECG documenting AF[6]
1909 — Lewis, Rothberger, and Winterberg confirmed the relationship between ECG-documented AF and the irregularly irregular pulse[6]
1998 — Haïssaguerre et al. demonstrated that ectopic firing from pulmonary vein myocardial sleeves triggers AF[7]
2000s onward — Development of direct oral anticoagulants (DOACs), advanced catheter ablation, and left atrial appendage occlusion devices[8]
Classification
By Temporal Pattern
| AF Type | Definition |
|---|---|
| Paroxysmal AF | Episodes lasting ≤7 days that terminate spontaneously or with intervention |
| Persistent AF | Continuous episodes lasting >7 days and/or requiring cardioversion |
| Long-standing persistent AF | Continuous AF of >12 months' duration |
| Permanent AF | AF accepted by patient and clinician; no further rhythm control pursued |
By Stage of Disease
| Stage | Description |
|---|---|
| Stage 1: At risk | AF risk factors present but no structural or electrical findings |
| Stage 2: Pre-AF | Structural or electrical atrial pathology without documented AF |
| Stage 3: AF | Documented paroxysmal, persistent, or long-standing persistent AF |
| Stage 4: Permanent AF | AF accepted; no further rhythm control attempted |
Valvular vs. Nonvalvular AF
Patients with moderate-to-severe mitral stenosis or a mechanical heart valve are classified as having valvular AF and require warfarin rather than DOACs.[7]
Pathophysiology
Initiation
Ectopic firing from pulmonary vein myocardial sleeves is the primary trigger for AF. Pulmonary vein features that increase vulnerability include a higher resting membrane potential, stretch-activated channels, and cross-myofiber orientation patterns.[7]
Electrical Remodeling
Electrical remodeling includes shortened action potentials due to decreased L-type Ca2+ current and increased IK1. Downregulation of connexin decreases gap junctions, promoting heterogeneous conduction and reentry. Calcium mishandling promotes delayed afterdepolarizations — the most likely trigger for AF initiation.[7]
Structural Remodeling
Structural remodeling includes interstitial fibrosis, myofibroblast activity, collagen deposition, fibrofatty infiltration, and inflammatory infiltrates.[7] Hypertension activates the renin-angiotensin-aldosterone system, inducing atrial fibrosis.[4] Obesity increases oxidative stress and abnormal Ca2+ cycling.[4]
Atrial Cardiomyopathy
Prothrombotic changes in the left atrium include increased endocardial expression of von Willebrand factor, increasing risk of thrombus formation and stroke.[7]
The "AF Begets AF" Paradigm
AF promotes further electrical and structural remodeling, creating a self-perpetuating cycle.[7][9]
Causes
Modifiable Risk Factors
Hypertension — highest population-attributable risk for AF[7]
Obesity — increases oxidative stress, inflammation, and abnormal calcium cycling[4]
Diabetes mellitus — worse glucose control correlates with higher AF probability[7]
Obstructive sleep apnea — alters atrial repolarization and promotes AF[4]
Alcohol use — dose-dependent increase in AF risk[4]
Smoking — cessation associated with decreased AF risk[7]
Physical inactivity — sedentary lifestyle increases risk; extreme endurance training may also increase risk[7]
Non-Modifiable Risk Factors
Older age — HR per 5-year increase: 1.66 (95% CI, 1.59–1.74)[4]
Male sex — higher prevalence globally[4]
Genetic factors — family history and polygenic risk scores modify lifetime risk[4]
Taller height and greater lean body mass[10]
Associated Conditions
Coronary artery disease, heart failure, valvular heart disease, hyperthyroidism, pericarditis, post-cardiac surgery, congenital heart disease, infiltrative diseases (amyloidosis, hemochromatosis, sarcoidosis)[1][10]
Differentiating Atrial Fibrillation from Other Diseases
| Arrhythmia | Rhythm | Atrial Activity | Key Features |
|---|---|---|---|
| Atrial fibrillation | Irregularly irregular | No discrete P waves; fibrillatory baseline | Absence of organized atrial activity |
| Atrial flutter | Regular or regularly irregular | Sawtooth F waves (leads II, III, aVF, V1) | Atrial rate 240–320 bpm; 2:1 block → ventricular rate ~150 bpm[2] |
| Multifocal atrial tachycardia | Irregularly irregular | ≥3 distinct P-wave morphologies | Associated with COPD; discrete P waves present |
| AVNRT | Regular | P waves buried in QRS | Abrupt onset/termination; responds to adenosine |
| AVRT | Regular | Retrograde P waves | Associated with WPW |
| Sinus tachycardia | Regular | Normal P-wave morphology | Gradual onset/offset |
AF with pre-excitation (WPW): wide-complex irregular tachycardia; AV nodal blocking agents (verapamil, digoxin, adenosine) are contraindicated[7]
Epidemiology and Demographics
Prevalence: 5.2 million in the U.S. (2010), projected 12.1 million by 2030; 59.0 million globally (2023)[7][3]
Age: Prevalence 0.2% in adults 55 years to ~10% in those ≥85 years[11]
Sex: More prevalent in men; lifetime risk 26% (men) vs 23% (women) in European descent[1]
Race: Lifetime risk ~30–40% in White, ~20% in African American, ~15% in Chinese individuals[7]
Mortality: 1.5- to 2-fold increased risk of death; 48.8% mortality at 5 years in Medicare beneficiaries[7]
Risk Factors
The 2023 ACC/AHA/ACCP/HRS Guideline emphasizes comprehensive risk factor management as a pillar of AF care.[7] The C2HEST score predicts incident AF risk (C statistic 0.749).[7]
Screening
| Guideline | Recommendation |
|---|---|
| 2023 ACC/AHA/ACCP/HRS | No recommendation for general population screening[7] |
| 2024 ESC/EACTS | Opportunistic screening ≥65 years; systematic screening ≥75 years (Class IIa)[12] |
| USPSTF (2022) | Insufficient evidence (I statement)[13] |
Wearable devices can detect AF with high sensitivity (94%) and specificity (93–96%); ECG confirmation is required.[14]
Natural History, Complications and Prognosis
AF tends to progress from paroxysmal to persistent to permanent forms.[7] In a Danish cohort, lifetime risk of AF increased from 24.2% (2000–2010) to 30.9% (2011–2022).[15]
In a meta-analysis of 104 cohort studies (9,686,513 participants), AF was associated with:[16]
| Outcome | Relative Risk (95% CI) |
|---|---|
| All-cause mortality | 1.46 (1.39–1.54) |
| Cardiovascular mortality | 2.03 (1.79–2.30) |
| Stroke | 2.42 (2.17–2.71) |
| Heart failure | 4.99 (3.04–8.22) |
| Sudden cardiac death | 1.88 (1.36–2.60) |
| Chronic kidney disease | 1.64 (1.41–1.91) |
After AF diagnosis, the most frequent complication was heart failure (lifetime risk 42.1%), followed by stroke (19.9%) and myocardial infarction (9.8%).[15]
Special Groups
Occurs in 20–50% of cardiac surgery patients and 5–10% after noncardiac thoracic surgery.[1]
AV nodal blocking agents are contraindicated. Treatment: procainamide, ibutilide, or urgent electrical cardioversion.[7]
AF occurs in ~25% of symptomatic hypertrophic cardiomyopathy (HCM) patients. Anticoagulation is recommended for all HCM patients with AF regardless of CHA2DS2-VASc score, with DOACs as first-line.[7][17]
AF occurs in 10–15% of patients with hyperthyroidism, more commonly in those >60 years. Treatment is directed primarily toward restoring a euthyroid state, which is usually associated with spontaneous reversion to sinus rhythm. Beta-blockers (preferably nonselective, e.g., propranolol) are recommended for rate control (Class I). Nondihydropyridine calcium channel blockers (diltiazem, verapamil) are second-line. Anticoagulation is recommended in patients with elevated stroke risk until thyroid function normalizes and sinus rhythm is maintained (Class I, LOE B-NR). Cardioversion is generally deferred until the euthyroid state is achieved.[7][1]
AF is common in patients with COPD and other pulmonary diseases. Treatment of the underlying lung disease and correction of hypoxia and acidosis are priorities. Theophylline and beta-agonists may precipitate AF. Nondihydropyridine calcium channel blockers are preferred for rate control; nonselective beta-blockers should be avoided in bronchospastic disease.[1]
New-onset AF in pregnancy usually indicates underlying heart disease. Key management principles per the 2023 ACC/AHA/ACCP/HRS Guideline and 2023 HRS Expert Consensus Statement:[7][18]
Cardioversion: Synchronized electrical cardioversion is safe for both mother and fetus (Class I)
Rate control: Beta-blockers with long record of safety (propranolol, metoprolol) and digoxin are first-line; atenolol is generally avoided due to intrauterine growth retardation concerns
Rhythm control: Flecainide and sotalol are reasonable for maintenance of sinus rhythm in structurally normal hearts (Class IIa). Amiodarone is generally avoided due to fetal toxicities (goiter, neurodevelopmental abnormalities, bradycardia)
Anticoagulation: DOACs are contraindicated in pregnancy. Warfarin may be used if dose ≤5 mg/day; otherwise low-molecular-weight heparin is used in the first trimester. Anticoagulation decisions require shared decision-making regarding risks to mother and fetus
In patients with AF requiring percutaneous coronary intervention, a DOAC-based regimen is preferred over warfarin. Triple therapy (OAC + dual antiplatelet) duration should be minimized. Dual therapy (OAC + single antiplatelet, usually clopidogrel) is recommended as early as possible to reduce bleeding risk.[7][10]
Diagnosis
Clinical Presentation
Typical symptoms include palpitations, dyspnea, chest pain, presyncope, exertional intolerance, and fatigue. Approximately 10–40% of patients are asymptomatic.[4]
Electrocardiographic Diagnosis
Diagnosis requires an ECG demonstrating: (1) "absolutely" irregular R-R intervals; (2) no distinct P waves; (3) atrial cycle length usually 200 ms. An episode lasting ≥30 seconds or documented on a 12-lead ECG is considered diagnostic.[19]
Initial Evaluation
12-lead ECG — confirm diagnosis, assess for WPW, LVH, QT prolongation
Transthoracic echocardiography — cardiac structure, chamber size, ventricular function, valvular pathology
Laboratory testing — complete blood count, basic metabolic panel, thyroid function tests, renal and liver function
Screening for sleep apnea when history is suggestive[7][4]
Stroke Risk Assessment
The CHA2DS2-VASc score is the most validated tool for stroke risk stratification:[7]
| Risk Factor | Points |
|---|---|
| Congestive heart failure / LV dysfunction | 1 |
| Hypertension | 1 |
| Age ≥75 years | 2 |
| Diabetes mellitus | 1 |
| Stroke / TIA / thromboembolism | 2 |
| Vascular disease (MI, PAD, aortic plaque) | 1 |
| Age 65–74 years | 1 |
| Sex category (female) | 1 |
Treatment
Initial Management
Hemodynamically unstable: Urgent synchronized electrical cardioversion[7]
Hemodynamically stable: Rate control and anticoagulation assessment; rhythm control based on symptom burden, AF duration, LVEF, and patient preference[14]
Medical Therapy
Anticoagulation
DOACs are recommended as first-line over warfarin for nonvalvular AF. In meta-analysis, DOACs vs warfarin showed: stroke RR 0.81 (95% CI, 0.73–0.91), mortality RR 0.90 (0.85–0.95), intracranial hemorrhage RR 0.48 (0.39–0.59).[7]
| CHA2DS2-VASc Score | Recommendation |
|---|---|
| 0 (males) or 1 (females, sex point only) | No anticoagulation |
| 1 (males) or 2 (females) | Anticoagulation may be considered (Class IIa) |
| ≥2 (males) or ≥3 (females) | Anticoagulation recommended (Class I) |
DOAC dosing by renal function:[7]
| DOAC | CrCl >50 mL/min | CrCl 31–50 | CrCl 15–30 | CrCl 15 or dialysis |
|---|---|---|---|---|
| Apixaban | 5 mg BID (or 2.5 mg BID) | 5 or 2.5 mg BID | 5 or 2.5 mg BID | 5 or 2.5 mg BID |
| Dabigatran | 150 mg BID | 150 mg BID | 75 mg BID | Contraindicated |
| Rivaroxaban | 20 mg daily | 15 mg daily | 15 mg daily | 15 mg daily |
| Edoxaban | 60 mg daily (contraindicated if CrCl >95) | 30 mg daily | 30 mg daily | Contraindicated |
Apixaban dose reduction to 2.5 mg BID if ≥2 of: age ≥80 years, weight ≤60 kg, serum creatinine ≥1.5 mg/dL
Warfarin remains indicated for moderate-to-severe mitral stenosis or mechanical heart valves. Aspirin alone does not provide adequate stroke protection and is not recommended.[20]
Rate Control
Beta-blockers (metoprolol, atenolol, carvedilol)
Nondihydropyridine calcium channel blockers (diltiazem, verapamil) — contraindicated in moderate-to-severe LV systolic dysfunction
Second-line:
Digoxin — adjunct therapy, especially in HFrEF
Amiodarone (IV) — critically ill patients or decompensated HF
Rate targets: Resting HR 110 bpm is reasonable initially (RACE II); stricter target 80 bpm for patients with LV dysfunction or tachycardia-mediated cardiomyopathy.[7]
Rhythm Control
Early rhythm control: The EAST-AFNET 4 trial demonstrated that early rhythm control (within 12 months of diagnosis) reduced cardiovascular death (HR 0.72; 95% CI, 0.52–0.98) and stroke (HR 0.65; 0.44–0.97) compared with usual care.[21] The benefit was mediated by the presence of sinus rhythm at 12 months, which explained 81% of the treatment effect.[22]
References:
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 January CT, Wann LS, Alpert JS, et al. (2014). "2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation". Circulation. 130 (23): e199–267. doi:10.1161/CIR.0000000000000041. PMID 24685669.
- ↑ 2.0 2.1 Fuster V, Rydén LE, Cannom DS, et al. (2011). "2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation". J Am Coll Cardiol. 57 (11): e101–98. doi:10.1016/j.jacc.2010.09.013. PMID 21392637.
- ↑ 3.0 3.1 Global Burden of Cardiovascular Diseases and Risks 2023 Collaborators (2025). "Global, regional, and national burden of cardiovascular diseases and risk factors in 204 countries and territories, 1990-2023". J Am Coll Cardiol. 86 (22): 2167–2243. doi:10.1016/j.jacc.2025.08.015. PMID 40990886 Check
|pmid=value (help). Vancouver style error: initials (help) - ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 Ko D, Chung MK, Evans PT, Benjamin EJ, Helm RH (2025). "Atrial fibrillation: a review". JAMA. 333 (4): 329–342. doi:10.1001/jama.2024.22451. PMID 39841539 Check
|pmid=value (help). - ↑ Potpara TS, Lip GY (2015). "A brief history of 'lone' atrial fibrillation". Curr Pharm Des. 21 (5): 679–96. doi:10.2174/1381612820666140929100209. PMID 25269559.
- ↑ 6.0 6.1 Prystowsky EN (2008). "The history of atrial fibrillation: the last 100 years". J Cardiovasc Electrophysiol. 19 (6): 575–82. doi:10.1111/j.1540-8167.2008.01184.x. PMID 18462324.
- ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 7.14 7.15 7.16 7.17 7.18 7.19 7.20 7.21 7.22 7.23 7.24 7.25 7.26 7.27 7.28 7.29 7.30 7.31 7.32 Joglar JA, Chung MK, Armbruster AL, et al. (2024). "2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation". J Am Coll Cardiol. 83 (1): 109–279. doi:10.1016/j.jacc.2023.08.017. PMID 38033089 Check
|pmid=value (help). - ↑ Millenaar D, Fehlmann T, Scholz S, et al. (2020). "Research in atrial fibrillation: a scientometric analysis". JACC Clin Electrophysiol. 6 (8): 1008–1018. doi:10.1016/j.jacep.2020.05.010. PMID 32819514 Check
|pmid=value (help). - ↑ Nattel S, Li D, Yue L (2000). "Basic mechanisms of atrial fibrillation". Annu Rev Physiol. 62: 51–77. doi:10.1146/annurev.physiol.62.1.51. PMID 10845084.
- ↑ 10.0 10.1 10.2 Chung MK, Refaat M, Shen WK, et al. (2020). "Atrial fibrillation: JACC Council perspectives". J Am Coll Cardiol. 75 (14): 1689–1713. doi:10.1016/j.jacc.2020.02.025. PMID 32273035 Check
|pmid=value (help). - ↑ Burns RB, Zimetbaum P, Lubitz SA, Smetana GW (2019). "Should this patient be screened for atrial fibrillation?". Ann Intern Med. 171 (11): 828–836. doi:10.7326/M19-1126. PMID 31791056.
- ↑ Rienstra M, Tzeis S, Bunting KV, et al. (2024). "Spotlight on the 2024 ESC/EACTS management of atrial fibrillation guidelines". Europace. 26 (12): euae298. doi:10.1093/europace/euae298. PMID 39716733 Check
|pmid=value (help). - ↑ US Preventive Services Task F (2022). "Screening for atrial fibrillation: USPSTF recommendation statement". JAMA. 327 (4): 360–367. doi:10.1001/jama.2021.23732. PMID 35040888 Check
|pmid=value (help). Vancouver style error: initials (help) - ↑ 14.0 14.1 Holder S, Amin P (2024). "Atrial fibrillation: common questions and answers". Am Fam Physician. 109 (5): 398–404. PMID 38804754 Check
|pmid=value (help). - ↑ 15.0 15.1 Vinter N, Cordsen P, Johnsen SP, et al. (2024). "Temporal trends in lifetime risks of atrial fibrillation and its complications". BMJ. 385: e077209. doi:10.1136/bmj-2023-077209. PMID 38631726 Check
|pmid=value (help). - ↑ Odutayo A, Wong CX, Hsiao AJ, et al. (2016). "Atrial fibrillation and risks of cardiovascular disease, renal disease, and death". BMJ. 354: i4482. doi:10.1136/bmj.i4482. PMID 27599725.
- ↑ Rowin EJ, Link MS, Maron MS, Maron BJ (2023). "Evolving contemporary management of atrial fibrillation in hypertrophic cardiomyopathy". Circulation. 148 (22): 1797–1811. doi:10.1161/CIRCULATIONAHA.123.065037. PMID 38011245 Check
|pmid=value (help). - ↑ Joglar JA, Kapa S, Saarel EV, et al. (2023). "2023 HRS expert consensus statement on the management of arrhythmias during pregnancy". Heart Rhythm. 20 (10): e175–e264. doi:10.1016/j.hrthm.2023.05.017. PMID 33832606 Check
|pmid=value (help). - ↑ Calkins H, Hindricks G, Cappato R, et al. (2017). "2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation". Heart Rhythm. 14 (10): e275–e444. doi:10.1016/j.hrthm.2017.05.012. PMID 28506916.
- ↑ 20.0 20.1 Michaud GF, Stevenson WG (2021). "Atrial fibrillation". N Engl J Med. 384 (4): 353–361. doi:10.1056/NEJMcp2023658. PMID 33497559 Check
|pmid=value (help). - ↑ Lane DA, Andrade JG, Arbelo E, Lip G (2026). "Atrial fibrillation". Lancet. 407 (10532): 1000–1013. doi:10.1016/S0140-6736(25)02166-X. PMID 41794418 Check
|pmid=value (help). Vancouver style error: initials (help) - ↑ Eckardt, L., Sehner, S., Suling, A., Borof, K., Breithardt, G., Crijns, H., Goette, A., Wegscheider, K., Zapf, A., Camm, J., Metzner, A., & Kirchhof, P. (2022). Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: The EAST-AFNET 4 trial. European Heart Journal, 43(40), 4127-4144. https://doi.org/10.1093/eurheartj/ehac471