Atrial fibrillation
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
|
Atrial Fibrillation Microchapters | |
|
Special Groups | |
|---|---|
|
Diagnosis | |
|
Treatment | |
|
Cardioversion | |
|
Anticoagulation | |
|
Surgery | |
|
Case Studies | |
|
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 may be classified by temporal pattern as follows:[7]
| 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
AF may also be classified according to stage of disease:[7][4]
| 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 |
Anticoagulation-Relevant Valve Disease
The terms "valvular AF" and "nonvalvular AF" are no longer preferred because definitions have varied across clinical trials and guidelines. For anticoagulant selection, the key distinction is the presence of moderate-to-severe mitral stenosis or a mechanical heart valve. Patients with AF and moderate-to-severe mitral stenosis or a mechanical heart valve should receive warfarin rather than a direct oral anticoagulant (DOAC).[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: AF is more prevalent in men globally.[4]
Race/ethnicity: Lifetime risk is approximately 30–40% in White individuals, approximately 20% in African American individuals, and approximately 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 routine 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 is common in patients with hypertrophic cardiomyopathy (HCM) and is associated with increased thromboembolic risk. Anticoagulation is recommended for all patients with HCM and AF regardless of CHA2DS2-VASc score, with DOACs generally preferred unless contraindicated.[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 most patients with AF, except in patients with moderate-to-severe mitral stenosis or a mechanical heart valve. 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), and 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 >95 mL/min | CrCl 51–95 mL/min | CrCl 31–50 mL/min | CrCl 15–30 mL/min | CrCl <15 mL/min or dialysis |
|---|---|---|---|---|---|
| Apixaban | 5 mg BID or 2.5 mg BID | 5 mg BID or 2.5 mg BID | 5 mg BID or 2.5 mg BID | 5 mg BID or 2.5 mg BID | 5 mg BID or 2.5 mg BID |
| Dabigatran | 150 mg BID | 150 mg BID | 150 mg BID | 75 mg BID | Contraindicated |
| Rivaroxaban | 20 mg daily | 20 mg daily | 15 mg daily | 15 mg daily | 15 mg daily |
| Edoxaban | Contraindicated | 60 mg daily | 30 mg daily | 30 mg daily | Contraindicated |
Apixaban dose reduction to 2.5 mg BID if ≥2 of the following are present: age ≥80 years, body weight ≤60 kg, or 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: A lenient rate-control target of resting heart rate <110 bpm is reasonable as an initial strategy in many stable patients. A stricter rate-control target may be considered in patients with persistent symptoms, left ventricular systolic dysfunction, or suspected tachycardia-mediated cardiomyopathy.[7]
Rhythm Control
Early rhythm control: In EAST-AFNET 4, early rhythm-control therapy in patients with recently diagnosed AF and cardiovascular conditions reduced the composite outcome of cardiovascular death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome compared with usual care.[21] Individual components included lower cardiovascular death and stroke in the early rhythm-control group.[22] The benefit was mediated by the presence of sinus rhythm at 12 months, which explained 81% of the treatment effect.[23]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 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 4.13 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). - ↑ Kirchhof P, Camm AJ, Goette A, et al. (2020). "Early rhythm-control therapy in patients with atrial fibrillation". N Engl J Med. 383 (14): 1305–1316. doi:10.1056/NEJMoa2019422. PMID 32865375 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, et al. (2022). "Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST-AFNET 4 trial". Eur Heart J. 43 (40): 4127–4144. doi:10.1093/eurheartj/ehac471. PMID 36168569 Check
|pmid=value (help).