Atrial fibrillation

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]

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]

AF may be classified by temporal pattern as follows:^[7]

AF may also be classified according to stage of disease:^[7][4]

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]

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 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 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]

Prothrombotic changes in the left atrium include increased endocardial expression of von Willebrand factor, increasing risk of thrombus formation and stroke.^[7]

AF promotes further electrical and structural remodeling, creating a self-perpetuating cycle.^[7][9]

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]

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]

Coronary artery disease, heart failure, valvular heart disease, hyperthyroidism, pericarditis, post-cardiac surgery, congenital heart disease, infiltrative diseases (amyloidosis, hemochromatosis, sarcoidosis)^[1][10]

AF with pre-excitation (WPW): wide-complex irregular tachycardia; AV nodal blocking agents (verapamil, digoxin, adenosine) are contraindicated^[7]

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]

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]

Wearable devices can detect AF with high sensitivity (94%) and specificity (93–96%); ECG confirmation is required.^[14]

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]

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]

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]

Typical symptoms include palpitations, dyspnea, chest pain, presyncope, exertional intolerance, and fatigue. Approximately 10–40% of patients are asymptomatic.^[4]

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]

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]

The CHA2DS2-VASc score is the most validated tool for stroke risk stratification:^[7]

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]

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]

DOAC dosing by renal function:^[7]

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]

First-line:^[7][20]

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]

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]