Genetics, age risk factor, and disease-related remodeling generate the AF substrate, defined as any combination of molecular, cellular, structural, or electrical changes to the atrium that increase susceptibility for and perpetuation of AF.
As AF advances, AF may become more persistent.
Importance In the US, approximately 10.55 million adults have atrial fibrillation (AF).
AF is associated with significantly increased risk of stroke, heart failure, myocardial infarction, dementia, chronic kidney disease, and mortality.
Symptoms of AF include palpitations, dyspnea, chest pain, presyncope, exertional intolerance, and fatigue, although approximately 10% to 40% of people with AF are asymptomatic.
AF can be detected incidentally via clinical encounters, with wearable devices, or through cardiac implanted electronic devices.
In patients presenting with ischemic stroke without diagnosed AF, an implantable loop recorder can evaluate patients for intermittent AF.
Guideline writing groups proposed 4 stages of AF evolution: stage 1, at risk, defined as patients with AF-associated risk factors (eg, obesity, hypertension); stage 2, pre-AF, signs of atrial pathology on electrocardiogram or imaging without AF; stage 3, the presence of paroxysmal (recurrent AF episodes lasting ≤7 days) or persistent (continuous AF episode lasting >7 days) AF subtypes; and stage 4, permanent AF.
Lifestyle and risk factor modifications are recommended for all stages: weight loss and exercise, to prevent AF onset, recurrence, and complications are recommended for all stages.
In patients with estimated risk of stroke and thromboembolic events of 2% or greater per year, anticoagulation with a vitamin K antagonist or direct oral anticoagulant reduces stroke risk by 60% to 80% compared with placebo.
In most patients, a direct oral anticoagulant, such as apixaban, rivaroxaban, or edoxaban, is recommended over warfarin because of lower bleeding risks.
Compared with anticoagulation, aspirin is associated with poorer efficacy and is not recommended for stroke prevention in AF,
Early rhythm control with antiarrhythmic drugs or catheter ablation to restore and maintain sinus rhythm is recommended for some patients with AF.
Catheter ablation is first-line therapy in patients with symptomatic paroxysmal AF to improve symptoms and slow progression to persistent AF.
Catheter ablation is also recommended for patients with AF who have heart failure with reduced ejection fraction (HFrEF) to improve quality of life, left ventricular systolic function, and cardiovascular outcomes of mortality and heart failure hospitalization.
AF is associated with increased rates of stroke, heart failure, and mortality.
Lifestyle and risk factor modification are recommended to prevent AF onset, recurrence, and complications, and oral anticoagulants are recommended for those with an estimated risk of stroke or thromboembolic events of 2% or greater per year.
Early rhythm control using antiarrhythmic drugs or catheter ablation is recommended in select patients with AF experiencing symptomatic paroxysmal AF or HFrEF.
In the US, atrial fibrillation (AF) affects up to 1 in 3 people in their lifetime and was estimated to affect approximately 10.55 million people by 2019.
Significant complications associated with AF include ischemic stroke, heart failure (HF), myocardial infarction, chronic kidney disease, dementia, and mortality.
Oral anticoagulants (OACs) have reduced rates of stroke and mortality in patients with AF.
In patients with estimated risk of ischemic stroke or thromboembolic events of 2% or greater per year, benefits of anticoagulation exceed risks of major bleeding.
Several risk scores identify patients at high risk of stroke, including CHA2DS2-VASc score, which assigns 1 point for congestive heart failure, 1 point for hypertension, 1 point for age 65 years and older, 2 points for age 75 years and older, 2 points for previous stroke or transient ischemic attack, 1 point for vascular disease, and 1 point for female sex.
Anticoagulation should be continued indefinitely unless a contraindication, such as bleeding, develops.
Lifestyle and risk factor modification, including weight loss, moderate exercise, smoking cessation, reducing alcohol consumption, and optimal blood pressure control, are recommended to prevent AF in patients at increased risk.
Patients younger than 70 years with new-onset AF may benefit from rhythm control with cardioversion and initiation of an antiarrhythmic drug, even if AF is asymptomatic.
Rhythm control should also be considered for patients with heart failure or left ventricular systolic dysfunction.
Anticoagulation should be initiated if the stroke or thromboembolic event risk score is 2% or greater per year.
The incidence, prevalence, and lifetime risk of AF are increasing, most likely due to population aging, increased detection rates, and increased survival with AF and other cardiovascular diseases.
Spanning 50 years of Framingham Heart Study participant surveillance (1958-1967 and 1998-2007), the age-adjusted incidence per 1000 person-years increased from 3.7 to 13.4 in men and 2.5 to 8.6 in women and the prevalence increased from 20.4 to 96.2 in men and 13.7 to 49.4 in women.7
The incidence and prevalence of AF vary by region and demographic factors, including sex and age.
In 2021, an estimated 52.55 million individuals worldwide had AF or atrial flutter, with the highest prevalence observed in high-income countries in North America, Australasia, and Western Europe..
The global prevalence is higher in men, 28 million vs women 25 million.
Older age is associated with higher incidence of AF.
Higher rates of AF seen with older age, current smoking, taller height, greater weight, higher blood pressure, hypertension treatment, presence of diabetes, and presence of heart disease are associated with higher rates of AF.
Risk of AF is affected by genetic factors: patients with individuals in the upper third of both clinical and polygenic risk (48.2%) and individuals in the lower third had less than half the lifetime risk of AF (22.3%).
Additional factors associated with increased AF risk include: more than moderate alcohol use, or binge drinking, sleep apnea, and hyperthyroidism.
Physical activity is associated with lower risk of AF.
However, male endurance athletes have higher risk of AF.
Studies support causal relations between multiple risk factors, including adiposity, smoking, alcohol consumption, and hypertension.
Ectopic atrial premature beats that initiate AF typically arise from myocardial cells that extend a few centimeters from the pulmonary vein–atrial junction into the pulmonary veins.
Atrial ectopy may initiate AF, its persistence isoften due to disease-specific atrial electrophysiologic, structural, and histopathologic changes that promote electrical reentry and AF continuance.
Hypertension activates the renin-angiotensin-aldosterone system, which induces atrial fibrosis and hypertrophy, slowing atrial conduction and promoting reentry and AF.
Obesity increases oxidative stress, systemic inflammation, and abnormal Ca2+cycling.
These effects increase atrial ectopy and pathologic changes that sustain arrhythmic activity.
Autonomic dysfunction alters atrial repolarization and promotes AF.
AF-associated diseases, such as hypertension, obesity, and valvular heart disease-mitral valve stenosis, mitral valve regurgitation, are associated with atrial pathology and AF.
The probability of AF detection increases with electrocardiogram (ECG) monitoring duration.
An implantable loop recorder (ILR) is a subcutaneous device that can continuously monitor heart rhythm for about 4 years: (AF was diagnosed in 31.8% of the ILR group vs 12.2% of the control group).
ILR is a reasonable diagnostic measure to increase probability of AF detection if maximum sensitivity is sought to identify patients who may benefit from oral anticoagulants for secondary stroke prevention.
In clinical trials of patients with ischemic stroke, rates of AF detection were 12% to 15%23-25 after 1 year and 30%23 by 3 years with ILR, compared with rates of 1.8% to 4.7% after 1 year and 3% after 3 years in those who received usual care or wore a 30-day monitor.
AF diagnosed during hospitalization for noncardiac illnesses, such as sepsis or noncardiac surgery, is associated with posthospital AF recurrence, stroke, and mortality.
In patients with severe sepsis, new-onset AF was associated with 2.7-fold (2.6% vs 0.6%) increased risk of in-hospital ischemic stroke and 7% (56% vs 39%) higher risk of in-hospital death, adjusting for demographics, comorbidities, and sepsis-associated factors.
Patients diagnosed with AF during hospitalization for noncardiac illness have 5-year recurrence rates of 42% to 68%:patients diagnosed with AF during hospitalization for noncardiac illness be counseled about their increased risk of recurrent AF
In patients without diagnosed AF who have cardiac implanted electronic devices, including an ILR, pacemaker, or implantable cardioverter-defibrillator, the incidence of atrial high-rate episodes with atrial rates >190 beats per minute, which include AF, atrial flutter, and atrial tachycardias detected is approximately 24.5% to 34.4% over 1 to 2.5 years of follow-up.
Atrial high rate episodes(AHREs) has varied among studies, from longer than 20 seconds to 24 hours, AHREs of greater than 6 minutes are associated with incident events.
AHREs were associated with 2.4-fold increased risk of stroke (1.89 per 100 person-years with vs 0.93 per 100 person-years without) that increased with AHRE duration
A meta-analysis of 2 randomized clinical trials that included 6548 patients studied whether OACs were associated with lower rates of stroke in those with AHRE lasting 6 minutes or longer: direct OACs (DOACs) were associated with lower relative risk (RR) of stroke by 32% (2.0% vs 3.0%), but were associated with 39% increased RR of major bleeding (4.8% vs 3.2%).
The ischemic stroke rate was 1% per patient-year in the control group (patients with AHREs not on DOACs), a significant stroke risk with AHREs, but lower than the literature-estimated 2% per patient-year for patients with diagnosed AF.
It is reasonable to initiate OACs for AHREs lasting longer than 24 hours in individuals with CHA2DS2-VASc scores of 2 or higher.
It may be reasonable for AHREs lasting longer than 5 minutes in those with CHA2DS2-VASc score of 3 or higher, but bleeding risk should be carefully considered.
Typical symptoms of AF include palpitations with or without dyspnea, chest pain, presyncope, exertional intolerance, and fatigue.
Approximately 10% to 40% of people with AF are asymptomatic.
Asymptomatic initial presentation of AF is more common in men (10% in men vs 3% in women) and older adults (mean age, 74 years vs 62 years for symptomatic people).
Diabetes is more common in those with asymptomatic AF.
Asymptomatic AF may also be discovered during evaluation of AF-related clinical outcomes, such as ischemic stroke, systemic thromboembolism, myocardial infarction, or HF.
AF and HF are predisposing conditions for each other and often coexist.
The diagnosis of AF is confirmed by identifying irregular atrial activity without discrete P waves on 12-lead ECG or lasting for longer than 30 seconds on rhythm strip.
AF is classified as paroxysmal (intermittent AF episodes lasting ≤7 days), persistent (continuous AF episodes lasting >7 days and/or requiring cardioversion), or long-standing persistent (AF episode lasting >1 year).
Evaluation of patients with newly identified AF includes transthoracic echocardiogram to assess cardiac structure and to identify possible causes for AF, such as valve disease, or outcomes associated with AF, such as reduced ventricular ejection function.
Basic laboratory testing, including complete blood count, metabolic panel, and thyroid function.
Cardiac stress testing in patients with newly diagnosed AF, is considered for angina or reduced ejection fraction.
Emergent cardioversion should be considered for hemodynamic instability attributable to AF.
The risk of thromboembolism is considered, particularly if a patient has not been on therapeutic anticoagulation or if the AF duration has persisted for longer than 48 hours and imaging with transesophageal echocardiogram or cardiac computed tomography to exclude left atrial thrombus is not immediately feasible.
AF is no longer categorized according to valvular or nonvalvular AF, and this distinction is currently used to guide OAC strategy.
Four AF stages have been proposed;
Individuals with modifiable and nonmodifiable risk factors, such as obesity or family history of AF, are classified as stage 1 at risk for AF.
Stage 2, pre-AF, is defined as the presence of atrial pathology, including left atrial enlargement, frequent atrial ectopy, or nonsustained atrial tachycardia, but without diagnosed AF.
Individuals with conditions associated with high incidence of AF, such as atrial flutter, HF, coronary artery disease, valvular heart disease, hypertrophic cardiomyopathy, neuromuscular diseases, and hyperthyroidism, are considered to have pre-AF; clinicians may consider increased AF surveillance consisting of a wearable or implantable monitor.
No randomized clinical trials have demonstrated that surveillance for AF prevents adverse outcomes.
Stage 3 AF is clinically apparent AF and is categorized as 1 of 4 subtypes 3a, paroxysmal (recurrent AF episodes lasting ≤7 days);
3C, persistent AF (continuous AF episode lasting >7 days);
3C, long-standing persistent AF (continuous AF episode lasting >1 year); or
3d, in which AF was treated successfully with catheter ablation.
After catheter ablation, AF episodes may be less symptomatic, less frequent, or shorter in duration.
Stage 4 AF have permanent AF, for which a decision has been made not to pursue rhythm control based on patient and clinical factors, such as age and AF duration.
AF is associated on metaanalyses with absolute risk increase per 1000 participant-years of approximately 3.6 for stroke, 11.1 for heart failure, 1.4 for ischemic heart disease, 6.6 for chronic kidney disease, and 3.8 for mortality.
A meta-analysis reported AF was associated with increased risk of Alzheimer disease and vascular dementia and in stroke-free patients cognitive impairment or dementia.
In randomized clinical trials evaluating DOACs vs warfarin, patients who received apixaban (HR, 0.79) had an annual stroke or systemic embolism rate of 1.3% compared with 1.6% for warfarin.
Clinical trials have not established treatments among people with AF that prevent HF.
In patients with AF who were taking DOACs there was as associated lower rates of acute kidney injury.
Treatments:
For patients at risk for AF (stages 1 or 2) or with AF (stages 3 or 4) consists of lifestyle and risk factor modification, such as weight loss, exercise, and targeted blood pressure control.
Except for hypertension treatment, randomized clinical trial evidence that these lifestyle and risk factors prevent AF does not exist.
Lifestyle and risk factor modification is also recommended for patients with AF who are treated with antiarrhythmic drugs (AADs) or ablation.
Guideline recommends lifestyle and risk factor modification for individuals with stages 1 and 2 AF, including treating obesity, diabetes, cigarette smoking, and hypertension, and recommendations to address physical inactivity and unhealthy alcohol consumption.
Intensive blood pressure control-lowering systolic blood pressure to <120 mm Hg, compared with <140 mm Hg) is associated with lower AF risk (6.21 vs 8.33 events per 1000 person-years.
A meta-analysis of 20 randomized clinical trials that included 63 604 patients with diabetes, HF, or kidney disease reported that sodium-glucose cotransporter-2 inhibitors were associated with reduced AF risk.
In patients with estimated risk of ischemic stroke or thromboembolic events 2% or greater per year (eg, CHA2DS2-VASc ≥2 for men, ≥3 for women), benefits of OACs exceed risks of major bleeding.
OAC therapy is associated with reduced rates of cognitive impairment and dementia.
CHA2DS2-VASc rsk score being the most widely validated, which assigns 1 point for congestive HF, 1 point for hypertension, 1 point for age 65 years and older, 2 points for age 75 years and older, 2 points for previous stroke or transient ischemic attack, 1 point for vascular disease, and 1 point for female sex.
In patients without mechanical heart valves or moderate to severe mitral stenosis, DOACs are preferred because they are associated with less bleeding than warfarin.
All DOACs reduce risk of intracranial hemorrhage by approximately half compared with warfarin.
After ablation, OACs should be continued for at least 3 months.
No definitive randomized clinical trials have directly compared the efficacy and safety of 1 DOAC with another.
The American Geriatrics Society recommends that because of higher bleeding rates compared with other DOACs, rivaroxaban should be avoided in adults 65 years and older with AF, except when once-daily dosing may improve medication adherence.
Apixaban and rivaroxaban are approved for patients receiving dialysis based on limited pharmacokinetic data.
In patients with AF eligible aspirin alone or aspirin plus clopidogrel as an alternative to OACs are considered harmful because they are less effective than OACs for preventing cardioembolic stroke in AF despite similar bleeding risk.
Compared with placebo, aspirin does not lower risk of stroke, but is associated with increased major bleeding risk.
Adding antiplatelet drugs to OACs increases risk of bleeding and is recommended only after acute coronary syndrome or percutaneous coronary intervention (PCI).
DOACs should be recommended instead of warfarin for patients with AF undergoing PCI.
Aspirin should be discontinued early (1-4 weeks) after PCI with continuation of OAC plus P2Y12 inhibitor (clopidogrel is preferred over ticagrelor or prasugrel) over triple antithrombotic therapy (OAC, aspirin, and P2Y12 inhibitor) to reduce clinically relevant bleeding risk.
OAC monotherapy is recommended over OAC plus single antiplatelet therapy in patients with AF and chronic coronary artery disease who have undergone coronary revascularization more than 1 year previously, unless the patient has a history of prior stent thrombosis.
In the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease (AFIRE) trial: rivaroxaban monotherapy was superior to rivaroxaban plus aspirin or P2Y12 inhibitors for preventing major bleeding and noninferior for major cardiovascular events.
For patients with recurrent bleeding requiring blood transfusions or who have spontaneous intracerebral hemorrhage, OACs may be contraindicated.
In these patients, percutaneous left atrial appendage occlusion (pLAAO) with a self-expanding, umbrella-like device is a reasonable alternative to prevent stroke.
No direct evidence from randomized clinical trials exists on benefits of pLAAO in OAC-ineligible patients.
pLAAO was US Food and Drug Administration–approved based on randomized clinical trials comparing pLAAO with warfarin in warfarin-eligible patients.
pLAAO is reasonable with the understanding that it requires at least 45 days of OACs followed by dual antiplatelet therapy for 6 months and lifelong aspirin (325 mg)
The 2 primary strategies for management of AF are rate control, in which the ventricular rate is slowed with drugs that prolong the AV nodal refractory period, and rhythm control, in which therapeutic interventions aim to restore or maintain sinus rhythm.
The choice of rate or rhythm control does not affect the decision for or duration of OAC.
Rhythm control interventions consist of antiarrhymic drugs (ADDs) cardioversion, and/or ablation.
The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) and Rate Control vs Electrical Cardioversion for Atrial Fibrillation (RACE) studies compared AF strategies and showed no significant differences in clinical outcomes, including mortality and stroke.
Studies reported the benefits of initiating rhythm control within 1 year of AF diagnosis with early rhythm control over rate control for reducing HF, stroke risk, and mortality in patients with paroxysmal and persistent
The benefit of early rhythm control was also observed in those with asymptomatic AF.
Rate control without attempts to treat rhythm is an appropriate strategy for patients who are unlikely to benefit from rhythm control with AADs or catheter ablation and for those in whom rhythm control is considered too risky: patients with amyloid cardiomyopathy or cor pulmonale are more likely to have recurrent AF following ablation, therefore rate control may be more appropriate.
Rate control is also appropriate for patients with stage 4, permanent, AF.
Atrial fibrillation rate control is achieved with single or drug combinations, including β-blockers such as metoprolol, esmolol, or atenolol, and nondihydropyridine calcium channel blockers, such as verapamil or diltiazem, to slow electrical conduction through the atrioventricular node.
Digoxin can be used as adjunctive therapy when ventricular rate remains poorly controlled or hypotension limits further titration of β-blockers or nondihydropyridine calcium channel blockers.
Drugs that slow atrioventricular conduction should be titrated to control symptoms and achieve resting heart rates less than 100 to 110 beats per minute.
Atrioventricular nodal ablation with pacemaker implant can control symptoms and improving quality of life (QOL) in patients with ineffectively controlled ventricular rates who have not improved or are not candidates for rhythm control.
Antiarrhythmic drugs may be used for acute conversion of AF to sinus rhythm or for suppression of AF when taken daily.
Treatment with flecainide or propafenone in conjunction with concomitant AV nodal agents may be useful for intermittent treatment of infrequent AF episodes.
Early rate vs rhythm randomized clinical trials did not demonstrate improved mortality or stroke risk with daily use of AAD compared with treatment with AV nodal agents.
Early Treatment of Atrial Fibrillation for Stroke Prevention Trial reported clinical benefit of rhythm control with daily AAD or catheter ablation over rate control therapy when rhythm control was initiated early.within 12 months of AF diagnosis/
EAST-AFNET 4 randomized 2789 patients within 1 year of AF onset (median time, 36 days) and mean CHA2DS2-VASc of 3.4 to rhythm control or rate control: The trial was stopped early due to a 21% reduction in the primary composite outcome of cardiovascular mortality, stroke, and hospitalizations for HF or acute coronary syndrome with rhythm control vs rate control (3.9 per 100 person-years vs 5.0 per 100 person-years).
The EAST-AFNET 4 trial reported that benefit of rhythm control extended to those with asymptomatic AF.
Focal ectopic impulses arising from the pulmonary veins often initiate AF and that ablation of these sources significantly reduced AF preceded development of catheter ablation procedures, which are effective for maintaining sinus rhythm.
Ablation destroys atrial tissue at the atrial–pulmonary vein junction to prevent ectopic impulses from the pulmonary vein from reaching the atrium (pulmonary vein isolation).
At 1-year follow-up, 89% of patients who underwent ablation remained AF-free vs 23% of patients treated with AAD.
A significant improvement in symptoms, QOL, and exercise capacity was also observed with ablation.
The Early Aggressive Invasive Intervention for Atrial Fibrillation (EARLY-AF) trial randomized 303 patients with symptomatic, untreated paroxysmal AF to cryoablation or AAD and monitored for recurrent AF using implantable loop recorder.
The primary end point was first recurrence of AF (or atrial tachyarrhythmia) of 30 seconds or longer; the secondary end point was overall burden of AF.
At 1-year follow-up, recurrence of AF was significantly less likely in those who underwent ablation (42.9%) compared with AADs (67.8%).
The mean time in AF was significantly lower with ablation (0.6%) vs AADs (3.9%).
Meta-analysis of 5 clinical trials that enrolled people with AF (predominately paroxysmal AF), reported a more than 2-fold greater freedom from AF at 1 year with radiofrequency ablation (77%) vs AAD (29%).
Ablation in patients with persistent AF, including long-standing persistent, with low prevalence of structural heart disease (eg, normal left ventricular function, normal to mild left atrial enlargement, and low prevalence of coronary artery disease or diabetes has comparable results to those with paroxysmal AF.
The Catheter Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation (CABANA) trial tested efficacy of ablation on clinical outcomes.
CABANA reported that ablation did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest, but reported significant improvement in QOL with ablation.
In prespecified subgroup analysis of CABANA, compared with medical treatment, patients who received ablation younger than 65 years had lower mortality, whereas those 75 years or older did not.85
Coexistence of HF and AF is associated with increased mortality compared with those with HF or AF alone.
Although AADs have limited benefit in AF patients with HFrEF, multiple randomized clinical trials and meta-analyses have shown superiority of rhythm control with ablation over medical therapy.
The Catheter Ablation Versus Standard Conventional Treatment in Patients with Left Ventricular Dysfunction and Atrial Fibrillation (CASTLE-AF) trial randomized patients with HF and left ventricular ejection fraction 35% or less to ablation or medical therapy: After median follow-up of 38 months, ablation was associated with significant reductions in the composite end point of death or hospitalization for HF (ablation, 28.5% vs medical therapy, 44.6%).
A meta-analysis of 3 trials that including patients with HF and AF reported that compared with medical therapy, ablation was associated with lower mortality rates and HF hospitalizations.
Few randomized clinical trials have studied the effects of ablation in people with AF and HFpEF.
CABANA was the only large randomized clinical trial in which nearly 80% of patients with HF had an ejection fraction of 50% or greater: ablation was associated with 43% reduction in all-cause mortality (6.1% ablation vs 9.3% medical therapy), 44% reduction in AF recurrence (56% ablation vs 72% medical therapy), and sustained improvement of QOL out to 5 years.
Individuals with AF who are women, Black, or Hispanic; with lower income or education; inadequate or lack of insurance; or who live in rural areas or with material deprivation are less likely to receive directed care and more likely to experience worse outcomes.
Prognosis: in a metaanalysis of patients compared with an absence of AF there is an absolute increase in 1000 participant years of approximately 3.for stroke, 11.1 for heart failure, 1.4 for ischemic heart disease, 6.6 for chronic kidney disease and 3.8 for mortality.
Meta analysis report increase risk of Alzheimer’s disease, vascular dementia, and cognitive impairment.
Incident rates for heart failure per hundred person years of follow up or a 2.13 for heart failure with reduced ejection fraction and 3.32 for heart failure with preserved ejection fraction: clinical trials have not established treatments among people with AF that prevent heart failure.