Atrial Fibrillation

Tania B. Babar, M.D.

Basic Information

Definition

Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by disorganized and rapid atrial activation and uncoordinated atrial contraction. AF occurs when structural and/or electrophysiologic abnormalities alter atrial tissue to promote abnormal impulse formation and/or propagation. The ventricular rate is dependent on the conduction properties of the atrioventricular (AV) node, which can be influenced by vagal/sympathetic tone, medications, or disease of the AV node.

Multiple classification schemes have been used in the past to characterize AF. The current classification scheme (divided into three major types) used by the ACC/AHA guideline committee is as follows:

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Paroxysmal AF—more than one episode of AF that terminate spontaneously or with intervention within 7 days
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Persistent AF—episodes of AF that last longer than 7 days
1. ○
  
  Early-persistent AF—AF that has been continuous for longer than 7 days but fewer than 3 months
2. ○
  
  Long-standing persistent AF—AF that has persisted for longer than 1 yr, either because cardioversion has failed or because cardioversion has not been attempted
•

Permanent AF: When patient and physician decide to stop pursuing restoring sinus rhythm
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In addition to the previous AF categories, which are mainly defined by episode timing and termination, the ACC/AHA/ESC guidelines describe additional AF categories in terms of other characteristics of the patient:
1. ○
  
  Lone atrial fibrillation (LAF)—generally refers to AF in younger patients without clinical or echocardiographic evidence of cardiopulmonary disease, diabetes, or hypertension
2. ○
  
  Nonvalvular AF—absence of rheumatic mitral valve disease, a mechanical or bioprosthetic heart valve, or mitral valve repair
3. ○
  
  Secondary AF—occurs in the setting of a primary condition that may be the cause of the AF, such as acute myocardial infarction, cardiac surgery, pericarditis, myocarditis, hyperthyroidism, pulmonary embolism, pneumonia, or other acute disease. It is considered separately because AF is less likely to recur once the precipitating condition has resolved
4. ○
  
  Silent AF—asymptomatic AF diagnosed by an ECG or rhythm strip

Synonyms

AF
PAF
AFib

ICD-10CM CODES
I48.0	Paroxysmal atrial fibrillation
I48.1	Persistent atrial fibrillation
I48.2	Chronic atrial fibrillation
I48.91	Unspecified atrial fibrillation

Epidemiology & Demographics

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The prevalence of AF increases with age, from 2% in adults <65 yr to 9% of those >65 yr.
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AF affects over 3 million people in the United States. AF is uncommon in infants and children and, when present, almost always occurs in association with structural heart disease.
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The incidence of AF is significantly higher in men than in women in all age groups (1.1% versus 0.8%). AF appears to be more common in whites than in blacks, who may have lower awareness of the disease.
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Stroke due to thromboembolism is the most common and dreaded complication of AF. The rate of ischemic stroke in patients with non-rheumatic AF averages 5% a year, which is somewhere between two and seven times the rate of stroke in patients without AF. The risk of stroke is not due solely to AF; changes in the endothelium and elevated markers of inflammation that may contribute to thrombosis are found in patients with AF, regardless of their rhythm at the time. The attributable risk of stroke from AF is estimated to be 1.5% for those aged 50 to 59 yr, and it approaches 36% for those aged 80 to 89 yr.

Physical Findings & Clinical Presentation

Clinical presentation is variable:

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Palpitations, dizziness, or lightheadedness
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Fatigue, weakness, or impaired exercise tolerance
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Angina
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Dyspnea
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Some patients are asymptomatic
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Cardiac auscultation revealing irregularly irregular rhythm
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Thromboembolic phenomenon such as stroke

Etiology

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The most frequent change in AF is the loss of atrial muscle mass and atrial fibrosis.
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Fibrillation is presumed to be caused by multiple wandering wavelets, usually originating from the pulmonary veins. Both reentrant and focal mechanisms have been proposed.
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Vascular causes: hypertensive heart disease
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Valvular heart disease
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Pulmonary causes: pulmonary embolism, chronic obstructive pulmonary disease, obstructive sleep apnea, carbon monoxide poisoning
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Structural cardiac disease: hypertrophic cardiomyopathy, congestive heart failure, coronary artery disease, myocardial infarction, congenital heart disease (especially those that lead to atrial enlargement such as atrial septal defect)
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Pericarditis and myocarditis
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Arrhythmias: atrial tachycardias and atrial flutters have been associated with atrial fibrillation, as has Wolff-Parkinson-White syndrome
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Endocrine: thyrotoxicosis, hyperthyroidism or subclinical hyperthyroidism, pheochromocytoma, obesity
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Surgery: both cardiac and noncardiac
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Electrolytes: hypokalemia, hypomagnesemia
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Systemic stress: fever, anemia, hypoxia, sepsis, infections (e.g., pneumonia)
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Medications/toxins: digitalis, adenosine, theophylline, amphetamines, cocaine, antihistamines, alcohol abuse and/or withdrawal, caffeine, steroidal antiinflammatory drugs (SAIDs), nonsteroidal antiinflammatory drugs (NSAIDs)
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Frequency of vigorous exercise is associated with an increased risk of developing AF in young men and joggers
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Porphyrias have been associated with autonomic dysfunction and increased risk of AF
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Patients with metabolic syndrome, excessive vitamin D intake, or excessive niacin intake have a higher risk of AF

Diagnosis

Differential Diagnosis

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Multifocal atrial tachycardia
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Atrial flutter
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Frequent atrial premature beats
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Atrial tachycardia
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AV nodal reentry tachycardia (AVNRT)
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Wolff-Parkinson-White syndrome

Workup

The evaluation of atrial fibrillation involves diagnosis, determination of the etiology, and classification of the arrhythmia. A minimal evaluation includes a history and physical examination, ECG, transthoracic echocardiogram, and case-specific laboratory work to rule out secondary AF.

Laboratory Tests

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Thyroid-stimulating hormone, free T₄
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Serum electrolytes
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Toxicity screen
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CBC count (looking for anemia, infection)
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Renal and hepatic function tests
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D-dimer/CT scan of chest PE protocol (if the patient has risk factors to merit a pulmonary embolism workup)

Imaging Studies

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ECG (Fig. 1)

FIG.1

Atrial fibrillation (AF) with slow ventricular rate.

A, The ventricular rhythm is irregular, indicating that it is the result of conducted atrial beats. B, The ventricular rhythm is regular, consistent with the presence of complete atrioventricular (AV) block and a regular junctional escape rhythm.

From Issa Z, et al.: Clinical arrhythmology and electrophysiology, ed 2, Philadelphia, 2012.
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Absence of P waves
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Fibrillatory or f waves at the isoelectric baseline with varying amplitude, morphology, and intervals
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Irregular ventricular rate
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Echocardiography to rule out structural heart disease (evaluate ventricular size, thickness, and function, atrial size, pericardial disease, and valve function)
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Chest radiography (if pulmonary disease or CHF is suspected)
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Transesophageal echocardiography (TEE): helpful to evaluate for left atrial thrombus (particularly in the LA appendage) to guide cardioversion or ablation (if thrombus is seen, cardioversion should be delayed)
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CT and MRI: in patients with a positive D-dimer result, chest CT angiogram may be necessary to rule out pulmonary embolus. Three-dimensional imaging technologies (CT scan or MRI) are often helpful to evaluate atrial anatomy if AF ablation is planned
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Six-minute walk test or exercise test: six-minute walk or exercise testing can help assess the adequacy of rate control. Exercise testing can also exclude ischemia prior to treatment of patients with class Ic antiarrhythmic drugs and can be used to reproduce exercise-induced AF
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Sleep study (if sleep apnea is suspected)
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Holter monitor or event recorder if the diagnosis of AF is in question and to assess AF burden
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Electrophysiologic study: when initiation of AF is secondary to a supraventricular tachycardia, such as AVNRT or Wolff-Parkinson-White syndrome

Treatment

Acute Treatment

Acute General Rx

New-onset AF:

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If the patient is hemodynamically unstable (hypotension, congestive heart failure, or angina), perform synchronized cardioversion after immediate conscious sedation with a rapid short-acting sedative (e.g., midazolam). The likelihood of cardioversion-related clinical thromboembolism is low in patients with AF lasting <48 hr. Patients with AF lasting >2 days have a 5% to 7% risk for clinical thromboembolism if cardioversion is not preceded by several weeks of anticoagulation therapy. However, if transesophageal echocardiography reveals no atrial thrombus, cardioversion may be performed safely after therapeutic anticoagulation has been achieved. Alternatively, patients can be safely anticoagulated for approximately 1 month and then undergo cardioversion without transesophageal echocardiogram. Anticoagulant therapy should be continued for at least 1 month after cardioversion to minimize the incidence of adverse thromboembolic events. It can be stopped after 1 month as long as AF has not recurred if the patient is deemed low risk of stroke using the CHA2DS2VASc scoring system (see the following).
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If the patient is hemodynamically stable, a rate-control strategy is typically pursued initially.
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Treatment options for rate control include the following:
1. 1.
  
  Diltiazem 0.25 mg/kg (maximum of 25 mg) given intravenously (IV) over 2 min followed by a second dose of 0.35 mg/kg (maximum of 25 mg) 15 min later if the rate is not slowed to <100 beats/min. May then follow with IV infusion 10 mg/hr (range, 5-15 mg/h) to achieve a resting heart rate of <100 beats/min. Onset of action after IV administration is usually within 3 min, with peak effect most often occurring within 10 min. After the ventricular rate is slowed, the patient can be changed to oral diltiazem 60 to 90 mg q4 to 6h. High doses of calcium channel blockers can exacerbate heart failure and thus should be used with caution in patients presenting with symptoms of heart failure or depressed ejection fraction.
2. 2.
  
  Verapamil 2.5 to 5 mg IV initially, then 5 to 10 mg IV 10 min later if the rate is still not slowed to <100 beats/min. After the ventricular rate is slowed, the patient can be changed to oral verapamil 80 to 120 mg q6 to 8h. Main concern is hypotension and heart failure with this medication, and it should not be used in patients with CHF.
3. 3.
  
  Esmolol and metoprolol are beta-blockers available in IV preparations that can be used. High doses of β-blockers can have negative inotropic effects in heart failure and should be used with caution.
4. 4.
  
  Digoxin is not a potent AV nodal blocking agent and has a potential for toxicity and therefore cannot be relied on for acute control of the ventricular response, but it may be used in conjunction with beta-blockers and calcium channel blockers. It may be a useful adjunct to a beta-blocker in the hypotensive or heart failure patient, which is not infrequent. When used, give 0.5 mg IV loading dose (slow) and then 0.25 mg IV 6 hr later. A third dose may be needed after 6 to 8 hr; the daily dose varies from 0.125 to 0.25 mg (decrease dosage in patients with renal insufficiency and elderly patients) depending on the heart rate and signs or symptoms of digoxin toxicity. Toxicity is manifested by GI and visual complaints, atrial tachyarrhythmias, heart block, and ventricular tachycardia.
5. 5.
  
  Amiodarone has a class IIa recommendation from the ACC/AHA/ESC for use as a rate-controlling agent for patients who are intolerant of or unresponsive to other agents, such as patients with heart failure who may otherwise not tolerate diltiazem or metoprolol. Caution should be exercised in those who are not receiving anticoagulation because amiodarone can promote cardioversion, thereby posing a thromboembolic risk.
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AV nodal blocking agents, particularly calcium channel blockers and digoxin, should be avoided in patients with Wolff-Parkinson-White syndrome and AF because, by blocking the AV node, AF impulses may be transmitted exclusively down the accessory pathway, which can result in ventricular fibrillation. If this happens, the patient will require immediate defibrillation. Procainamide, flecainide, or amiodarone can be used instead if Wolff-Parkinson-White syndrome is suspected.
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In the acute setting, pharmacologic cardioversion (e.g., ibutilide, dofetilide) is less commonly used than electrical cardioversion. A major disadvantage with pharmacologic cardioversion is the risk of development of ventricular tachycardia and other serious arrhythmias, especially due to acute prolongation of the QT interval.

Chronic Therapy

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Avoidance of alcohol in patients with suspected excessive alcohol use.
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Treatment of underlying source or cause, if any found.
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Treatment of modifiable risk factors such as obstructive sleep apnea, hypertension, and obesity have been shown to decrease AF burden in patients.
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Per the AFFIRM and RACE trials, either rate control or rhythm control strategies show no difference in composite cardiovascular end points of death, CHF, bleeding, drug side effects, or thromboembolism. Both approaches have similar outcomes as long as appropriate anticoagulation is maintained based on the individual’s stroke risk.
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For patients without symptomatic AF, a rate-control strategy with calcium channel blockers, beta-blockers, or digoxin is a reasonable option. The RACE 2 trial indicates that a lenient rate control strategy, with a target resting heart rate of <110 beats/min, is noninferior to a strict control strategy, with a target resting heart rate of <80 beats/min and an exercise heart rate of <110 beats/min. Most recent ACC/AHA guidelines, however, recommend targeting a HR <80 beats/min over a target of <110 beats/min.
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In patients with symptomatic AF, younger patients, or those with difficult to control heart rate, an attempt should be made to maintain sinus rhythm with antiarrhythmic agents. Options of antiarrhythmic agents include amiodarone, dronedarone, (paroxysmal atrial fibrillation only without heart failure), dofetilide, flecainide, propafenone (contraindicated with structural heart disease), or sotalol. The decision of which strategy to follow should be best made in consultation with a cardiologist. Use of dronedarone should be avoided in patients with persistent or permanent atrial fibrillation because of worsened cardiovascular outcomes, especially in those with concomitant symptomatic heart failure (see Fig. 2 for a proposed algorithm to guide maintenance of sinus rhythm).

FIG.2

Therapy to maintain sinus rhythm in patients with recurrent paroxysmal or persistent atrial fibrillation.

Drugs are listed alphabetically and not in order of suggested use. The seriousness of heart disease progresses from left to right, and selection of therapy in patients with multiple conditions depends on the most serious condition present. LVH, Left ventricular hypertrophy.

From 2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation [Updating the 2006 Guideline]: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol 57[2]:223-242, 2011.

Nonpharmacologic Therapy

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Catheter ablation of AF has become a common procedure for symptomatic drug-refractory or drug-intolerant patients. Sinus rhythm can be maintained long term in the majority of patients with PAF by circumferential pulmonary vein ablation performed in experienced centers. Established centers have reported success rates of 70% to 85% in patients with paroxysmal AF, but up to 50% of patients may require more than one ablation to achieve success. Complication rates are 4.5% in the largest international survey of hospitals performing this procedure. Success with persistent AF is much lower, with long-term success rates of 40% to 50% in many studies, and such patients often require more than one procedure. The most common techniques used to isolate the pulmonary veins are radiofrequency ablation and cryoballoon ablation, which have shown similar results for patients with PAF.
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Pulmonary vein isolation is being increasingly used to treat AF in patients with heart failure. Trials have shown that pulmonary vein isolation is superior to AV node ablation with biventricular pacing in patients with heart failure who have drug-refractory AF.
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AV nodal ablation with permanent pacemaker implantation may become necessary in some patients in whom rate and rhythm are difficult to control despite drugs and cardioversion, although it is generally used as a therapy of last resort.
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The Cox-Maze III surgical procedure, with its modifications creating electrical barriers to the macroreentrant circuits that are believed to underlie AF, is being performed with good results in some medical centers (preservation of sinus rhythm in 70% to 95% of patients without the use of long-term antiarrhythmic medication). Success rates are higher in paroxysmal than in persistent or permanent atrial fibrillation. Surgical ablation is often used for patients undergoing aortic or mitral valve surgery. As a stand-alone procedure, it is a Class IIb recommendation per ACC/AHA Guidelines in 2017. Some centers perform surgical pulmonary vein isolation similar to this procedure using a mini-thoracotomy or video thorascopic “Mini-Maze” approach. Another surgical method is a pericardioscopic approach that allows extensive posterior wall ablation and, when combined with catheter ablation in a “hybrid” approach, has shown promising results for patients with persistent AF.
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It is important to understand that ablation therapy will not eliminate the need to take anticoagulant drugs. Even after ablation, patients with AF face increased risk of thromboembolic events and most electrophysiologists suggest lifelong anticoagulation for patients with elevated stroke risk score. Due to the increasing success rate of ablation, catheter-based therapy is considered the first-line treatment for paroxysmal AF patients intolerant or refectory to one medication or IIa for persistent patients in the ACC/AHA AF Ablation Guidelines in 2017. It remains a IIb indication for patients in long-standing persistent atrial fibrillation.

Stroke Prevention

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The decision whether to pursue long-term anticoagulation must be made in light of the patient’s risk for a cardioembolic event versus risk for a bleeding event. In nonvalvular AF, CHA2DS2-VASc has superseded the CHADS2 scoring system (C = congestive heart failure; H = hypertension; A = age [>75 years is 2 points]; D = diabetes; S = stroke, transient ischemic attack, or thromboembolic disease [2 points]; V = vascular disease, A = age 65-74 years; and Sc = sex category, with females getting 1 extra point). Patients with a CHA2DS2-VASc score of 0 are considered low risk, 1 to 2 are considered moderate risk, and >2 are considered high risk. Per guidelines, patients with a score of 0 do not merit anticoagulation. Patients with a score of 1 can be treated at the discretion of the physician with either aspirin or an oral anticoagulant (warfarin or a novel oral anticoagulant). Anticoagulation with either warfarin or a novel oral anticoagulant is recommended for all patients with a CHADS2VASC score of 2 or above.
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Increasing amounts of evidence now show that aspirin likely does not protect a person from stroke in AF and has recently been dropped from most of the ACC/AHA and European Atrial Fibrillation guidelines. Target INR for patients with a CHADS-VASc score of >1 is 2 to 3 and should be diligently monitored to avoid risk of stroke versus bleeding. Patients with hypertrophic cardiomyopathy or thyrotoxicosis with AF also have a high risk of stroke and should be anticoagulated irrespective of their CHADS-VASc score.
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Alternatives to warfarin now include several factor Xa inhibitors and a direct thrombin inhibitor.
1. 1.
  
  Dabigatran is a direct thrombin inhibitor indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In the RE-LY trial of 18,113 patients with mean CHADS2 score of 2.1, dabigatran 110 mg bid was noninferior to warfarin, and 150 mg bid was superior to warfarin in prevention of thromboembolic events. Bleeding risk was similar to that of warfarin for both doses. Idarucizumab has been approved as a dabigatran reversal agent. Onset is immediate, and it provides full reversal for at least 24 hours in most patients.
2. 2.
  
  Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) are also effective in reducing stroke and systemic embolism in patients with atrial fibrillation. The ARISTOTLE trial in patients at high risk for stroke (mean CHADS2 score 2.1) using apixaban, the ROCKET AF trial using rivaroxaban in patients with CHADS2 score 3.5, and the ENGAGE-AF trial using edoxaban in patients with a CHADS2 score of at least 2, showed that these anticoagulants reduce the risk of stroke, systemic embolism, and serious bleeding compared with warfarin. Rivaroxaban showed noninferior efficacy to warfarin in prevention of thromboembolism. Apixaban showed superior stroke reduction, reduced bleeding events, and an overall mortality benefit when compared with warfarin. Edoxaban showed noninferiority to warfarin with respect to stroke and systemic embolism prevention, with lower rates of bleeding and death from cardiovascular causes, but benefit was limited to patients with moderately impaired renal function. Rivaroxaban and edoxaban are dosed once a day, and apixaban is dosed twice a day. A factor Xa reversal agent, andexanet alfa, is awaiting FDA approval as a reversal for the anticoagulant effect of these agents.
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The decision to anticoagulate should be made irrespective of whether the atrial fibrillation is paroxysmal, persistent or permanent.
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For patients in whom anticoagulation with warfarin or other anticoagulants is contraindicated due to high bleeding risk, left atrial appendage exclusion is an alternative. Several methods can be used, including the Lariat procedure and the Atriclip, but these are still considered unproven for stroke prevention in AF. The Watchman device is a left atrial appendage occlusion device and is the only device approved by the FDA for stroke prevention specifically for patients with AF that require anticoagulation but have an appropriate reason to seek an alternative. Patients with surgical ligation of the LAA still require anticoagulation due to lack of clinical trials showing a stroke risk reduction and inconsistent techniques.
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Perioperative bridging anticoagulation in patients with AF: current guidelines advise perioperative continuation of warfarin in low-risk patients (CHADS2 score 0 to 2) and bridging anticoagulation in those at highest risk of thromboembolism (CHADS2 score 5 to 6). The recent BRIDGE Study found that for patients who require procedure-related warfarin interruption, forgoing bridging anticoagulation was noninferior to perioperative bridging with LMWH and decrease the risk of major bleeding. Based on this study, a no-bridging strategy is appropriate for lower-risk AF and minor procedures but in high-risk patients having major surgery the answer remains debatable.

Prognosis

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AF is associated with a 1.5- to 1.9-fold higher risk of death, which is in part due to the strong association between AF and thromboembolic events.
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AF is also independently associated with an increased risk of incident MI, especially in women and blacks.
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Development of AF predicts heart failure and is associated with a worse New York Heart Association Heart Failure classification. AF may also worsen heart failure in individuals who are dependent on the atrial component of the cardiac output.
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AF in the setting of acute myocardial infarction was associated with a 40% increase in mortality compared to patients in sinus rhythm.

Disposition

Factors associated with maintenance of sinus rhythm after cardioversion include:

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Left atrium diameter <60 mm
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Absence of mitral valve disease
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Short duration of AF

Referral

Refer to a cardiologist those patients in whom antiarrhythmic therapy or catheter-based/surgical intervention is being considered.

Pearls & Considerations

Comments

The number of patients anticoagulated in the United States is approximately half the amount that should be anticoagulated for AF, resulting in a large burden of stroke. The exact burden of AF needed to trigger the need for anticoagulation is not known, though recent pacemaker trials have suggested that as little as 6 min confers significant stroke risk. Reversal agents for the new class of anticoagulation are now available: idarucizumab for reversal of dabigatran; andexanet alfa for reversal of apixaban and rivaroxaban (pending FDA approval).

The American Academy of Family Physicians and the American College of Physicians provide the following recommendations for the management of newly detected AF:

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Rate control with chronic anticoagulation is the recommended strategy for the majority of asymptomatic patients with chronic AF. Rhythm control has not been shown to be superior to rate control (with chronic anticoagulation) in reducing morbidity and mortality, and may be inferior in some patient subgroups to rate control. Rhythm control is appropriate when based on other special considerations, such as patient symptoms, exercise tolerance, and patient preference.
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Patients with AF should receive chronic anticoagulation, unless they are at low risk for stroke as stated earlier or have specific contraindications.
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For patients with AF, the following drugs are recommended for their demonstrated efficacy in rate control during exercise and while at rest: atenolol, metoprolol, diltiazem, and verapamil (drugs listed alphabetically by class). Digoxin is effective only for rate control at rest and, therefore, should be used only as a second-line agent for rate control in AF.
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For patients who elect to undergo acute cardioversion to achieve sinus rhythm in AF, both direct-current cardioversion and pharmacologic conversion are appropriate options in an otherwise healthy patient.
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Both transesophageal echocardiography with short-term prior anticoagulation followed by early acute cardioversion (in absence of intracardiac thrombus) with postcardioversion anticoagulation vs. delayed cardioversion with preanticoagulation and postanticoagulation are appropriate management strategies for patients who elect to undergo cardioversion.
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Among patients with paroxysmal AF without previous antiarrhythmic drug treatment, ablation compared with antiarrhythmic drugs resulted in a lower rate of recurrent atrial tachyarrhythmias at 2 years. However, recurrence was frequent in both groups.
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Among patients with atrial fibrillation who undergo PCV, the risk of bleeding is lower among those who receive dual therapy with dabigatran and a P2Y₁₂ inhibitor (clopidogrel or ticagrelor) than among those who receive triple therapy with warfarin, a P2Y₁₂ inhibitor, and aspirin. Dual therapy has been shown to be noninferior to triple therapy with respect to the risk of thromboembolic events.¹

Ferri – Atrial Fibrillation