1. 1
    Current Diagnosis

    • Detailed history and physical examination are important.

    • Symptoms fall on a broad spectrum from asymptomatic to palpitations, chest discomfort, shortness of breath, and decreased exercise tolerance.

    • Signs include irregular pulse, irregular jugular venous pulsations, variations in the intensity of the first heart sound, and loss of S4 heard in sinus rhythm.

    • Investigation includes 12-lead electrocardiogram (ECG) for confirmation, transthoracic echocardiogram for valvular abnormalities, and blood tests for thyroid, renal, and hepatic function.

    • Additional evaluations include Holter monitoring, event recording, electrophysiological studies, and chest radiograph.

  2. 2
    Current Therapy

    Heart Rate Control

    • β-Blockers: metoprolol (Lopressor, Toprol XL),1 propranolol (Inderal)

    • Non-dihydropyridine calcium channel blockers: diltiazem (Cardizem), Verapamil (Calan)

    •   Digoxin (Lanoxin)

    •   Amiodarone (Cordarone)1

    Rhythm Control

    • Antiarrhythmic drugs: amiodarone,1 flecainide (Tambocor), propafenone (Rythmol), sotalol (Betapace)

    •   Pharmacologic and electric cardioversion

    •   Ablation

    •   Suppression of AF through pacing

    Thromboembolism Prevention

    •   Aspirin 81 to 325 mg

    •   Warfarin (Coumadin)

    •   Dabigatran (Pradaxa)

    1 Not FDA approved for this  indication.

    1 Not FDA approved for this  indication.

  3. 3

    Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Current prevalence of 1% to 2% of populations is estimated to at least double in next 50 years. It is a very costly public health problem, with $3600 spent annually per patient in the European Union. The prevalence of AF increases with age, from less than 0.5% at age 40 to 50 years up to 8% to 10% in those older than 80 years. The lifetime risk of developing AF in 40-year-olds is about 25%. Men are more often affected than women, with the exception of women 75 years or older. The prevalence and incidence in the nonwhite population is less well studied.

  4. 4

    Atrial Factors

    Any kind of structural heart disease can trigger remodeling of both atria and ventricles. Structural remodeling facilitates initiation and perpetuation of AF. Atrial refractoriness shortens within the first days of new-onset AF. Even in patients with a single episode of AF, fibrosis and inflammatory changes have been documented.

    Electrophysiologic Mechanisms

    Focal mechanisms of triggered activity and re-entry have attracted much attention. The wavelet hypothesis suggests several independent wavelets propagating AF rather than a single focus. A familial component should be investigated with early-onset AF.

    AF reduces left atrial flow velocities, which causes delayed emptying from the atrial appendage and is implicated in thrombus formation.

  5. 5
    Causes and Risk Factors

    Reversible Causes

    AF can be related to temporary causes including alcohol use (holiday heart syndrome), surgery, myocardial infarction, pericarditis, pulmonary embolism, electrocution, hyperthyroidism, and other metabolic syndromes. AF remains a common early postoperative complication of cardiothoracic surgery. Successful treatment of underlying medical problems often causes termination of AF (Table 1).

    Table 1

    Types of Atrial Fibrillation

    Abbreviations: AF = atrial fibrillation; ECG =  electrocardiogram.

    Obesity is an important risk factor for development of AF. Studies suggest a possible physiologic basis. Increasing left atrial size correlates with increase in weight and regression.

    In young adults, 30% to 45% of cases of paroxysmal AF have no demonstrable underlying heart disease.

    Cardiovascular conditions associated with AF include mitral valve disease, heart failure, coronary artery disease, and hypertension associated with left ventricular hypertrophy. Other associations include hypertrophic obstructive cardiomyopathy, dilated cardiomyopathy, atrial septal defect, restrictive cardiomyopathies, cardiac tumors, and constrictive pericarditis. AF is commonly found in patients with obstructive sleep apnea.


  6. 6
    Clinical Manifestations

    Patients might or might not have symptoms with AF. Commonly associated symptoms include palpitations, shortness of breath, fatigue, decreasing exercise tolerance, and chest discomfort.

    Intermittent episodes of AF can progress in duration and frequency, and over time many patients develop sustained AF.

    An irregular pulse should raise the suspicion for AF. Patients might present initially with transient ischemic attack or ischemic stroke.

    Most patients experience asymptomatic episodes of arrhythmias before the AF is diagnosed. Patients with mitral valve disease and heart failure often have higher incidence of AF. For a patient with newly diagnosed AF, reversible causes such as pulmonary embolism, hyperthyroidism, pericarditis, and myocardial infarction should be investigated.

  7. 7

    An irregular pulse can raise the suspicion for AF, but ECG remains essential in diagnosing AF. AF is defined with the following characteristics:

    •   Arrhythmia absoluta: Absolutely irregular RR intervals

    •   No distinct P waves on ECG. Regular atrial activity is occasionally noted on lead V1.

    •   Atrial cycle length (interval between two atrial activations) is usually variable and less than 200 msec (> 300 beats/min).

    Numerous options are available to capture AF rhythm depending on the frequency of symptoms. A 12-lead ECG is recommended as a first step (Figure 1). Noncontinuous ECG methods include scheduled or symptom-activated ECGs, Holter monitoring (24 hours to 7 days), and an external loop recorder. An implantable loop recorder can be used to monitor over a 2-year period.

    FIGURE 1    Atrial fibrillation 12-lead electrocardiogram.

  8. 8
    Differential Diagnosis

    Arrhythmias that can mimic AF include atrial tachycardia, atrial flutter with variable atrioventricular (AV) block, frequent atrial ectopies, and antegrade AV node conduction. Any episode of suspected AF should be recorded by a 12-lead ECG. An ECG recording will help in differentiating AF from rare supraventricular arrhythmias with irregular RR intervals.

    Occasionally, use of AV node blocking using the Valsalva maneuver, carotid massage, or intravenous adenosine (Adenocard)1 may be necessary to establish the diagnosis.

  9. 9

    Management of patients with AF is aimed at reducing symptoms by rate control or correction of rhythm disturbances and prevention of thromboembolism. Rate control strategy attempts control of ventricular rate without restoration or maintenance of sinus rhythm. Rhythm control strategy attempts restoration and maintenance of sinus rhythm with attention to rate control. Regardless of the strategy chosen, the need for anticoagulation depends upon stroke risk and not on type of rhythm.

    Risk Stratification for Stroke and Thromboembolism

    The risk factor–based approach for patients with nonvalvular AF is CHA2DS2-VASc (Table 2). This new risk-stratification scheme builds on the original CHADS2 scheme by considering additional risk factors. Major risk factors are prior stroke or TIA or thromboembolism, and older age (≥ 75 years). Clinically relevant nonmajor risk factors include heart failure, moderate to severe systolic LV dysfunction (LV ejection fraction less than 40%), hypertension, diabetes, female sex, age 65 to 74 years, and vascular disease (myocardial infarction, peripheral artery disease, complex aortic plaque).

    Table 2

    CHA2DS2-VASc Score

    Risk Factor                                                                  Score
    Congestive heart failure, LV dysfunction 1
    Hypertension 1
    Age ≥ 75 years 2
    Diabetes mellitus 1
    Stroke, TIA, or thromboembolism 2
    Vascular disease (MI, PAD, complex aortic plaque) 1
    Age 65–74 years 1
    Sex category: female 1
    Maximum score 9

    Abbreviations: LV = left ventricular; MI = myocardial infarction; PAD = peripheral artery disease; TIA = transient ischemic  attack.

    There is a clear relationship between the CHA2DS2-VASc score and stroke rate. In patients with a CHA2DS2-VASc score of 2 or more, chronic anticoagulation therapy is recommended unless contraindicated. When using warfarin, the goal international normalized ratio (INR) is in the range of 2.0 to 3.0 (Table 3). An assessment of bleeding risk should be part of the patient assessment before starting anticoagulation. It is reasonable to use HAS-BLED (hypertension, abnormal kidney or liver function, stroke, bleeding history or predisposition, labile INR, elderly [more than 65 years old], drugs or alcohol use) to assess the bleeding risk in atrial fibrillation patients. The risk of falls is usually overstated. The patient needs to fall approximately 300 times per year for the risk of intracranial hemorrhage to outweigh the benefits of anticoagulation in the stroke prevention.

    Table 3

    Approach to Thromboprophylaxis

    CHA2DS2-VASc Score Recommended Therapy
    2 or more Anticoagulation
    1 Anticoagulation or aspirin 75–325 mg daily
    0 Aspirin 75–325 mg daily or no antithrombotic therapy

    Dabigatran has been approved by the FDA for nonvalvular AF. Dabigatran is a prodrug that is rapidly converted to an active direct thrombin inhibitor independent of cytochrome P-450.

    Rate Control

    The AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial found no difference in mortality or stroke rate between the patients assigned to either rhythm control or ventricular rate control strategies. The RACE (Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation) trial found rate control was not inferior to rhythm control for prevention of death.

    The RACE II study shows that lenient ventricular rate control less than 110 beats/min is not inferior to the strict rate control less than 80 beats/min. Lenient rate control is generally more convenient and requires fewer outpatient visits and generally fewer medications.

    None of the major trials demonstrated any significant difference in the quality of life with ventricular rate control compared to rhythm control. In older patients with persistent AF along with hypertension or heart disease, rate control is a reasonable initial therapy.

    Ventricular rates between 60 and 80 beats/min at rest and between 90 and 115 beats/min during moderate exercise is considered a goal for patients opting for rate control.

    Negative chronotropic medications like β-blockers, amiodarone,1 digitalis glycosides, or non-dihydropyridine calcium channel antagonists prolong the refractory period of the AV node, thus effectively controlling the heart rate (Table 4). Bradycardia and heart blocks are some of the side effects of these medications.

    Table 4

    Medications for Rate Control

    Abbreviation: N/A = not applicable.

    1  Not FDA approved for this indication.

    Rhythm Control

    Rhythm control in certain studies resulted in better exercise tolerance than rate control but did not show any improvement in the quality of life. In younger patients with paroxysmal atrial fibrillation, ablation is considered a better approach. For patients remaining symptomatic despite an adequately controlled ventricular rate, rhythm control is an appropriate next step. Antiarrhythmic agents (Table 5) significantly reduce the rate of recurrence of atrial fibrillation; the likelihood of maintaining the sinus rhythm is approximately doubled with the use of antiarrhythmic drugs. If one antiarrhythmic drug fails, it is acceptable to try another. QT prolongation and drug-induced torsades de pointes are some of the significant side effects of these medications. Amiodarone,1 flecainide (Tambocor), propafenone (Rythmol), and sotalol (Betapace) are often used in Western countries.

    Table 5

    Medications for Rhythm Control

    1  Not FDA approved for this indication.

    2  Not available in the United States.


    Cardioversion may be considered emergently or electively to restore the sinus rhythm in patients with atrial fibrillation. Anticoagulation is considered mandatory before elective cardioversion for atrial fibrillation of more than 48 hours or atrial fibrillation of unknown duration because of the increased risk of thromboembolism following cardioversion. The current data suggest patients need to be anticoagulated for at least 3 weeks before cardioversion. Immediate cardioversion should be performed in hemodynamically unstable patients, and patients should be anticoagulated before cardioversion. Transesophageal echo-guided cardioversion strategy may be applied as an alternative to precardioversion anticoagulation. Cardioversion can be performed with the help of drugs or electrical shocks.

    Dofetilide (Tikosyn) or flecainide (Tambocor) are usually tried before a direct current cardioversion. Pharmacologic cardioversion is usually most effective within 7 days after the onset of an episode of atrial fibrillation.


    Patients who are symptomatic or who have tachycardia-mediated cardiomyopathy that is related to the rapid ventricular rate and that cannot be controlled adequately with pharmacologic agents are most likely to benefit from AV node ablation in conjunction with permanent pacemaker implantation. Postablation anticoagulation should be continued for a minimum of 3 months and thereafter depending upon the individual stroke risk.


  10. 10

    Measures for primary prevention of AF have not been widely studied. Losartan (Cozaar)1 (LIFE trial) and candesartan (Atacand)1 (CHARM trial) reduced incidence of AF in hypertensive patients with LV hypertrophy and symptomatic heart failure, respectively. These results suggest a role for an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker in primary prevention of AF associated with hypertension, myocardial infarction, heart failure, or diabetes. Statins might protect against AF, but this has been inadequately explored. Dietary interventions, pharmacologic interventions, and pacing have insufficient data supporting their utility in preventing AF.


  11. 11
    Special Considerations

    Elderly Patients

    Elderly patients usually have multiple medical problems including cardiovascular comorbidities such as a higher incidence and prevalence rate of AF, higher thromboembolic risk, and higher bleeding risk. The prevalence of AF is as high as 18% in those older than 85 years. The Screening for Atrial Fibrillation in the Elderly (SAFE) trial found that ECG for irregular pulse is an effective screening tool. All patients older than 75 years who have AF should be considered for anticoagulation. In elderly patients, sinus rhythm is often difficult to maintain. For rate control, β-blockers and non- dihydropyridine calcium channel antagonists can be considered.

    Postoperative Atrial Fibrillation

    Atrial fibrillation is the most common complication after coronary artery bypass graft (CABG) surgery (30%), valvular surgery (40%), and combined CABG and valvular surgery (50%). The peak incidence of AF is during postoperative days 2 and 4. β-Blocker therapy is most effective in preventing postoperative atrial fibrillation. Prophylactic amiodarone1 decreases the incidence of postoperative AF and significantly shortens the duration of hospital stay.

    Hypomagnesaemia is an independent risk factor for postoperative AF. The use of statins is associated with lower risk of postoperative AF. The majority of the postoperative hemodynamically stable patients convert spontaneously to sinus rhythm within 24 hours of initial management, which includes correction of predisposing factors such as pain management, correcting electrolytes and metabolic abnormalities, addressing hypoxia, addressing anemia, and hemodynamic optimization.

  12. 12

    Camm A.J., Kirchhof P., Lip G.Y.H., et al. Guidelines for the management of atrial fibrillation. The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31:2369–2429.

    Hagens V.E., Crijins H.J., Veldhuisen D.J., et al. Rate control versus rhythm control for patients with persistent atrial fibrillation with mild to moderate heart failure: Results from the Rate Control versus Electrical cardioversion (RACE) study. Am Heart J. 2005;149:1106–1111.

    Lip G.Y.H., Nieuwlaat R., Pisters R., et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor–based approach: The Euro heart survey on atrial fibrillation. Chest.


    Olshansky B., Rosenfeld L.E., Warner A.L., et al. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: Approaches to control rate in atrial fibrillation. J Am Coll Cardiol. 2004;43:1201–1208.

    Van Gelder I.C., Groenveld H.F., et al. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med.


    Wann L.S., Curtis A., January C.T., et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on dabigatran): American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011;57:223– 242.

    1  Not FDA approved for this  indication.

    1  Not FDA approved for this  indication.

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