'Atrial fibrillation' ('AF' or 'afib') is a
cardiac arrhythmia (abnormal heart rhythm) that involves the
two upper chambers (atria) of the
heart. It is the most common arrhythmia; risk increases with age, with 8% of people over 80 having AF. In atrial fibrillation, the electrical impulses that are normally generated by the
sinoatrial node are replaced by disorganized activity in the atria, leading to irregular conduction of impulses to the
ventricles that generate the heartbeat. The result is an irregular heartbeat. This may be continuous (persistent or permanent AF) or alternating between periods of a normal heart rhythm (paroxysmal AF).
Atrial fibrillation is often asymptomatic, but may result in symptoms of
palpitations,
fainting,
chest pain, or even
heart failure. It is also a leading cause of
stroke as the erratic motion of the atria leads to
blood stagnation which increases the risk of
blood clots that may travel from the heart to the
brain and other areas.
Atrial fibrillation may be treated with medications which either slow the heart rate or revert the heart rhythm back to normal. Synchronized electrical
cardioversion may also be used to convert AF to a normal heart rhythm. Surgical and catheter-based therapies may also be used to prevent atrial fibrillation in certain individuals. People with AF are often given
anticoagulants such as
warfarin to protect them from stroke.
Classification
The
American Heart Association,
American College of Cardiology, and the
European Society of Cardiology have proposed the following classification system based on simplicity and clinical relevance.
[1]
★ ''First detected atrial fibrillation'': any patient newly diagnosed with atrial fibrillation fits in this category, as the exact onset and chronicity of the disease is often uncertain.
★ ''Recurrent atrial fibrillation'': any patient with 2 or more identified episodes of atrial fibrillation is said to have ''recurrent'' atrial fibrillation. This is further classified into ''paroxysmal'' and ''persistent'' based on when the episode terminates without therapy. Atrial fibrillation is said to be paroxysmal when it terminates spontaneously within 7 days, most commonly within 24 hours. Persistent or chronic atrial fibrillation is AF established for more than seven days. Differentiation of paroxysmal from chronic or established AF is based on the history of recurrent episodes and the duration of the current episode of AF.
★ ''Lone atrial fibrillation'' (LAF) is defined as atrial fibrillation in the absence of clinical or echocardiographic findings of cardiopulmonary disease.
Patients with LAF who are under 65 have the best prognosis.
Signs and symptoms
Atrial fibrillation is usually accompanied by symptoms related to the rapid heart rate. Rapid and irregular heart rates may be perceived as
palpitations, exercise intolerance, and occasionally produce
angina (if the rate is fast and puts the heart under strain) and
congestive symptoms of
shortness of breath or
edema. Sometimes the arrhythmia will be identified only with the onset of a stroke or a
transient ischemic attack (TIA, stroke symptoms resolving within 24 hours). It is not uncommon to identify atrial fibrillation on a routine physical examination or
electrocardiogram (ECG/EKG), as it may be asymptomatic in many cases.
As most cases of atrial fibrillation are secondary to other medical problems, the presence of
chest pain or
angina, symptoms of
hyperthyroidism (an overactive
thyroid gland) such as
weight loss and
diarrhoea, and symptoms suggestive of lung disease would indicate an underlying cause. A previous history of stroke or TIA, as well as
hypertension (high blood pressure),
diabetes,
heart failure and
rheumatic fever, may indicate whether someone with atrial fibrillation is at a higher risk of complications.
Diagnosis
Routine primary care visit
This estimated
sensitivity of the routine primary care visit is 64%. This low result probably reflects the pulse not being checked routinely or carefully.
[4]
Electrocardiogram
ECG of atrial fibrillation (top) and sinus rhythm (bottom). The purple arrow indicates a P wave, which is lost in atrial fibrillation.
Atrial fibrillation is diagnosed on an
electrocardiogram, an investigation performed routinely whenever irregular heart beat is suspected. Characteristic findings are the absence of P waves, with unorganized electrical activity in their place, and irregularity of R-R interval due to irregular conduction of impulses to the ventricles.
When electrocardiograms are used for screening, the SAFE trial found that electronic software,
primary care physicians and the combination of the two had the following sensitivities and specificities:
[5]:
★ Interpreted by software:
sensitivity = 83%,
specificity = 99%
★ Interpreted by a primary care physician: sensitivity = 80%, specificity = 92%
★ Interpreted by a primary care physician with software: sensitivity = 92%, specificity = 91%
If paroxysmal AF is suspected but the
electrocardiogram shows a regular rhythm, episodes may be documented with the use of
Holter monitoring (continuous ECG recording for 24 hours). If the symptoms are very infrequent, longer periods of continuous monitoring may be required.
Other investigations
While many cases of AF have no definite cause, it may be the result of various other problems (see below). Hence,
renal function and
electrolytes are routinely determined, as well as
thyroid-stimulating hormone (commonly suppressed in
hyperthyroidism and of relevance if
amiodarone is administered for treatment) and a
blood count.
A
chest X-ray is generally performed. This may reveal an underlying problem in the lungs or the blood vessels in the chest.
An
echocardiogram is generally performed in newly diagnosed AF, as well as if there is a major change in the patient's clinical state. This ultrasound-based scan of the heart may help identify
valvular heart disease (which may increase the risk of stroke manifold), left and right atrial size (which indicates likelihood that AF may become permanent), left ventricular size and function, peak right ventricular pressure (
pulmonary hypertension), presence of left ventricular hypertrophy and pericardial disease. Normal echocardiography (transthoracic or TTE) has a low sensitivity for identifying
thrombi (blood clots) in the heart; if this is suspected - e.g. when planning urgent electical cardioversion - a
transesophageal echocardiogram is preferred.
In acute-onset AF associated with
chest pain,
cardiac troponins or other markers of damage to the heart muscle may be ordered.
Coagulation studies (
INR/aPTT) are usually performed, as
anticoagulant medication may be commenced.
Causes
AF is linked to several cardiac causes, but may occur in otherwise normal hearts. Known associations include:
★ Primary heart diseases
coronary artery disease,
mitral stenosis (e.g. due to
rheumatic heart disease or
mitral valve prolapse),
mitral regurgitation,
hypertrophic cardiomyopathy (HCM),
pericarditis,
congenital heart disease, previous
heart surgery
★ Lung diseases (such as
pneumonia,
lung cancer,
pulmonary embolism,
sarcoidosis)
★
High blood pressure
★ Excessive
alcohol consumption ("
binge drinking" or "
holiday heart syndrome")
★
Hyperthyroidism
★
Carbon monoxide poisoning
★ Dual-chamber
pacemakers in the presence of normal atrioventricular conduction.
[6]
Genetics
A
family history of AF increases risk by 30% increased risk.
[7] Various genetic mutations may be responsible.
[8]
Pathophysiology
| Conduction |
| Sinus rhythm | Atrial fibrillation | |
The normal
electrical conduction system of the heart allows the impulse that is generated by the
sinoatrial node (SA node) of the heart to be propagated to and stimulate the
myocardium (muscle of the heart). When the myocardium is stimulated, it contracts. It is the ordered stimulation of the myocardium that allows efficient contraction of the heart, thereby allowing blood to be pumped to the body.
In atrial fibrillation, the regular impulses produced by the sinus node to provide rhythmic contraction of the heart are overwhelmed by the rapid randomly generated electrical discharges produced by larger areas of atrial tissue, often localized to the
pulmonary veins. It can be distinguished from
atrial flutter, which is a more organized electrical circuit usually in the right atrium that produces characteristic saw-toothed p-waves on the electrocardiogram; in atrial flutter, the discharges circulate rapidly (at a rate of 300 beats per minute) around the atrium; in AF, there is no regularity of this kind at all.
An organized electrical impulse in the atrium produces atrial contraction; the lack of such an impulse, as in atrial fibrillation, produces stagnant blood flow, especially in the atrial appendage and predisposes to
clotting. The dislodgement of a clot from the atrium results in an embolus, and the damage produced is related to where the circulation takes it. An embolus to the brain produces the most feared complication of atrial fibrillation, namely stroke, while an embolus may also lodge in the mesenteric circulation (the circulation supplying the abdominal organs) or digit, producing organ-specific damage such a
bowel ischemia or ischemia of the fingers or toes.
Treatment
The main goals of treatment of atrial fibrillation are to prevent temporary circulatory instability and to prevent
stroke. Rate and rhythm control are principally used to achieve the former, while
anticoagulation may be required to decrease the risk of the latter.
[9] In emergencies, when circulatory collapse is imminent due to uncontrolled
tachycardia, immediate
cardioversion may be indicated.
The primary factors determining atrial fibrillation treatment are duration and evidence of hemodynamic instability.
Cardioversion is indicated with new onset AF (for less than 48 hours) and with hemodynamic instability. If rate and rhythm control can not be maintained by medication or cardioversion,
electrophysiological studies with pathway
ablation may be required.
Rate and rhythm control
AF can cause disabling and annoying symptoms.
Palpitations,
angina, lassitude (weariness), and decreased exercise tolerance are related to rapid heart rate and inefficient cardiac output caused by AF. Furthermore, AF with a persistent rapid rate can cause a form of
heart failure called
tachycardia induced cardiomyopathy. This can significantly increase mortality and morbidity, which can be prevented by early and adequate treatment of the AF.
There are two ways to approach these symptoms: rate control and rhythm control. ''Rate control'' treatments seek to reduce the heart rate to normal, usually 60 to 100 beats per minute. ''Rhythm control'' seeks to restore the normal heart rhythm, called normal sinus rhythm. Studies suggest that rhythm control is mainly a concern in newly diagnosed AF, while rate control is more important in the chronic phase. Rate control with anticoagulation is as effective a treatment as rhythm control in long term mortality studies, the AFFIRM Trial.
[ A comparison of rate control and rhythm control in patients with atrial fibrillation, Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD, , , N Engl J Med, 2002 PMID 12466506]
Rate control
Rate control is achieved with medications that work by slowing the generation of impulses from the atria and the conduction of those impulses from the atria to the ventricles. This can be done with:
★
Beta blockers (preferably the "cardioselective" beta blockers such as
metoprolol,
atenolol,
bisoprolol)
★
Cardiac glycosides (i.e.
digoxin)
★
Calcium channel blockers (i.e.
diltiazem or
verapamil)
In refractory cases, where none of the above drugs are sufficient, a variety of other antiarrhythmic drugs may be used, most commonly including
quinidine,
flecainide,
propafenone,
disopyramide,
sotalol, or
amiodarone. Of these, only propafenone, sotalol, and amiodarone (which possess some beta blocking activity) control the ventricular rate; the others may maintain sinus rhythm, but may actually increase the ventricular rate. Many of these drugs are less frequently used today than in the past. All (with the possible exception of amiodarone) increase the risk of
ventricular tachycardia. In symptomatic patients with normal heart function, however, the small increase in risk is usually felt to be acceptable. In the presence of heart failure, the only antiarrhythmic drugs thought to be safe are amiodarone and dofetilide. In the United States, many of these agents are not approved by the
FDA for this use.
Rhythm control
Rhythm control methods include electrical and chemical cardioversion:
★ ''
Electrical cardioversion'' involves the restoration of normal heart rhythm through the application of a DC electrical shock.
★ ''
Chemical cardioversion'' is performed with drugs, such as
amiodarone,
dronedarone[10],
procainamide,
ibutilide,
propafenone or
flecainide.
The
anti-arrhythmic medications often used in either pharmacological cardioversion or in the prevention of relapse to AF alter the flux of ions in heart tissue, making them less excitable, setting the stage for spontaneous and durable cardioversion. These medications are often used in concert with electrical cardioversion. However, the AFFIRM study showed no difference in risk of stroke in patients who have converted to a normal rhythm with anti-arrhythmic treatment, compared to those who have only rate control.
The main risk of cardioversion is systemic embolization of a thrombus (blood clot) from the previously fibrillating left atrium. Cardioversion should not be performed without adequate anticoagulation in patients with more than 48 hours of atrial fibrillation. Cardioversion may be performed in instances of AF lasting more than 48 hours if a transesophogeal echocardiogram (TEE) demonstrates no evidence of clot within the heart.
Whichever method of cardioversion is used, approximately 50% of patient relapse within one year, although the continued daily use of oral antiarrhythmic drugs may extend this period. The key risk factor for relapse is duration of AF, although other risk factors that have been identified include the presence of structural heart disease, and increasing age.
Radiofrequency ablation
In patients with AF where rate control drugs are ineffective and it is not possible to restore sinus rhythm using cardioversion, non-pharmacological alternatives are available. For example, to control rate it is possible to destroy the bundle of cells connecting the upper and lower chambers of the heart - the atrioventricular node - which regulates heart rate, and to implant a pacemaker instead. A more complex technique, which avoids the need for a pacemaker, involves ablating groups of cells near the pulmonary veins where atrial fibrillation is thought to originate, or creating more extensive lesions in an attempt to prevent atrial fibrillation from establishing itself.
Ablation is a newer technique and has shown some promise for cases of recurrent AF that are unresponsive to conventional treatments. Radiofrequency ablation (RFA) uses radiofrequency energy to destroy abnormal electrical pathways in heart tissue. The energy emitting probe (electrode) is placed into the heart through a catheter inserted into veins in the groin or neck. Electrodes that can detect electrical activity from inside the heart are also inserted, and the electrophysiologist uses these to "map" an area of the heart in order to locate the abnormal electrical activity before eliminating the responsible tissue.
Most AF ablations consist of isolating the pulmonary veins (PV), which are located on the posterior wall of the left atrium. All veins from the body (including neck and groin) lead to the right atrium. In order to get to the left atrium the catheters must get across the atrial septum. This is done by piercing a small hole in the septal wall. This is called a transeptal approach. Once in the left atrium, the physician may perform ''Wide Area Circumferential Ablation'' (WACA) to electrically isolate the PVs from the left atrium.
Some more recent approaches to ablating AF is to target sites that are particularly disorganized in both atria as well as in the coronary sinus (CS). These sites are termed ''complex fractionated atrial electrogram'' (CFAE) sites.[11]. It is believed by some that the CFAE sites are the cause of AF, or a combination of the PVs and CFAE sites are to blame. New techniques include the use of cryoablation (tissue freezing using a coolant which flows through the catheter), and microwave ablation, where tissue is ablated by the microwave energy "cooking" the adjacent tissue.
This is an area of active research, especially with respect to the RF ablation technique and emphasis on isolating the pulmonary veins that enter into the left atrium. The main problem in 2006 is that the procedure is only 70-80% effective at best -- and causes stroke in about 1% of patients.
Surgery
Main articles: Maze procedure
James Cox, MD, and associates developed the Cox maze procedure, an open-heart surgical procedure intended to eliminate atrial fibrillation, and performed the first one in 1987. "Maze" refers to the series of incisions made in the atria (upper chambers of the heart), which are arranged in a maze-like pattern. The intention was to eliminate AF by using incisional scars to block abnormal electrical circuits (atrial macroreentry) that AF requires. This procedure required an extensive series of endocardial (from the inside of the heart) incisions through both atria, a median sternotomy (vertical incision through the breastbone) and cardiopulmonary bypass (heart-lung machine). A series of improvements were made, culminating in 1992 in the Cox maze III procedure, which is now considered to be the "gold standard" for effective surgical cure of AF. The Cox maze III is sometimes referred to as the "traditional maze", the "cut and sew maze", or simply the "maze".[12] Minimaze surgery is minimally invasive cardiac surgery similarly intended to cure atrial fibrillation. "Minimaze" refers to "mini" versions of the original maze procedure. These procedures are less invasive than the Cox maze procedure and do not require a median sternotomy (vertical incision in the breastbone) or cardiopulmonary bypass (heart-lung machine). These procedures use microwave, radiofrequency, or acoustic energy to ablate atrial tissue near the pulmonary veins.
Anticoagulation
The underlying problem is that if a patient has a yearly risk of stroke that is less than 2%, then the risks associated with taking warfarin outweigh the risk of getting a stroke.[13][14]
Determining risk
The risk of systemic embolization (atrial clots migrating to other organs) depends strongly on whether there is an underlying structural problem with the heart (e.g. mitral stenosis) and on the presence of other risk factors, such as diabetes and high blood pressure. Finally, patients under 65 are much less likely to develop embolization compared with patients over 75. In young patients with few risk factors and no structural heart defect, the benefits of anticoagulation may be outweighed by the risks of hemorrhage (bleeding). Those at a low risk may benefit from mild (and low-risk) anticoagulation with aspirin (or clopidogrel in those who are allergic to aspirin). In contrast, those with a high risk of stroke derive most benefit from anticoagulant treatment with warfarin or similar drugs.
In the United Kingdom, the NICE guidelines recommend an algorithm approach.[15]
The CHADS2 score is the best validated clinical prediction rule for determining risk of stroke (and therefore who should be anticoagulated); it assigns points (totaling 0-6) depending on the presence or absence of:
★ 'C'—congestive heart failure
★ 'H'—hypertension
★ 'A'—age 75 or older
★ 'D'—diabetes mellitus
★ 'S2'—previous stroke or transient ischemic attack
Patients with a CHADS2-score of 0 are a low risk (aspirin only), 1-2 moderate risk (aspirin ''or'' warfarin advised), and 3 high risk (warfarin advised).[16]
Chronic anticoaguation
Among patients with "non-valvular" atrial fibrillation, anticoagulation can reduce stroke by 60% while antiplatelet agents can reduce stroke by 20%. [17][18]. There is evidence that aspirin and clopidogrel are effective when used together, but the combination is still inferior to warfarin.[19]
Warfarin treatment requires frequent monitoring with a blood test called the internation normalized ratio (INR); this determines whether the correct dose is being used. In atrial fibrillation, the usual target INR is between 2.0 and 3.0 (higher targets are used in patients with mechanical artificial heart valves, many of whom may also have atrial fibrillation). A high INR may indicate increased bleeding risk, while a low INR would indicate that there is insufficient protection from stroke.
Acute anticoagulation
If anticoagulation is required urgenty (e.g. for cardioversion), heparin or similar drugs achieve the required level of protection much quicker than warfarin, which may take several days to reach adequate levels.
In the initial stages after an embolic stroke, anticoagulation may be risky, as the damaged area of the brain is relatively prone to bleeding (hemorrhagic transformation).[20] As a result, a clinical practice guideline by National Institute for Health and Clinical Excellence recommends that anticoagulation should begin two weeks after stroke if no hemorrhage occurred.
Elderly patients
The very elderly (patients aged 75 years or more) may benefit from anticoagulation provided the their anticoaguation does not increase hemorrhagic complications, which is a difficult goal. Patients aged 80 years or more may be especially susceptible to bleeding complications, with a rate of 13 bleeds per 100 person-years.[21] A rate of 13 bleeds per 100 person years would seem to preclude use of warfarin; however, a randomized controlled trial found benefit in treating patients 75 years or over with a number needed to treat of 50.[22] Of note, this study had very low rate of hemorrhagic complications in the warfarin group.
Prognosis
Atrial fibrillation can usually be controlled with treatment. The natural tendency of atrial fibrillation, however, is to become a chronic condition. Chronic AF leads to an increased risk of death. Patients with atrial fibrillation are at significantly increased chance of stroke (about 2 to 7 times the regular population).
Patients with atrial fibrillation, even lone atrial fibrillation without other evidence of heart disease, are at increased risk of stroke during long term follow up.[23]A systematic review of risk factors for stroke in patients with nonvalvular atrial fibrillation concluded that the prior stroke/TIA is the most powerful risk factor for future stroke, followed by advancing age, hypertension, diabetes.[24] The risk of stoke whether the lone atrial fibrillation was an isolated episode, recurrent, or chronic.[25]
Screening
Screening for atrial fibrillation is not generally performed, although a study of routine pulse checks or electrocardiograms during routine office visits, found that the annual rate of detection of atrial fibrillation in elderly patients improved from 1.04% to 1.63%; selection of patients for prophylactic anticoagulation would improve stroke risk in that age category.[4]
Epidemiology
Atrial fibrillation is common among older adults. Prevalence in people over 80 is about 8%.[27] In developed countries, the number of patients with atrial fibrillation is likely to increase during the next 50 years, due to the growing proportion of elderly individuals.[28]
History
Because the diagnosis of atrial fibrillation requires measurement of the electrical activity of the heart, atrial fibrillation was not truly described until 1874, when Edmé Félix Alfred Vulpian observed the irregular atrial electrical behavior that he termed ''"fremissement fibrillaire"'' in dog hearts.[29] In the mid-eighteenth century, Jean-Baptiste de Sénac made note of dilated, irritated atria in people with mitral stenosis.[30] The irregular pulse associated with AF was first recorded in 1876 by Carl Wilhelm Hermann Nothnagel and termed ''"delirium cordis"'', stating that "[I]n this form of arrhythmia the heartbeats follow each other in complete irregularity. At the same time, the height and tension of the individual pulse waves are continuously changing".[31] Correlation of delirium cordis with the loss of atrial contraction as reflected in the loss of ''a waves'' in the jugular venous pulse was made by Sir James MacKenzie in 1904.[32] Willem Einthoven published the first electrocardiogram showing AF in 1906.[33] The connection between the anatomic and electrical manifestations of AF and the irregular pulse of delirium cordis was made in 1909 by Carl Julius Rothberger, Heinrich Winterberg, and Sir Thomas Lewis.[34][35][36]
See also
★ Atrial flutter
★ Ashman phenomenon
References
1. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society, Fuster V, Rydén LE, Cannom DS, ''et al'', , , Circulation, 2006
2. Epidemiology and classification of atrial fibrillation, Levy S, , , J Cardiovasc Electrophysiol, 1998 PMID 9727680
3. Classification system of atrial fibrillation, Levy S, , , Curr Opin Cardiol, 2000 PMID 10666661
4. Screening versus routine practice in detection of atrial fibrillation in patients aged 65 or over: cluster randomised controlled trial, Fitzmaurice DA, Hobbs FD, Jowett S, ''et al'', , , , 2007
5. Accuracy of diagnosing atrial fibrillation on electrocardiogram by primary care practitioners and interpretative diagnostic software: analysis of data from screening for atrial fibrillation in the elderly (SAFE) trial, Mant J, Fitzmaurice DA, Hobbs FD, ''et al'', , , , 2007
6. Michael O. Sweeney et al., “Minimizing Ventricular Pacing to Reduce Atrial Fibrillation in Sinus-Node Disease,” N Engl J Med 357, no. 10 (September 6, 2007): 1000-1008, http://content.nejm.org/cgi/content/abstract/357/10/1000 (accessed September 6, 2007).
7. Parental atrial fibrillation as a risk factor for atrial fibrillation in offspring, Fox CS, Parise H, D'Agostino RB, ''et al'', , , JAMA, 2004
8. Connexins, conduction, and atrial fibrillation, Saffitz JE, , , N. Engl. J. Med., 2006
9. Management of atrial fibrillation: therapeutic options and clinical decisions, Prystowsky EN, , , Am J Cardiol, 2000 PMID 10822035
10. Bramah N. Singh et al., “Dronedarone for Maintenance of Sinus Rhythm in Atrial Fibrillation or Flutter,” N Engl J Med 357, no. 10 (September 6, 2007): 987-999, http://content.nejm.org/cgi/content/abstract/357/10/987 (accessed September 6, 2007).
11. A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate, Nademanee K, McKenzie J, Kosar E, Schwab M, Sunsaneewitayakul B, Vasavakul T, Khunnawat C, Ngarmukos T., , , J Am Coll Cardiol, 2004
12. An 8 1/2-year clinical experience with surgery for atrial fibrillation, Cox JL, Schuessler RB, Lappas DG, Boineau JP, , , Ann. Surg., 1996
13. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis, van Walraven C, Hart RG, Singer DE, ''et al.'', , , JAMA, 2002
14. Cost-effectiveness of preference-based antithrombotic therapy for patients with nonvalvular atrial fibrillation, Gage BF, Cardinalli AB, Owens D., , , Stroke, 1998
15. Clinical Guideline 36 - Atrial fibrillation National Institute for Health and Clinical Excellence
16. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation, Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ., , , JAMA, 2001
17. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation, Hart RG, Pearce LA, Aguilar MI, , , Ann Intern Med, 2007
18. Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks, Aguilar M, Hart R, Pearce L, , , Cochrane Database Syst Rev, 2007
19. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial, Connolly S, Pogue J, Hart R, ''et al'', , , Lancet, 2006
20. Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: a meta-analysis of randomized controlled trials, Paciaroni M, Agnelli G, Micheli S, Caso V, , , Stroke, 2007 ACP JC synopsis
21. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation, Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S, , , Circulation, 2007
22. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial, Mant J et al, , , Lancet, 2007
23. Characteristics and prognosis of lone atrial fibrillation. 30-year follow-up in the Framingham Study, Brand FN, Abbott RD, Kannel WB, Wolf PA, , , JAMA, 1985
24. Independent predictors of stroke in patients with atrial fibrillation: a systematic review, , , , Neurology, 2007
25. The natural history of lone atrial fibrillation. A population-based study over three decades, Kopecky SL, Gersh BJ, McGoon MD, ''et al'', , , N. Engl. J. Med., 1987
26. Screening versus routine practice in detection of atrial fibrillation in patients aged 65 or over: cluster randomised controlled trial, Fitzmaurice DA, Hobbs FD, Jowett S, ''et al'', , , , 2007
27. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study), Furberg CD, Psaty BM, Manolio TA, Gardin JM, Smith VE, Rautaharju PM, , , Am. J. Cardiol., 1994
28. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study, Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE, , , JAMA, 2001 PMID 11343485
29. Vulpian A. (1874). Note sur les effets de la faradisation directe des ventricules du coeur chez le chien. ''Archives de Physiologie Normale et Pathologique'' '6':975.
30. McMichael J. (1982). History of atrial fibrillation 1628-1819 Harvey-de Senac-Laennec. ''Br Heart J'' '48': 193-7. PMID 7049202.
31. Nothnagel H. (1876). Ueber arythmische Herzthatigkeit. ''Deutsches Archiv fur Klinische Medizin'' '17': 190-220.
32. MacKenzie J. (1904). The inception of the rhythm of the heart by the ventricle. ''Br Med J'' '1': 529-36.
33. Einthoven W. (1906). Le telecardiogramme. ''Archives Internationales de Physiologie'' '4': 132-64.
34. Rothberger CJ, Winterberg H. (1909). Vorhofflimmern und Arhythmia perpetua. ''Wiener Klinische Wochenschrift'' '22': 839-44
35. Lewis T (1909). Auricular fibrillation: a common clinical condition. ''Br Med J'' '2': 1528
36. From delirium cordis to atrial fibrillation: historical development of a disease concept, Flegel KM, , , Ann. Intern. Med., 1995
External links
★ American Heart Association page on atrial fibrillation
★ Atrial fibrillation at patient.co.uk
★ Bandolier (evidence-based medicine) resource on atrial fibrillation
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