The prevalence, presentation, clinical significance, and long - term implications of atrial fibrillation depend heavily upon the clinical circumstance in which it occurs. Among the cross-sectional studies of prevalence, there is a large gradient across age categories, ranging from less than 0.5% in young adults to the range of 1 to5% through the decades from 40 to 70 years and reaching rates in excess of 10% in some beyond age 70. At each age, however, prevalence is powerfully influenced by the presence of disease, especially rheumatic mitral valve disease, but also nonrheumatic abnormalities.

The clinical presentation ranges ranges from a minimally symptomatic or asymptomatic incidental finding to acute pulmonary edema (fluid in the lungs) in patients with advanced mitral or aortic stenosis. Between these extremes atrial fibrillation may herald the presence of noncardiac disorders (e.g., thyrotoxicosis), alert to the significance of another cardiac disorder (e.g., Wolff-Parkinson-White syndrome), constitute a transient complicating factor of another cardiac disorder (e.g., acute myocardial infarction or systemic arterial hypertension), or occur as an isolated event having no inherent significance (e.g., lone paroxysmal atrial fibrillation in healthy young adults).

The hemodynamic consequences of artial fibrillation are due to two factors:

(1) the loss of atrial systole may impair ventricular function in the noncompliant ventricle (e.g., aortic stenosis, left ventricular hypertrophy) or the dilated ventricle with systolic dysfunction and
(2) a rapid ventricular rate encroaches upon diastolic filling of the left ventricle and the coronary arteries.

The risk of of embolism (dislodgement of heart chamber blood clot, which goes to the brain and blocks a blood vessel) and a resultant stroke is a long-term concern of special importance. Atrial fibrillation may occur in paroxysmal, persistent, and chronic patterns.

Figure 15b-1: Calcified left atrial thrombus. From J.M.Pappachan,M.D. and B.C. Bino M.D., Calcified Left Atrial Thrombus; Images in Clinical Medicine ,Volume 356:e9, New England Journal Medicine, March 8, 2007.

Figure 15b-2: Above thrombus in various positions(4) in left atrium due to contraction of cardiac muscle.

Atrial fibrillation is an arrhythmia, characterized by grossly disorganized atrial electrical activity, which is irregular in respect to both rate and rhythm (see figures 14, 15a, 15b).

Atrial fibrillatory waves are best seen in leads V1 and usually clearly evident in II, III, AVF of the EKG. The waves are large, coarse or almost imperceptible (see figure 14).

In absence of discernible atrial electrical activity, a grossly irregular ventricular rhythm still suggest the presence of atrial fibrillation. Coarse atrial fibrillation waves (f) may be confused with atrial flutter, but the irregular ventricular response is helpful in making the distinction (see figure 15a).

In contrast, obvious, coarse flutter waves (really "f" waves) with a regular ventricular response, especially if slow, suggest the coexistence of high grade AV block with atrial fibrillation.

Origin of atrial fibrillation

1). A discharge from a single rapidly firing focus (or foci), usually located in or near the pulmonary veins can precipitate and perpetuate this tachycardia (see figure 11h). These foci may mimic the appearance of atrial fibrillation on the surface electrocardiogram or, more commonly, may degenerate or trigger classic atrial fibrillation. Repeated episodes of this arrhythmia can result in a marked shortening of the atrial refractory period and a loss of the normal lengthening of atrial refractiveness at slower heart rates. This phenomenon called atrial remodelling may be reversible with maintenance of sinus rhythm.

Pretreatment with verapamil, a calcium channel blocker, may markedly reduce the extent of remodelling, suggesting that cytosolic calcium overload is a contributory factor. The use of verapamil in conjunction with antiarrhythmic drugs before cardioversion may reduce the risk of recccurence of arrhythmia.

2). Multiple, small wavelets (circuits) of reentry are involved in most cases of atrial fibrillation, arising constantly in the atria, which are diseased by fibrosis and/or inflammation (see animation, figure 159). These circuits collide, become extinguished and arise again. The" life-time" of each individual wavelet is rather short; within either the left or right atrium, a whirling wavelet seldom survives a period of longer than a few hundred milliseconds. It is crucial to the perpetuation of atrial fibrillation that each atrium gets a constant supply of "new" impulses from the other atrium.

A critical mass of atrial tissue is required to sustain the minimal number of simultaneous circuits necessary for the perpetuation of the arrhythmia. The critical number of wandering wavelets for perpetuation of fibrillation is higher than three and less than or equal to six. The number of wavelets at any given moment is determined by the balance between the disappearance of "old " wavelets and the genesis of new "ones". Dying out of existing wavelets can be caused by fusion or collision with another wavelet, by reaching the border of the atrium, and because the advancing depolarization wave meets an area where the myocardium has not recovered its excitability from a foregoing activation.

New wavelets are formed by the division of an existing wave at a local area of conduction block, an offspring traversing toward the other atrium, and possible sources of impulse formation (see animation, figure 160). The multiple fragmented wavelets, which continuously change their width and direction and constantly travel in only partially recovered tissue, are propagating with highly varying velocity.

The two above explanations for fibrillation are not necessarily mutually exclusive. It is quite conceivable that in cases in which fibrillation continues for many years, both mechanisms act together.

Reference:Alessie,A. and others,Experimental Evaluation of Moe's Multiple Wavelet Hypothesis of Atrial Fibrillation,Zipes,D.P. and Others,Cardiac electrophysiology and Arrhythmias;Orlando,Fa.,Grune and Stratton,1985,265-75.

Triggers that may initiate the arrhythmia include changes in autonomic tone (see definition autonomic nervous system), acute or chronic changes in in atrial wall tension, atrial ectopic foci (including foci from pulmonary veins), and local factors.

Drugs can prevent atrial fibrillation by increasing the circuit wavelength, and invasive techniques can prevent it by decreasing the size of the atrial segments.

For example, the maze procedure (requiring cardiopulmonary bypass) consists of the excision of the atrial appendages, isolation of the pulmonary veins, and creation of a narrow, tortuous path of atrial tissue by carefully placed incisions, which directs the sinus node impulses across the atria to the atrioventricular node. The incisions are placed so that no area is wide enough to sustain multiple reentry circuits, and thus atrial fibrillation cannot occur. Several dead-end alleyways create a maze-like pathway and permit the depolarization of all the atrial tissue.

There is evidence that minimally invasive surgery and cryoablation can be used to accomplish the maze procedure in the beating heart without cardiopulmonary bypass.

Reference:Falk,R.H.,Atrial Fibrillation,N Engl J Med,Vol.344,No.14,April5,2001,1067-1078.

Figure 11h click for larger picture

The fact that a single focus can definitely cause some forms of atrial fibrillation facilitates catheter ablation to eliminate the arrhythmia and thus, offer a cure for some patients (see figure 11e). Patients with this type of atrial fibrillation are frequently young with structurally normal hearts, have paroxymal episodes, and the EKG often often shows bursts of an atrial tachycardia or frequent premature atrial complexes, sometimes initiating the atrial fibrillation.

Figure11e click for larger picture	Figure11g click for larger picture

The atrial focus is most commonly located in the pulmonary veins (figures 104b, 105a), more often in the upper than in the lower (see figure 11g), and can be ablated by transseptal techniques (passing special catheters and guidewires across the interatrial septum into the left atrium and on into the pulmonary veins and delivering radiofrequency energy to the suspected pulmonary vein focus).

Figure 11a click for big picture

The ostia of the pulmonary veins are explored to 15mms. into the vessel from the ostia to prevent stenosis, where the radiofrequency ablation is applied (see figures 11a, 11b, 11c)

Figure 11b click for big picture		Figure 11c click for big picture

Reference:Haissaguerre M. and others,Catheter ablation of chronic atrial fibrillation targeting the reinitiating triggers,J.Cardiovasc. Electrophysiol.2000;1112-10).

The P-wave morphology of the PAC or atrial tachycardia from the pulmonary vein can be used to help locate the responsible pulmonary vein for the atrial fibrillation.

The site of focal atrial fibrillation can be predicted from close analysis of mapping the sequence of coronary sinus activation and its relationship to right atrial eletrograms, which may limit the mapping of all the pulmonary veins. It has been found that left upper and lower PV pacing is associated with early activation of distal coronary sinus (CS). Left upper PV pacing is associated with high right atrial activation (HRA) and HIS atrial activation prior to proximal CS. Pacing of right sided PVs is associated with proximal to distal CS activation. Right upper PV pacing is associated with early activation of HRA prior to HIS and CS activation. Right lower PV pacing is associated with HIS atrial activation prior to HRA.

Reference:Zipes Douglas,MD, Journal of American College of Cardiology,vol.36,no.6,2000,Nov.15,pp.1746-8l.

Reference:Davendra,M. AND OTHERS,JACC, Abstracts,Cardiac Arrhythmias, Prediction of Site of Focal Atrial Fibrillation from Sequence of Coronary Activation and its Relationship to Right Atrial Electrograms,Feb.2001,p.118a

Atrial fibrillation may be minimally symptomatic to asymptomatic, or associated with fatigue, palpitations, nonspecific symptoms, reduced quality of life, reduced memory in elder patients, acute pulmonary edema (lungs full of fluid with severe shortness of breath) occurring in mitral stenosis or aortic stenosis.

It may be associated with thyrotoxicosis (excess thyroid hormone in the blood stream), WPW syndrome (an atrial tachycardia), hypertension, complication of acute myocardial infarction (heart attack).
It may also be of no significance.
See below for continuation.

Prevalence in young adults is less than 0.5%, but is 1 to 5% in ages 40 to 70, and over 10% in those over 70 years.
The incidence is influenced by the presence of mitral valve disease.

It can be caused by noncardiac disorders like thyrotoxicosis (excessive levels of throid hormone in the blood) as well as other cardiac disorders like WPW syndrome (see figure 3,3a), acute myocardial infarction(see definition electrocardiogram on this website,figures94-2,94-6,94-7,94-8 table 1), and hypertension (high blood pressure, see definition" hypertension" on this website). It can occur even in healthy people.

Figure 3 click for big picture

The consequences include loss of atrial systole (contraction)causing a decrease in ventricular stroke volume of up to 20% and rapid irregular ventricular rates with wide swings, risk of embolism (dislodgement of blood clots formed in the heart chambers with dissemination into other arteries through the body) and stroke. The tachycardia can cause in ultrastructural changes that cause a reversible ventricular dysfunction.
EKG features (see figures 14, 15a, 15b): The ventricular response is irregular, whereas in atrial flutter it is regular.

A thorough investigation is necessary to determine the cause:

1) Primary electrical cause
2) Hemodynamic abnormalities
3) Systemic abnormalities like thyrotoxicosis
4) Unrecognized heart disease must be ruled out (echocardiography is invaluable for evaluating cardiac abnormalities).
5) Pulmonary embolism and thyroid disease (detected with thyriod function tests) must be considered
6) If no etiology is found, then lone atrial fibrillation carries a good prognosis.

Chronic lone atrial fibrillation could indicate a higher risk. However, excessive cigarettes, alcohol and/or coffee consumption, stress, and fatigue may be causative factors.

If organic heart disease is found, it should be treated appropriately.

In the absence of heart disease, episodes of A.F. of less than 48 hours are managed conservatively. Rest, mild sedation, adding digoxin, intravenous(iv) diltiazem, iv beta-blocker, or some combination for control of the ventricular rate is an acceptable approach (see tables 1 and 2).

Although the atrial rate usually exceeds 350 beats/min., the mean resting ventricular rate in a patient with atrial fibrillation of new onset is between 110 and 130/min. In patients with the Wolff-Parkinson-White syndrome and a short refractory period of the accessory pathway, the ventricular response may exceed 250/min. In such cases, the electrocardiogram demonstrates a wide-complex QRS tachycardia, due to predominant accessory pathway conduction (see figure 3). A resting ventricular rate higher than 150/min. in the absence of preexcitation should raise the suspicion of a hyperadrenergic state such as occurs in thyrotoxicosis, fever, or acute gastrointestinal bleeding. A slow rate in the absence of medication may occur with high vagal tone in young athletes or in patients with conduction-system disease.

If heart disease is present and especially if the hemodynamic (stiff ventricles with low output due to heart muscle weakness, and mitral valve disease and/or coronary atherosclerosis) condition require either the mechanical benefit of atrial systole or a slow ventricular rate for adequate diastolic filling of the ventricles, immediate reversion to a sinus rhythm or slowing of the ventricular rate may be mandatory.

Immediate cardioversion (electrical shock to the chest overlying the heart) may be needed, if there are signs of heart failure. If the patient is stable, digoxin, intravenous (IV) verapamil (beta-blocker, medication), iv diltiazem, or procainamide (antiarrhythmic drug) or some combination may be tried (see table 1 and 2).

Even if their condition is clinically stable, patients with atrial fibrillation and a wide-complex (QRS) ventricular response related to the preexcitation syndrome should also be considered for early electrical cardioversion, since the response to antiarrhythmic agents is unpredictable in such patients and most agents used for control are contraindicated.

In the absence of underlying heart disease long term pharmacologic therapy may be used to prevent recurrence (see table 2).

In trials of anticoagulant therapy, patients with paroxysmal atrial fibrillation had the same risk as subjects with persistent atrial fibrillation. Thus, unless a patient with paroxysmal arrhythmia is younger than 65 years old and has no hypertension or underlying herat disease, long term warfarin therapy should be instituted.

Antiarrhythmic-Drug Therapy

Several drugs have been shown to be effective in the treatment of paroxysmal atrial fibrillation, including propafenone, flecainide, and sotalol (see table 2). These agents often do not totally abolish the arrhythmia, but the increase the length of the interval between the paroxysms and reduce the symptoms but not necessarially the risk of thromboembolism. Also, patients with symptomatic arrhythmia may have numerous episodes of asymptomatic atrial fibrillation, which pose a risk of thromboembolism.

Use of antiarrhythmic-drugs by slowing the heart rate can convert symptomatic episodes to asymptomatic ones, but the risk of a stroke still remains. Holter monitoring (see definition of Holter monitoring) may be helpful inassessing these episodes.

Reference:Falk,R.H.,Atrial Fibrillation,N Engl J Med,Vol.344,No.14,April5,2001,1067-1078.

Once an episode of atrial fibrillation has lasted more than seven days, spontaneous conversionis rare and the condition is defined as persistent. Restoration of sinus rhythm has to balanced against relief of symptoms if present versus the likelihood of side effects, especially proarrhythmia. Pharmacologicconversion is successful in 10 to 30 % of cases, depending on the duration of the arrhythmia and the drug used.

So synchronized, direct-current cardioversion is usually required in order to restore sinus rhythm. This involves using at least 300 J of energy with most defibrillators currently in use. But the recent introduction of defibrillators with a biphasic wave form, rather than the traditional monophasic damped-sine wave form, is associated with a marked decrease in the energy rquired for atrial fibrillation and with fewer failures.

Failure to terminate an arrhythmia with a specific arrhythmic agent does not mean that the same drug will be ineffective in maintaining sinus rhythm after electrical cardioversion.

In some cases, sinus rhythm is not restored or is restored only briefly by electical cardioversion. In such a case, the use of intravenous ibutilide followed by another shock increases the likelihood of restoration and maintenance of sinus rhythm. But ibutilide has to be used with caution in patient with impaired ventricular function, since it may cause torsade de pointes (see defintion ventricular tachycardia) and the safety of this approach in patients already receiving another antiarrhythmic drug has not been established. If a patient fails to return to sinus rhythm even for one or two beats despite these measures, transvenous internal cardioversion may be successful.

Amiodarone has been shown to be superior to both sotalol and propafenone for the maintenance of sinus rhythm. To date, only dofetilide and amiodarone have been shown not to increase mortality when prescribed to patients with heart failure.

Reference:Falk,R.H.,Atrial Fibrillation,N Engl J Med,Vol.344,No.14,April5,2001,1067-1078.

Heart-rate control

The aims of pharmacologic control of the heart rate in patients with persistent atrial fibrillation are to minimize symptoms related to swings in heart rate and prevent excessive tachycardia during normal daily activities. Digoxin may be acceptable as the sole therapy in an elderly, sedentary patient, but ir is not very effective for preventing excessive tachycardia during moderate exertion. Beta-blocking agents, verapmil, and diltiazem are much more effective, and there is synergism between these drugs and digoxin. Beta-blocking agents are probably the drugs of choice in patients with atrial fibrillation and coronary artery disease, and they may also be valuable when systolic dysfunction is present.

Reference:Falk,R.H.,Atrial Fibrillation,N Engl J Med,Vol.344,No.14,April5,2001,1067-1078.

If elective cardioversion is to be used, 3 weeks of anticoagulation (use of coumadin (warfarin) to lower prothrom time, a measure of a protein produced by the liver) should proceed the procedure (to prevent blood clots and emboli) and should be continued until sinus rhythm has been maintained for four weeks after cardioversion.

An alternative approach has recently been suggested in patients who have been shown by transesophageal echocardiography(TEE) to be free of thrombi in the left atrium and its appendage (figures 146, 147, 148). They receive short term anticoagulant therapy with the use of low molecular weight heparin (as outpatients), which can serve as a bridge therapy to warfarin (versus intravenous unfractioned heparin for inpatients for 4-5 days as bridge therapy to warfarin).

There are certain subgroups that may benefit from the TEE-guide strategy. First, the inpatientwith new-onset AF (< 4 weeks duration), regardless of risk profile, may benefit from early cardioversion using the TEE strategy. This may be particularly important for high risk patients (such as those with congestive heart failure, previous embolism or hemodynamic instability) in whom the prompt return of normal sinus rhythm would be beneficial.

Second, the high risk patient may benefit from further risk stratification by TEE to identify left atrial appendage thrombus, severe spontaneous echocardiographic contrast or complex atheroma (figures 146, 147, 148). The identification of a thrombus before cardioversion would lead to cancellation of the cardioversion and more prolonged anticoaglation therapy.

Third, even for patients in whom the likehood of thrombus is low, eliminating the need for prolonged anticoagulation pre-cardioversion by ruling out the presence of thrombus would allow early cardioversion and avoid the delay for return of sinus rhythm.

Reference:Klein,A.L.,and others,Role of TEE-Guided Cardioversion of Patients With AF,JACC,Vol.37,No.3,2001,pp.691-701.

In a recent study of 1222 patients with atrial fibrillation of more than two days duration assigned to either treatment guided by findings on TEE or conventional therapy, it was found that there was no significant difference between the two groups in the rate of embolic events.But the rate of hemorrhagic events was significantly lower in the TEE group (apparently due to the duration of anticoagulation in the conventional group being almost double that with the other approach allowing more opportunity for bleeding), who also had a shorter time to cardioversion and a greater rate of successful restoration of sinus rhythm. At eight weeks, there were no significant differences between the two groups in the rates of death or maintenance of sinus rhythm or in functional status. Thus, the strategy of using TEE to guide treatment may be considered a safe and clinically effective alternative to the conventional treatment strategy.

Reference: Klein,A.L.,and others,USE OF TEE TO GUIDE CARDIOVERSION IN PATIENTS WITH ATRIAL FIBFILLATION,N ENGL MED,VOL.344,NO.19,MAY10,2001,1411-1420.

If cardioversion is not attempted, and there are recurring episodes of atrial fibrillation, then long term anticoagulation with coumadin (warfarin,a drug which lowers the prothrombin protein to prevent coagulation) is indicated to prevent emboli.

Pharmacologic or electrical cardioversion has not had a high rate of success. Usually only one attempt is made to convert with electrical cardioversion (1/3 will revert back to A.F.).

Catheter modification of the AV juncture (AV node) or complete ablation of the AV junction with permanent pacing may provide heart rate control.

A recent study reports that in the absence of underlying heart disease, survival among patients with atrial fibrillation after ablation of the artioventricular node is similar to expected survival in the general population. Long term survival is similar for patients with atrial fibrillation, whether they receive ablation or drug therapy. Control of the ventricular rate by ablation of the atrioventricular node and permanent pacing does not adverselly affect long term survival.

See use of radiofrequency ablation in cases of atrial fibrillation originating in the pulmonary veins described above.

Zipes Douglas,MD,Journal of American College of Cardiology,vol.36,no.6,2000,Nov.15,pp.1746-8l.

Ozcan,C. and others, LONG TERM SURVIVAL AFTER ABLATION OF THE ATRIOVENTRICULAR NODE AND IMPLANTATION OF A PERMANENT PACEMAKER IN PATIENTS WITH ATRIAL FIBRILLATION NEng J Med,Vol.344,No.14,April5,2001.

Anticoagulation (use of medicines like warfarin or heparin to prevent coagulation of blood to a degree to prevent blood clots from forming in the heart and other vessels).

This is very important in the management of patients with persistent or chronic atrial fibrillation, since patients with atrial fibrillation have a five fold increase in risk of stroke from embolism (blood clots thrown from heart to other vessels in the body).

Prolonged episodes of atrial fibrillation frequently cause mechanical dysfunction of the atrium. Restoration of sinus rhythm is generally associated with the normalization of function over a period of two to four weeks. Possibly because of the delayed recovery of atrial mechanical function, the risk of thromboembolism posed by atrial fibrillation seems to persist for a few weeks after cardioversion.

In rheumatic heart disease, the risk increases to 17 times a control group. Other high risk groups include dilated hearts due to cardiomyopathy, dilated left atrium, atrial fibrillation of recent onset, history of prior embolism, left ventricular wall increase thickness (hypertrophy), thyrotoxicosis, greater than 60 years of age, and prior to elective electrical cardioversion.

Bleeding is a risk when on long term anticoagulation therapy. Intracranial bleeding is one of its major complications.