Atrial Fibrillation

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Atrial fibrillation (AF or afib) is an abnormal heart rhythm (cardiac arrhythmia) which involves the two small, upper heart chambers (the atria). Heart beats in a normal heart begin after electricity generated in the atria by the sinoatrial node spreads through the heart and causes contraction of the heart muscle and pumping of blood. In AF, the regular electrical impulses of the sinoatrial node are replaced by disorganized, rapid electrical impulses which result in irregular heart beats.

Atrial fibrillation is the most common cardiac arrhythmia. The risk of developing atrial fibrillation increases with age — AF affects four percent of individuals in their 80s. An individual may spontaneously alternate between AF and a normal rhythm (paroxysmal atrial fibrillation) or may continue with AF as the dominant cardiac rhythm without reversion to the normal rhythm (chronic atrial fibrillation). This variety of disorder is sometimes associated with the secretion of adrenalin under conditions of emotional stress in this age group.

Atrial fibrillation is often asymptomatic, but may result in symptoms of palpitations, fainting, chest pain, or even heart failure. These symptoms are especially common when atrial fibrillation results in a heart rate which is either too fast or too slow. In addition, the erratic motion of the atria leads to blood stagnation (stasis) which increases the risk of blood clots that may travel from the heart to the brain and other areas. Thus, AF is an important risk factor for stroke, the most feared complication of atrial fibrillation.

The symptoms of atrial fibrillation may be treated with medications which slow the heart rate. Several medications as well as electrical cardioversion may 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 blood thinners such as warfarin to protect them from strokes.

Current Research

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For current research articles click - here

Classification

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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.

First Detected

Any patient newly diagnosed with atrial fibrillation fits in this category, as the exact onset and chronicity of the disease is often uncertain.

Recurrent

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

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

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Atrial fibrillation is usually accompanied by symptoms related to either the rapid heart rate or embolization. Rapid and irregular heart rates may be perceived as palpitations, exercise intolerance, and occasionally produce angina and congestive symptoms of shortness of breath or edema. Sometimes the arrhythmia will be identified with the onset of a stroke or a transient ischemic attack (TIA). It is not uncommon to identify atrial fibrillation on a routine physical examination or electrocardiogram (ECG/EKG), as it may be asymptomatic in some cases.

Paroxysmal atrial fibrillation is the episodic occurrence of the arrhythmia and may be difficult to diagnose. Episodes may occur with sleep or with exercise, and their episodic nature may require prolonged ECG monitoring (e.g. a Holter monitor) for diagnosis.

Diagnosis

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Electrocardiogram

Atrial fibrillation is diagnosed on an electrocardiogram, an investigation performed routinely whenever irregular heart beat is suspected. Characteristic findings are (a "rhythm strip" of lead II is shown):

• * Absence of P waves
• * Unorganized electrical activity in their place
• * Irregularity of R-R interval due to irregular conduction of impulses to the ventricles

If paroxysmal AF is suspected, episodes may be documented with the use of Holter monitoring (continuous ECG recording for 24 hours or longer).

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. 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. A transesophageal echocardiogram may be indicated to identify any intracardiac thrombus.

Causes

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AF is linked to several cardiac causes, but may occur in otherwise normal hearts. Known associations include:

• Carbon monoxide poisoning
• High blood pressure
• Mitral stenosis (e.g. due to rheumatic heart disease or mitral valve prolapse)
• Mitral regurgitation
• Heart surgery
• Coronary artery disease
• Hypertrophic cardiomyopathy
• Excessive alcohol consumption ("binge drinking" or "holiday heart syndrome")
• Hyperthyroidism
• Hyperstimulation of the vagus nerve, usually by having large meals ("binge eating")
• Lung pathology (such as pneumonia, lung cancer, pulmonary embolism, Sarcoidosis)
• Pericarditis
• Intense emotional turmoil
• Congenital heart disease

Pathophysiology

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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 discharges produced by larger areas of atrial tissue. It can be distinguished from atrial flutter, which is a more organized electrical circuit usually in the right atrium that produces characteristic saw toothed waves on the electrocardiogram.

Often, the rhythm produced is more rapid than normal, but the difficulty is in obtaining control of the heart rate both at rest and with exercise. Good rate control will usually require two drugs, and can only be checked by observing heart rate response to exercise.

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, stroke, while an embolus may also lodge in the mesenteric circulation (the circulation supplying the abdominal organs) or digit, producing organ-specific damage.

Treatment

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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. 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.

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. 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 (Wyse et al., 2002).

AF with a persistent rapid rate can cause a form of heart failure called tachycardia induced cardiomyopathy. This can significantly increase mortality and morbidity. The early treatment of AF through either rate-control or rhythm-control can prevent this condition and thereby improve mortality and morbidity.

Rate Control

Rate control methods include:

• Beta blockers (e.g. metoprolol)
• Cardiac glycosides (i.e. digoxin)
• Calcium channel blockers (i.e. diltiazem or verapamil)

These medications work by slowing the generation of impulses from the atria and the conduction of those impulse from the atria to the ventricles.

In refractory cases where none of the above drugs are sufficient, a variety of other antiarrhythmic drugs, most commonly including quinidine, flecainide, propafenone, disopyramide, sotalol, or amiodarone may be used. 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, which can be fatal. 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, it should be noted that many of these agents are not approved by the FDA for this use.

In emergencies, when circulatory collapse is imminent due to uncontrolled tachycardia, immediate cardioversion may be indicated.

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, 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 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

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 practitioner 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 peircing a small hole in the septal wall. This is called a transeptal approach. Once in the left atrium, the physician may perform Wide Area Circumferencial Ablation (WACA) to electrically isolate the PVs from the left atrium.

Some more recent approaches to ablating AF is to target sights that are particularly dissorganized in both atria as well as in the coronary sinus (CS). These sites are termed complex fractionated atrial electrogram (CFAE) sites. 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.

Cox 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".

Minimaze Surgical Procedures

Minimaze surgery is minimally invasive cardiac surgery 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

In confirmed AF, anticoagulant treatment is a crucial way to prevent stroke. Treatment of AF patients over age 60, who also have one or more of: previous strokes (or warning strokes), hypertension (high blood pressure), diabetes, or congestive heart failure, with warfarin (also known as Coumadin® or Marevan®) results in a 60 to 70 percent reduction in the subsequent risk of stroke. Patients under age 65 who have any structural heart disease (i.e. valvular heart disease, ejection fraction <= 35%, history of heart attack) may also benefit from warfarin.

The use of warfarin is associated with a delayed clinical effect. It typically takes three to five days to achieve a demonstrable anticoagulant effect. Hence, if an immediate anticoagulant effect is required, physicians could use heparin or other heparinoids such as enoxaparin to provide early anticoagulation. In practice, urgent anticoagulation is seldom indicated. Even in the setting of stroke complicating atrial fibrillation, clinical trial results do not support the routine use of immediate anticoagulation.

Patients under age 65 who do not have structural heart disease (i.e. with LAF) do not require warfarin, and can be treated with aspirin or clopidogrel. There is evidence that aspirin and clopidogrel are effective when used together, but the combination is still inferior to warfarin. The new anticoagulant ximelagatran has been shown to prevent stroke with equal efficacy as warfarin, without the difficult monitoring process associated with warfarin and with possibly fewer adverse haemorrhagic events. Unfortunately, ximegalatran and other similar anticoagulant drugs (commonly referred to as direct thrombin inhibitors), have yet to be widely licensed. License applications for ximelegatran (made by AstraZeneca) have been rejected by both American and European licensing authorities, and its evaluation has been suspended in the UK. This is primarily due to concerns over possible liver toxicity. Determining who should and should not receive anti-coagulation with warfarin is not easy. The CHADS2 score is the best validated method of determining risk of stroke (and therefore who should be anticoagulated). The UK NICE guidelines have instead opted for an algorithm approach. 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.

It is worth noting that patient with AF who are being rhythm controlled are not treated any differently from patients with permanent AF when it comes to determining anticoagulation.

Prognosis

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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)

Epidemiology

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Atrial fibrillation is common among older adults. 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.

History

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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. However, the irregular pulse and its association with disease have been recognized since antiquity. Direct visualization of cardiac fibrillation was first described in 1628 by William Harvey in dying animals. In the mid-eighteenth century, Jean Baptiste de Sénac made note of dilated, irritated atria in people with mitral stenosis. The irregular pulse associated with AF was first recorded in 1876 by Carl Wilhelm Hermann Nothnagel and termed "delirium cordis" stating, "In 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. "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. Willem Einthoven published the first electrocardiogram showing AF in 1906. 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.


(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Clinical_trial)