Management of atrial fibrillation
Encyclopedia
The main goals in the management of atrial fibrillation
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...

(AF) are to prevent temporary circulatory instability and to prevent stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

. Control of heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....

 and rhythm are principally used to achieve the former, while anticoagulation may be required to decrease the risk of stroke. In emergencies, when circulatory collapse
Circulatory collapse
A circulatory collapse is defined as a general or specific failure of the circulation, either cardiac or peripheral in nature. A common cause of this could be shock or trauma from injury or surgery...

 is imminent due to uncontrolled rapid heart rate
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

, immediate cardioversion
Cardioversion
Cardioversion is a medical procedure by which an abnormally fast heart rate or cardiac arrhythmia is converted to a normal rhythm, using electricity or drugs. Synchronized electrical cardioversion uses a therapeutic dose of electric current to the heart, at a specific moment in the cardiac cycle...

 may be indicated.

The primary factors determining AF treatment are duration and evidence of circulatory instability. Cardioversion is indicated with new onset AF (for less than 48 hours) and with circulatory instability. If rate and rhythm control cannot be maintained by medication or cardioversion, it may be necessary to perform electrophysiological studies
Cardiac electrophysiology
Cardiac electrophysiology is the science of elucidating, diagnosing, and treating the electrical activities of the heart. The term is usually used to describe studies of such phenomena by invasive catheter recording of spontaneous activity as well as of cardiac responses to programmed electrical...

 with ablation
Radiofrequency ablation
Radio frequency ablation is a medical procedure where part of the electrical conduction system of the heart, tumor or other dysfunctional tissue is ablated using the heat generated from the high frequency alternating current to treat a medical disorder...

 of abnormal electrical pathways.

Anticoagulation

Most patients with AF are at increased risk of stroke. The possible exceptions are those with lone AF (LAF), characterized by absence of clinical or echocardiographic findings of other cardiovascular disease (including hypertension), related pulmonary disease, or cardiac abnormalities such as enlargement of the left atrium, and age under 60 years . The incidence of stroke associated with AF is 3 to 5 percent per year in the absence of anticoagulation, which is significantly higher compared to the general population without AF (relative risk 2.4 in men and 3.0 in women). A systematic review
Systematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...

 of risk factors for stroke in patients with nonvalvular AF concluded that a prior history of stroke or TIA is the most powerful risk factor for future stroke, followed by advancing age, hypertension, and diabetes. For patients with LAF, the risk of stroke is very low and is independent of whether the LAF was an isolated episode, paroxysmal, persistent, or permanent. 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
Mitral stenosis
Mitral stenosis is a valvular heart disease characterized by the narrowing of the orifice of the mitral valve of the heart.-Signs and symptoms:Symptoms of mitral stenosis include:...

) 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
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

 (or clopidogrel
Clopidogrel
Clopidogrel is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. The drug works by irreversibly...

 in those who are allergic to aspirin). In contrast, those with a high risk of stroke derive most benefit from anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...

 treatment with warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...

 or similar drugs. A new class of anticoagulant drugs, the direct thrombin inhibitors (Dabigatran
Dabigatran
Dabigatran is an oral anticoagulant from the class of the direct thrombin inhibitors...

), has recently arrived on the scene and shown efficacy in treating complications of nonvalvular chronic AF.

In the United Kingdom, the NICE
National Institute for Health and Clinical Excellence
The National Institute for Health and Clinical Excellence is a special health authority of the English National Health Service , serving both English NHS and the Welsh NHS...

 guidelines recommend using a clinical prediction rule
Clinical prediction rule
A clinical prediction rule is type of medical research study in which researchers try to identify the best combination of medical sign, symptoms, and other findings in predicting the probability of a specific disease or outcome....

 for this purpose. The CHADS2
CHADS Score
The CHADS2 score is a clinical prediction rule for estimating the risk of stroke in patients with non-rheumatic atrial fibrillation , a common and serious heart arrhythmia associated with thromboembolic stroke...

score is a well-validated simple clinical prediction rule for determining the risk of stroke (and therefore who should and should not be anticoagulated with warfarin); it assigns points (totaling 0-6) depending on the presence or absence of co-morbidities such as hypertension and diabetes. In a comparison of seven prediction rules, the best was CHADS2
CHADS Score
The CHADS2 score is a clinical prediction rule for estimating the risk of stroke in patients with non-rheumatic atrial fibrillation , a common and serious heart arrhythmia associated with thromboembolic stroke...

 which performed similarly to the SPAF and Framingham
Framingham Heart Study
The Framingham Heart Study is a long-term, ongoing cardiovascular study on residents of the town of Framingham, Massachusetts. The study began in 1948 with 5,209 adult subjects from Framingham, and is now on its third generation of participants...

 prediction rules.

The following treatment strategy is based on the CHADS2 score:
CHADS2 Score Risk Anticoagulation Therapy Considerations
0
Low Aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

325 mg/day although lower doses may be similarly efficacious
1
Moderate Aspirin or Warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...

, or other Oral anticoagulant
Aspirin daily or raise INR to 2.0-3.0, depending on factors such as patient preference
≥ 2
Moderate or High Warfarin, or other Oral anticoagulant Increase INR to 2.0-3.0, unless contraindicated (e.g., history of falls, clinically significant GI bleeding, inability to obtain regular INR screening)

More recently, the 2010 European Society of Cardiology (ESC) guidelines have recommended a risk factor based approach to stroke prevention, and de-emphasised the artificial stratification into low/moderate/high risk, given the poor predictive value of these 3 categories. To complement the CHADS2
CHADS Score
The CHADS2 score is a clinical prediction rule for estimating the risk of stroke in patients with non-rheumatic atrial fibrillation , a common and serious heart arrhythmia associated with thromboembolic stroke...

score, the ESC guidelines on atrial fibrillation management recommend using the new CHA2DS2-VASc score (Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, Stroke (doubled), Vascular disease, Age 65–74 years, Sex category], which is more inclusive of 'stroke risk modifier' risk factors. The new CHA2DS2-VASc score (Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, Stroke (doubled), Vascular disease, Age 65–74 years, Sex category] has also been validated in other large independent cohorts.

The most recent validation study used nationwide data on 73,538 hospitalized non-anticoagulated patients with AF in Denmark, whereby in ‘low risk’ subjects (score=0), the rate of thromboembolism per 100 person-years was 1.67 (95% confidence interval 1.47 to 1.89) with CHADS2 and 0.78 (0.58 to 1.04) with CHA2DS2-VASc score, at 1 year follow-up . Thus, those categorised as ‘low risk’ using CHA2DS2-VASc score were ‘truly low risk’ for thromboembolism, and consistent with other cohorts , CHA2DS2-VASc score performed better than CHADS2 in identifying these 'low risk' patients. The c-statistics at 10 years follow-up were 0.812 (0.796 to 0.827) with CHADS2 and 0.888 (0.875 to 0.900) with CHA2DS2-VASc, respectively - and suggests that CHA2DS2-VASc score also performed better than CHADS2 in predicting ‘high risk’ patients.

To compensate for the increased risk of stroke, anticoagulants may be required. However, in the case of warfarin, if someone with AF 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 from AF. However, since these older data, there is now greater recognition of the importance of good anticoagulation control (as reflected by time in therapeutic range) as well as greater awareness of bleeding risk factors as well as data from recent trials that aspirin carries a similar rate of major bleeding to warfarin, especially in the elderly.

The new ESC guidelines on atrial fibrillation recommend assessment of bleeding risk in AF using the HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile International Normalized Ratio, Elderly, Drugs/alcohol concomitantly) bleeding risk schema as a simple, easy calculation, whereby a score of ≥3 indicates "high risk" and some caution and regular review of the patient is needed. The HAS-BLED score has also been validated in an anticoagulated trial cohort of 7329 patients with AF - in this study, the HAS-BLED score offered some improvement in predictive capability for bleeding risk over previously published bleeding risk assessment schemas and was simpler to apply. With the likely availability of new oral anticoagulants that avoid the limitations of warfarin (and may even be safer), more widespread use of oral anticoagulation therapy for stroke prevention in AF is likely.

AF in the context of mitral stenosis is associated with a seventeenfold increase in stroke risk.

Acute anticoagulation

If anticoagulation is required urgently (e.g. for cardioversion), heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...

 or similar drugs achieve the required level of protection much quicker than warfarin, which will 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). As a result, a clinical practice guideline by National Institute for Health and Clinical Excellence
National Institute for Health and Clinical Excellence
The National Institute for Health and Clinical Excellence is a special health authority of the English National Health Service , serving both English NHS and the Welsh NHS...

 recommends that anticoagulation should begin two weeks after stroke if no hemorrhage occurred.

In cases of chronic stable AF without any other risk factors for thromboembolism, the Seventh American College of Chest Physicians (ACCP) Conference on Antithrombotic and Thrombolytic Therapy recommends initiating warfarin without heparin bridging. While there is a theoretical concern of causing a transient prothrombotic state with the initiation of warfarin, a study comparing the initiation of warfarin alone with warfarin and low molecular weight heparin
Low molecular weight heparin
In medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....

 shows no significant difference in the concentrations of endogenous anticoagulants or in markers of active clot formation.

Chronic anticoagulation

Among patients with nonvalvular AF, anticoagulation with warfarin can reduce stroke by 60% while antiplatelet agents can reduce stroke by 20%. The combination of aspirin and clopidogrel
Clopidogrel
Clopidogrel is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. The drug works by irreversibly...

 reduced the risk of stroke by 25%, but increased the risk of major bleeding by 57%, which means that this combination is inferior to warfarin, and is not an alternative for patients who are judged to be at high risk of bleeding on warfarin therapy.

Warfarin treatment requires frequent monitoring with a blood test called the international normalized ratio
Prothrombin time
The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...

 (INR); this determines whether the correct dose is being used. In AF, the usual target INR is between 2.0 and 3.0 (a higher target, INR between 2.5 and 3.5, is used in patients with prior thromboembolism, rheumatic heart disease, and mechanical artificial heart valve
Artificial heart valve
An artificial heart valve is a device implanted in the heart of a patient with heart valvular disease. When one of the four heart valves malfunctions, the medical choice may be to replace the natural valve with an artificial valve. This requires open-heart surgery.Valves are integral to the normal...

s, many of whom may also have AF). A high INR may indicate increased bleeding risk, while a low INR would indicate that there is insufficient protection from stroke.

An attempt was made to find a better method of implementing warfarin therapy without the inconvenience of regular monitoring and risk of intracranial hemorrhage. A combination of aspirin and fixed-dose warfarin (initial INR 1.2-1.5) was tried. Unfortunately, in a study of AF patients with additional risk factors for thromboembolism, the combination of aspirin and the lower dose of warfarin was significantly inferior to the standard adjusted-dose warfarin (INR 2.0-3.0), yet still had a similar risk of intracranial hemorrhage.

The U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 (FDA) approved Dabigatran
Dabigatran
Dabigatran is an oral anticoagulant from the class of the direct thrombin inhibitors...

 ("Pradaxa," and other names) on October 19, 2010, for prevention of stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

 in patients with non-valvular atrial fibrillation
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...

. The approval came after an advisory committee recommended the drug for approval on September 20, 2010 although caution is still urged by reviewers. Dabigatran is an anticoagulant that works as a direct thrombin
Thrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...

 inhibitor, and does not require blood tests for INR monitoring, while offering similar results in terms of efficacy in the treatment of non-valvular AF. The place of the new thrombin inhibitor class of drugs in the treatment of chronic AF is still being worked out.

Elderly patients

The very elderly (patients aged 75 years or more) may benefit from anticoagulation provided that their anticoagulation 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. This bleed rate would seem to preclude use of warfarin; however, a randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...

 found benefit in treating patients 75 years or over with a number needed to treat
Number needed to treat
The number needed to treat is an epidemiological measure used in assessing the effectiveness of a health-care intervention, typically a treatment with medication. The NNT is the average number of patients who need to be treated to prevent one additional bad outcome...

 of 50. Of note, this study had very low rate of hemorrhagic complications in the warfarin group.

Left atrial appendage occlusion

Left atrial appendage occlusion
Left atrial appendage occlusion
Left atrial appendage occlusion is a treatment strategy to prevent blood clot formation in atrial fibrillation . In this heart rhythm disorder, blood clots form in the left atrial appendage in 90% of cases....

 is an experimental alternative to anticoagulants. During cardiac catheterization
Cardiac catheterization
Cardiac catheterization is the insertion of a catheter into a chamber or vessel of the heart. This is done for both investigational and interventional purposes...

, a device (such as the Watchman device) consisting of an expandable nitinol frame is introduced into the left atrial appendage, the source of blood clots in more than 90% of cases. A trial comparing closure against warfarin therapy found closure to be non-inferior when measured against a composite end point of stroke, cardiovascular death and systemic embolism.

The left atrial appendage can also be surgically amputated, sutured or stapled simultaneous with other cardiac procedures such as the maze procedure or during mitral valve
Mitral valve
The mitral valve is a dual-flap valve in the heart that lies between the left atrium and the left ventricle...

 surgery.

Rate control versus rhythm control using drugs

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 using drugs: rate control and rhythm control. Rate control seeks to reduce the heart rate to one that is closer to normal, usually 60 to 100 bpm, without trying to convert to a regular rhythm. Rhythm control seeks to restore with cardioversion the regular heart rhythm and maintain it with drugs. 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.

The AFFIRM study showed no difference in risk of stroke in patients who have converted to a normal rhythm with antiarrhythmic treatment, compared to those who have only rate control. AF is associated with a reduced quality of life, and while some studies indicate that rhythm control leads to a higher quality of life, the AFFIRM study did not find a difference.

A further study focused on rhythm control in patients with AF and simultaneous heart failure, based on the premise that AF confers a higher mortality risk in heart failure. In this setting, too, rhythm control offered no advantage compared to rate control.

In patients with a fast ventricular response, intravenous magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...

 significantly increases the chances of successful rate and rhythm control in the urgent setting without significant side-effects.

Cardioversion

Cardioversion
Cardioversion
Cardioversion is a medical procedure by which an abnormally fast heart rate or cardiac arrhythmia is converted to a normal rhythm, using electricity or drugs. Synchronized electrical cardioversion uses a therapeutic dose of electric current to the heart, at a specific moment in the cardiac cycle...

 is a noninvasive conversion of an irregular heartbeat to a normal heartbeat using electrical or chemical means:
  • 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
    Amiodarone
    Amiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...

    , dronedarone
    Dronedarone
    Dronedarone is a drug by Sanofi-Aventis, mainly for the indication of cardiac arrhythmias. It was approved by the FDA on July 2, 2009. It is now available as 400 mg tablets in 20, 60 and 100 count packages...

    , procainamide
    Procainamide
    Procainamide INN is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias, classified by the Vaughan Williams classification system as class Ia.-History:...

    , ibutilide
    Ibutilide
    Ibutilide is a Class III antiarrhythmic agent that is indicated for acute cardioconversion of atrial fibrillation and atrial flutter of a recent onset to sinus rhythm. It exerts its antiarrhythmic effect by induction of slow inward sodium current, which prolongs action potential and refractory...

    , propafenone
    Propafenone
    Propafenone is a class Ic anti-arrhythmic medication, which treats illnesses associated with rapid heart beats such as atrial and ventricular arrhythmias.-Mechanism of action:...

     or flecainide
    Flecainide
    Flecainide acetate is a class Ic antiarrhythmic agent used to prevent and treat tachyarrhythmias . It is used to treat a variety of cardiac arrhythmias including paroxysmal atrial fibrillation , paroxysmal supraventricular tachycardia Flecainide acetate is a class Ic antiarrhythmic agent used to...

    .


The main risk of cardioversion is systemic embolization of a thrombus
Thrombus
A thrombus , or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system...

 (blood clot) from the previously fibrillating left atrium. Cardioversion should not be performed without adequate anticoagulation in patients with more than 48 hours or unknown duration of AF. Anticoagulation is adequate if warfarin is given with target INR between 2 and 3 for three to four weeks prior to cardioversion, and continued for at least four weeks after cardioversion. 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 patients relapse
Relapse
Relapse, in relation to drug misuse, is resuming the use of a drug or a dependent substance after one or more periods of abstinence. The term is a landmark feature of both substance dependence and substance abuse, which are learned behaviors, and is maintained by neuronal adaptations that mediate...

 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.

Rate control

Rate control is achieved with medications that work by increasing the degree of block at the level of the AV node, effectively decreasing the number of impulses that conduct down into the ventricles. This can be done with:
  • Beta blockers (preferably the "cardioselective" beta blockers such as metoprolol
    Metoprolol
    Metoprolol is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate...

    , atenolol, bisoprolol
    Bisoprolol
    Bisoprolol is a drug belonging to the group of beta blockers, a class of drugs used primarily in cardiovascular diseases. More specifically, it is a selective type β1 adrenergic receptor blocker. The FDA approved Duramed Pharmaceutical's application for Zebeta Oral Tablets as a new molecular...

    )
  • Calcium channel blocker
    Calcium channel blocker
    A calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with...

    s (i.e. diltiazem
    Diltiazem
    Diltiazem is a non-dihydropyridine member of the class of drugs known as calcium channel blockers, used in the treatment of hypertension, angina pectoris, and some types of arrhythmia....

     or verapamil
    Verapamil
    Verapamil is an L-type calcium channel blocker of the phenylalkylamine class. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, cluster headaches. It is also an effective preventive medication for migraine...

    )
  • Cardiac glycosides (i.e. digoxin
    Digoxin
    Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...

    ) - have limited use, apart from in the sedentary elderly patient


In addition to these agents, amiodarone has some AV node blocking effects (particularly when administered intravenously), and can be used in individuals when other agents are contraindicated or ineffective (particularly due to hypotension).

Diltiazem has been shown to be more effective than either digoxin or amiodarone.

Drugs used to control the rate of AF may cause side effects, especially fatigue and dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...

. These are avoided by the more radical "ablate and pace" treatment (see below).

Maintenance of sinus rhythm

The mainstay of maintaining sinus rhythm is the use of antiarrhythmic agents. Recently, other approaches have been developed that promise to decrease or eliminate the need for antiarrhythmic agents.

Antiarrhythmic agents

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. The agents work by prolonging the Effective Refractory Period
Effective Refractory Period
In electrocardiography, during a cardiac cycle, once an action potential is initiated, there is a period of time that a new action potential cannot be initiated. This is termed the effective refractory period of the tissue...

 (ERP) either by blocking sodium ions (Class I drugs) or by blocking potassium ions (Class III drugs) or a mixture of both. These medications are often used in concert with electrical cardioversion.

Catheter 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
Atrioventricular node
The atrioventricular node is a part of the electrical control system of the heart that coordinates heart rate. It electrically connects atrial and ventricular chambers...

 - which regulates heart rate, and to implant a pacemaker
Artificial pacemaker
A pacemaker is a medical device that uses electrical impulses, delivered by electrodes contacting the heart muscles, to regulate the beating of the heart...

 instead. This "ablate and pace" technique has an important place in the treatment of AF as it is the only reliably effective method for relieving the symptoms of the arrhythmia and can be used when other methods have failed (as they do in up to 50% of cases of persistent AF). Although this procedure results in a regular (paced) heart rhythm it does not prevent the atria from fibrillating and therefore long-term warfarin anticoagulation may still be required.

A more complex technique, which avoids the need for a pacemaker, involves ablating groups of cells near the pulmonary veins where AF is thought to originate, or creating more extensive lesions in an attempt to prevent AF from establishing itself. The technique has first been suggested by French electrophysiologist Michel Haïssaguerre
Michel Haïssaguerre
Michel Haïssaguerre is a prominent French cardiac electrophysiologist. He was born in Bayonne, France, on October 5, 1955. He became a Professor of Cardiology in 1994. His present position is Professor at the Hôpital Cardiologique du Haut–Lévèque, Bordeaux–Pessac...

.

Ablation
Ablation
Ablation is removal of material from the surface of an object by vaporization, chipping, or other erosive processes. This occurs in spaceflight during ascent and atmospheric reentry, glaciology, medicine, and passive fire protection.-Spaceflight:...

 (AF ablation) is a method that increasingly is used to treat cases of recurrent AF that are unresponsive to conventional treatments. Radiofrequency ablation
Radiofrequency ablation
Radio frequency ablation is a medical procedure where part of the electrical conduction system of the heart, tumor or other dysfunctional tissue is ablated using the heat generated from the high frequency alternating current to treat a medical disorder...

 (RFA) uses radiofrequency energy to destroy abnormal electrical pathways in heart tissue. Other energy sources include laser, cryothermy and high intensity ultrasound. The energy emitting probe (electrode
Electrode
An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit...

) is placed into the heart through a catheter
Catheter
In medicine, a catheter is a tube that can be inserted into a body cavity, duct, or vessel. Catheters thereby allow drainage, administration of fluids or gases, or access by surgical instruments. The process of inserting a catheter is catheterization...

 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. The cardiac catheterization procedure may be performed by hand, or with the help of a robotic catheterization system such as Stereotaxis remote magnetic navigation (RMN) or the Hansen Medical
Hansen Medical
Hansen Medical, headquartered in Mountain View, California, designs and manufactures medical robotics for the accurate positioning and control of catheter-based technologies. The Company manufactures Sensei Robotic Catheter Systems, including next-generation Sensei X Robotic Catheter Systems, and...

 Sensei robotic catheter system
Sensei robotic catheter system
The Sensei X robotic catheter is a medical robot designed to enhance a physician’s ability to perform complex operations using a small flexible tube called a catheter. As open surgical procedures that require large incisions have given way to minimally invasive surgeries in which the surgeon gains...

. Robotic atrial mapping and ablation procedures allow better visualization and control of the catheter. The Stereotaxis system has shown to have higher efficacy, shorter procedure times and lower complication rates than any other manual or robotic procedure. The Sensei robot has been shown to have mixed success rates, longer procedure times, higher complication rates and lower flouroscopy dosages to the patient compared to manual procedures.

Most AF ablations consist of isolating the electrical pathways from the pulmonary vein
Pulmonary vein
The pulmonary veins are large blood vessels that carry blood from the lungs to the left atrium of the heart. In humans there are four pulmonary veins, two from each lung...

s (PV), which are located on the posterior wall of the left atrium, in a procedure known as a pulmonary vein ablation (PV ablation or PVA). All other veins from the body (including neck and groin) lead to the right atrium, so 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 transseptal 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
Coronary sinus
The coronary sinus is a collection of veins joined together to form a large vessel that collects blood from the myocardium of the heart. It is present in all mammals, including humans...

 (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
Cryoablation
Cryoablation is a process that uses extreme cold to remove tissue .Cryoablation is used in a variety of clinical applications using hollow needles through which cooled, thermally conductive, fluids are circulated...

 (tissue freezing using a coolant which flows through the catheter), microwave ablation, where tissue is ablated by the microwave energy "cooking" the adjacent tissue, and high intensity focused ultrasound (HIFU), which destroys tissue by heating. 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.

Efficacy and risks of catheter ablation of AF are areas of active debate. A worldwide survey of the outcomes of 8745 ablation procedures demonstrated a 52% success rate (ranging from 14.5% to 76.5% among centers), with an additional 23.9% of patients becoming asymptomatic with addition of an antiarrhythmic medication. In 27.3% of patients, more than one procedure was required to attain these results. There was at least one major complication in 6% of patients. Death has been found to occur in 1 in 1000 people who undergo this procedure. A thorough discussion of results of catheter ablation was published in 2007; it notes that results are widely variable, due in part to differences in technique, follow-up, definitions of success, use of antiarrhythmic therapy, and in experience and technical proficiency.

This relatively low success rate, the significant complications and a lack of long-term (more than 5 years) follow-up data for this operation make the simple "ablate and pace" treatment an attractive option especially for older patients and those who are looking for a definitive procedure to relieve their AF symptoms.

Cox maze

The Cox maze procedure
Cox maze procedure
The Cox maze procedure is a type of heart surgery for atrial fibrillation."Maze" refers to the series of incisions arranged in a maze-like pattern in the atria...

 is an open-heart surgical procedure intended to eliminate AF and was first performed at St. Louis' Barnes Hospital—now Barnes-Jewish Hospital
Barnes-Jewish Hospital
Barnes-Jewish Hospital is the largest hospital in the U.S. state of Missouri. It is the adult teaching hospital for Washington University School of Medicine, and is located in St. Louis, Missouri. It is consistently rated one of the top hospitals in the United States by U.S. News & World Report...

 -- in 1987. "Maze" refers to the series of incisions made in the atria, 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".

Minimally invasive maze procedures

Minimaze
Minimaze
The mini-maze procedures are cardiac surgery procedures intended to cure atrial fibrillation , a common disturbance of heart rhythm. They are procedures derived from the original maze procedure developed by James Cox, MD....

 procedures are minimally invasive versions of the original Cox maze procedure
Cox maze procedure
The Cox maze procedure is a type of heart surgery for atrial fibrillation."Maze" refers to the series of incisions arranged in a maze-like pattern in the atria...

 but without cardiac incisions. These procedures do not require a median sternotomy (vertical incision in the breastbone) or cardiopulmonary bypass (heart-lung machine). They use laser, cryothermy, radiofrequency, or acoustic energy to ablate atrial tissue near the pulmonary veins and make other required ablations to mimic the maze.

Minimally invasive surgical (endoscopic) maze procedures are now routinely conducted at hospitals around the US. This approach was developed in the early 2000s.

The Ex-Maze is a minimally invasive procedure, first reported in 2007, that also creates a lesion pattern across both atria epicardially on the beating heart. As with other procedures off-bypass, the surgeon can confirm that AF corrects to normal sinus rhythm during the procedure. Laparoscopic instruments are used to access the pericardium through the diaphragm. Like many heart-cauterizing instruments, the Ex-Maze device uses heat generated by a radiofrequency coil. The coil is inside a plastic tube that uses suction to maintain contact against the beating heart’s surface.
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