Surgical boon in the therapy of atrial fibrillation

0137PY061052

INTRODUCTION
Atrial fibrillation (AF or afib) is the most common cardiac arrhythmia (abnormal heart rhythm) and
involves the two upper chambers (atria) of the heart. Its name comes from the fibrillating (i.e. quivering) of
the heart muscles of the atria, instead of a coordinated contraction. It can often be identified by taking a
pulse and observing that the heartbeats don't occur at regular intervals. However, a conclusive indication of
AF is the absence of P waves on an electrocardiogram (ECG), which are normally present when there is a
coordinated atrial contraction at the beginning of each heart beat. Risk increases with age, with 8% of
people over 80 having AF.

LNCP
1
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

In AF, the normal electrical impulses that are generated by the sinoatrial node are overwhelmed by
disorganized electrical impulses that originate in the atria and pulmonary veins, leading to conduction of
irregular impulses to the ventricles that generate the heartbeat. The result is an irregular heartbeat which
may occur in episodes lasting from minutes to weeks, or it could occur all the time for years. The natural
tendency of AF is to become a chronic condition. Chronic AF leads to a small increase in the risk of death.

Atrial fibrillation is often asymptomatic, and is not in itself generally life-threatening, but may result in
palpitations, fainting, chest pain, or congestive heart failure. People with AF usually have a significantly
increased risk of stroke (up to 7 times that of the general population). Stroke risk increases during AF
because blood may pool and form clots in the poorly contracting atria and especially in the left atrial
appendage (LAA). The level of increased risk of stroke depends on the number of additional risk factors. If
a person with AF has none, the risk of stroke is similar to that of the general population. However, many
people with AF do have additional risk factors and AF is a leading cause of stroke.

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 recurrence of AF in certain
individuals. People with AF are often given anticoagulants such as warfarin to protect them from stroke.

Epidemiology
Atrial fibrillation is the most common arrhythmia found in clinical practice. It also accounts for 1/3 of
hospital admissions for cardiac rhythm disturbances , and the rate of admissions for AF has risen in recent
years. Approximately 2.2 million individuals in the United States and 4.5 million in the European Union
have AF.

LNCP
2
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

The incidence of atrial fibrillation increases with age. The prevalence in individuals over the age of 80 is
about 8%. 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
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.[65] In the mid-eighteenth century,
Jean-Baptiste de Sénac made note of dilated, irritated atria in people with mitral stenosis.[66] 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". 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 ECG 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.

HEART

Heart Anatomy
Simply click on a region of the heart on the diagrams or the hyperlinks listed below to learn more about the
structures of the heart.

LNCP
3
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

9. Right Atrium
1. Right Coronary
10. Right Ventricle
2. Left Anterior
11. Left Atrium
Descending
12. Left Ventricle
3. Left Circumflex
13. Papillary Muscles
4. Superior Vena Cava
14. Chordae Tendineae
5. Inferior Vena Cava
15. Tricuspid Valve
6. Aorta
16. Mitral Valve
7. Pulmonary Artery
17. Pulmonary Valve
8. Pulmonary Vein

Coronary Arteries

Because the heart is composed primarily of cardiac muscle tissue that continuously contracts and relaxes, it
must have a constant supply of oxygen and nutrients. The coronary arteries are the network of blood vessels
that carry oxygen- and nutrient-rich blood to the cardiac muscle tissue.

The blood leaving the left ventricle exits through the aorta, the body’s main artery. Two coronary arteries,
referred to as the "left" and "right" coronary arteries, emerge from the beginning of the aorta, near the top of
the heart.

The initial segment of the left coronary artery is called the left main coronary. This blood vessel is
approximately the width of a soda straw and is less than an inch long. It branches into two slightly smaller
arteries: the left anterior descending coronary artery and the left circumflex coronary artery. The left
anterior descending coronary artery is embedded in the surface of the front side of the heart. The left
circumflex coronary artery circles around the left side of the heart and is embedded in the surface of the
back of the heart.

LNCP
4
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

Just like branches on a tree, the coronary arteries branch into progressively smaller vessels. The larger
vessels travel along the surface of the heart; however, the smaller branches penetrate the heart muscle. The
smallest branches, called capillaries, are so narrow that the red blood cells must travel in single file. In the
capillaries, the red blood cells provide oxygen and nutrients to the cardiac muscle tissue and bond with
carbon dioxide and other metabolic waste products, taking them away from the heart for disposal through
the lungs, kidneys and liver.

When cholesterol plaque accumulates to the point of blocking the flow of blood through a coronary artery,
the cardiac muscle tissue fed by the coronary artery beyond the point of the blockage is deprived of oxygen
and nutrients. This area of cardiac muscle tissue ceases to function properly. The condition when a coronary
artery becomes blocked causing damage to the cardiac muscle tissue it serves is called a myocardial
infarction or heart attack.

Superior Vena Cava

The superior vena cava is one of the two main veins bringing de-oxygenated blood from the body to the
heart. Veins from the head and upper body feed into the superior vena cava, which empties into the right
atrium of the heart.

Inferior Vena Cava

The inferior vena cava is one of the two main veins bringing de-oxygenated blood from the body to the
heart. Veins from the legs and lower torso feed into the inferior vena cava, which empties into the right
atrium of the heart.

Aorta

The aorta is the largest single blood vessel in the body. It is approximately the diameter of your thumb. This
vessel carries oxygen-rich blood from the left ventricle to the various parts of the body.

Pulmonary Artery

The pulmonary artery is the vessel transporting de-oxygenated blood from the right ventricle to the lungs. A
common misconception is that all arteries carry oxygen-rich blood. It is more appropriate to classify arteries
as vessels carrying blood away from the heart.

Pulmonary Vein

The pulmonary vein is the vessel transporting oxygen-rich blood from the lungs to the left atrium. A
common misconception is that all veins carry de-oxygenated blood. It is more appropriate to classify veins
as vessels carrying blood to the heart.

Right Atrium

The right atrium receives de-oxygenated blood from the body through the superior vena cava (head and
upper body) and inferior vena cava (legs and lower torso). The sinoatrial node sends an impulse that causes

LNCP
5
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

the cardiac muscle tissue of the atrium to contract in a coordinated, wave-like manner. The tricuspid valve,
which separates the right atrium from the right ventricle, opens to allow the de-oxygenated blood collected
in the right atrium to flow into the right ventricle.

Right Ventricle

The right ventricle receives de-oxygenated blood as the right atrium contracts. The pulmonary valve leading
into the pulmonary artery is closed, allowing the ventricle to fill with blood. Once the ventricles are full,
they contract. As the right ventricle contracts, the tricuspid valve closes and the pulmonary valve opens. The
closure of the tricuspid valve prevents blood from backing into the right atrium and the opening of the
pulmonary valve allows the blood to flow into the pulmonary artery toward the lungs.

Left Atrium

The left atrium receives oxygenated blood from the lungs through the pulmonary vein. As the contraction
triggered by the sinoatrial node progresses through the atria, the blood passes through the mitral valve into
the left ventricle.

Left Ventricle

The left ventricle receives oxygenated blood as the left atrium contracts. The blood passes through the
mitral valve into the left ventricle. The aortic valve leading into the aorta is closed, allowing the ventricle to
fill with blood. Once the ventricles are full, they contract. As the left ventricle contracts, the mitral valve
closes and the aortic valve opens. The closure of the mitral valve prevents blood from backing into the left
atrium and the opening of the aortic valve allows the blood to flow into the aorta and flow throughout the
body.

Papillary Muscles

The papillary muscles attach to the lower portion of the interior wall of the ventricles. They connect to the
chordae tendineae, which attach to the tricuspid valve in the right ventricle and the mitral valve in the left
ventricle. The contraction of the papillary muscles opens these valves. When the papillary muscles relax,
the valves close.

Chordae Tendineae

The chordae tendineae are tendons linking the papillary muscles to the tricuspid valve in the right ventricle
and the mitral valve in the left ventricle. As the papillary muscles contract and relax, the chordae tendineae
transmit the resulting increase and decrease in tension to the respective valves, causing them to open and
close. The chordae tendineae are string-like in appearance and are sometimes referred to as "heart strings."

Tricuspid Valve

The tricuspid valve separates the right atrium from the right ventricle. It opens to allow the de-oxygenated
blood collected in the right atrium to flow into the right ventricle. It closes as the right ventricle contracts,

LNCP
6
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

preventing blood from returning to the right atrium; thereby, forcing it to exit through the pulmonary valve
into the pulmonary artery.

Mitral Value

The mitral valve separates the left atrium from the left ventricle. It opens to allow the oxygenated blood
collected in the left atrium to flow into the left ventricle. It closes as the left ventricle contracts, preventing
blood from returning to the left atrium; thereby, forcing it to exit through the aortic valve into the aorta.

Pulmonary Valve

The pulmonary valve separates the right ventricle from the pulmonary artery. As the ventricles contract, it
opens to allow the de-oxygenated blood collected in the right ventricle to flow to the lungs. It closes as the
ventricles relax, preventing blood from returning to the heart.

Aortic Valve

The aortic valve separates the left ventricle from the aorta. As the ventricles contract, it opens to allow the
oxygenated blood collected in the left ventricle to flow throughout the body. It closes as the ventricles relax,
preventing blood from returning to the heart.

UNDERSTANDING THE ELECTRICAL PROBLEM IN

ATRIAL FIBRILLATION
In AF, the heart’s electrical signal begins in a different part of the atria or the nearby pulmonary veins and is
conducted abnormally. The signal doesn’t travel through normal pathways, but may spread throughout the
atria in a rapid, disorganized way. This can cause the atria to beat more than 300 times a minute in a chaotic
fashion. The atria’s rapid, irregular, and uncoordinated beating is called fibrillation.

The abnormal signal from the SA node floods the AV node with electrical impulses. As a result, the
ventricles also begin to beat very fast. However, the AV node can’t conduct the signals to the ventricles as

LNCP
7
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

fast as they arrive, so even though the ventricles may be beating faster than normal, they aren’t beating as
fast as the atria. The atria and ventricles no longer beat in a coordinated fashion, creating a fast and irregular
heart rhythm. In AF, the ventricles may beat up to 100–175 times a minute, in contrast to the normal rate of
60–100 beats a minute.

When this happens, blood isn’t pumped into the ventricles as well as it should be, and the amount of blood
pumped out of the ventricles is based on the randomness of the atrial beats. In AF, instead of the body
receiving a constant, regular amount of blood from the ventricles, it receives rapid, small amounts and
occasional random, larger amounts, depending on how much blood has flowed from the atria to the
ventricles with each beat.

Most of the symptoms of AF are related to how fast the heart is beating. If medicines or age slow the heart
rate, the effect of the irregular beats is minimized.

AF may be brief, with symptoms that come and go and end on their own, or it may be persistent and require
treatment. Or, AF can be permanent, in which case medicines or other interventions can’t restore a normal
rhythm.

COMPARISION BETWEEN NORMAL AND FIBRILLATION

CLASSIFICATION
The American College of Cardiology (ACC), American Heart Association (AHA), and the European
Society of Cardiology (ESC) recommend in their guidelines the following classification system based on
simplicity and clinical relevance.

All atrial fibrillation patients are initially in the category called first detected AF. These patients may or may
not have had previous undetected episodes. If a first detected episode self-terminates in less than 7 days and
then another episode begins later on, the case has moved into the category of paroxysmal AF. Although

LNCP
8
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

patients in this category have episodes lasting up to 7 days, in most cases of paroxysmal AF the episodes
will self-terminate in less than 24 hours. If instead the episode lasts for more than 7 days, it is unlikely to
self-terminate[8] and it is called persistent AF. In this case, the episode may be terminated by cardioversion.
If cardioversion is unsuccessful or it is not attempted, and the episode is ongoing for a long time (e.g. a year
or more), the patient's AF is called permanent.

Episodes that last less than 30 seconds are not considered in this system. Also, this system does not apply to
cases where the AF is a secondary condition that occurs in the setting of a primary condition that may be the
cause of the AF.

Using this system, it's not always clear what an AF case should be called. For example, a case may fit into
the paroxysmal AF category some of the time, while other times it may have the characteristics of persistent
AF. One may be able to decide which category is more appropriate by determining which one occurs most
often in the case under consideration.

In addition to the four categories in the above system, which are mainly defined by episode timing and
termination, the ACC/AHA/ESC guidelines describe additional AF categories in terms of other
characteristics of the patient.[7]

• Lone atrial fibrillation (LAF) - absence of clinical or echocardiographic findings of other

cardiovascular disease (including hypertension) or related pulmonary disease, and age under
60 years
• Nonvalvular AF - absence of rheumatic mitral valve disease, a prosthetic heart valve, or mitral valve
repair
• Secondary AF - occurs in the setting of a primary condition which may be the cause of the AF, such
as acute myocardial infarction, cardiac surgery, pericarditis, myocarditis, hyperthyroidism,
pulmonary embolism, pneumonia, or other acute pulmonary disease

AF Category-Defining Characteristics

First detected- : only one diagnosed episode

Paroxysmal- : recurrent episodes that self-terminate in less than 7 days

Persistent- : recurrent episodes those last more than 7 days

Permanent- : an ongoing long-term episode1

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

• Hypertension (High blood pressure)

LNCP
9
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

• Primary heart diseases including 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)
• Excessive alcohol consumption ("binge drinking" or "holiday heart syndrome"). Even otherwise
healthy middle-aged women who consumed more than 2 drinks daily were 60% more likely to
develop AF.
• Hyperthyroidism
• Carbon monoxide poisoning
• Dual-chamber pacemakers in the presence of normal atrioventricular conduction.
• A family history of AF may increases the risk of AF. A study of more than 2,200 AF patients found
that 30 per cent had parents with AF.[13] Various genetic mutations may be responsible.

PATHOPHYSIOLOGY

MORPHOLOGY

The primary pathologic change seen in atrial fibrillation is the progressive fibrosis of the atria. This fibrosis
is primarily due to atrial dilation, however genetic causes and inflammation may have a cause in some
individuals.

Dilation of the atria can be due to almost any structural abnormality of the heart that can cause a rise in the
intra-cardiac pressures. This includes valvular heart disease (such as mitral stenosis, mitral regurgitation,
and tricuspid regurgitation), hypertension, and congestive heart failure. Any inflammatory state that affects

LNCP
10
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

the heart can cause fibrosis of the atria. This is typically due to sarcoidosis but may also be due to
autoimmune disorders that create autoantibodies against myosin heavy chains. Mutation of the lamin AC
gene is also associated with fibrosis of the atria that can lead to atrial fibrillation.

Once dilation of the atria has occurred, this begins a chain of events that leads to the activation of the renin
aldosterone angiotensin system (RAAS) and subsequent increase in matrix metaloproteinases and
disintegrin, which leads to atrial remodeling and fibrosis, with loss of atrial muscle mass.

This process is not immediate, and experimental studies have revealed patchy atrial fibrosis may precede
the occurrence of atrial fibrillation and may progress with prolonged durations of atrial fibrillation.

Fibrosis is not limited to the muscle mass of the atria, and may occur in the sinus node (SA node) and
atrioventricular node (AV node), correlating with sick sinus syndrome. Prolonged episodes of atrial
fibrillation have been shown to correlate with prolongation of the sinus node recovery time, [7][15][16]
suggesting that dysfunction of the SA node is progressive with prolonged episodes of atrial fibrillation.

SIGNS, SYMPTOMS AND DIAGNOSIS

Atrial fibrillation is usually accompanied by symptoms related to a rapid heart rate. Rapid and irregular
heart rates may be perceived as palpitations, exercise intolerance, and occasionally produce angina (if the
rate is faster 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

LNCP
11
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

(TIA). It is not uncommon for a patient to first become aware of AF from a routine physical examination or
ECG, 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 diarrhea, 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 AF is at a higher risk of complications.

The evaluation of atrial fibrillation involves diagnosis, determination of the etiology of the arrhythmia, and
classification of the arrhythmia. A minimal evaluation should be performed in all individuals with AF. This
includes a history and physical examination, ECG, transthoracic echocardiogram, and routine bloodwork.
Certain individuals may benefit from an extended evaluation which may include an evaluation of the heart
rate response to exercise, exercise stress testing, a chest x-ray, trans-esophageal echocardiography, and
other studies.

Screening

Screening for atrial fibrillation is not generally performed, although a study of routine pulse checks or ECGs
during routine office visits found that the annual rate of detection of AF in elderly patients improved from
1.04% to 1.63%; selection of patients for prophylactic anticoagulation would improve stroke risk in that age
category.[9]

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.[9]

Minimal evaluation

The minimal evaluation of atrial fibrillation should generally be performed in all individuals with AF. The
goal of this evaluation is to determine the general treatment regimen for the individual. If results of the
general evaluation warrant it, further studies may be then performed.

History and physical examination

The history of the individual's atrial fibrillation episodes is probably the most important part of the
evaluation. Distinctions should be made between those who are entirely asymptomatic when they are in AF
(in which case the AF is found as an incidental finding on an ECG or physical examination) and those who
have gross and obvious symptoms due to AF and can pinpoint whenever they go into AF or revert to sinus
rhythm.

LNCP
12
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

Routine blood work

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.[7]

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.[7]

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 (ECG), 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.[7]

When ECGs 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:[10]:

• 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 an ECG during an office visit only shows a regular rhythm, AF episodes
may be detected and documented with the use of ambulatory Holter monitoring (e.g. for a day). If the
episodes are too infrequent to be detected by Holter monitoring with reasonable probability, then the patient
can be monitored for longer periods (e.g. a month) with an ambulatory event monitor.[7]

Echocardiography

A non-invasive transthoracic echocardiogram (TTE) 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 greatly increase the risk of stroke), 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.

Significant enlargement of both the left and right atria is associated with long-standing atrial fibrillation
and, if noted at the initial presentation of atrial fibrillation, suggests that the atrial fibrillation is likely to be
of a longer duration than the individual's symptoms.

LNCP
13
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

Extended evaluation

An extended evaluation is generally not necessary in most individuals with atrial fibrillation, and is only
performed if abnormalities are noted in the limited evaluation, if a reversible cause of the atrial fibrillation
is suggested, or if further evaluation may change the treatment course.

Chest X-ray

A chest X-ray is generally only performed if a pulmonary cause of atrial fibrillation is suggested, or if other
cardiac conditions are suspected (particularly congestive heart failure.) This may reveal an underlying
problem in the lungs or the blood vessels in the chest. [7] In particular, if an underlying pneumonia is
suggested, then treatment of the pneumonia may cause the atrial fibrillation to terminate on its own.

Transesophageal echocardiogram

A 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 electrical cardioversion - a
transesophageal echocardiogram (TEE) is preferred.[7]

The TEE has much better visualization of the left atrial appendage than transthoracic echocardiography.
This structure, located in the left atrium, is the place where thrombus is formed in more than 90% of cases
in non-valvular (or non-rheumatic) atrial fibrillation or flutter. TEE has a very high sensitivity for locating
thrombus in this area and can also detect sluggish bloodflow in this area that is suggestive of thrombus
formation

If no thrombus is seen on TEE, the incidence of stroke immediately after cardioversion is performed is very
low.[citation needed]

Ambulatory holter monitoring

A holter monitor is a wearable ambulatory heart monitor that continuously monitors the heart rate and heart
rhythm for a short duration, typically 24 hours. In individuals with symptoms of significant shortness of
breath with exertion or palpitations on a regular basis, a holter monitor may be of benefit to determine if
rapid heart rates (or unusually slow heart rates) during atrial fibrillation are the cause of the symptoms.

Exercise stress testing

Some individuals with atrial fibrillation do well with normal activity but develop shortness of breath with
exertion. It may be unclear if the shortness of breath is due to a blunted heart rate response to exertion due
to excessive AV node blocking agents, a very rapid heart rate during exertion, or due to other underlying
conditions such as chronic lung disease or coronary ischemia. An exercise stress test will evaluate the
individual's heart rate response to exertion and determine if the AV node blocking agents are contributing to
the symptoms.

LNCP
14
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

RECENT DEVELOPMENTS IN ATRIAL FIBRILLATION THERAPY

Cardioversion to sinus rhythm

As a result of atrial remodelling, the longer the duration of atrial fibrillation the less successful is the
cardioversion. Predictors of recurrence of atrial fibrillation include long standing atrial fibrillation (duration
greater than three months), heart failure, structural heart disease, hypertension, increasing age (over 70), and
increased left atrial size. Although left atrial size is related to the duration of atrial fibrillation, a left atrial
diameter greater than 6.5 cm is associated with an increased risk of recurrence. Cardioversion carries a 5-
7% risk of thromboembolism without anticoagulation and a 1-2% risk after conventional anticoagulation.
Prolonged anticoagulation is not needed when patients present within 48 hours of onset of atrial fibrillation.
Such patients may be safely cardioverted irrespective of whether heparin has been administered since
presentation. Administration of heparin is recommended to all patients with an acute presentation, however,
to allow flexibility in subsequent management of the arrhythmia. For stable patients, in whom the onset of
atrial fibrillation is uncertain or greater than 48 hours, anticoagulation for a minimum of three weeks before
cardioversion is recommended, to allow resolution of potential thrombi. As atrial mechanical activity may
not resume concurrently with electrical activity, anticoagulation should be continued for at least four weeks
after cardioversion.

An alternative approach is to use transoesophageal echocardiography to exclude atrial thrombi before

cardioversion is attempted. The presence of an atrial thrombus necessitates four to six weeks of
anticoagulation before cardioversion. Even with this strategy, anticoagulation should be continued for at
least four weeks after cardioversion.

Pharmacological cardioversion
Pharmacological cardioversion is often effective when initiated within seven days of onset of the
arrhythmia. In general, class I and class III antiarrhythmic agents are commonly used for pharmacological
cardioversion and maintenance of sinus rhythm.

In a randomised trial comparing flecainide, propafenone, and amiodarone for cardioversion of recent onset
atrial fibrillation, conversion to sinus rhythm occurred in 90%, 72%, and 64% of patients respectively. Class
IC drugs (flecainide and propafenone) should be avoided in patients with underlying ischaemic heart disease
or impaired left ventricular function. Amiodarone can be used in such patients, although the time to
conversion can range from days to weeks. Dofetilide and ibutilide, newer pure class III agents not currently
licensed in the United Kingdom, can also be used for cardioversion. With the potential side effects of
antiarrhythmic drugs, pharmacological cardioversion should be reserved for haemodynamically stable
patients with symptoms.

Electrical cardioversion
Synchronised external direct current cardioversion is a safe procedure with success rates of 70-90%. It is
used acutely in patients who are haemodynamically compromised or electively as an alternative to
pharmacological cardioversion. Electrical cardioversion for atrial fibrillation is usually done under general
anaesthesia but has more recently been done under conscious sedation. The current recommendation is to
start at 200 J, increasing to 360 J if necessary. If this is unsuccessful, adjunctive antiarrhythmic treatment
with class III agents such as dofetilide, sotalol, and amiodarone can help to restore sinus rhythm

LNCP
15
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

VENTRICULAR RATE CONTROL

"Rhythm control" and "rate control" are two strategies used in managing atrial fibrillation (boxes 2 and 3).
Each strategy has its merits and drawbacks . Recent studies have shown that rate control can be considered
as a valid alternative to rhythm control (table A on bmj.com). Rhythm control was associated with higher
rates of admission to hospital and drug adverse effects, and in one study exercise tolerance was found to be
better with rhythm control.w1 In the AFFIRM study of 4060 patients, for example, mortality was higher in
the rhythm control arm, although this difference was not statistically significant (22.6% v 17.2%, P = 0.08).
However, these "rate versus rhythm" trials have been debated in relation to their applicability to clinical
practice, especially as the rate of cross over between study interventions was high, and limited data are
available on patients with new onset atrial fibrillation, severe heart failure, or high levels of symptoms, in
whom a rhythm control strategy may be unavoidable. None the less, cardioversion should not be done
simply as a means of stopping anticoagulation in asymptomatic patients with risk factors for
thromboembolism. Indeed, anticoagulation may need to be continued in the long term in patients with such
risk factors or those at high risk of recurrence of arrhythmia.

1. Identify and treat all reversible causes of atrial fibrillation before considering drug treatment for
maintenance of sinus rhythm
2. The selection of antiarrhythmic drug needs to be tailored individually to the patient, depending on
cardiac status, comorbidities, and contraindications
3. In patients with good left ventricular function and no coronary artery disease, flecainide and
propafenone can be used. Sotalol or amiodarone can also be used in such patients
4. Amiodarone can be used to maintain sinus rhythm in patients with heart failure. Although not
currently licensed in the United Kingdom, dofetilide is an alternative
5. Blockers are the drugs of choice for patients with coronary artery disease
6. If sinus rhythm cannot be maintained despite repeated cardioversions and antiarrhythmic treatment, a
"rate control" strategy should be adopted. This has been shown to be as effective as rhythm control
7. Patients who find the symptoms of the arrhythmia unacceptable despite rate control may be
considered for non-pharmacological methods to restore sinus rhythm

MODIFICATION OF THE MAZE PROCEDURE FOR ATRIAL

FLUTTER AND ATRIAL FIBRILLATION
The original maze procedure that was described for the treatment of patients with atrial fibrillation was
followed by an unacceptable incidence of two problems:

LNCP
16
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

The frequent inability to generate an appropriate sinus tachycardia in response to maximal exercise
Occasional left atrial dysfunction.

In an effort to overcome these problems, we modified the original technique (maze I) twice. The
results of these modifications culminated in the maze III procedure, which is associated with a higher
incidence of postoperative sinus rhythm, improved long-term sinus node function, fewer pacemaker
requirements, less arrhythmia recurrence, and improved long-term atrial transport function. In addition, the
maze III procedure is technically less demanding than either the maze I or maze II procedure. Therefore, the
maze III procedure is now the technique of choice for the management of medically refractory atrial
fibrillation.

The presence of an atrial pacemaker complex both in dogs and in human beings.The atrial
pacemaker complex, an area of 2 by 5 cm, is centered about the anatomic sinoatrial (SA) node. Points of
earliest activation can occur anywhere within this area, and the site of impulse origin changes, together with
changes in rate, in response to differing humoral and neural inputs. For example, during humorally mediated
sinus bradycardia (e.g., propranolol-induced), the sinus impulse usually originates from the lower portion of
the atrial pacemaker complex near the orifice of the inferior vena cava (IVC) below the anatomic SA node.
On the contrary, sinus tachycardia, whether humorally or neurally mediated, can originate from the region
of the right atrium immediately anterior to the junction of the superior vena cava (SVC) with the right atrium

The original animal studies evaluating the effects of the maze I procedure on atrial blood flow confirmed
that the multiple atriotomies did not cause any early or late atrial myocardial ischemia. Therefore, the
apparent lack of left atrial function in some patients after the operation prompted a search for other causes.
Because the right atrium was documented to function normally in all patients both early and late after the
operation, it seemed that the most likely explanation for the occasional absence of left atrial function was
interatrial conduction delay. The relationship between delayed interatrial conduction and the absence of
detectable left atrial function can be explained as follows.
Normally, the sinus impulse originates near the top of the right atrium and propagates rapidly (within
approximately 40 msec) to the top of the left atrium across Bachmann's bundle, a thick band of atrial muscle
fibers extending from the region of the SA node to the top of the left atrium.This early arrival of the sinus
impulse in the left atrium allows both atria to activate almost simultaneously from top to bottom, which
thereby forces blood into their respective ventricles in the most efficient manner. Bachmann's bundle is

LNCP
17
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

either divided or incorporated in the left atrial dome incision in the maze I and maze II procedures,
respectively. Therefore, it is not always possible for the sinus impulse to arrive as early as normal in the left
atrium. Indeed, after the maze I and maze II procedures, it may occasionally take as long as 150 msec for the
sinus impulse to propagate from the right atrium to the left atrium in some patients. If the atrioventricular
(AV) interval in such a patient is also 150 msec, the sinus impulse will arrive in the left atrium and the left
ventricle at virtually the same time. As a result, the left atrium and left ventricle will contract simultaneously
and therefore effective left atrial contraction will not occur. However, because right atrial activation will still
precede right ventricular contraction by 150 msec, right atrial function will appear to be normal. In such a
patient, the follow-up studies of atrial transport function will document normal right atrial function with no
left atrial function.
In an effort to overcome this problem of prolonged interatrial conduction time, we modified the maze II
procedure by moving the entire left atrial dome incision more posteriorly this, in turn, caused the atrial
septotomy to be moved more posteriorly as well. This rather minor modification resulted in several dramatic
technical and functional improvements in the maze procedure concept. First, with the atrial septotomy now
being posterior to the SVC, the exposure of the left side of the heart is superb. Furthermore, in the maze III
procedure, only one incision extends into the SVC orifice therefore, pericardial patching is no longer
necessary. The maze III procedure thus addresses both the chronotropic incompetence of the sinus node and
the occasional dysfunction of the left atrium while making the procedure much easier to perform
technically.

CIRCUMFERENTIAL RADIOFREQUENCY ABLATION OF

PULMONARY VEIN OSTIA
Radiofrequency energy uses an alternating current from 350 kHz to 1 MHz to heat tissue, resulting in
thermal injury. There has been a significant experience accumulated using radiofrequency ablation to treat
patients via catheter-based approaches .This success has led to the development of a number of
radiofrequency energy probes that are useful for application to atrial tissue during cardiac surgery These

LNCP
18
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

probes can be applied to either endocardial or epicardial heart surfaces to create transmural linear lesions
that block atrial conduction. Radiofrequency ablation by epicardial application holds promise for
developing off-pump and minimally invasive procedures for AF.

The majority of radiofrequency ablation procedures to date have been performed with unipolar systems in
which the patient is grounded by an indifferent skin electrode. In such systems, current flows from the
radiofrequency probe to contacted atrial tissue, where thermal energy is released as a result of resistance to
conduction. Unipolar systems have a number of limitations related to the unfocused nature of the energy
that is delivered. Local temperatures can exceed 100 degrees C, leading to surface charring and potential
thromboembolic complications. Heat is conducted to surrounding tissues, raising the risk of damage to
surrounding structures. Esophageal perforations have been reported with this technique. Consistent surface
application to make uniform lesions is difficult and there is no indication when a transmural lesion has been
made. Recently developed bipolar radiofrequency clamps address these limitations and allow creation of
more precise and uniform transmural lesions. The early clinical experience with bipolar radiofrequency
ablation has demonstrated consistent conduction block with epicardial and off-pump application
Experimental studies have demonstrated its potential in epicardial, off-pump approaches to AF surgery

Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity and mortality. For
many years, the only curative treatment has been surgical, with extensive atrial incisions used to
compartmentalize the atrial mass below that critical for perpetuating AF. Recently, transcatheter linear
radiofrequency (RF) ablation in the right atrium (RA) and/or left atrium (LA) has been used to replicate the
surgical procedures in patients with paroxysmal or chronic AF. However, uncertainty remains concerning
the requisite number of lesions, their optimal location, and the need for continuous lines. Indeed, focal
ablation has been proposed as an alternative approach on the basis of the demonstration that ectopic beats
originating within or at the ostium of the pulmonary veins (PVs) may be the source of paroxysmal and even
persistent AF. Despite high acute success rates, the feasibility of this technique is limited by the difficulty in
mapping the focus if the patient is in AF or has no consistent firing, the frequent existence of multiple foci
causing high recurrence rates, and an incidence of PV narrowing as high as 42%.5 To circumvent these
limitations, we developed an anatomic approach in which circumferential RF lesions are created around the
ostia of each PV, with the aim to isolate these veins from the LA while reducing the risk of PV stenosis. A
nonfluoroscopic 3D electroanatomic navigation system was used for generating and validating the continuity

LNCP
19
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

of circular lines. We report the feasibility, safety, and clinical outcome of this technique in patients with
resistant AF, either paroxysmal or permanent.

METHODS

CATHETER PLACEMENT
Antiarrhythmic drugs (except amiodarone) and digoxin were discontinued for 5 half-lives. Quadripolar 6F
catheters were placed in the coronary sinus (CS), RA, and right ventricular apex. The LA and PVs were

LNCP
20
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

explored through transseptal catheterization. Heparin was titrated to maintain a partial thromboplastin time
of 60 to 90 seconds.

MAPPING PROCESS

The nonfluoroscopic navigation system (CARTO; Biosense Webster) has been described elsewhere. With
use of a special mapping and ablation catheter, 3D electroanatomic maps are reconstructed that display the
spatial distribution of local endocardial activation times (LATs) relative to a reference electrogram.

The navigator catheter was placed 2 to 4 cm into each PV and slowly pulled back. Along pullback, multiple
locations were recorded to tag the vein. The ostium was identified by fluoroscopic visualization of the
catheter tip entering the cardiac silhouette with simultaneous impedance decrease and appearance of atrial
potential. Three locations were recorded along the mitral annulus to tag valve orifice. LA maps were
obtained by sequentially acquiring a minimum of 50 points.

ABLATION PROCEDURE

RF pulses were delivered in unipolar mode to a cutaneous ground patch via the distal catheter electrode.
Because all 4 PVs may serve as a source of AF,4 our end point was the creation of circumferential lines of
conduction block around each PV. These lines consisted of contiguous focal lesions deployed at a distance
5 mm from the ostia. With a maximum temperature setting of 60°C, RF energy (up to 50 W) was applied for
60 to 120 seconds until local electrogram amplitude was reduced by 80%. During AF, the same power
titration technique was used, but current was always delivered for 60 to 120 seconds. If there was an
impedance rise, or the patient had cough, burning pain, or severe bradycardia, RF delivery was stopped.

REMAP PROCESS AND LESION VALIDATION

In patients in SR, postablation remap was performed utilizing the preablation anatomic map for the
acquisition of new points to allow accurate comparison of pre- and post-RF activation sequence. In patients
in AF, after restoration of SR, the remap was done with the anatomic map acquired during AF, to maintain

LNCP
21
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

the same landmarks and lesion tags for reliable lesion verification. We found a small intrapatient difference
between the anatomic map of a fibrillating, noncontracting atrium and the map during pacing, in which
locations are recorded at end diastole. This was validated by measuring the distance between corresponding
locations acquired during AF and pacing. We tested a set of 5 points per patient in a sample of 10 patients.
No differences were noted between 3 paired measurements (mean difference 0.18±0.05 mm, t=0.74,
P=0.86).

Lesion validation required acquisition of 2 maps during CS and RA pacing for the lateral and septal PVs,
respectively. The rationale behind this setting was to pace from a site close to the lesions and shorten
conduction time to the ablation site, thereby allowing detection of delayed activation inside the circular line.

This study lends further evidence to the concept of the dominance of the LA in the region of the PVs in the
initiation and/or maintenance of AF. The efficacy of PV isolation in both paroxysmal and permanent AF
supports the current notion of a common pathogenesis (involving various combinations of focal activity and
reentry) with a spectrum of clinical presentations. On the basis of our findings, one can envision that PV
isolation may be proposed as a valuable alternative to either focal ablation or biatrial compartmentalization.

CRYOTHERMY

Cryoablation is performed with a nitrous oxide cooled probe that when applied to atrial tissue at -60 degrees
C for 2 minutes reliably produces transmural lesions that block atrial conduction. An advantage of this
technique is that there is no tissue vaporization or charring and the endocardial surface remains smooth
following cryoablation. Cox and colleagues were the first to incorporate this modality into surgery for AF
and it remains an important component of the Cox-Maze III procedure .

Cox and colleagues have subsequently published results for the 'cryo-Maze' procedure in which the lesions
of the Cox-Maze III operation are performed solely by cryoablation . Other groups (Sueda, others) have
demonstrated the feasibility of left sided partial Maze procedures using cryoablation . Ongoing development
of minimally invasive procedures using cryoablation has been somewhat limited by currently available
cryoprobe systems, which are rigid .

LNCP
22
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

MICROWAVE

Microwave ablation makes use of high-frequency electromagnetic radiation, which upon application to
atrial tissue causes oscillation of water molecules, converting electromagnetic energy into kinetic energy
and producing heat. This heat causes thermal injury leading to conduction block. However, unlike
radiofrequency heating, microwave heating does not cause endocardial surface charring, which may reduce
the risk of thromboembolism . Microwave ablation has greater tissue penetration than radiofrequency
ablation, increasing the likelihood of a transmural lesion. These advantages have led to an increasing
interest in the use of microwave ablation in surgical procedures for atrial fibrillation. Microwave ablation
probes are commercially available and have been successfully used in partial Maze operations to treat
chronic AF .

ULTRASOUND

Focused ultrasound (8-10 MHz) can be used to deliver energy to atrial tissue which results in deep heating,
coagulation necrosis, and conduction block. The feasibility of this modality for the treatment of atrial
fibrillation in humans has been demonstrated in early catheter-based approaches . Systems used in these
studies make use of tubular transducers that deliver cylindrical zones of ultrasonic waves to produce
circumferential lesions around individual pulmonary veins This characteristic lesion pattern has potential
applications in minimally invasive surgical approaches to AF. Planar ultrasound transducers could be used
to produce linear lesions and for epicardial application

LASER

Light energy has been used experimentally to produce linear myocardial lesions with both
neodymium:yttrium-aluminum garnet (Nd:YAG) lasers and an infrared coagulator These methods produce
well-demarcated transmural photocoagulation necrosis with relatively low peak tissue temperatures and
without tissue vaporization. Light energy from a Nd:YAG laser has been delivered radially through flexible

LNCP
23
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

optical fibers oriented parallel to myocardium surfaces to produce long linear lesions in a single application
Light energy from the commercially available infrared coagulator is delivered via a light-conducting quartz
rod that is applied to the myocardial surface. The efficacy of both methods has been evaluated
experimentally with epicardial as well as endocardial application.

DRUGS IN THE MANGEMENT OF ATRIAL FIBRILATION

1. THE ORAL DIRECT THROMBIN INHIBITORS—
2. COMBINATION OF TWO ANTIPLATELET AGENTS—
ASPIRIN PLUS
CLOPIDOGREL—WITH STANDARD WARFARIN THERAPY.

LNCP
24
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

THE ORAL DIRECT THROMBIN INHIBITORS

XIMELAGRATAN

Ethyl 2-[[(1R)-1-cyclohexyl-2- [(2S)-2-[[4-(N'-hydroxycarbamimidoyl)

phenyl]methylcarbamoyl]azetidin-1-yl]- 2-oxo-ethyl]amino]acetate

Oral direct thrombin inhibitors are a new class of anticoagulants currently developed for stroke prevention
in AF. Ximelagratan has been the first such compound that has been thoroughly evaluated in clinical trials.
The compound has a predictable pharmacokinetic profile that is stable over time. With a rapid onset of
action and metabolism independent of the hepatic cytochrome P450 enzyme system, ximelagratan has a low
potential for drug interactions and no known food interactions, making coagulation monitoring and dose
adjustments unnecessary. Two large pivotal trials have been carried out comparing the efficacy and safety
of ximelagratan with that of warfarin. The Stroke Prevention using an Oral Thrombin Inhibitor in Atrial
Fibrillation (SPORTIF) III study was a European long-term phase III study, and similar to the North
American SPORTIF V study. The major difference between the trials was that SPORTIF III was an open-
label, randomized trial whereas anticoagulation was administered in a double-blind fashion in SPORTIF V.

ACTION
Ximelagatran, a direct thrombin inhibitor, was the first member of this class that can be taken orally.
It acts solely by inhibiting the actions of thrombin. It is taken orally twice daily, and rapidly absorbed by the
small intestine. Ximelagatran is a prodrug, being converted in vivo to the active agent melagatran. This

LNCP
25
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

conversion takes place in the liver and many other tissues through dealkylation and dehydroxylation
(replacing the ethyl and hydroxyl groups with hydrogen).

ASPIRIN AND CLOPIDOGREL

CLOPIDORGREL

(+)-(S)-methyl 2-(2-chlorophenyl)- 2
-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate
2- acetoxybenzoic acid(aspirin)

Aspirin and clopidogrel are antiplatelet agents that act through different mechanisms. Aspirin reduces the
risk of stroke in patients with AF by approximately 20%.1–3 The additive benefits of combining a
thienopyridine with aspirin have been clearly demonstrated in patients undergoing percutaneous coronary
intervention and in those with acute coronary syndrome or acute myocardial infarction.

LNCP
26
Surgical boon in the therapy of atrial fibrillation
0137PY061052

LNCP
27
Surgical boon in the therapy of atrial fibrillation
0137PY061052

LNCP
28
Surgical boon in the therapy of atrial fibrillation
0137PY061052

LNCP
29
Surgical boon in the therapy of atrial fibrillation
0137PY061052

LNCP
30
Surgical boon in the therapy of atrial fibrillation
0137PY061052

LNCP
31
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

REFERNECE

1. Fuster V, Rydén LE, Cannom DS, et al. (2006). "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". Circulation 114 (7): e257–
354.
2. Friberg J, Buch P, Scharling H, Gadsbphioll N, Jensen GB. (2003). "Rising rates of hospital
admissions for atrial fibrillation". Epidemiology 14 (6): 666–72.
3. "Atrial Fibrillation (for Professionals)". American Heart Association, Inc.. 2008-12-04. Archived
from the original on 2009-03-28. http://www.webcitation.org/5fcMx8BUx.
4. http://circ.ahajournals.org/cgi/content/full/102/21/2619#F1
a. Hobbs WJ, Van Gelder IC, Fitzpatrick AP, et al. The role of atrial electrical remodeling in
the progression of focal atrial ectopy to persistent atrial fibrillation. J Cardiovasc
Electrophysiol. 1999;10:866–870.
b. Kuck KE, Ernst S, Cappato R, et al. Nonfluoroscopic endocardial catheter mapping of atrial
fibrillation. J Cardiovasc Electrophysiol. 1998;9:S57–S62.
c. Yen H S, Sanchez-Quintana D, Cabrera JA, et al. Anatomy of the left atrium: implications
for radiofrequency ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 1999;10:1525–
1533.

5. Cox JL, Schuessler RB, Boineau JP. The surgical treatment of atrial fibrillation. I. Summary of the
current concepts of the mechanisms of atrial flutter and atrial fibrillation. J THORAC CARDIOVASC
SURG 1991;101:402-5.

6. Cox JL, Canavan TE, Schuessler RB, et al. The surgical treatment of atrial fibrillation. II.
Intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial
flutter and atrial fibrillation. J THORAC CARDIOVASC SURG 1991;101:406-26.

LNCP
32
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

7. Cox JL, Schuessler RB, D'Agostino HJ Jr, Stone CM, Chang BC, Cain ME. The surgical treatment
of atrial fibrillation. III. Development of a definite surgical procedure. J THORAC CARDIOVASC
SURG 1991;101:569-83.
8. Executive Steering Committee on behalf of the SPORTIF III Investigators, Stroke prevention with
the oral direct thrombin inhibitor Ximelagratan compared with warfarin in patients with non-
valvular atrial fibrillation (SPORTIF III): randomized controlled trial, Lancet, 2003;362:1691–8.
9. Executive Steering Committee for the SPORTIF V Investigators, Ximelagratan vs. warfarin for
stroke prevention in patients with non-valvular atrial fibrillation. A randomized trial, JAMA,
2005;293:690–98.
10. Ho SJ, Brighton TA (2006). "Ximelagatran: direct thrombin inhibitor". Vasc Health Risk Manag 2
(1): 49–58. PMID 17319469
11. Lip GYH, Edwards SJ, Stroke prevention with aspirin, warfarin, and Ximelagratan in patients with
non-valvular atrial fibrillation: asystematic review and metaanalysis, Thrombosis Res, 2006;118:
321–33.
12. Atrial Fibrillation Investigators, Risk factors for stroke and efficacy of antithrombotic therapy in
atrial fibrillation: analysis of pooled data from five randomized controlled trials, Arch Intern
Med,1994;154:1449–57.
13. Hart RG, Benavente O, McBride R, Pearce LA, Antithrombotic therapy to prevent stroke in patients
with atrial fibrillate.
14. F. W. Mohr, A. M. Fabricius, V. Falk, et al. Curative treatment of atrial fibrillation with
intraoperative radiofrequency ablation: short-term and midterm results. Journal of Thoracic &
Cardiovascular Surgery 2002; 123:919-27.
15. M. R. Williams, J. R. Stewart, S. F. Bolling, et al. Surgical treatment of atrial fibrillation using
radiofrequency energy. Annals of Thoracic Surgery 2001;71:1939-43; discussion 43-4.
16. G. Hindricks, F. W. Mohr, R. Autschbach and H. Kottkamp. Antiarrhythmic surgery for treatment of
atrial fibrillation--new concepts. Thoracic & Cardiovascular Surgeon. 1999; 47: 365-9.
17. H. T. Sie, W. P. Beukema, A. R. Misier, et al. Radiofrequency modified maze in patients with atrial
fibrillation undergoing concomitant cardiac surgery.[comment]. Journal of Thoracic &
Cardiovascular Surgery. 2001; 122: 249-56.
18. H. T. Sie, W. P. Beukema, A. R. Ramdat Misier, A. Elvan, J. J. Ennema and H. J. Wellens. The
radiofrequency modified maze procedure. A less invasive surgical approach to atrial fibrillation
during open-heart surgery. European Journal of Cardio-Thoracic Surgery. 2001; 19: 443-7.
19. M. Haissaguerre, P. Jais, D. C. Shah, et al. Right and left atrial radiofrequency catheter therapy of
paroxysmal atrial fibrillation. Journal of Cardiovascular Electrophysiology. 1996; 7: 1132-44.
20. F. Gaita, R. Riccardi, L. Calo, et al. Atrial mapping and radiofrequency catheter ablation in patients
with idiopathic atrial fibrillation. Electrophysiological findings and ablation results.
Circulation 1998;97: 2136-45.
21. http://www.ijp-online.com/temp/IndianJPharmacol414153-1997995_053259.pdf
a. Recent advances in the pharmacotherapy of atrial fibrillation, J.Singh and JS Braich, Dept. of
Pharmacology Pt. BD Sharma PGIMS, Rohtak.
b. Reference:
• Nattel S. Therapeutic Implication Of Atrial Fibrillation Mechanism; Can
Mechanistic Insights Be Used To Improve AF Management? Cardiovas Res 2002;
54; 347-80.

LNCP
33
 Surgical boon in the therapy of atrial fibrillation
0137PY061052

• Singh BN, Aliot E. Newer Antiarrythmic Agents For Maintaining Sinus Rhythm In

Atrial Fibrillation ;Simplicity Or Complexity? Eur Heart J 2007;9;G17-25.

LNCP
34