Atrial Fibrillation

THE TERM ATRIAL FIBRILLATION IS USED TO
describe an abnormal rhythm of the heartbeat; instead of
beating regularly, the heart beats very erratically. The
irregular heartbeats may speed up, and the heart rate
may be as fast as 120–180 beats per minute. These fast
and strong beats may be sensed as palpitations. Atrial
fibrillation is the most common persistent heart rhythm
abnormality observed in medical practice.

The adequate management of atrial fibrillation has
resisted the major advances in cardiology that have been
made in the past 40 years. This stubborn and bothersome
arrhythmia has increased to epidemic proportions over the
past 20 years, particularly because of an aging population
and beneficial treatments for many other heart disease
processes that are complicated by atrial fibrillation. The
only test available for the diagnosis of atrial fibrillation is
the simple, an inexpensive ECG, a clinical test that has
remained virtually unchanged since its inception in the
1940s.

Figure 1 shows the electrical system of the heart, the
conduction system that transports the current of energy
initiated in the sinus node which is then delivered to the
ventricular structures to initiate the heartbeat. The ECG
picks up the heart’s electrical impulses transmitted through
the skin of the chest. The normal physiologic process
should be understood in order to recognize the clinical
features and electrocardiographic findings observed in
atrial fibrillation.

The sinoatrial (SA) node is unique and has no steady
resting potential. After repolarization, slow spontaneous
depolarization occurs. Thus, this unique pacemaker
provides individuals with an automatic, infinitesimal
current that sets the electrical activity and contraction of
the heart. The SA discharge rate, usually 50–100 per
minute, is under autonomic, chemical, and hormonal
influence.

In the electrical system the atrioventricular (AV ) node
provides a necessary physiologic delay of the electrical
currents. This allows the atria to fill the ventricles with
blood before ventricular contraction or systole from the
AV node, a physiologic ‘‘tollgate,’’ the electrical current
rapidly traverses the right and left bundle branches, the
specialized conductive tissues of the ventricles, and the
entire ventricular myocardium is depolarized. The transient
halt and slowing of conduction through the
specialized AV node fibers play an important protective
role in patients with atrial flutter and atrial fibrillation.
In these conditions, a rapid atrial focus fires at a rate of
300–600 beats per minute and these rapid beats reach the
AV node; fortunately, this AV tollgate reduces the electrical
traffic that reaches the super highway which traverses the
ventricles at approximately 80–180 beats per minute, and
serious life-threatening events are prevented as the rapid
rates are slowed.

DIAGNOSIS
Diagnosis of atrial fibrillation is based on history, clinical
examination, and confirmation with an ECG. The patient
may experience rapid and irregular heartbeats usually from
one to several hours. Associated symptoms include mild
shortness of breath that can become severe if serious
underlying heart disease is present. During atrial fibrillation
the atrium does not contract normally and blood is
therefore not delivered rapidly into the left ventricle. Poor
filling of the ventricle and the fast ventricular rate may
cause a fall in blood pressure resulting in lightheadedness
and dizziness. Because the atrium is fibrillating and not
contracting, there is stasis of blood in the atrial appendage.
Stasis predisposes the patient to clot formation and these
thrombi may be dislodged and fly into the circulation and
travel to other organs (embolize). The embolus can block
an artery in the brain and cause a stroke.

Atrial fibrillation may last several hours to a couple of
days and then disappear for several days to weeks; this
condition is referred to as paroxysmal atrial fibrillation.
These patients may have no symptoms from 6 months
up to 2 years and then fibrillation may recur. Atrial
fibrillation, therefore, does not always cause symptoms and
the disease can be misdiagnosed. In the Cardiovascular
Health study, 12% of new cases of atrial fibrillation were
diagnosed on the basis of ECG screening alone and these
individuals presumably had no symptoms.

In patients presenting with atrial fibrillation it is
imperative to exclude structural heart disease, particularly
mitral stenosis which has a typical murmur that can be
missed because of the fast heart rate. The echocardiogram
does not help with diagnosing atrial fibrillation, but it is
useful when detecting underlying structural heart disease.

CAUSES AND RESEARCH IMPLICATIONS
Diseases or disorders that cause atrial fibrillation are shown
in Fig. 2. Due to the vast number of both serious diseases
and disorders that cause atrial fibrillation, it is not surprising
that a definitive cure is rarely possible. This has
become most frustrating for cardiologists and technologists
who strive to provide advances in technologic equipment
and strategies for the management of atrial fibrillation.
The prevention of atrial fibrillation is therefore of paramount
importance. There has been little focus in the past
20 years on the prevention of this abnormality.

A. Hypertension
Because the cure and management of atrial fibrillation is
most often difficult, it is necessary to prevent the
occurrence of atrial fibrillation by aggressive management
of conditions that cause atrial fibrillation. The aggressive
management of hypertension is very important. Unfortunately,
despite more than 50 years of extensive research by
national bodies and pharmaceutical firms and the major
advertisement of new drugs available for the management
of hypertension, only four antihypertensive agents are
available.

These agents include diuretics, beta-blockers, calcium
blockers, and ACE inhibitors. The recently added new
agents, angiotensin receptor blockers, are really no
different from ACE inhibitors but appear to have a lesser
incidence of adverse effects. There are more than 12
diuretics, 15 beta-blockers, 10 calcium antagonists, 14
ACE inhibitors, and 6 angiotensin receptor blockers
available, but these represent only 4 active agents.
In addition diuretics, beta-blockers, or ACE inhibitors
achieve the goal blood pressure of less than 140 mmHg in
less than 50% of patients. Often two drugs must be used
for control, thus reducing patient compliance. Calcium
antagonists are effective in approximately 65% of patients,
but they are not cardioprotective and carry increased risk
for the causation of heart failure in the elderly and in
patients with heart disease.

Excellent control of hypertension, therefore, has not
been achieved worldwide and this will not occur until the
medical profession and pharmaceutical firms recognize the
root of the problem. Only four antihypertensive agents are
available and they are only mildly beneficial. The fifth
group of antihypertensive agents is the alpha-blockers.
They have been shown to increase the incidence of heart
failure in the recently completed ALLHAT trial.
All editorials in clinical medical journals purport the idea
that available antihypertensive agents are all beneficial and
with combination therapy control is possible.

B. Heart Failure
There is a worldwide epidemic of heart failure. It is caused
by most of the conditions listed above, but it has other
causes and precipitating factors. Heart failure causes
the left atrium to enlarge even further and this enlargement
enhances the occurrence of atrial fibrillation. Early
aggressive treatment of mild heart failure, New York Heart
Association class I and II, with beta-adrenergic blocking
drugs and ACE inhibitors may prevent progression to class
III heart failure and may prevent atrial fibrillation in some
patients.

C. Valvular Heart Disease
Diseases of heart valves, particularly mitral stenosis, mitral
regurgitation, aortic stenosis, and regurgitation, are
commonly associated with atrial fibrillation. Many patients
following valvular heart surgery develop atrial fibrillation.

D. Chronic Coronary Artery Disease
The prevention of coronary artery disease would obviously
lead to a decrease in the prevalence of atrial fibrillation.
Atrial fibrillation occurs in more than 15% of patients
during the first few days of acute myocardial infarction.
Chronic coronary artery disease does not commonly cause
atrial fibrillation, but because the disease is common it is
responsible for more than 5% of cases of atrial fibrillation.
Coronary artery disease is caused by obstruction of arteries
by atheroma. After more than 50 years of research it is still
impossible to prevent atheroma formation in arteries.
Treatment with statins, aspirin, ACE inhibitors, and all the
new wonder drugs proclaimed by manufacturers and
medical experts only prevent complications of atheroma in
approximately 25% of patients, but they do not prevent
the disease process. It is obvious that more extensive
research is required to halt the epidemic of atheromatous
coronary artery disease worldwide (see the chapter
Atherosclerosis/Atheroma).

E. Sick Sinus Syndrome
Patients with sick sinus syndrome (sinus node dysfunction)
have degenerative disease of the sinus node. The natural
generator that emits an electrical impulse causing the
heartbeat is diseased in sick sinus syndrome. Bradycardia of
less than 45 beats per minute along with greater than
4-second pauses may result in loss of consciousness. In
addition, because of the slow heart rate foci in the atrial
takeover the electrical circuit and cause rapid heart beats,
tachycardia, ranging from 120 to 160 beats per minute.
The slow regular rhythm may change to atrial fibrillation
often at a fast heart rate, (tachycardia) followed within
hours by slow heart rates (bradycardia) — thus the term
bradytachy syndrome. These patients are best managed by
implantation of a pacemaker.

F. Thyrotoxicosis
Thyrotoxicosis is caused by hyperthyroidism. The thyroid
glands produces excessive amounts of thyroxine with
resultant stimulation of the heart and tachycardia. Atrial
fibrillation is a well-known complication and bothersome
palpitations with tachycardia of 120–180 beats per minute
may occur. The tachycardia is controlled with betablocking
drugs such as propranolol, and the thyroid
gland is treated with medications or radioactive iodine.

G. Idiopathic Atrial Fibrillation
It is not uncommon for atrial fibrillation to occur in the
absence of an abnormal structural or functioning heart.
This condition is called lone atrial fibrillation. Data from
various countries are not available, but in the United States
approximately 15% of patients are found to have lone
atrial fibrillation. In some of these patients, and particularly
in those with paroxysmal atrial fibrillation, recent
investigations have revealed foci located in the proximal
pulmonary veins that may cause ectopic atrial activation.

PATHOPHYSIOLOGY
During the past 50 years different theories have been
proposed to explain the mechanism underlying atrial
fibrillation, but many controversies surrounded these
mechanisms. In the past decade it seems well accepted
that both focal and reentrant mechanisms are involved,
playing a different role in the initiation and perpetuation
of the arrhythmia. Several recent human multielectrode
mapping systems and other studies indicate that in atrial
fibrillation the dominant mechanism incorporates multiple
meandering wavelets, both in the acute and chronic form
of this condition. Multiple wavelengths of excitation
propagate around the atrial myocardium and the arrhythmia
is perpetuated because of an abnormal atrial tissue
substrate, particularly in patients with structural heart
disease and permanent atrial fibrillation. Patients with
paroxysmal atrial fibrillation with no evidence of structural
heart disease appear to have a trigger-predominant
mechanism, but the two basic mechanisms reflect a large
overlap. After very long periods of permanent atrial
fibrillation, if sinus rhythm is restored, reverse remodeling
usually fails to occur. This may explain why in patients
with persistent atrial fibrillation for more than 12 months
it is difficult to maintain sinus rhythm following
cardioversion.

Atrial fibrillation may be triggered by focal initiators.
Recent experimental work indicates that ectopic atrial
activation may emerge from one more foci located in the
muscular sleeves of the proximal pulmonary veins as single
beats or repetitive bursts of activity. This focal-triggered
atrial fibrillation is often paroxysmal in its early stages, and
it may be observed in individuals with structurally normal
hearts. The focal-triggered mechanism may also underlie
some cases of persistent atrial fibrillation in the presence or
absence of structural heart disease. It appears that the
presence of atrial foci functioning as triggers localized in
the pulmonary veins is a finding in many patients with
lone or idiopathic and paroxysmal atrial fibrillation. In this
group of patients, segmental or circumferential pulmonary
vein ablation has an emerging role.

CLASSIFICATION AND MANAGEMENT
A. Acute Atrial Fibrillation
An episode of atrial fibrillation observed within 48 h of its
onset is described as acute. If the ventricular rate is greater
than 160 beats per minute and results in acute cardiovascular
decompensation manifested by hypotension,
shortness of breath, chest pain, confusion, or heart failure,
the rhythm should be converted to normal sinus rhythm.
DC cardioversion is usually the initial treatment of choice.
Figure 3A shows the ECG tracing of a patient with acute
atrial fibrillation and a fast ventricular rate of 160 beats per
minute. Figure 3B shows the same patient hours later after
the rate had been decreased by a beta-blocking drug. It also
shows spontaneous reversion to normal sinus rhythm.
The diagnostic points of the ECG are as follows: the
rhythm is completely irregular, the R-to-R intervals are
irregular, there are no visible P-waves, and the baseline
shows irregular undulations.

If there are no signs of cardiovascular decompensation
and the arrhythmia is well-tolerated, diltiazem (a calcium
antagonist), esmolol, or other beta-blocking drugs
administered intravenously can be used to slow the
ventricular response to less than 110 beats per minute,
with the hope that normal sinus rhythm may return
spontaneously within 12–24 h of onset. Sinus rhythm may
return spontaneously if atrial fibrillation is due to an
extracardiac cause that is corrected or if the left atrium is
not enlarged. If spontaneous sinus rhythm does not occur,
conversion to sinus rhythm may be attempted with
pharmacologic agents such as ibutilide.

Ibutilide should not be used in patients with a low
serum potassium level or prolonged QT interval because
torsades de pointes may be precipitated. There is a 5%
If there is no hemodynamic compromise and the patient
is stable in the presence of acute atrial fibrillation, the
reasons for conversion to sinus rhythm should be strongly
examined. Although electrical cardioversion may establish
sinus rhythm in more than 90% of patients, after 6 months
less than 30% of patients remain in sinus rhythm.
If atrial fibrillation occurs with very fast heart rates of
200–240 per minute, Wolff-Parkinson-White syndrome
may be the underlying cause. This disease is caused by an
anomalous pathway that is capable of conducting rapidly.
Drugs that are commonly used to manage chronic atrial
fibrillation such as digoxin, beta-blockers, and calcium
antagonists are contraindicated.

B. Paroxysmal Atrial Fibrillation
These patients experience intermittent, recurrent, and selfterminating
episodes of atrial fibrillation. Episodes are
considered paroxysmal atrial fibrillation if they terminate
spontaneously. Some patients tolerate these short bouts of
irregular, abnormal heart rhythms without symptoms,
especially if they are in the range of 100–140 beats per
minute. Many elderly patients tolerate atrial fibrillation
well without therapy or with minimum therapy, because
the ventricular rate is slow (80–120 beats per minute) and
because they have concomitant atrioventricular (AV ) nodal
disease. AV nodal disease blocks conduction from the
atrium to the ventricle slowing the ventricular response
and heart rate. This slow ventricular response happens
because several of the drugs used (digoxin, beta-blockers,
calcium antagonists) to control the fast heart rates cause a
partial blockage of the electrical impulse as it traverses the
AV node to reach the ventricle.

Other patients experience rapid heart rates of 160–190
beats per minute that may recur twice a year or two or
three times weekly for a few months then recur months
later. Paroxysmal atrial fibrillation of this type is extremely
bothersome to many patients who may have to attend
emergency rooms or must receive antiarrhythmic drugs or
pacemaker therapy.

Paroxysmal atrial fibrillation accounts for 35–50% of all
cases of atrial fibrillation. It is most common in patients in
their 50s and 60s with prevalence peaking between the ages
of 50 and 70. This condition is three times more common
in men than in women. The probability that lone atrial
fibrillation will progress from paroxysmal to permanent is
approximately 20%. Paroxysmal atrial fibrillation occurs in
patients with structurally normal hearts, but it also occurs
in patients with structural heart disease.

Paroxysmal atrial fibrillation remains a difficult problem
to manage. The rapid heart rates are difficult to control
with available agents, which include beta-blockers, calcium
antagonists, digoxin, and amiodarone. Sotalol 160–240 mg
daily may cause maintenance of sinus rhythm in less than
50% of patients. Breakthrough atrial fibrillation
commonly occurs and anticoagulation with warfarin or
ximelagatran becomes necessary to prevent stroke.

Paroxysms with a ventricular rate of 140–180 beats per
minute can be managed with diltiazem or esmolol
intravenously to reduce the rapid heart rate to less than
110 beats minute until spontaneous revision to sinus
rhythm occurs. Digoxin is usually not effective in reducing
rapid ventricular rates during paroxysms and is not
advisable in patients with paroxysmal atrial fibrillation
except when combined with a beta-blocking drug.
The combination of a beta-blocking drug with the calcium
blocker diltiazem plays a role in controlling rapid
ventricular rates.

In patients with paroxysmal atrial fibrillation resistant to
drug therapy there are three options: Complications of
these procedures must be outlined in detail to the patient.

1. Pulmonary Vein Ablation
In pulmonary vein ablation percutaneous catheters are
used to identify the location of arrhythmogenic foci within
all four pulmonary veins. Either segmental pulmonary vein
isolation or circumferential pulmonary vein ablation
techniques are used at different centers. In skilled hands
and in patients with one focus, the success rate approaches
80%. The success rate is low in patients with persistent
atrial fibrillation and lower in those with structural heart
disease than in those without. Left atrial ablation to
encircle the pulmonary veins has been shown to improve
survival, reduce the risk of heart failure and stroke, and
improve quality of life when compared with medical
therapy.

Patients not suitable for pulmonary vein ablation
include those with a large left atrium of greater than
60 mm, patients with contraindications to anticoagulants,
and the elderly over 75 years of age. Before considering
pulmonary vein ablation, sinus node dysfunction (sick
sinus syndrome), thyrotoxicosis, AV nodal reentrant
tachycardia, and Wolff-Parkinson-White syndrome must
be excluded.

C. Persistent Atrial Fibrillation
This form of atrial fibrillation will not self-terminate, but
it can be effectively cardioverted to sinus rhythm with DC
cardioversion or pharmacologic agents. Some patients with
valvular heart disease may be converted easily provided
that the left atrium is not large. A large left atrium greater
than 5 cm is a risk factor for the causation of atrial
fibrillation and often predicts a recurrence in a few months
following cardioversion to sinus rhythm.
A major randomized clinical trial involving more than
4500 patients, randomized to either rate control of
persistent atrial fibrillation or rhythm control (suppression
of atrial fibrillation), showed no significant differences in
mortality, morbidity, or quality of life between the two
strategies.

Patients with drug-refractory persistent atrial fibrillation
may require intervention that includes pulmonary
vein ablation or intraoperative radiofrequency ablation
utilizing a specific left atrial linear lesion line concept, as
described above.

1. Synchronized DC Cardioversion
Attempting DC conversion of atrial fibrillation is always
considered carefully. Immediate DC cardioversion is
indicated for patients who are hemodynamically unstable.
It is usually contraindicated in permanent atrial fibrillation
with a duration of greater than one year because sinus
rhythm is usually not maintained and in patients with a
left atrial size greater than 5.5 cm. Patients with atrial
fibrillation of less than one week’s duration usually regain
atrial function after conversion. Embolization occurs in
about 2% of patients and anticoagulation is necessary
before cardioversion. Conversion should not be attempted
in patients with suspected digitalis toxicity because of the
risk of precipitating ventricular fibrillation. Patients with
sick sinus syndrome (sinus node dysfunction) should not
be considered as conversion may cause prolonged pauses.
Anticoagulants are not used in DC conversion if the atrial
fibrillation has been present for less than 24 h; patients
with valvular heart disease, particularly mitral stenosis, may
have thrombus in the left atrial appendage and transesophageal
echocardiography is warranted to exclude thrombi.
In patients with a duration over 24 h but less than 48 h,
IV heparin may be used for anticoagulation to allow
conversion within 24 h. Patients with atrial fibrillation for
greater than 48 h should be anticoagulated for at least
3 weeks prior to conversion and anticoagulation should
be continued for more than three weeks following
conversion. Light anesthesia with a standby anesthesiologist
is necessary during the procedure.

D. Permanent Atrial Fibrillation
Atrial fibrillation that cannot be terminated by cardioversion,
that can be terminated only for brief intervals, or that
lasts longer than one year without cardioversion having
been attempted is classified as permanent. Chronic atrial
fibrillation implies continuing atrial fibrillation and does
not address the important clinical distinction between
persistent and permanent atrial fibrillation.
In the vast majority of patients with permanent atrial
fibrillation, slowing of the ventricular response to 70–90
beats per minute will be helpful. A beta-blocking drug such
as metoprolol, bisoprolol, or atenolol should slow down
the ventricular response. These agents are also a good
choice in patients with concomitant congestive heart
failure New York heart Association class I–III. Digoxin
was commonly used for this condition from the 1950s to
1990, but during the past decade beta-blockers have
become the agents of choice, mainly because it became
apparent that digoxin does not achieve the control of a fast
ventricular rate associated with exercise. In patients in
whom beta-blockers cannot be used safely, the ventricular
rate can be slowed sufficiently with the inexpensive digoxin
administered once daily. Occasionally a combination of a
beta-blocker and digoxin becomes necessary.
All of the available beta-blocking drugs can be used
safely with the exception of sotalol. This drug must not be
used in the management of permanent (chronic) atrial
fibrillation because it carries a risk of torsades de pointes.
Other beta-blockers do not have this adverse side effect.
A recent clinical trial confirmed that it is safer to manage
patients with permanent atrial fibrillation by controlling
their ventricular rate (heart rate) rather then attempting to
cardiovert to sinus rhythm or use pharmacologic agents to
maintain sinus rhythm. Patients after conversion do not
often remain in sinus rhythm and pharmacologic agents
(amiodarone, flecainide, propafenone, sotalol, and quinidine)
necessary to maintain sinus rhythm are usually not
successful and produce life-threatening adverse effects.

ANTICOAGULANTS
A. Warfarin
Patients with atrial fibrillation considered high risk for
stroke require anticoagulation with warfarin to maintain
an INR of 2–3 to prevent stroke. An INR of 1.4–1.9 has
been shown to be associated with a stroke or mortality rate
similar to that for an INR of less than 1.5. The loss of
atrial contraction leads to stasis of blood in the atrium and
is more marked in the left atrial appendage, the most
common site for clot formation. Stasis is accompanied by
hypercoagulability and there is increased concentrations
of fibrinogen and fibrin D-dimer and increased concentrations
of von Willebrand factor. These derangements all
contribute to the development of a prothrombotic state
and embolization. Five randomized clinical trials indicate
that warfarin anticoagulation reduces the risk of stroke
by 68% and lowers mortality by 33%. The risk of
hemorrhagic complications, particularly cerebral hemorrhage,
rises greatly when the INR exceeds 3.9. Patients on
oral anticoagulants should have blood tests every 2–3
weeks to maintain an INR of 2–3 in order to prevent
serious hemorrhagic events. In patients over 80 years of age
and in those with small risk of bleeding, the INR is
maintained at 1.8–2.8. Patients at high risk for bleeding
are not given anticoagulants.

Aspirin is only recommended for patients with lone
atrial fibrillation who are younger than 65 and with no
other risk factors for thromboembolism and for those who
are intolerant to warfarin administration. Aspirin’s risk
reduction of stroke is less than 20%. Patients with lone
atrial fibrillation who are younger than 65 have a low
stroke rate of approximately 1% versus patients over age 75
with one or more additional risk factors for thromboembolism
who have a stroke rate of greater than 8%. Lone
atrial fibrillation is indicated by the absence of hypertension
and valvular and other heart disease.

B. New Anticoagulant: Ximelagatran
This direct thrombin inhibitor has been shown to be as
effective as warfarin in preventing stroke and does not
require monitoring with blood tests. The drug represents a
major breakthrough for management of atrial fibrillation
and control of thromboembolism. The stroke prevention
with the oral direct thrombin inhibitor ximelagatran,
compared with warfarin in patients with nonvalvular atrial
fibrillation (SPORTIF) III and V randomized trials,
studied patients at moderate risk. Patients with mitral
stenosis, significant valve disease, or previous valvular heart
surgery were excluded. Thus the new agent if approved
should be used only in patients similar to those in the
SPORTIF trials. Caution: in both trials the new drug
caused substantial but usually transient increases in liver
enzyme concentrations in 6% of patients. Enzyme elevations
reached greater than five times the upper limits of
normal in 3.4% of ximelagatran-treated patients (see the
chapter Blood Clots). Hepatotoxicity limits the use of the
drug and similar agents should be sought.

ELECTRONIC PACING
It is known that conversion of atrial fibrillation to sinus
rhythm does not improve survival. The reason for trying to
maintain sinus rhythm is mainly to control symptoms.
Neither antiarrhythmic drugs nor atrial pacing alone have
been successful in suppressing atrial fibrillation.
A. Atrial Pacing
Recently, dual-site right atrial pacing has been shown in
small studies to achieve partial suppression of arrhythmia
in patients with bradycardia and atrial fibrillation on
antiarrhythmic drugs. The trials, however, do not support
the use of atrial pacing as monotherapy in symptomatic
atrial fibrillation.

B. Ablation of the AV node and Implantation of
a Permanent Pacemaker
This procedure is a last resort for patients with bothersome
atrial fibrillation refractory to other treatments. The
ablation of the AV node produces rate control and regular
ventricular contractions, but the atria continue to fibrillate
and the risk of stroke remains. Mortality is not improved
by this procedure. The combined incidence rate of sudden
death and malignant ventricular arrhythmias is approximately
7%.

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