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REVIEW
The Patient with Atrial Fibrillation Julia Heisler Indik, MD, PhD, Joseph S. Alpert, MDSarver Heart Center, College of Medicine, University of Arizona, Tucson.
ABSTRACT
Atrial fibrillation is a frequently encountered arrhythmia, particularly affecting the elderly. Patients at
significant risk for stroke should be considered for anticoagulation with warfarin. Management of atrial
fibrillation revolves around either controlling the ventricular rate response or trying to maintain sinus
rhythm with either pharmacologic or nonpharmacologic therapies. There are many treatment options to
consider, based upon the patient’s expectations, symptoms, and comorbid conditions. Therefore, the
treatment of atrial fibrillation must be individualized.
© 2009 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2009) 122, 415-418
KEYWORDS: Ablation; Antiarrhythmic medication; Anticoagulation; Atrial fibrillation; Stroke
Atrial fibrillation is the most common sustained arrhythmia
in North America and Europe. In the United States, atrial
fibrillation affects approximately 2.2 million adults whose
median age is 75 years, and nearly 10% of individuals over
the age of 80 years, with a clear increase in incidence and
prevalence with age.1,2 During the late 20th century, the
Framingham Heart Study population demonstrated a 7.8%
prevalence of atrial fibrillation in men aged 65-74 years,
with a corresponding prevalence in men aged 75-84 years of 11.7%. As the population of older individuals has increased,
the prevalence of atrial fibrillation also has grown.1-3 How-
ever, even age-adjusted prevalence of atrial fibrillation has
increased in recent years, suggesting that age alone does not
account for all aspects of the increased frequency of en-
countering this arrhythmia.3
Atrial fibrillation occurs approximately 1.5 times more
frequently in men than in women. In the Framingham Heart
Study, the prevalence of atrial fibrillation in men without a
prior myocardial infarction was 8.7%. A similar cohort of
women had a prevalence of atrial fibrillation of only 5.2%.
Despite the sex difference in prevalence, the overall numberof female patients with atrial fibrillation exceeds the number
of men with this condition because of greater longevity in
women. Thus, the most common hospitalized patient with
atrial fibrillation in US hospitals is an elderly woman.
The majority of patients with atrial fibrillation have some
form of cardiovascular disease. Common cardiovascular
conditions predisposing to atrial fibrillation include hyper-
tension, valvular heart disease (especially mitral valve dis-
ease), arteriosclerotic heart disease with and without a prior
myocardial infarction, pericardial disease, and heart failure.Noncardiovascular diseases that predispose to atrial fibril-
lation include diabetes mellitus, hyperthyroidism, acute and
chronic alcohol abuse, and a variety of pulmonary diseases
such as chronic obstructive lung disease, pneumonia, and
pulmonary embolism. Finally, iatrogenic causes of atrial
fibrillation include cardiac and noncardiac surgery as well
as therapy with bronchodilating beta agonists, nonprescrip-
tion cold remedies, antihistamines, and local anesthetics.4
Recent investigation has revealed that inflammation in the
atria might play an important role in the initiation, mainte-
nance, and perpetuation of atrial fibrillation.5 Unfortunately,
the underlying etiology of atrial fibrillation is often not wellunderstood in individual patients, although there is increasing
evidence for a genetic predisposition.6 Families with auto-
somal dominant inheritance of atrial fibrillation have been
reported.7 In familial forms of atrial fibrillation, mutations have
been described affecting both potassium and sodium channels,
with associations with other inherited rhythm disorders such as
Brugada syndrome, short QT syndrome, and, most recently, in
a form of long QT syndrome.8
Idiopathic or “lone” atrial fibrillation is not as benign an
entity as once thought. Jouven et al observed a 4-fold
Funding: There are no funding sources for this manuscript.
Conflicts of Interest: There is no conflict of interest to disclose from
Dr. Indik or Dr. Alpert.
Authorship: Both authors had access to the data and content of this
manuscript and had a role in the writing of the manuscript.
Requests for reprints should be addressed to Julia Heisler Indik, MD,
University of Arizona, Sarver Heart Center, 1501 N. Campbell Ave.,
Tucson, AZ 85724.
E-mail address: [email protected]
0002-9343/$ -see front matter © 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjmed.2008.12.012
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increase in cardiovascular mortality and a 2-fold increase in
all-cause mortality for middle-aged French men with lone
atrial fibrillation.9 A recent community-based study from
Omstead County in Minnesota and the EuroHeart Failure
Survey demonstrated that patients with newly diagnosed
atrial fibrillation with or without
heart failure had a high mortality
risk as well as prolonged hospital-ization, especially within the first
4 months following diagnosis.10,11
Of further concern are recent re-
ports that atrial fibrillation in pa-
tients without any evidence of
stroke are associated with memory
impairment, dementia, and hip-
pocampal atrophy.12,13 In patients
with paroxysmal atrial fibrillation,
a precipitating event, for example,
binge drinking, heavy exertion, or
emotional upset, can be identifiedin approximately 40% of individ-
uals.14 The most common precip-
itant was exercise, present in nearly 19% of patients, fol-
lowed by eating in 8%. Caffeine-containing beverages
precipitated atrial fibrillation in only 2.4% of patients.
The diagnosis of atrial fibrillation is usually straightfor-
ward, depending on the recognition of a randomly irregular
heart rhythm on physical exami-
nation or electrocardiogram. Atrial
fibrillation is further characterizedby whether it terminates spontane-
ously, “paroxysmal atrial fibrilla-
tion,” or requires cardioversion to
restore sinus rhythm, “persistent
atrial fibrillation.” There are 2 po-
tential strategies to manage atrial
fibrillation: control of the ventric-
ular heart rate, or restoration of
sinus rhythm. In patients over the
age of 65 years with at least one
risk factor for stroke, the Atrial
Fibrillation Follow-up Investiga-tion of Rhythm Management
(AFFIRM) trial demonstrated that
Figure 1 To employ a rate control strategy to manage atrial fibrillation, patients should first be
assessed for the risk for stroke to determine the need for anticoagulation. For patients with rapid
ventricular rates in atrial fibrillation, AV nodal blocking medications are utilized, which include
beta-blockers, calcium channel blockers, and digoxin. Pacemaker and AV node ablation is reserved
for patients who cannot be successfully managed medically. To employ a rhythm control strategy to
manage atrial fibrillation, patients also should first be assessed for the need for anticoagulation.
Antiarrhythmic drug (AAD) therapy and cardioversion are utilized as needed to maintain sinus
rhythm, and catheter ablation is reserved for patients who have symptomatic atrial fibrillation not
adequately controlled by pharmacologic therapy.
CLINICAL SIGNIFICANCE
● Atrial fibrillation is the most commonarrhythmia in this country, with a prev-
alence that has been increasing.
● Patients with atrial fibrillation need to beconsidered for the need for anticoagula-
tion, based upon their risk for stroke.
● Atrial fibrillation can be managed with
either rate or rhythm control strategies,
which are based upon both pharmaco-
logic and nonpharmacologic methods,
including catheter ablation.
416 The American Journal of Medicine, Vol 122, No 5, May 2009
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there is no difference in survival using either a rate control
or rhythm control strategy.15 In the AFFIRM study, the rate
control strategy predominantly relied upon the use of atrio-
ventricular (AV) nodal blocking medications, while the
rhythm control strategy predominantly relied upon cardio-
version and the use of antiarrhythmic medications, most
commonly amiodarone. Whether rate and rhythm control
strategies are equivalent in younger patients (under the ageof 65 years) is unknown. Of note, newer techniques to
maintain sinus rhythm, including catheter ablation, were not
studied in the AFFIRM trial. Randomized trials are under-
way to assess whether ablation for atrial fibrillation can
favorably alter cardiovascular outcomes.
Which therapy strategy is chosen depends upon the
symptoms of the patient and comorbidities. In particular,
patients with infrequent symptoms may not require any
further treatment. However, many individuals have frequent
episodes of symptomatic atrial fibrillation, including fatigue
and dyspnea. Indeed, quality of life and exercise tolerance
are decreased in patients with atrial fibrillation, and both of these variables improve when sinus rhythm is restored.16
For rhythm control, many patients will require antiarrhyth-
mic drug therapy to maintain sinus rhythm (Figure 1). An-
tiarrhythmic drugs include the Vaughn-Williams Class IC
agents, such as propafenone or flecainide, and Class III
agents such as sotalol, dofetilide, or amiodarone. The choice
of antiarrhythmic medication is dependent on whether there
is any other heart disease such as significant hypertrophy,
systolic heart failure, or coronary artery disease (Figure 2).
Dronedarone is a new antiarrhythmic drug—awaiting Food
and Drug Administration approval—that is related to ami-
odarone but without iodine on its aromatic ring, which isresponsible for the long-term toxicity of amiodarone.
Dronedarone may be approved for management in a broad
group of patients, except for severe systolic heart failure,
where there has been concern for an increase in mortality
seen in the Antiarrhythmic Trial with Dronedarone in
Moderate to Severe CHF Evaluating Morbidity Decrease
(ANDROMEDA) trial.17 Patients who are not adequately
controlled on an antiarrhythmic medication can be con-
sidered for catheter ablation for atrial fibrillation.18
Other patients hardly seem to notice when they are inatrial fibrillation, as long as their heart rate is controlled.
Pharmacologic options to achieve rate control include
digoxin, beta-blockers, and calcium channel blockers (Fig-
ure 1). If such medications are not tolerated or are ineffec-
tive, then pacemaker implantation with AV node ablation
can be considered. Ablation of the AV node does not restore
sinus rhythm, but controls the consequence of atrial fibril-
lation, a rapid ventricular heart rate. It should be noted that,
for rate control patients, digoxin therapy slows resting but
not exercise heart rate, and this agent does not prevent
recurrent episodes of atrial fibrillation, although beta-
blocker administration can accomplish this goal.19 Digoxinalso should be used cautiously in the elderly and in patients
with chronic kidney disease, as the drug is cleared by the
kidneys.
The presence of atrial fibrillation markedly increases the
patient’s risk for developing arterial embolism and stroke,
depending on the presence of other clinical conditions, such
as hypertension and diabetes. Consequently, most patients
with atrial fibrillation should receive antithrombotic therapy
with warfarin. Even patients in whom rhythm control is
established should continue on warfarin because silent ep-
isodes of atrial fibrillation may still be occurring, for exam-
ple, at night during sleep. The Cardiac Failure, Hyperten-sion, Age, Diabetes, Stroke (Doubled) (CHADS2) score was
developed to identify patients who are at high enough risk
Figure 2 Antiarrhythmic drug therapy is chosen according to whether the patient has
heart disease, including systolic heart failure, coronary artery disease, and substantial left
ventricular hypertrophy. Dronedarone, indicated in parentheses, may be approved as an
appropriate choice for a broad range of patients, except in those with systolic heart failure.
417Indik and Alpert Management of Atrial Fibrillation
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for stroke to warrant anticoagulation with warfarin.20 Pa-
tients with 2 moderate risk factors (age over 75 years,
hypertension, diabetes, or heart failure) or one high risk
factor (prior stroke, prosthetic heart valve, or mitral steno-
sis) have an estimated risk of stroke of 3.1%-5.1% per year
and should be anticoagulated with warfarin.20 If the risk of
bleeding is markedly increased, then aspirin may be the
therapy of choice because hemorrhage is less common withthis agent than with warfarin.
The presence of atrial fibrillation can contribute to pa-
tient morbidity. A rapid ventricular response can produce
myocardial ischemia or even infarction in a patient with
underlying coronary artery disease. Whether atrial fibrilla-
tion worsens prognosis in patients with acute myocardial
infarction or new-onset heart failure has been the subject of
considerable debate. Interestingly, some studies have re-
ported that atrial fibrillation independently worsens progno-
sis in patients with heart failure or myocardial infarction,
whereas other observers have found no effect of associated
atrial fibrillation on outcomes.20-25Despite the generally worsened prognosis for patients with
atrial fibrillation, many patients do well for years and even
decades. Therefore, the prognosis for the individual patient is
variable. As noted earlier, excellent rate control with beta-
blockers, nondihydroperidine calcium blockers (diltiazem and
verapamil) and digoxin, along with anticoagulation and control
of other cardiovascular risk factors, can stabilize patients with
atrial fibrillation for years. In this regard, it is of interest that 2
studies have documented significant improvement in prognosis
for patients with atrial fibrillation treated during the 1990s as
compared with individuals managed during the 1980s.26,27 In
our own practice, we work hard with patients to assess theirsymptoms and expectations with regard to choosing a rate or
rhythm control strategy.
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