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Levels of evidence
Level Type of Evidence
Ia Evidence obtained from meta-analysis of randomised controlled trials.
Ib Evidence obtained from at least one randomised controlled trial.
IIa Evidence obtained from at least one well-designed controlled study without
randomisation.
IIb Evidence obtained from at least one other type of well-designed
quasi-experimental study.
III Evidence obtained from well-designed non-experimental descriptive
studies, such as comparative studies, correlation studies and case studies.
IV Evidence obtained from expert committee reports or opinions and/or
clinical experiences of respected authorities.
Grades of recommendation
Grade Recommendation
A Requires at least one randomised controlled trial, as part
(evidence levels Ia, Ib) of the body of literature of overall good quality and
consistency, addressing the specific recommendation.
B Requires availability of well conducted clinical studies,
(evidence levels IIa, but no randomised clinical trials on the topic of
IIb, III) recommendation.
Management of Atrial
Fibrillation
ISBN 981-05-1856-0
Statement of Intent
Atrial fibrillation is the most common arrhythmia you are likely to encounter
in your clinical practice. Patients may experience palpitations, dizziness, fatigue
and shortness of breath symptoms that may be debilitating for badly affected
patients. Furthermore, atrial fibrillation can give rise to clot formation and a
subsequent thromboembolic stroke.
The prevalence of atrial fibrillation increases with age and as our population
ages, the number of patients with atrial fibrillation will increase. It is timely to
publish these clinical practice guidelines on the management of atrial
fibrillation.
PROFESSOR K SATKU
DIRECTOR OF MEDICAL SERVICES
Contents
Page
Executive summary of recommendations 1
1. Introduction 2
2. Definition of AF 4
6. Rhythm Control 16
References 47
Self-assessment (MCQs) 57
Workgroup members 61
Executive summary of recommendations
Details of recommendations can be found in the main text at the pages indicated. Where
differences exist between this executive summary and the main text, please take reference
from the main text.
1
1 Introduction
2
Figure 2 ECG showing atrial flutter with 2:1 ventricular
response
3
2 Definition of AF
2.1 Definition
2.2 Classification of AF
Acute AF
Acute AF is AF with onset within 24-48 hrs and is distinguished by a
high chance of successful cardioversion, either spontaneously or using
antiarrhythmic drugs. Also anticoagulation may not be necessary if
the onset of the AF can be accurately determined.
Paroxysmal AF
Paroxysmal AF is characterized by recurrent episodes of AF alternating
with sinus rhythm. The hallmark of paroxysmal AF is that most of the
episodes terminate spontaneously < 7 days.
Persistent AF
In persistent AF, the atria continue to fibrillate for over 48 hrs or until
cardioversion is performed. The distinction between persistent and
paroxysmal AF is not absolute but generally persistent AF has persisted
for more than 7 days.
4
Permanent AF
In permanent AF attempts at restoration of sinus rhythm have failed or
the AF has lasted for more than 1 year and the probability of successful
cardioversion is considered so low that no attempt is made and the
patient is left in AF.
2.3 Epidemiology
5
Table 1 Etiologic causes of AF
Cardiac
Common
Hypertension
Ischemic heart disease & acute myocardial infarction
Valvular heart disease
Sick sinus syndrome
Lone AF
Cardiomyopathy
Post cardiac surgery
Less common
Pericarditis & myocarditis
Cor pulmonale
Preexcitation syndrome
Tachycardia induced tachycardia (e.g. PSVT, atrial flutter)
Atrial septal defect
Acute pulmonary embolism
Non-cardiac
Alcohol
Thyrotoxicosis
Diabetes mellitus
Sepsis, especially pneumonia in the elderly
Other intrathoracic abnormalities (e.g. pleural effusion)
6
2.5 Pathophysiology of AF
7
3 Clinical presentation and importance of AF
8
4 Evaluation of the AF patient
9
heart disease, hypertension, diabetes or previous stroke. This is a
diagnosis of exclusion and requires completely normal blood tests and
a normal echocardiogram. Patients with lone AF are usually younger
and are likely to present with paroxysmal rather than persistent or
chronic AF.
10
All patients with AF should at least have one baseline transthoracic
echocardiogram. This test is very useful for documentation of structural
heart disease, assessment of cardiac chamber sizes, in particular left
atrial and left ventricular size and function. Structural heart disease
due to cardiomyopathies, pericardial or valvular heart disease and
intracardiac shunt can all be diagnosed with this test. The information
obtained from the echocardiogram can help decide whether to
cardiovert, control the ventricular rate, anticoagulate or use
antiarrhythmic drugs for the patient with AF. The presence of left atrial
thrombus is often sought but the ability of this test to detect thrombus
is very low.
This may be useful when the AF episodes are infrequent and brief. It is
also useful for monitoring asymptomatic episodes.
11
if there is any suspicion that the patient has ischemic heart disease or
that myocardial ischaemia has precipitated the arrhythmia. Hence, in
older patients (> 40 years old) and patients with significant coronary
risk factors, exercise stress test should be routinely performed. In
addition, exercise testing can be used to explore the safety of using
certain antiarrhythmic drugs (especially class Ic antiarrhythmic drugs)
and to assess the rate control during exercise. A routine coronary
angiogram is, however, not indicated unless the stress test is positive
or the pretest likelihood for coronary artery disease is very high.
12
Table 2 Clinical evaluation
Confirm diagnosis of AF
Determine pattern of AF attacks
Determine underlying etiology or precipitating factors
Determine risk for complications from AF
BASIC EVALUATION
ADDITIONAL INVESTIGATIONS
Holter monitoring
Transtelephonic event recorder
Exercise stress testing
Transoesophageal echocardiogram
Electrophysiological study
13
5 Management of Atrial Fibrillation
The treatment has three main goals. These are (i) control the ventricular
rate (ii) reestablish sinus rhythm and (iii) prevent thromboembolism.
Patients who present with the first attack of AF not associated with
severe symptoms or hemodynamic instability and terminating
spontaneously may not require any long-term prophylactic treatment,
unless they have significant risk factors for thromboembolism.
14
Long-term anticoagulation should be considered in all patients with
AF regardless of presentation of the AF if risk factors for embolic
complications are present.
In some cases when drug therapy alone is unable to achieve rate control
or maintain sinus rhythm, non-pharmacological therapies with
pacemakers, defibrillators or catheter ablation should be considered.
15
6 Rhythm Control
6.2 Cardioversion
i) Pharmacological cardioversion:
18
Internal cardioversion with percutaneous electrode catheters, or via an
implantable atrial defibrillator, are currently being evaluated.
19
Recommendations for pharmacological or
Level of
electrical DC cardioversion for patients with AF Grade
evidence
(cont)
5. Pharmacologic cardioversion for patients with C IV
persistent AF.
6. Repeated cardioversion followed by prophylatic C IV
drug therapy in patients who relapse to AF without
anti-arrhythmic agents after successful
cardioversion.
20
6.3 Rhythm control with non-pharmacological therapies
Permanent pacing
Catheter ablation
Surgical ablation
21
B Hence in patients with highly symptomatic AF who require open-
heart operation for valvular, ischemic or congenital heart disease,
consideration should be given to performing a concomitant Maze
operation for AF.
Grade B, Level III
22
7 Maintenance of Sinus Rhythm
Level of
Recommendations Grade
evidence
1. Base selection of antiarrhythmic drug B IIa
predominantly on safety.
2. Treat precipitating or reversible causes of AF C IV
before initiation of anti-arrhythmic drug therapy.
3. Administer pharmacological therapy to maintain C IV
sinus rhythm to prevent progression of
tachycardia-induced cardiomyopathy due to AF.
4. Outpatient initiation of anti-arrhythmic drug B IIa
therapy is appropriate in selected patients.
5. Administer pharmacological therapy to maintain C IV
sinus rhythm in asymptomatic patients to prevent
atrial remodeling.
6. Administer pharmacological therapy to maintain C IV
sinus rhythm to prevent heart failure or
thromboembolism in selected patients.
24
Figure 3 Pharmacological management of recurrent
paroxysmal or persistent AF
Anti-arrhythmic drug
therapy for rhythm
control
Continue anticoagulation
as needed and therapy to
maintain sinus rhythm
25
Table 4 Recommended drugs and typical doses for
maintenance of sinus rhythm
26
Figure 4 Anti-arrhythmic drug therapy to maintain sinus rhythm in
recurrent paroxysmal or persistent AF
Heart Disease
Flecainide
Amiodarone
Propafenone
Amiodarone
* For adrenergic AF, beta blockers or sotalol are the Dofetilide
initial drugs of choice. Sotalol
HF = heart failure
CAD = coronary artery disease
LVH = left ventricular hypertrophy
27
8 Rate Control During AF
There are no definite criteria agreed but the rate is generally considered
controlled when the ventricular response ranges between 60 and 90
beats per minute at rest and between 100 and 120 beats per minute
during moderate exercise. The heart rate response should be measured
both at rest and during exercise to assess the control of the rate with
pharmacological agents to the physiological range.
Digoxin
In the past, digoxin was the first-line agent for AF, but even with
intravenous digoxin, the onset of therapeutic effect takes at least 60
minutes, and its peak effect does not develop till 6 hours later. It is
however still very useful in patients with heart failure and AF.33
According to a recent meta-analysis,34 digoxin administered alone slows
28
the resting heart rate more than placebo. Its efficacy is reduced in
states of high sympathetic tone, such as during febrile states, sepsis
and during exercise which are common precipitants of paroxysmal AF.
A combination of digoxin and atenolol has been shown to be especially
effective for ventricular rate control.35 Digoxin must be used with
caution in the elderly and in patients with renal dysfunction.
Beta-Blockers
Beta blockers are considered first-line therapy for controlling heart rate
in AF especially in states of high adrenergic tone (e.g. postoperative
AF) but may have serious adverse effects. They may worsen heart failure
symptoms and cause bronchospasm in patients with asthma. In 7 of 12
comparisons with placebo, beta-blockers were effective at controlling
resting heart rate, with nadolol and atenolol being most efficacious.
All 9 comparisons demonstrated good rate control with beta-blockers,
but exercise tolerance was compromised in 3 of 9 studies.34 Atenolol
provided better control of exercise-induced tachycardia than digoxin
alone.36 Beta-blockers should be initiated cautiously in patients with
history of heart failure.39
Sotalol
29
Amiodarone
Combination Therapy
Permanent pacing
Ventricular pacing may prove useful for patients with marked variability
in ventricular rates and for those who develop intermittent resting
bradycardia during treatment with medications prescribed to control
rapid ventricular rates during exertion.
C Hence catheter ablation for rate control should not be done without
prior attempt at medical therapy to control AF.
Grade C, Level IV
31
Recommendations for Heart Rate Control in Level of
Grade
Patients With AF Evidence
Administer intravenous beta-blockers or calcium A Ib
channel antagonists (verapamil, diltiazem) in the
acute setting to slow the ventricular response to AF
in the absence of conduction over an accessory
pathway, exercising caution in patients with hypo-
tension or heart failure.
Perform immediate electrical cardioversion in pa- C IV
tients with acute paroxysmal AF and a rapid ven-
tricular response associated with acute myocardial
infarction, symptomatic hypotension, angina, or
cardiac failure that does not respond promptly to
pharmacological measures.
Administer a combination of digoxin and a beta- A Ia
blocker or calcium channel antagonist to control the
heart rate at rest and during exercise in patients with
AF. The choice of medication should be
individualized and the dose modulated to avoid
bradycardia.
Employ nonpharmacological therapy to control heart B IIb
rate when pharmacological therapy is insufficient.
Administer digoxin as the sole agent to control heart B IIb
rate at rest in patients with persistent AF.
32
Tables 5 Recommended intravenous or oral drugs and
typical doses for heart rate control in AF
33
9 Prevention of Thromboembolic Complication
A Patients with AF who are 60-75 years old with any one of the other
moderate risk factors (history of hypertension, congestive heart failure
or echocardiographically confirmed poor left ventricular function,
diabetes mellitus, coronary artery disease, and thyrotoxocosis) have
been demonstrated to have increased thromboembolic risks. Such
patients should also be anticoagulated to an INR of 2.0-3.0.
Grade A, Level Ia
Although it is well established that both the risk of stroke and the
prevalence of AF increases with age, advanced age may also exclude
an AF patient from anticoagulant therapy because of increased risks of
falls, bleeding, and warfarin sensitivity. It is also important to take
into consideration whether adequate monitoring and support is available
for patients put on long-term oral anticoagulation, and that the local
incidence of haemorrhagic stroke is higher in Singapore than that of
most Western countries. It is hence very important to risk stratify the
patients further and decide on whether anticoagulation or aspirin therapy
is preferable as shown in Table 6 on page 38.
A The need for anticoagulation and risk for complications (see Table
7 on page 39) from anticoagulation should be evaluated at regular
intervals and if any contraindications develop, the need and safety for
anticoagulation should be reassessed.
Grade A, Level Ia
36
9.3 Type and level of anticoagulation
C A higher target INR of 3.0 (range 2.5-3.5) may be chosen for patients
with mechanical prosthetic heart valves, anti-phospholipid antibody
syndrome, or have recurrent stroke despite anticoagulation.
Grade C, Level IV
Monitor the INR at least weekly during initial dosing and then every
6-8 weeks once stable therapeutic INR is achieved. In patients with a
proven record of excellent compliance and stable INRs, follow-up INR
monitoring may be extended to once every 8-12 weeks and the patient
advised to come immediately for a review if there is any spontaneous
bruising or bleeding. The dose of warfarin may need to be adjusted
after any change in drugs which have interaction with warfarin, e.g.
amiodarone, that is commonly used in patients with AF. Most surgical
or invasive procedures require a temporary discontinuation of warfarin,
usually about 5 days, until the INR is < 1.5 before the procedure can
be done. The anticoagulation can be restarted once there is no evidence
of bleeding.
37
Table 6 Recommendations for antithrombotic therapy in
patients with AF
Age
< 60 60-75 > 75
No risk factor Aspirin or no Aspirin or Anticoagulate
treatment anticoagulate INR 1.6-2.5
INR 2.0-3.0
History of:
Hypertension Aspirin or Anticoagulate Anticoagulate
Diabetes mellitus anticoagulate INR 2.0-3.0 INR 1.6-2.5
Thyrotoxicosis INR 2.0-3.0*
Coronary artery disease
Significant valvular heart
disease (except mitral
stenosis)
Heart Failure
LVEF < 35%
History of:
Stroke/TIA Anticoagulate Anticoagulate Anticoagulate
LA thrombus INR 2.0-3.0 INR 2.0-3.0 INR 1.6-2.5
Mitral stenosis
History of:
Mechanical prosthetic Anticoagulate Anticoagulate Anticoagulate
valve INR 2.5-3.5 INR 2.5-3.5 INR 2-3
38
Table 7 Risk factors for bleeding complications with oral
anticoagulation
39
10 Special Considerations
This refers to recent onset AF after open heart surgery. The incidence
of atrial arrhythmias, including AF, after open heart surgery is between
20-50%.58-69
40
Recommendations for AF management in acute Level of
Grade
myocardial infarction 14,72 evidence
1. Electrical cardioversion for patients who are C IV
haemodynamically unstable or who have intractable
ischaemia.
2. Intravenous beta-blockers (in patients without C IV
contraindications), digoxin or amiodarone to control
rate.
41
10.4 Atrial Fibrillation in patients with Hyperthyroidism
42
10.6 Atrial Fibrillation in patients with Hypertrophic
Cardiomyopathy (HCM)
Level of
Recommendations for management14 Grade
evidence
1. Use amiodarone or dofetilide to maintain sinus C IV
rhythm or attempt pharmacological cardioversion.
2. Consider non-pharmacological options to C IV
maintain sinus rhythm if drug failure occurs.
3. Chronic oral anti-coagulant therapy unless C IV
contraindicated.
43
Level of
Recommendations for management14 Grade
evidence
1. Use beta-blockers or sotalol as initial anti- C IV
arrhythmic agent if there are no contraindications.
2. Amiodarone, may be used if beta-blockers are C IV
contraindicated or ineffective.
3. Calcium antagonists (verapamil, diltiazem) may C IV
be used for rate control.
4. Administer anti-thrombotic therapy (oral anti- C IV
coagulation or aspirin), the selection of which is
based upon the assessment of the risk benefit ratio
of stroke and bleeding for each individual patient.
Level of
Recommendations for management14 Grade
evidence
1. Use propafenone or flecainide in the absence of C IV
CAD or marked LV hypertrophy (LV thickness of
> 1.4 cm).
2. Use amiodarone or sotalol as second line agents C IV
in the absence of LV hypertrophy.
3. Use amiodarone when marked hypertrophy (LV C IV
thickness of > 1.4 cm) is present.
44
and electrical cardioversion may be ineffective until the respiratory
decompensation has been corrected. Beta-blockers, propafenone or
adenosine must not be used in such patients.83
Level of
Recommendations for management14 Grade
evidence
1. Correct hypoxemia and acidosis of acute C IV
exacerbation of chronic pulmonary disease.
2. Use a calcium channel blocker such as diltiazem C IV
or verapamil for ventricular rate control.
3. Electrical cardioversion in haemodynamically C IV
unstable patients.
45
11 Clinical Quality Improvement
46
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81. Singh SN, Fletcher RD, Fisher SG et al. Amiodarone in patients with
congestive heart failure and asymptomatic ventricular arrhythmia:
Survival Trial of Antiarrhythmic therapy in Congestive Heart Failure.
N Engl J Med 1995; 333: 77-82.
82. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker
AH, et al. Mortality and morbidity in patients receiving encainide,
flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N
Engl J Med; 1991; 324:781-8.
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Self-assessment (MCQs)
After reading the Clinical Practice Guidelines, you can claim one CME
point under Category III (Self-Study) of the SMC Online CME System.
Before you login to claim the CME point, we encourage you to evaluate
whether you have mastered the key points in the Guidelines by completing
this set of MCQs. This is an extension of the learning process and is not
intended to judge your knowledge and is not compulsory. The answers
can be found at the end of the questionnaire.
57
4) The following medications have NOT been shown to be useful in
the pharmacological cardioversion of atrial fibrillation to sinus
rhythm:
A) amiodarone
B) propafenone
C) flecainide
D) digoxin
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9) The results of the AFFIRM trial suggest that rate control can serve
as a primary therapy in patients at high risk for stroke.
A) True
B) False
10) Which of the following are drugs of choice for sinus rhythm
maintenance in congestive heart failure?
A) Amiodarone
B) Procanamide
C) Quinidine
D) Flecainide
E) Propafenone
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Answer
1. E
2. D
3. C
4. D
5. C
6. B
7. E
8. E
9. A
10. A
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Workgroup members
Members
Anti-arrhythmic drug
therapy for rhythm
control
Continue anticoagulation
as needed and therapy to
maintain sinus rhythm
2
Anti-arrhythmic drug therapy to maintain sinus rhythm in
recurrent paroxysmal or persistent AF
Heart Disease
Flecainide
Amiodarone
Propafenone
Amiodarone
* For adrenergic AF, beta blockers or sotalol are the Dofetilide
initial drugs of choice. Sotalol
HF = heart failure
CAD = coronary artery disease
LVH = left ventricular hypertrophy