3. 702 Circulation August 15, 2006
a. Surgical Ablation . . . . . . . . . . . . . . . . . . .735 statements of all such relationships that might be perceived as real
b. Catheter Ablation . . . . . . . . . . . . . . . . . . .736 or potential conflicts of interest. Writing Committee members are
c. Suppression of Atrial Fibrillation also strongly encouraged to declare a previous relationship with
Through Pacing . . . . . . . . . . . . . . . . . . . .737 industry that might be perceived as relevant to guideline develop-
d. Internal Atrial Defibrillators . . . . . . . . . .737 ment. If a Writing Committee member develops a new relationship
C. Primary Prevention. . . . . . . . . . . . . . . . . . . . . . .737 with industry during his or her tenure, he or she is required to notify
IX. Proposed Management Strategies . . . . . . . . . . . . . .737
guideline staff in writing. The continued participation of the Writing
A. Overview of Algorithms for Management
of Patients With Atrial Fibrillation . . . . . . . . . .738 Committee member will be reviewed. These statements are re-
1. Newly Discovered Atrial Fibrillation. . . . . .738 viewed by the parent Task Force, reported orally to all members of
2. Recurrent Paroxysmal Atrial Fibrillation . . . .738 the Writing Committee at each meeting, and updated and reviewed
3. Recurrent Persistent Atrial Fibrillation . . . .739 by the Writing Committee as changes occur. Please refer to the
4. Permanent Atrial Fibrillation . . . . . . . . . . . .739 methodology manuals for further description of the policies used in
Appendix I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .740 guideline development, including relationships with industry, avail-
Appendix II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .741 able on the ACC, AHA, and ESC World Wide Web sites (http://
Appendix III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .743 www.acc.org/clinical/manual/manual_introltr.htm, http://circ.aha-
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .745 journals.org/manual/ and http://www.escardio.org/knowledge/
Preamble guidelines/Rules/). Please see Appendix I for author relationships
It is important that the medical profession play a significant role with industry and Appendix II for peer reviewer relationships with
in critically evaluating the use of diagnostic procedures and industry that are pertinent to these guidelines.
therapies as they are introduced and tested in the detection, These practice guidelines are intended to assist healthcare
management, or prevention of disease states. Rigorous and providers in clinical decision making by describing a range of
expert analysis of the available data documenting absolute and generally acceptable approaches for the diagnosis, manage-
relative benefits and risks of those procedures and therapies can ment, and prevention of specific diseases and conditions.
produce helpful guidelines that improve the effectiveness of These guidelines attempt to define practices that meet the
care, optimize patient outcomes, and favorably affect the overall needs of most patients in most circumstances. These guide-
cost of care by focusing resources on the most effective strategies. line recommendations reflect a consensus of expert opinion
The American College of Cardiology Foundation (ACCF) after a thorough review of the available, current scientific
and the American Heart Association (AHA) have jointly en- evidence and are intended to improve patient care. If these
gaged in the production of such guidelines in the area of guidelines are used as the basis for regulatory/payer deci-
cardiovascular disease since 1980. The ACC/AHA Task Force sions, the ultimate goal is quality of care and serving the
on Practice Guidelines, whose charge is to develop, update, or patient’s best interests. The ultimate judgment regarding care
revise practice guidelines for important cardiovascular diseases of a particular patient must be made by the healthcare
and procedures, directs this effort. The Task Force is pleased to provider and the patient in light of all of the circumstances
have this guideline developed in conjunction with the European presented by that patient. There are circumstances in which
Society of Cardiology (ESC). Writing committees are charged deviations from these guidelines are appropriate.
with the task of performing an assessment of the evidence and The guidelines will be reviewed annually by the ACC/AHA
acting as an independent group of authors to develop or update Task Force on Practice Guidelines and the ESC Committee for
written recommendations for clinical practice. Practice Guidelines and will be considered current unless they are
Experts in the subject under consideration have been selected updated, revised, or sunsetted and withdrawn from distribution. The
from all 3 organizations to examine subject-specific data and to executive summary and recommendations are published in the
write guidelines. The process includes additional representatives August 15, 2006, issue of the Journal of the American College of
from other medical practitioner and specialty groups when appro- Cardiology, August 15, 2006, issue of Circulation, and August 16,
priate. Writing committees are specifically charged to perform a 2006, issue of the European Heart Journal. The full-text guidelines
formal literature review, weigh the strength of evidence for or are e-published in the same issues of the Journal of the American
against a particular treatment or procedure, and include estimates of College of Cardiology and Circulation and published in September
expected health outcomes where data exist. Patient-specific modi- 9, 2006, issue of Europace, as well as posted on the ACC
fiers, comorbidities, and issues of patient preference that might (www.acc.org), AHA (www.americanheart.org), and ESC (www.
influence the choice of particular tests or therapies are considered as escardio.org) World Wide Web sites. Copies of the full text and the
well as frequency of follow-up and cost-effectiveness. When executive summary are available from all 3 organizations.
available, information from studies on cost will be considered; Sidney C. Smith, Jr, MD, FACC, FAHA, FESC, Chair,
however, review of data on efficacy and clinical outcomes will ACC/AHA Task Force on Practice Guidelines
constitute the primary basis for preparing recommendations in Silvia G. Priori, MD, PhD, FESC, Chair, ESC Committee
these guidelines. for Practice Guidelines
The ACC/AHA Task Force on Practice Guidelines and the ESC
Committee for Practice Guidelines make every effort to avoid any I. Introduction
actual, potential, or perceived conflict of interest that might arise as A. Organization of Committee and Evidence
a result of an outside relationship or personal interest of the Writing Review
Committee. Specifically, all members of the Writing Committee Atrial fibrillation (AF) is the most common sustained cardiac
and peer reviewers of the document are asked to provide disclosure rhythm disturbance, increasing in prevalence with age. AF is
4. TABLE 1. Applying Classification of Recommendations and Level of Evidence†
Size of Treatment Effect
Class I Class IIa Class IIb Class III
Benefit Risk Benefit Risk Benefit Risk Risk Benefit
Additional studies with focused objectives Additional studies with broad objectives needed; No additional studies needed
needed additional registry data would be helpful
Procedure/treatment SHOULD be IT IS REASONABLE to perform Procedure/treatment MAY BE CONSIDERED Procedure/treatment should NOT be
performed/administered procedure/administer treatment performed/administered SINCE IT IS NOT HELPFUL
AND MAY BE HARMFUL
Level A • Recommendation that procedure or • Recommendation in favor of treatment or • Recommendation’s usefulness/efficacy less well • Recommendation that procedure or treatment is
Multiple (3 to 5) population treatment is useful/effective procedure being useful/effective established not useful/effective and may be harmful
risk strata evaluated* • Sufficient evidence from multiple • Some conflicting evidence from multiple • Greater conflicting evidence from multiple • Sufficient evidence from multiple randomized trials
General consistency of randomized trials or meta-analyses randomized trials or meta-analyses randomized trials or meta-analyses or meta-analyses
direction and magnitude of
effect
Level B • Recommendation that procedure or • Recommendation in favor of treatment or • Recommendation’s usefulness/efficacy less well • Recommendation that procedure or treatment is
Fuster et al
Limited (2 to 3) population risk treatment is useful/effective procedure being useful/effective established not useful/effective and may be harmful
strata evaluated* • Limited evidence from single randomized • Some conflicting evidence from single • Greater conflicting evidence from single • Limited evidence from single randomized trial or
trial or nonrandomized studies randomized trial or nonrandomized studies randomized trial or nonrandomized studies nonrandomized studies
Level C • Recommendation that procedure or • Recommendation in favor of treatment or • Recommendation’s usefulness/efficacy less well • Recommendation that procedure or treatment is
Very limited (1 to 2) population treatment is useful/effective procedure being useful/effective established not useful/effective and may be harmful
risk strata evaluated* • Only expert opinion, case studies, or • Only diverging expert opinion, case studies, or • Only diverging expert opinion, case studies, or • Only expert opinion, case studies, or
standard-of-care standard-of-care standard-of-care standard-of-care
Estimate of Certainty (Precision) of Treatment Effect
*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. A
recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not
available, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.
†In 2003, the ACC/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guideline recommendations have been written in full sentences that express a complete
thought, such that a recommendation, even if separated and presented apart from the rest of the document (including headings above sets of recommendations), would still convey the full intent of the recommendation. It is hoped that this
will increase readers’ comprehension of the guidelines and will allow queries at the individual recommendation level.
ACC/AHA/ESC Practice Guidelines
703
5. 704 Circulation August 15, 2006
often associated with structural heart disease, although a AF and its pathogenesis and the general priorities of rate
substantial proportion of patients with AF have no detect- control, prevention of thromboembolism, and methods avail-
able heart disease. Hemodynamic impairment and throm- able for use in selected patients to correct the arrhythmia and
boembolic events related to AF result in significant mor- maintain normal sinus rhythm. Advances in catheter-based
bidity, mortality, and cost. Accordingly, the American ablation technologies are incorporated in expanded sections
College of Cardiology (ACC), the American Heart Asso- and recommendations, with the recognition that such vital
ciation (AHA), and the European Society of Cardiology details as patient selection, optimum catheter positioning,
(ESC) created a committee to establish guidelines for absolute rates of treatment success, and the frequency of
optimum management of this frequent and complex complications remain incompletely defined. Sections on drug
arrhythmia. therapy have been confined to human studies with com-
The committee was composed of representatives of the pounds approved for clinical use in North America and/or
ACC, AHA, ESC, the European Heart Rhythm Association Europe. As data on the management of patients prone to AF
(EHRA), and the Heart Rhythm Society (HRS). The docu- in special circumstances are more robust, recommendations
ment was reviewed by reviewers nominated by these organi- are based on a higher level of evidence than in the first edition
zations and will be reviewed annually by the Task Force and of these guidelines. Every effort was made to maintain
considered current unless the Task Force revises or with- consistency with other ACC/AHA and ESC practice
draws it from distribution. guidelines.
The ACC/AHA/ESC Writing Committee to Revise the
2001 Guidelines for the Management of Patients With Atrial C. Recommendations for Management of Patients
Fibrillation conducted a comprehensive review of the rele- With Atrial Fibrillation
vant literature from 2001 to 2006 using the PubMed/MED- Classification of Recommendations and Level of Evidence
LINE and Cochrane Library databases. Searches focused on are expressed in the ACC/AHA/ESC format as follows and
English-language sources and studies in human subjects. described in Table 1. Recommendations are evidence
Articles related to animal experimentation were cited when based and derived primarily from published data. The
important to understanding concepts pertinent to patient reader is referred to the full-text guidelines for a complete
management. description of the rationale and evidence supporting these
recommendations.
Classification of Recommendations
Recommendations
• Class I: Conditions for which there is evidence and/or
general agreement that a given procedure/therapy is bene- 1. Pharmacological Rate Control During Atrial
ficial, useful, and effective. Fibrillation
• Class II: Conditions for which there is conflicting evidence
and/or a divergence of opinion about the usefulness/ Class I
efficacy of performing the procedure/therapy. 1. Measurement of the heart rate at rest and control
Class IIa: Weight of evidence/opinion is in favor of of the rate using pharmacological agents (either a
usefulness/efficacy. beta blocker or nondihydropyridine calcium
Class IIb: Usefulness/efficacy is less well established by channel antagonist, in most cases) are recom-
evidence/opinion. mended for patients with persistent or permanent
• Class III: Conditions for which there is evidence and/or AF. (Level of Evidence: B)
general agreement that a procedure/therapy is not useful or 2. In the absence of preexcitation, intravenous ad-
effective and in some cases may be harmful. ministration of beta blockers (esmolol, metopro-
Level of Evidence lol, or propranolol) or nondihydropyridine cal-
The weight of evidence was ranked from highest (A) to cium channel antagonists (verapamil, diltiazem) is
lowest (C), as follows: recommended to slow the ventricular response to
AF in the acute setting, exercising caution in
patients with hypotension or heart failure (HF).
• Level of Evidence A: Data derived from multiple random-
(Level of Evidence: B)
ized clinical trials or meta-analyses.
3. Intravenous administration of digoxin or amiod-
• Level of Evidence B: Data derived from a single random-
arone is recommended to control the heart rate in
ized trial, or nonrandomized studies.
patients with AF and HF who do not have an
• Level of Evidence C: Only consensus opinion of experts,
accessory pathway. (Level of Evidence: B)
case studies, or standard-of-care.
4. In patients who experience symptoms related to AF
B. Changes Since the Initial Publication of These during activity, the adequacy of heart rate control
should be assessed during exercise, adjusting phar-
Guidelines in 2001 macological treatment as necessary to keep the rate
The Writing Committee considered evidence published since in the physiological range. (Level of Evidence: C)
2001 and drafted revised recommendations to incorporate 5. Digoxin is effective following oral administration
results from major clinical trials such as those that compared to control the heart rate at rest in patients with AF
rhythm control and rate control approaches to long-term and is indicated for patients with HF, left ventric-
management. The text has been reorganized to reflect the ular (LV) dysfunction, or for sedentary individu-
implications for patient care, beginning with recognition of als. (Level of Evidence: C)
6. Fuster et al ACC/AHA/ESC Practice Guidelines 705
Class IIa Class I
1. A combination of digoxin and either a beta 1. Antithrombotic therapy to prevent thromboem-
blocker or nondihydropyridine calcium channel bolism is recommended for all patients with AF,
antagonist is reasonable to control the heart rate except those with lone AF or contraindications.
both at rest and during exercise in patients with (Level of Evidence: A)
AF. The choice of medication should be individu- 2. The selection of the antithrombotic agent should be
alized and the dose modulated to avoid bradycar- based upon the absolute risks of stroke and bleeding
dia. (Level of Evidence: B) and the relative risk and benefit for a given patient.
2. It is reasonable to use ablation of the AV node or (Level of Evidence: A)
accessory pathway to control heart rate when phar- 3. For patients without mechanical heart valves at
macological therapy is insufficient or associated with high risk of stroke, chronic oral anticoagulant
side effects. (Level of Evidence: B) therapy with a vitamin K antagonist is recom-
3. Intravenous amiodarone can be useful to con- mended in a dose adjusted to achieve the target
trol the heart rate in patients with AF when intensity international normalized ratio (INR)
other measures are unsuccessful or contraindi- of 2.0 to 3.0, unless contraindicated. Factors
cated. (Level of Evidence: C) associated with highest risk for stroke in pa-
4. When electrical cardioversion is not necessary tients with AF are prior thromboembolism
in patients with AF and an accessory pathway, (stroke, transient ischemic attack [TIA], or sys-
intravenous procainamide or ibutilide is a rea- temic embolism) and rheumatic mitral stenosis.
sonable alternative. (Level of Evidence: C) (Level of Evidence: A)
4. Anticoagulation with a vitamin K antagonist is
Class IIb recommended for patients with more than 1 mod-
1. When the ventricular rate cannot be adequately erate risk factor. Such factors include age 75 y or
controlled both at rest and during exercise in greater, hypertension, HF, impaired LV systolic
patients with AF using a beta blocker, nondihy- function (ejection fraction 35% or less or frac-
dropyridine calcium channel antagonist, or tional shortening less than 25%), and diabetes
digoxin, alone or in combination, oral amiodarone mellitus. (Level of Evidence: A)
may be administered to control the heart rate. 5. INR should be determined at least weekly during
(Level of Evidence: C) initiation of therapy and monthly when anticoagu-
2. Intravenous procainamide, disopyramide, ibuti- lation is stable. (Level of Evidence: A)
lide, or amiodarone may be considered for 6. Aspirin, 81–325 mg daily, is recommended as an
hemodynamically stable patients with AF in- alternative to vitamin K antagonists in low-risk
volving conduction over an accessory pathway. patients or in those with contraindications to oral
(Level of Evidence: B) anticoagulation. (Level of Evidence: A)
3. When the rate cannot be controlled with pharma- 7. For patients with AF who have mechanical
cological agents or tachycardia-mediated cardio- heart valves, the target intensity of anticoagu-
myopathy is suspected, catheter-directed ablation lation should be based on the type of prosthesis,
of the AV node may be considered in patients with maintaining an INR of at least 2.5. (Level of
AF to control the heart rate. (Level of Evidence: C) Evidence: B)
8. Antithrombotic therapy is recommended for
Class III patients with atrial flutter as for those with AF.
1. Digitalis should not be used as the sole agent to (Level of Evidence: C)
control the rate of ventricular response in patients
with paroxysmal AF. (Level of Evidence: B) Class IIa
2. Catheter ablation of the AV node should not be 1. For primary prevention of thromboembolism
attempted without a prior trial of medication to in patients with nonvalvular AF who have
control the ventricular rate in patients with AF. just 1 of the following validated risk factors,
(Level of Evidence: C) antithrombotic therapy with either aspirin or
3. In patients with decompensated HF and AF, a vitamin K antagonist is reasonable, based
intravenous administration of a nondihydro- upon an assessment of the risk of bleeding
pyridine calcium channel antagonist may exac- complications, ability to safely sustain ad-
erbate hemodynamic compromise and is not justed chronic anticoagulation, and patient
recommended. (Level of Evidence: C) preferences: age greater than or equal to 75 y
4. Intravenous administration of digitalis glyco- (especially in female patients), hypertension,
sides or nondihydropyridine calcium channel HF, impaired LV function, or diabetes melli-
antagonists to patients with AF and a preexci- tus. (Level of Evidence: A)
tation syndrome may paradoxically accelerate 2. For patients with nonvalvular AF who have 1 or
the ventricular response and is not recom- more of the following less well-validated risk fac-
mended. (Level of Evidence: C) tors, antithrombotic therapy with either aspirin or
a vitamin K antagonist is reasonable for preven-
2. Preventing Thromboembolism tion of thromboembolism: age 65 to 74 y, fe-
(For recommendations regarding antithrombotic male gender, or CAD. The choice of agent should
therapy in patients with AF undergoing cardiover- be based upon the risk of bleeding complications,
sion, see Section I.C.3.d.) ability to safely sustain adjusted chronic anticoag-
7. 706 Circulation August 15, 2006
ulation, and patient preferences. (Level of Evi- 5. In patients with AF younger than 60 y without
dence: B) heart disease or risk factors for thromboembolism
3. It is reasonable to select antithrombotic therapy (lone AF), the risk of thromboembolism is low
using the same criteria irrespective of the pat- without treatment and the effectiveness of aspirin
tern (i.e., paroxysmal, persistent, or permanent) for primary prevention of stroke relative to the
of AF. (Level of Evidence: B) risk of bleeding has not been established. (Level of
4. In patients with AF who do not have mechanical Evidence: C)
prosthetic heart valves, it is reasonable to inter- 6. In patients with AF who sustain ischemic stroke
rupt anticoagulation for up to 1 wk without or systemic embolism during treatment with low-
substituting heparin for surgical or diagnostic intensity anticoagulation (INR 2.0 to 3.0), rather
procedures that carry a risk of bleeding. (Level than add an antiplatelet agent, it may be reason-
of Evidence: C) able to raise the intensity of the anticoagulation to
5. It is reasonable to reevaluate the need for a maximum target INR of 3.0 to 3.5. (Level of
anticoagulation at regular intervals. (Level of Evidence: C)
Evidence: C)
Class III
Class IIb Long-term anticoagulation with a vitamin K an-
1. In patients 75 y of age and older at increased risk tagonist is not recommended for primary preven-
of bleeding but without frank contraindications to tion of stroke in patients below the age of 60 y
oral anticoagulant therapy, and in other patients without heart disease (lone AF) or any risk factors
with moderate risk factors for thromboembolism for thromboembolism. (Level of Evidence: C)
who are unable to safely tolerate anticoagulation
at the standard intensity of INR 2.0 to 3.0, a lower 3. Cardioversion of Atrial Fibrillation
INR target of 2.0 (range 1.6 to 2.5) may be
considered for primary prevention of ischemic a. Pharmacological Cardioversion
stroke and systemic embolism. (Level of Evidence:
C) Class I
2. When surgical procedures require interruption Administration of flecainide, dofetilide,
of oral anticoagulant therapy for longer than 1 propafenone, or ibutilide is recommended for
wk in high-risk patients, unfractionated hepa- pharmacological cardioversion of AF. (Level of
rin may be administered or low-molecular- Evidence: A)
weight heparin given by subcutaneous injection,
although the efficacy of these alternatives in this Class IIa
situation is uncertain. (Level of Evidence: C) 1. Administration of amiodarone is a reasonable
3. Following percutaneous coronary intervention or option for pharmacological cardioversion of
revascularization surgery in patients with AF, AF. (Level of Evidence: A)
low-dose aspirin (less than 100 mg per d) and/or 2. A single oral bolus dose of propafenone or
clopidogrel (75 mg per d) may be given concur- flecainide (“pill-in-the-pocket”) can be ad-
rently with anticoagulation to prevent myocardial ministered to terminate persistent AF outside
ischemic events, but these strategies have not been the hospital once treatment has proved safe in
thoroughly evaluated and are associated with an hospital for selected patients without sinus or
increased risk of bleeding. (Level of Evidence: C) AV node dysfunction, bundle-branch block,
4. In patients undergoing percutaneous coronary QT-interval prolongation, the Brugada syn-
intervention, anticoagulation may be inter- drome, or structural heart disease. Before
rupted to prevent bleeding at the site of periph- antiarrhythmic medication is initiated, a beta
eral arterial puncture, but the vitamin K antag- blocker or nondihydropyridine calcium chan-
onist should be resumed as soon as possible nel antagonist should be given to prevent
after the procedure and the dose adjusted to rapid AV conduction in the event atrial flut-
achieve an INR in the therapeutic range. Aspi- ter occurs. (Level of Evidence: C)
rin may be given temporarily during the hiatus, 3. Administration of amiodarone can be benefi-
but the maintenance regimen should then con- cial on an outpatient basis in patients with
sist of the combination of clopidogrel, 75 mg paroxysmal or persistent AF when rapid res-
daily, plus warfarin (INR 2.0 to 3.0). Clopi- toration of sinus rhythm is not deemed nec-
dogrel should be given for a minimum of 1 mo essary. (Level of Evidence: C)
after implantation of a bare metal stent, at least
3 mo for a sirolimus-eluting stent, at least 6 mo Class IIb
for a paclitaxel-eluting stent, and 12 mo or Administration of quinidine or procainamide might
longer in selected patients, following which war- be considered for pharmacological cardioversion of
farin may be continued as monotherapy in the AF, but the usefulness of these agents is not well
absence of a subsequent coronary event. When established. (Level of Evidence: C)
warfarin is given in combination with clopi-
dogrel or low-dose aspirin, the dose intensity Class III
must be carefully regulated. (Level of Evidence: 1. Digoxin and sotalol may be harmful when
C) used for pharmacological cardioversion of
8. Fuster et al ACC/AHA/ESC Practice Guidelines 707
AF and are not recommended. (Level of Evi- tion of antiarrhythmic medication. (Level of
dence: A) Evidence: C)
2. Quinidine, procainamide, disopyramide, and
dofetilide should not be started out of hospital Class IIb
for conversion of AF to sinus rhythm. (Level 1. For patients with persistent AF, administration
of Evidence: B) of beta blockers, disopyramide, diltiazem,
dofetilide, procainamide, or verapamil may be
b. Direct-Current Cardioversion
considered, although the efficacy of these agents
to enhance the success of direct-current cardio-
Class I
version or to prevent early recurrence of AF is
1. When a rapid ventricular response does not
uncertain. (Level of Evidence: C)
respond promptly to pharmacological mea-
2. Out-of-hospital initiation of antiarrhythmic
sures for patients with AF with ongoing myo- medications may be considered in patients
cardial ischemia, symptomatic hypotension, without heart disease to enhance the success
angina, or HF, immediate R-wave synchro- of cardioversion of AF. (Level of Evidence: C)
nized direct-current cardioversion is recom- 3. Out-of-hospital administration of antiar-
mended. (Level of Evidence: C) rhythmic medications may be considered to
2. Immediate direct-current cardioversion is enhance the success of cardioversion of AF in
recommended for patients with AF involving patients with certain forms of heart disease
preexcitation when very rapid tachycardia or once the safety of the drug has been verified
hemodynamic instability occurs. (Level of Ev- for the patient. (Level of Evidence: C)
idence: B)
3. Cardioversion is recommended in patients d. Prevention of Thromboembolism in Patients With
without hemodynamic instability when symp- Atrial Fibrillation Undergoing Cardioversion
toms of AF are unacceptable to the patient. In
case of early relapse of AF after cardiover- Class I
sion, repeated direct-current cardioversion 1. For patients with AF of 48-h duration or
attempts may be made following administra- longer, or when the duration of AF is unknown,
tion of antiarrhythmic medication. (Level of anticoagulation (INR 2.0 to 3.0) is recom-
Evidence: C) mended for at least 3 wk prior to and 4 wk after
cardioversion, regardless of the method (elec-
Class IIa trical or pharmacological) used to restore sinus
1. Direct-current cardioversion can be useful to rhythm. (Level of Evidence: B)
restore sinus rhythm as part of a long-term 2. For patients with AF of more than 48-h
management strategy for patients with AF. duration requiring immediate cardioversion
(Level of Evidence: B) because of hemodynamic instability, heparin
2. Patient preference is a reasonable consideration should be administered concurrently (unless
in the selection of infrequently repeated cardio- contraindicated) by an initial intravenous bo-
versions for the management of symptomatic or lus injection followed by a continuous infu-
recurrent AF. (Level of Evidence: C) sion in a dose adjusted to prolong the acti-
vated partial thromboplastin time to 1.5 to 2
Class III times the reference control value. Thereafter,
1. Frequent repetition of direct-current cardio- oral anticoagulation (INR 2.0 to 3.0) should
version is not recommended for patients who be provided for at least 4 wk, as for patients
have relatively short periods of sinus rhythm undergoing elective cardioversion. Limited
between relapses of AF after multiple cardio- data support subcutaneous administration of
version procedures despite prophylactic antiar- low-molecular-weight heparin in this indica-
rhythmic drug therapy. (Level of Evidence: C) tion. (Level of Evidence: C)
2. Electrical cardioversion is contraindicated in 3. For patients with AF of less than 48-h duration
patients with digitalis toxicity or hypokale- associated with hemodynamic instability (an-
mia. (Level of Evidence: C) gina pectoris, myocardial infarction [MI],
shock, or pulmonary edema), cardioversion
c. Pharmacological Enhancement of Direct-Current should be performed immediately without de-
Cardioversion lay for prior initiation of anticoagulation. (Level
of Evidence: C)
Class IIa
1. Pretreatment with amiodarone, flecainide, Class IIa
ibutilide, propafenone, or sotalol can be use- 1. During the 48 h after onset of AF, the need
ful to enhance the success of direct-current for anticoagulation before and after cardio-
cardioversion and prevent recurrent AF. version may be based on the patient’s risk of
(Level of Evidence: B) thromboembolism. (Level of Evidence: C)
2. In patients who relapse to AF after successful 2. As an alternative to anticoagulation prior to car-
cardioversion, it can be useful to repeat the dioversion of AF, it is reasonable to perform
procedure following prophylactic administra- transesophageal echocardiography (TEE) in
9. 708 Circulation August 15, 2006
search of thrombus in the left atrium (LA) or left 5. Sotalol can be beneficial in outpatients in sinus
atrial appendage (LAA). (Level of Evidence: B) rhythm with little or no heart disease, prone to
2a. For patients with no identifiable throm- paroxysmal AF, if the baseline uncorrected QT
bus, cardioversion is reasonable imme- interval is less than 460 ms, serum electrolytes
diately after anticoagulation with un- are normal, and risk factors associated with
fractionated heparin (e.g., initiated by class III drug–related proarrhythmia are not
intravenous bolus injection and an infu- present. (Level of Evidence: C)
sion continued at a dose adjusted to 6. Catheter ablation is a reasonable alternative to
prolong the activated partial thrombo- pharmacological therapy to prevent recurrent
plastin time to 1.5 to 2 times the control AF in symptomatic patients with little or no LA
value until oral anticoagulation has enlargement. (Level of Evidence: C)
been established with an oral vitamin K
antagonist (e.g., warfarin) as evidenced Class III
by an INR equal to or greater than 2.0). 1. Antiarrhythmic therapy with a particular drug
(Level of Evidence: B) Thereafter, con- is not recommended for maintenance of sinus
tinuation of oral anticoagulation (INR rhythm in patients with AF who have well-
2.0 to 3.0) is reasonable for a total defined risk factors for proarrhythmia with
anticoagulation period of at least 4 wk, that agent. (Level of Evidence: A)
as for patients undergoing elective car- 2. Pharmacological therapy is not recommended for
dioversion. (Level of Evidence: B) Lim- maintenance of sinus rhythm in patients with
ited data are available to support the advanced sinus node disease or atrioventricular
subcutaneous administration of a low- (AV) node dysfunction unless they have a func-
molecular-weight heparin in this indica- tioning electronic cardiac pacemaker. (Level of
tion. (Level of Evidence: C) Evidence: C)
2b. For patients in whom thrombus is identi-
fied by TEE, oral anticoagulation (INR 5. Special Considerations
2.0 to 3.0) is reasonable for at least 3 wk
prior to and 4 wk after restoration of a. Postoperative Atrial Fibrillation
sinus rhythm, and a longer period of
anticoagulation may be appropriate even Class I
after apparently successful cardioversion, 1. Unless contraindicated, treatment with an
because the risk of thromboembolism of- oral beta blocker to prevent postoperative AF
ten remains elevated in such cases. (Level is recommended for patients undergoing car-
of Evidence: C) diac surgery. (Level of Evidence: A)
3. For patients with atrial flutter undergoing 2. Administration of AV nodal blocking agents
cardioversion, anticoagulation can be benefi- is recommended to achieve rate control in
cial according to the recommendations as for patients who develop postoperative AF.
patients with AF. (Level of Evidence: C) (Level of Evidence: B)
4. Maintenance of Sinus Rhythm Class IIa
1. Preoperative administration of amiodarone re-
Class I duces the incidence of AF in patients undergo-
Before initiating antiarrhythmic drug therapy, ing cardiac surgery and represents appropriate
treatment of precipitating or reversible causes of prophylactic therapy for patients at high risk
AF is recommended. (Level of Evidence: C) for postoperative AF. (Level of Evidence: A)
2. It is reasonable to restore sinus rhythm by
Class IIa pharmacological cardioversion with ibutilide
1. Pharmacological therapy can be useful in pa- or direct-current cardioversion in patients
tients with AF to maintain sinus rhythm and who develop postoperative AF as advised for
prevent tachycardia-induced cardiomyopathy. nonsurgical patients. (Level of Evidence: B)
(Level of Evidence: C) 3. It is reasonable to administer antiarrhythmic
2. Infrequent, well-tolerated recurrence of AF is medications in an attempt to maintain sinus
reasonable as a successful outcome of antiar- rhythm in patients with recurrent or refractory
rhythmic drug therapy. (Level of Evidence: C) postoperative AF, as recommended for other
3. Outpatient initiation of antiarrhythmic drug patients who develop AF. (Level of Evidence: B)
therapy is reasonable in patients with AF who 4. It is reasonable to administer antithrombotic
have no associated heart disease when the agent medication in patients who develop postoper-
is well tolerated. (Level of Evidence: C) ative AF, as recommended for nonsurgical
4. In patients with lone AF without structural patients. (Level of Evidence: B)
heart disease, initiation of propafenone or fle-
cainide can be beneficial on an outpatient basis Class IIb
in patients with paroxysmal AF who are in sinus Prophylactic administration of sotalol may be
rhythm at the time of drug initiation. (Level of considered for patients at risk of developing AF
Evidence: B) following cardiac surgery. (Level of Evidence: B)
10. Fuster et al ACC/AHA/ESC Practice Guidelines 709
b. Acute Myocardial Infarction (ECG) (greater than or equal to 120-ms du-
ration) or with a rapid preexcited ventricular
Class I response. (Level of Evidence: C)
1. Direct-current cardioversion is recom-
mended for patients with severe hemodynam- Class IIa
ic compromise or intractable ischemia, or Intravenous flecainide or direct-current cardio-
when adequate rate control cannot be version is reasonable when very rapid ventricu-
achieved with pharmacological agents in pa- lar rates occur in patients with AF involving
tients with acute MI and AF. (Level of Evi- conduction over an accessory pathway. (Level of
dence: C) Evidence: B)
2. Intravenous administration of amiodarone is
recommended to slow a rapid ventricular Class IIb
response to AF and improve LV function in It may be reasonable to administer intravenous
patients with acute MI. (Level of Evidence: C) quinidine, procainamide, disopyramide, ibutil-
3. Intravenous beta blockers and nondihydro- ide, or amiodarone to hemodynamically stable
pyridine calcium antagonists are recom- patients with AF involving conduction over an
mended to slow a rapid ventricular response accessory pathway. (Level of Evidence: B)
to AF in patients with acute MI who do not
display clinical LV dysfunction, bronchos- Class III
pasm, or AV block. (Level of Evidence: C) Intravenous administration of digitalis glyco-
4. For patients with AF and acute MI, adminis- sides or nondihydropyridine calcium channel
tration of unfractionated heparin by either con- antagonists is not recommended in patients with
tinuous intravenous infusion or intermittent WPW syndrome who have preexcited ventricu-
subcutaneous injection is recommended in a lar activation during AF. (Level of Evidence: B)
dose sufficient to prolong the activated partial
thromboplastin time to 1.5 to 2 times the con- d. Hyperthyroidism
trol value, unless contraindications to anticoag-
ulation exist. (Level of Evidence: C) Class I
1. Administration of a beta blocker is recom-
Class IIa mended to control the rate of ventricular
Intravenous administration of digitalis is rea- response in patients with AF complicating
sonable to slow a rapid ventricular response and thyrotoxicosis, unless contraindicated. (Level
improve LV function in patients with acute MI of Evidence: B)
and AF associated with severe LV dysfunction 2. In circumstances when a beta blocker cannot
and HF. (Level of Evidence: C) be used, administration of a nondihydropyr-
idine calcium channel antagonist (diltiazem
Class III or verapamil) is recommended to control the
The administration of class IC antiarrhythmic ventricular rate in patients with AF and
drugs is not recommended in patients with AF in thyrotoxicosis. (Level of Evidence: B)
the setting of acute MI. (Level of Evidence: C) 3. In patients with AF associated with thyrotox-
icosis, oral anticoagulation (INR 2.0 to 3.0) is
c. Management of Atrial Fibrillation Associated With recommended to prevent thromboembolism,
the Wolff-Parkinson-White (WPW) Preexcitation as recommended for AF patients with other
Syndrome risk factors for stroke. (Level of Evidence: C)
4. Once a euthyroid state is restored, recom-
Class I mendations for antithrombotic prophylaxis
1. Catheter ablation of the accessory pathway is are the same as for patients without hyper-
recommended in symptomatic patients with thyroidism. (Level of Evidence: C)
AF who have WPW syndrome, particularly
those with syncope due to rapid heart rate or e. Management of Atrial Fibrillation During Pregnancy
those with a short bypass tract refractory
period. (Level of Evidence: B) Class I
2. Immediate direct-current cardioversion is 1. Digoxin, a beta blocker, or a nondihydropyr-
recommended to prevent ventricular fibrilla- idine calcium channel antagonist is recom-
tion in patients with a short anterograde mended to control the rate of ventricular
bypass tract refractory period in whom AF response in pregnant patients with AF. (Level
occurs with a rapid ventricular response as- of Evidence: C)
sociated with hemodynamic instability. (Level 2. Direct-current cardioversion is recom-
of Evidence: B) mended in pregnant patients who become
3. Intravenous procainamide or ibutilide is rec- hemodynamically unstable due to AF. (Level
ommended to restore sinus rhythm in pa- of Evidence: C)
tients with WPW in whom AF occurs without 3. Protection against thromboembolism is rec-
hemodynamic instability in association with a ommended throughout pregnancy for all pa-
wide QRS complex on the electrocardiogram tients with AF (except those with lone AF
11. 710 Circulation August 15, 2006
and/or low thromboembolic risk). Therapy pulmonary illness or exacerbation of chronic
(anticoagulant or aspirin) should be chosen pulmonary disease. (Level of Evidence: C)
according to the stage of pregnancy. (Level of 2. A nondihydropyridine calcium channel an-
Evidence: C) tagonist (diltiazem or verapamil) is recom-
mended to control the ventricular rate in
Class IIb patients with obstructive pulmonary dis-
1. Administration of heparin may be consid- ease who develop AF. (Level of Evidence: C)
ered during the first trimester and last 3. Direct-current cardioversion should be at-
month of pregnancy for patients with AF tempted in patients with pulmonary disease
and risk factors for thromboembolism. Un- who become hemodynamically unstable as
fractionated heparin may be administered a consequence of AF. (Level of Evidence: C)
either by continuous intravenous infusion
in a dose sufficient to prolong the activated Class III
partial thromboplastin time to 1.5 to 2 1. Theophylline and beta-adrenergic agonist
times the control value or by intermittent agents are not recommended in patients with
subcutaneous injection in a dose of 10 000 bronchospastic lung disease who develop AF.
to 20 000 units every 12 h, adjusted to (Level of Evidence: C)
prolong the mid-interval (6 h after injec- 2. Beta blockers, sotalol, propafenone, and
tion) activated partial thromboplastin time adenosine are not recommended in patients
to 1.5 times control. (Level of Evidence: B) with obstructive lung disease who develop
2. Despite the limited data available, subcuta- AF. (Level of Evidence: C)
neous administration of low-molecular-
weight heparin may be considered during
the first trimester and last month of preg-
nancy for patients with AF and risk factors
for thromboembolism. (Level of Evidence:
II. Definition
C)
3. Administration of an oral anticoagulant may A. Atrial Fibrillation
be considered during the second trimester for AF is a supraventricular tachyarrhythmia characterized by
pregnant patients with AF at high thrombo- uncoordinated atrial activation with consequent deteriora-
embolic risk. (Level of Evidence: C) tion of mechanical function. On the ECG, rapid oscilla-
4. Administration of quinidine or procainamide tions, or fibrillatory waves that vary in amplitude, shape,
may be considered to achieve pharmacologi- and timing, replace consistent P waves, and there is an
cal cardioversion in hemodynamically stable
irregular ventricular response that is rapid when conduc-
patients who develop AF during pregnancy.
tion is intact.1 The ventricular response depends on elec-
(Level of Evidence: C)
trophysiological properties of the AV node and other
f. Management of Atrial Fibrillation in Patients With conducting tissues, vagal and sympathetic tone, the pres-
Hypertrophic Cardiomyopathy (HCM) ence or absence of accessory pathways, and the action of
drugs.2 When AV block or ventricular or AV junctional
Class I tachycardia is present, the cardiac cycles (R-R intervals)
Oral anticoagulation (INR 2.0 to 3.0) is recom- may be regular. In patients with pacemakers, diagnosis of
mended in patients with HCM who develop AF, AF may require pacemaker inhibition to expose fibrillatory
as for other patients at high risk of thromboem-
activity. An irregular, sustained, wide-QRS-complex
bolism. (Level of Evidence: B)
tachycardia suggests AF with conduction over an acces-
Class IIa sory pathway or AF with bundle-branch block. Atrial
Antiarrhythmic medications can be useful to flutter is usually readily distinguished from AF. Extremely
prevent recurrent AF in patients with HCM. rapid rates (greater than 200 beats per minute) suggest an
Available data are insufficient to recommend accessory pathway or ventricular tachycardia.
one agent over another in this situation, but (a)
disopyramide combined with a beta blocker or
nondihydropyridine calcium channel antagonist B. Related Arrhythmias
or (b) amiodarone alone is generally preferred. AF may occur in association with atrial flutter or atrial
(Level of Evidence: C) tachycardia. The typical form of atrial flutter is characterized
by a saw-tooth pattern of regular atrial activation called
g. Management of Atrial Fibrillation in Patients With flutter (ƒ) waves on the ECG, particularly visible in leads II,
Pulmonary Disease
III, aVF, and V1. If untreated, the atrial rate typically ranges
Class I from 240 to 320 beats per minute, with ƒ waves inverted in
1. Correction of hypoxemia and acidosis is the ECG leads II, III, and aVF and upright in lead V1. The
recommended primary therapeutic measure direction of activation in the right atrium (RA) may be
for patients who develop AF during an acute reversed, resulting in upright ƒ waves in leads II, III, and aVF
12. Fuster et al ACC/AHA/ESC Practice Guidelines 711
Figure 1. Patterns of atrial fibrillation (AF). 1,
Episodes that generally last 7 d or less (most
less than 24 h); 2, episodes that usually last
more than 7 d; 3, cardioversion failed or not
attempted; and 4, both paroxysmal and persis-
tent AF may be recurrent.
and inversion in lead V1. Atrial flutter may degenerate into to how long the diagnosis has been present in a given patient.
AF, and AF may convert to atrial flutter. Atrial flutter is Thus, in a patient with paroxysmal AF, episodes lasting
usually readily distinguished from AF, but misdiagnosis may seconds to hours may occur repeatedly for years.
occur when fibrillatory atrial activity is prominent in more This terminology applies to episodes lasting longer than
than 1 ECG lead.3 30 s without a reversible cause. Secondary AF in the setting
Focal atrial tachycardias, AV reentrant tachycardias, and of acute MI, cardiac surgery, pericarditis, myocarditis, hyper-
AV nodal reentrant tachycardias may also trigger AF. In these thyroidism, or acute pulmonary disease is considered sepa-
tachycardias, distinct P waves are typically separated by an rately. In these situations, AF is not the primary problem, and
isoelectric baseline, and their morphology may localize the concurrent treatment of the underlying disorder usually ter-
origin of the arrhythmia. minates the arrhythmia. Conversely, when AF occurs in the
course of a concurrent disorder like well-controlled hypothy-
III. Classification roidism, the general principles for management of the ar-
Various classification systems have been proposed for AF rhythmia apply.
based on the ECG pattern,1 epicardial4 or endocavitary The term lone AF applies to individuals younger than 60 y
recordings, mapping of atrial electrical activity, or clinical
without clinical or echocardiographic evidence of cardiopul-
features. Although the pattern of AF can change over time, it
monary disease, including hypertension.5 These patients have
may be helpful to characterize the arrhythmia at a given
a favorable prognosis with respect to thromboembolism and
moment. The classification scheme recommended here rep-
mortality. Over time, patients move out of the lone AF
resents a consensus driven by a desire for simplicity and
category due to aging or development of cardiac abnormali-
clinical relevance.
ties such as enlargement of the LA, and the risks of throm-
The clinician should distinguish a first-detected episode of
boembolism and mortality rise. The term nonvalvular AF
AF, whether or not symptomatic or self-limited, recognizing
refers to cases without rheumatic mitral valve disease, pros-
the uncertainty about the actual duration of the episode and
about previous undetected episodes (Fig. 1). After 2 or more thetic heart valve, or valve repair.
episodes, AF is considered recurrent. If the arrhythmia
terminates spontaneously, recurrent AF is designated parox- IV. Epidemiology and Prognosis
ysmal; when sustained beyond 7 d, it is termed persistent. AF is the most common arrhythmia in clinical practice,
Termination with pharmacological therapy or direct-current accounting for approximately one third of hospitalizations for
cardioversion does not alter the designation. First-detected cardiac rhythm disturbances. An estimated 2.3 million people
AF may be either paroxysmal or persistent. The category of in North America and 4.5 million people in the European
persistent AF also includes cases of long-standing AF (e.g., Union have paroxysmal or persistent AF.9 During the past
longer than 1 y), usually leading to permanent AF, in which 20 y, hospital admissions for AF have increased by 66%7 due
cardioversion has failed or has been foregone. to the aging of the population, a rising prevalence of chronic
These categories are not mutually exclusive, and a partic- heart disease, more frequent diagnosis through use of ambu-
ular patient may have several episodes of paroxysmal AF and latory monitoring devices, and other factors. AF is an
occasional persistent AF, or the reverse, but it is practical to extremely expensive public health problem (approximately
categorize a given patient by his or her most frequent €3000 [approximately U.S. $3600] annually per patient)8; the
presentation. The definition of permanent AF is often arbi- total cost burden approaches €13.5 billion (approximately
trary, and the duration refers both to individual episodes and U.S. $15.7 billion) in the European Union.
13. 712 Circulation August 15, 2006
A. Prevalence
The estimated prevalence of AF is 0.4% to 1% in the general
population,9 increasing with age to 8% in those older than
80 y.10 Among men, the age-adjusted prevalence has more
than doubled over a generation,10 while the prevalence in
women has remained constant.11 The median age of patients
with AF is about 75 y. The number of men and women with
AF is about equal, but approximately 60% of those over 75 y
old are female. Based on limited data, the age-adjusted risk of
developing AF in blacks seems less than half that in whites.
In population-based studies, patients with no history of Figure 2. Posterior view of principal electrophysiological mecha-
cardiopulmonary disease account for fewer than 12% of all nisms of atrial fibrillation. A, Focal activation. The initiating focus
(indicated by the star) often lies within the region of the pulmo-
cases of AF.10 In case series, however, the observed propor- nary veins. The resulting wavelets represent fibrillatory conduc-
tion of lone AF was sometimes greater than 30%.12 tion, as in multiple-wavelet reentry. B, Multiple-wavelet reentry.
Wavelets (indicated by arrows) randomly re-enter tissue previ-
B. Incidence ously activated by the same or another wavelet. The routes the
In prospective studies, the incidence of AF increases from wavelets travel vary. Reproduced with permission from Konings
KT, Kirchhof CJ, Smeets JR, et al. High-density mapping of
less than 0.1% per year in people younger than 40 y to over electrically induced atrial fibrillation in humans. Circulation
1.5% per year among women and 2% among men older than 1994;89:1665–1680.45 LA indicates left atrium; PV, pulmonary
80 y.13 In patients treated for HF, the 3-y incidence of AF was vein; ICV, inferior vena cava; SCV, superior vena cava; and RA,
almost 10%.14 Angiotensin inhibition may be associated with right atrium.
a reduced incidence of AF in patients with HF15 and
hypertension.16 distinguish changes due to AF from those due to associated heart
disease. Atrial fibrosis may precede the onset of AF,26 and
C. Prognosis juxtaposition of patchy fibrosis with normal atrial fibers may
AF is associated with an increased long-term risk of stroke,17 account for nonhomogeneity of conduction.27 Interstitial fibrosis
HF, and all-cause mortality, especially among women.18 The may result from apoptosis leading to replacement of atrial
mortality rate of patients with AF is about double that of myocytes,28 loss of myofibrils, accumulation of glycogen gran-
patients in normal sinus rhythm and is linked to the severity ules, disruption of cell coupling at gap junctions,29 and organelle
of underlying heart disease.19 In the Etude en Activité aggregates30 and may be triggered by atrial dilation in any type
Libérale sur la Fibrillation Auriculaire Study (ALFA), about of heart disease associated with AF.
two thirds of the 5% annualized mortality was attributed to Patients with valvular heart disease who have mild fibrosis
cardiovascular causes.12 In large HF trials (COMET [Carve- respond more successfully to cardioversion than those with
dilol Or Metoprolol European Trial], Val-HeFT [Valsartan severe fibrosis, and fibrosis is thought to contribute to
Heart Failure Trial]), AF was a strong independent risk factor persistent AF.31 The concentration of membrane-bound gly-
for mortality and morbidity.20,21 HF promotes AF, AF aggra- coproteins that regulate cell– cell and cell–matrix interactions
vates HF, and individuals with either condition who develop (disintegrin and metalloproteinases) in human atrial myocar-
the alternate condition share a poor prognosis.22 Thus, man- dium has been reported to double during AF, and these
aging patients with the associated conditions is a major
changes may contribute to atrial dilation in patients with
challenge, and randomized trials are needed to investigate the
longstanding AF. Dilation of the atria activates several
impact of AF on prognosis in HF.
molecular pathways, including the renin-angiotensin-aldoste-
The rate of ischemic stroke among patients with nonval-
rone system (RAAS). Angiotensin II is upregulated in re-
vular AF averages 5% per year, 2 to 7 times that of people
sponse to stretch,32 and atrial tissue from patients with
without AF.23 One of every 6 strokes occurs in a patient with
AF, and when TIAs and clinically “silent” strokes detected by persistent AF demonstrates increased expression of angioten-
brain imaging are considered, the rate of brain ischemia sin-converting enzyme (ACE).33 Angiotensin inhibition may
accompanying nonvalvular AF exceeds 7% per year.24 In prevent AF by reducing fibrosis.34 Atrial dilation and inter-
patients with rheumatic heart disease and AF in the Framing- stitial fibrosis in HF facilitate sustained AF.35 The regional
ham Heart Study, stroke risk was increased 17-fold compared electrical silence (suggesting scar), voltage reduction, and
with age-matched controls,25 and attributable risk was 5 times conduction slowing described in patients with HF are similar
greater than in those with nonrheumatic AF.23 The risk of to changes in the atria that occur as a consequence of aging.36
stroke increased with age; the annual risk of stroke attribut-
2. Mechanisms of Atrial Fibrillation
able to AF was 1.5% in participants aged 50 to 59 y and Available data support a “focal” triggering mechanism involving
23.5% in those aged 80 to 89 y.23 automaticity or multiple reentrant wavelets, but these mecha-
nisms are not mutually exclusive and may coexist (Fig. 2).
V. Pathophysiological Mechanisms The important observation that a focal source for AF could
A. Atrial Factors be identified and ablation of this source could extinguish
1. Atrial Pathology as a Cause of Atrial Fibrillation AF37 supported a focal origin. While pulmonary veins (PVs)
The most frequent histopathological changes in AF are atrial are the most frequent source of these rapidly atrial impulses,
fibrosis and loss of atrial muscle mass, but it is difficult to foci have also been found in the superior vena cava, ligament
