Atrial Fibrillation

26/6/2019 DynaMed Plus: Atrial fibrillation
Atrial fibrillation
Overview and Recommendations
Background
Atrial fibrillation (AF) is a common supraventricular tachyarrhythmia caused by uncoordinated atrial

activation and associated with an irregularly irregular ventricular response.
Causes of atrial fibrillation include an underlying structural heart disease, metabolic disorders, endocrine
diseases, and certain medications.
The prevalence of AF is approximately 1%-2% in the general population of developed countries.
Definitions of AF:
Paroxysmal AF is recurrent atrial fibrillation that terminates spontaneously, lasting possibly up to 7
days, but usually < 48 hours.
Persistent AF is atrial fibrillation that is sustained > 7 days or requires termination by cardioversion.
Longstanding persistent AF is atrial fibrillation that is persistent for > 1 year.
Permanent AF refers to atrial fibrillation where the patient and physician agree to stop additional
attempts to restore normal sinus rhythm because atrial fibrillation cannot be converted anymore.
Lone AF is historic term used to describe atrial fibrillation in younger patients (such as patients < 65
years old) with no clinical history or echocardiographic evidence of cardiovascular disease,
hypertension, or diabetes, but lacks standard definition and may be paroxysmal, persistent, or
permanent.
Patients with AF are often at a significantly increased risk of thromboembolism and, in particular, stroke.
Evaluation
Suspect a diagnosis of atrial fibrillation (AF) on a physical exam when an irregularly irregular heart
rhythm is detected by the palpation of a pulse or the auscultation of heart sounds.
Obtain an electrocardiogram (ECG) to establish the diagnosis. Characteristic findings include:
rapid oscillatory ('fibrillatory') baseline waves varying in amplitude, shape, and timing
absence of P waves
irregularly irregular ventricular response
In patients with paroxysmal AF, an ambulatory electrocardiogram (Holter monitor, event monitor, loop
monitor) may be needed to make the diagnosis.
Obtain a transthoracic echocardiogram to assess cardiac dimensions and function and to exclude valvular
disease and pericardial disease.
Factors that contribute to the development of AF include the presence of chronic diseases such as
hypertension, coronary heart disease, valvular heart disease, and diabetes mellitus.
Assess the following factors in patients with AF to assist in the approach to management:
hemodynamic stability
concurrent cardiovascular symptoms such as shortness of breath or chest pain
identification of possible contributing factors
duration of atrial fibrillation
Management
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Immediate direct current (DC) electrical cardioversion of atrial fibrillation may be necessary for patients
with hemodynamic instability and/or cardiovascular symptoms. (Also see the overview of cardioversion of
atrial fibrillation below.)
Other specific treatment modalities include:
rate control of atrial fibrillation (AF) (overview below or see topic Rate control in atrial fibrillation
for complete information)
rhythm control of AF (overview below or see topic Rhythm control in atrial fibrillation for complete
information)
thromboembolic prophylaxis in AF (overview below or see topic Thromboembolic prophylaxis in
atrial fibrillation for complete information)
ablation therapy for AF (overview below or see topic Ablation therapy for atrial fibrillation for
complete information)
Prevention
Offer beta blockers for patients undergoing cardiac surgery to prevent perioperative atrial fibrillation
(Strong recommendation).
Consider the following medications for the prevention of atrial fibrillation in patients with cardiovascular
disease:
angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (Weak recommendation)
statins, particularly in those with heart failure or who have had or are undergoing coronary artery
bypass grafting surgery (Weak recommendation)
Related Summaries
Atrial fibrillation screening
Thromboembolic prophylaxis in atrial fibrillation
Cardioversion of atrial fibrillation
Rate control in atrial fibrillation
Rhythm control in atrial fibrillation
Ablation therapy for atrial fibrillation
General Information
Description
supraventricular tachyarrhythmia caused by uncoordinated atrial activation and usually associated with
irregular ventricular response(1)
Also called
AF
a fib
Definitions
first-diagnosed or first-time atrial fibrillation, often called new-onset atrial fibrillation, is when it is newly
diagnosed in a patient, regardless of duration of atrial fibrillation or presence and severity of symptoms
paroxysmal atrial fibrillation defined as
atrial fibrillation that terminates within 7 days of onset (usually < 48 hours) either spontaneously or
with interventions
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may recur with variable frequency

recurrent atrial fibrillation defined as ≥ 2 episodes of atrial fibrillation
persistent atrial fibrillation defined as atrial fibrillation that is sustained > 7 days or requires termination
by cardioversion
longstanding persistent atrial fibrillation defined as atrial fibrillation persistent > 1 year with decision to
adopt rhythm control strategy
permanent atrial fibrillation refers to
joint decision by patient and clinician to stop additional attempts to restore and maintain normal
sinus rhythm
reasonable for acceptance to change based on evolution of symptoms, efficacy of therapeutic
interventions, and patient and clinician preferences
lone atrial fibrillation is a historic term used to describe atrial fibrillation in younger patients (such as
patients < 65 years old) with no history or echocardiographic evidence of cardiovascular disease,
hypertension, or diabetes but lacks standard definition
References - Circulation 2014 Dec 2;130(23):e199 full-text, also published in J Am Coll Cardiol 2014
Dec 2;64(21):e1 full-text, corrections can be found in Circulation 2014 Dec 2;130(23):e272 and J Am Coll
Cardiol 2014 Dec 2;64(21):2305; Europace 2016 Nov;18(11):1609 full-text
classification of severity of atrial fibrillation

Canadian Cardiovascular Society (CCS) Severity of Atrial Fibrillation (SAF) score
0 asymptomatic
1 minimal effect on quality of life
2 modest effect on quality of life
3 moderate effect on quality of life
4 severe effect on quality of life
European Heart Rhythm Association (EHRA) class
I no symptoms
II mild symptoms
III severe symptoms; daily activity affected
IV disabling symptoms; normal daily activity discontinued
Reference - Can J Cardiol 2011 Jan-Feb;27(1):7
Epidemiology
Incidence/Prevalence
most common arrhythmia ( Dis Mon 2013 Mar;59(3):67)

reported prevalence about 3% in adults > 20 years old(2)
prevalence of primary atrial fibrillation 268 per 100,000 in the United States in 2014
based on cross-sectional study
adult patient data from the United States Nationwide Emergency Department Sample (NEDS),
National Inpatient Sample (NIS), and National Vital Statistics System (NVSS) in 2014 was
analyzed
primary atrial fibrillation or flutter in 268 per 100,000 persons
comorbid atrial fibrillation or flutter in 1,835 per 100,000 persons
0.5% of all emergency department visits, 1.5% of all hospitalizations, and 0.8% of all deaths were
due to atrial fibrillation
Reference - Am J Cardiol 2017 Dec 1;120(11):1966
prevalence of atrial fibrillation 1.31% in men and 1.15% in women in United Kingdom in 2003
based on retrospective review
131 general practices in United Kingdom representing about 1 million patients included
prevalence increased from 0.78% in men and 0.79% in women in 1993
Reference - Heart 2006 Aug;92(8):1064 full-text
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atrial fibrillation common among the elderly

based on retrospective record review
17,974 adults > 20 years old with atrial fibrillation identified in large California, United States
health maintenance organization population of 1.89 million included
overall prevalence 0.95% in adults > 20 years old (95% CI 0.94%-0.96%)
more common in men (1.1%) than women (0.8%)
prevalence increased with age from 0.1% persons aged 20-55 years to 9% persons > 80 years old
estimated 2.3 million United States adults with atrial fibrillation and > 5.6 million by 2050
Reference - JAMA 2001 May 9;285(18):2370
lifetime risk of atrial fibrillation/atrial flutter at age 40 years 26% for men and 23% for women
based on retrospective cohort study
8,725 men and women > 40 years old from Framingham Heart Study followed for up to 31 years
Reference - Circulation 2004 Aug 31;110(9):1042 full-text
incidence of atrial fibrillation increased between 1980 and 2000 in Minnesota, United States
4,618 adults with atrial fibrillation identified in Olmsted County, Minnesota
age- and sex-adjusted incidence per 1,000 people per year 3.04 in 1980 and 3.68 in 2000
Reference - Circulation 2006 Jul 11;114(2):119 full-text
10.4% of 528 persons > 85 years old had atrial fibrillation in 1 series, 42% of cases were previously
undetected ( BMJ 2003 Jul 19;327(7407):131 full-text)
incidence of paroxysmal atrial fibrillation 1 per 1,000 people per year among patients aged 40-89
years in United Kingdom general practices
418 patients with paroxysmal atrial fibrillation were followed for mean 2.7 years and 70 (17%)
progressed to chronic atrial fibrillation
paroxysmal atrial fibrillation not associated with mortality risk
Reference - BMC Cardiovasc Disord 2005 Jul 11;5:20 full-text
Likely risk factors
Cardiac abnormalities
subclinical atherosclerosis (carotid-intima media thickness and carotid plaque) associated with
atrial fibrillation
based on cohort study
4,407 persons > 55 years old followed for median 7.5 years
factors associated with increased risk of atrial fibrillation
carotid intima-media thickness (relative risk [RR] 1.9, 95% CI 1.2-3)
severity of carotid plaque (RR 1.49, 95% CI 1.06-2.1)
Reference - Arch Intern Med 2007 Feb 26;167(4):382
increased left atrial size associated with increased risk for atrial fibrillation
1,655 patients > 65 years old followed mean 4 years
multiple exclusions for cardiovascular conditions associated with atrial fibrillation
5-year cumulative risk of atrial fibrillation by quartiles of left atrial volume were 3%, 12%, 15%,
and 26%
Reference - Mayo Clin Proc 2001 May;76(5):467
mitral regurgitation associated with high rate of atrial fibrillation
360 patients with mitral regurgitation due to flail leaflets
atrial fibrillation occurred in 18% at 5 years and 48% at 10 years
similar rates in 89 patients with grade 3 or 4 mitral regurgitation due to mitral valve prolapse
Reference - J Am Coll Cardiol 2002 Jul 3;40(1):84 in J Watch Online 2002 Aug 23
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left anterior fascicular block has conflicting evidence; differences in study populations, duration of follow-
up, and number of patients in each study may explain conflicting findings
left anterior fascicular block associated with increased risk of atrial fibrillation at 15 years in
elderly patients without overt cardiovascular disease
based on prospective cohort study
1,664 patients ≥ 65 years old from Cardiovascular Health Study without overt cardiovascular
disease at baseline were analyzed
at baseline 2.3% (39 patients) had left anterior fascicular block
median follow-up 15.7 years
23% developed atrial fibrillation and 57% died
left anterior fascicular block associated with increased risk of
atrial fibrillation (adjusted HR 1.89, 95% CI 1.11-3.24)
all-cause death (adjusted HR 1.57, 95% CI 1.08-2.26)
cardiovascular death (adjusted HR 2.02, 95% CI 1.08-3.77)
Reference - JAMA 2013 Apr 17;309(15):1587 full-text
left anterior fascicular block not associated with increased risk of atrial fibrillation or
cardiovascular death in patients aged 41-63 years without overt cardiovascular disease
227,543 primary care patients ≥ 25 years old (age range 41-63 years) and without overt
cardiovascular disease had electrocardiogram (ECG) at request of their general practitioner
and followed for median 5.7 years (range 3-8.4 years)
3,641 had left anterior fascicular block
6,718 developed atrial fibrillation and 17,531 died (3,679 from cardiovascular causes)
left anterior fascicular block not associated with increased risk of atrial fibrillation or
cardiovascular death (adjusted for age and other factors)
Reference - JAMA Intern Med 2014 Jun;174(6):1001
premature atrial contractions associated with increased risk of atrial fibrillation and overall and
cardiovascular mortality
1,260 adults ≥ 65 years old without prevalent atrial fibrillation in the Cardiovascular Health Study
followed for median 13 years
27% developed incident atrial fibrillation
66% died (39% of a cardiovascular cause)
median baseline hourly premature atrial contractions (PAC) count 5.3 beats/hour in patients who
developed atrial fibrillation vs. 1.8 beats/hour in patients without atrial fibrillation (p < 0.001)
compared with lowest quartile for premature atrial contraction count, highest quartile associated
with increased risk of
incident atrial fibrillation (adjusted hazard ratio [HR] 4.92, 95% CI 3.39-7.16)
overall mortality (adjusted HR 1.35, 95% CI 1.1-1.66)
cardiovascular mortality (adjusted HR 1.5, 95% CI 1.08-2.08)
Reference - Ann Intern Med 2013 Dec 3;159(11):721, editorial can be found in Ann Intern Med
2013 Dec 3;159(11):787
Subclinical hyperthyroidism
subclinical hyperthyroidism may increase risk for mortality, coronary heart disease, and atrial
fibrillation
based on systematic review
systematic review of 10 prospective cohort studies evaluating coronary heart disease and total
mortality associated with endogenous subclinical hyperthyroidism
10 studies included 52,674 patients followed for median 8.8 years
4.2% had subclinical hyperthyroidism (thyrotropin level < 0.45 milliunits/L with normal free
thyroxine levels)
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subclinical hyperthyroidism associated with increased risk for

coronary heart disease mortality (adjusted hazard ratio [HR] 1.29, 95% CI 1.02-1.62) in
analysis of 10 studies with 4% mortality from coronary heart disease
total mortality (adjusted HR 1.24, 95% CI 1.06-1.46) in analysis of 10 studies with 16% total
mortality
coronary heart disease events (adjusted HR 1.21, 95% CI 0.99-1.46) in analysis of 6 studies
with 22,437 patients and 16% incidence of coronary heart disease events
incident atrial fibrillation (adjusted HR 1.68, 95% CI 1.16-2.43) in analysis of 5 studies with
8,711 patients and 9% incidence of atrial fibrillation
Reference - Arch Intern Med 2012 May 28;172(10):799 full-text, editorial can be found in Arch
Intern Med 2012 May 28;172(10):809
subclinical hyperthyroidism associated with atrial fibrillation

based on 2 cohort studies not included in Arch Intern Med 2012 systematic review
5,860 persons > 65 years old, excluding patients treated for thyroid dysfunction or with history of
hyperthyroidism
14 (0.2%) had undiagnosed overt hyperthyroidism, 126 (2.2%) had subclinical
hyperthyroidism, 168 (2.9%) had subclinical hypothyroidism, 23 (0.4%) had overt
hypothyroidism
prevalence of atrial fibrillation was 6.6% in men and 3.1% in women overall
adjusted prevalence of atrial fibrillation was 9.5% with subclinical hyperthyroidism vs. 4.7%
with euthyroidism (p = 0.01)
Reference - Arch Intern Med 2007 May 14;167(9):928
1,426 patients > 55 years old with thyroid-stimulating hormone (TSH) levels in normal range and
without atrial fibrillation at baseline followed for median 8 years
patients stratified by TSH levels
risk of atrial fibrillation increased for lowest quartile of TSH level compared to highest
(hazard ratio 1.94, p < 0.02)
risk of atrial fibrillation associated with increasing levels of free thyroxine (p for trend 0.06)
Reference - Arch Intern Med 2008 Nov 10;168(20):2219
subclinical hyperthyroidism associated with increased risk of new-onset atrial fibrillation in adults
586,460 adults ≥ 18 years old without previous thyroid disease or atrial fibrillation were evaluated
and followed for median 5.5 years
96% had euthyroidism (defined as thyroid-stimulating hormone [TSH] level 0.2-5
milliunits/L and free thyroxine 9-22 pmol/L)
0.7% had overt hyperthyroidism (TSH < 0.2 milliunits/L and free thyroxine > 22 pmol/L)
1% had subclinical hyperthyroidism (TSH < 0.2 milliunits/L and free thyroxine 9-22 pmol/L)
0.3% had overt hypothyroidism (TSH > 5 milliunits/L and free thyroxine < 9 pmol/L)
2% had subclinical hypothyroidism (TSH > 5 milliunits/L and free thyroxine 9-22 pmol/L)
2.9% had hospital diagnosis of first-time atrial fibrillation
compared with euthyroidism, risk of atrial fibrillation appears
increased with overt hyperthyroidism (incidence rate ratio [IRR] 1.41, 95% CI 1.22-1.63)
increased with subclinical hyperthyroidism (IRR 1.3, 95% CI 1.18-1.43)
decreased with overt hypothyroidism (IRR 0.67, 95% CI 0.5-0.92)
decreased with subclinical hypothyroidism (IRR 0.88, 95% CI 0.79-0.97)
compared with normal euthyroidism (TSH 0.4-5 milliunits/L), atrial fibrillation associated with
increased risk with high-normal euthyroidism (TSH 0.2-0.4 milliunits/L) (IRR 1.12, 95% CI
1.03-1.21)
nonsignificant increased risk with subclinical hyperthyroidism with reduced TSH (TSH 0.1-
0.2 milliunits/L) (IRR 1.16, 95% CI 0.99-1.36)
increased risk with subclinical hyperthyroidism with suppressed TSH (TSH < 0.1
milliunits/L) (IRR 1.41, 95% CI 1.25-1.59)
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Reference - BMJ 2012 Nov 27;345:e7895 full-text
Alcohol consumption
heavy alcohol consumption associated with increased risk of atrial fibrillation

based on systematic review and 2 prospective cohort studies
systematic review of 14 observational studies (9 cohort studies, 5 case-control) reporting alcohol
consumption and incidence of atrial fibrillation in 130,830 persons
7,558 cases of atrial fibrillation were reported
each 10-g increase in alcohol consumption daily associated with increased risk of atrial
fibrillation (risk ratio [RR] 1.08, 95% CI 1.05-1.1)
Reference - J Am Coll Cardiol 2011 Jan 25;57(4):427, editorial can be found in J Am Coll
Cardiol 2011 Jun 21;57(25):2545
prospective cohort study of 16,415 men and women
1,071 developed atrial fibrillation during follow-up
consumption of 35 or more drinks per week among men associated with atrial fibrillation
(hazard ratio [HR] 1.45, adjusted HR 1.63)
few women consumed 35 or more drinks per week
Reference - Circulation 2005 Sep 20;112(12):1736 full-text
prospective cohort study of 79,019 men and women with 859,420 person-years of follow-up from
1998 to 2009
9.2% developed atrial fibrillation
compared with current drinkers of < 1 drink/week, risk of atrial fibrillation increased with
15-21 drinks/week (adjusted relative risk 1.14, 95% CI 1.01-1.28)
> 21 drinks/week (adjusted relative risk 1.39, 95% CI 1.22-1.58)
similar results noted after excluding binge drinkers
consistent findings in meta-analysis of 7 prospective cohort studies including 12,554 cases of
atrial fibrillation
Reference - J Am Coll Cardiol 2014 Jul 22;64(3):281
alcohol consumption may have modest effect on risk of atrial fibrillation or flutter in men
47,949 Danish persons (mean age 56 years) followed for mean 5.7 years
compared to lowest quintile of alcohol use, higher levels of alcohol use had
1.04-1.46 times higher incidence of atrial fibrillation or flutter in men (p = 0.04)
1.09-1.27 times higher incidence in women (p = 0.69)
Reference - Arch Intern Med 2004 Oct 11;164(18):1993
alcohol and illicit drugs associated with atrial fibrillation in patients ≤ 45 years old in case series and
literature review ( Am J Med 2009 Sep;122(9):851)
Obesity
obesity associated with increased risk of new-onset atrial fibrillation in men and women
based on 1 systematic review and 2 prospective cohort studies
systematic review of 16 prospective cohort studies evaluating effect of obesity on atrial fibrillation
in 587,372 persons
prevalence of obesity ranged from 1.8%-53.6%
atrial fibrillation diagnosis based electrocardiogram or ICD codes in registry review
incidence of atrial fibrillation 6.3% in patients with obesity vs. 3.1% in nonobese persons (p <
0.0001)
increased risk for atrial fibrillation associated with
obesity overall (risk ratio [RR] 1.51, 95% CI 1.35-1.68) in analysis of all studies
obesity in men (RR 1.41, 95% CI 1.24-1.62) in analysis of 7 studies with 611,16 men
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obesity in women (RR 1.53, 95% CI 1/19-1.97) in analysis of 6 studies with 422,585
women
Reference - J Cardiovasc Electrophysiol 2018 May;29(5):725
34,309 women health professionals without previous history of cardiovascular disease were
followed for mean of 12.9 person-years
834 incident atrial fibrillation events occurred
atrial fibrillation risk was 4.7% (95% CI 3.4-6.1) higher per unit increment increase in body
mass index (BMI)
hazard ratios for adjusted short-term atrial fibrillation risk compared to women with normal
BMI
1.22 (95% CI 1.02-1.45) for overweight women (25-29.9 kg/m2)
1.65 (95% CI 1.36-2) for obese women (≥ 30 kg/m2)
women who became obese during initial 60 months had 41% adjusted increase risk of atrial
fibrillation compared to women maintaining BMI < 30 kg/m2 (p = 0.02)
Reference - J Am Coll Cardiol 2010 May 25;55(21):2319
5,282 persons aged 35-90 years (55% women) followed for mean 13.7 years
age-adjusted incidence rates for atrial fibrillation per 1,000 person-years
in men 9.7 with BMI < 25 kg/m2, 10.7 with BMI 25-30 kg/m2, and 14.3 with BMI > 30
kg/m2
in women 5.1 with BMI < 25 kg/m2, 8.6 with BMI 25-30 kg/m2, and 9.9 with BMI >
30 kg/m2
BMI no longer predicted risk after adjusting for left atrial diameter
Reference - JAMA 2004 Nov 24;292(20):2471, editorial can be found in JAMA 2004 Nov
24;292(20):2519, commentary can be found in JAMA 2005 Apr 27;293(16):1974
morbid obesity associated with new-onset atrial fibrillation
based on case-control study
425 patients with new-onset atrial fibrillation and 707 controls included
atrial fibrillation risk was on average 3% higher (95% CI 1%-5%) per unit increment in BMI
odds ratios for atrial fibrillation compared to persons with normal BMI
0.97 (95% CI 0.68-1.38) for overweight (BMI 25-29.9 kg/m2)
1.18 (95% CI 0.8-1.73) for class 1 obesity (BMI 30-34.9 kg/m2)
1.34 (95% CI 0.82-2.18) for class 2 obesity (BMI 35-39.9 kg/m2)
2.31 (95% CI 1.36-3.91) for class 3 obesity (BMI > 40 kg/m2, morbid obesity)
Reference - Arch Intern Med 2006 Nov 27;166(21):2322, commentary can be found in Arch Intern
Med 2007 Jul 23;167(14):1552
obesity associated with progression from paroxysmal to permanent atrial fibrillation
3,248 patients (mean age 71 years) with paroxysmal atrial fibrillation were followed for median 5.1
years
17% developed permanent atrial fibrillation
hazard ratio for risk of permanent atrial fibrillation (compared with normal BMI 18.5-24.9 kg/m2)
1.54 (95% CI 1.2-2) for obesity (30-34.9 kg/m2)
1.87 (95% CI 1.4-2.5) for severe obesity (≥ 35 kg/m2)
left atrial volume did not affect association between BMI and progression to permanent atrial
fibrillation
Reference - Eur Heart J 2008 Sep;29(18):2227
increased body mass index associated with increased risk of atrial fibrillation in Mendelian randomization
analysis of 7 population-based cohorts ( Circulation 2017 Feb 21;135(8):741 full-text)
NSAIDs and COX-2 inhibitors
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nonaspirin NSAID use associated with increased risk of atrial fibrillation

based on systematic review of observational studies
systematic review of 5 observational studies (2 cohort and 3 case-control studies) evaluating
association between nonaspirin nonsteroidal anti-inflammatory drug (NSAID) use and risk of atrial
fibrillation in 7,250,695 persons
increased risk of atrial fibrillation associated with
overall nonaspirin NSAID use (relative risk [RR] 1.12, 95% CI 1.06-1.18) in analysis of all
studies, results limited by significant heterogeneity
new nonaspirin NSAID use (RR 1.53, 95% CI 1.37-1.7) in analysis of 4 studies
current nonaspirin NSAID use (RR 1.18, 95% CI 1.13-1.23) in analysis of all studies
long-term nonaspirin NSAID use (RR 1.09, 95% CI 1.04-1.14) in analysis of 4 studies
risk of atrial fibrillation with current nonaspirin NSAID use was highest in patients with heart
failure or chronic kidney disease
Reference - Am J Cardiol 2014 Nov 15;114(10):1523
COX-2 inhibitor etoricoxib (but not celecoxib) associated with increased risk for atrial
fibrillation
6,991,645 adults > 18 years old without cardiovascular disease were followed from 2005 to
2008 (after withdrawal of rofecoxib) and assessed for use of cyclooxygenase-2 (COX-2)
inhibitors
COX-2 inhibitors studied included etoricoxib in 58.2% of patients and celecoxib in 41.8% of
patients
COX-2 inhibitor use associated with increased risk of atrial fibrillation
hazard ratio 1.16 (95% CI 1.05-1.29) for any COX-2 inhibitor
hazard ratio 1.35 (95% CI 1.19-1.54) for etoricoxib
no significant associations found between
COX-2 inhibitors and risk for myocardial infarction, ischemic stroke, or heart failure
celecoxib use and atrial fibrillation
Reference - Eur Heart J 2012 Aug;33(15):1928
use of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) and selective
cyclooxygenase-2 (COX-2) inhibitors associated with increased risk of atrial fibrillation or
flutter
32,602 patients with first inpatient or outpatient hospital diagnosis of atrial fibrillation or
flutter were compared to 325,918 controls
current use defined as exposure to NSAIDs at time of admission and new use defined as first
ever prescription redemption within 60 days before diagnosis date
2,925 cases (9%) and 21,871 controls (7%) were current users of either nonselective NSAIDs
or COX-2 inhibitors
comparing current use of nonselective NSAIDs or COX-2 inhibitors to no use
current use associated with increased risk of atrial fibrillation or flutter
incidence rate ratio 1.17 (95% CI 1.1-1.24) for nonselective NSAIDs in adjusted
analyses
incidence rate ratio 1.27 (95% CI 1.2-1.34) for COX-2 inhibitors in adjusted
analyses
comparing new use of nonselective NSAIDs or COX-2 inhibitors to no use
new use associated with increased risk of atrial fibrillation or flutter
incidence rate ratio 1.46 (95% CI 1.33-1.62) for nonselective NSAIDs in adjusted
analyses
incidence rate ratio 1.71 (95% CI 1.56-1.88) for COX-2 inhibitors in adjusted
analyses
Reference - BMJ 2011 Jul 4;343:d3450
Other likely risk factors

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obstructive sleep apnea associated with increased risk of incident atrial fibrillation in patients
referred for diagnostic polysomnogram
3,542 adults (mean age 49 years, 66% men) without history of atrial fibrillation referred for
diagnostic polysomnogram from 1987 to 2003 included
74% of patients had obstructive sleep apnea
3.8% incidence of atrial fibrillation during mean follow-up of 4.7 years
obstructive sleep apnea associated with increased risk of incident atrial fibrillation (hazard ratio
2.18, 95% CI 1.34-3.54)
Reference - J Am Coll Cardiol 2007 Feb 6;49(5):565 full-text
increased epicardial fat volume, waist circumference, waist-to-hip ratio, and BMI each associated
with higher risk of atrial fibrillation
systematic review of 63 studies evaluating risk of atrial fibrillation in 352,275 patients
34 studies evaluated epicardial fat, 5 evaluated waist circumference, 4 evaluated waist-to-hip ratio,
and 25 evaluated body mass index (BMI)
increased risk of atrial fibrillation associated with increased
epicardial fat volume (odds ratio [OR] 2.61, 95% CI 1.89-3.6 per 1 standard deviation [SD]
increase) in analysis of 10 studies, results limited by significant heterogeneity
waist circumference (relative risk [RR] 1.32, 95% CI 1.25-1.41 per 1 SD increase) in analysis
of 5 studies
waist-to-hip ratio (RR 1.11. 95% CI 1.08-1.14 per 1 SD increase) in analysis of 4 studies
BMI (RR 1.22, 95% CI 1.17-1.27 per 1 SD increase) in analysis of 25 studies, results limited
by significant heterogeneity
Reference - Circ Arrhythm Electrophysiol 2016 Dec;9(12): full-text
risk factors in retrospective analysis of 4,764 participants aged 45-95 years without atrial fibrillation in
Framingham Heart study
body mass index ≥ 30 kg/m2
systolic blood pressure ≥ 160 mm Hg
treatment for hypertension
PR interval ≥ 160 milliseconds
increasing age
Reference - Lancet 2009 Feb 28;373(9665):739 full-text, editorial can be found in Lancet 2009 Feb
28;373(9665):698, commentary can be found in Lancet 2009 May 2;373(9674):1523
risk algorithm derived in above study validated in cohorts of 4,238 white patients from Iceland and
5,410 African American patients ( Arch Intern Med 2010 Nov 22;170(21):1909), editorial can be
found in Arch Intern Med 2010 Nov 22;170(21):1874
addition of premature atrial contraction count to Framingham atrial fibrillation risk
algorithm may improve risk prediction
1,260 adults ≥ 65 years old without prevalent atrial fibrillation in the Cardiovascular Health
Study followed for median 13 years
27% developed incident atrial fibrillation
compared with Framingham atrial fibrillation risk algorithm alone
premature atrial contraction (PAC) count alone associated with
similar atrial fibrillation risk discrimination at 5- and 10-year follow-up
improved atrial fibrillation risk discrimination at 15-year follow-up (p < 0.001)
addition of PAC count associated with improved atrial fibrillation risk discrimination at
5, 10, and 15 years (p < 0.001 for each)
Reference - Ann Intern Med 2013 Dec 3;159(11):721, editorial can be found in Ann Intern
Med 2013 Dec 3;159(11):787
increased systolic blood pressure associated with increased risk of incident atrial fibrillation
based on prospective population-based cohort study
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3,956 persons (mean age 43 years) from 5 European countries were randomly selected for
ambulatory blood pressure monitoring (ABP) and followed for mean 14 years
2,776 persons completed 24-hour ABP monitoring during both daytime and nighttime periods
4% of persons with complete ABP monitoring developed atrial fibrillation
each standard deviation increase in baseline systolic blood pressure was associated with increased
risk of incident atrial fibrillation for all blood pressure measurements
adjusted hazard ratio (HR) 1.19 for each 17 mm Hg increase (95% CI 0.99-1.43) for
conventional blood pressure measurement
adjusted HR 1.27 for each 11 mm Hg increase (95% CI 1.07-1.51) for 24-hour ABP
measurement
adjusted HR 1.22 for each 12 mm Hg increase (95% CI 1.02-1.46) for daytime blood pressure
measurement
adjusted HR 1.2 for each 12 mm Hg increase (95% CI 1.02-1.42) for nighttime blood pressure
measurement
Reference - Heart 2018 Aug;104(15):1263
orthostatic hypotension associated with increased risk of new-onset atrial fibrillation
1,736 persons (mean age 72 years, 60% female) from Framingham Heart Study without preexisting
atrial fibrillation were assessed for orthostatic hypotension at baseline and prospectively followed
orthostatic hypotension defined as decrease in systolic blood pressure ≥ 20 mm Hg or diastolic
blood pressure ≥ 10 mm Hg from supine to standing
14.8% had orthostatic hypotension at baseline
224 patients developed incident atrial fibrillation during mean follow-up of 8.3 years
orthostatic hypotension associated with increased risk of developing atrial fibrillation (adjusted
hazard ratio 1.61, 95% CI 1.17-2.2) at 10 years of follow-up, with analysis adjusted for systolic
blood pressure, diastolic blood pressure, hypertension treatment, and other risk factors associated
with atrial fibrillation
Reference - Am J Cardiol 2018 Mar 1;121(5):596
higher pulse pressure is risk factor for atrial fibrillation
5,331 persons > 35 years old from Framingham Heart study followed for median 12 years
698 (13%) developed atrial fibrillation
cumulative 20-year incidence of atrial fibrillation increased from 5.6% for pulse pressure < 40 mm
Hg to 23.3% for pulse pressure > 61 mm Hg
Reference - JAMA 2007 Feb 21;297(7):709
rheumatoid arthritis (RA) associated with increased risk of atrial fibrillation and stroke
4,182,335 persons > 15 years old without RA, atrial fibrillation, or stroke at baseline were followed
from 1997 to 2009
0.44% (mean age 59 years) diagnosed with RA during median 4.8 years of follow-up
RA associated with increased risk of
atrial fibrillation (adjusted incidence rate ratio [IRR] 1.41, 95% CI 1.31-1.51)
stroke (adjusted IRR 1.32, 95% CI 1.22-1.42)
Reference - BMJ 2012 Mar 8;344:e1257 full-text
familial atrial fibrillation associated with increased risk of new-onset atrial fibrillation
4,421 Framingham cohort members ≥ 30 years old without atrial fibrillation and with ≥ 1 parent or
sibling enrolled in Framingham study were followed for 8 years
familial atrial fibrillation defined as occurrence of atrial fibrillation in first-degree relative
9.9% developed atrial fibrillation
familial atrial fibrillation in 26.8% and premature familial atrial fibrillation (onset ≤ 65 years old) in
7.9%
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familial atrial fibrillation associated with increased risk of new-onset atrial fibrillation (adjusted
hazard ratio 1.4, 95% CI 1.13-1.74)
Reference - JAMA 2010 Nov 24;304(20):2263 full-text
parental history of atrial fibrillation associated with increased of developing atrial fibrillation
2,243 Framingham cohort offspring > 30 years old, 70 of whom developed atrial fibrillation
parental history of atrial fibrillation associated with increased risk of developing atrial fibrillation
(odds ratio 1.85, 95% CI 1.12-3.06)
Reference - JAMA 2004 Jun 16;291(23):2851, commentary can be found in JAMA 2004 Sep
8;292(10):1174
perioperative milrinone use associated with increased risk of atrial fibrillation following cardiac
surgery
232 patients having elective cardiac surgery included
28.9% developed atrial fibrillation at mean 2.9 days after surgery
atrial fibrillation in 58.2% of patients taking milrinone compared to 26.1% of patients not taking
milrinone (p < 0.001, NNH 3)
Reference - Circulation 2008 Oct 14;118(16):1619 full-text
history of maternal placental syndrome associated with increased risk of hospitalization for heart
failure and atrial dysrhythmia
1,130,764 pregnant women in Ontario, Canada free from cardiovascular or thyroid disease before
first documented delivery at ages 14-50 years were followed for median 7.8 years
6.7% had maternal placental syndrome (MPS) defined as gestational hypertension, preeclampsia, or
placental abruption and/or infarction at baseline
rate of hospitalization for heart failure or atrial or ventricular dysrhythmia starting 1 year after
delivery
2.54 per 10,000 person-years in women with MPS
1.28 per 10,000 person-years in women without MPS
history of MPS associated with
increased risk of hospitalization for heart failure or atrial or ventricular dysrhythmia (adjusted
hazard ratio [HR] 1.61, 95% CI 1.35-1.91)
increased risk of hospitalization for heart failure (adjusted HR 1.8, 95% CI 1.42-2.29)
increased risk of hospitalization for atrial dysrhythmia (adjusted HR 1.48, 95% CI 1.1-1.98)
nonsignificantly increased risk of hospitalization for ventricular dysrhythmia (adjusted HR
1.41, 95% CI 0.96-2.07)
Reference - Heart 2012 Aug;98(15):1136, editorial can be found in Heart 2012 Aug;98(15):1109
Possible risk factors
Corticosteroids
current glucocorticoid use associated with risk of atrial fibrillation and atrial flutter
based on population-based case-control study
20,221 patients with atrial fibrillation or atrial flutter were compared to 10 matched controls per
case
current glucocorticoid use in 6.4% of cases compared to 2.6% of controls
current glucocorticoid use associated with increased risk of atrial fibrillation or flutter compared to
never-use (adjusted odds ratio 1.92, 95% CI 1.79-2.06)
risk higher among new users compared to long-term users
Reference - Arch Intern Med 2009 Oct 12;169(18):1677
high-dose corticosteroid therapy may increase risk of developing atrial fibrillation
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385 cases of new-onset atrial fibrillation compared to 6,364 controls
corticosteroid use in prior month associated with atrial fibrillation (odds ratio 3.75, 95% CI 2.38-
5.87)
significant association limited to high-dose corticosteroids defined equivalent to prednisone 7.5 mg
daily or higher (odds ratio 6.07, 95% CI 3.9-9.42)
Reference - Arch Intern Med 2006 May 8;166(9):1016, commentary can be found in Arch Intern
Med 2006 Sep 18;166(16):1784, 1785, 1785
Genetic factors
multiple susceptibility signals on chromosome 4q25 may identify patients with increased risk of atrial
fibrillation ( Circulation 2010 Sep 7;122(10):976)
SCN5A mutation associated with dilated cardiomyopathy and atrial fibrillation ( JAMA 2005 Jan
26;293(4):447), editorial can be found in JAMA 2005 Jan 26;293(4):491
mutations in connexin 40 gene (GJA5) identified in 4 of 15 patients with idiopathic atrial fibrillation ( N
Engl J Med 2006 Jun 22;354(25):2677), editorial can be found in N Engl J Med 2006 Jun
22;354(25):2712
atrial fibrillation locus on chromosome 1p36-p35 found in family with 11 clinically affected members ( N
Engl J Med 2008 Jul 10;359(2):158)
Other risk factors
diabetes mellitus associated with increased risk of atrial fibrillation

systematic review of 11 observational studies (7 prospective cohort studies and 4 case-control
studies) evaluating 1,686,097 patients with 108,703 cases of atrial fibrillation
higher risk of atrial fibrillation in patients with diabetes compared to general population (relative
risk 1.34, 95% CI 1.07-1.68)
Reference - Am J Cardiol 2011 Jul 1;108(1):56
sedentary lifestyle associated with increased risk of atrial fibrillation in men and women, and
moderate physical activity associated with decreased risk; effect of vigorous physical activity on risk
of atrial fibrillation appears to be gender dependent
systematic review of 22 observational studies evaluating association between exercise intensity and
risk of atrial fibrillation in 656,700 adults
definition of activity levels varied across studies
moderate physical activity defined as > 4 hours per week of walking, cycling, or light
physical work (such as walking a lot, climbing stairs, or carrying light objects) in 4 studies
with 110,951 men
vigorous physical activity defined as competitive athletics or sports practice in 7 studies with
6,835 men
sedentary lifestyle associated with increased risk of atrial fibrillation compared to moderate or
vigorous physical activity (odds ratio [OR] 2.47, 95% CI 1.25-3.7) in analysis of 7 studies with
93,995 men and women
compared to sedentary lifestyle
moderate physical activity associated with decreased risk of atrial fibrillation
in women (OR 0.91, 95% CI 0.77-0.97) in analysis of 149,048 women in 2 studies
in men (OR 0.81, 95% CI 0.26-1.004) in analysis of 110,951 men in 4 studies
vigorous physical activity associated with
decreased risk of atrial fibrillation in women (OR 0.72, 95% CI 0.57-0.88) in analysis
of 103,298 women in 6 studies
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increased risk of atrial fibrillation in men (OR 3.3, 95% CI 1.97-4.63) in analysis of
85,024 men in 13 studies, results limited by significant heterogeneity
Reference - J Cardiovasc Electrophysiol 2016 Sep;27(9):1021
working ≥ 55 hours per week associated with increased risk of developing atrial fibrillation
85,494 workers (65% women, aged 17-70 years) without atrial fibrillation at baseline were followed
for mean 10 years
5.2% had long working hours (≥ 55 hours per week) and 62.5% had standard working hours (35-40
hours per week) at baseline
1,061 workers (1.2%) developed atrial fibrillation during follow-up
long working hours associated with increased risk of atrial fibrillation compared with standard
working hours (adjusted hazard ratio 1.42, 95% CI 1.13-1.8)
Reference - Eur Heart J 2017 Sep 7;38(34):2621 full-text
calcium channel blockers associated with higher risk of atrial fibrillation than angiotensin-
converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta blockers
4,661 patients with atrial fibrillation were compared to 18,642 matched controls
all patients were receiving antihypertensive drugs
current exclusive treatment with calcium channel blockers associated with increased risk of atrial
fibrillation compared to current exclusive use of (with odds ratios [OR] compared to calcium
channel blockers)
ACE inhibitors (OR 0.81, 95% CI 0.71-0.94) in analysis of 5,288 patients
ARBs (OR 0.74, 95% CI 0.6-0.91) in analysis of 3,274 patients
beta blockers (OR 0.81, 95% CI 0.7-0.94) in analysis of 4,750 patients
Reference - Ann Intern Med 2010 Jan 19;152(2):78
opioid use associated with increased risk of atrial fibrillation
based on cross-sectional analysis of data from Reasons for Geographic and Racial Differences in
Stroke (REGARDS) population-based longitudinal study
24,632 adults (mean age 65 years) evaluated
8.5% had atrial fibrillation and 7.7% reported opioid use (most commonly hydrocodone, followed
by propoxyphene and tramadol)
opioid use associated with increased risk of atrial fibrillation (adjusted odds ratio 1.35, 95% CI
1.16-1.57)
Reference - JAMA Intern Med 2015 Jun 1;175(6):1058
elevated C-reactive protein (CRP) levels associated with increased prevalence of atrial fibrillation
5,806 patients in Cardiovascular Health Study in United States followed for mean 7 years
315 patients (5%) had atrial fibrillation at base line; 897 developed atrial fibrillation during follow-
up
compared to lowest quartile of CRP level, highest quartiles of CRP level associated with
increased rate of atrial fibrillation at baseline (7.4% vs. 3.7%, p = 0.002)
increased risk for developing atrial fibrillation during follow-up (hazard ratio 1.31, 95% CI
1.08-1.58)
Reference - Circulation 2003 Dec 16;108(24):3006
Risk prediction
estimated lifetime risk of atrial fibrillation after age 55 years 22%-48% depending on genetic and
clinical risk factors
4,606 adults from Framingham Heart Study without atrial fibrillation at age 55 years were evaluated
for lifetime risk of developing atrial fibrillation based on genetic and clinical risk factors
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genetic risk calculated from 30 groups of nearly 1,000 single nucleotide polymorphisms in
genes associated with atrial fibrillation
clinical risk calculated using factors such as height, weight, blood pressure, current smoking
status, antihypertensive medication use, diabetes, history of myocardial infarction, and history
of heart failure
13% developed atrial fibrillation during median follow-up of 9.4 years
estimated lifetime risk of atrial fibrillation (based on genetic and clinical risk) after age 55 years
37.1% (95% CI 34.6%-39.6%) overall
22.3% (95% CI 15.4%-29.1%) among adults in low genetic and clinical risk tertiles (low risk)
48.2% (95% CI 41.3%-55.1%) among adults in high genetic and clinical risk tertiles (high
risk)
Reference - Circulation 2018 Mar 6;137(10):1027
38% estimated overall lifetime risk of atrial fibrillation in 3,676 persons aged 55 years and older with at
least 1 elevated risk factor in cohort study of 5,338 adults from Framingham Heart Study without atrial
fibrillation ( BMJ 2018 Apr 26;361:k1453 full-text)
Factors not associated with increased risk

bisphosphonates not associated with statistically significant increased risk for atrial fibrillation, but
risk cannot be ruled out
see Bisphosphonates for treatment and prevention of osteoporosis for details
coffee consumption > 5 cups per day may not be associated with increased risk of atrial fibrillation
or flutter compared to < 2 cups a day
systematic review of 6 prospective cohort studies evaluating association between coffee
consumption and risk of atrial fibrillation or flutter in 248,910 persons
comparing highest quintile of coffee consumption (> 5 cups per day) to control (< 2 cups per day),
no significant difference in risk of atrial fibrillation or flutter in analysis of all studies, results
limited by significant heterogeneity
Reference - BMC Med 2015 Sep 23;13:207, editorial can be found at Heart 2013 Oct;99(19):1377
caffeine consumption not associated with increased risk of atrial fibrillation or flutter
systematic review of 7 observational studies evaluating association between caffeine consumption
and risk of atrial fibrillation or flutter in 115,993 persons
comparing caffeine consumption to control (no caffeine consumption or lowest quintile of
consumption), no significant difference in risk of atrial fibrillation or flutter in analysis of all
comparing low caffeine consumption (< 350 mg/day) to control, low caffeine consumption
associated with reduced risk of atrial fibrillation or flutter (odds ratio 0.85, 95% CI 0.78-0.92) in
subgroup analysis of 5 studies
Reference - Heart 2013 Oct;99(19):1383, editorial can be found at Heart 2013 Oct;99(19):1377
< 2 alcoholic drinks daily not associated with increased risk of atrial fibrillation in women
34,715 women > 45 years old without atrial fibrillation reported alcohol consumption and were
followed for median 12.4 years
653 cases of atrial fibrillation occurred
atrial fibrillation events occurred in
1.9% of women consuming 0 drinks daily
1.8% of women consuming > 0 and < 1 drink daily (not significant vs. 0 drinks)
1.6% of women consuming between 1 and < 2 drinks daily (not significant vs. 0 drinks)
2.9% of women consuming ≥ 2 drinks daily (p < 0.05 vs. 0 drinks)
increased risk with ≥ 2 drinks daily remained significant after multiple adjustments
Reference - JAMA 2008 Dec 3;300(21):2489
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Associated conditions
atrial fibrillation with or without history of stroke associated with increased risk of cognitive
impairment
systematic review of 21 studies evaluating association between atrial fibrillation and cognitive
impairment in 92,748 patients
atrial fibrillation associated with increased risk of cognitive impairment in patients
with or without history of stroke (relative risk [RR] 1.4, 95% CI 1.19-1.64) in analysis of 14
with incident or recurrent stroke (RR 2.7, 95% CI 1.82-4) in analysis of 7 studies
without history of stroke (RR 1.34, 95% CI 1.13-1.58) in analysis of 10 studies, results
limited by significant heterogeneity
Reference - Ann Intern Med 2013 Mar 5;158(5 Pt 1):338
atrial fibrillation associated with dementia
based on 1 systematic review and 2 cohort studies
systematic review of 15 cohort studies reporting association between baseline atrial fibrillation and
dementia
atrial fibrillation associated with increased risk of dementia (odds ratio 2, 95% CI 1.4-2.7) in
analysis of 14 studies, results limited by significant heterogeneity
Reference - Neurology 2011 Mar 8;76(10):914
cohort study of 10,214 persons followed for mean 26.6 years
9% developed atrial fibrillation and 3% developed dementia
atrial fibrillation associated with increased risk of dementia (adjusted hazard ratio 1.87, 95%
CI 1.37-2.55)
Reference - Eur Heart J 2017 Sep 7;38(34):2612 full-text
cohort study of 2,837 elderly patients without cognitive dysfunction or stroke diagnosed with first
atrial fibrillation were followed for median 4.6 years
299 patients (10.5%) were diagnosed with dementia
cumulative rate of dementia 2.7% at 1 year and 10.5% at 5 years
atrial fibrillation associated with increased risk of myocardial infarction, especially in women and
black patients
23,928 community-dwelling adults ≥ 45 years old without coronary heart disease at baseline
included
648 incident myocardial infarction events (fatal and nonfatal) occurred over 6.9 years of follow-up
atrial fibrillation associated with increased risk of myocardial infarction
overall (adjusted hazard ratio [HR] 1.7, 95% CI 1.26-2.3)
in women (adjusted HR 2.16, 95% CI 1.41-3.31)
in black patients (adjusted HR 2.53, 95% CI 1.67-3.86)
no significant difference in risk of myocardial infarction associated with atrial fibrillation in older (≥
75 years old) vs. younger (< 75 years old) patients
Reference - JAMA Intern Med 2014 Jan 1;174(1):107 full-text, correction can be found in JAMA
Intern Med 2014 Feb 1;174(2):308, editorial can be found in JAMA Intern Med 2014 Jan 1;174(1):5
Etiology and Pathogenesis

Causes
cardiac abnormalities
structural abnormalities
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left atrial enlargement

mitral stenosis
mitral regurgitation
aortic stenosis
aortic regurgitation
cardiomyopathy (dilated, hypertrophic, restrictive, obstructive)
malignancy (involving atrium)
Reference - Dis Mon 2013 Mar;59(3):67
atrial septal defect
conduction abnormalities
tachycardia-bradycardia syndrome (sick sinus syndrome) (Dis Mon 2013 Mar;59(3):67)
Wolff-Parkinson-White (WPW) syndrome (Dis Mon 2013 Mar;59(3):67)
short QT syndrome (CMAJ 2005 Nov 22;173(11):1349 full-text)
functional abnormalities or conditions stressing cardiac function
myocardial infarction
pericarditis
pulmonary embolism (PE)
coronary artery disease (CAD)
rheumatic heart disease
hypertension
metabolic causes
carbon monoxide poisoning
hypoxemia
hypokalemia
hypomagnesemia
hypercalcemia
drugs
theophylline
albuterol
tricyclic antidepressants
digoxin
ophthalmic atropine
sympathomimetics
adenosine
nicotine
Reference - J Am Coll Cardiol 2004 Dec 7;44(11):2117 full-text
case report of atrial fibrillation with sumatriptan (BMJ 2000 Jul 29;321(7256):275 full-text)
may be idiopathic (Dis Mon 2013 Mar;59(3):67)
transient hyperadrenergic state
postoperative (especially coronary artery bypass graft [CABG] surgery)
hyperthyroidism
obstructive sleep apnea
alcohol abuse (holiday heart syndrome)
exacerbation of pulmonary disease (COPD)
other hyperadrenergic states
hypoglycemia
pheochromocytoma
drug or alcohol withdrawal
single nucleotide polymorphism rs10824026 on chromosome 10q22 may mediate modest proportion of
increased risk for atrial fibrillation among white patients compared to black patients, possibly through
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interaction with expression of MYOZ1, in 3 population-based cohorts (JAMA Cardiol 2016 Jul
1;1(4):442 full-text )
review of genomic basis of atrial fibrillation can be found in Heart 2018 Feb;104(3):201
vagally mediated atrial fibrillation, especially in young healthy patients (case report and discussion can be
found in Arch Fam Med 2000 Apr;9(4):389), commentary can be found in Arch Fam Med 2000
Jul;9(7):587
Pathogenesis
hypothesized pathogenesis of atrial fibrillation includes
causes may trigger cellular hypertrophy, activation of fibroblasts, and/or tissue fibrosis that lead to
alterations in ion channel functioning, calcium homeostasis, and atrial structure
cardiac structural and electrophysiological changes lead to atrial remodeling
atrial remodeling can both generate and further perpetuate atrial arrhythmia
Reference - Physiol Rev 2011 Jan;91(1):265 full-text, correction can be found in Physiol Rev 2011
Oct;91(4):1533
atrial fibrillation reduces velocity of left atrial flow and causes lag during emptying from left atrial
appendage (Dis Mon 2013 Mar;59(3):67)
symptoms may be caused by reduced cardiac output due to loss of atrial contraction(1)
left atrium or left atrial appendage thrombi can form in any patient and may be due to any(1)
Virchow's triad of stasis
endothelial dysfunction
hypercoagulable state
atrial fibrillation often associated with other supraventricular arrhythmias
Atrial fibrillation. : Atrial tachycardias. Diagram summarizing types of atrial tachycardias often
encountered in patients with a history of AF, including those seen after catheter or surgical ablation
procedures. P-wave morphologies are shown for common types of atrial flutter; however, the P-wave
morphology is not always a reliable guide to the reentry circuit location or the distinction between
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common atrial flutter and other macroreentrant atrial tachycardias. * Exceptions to P-wave morphology
and rate are common in scarred atria. Abbreviations: AF, atrial fibrillation; bpm, beats per minute; ECG,
electrocardiogram.
History and Physical

History
Chief concern (CC)
patient may be asymptomatic (especially with chronic atrial fibrillation)(1)

symptoms may include(1)
palpitations
shortness of breath (with heart failure)
lightheadedness/dizziness (presyncope/actual syncope uncommon)
focal neurological deficit (with embolic stroke)
History of present illness (HPI)
heterogenous presentation (onset, duration, frequency, triggers highly variable from patient to patient)(1)
when present, symptoms vary according to ventricular response and overall functional status of individual
patient(1)
history should(3)
establish pattern - new onset, paroxysmal, persistent, permanent
establish severity, including impact on quality of life
identify potentially treatable or reversible causes such as
endocrine abnormalities (for example, hyperthyroidism)
obstructive sleep apnea
excessive alcohol consumption
identify risk factors for recurrence or poor prognosis, including
hypertension
sleep apnea
left ventricular dysfunction
establish bleeding risk for management of antiplatelet or antithrombotic treatment
review efficacy and adverse effects of previous atrial fibrillation medications
Past medical history (PMH)
most commonly occurs in setting of underlying structural heart disease, such as hypertensive heart
disease(1)
Family history (FH)
obtain family history to determine heritable causes, especially in younger patients or those without
apparent cause of atrial fibrillation(3)
Social history (SH)
obtain social history to identify possible triggers such as alcohol or intense aerobic exercise(3)
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Physical
General physical
obtain(3)
blood pressure
heart rate
height
weight
assess for possible structural heart disease with(3)
comprehensive precordial cardiac examination
jugular venous pressure assessment
carotid and peripheral pulse assessment
absence of irregular pulse on radial artery palpation appears useful to exclude diagnosis of atrial
fibrillation (level 2 [mid-level] evidence)
based on systematic review of mostly moderate quality trials
systematic review of 3 studies of 2,385 patients > 65 years old with atrial fibrillation having pulse
palpation and electrocardiogram (ECG)
2 of 3 included studies considered to be of moderate quality only
pooled test characteristics for using irregular radial pulse for diagnosis of atrial fibrillation
sensitivity 94% (95% CI 84%-97%)
specificity 72% (95% CI 69%-75%) - authors note high prevalence of other pulse
abnormalities resulting in high rate of false-positive testing
positive likelihood ratio 3.4 (95% CI 3.2-3.7) - irregular pulse only moderately helpful for
diagnosing atrial fibrillation
negative likelihood ratio 0.11 (95% CI 0.06-0.2) - absence of irregular pulse excludes
diagnosis with reasonable confidence
Reference - J Fam Pract 2006 Feb;55(2):130
Neck
findings may include(1)

irregular jugular venous pulsations (JVP)
elevated JVP with concomitant heart failure
Cardiac
irregularly irregular rhythm detected by palpation of a pulse or auscultation(1)

heart sounds heard during auscultation may include(1)
variable intensity of first heart sound (S1)
absence of a fourth heart sound (S4) heard previously during sinus rhythm
Lungs
bibasilar rales (with concomitant heart failure)(1)
Extremities
edema (with concomitant heart failure)(1)
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Diagnosis
Making the diagnosis
electrocardiogram (ECG) shows(1)

rapid oscillatory ('fibrillatory') baseline waves varying in amplitude, shape, and timing
absence of P waves
irregularly irregular ventricular response
European Society of Cardiology (ESC) definition of atrial fibrillation(2)
surface ECG shows absolutely irregular RR intervals
no distinct P waves on surface ECG
Differential diagnosis
other irregular narrow complex tachyarrhythmias including

premature atrial contractions (PACs)
atrial flutter with variable block
multifocal atrial tachycardia (MAT)
Testing overview
minimum baseline evaluation should include

electrocardiogram during arrhythmia to document presence of atrial fibrillation
transesophageal echocardiography to exclude left atrial appendage thrombus and aid cardioversion
in patients not taking oral anticoagulants
blood tests indicated at least once in evaluation of atrial fibrillation
full cardiovascular evaluation, including history, physical exam, and evaluation for concomitant
conditions recommended in all patients with atrial fibrillation (ESC Class I, Level C)(2)
additional testing may include
chest x-ray if clinical findings suggest pulmonary abnormality(1, 3)
useful to detect underlying concurrent pulmonary disease and evaluate pulmonary vasculature
may detect enlargement of cardiac chambers with heart failure
as baseline testing in patients taking amiodarone
ambulatory electrocardiogram (Holter monitor, event monitor, loop monitor)(3)
to document atrial fibrillation
to rule out alternative diagnosis
to assess ventricular rate control
to correlate symptoms with rhythm disturbance (if paroxysmal atrial fibrillation)
ambulatory blood pressure monitoring (if borderline hypertension)(3)
6-minute walk test (if adequacy of rate control uncertain)(1)
exercise treadmill testing(1, 3)
if adequacy of rate control uncertain
to reproduce exercise-induced atrial fibrillation
for suspected myocardial ischemia
electrophysiological study (for consideration of curative ablation for patients with documented
regular supraventricular tachycardia)(1, 3)
sleep study (ambulatory oximetry or polysomnography)(3)
for patients with symptoms of obstructive sleep apnea
for select patients with advanced symptomatic heart failure
genetic testing in rare cases of apparent familial disease (especially if onset at young age)(3)
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Blood tests
blood tests to be considered at least once in evaluation of atrial fibrillation (CCS Strong recommendation,
Low-quality evidence)(1, 3)
thyroid-stimulating hormone (TSH)
electrolytes
renal function tests
liver function tests
complete blood count
coagulation profile
fasting lipid profile
fasting glucose
consider serum calcium and magnesium(3)
if suspected deficiency (such as gastrointestinal losses or diuretic use)
if it may influence treatment (such as with sotalol or dofetilide)
serum levels of B-type natriuretic peptide (BNP) (assessed by measuring BNP or N-terminal pro-BNP)
and atrial natriuretic peptide (ANP); both are elevated in patients with paroxysmal or persistent atrial
fibrillation but decrease rapidly after restoration of normal sinus rhythm(1)
Imaging studies
Echocardiography
Indications
all patients with atrial fibrillation should have Doppler echocardiography performed to assess cardiac
dimensions and function and to exclude valvular disease and pericardial disease (CCS Strong
recommendation, Low-quality evidence)(1, 3)
transthoracic echocardiography recommended in all patients with atrial fibrillation to guide therapy (ESC
Class I, Level C)(2)
echocardiogram used to(3)
assess left atrial size (if possible, left atrial volume)
record ventricular size, wall thickness, and function
rule out significant valvular or congenital heart disease, especially atrial septal defects
estimate ventricular filling pressures and pulmonary arterial pressure
left atrial enlargement and left ventricular dysfunction by echocardiography are risk factors for stroke
Transesophageal echocardiogram (TEE) for timing of cardioversion
transesophageal echocardiogram to guide timing of cardioversion as effective as conventional

approach (warfarin for 3 weeks before cardioversion) and associated with fewer hemorrhagic
complications, but nonsignificant increase in mortality (level 2 [mid-level] evidence)
based on randomized trial with inadequate statistical power for mortality outcome
1,222 patients with atrial fibrillation > 2 days duration were randomized to transesophageal
echocardiogram (TEE) (direct current cardioversion within 24 hours if no thrombi) vs. conventional
approach
for TEE patients, inpatients received IV heparin and TEE within 24 hours, outpatients
received warfarin and TEE 5 days later
both groups received warfarin for 4 weeks after cardioversion
comparing TEE protocol vs. conventional approach
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primary composite endpoint of stroke, transient ischemic attack, or peripheral embolism

within 8 weeks in 0.8% vs. 0.5% (not significant)
hemorrhagic events in 2.9% vs. 5.5% (p = 0.03, NNT 39)
mean time to cardioversion 3 days vs. 30.6 days (p < 0.001)
successful restoration of sinus rhythm in 71.1% vs. 65.2% (p = 0.03, NNT 17)
no significant differences at 8 weeks in death, maintenance of sinus rhythm, or functional
status
overall mortality 2.4% vs. 1% (p = 0.06, NNH 71, potentially clinically important but not
reaching conventional statistical significance)
Reference - ACUTE trial (N Engl J Med 2001 May 10;344(19):1411), editorial can be found in N
Engl J Med 2001 May 10;344(19):1468, commentary can be found in N Engl J Med 2001 Sep
13;345(11):837
TEE-guided early direct current cardioversion may reduce atrial fibrillation recurrence compared
to conventional approach (cardioversion after 3 weeks of anticoagulation) in patients with atrial
fibrillation for < 60 days, but not in patients with atrial fibrillation for > 60 days (level 2 [mid-level]
evidence)
based on randomized trial with baseline differences
126 patients with persistent atrial fibrillation were randomized to TEE-guided early direct current
cardioversion vs. direct current cardioversion after 3 weeks of anticoagulation with dabigatran
(conventional approach) and were followed for 1 year
patients in TEE-guided early cardioversion group had TEE within first 48 hours and
cardioversion was performed if no thrombi
both groups received dabigatran for 4 weeks after cardioversion
patients were stratified by duration of atrial fibrillation (< 60 days and > 60 days)
patients in TEE-guided early cardioversion group were significantly younger than patients in
conventional approach group
atrial fibrillation recurrence lasting ≥ 30 seconds was recorded by 48-hour Holter monitoring or
electrocardiogram at 28 days, 3 months, 6 months, and 1 year
all patients had successful cardioversion
comparing TEE-guided early cardioversion vs. conventional approach
1-year recurrence-free survival 38% vs. 8% (p = 0.003, NNT 4) in patients with atrial
fibrillation for < 60 days
1-year recurrence-free survival 18% vs. 25% (not significant) in patients with atrial
fibrillation for > 60 days
mean duration of atrial fibrillation-related hospitalization 1.13 days vs. 3.03 days (p = 0.0004)
mean number of atrial fibrillation-related outpatient visits 2.88 vs. 4.47 (p = 0.0001)
consistent findings for recurrence-free survival at 28 days, 3 months, and 6 months
early cardioversion appears safe and effective in patients without left atrial thrombi detected on
TEE (level 2 [mid-level] evidence)
539 patients with history of atrial fibrillation (majority had recently been diagnosed within previous
3 weeks) had TEE performed
atrial thrombi identified in only 70 (13.1%) of patients (95% of patients on therapeutic
anticoagulation at time of echocardiography)
successful cardioversion performed in 413 patients without evidence of atrial thrombus on TEE with
subsequent thromboembolism documented in only 1 patient (0.24%, 95% CI 0%-0.8%)
comparing patients with history of atrial fibrillation < 3 weeks vs. patients with unknown duration
1-year recurrence rate of atrial fibrillation 41.1% vs. 57.9% (p < 0.01)
prevalence of sinus rhythm at 1 year 65.8% vs. 51.3% (p < 0.03)
Reference - Am J Med 2001 Jun 15;110(9):694, commentary can be found in J Fam Pract 2001
Nov;50(11):925
Intracardiac echocardiography
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intracardiac echocardiography may detect left atrial or right atrial appendage thrombi as often as
transesophageal echocardiography (level 2 [mid-level] evidence)
based on diagnostic cohort study without reference standard
71 patients (mean age 60.5 years) with atrial fibrillation or flutter having catheter ablation were
evaluated for presence of left atrial appendage (LAA) or right atrial appendage (RAA) thrombi
71 patients had intracardiac echocardiography (ICE)
69 patients had TEE (2 patients unable to have TEE due to inability to intubate esophagus)
ICE images obtained from right atrium (RA), right ventricular outflow tract (RVOT), and
pulmonary artery (PA)
diagnosis of thrombosis defined as discrete echo-dense mass with defined margins, distinct from
endocardium and seen throughout diastole and systole via ICE or TEE by ≥ 2 independent
echocardiographers
diagnostic imaging defined as presence of either
excellent visualization of entire left atrial appendage
lower but diagnostic quality imaging permitting confident determination of presence or
absence of thrombus
diagnostic imaging of LAA achieved in 100% of patients using ICE and 87.3% of patients using
TEE
4 definite thrombi diagnosed (3 in LAA and 1 in right atrial appendage)
ICE detected all thrombi (main PA position had superior diagnostic image quality vs. both RA
and RVOT)
TEE detected 1 of 4 thrombi (thrombi in LAA)
complications occurred in
0 patients who had ICE
2 patients who had TEE (oropharyngeal bleeding due to traumatic prober insertion)
Reference - Heart Rhythm 2014 Nov;11(11):1890
intracardiac echocardiography (limited to right atrium position) may have limited utility for
detection of left atrial and left atrial appendage thrombi in patients with atrial fibrillation (level 2
[mid-level] evidence)
based on diagnostic cohort study with test under investigation not applied to all patients
95 patients (mean age 58 years) with atrial fibrillation having right heart catheterization had
interatrial septal imaging by ICE and TEE (reference standard) for detection of LAA thrombus
82 patients had both echocardiography techniques completed
ICE images obtained from right atrium
prevalence of left atrial (LA) or LAA thrombus 6.9% by reference standard
for detection of left atrial or left atrial appendage thrombus, ICE had 69% sensitivity and 67%
specificity
Reference - ICE-CHIP trial Circ Arrhythm Electrophysiol 2010 Dec 1;3(6):571 full-text, editorial
can be found in Circ Arrhythm Electrophysiol 2010 Dec 1;3(6):564
Computed tomography
dual-enhancement cardiac CT diagnoses and rules out left atrial thrombus or circulatory stasis in
patients having catheter ablation of atrial fibrillation (level 1 [likely reliable] evidence)
based on diagnostic cohort study
101 patients (mean age 62 years, 70% men) with symptomatic atrial fibrillation scheduled for
radiofrequency catheter ablation were assessed with dual-enhancement cardiac computed
tomography (CT) and transesophageal echocardiography (reference standard) on same day prior to
catheter ablation
on CT, thrombus defined as filling defect with oval or round shape, and circulatory stasis
(spontaneous echo contrast [SEC]) defined as filling defect with triangular shape
9% had left atrial appendage thrombus and 18% had SEC by reference standard
diagnostic performance of dual-enhancement cardiac CT
for detection of thrombus or circulatory stasis
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sensitivity 100%
specificity 100%
positive predictive value 100%
negative predictive value 100%
1 thrombus was misclassified as circulatory stasis on CT
for detection of thrombus only
sensitivity 89%
specificity 100%
no significant difference in diagnostic performance comparing patients with high risk of
stroke (CHADS2 ≥ 2) vs. other patients
for distinguishing thrombus from circulatory stasis, quantitative assessment of CT with cutoff
Hounsfield ratio > 0.24 had sensitivity 100% and specificity 94% in subgroup analysis
64-slice cardiac computed tomographic angiography may rule out left atrial appendage thrombus in
patients with atrial fibrillation, but positive predictive value appears low (level 2 [mid-level]
evidence)
based on retrospective diagnostic cohort study with time delay between test and reference
84 patients (mean age 64 years) with atrial fibrillation who were referred for pulmonary vein antral
isolation procedure had 64-slice cardiac computed tomographic angiography (CCTA) and
transesophageal echocardiography (reference standard) for detection of LAA thrombus
mean interval 24 days between test and reference
positive result on CCTA defined
qualitatively as area of low attenuation (dark) that persisted in delayed scan (40-second delay,
second scan without contrast administration)
quantitatively as attenuation with density cutoff 119 Hounsfield units
prevalence of LAA thrombus was 19% by reference standard (transesophageal echocardiography)
diagnostic performance of CCTA for detection of LAA thrombus
for qualitative assessment
sensitivity 100%
specificity 78%
for quantitative assessment
sensitivity 88%
specificity 86%
similar diagnostic performance found using Hounsfield unit density ratio of LAA to
ascending aorta with cutoff 0.242
Reference - Am J Cardiol 2014 Jan 1;113(1):173
Electrocardiography (ECG)
Indications for ECG and ECG images
ECG indicated in patients with suspected or confirmed atrial fibrillation to (CCS Strong recommendation,
Low-quality evidence ; ESC Class I, Level B )(1, 2, 3)
verify diagnosis
absence of P waves
rapid oscillatory ('fibrillatory') baseline waves varying in amplitude, shape and timing, and
associated with irregular ventricular response
may have rapid ventricular response with intact atrioventricular conduction
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screen for presence of other concurrent arrhythmias (especially other atrial arrhythmias, bundle
branch block, or preexcitation)
screen for presence of myocardial infarction or left ventricular hypertrophy
monitor intervals (R-R, QRS, QT) in conjunction with antiarrhythmic drug therapy
consider long term ECG monitoring to evaluate adequacy of rate control in select asymptomatic patients
to relate symptoms with atrial fibrillation episodes (ESC Class IIa, Level C)(2)
for athletes, evaluate ventricular rate while exercising using symptoms and/or ECG monitoring and titrate
rate control (ESC Class IIa, Level C)(2)
Atrial fibrillation. : Rhythm: atrial fibrillation. Morphology: left bundle branch block.
Atrial fibrillation. : Rhythm: atrial fibrillation. Morphology: narrow QRS. ST segment: nonspecific ST/T
changes.
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Atrial fibrillation. : Rhythm: atrial fibrillation with rapid ventricular response; otherwise, normal intervals,
normal QRS axis.
Atrial Fibrillation. : Atrial fibrillation with rapid ventricular response. There are normal intervals.
Occasional aberration is seen.
Atrial fibrillation with aberrant conduction. : Atrial fibrillation with ventricular pre-excitation and very
rapid ventricular response.
Evidence for ECG detection of atrial fibrillation
transtelephonic event monitoring may be more likely than ambulatory (Holter) monitoring to detect
clinically significant arrhythmias (level 2 [mid-level] evidence)
based on randomized crossover trial without blinding of patients
43 patients (mean age 45 years, 88% women) with history of previously uninvestigated palpitations
randomized to event monitoring (3 months or 2 triggered recordings) vs. Holter monitoring (48
hours) then crossed over
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diagnostic rhythm strip obtained in 67% with event monitors vs. 35% with Holter monitoring (p <
0.001)
event monitors detected 8 cases of clinically significant arrhythmias (6 supraventricular
tachycardia/2 atrial fibrillation/flutter) that Holter monitors did not
Reference - Ann Intern Med 1996 Jan 1;124(1 Pt 1):16
detection of atrial fibrillation after stroke

10-day enhanced and prolonged Holter monitoring may increase detection rate of atrial
fibrillation compared to standard care following ischemic stroke (level 2 [mid-level] evidence)
based on randomized trial with incomplete blinding
398 patients ≥ 60 years old with acute ischemic stroke (symptoms for ≤ 7 days) in sinus
rhythm and without history of atrial fibrillation were randomized to 10-day enhanced and
prolonged monitoring by Holter-ECG vs. standard care procedures and followed for 12
months
Holter-ECG group had 10-day monitoring at baseline, 3 months, and 6 months
standard care included ≥ 24 hours of rhythm monitoring
90% completed 6-month follow-up, 100% included in analyses
patients and caregivers were not blinded, but outcome assessors were blinded to intervention
median duration of longest atrial fibrillation episode in 10-day Holter-ECG group was 5 hours
comparing 10-day Holter-ECG vs. standard care
atrial fibrillation within 6 months detected in 13.5% vs. 4.5% (p = 0.002)
atrial fibrillation within 12 months detected in 13.5% vs. 6.1% (p = 0.02)
Reference - Lancet Neurol 2017 Apr;16(4):282
longer duration of electrocardiographic monitoring following ischemic stroke or transient
ischemic attack associated with increased detection rate of atrial fibrillation (level 2 [mid-
level] evidence)
based on systematic review without assessment of trial quality
systematic review of 3 randomized trials comparing long-term (≥ 7 days) vs. short-term
monitoring (≤ 72 hours) for detection of atrial fibrillation and 28 prospective observational
studies evaluating proportion of atrial fibrillation detected in 8,715 patients with newly
diagnosed ischemic stroke or transient ischemic attack
long-term monitoring associated with increased detection of atrial fibrillation compared to
traditional short-term monitoring (odds ratio 7.26, 95% CI 4.04-13.04) in analysis of 3
randomized trials with 1,113 patients
proportion with newly diagnosed cases of atrial fibrillation in prospective observational
studies
5.1% (95% CI 3.4%-7.5%) in analysis of 15 studies with short-term ECG monitoring,
results limited by significant heterogeneity
15% (95% CI 11%-19%) in analysis of 16 studies with long-term ECG monitoring,
Reference - Circ Arrhythm Electrophysiol 2015 Apr;8(2):263 full-text, editorial can be found
in Circ Arrhythm Electrophysiol 2015 Apr;8(2):263
similar findings in systematic review of 5 prospective cohort studies evaluating noninvasive
methods of continuous cardiac monitoring after stroke or TIA in 736 patients ( Stroke 2007
Nov;38(11):2935 full-text)
noninvasive ambulatory ECG monitoring for 30 days may increase detection rate of
atrial fibrillation and initiation of oral anticoagulant treatment compared to 24-hour
ECG monitoring in patients with cryptogenic ischemic stroke or transient ischemic
attack (level 2 [mid-level] evidence)
based on randomized trial without blinding of outcome assessors
572 patients ≥ 55 years old with cryptogenic ischemic stroke (63%) or transient
ischemic attack (TIA, 37%) within past 6 months were randomized to ECG monitoring
with 30-day event-triggered loop recorder vs. 24-hour Holter monitor and followed for
90 days
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cause of stroke or TIA was unknown following standard tests, including 24-hour ECG
all patients had no history of atrial fibrillation
82% of patients with 30-day ECG monitoring completed ≥ 3 weeks of monitoring
comparing 30-day ECG monitoring vs. 24-hour ECG monitoring
atrial fibrillation for ≥ 30 seconds in 16.1% vs. 3.2% (p < 0.001, number needed
to screen 8)
atrial fibrillation for ≥ 2.5 minutes in 9.9% vs. 2.5% (p < 0.001, number needed
to screen 14)
receipt of oral anticoagulant therapy 18.6% vs. 11.1% (p = 0.01)
Reference - EMBRACE trial ( N Engl J Med 2014 Jun 26;370(26):2467 full-text ),
editorial can be found in N Engl J Med 2014 Jun 26;370(26):2532
noninvasive cardiac event monitoring for 7 days associated with increased detection of
paroxysms of atrial fibrillation and increased anticoagulation treatment within 90 days
of ischemic stroke (level 2 [mid-level] evidence)
based on randomized trial without allocation concealment
100 patients with ischemic stroke in previous 7 days were randomized to noninvasive
cardiac event monitoring plus standard investigations vs. standard investigations alone
and followed to 90 days
noninvasive cardiac monitoring used light-weight (50 g) device to capture 30-
second cardiac rhythm data over 7 days
cardiac rhythm data transferred to central electrocardiogram (ECG) laboratory for
analysis, and recordings with suspected atrial fibrillation were reviewed by
experienced electrocardiologist
standard investigations were consistent with guidelines and may have included
12-lead ECG after hospitalization, 24-hour Holter monitoring, and
echocardiography with ECG
all patients presented in sinus rhythm and had no history of atrial fibrillation
sustained paroxysms of atrial fibrillation defined as duration ≥ 20 seconds and
nonsustained paroxysms of atrial defibrillation defined as ≥ 6 conducted ventricular
complexes with duration < 20 seconds
comparing noninvasive cardiac event monitoring vs. standard investigations at 14 days
sustained or nonsustained paroxysms of atrial fibrillation detected in 44% vs. 4%
(p < 0.001, number needed to screen 3)
anticoagulation treatment for atrial fibrillation thromboembolism prophylaxis in
16% vs. 0% (p < 0.01, number needed to screen 7)
consistent results at 90 days
noninvasive cardiac event monitoring associated with significantly increased detection
of sustained paroxysms of atrial fibrillation at 14 days but difference was no longer
significant at 90 days
Reference - Stroke 2013 Sep;44(9):2525 full-text, commentary can be found in Evid
Based Med 2014 Aug;19(4):152
monitoring with insertable cardiac monitor may increase detection of atrial fibrillation
compared to conventional follow-up in patients with cryptogenic stroke or TIA (level 2
based on randomized trial with allocation concealment not stated
441 patients ≥ 40 years old with cryptogenic stroke or TIA (91% with nonlacunar
stroke) within past 90 days were randomized to 1 of 2 ECG monitoring interventions
implantation of cardiac monitor for ECG monitoring within 10 days
conventional follow-up with ECG monitoring performed at discretion of site
investigator
all patients had no history of atrial fibrillation or atrial flutter and cause of stroke or
TIA was unknown following standard tests, including ECG monitoring for ≥ 24-hour
5% of patients with implantable cardiac monitor crossed over to conventional ECG
monitoring and 2.7% of patients with conventional ECG monitoring crossed over to
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implantable cardiac monitor (no p value reported)

comparing insertable cardiac monitor vs. conventional follow-up
atrial fibrillation > 30 seconds at 6 months in 8.9% vs. 1.4% (p < 0.001)
atrial fibrillation > 30 seconds at 1 year in 12.4% vs. 2% (p < 0.001)
insertable cardiac monitor was removed in 2.4% due to infection at insertion site or
pocket erosion
Reference - CRYSTAL AF trial ( N Engl J Med 2014 Jun 26;370(26):2478 full-text),
editorial can be found in N Engl J Med 2014 Jun 26;370(26):2532
DynaMed commentary --trial sponsor (Medtronic) had nonvoting membership on
steering committee and assisted in study design, data collection, data analysis, and
manuscript technical content and review
consistent findings at 3 years
based on follow-up of CRYSTAL AF trial
11% of patients had follow-up data available at 3 years
comparing insertable cardiac monitor vs. conventional follow-up
estimated atrial fibrillation detection rate 30% vs. 3% (p < 0.0001)
first episodes detected that were asymptomatic 81% vs. 40% (no p value
reported)
Reference - Circ Arrhythm Electrophysiol 2016 Jan;9(1):e003333 full-text
increased baseline atrial premature beat count on 24-hour Holter ECG may predict atrial
fibrillation in patients with cryptogenic stroke or TIA (level 2 [mid-level] evidence)
based on cohort analysis of data from EMBRACE trial
237 patients ≥ 55 years old with cryptogenic stroke or TIA within past 6 months and without
history of atrial fibrillation in intervention arm of EMBRACE trial were assessed
intervention was 30-day ECG monitoring with event-triggered external recorder
all patients had 24-hour Holter ECG at baseline
≥ 1 episode of atrial fibrillation lasting ≥ 30 seconds detected by clinical evaluation in 16% at
90 days
median 24-hour atrial premature beat count at baseline 629 beats in patients with atrial
fibrillation vs. 45 beats in patients without atrial fibrillation (p < 0.001)
increased baseline atrial premature beat count associated with increased risk of atrial
fibrillation at 30 days (p < 0.0001) and at 90 days (p = 0.0017)
Reference - Stroke 2015 Apr;46(4):936 full-text
Holter monitoring for 72 hours may increase detection of silent paroxysmal atrial fibrillation
compared to Holter monitoring for 24 hours after ischemic stroke (level 2 [mid-level]
evidence)
1,135 patients (mean age 67 years) with ischemic stroke and without known atrial fibrillation
had standardized stroke workup and Holter monitoring for 72 hours
atrial fibrillation defined as ≥ 1 period of ≥ 30 seconds duration of absolute arrhythmia
without detectable P waves and without pattern more consistent with alternative diagnosis
silent atrial fibrillation diagnosis in 49 patients
29 patients diagnosed during first 24 hours of monitoring
20 additional patients diagnosed between 24-72 hours of monitoring
number needed to screen by 72-hour Holter monitoring was 55 patients for each additional
atrial fibrillation diagnosis
Reference - Stroke 2013 Dec;44(12):3357 full-text
about 24% diagnosed with atrial fibrillation during post-stroke or transient ischemic attack
cardiac monitoring phases
systematic review of 50 studies evaluating rates of newly diagnosed atrial fibrillation during 4
sequential phases of cardiac monitoring in 11,658 patients after stroke or TIA
emergency department admission ECG (phase 1)
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in-hospital monitoring including serial ECG, continuous ECG, continuous cardiac

telemetry, and Holter monitoring (phase 2)
first ambulatory period consisting of Holter monitoring (phase 3)
second ambulatory period consisting of mobile cardiac outpatient telemetry, external
loop recording, and implantable loop recording (phase 4)
23.7% overall atrial fibrillation (any form of atrial fibrillation or atrial flutter, chronic or
paroxysmal, regardless of duration) detection yield after all phases of sequential cardiac
monitoring
proportion of patients newly diagnosed with atrial fibrillation
7.7% in phase 1
5.1% in phase 2
10.7% in phase 3
16.9% in phase 4
Reference - Lancet Neurol 2015 Apr;14(4):377, editorial can be found in Lancet Neurol 2015
Apr;14(4):345
24% diagnosed with atrial fibrillation during monitoring with implantable loop recorder in
patients with embolic stroke of undermined origin
123 patients with embolic stroke of undetermined origin received implantable loop recorder
(ILR) with daily remote monitoring and were followed every 6 months
ILR was implanted mean 20 days after stroke
atrial fibrillation was documented on ILR and manually confirmed in 24% of patients during
mean follow-up of 12.7 months
first atrial fibrillation detection occurred after mean 3.6 months of monitoring
Reference - Thromb Haemost 2017 Oct 5;117(10):1962
Interpretive software for ECG
interpretive software might perform better than generalist physicians and nurse practitioners for
diagnosing atrial fibrillation on ECG (level 2 [mid-level] evidence)
based on diagnostic study involving small sample of clinicians
2,556 randomly selected ECGs from studies done on 9,866 patients in SAFE study were interpreted
by 1 general practitioner, 1 practicing nurse, and a computer program (Biolog interpretative
software)
results compared with interpretation of 2 consultant cardiologists as reference standard, third
consultant cardiologist used to break a tie if needed
Diagnostic Performance:
General Practitioner Nurse Computer Program
Number of ECGs
1,426 1,454 2,556
evaluated
Atrial fibrillation on
6.7% 6.8% 8.4%
reference standard
Sensitivity 77% 80% 83%
Specificity 85% 91.4% 94.9%
Positive predictive
27% 41% 89.5%
value
Negative predictive
98.1% 98.4% 98.8%
value
Abbreviation: ECG, electrocardiogram.
Reference - BMJ 2007 Aug 25;335(7616):380 full-text, editorial can be found in BMJ 2007 Aug
25;335(7616):355, commentary can be found in Evid Based Med 2008 Apr;13(2):58 (correction can
be found in Evid Based Med 2008 Jun;13(3):91)
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interpretive software reported to INCORRECTLY diagnose atrial fibrillation in a significant

minority of normal ECGs (level 2 [mid-level] evidence)
based on diagnostic cohort study with final interpretation by electrophysiologists (reference
standard) not conducted blinded to initial computerized interpretation
2,298 ECGs from 1,085 patients with initial computerized ECG interpretation of atrial fibrillation or
atrial flutter (atrial flutter considered atrial fibrillation for purposes of this study) reviewed
final diagnosis made by 2 cardiac electrophysiologists (who reached consensus in cases of
disagreement)
atrial fibrillation found to have been incorrectly diagnosed in 442 ECGs (19%) in 382 patients
(35%)
computer misinterpretation resulted in
hospital admission for 9 patients
cardiology consultations for 16 patients
initiation of anticoagulation therapy in 12 patients (1 developed hematuria)
use of rate-slowing drugs in 16 patients (1 developed symptomatic bradycardia)
most errors due to electrical artifacts or atrial premature beats
Reference - Am J Med 2004 Nov 1;117(9):636
Mobile technology
mobile phone facial and finger photoplethysmography may have high sensitivity and specificity for
detecting atrial fibrillation (level 2 [mid-level] evidence)
based on diagnostic cohort study with sample not representative of patients for whom testing would
be appropriate
217 hospitalized patients (mean age 70 years, 71% men) were assessed with smartphone application
recognizing facial photoplethysmographic and fingertip photoplethysmographic signals, and 12-lead
electrocardiogram (ECG) to detect atrial fibrillation
facial (using smartphone fixed to desk) and fingertip (using handheld smartphone)
measurements were made simultaneously for 3 measurements 20 seconds each
12-lead ECG performed immediately after photoplethysmography
atrial fibrillation defined as pulse irregularity in ≥ 1 photoplethysmographic reading or 3
uninterpretable readings
34.6% had atrial fibrillation by 12-lead ECG (reference standard)
smartphone application to be used in community setting was assessed in hospitalized patients
diagnostic performance of tests to detect atrial fibrillation
for Cardiio Rhythm facial photoplethysmographic application
sensitivity 95%
specificity 96%
positive likelihood ratio 22.4
negative likelihood ratio 0.06
for fingertip photoplethysmography
sensitivity 95%
specificity 93%
positive likelihood ratio 13.4
negative likelihood ratio 0.06
Reference - J Am Heart Assoc 2018 Apr 5;7(8):e008585 full-text
mobile phone mechanocardiography may have high sensitivity and specificity for detecting atrial
based on diagnostic case-control study
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150 patients with atrial fibrillation and 150 age- and sex-matched patients in sinus rhythm had 3-
minute mechanocardiography recording (measurement of mechanical cardiac activity using
accelerometers and gyroscopes) using Sony Xperia smartphone placed on sternum
all patients were recruited from cardiology and internal medicine hospital departments (mean age
74.8 years, 44% women)
reference standard was 5-lead telemetry electrocardiography, measured simultaneous to smartphone
recording
for detecting atrial fibrillation, mechanocardiography had
sensitivity 95.3%
specificity 96%
compared to patients with true-negative result, patients with false-positive result had higher median
ventricular extrasystole count (1 vs. 0) and more often had history of heart failure or pulmonary
edema on chest x-ray (p < 0.05)
Reference - Circulation 2018 Apr 3;137(14):1524
Management
Management overview
for specific treatment modalities

see overview of rate control in atrial fibrillation below or navigate to topic Rate control in atrial
fibrillation for complete information
see overview of rhythm control in atrial fibrillation below or navigate to topic Rhythm control in
atrial fibrillation for complete information
see overview of cardioversion of atrial fibrillation below or navigate to topic Cardioversion of atrial
fibrillation for complete information
see overview of ablation therapy for atrial fibrillation below or navigate to topic Ablation therapy
for atrial fibrillation for complete information
for thromboembolic prophylaxis
see overview of thromboembolic prophylaxis in atrial fibrillation below or navigate to topic
Thromboembolic prophylaxis in atrial fibrillation for complete information
percutaneous left atrial appendage closure
consider LAA occlusion in patients at risk for stroke who have contraindications for long-
term anticoagulation treatment, such as previous life-threatening bleeding event without
reversible cause (ESC Class IIb, Level A)
surgical excision or occlusion of left atrial appendage may be considered in patients having
open heart surgery (ACC/AHA Class IIb, Level C; ESC Class IIb, Level B) or thorascopic
atrial fibrillation surgery (ESC Class IIb, Level B)
consider left atrial appendage closure (excision or ablation) as part of surgical ablation for
atrial fibrillation if no increased risk in patients having other surgeries, including any (CCS
Conditional recommendation, Low-quality evidence)
mitral valve surgery
aortic valve surgery
coronary artery bypass graft (CABG) surgery
percutaneous closure of left atrial appendage (compared to continued warfarin therapy in
patients with nonvalvular atrial fibrillation) might have lower overall mortality and might
have similar stroke rates (possibly with more ischemic and fewer hemorrhagic strokes) (level
2 [mid-level] evidence)
considerations for treatment setting, weight loss interventions, and other procedures
hospital admission may not be necessary for all patients with new-onset atrial fibrillation (level 2
[mid-level] evidence); suggested to limit hospital admission to highly symptomatic patients with
failure to achieve adequate rate control (CCS Conditional recommendation, Low-quality evidence)
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or who have decompensated heart failure or myocardial ischemia (CCS Strong recommendation,
Low-quality evidence)
addition of weight loss intervention to intensive risk factor management may reduce frequency,
duration, and severity of atrial fibrillation episodes (level 2 [mid-level] evidence)
atrial defibrillator reported to abort episodes of atrial fibrillation in some severe cases (level 3
[lacking direct] evidence)
biventricular pacing improves cardiac parameters (level 3 [lacking direct] evidence) but not clinical
outcomes (level 2 [mid-level] evidence) compared to right ventricular pacing in patients with
refractory atrial fibrillation treated with atrioventricular nodal ablation
prevention of atrial fibrillation in patients with cardiovascular disease
angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)
should be considered for prevention of new-onset atrial fibrillation in patients with
hypertension, particularly with left ventricular hypertrophy (ESC Class IIa, Level B)
ACE inhibitors and ARBs each may reduce risk for atrial fibrillation (level 2 [mid-level]
evidence)
not recommended for
primary prevention of atrial fibrillation in patients without cardiovascular disease (ESC
Class III, Level C)
secondary prevention of paroxysmal atrial fibrillation in patients without cardiovascular
disease (ESC Class III, Level B)
addition of ARB to ACE inhibitor and beta blocker suggested for prevention of new-onset atrial
fibrillation in patients with heart failure and reduced ejection fraction (ESC Class IIa, Level A)
statins
should be considered for prevention of new-onset atrial fibrillation in patients with underlying
heart disease, particularly heart failure (ESC Class IIb, Level B)
statins associated with reduced risk of atrial fibrillation (level 3 [lacking direct] evidence)
not recommended for primary prevention of atrial fibrillation in patients without
cardiovascular disease (ESC Class III, Level C)
moderate physical activity may be associated with reduced risk for atrial fibrillation in older adults
(level 2 [mid-level] evidence)
perioperative prevention of atrial fibrillation
medications for patients having cardiac surgery may include
beta blockers (ACC/AHA Class I, Level A; CCS Strong recommendation, High-quality
evidence ; ESC Class I, Level B )
amiodarone if contraindicated to beta blockers (CCS Strong recommendation, High-quality
evidence) and in high-risk patients (ACC/AHA Class IIa, Level A)
for patients with contraindication to beta blocker and amiodarone before or after cardiac
surgery, consider prophylactic therapy with any (CCS Conditional recommendation, Low- to
Moderate-quality evidence)
IV magnesium
colchicine
temporary biatrial pacing with epicardial leads
sotalol may be considered in high-risk patients (CCS Conditional recommendation, Low- to
Moderate-quality evidence)
≥ 2 of beta blocker, amiodarone, IV magnesium, or biatrial pacing suggested for patients at high risk
of postoperative atrial fibrillation (CCS Conditional recommendation, Low- to Moderate-quality
evidence)
antiarrhythmic drugs that decrease postoperative atrial fibrillation after heart surgery include sotalol,
amiodarone, and beta blockers (level 2 [mid-level] evidence)
magnesium may reduce postoperative atrial fibrillation following heart surgery (level 2 [mid-level]
evidence)
nonpharmacologic interventions that may reduce postoperative atrial fibrillation after heart surgery
include atrial pacing and posterior pericardiotomy (level 2 [mid-level] evidence)
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Treatment setting
Canadian Cardiovascular Society (CCS) recommendations

hospital admission recommended for highly symptomatic patients with decompensated heart failure
or myocardial ischemia (CCS Strong recommendation, Low-quality evidence)
suggested to limit hospital admission to highly symptomatic patients with failure to achieve
adequate rate control (CCS Conditional recommendation, Low-quality evidence)
hospital admission may not be necessary for all patients with new-onset atrial fibrillation (level 2
based on 2 retrospective cohort studies
216 adults with new-onset atrial fibrillation in hospital emergency department included
admissions considered justifiable if systolic blood pressure < 90 mm Hg, another diagnosis
required admission or significant complication occurred in emergency department or
subsequent hospitalization
143 admissions (66%) were considered medically justifiable and 98% of these were identified
in the emergency department
Reference - Acad Emerg Med 1996 Feb;3(2):114
168 patients making 289 emergency department visits for acute atrial fibrillation (duration < 48
hours) excluding patients with other reasons for hospital admission
80 (28%) had attempted electrical cardioversion with 89% success rate, 180 (62%) had
attempted chemical cardioversion with 50% success rate
only 3% visits resulted in hospitalization
overall 6% complication rate, mostly minor
only major complication reported was 1 femoral artery embolism
References - Ann Emerg Med 1999 Apr;33(4):379
emergency department observation unit care may reduce hospital stay compared to usual care
hospital admission (level 2 [mid-level] evidence)
based on randomized trial with blinding not stated
153 patients (mean age 58 years) with hemodynamically stable new-onset atrial fibrillation < 48
hours randomized to emergency department observation unit for 8 hours vs. routine inpatient care
and followed for 6 months
emergency department observation unit protocol included pulse rate control and cardiac
monitoring (reassessed at 6 hours)
patients with continued atrial fibrillation had electrical cardioversion
patients reverting to sinus rhythm discharged with cardiology follow-up in 3 days
without antiarrhythmic medication or anticoagulation
patients with continued atrial fibrillation admitted
routine inpatient care included cardiac monitoring, IV medications, and IV heparin
coronary artery disease in 20.3%
previous atrial fibrillation or flutter in 62.7%
diabetes in 1%
47% of emergency department observation unit group vs. 31% of routine care group were female
patients (p < 0.05)
comparing emergency department observation unit vs. routine hospital care
conversion to sinus rhythm in 85% vs. 73% (p = 0.06)
median length of stay 10.1 hours vs. 25.2 hours (p < 0.001)
recurrence of atrial fibrillation in 10% vs. 10% (not significant)
no significant difference in frequency of hospitalization, number of tests, adverse events,
cardiovascular events, or death between groups
Reference - Ann Emerg Med 2008 Oct;52(4):322
Rate control
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drugs for acute rate control of symptomatic atrial fibrillation with rapid ventricular response
in patients without heart failure and without preexcitation , IV beta blocker or nondihydropyridine
calcium channel blocker recommended (ACC/AHA Class I, Level B; ESC Class I, Level A)
esmolol 500 mcg/kg IV over 1 minute, then 50-300 mcg/kg/minute IV
metoprolol 2.5-5 mg IV bolus over 2 minutes, up to 3 doses (ACC/AHA Class I, Level C)
propranolol 1 mg IV over 1 minute, up to 3 doses at 2-minute intervals
diltiazem 0.25 mg/kg IV over 2 minutes, then 5-15 mg IV/hour (ACC/AHA Class I, Level B)
verapamil 0.075-0.15 mg/kg IV over 2 minutes (ACC/AHA Class I, Level B)
IV diltiazem may be more effective than IV amiodarone or digoxin for ventricular rate control
in patients with acute uncomplicated atrial fibrillation (level 3 [lacking direct] evidence)
in patients with heart failure and without preexcitation
IV beta blocker (or IV nondihydropyridine calcium channel antagonist for patients with heart
failure with preserved ejection fraction) recommended but exercise caution in patients with
significant congestion, hypotension, or heart failure with reduced ejection fraction
(ACC/AHA Class I, Level B )
IV beta blocker or digoxin recommended in patients with left ventricular ejection fraction
(LVEF) < 40% or signs of heart failure (ESC Class I, Level B)
digoxin recommended for patients with heart failure with reduced ejection fraction
(ACC/AHA Class I, Level C), with dosing of 0.5 mg IV bolus (0.75-1.5 mg over 24 hours in
divided doses)
amiodarone may be considered if
contraindications to or failure of other medications (ACC/AHA Class IIa, Level B ),
with dosing of 300 mg IV over 1 hour, then 10-50 mg/hour over 24 hours (note that
amiodarone can convert atrial fibrillation to sinus rhythm)
hemodynamic instability or severely reduced LVEF (ESC Class IIb, Level B)
use of IV beta blocker, IV nondihydropyridine calcium channel blocker, and dronedarone not
recommended in patients with decompensated heart failure (ACC/AHA Class III, Level C)
in patients with preexcitation (accessory pathway)
IV procainamide and ibutilide recommended to restore sinus rhythm or slow rapid ventricular
response in hemodynamically stable patients (ACC/AHA Class I, Level C )
use of digoxin, adenosine, or nondihydropyridine calcium channel antagonists not
recommended (ACC/AHA Class III, Level B ; ESC Class III, Level C; CCS Strong
recommendation, Low-quality evidence )
guidelines differ regarding use of other medications in this setting
beta blockers not recommended (ESC Class III, Level C; CCS Strong recommendation,
Low-quality evidence )
amiodarone not recommended (ACC/AHA Class III, Level B)
in patients with acute coronary syndrome
IV beta blockers recommended to slow rapid ventricular response for patients without heart
failure, hemodynamic instability, or bronchospasm (ACC/AHA Class I, Level C)
IV amiodarone or digoxin may be considered to slow rapid ventricular response if patient has
severe left ventricular dysfunction and heart failure or hemodynamic instability (ACC/AHA
Class IIb, Level C)
nondihydropyridine calcium channel antagonists might be considered to slow rapid
ventricular response if patient has no significant heart failure or hemodynamic instability
(ACC/AHA Class IIb, Level C)
in patients with hyperthyroidism and thyrotoxicosis
beta blockers recommended unless contraindicated (ACC/AHA Class I, Level C)
nondihydropyridine calcium channel antagonists recommended if beta blockers cannot be
used (ACC/AHA Class I, Level C)
avoid amiodarone in patients with thyrotoxicosis due to potential to cause thyroid dysfunction
additional considerations
in patients with chronic obstructive pulmonary disease (COPD), nondihydropyridine calcium
antagonists recommended (ACC/AHA Class I, Level C)
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IV amiodarone
may be useful for rate control in critically ill patients without preexcitation (ACC/AHA
Class IIa, Level B)
may be considered when other measures fail to control heart rate or are contraindicated
(ACC/AHA Class IIa, Level C)
target heart rate
lenient rate control with target resting heart rate < 100-110 beats/minute reasonable for initial
treatment as long as the patient remains asymptomatic and left ventricular systolic function is
preserved (ACC/AHA Class IIb, Level B; CCS Strong recommendation, High-quality evidence;
ESC Class IIa, Level B)
lenient rate control (resting heart rate < 110 beats/minute) and strict rate control (resting heart rate <
80 beats/minute) in patients with permanent atrial fibrillation appear to have similar cardiovascular
outcomes (level 2 [mid-level] evidence)
target resting heart rate < 80 beats/minute is suggested for patients with symptomatic atrial
fibrillation (ESC Class IIa, Level B)
assess heart rate during exercise if exertional symptoms (ACC/AHA Class I, Level C; ESC Class I,
Level C; CCS Strong recommendation, Moderate-quality evidence)
strict rate control (with event monitor to assess safety) reasonable if symptoms persist despite
lenient rate control (ESC Class IIa, Level B)
strict rate control (heart rate < 80 beats/minute at rest or < 110 beats/minute during 6-minute walk)
is not beneficial compared to achieving resting heart rate < 110 beats/minute in patients with
persistent atrial fibrillation who have both (ACC/AHA Class III, Level B)
stable ventricular function (left ventricular ejection fraction > 40%)
no or acceptable symptoms related to the arrhythmia
drugs for long-term rate control
beta blocker or nondihydropyridine calcium channel blocker considered drug of choice for long-
term rate control in patients with paroxysmal, persistent, or permanent atrial fibrillation (ACC/AHA
Class I, Level B; ESC Class I, Level B; CCS Strong recommendation, Moderate-quality evidence)
metoprolol 25-200 mg orally twice daily
metoprolol succinate (extended release) 50-400 mg orally once daily
propranolol 10-40 mg orally twice or 4 times daily
diltiazem 120-360 mg orally once daily for extended release
verapamil 180-480 mg orally once daily for extended release
atenolol 25-100 mg orally once daily
carvedilol 3.125-25 mg orally twice daily
bisoprolol 2.5-10 mg orally once daily
dronedarone not recommended for patients with permanent atrial fibrillation (ACC/AHA Class III,
Level B)
digoxin
not recommended as monotherapy to control ventricular rate in patients with paroxysmal
atrial fibrillation (ESC Class III, Level B)
indicated for rate control in patients with heart failure, left ventricular dysfunction, or for
sedentary individuals (ACC/AHA Class I, Level C; ESC Class IIa, Level C; CCS Conditional
recommendation, Moderate-quality evidence)
combination therapy with any of digoxin, beta blocker, or nondihydropyridine calcium channel
blocker may be used to control heart rate at rest and with exercise (ACC/AHA Class IIa, Level B ;
CCS Conditional recommendation, Moderate-quality evidence)
drugs which appear effective for rate control include some beta blockers, verapamil, diltiazem, and
(if rate control during exercise is not needed) digoxin, but effect on exercise tolerance uncertain
(level 2 [mid-level] evidence); comparative efficacy data limited
oral amiodarone may be useful for ventricular rate control when other measures are unsuccessful or
contraindicated (ACC/AHA Class IIb, Level C; ESC Class IIa, Level C; CCS Conditional
recommendation, Low-quality evidence)
considerations for specific patient populations
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in patients with preexcitation, propafenone or amiodarone preferred (ESC Class I, Level C)

in patients with heart failure
for patients with heart failure with preserved ejection fraction and persistent or
permanent atrial fibrillation, beta blocker or nondihydropyridine calcium channel
blocker recommended (ACC/AHA Class I, Level B)
if no preexcitation, IV digoxin or amiodarone recommended to control heart rate
acutely (ACC/AHA Class I, Level B)
combination digoxin and beta blocker reasonable to control heart rate at rest and during
exercise (ACC/AHA Class IIa, Level B)
combination digoxin and nondihydropyridine calcium channel antagonist reasonable to
control heart rate at rest and during exercise for patients with heart failure with
preserved ejection fraction (ACC/AHA Class IIa, Level B)
consider amiodarone when heart rate not controlled by beta blocker,
nondihydropyridine calcium channel antagonist, or digoxin alone or in combination
(ACC/AHA Class IIa, Level B)
in patients with chronic obstructive pulmonary disease (COPD)
nondihydropyridine calcium channel blocker (diltiazem or verapamil) recommended to
control ventricular rate (ACC/AHA Class I, Level C)
non-beta-1 selective beta blockers are contraindicated in patients with bronchospasm
for postoperative atrial fibrillation
beta blocker recommended unless contraindicated (ACC/AHA Class I, Level A)
nondihydropyridine calcium channel blocker recommended if beta blocker ineffective
(ACC/AHA Class I, Level B)
consider atrioventricular (AV) nodal ablation in symptomatic patients with atrial fibrillation who have
failed medical therapy to control heart rate
should not be attempted unless previous trial of medical therapy has failed to adequately control
heart rate (ACC/AHA Class III, Level C; ESC Class III, Level C)
ablation of atrioventricular node and pacemaker implantation may be indicated when medical
therapy fails to control heart rate or produces intolerable side effects (ACC/AHA Class IIa, Level B;
ESC Class IIa, Level B; CCS Strong recommendation, Moderate-quality evidence)
see Rate control in atrial fibrillation for details
Cardioversion
spontaneous cardioversion (return to sinus rhythm) may occur, especially in first few days of atrial
fibrillation
direct current (DC) cardioversion
contraindicated if digitalis toxicity or hypokalemia (ACC/AHA Class III, Level C; ESC Class III,
Level C)
immediate DC cardioversion recommended for
acute hemodynamic instability to restore cardiac output (ESC Class I, Level B)
rapid ventricular rate unresponsive to medications and ongoing myocardial ischemia,
symptomatic hypotension, or heart failure (ACC/AHA Class I, Level C; ESC Class I, Level
C; CCS Strong recommendation, Low-quality evidence)
atrial fibrillation involving preexcitation with very rapid tachycardia or hemodynamic
instability (ACC/AHA Class I, Level B; ESC Class I, Level B; CCS Strong recommendation,
elective DC cardioversion may be useful to start rhythm control strategy for atrial fibrillation
(ACC/AHA Class IIa, Level B; ESC Class IIa, Level B; CCS Strong recommendation, Low-quality
evidence)
pretreatment with amiodarone, flecainide, ibutilide, propafenone, or sotalol before DC cardioversion
may increase success rate and prevent recurrent atrial fibrillation (ACC/AHA Class IIa, Level B;
ESC Class IIa, Level B; CCS Conditional recommendation, Low-quality evidence)
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electrical cardioversion may be done in emergency department with 150-200 joules (J) synchronized
biphasic waveform as initial energy setting (CCS Strong recommendation, Low-quality evidence)
initial energy of 200 J is more effective than initial energy of 100 J (in escalating protocol) for
achieving first-shock success (level 3 [lacking direct] evidence)
pharmacologic cardioversion
recommended drugs with established efficacy for atrial fibrillation ≤ 7 days duration
if no structural or ischemic heart disease
flecainide 200-300 mg orally, or 1.5-3 mg/kg IV over 10-20 minutes (ACC/AHA Class
I, Level A; ESC Class I, Level A)
dofetilide 500 mcg orally twice daily (reduce dose if creatinine clearance ≤ 60
mL/minute) (ACC/AHA Class I, Level A)
propafenone 600 mg orally, or 1.5-2 mg/kg IV over 10-20 minutes (ACC/AHA Class I,
Level A; ESC Class I, Level A)
ibutilide 1 mg IV over 10 minutes, repeat 1 mg if needed (ACC/AHA Class I, Level A;
ESC Class IIa, Level B)
vernakalant 3 mg/kg IV over 10 minutes, may repeat with 2 mg/kg after 15 minutes
(ESC Class I, Level A)
if structural or ischemic heart disease, amiodarone orally or IV (ACC/AHA Class IIa, Level
A; ESC Class I, Level A)
consider "pill-in-the-pocket" approach for single high-dose propafenone or flecainide outpatient
treatment in selected patients with paroxysmal atrial fibrillation if treatment proven safe in hospital
(ACC/AHA Class IIa, Level C; ESC Class IIa, Level B; CCS Strong recommendation, Moderate-
quality evidence)
flecainide 300 mg orally and propafenone 600 mg orally each appear effective for
cardioversion of recent-onset atrial fibrillation (level 3 [lacking direct] evidence)
comparative efficacy for acute conversion of atrial fibrillation
flecainide or ibutilide may be more effective than sotalol or procainamide (level 3 [lacking
direct] evidence)
IV flecainide associated with higher rate of sinus rhythm conversion at 12 hours compared to
propafenone and amiodarone in patients with acute atrial fibrillation (level 3 [lacking direct]
evidence)
oral propafenone may be more effective than quinidine or amiodarone, and oral flecainide
may be more effective than amiodarone for conversion of recent onset atrial fibrillation (level
3 [lacking direct] evidence)
vernakalant improves symptoms compared with amiodarone in patients with recent-onset
atrial fibrillation (level 1 [likely reliable] evidence)
thromboembolic prophylaxis in patients to be cardioverted
for atrial fibrillation of known duration < 48 hours
immediate cardioversion indicated without delay for anticoagulation if hemodynamic
instability (ACC/AHA Class I, Level C; ACCP Grade 2C)
starting anticoagulation (with low-molecular-weight heparin [LMWH] or IV unfractionated
heparin at full venous thromboembolism treatment doses) before cardioversion suggested if
possible (ACCP Grade 2C; ESC Class I, Level C)
duration of anticoagulation after cardioversion
in patients at risk for stroke, continue anticoagulation therapy long-term according to
recommendations, regardless of method of cardioversion or maintenance of sinus
rhythm (ESC Class I, Level B) (see also Thromboembolic prophylaxis in atrial
fibrillation)
in patients without stroke risk factors, continue anticoagulation for 4 weeks after
cardioversion (ESC Class I, Level B)
for atrial fibrillation of > 48 hours or of unknown duration
initial therapeutic anticoagulation recommended with either of
therapeutic anticoagulation (adjusted-dose vitamin K antagonist [VKA] therapy to
target INR range 2-3, LMWH at full venous thromboembolism treatment doses,
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dabigatran, rivaroxaban, or apixaban) for at least 3 weeks before cardioversion (ACCP

Grade 1B; ACC/AHA Class I, Level B; ESC Class I, Level B; CCS Strong
transesophageal echocardiography (TEE)-guided approach with initial anticoagulation
(LMWH or IV heparin) then cardioversion within 24 hours of confirmation of no
thrombus while maintaining therapeutic anticoagulation (ACCP Grade 1B; ACC/AHA
Class IIa, Level B; CCS Conditional recommendation, High-quality evidence)
postcardioversion anticoagulation recommended for ≥ 4 weeks (ACCP Grade 1B; ACC/AHA
Class I, Level B; ESC Class I, Level B; CCS Strong recommendation, Moderate-quality
evidence)
long-term anticoagulation recommended according to guidelines in patients at risk for stroke,
regardless of cardioversion method or maintenance of sinus rhythm (ESC Class I, Level B)
(see also Thromboembolic prophylaxis in atrial fibrillation)
TEE to guide timing of cardioversion as effective as conventional approach (warfarin for 3 weeks
before cardioversion) and associated with less hemorrhagic complications, but nonsignificant
increase in mortality (level 2 [mid-level] evidence)
see Cardioversion of atrial fibrillation for details
Rhythm control
rhythm control is used to restore or maintain sinus rhythm in patients with a history of atrial fibrillation
(AF)
overall efficacy and adverse events of antiarrhythmic drugs
most antiarrhythmic drugs appear effective for maintaining normal sinus rhythm (level 3 [lacking
direct] evidence) but also appear to increase risk for other arrhythmias (level 2 [mid-level]
evidence)
torsades de pointes is a potential adverse effect with dofetilide and sotalol
ventricular tachycardia or conversion to atrial flutter with 1:1 atrioventricular conduction and
rapid ventricular response is a potential adverse effect with flecainide and propafenone
antiarrhythmic drugs associated with increased mortality include sotalol, quinidine, and possibly
disopyramide (level 2 [mid-level] evidence)
antiarrhythmic drug selection
selection of antiarrhythmic medications depends on patient comorbidities ; doses include
disopyramide 100-200 mg orally once every 6 hours or 200-400 mg orally once every 12
hours for extended release
quinidine gluconate 324-648 mg orally every 8 hours
flecainide 50-150 mg orally once every 12 hours
propafenone 150-300 mg orally every 8 hours or 225-425 mg orally every 12 hours for
extended release
amiodarone
400-600 mg orally daily in divided doses for 2-4 weeks then 100-200 mg orally twice
daily thereafter
150 mg IV administered within 10 minutes then 1 mg/minute for 6 hours, then 0.5
mg/minute for 18 hours or switch to oral dosing and consider decreasing to 0.25
mg/minute after 24 hours
dofetilide 125-500 mcg orally every 12 hours
dronedarone 400 mg orally once every 12 hours
sotalol 80-160 mg orally once every 12 hours
treat precipitating or reversible causes of atrial fibrillation (if possible) before starting
antiarrhythmic drug therapy (ACC/AHA Class I, Level C)
most effective drugs in decreasing order of efficacy (based on indirect comparisons) are
amiodarone, flecainide, propafenone, and dofetilide (level 3 [lacking direct] evidence)
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beta blockers reduce recurrence rate after cardioversion of persistent atrial fibrillation (level 1
[likely reliable] evidence), and may be considered for rate and rhythm control after first episode of
atrial fibrillation (ESC Class IIa, Level C)
dronedarone (Multaq)
do not use in patients with permanent atrial fibrillation or for sole purpose of rate control
(CCS Strong recommendation, High-quality evidence)
not recommended in patients with severe heart failure (ACC/AHA Class III, Level B; ESC
Class III, Level B) or permanent atrial fibrillation (ESC Class III, Level B)
dronedarone may increase risk for death, stroke, and heart failure in patients with
permanent atrial fibrillation (level 2 [mid-level] evidence)
dronedarone associated with increased mortality in patients with heart failure (level 2
reasonable to use to decrease the need for hospitalization for cardiovascular events in patients
with paroxysmal atrial fibrillation or after conversion of persistent atrial fibrillation
(ACC/AHA Class IIa, Level B)
dronedarone may reduce risk for cardiovascular death, hospitalization, and
symptomatic atrial fibrillation recurrence in patients with nonpermanent atrial
amiodarone
amiodarone may reduce risk for atrial fibrillation recurrence compared to dronedarone,
sotalol, and class I antiarrhythmic drugs (level 3 [lacking direct] evidence)
amiodarone and sotalol each appear effective for maintaining sinus rhythm, but amiodarone
may maintain sinus rhythm longer than sotalol unless patients have ischemic heart disease
(level 3 [lacking direct] evidence)
amiodarone associated with thyroid, pulmonary, hepatic, neurologic, and ocular toxicity, and
has many drug interactions
intermittent antiarrhythmic drug therapy
suggested for selected patients without risk factors for complications (ACC/AHA Class IIa, Level
C; ESC Class IIa, Level B; CCS Strong recommendation, Moderate-quality evidence)
pill-in-the-pocket strategy appears slightly less effective but more cost effective than continuous
antiarrhythmic drugs or in-hospital treatment (level 3 [lacking direct] evidence)
flecainide 300 mg orally and propafenone 600 mg orally each appear effective for cardioversion of
recent-onset atrial fibrillation (level 3 [lacking direct] evidence)
ablation therapy
includes catheter ablation, or surgical ablation in patients having cardiac surgery for other reasons
recommended for patients with symptomatic paroxysmal atrial fibrillation after failure of
antiarrhythmic drugs (HRS/EHRA/ECAS Class I, Level A; ACC/AHA Class I, Level A; ESC Class
I, Level A; CCS Conditional recommendation, Moderate-quality evidence)
may be considered in patients with symptomatic persistent atrial fibrillation (HRS/EHRA/ECAS
Class IIa, Level B; ACC/AHA Class IIa, Level A; ESC Class IIa, Level B)
see Ablation therapy for atrial fibrillation for details
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Management of patients with atrial fibrillation. : Strategies for rhythm control in patients with
paroxysmal* and persistent AF. Drugs are listed alphabetically. * Catheter ablation is only
recommended as first-line therapy for patients with paroxysmal AF (AHA/ACC/HRSA Class IIa
recommendation). ‡ Depending on patient preference when performed in experienced centers. § Not
recommended with severe LVH (wall thickness > 1.5 cm).|| Should be used with caution in patients
at risk for torsades de pointes ventricular tachycardia. ¶ Should be combined with AV nodal
blocking agents. Abbreviations: AF, atrial fibrillation; AHA/ACC/HRSA, American Heart
Association/American College of Cardiology/Heart Rhythm Society; AV, atrioventricular; CAD,
coronary artery disease; HF, heart failure; LVH, left ventricular hypertrophy.
see Rhythm control in atrial fibrillation for details
Rate vs. rhythm control

rate control generally preferred for patients with minimal symptoms, except for patients with
reversible atrial fibrillation
heart failure thought to be caused by atrial fibrillation
new-onset atrial fibrillation
atrial flutter appropriate for ablation therapy
a clinical condition for whom a rhythm-control strategy would be more suitable based on clinical
judgement
recommendations:
rhythm control recommended in symptomatic patients with symptomatic atrial fibrillation despite
rate-control strategy (ESC Class I, Level B; CCS Strong recommendation, High-quality evidence)
antiarrhythmic drug therapy not recommended in patients with any (ESC Class III, Level C)
prolonged QT interval (> 0.5 seconds)
advanced sinus node disease or atrioventricular node dysfunction unless they have
functioning permanent pacemaker
rate control should be continued throughout rhythm-control approach (ESC Class I, Level A)
comparative evidence for rate- and rhythm-control strategies
pharmacologic rate- and rhythm-control strategies appear similarly effective regarding mortality and
stroke in older adults with mild atrial fibrillation (level 2 [mid-level] evidence)
rate-control strategy is at least as effective as rhythm-control strategy for preventing stroke and
death in atrial fibrillation (level 1 [likely reliable] evidence)
rhythm-control strategy starting with electrical cardioversion may improve quality of life but may
increase risk for stroke compared to rate-control strategy (level 2 [mid-level] evidence)
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pharmacologic rhythm-control strategy associated with more hospitalizations and adverse events
without apparent benefit compared to rate-control strategy in atrial fibrillation (level 2 [mid-level]
evidence)
rhythm-control and rate-control approaches associated with similar rates of stroke and mortality in
patients with atrial fibrillation and heart failure (level 2 [mid-level] evidence)
see rate control vs. rhythm control for additional information
Thromboembolic prophylaxis
thromboembolism is a major complication of atrial fibrillation which may result in stroke or death
risk of thromboembolism can be significantly reduced by appropriate use of antithrombotic therapy
consider risk of thromboembolism and bleeding when selecting type of thromboembolic prophylaxis
recommendations apply to patients with permanent, persistent, or paroxysmal atrial fibrillation, atrial
flutter, and patients managed with rhythm-control strategy
for stroke risk stratification use CHADS2 score (CCS Strong recommendation, High-quality evidence) or
CHA2DS2-VASc score (ESC Class I, Level A; ACC/AHA Class I, Level B)
CHADS2 score is 1 point for each of heart failure, hypertension, age ≥ 75 years, diabetes mellitus; 2
points for prior stroke or transient ischemic attack
CHA2DS2-VASc score is 1 point each for female sex, age 65-74 years, heart failure or left
ventricular dysfunction, hypertension, diabetes mellitus, history of myocardial infarction, or
peripheral artery disease; 2 points for age ≥ 75 years; 2 points for history of stroke, transient
ischemic attack, or thromboembolism
CHA2DS2-VASc score 0 associated with lower risk of thromboembolism than CHADS2 score 0 in
patients with atrial fibrillation (level 2 [mid-level] evidence)
R2CHADS2 score predicts risk of stroke or systemic embolism in patients with nonvalvular atrial
fibrillation (level 1 [likely reliable] evidence); comparative accuracy is unclear but R2CHADS2
score of 0 may have lower risk than CHADS2 score of 0 (level 2 [mid-level] evidence)
for risk of bleeding
HAS-BLED score predicts risk of bleeding in patients with atrial fibrillation taking warfarin (level 1
[likely reliable] evidence)
consider using HAS-BLED score to assess bleeding risk in patients with nonvalvular atrial
fibrillation (ESC Class IIa, Level A)
consider oral anticoagulant therapy based on assessment of risk of bleeding complications and
patient preferences (ESC Class IIa, Level A)
guidelines consistently agree that most patients with atrial fibrillation or atrial flutter should receive
antithrombotic therapy (ACC/AHA Class I, Level A; ESC Class I, Level A; CCS Strong recommendation,
High-quality evidence)
oral anticoagulation consistently recommended for patients with high risk for stroke based on
(ACC/AHA Class I, Level A; ACCP Grade 1A compared to no therapy; ACCP Grade 1B compared
to antiplatelet therapy; ESC Class I, Level A; CCS Strong recommendation, High-quality evidence)
history of cardioembolic stroke or transient ischemic attack (TIA)
CHADS2 score ≥ 2
mitral stenosis
if intermediate risk for stroke (for example, CHADS2 score = 1), 3 of 4 guidelines recommend oral
anticoagulation over antiplatelet therapy or no therapy (ESC Class IIa, Level A; CCS Strong
recommendation, High-quality evidence; ACCP Grade 1B compared to no therapy; ACCP Grade
2B compared to antiplatelet therapy)
if low risk for stroke based on certain risk factors (female, age 65-74 years, history of vascular
disease) guidelines vary regarding choice of oral anticoagulant therapy, antiplatelet therapy, or no
therapy
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if very low risk for stroke (for example, CHA2DS2-VASc score = 0 or lone atrial fibrillation and no
risk factors), omitting antithrombotic therapy recommended over antithrombotic therapy
(ACC/AHA Class IIa, Level B; ACCP Grade 2B; ESC Class I, Level B; CCS Conditional
American, European, and Canadian guidelines recommend direct oral anticoagulants over warfarin
(ACCP Grade 2B; ESC Class I, Level A; CCS Strong recommendation, High-quality evidence); options
include
dabigatran (ACCP Grade 2B)
rivaroxaban
apixaban
warfarin recommended over direct oral anticoagulants for patients with any of the following: (ACC/AHA
Class I, Level B; CCS Strong recommendation, Moderate-quality evidence)
mechanical prosthetic valve (ACC/AHA Class I, Level B)
rheumatic mitral stenosis
estimated glomerular filtration rate of 15-30 mL/minute/1.73 m2
efficacy and comparative efficacy for oral anticoagulant therapy
warfarin with target INR 2-3 reduces risk of stroke in patients with or without history of stroke or
TIA (level 1 [likely reliable] evidence) and appears more effective than aspirin (level 2 [mid-level]
evidence) or aspirin plus clopidogrel (level 2 [mid-level] evidence)
warfarin has higher rate of major bleeding compared to placebo, but may not have higher risk for
major bleeding than antiplatelet therapy (level 2 [mid-level] evidence)
apixaban reduces risk of stroke without increased risk of major bleeding or intracranial hemorrhage
compared to aspirin in patients with atrial fibrillation for whom vitamin K antagonist (VKA) is
unsuitable (level 1 [likely reliable] evidence)
compared to warfarin
direct oral anticoagulants (DOACs) reduce cardioembolic events (all-cause stroke or systemic
embolism) and intracranial bleeding (level 1 [likely reliable] evidence) and may reduce
mortality (level 2 [mid-level] evidence) compared to warfarin in patients with atrial
fibrillation
dabigatran (Pradaxa) 150 mg twice daily further reduces risk for stroke with similar bleeding
risk but slightly increases gastrointestinal bleeding risk (level 1 [likely reliable] evidence) and
might reduce risk of mortality (level 2 [mid-level] evidence) but might increase risk of
myocardial infarction (level 2 [mid-level] evidence) and nonbleeding upper gastrointestinal
adverse events (level 2 [mid-level] evidence); lower doses (110 mg twice daily in Europe, 75
mg twice daily in United States) used if moderate renal impairment or higher bleeding risk
rivaroxaban (Xarelto) 20 mg once daily (15 mg if creatinine clearance 30-49 mL/minute) may
be as effective for preventing stroke or systemic embolism in patients with nonvalvular atrial
apixaban (Eliquis) 5 mg twice daily associated with reduced risk of stroke and major bleeding
and might reduce risk of mortality (level 2 [mid-level] evidence)
if patient is unsuitable for or chooses not to take oral anticoagulant (for reasons other than concerns about
major bleeding) - consider aspirin 75-325 mg/day or combination of aspirin 75-100 mg/day plus
clopidogrel 75 mg/day
combination therapy with aspirin and clopidogrel suggested rather than aspirin alone if low bleeding
risk (ACC/AHA Class IIb, Level B; ESC Class IIa, Level B; ACCP Grade 2B for intermediate-risk
patients; ACCP Grade 1B for high-risk patients)
aspirin might reduce risk of stroke and major vascular events in patients not receiving anticoagulant
therapy (level 2 [mid-level] evidence), but evidence limited and inconsistent
addition of clopidogrel to aspirin associated with reduced risk for major vascular events and
increased risk for major hemorrhage in patients with atrial fibrillation for whom VKA therapy is
unsuitable (level 2 [mid-level] evidence)
addition of aspirin to anticoagulant may not reduce stroke but may increase bleeding in high-risk patients
with atrial fibrillation (level 2 [mid-level] evidence)
see Thromboembolic prophylaxis in atrial fibrillation for details
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see Left atrial appendage closure (below) for additional information about thromboembolic prophylaxis
Activity
Exercise
after taking pill-in-pocket flecainide or propafenone, avoidance of physical activity suggested as long as
atrial fibrillation persists and until two half-lives of antiarrhythmic drug therapy elapsed (ESC Class IIa,
Level C)(2)
exercise-based interventions might improve exercise capacity but not physical or mental health-
related quality of life in patients with atrial fibrillation (level 2 [mid-level] evidence)
based on Cochrane review with limited evidence
systematic review of 6 randomized trials comparing exercise-based interventions vs. no exercise in
421 adults with atrial fibrillation
exercise-based interventions were aerobic exercise and resistance training in 4 trials,
traditional Chinese Qi-gong in 1 trial, and inspiratory muscle training in 1 trial
exercises were supervised or unsupervised and varied in duration (8-16 weeks), frequency (2
times daily to 2-3 sessions per week), and session length (15-90 minutes per session)
exercise capacity measured using 6-minute walk test in 3 trials, peak oxygen uptake (VO2 peak) in
2 trials, and cycle ergometer test in 1 trial
exercise-based intervention associated with improvement in exercise capacity at 8 weeks to 4
months in analysis of 6 trials with 359 patients, results limited by significant heterogeneity
no significant differences in physical or mental health-related quality of life at 20 weeks to 6 months
in analysis of 2 trials with 224 patients
total of 2 deaths and 8 serious adverse events overall with no significant differences between groups
Reference - Cochrane Database Syst Rev 2017 Feb 9;(2):CD011197
addition of weight loss intervention to intensive risk factor management may reduce frequency,
duration, and severity of atrial fibrillation episodes (level 2 [mid-level] evidence)
based on randomized trial with high dropout rate and without attention control
150 patients aged 21-75 years with symptomatic paroxysmal or persistent atrial fibrillation and with
body mass index ≥ 27 kg/m2 were randomized to 1 of 2 interventions
weight loss intervention with low-calorie diet (800-1,200 kcal/day) for 8 weeks followed by
gradual replacement with low glycemic index diet plus low-intensity exercise (walking or
cycling 20-45 minutes 3 times weekly) plus clinic visits, e-mail, and telephone support
written and verbal nutrition and exercise advice at baseline (control)
all patients received intensive management of cardiometabolic risk factors including hypertension,
hyperlipidemia, glucose intolerance or diabetes, sleep apnea, and alcohol and tobacco use
atrial fibrillation symptom burden was assessed by Atrial Fibrillation Severity Scale (range 3.25-30)
with lower scores indicating less disease burden (mean 21.3 at baseline)
median follow-up 15 months
46% did not complete trial and were excluded from analyses
comparing weight loss intervention vs. control
mean reduction in atrial fibrillation episodes 2.5 episodes/week vs. 0 episodes/week (p =
0.01)
mean change in cumulative duration of atrial fibrillation episodes -692 minutes/week vs. +
419 minutes/week (p = 0.002)
weight loss intervention associated with significantly greater improvement in symptom severity
scores
Reference - JAMA 2013 Nov 20;310(19):2050
Sexual activity
45/105
American Heart Association (AHA) recommendations for sexual activity in patients with atrial fibrillation
sexual activity reasonable for patients with atrial fibrillation and well-controlled ventricular rate
(AHA Class IIa, Level C)
defer sexual activity in patients with atrial fibrillation and poorly controlled ventricular rate until
condition optimally managed (AHA Class III, Level C)
do not withhold cardiovascular drugs that may improve symptoms and survival because of concerns
about potential impact on sexual function (AHA Class III, Level C)
Reference - Circulation 2012 Feb 28;125(8):1058 full-text
Driving
American College of Cardiology/American Heart Association (ACC/AHA) guidelines on atrial fibrillation

do not explicitly mention driving(1)
European Society of Cardiology (ESC) guidelines on atrial fibrillation do not explicitly mention driving
except for recommendation for catheter ablation for patients with high-risk professions (such as public
transport drivers) and overt but asymptomatic accessory pathway conduction on surface electrocardiogram
(ECG) (ESC Class I, Level B)(2)
no driving restrictions recommended for patients with paroxysmal, persistent, or permanent atrial
fibrillation ( Can J Cardiol 2004 Nov;20(13):1314)
Surgery and procedures
Ablation therapy
catheter ablation
potential indications
symptomatic paroxysmal atrial fibrillation in patients who failed antiarrhythmic drug and
have no structural heart disease (HRS/EHRA/ECAS Class I, Level A; ACC/AHA Class I,
Level A; ESC Class I, Level A; CCS Strong recommendation, Moderate-quality evidence)
symptomatic paroxysmal atrial fibrillation in patients who failed antiarrhythmic drug and
have significant left atrial dilatation or left ventricular dysfunction (ACC/AHA Class IIb,
Level A; CCS Conditional recommendation, Moderate-quality evidence)
symptomatic persistent atrial fibrillation in patients who failed antiarrhythmic drugs
(HRS/EHRA/ECAS Class IIa, Level B; ACC/AHA Class IIa, Level A; ESC Class IIa, Level
B; CCS Strong recommendation, Moderate-quality evidence)
symptomatic longstanding persistent atrial fibrillation in patients who failed antiarrhythmic
drugs (HRS/EHRA/ECAS Class IIb, Level B; ESC Class IIa, Level C; CCS Strong
symptomatic paroxysmal atrial fibrillation prior to trial of antiarrhythmic drug
(HRS/EHRA/ECAS Class IIa, Level B; ESC Class IIb, Level B; CCS Conditional
symptomatic persistent atrial fibrillation prior to trial of antiarrhythmic drug
(HRS/EHRA/ECAS Class IIb, Level C)
efficacy compared to drug therapy
catheter ablation may reduce recurrence of atrial fibrillation compared with medical treatment
in patients with paroxysmal or persistent atrial fibrillation (level 2 [mid-level] evidence)
radiofrequency catheter ablation may reduce symptomatic atrial fibrillation compared to
antiarrhythmic drug therapy in patients with paroxysmal atrial fibrillation without previous
treatment with antiarrhythmic drugs (level 2 [mid-level] evidence)
in patients with heart failure
radiofrequency catheter ablation might improve exercise performance and quality of
life compared to rate control therapy in adults with persistent atrial fibrillation and heart
failure (level 2 [mid-level] evidence)
46/105
pulmonary vein isolation associated with improved quality of life compared to

atrioventricular node ablation with biventricular pacing in patients with drug-refractory
atrial fibrillation and heart failure (level 2 [mid-level] evidence)
medications after ablation
antithrombotic therapy recommendations similar to recommendations after cardioversion,
except continuing anticoagulation for at least 2-3 months after ablation recommended
corticosteroids for 3 days after radiofrequency catheter ablation may decrease immediate and
long-term atrial fibrillation recurrence (level 2 [mid-level] evidence)
antiarrhythmic drugs may reduce atrial fibrillation-related events while on therapy (up to 90
days) but benefit may not persist after therapy discontinued (up to 1 year) (level 2 [mid-level]
evidence)
surgical ablation
in patients having cardiac surgery for other reasons, consider concomitant surgical ablation (such as
maze procedure) for symptomatic atrial fibrillation (HRS/EHRA/ECAS Class IIa, Level C; ESC
Class IIa, Level A; CCS Strong recommendation, Moderate-quality evidence) and possibly for
asymptomatic atrial fibrillation (ESC Class IIb, Level C)
in patients not having concomitant cardiac surgery, minimally invasive surgical ablation may be
done for symptomatic atrial fibrillation after failure of catheter ablation (ESC Class IIa, Level B;
HRS/EHRA/ECAS Class IIb, Level C) or in patients who prefer a surgical approach
(HRS/EHRA/ECAS Class IIb, Level C)
surgical ablation appears to increase freedom from atrial fibrillation, but does not appear to affect
mortality (level 2 [mid-level] evidence)
surgical ablation may be as effective as radiofrequency-microwave or cryoablation for conversion to
sinus rhythm in patients with atrial fibrillation (level 3 [lacking direct] evidence)
surgical ablation may be more effective than catheter ablation for reducing left atrial arrhythmia
(level 3 [lacking direct] evidence) but associated with more procedural adverse events (level 2 [mid-
level] evidence) in patients with atrial fibrillation refractory to antiarrhythmic drugs
atrioventricular (AV) node ablation
should not be attempted unless previous trial of medical therapy has failed to adequately control
heart rate (ACC/AHA Class III, Level C; ESC Class III, Level C)
may be considered for rate control if drugs are ineffective or not tolerated, recognizing that patient
will be pacemaker dependent (ACC/AHA Class IIa, Level B; ESC Class IIa, Level B; CCS Strong
in patients with heart failure and indications for cardiac resynchronization therapy
consider AV node ablation for patients with permanent atrial fibrillation (ESC Class IIa, Level
B)
atrioventricular junction ablation may improve multiple outcomes (survival, hospitalization,
surrogate outcomes) compared to pharmacologic rate control (level 2 [mid-level] evidence)
ablation of accessory pathway in patients with Wolff-Parkinson-White syndrome

catheter ablation of accessory pathway recommended in symptomatic patients with evidence of
ventricular preexcitation during atrial fibrillation, especially if syncope or pathway with short
refractory period (ACC/AHA Class I, Level B; ESC Class I, Level A; CCS Strong recommendation,
catheter ablation recommended for patients with asymptomatic overt accessory pathway conduction
on surface electrocardiogram (ECG) if high-risk profession such as pilot or public transport driver
(ESC Class I, Level B)
see Ablation therapy for atrial fibrillation for details
Implantable atrial defibrillator
atrial defibrillator reported to terminate episodes of atrial fibrillation via cardioversion in some
severe cases (level 3 [lacking direct] evidence)
47/105
based on 2 case series

105 patients with recurrent, symptomatic, drug-refractory atrial fibrillation had implantation of atrial
defibrillator
412 outpatient episodes recorded of which 388 were treated with total 897 shocks
defibrillator restored sinus rhythm via cardioversion in 95% of the treated episodes, but 26%
of the episodes had recurrence of atrial fibrillation within minutes (patients reported moderate
discomfort with shocks)
device removed in 14%, most commonly due to inadequate control of atrial fibrillation
Reference - Circulation 2000 Sep 19;102(12):1407 full-text
implantable cardioverter (Atrioverter) described in 51 patients with recurrent atrial fibrillation who
had not responded to antiarrhythmic drugs
procedure requires permanent leads placed in 3 parts of right heart but does not require
thoracotomy
51 patients received total 670 shocks for 227 spontaneous episodes of atrial fibrillation over
mean 8.6 months with device terminating 96% episodes
complications of 2 subclavian venous thromboses and 1 cardiac tamponade
clinical advantages not yet shown
Reference - Circulation 1998 Oct 20;98(16):1651 full-text
review of internal atrial defibrillation can be found in J Interv Card Electrophysiol 2005 Aug;13 Suppl
1:61
Pacing
complete pacing may reduce risk of permanent atrial fibrillation but does not appear to reduce all-
cause mortality compared to standard dual-chamber pacing in patients with bradycardia and prior
atrial tachyarrhythmias (level 2 [mid-level] evidence)
based on randomized trial without blinding of outcome assessors
1,166 patients (mean age 74 years) with bradycardia and prior atrial tachyarrhythmia (including
atrial fibrillation) who had recent implantation of dual-chamber pacemaker were randomized to 1 of
3 pacing modalities and followed for 2 years
atrial preventive and antitachycardia pacing plus managed ventricular pacing (complete
pacing)
managed ventricular pacing
standard dual-chamber pacing (DDD)
indications for permanent pacemaker implantation included sick sinus syndrome in 83%,
atrioventricular block in 10%, and other indications in 7%
all patients had managed ventricular pacing for 1 month before randomization to stabilize and
ensure not dependent on ventricular pacing
no patients had history of permanent atrial fibrillation or cardiac surgery
84% completed follow-up, all patients included in analyses
permanent atrial fibrillation in
3.4% with complete pacing
p = 0.004 vs. standard pacing (NNT 20)
p = 0.03 vs. managed ventricular pacing (NNT 30)
6.8% with managed ventricular pacing (not significant vs. standard pacing)
8.6% with standard pacing
no significant differences in all-cause mortality or cardiovascular-related hospitalization among
groups
Reference - MINERVA trial ( Eur Heart J 2014 Sep 14;35(35):2352 full-text)
biventricular pacing improves cardiac parameters (level 3 [lacking direct] evidence) but not clinical
outcomes (level 2 [mid-level] evidence) compared to right ventricular pacing in patients with
refractory atrial fibrillation treated with atrioventricular nodal ablation
based on randomized trial with allocation concealment not stated
48/105
127 patients with refractory atrial fibrillation had atrioventricular node ablation then randomized in
2:2:1 ratio to biventricular pacing with closed loop stimulation vs. biventricular pacing with
accelerometer vs. right ventricular pacing
both groups had similar improvement in 6-minute walk test and quality of life-scores at 6 months
compared to baseline
compared to right ventricular pacing, biventricular pacing associated with
smaller left atrial (p = 0.002) and left ventricular end-systolic volumes (p < 0.001)
smaller left ventricular mass (p = 0.007)
improved ejection fraction (+3.3 vs. -2.6, p = 0.005)
decrease in intraventricular conduction delay (p = 0.023)
Reference - Am Heart J 2010 Feb;159(2):264
after atrioventricular nodal ablation, addition of para-Hisian pacing (dual-chamber pacemaker

with screw-in lead close to His bundle) to right ventricular apical pacing associated with improved
New York Heart Association (NYHA) functional class and 6-minute walk distance (level 2 [mid-
level] evidence)
based on small randomized crossover trial
16 patients implanted with dual-chamber pacemaker after atrioventricular nodal ablation
randomized to right ventricular apical pacing vs. para-Hisian pacing for 6 months each
compared to right ventricular apical pacing, para-Hisian pacing associated with greater
improvements in
NYHA functional class (p < 0.05)
6-minute walk test (p < 0.05)
degree of mitral and tricuspid regurgitation (p < 0.05)
Reference - J Am Coll Cardiol 2006 May 16;47(10):1938 full-text
American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS)

guideline on device-based therapy of cardiac rhythm abnormalities can be found in Circulation 2008 May
27;117(21):e350 full-text
review of pacemaker therapy can be found in Am Fam Physician 2005 Apr 15;71(8):1563 full-text
review of cardiac pacing can be found in Lancet 2004 Nov 6-12;364(9446):1701
Left atrial appendage closure
description of left atrial appendage closure (LAAC)

in patients with atrial fibrillation, left atrial appendage is main site of thrombus formation which
causes ischemic stroke
occlusion of left atrial appendage may decrease risk of stroke
surgical approaches include direct suture, excision and suture, stapling, and clipping
percutaneous approaches may be endocardial, epicardial, or hybrid endocardial-epicardial
techniques
self-expanding devices transseptally placed in left atrial appendage include WATCHMAN system
and Amplatzer Cardiac Plug
complications include
pericardial effusion
air embolism
thrombus formation during device implantation
early or late device embolization
leak
Reference - Cardiol Clin 2016 May;34(2):329
recommendations from professional associations (for patients with atrial fibrillation)
consider LAA occlusion in patients at risk for stroke who have contraindications for long-term
anticoagulation treatment, such as previous life-threatening bleeding event without reversible cause
(ESC Class IIb, Level A)
49/105
unclear if closure of left atrial appendage with WATCHMAN device useful in patients with atrial
fibrillation and ischemic stroke or transient ischemic attack (AHA/ASA Class IIb, Level B)
consider left atrial appendage closure (excision or ablation) as part of surgical ablation for atrial
fibrillation in no increased risk in patients having other surgeries, including any (CCS Conditional
mitral valve surgery
aortic valve surgery
coronary artery bypass graft (CABG) surgery
use of nonapproved left atrial appendage closure devices is not suggested for patients with a
CHADS2 score ≥ 2 who are unable to receive antithrombotic therapy (CCS Conditional
surgical excision or occlusion of left atrial appendage may be considered in patients having open
heart surgery (ACC/AHA Class IIb, Level C; ESC Class IIb, Level B) or thorascopic atrial
fibrillation surgery (ESC Class IIb, Level B)
National Institute for Health and Clinical Excellence (NICE) recommendations
if anticoagulation is contraindicated or not tolerated, consider left atrial appendage occlusion
and discuss benefits and risks with patient
do not offer left atrial appendage occlusion instead of anticoagulation therapy unless
anticoagulation contraindicated or not tolerated
References
American College of Cardiology/American Heart Association (ACC/AHA) guideline on the
management of patients with atrial fibrillation ( J Am Coll Cardiol 2014 Dec 2;64(21):e1)
American Heart Association/American Stroke Association (AHA/ASA) guidelines for
prevention of stroke in patients with stroke or transient ischemic attack ( Stroke 2014
Jul;45(7):2160 full-text), correction can be found in Stroke 2015 Feb;46(2):e54
Canadian Cardiovascular Society (CCS) 2014 focused update of the guidelines for the
management of atrial fibrillation ( Can J Cardiol 2014 Oct;30(10):1114)
CCS 2016 focused update on the guidelines for the management of atrial fibrillation ( Can J
Cardiol 2016 Oct;32(10):1170)
European Society of Cardiology (ESC) guideline for the management of atrial fibrillation (
Europace 2016 Nov;18(11):1609 )
National Institute for Health and Clinical Excellence (NICE) guidance for management of
atrial fibrillation ( BMJ 2014 Jun 19;348:g3655)
Centers for Medicare and Medicaid Services (CMS) decision summary for percutaneous LAAC therapy -
criteria for funding coverage for percutaneous LAAC in patients with nonvalvular atrial fibrillation
LAACs are covered when the device has received FDA Premarket Approval (PMA) for that
device’s FDA-approved indication and all of the following are met
patient has met all of
CHADS2 score ≥ 2 or CHA2DS2-VASc score ≥ 3
formal shared decision-making interaction with an independent noninterventional
physician using an evidence-based decision tool on oral anticoagulation prior to LAAC
and the shared decision-making interaction must be documented in the medical record
suitability for short-term warfarin but deemed unable to take long-term oral
anticoagulation following the conclusion of shared decision making
LAAC is only covered as a second-line therapy to oral anticoagulants
patient (preoperatively and postoperatively) is under the care of a
multidisciplinary team (MDT) of medical professionals
procedure must occur in a hospital with an established structural heart disease
(SHD) and/or electrophysiology (EP) program
procedure must be performed by an interventional cardiologist(s),
electrophysiologist(s), or cardiovascular surgeon(s) that meet the following criteria
has received training prescribed by the manufacturer on the safe and effective use
of the device prior to performing LAAC
50/105
has performed ≥ 25 interventional cardiac procedures that involve transseptal

puncture through an intact septum
continues to perform ≥ 25 interventional cardiac procedures that involve
transseptal puncture through an intact septum, of which at least 12 are LAAC,
over a 12-year period
patient is enrolled in, and the MDT and hospital must participate in a prospective, national,
audited registry that consecutively enrolls LAAC patients and tracks the following annual
outcomes for each patient for a period of ≥ 4 years from the time of LAAC
operator-specific complications
device-specific complications including device thrombosis
stroke, adjudicated, by type
transient ischemic attack (TIA)
systemic embolism
death
major bleeding, by site and severity
LAAC is covered for nonvalvular atrial fibrillation patients not included in above criteria when
performed within an FDA-approved randomized controlled trial (RCT) if such trials follow
standards of scientific integrity and relevance to the Medicare population (see reference below for
details) and as a fully-described written part of its protocol, the RCT must critically answer, in
comparison to optimal medical therapy, the following
As a primary endpoint, what is the true incidence of ischemic stroke and systemic embolism?
As a secondary endpoint, what is cardiovascular mortality and all-cause mortality?
LAAC is not covered for the treatment of nonvalvular atrial fibrillation when not furnished under
Coverage with Evidence Development (CED) according to the above criteria
Reference - Final Decision Memorandum for Percutaneous Left Atrial Appendage Closure (LAAC)
Therapy (CMS Decision Memo 2016 Feb 8:CAG-00445N)
LAAC device complications
reported rate of procedural complications in 3,822 consecutive patients who had LAAC with
Watchman device after FDA approval
procedure success in 3,653 (96%)
mortality 0.1% (due to pericardial effusion or pulmonary embolism)
device embolization in 0.24%
stroke in 0.08%
pericardial effusion requiring intervention in 1.02%
Reference - J Am Coll Cardiol 2017 Jan 24;69(3):253 full-text
device-related thrombus detected in 3.7% of patients with Watchman device
based on meta-analysis of patient-level data from randomized trials and registries
1,876 patients who received Watchman device in PROTECT-AF trial, PREVAIL trial, or their
continued access registries were evaluated
all patients had transesophageal echocardiography to assess device-related thrombus at
45 days and 12 months
mean CHA2DS2-VASc score 4, and mean HAS-BLED score 2
1,739 patients (mean age 73 years, 66% male) with successful implantation of LAAC device
were analyzed
3.7% had device-related thrombus
increased risk of device-related thrombus associated with
history of transient ischemic attack or stroke (adjusted odds ratio [OR] 2.31, 95% CI
1.26-4.25)
permanent atrial fibrillation (adjusted OR 2.24, 95% CI 1.19-4.2)
vascular disease (adjusted OR 2.06, 95% CI 1.08-3.91)
left atrial appendage diameter (adjusted OR 1.06, 95% CI 1.01-1.12 per 1 mm increase)
decreased risk of device-related thrombus associated with higher left ventricular ejection
fraction (adjusted OR 0.96, 95% CI 0.94-0.99 per 1% increase)
51/105
events per 100 person-years comparing device-related thrombus vs. no device-related

thrombus
ischemic stroke or systemic embolism 6.28 vs. 1.65 (adjusted rate ratio [RR] 3.22, 95%
CI 1.9-5.45)
ischemic stroke 5.1 vs. 1.65 (adjusted RR 2.6, 95% CI 1.46-4.64)
hemorrhagic stroke 1.18 vs. 0.13 (adjusted RR 7.98, 95% CI 2.12-29.94)
major bleeding 7.85 vs. 4.11 (adjusted RR 1.78, 95% CI 1.13-2.81)
Reference - Circulation 2018 May 11 early online
incidence of major adverse events in retrospective cohort study of 469 patients (mean age 74 years,
61% male) with atrial fibrillation who had LAAC using either Watchman nitinol cage device (58%)
or Amplatzer nitinol plug device (42%) prospectively followed for mean 13 months
death in 6.9%
ischemic stroke in 4%
transient ischemic attack in 0.4%
major hemorrhage in 3.8%
thrombus on device in 7.2% of 339 patients with left atrial appendage imaging with TEE or
computed tomography
Reference - J Am Coll Cardiol 2018 Apr 10;71(14):1528
left atrial appendage closure (LACC) device-related thrombus (DRT) on imaging associated with
increased risk of stroke or systemic embolism - see prognosis section of atrial fibrillation for details
review of left atrial appendage and closure can be found in Circ Cardiovasc Interv 2016 May;9(5)
left atrial appendage (LAA) closure (Watchman device) compared to warfarin

percutaneous LAA closure might reduce mortality and might have similar stroke rates
compared to warfarin in patients with atrial fibrillation and CHADS2 risk score ≥ 1 (level 2
based on randomized trial without blinding and limited precision for effect estimates
707 patients > 18 years old with nonvalvular atrial fibrillation and specific risk factors for
stroke were randomized to percutaneous closure of LAA (WATCHMAN device) and warfarin
discontinuation 45 days after device implantation vs. continued warfarin therapy with target
INR 2-3
all patients had ≥ 1 specific risk factor of age ≥ 75 years, previous stroke or transient ischemic
attack, heart failure, diabetes, or hypertension; this is also defined as CHADS2 risk score ≥ 1
patients who had device implantation received warfarin plus aspirin 81 mg/day for 45 days
after implantation, discontinuation of warfarin if complete closure of left atrial appendage
confirmed, and then clopidogrel 75 mg/day plus aspirin 81-325 mg/day for 6 months, then
continued aspirin indefinitely
device successfully implanted in 408 of 463 (88%) patients assigned to left atrial appendage
closure, and 355 patients (77% of those randomized to closure) were able to discontinue
warfarin
mean follow-up 18 months, aggregate follow-up 1,065 patient-years
observed rate (events per 100 patient-years) comparing percutaneous LAA closure vs.
continued warfarin
all-cause mortality 3 vs. 4.8 (not significant)
cardiovascular or unexplained death 0.7 vs. 2.7 (p < 0.05)
ischemic stroke 2.2 vs. 1.6 (not significant)
any stroke 2.3 vs. 3.2 (not significant)
hemorrhagic stroke 0.1 vs. 1.6 (p < 0.05)
systemic embolism 0.3 vs. 0 (no p value reported)
adverse events related to excessive bleeding (including intracranial or gastrointestinal
bleeding) or procedure-related complications (including serious pericardial effusion,
device embolization, procedure-related stroke) (also called primary safety events) 7.4
vs. 4.4 (p < 0.05)
52/105
all-cause mortality 4.5% with device vs. 7.4% with continued warfarin (not significant)
adverse events comparing percutaneous LAA closure vs. continued warfarin
pericardial effusion needing percutaneous or surgical drainage in 4.8% vs. 0% (NNH
20)
major bleeding (needing at least 2 units of packed red blood cells or surgery) in 3.5%
vs. 4.1%
procedure-related ischemic stroke in 1.1% vs. 0%
device embolization in 0.6% vs. 0%
hemorrhagic stroke in 0.2% vs. 2.5% (NNT 44)
esophageal tear in 0.2% (1 patient) vs. 0%
procedure-related arrhythmia in 0.2% (1 patient) vs. 0%
7-day procedural complication rate 8.7%
Reference - PROTECT AF trial (Lancet 2009 Aug 15;374(9689):534), correction can be
found in Lancet 2009 Nov 7;374(9701):1596, editorial can be found in Lancet 2009 Aug
15;374(9689):504, commentary can be found in Lancet 2009 Nov 21;374(9703):1742
consistent findings at 2 years in PROTECT AF trial
82% completed mean 2.3-year follow-up but all patients were included in analyses
control
all-cause mortality 3.2 vs. 4.5 (not significant)
cardiovascular or unexplained death 1 vs. 2.8 (p < 0.05)
any stroke 2 vs. 2.7 (not significant)
primary safety events 5.5 vs. 3.6 (not significant)
all-cause mortality 7.3% with device vs. 10.7% with continued warfarin (not
significant)
Reference - Circulation 2013 Feb 12;127(6):720 full-text
consistent findings at 4 years in PROTECT AF trial and difference in all-cause mortality
becomes statistically significant
601 patients (85%) completed mean 3.8-year follow-up but all patients were included in
analyses
control
all-cause mortality 3.2 vs. 4.8 (p = 0.04)
cardiovascular or unexplained death 1 vs. 2.4 (p < 0.05)
any stroke 1.5 vs. 2.2 (not significant)
primary safety events 3.6 vs. 3.1 (not significant)
all-cause mortality 12.3% with device vs. 18% with continued warfarin (p = 0.04, NNT
18)
Reference - JAMA 2014 Nov 19;312(19):1988, editorial can be found in JAMA 2014
Nov 19;312(19):1979
percutaneous closure of left atrial appendage associated with improved health-related
quality of life at 1 year (level 2 [mid-level] evidence)
based on secondary analysis of PROTECT AF trial
547 patients with quality-of-life data available at baseline and at 1 year were analyzed
compared to warfarin, percutaneous closure of left atrial appendage associated with
improved health-related quality-of-life physical component (p = 0.01) and
nonsignificant improvement in health-related quality-of-life mental component (p =
0.06)
53/105
Reference - J Am Coll Cardiol 2013 Apr 30;61(17):1790 full-text

LAA closure might not be as effective as warfarin for decreasing composite of stroke, systemic
embolism, and cardiovascular or unexplained death in patients with atrial fibrillation and
CHADS2 score ≥ 2 or CHADS2 score of 1 plus additional stroke risk factors (level 2 [mid-
level] evidence)
based on randomized noninferiority trial with unclear blinding of outcome assessors
407 adults (mean age 74 years, 70% male) with nonvalvular atrial fibrillation and specific risk
factors for stroke were randomized 2:1 to LAA closure (Watchman device) and warfarin
discontinuation 45 days after device implantation vs. continued warfarin therapy with target
INR 2-3
patients were higher-risk group than PROTECT AF trial and included patients with CHADS2
risk score ≥ 2, or patients with CHADS2 risk score of 1 and any of
female and age > 75 years
baseline ejection fraction ≥ 30% and < 35%
aged 65-74 years and either diabetes or coronary disease
aged > 65 years and heart failure
patients were excluded if chronic warfarin therapy was contraindicated
patients who had device implantation received warfarin plus aspirin 81 mg/day for 45 days
after implantation, discontinuation of warfarin if complete closure of left atrial appendage
confirmed, and then clopidogrel 75 mg/day plus aspirin 81-325 mg/day for 6 months, then
continued aspirin indefinitely
median follow-up 12 months (range 0.03-25.9 months)
late ischemia defined as stroke or systemic embolism at > 7 days after randomization
comparing LAA closure vs. warfarin
18-month rate of composite outcome of stroke, systemic embolism, and cardiovascular
or unexplained death 6.4% vs. 6.3% (rate ratio 1.07, 95% credible interval for rate ratio
0.57-1.89, noninferiority criterion of upper limit < 1.75 was not met)
cardiovascular or unexplained death in 2.6% vs. 2.2% (no p value reported)
any stroke in 2.3% vs. 0.7% (no p value reported)
ischemic stroke in 1.9% vs. 0.7% (no p value reported)
hemorrhagic stroke in 0.4% vs. 0% (no p value reported)
systemic embolism in 0.4% vs. 0% (no p value reported)
all-cause mortality not reported
7-day procedural complication rates (in PREVAIL trial and in PROTECT AF trial)
overall rate 4.5% (and 8.7% in PROTECT AF trial)
pericardial effusion requiring drainage (percutaneous or surgical) 1.9% (and 4% in
PROTECT AF trial)
procedure-related strokes 0.7% (and 1.1% in PROTECT AF trial)
device embolization 0.7% (and 0.4% in PROTECT AF trial)
other serious procedure-related adverse events reported in PREVAIL trial included 1
case each of arteriovenous fistula, cardiac perforation, pericardial effusion with cardiac
tamponade, and major bleed requiring transfusion
Reference - PREVAIL trial (J Am Coll Cardiol 2014 Jul 8;64(1):1), editorial can be found in J
Am Coll Cardiol 2014 Jul 8;64(1):13
LAA closure might reduce cardiovascular mortality and might have similar combined stroke
rates (hemorrhagic and ischemic) compared to warfarin in patients with atrial fibrillation
based on meta-analysis of individual patient data
meta-analysis of individual patient data from 2 trials (PROTECT AF and PREVAIL)
comparing LAA closure vs. warfarin in 1,114 patients with atrial fibrillation
mean follow-up ranged from 0.6 years to 4 years (total follow-up 5,931 patient-years)
comparing LAA closure vs. chronic warfarin therapy
all-cause mortality (hazard ratio 0.73, 95% CI 0.52-1.00, p = 0.07)
cardiovascular/unexplained mortality (per 100 person-years) 1.1 vs. 2.3 (p = 0.006)
54/105
any stroke or systemic embolism (per 100 patient-years) 1.75 vs. 1.87 (not significant)
hemorrhagic stroke rate (per 100 patient-years) 0.15 vs. 0.96 (p = 0.004)
ischemic stroke or systemic embolism (per 100 patient-years) 1.6 vs. 0.9 (p = 0.05)
composite outcome of stroke, systemic embolism, and cardiovascular death (per 100
patient-years) 2.72 vs. 3.5 (hazard ratio 0.79, 95% CI 0.53-1.12)
all major bleeding (hazard ratio 1.00, 95% CI 0.69-1.4)
major nonprocedural bleeding in 6% vs. 11.3% (p = 0.006)
consistent results in meta-analysis of individual patient data from 4 studies (PROTECT AF
and PREVAIL trials and their respective nonrandomized continued access registries)
evaluating LAA closure vs. chronic warfarin therapy in 2,406 patients with nonvalvular atrial
fibrillation
Reference - J Am Coll Cardiol 2015 Jun 23;65(24):2614
left atrial appendage (LAA) closure compared to direct oral anticoagulants (DOACs)
left atrial appendage closure reported to be similar to direct oral anticoagulants (DOACs) and
more effective than antiplatelet therapy for reducing mortality and stroke or systemic
embolism in patients with nonvalvular atrial fibrillation (level 3 [lacking direct] evidence)
based on systematic review without direct comparisons
network meta-analysis of 19 randomized trials evaluating left atrial appendage closure
(LAAC), antiplatelet therapy, and nonvitamin K antagonists for stroke prophylaxis in 87,831
patients with nonvalvular atrial fibrillation
in meta-analysis of indirect comparisons
no significant differences comparing LAAC for
mortality compared to DOACs (hazard ratio [HR] 0.76, 95% CI 0.5-1.16) in
analysis of 7 trials with 74,075 patients, but confidence interval includes
possibility of benefit or harm
risk of stroke or systemic embolism compared to DOACs (HR 1.01, 95% CI 0.53
to 1.92) in analysis of 8 trials with 74,409 patients, but confidence interval
includes possibility of benefit or harm
rates of major bleeding compared to
placebo (HR 2.33, 95% CI 0.67-8.09) in analysis of 4 trials with 2,238
patients, but confidence interval includes possibility of benefit or harm
antiplatelet therapy (HR 0.75, 95% CI 0.3-1.88) in analysis of 10 trials
with 13,080 patients, but confidence interval includes possibility of benefit
or harm
DOACs (HR 0.8, 95% CI 0.33-1.94) in analysis of 6 trials with 72,724
patients, but confidence interval includes possibility of benefit or harm
LAAC associated with
reduced mortality in analysis of 16 trials with 81,316 patients compared to
placebo (HR 0.38, 95% CI 0.22-0.67)
antiplatelet therapy (HR 0.58, 95% CI 0.37-0.91)
reduced risk of stroke or systemic embolism in analysis of 17 trials with 86,013
patients compared to
placebo (HR 0.24, 95% CI 0.11-0.52)
antiplatelet therapy (HR 0.44, 95% CI 0.23-0.86)
Reference - Heart 2017 Jan 15;103(2):139, editorial can be found in Heart 2017 Jan
15;103(2):93
left atrial appendage closure and direct oral anticoagulants reported to have similar efficacy
for stroke prevention in patients with atrial fibrillation (level 3 [lacking direct] evidence)
based on systematic review without direct comparisons
systematic review of 6 randomized trials and 27 observational studies evaluating LAAC and
DOACs for stroke prevention in patients with atrial fibrillation
2 trials (PROTECT AF and PREVAIL) evaluated left atrial appendage closure using
WATCHMAN device compared to warfarin
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4 trials (RE-LY trial, ARISTOTLE trial, ROCKET AF, and ENGAGE AF-TIMI 48)
evaluated DOACs including dabigatran, apixaban, rivaroxaban, or edoxaban compared
to warfarin
follow-up ranged from 1.8 to 4 years among trials
in network meta-analysis of 6 trials with indirect comparisons, no significant differences in
risk of stroke (odds ratio 0.86, 95% CI 0.34-1.75), but confidence interval includes
possibility of benefit or harm
risk of major bleeding (odds ratio 0.66, 95% CI 0.29 -1.45), but confidence interval
includes possibility of benefit or harm
rate of stroke per 100 patient-years in observational studies
1.8 events with left atrial appendage closure (WATCHMAN or AMPLATZER device)
in analysis of 22 studies with 4,312 patients
2.4 events with DOACs in analysis of 8 studies with 32,736 patients, results limited by
significant heterogeneity
Reference - Heart Rhythm 2016 Jun;13(6):1203
LAA occlusion during cardiac surgery
left atrial appendage (LAA) occlusion during cardiac surgery associated with reduced all-
cause mortality and readmission rate for thromboembolism at 3 years in older adults with
atrial fibrillation (level 2 [mid-level] evidence)
10,524 patients ≥ 65 years old with atrial fibrillation having cardiac surgery with or without
concomitant LAA occlusion were followed for 3 years
all patients were at high risk for stroke (median CHA2DS2-VASc score 4 points)
cardiac surgery included coronary artery bypass grafting (CABG), mitral valve surgery
with or without CABG, or aortic valve surgery with or without CABG
37% had concomitant LAA occlusion and 63% had no concomitant LAA occlusion
overall, 5.4% were readmitted for thromboembolism, 0.9% were readmitted for hemorrhagic
stroke, and 21.5% died
comparing concomitant LAA occlusion vs. no LAA occlusion at 3 years
all-cause mortality 17.3% vs. 23.9% (p < 0.001)
readmission for thromboembolism in 4.2% vs. 6.2% (p < 0.001)
readmission for hemorrhagic stroke 0.9% vs. 0.9% (not significant)
among patients discharged without anticoagulation, LAA occlusion significantly reduced risk
of readmission for thromboembolism at 3 years compared to no LAA occlusion
consistent results in propensity score-matched analysis
Reference - JAMA 2018 Jan 23;319(4):365, editorial can be found in JAMA 2018 Jan
23;319(4):345
LAA occlusion during cardiac surgery associated with reduced all-cause mortality and stroke
rate in adults with atrial fibrillation (level 2 [mid-level] evidence)
75,782 adults (mean age 66 years, 71% male) who had CABG or valve surgery with or
without LAA occlusion between 2009 and 2017 were evaluated
5.8% had LAA occlusion during surgery
propensity scores for likelihood of having concomitant LAA occlusion were calculated for
each patient based on 76 baseline factors
4,295 patients who had concomitant LAA occlusion during cardiac surgery and 4,295
propensity score-matched patients who did not have concomitant LAA occlusion were
analyzed
75% had atrial fibrillation at baseline
mean follow-up 2.1 years
23.9% of patients without atrial fibrillation at baseline developed new atrial fibrillation ≤ 30
days after surgery
comparing concomitant LAA occlusion vs. no LAA occlusion
in patients with atrial fibrillation at baseline
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death 3.22 per 100 person-years vs. 4.93 per 100 person-years (p < 0.001)
rate of stroke 1.11 per 100 person-years vs. 1.71 per 100 person-years (p = 0.01)
atrial fibrillation-related outpatient visits 14.74 per 1 person-year vs. 13.11 per 1
person-year (p < 0.001)
atrial fibrillation-related hospitalizations 0.44 per 1 person-year vs. 0.41 per 1
person-year (p = 0.03)
in patients without atrial fibrillation at baseline
new atrial fibrillation ≤ 30 days in 27.7% vs. 20.2% (p < 0.001)
atrial fibrillation-related outpatient visits 3.01 per 1 person-year vs. 2.05 per 1
atrial fibrillation-related hospitalizations 0.08 per 1 person-year vs. 0.06 per 1
Reference - JAMA 2018 May 22;319(20):2116
Follow-up
nurse-led standardized care reduces cardiovascular mortality and hospitalizations compared to
usual care by cardiologist in patients with stable atrial fibrillation (level 1 [likely reliable] evidence)
based on randomized trial
712 patients with stable atrial fibrillation randomized to nurse-led outpatient clinic care vs. usual
care provided by cardiologist and followed for > 1 year
nurse-led care used decision support software (CardioConsult AF) and supervised by cardiologist
comparing nurse-led care vs. usual care with mean follow-up 22 months
cardiovascular mortality 1.1% vs. 3.9% (p = 0.025, NNT 36)
cardiovascular hospitalization in 13.5% vs. 19.1% (p = 0.029, NNT 18)
adherence to all 6 assessed guidelines significantly better in nurse-led care group
Reference - Eur Heart J 2012 Nov;33(21):2692
atrial fibrillation-specific management intervention does not reduce recurrent hospital admissions
or event-free survival in patients with persistent atrial fibrillation (level 1 [likely reliable] evidence)
335 patents (mean age 72 years) hospitalized with atrial fibrillation (23% newly diagnosed and 90%
persistent) and without heart failure were randomized to atrial fibrillation-specific management
(SAFETY) intervention vs. usual care and followed for ≥ 2 years (median 905 days)
SAFETY intervention consisted of home visit and Holter monitoring for 7-14 days post discharge
by cardiac nurse plus prolonged follow-up and multidisciplinary support as needed
64% had rate control-based treatment
no significant differences in unplanned admissions or total admissions per patient
comparing SAFETY intervention vs. usual care
median unplanned readmissions per patient 2 vs. 2 (not significant)
median total readmissions per patient 3 vs. 3 (not significant)
median event-free survival (all-cause death or unplanned readmission) 183 days vs. 199 days
(not significant)
mean percent days alive and out of hospital 92% vs. 89% (not significant)
Reference - SAFETY trial ( Lancet 2015 Feb 28;385(9970):774), editorial can be found in Lancet
2015 Feb 28;385(9970):752
mobile atrial fibrillation app with clinical decision support, patient education, self-care, and
structured follow-up components may improve drug adherence, satisfaction with anticoagulation,
and quality of life (level 2 [mid-level] evidence)
based on cluster-randomized trial with baseline differences
209 adults with nonvalvular atrial fibrillation in 2 Chinese hospitals were randomized to mobile
atrial fibrillation (mAF) app vs. usual care
mAF app offers clinical decision support, patient education, self-care, and structured follow-
up components
structured follow-up was planned at 1, 3, 6, 9, and 12 months
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patients in mAF app group were younger and more likely to have history of atrial fibrillation
ablation at baseline compared to patients in usual care group
compared to usual care at 1 and 3 months, mAF app significantly increased (p < 0.05 for all)
drug adherence as assessed by Pharmacy Quality Alliance adherence measures scores
anticoagulation satisfaction (perciving anticoagulation as benefit vs. burden)
quality of life
Reference - Am J Med 2017 Dec;130(12):1388 full-text
discussion on management of hypertension according to 2017 American College of Cardiology/American

Heart Association (ACC/AHA) guideline newly-defined threshold (≥ 130/80 mm Hg) in patients with AF
can be found in J Am Coll Cardiol 2018 Sep 11;72(11):1233
Complications and Prognosis

Complications
systemic embolization (from atrial thrombus)

stroke
in 4,117 patients with first atrial fibrillation and no previous stroke in Olmsted County,
Minnesota during 1980-2000, 446 (11%) had first ischemic stroke during mean follow-up 5.5
years ( Stroke 2005 Nov;36(11):2362)
see Thromboembolic prophylaxis in atrial fibrillation for risk factors and risk prediction
extracranial systemic embolic events represent 11.5% of thromboembolic events in patients
with nonvalvular atrial fibrillation, with visceral-mesenteric events associated with highest 30-
day mortality among all systemic embolic events
based on pooled analysis of individual patient data without assessment of trial quality
37,973 patients with nonvalvular atrial fibrillation from 4 randomized trials of anticoagulation
were evaluated
during mean follow-up 2.4 years
219 patients had extracranial systemic embolic events, defined as clinical and objective
evidence of sudden loss of perfusion of a limb or organ (incidence 0.24 per 100 patient-
years)
1,722 patients had stroke (incidence 1.92 per 100 patient-years)
extracranial systemic embolic events represented 11.5% of clinically recognized
thromboembolic events and most commonly involved lower extremities (58%), visceral-
mesenteric circulation (31%), and upper extremities (11%)
30-day mortality by type of systemic embolic event
55% after visceral-mesenteric embolic events (p < 0.001 vs. each of other systemic
embolic events)
17% after lower extremity embolic events (not significant vs. upper-extremity events)
(p = 0.004 vs. stroke alone)
9% after upper extremity embolic events (p = 0.033 vs. stroke alone)
25% after stroke alone
Reference - Circulation 2015 Sep 1;132(9):796 full-text , editorial can be found in Circulation
2015 Sep 1;132(9):787
incident heart failure and progression of prevalent heart failure
incidence of heart failure 4.4% per year in patients with atrial fibrillation
3,288 patients (mean age 71 years) with first diagnosis of atrial fibrillation and no current or
prior heart failure at baseline included
790 patients (24%) developed heart failure during mean follow-up 6.1 years (incidence 4.4%
per year)
Reference - Eur Heart J 2006 Apr;27(8):936
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previously unrecognized heart failure common in patients with atrial fibrillation at risk for
heart failure
based on individual patient data metal-analysis from observational studies
1,941 community-dwelling persons ≥ 60 years old at risk for heart failure from 4 heart failure
screening studies included
10.1% prevalence of atrial fibrillation
previously unrecognized heart failure was detected in 43% of patients with prevalent atrial
fibrillation and 22% of patients without prevalent atrial fibrillation (no p value reported)
Reference - Heart 2018 Aug;104(15):1236
new-onset atrial fibrillation associated with increased risk of mortality and hospitalization in
patients with heart failure
based on cohort analysis of data from randomized trial
2,392 patients with heart failure (New York Heart Association Class III-IV symptoms and left
ventricular ejection fraction ≤ 35%) and without atrial fibrillation at randomization were
evaluated
7.9% (190) developed new-onset atrial fibrillation
for mortality analysis, mean follow-up 413 days for patients who developed atrial fibrillation
and 723 days for patients without atrial fibrillation
for hospitalization data, mean follow-up 792 days for patients who developed atrial
fibrillation and 723 days for patients without atrial fibrillation
comparing patients with new-onset atrial fibrillation vs. without atrial fibrillation
all-cause mortality 36.3% vs. 29.8% (adjusted hazard ratio [HR] 2.03, 95% CI 1.57-
2.61)
cardiovascular mortality 32.1% vs. 25.3% (adjusted HR 2.07, 95% CI 1.58-2.71)
heart failure mortality 28.4% vs. 23% (adjusted HR 2, 95% CI 1.5-2.67)
mean all-cause hospitalization days per patient 25.1 vs. 12.6 (p < 0.0001)
mean heart failure hospitalization days per patient 15.4 vs. 6.9 (p < 0.0001)
Reference - Am J Med 2014 Oct;127(10):963
Prognosis
Prognosis based on atrial fibrillation burden
atrial fibrillation burden

atrial fibrillation burden refers to atrial fibrillation as a quantifiable amount of atrial fibrillation
rather than a binary (present or absent) condition
atrial fibrillation burden can be defined in many ways, such as
proportion of time in atrial fibrillation during a monitoring period expressed as % of time
(ideal definition but required ambulatory monitoring to define)
duration of longest atrial fibrillation episode during discrete monitoring period
number of atrial fibrillation episodes during discrete monitoring period
duration of atrial fibrillation detected on cardiac implantable electronic device
atrial fibrillation burden most often described using the following terms
paroxysmal (atrial fibrillation sustained for < 7 days of onset)
persistent (atrial fibrillation sustained for > 7 days)
permanent (joint decision by patient and clinician to stop additional attempts to restore and
maintain sinus rhythm)
estimation of stroke risk and recommendations for antithrombotic therapy are based on individual
patient risk, regardless of atrial fibrillation burden (see also thromboembolic prophylaxis in atrial
fibrillation)
Reference - American Heart Association (AHA) scientific statement on atrial fibrillation burden (
Circulation 2018 May 15;137(20):e623)
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persistent or permanent atrial fibrillation associated with greater all-cause mortality and risk for stroke or
systemic embolism than paroxysmal atrial fibrillation in patients receiving anticoagulation (warfarin or
direct oral anticoagulants [DOACs]) in cohort analyses of randomized trials
persistent atrial fibrillation associated with increased all-cause mortality compared to
paroxysmal atrial fibrillation
based on cohort analysis of data from ROCKET AF trial
14,062 patients who were randomized to rivaroxaban vs. warfarin were analyzed by type of
atrial fibrillation
82% had persistent atrial fibrillation and 18% had paroxysmal atrial fibrillation
comparing patients with persistent vs. paroxysmal atrial fibrillation (rates per 100 patient-
years)
all-cause mortality 4.78 vs. 3.52 (p = 0.006)
stroke or systemic embolism rate 2.18 vs. 1.73 (p = 0.048)
major bleeding rate 3.55 vs. 3.31 (not significant)
no significant differences between treatment groups by type of atrial fibrillation
Reference - Eur Heart J 2015 Feb 1;36(5):288 full-text
persistent and permanent atrial fibrillation each associated with greater all-cause mortality
and risk of stroke or systemic embolism than paroxysmal atrial fibrillation
based on cohort analysis of data from ENGAGE AF-TIMI 48 trial
21,105 patients who were randomized to edoxaban vs. warfarin were analyzed by pattern of
atrial fibrillation
25.4% had paroxysmal atrial fibrillation, 23.1% had persistent atrial fibrillation, and 51.5%
had permanent atrial fibrillation
comparing patients with paroxysmal vs. persistent vs. permanent atrial fibrillation
paroxysmal atrial fibrillation associated with reduced
all-cause mortality
adjusted hazard ratio [HR] 0.73 (95% CI 0.64-0.83) compared to persistent
atrial fibrillation
adjusted HR 0.78 (95% CI 0.69-0.87) compared to permanent atrial
fibrillation
risk of stroke or systemic embolism
adjusted HR 0.79 (95% CI 0.66-0.9) compared to persistent atrial
fibrillation
adjusted HR 0.78 (95% CI 0.67-0.93) compared to permanent atrial
fibrillation
no significant difference between groups in bleeding
no significant difference between treatment groups by pattern of atrial fibrillation
Reference - Circ Arrhythm Electrophysiol 2017 Jan;10(1) early online full-text
persistent or permanent atrial fibrillation associated with higher risk of stroke or systemic
embolism than paroxysmal atrial fibrillation
based on cohort analysis of data from ARISTOTLE trial
18,198 patients who were randomized to apixaban vs. warfarin were analyzed by pattern of
atrial fibrillation
15% had paroxysmal atrial fibrillation and 85% had persistent or permanent atrial fibrillation
event rates per 100 patient-years comparing patients with paroxysmal atrial fibrillation vs.
persistent or permanent atrial fibrillation
stroke or systemic embolism in 1% vs. 1.5% (adjusted hazard ratio 0.7, 95% CI 0.51-
0.93)
all-cause mortality 2.8% vs. 3.9% (adjusted p = 0.066)
major bleeding in 2.2% vs. 2.7% (adjusted p = 0.068)
Recurrence risk
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atrial fibrillation progression may be common in patients taking non-vitamin K antagonists oral
anticoagulation
3,210 adults (mean age 73 years, 60% male) with atrial fibrillation taking non-vitamin K antagonist
oral anticoagulant and ≥ 1 year follow-up from PREFER in AF prolongation registry were analyzed
by pattern of atrial fibrillation
42% had paroxysmal atrial fibrillation, 25% had persistent atrial fibrillation, and 33% had
permanent atrial fibrillation
17% had progression to more frequent atrial fibrillation pattern during follow-up
permanent atrial fibrillation associated with increased risk of incident heart failure at 1 year
compared to paroxysmal atrial fibrillation (odds ratio 1.8, 95% CI 1.06-3.07), but association not
significant after multivariable adjustment
Reference - Heart 2018 Mar 17 early online
paroxysmal atrial fibrillation may progress to chronic atrial fibrillation
757 Canadian patients with first diagnosis of paroxysmal atrial fibrillation followed for median 8
years
63.2% risk of recurrent atrial fibrillation (chronic or paroxysmal) at 5 years
risk of progression to chronic atrial fibrillation was 8.6% at 1 year and 24.7% at 5 years
independent risk factors for progression to chronic atrial fibrillation were
older age
moderate-to-severe aortic stenosis or mitral regurgitation
left atrial enlargement
diagnosis of cardiomyopathy
less rapid heart rate during atrial fibrillation
Reference - Am Heart J 2005 Mar;. 49(3):489
inconsistent evidence for effect of atrial fibrillation type on recurrence rate after radiofrequency
ablation
based on systematic review limited by heterogeneity
systematic review of 45 randomized trials and observational studies evaluating preprocedure
predictors for atrial fibrillation recurrence after radiofrequency ablation
heterogeneity in study design, patient populations, and radiofrequency ablation techniques limited
analyses
nonparoxysmal atrial fibrillation associated with greater risk of recurrence compared to paroxysmal
atrial fibrillation (relative risk 1.59, 95% CI 1.38-1.82) in univariate analysis of 14 trials with 4,394
patients, results limited by significant heterogeneity (p = 0.04)
multivariate analysis of 17 trials did not find an association between atrial fibrillation type and
recurrence
Reference - J Cardiovasc Electrophysiol 2010 Nov;21(11):1208
atrial fibrillation recurrence may be common in patients with new-onset atrial fibrillation secondary
to precipitating event
1,409 patients (mean age 74 years) with new-onset atrial fibrillation from Framingham Heart Study
included
439 Patients (31%) had atrial fibrillation secondary to precipitating event, such as surgery, infection,
acute myocardial infarction, thyrotoxicosis, acute alcohol consumption, acute pericardial disease,
pulmonary embolism, or other acute pulmonary disease
cumulative incidence of atrial fibrillation recurrence in patients with secondary precipitating events
42% at 5 years
56% at 10 years
62% at 15 years
Reference - Circulation 2015 May 12;131(19):1648 full-text
after cardioversion
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left atrial diameter > 4.5 cm and thickened mitral valve each associated with increased risk of
need for multiple subsequent cardioversions in patients with history of atrial fibrillation being
treated with rhythm-control strategy
based on secondary analysis of data from a randomized trial
1,293 patients with history of atrial fibrillation ≥ 48 hours successfully terminated with
electrical or chemical cardioversion, and then randomized to regimen of rate control or
rhythm control and followed for 1 year
multivariate risk factors for > 2 subsequent cardioversions (rhythm control group)
left atrial diameter > 4.5 cm (hazard ratio [HR] 1.86, 95% CI 1.2-2.8)
thickened mitral valve (HR 2.36, 95% CI 1.46-3.8)
Reference - Am Heart J 2006 Feb;151(2):390
smaller atrial area and higher flow parameters associated with maintenance of sinus rhythm
post cardioversion
18 patients with diagnosis of atrial fibrillation in previous 6 months had cardioversion and
both transthoracic and transesophageal echocardiogram each before and after cardioversion
8 patients reverted to atrial fibrillation in subsequent 30-day period
significant findings on transthoracic echocardiogram or transesophageal echocardiogram
associated with maintenance of sinus rhythm
smaller left atrial area (21 cm2 vs. 28 cm2, p = 0.009) measured precardioversion
higher postcardioversion mitral (p = 0.003) and atrial (p = 0.002) flow indices
Reference - Echocardiography 2001 Oct;18(7):545
obstructive sleep apnea (OSA) associated with recurrent atrial fibrillation after treatment for atrial
fibrillation
OSA associated with increased risk of recurrent atrial fibrillation after catheter ablation for
atrial fibrillation
systematic review of 6 observational studies reporting association between OSA and atrial
fibrillation recurrence after catheter-based pulmonary vein ablation in 3,995 patients
OSA associated with increased risk of recurrence after catheter ablation (risk ratio [RR] 1.25,
95% CI 1.08-1.45)
association stronger for obstructive sleep apnea diagnosed using polysomnography (RR 1.4,
95% CI 1.16-1.68)
OSA associated with recurrent atrial fibrillation following cardioversion
based on small cohort study
39 patients with OSA and 79 controls without previous sleep study who had cardioversion of
atrial fibrillation were followed for 12 months
recurrence of atrial fibrillation occurred in
53% of 79 controls
42% of 12 OSA patients who had adequate continuous positive airway pressure (CPAP)
treatment
82% of 27 OSA patients with no or inadequate CPAP treatment (p = 0.013 vs. treated
OSA, p = 0.009 vs. control)
Reference - Circulation 2003 May 27;107(20):2589 full-text
Embolic stroke and thromboembolism
1-year worldwide stroke incidence 4% in patients with atrial fibrillation, but incidence varies widely
(1%-8%) among geographical regions
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15,361 patients with atrial fibrillation in 47 countries across 8 geographical regions were followed
for 1 year after admission to emergency department
geographical regions were North America, western Europe, and Australia; South America; eastern
Europe; Middle East and Mediterranean crescent; sub-Saharan Africa; India; China; and southeast
Asia
1-year stroke incidence was 4% worldwide, but incidence varied significantly among geographic
regions
lowest incidence in India (1%) and North America, western Europe, and Australia (2%)
highest incidence in southeast Asia (7%), China (7%), and Africa (8%)
variation among regions persisted after adjustment for patient characteristics, treatment, and
economic factors
patients with primary diagnosis of atrial fibrillation had lower incidence of stroke compared to
patients with atrial fibrillation as secondary diagnosis (3% vs. 5%, p < 0.0001)
Reference - Lancet 2016 Sep 17;388(10050):1161, editorial can be found in Lancet 2016 Sep
17;388(10050):1131
prediction of stroke risk
various risk scores predict risk for stroke
CHADS2 risk score may be more accurate than many other risk scores (level 2 [mid-level]
evidence)
CHADS2 score suggests increasing risk for stroke with any of heart failure, hypertension, age
≥ 75 years, diabetes mellitus, and prior stroke or transient ischemic attack
see DynaMed calculator for Atrial Fibrillation CHADS2 Score for Stroke Risk
CHA2DS2-VASc score 0 associated with lower risk of thromboembolism than CHADS2 score 0 in
patients with atrial fibrillation (level 2 [mid-level] evidence)
CHA2DS2-VASc score is like CHAD2 score but adds female gender, age ≥ 65 years, left
ventricular dysfunction, history of thromboembolism, and history of myocardial infarction,
peripheral artery disease, or aortic plaque
see DynaMed calculator for Atrial Fibrillation CHA(2)DS(2)-VASc Score for Stroke Risk
R2CHADS2 score predicts risk of stroke or systemic embolism in patients with nonvalvular atrial
fibrillation (level 1 [likely reliable] evidence)
R2CHADS2 score adds creatinine clearance < 60 mL/minute to CHADS2 score
comparative accuracy is unclear, but R2CHADS2 score of 0 may have lower risk than
CHADS2 score of 0 (level 2 [mid-level] evidence)
see DynaMed calculators for
Atrial Fibrillation Five Year Risk of Stroke
Atrial Fibrillation Five Year Risk of Stroke or Death
Atrial Fibrillation and Arterial Thromboembolism Risk
see Thromboembolic prophylaxis in atrial fibrillation for details
resolved atrial fibrillation associated with increased risk of stroke or transient ischemic attack and
all-cause death compared to patients without atrial fibrillation
48,484 adults (median age 71 years) without prior stroke or transient ischemic attack were evaluated
23% had resolved atrial fibrillation
31% matched controls had ongoing atrial fibrillation
46% matched controls had no atrial fibrillation
incidence of stroke or transient ischemic attack per 1,000 person-years
12.1 in patients with resolved atrial fibrillation (adjusted p < 0.001 vs. controls with ongoing
atrial fibrillation or controls without atrial fibrillation)
16.7 in controls with ongoing atrial fibrillation
7.4 in controls without atrial fibrillation
incidence of all-cause death per 1,000 person-years
63/105
30 in patients with resolved atrial fibrillation (adjusted p < 0.001 vs. controls with ongoing
atrial fibrillation or controls without atrial fibrillation)
60.3 in controls with ongoing atrial fibrillation
24.4 in controls without atrial fibrillation
consistent results comparing patients with resolved but no documented recurrent atrial fibrillation
vs. controls without atrial fibrillation
Reference - BMJ 2018 May 9;361:k1717 full-text
sustained atrial fibrillation associated with increased risk of stroke or systemic embolism compared
to paroxysmal atrial fibrillation in patients with previous ischemic stroke or transient ischemic
attack
1,192 adults with nonvalvular atrial fibrillation and acute ischemic stroke or transient ischemic
attack (most of whom were taking anticoagulants) were followed for median 1.8 years
64% had sustained atrial fibrillation and 36% had paroxysmal atrial fibrillation
compared to paroxysmal atrial fibrillation, sustained atrial fibrillation associated with increased risk
of stroke or systemic embolism (adjusted hazard ratio 1.95, 95% CI 1.26-3.14)
no significant difference in major bleeding events
Reference - Stroke 2016 Oct;47(10):2582 full-text
persistently elevated cardiac troponin-I or N-terminal-B-type natriuretic peptide over 3 months
may be associated with increased risk of vascular death and adverse thromboembolic events in
patients with atrial fibrillation
2,514 patients with atrial fibrillation plus ≥ 1 stroke risk factor from RE-LY trial with available
plasma samples collected at baseline and at 3 months were evaluated
rates of persistent elevation (at baseline and at 3 months)
48.4% for cardiac troponin-I (defined as level > 0.01 mcg/L)
39.7% for N-terminal-B-type natriuretic peptide (NT-proBNP) (defined as level ≥ 778 ng/L)
23.6% for both cardiac troponin-I and NT-proBNP
composite thromboembolic outcome included ischemic stroke, systemic embolism, myocardial
infarction, pulmonary embolism, or vascular death, but excluded hemorrhagic death
64 strokes or systemic embolism events, 108 vascular deaths, and 168 composite thromboembolic
outcomes occurred during median 2-year follow-up
compared to no elevation
persistent elevation of cardiac troponin-I associated with increased risk of
vascular death (hazard ratio [HR] 6.1, 95% CI 2.64-14.09)
composite thromboembolic outcome (HR 3.66, 95% CI 2.12-6.31)
stroke or systemic embolism (HR 2.64, 95% CI 1.23-5.69)
persistent elevation of NT-proBNP associated with increased risk of
vascular death (HR 4.15, 95% CI 2.33-7.38)
persistent elevation of both cardiac troponin-I and NT-proBNP associated with increased risk
of
vascular death (HR 8.62, 95% CI 2.64-28.08)
stroke or systemic embolism (HR 4.54, 95% CI 1.34-15.41)
no significant association between outcomes and transient elevation of either or both markers
Reference - Heart 2014 Aug;100(15):1193, editorial can be found in Heart 2014 Aug;100(15):1151
left atrial appendage closure (LACC) device-related thrombus (DRT) on imaging associated with
increased risk of stroke or systemic embolism
based on meta-analysis of patient-level data from randomized trials and registries and retrospective
cohort study
1,876 patients with atrial fibrillation from PROTECT-AF [n = 463] and PREVAIL [n = 269]
randomized trials and 2 registries (Continued Access to PROTECT AF [n = 566], and Continued
Access to PREVAIL [n = 578]) included
64/105
1,739 patients (mean age 73 years, 66% male) with successful implantation of LACC device
were analyzed
all patients had Watchman device implanted for left atrial appendage closure
transesophageal echocardiography used to assess DRT at 45 days and 12 months in all
patients
mean CHA2DS2-VASc score 4, and mean HAS-BLED score 2
DRT in 3.7%
outcomes per 100 patient-years comparing patients with DRT vs. patients without DRT
any post-procedure stroke or systemic embolism in 7.46 vs. 1.78 (adjusted rate ratio
[RR] 3.55, 95% CI 2.18-5.79)
ischemic post-procedure stroke or systemic embolism in 6.28 vs. 1.65 (adjusted RR
3.22, 95% CI 1.9-5.45)
major bleeding in 7.85 vs. 4.11 (adjusted RR 1.78, 95% CI 1.13-2.81)
no significant association between DRT and increased risk of cardiovascular or all-cause
mortality
Reference - Circulation 2018 May 11 early online
469 consecutive patients (mean age 74 years, 61% male) with atrial fibrillation had LAAC using
either Watchman nitinol cage device (58%) or Amplatzer nitinol plug device (42%) and were
prospectively followed for mean 13 months
DRT in 7.2% of 339 patients who had left atrial imaging with TEE or computed tomography
thrombus on device associated with increased risk of ischemic stroke or transient ischemic
attacksin patients with LAA imaging (hazard ratio 4.39, 95% CI 1.05-18.43) (with follow-up
starting from first post-procedure LAA imaging)
Reference - J Am Coll Cardiol 2018 Apr 10;71(14):1528
absence of symptoms associated with increased risk for atrial fibrillation progression and ischemic
stroke in patients with newly diagnosed nonvalvular atrial fibrillation
1,100 patients (mean age 53 years) with newly diagnosed nonvalvular atrial fibrillation included
13.3% had asymptomatic atrial fibrillation
at baseline
asymptomatic patients were significantly more likely to be taking oral anticoagulant and
amiodarone compared to symptomatic patients
no significant difference between groups in CHADS2 score, but asymptomatic patients had
significantly greater prevalence of CHA2DS2-VASc score = 0 compared to symptomatic
patients
mean follow-up 9.9 years (all patients completed 5-year follow-up but 22.8% of patients were lost
to follow-up after 5 years)
compared to symptomatic atrial fibrillation, asymptomatic atrial fibrillation associated with
increased risk of
progression to permanent atrial fibrillation (adjusted hazard ratio 1.6, 95% CI 1.1-2.2)
ischemic stroke (adjusted hazard ratio 1.8, 95% CI 1-3.4), not significant, but CI includes
differences that may be clinically important
no significant differences between groups in heart failure, any stroke or systemic embolism,
cardiovascular mortality, or all-cause mortality
Reference - Int J Cardiol 2013 Oct 12;168(5):4744
asymptomatic atrial fibrillation associated with increased mortality and risk for cerebrovascular
events compared to presence of typical symptoms in patients with newly detected atrial fibrillation
476 patients (mean age 69 years) with newly detected atrial fibrillation in Olmstead County,
Minnesota included
presentation of atrial fibrillation was typical symptoms (palpitations) in 193 patients, atypical
symptoms in 122 patients, and asymptomatic in 161 patients
CHA2DS2-VASc score at baseline
65/105
CHA2DS2-VASc score was 0-1 in 28.2% of patients and ≥ 4 in 38.9% of patients

compared to patients with typical symptoms, mean CHA2DS2-VASc score was significantly
higher in patients without symptoms (mean score 3.3 vs. 2.3) and in patients with atypical
symptoms (mean score 3.2 vs. 2.3)
warfarin was used in 59.6% of patients with typical symptoms, 71.3% of patients with atypical
symptoms, and 70% of patients without symptoms
outcomes overall
all-cause death in 31% during median follow-up of 6 years
cardiovascular death in 10% during median follow-up of 6 years
cerebrovascular events (ischemic stroke and transient ischemic attack) in 12% during median
follow-up of 5.6 years
compared to presence of typical symptoms in multivariable analysis
asymptomatic presentation associated with
increased all-cause mortality (adjusted hazard ratio [HR] 4.01, 95% CI 2.32-6.91)
increased cardiovascular mortality (adjusted HR 3.4, 95% CI 1.3-8.9)
increased risk of cerebrovascular events (adjusted HR 2.6, 95% CI 1.1-6.11)
atypical symptoms associated with
increased all-cause mortality (adjusted HR 3.19, 95% CI 1.78-5.71)
increased risk of cerebrovascular events (adjusted HR 3.12, 95% CI 1.27-7.66)
Reference - Heart Rhythm 2016 Jul;13(7):1418 full-text
triallelic polymorphism (A-390 or T-390 allele) of C-reactive protein gene and higher C-reactive protein
levels each associated with increased risk of incident thromboembolic stroke in longitudinal > 10-year
follow-up of 725 patients with atrial fibrillation ( J Thromb Haemost 2017 Aug;15(8):1541 )
Cardiovascular disease
atrial fibrillation associated with increased risk of adverse cardiovascular events and sudden
cardiac death
based on systematic review of cohort studies
systematic review of 104 cohort studies evaluating association between atrial fibrillation and risk of
adverse cardiovascular events, chronic kidney disease, and death in 9,686,513 adults
6% had atrial fibrillation
all analyses limited by significant statistical heterogeneity
atrial fibrillation associated with increased risk of
heart failure (relative risk [RR] 4.99, 95% CI 3.04-8.22) in analysis of 6 studies
cardiovascular death (RR 2.03, 95% CI 1.79-2.3) in analysis of 14 studies
sudden cardiac death (RR 1.88, 95% CI 1.36-2.6) in analysis of 7 studies
ischemic heart disease (RR 1.61, 95% CI 1.38-1.87) in analysis of 86 studies
any stroke (RR 2.42, 95% CI 2.17-2.71) in analysis of 96 studies
ischemic stroke (RR 2.33, 95% CI 1.84-2.94) in analysis of 87 studies
chronic kidney disease (RR 1.64, 95% CI 1.41-1.91) in analysis of 3 studies
no significant difference in risk of hemorrhagic stroke (RR 2, 95% CI 0.67-5.96) in analysis of 3
studies
Reference - BMJ 2016 Sep 6;354:i4482 full-text
atrial fibrillation associated with higher risk of cardiac events, stroke, and heart failure in women
compared to men
systematic review of 30 cohort studies evaluating gender-specific association between atrial
fibrillation and risk of cardiovascular disease or death in 4,371,714 adults
1.5% had atrial fibrillation
atrial fibrillation associated with significantly increased risk of cardiac events, stroke, and heart
failure in women and men, but risk higher in women compared to men
relative risk (RR) ratio for cardiac events 1.55 (95% CI 1.15-2.08) in analysis of 7 studies
66/105
RR ratio for stroke 1.99 (95% CI 1.46-2.71) in analysis of 13 studies

RR ratio for heart failure 1.16 (95% CI 1.07-1.27) in analysis of 3 studies
Reference - BMJ 2016 Jan 19;532:h7013 full-text
lone atrial fibrillation after age 60 years associated with increased risk for cardiovascular events
55 patients aged 61-97 years with lone atrial fibrillation followed median 9.6 years
26 had 31 cardiovascular events during follow-up occurring median 5.1 years after diagnosis (range
0.7-18 years) including 6 transient ischemic attacks and 5 strokes
event rates (compared with age- and sex-matched controls) were 0.9%/person-year for stroke (vs.
0.2%), 1.1%/person-year for transient cerebral ischemia (vs. 0%), 2.6%/person-year for myocardial
infarction (vs. 1.1%) and 5%/person-year for total cardiovascular event rate (vs. 1.3%, significantly
different at p < 0.1)
no significant difference in survival compared with control group
Reference - Arch Intern Med 1999 May 24;159(10):1118
lone atrial fibrillation not associated with short-term increased risk of cardiovascular events, but
may be associated with increased risk of cerebrovascular event after 25 years
76 patients (mean age 44.2 years) with lone atrial fibrillation compared to age- and sex-matched
controls and followed mean 25.2 years
progression to permanent atrial fibrillation in 31% (22 of 71 patients with paroxysmal or persistent
atrial fibrillation)
heart failure in 18.4%
overall survival 92% at 15 years and 68% at 30 years (similar to rates for controls)
risk for stroke or transient ischemic attack similar to controls during initial 25 years but increased
after 25 years (p = 0.004), although confidence intervals were wide
Reference - Circulation 2007 Jun 19;115(24):3050 full-text, editorial can be found in Circulation
2007 Jun 19;115(24):3040, commentary can be found in Evid Based Med 2008 Feb;13(1):24
progression from lone to permanent atrial fibrillation associated with increased risk for
thromboembolism and heart failure
346 patients with newly diagnosed lone atrial fibrillation followed for mean 12.1 years
permanent atrial fibrillation in 7.8% at baseline and 38.7% at follow-up
annual rate of thromboembolism 0.4% and heart failure annual rate 0.4%
progression to permanent atrial fibrillation associated with
development of thromboembolism (hazard ratio 3.4, 95% CI 1.2-10)
development of heart failure (hazard ratio 23.2, 95% CI 4.8-46.8)
older age at diagnosis (p < 0.01)
Reference - Chest 2012 Feb;141(2):339, editorial can be found in Chest 2012 Feb;141(2):290
incidence of cardiovascular events about 3% per year in elderly patients with atrial fibrillation
taking vitamin K antagonists, and metabolic syndrome associated with increased risk
1,019 patients (mean age 73 years, 44% women) in Italy with atrial fibrillation and thromboembolic
risk who were taking oral vitamin K antagonists were followed for median of 34 months
cardiovascular events (myocardial infarction, revascularization, or cardiovascular death) in 11%
(incidence 3.4% per year)
metabolic syndrome in 64.9% of patients with cardiovascular events vs. 50.6% of patients without
events
metabolic syndrome independently associated with increased risk of myocardial infarction (MI) or
vascular death (adjusted hazard ratio 1.66, 95% CI 1.11-2.5)
heart failure and history of cerebrovascular events or cardiac events also associated with increased
risk of MI or vascular death
Reference - Chest 2015 Jun 1;147(6):1644
67/105
left atrial volume > 32 mL/m2 associated with increased risk of cardiovascular events in patients
with lone atrial fibrillation
46 patients aged ≤ 60 years old with lone atrial fibrillation who had ≥ 1 transthoracic
echocardiographic evaluation were followed for mean 28 years
23 patients (50%) had cardiovascular events
left atrial volume > 32 mL/m2 before cardiovascular event associated with increased risk of
cardiovascular events (adjusted hazard ratio 4.46, 95% CI 1.56-12.74)
Reference - Eur Heart J 2005 Dec;26(24):2556
silent ischemic stroke on brain magnetic resonance imaging (MRI) associated with increased risk of
symptomatic stroke in patients with atrial fibrillation
400 patients with atrial fibrillation who had brain MRI during routine health visits were analyzed
57% of patients were taking antithrombotic therapy (31% of patients had aspirin and 26% of
patients had warfarin)
28.3% had silent ischemic stroke on MRI
overall symptomatic stroke rate 3.6% per year during mean follow-up of 67 months
symptomatic stroke rate 5.6% per year with silent stroke vs. 2.7% per year with no silent stroke (p =
0.022)
no significant association between silent ischemic stroke and either risk of dementia or risk of
cognitive disorders
Reference - Am J Cardiol 2014 Feb 15;113(4):655
atrial fibrillation during acute myocardial infarction associated with increased mortality
based on systematic review of mostly observational studies
systematic review of 43 studies evaluating mortality associated with atrial fibrillation in 278,854
patients with acute myocardial infarction
atrial fibrillation during acute myocardial infarction associated with increased mortality (odds ratio
1.46, 95% CI 1.35-1.58) in analysis of 23 studies; risk increased with both new or prior history of
atrial fibrillation
Reference - Circulation 2011 Apr 19;123(15):1587 full-text
cohort study of readmission rates after ablation therapy in patients with coexisting atrial fibrillation and
heart failure can be found in Am J Cardiol 2017 Nov 1;120(9):1572
Mortality risk
1-year worldwide mortality 11% in patients with atrial fibrillation, but mortality varies widely
(9%-20%) among geographic regions
15,361 patients with atrial fibrillation in 47 countries across 8 geographical regions were followed
for 1 year after admission to emergency department
geographical regions were North America, western Europe, and Australia; South America; eastern
Europe; Middle East and Mediterranean crescent; sub-Saharan Africa; India; China; and southeast
Asia
1-year mortality was 11% worldwide, but mortality varied significantly among geographic regions
lowest mortality in southeast Asia, India, and eastern Europe (9% each)
highest mortality in South America (17%) and Africa (20%)
variation among regions persisted after adjustment for patient characteristics, treatment, and
economic factors
heart failure was most common cause of death (30%) in all regions except for South America and
southeast Asia, where infectious causes were more common
68/105
patients with primary diagnosis of atrial fibrillation had lower mortality compared to patients with
secondary diagnosis (6% vs. 16%, p < 0.0001)
Reference - Lancet 2016 Sep 17;388(10050):1161, editorial can be found in Lancet 2016 Sep
17;388(10050):1131
atrial fibrillation associated with increased all-cause mortality

systematic review of 104 cohort studies evaluating association between atrial fibrillation and risk of
adverse cardiovascular events, chronic kidney disease, and death in 9,686,513 adults with and
without cardiovascular disease
6% had atrial fibrillation
atrial fibrillation associated with increased all-cause mortality (relative risk 1.46, 95% CI 1.39-1.54)
in analysis of 66 studies, analysis limited by significant heterogeneity
Reference - BMJ 2016 Sep 6;354:i4482 full-text
atrial fibrillation associated with higher cardiovascular mortality in women compared to men
systematic review of 30 cohort studies evaluating gender-specific association between atrial
fibrillation and risk of cardiovascular disease or death in 4,371,714 adults
1.5% had atrial fibrillation
atrial fibrillation associated with
significantly increased cardiovascular mortality in women and nonsignificant increase in
cardiovascular mortality in men in analysis of 4 studies (relative risk ratio comparing women
to men 1.12, 95% CI 1.07-1.17)
significantly increased all-cause mortality in women and men in analysis of 19 studies, but
mortality higher in women compared to men (relative risk ratio 1.12, 95% CI 1.07-1.17)
Reference - BMJ 2016 Jan 19;532:h7013 full-text
atrial fibrillation might increase risk of composite all-cause mortality or hospitalization in patients
with chronic heart failure with reduced ejection fraction
based on cohort analysis of data from HF-ACTION trial
1,984 patients with New York Heart Association (NYHA) class II-IV heart failure with ejection
fraction ≤ 35% were evaluated
at baseline, 382 patients had atrial fibrillation and 1,602 patients had sinus rhythm
patients with atrial fibrillation were older and had lower exercise capacity and increased use of anti-
arrhythmic medications at baseline compared to patients with sinus rhythm (p < 0.05 for each)
outcome rates per 100 person-years comparing atrial fibrillation vs. sinus rhythm at median 2.6
years
composite rate of all-cause mortality or hospitalization 64.6 vs. 40.8 (adjusted p = 0.09)
all-cause mortality 10.6 vs. 5.2 (not significant in adjusted analysis)
cardiovascular mortality or hospitalization rate for heart failure 21 vs. 11.8 (adjusted p = 0.06)
among patients with atrial fibrillation at baseline, subsequent atrial fibrillation at median 2.6 years
in 10.9% with exercise training vs. 9% with usual care (not significant)
exercise training associated with similar improvement in 6-minute walking distance at 3 months
regardless of atrial fibrillation status at baseline
Reference - J Am Coll Cardiol 2017 Apr 4;69(13):1683 full-text
atrial fibrillation or atrial flutter associated with increased mortality and incidence of stroke and
heart failure in patients with hypertension
based on subgroup analysis of ALLHAT trial
33,357 patients > 55 years old with hypertension and at least 1 other coronary risk factor at baseline
were randomized to chlorthalidone 12.5-25 mg/day vs. amlodipine 2.5-10 mg/day vs. lisinopril 10-
40 mg/day for mean 4.9 years
preexisting atrial fibrillation/atrial flutter in 1.1%
new-onset atrial fibrillation/atrial flutter in 2%
preexisting atrial fibrillation/atrial flutter associated with
69/105
mortality (hazard ratio [HR] 2.82, 95% CI 2.36-3.37)

stroke (HR 3.63, 95% CI 2.72-4.86)
heart failure (HR 3.17 95% CI 2.38-4.25)
fatal coronary heart disease or nonfatal myocardial infarction (HR 1.64, 95% CI 1.22-2.21)
preexisting or new-onset atrial fibrillation/atrial flutter associated with increased mortality (HR
2.42, 95% CI 2.11-2.77)
no significant difference in atrial fibrillation or atrial flutter between treatment groups with
antihypertensive drugs (excluding doxazosin) or pravastatin vs. usual care
Reference - J Am Coll Cardiol 2009 Nov 24;54(22):2023
electrocardiographic left ventricular hypertrophy associated with increased risk of all-cause death
in patients with atrial fibrillation receiving anticoagulation therapy
based on cohort analysis of data from RE-LY trial
10,372 patients from the RE-LY trial with available electrocardiography data for left ventricular
hypertrophy analysis were evaluated
electrocardiographic left ventricular hypertrophy defined as strain pattern or Cornell voltage (R
wave in aVL plus S wave in V3) > 2 millivolt (mV) (women) or > 2.4 mV (men)
prevalence of electrocardiographic left ventricular hypertrophy was 22.7% during median 2 years
follow-up
comparing electrocardiographic left ventricular hypertrophy vs. no electrocardiographic left
ventricular hypertrophy
annualized all-cause mortality 6% vs. 3.1% (hazard ratio 2, 95% CI 1.7-2.3)
annualized cardiovascular mortality 4.5% vs. 1.8% (hazard ratio 2.6, 95% CI 2.1-3.1)
annualized myocardial infarction rate 1.1% vs. 0.6% (hazard ratio 2.1, CI 1.5-2.9)
QRS duration > 120 milliseconds and PR interval > 200 milliseconds each associated with increased
cardiovascular and arrhythmic mortality in patients with nonpermanent atrial fibrillation
based on cohort analysis of data from 2 randomized trials
5,436 patients (mean age 68 years, 35% female) with nonpermanent atrial fibrillation from AFFIRM
and AF-CHF trials were evaluated
death in 19.7% during mean follow-up of 40.8 months
in patients presenting with atrial fibrillation, QRS duration > 120 milliseconds on baseline
electrocardiogram associated with increased
all-cause mortality (adjusted hazard ratio [HR] 1.46, 95% CI 1.21-1.76)
cardiovascular mortality (adjusted HR 1.56, 95% CI 1.27-1.93)
arrhythmic mortality (adjusted HR 1.84, 95% CI 1.35-2.51)
any hospitalization (adjusted HR 1.15, 95% CI 1.02-1.29)
cardiovascular hospitalization (adjusted HR 1.21, 95% CI 1.06-1.37)
in patients presenting with sinus rhythm, QRS duration > 120 milliseconds at baseline associated
with increased cardiovascular (adjusted HR 1.75, 95% CI 1.15-2.65) and arrhythmic (adjusted HR
1.9, 95% CI 1.09-3.32) mortality, but no significant differences in all-cause mortality or
hospitalization
in all patients, PR interval > 200 milliseconds at baseline associated with increased
cardiovascular mortality (adjusted HR 1.56, 95% CI 95% CI 1.11-2.21)
arrhythmic mortality (adjusted HR 1.91, 95% CI 1.14-3.18)
Reference - J Cardiovasc Electrophysiol 2016 Apr;27(4):404
rhythm control associated with increased all-cause mortality in patients with atrial fibrillation and
severely increased left ventricular mass
based on cohort analysis of patient data from randomized trial
4,060 patients ≥ 65 years old with atrial fibrillation and ≥ 1 risk factor for stroke were randomized
to rate control vs. rhythm control
2,105 patients with echocardiographic data on left ventricular mass (34% with severely increased
left ventricular mass) were analyzed
median follow-up 41.5 months
all-cause mortality 15.7%
70/105
compared to normal left ventricular mass, severely increased left ventricular mass
associated with increased all-cause mortality in patients who received rhythm control
(adjusted hazard ratio 1.57, 95% CI 1.07-2.31)
not associated with all-cause mortality in patients who received control
Reference - Am J Cardiol 2014 Apr 1;113(7):1159
nonfatal vascular events associated with subsequent increased mortality in patients with atrial
fibrillation
based on cohort analysis of data from ACTIVE-W trial
6,706 patients with atrial fibrillation and ≥ 1 risk factor for stroke were randomized to
thromboembolic prophylaxis with warfarin (target INR 2-3) vs. clopidogrel 75 mg/day plus aspirin
75-100 mg/day
trial stopped early due to clear superiority for warfarin
randomized groups were combined for analysis
893 nonfatal vascular events occurred in median 1.28 years follow-up
139 strokes (88% ischemic, 56% disabling)
87 transient ischemic events
53 myocardial infarctions
21 noncentral nervous system (non-CNS) systemic embolisms
593 bleeding events (31% major bleeding)
mortality comparing patients with vascular event vs. patients without vascular event
for any stroke 22.3% vs. 4.4% (adjusted hazard ratio [HR] 9.3, p < 0.0001)
for disabling stroke (modified Rankin score ≥ 3) 34.6% vs. 4.4% (adjusted HR 14.3, p <
0.0001)
for myocardial infarction 22.6% vs. 4.6% (adjusted HR 7.3, p < 0.0001)
for non-CNS systemic embolism 14.3% vs. 4.7% (adjusted HR 6.5, p < 0.0001)
for major bleeding event 13.3% vs. 4.5% (adjusted HR 4.2, p < 0.0001)
for minor bleeding event 5.3% vs. 4.7% (adjusted HR .6, p = 0.036)
Reference - Eur Heart J 2010 Sep;31(17):2133 full-text
about 10% of deaths in patients with atrial fibrillation receiving anticoagulation treatment may be
stroke- or hemorrhage-related
based on cohort analysis of data from RE-LY trial
18,113 patients (mean age 72 years and 64% male) with atrial fibrillation from RE-LY trial received
dabigatran vs. warfarin and were followed for median 2 years
1,371 deaths occurred (annual mortality rate 3.84%)
10% were due to stroke or hemorrhage
37% were due to sudden cardiac death or progressive heart failure
Reference - Circulation 2013 Nov 12;128(20):2192
AFTER Part 2 clinical decision tool helps predict risk of all-cause death or cardiovascular-related
rehospitalization within 30 days in patients presenting to emergency department with atrial
fibrillation (level 1 [likely reliable] evidence)
based on prognostic study with independent derivation and validation cohorts
derivation cohort included 2,343 patients (mean age 68 years) presenting to emergency department
with atrial fibrillation
validation cohort included 1,167 similar patients
9.7% in derivation cohort and 10.7% in validation cohort had died or were rehospitalized for
cardiovascular reasons within 30 days
oral anticoagulation use was assessed using INR and defined as no oral anticoagulation use,
subtherapeutic INR (< 2), therapeutic INR (2-3), and supratherapeutic INR (> 3)
AFTER Part 2 clinical decision tool developed using factors significantly associated with all-cause
death or rehospitalization for cardiovascular reasons within 30 days in derivation cohort
age, per decade increase = 10 points
troponin positive = 41 points
INR > 3 = 37 points
INR < 2 = 6 points
71/105
no anticoagulation = 39 points
HAS-BLED score ≥ 3 = 13 points
creatinine > 200 mcmol/L (2.26 mg/dL) = 49 points
evidence of heart failure = 28 points
given furosemide in emergency department = 42 points
history of chronic obstructive pulmonary disease (COPD) = 22 points
history of major cancer = 22 points
history of dementia = 24 points
AFTER Part 2 risk categories were based on 5 equally-sized strata in the derivation cohort (≤ 60
points, 61-80 points, 81-98 points, 99-126 points, and ≥ 127 points)
rates of death or rehospitalization for cardiovascular reasons within 30 days stratified by risk
category
Rates of Death or Rehospitalization for Cardiovascular
Score Reasons within 30 days
Derivation Cohort Validation Cohort
≤ 60 points 2.1% 2%
61-80 points 5.7% 6.6%
81-98 points 4.9% 10.7%
99-126 points 10.6% 12.5%
≥ 127 points 23.8% 20%
Reference - Am Heart J 2018 Sep;203:85
biomarkers associated with increased mortality
increased growth differentiation factor 15 levels associated with increased risk of all-cause
death and major bleeding in patients with atrial fibrillation
14,798 patients (81%) with atrial fibrillation in ARISTOTLE trial had biomarkers measured
at baseline and were followed for median 1.9 years
patients were stratified into quartiles by growth differentiation factor 15 (GDF-15) levels (≤
977 ng/L, 978-1,393 ng/L, 1,384-2,052 ng/L, and > 2,052 ng/L)
compared to lowest quartile in adjusted analyses, GDF-15 levels > 977 ng/L associated with
increased risk of all-cause death and major bleeding (p < 0.0001 for each)
nonsignificant increase in risk of cardiovascular death (p = 0.066)
GDF-15 levels not significantly associated with increased risk of stroke or systemic
embolism, or myocardial infarction
apixaban associated with significantly reduced risk of stroke, bleeding, and death regardless
of GDF-15 levels
Reference - Circulation 2014 Nov 18;130(21):1847, editorial can be found in Circulation
2014 Nov 18;130(21):1837
higher levels of interleukin 6 or C-reactive protein associated with increased all-cause
mortality in patients with atrial fibrillation receiving oral anticoagulation therapy
14,954 patients with atrial fibrillation in ARISTOTLE trial had interleukin-6 (IL-6) and C-
reactive protein (CRP) measured at baseline and were followed for median 1.9 years
median IL-6 level was 2.3 ng/L and median CRP level was 2.2 mg/L
patients were stratified into quartiles by IL-6 levels (≤ 1.5 ng/L, > 1.5-2.3 ng/L, > 2.3-2.9
ng/L, and > 3.9 ng/L) and by CRP levels (≤ 1 mg/L, > 1-2.2 mg/L, > 2.2-4.8 mg/L, and > 4.8
mg/L)
analyses were adjusted for clinical risk factors, demographic characteristics, cardiovascular
biomarkers, and renal biomarkers
compared to lowest quartile in adjusted analyses,
increased risk of all-cause mortality associated with
IL-6 > 2.3-2.9 ng/L (adjusted hazard ratio [HR] 1.34, 95% CI 1.09-1.66)
72/105
IL-6 > 3.9 ng/L (adjusted HR 1.71, 1.38-2.1)

CRP > 4.8 mg/L (adjusted HR 1.49, 95% CI 1.24-1.79)
increased risk of cardiovascular mortality associated with
Il-6 > 2.3-2.9 ng/L (adjusted HR 1.38, 95% CI 1.03-1.85)
IL-6 > 3.9 ng/L (adjusted HR 1.41, 95% CI 1.05-1.88)
no significant association between increasing IL-6 or CRP levels and risk of stroke or
systemic embolism, myocardial infarction, or major bleeding
apixaban or warfarin did not influence associations of IL-6 or CRP with outcomes
Reference - Heart 2016 Apr 1;102(7):508
Prevention and Screening

Prevention
Prevention of recurrent atrial fibrillation
see Rhythm control in atrial fibrillation
ACE inhibitors and ARBs for prevention
American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines -
Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults
consider treatment of hypertension with angiotensin receptor blocker (ARB) for prevention of
recurrence of atrial fibrillation (ACC/AHA Class IIa, Level B-R)
Reference - Hypertension 2018 Jun;71(6):1269
European Society of Cardiology (ESC) recommendations for primary prevention of atrial fibrillation with
"upstream" therapy(2)
angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) should
be considered for prevention of new-onset atrial fibrillation in patients with hypertension,
particularly with left ventricular hypertrophy (ESC Class IIa, Level B)
upstream therapies with ACE inhibitors and ARBs are not recommended for
primary prevention of atrial fibrillation in patients without cardiovascular disease (ESC Class
III, Level C) ( Eur Heart J 2010 Oct;31(19):2369 full-text), correction can be found in Eur
Heart J 2011 May;32(9):1172
secondary prevention of paroxysmal atrial fibrillation in patients without cardiovascular
disease (ESC Class III, Level B)
addition of ARB to ACE inhibitor and beta blocker suggested for prevention of new-onset atrial
fibrillation in patients with heart failure and reduced ejection fraction (ESC Class IIa, Level A)
evidence for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)
ACE inhibitors and ARBs each may reduce risk for atrial fibrillation (level 2 [mid-level]
evidence)
based on 2 systematic reviews limited by statistical heterogeneity
systematic review of 26 trials evaluating ACE inhibitors or ARBs for ≥ 24 months in patients
with or without atrial fibrillation
ACE inhibitor or ARB associated with significantly lower risk of atrial fibrillation
(odds ratio [OR] 0.65, 95% CI 0.55-0.76) in analysis of 23 trials with 80,524 patients,
but results limited by substantial statistical heterogeneity
subgroup analyses limited to ACE inhibitor or ARB alone found similar results and
were limited by similar degree of heterogeneity
Reference - Clin Pharmacol Ther 2010 Oct;88(4):521
systematic review of 23 trials evaluating effects of treatment with ACE inhibitors or ARBs in
primary or secondary prevention of atrial fibrillation in 87,048 patients
73/105
renin-angiotensin system inhibition associated with decreased risk of primary or

secondary atrial fibrillation in analysis of 23 trials with 87,048 patients
odds ratio (OR) 0.67 (95% CI 0.57-0.78)
NNT 35-69 assuming 7% atrial fibrillation in controls
meta-analysis limited by statistical heterogeneity
similar benefits observed when ACE inhibitors and ARBs considered separately
Reference - J Am Coll Cardiol 2010 May 25;55(21):2299
ACE inhibitors and ARBs each may reduce risk for atrial fibrillation in patients with heart
failure or following cardioversion for atrial fibrillation (level 2 [mid-level] evidence)
based on systematic review with clinical heterogeneity
systematic review of 11 randomized trials of ACE inhibitors or ARBs with data on atrial
fibrillation development in 56,309 patients
4 trials were in heart failure, 3 trials in hypertension, 2 trials following cardioversion for atrial
fibrillation, and 2 trials following myocardial infarction
trial durations varied from 42 days to 6 years
unclear if meta-analysis appropriate given the varied conditions and interventions
rates of atrial fibrillation comparing intervention vs. control
overall meta-analysis 4.9% vs. 6.9% (NNT 53, 95% CI 37-98)
for ACE inhibitors 4.9% vs. 6.8% (NNT 53, 95% CI 34-212)
for ARBs 5% vs. 7% (NNT 49, 95% CI 36-89)
for heart failure 4.8% vs. 8.6% (NNT 27, 95% CI 19-78)
following cardioversion 19% vs. 36% (NNT 6, 95% CI 5-14)
for hypertension 4.6% vs. 5.2% (not significant)
following myocardial infarction 5.8% vs. 7.9% (not significant)
Reference - J Am Coll Cardiol 2005 Jun 7;45(11):1832, commentary can be found in J Am
Coll Cardiol 2006 Feb 21;47(4):889, Evid Based Med 2006 Feb;11(1):15
ARBs associated with reduced risk of recurrent atrial fibrillation in patients with persistent or
paroxysmal atrial fibrillation (level 2 [mid-level] evidence)
systematic review of 15 randomized trials comparing ARB vs. placebo or alternative therapy
after cardioversion of persistent atrial fibrillation or conventional medical therapy for
paroxysmal atrial fibrillation in 3,972 patients
comparing ARBs vs. placebo or alternative therapy in patients with persistent atrial
fibrillation
ARBs associated with reduced recurrent atrial fibrillation in analysis of 9 trials with
2,165 patients, results limited by significant heterogeneity
odds ratio 0.56 (95% CI 0.37-0.86)
NNT 5-27 with atrial fibrillation in 50% of control
no significant differences in
all-cause mortality in analysis of 9 trials with 2,165 patients
adverse effects in analysis of 6 trials with 2,030 patients
comparing ARBs vs. conventional medical therapy in patients with paroxysmal atrial
fibrillation
ARBs associated with
reduced recurrent atrial fibrillation in analysis of 6 trials with 1,807 patients,
odds ratio 0.45 (95% CI 0.3-0.68)
NNT 4-11 with atrial fibrillation in 58.4% of control
nonsignificant reduction in adverse effects (p = 0.06) in analysis of 5 trials with
1,489 patients
no significant differences in all-cause mortality in analysis of 6 trials with 1,807
patients
Reference - Int J Clin Pract 2013 Jun;67(6):536
74/105
achieving systolic blood pressure ≤ 130 mm Hg with antihypertensive treatment may reduce risk of
new-onset AF in older patients with hypertension (level 2 [mid-level] evidence)
8,831 adults (mean age 67 years) with hypertension (mean systolic blood pressure [SBP] 174 mm
Hg at baseline) and with no history of atrial fibrillation (AF) who were randomized to losartan-
based vs. atenolol-based antihypertensive treatment for at least 4 years in LIFE trial were stratified
by last measurement of in-treatment SBP
all patients were in sinus rhythm at baseline and had left ventricular hypertrophy
achieved SBP ≤ 130 mm Hg in 20% and ≥ 142 mm Hg in 50%
new-onset AF in 7.9% overall during mean 4.6-year follow-up
compared to SBP ≥ 142 mm Hg, reduced risk of new-onset AF associated with
achieving SBP ≤ 130 mm Hg (adjusted hazard ratio 0.6, 95% CI 0.45-0.82)
achieving SBP 131-141 mm Hg (adjusted hazard ratio 0.76, 95% CI 0.62-0.93)
Reference - Hypertension 2015 Aug;66(2):368
Statins
ESC recommendations for primary prevention of atrial fibrillation with "upstream" therapy
statins should be considered for prevention of new-onset atrial fibrillation in patients with
underlying heart disease, particularly heart failure (ESC Class IIb, Level B)
upstream therapies with statins are not recommended for primary prevention of atrial fibrillation in
patients without cardiovascular disease (ESC Class III, Level C)
Reference - Eur Heart J 2010 Oct;31(19):2369 full-text, correction can be found in Eur Heart J 2011
May;32(9):1172
statins for ≥ 6 months may not reduce risk of atrial fibrillation, but in patients with cardiovascular
disease awaiting cardiac procedures, statins may reduce short-term risk (level 3 [lacking direct]
evidence)
based on systematic review without clinical outcomes
systematic review of 40 randomized trials evaluating statins in 139,169 patients with or without
cardiovascular disease
comparing statins to no statins
no significant difference in atrial fibrillation at ≥ 6 months (odds ratio [OR] 0.95, 95% CI
0.88-1.03) in analysis of 22 trials with 105,791 patients
statins associated with reduced atrial fibrillation at < 6 months in analysis of 13 trials with
4,414 patients with cardiovascular disease awaiting cardiac procedures
OR 0.61 (95% CI 0.51-0.74)
results limited by heterogeneity
no significant difference in atrial fibrillation at ≥ 6 months comparing high- to low-dose statin (OR
1, 95% CI 0.9-1.12) in analysis of 7 trials with 28,964 patients, results limited by heterogeneity
Reference - BMJ 2011 Mar 16;342:d1250
statins associated with reduced risk of atrial fibrillation (level 3 [lacking direct] evidence)
systematic review of 20 trials assessing effect of statins on risk of atrial fibrillation in 32,311
patients with or without history of atrial fibrillation
statins associated with reduced risk of atrial fibrillation
in overall analysis (odds ratio (OR) 0.59, 95% CI 0.45-0.76) in analysis of all trials
in patients without history of atrial fibrillation (OR 0.67, 95% CI 0.51-0.88) in analysis of 14
trials
in patients with history of atrial fibrillation (OR 0.4, 95% CI 0.2-0.83) in analysis of 6 trials
Reference - Pharmacotherapy 2011 Nov;31(11):1051
rosuvastatin might reduce incidence of atrial fibrillation in patients with chronic heart failure (level
2 [mid-level] evidence)
based on subgroup analysis of randomized trial
GISSI-HF trial conducted in 357 cardiology or internal medicine centers in Italy
75/105
4,631 patients (mean age 68 years) with chronic heart failure (New York Heart Association [NYHA]
class II-IV) not taking statins randomized to rosuvastatin 10 mg vs. placebo once daily
rosuvastatin did not reduce morbidity or mortality in patients with chronic heart failure (level 1
[likely reliable] evidence) in primary analysis of GISSI-HF trial ( Lancet 2008 Oct
4;372(9645):1231)
3,690 patients (80.7%) had no atrial fibrillation at baseline
atrial fibrillation developed in 13.9% with rosuvastatin vs. 16% with placebo (p = 0.038 after
adjusting for clinical variables, laboratory examinations, and background therapies)
Reference - Eur Heart J 2009 Oct;30(19):2327, editorial can be found in Eur Heart J 2009
Oct;30(19):2302
atorvastatin 80 mg once daily after stroke or transient ischemic attack (TIA) may not reduce risk of
atrial fibrillation (level 3 [lacking direct] evidence)
based on post hoc analysis of SPARCL trial without clinical outcomes
4,731 patients with stroke or TIA within prior 1-6 months were randomized to atorvastatin 80 mg
vs. placebo once daily
patients with chronic or paroxysmal atrial fibrillation or who were taking medications for treatment
or prophylaxis of atrial fibrillation were excluded from trial
no significant differences in incidence of atrial fibrillation
Reference - Am Heart J 2011 May;161(5):993
Physical activity
moderate regular physical activity recommended to prevent atrial fibrillation (counsel athletes about
potential for long lasting intense sports to promote atrial fibrillation) (ESC Class IIa, Level B)(2)
moderate physical activity may be associated with reduced risk for atrial fibrillation in older adults
5,446 adults ≥ 65 years old evaluated for leisure activity, exercise intensity, walking habits, and
incident atrial fibrillation
1,061 new incidences of atrial fibrillation occurred during 47,280 person-years of follow-up
decreased incidence of atrial fibrillation associated with
leisure-time activity in quintiles 3, 4, and 5 compared to quintile 1 (p < 0.001)
moderate-intensity exercise compared to no exercise (hazard ratio 0.72, 95% CI 0.58-0.89)
walking distance and pace, each in graded manner (p < 0.001)
combined walking distance and pace in quintiles 2, 3, and 4 compared to quintile 1 (p < 0.05)
high-intensity exercise not associated with reduced risk for atrial fibrillation
Reference - Circulation 2008 Aug 19;118(8):800
Sick sinus syndrome
dual-chamber pacing may reduce risk of atrial fibrillation and pacemaker syndrome and increase
exercise capacity compared to single-chamber ventricular pacing in adults with sick sinus syndrome
and/or atrioventricular block (level 2 [mid-level] evidence)
based on Cochrane review of trials with methodologic limitations
systematic review of 31 randomized trials (including 26 crossover trials) comparing dual-chamber
pacing vs. single-chamber pacing for ≥ 48 hours in adults where > 50% had sick sinus syndrome,
atrioventricular (AV) block, or both
all trials had ≥ 1 of these limitations
unclear or inadequate blinding
inadequate allocation concealment
high loss to follow-up
76/105
no intention-to-treat analysis performed

inadequate washout period
in 4 trials evaluating mortality and atrial fibrillation in 5,183 patients
58% had sick sinus syndrome
30% had AV block
8% had sick sinus syndrome and AV block
4% had other indications for pacing
compared to single-chamber pacing, dual-chamber pacing associated with
reduced risk of atrial fibrillation in analysis of 4 trials with 5,183 patients
odds ratio (OR) 0.79 (95% CI 0.68-0.93)
NNT 22-105 with atrial fibrillation in 16% of single-chamber pacing group
reduced risk of pacemaker syndrome in analysis of 4 trials with 5,183 patients
OR 0.11 (95% CI 0.08-0.14)
NNT 6 with pacemaker syndrome in 20% of single-chamber pacing group
increased exercise capacity (mean difference 0.24, 95% CI 0.03-0.45) in analysis of 10
crossover trials with 356 patients
no significant difference in
all-cause mortality in analysis of 4 trials with 5,183 patients
stroke in analysis of 4 trials with 5,195 patients
heart failure in analysis of 3 studies with 4,985 patients
Reference - Cochrane Database Syst Rev 2004;(2):CD003710
DynaMed commentary -- The results of the pooled analysis of the mixed population (sick sinus
syndrome and AV block) may be driven by a high percentage of patients with sick sinus syndrome.
see Sick sinus syndrome for details
Perioperative prevention of atrial fibrillation
Recommendations for perioperative prevention of atrial fibrillation

recommendations
unless contraindicated, oral beta blocker recommended to prevent postoperative atrial fibrillation in
patients having cardiac surgery (ACC/AHA Class I, Level A)
for patients at high risk for postoperative atrial fibrillation, preoperative amiodarone reduces
incidence of atrial fibrillation in patients having cardiac surgery and is considered appropriate
prophylactic therapy (ACC/AHA Class IIa, Level A)
prophylactic sotalol may be considered to prevent postoperative atrial fibrillation in patients having
cardiac surgery (ACC/AHA Class IIb, Level B)
Reference - J Am Coll Cardiol 2014 Dec 2;64(21):e1, correction can be found in J Am Coll Cardiol
2014 Dec 2;64(21):2305
Canadian Cardiovascular Society (CCS) recommendations for prevention of postoperative atrial
fibrillation
beta blocker
continuation of beta blocker through surgery recommended in patients receiving beta blockers
before surgery, unless new contraindication (CCS Strong recommendation, High-quality
evidence)
starting beta blocker immediately before or after surgery suggested in patients not receiving
beta blockers before surgery, unless contraindicated (CCS Conditional recommendation,
consideration of amiodarone to prevent postoperative atrial fibrillation recommended in patients
with contraindication to beta blocker therapy before or after cardiac surgery (CCS Strong
recommendation, High-quality evidence)
77/105
for patients with contraindication to beta blocker and amiodarone before or after cardiac surgery,
consider prophylactic therapy with any (CCS Conditional recommendation, Low-quality evidence)
IV magnesium
colchicine
temporary biatrial pacing with epicardial leads
Reference - Can J Cardiol 2016 Oct;32(10):1170
sotalol or combination treatment including ≥ 2 of beta blocker, amiodarone, IV magnesium, or
biatrial pacing suggested for patients at high risk of postoperative atrial fibrillation (CCS
Conditional recommendation, Low- to Moderate-quality evidence)
European Society of Cardiology (ESC) recommendations for prevention of postoperative atrial fibrillation
perioperative beta blockers recommended to prevent postoperative atrial fibrillation after cardiac
surgery (ESC Class I, Level B)
perioperative amiodarone suggested as prophylactic therapy to prevent atrial fibrillation after
cardiac surgery (ESC Class IIa, Level A)
Reference - Europace 2016 Nov;18(11):1609
Antiarrhythmic drugs (amiodarone, beta blockers, sotalol)
antiarrhythmic drugs that decrease postoperative atrial fibrillation after heart surgery include
sotalol, amiodarone, and beta blockers (level 2 [mid-level] evidence)
based on Cochrane review limited by heterogeneity
systematic review of 118 randomized trials evaluating interventions for prevention of postoperative
atrial fibrillation in 17,364 adults having heart surgery
trials evaluating digoxin, potassium, or steroids not included
heart surgeries included coronary artery bypass graft (CABG) and valvular and combined
procedures with or without cardiopulmonary bypass
data not available to distinguish between symptomatic and asymptomatic atrial fibrillation
antiarrhythmic drugs associated with reduced postoperative atrial fibrillation or supraventricular
tachycardia compared to control include
sotalol in analysis of 11 trials with 1,609 adults
odds ratio (OR) 0.34 (95% CI 0.26-0.43)
NNT 4-6 with atrial fibrillation or supraventricular tachycardia in 40% of control group
analysis includes 1 high-quality trial with significant benefit but limited by
heterogeneity
amiodarone in analysis of 33 trials with 5,402 adults
OR 0.43 (95% CI 0.34-0.54)
beta blockers in analysis of 33 trials with 4,698 adults
OR 0.33 (95% CI 0.26-0.43)
Reference - Cochrane Database Syst Rev 2013 Jan 31;(1):CD003611
similar findings reported in systematic review of 52 trials ( Circulation 2002 Jul 2;106(1):75 full-
text)
amiodarone
perioperative amiodarone for open heart surgery decreases postoperative atrial fibrillation
and stroke (level 1 [likely reliable] evidence)
220 patients undergoing open heart surgery randomized to perioperative amiodarone vs.
placebo
comparing amiodarone vs. placebo
78/105
any atrial fibrillation in 22.5% vs. 38% (p = 0.01)

symptomatic atrial fibrillation in 4.2% vs. 18% (p = 0.001, NNT 8)
stroke in 1.7% vs. 7% (p = 0.04, NNT 19)
postoperative ventricular tachycardia in 1.7% vs. 7% (p = 0.04, NNT 19)
30-day mortality 3.3% vs. 4% (not significant)
nausea in 26.7% vs. 16% (not significant, NNH 9)
Reference - AFIST trial ( Lancet 2001 Mar 17;357(9259):830), correction can be found in
Lancet 2001 Jul 21;358(9277), commentary can be found in Lancet 2001 Jul
14;358(9276):147, summary can be found in Am Fam Physician 2001 Oct 15;64(8):1436
perioperative amiodarone does not decrease postoperative atrial fibrillation in patients having
cardiac valvular surgery (level 1 [likely reliable] evidence)
120 patients (mean age 65 years) having cardiac valvular surgery randomized to amiodarone
300 mg loading dose in the operating room followed by 2-day perfusion vs. placebo
postoperative atrial fibrillation in 59.3% amiodarone group vs. 40% placebo group (p =
0.035)
factors independently associated with increased risk of postoperative atrial fibrillation
older age (p = 0.0003)
recent (within 6 months) myocardial infarction (p = 0.026)
preoperative angina (p = 0.0326)
preoperative use of calcium channel blocker (p = 0.0078)
Reference - Anesthesiology 2010 Jan;112(1):128
postoperative amiodarone reduces atrial fibrillation after pulmonary resection (level 1 [likely
reliable] evidence)
based on 2 randomized trials
254 patients having surgery for lung cancer randomized to amiodarone (300 mg IV over 20
minutes immediately after surgery, then 600 mg orally twice daily for first 5 postoperative
days) vs. placebo
12 patients excluded before receiving randomized intervention due to not having
lobectomy or to having preoperative atrial fibrillation, 242 patients included in
intention-to-treat analysis
comparing amiodarone vs. placebo
symptomatic atrial fibrillation in 2.5% vs. 9.2% (p = 0.029, NNT 15, 95% CI 8-
116)
overall atrial fibrillation in 9% vs. 32% (p = 0.001, NNT 5, 95% CI 3-8)
Reference - Ann Thorac Surg 2012 Aug;94(2):339
130 patients having lobectomy, bilobectomy, or pneumonectomy randomized to amiodarone
vs. no prophylaxis
trial without blinding
amiodarone given as 1,050 mg continuous IV infusion over 24 hours (initiated at
anesthesia) then 400 mg orally twice daily (until hospital discharge or maximum 6
days)
comparing amiodarone vs. no prophylaxis
atrial fibrillation in 13.8% vs. 32.3% (p = 0.02, NNT 6)
median intensive care unit stay 46 hours vs. 84 hours (p = 0.03)
median length of hospital stay
pulmonary complications
adverse events
Reference - Ann Thorac Surg 2009 Sep;88(3):886
amiodarone may reduce risk for atrial fibrillation after transthoracic esophagectomy (level 2
based on randomized trial without blinding
79/105
80 patients having transthoracic esophagectomy randomized to amiodarone 0.73 mg/minute

(43.75 mg/hour) by continuous infusion starting at anesthesia induction for 96 hours (total
dose 4,200 mg) vs. no prophylaxis
atrial fibrillation requiring treatment in 15% vs. 40% (p = 0.02, NNT 4)
hospital stay
median intensive care unit stay
adverse effects
Reference - J Thorac Cardiovasc Surg 2010 Jul;140(1):45
carvedilol may reduce risk of postoperative atrial fibrillation compared to metoprolol in patients
having coronary artery bypass graft (level 3 [lacking direct] evidence)
based on nonclinical outcome from systematic review
systematic review of 4 randomized trials comparing carvedilol to metoprolol in 601 patients having
coronary artery bypass graft
carvedilol associated with reduced risk of postoperative atrial fibrillation in analysis of 4 trials with
497 patients
odds ratio 0.5 (95% CI 0.32-0.8)
NNT 5-21 with postoperative atrial fibrillation in 34% of controls
no significant difference in risk of direct current cardioversion in 1 trial with 110 patients
similar results in systematic review of 6 randomized and nonrandomized trials (including 3
randomized trials in systematic review above) ( PLoS One 2014;9(4):e94005 full-text)
amiodarone and metoprolol appear similarly effective for atrial fibrillation prophylaxis following
cardiac surgery (level 2 [mid-level] evidence)
316 stable patients (mean age 64 years, 81% men) who had cardiac surgery and were off mechanical
ventilation were randomized to amiodarone vs. metoprolol for 48-hour infusion beginning 15-21
hours after surgery
amiodarone 15 mg/kg IV daily (maximum daily dose 1,000 mg)
metoprolol 1-3 mg/hour IV (dose dependent upon heart rate)
comparing amiodarone vs. metoprolol
atrial fibrillation during treatment in 24.8% vs. 23.9% (not significant)
atrial fibrillation after treatment but prior to discharge in 16.9% vs. 17.7% (not significant)
Reference - Ann Intern Med 2010 Dec 7;153(11):703
sotalol appears to reduce risk of supraventricular tachyarrhythmias after cardiac surgery and may
be more effective than beta blockers (level 3 [lacking direct] evidence)
based on nonclinical outcomes from systematic review
systematic review of 15 randomized trials evaluating sotalol for prevention of supraventricular
tachyarrhythmia after cardiac surgery
no assessment of trial quality reported
sotalol associated with reduced incidence of postoperative supraventricular tachyarrhythmias
compared to
placebo in analysis of 5 trials with 988 patients
relative risk (RR) 0.55 (95% CI 0.45-0.67)
NNT 4-6 with supraventricular tachyarrhythmias in 51.5% for placebo group
beta blockers in analysis of 5 trials with 1,043 patients
RR 0.64 (95% CI 0.49-0.84)
NNT 9-28 with supraventricular tachyarrhythmias in 23% for beta blocker group
no treatment in analysis of 6 trials with 615 patients
RR 0.33 (95% CI 0.24-0.46)
NNT 4-5 with supraventricular tachyarrhythmias in 39% for controls
no significant differences in postoperative supraventricular tachyarrhythmias comparing sotalol to
80/105
amiodarone in analysis of 2 trials with 285 patients

magnesium in 1 trial with 105 patients
Reference - Am J Med 2011 Sep;124(9):875.e1
antiarrhythmic drugs that may decrease postoperative atrial fibrillation include amiodarone and
beta blockers, but beta blockers associated with increased risk of death and bradycardia (level 2
systematic review of 21 randomized trials evaluating pharmacologic prophylaxis of postoperative
atrial fibrillation in 11,608 patients undergoing noncardiac surgery
type of surgery was vascular in 30%, thoracic in 24%, general in 20%, orthopedic in 15%, and other
in 11%
definition of atrial fibrillation varied across studies and not all trials excluded patients with history
of paroxysmal atrial fibrillation
7.3% incidence of postoperative atrial fibrillation
drugs associated with reduced postoperative atrial fibrillation compared to placebo or active
controls include
amiodarone in analysis of 5 trials with 954 patients
risk ratio 0.42 (95% CI 0.26-0.67)
NNT 6-13 with outcome in 23% of control and active placebo group
beta blockers in analysis of 4 trials with 8,677 patients
risk ratio 0.32 (95% CI 0.11-0.87)
NNT 28-192 with outcome in 4% of control and active placebo group
consistent results for amiodarone in analysis of trials compared to placebo, but beta blockers no
longer significantly associated with postoperative atrial fibrillation in analysis of trials compared to
placebo
amiodarone not significantly associated with mortality, myocardial infarction, or complications
compared to placebo or active control, beta blockers associated with increased
mortality (relative risk 1.33, 95% CI 1.03-1.37) in analysis of 3 trials
bradycardia (relative risk 2.74, 95% CI 2.19-3.43)
Reference - Am J Med 2018 Jul;131(7):795
prophylactic metoprolol or losartan may each reduce risk of postoperative atrial fibrillation
after lung cancer surgery in patients with elevated perioperative NT-proBNP levels (level 2
320 patients (mean age 62 years) with elevated perioperative N-terminal pro-brain natriuretic
peptide (NT-proBNP) levels having lung cancer surgery were randomized to 1 of 3 groups
within 12 hours after surgery
prophylactic metoprolol 25 mg orally twice daily, then increased to 100 mg twice daily
prophylactic losartan 12.5 mg orally twice daily, then increased to 50 mg/day
no treatment (control)
1.6% discontinued treatment and were excluded from analyses
more patients in losartan (64%) and control (61%) groups were current or past smokers at
baseline than in metoprolol group (49%, p = 0.06 among groups)
postoperative atrial fibrillation in
6% with metoprolol (p < 0.001 vs. control, NNT 3) (not significant vs. losartan, but
trial not powered to detect differences between treatments)
12% with losartan (p < 0.001 vs. control, NNT 4)
40% with control
patients in control group had longer mean postoperative length of stay (8.6 days) than
metoprolol (6.8 days) or losartan (7.2 days) groups (p = 0.019 among groups)
no significant differences among groups in risk of postoperative complications, but
cumulative risk was highest in control group
81/105
in subgroup analyses, patients with high preoperative NT-proBNP levels had higher risk of
atrial fibrillation compared to patients with high postoperative NT-proBNP levels (p < 0.001)
Reference - PRESAGE trial ( Ann Surg 2016 Aug;264(2):244)
landiolol prophylaxis reduces incidence of postoperative atrial fibrillation and other postoperative
complications in adults having esophagectomy for thoracic esophageal carcinoma (level 1 [likely
reliable] evidence)
100 adults in Japan with thoracic esophageal carcinoma scheduled for transthoracic esophagectomy
were randomized to landiolol hydrochloride vs. placebo on postoperative day 1 and monitored by
electrocardiogram for 1 week after surgery
surgical procedure was either minimally invasive thoracoscopic esophagectomy or open right
transthoracic esophagectomy with 2-field or 3-field lymph node dissections
landiolol hydrochloride was administered through central vein at 3 mcg/kg/minute and discontinued
after 72 hours
postoperative atrial fibrillation defined as persistence of arrhythmia for ≥ 5 minutes on 12-lead
electrocardiogram
patients who had atrial fibrillation during blinded treatment were switched to open-label landiolol at
3-5 mcg/kg/minute
comparing landiolol vs. placebo
postoperative atrial fibrillation in 5% vs. 30% (p = 0.012, NNT 4)
postoperative complications ≥ grade II in 20% vs. 30% (p = 0.046, NNT 10)
postoperative complications > grade IIIa in 8% vs. 32% (p = 0.003, NNT 5)
all events of atrial fibrillation occurred within 5 days after surgery
no drug-related adverse events (National Cancer Institute Common Toxicity Criteria) > grade 2
reported
Reference - Br J Surg 2017 Jul;104(8):1003
Statins for perioperative prevention
in adults having cardiac surgery, preoperative statins reduce postoperative atrial fibrillation (level 1
[likely reliable] evidence) and length of hospital stay (level 2 [mid-level] evidence) but may not
reduce perioperative mortality (level 2 [mid-level] evidence)
based on withdrawn Cochrane review limited by heterogeneity (hospital stay) and wide confidence
intervals (mortality)
systematic review of 17 randomized trials comparing preoperative statin therapy vs. control
(placebo, no statins) in 2,138 adults having on-pump or off-pump cardiac surgery
statin regimens included atorvastatin 20-40 mg (11 trials), simvastatin 20 mg (3 trials), fluvastatin
80 mg (1 trial), rosuvastatin 20 mg (1 trial), and pravastatin 40 mg (1 trial)
preoperative statin therapy was initiated between 4 weeks before surgery and evening before
surgery, and 6 trials reinitiated statin therapy following surgery
mean trial duration 16 months
preoperative statin therapy associated with
decreased atrial fibrillation in analysis of 12 trials with 1,765 adults
odds ratio (OR) 0.54 (95% CI 0.43-0.67)
NNT 7-13 with atrial fibrillation in 32% of control group
shorter length of hospital stay (mean difference -0.41 days, 95% CI -0.73 to -0.08 days) in
analysis of 11 trials with 1,137 adults, results limited by significant heterogeneity
shorter length of intensive care unit stay (mean difference -2.54 hours, 95% CI -4.72 to -0.36
hours) in analysis of 9 trials with 721 adults, results limited by significant heterogeneity
nonsignificant lower risk of myocardial infarction (OR 0.48, 95% CI 0.21-1.13) in analysis of
7 trials with 901 adults
nonsignificant lower risk of renal failure (OR 0.57, 95% CI 0.3-1.1) in analysis of 5 trials
with 487 adults
82/105
no significant differences between groups in

perioperative mortality (OR 1.8, 95% CI 0.38-8.54) in analysis of 2 trials with 300 adults, but
wide confidence intervals cannot exclude clinically meaningful differences
stroke in analysis of 2 trials with 264 adults
Reference - Cochrane Database Syst Rev 2015 Aug 13;(8):CD008493
DynaMed commentary -- Cochrane review withdrawn 2016 May 19 as new evidence has come
available that could potentially change conclusions of review
preoperative statin therapy may reduce risk of postoperative atrial fibrillation in patients having
CABG (level 2 [mid-level] evidence)
systematic review of 12 randomized trials comparing preoperative statin therapy vs. placebo in
2,980 patients having coronary artery bypass graft surgery (CABG)
statins included atorvastatin in 8 trials, rosuvastatin in 2 trials, simvastatin in 1 trial, and
pravastatin in 1 trial
5 trials excluded patients with history of atrial fibrillation, 1 trial included patients with atrial
fibrillation (11%), and 6 trials did not specify atrial fibrillation in inclusion or exclusion
criteria
preoperative statin therapy associated with reduced risk of postoperative atrial fibrillation in
analysis of all trials, results limited by significant heterogeneity
odds ratio 0.42 (95% CI 0.27-0.66)
NNT 6-14 with atrial fibrillation in 26% of placebo group
consistent results with atorvastatin, but no significant differences with rosuvastatin
Reference - Am J Cardiol 2015 Jun 1;115(11):1523
preoperative statin therapy may reduce postoperative mortality, stroke, and atrial fibrillation in
patients having isolated coronary artery bypass graft surgery (level 2 [mid-level] evidence)
based on systematic review of mostly observational studies
systematic review of 10 randomized trials and 26 observational studies evaluating preoperative
statin therapy in patients having isolated CABG or aortic valve replacement surgery
32 studies evaluated preoperative statin therapy in 36,053 patients having isolated CABG
comparing statin therapy to no statin therapy in patients having CABG
statin therapy associated with reduced
mortality (odds ratio [OR] 0.67, 95% CI 0.54-0.82) in analysis of 28 studies with
33,164 patients
stroke (OR 0.81, 95% CI 0.67-0.97) in analysis of 16 studies with 24,707 patients
atrial fibrillation (OR 0.72, 95% CI 0.59-0.87) in analysis of 18 studies with 14,510
patients, result limited by significant heterogeneity
myocardial infarction in analysis of 20 studies with 21,442 patients
renal failure in analysis of 11 studies with 15,564 patients
Reference - Ann Thorac Surg 2013 Oct;96(4):1508
high-dose atorvastatin may not be more effective than low-dose atorvastatin at decreasing risk of
postsurgical atrial fibrillation after coronary artery bypass graft or aortic valve replacement (level 2
based on randomized trial with baseline differences
104 patients without history of atrial fibrillation having coronary artery bypass or aortic valve
replacement randomized to atorvastatin 80 mg vs. 10 mg for 7 days before surgery
higher rate of beta blocker use and previous myocardial infarction in 10-mg group at baseline (p <
0.05)
postoperative atrial fibrillation 29% with 80 mg vs. 36% with 10 mg (not significant)
Reference - J Thorac Cardiovasc Surg 2011 Jan;141(1):244
statins may reduce postoperative atrial fibrillation and myocardial infarction in patients having
noncardiac surgery (level 2 [mid-level] evidence)
83/105

systematic review of 21 randomized trials evaluating pharmacologic prophylaxis of postoperative
atrial fibrillation in 11,608 patients undergoing noncardiac surgery
type of surgery was vascular in 30%, thoracic in 24%, general in 20%, orthopedic in 15%, and other
in 11%
definition of atrial fibrillation varied across studies and not all trials excluded patients with history
of paroxysmal atrial fibrillation
2 trials evaluated statins compared to placebo in 637 patients
statins associated with reduced
postoperative atrial fibrillation
risk ratio 0.43 (95% CI 0.27-0.68)
NNT 8-19 with outcome in 17% of placebo group
myocardial infarction (relative risk 0.32, 95% CI 0.12-0.82)
Reference - Am J Med 2018 Jul;131(7):795
Magnesium for perioperative prevention
magnesium may reduce postoperative atrial fibrillation following heart surgery (level 2 [mid-level]
evidence)
based on 3 systematic reviews including Cochrane review limited by heterogeneity
Cochrane review of 118 randomized trials evaluating interventions for prevention of postoperative
heart surgeries included CABG and valvular and combined procedures with or without
cardiopulmonary bypass
most trials included concurrent use of beta blockers
IV magnesium associated with reduced postoperative atrial fibrillation or supraventricular
tachycardia compared to control in analysis of 21 trials with 2,988 adults
odds ratio 0.55 (95% CI 0.41-0.73)
NNT 8-18 with atrial fibrillation or supraventricular tachycardia in 26% of control
group
systematic review limited by clinical heterogeneity
systematic review of 21 randomized trials comparing IV magnesium sulfate vs. placebo for
atrial fibrillation prophylaxis in adults having cardiac surgery
heterogeneity in dose, timing, use of other medications (including beta blockers), and duration
of magnesium and possible publication bias limited analyses
magnesium significantly reduced risk of atrial fibrillation in overall analysis of 21 trials
odds ratio (OR) 0.58 (95% CI 0.43-0.79)
results limited by heterogeneity which was not explained by differences in dose or
duration
no significant difference in atrial fibrillation in analysis restricted to 5 double-blind trials
reporting atrial fibrillation as primary outcome (OR 0.94, 95% CI 0.61-1.44)
Reference - Ann Thorac Surg 2013 Feb;95(2):533
systematic review of 15 trials comparing magnesium sulfate with placebo or control in patients
having CABG surgery
no trials compared magnesium sulfate with sotalol
postoperative atrial fibrillation in 21% with magnesium vs. 30% with placebo or control (odds
ratio [OR] = 0.65, 95% CI 0.53-0.79, p < 0.0001, but with significant heterogeneity [p =
0.0005])
Reference - Health Technol Assess 2008 Jun;12(28):iii
addition of IV magnesium sulfate may not reduce atrial arrhythmias in patients taking atenolol
84/105
based on randomized trial without blinding and allocation violations

927 patients having coronary artery bypass grafting and/or valve surgery were randomized to IV
magnesium sulfate vs. placebo
treatment included magnesium sulfate 5 g IV on removal of cross-clamp then magnesium sulfate 5 g
IV/day from postoperative day 1 until postoperative day 4
all patients received oral atenolol
29% did not receive allocated treatment
atrial arrhythmias occurred in 26.4% with IV magnesium sulfate vs. 24.3% with placebo in
intention-to-treat analysis (not significant)
Reference - Circulation 2009 Sep 15;120(11 Suppl):S163
Steroids for perioperative prevention
prophylactic steroid use associated with reduction in new-onset atrial fibrillation and reduced
duration of intensive care unit stay after cardiopulmonary bypass surgery (level 2 [mid-level]
evidence)
systematic review of 44 randomized trials evaluating effects of prophylactic steroids on clinical
outcomes after cardiopulmonary bypass surgery in 3,205 patients
overall mortality 3.2%
comparing steroid vs. placebo
mortality 2.7% vs. 3.7% in 16 trials (not significant)
new-onset atrial fibrillation in 24.8% vs. 35.5% in 14 trials (p < 0.05)
steroid associated with reduction in duration of intensive care unit stay in analysis of 22 trials with
1,268 patients (p = 0.006, results limited by significant heterogeneity)
Reference - Eur Heart J 2008 Nov;29(21):2592 full-text
hydrocortisone IV reduces incidence of atrial fibrillation after cardiac surgery (level 3 [lacking
direct] evidence)
based on randomized trial without significant differences in clinical outcomes
241 Finnish patients aged 30-85 years having first cardiac surgery (on-pump coronary artery bypass
graft, aortic valve replacement, or both) and no prior atrial fibrillation or flutter were randomized to
hydrocortisone 100 mg vs. placebo IV every 8 hours for 3 days starting the evening of operative day
all patients given oral metoprolol 50-150 mg/day titrated to heart rate
follow-up for first 84 hours after cardiac surgery
comparing hydrocortisone vs. placebo
atrial fibrillation in 30% vs. 48% (p = 0.01, NNT 6)
in-hospital atrial fibrillation in 36% vs. 52% (p = 0.02, NNT 7)
in-hospital mortality 1% vs. 1% (not significant)
resternotomy due to bleeding in 4% vs. 3% (not significant)
stroke in 1% vs. 1% (not significant)
perioperative myocardial infarction in 5% vs. 2% (not significant)
superficial wound infections in 14% vs. 14% (not significant)
no cases of perioperative mediastinitis reported
meta-analysis combined this trial with 2 other trials
total 3 trials with 621 patients
27.4% hydrocortisone vs. 40.8% placebo patients had atrial fibrillation (p = 0.001, NNT 8)
Reference - JAMA 2007 Apr 11;297(14):1562, commentary can be found in JAMA 2007 Jul
18;298(3):283, ACP J Club 2007 Sep-Oct;147(2):36
neither perioperative corticosteroids for 24 hours nor hemofiltration during cardiopulmonary
bypass associated with reduced risk for atrial fibrillation after cardiac surgery (level 3 [lacking
direct] evidence)
based on secondary analysis of randomized trial without clinical outcomes
192 patients having cardiac surgery were randomized to perioperative corticosteroid therapy vs.
hemofiltration during cardiopulmonary bypass vs. control
85/105
perioperative corticosteroid therapy consisted of methylprednisolone 1 g IV immediately before

induction of anesthesia followed by dexamethasone 4 g IV every 6 hours for 24 hours
185 patient records were reviewed retrospectively to assess for new-onset atrial fibrillation
60 patients (32%) had new-onset atrial fibrillation after cardiac surgery
postoperative atrial fibrillation in 21% with perioperative corticosteroids vs. 41% with
hemofiltration vs. 36% in control group (not significant)
Reference - Anesth Analg 2010 Feb 1;110(2):329
Omega-3 fatty acids for perioperative prevention
American Heart Association (AHA) scientific statement on omega-3 polyunsaturated fatty acid (fish oil)
supplementation for prevention of clinical cardiovascular disease
treatment NOT indicated for
prevention of atrial fibrillation after cardiac surgery (AHA Class III, Level A)
secondary prevention of atrial fibrillation in patients with prior atrial fibrillation (AHA Class
III, Level A)
Reference - Circulation 2017 Apr 11;135(15):e867 full text
preoperative omega-3 fatty acids might reduce atrial fibrillation after cardiac surgery (level 3
systematic review of 8 randomized trials comparing omega-3 fatty acids to olive oil, other vegetable
oils, or usual care (control) for prevention of atrial fibrillation following open heart surgery in 2,687
patients
omega-3 fatty acids associated with
nonsignificant reduction in postoperative atrial fibrillation compared to control in overall
analysis of 8 trials with 2,687 patients (odds ratio 0.75, 95% CI 0.57-1)
significantly reduced postoperative atrial fibrillation in subgroup analysis of isolated coronary
artery bypass graft surgery from 7 trials with 1,028 patients (odds ratio 0.66, 95% CI 0.5-
0.87)
Reference - J Thorac Cardiovasc Surg 2013 Oct;146(4):906
omega-3 fatty acids may not reduce risk for atrial fibrillation after cardiac surgery (level 2 [mid-
level] evidence)
systematic review of 10 randomized trials comparing omega-3 fatty acids to placebo or usual care in
1,955 patients with initial or recurrent atrial fibrillation
5 trials evaluated new-onset atrial fibrillation after cardiac surgery
no significant difference between groups in new-onset atrial fibrillation in analysis of 5 trials with
776 patients, but results limited by significant heterogeneity
Reference - Heart 2011 Jul;97(13):1034
omega-3 fatty acids may not reduce risk of atrial fibrillation after cardiac surgery (level 3 [lacking
direct] evidence)
based on nonclinical outcome from randomized trial
1,516 patients (mean age 64 years and 72% male) scheduled for cardiac surgery randomized to
omega-3 fatty acids vs. placebo until hospital discharge or postoperative day 10
omega-3 fatty acid group received fish oil (each 1 g capsule containing ≥ 840 mg n-3-
polyunsaturated fatty acids as ethyl esters) with dosing schedule of 10 g divided over 3-5 days (or 8
g over 2 days) preoperatively followed by 2 g/day postoperatively
51.8% had valvular surgery
postoperative atrial fibrillation lasting > 30 seconds and documented by rhythm strip or 12-lead
electrocardiogram in 30% with omega-3 fatty acids vs. 30.7% with placebo (not significant)
no significant difference in
sustained, symptomatic, or treated postoperative atrial fibrillation
postoperative atrial fibrillation episodes (1, 2, or ≥ 3 episodes)
86/105
Reference - OPERA trial ( JAMA 2012 Nov 21;308(19):2001), correction can be found in JAMA
2013 Mar 6;309(9):876
perioperative fish oil does not appear to decrease atrial fibrillation after cardiac surgery (level 3
based on nonclinical outcome from randomized trial
200 patients > 18 years old having coronary artery bypass graft and/or valve repair or replacement
were randomized to fish oil 15 mL/day vs. placebo oil for 3 weeks prior to surgery and for 6 days
after surgery or until discharge
fish oil dose provided eicosapentaenoic acid 2.7 g/day and docosahexaenoic acid 1.9 g/day
6 patients who did not have surgery were excluded from analysis
comparing fish oil vs. placebo
in-hospital atrial fibrillation in 37% vs. 48% (not significant)
mean cardiac intensive care unit stay 67 hours vs. 95 hours (p = 0.005)
mean hospital stay 8.6 days vs. 9.9 days (not significant)
no significant differences in in-hospital mortality, ventricular arrhythmia, respiratory failure,
cardiogenic shock, myocardial infarction, stroke, infections, blood loss, or major bleeding episodes
fish oil was associated with nonsignificant increase in delay of time to onset of atrial fibrillation
(hazard ratio 0.66, p = 0.06)
Reference - Am J Cardiol 2011 Sep 15;108(6):851
Other medications for perioperative prevention
ascorbic acid may reduce risk of atrial fibrillation after coronary artery bypass graft (level 2 [mid-
level] evidence)
systematic review of 11 randomized trials evaluating preoperative ascorbic acid (IV or oral
administration) for prevention of atrial fibrillation in 1,390 patients undergoing cardiac surgery
all trials evaluated patients undergoing coronary artery bypass graft (CABG) with or without
valve replacement
ascorbic acid 2 g was given night before CABG in most trials and was continued at dose of
500 mg or 1 g twice daily for 4-5 days after CABG
7 trials evaluated ascorbic acid compared to placebo and 4 trials evaluated ascorbic acid compared
to nonplacebo control
ascorbic acid associated with reduced frequency of postoperative atrial fibrillation (pooled odds
ratio 0.44, 95% CI 0.32-0.61) in pooled analysis of 11 trials
Reference - Am J Health Syst Pharm 2016 Dec 15;73(24):2056
prophylactic metoprolol or losartan may each reduce risk of postoperative atrial fibrillation after
lung cancer surgery in patients with elevated perioperative NT-proBNP levels (level 2 [mid-level]
evidence)
320 patients (mean age 62 years) with elevated perioperative N-terminal pro-brain natriuretic
peptide (NT-proBNP) levels having lung cancer surgery were randomized to 1 of 3 groups within 12
hours after surgery
prophylactic metoprolol 25 mg orally twice daily, then increased to 100 mg twice daily
prophylactic losartan 12.5 mg orally twice daily, then increased to 50 mg/day
no treatment (control)
1.6% discontinued treatment and were excluded from analyses
more patients in losartan (64%) and control (61%) groups were current or past smokers at baseline
than in metoprolol group (49%, p = 0.06 among groups)
6% with metoprolol (p < 0.001 vs. control, NNT 3) (not significant vs. losartan, but trial not
powered to detect differences between treatments)
12% with losartan (p < 0.001 vs. control, NNT 4)
87/105
40% with control

patients in control group had longer mean postoperative length of stay (8.6 days) than metoprolol
(6.8 days) or losartan (7.2 days) groups (p = 0.019 among groups)
no significant differences among groups in risk of postoperative complications, but cumulative risk
was highest in control group
in subgroup analyses, patients with high preoperative NT-proBNP levels had higher risk of atrial
fibrillation compared to patients with high postoperative NT-proBNP levels (p < 0.001)
Reference - PRESAGE trial ( Ann Surg 2016 Aug;264(2):244)
postoperative colchicine may reduce risk of atrial fibrillation after cardiac surgery (level 3 [lacking
direct] evidence)
based on nonclinical outcome in substudy of COPPS randomized trial
360 patients on third day after cardiac surgery randomized to colchicine vs. placebo
colchicine dosing was 1 mg twice daily on postoperative day 3, then 0.5 mg twice daily for 1
month in patients ≥ 70 kg (154 lbs)
doses reduced by 50% for patients < 70 kg (154 lbs) or intolerant to highest dose
24 patients with chronic preoperative atrial fibrillation or persistent postoperative atrial fibrillation
at start of study drug were excluded from analysis
comparing colchicine vs. placebo
postoperative atrial fibrillation in 12% vs. 22% (p = 0.021, NNT 10)
death or stroke in 1.2% vs. 1.2% (not significant)
gastrointestinal side effects in 9.5% vs. 4.2% (p = 0.082)
drug withdrawal in 11.8% vs. 6.6% (not significant)
mean hospital stay (in-hospital and rehabilitation) 21.4 days vs. 24.2 days (p = 0.03)
mean rehabilitation stay 12.1 days vs. 13.9 days (p = 0.009)
Reference - Circulation 2011 Nov 22;124(21):2290 full-text, editorial can be found in Circulation
2011 Nov 22;124(21):2281 full-text
N-acetylcysteine (NAC)
perioperative N-acetylcysteine may decrease risk of postoperative atrial fibrillation during
hospitalization (level 3 [lacking direct] evidence)
based on randomized trial without clinical outcomes
115 adults (mean age 58 years) had primary coronary artery and/or valve surgery randomized
to IV NAC 50 mg/kg for 1 hour preoperatively and NAC 50 mg/kg daily for 48 hours
postoperatively vs. saline placebo
comparing NAC vs. placebo
atrial fibrillation developed in 5.1% vs. 21.1% (p = 0.019, NNT 7)
mean hospitalization days 7.7 vs. 7.9 (not significant)
Reference - Eur Heart J 2008 Mar;29(5):625 full-text
addition of NAC to carvedilol may reduce postoperative atrial fibrillation compared to beta
blocker alone (level 3 [lacking direct] evidence)
based on randomized trial without clinical outcomes
311 patients (mean age 63 years) having cardiac bypass surgery randomized to NAC plus
carvedilol vs. carvedilol alone vs. metoprolol alone
NAC 50 mg/kg IV given 1 hour prior to surgery continued for 48 hours after surgery
carvedilol 6.25 mg twice daily for 7 days
metoprolol 50 mg/day for 7 days and titrated as tolerated
35.9% with metoprolol
24% with carvedilol
8.7% with NAC plus carvedilol (p < 0.001, NNT 4 compared to metoprolol; p < 0.03,
NNT 7 compared to carvedilol)
NAC plus carvedilol associated with decreased hospital stay compared to metoprolol
(difference of 2 days, p = 0.004)
Reference - Eur Heart J 2013 Feb;34(8):597
88/105
sodium nitroprusside may reduce incidence and duration of atrial fibrillation following coronary
artery bypass graft (level 3 [lacking direct] evidence)
based on nonclinical outcome from randomized trial with allocation concealment and method of
randomization not described
100 consecutive patients having elective initial CABG surgery randomized to sodium nitroprusside
during postoperative rewarming vs. placebo
patients excluded if having other surgery in addition to CABG
sodium nitroprusside initially 0.5 mcg/kg/minute and titrated to maintain arterial pressure about 65
mm Hg for 1 hour
comparing sodium nitroprusside vs. placebo at 5 days postoperatively
atrial fibrillation in 12% vs. 36% (p = 0.005, NNT 5)
mean duration of atrial fibrillation 5.33 hours vs. 7.55 hours in 24 patients with atrial
fibrillation (p = 0.023)
mean hospital stay 7.3 days vs. 9.1 days (p < 0.001)
no myocardial infarction or death in either group
Reference - Circulation 2008 Jul 29;118(5):476
low-dose IV atrial natriuretic peptide may reduce postoperative atrial fibrillation in patients with
non-small cell lung cancer and elevated B-type natriuretic peptide levels having pulmonary
resection (level 3 [lacking direct] evidence)
based nonclinical outcome in small randomized trial
40 patients with non-small cell lung cancer and B-type natriuretic peptide ≥ 30 pg/mL having
pulmonary resection were randomized to atrial natriuretic peptide 0.025 mg/kg/minute IV (without
bolus) vs. placebo for 3 days
postoperative atrial fibrillation in 10% for atrial natriuretic peptide vs. 60% for placebo (p < 0.001,
NNT 2)
Reference - J Thorac Cardiovasc Surg 2012 Feb;143(2):488
perioperative vitamin C may not prevent atrial fibrillation in patients having coronary artery
bypass graft (level 3 [lacking direct] evidence)
based on nonclinical outcome in randomized trial with baseline differences
198 patients (mean age 63 years) having coronary artery bypass graft randomized to perioperative
vitamin C vs. placebo
vitamin C given as 2 g orally evening before surgery followed by 1 g orally or enterally twice daily
for 5 days postoperatively
at baseline, fewer patients in vitamin C group were Caucasian (p = 0.011), smokers (p = 0.082), or
taking angiotensin-converting enzyme inhibitors (p = 0.081)
atrial fibrillation in 30.3% with vitamin C vs. 30.2% with placebo (not significant)
no significant differences in mortality, atrial flutter without atrial fibrillation, cardioversion, cardiac
arrest, stroke, sepsis, or hospital stay
Reference - Am J Surg 2012 Dec;204(6):862
Nonpharmacologic interventions for perioperative prevention
nonpharmacologic interventions that may reduce postoperative atrial fibrillation after heart
surgery include atrial pacing and posterior pericardiotomy (level 2 [mid-level] evidence)
based on Cochrane review limited by heterogeneity
systematic review of 118 randomized trials evaluating interventions for prevention of postoperative
heart surgeries included CABG and valvular and combined procedures with or without
cardiopulmonary bypass
data not available to distinguish between symptomatic and asymptomatic atrial fibrillation
nonpharmacologic interventions associated with reduced postoperative atrial fibrillation or
supraventricular tachycardia compared to control include
89/105
atrial pacing in analysis of 21 trials with 2,933 adults, results limited by significant
heterogeneity
odds ratio (OR) 0.47 (95% CI 0.36-0.61)
group
posterior pericardiotomy in analysis of 6 trials with 763 adults, results limited by
heterogeneity
OR 0.35 (95% CI 0.18-0.67)
group
Screening
screening for atrial fibrillation is most often performed to detect silent atrial fibrillation before symptom
onset in community-dwelling older persons and to detect atrial fibrillation in patients with recent stroke
indications for screening
in community-dwelling older persons
opportunistic screening for atrial fibrillation is recommended in patients ≥ 65 years old using
pulse-taking or electrocardiogram (ECG) (ESC Class I, Level B)
consider systematic ECG screening to detect atrial fibrillation in patients > 75 years old or at
high risk for stroke (ESC Class IIb, Level B)
in patients with stroke
screening for atrial fibrillation recommended in patients with ischemic stroke or transient
ischemic attack using short-term ECG followed by continuous ECG monitoring for ≥ 72
hours (ESC Class I, Level B)
additional ECG monitoring by long-term noninvasive ECG monitors or implanted loop
recorders suggested to document silent atrial fibrillation (ESC Class IIa, Level B)
in patients with pacemakers or implantable cardioverter-defibrillators (ESC Class I, Level B)
regular device interrogation recommended for atrial high-rate episodes
if atrial high-rate episode detected, monitor with ECG monitoring to document atrial
fibrillation before starting therapy (ECG monitoring may include resting ECG, ambulatory
ECG monitoring, patient-operated ECG devices, or reviewing ECG recorded on pacemaker or
implantable cardioverter-defibrillator if available)
screening yield depends on population screened, duration of screening, and method of screening
previously unknown atrial fibrillation detected on screening with ECG or pulse palpation in
ambulatory adults in 1% overall and 1.4% in patients ≥ 65 years old
during poststroke or transient ischemic attack cardiac monitoring phases, atrial fibrillation detected
in about 24%
subclinical atrial tachyarrhythmias detected on implanted pacemaker or defibrillator in 10.1% of
patients ≥ 65 years old with hypertension
subclinical atrial fibrillation detection rate on implantable cardiac monitor 34.4% per year in
patients ≥ 65 years old with risk factors for atrial fibrillation
screening performance
effect on clinical outcomes
remote electrocardiographic screening performed twice weekly does not reduce mortality or
embolic events, but helps identify incident atrial fibrillation in older patients at risk for stroke
(level 1 [likely reliable] evidence)
anticoagulation therapy based on remote rhythm monitoring may not reduce composite
outcome of stroke, systemic embolism, or major bleeding compared to anticoagulation based
on usual office-based follow-up in patients with implanted defibrillators (level 2 [mid-level]
evidence)
systematic and opportunistic screening each may modestly increase detection of new cases of atrial
fibrillation in older adults in primary care (level 1 [likely reliable] evidence)
90/105
10-day enhanced and prolonged Holter monitoring may increase detection rate of atrial fibrillation
compared to standard care following ischemic stroke (level 2 [mid-level] evidence)
see atrial fibrillation screening for details

CHADS2 and CHA2DS2-VASc score for identifying patients at risk for stroke
higher CHADS 2 score may help identify patients with increased risk of new-onset or
recurrent atrial fibrillation (level 2 [mid-level] evidence)
systematic review of 16 cohort and 3 case-control studies evaluating association between
CHADS2 score and risk of new-onset or recurrent atrial fibrillation in 714,672 patients
patient populations varied by study in age, history of and treatment for atrial fibrillation,
stroke, and other cardiovascular disease, comorbidities including hypertension and diabetes
mellitus, and follow-up duration (range 5 days to 9 years)
higher CHADs 2 score associated with increased risk of new-onset or recurrent atrial
fibrillation, results limited by significant heterogeneity
with CHADs 2 as continuous variable (odds ratio 1.43, 95% CI 1.1-1.86) in analysis of
12 studies with 709,972 patients, results limited by significant heterogeneity
with CHADs 2 as categorical variable (odds ratio 3.37, 95% CI 2.65-4.28) in analysis of
9 studies with 7,067 patients
consistent results in analyses of studies by patient population, including post-myocardial
infarction (2 studies), catheter ablation (2 studies), pacemaker (2 studies), and cardiac surgery
(2 studies)
Reference - Am J Cardiol 2015 Aug 15;116(4):554
increasing CHA2DS2-VASc score associated with increasing risk for incident atrial fibrillation
in patients with ischemic stroke and no history of atrial fibrillation
240,459 adults (mean age 71 years) with acute ischemic stroke and without atrial fibrillation
at baseline were evaluated for risk of incident atrial fibrillation
6% of patients were diagnosed with atrial fibrillation during mean follow-up of 7.9 years
annual incidence rate for atrial fibrillation in patients with ischemic stroke was 8.9 per 100
person-years
increasing CHA2DS2-VASc score associated with increased risk of new-onset atrial
fibrillation (hazard ratio 1.43, 95% CI 1.41-1.45)
Quality Improvement
Physician Quality Reporting System Quality Measures
326. Atrial Fibrillation and Atrial Flutter: Chronic Anticoagulation Therapy

Percentage of patients ≥ 18 years old with a diagnosis of nonvalvular atrial fibrillation (AF) or atrial
flutter whose assessment of specified thromboembolic risk factors indicate ≥ 1 high-risk factors or >
1 moderate risk factor, as determined by CHADS2 risk stratification, who are prescribed warfarin
OR another oral anticoagulant drug that is FDA approved for the prevention of thromboembolism
392. HRS-12: Cardiac Tamponade and/or Pericardiocentesis Following Atrial Fibrillation Ablation
Rate of cardiac tamponade and/or pericardiocentesis following atrial fibrillation ablation. This
measure is reported as four rates stratified by age and gender. Reporting Age Criteria:
Females 18-64 years old
Males 18-64 years old
Females ≥ 65 years old
91/105
Males ≥ 65 years old
see Physician Quality Reporting System Quality Measures for additional information
American College of Cardiology (ACC)/American Heart Association (AHA) Performance

Measures
ACC/AHA 2016 clinical performance measures for adults with nonvalvular atrial fibrillation or atrial
flutter can be found in
J Am Coll Cardiol 2016 Aug 2;68(5):525 full-text
Circ Cardiovasc Qual Outcomes 2016 Jul;9(4):443
Quality and Outcomes Framework Indicators
AF1. Contractor establishes and maintains register of patients with atrial fibrillation
AF6 (NM81). Percentage of patients with atrial fibrillation in whom stroke risk has been assessed using
CHADS2-VASc score risk stratification scoring system in preceding 12 months (excluding patients with
previous CHADS2 or CHADS2-VASc score of ≥ 2)
AF7 (NM82). Percentage of patients with atrial fibrillation with record of CHADS2-VASc score ≥ 2,
currently treated with anticoagulation drug therapy
see Quality and Outcomes Framework Indicators for additional information
Guidelines and Resources

Guidelines
International guidelines
European Heart Rhythm Association/European Association of Cardiovascular Prevention and

Rehabilitation (EHRA/EACPR) position paper on how to prevent atrial fibrillation endorsed by Heart
Rhythm Society (HRS) and Asian Pacific Heart Rhythm Society (APHRS) can be found in Europace 2017
Feb 1;19(2):190 full-text
Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society/Asia

Pacific Heart Rhythm Society/Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología
(HRS/EHRA/ECAS/APHRS/SOLAECE) expert consensus statement on catheter and surgical ablation of
atrial fibrillation can be found in Europace 2018 Jan 1;20(1):e1 full-text or in Heart Rhythm 2017
Oct;14(10):e275 full-text, executive summary can be found in Europace 2018 Jan 1;20(1):157, J Arrhythm
2017 Oct;33(5):369 full-text, J Interv Card Electrophysiol 2017 Oct;50(1):1 full-text
previous version can be in Heart Rhythm 2012 Apr;9(4):632, also published in Europace 2012
Apr;14(4):528 full-text
2016 North American expert consensus on antithrombotic therapy in patients with atrial fibrillation
undergoing percutaneous coronary intervention can be found in Circ Cardiovasc Interv 2016
Nov;9(11):e004395
previous version can be found in Thromb Haemost 2011 Oct;106(4):572, editorial can be found in
Thromb Haemost 2011 Oct;106(4):569, executive summary can be found in Circ Cardiovasc Interv
2011 Oct 1;4(5):522 full-text
92/105
United States guidelines
Society of Thoracic Surgeons (STS) 2017 clinical practice guideline on surgical treatment of atrial
fibrillation can be found in Ann Thorac Surg 2017 Jan;103(1):329 PDF

focused update of 2014 guideline on management of patients with atrial fibrillation can be found in
Circulation 2019 Jan 28 early online, Heart Rhythm 2019 Jan 28 early online, or in J Am Coll
Cardiol 2019 Jan 21 early online
guideline on management of patients with atrial fibrillation can be found in Circulation 2014 Dec
2;130(23):e199 full-text or in J Am Coll Cardiol 2014 Dec 2;64(21):e1 full-text, corrections can be
found in Circulation 2014 Dec 2;130(23):e272 and in J Am Coll Cardiol 2014 Dec 2;64(21):2305
previous 2013 ACC/AHA/HRS version can be found in Circulation 2013 May
7;127(18):1916
previous 2011 ACC/AHA/HRS version can be found in Circulation 2011 Jan 4;123(1):104,
Circulation. 2011 Aug 2;124(5):e173
previous 2006 ACC/AHA version (with ESC) can be found in Circulation 2006 Aug
15;114(7):e257 full-text, correction can be found in Circulation 2007 Aug 7;116(6):e138
American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines for
Antithrombotic Therapy and Prevention of Thrombosis (Ninth Edition) guideline and expert panel report
on antithrombotic therapy for atrial fibrillation can be found in Chest 2018 Nov;154(5):1121
American Heart Association/American Stroke Association (AHA/ASA) guideline on prevention of stroke

in patients with stroke or transient ischemic attack can be found in Stroke 2014 Jul;45(7):2160, correction
can be found in Stroke 2015 Feb;46(2):e54, commentary can be found in Stroke 2015 Apr;46(4):e85
American Academy of Neurology (AAN) summary of evidence-based guideline update on prevention of

stroke in nonvalvular atrial fibrillation can be found in Neurology 2014 Feb 25;82(8):716 full-text,
correction can be found in Neurology 2014 Apr 22;82(16):1481
American Academy of Family Physicians (AAFP) guideline on pharmacologic management of newly

detected atrial fibrillation can be found in Am Fam Physician 2017 Sep 1;96(5):332
American Heart Association/American College of Cardiology (AHA/ACC) scientific statement on

competitive athletes with cardiovascular abnormalities (Task Force 9): arrhythmias and conduction defects
can be found in Circulation 2015 Dec 1;132(22):e315 full-text or in J Am Coll Cardiol 2015 Dec
1;66(21):2412 full-text
American Heart Association/American College of Cardiology (AHA/ACC) 2015 recommendations for

preparticipation screening for cardiovascular abnormalities in competitive athletes can be found in
Circulation 2015 Dec 1;132(22):e267 full-text or in J Am Coll Cardiol 2015 Dec 1;66(21):2356 full-text
North American Thrombosis Forum (NATF) action initiative consensus document on atrial fibrillation can
be found in Am J Med 2016 May;129(5 Suppl):S1
University of Michigan Health System (UMHS) guideline on management of acute atrial fibrillation and
atrial flutter in nonpregnant hospitalized adults can be found at UMHS 2014 May PDF
American College of Cardiology/American Heart Association/American Academy of Physician

Assistants/Association of Black Cardiologists/American College of Preventive Medicine/American
Geriatrics Society/American Pharmacists Association/American Society of Hypertension/American
Society for Preventive Cardiology/National Medical Association/Preventive Cardiovascular Nurses
Association (ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA) guideline on
93/105
prevention, detection, evaluation, and management of high blood pressure in adults can be found in
Hypertension 2018 Jun;71(6):e13
updated guideline on device-based therapy of cardiac rhythm abnormalities can be found in Circulation
2013 Jan 22;127(3):e283 full-text or in J Am Coll Cardiol 2013 Jan 22;61(3):e6 full-text, original 2008
version can be found in Circulation 2008 May 27;117(21):e350 full-text, correction can be found in
Circulation 2009 Aug 4; 120(5):e34
American College of Cardiology/American Heart Association (ACC/AHA) updated clinical competence
statement on invasive electrophysiological studies, catheter ablation, and cardioversion can be found in
Heart Rhythm 2016 Jan;13(1):e3, J Am Coll Cardiol 2015 Dec 22;66(24):2767 full-text or in Circ
Arrhythm Electrophysiol 2015 Dec;8(6):1522 full-text, previous version can be found in Circulation 2006
Oct 10;114(15):1654 PDF
American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society

(AHA/ACCF/HRS) recommendations and scientific statements on standardization and interpretation of
electrocardiograms (ECGs)
review of ECG technology and improving accuracy and clinical utility in practice can be found in J
Am Coll Cardiol 2007 Mar 13;49(10):1109, Heart Rhythm 2007 Mar;4(3):394 or in Circulation
2007 Mar 13;115(10):1306 full-text
statement on diagnostic terms for ECG interpretation can be found in J Am Coll Cardiol 2007 Mar
13;49(10):1128, Heart Rhythm 2007 Mar;4(3):413 or in Circulation 2007 Mar 13;115(10):1325 full-
text
statement on intraventricular conduction disturbances can be found in J Am Coll Cardiol 2009 Mar
17;53(11):976 or in Circulation 2009 Mar 17;119(10):e235 full-text
statement on T segment, T and U waves, and QT interval can be found in J Am Coll Cardiol 2009
Mar 17;53(11):982 or in Circulation 2009 Mar 17;119(10):e241 full-text
statement on ECG changes associated with cardiac chamber hypertrophy can be found in J Am Coll
Cardiol 2009 Mar 17;53(11):992 or in Circulation 2009 Mar 17;119(10):e251 full-text
statement on acute ischemia/infarction can be found in J Am Coll Cardiol 2009 Mar 17;53(11):1003
or in Circulation 2009 Mar 17;119(10):e262 full-text
American Heart Association (AHA) scientific statement on sexual activity and cardiovascular disease can
be found in Circulation 2012 Feb 28;125(8):1058 full-text, commentary can be found in Eur Urol 2012
Aug;62(2):349
American Heart Association/European Society of Cardiology (AHA/ESC) consensus document on sexual
counseling for individuals with cardiovascular disease and their partners can be found in Circulation 2013
Oct 29;128(18):2075 full-text
United Kingdom guidelines
Royal College of Physicians of Edinburgh (RCPE) consensus statement on approaching comprehensive

management of atrial fibrillation can be found in Expert Rev Cardiovasc Ther 2012 Jun;10(6):697
National Institute for Health and Care Excellence (NICE) guideline on management of atrial fibrillation
can be found at NICE 2014 Jun:CG180 PDF, summary can be found in BMJ 2014 Aug 5;348:g3655,
correction can be found in BMJ 2014;349:g4440
National Institute for Health and Care Excellence (NICE) quality standard on atrial fibrillation can be
found at NICE 2018 Feb:QS93 PDF
National Institute for Health and Care Excellence (NICE) guidance on

edoxaban for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation
can be found at NICE 2015 Sep 23:TA355 PDF
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apixaban for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation
can be found at NICE 2013 Feb 27:TA275 PDF
National Institute of Health and Care Excellence (NICE) guidance on dabigatran etexilate for prevention
of stroke and systemic embolism in atrial fibrillation can be found at NICE 2012 Mar:TA249 PDF
National Institute of Health and Care Excellence (NICE) guidance on rivaroxaban for preventing stroke
and systemic embolism in people with atrial fibrillation can be found at NICE 2012 May 23:TA256 PDF
National Institute of Health and Clinical Excellence (NICE) guidance on dronedarone for nonpermanent
atrial fibrillation can be found at NICE 2012 Dec:TA197 PDF
National Institute of Health and Clinical Excellence (NICE) guidance on percutaneous endoscopic laser
balloon pulmonary vein isolation for atrial fibrillation can be found at NICE 2016 Jul:IPG563 PDF
National Institute of Health and Clinical Excellence (NICE) guidance on percutaneous balloon
cryoablation for pulmonary vein isolation in atrial fibrillation can be found at NICE 2012
May:IPG427 PDF
National Institute of Health and Clinical Excellence (NICE) guidance on atrial fibrillation and heart valve
disease: self-monitoring coagulation status using point-of-care coagulometers (CoaguChek XS system)
can be found at NICE 2017 Dec:DG14 PDF
Canadian guidelines
British Columbia Ministry of Health (BCMOH) guidelines on

diagnosis and management of atrial fibrillation can be found at BCMOH 2015 Apr PDF
use of nonvitamin K antagonist oral anticoagulants (NOAC) in nonvalvular atrial fibrillation can be
found at BCMOH 2015 Nov PDF
Canadian Agency for Drugs and Technologies in Health (CADTH) recommendations for antithrombotic
agents for prevention of stroke and systemic embolism in patients with atrial fibrillation can be found at
CADTH 2013 Mar PDF
Canadian Agency for Drugs and Technologies in Health (CADTH) recommendations on new oral
anticoagulants for prevention of thromboembolic events in patients with atrial fibrillation can be found at
CADTH 2012 Jun PDF
Canadian Agency for Drugs and Technologies in Health (CADTH) recommendations on optimal warfarin
management for prevention of thromboembolic events in patients with atrial fibrillation can be found at
CADTH 2011 Nov PDF
Canadian Cardiovascular Society (CCS)

focused 2018 update of CCS atrial fibrillation guideline: management of atrial fibrillation can be
found in Can J Cardiol 2018 Nov;34(11):1371
found in Can J Cardiol 2016 Oct;32(10):1170
found in Can J Cardiol 2014 Oct;30(10):1114, corrections can be found in Can J Cardiol 2014
Dec;30(12):1495 and Can J Cardiol 2015 Oct;31(10):1302
focused 2012 update of CCS atrial fibrillation guideline: recommendations on stroke prevention and
rate/rhythm control can be found in Can J Cardiol 2012 Mar-Apr;28(2):125, correction can be found
in Can J Cardiol 2012 May;28(3):396
CCS 2010 atrial fibrillation guidelines on
etiology and initial investigations can be found in Can J Cardiol 2011 Jan-Feb;27(1):31
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management of recent-onset atrial fibrillation and flutter in emergency department can be

found in Can J Cardiol 2011 Jan-Feb;27(1):38, correction can be found in Can J Cardiol 2012
Mar-Apr;28(2):244
rate and rhythm management can be found in Can J Cardiol 2011 Jan-Feb;27(1):47,
correction can be found in Can J Cardiol 2011 May-Jun;27(3):388
catheter ablation for atrial fibrillation/atrial flutter can be found in Can J Cardiol 2011 Jan-
Feb;27(1):60
surgical therapy can be found in Can J Cardiol 2011 Jan-Feb;27(1):67
prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter can be
found in Can J Cardiol 2011 Jan-Feb;27(1):74
prevention and treatment of atrial fibrillation following cardiac surgery can be found in Can J
Cardiol 2011 Jan-Feb;27(1):91
Canadian Cardiovascular Society consensus conference on management of heart disease in the elderly
patient can be found in Can J Cardiol 2004 May;20 Suppl A:7A or at CCS 2002 PDF
Canadian Stroke Network/Heart and Stroke Foundation of Canada best practice recommendations on
secondary prevention of stroke can be found at Canadian Stroke Best Practices 2017 PDF
European guidelines
Italian Association of Arrhythmology and Cardiac Pacing (AIAC) guideline on management and
treatment of atrial fibrillation can be found in G Ital Cardiol (Rome) 2011 Jan;12(1 Suppl 1):7 [Italian]
European Society of Cardiology (ESC) guideline on management of atrial fibrillation can be found in Eur
J Cardiothorac Surg 2016 Nov;50(5):e1 or in Europace 2016 Nov;18(11):1609
ESC Working Group on Thrombosis expert consensus on management of antithrombotic therapy after
bleeding in patients with coronary artery disease and/or atrial fibrillation can be found in Eur Heart J 2017
May 14;38(19):1455 full-text
European Society of Cardiology/European Association of Percutaneous Cardiovascular

Interventions/Acute Cardiovascular Care Association (ESC/EAPCI/ACCA) consensus guideline on
management of antithrombotic therapy in patients with atrial fibrillation presenting with acute coronary
syndrome and/or undergoing percutaneous coronary intervention can be found in Eur Heart J 2014 Dec
1;35(45):3155, commentary can be found in Europace 2015 Sep;17(9):1319
European Heart Rhythm Association/ESC Working Group on Thrombosis consensus on antithrombotic

therapy in atrial fibrillation associated with valvular heart disease can be found in Europace 2017 Nov
1;19(11):1757 full-text, executive summary can be found in Thromb Haemost 2017 Dec;117(12):2215
European Heart Rhythm Association (EHRA) position document on bleeding risk assessment and
management in atrial fibrillation patients can be found in Europace 2011 May;13(5):723
EHRA consensus statement on screening for atrial fibrillation can be found in Europace 2017 Oct
1;19(10):1589 full-text
EHRA updated practical guide on use of non-vitamin K antagonist anticoagulants in patients with
nonvalvular atrial fibrillation can be found in Eur Heart J 2018 Apr 21;39(16):1330 full-text
EHRA practice guideline on indications and use of diagnostic implantable and external ECG loop
recorders can be found in Europace 2009 May;11(5):671 full-text, correction can be found in Europace
2009 Jun;11(6):836, commentary can be found in Europace 2009 Nov;11(11):1566 full-text
European Association of Cardiovascular Imaging/European Heart Rhythm Association (EACVI/EHRA)
expert consensus statement on role of multimodality imaging for evaluation of patients with atrial
fibrillation can be found in Eur Heart J Cardiovasc Imaging 2016 Apr;17(4):355 full-text
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European Heart Rhythm Association/European Association of Percutaneous Coronary Interventions

(EHRA/EAPCI) expert consensus statement on catheter-based left atrial appendage occlusion can be
found in EuroIntervention 2015 Jan;10(9):1109 or in Europace 2014 Oct;16(10):1397 full-text,
commentary can be found in Europace 2015 Dec;17(12):1880
Atrial Fibrillation Competence NETwork/European Heart Rhythm Association (AFNET/EHRA)
consensus conference report on improving quality of atrial fibrillation management can be found in
Europace 2016 Jan;18(1):37 full-text
AFNET/EHRA consensus conference report on comprehensive risk reduction in patients with atrial
fibrillation can be found in Europace 2012 Jan;14(1):8, executive summary can be found in Thromb
Haemost 2011 Dec;106(6):1012
European Heart Rhythm Association/European Association for Cardiovascular Prevention and
Rehabilitation (EHRA/EACPR) position statement on preparticipation cardiovascular evaluation for
athletic participants to prevent sudden death can be found in Europace 2017 Jan;19(1):139 full-text or in
Eur J Prev Cardiol 2017 Jan;24(1):41
Italian Federation of Thrombosis Centers (Federazione Centri per la diagnosi della trombosi e la
Sorveglianza delle terapie Antitrombotiche [FCSA]) consensus report on questions and answers on use of
dabigatran and perspectives on use of other new oral anticoagulants in patients with atrial fibrillation can
be found in Thromb Haemost 2011 Nov;106(5):868
Italian Federation of Thrombosis Centers/ Society for the Study of Haemostasis and Thrombosis
(Federazione Centri per la diagnosi della trombosi e la Sorveglianza delle terapie Antitrombotiche/Società
Italiana per lo Studio dell’Emostasi e della Trombosi [FCSA/SISET]) recommendations on use of
dabigatran (Pradaxa) can be found at FCSA 2013 PDF [Italian]
Asian guidelines
Taiwan Heart Rhythm Society/Taiwan Society of Cardiology guideline on management of atrial

fibrillation can be found in J Formos Med Assoc 2016 Nov;115(11):893 full-text
Japanese Circulation Society (JCS) 2013 guideline on pharmacotherapy of atrial fibrillation can be found
at JCS 2013 PDF [Japanese 日本語], short version can be found in Circ J 2014;78(8):1997 full-text
[English]
Japanese Circulation Society (JCS) guideline on drug treatment of arrhythmias can be found at JCS 2009
PDF [Japanese 日本語]
Japanese Circulation Society (JCS) guideline on nonpharmacological therapy of cardiac arrhythmias can
be found at JCS 2011 PDF [Japanese 日本語], short version can be found in Circ J 2013;77(1):249 PDF
[English]
Japanese Circulation Society (JCS) guideline on catheter ablation adaptation and procedure can be found
at JCS 2012 PDF [Japanese 日本語]
Australian and New Zealand guidelines
National Heart Foundation of Australia (NHFA) and Cardiac Society of Australia and New Zealand
(CSANZ) guideline on diagnosis and management of atrial fibrillation can be found in Heart Lung Circ
2018 Oct;27(10):1209 full-text
Middle Eastern guidelines
Oman Heart Association protocol on management of acute atrial fibrillation can be found in Crit Pathw
Cardiol 2014 Sep;13(3):117
Quality indicators
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21 quality indicators for care of atrial fibrillation in vulnerable elders can be found in J Am Geriatr Soc
2007 Oct;55 Suppl 2:S431
Review articles
reviews can be found in
Heart 2018 Jun;104(11):882
Am Fam Physician 2016 Sep 15;94(6):442
BMJ 2013 Jun 17;346:f3719
Lancet 2012 Feb 18;379(9816):648
BMJ 2009 Dec 23;339:b5216, commentary can be found in BMJ 2010 Jan 19;340:c285
American Heart Association scientific statement about defining and measuring atrial fibrillation burden
and its relationship to cardiovascular and neurological outcomes can be found in Circulation 2018 May
15;137(20):e623
review of atrial fibrillation in intensive care unit can be found in Chest 2018 Apr 5 early online
reviews on risk factors and associated conditions
review of obesity and atrial fibrillation prevalence, pathogenesis, and prognosis: effects of weight
loss and exercise can be found in J Am Coll Cardiol 2017 Oct 17;70(16):2022
review of modifiable risk factors and atrial fibrillation can be found in Circulation 2017 Aug
8;136(6):583
reviews of genetics in atrial fibrillation
review of genomic basis of atrial fibrillation can be found in Heart 2018 Feb;104(3):201
review of gene therapy approaches for treating atrial fibrillation can be found in J Am Coll Cardiol
2017 Apr 25;69(16):2088
review of clinical applications of biomarkers in atrial fibrillation can be found in Am J Med 2017
Dec;130(12):1351
reviews on treatment
review of treatment of atrial fibrillation can be found in JAMA 2015 Jul 21;314(3):278
review of treatment of atrial fibrillation can be found in Med Lett Drugs Ther 2014 Jul
7;56(1446):53
review of anticoagulation and invasive management strategies can be found in Mayo Clin Proc 2009
Jul;84(7):643
review with focus on invasive treatments for atrial fibrillation can be found in Adv Stud Med 2006
Jun;6(6):275 PDF
review of surgical treatment of atrial fibrillation can be found in World J Surg 2008 Mar;32(3):346
review of management of atrial fibrillation can be found in Lancet 2007 Aug 18;370(9587):604,
commentary can be found in Lancet 2007 Nov 10;370(9599):1607
review of rate and rhythm control in atrial fibrillation can be found in Nat Clin Pract Cardiovasc
Med 2005 Oct;2(10):514
review of nonpharmacological therapies for atrial fibrillation can be found in Cardiovasc Ther 2010
Oct;28(5):264
reviews of thrombogenesis and thromboembolic prophylaxis in atrial fibrillation
review of mechanisms of thrombogenesis in atrial fibrillation can be found in Lancet 2009 Jan
10;373(9658):155, commentary can be found in Lancet 2009 Mar 21;373(9668):1005
review of thromboembolic prophylaxis in atrial fibrillation atrial can be found in Stroke 2011
Nov;42(11):3316 full-text
review from perspective of patients, physicians, and society on stroke prevention in nonvalvular atrial
fibrillation can be found in J Am Coll Cardiol 2018 Jun 19;71(24):2790
review of the overlap between atrial fibrillation and geriatric syndromes such as impaired physical
function, polypharmacy, and falls can be found in J Am Med Dir Assoc 2018 Sep 27;:
case reports
case presentation and review of rapid irregular rhythm in a healthy, young patient: how fast can you
go? can be found in JAMA Intern Med 2018 Jan 1;178(1):138
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case presentation of catheter ablation for atrial fibrillation can be found in N Engl J Med 2011 Dec
15;365(24):2296
case report of atrial fibrillation in pregnancy can be found in Obstet Gynecol 2011 Feb;117(2 Pt
2):489
case report of bleeding events in 2 elderly women taking dabigatran for atrial fibrillation can be
found in Arch Intern Med 2011 Jul 25;171(14):1285, commentary can be found in Arch Intern Med
2011 Jul 25;171(14):1287
MEDLINE search
to search MEDLINE for (Atrial fibrillation) with targeted search (Clinical Queries), click therapy,
diagnosis, or prognosis
Patient Decision Aids

interactive clinician and patient decision aid for starting anticoagulant medication for patients with atrial
fibrillation can be found at HealthDecision
Patient Information
handouts from EBSCO Health Library on
atrial fibrillation or in Spanish
arrhythmia or in Spanish
ambulatory cardiac monitoring or in Spanish
electrocardiogram or in Spanish
handouts from American Heart Association on
atrial fibrillation PDF or in Spanish
atrial fibrillation in children
handout from American College of Cardiology
handouts from Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) on
atrial fibrillation in English PDF or in German PDF
atrial fibrillation and preventing strokes in English PDF or in German PDF
handout on arrhythmia from American Academy of Family Physicians or in Spanish
ICD Codes
ICD-10 codes
I48 atrial fibrillation and flutter

I48.0 paroxysmal atrial fibrillation
I48.1 persistent atrial fibrillation
I48.2 chronic atrial fibrillation
I48.3 typical atrial flutter
I48.4 atypical atrial flutter
I48.91 unspecified atrial fibrillation
References
General references used
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1. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of
Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for
Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients
With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the
Heart Rhythm Society. Circulation. 2006 Aug 15;114(7):e257-354 full-text, correction can be found in
Circulation 2007 Aug 7;116(6):e138
2. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation
developed in collaboration with EACTS. Europace. 2016 Nov;18(11):1609-1678
3. Healey JS, Parkash R, Pollak T, Tsang T, Dorian P; CCS Atrial Fibrillation Guidelines Committee.
Canadian Cardiovascular Society atrial fibrillation guidelines 2010: etiology and initial investigations.
Can J Cardiol. 2011 Jan-Feb;27(1):31-7
4. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of
Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2014 Dec
2;130(23):e199-267 PDF, also published in J Am Coll Cardiol 2014 Dec 2;64(21):e1, corrections can be
found in Circulation 2014 Dec 2;130(23):e272 and J Am Coll Cardiol 2014 Dec 2;64(21):2305
Recommendation grading systems used

American College of Cardiology/American Heart Association (ACC/AHA) 2017 grading system for
recommendations
classifications of recommendations
Class I - procedure or treatment should be performed or administered
Class IIa - reasonable to perform procedure or administer treatment, but additional studies
with focused objectives needed
Class IIb - procedure or treatment may be considered; additional studies with broad objectives
needed, additional registry data would be useful
Class III - procedure or treatment should not be performed or administered because it is not
helpful or may be harmful
Class III ratings may be subclassified as Class III No Benefit or Class III Harm
levels of evidence
Level A - high-quality evidence from > 1 randomized controlled trial or meta-analysis of
high-quality randomized controlled trials
Level B-R - moderate-quality evidence from ≥ 1 randomized controlled trial or meta-analysis
of moderate-quality randomized controlled trials
Level B-NR - moderate-quality evidence from ≥ 1 well-designed nonrandomized trial,
observational studies, or registry studies, or meta-analysis of such studies
Level C-LD - randomized or nonrandomized studies with methodological limitations or meta-
analyses of such studies
Level C-EO - consensus of expert opinion based on clinical experience
References
ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline on
prevention, detection, evaluation, and management of high blood pressure in adults
(Hypertension 2018 Jun;71(6):e13)
AHA scientific statement on omega-3 polyunsaturated fatty acid (fish oil) supplementation
and prevention of clinical cardiovascular disease (Circulation 2017 Apr 11;135(15):e867)
American College of Cardiology/American Heart Association (ACC/AHA) grading system prior to 2017
Class I - procedure or treatment should be performed or administered
Class IIa - reasonable to perform procedure or administer treatment, but additional studies
with focused objectives needed
Class IIb - procedure or treatment may be considered; additional studies with broad objectives
needed, additional registry data would be useful
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Class III - procedure or treatment should not be performed or administered because it is not
helpful or may be harmful
Class III ratings may be subclassified as Class III No Benefit or Class III Harm
levels of evidence
Level A - data derived from multiple randomized clinical trials or meta-analyses
Level B - data derived from single randomized trial or nonrandomized studies
Level C - only expert opinion, case studies, or standard of care
References
2014 AHA/ACC/Heart Rhythm Society (HRS) guideline on management of patients with
atrial fibrillation (Circulation 2014 Dec 2;130(23):e199 PDF), also published in J Am Coll
Cardiol 2014 Dec 2;64(21):e1, corrections can be found in Circulation 2014 Dec
2;130(23):e272 and J Am Coll Cardiol 2014 Dec 2;64(21):2305
AHA scientific statement on sexual activity and cardiovascular disease (Circulation 2012 Feb
28;125(8):1058 full-text)
ACC/AHA/European Society of Cardiology (ESC) 2006 guidelines for management of
patients with atrial fibrillation (Circulation 2006 Aug 15;114(7):e257 full-text), correction can
be found in Circulation 2007 Aug 7;116(6):e138
Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society
(HRS/EHRA/ECAS) grading system
Class I - benefits of procedure markedly exceed risks; procedure should be performed
Class IIa - benefits of procedure exceed risks; it is reasonable to perform procedure
Class IIb - benefit of procedure is greater than or equal to risks; procedure may be considered
Class III - procedure is of no proven benefit and is not recommended
levels of evidence
Level A - data derived from multiple randomized clinical trials or meta-analyses (of selected
studies) or selected meta-analyses
Level B - data derived from single randomized trial or nonrandomized studies
Level C - consensus opinion, case studies, or standard of care; or expert consensus and
clinical experience if inadequate data available
Reference - HRS/EHRA/ECAS 2012 expert consensus statement on catheter and surgical ablation
of atrial fibrillation: recommendations for patient selection, procedural techniques, patient
management and follow-up, definitions, endpoints, and research trial design (Europace 2012
Apr;14(4):528 full-text), also published in Heart Rhythm 2012 Apr;9(4):632
European Society of Cardiology (ESC) grading system for recommendations

classes of recommendations
Class I - evidence and/or general agreement that given treatment or procedure is beneficial,
useful, and effective
Class II - conflicting evidence and/or divergence of opinion about usefulness/efficacy of
given treatment or procedure
Class IIa - weight of evidence/opinion in favor of usefulness/efficacy
Class IIb - usefulness/efficacy less well-established by evidence/opinion
Class III - evidence or general agreement that given treatment or procedure is not
useful/effective, and in some cases may be harmful
levels of evidence
Level A - data derived from multiple randomized clinical trials or meta-analyses
Level B - data derived from single randomized trial or large nonrandomized studies
Level C - consensus of opinion of experts and/or small studies, retrospective studies,
registries
References
ESC guideline on diagnosis and management of acute pulmonary embolism (Eur Heart J 2014
Nov 14;35(43):3033 full-text), corrections can be found in Eur Heart J 2015 Oct
101/105
14;36(39):2642 and Eur Heart J 2015 Oct 14;36(39):2666, commentary can be found in Rev
Esp Cardiol (Engl Ed) 2015 Jan;68(1):10
ESC guideline on management of atrial fibrillation (Eur J Cardiothorac Surg 2016
Nov;50(5):e1 full-text)
Canadian Cardiovascular Society (CCS) grading system for recommendations

strength of recommendation
Strong
Conditional (weak)
quality of evidence
High - future research unlikely to change confidence in estimate of effect; multiple well-
designed, well-conducted clinical trials
Moderate - further research likely to have important impact on confidence in estimate of
effect and may change estimate; limited clinical trials, inconsistency of results, or study
limitations
Low - further research very likely to have significant impact on estimate of effect and is likely
to change estimate; small number of clinical studies or cohort observations
Very Low - estimate of effect is very uncertain; case studies or consensus opinion
References
CCS atrial fibrillation guidelines 2010: rate and rhythm management (Can J Cardiol 2011
Jan-Feb;27(1):47, Can J Cardiol 2011 Jan-Feb;27(1):27)
CCS focused 2012 update of atrial fibrillation guidelines: recommendations for stroke
prevention and rate/rhythm control (Can J Cardiol 2012 Mar-Apr;28(2):125)
CCS focused 2014 update of atrial fibrillation guidelines: management of atrial fibrillation
(Can J Cardiol 2014 Oct;30(10):1114)
CCS focused 2016 update on atrial fibrillation guidelines: management of atrial fibrillation
(Can J Cardiol 2016 Oct;32(10):1170)
American College of Chest Physicians (ACCP) grades

Grade 1A - strong recommendation, high-quality evidence
benefits clearly outweigh risk and burdens, or vice versa
consistent evidence from randomized controlled trials without important limitations or
exceptionally strong evidence from observational studies
recommendation can apply to most patients in most circumstances
further research very unlikely to change confidence in estimate of effect
Grade 1B - strong recommendation, moderate-quality evidence
evidence from randomized controlled trials with important limitations (inconsistent results,
methodologic flaws, indirect or imprecise), or very strong evidence from observational
studies
recommendation can apply to most patients in most circumstances
higher-quality research may have important impact on confidence in estimate of effect and
may change estimate
Grade 1C - strong recommendation, low-quality evidence
evidence for ≥ 1 critical outcome from observational studies or case series, or from
randomized, controlled trials with serious flaws or indirect evidence
recommendation can apply to most patients in many circumstances
higher-quality research likely to have important impact on confidence in estimate of effect
and may change estimate
Grade 2A - weak recommendation, high-quality evidence
benefits closely balanced with risks and burdens
consistent evidence from randomized controlled trials without important limitations or
exceptionally strong evidence from observational studies
102/105
best action may differ depending on circumstances or patients' or societal values

further research very unlikely to change confidence in estimate of effect
Grade 2B - weak recommendation, moderate-quality evidence
benefits closely balanced with risks and burdens
evidence from randomized controlled trials with important limitations (inconsistent results,
methodologic flaws, indirect or imprecise) or very strong evidence from observational studies
best action may differ depending on circumstances or patients' or societal values
higher-quality research may have important impact on confidence in estimate of effect and
may change estimate
Grade 2C - weak recommendation, low- or very-low-quality evidence
uncertainty in estimates of benefits, risks, and burdens; benefits, risks, and burdens may be
closely balanced
evidence for ≥ 1 critical outcome from observational studies or case series, or from
randomized controlled trials with serious flaws or indirect evidence
other alternatives may be equally reasonable
higher-quality research likely to have important impact on confidence in estimate of effect
and may change estimate
References
ACCP methodology for development of antithrombotic therapy and prevention of thrombosis
guidelines (Chest 2012 Feb;141(2 Suppl):53S full-text), commentary can be found in Chest
2013 Apr;143(4):1190
ACCP Evidence-Based Clinical Practice Guidelines for Antithrombotic Therapy and
Prevention of Thrombosis (Ninth Edition) recommendations on antithrombotic therapy for
atrial fibrillation (Chest 2012 Feb;141(2 Suppl):e531S full-text)
Synthesized Recommendation Grading System for DynaMed Plus

DynaMed systematically monitors clinical evidence to continuously provide a synthesis of the most valid
relevant evidence to support clinical decision-making (see 7-Step Evidence-Based Methodology).
Guideline recommendations summarized in the body of a DynaMed topic are provided with the
recommendation grading system used in the original guideline(s), and allow DynaMed users to quickly see
where guidelines agree and where guidelines differ from each other and from the current evidence.
In DynaMed Plus (DMP), we synthesize the current evidence, current guidelines from leading authorities,
and clinical expertise to provide recommendations to support clinical decision-making in the Overview &
Recommendations section.
We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to classify
synthesized recommendations as Strong or Weak.
Strong recommendations are used when, based on the available evidence, clinicians (without
conflicts of interest) consistently have a high degree of confidence that the desirable consequences
(health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs,
burdens).
Weak recommendations are used when, based on the available evidence, clinicians believe that
desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about
the magnitude of expected consequences (benefits and harms). Weak recommendations are used
when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in
their judgments. Weak recommendations are also used when the range of patient values and
preferences suggests that informed patients are likely to make different choices.
DynaMed Plus (DMP) synthesized recommendations (in the Overview & Recommendations section) are
determined with a systematic methodology:
Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological
expertise and ≥ 1 with content domain expertise) aware of the best current evidence for benefits and
harms, and the recommendations from guidelines.
Recommendations are phrased to match the strength of recommendation. Strong recommendations
use "should do" phrasing, or phrasing implying an expectation to perform the recommended action
103/105
for most patients. Weak recommendations use "consider" or "suggested" phrasing.

Recommendations are explicitly labeled as Strong recommendations or Weak recommendations
when a qualified group has explicitly deliberated on making such a recommendation. Group
deliberation may occur during guideline development. When group deliberation occurs through
DynaMed-initiated groups:
Clinical questions will be formulated using the PICO (Population, Intervention, Comparison,
Outcome) framework for all outcomes of interest specific to the recommendation to be
developed.
Systematic searches will be conducted for any clinical questions where systematic searches
were not already completed through DynaMed content development.
Evidence will be summarized for recommendation panel review including for each outcome,
the relative importance of the outcome, the estimated effects comparing intervention and
comparison, the sample size, and the overall quality rating for the body of evidence.
Recommendation panel members will be selected to include at least 3 members that together
have sufficient clinical expertise for the subject(s) pertinent to the recommendation,
methodological expertise for the evidence being considered, and experience with guideline
development.
All recommendation panel members must disclose any potential conflicts of interest
(professional, intellectual, and financial), and will not be included for the specific panel if a
significant conflict exists for the recommendation in question.
Panel members will make Strong recommendations if and only if there is consistent
agreement in a high confidence in the likelihood that desirable consequences outweigh
undesirable consequences across the majority of expected patient values and preferences.
Panel members will make Weak recommendationsif there is limited confidence (or
inconsistent assessment or dissenting opinions) that desirable consequences outweigh
undesirable consequences across the majority of expected patient values and preferences. No
recommendation will be made if there is insufficient confidence to make a recommendation.
All steps in this process (including evidence summaries which were shared with the panel,
and identification of panel members) will be transparent and accessible in support of the
recommendation.
Recommendations are verified by ≥ 1 editor with methodological expertise, not involved in
recommendation drafting or development, with explicit confirmation that Strong recommendations
are adequately supported.
Recommendations are published only after consensus is established with agreement in phrasing and
strength of recommendation by all editors.
If consensus cannot be reached then the recommendation can be published with a notation of
"dissenting commentary" and the dissenting commentary is included in the topic details.
If recommendations are questioned during peer review or post publication by a qualified individual,
or reevaluation is warranted based on new information detected through systematic literature
surveillance, the recommendation is subject to additional internal review.
DynaMed Editorial Process

DynaMed topics are created and maintained by the DynaMed Editorial Team and Process.
All editorial team members and reviewers have declared that they have no financial or other competing
interests related to this topic, unless otherwise indicated.
DynaMed provides Practice-Changing DynaMed Updates, with support from our partners, McMaster
University and F1000.
Special acknowledgements
Panagiotis Papageorgiou, MD, PhD (Assistant Professor of Medicine, Harvard Medical School;
Massachusetts, United States)
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Dr. Papageorgeiou declares no relevant financial conflicts of interest.
Amir Qaseem, MD, PhD, MHA, FACP (Vice President of Clinical Policy, American College of
Physicians; Pennsylvania, United States; President Emeritus, Guidelines International Network (GIN);
Germany)
Dr. Qaseem declares no relevant financial conflicts of interest.
Peter Oettgen MD, FACC, FAHA, FACP (Editor in Chief; Cardiologist, Beth Israel Deaconess Medical
Center; Associate Professor of Medicine, Harvard Medical School, Massachusetts, United States)
Dr. Oettgen declares no relevant financial conflicts of interest.
The American College of Physicians (Marjorie Lazoff, MD, FACP; ACP Deputy Editor, Clinical
Decision Resource) provided review in a collaborative effort to ensure DynaMed provides the most valid
and clinically relevant information in internal medicine.
DynaMed Plus topics are written and edited through the collaborative efforts of the above individuals.
Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice.
Recommendations Editors are actively involved in development and/or evaluation of guidelines.
Editorial Team role definitions

Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and
suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic
Editors also serve as consultants for the internal DynaMed Plus Editorial Team during the writing and
editing process, and review the final topic drafts prior to publication.
Section Editors have similar responsibilities to Topic Editors but have a broader role that includes the
review of multiple topics, oversight of Topic Editors, and systematic surveillance of the medical
literature.
Recommendations Editors provide explicit review of DynaMed Plus Overview and Recommendations
sections to ensure that all recommendations are sound, supported, and evidence-based. This process is
described in "Synthesized Recommendation Grading."
Deputy Editors are employees of DynaMed and oversee DynaMed Plus internal publishing groups. Each
is responsible for all content published within that group, including supervising topic development at all
stages of the writing and editing process, final review of all topics prior to publication, and direction of
an internal team.
How to cite
National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):
DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T115288,
Atrial fibrillation; [updated 2018 Nov 30, cited place cited date here]. Available from
https://www.dynamed.com/topics/dmp~AN~T115288. Registration and login required.
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Atrial Fibrillation

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Atrial Fibrillation

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26/6/2019 DynaMed Plus: Atrial fibrillation

Atrial fibrillation (AF) is a common supraventricular tachyarrhythmia caused by uncoordinated atrial

may recur with variable frequency

classification of severity of atrial fibrillation

most common arrhythmia ( Dis Mon 2013 Mar;59(3):67)

atrial fibrillation common among the elderly

Likely risk factors

subclinical hyperthyroidism associated with increased risk for

subclinical hyperthyroidism associated with atrial fibrillation

Reference - BMJ 2012 Nov 27;345:e7895 full-text

heavy alcohol consumption associated with increased risk of atrial fibrillation

NSAIDs and COX-2 inhibitors

nonaspirin NSAID use associated with increased risk of atrial fibrillation

Other likely risk factors

Possible risk factors

based on case-control study

Other risk factors

diabetes mellitus associated with increased risk of atrial fibrillation

Factors not associated with increased risk

Etiology and Pathogenesis

left atrial enlargement

History and Physical

Chief concern (CC)

patient may be asymptomatic (especially with chronic atrial fibrillation)(1)

History of present illness (HPI)

Past medical history (PMH)

Family history (FH)

Social history (SH)

findings may include(1)

irregularly irregular rhythm detected by palpation of a pulse or auscultation(1)

bibasilar rales (with concomitant heart failure)(1)

edema (with concomitant heart failure)(1)

electrocardiogram (ECG) shows(1)

other irregular narrow complex tachyarrhythmias including

minimum baseline evaluation should include

Transesophageal echocardiogram (TEE) for timing of cardioversion

transesophageal echocardiogram to guide timing of cardioversion as effective as conventional

primary composite endpoint of stroke, transient ischemic attack, or peripheral embolism

Indications for ECG and ECG images

Evidence for ECG detection of atrial fibrillation

detection of atrial fibrillation after stroke

implantable cardiac monitor (no p value reported)

in-hospital monitoring including serial ECG, continuous ECG, continuous cardiac

Interpretive software for ECG

interpretive software reported to INCORRECTLY diagnose atrial fibrillation in a significant

for specific treatment modalities

Canadian Cardiovascular Society (CCS) recommendations

in patients with preexcitation, propafenone or amiodarone preferred (ESC Class I, Level C)

dabigatran, rivaroxaban, or apixaban) for at least 3 weeks before cardioversion (ACCP

see Cardioversion of atrial fibrillation for details

see Rhythm control in atrial fibrillation for details

Rate vs. rhythm control

American College of Cardiology/American Heart Association (ACC/AHA) guidelines on atrial fibrillation

Surgery and procedures

pulmonary vein isolation associated with improved quality of life compared to

ablation of accessory pathway in patients with Wolff-Parkinson-White syndrome

see Ablation therapy for atrial fibrillation for details

Implantable atrial defibrillator

based on 2 case series

after atrioventricular nodal ablation, addition of para-Hisian pacing (dual-chamber pacemaker

American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS)

Left atrial appendage closure

description of left atrial appendage closure (LAAC)

has performed ≥ 25 interventional cardiac procedures that involve transseptal