Acute M anagement o f

Atrial Fibrillation
From Emergency Department
to Cardiac Care Unit
Clare L. Atzema, MD, MSc, FRCPCa,*,
Sheldon M. Singh, MD, FRCPCb

KEYWORDS
 Atrial fibrillation  Acute care  Emergency department  Rate control  Rhythm control
 Anticoagulation

KEY POINTS
 Atrial fibrillation (AF) causing true patient instability (eg, clinically significant hypotension) is very
rare: search out and treat other causes (eg, sepsis).
 The decision to implement rate versus rhythm control should be guided by patient symptoms and
age.
 Rhythm control with either electricity or medication can be safely provided in the emergency
department setting.
 Stroke risk should be assessed using a guidelines-endorsed risk score, and oral anticoagulation
with either a direct oral anticoagulant or a vitamin K antagonist should be initiated based on the
score, regardless of the discharge rhythm.
 Patients being discharged need to have follow-up care; subsequent AF care can usually be pro-
vided on an outpatient basis.

INTRODUCTION department visits and hospitalizations, and

Atrial fibrillation (AF) is a common arrhythmia and
is frequently encountered by clinicians who work
in the emergency department and in-hospital
settings. Mortality in patients with AF is the highest
in the first 4 months following diagnosis.1 Manag-
ing physicians need to be facile in the diagnosis
and management of AF in order to decrease
the risk of mortality, reduce return emergency
improve patient quality of life.
Definition
AF is a supraventricular tachyarrhythmia charac-
terized by a rapid, irregular heart rate and ineffec-
tive atrial contractions. Atrial activity is chaotic,
and atrial rates often exceed 300 beats per minute
(bpm) (Fig. 1).

Disclosure: Dr C.L. Atzema is funded by a New Investigator Award from the Heart and Stroke Foundation of
Canada, Sunnybrook Research Institute, and the Institute for Clinical Evaluative Sciences. Dr S.M. Singh has
cardiology.theclinics.com

nothing to disclose.
a
Division of Emergency Medicine, Department of Medicine, University of Toronto, Sunnybrook Health Sci-
ences Centre, Institute for Clinical Evaluative Sciences, 2075 Bayview Avenue, G146, Toronto, ON M4N 3M5,
Canada; b Division of Cardiology, Department of Medicine, University of Toronto, Schulich Heart Program,
Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, A222, Toronto, ON M4N 3M5, Canada
* Corresponding author.
E-mail address: clare.atzema@ices.on.ca
; @Atzema (C.L.A.)

Cardiol Clin - (2017) -–-

https://doi.org/10.1016/j.ccl.2017.08.008
0733-8651/17/Ó 2017 Elsevier Inc. All rights reserved.
2 Atzema & Singh
Fig. 1. An electrocardiogram of AF.
Epidemiology and Economic Implications
Worldwide over 33 million persons have AF,2 and
the prevalence is predicted to increase by 250%
by the year 2050.3,4 The prevalence of atrial flutter
is less than one-tenth that of AF, and many of
these patients also have AF. The most common
cause of AF is hypertension; however, there are
a myriad of potential causes (Box 1).
The economic cost of AF is huge, with more than
$3.5 billion dollars spent annually on AF care in the
United States.5 In the United Kingdom, 1% of the
National Health Service budget goes to AF care.6
The largest component of expenditures is hospi-
talization.7 Hospitalization rates vary greatly by
country and region. In the United States, 69% of
AF emergency department visits end in hospitali-
zation, compared with 37% in Canada’s largest
province.8 The differences may be caused in part
by emergency department cardioversions, after
which patients are typically discharged home: US
emergency physicians are less likely to perform
these relative to their Canadian colleagues.8,9
However, even within the United States, admis-
sion rates vary widely by region,10 suggesting
that other factors, such as access to follow-up
care, fear of litigation, patient and family prefer-
ences, and local practice patterns, play a role in
admission decisions.
Morbidity and Mortality
AF has been independently associated with
increased mortality in both men and women.2,11
AF-related deaths are most commonly caused
by sudden death, heart failure, and stroke.12
Strokes caused by AF are usually severe, and
are associated with a 50% 1-year mortality.13
Box 1
Causes of atrial fibrillation
Hypertension
Obesity
Valvular heart diseasea
Pulmonary embolus
Postoperative
Heart failure
Acute myocardial infarction
Pericardial disease (pericarditis, myocarditis)
Hyperthyroidism
Toxicologic causes
Sleep apnea
Chronic obstructive pulmonary disease
Alcohol: acute (so-called holiday heart) and
chronic
Hypothermia
a
Valvular heart disease refers to patients with either
rheumatic heart disease (predominantly mitral stenosis)
or mechanical heart valves; other valvular diseases, such
as aortic disease or mitral regurgitation, do not
currently have evidence to suggest that they should
alter usual decision making around oral anticoagulants.
 Acute Management of Atrial Fibrillation 3

Anticoagulation can mitigate stroke-related Table 1

deaths in patients with AF14; however, death sec- Classification of atrial fibrillation
ondary to heart failure and sudden death remain
common despite evidence-based therapy.15 AF Pattern Definition
independently worsens the prognosis for patients
Paroxysmal Paroxysms of AF that either
with sepsis,16 acute myocardial infaction,17 and self-terminate or are
heart failure,18,19 and it has been associated successfully cardioverted
with cognitive decline and dementia.20 Patient within 7 d
quality of life can be diminished secondary to Persistent AF that lasts more than 7 d
symptoms,20,21 which can also lead to high
Long-standing Continuous AF that lasts for
rates of emergency department visits and persistent a year or longer when it is
hospitalizations.22,23 decided to adopt a rhythm
The published literature on AF in the emergency control strategy
setting often differentiates patients with a primary Permanent AF that is accepted by the
emergency department diagnosis of AF from other patient and physician,
patients with AF (eg, presenting with pneumonia, such that no rhythm
found to be in new AF)24–26; this is because the control is pursued
latter group have an almost 3-fold higher 1-year
mortality than patients seen primarily for AF.24,26
rate is typically up to w190 bpm, depending on
Pathophysiology the conduction and refractory properties of the
AF is caused by remodeling of the atria via con- AV node. Higher heart rates suggest hyperthyroid-
nective tissue deposition, fibroblast activation ism or an accessory pathway.
and inflammation, fibrosis, and dilatation.27 This
process alters conduction pathways in the atria, Atrial Fibrillation in Unstable Patients
promoting localized reentry of electrical impulses.
AF promotes this milieu, which may explain the Advanced cardiovascular life support (ACLS) pro-
observation that AF begets AF. tocols define instability as hypotension, heart fail-
Loss of atrial contraction generally only affects ure, or an acute coronary syndrome (ACS).
hemodynamic stability in the setting of decreased Although all AF guidelines advise immediate elec-
filling capability, such as with severe mitral steno- trical cardioversion for unstable AF, it is important
sis or a hypertrophic or restrictive cardiomyopa- to remember that AF as the cause of hemody-
thy.28,29 Patients with diastolic heart failure and namic instability is very rare in the emergency
severe left ventricular dysfunction can be similarly department setting. Instability is far more
affected. An abnormally fast or slow ventricular commonly caused by sepsis, gastrointestinal
rate can also contribute to stability and symptoms. bleeding, pulmonary embolus, toxicologic causes,
and other acute states that can diminish the rate
Classification control in established AF. There is the potential
for stroke with immediate cardioversion,
AF is classified into 4 types, based on duration of
the arrhythmia (Table 1). The type of AF alters
the management options. Box 2
Management goals of acute atrial fibrillation
INITIAL MANAGEMENT OF PATIENTS WITH 1. Accurate diagnosis
ATRIAL FIBRILLATION
2. Patient stabilization
The management goals in acute AF are listed in 3. Recognition and treatment of reversible
Box 2. The most common symptoms experienced causes
by patients who present to an emergency depart-
 May require further investigations
ment are palpitations, shortness of breath, and
chest pain.30,31 Fatigue and other nonspecific 4. Symptom management
symptoms are frequent in elderly patients.31 The  Select rhythm or rate-control strategy
diagnosis of AF is made using the electrocardio-
gram (ECG). The cardinal signs are an irregular 5. Stroke prevention
RR interval with no discernible, distinct P waves. 6. Patient education
In the setting of intact atrioventricular (AV) conduc- 7. Arranging follow-up care
tion and no accessory pathway, the ventricular
4 Atzema & Singh

particularly in people who have been in AF for
more than 48 hours without anticoagulation. One
retrospective study found that cardioverting these
acutely ill patients was associated with worse out-
comes.25 Therefore it is prudent to perform a quick
but thorough search for evidence of long-standing
AF before cardioversion, along with another
source of hemodynamic instability (eg, fever, pos-
itive Hemoccult) (Fig. 2).
In addition, clinicians should have a nuanced
approach to the ACLS definition of instability. For
example, hypotension with a systolic blood pres-
sure of 85 mm Hg in patients who are alert and
not confused indicates that they are perfusing their
brain well, and in that scenario there is more time
to investigate other causes of the hypotension,
compared with the same blood pressure in pa-
tients with a decreasing level of consciousness
who are not responding to fluids. In patients with
heart failure, if the blood pressure is stable, then
a trial of intravenous diuretics may avoid an imme-
diate, unprepared cardioversion. In a patient
with ST-elevation myocardial infarction (STEMI),
the priority should be getting the patients to the
cardiac catheterization laboratory (or thromboly-
sis, depending on access), not immediate restora-
tion of sinus rhythm.
If another source of instability is identified,
aggressive treatment of that source is indicated.
If the source is thought to be AF after consider-
ation (and investigation, where possible) of other
causes, and the patient has been in AF for more
than 48 hours (or the duration is unknown) without
3 weeks of effective anticoagulation, transesopha-
geal echocardiography (TEE) should be performed
to exclude atrial thrombus. If TEE is not feasible
and cardioversion deemed necessary, immediate
heparin administration (and subsequent continua-
tion of anticoagulation) should be performed to
minimize delayed thromboembolism with restora-
tion of sinus rhythm.
Atrial Fibrillation in Stable Patients
Management of stable patients with AF depends
on the duration of AF and associated symptoms.
There are several management options if the pa-
tient has been in AF for less than 48 hours (ie,

Fig. 2. Evidence of long-standing AF. a Some guidelines recommend giving anticoagulation even if the stroke risk
score is too low to qualify for OAC.33 CV, cardioversion; GI, gastrointestinal; MS, mitral stenosis; OAC, oral anti-
coagulant; PE, pulmonary embolism; TIA, transient ischemic attack.

paroxysmal AF) and has no high-risk features for
stroke (ie, mechanical valve, rheumatic heart dis-
ease, recent stroke or transient ischemic attack).
A rhythm-control option may be selected, or pa-
tients may simply be rate controlled. Which option
is better depends on patient symptoms and
age.32,33
There is excellent evidence showing that rhythm
control does not lead to better outcomes 5 years
later, compared with rate control, including in pa-
tients who also have heart failure.34–36 Although
this finding likely extends beyond 5 years, the au-
thors do not have evidence on the impact of being
in AF for 10 or 20 years, which is the life expec-
tancy for many younger patients seen in the emer-
gency department. Therefore, in older patients, it
is clear that the decision should be made primarily
based on symptoms,32,33 which are often effec-
tively controlled with rate-control medications.
On discharge, outpatient follow-up should be ar-
ranged to reassess patient symptoms, because
delayed cardioversion is always an option: cardio-
version to sinus rhythm from persistent AF need
only be done within w 6 months (after which
time it is less likely to be successful).37 Thus dis-
charging a patient in AF will not condemn them
to a lifetime of AF. In younger patients (who are
more likely to experience more symptoms),32
both symptoms and the long-term effect of staying
in AF for decades should be considered.32,38 Note
that patients with high-risk features of stroke
should not be cardioverted without 3 weeks of
antecedent, effective anticoagulation.
For stable patients who have been in AF for
greater than 48 hours, the option for rhythm con-
trol must be balanced with the risk of stroke
related to suboptimal anticoagulation. If effectively
anticoagulated for 3 weeks before presentation
(typically with weekly International Normalized Ra-
tios [INRs] for patients taking vitamin K antagonists
[VKAs]), rhythm control is an option. Rhythm con-
trol can also be considered if TEE can be per-
formed before cardioversion (which must be
followed by 4 weeks of anticoagulation, regardless
of the stroke risk score32,33). Alternatively, the
managing clinician may rate control the patient,
initiate oral anticoagulant (OAC), and arrange for
an outpatient cardioversion after 3 weeks of OAC.
Acute rhythm control
Cardioversion can be performed either electrically
or pharmacologically. The former is w 90% effec-
tive in the emergency department setting, whereas
pharmacologic options are 50% to 60% effec-
tive.31,39 Electrically cardioverted patients often
go home an hour or so following initiation of car-
dioversion9; however, the procedure requires
Acute Management of Atrial Fibrillation 5
a procedural sedation, a monitored bed, and a
dedicated nurse. Contraindications to electrical
cardioversion include digoxin toxicity and severe
hypokalemia.32
When performing electrical cardioversion, patient
consent should be obtained (Fig. 3). Atropine and
temporary transcutaneous pacing should be avail-
able in case of postcardioversion bradycardia (eg,
patients with underlying sick sinus syndrome).33
Whenever possible, sedate the patient. Apply the
pads either in an anterior-posterior (AP) or antero-
lateral position on the chest, avoiding bone (eg,
sternum) and fat (eg, breast tissue) where possible
(both increase the energy required to convert the
patient).40,41 Although transthoracic impedance
has been shown to be less in the AP position, car-
dioversion success rates do not seem to differ by
pad position; however, this may vary depending
on type of machine used (monophasic vs
biphasic).42 Ensure that the device is set to syn-
chronize. Start with 150 to 200 J on a biphasic ma-
chine (200–300 J on a monophasic machine) to
avoid having to administer multiple shocks and
give more cumulative energy to the patient. Choose
higher energies for obese patients, and lower in
very thin patients, in order to avoid skin burns. In
very obese patients, consider using the paddles
to apply pressure, because this improves conduc-
tion and increases the chances of success.32
If unsuccessful, do not repeat the same shock:
change the pad position, increase the energy,
and/or apply pressure with paddles.32 If time al-
lows, an antiarrhythmic (eg, sotalol, ibutilide) may
be administered 30 minutes in advance of cardio-
version, in order to lower the defibrillation
threshold and facilitate acute maintenance of si-
nus rhythm.32,33
Alternatively, medication can be used to convert
the patient to sinus rhythm. In Canada, where
pharmacologic cardioversion is common in the
emergency setting (particularly compared with
the United States),8 almost all emergency physi-
cians have used intravenous procainamide since
the 1990s, for which complications are rare and
easily managed.31,43 However, cardiovascular
guidelines have not incorporated this evidence
and do not list procainamide as an option (except
for preexcitation).32,33,44 Instead they recommend
flecainide, dofetilide, propafenone (class I), and
intravenous ibutilide (class I by American Heart As-
sociation [AHA], IIa by European Society of Cardi-
ology [ESC]) for pharmacologic cardioversion,32,33
which are much less frequently used in the emer-
gency department (Table 2).
Procainamide requires a monitored bed and
close attention to rhythm and hemodynamic
changes by the managing nurse (eg, hypotension,
6 Atzema & Singh

1. Consider risk factors for contraindications

● Digoxin toxicity
● Severe hypokalemia

2. Obtain patient consent

3. Prepare for procedural sedation

● Patient anesthetic evaluation (eg, airway evaluation, presence of reactive airways disease and American Society of
Anesthesiologists (ASA) score, allergies, last meal, previous sedations)
● Appropriate staff (dedicated nurse, minimum 2 staff [second physician ideal])
● Monitored bed
● Preoxygenation, intravenous line flowing, equipment check
● Medication selection: eg, propofol, fentanyl, midazolam, etomidate

4. Pad placement, synchronization engaged, select energy (higher for larger patients, lower for small patients)
● 150–200 J for biphasic machines
● 200–300 J for monophasic machines

5. When patient is properly sedated, ensure all staff are clear and cardiovert (hold buttons down; there may be a
delay to synchronization with the p waves)

6. Post cardioversion assessment

● If successful, monitor until patient awake; may be discharged once tolerating fluids
● If unsuccessful (ie, no sinus rhythm at any time), change a component prior to second attempt:
● increase the energy, move the pads, or apply pressure through paddles
● If still unsuccessful and sinus rhythm still desired, admission (or clinical decision unit) for receipt of an antiarrhythmic,
then repeat cardioversion

Fig. 3. Performing electrical cardioversion.

widening of the QRS by >50%, runs of ventricular
tachycardia), which are infrequent but require
either slowing or cessation of the infusion.45 Time
from initiation of procainamide to emergency
department discharge is w3 hours (including
time for subsequent electrical cardioversion in pa-
tients who do not convert).9
A pill-in-the-pocket approach can be taken
with propafenone (450–600 mg) or flecainide
(200–300 mg), but the onset takes 4 to 6 hours,
blocking an emergency bed for that time period.
A b-blocker (BB) is usually given at least 30 mi-
nutes before administration to prevent potential
1:1 AV conduction of atrial flutter.46 In addition,
neither medication should be administered to
patients with structural heart disease33; although
this can be assessed in the in-hospital setting,
in the emergency department this determination
may be impractical. In favor of the pill-in-the-
pocket approach, if effective it can be used
to prevent future emergency visits for parox-
ysmal AF.
Vernakalant is another option for pharmacologic
cardioversion in patients without hypotension or a
history of ischemic or structural heart disease, as
is ibutilide for patients without ischemic or struc-
tural heart disease.32,33 Ibutilide was more effec-
tive than procainamide in a study of patients with
longer duration of AF (mean, 21 days)47 but carries
a black box warning because of a risk of torsades
de pointes. Further downsides include the poten-
tial need for pretreatment with magnesium, pro-
longed monitoring after the infusion (4 hours),
and cost. In patients with ischemic or structural
heart disease, amiodarone is recommended by
the ESC (class I),33 whereas the AHA guidelines
list it as a second-line agent (class IIa) for rhythm
control overall.32 In patients with significant bron-
chospasm, propafenone and sotalol should be
avoided, along with nonselective BBs.
 Acute Management of Atrial Fibrillation 7

Table 2
Approach to pharmacologic cardioversion

Medication Pretreatment First Dose Follow-up Dose Risks

Procainamide a
— 15 mg/kg IV over 30– NA  Hypotension
60 min, maximum rate  QT and QRS
20 mg/min (stop or prolongation
slow rate if  Nonsustained
hypotension ventricular
develops, QRS arrhythmias
lengthens by >50%,
or runs of PVCs)
Flecainide Diltiazem 200–300 mg PO NA  Hypotension
30 mg PO or  1:1 flutter
metoprolol  Bradycardia
25 mg PO  Avoid in IHD or
Propafenone Diltiazem 450–600 mg PO NA significant structural
30 mg PO or heart disease
metoprolol  Delayed time to
25 mg PO conversion
Amiodarone — 5–7 mg/kg over 1–2 h 50 mg/h, max  Hypotension,
1.0 g over bradycardia
24 h bradycardia/AV block
 Phlebitis
 Delayed time to
conversion (8–12 h)
Ibutilide MgSO4 2–4 g IV 1 mg IV over Minimum of  2%–3% torsades de
10 min 10 min later, pointes
repeat 1 mg  Avoid if K <4.0 mEq/L,
over 10 min severe LVH, low EF
if necessary  Postinfusion 4-h
monitoring
Vernakalant — 3 mg/kg over 10 min 2 mg/kg over  Hypotension
10 min after  QT and QRS
waiting for prolongation
15 min  Nonsustained ventric-
ular arrhythmias
 Avoid if SBP
<100 mm Hg, recent
ACS, NYHA class III/IV
heart failure, QT
prolongation

Abbreviations: EF, ejection fraction; IHD, ischemic heart disease; IV, intravenous; LVH, left ventricular hypertrophy; NA, not
available; NYHA, New York Heart Association; PO, by mouth; PVCs, premature ventricular contractions; SBP, systolic blood
pressure.
a
The medication used most frequently for pharmacologic cardioversion in the emergency department in the last
20 years.

Recently the 48-hour cardioversion guideline
has come under scrutiny. Although many small
studies found no increased risk of subsequent
stroke in cardioverted patients using this cutoff, a
recent retrospective cohort study found an
increased risk of stroke in high-risk (high CHADS2
[congestive heart failure, hypertension, age, dia-
betes, prior stroke] scores) patients who were car-
dioverted between 12 and 48 hours, compared
with less than 12 hours.48 Note that none of these
patients were started on OAC according to their
stroke risk score, which is not congruent with cur-
rent guidelines.32,33,49 All patients with a risk score
meriting stroke prevention should be started on
OAC, regardless of their final rhythm. On the rare
occasions when a high-risk patient with parox-
ysmal AF presents well after 12 hours of onset,
consider providing 3 weeks of OAC along with
referral for outpatient cardioversion.33 It is still
not clear whether patients with no stroke risk
8 Atzema & Singh
factors who were cardioverted within 48 hours of
AF onset require OAC for a brief period (to avoid
thrombus related to mechanical stunning of the
left atrium). The ESC guidelines make a class I
(level of evidence B) recommendation to give
OAC for 4 weeks to these patients,33 whereas
the other major guidelines do not.32,49
Chronic rhythm control
After conversion to sinus rhythm, either in the
emergency department or in hospital, long-term
rhythm control can be considered (Table 3). The
risk for bradyarrhythmias, risk factors for QT pro-
longation and torsades de pointes, and renal/he-
patic clearance should be assessed. Because of
the complicated nature of the side effects of anti-
arrhythmics (which require ongoing evaluation,
something emergency physicians do not typically
provide), the authors recommend that emergency
physicians defer such decisions to their cardiology
colleagues. Patients who are still symptomatic
despite long-term antiarrhythmic drug therapy
should be referred to a cardiac electrophysiologist
for consideration of catheter ablation, as can pa-
tients who choose not to take antiarrhythmic
drug therapy but are symptomatic.32,33
Acute rate control
First-line rate-control agents include BBs or nondi-
hydropyridine calcium channel blockers (CCBs)
(Table 4).32,33 Typically the intravenous formulation
is administered, followed by the oral form. It is impor-
tant not to delay administration of the oral medica-
tion; such delays may lead to recurrent increase
of the heart rate and wasted time (and potentially
an avoidable admission).50 Once rate control has
been achieved with the intravenous formulation,
administer the oral form (eg, 25–50 mg of metoprolol
Table 3
Initiation of long-term rhythm control options
Clinical Situation
Minimal or no heart disease
Heart failure
Coronary artery disease
Significant valvular disease
Significant left ventricular hypertrophy
a
Not to be used in permanent AF.
b
Risk of QT prolongation and proarrhythmia.
c
Usually done only in heart failure patients with tachycardiomyopathy.
From Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in
collaboration with EACTS. Eur Heart J 2016;37(38):2893–962; with permission.
or 120–180 mg of diltiazem [long acting, although
60 mg of short acting could be used as well]). Guide-
lines recommend avoiding nondihydropyridines in
the setting of decompensated heart failure with
reduced ejection fraction.32,33
The goal is a resting heart rate of less than or equal
to 100 bpm, and/or a walking heart rate of less than
or equal to 110 bpm49,51 (considered a lenient strat-
egy52). If the maximum dose is not effective, consider
adding digoxin (adding a BB to a CCB or vice versa
can lead to severe bradycardia and hypotension).
Amiodarone also has rate-control properties (but
even slower onset than digoxin) and is another
second-line option if rate control is not achieved
with a BB or a CCB.32,33 Decisions on the use of
additional rate-control agents, such as digoxin,
should be made with knowledge of the patient’s
blood pressure, renal function, and left ventricular
systolic function, and require time to accurately eval-
uate the effects; therefore, these are likely best done
in hospital or in a clinical decision unit.
Chronic rate control
Although long-term rate control has not been
associated with a reduction in morbidity and mor-
tality, it is important to prevent symptoms and it
may preserve cardiac function.53 Early outpatient
follow-up is important to assess the adequacy of
rate control and to offer medication uptitration if
required. First-line agents include nondihydropyri-
dine CCBs and BBs. Digoxin is not effective at
controlling the ventricular response during exer-
cise,54 therefore digoxin is not first line. Several
observational studies have suggested that digoxin
is associated with increased mortality in AF55,56;
however, it is likely that the strong selection bias
for digoxin (older, frail patients)57 could not
be completely removed with statistical
Antiarrhythmic Alternative
Flecainide (IA) Catheter ablation (IIaB)
Propafenone (IA)
Dronedarone (IA)a
Sotalol (IA)b
Amiodarone (IA) Catheter ablation (IIaB)b
Dronedarone (IA)a Catheter ablation (IIaB)
Sotalol (IA)b
Amiodarone (IA)c
 Acute Management of Atrial Fibrillation 9

Table 4
Rate-control agents

Acute Rate Control

Acute or Chronic Rate
Medication First Dose Follow-up Dose Control
Nondihydropyridine CCBs
Diltiazem 0.25 mg/kg IV over 10 min Repeat q 15–20 min at  60 mg TID, up to 60 mg
0.35 mg/kg, up to total daily dose
3 doses  120–360 mg OD
Verapamil 2.5–10 mg IV bolus Repeat as needed  40–120 mg TID
 120–480 mg OD
b-Blockers
Metoprolol 2.5–5 mg IV over 2 min Repeat q 15–20 min 25–100 mg PO BID
up to 3 doses
Esmolol 0.5 mg/kg intravenous — NA
bolus over 1 min; then
0.05–0.25 mg/kg/min
Bisoprolol NA NA 1.25–20 mg OD or split BID
Carvedilol NA NA 3.125–50 mg PO BID
Cardiac Glycosides
Digoxin 0.25–0.5 mg IV 0.25 q 2 h, up to 1.5 mg 0.0625–0.25 mg PO OD
total dose
Other
Amiodarone 300 mg IV in 250 mL of 5% — 200 mg PO OD
(only as final dextrose, over 30–60 min
line)

Abbreviations: BID, twice a day; q, every; ID, 3 times a day; OD, once daily.
From Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in
collaboration with EACTS. Eur Heart J 2016;37(38):2893–962; with permission.

adjustment.33,58 If digoxin is added as a chronic
second-line agent, drug interactions must be care-
fully checked to avoid drug toxicity caused by
many other medications. Amiodarone is another
potential second-line rate-control agent, although
the numerous adverse effects of chronic use (eg,
pulmonary toxicity, thyroid dysfunction) make it a
last resort.32,33 In patients with active chronic
obstructive pulmonary disease, a nondihydropyri-
dine CCB is recommended for rate control32 (a b-1
selective blocker such as bisoprolol is usually well
tolerated if there is no acute bronchospasm).33
Should rate control be ineffective, long-term con-
siderations include rhythm control, pulmonary
vein isolation ablation, or insertion of a pacemaker
with subsequent AV node ablation.
Oral anticoagulation
Oral anticoagulation decreases the risk of a stroke by
more than 60%,14,59 which is a large risk reduction
compared with many therapies. Guidelines by the
AHA, Canadian Cardiovascular Society (CCS), and
ESC are similar in their recommendations for OAC
use, with some differences (Fig. 4).32,33,49 Both the
AHA and the ESC use CHA2DS2-VASc (congestive
heart failure; hypertension; age 75 years; diabetes
mellitus; prior stroke, transient ischemic attack, or
thromboembolism; vascular disease; age 65–74
years; sex category): both use a score of 2 to indicate
clear need for OAC, but the ESC now uses a score of
3 specifically for women.32,33 This recommendation
is a change from the previous ESC recommenda-
tions, which considered female sex a significant
risk factor.60 Current CCS guidelines do not consider
female sex a significant risk.49
In the CCS guidelines, aspirin is indicated only
for patients whose sole risk factor is vascular dis-
ease, the ESC guidelines do not recommend
aspirin monotherapy for any AF group,33 and the
AHA guidelines list it as a class IIb consideration
for a CHA2DS2-VASc score of 1.32 It can be used
in conjunction with clopidogrel in patients who
have a contraindication to OAC but are at risk of
stroke.61
The CCS and ESC guidelines recommend
direct OACs (DOACs) rather than VKAs (eg,
warfarin),33,58 whereas the AHA guidelines recom-
mend either.32 VKAs should be used for patients
10 Atzema & Singh
Fig. 4. Guidelines by the AHA, CCS, and ESC. ASA, aspirin; CABG, coronary artery bypass graft; CAD, coronary ar-
tery disease; HF, heart failure; TE, thromboembolism; PAD, peripheral artery disease; CHA2DS2-VASc, congestive
heart failure; hypertension; age 75 years; diabetes mellitus; prior stroke, TIA, or thromboembolism; vascular dis-
ease; age 65–74 years; sex category.
with a mechanical valve, or in those with rheumatic
or moderate to severe nonrheumatic mitral steno-
sis.32,33,49 DOACs have not been well studied for
bioprosthetic heart valves. For patients who are
already on warfarin with good time in therapeutic
range (ie, INR, 2–3 for 70% of the time33), there is
no immanent need to switch them to a DOAC.32 All
of the DOACs have been shown in randomized trials
to be as effective, or more effective, at preventing
stroke and thromboembolism, and all have a signif-
icantly lower risk of the most serious complication,
intracranial hemorrhage (including hemorrhagic
stroke) (Table 5).62–65 Gastrointestinal bleeding is
worse with several DOACs but similar to warfarin
for apixaban and the lower dose of dabigatran.
Which DOAC to choose depends on the age of
the patient, the bleeding risk, kidney function, and
predicted compliance with daily versus twice-
daily dosing (Table 6). Rivaroxaban and edoxaban
are once-a-day dosing, which may be preferred in
younger patients who are on no twice-daily medi-
cations. Apixaban may be suitable for elderly pa-
tients who are already on twice-daily medications,
and/or who have a higher risk of bleeding. Apixaban
is the only medication that uses the creatinine level
(in addition to age and weight) to determine dosing,
which time-pressured emergency physicians may
find easier to prescribe. Unlike the other DOACs,
dabigatran clearance is predominantly renal, which
increases the risk of bleeding in patients with a low
creatinine clearance.
If warfarin is selected, a standard starting dose
is 5 mg a day in most patients, and 2 mg in older,
frail patients. INR testing should be arranged for
within a week. A list of drug interactions is shown
in Table 7: clinicians should advise patients to
go to their usual pharmacies to fill the warfarin pre-
scription, to have the pharmacists review their
medications for interactions with warfarin. The
SAMe-TT2R2 (Sex [female], Age<60, Medical his-
tory, Treatment interacting medications, Tobacco
Use, Race [non-Caucasian]) score may be useful
in determining whether a patient is likely to achieve
a good time in therapeutic range on warfarin.66
Bleeding risk is assessed most commonly using
HAS-BLED (uncontrolled hypertension, abnormal
renal/liver function, stroke, bleeding history or pre-
disposition, labile International Normalized Ratio,
elderly, drugs/[antiplatelet agents or NSAIDS] or
alcohol; Table 8).67 The goal of reviewing HAS-
BLED is to remind clinicians to alter risk factors
for bleeding if possible: stop nonsteroidal antiin-
flammatory drugs (except ASA if recent percuta-
neous coronary intervention), council patients
regarding excessive alcohol use, improve control
of hypertension, and so forth. These risk factors
 Table 5
Risk of events in randomized controlled trials, direct oral anticoagulants (DOACs) versus warfarin

Dabigatran, RR (95% CI) Edoxaban, HR (95% CI)

Apixaban, HR (95% Rivaroxaban, HR
Event 150 mg 110 mg CI) (95% CI) 60 mg 30 mg
Stroke and systemic 0.65 (0.52–0.81) NI 0.89 (0.79–1.09) NI 0.79 (0.66–0.95) NI 0.88 (0.75–1.03) NI 0.87 (0.73–1.04) NI 1.13 (0.96–1.34) NI
embolism and Sup P<.001 P<.001 P<.001, Sup P 5 .01 P<.001 P<.001 P 5 .005
Ischemic stroke 0.76 (0.59–0.97) 1.10 (0.88–1.37) 0.92 (0.74–1.13) 0.94 (0.75–1.17) 1.00 (0.83–1.19) 1.41 (1.19–1.67)
Hemorrhagic stroke 0.26 (0.14–0.49) 0.31 (0.17–0.56) 0.51 (0.35–0.75) 0.59 (0.37–0.93) 0.54 (0.38–0.77) 0.33 (0.22–0.50)

Acute Management of Atrial Fibrillation

Intracranial bleeding 0.42 (0.29–0.61) 0.29 (0.19–0.45) 0.42 (0.30–0.58) 0.67 (0.47–0.93) 0.47 (0.34–0.63) 0.30 (0.21–0.43)
Major bleeding 0.94 (0.82–1.08) 0.80 (0.70–0.93) 0.69 (0.60–0.80) 1.04 (0.90–2.30) 0.80 (0.71–0.91) 0.47 (0.41–0.55)
Gastrointestinal 1.48 (1.19–1.86) 1.04 (0.82–1.33) 0.89 (0.70–1.15) 1.61 (1.30–1.99) 1.23 (1.02–1.50) 0.67 (0.53–0.83)
bleeding
All-cause death 0.88 (0.77–1.00) 0.91 (0.80–1.03) 0.89 (0.80–0.99) 0.85 (0.70–1.02) 0.92 (0.83–1.01) 0.87 (0.79–0.96)

Abbreviations: CI, confidence interval; HR, hazard ratio; NI, noninferiority; RR, relative risk; Sup, superiority.

11
12 Atzema & Singh

Table 6
Considerations for which direct oral anticoagulant to use

Patient Profilea Options

Older age with high risk of bleeding/frailty Apixaban
Preference for OD dosing Rivaroxaban, edoxaban, warfarin
Renal impairment Apixaban 5 mg BID; rivaroxaban 15 mg OD; edoxaban
30 mg OD
Patient with low risk of bleed, high risk of Dabigatran 150 mg BID; apixaban 5 mg BID
ischemic stroke
Younger patient with low risk of bleeding Dabigatran 150 mg BID; rivaroxaban 20 mg OD;
apixaban 5 mg BID; edoxaban 60 mg ODa
Asian patient (increased risk of intracranial Apixaban 5 mg BID
bleed, major bleed)
Specific Situations to Avoid
Mechanical valve, rheumatic MS or All DOACs
nonrheumatic moderate to severe MS
ESRD or CrClb <15 mL/min All DOACs
Dyspepsia, PUD, or gastritis Dabigatran
High-risk GI bleed Dabigatran 150 mg, rivaroxaban, edoxaban 60 mg (all
significantly increased risk)
High creatinine clearance Edoxaban (FDA recommendation because of potential
(CrCl >95 mL/min) for reduced efficacy)
Prescribing
Apixaban 5 mg BID
Reduce dose to 2.5 mg BID if 2 of the following are
present: age 80 y, body weight 60 kg, or serum
creatinine 133 mmol/L (1.5 mg/dL)
Dabigatran CrClc >50 mL/min: 150 mg BID
CrCl 30–50 mL/min: 150 mg BID, or 75 mg BIDd if age 80
y or age 75 y with 1 or more bleeding risk factor
CrCl 15–30 mL/min: FDA has approved 75 mg BID but this
has never been formally tested
Rivaroxaban CrCl >50 mL/min: 20 mg OD
CrCl 30–50 mL/min: 15 mg OD
Edoxaban CrCl >50 to 95 mL/min: 60 mg OD. FDA advises not to
use in patients with CrCl >95 mL/min
CrCl 15–50 mL/min: 30 mg OD
Abbreviations: CrCl, creatinine clearance; ESRD, end-stage renal disease; FDA, US Food and Drug Administration; GI,
gastrointestinal; MS, mitral stenosis; PUD, peptic ulcer disease.
a
Adapted from Freedman B, Potpara TS, Lip GYH. Stroke prevention in atrial fibrillation. Lancet 2016;388:806–17; with
permission.
b
Calculated using the Cockroft-Gault formula.
c
FDA-approved dosing. Other countries use 110 mg for reduced dosing, consistent with the RE-LY (Randomized Eval-
uation of Long-Term Anticoagulation Therapy) trial.59
d
AHA guidelines also list this dose for 15 to 30 mL/min.32

should be addressed in hospital, or, if discharged
from the emergency department, in the outpatient
setting during follow-up care.
Emergency department discharge versus
admission
The only recommendations regarding hospital
admission from the emergency department are
based on expert opinion; they advise admission
only for patients with acute heart failure, ACS, or
who have failed rate control.51 This constitutes
less than 10% of patients who have a primary
emergency department diagnosis of AF.30,31
Access to follow-up care is pivotal to the
disposition decision.68 After an emergency visit
for AF, patients need to be followed for ongoing
care: to ensure that rate control is effective (the
dose or medication changed based on heart
rate and side effects), to institute or continue
stroke prevention, to refer to an
 Acute Management of Atrial Fibrillation 13

Table 7
Drugs that interact with warfarin (not a comprehensive list)

Cytochrome
Affected [ Potency Y Potency
CYP2C9 Carbamazepine, phenobarbital, Amiodarone, capecitabine, cotrimoxazole,
rifampin fluconazole, fluvastatin, fluvoxamine,
metronidazole miconazole, tigecycline,
voriconazole, zafirlukast
CYP1A2 Montelukast, omeprazole, Acyclovir, allopurinol, caffeine, cimetidine,
phenobarbital, phenytoin, ciprofloxacin, disulfiram, enoxacin, famotidine,
cigarette smoking fluvoxamine, norfloxacin, oral contraceptives,
propafenone, propranolol, terbinafine,
thiabendazole, ticlopidine, verapamil
CYP3A4 Carbamazepine, nafcillin, Alprazolam, amiodarone, amlodipine, atorvastatin,
phenytoin, pioglitazone, cimetidine, ciprofloxacin, clarithromycin,
prednisone, rifampin cyclosporine, diltiazem, erythromycin,
fluconazole, fluoxetine, fluvoxamine, isoniazid,
itraconazole, ketoconazole, nefazodone, oral
contraceptives, posaconazole, ranitidine, many
antiretrovirals (anti-HIV medications)

Abbreviations: CYP, cytochrome P; HIV, human immunodeficiency virus.

electrophysiology clinic for cardioversion if indi- obesity and exercise, sleep apnea) should be
cated, and to arrange investigations such as an addressed. Follow-up is needed to answer pa-
echocardiogram (particularly if the AF diagnosis tient questions, to discuss what to do if the AF
is new32,33). Precipitating factors of AF (eg, reoccurs or if OAC medications cause bleeding,
and to discuss lifestyle and modifications of
bleeding risk factors. Stroke prevention can be
Table 8 reviewed using patient aids that promote shared
HAS-BLED scoring system for bleeding risk decision making.69
(score ‡3 is high risk) All of these issues can be addressed in the
outpatient setting; therefore, admission is not
Letter Acronym Definition Points
necessary for most patients if they have timely ac-
H Hypertension, uncontrolleda 1 cess to outpatient care. Although rate control can
A Abnormal renalb and liverc 1 or 2 be established more easily in hospital, the costs of
function (1 point each) hospitalization are not sustainable in the long term.
S Stroke 1 In addition, hospitalization exposes patients to
B Bleeding (history or 1 hospital-acquired infections, and, by removing
predisposition) elderly patients from their homes, it puts them at
L Labile INRs (eg, <60% of TTR) 1 risk of delirium and permanent cognitive
decline.70,71 With the introduction of the DOACs
E Elderly (>65 y) 1
and removal of INR monitoring, discharge is
D Drugsd or alcohole (1 point 1 or 2
further simplified. The decision to admit must be
each)
made in light of these pros and cons, as well as
Total score /9 the patient’s social situation and family wishes
Abbreviation: TTR, time in therapeutic range. (eg, caregiver burnout).
a
Systolic blood pressure > 160 mm Hg. For patients who are discharged from the emer-
b
Dialysis or renal transplant or serum creatinine level gency department, key issues that need to be
greater than or equal to 200 mmol/L (2.26 mg/dL).
c addressed before discharge are shown in Fig. 5.
Chronic hepatic disease (eg, cirrhosis) or biochemical
evidence (eg, liver function tests) of significant hepatic There are no guidelines regarding how soon pa-
derangement. tients with AF should be seen following hospital
d
Antiplatelet agents, nonsteroidal antiinflammatory or emergency department discharge. In related
drugs. research, patients with heart failure discharged
e
Eight or more alcoholic drinks per week.
From Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban
from hospital were less likely to be readmitted
versus warfarin in nonvalvular atrial fibrillation. N Engl J within a month if they were seen within 7 days.72
Med 2011;365(10):883–91; with permission. Most emergency physicians advise patients with
14 Atzema & Singh
ambulatory cardiovascular diseases to have
follow-up with a physician within 7 days.73
Management in Specific Situations
Atrial fibrillation complicating acute coronary
syndrome
ACS is a known cause of AF, and AF in the setting
of ACS is associated with worse outcomes.17
Diagnosis of ACS (ie, an acute coronary plaque
rupture) in the setting of AF can be difficult, given
that one of the key criteria of an acute myocardial
Fig. 5. Emergency department
discharge. a Using CHADS-VASc or
CHADS-65, HAS-BLED.32,33,56 b For
example, tell the patient that in pa-
tients aged  65 years without other
risk factors for stroke, warfarin
decreased the annual risk of stroke
from 2.1% to 0.7% and increased
the risk of major bleeding by approx-
imately 0.5% per year to 1.0%. Use vi-
sual supports where possible. BP,
blood pressure; EP, emergency physi-
cian; EtOH, alcohol; HR, heart rate;
NSAIDs, nonsteroidal antiinflamma-
tory drugs.
infarction is troponin level increase:74 troponin can
increase in response to the fast heart rates of AF
(ie, demand-related ischemia).
Managing physicians should rely primarily on
the patient history to determine the diagnosis.
Symptoms of ACS (chest pain, SOB, and so forth)
that began before the sensation of palpitations
direct the physician toward an ACS diagnosis.
Some nonspecific ECG changes may be expected
because of rate-related demand, but clear
ST-elevation in 2 contiguous leads remains diag-
nostic for an STEMI.75 However, ECG changes

that resolve with rate control32 suggest demand-
related ischemia (which does not require percuta-
neous coronary intervention [PCI] or thrombo-
lytics). Patients with an increased troponin levels
should receive expert consultation for further risk
stratification and inpatient management.
Patients with AF who have a low stroke risk (eg,
CHA2DS2-VASc 5 0) do not require changes to usual
ACS management.32,33,58 Those with a high stroke
risk who experience ACS still need stroke preven-
tion, in addition to the antiplatelet agents for ACS.
Triple therapy (TT) includes OAC, aspirin, and clopi-
dogrel. It is associated with a markedly increased
risk of bleeding,76 therefore should be used for as
short a period as possible.33,58 Ticagrelor and prasu-
grel should not be used in the TT regimen because of
their increased risk of bleeding relative to clopidog-
rel. Guidelines vary in their recommendations; con-
sult them directly for the exact timing of TT, dual
therapy (OAC and single antiplatelet), and OAC
monotherapy after ACS (with and without PCI) and
elective PCI.32,33,58 ESC and CCS guidelines both
include TT for patients with ACS receiving PCI. The
AHA guidelines do not recommend TT for patients
undergoing revascularization, based on the WOEST
(What is the Optimal antiplatElet and anticoagulant
therapy in patients with oral anticoagulation and cor-
onary StenTing) trial.76 The recent PIONEER AF-PCI
(Open-Label, Randomized, Controlled, Multicenter
Study Exploring Two Treatment Strategies of Rivar-
oxaban and a Dose-Adjusted Oral Vitamin K Antag-
onist Treatment Strategy in Subjects with Atrial
Fibrillation who Undergo Percutaneous Coronary
Intervention) trial had lower rates of bleeding with
low-dose rivaroxaban and either a single antiplatelet
agent or dual-antiplatelet therapy, compared with
Fig. 6. Arrow points to the delta wave.
Acute Management of Atrial Fibrillation 15
TT.77 Ongoing clinical trials evaluating the use of
DOACs in this setting will provide additional clarity
on the management of these patients.
Ways to minimize bleeding risk on TT include
targeting a lower INR (2.0–2.5) if using warfarin, us-
ing the lower dose of DOACs, and adding a proton
pump inhibitor. A bare metal stent has the lowest
risk of occlusion, followed by a newer-generation
drug-eluting stent (DES), then an older DES.78
Atrial fibrillation and bradycardia
AF is included in the spectrum of sick sinus syn-
drome. These patients may have rapid rates
when in AF, and sinus bradycardia when AF termi-
nates; this may be exacerbated by medications
used to treat AF. These patients require careful
review of drug therapies that exacerbate brady-
cardia and referral for consideration of pacemaker
placement.32,33
Wolfe-Parkinson-White syndrome
Patients with AF and preexcitation from Wolfe-
Parkinson-White (WPW) are at risk of developing
ventricular fibrillation (VF) because of an accessory
pathway with the ability for rapid anterograde con-
duction. The cardinal sign of WPW on ECG is the
presence of a delta wave (or a slurred upstroke
instead of a sharp takeoff of the QRS complex)
(Fig. 6). A wide-complex tachycardia with irregu-
larity in rate is suggestive of AF with WPW
(Fig. 7). In this situation, AV nodal blockade (eg,
BB, CCB, digoxin, adenosine, and amiodarone)
should be avoided, because it may result in unop-
posed accessory pathway conduction, in turn pro-
ducing VF.32,33 In this setting, clinicians should
restore sinus rhythm. Options for chemical
16 Atzema & Singh
Fig. 7. AF with Wolfe-Parkinson-White syndrome.
cardioversion include procainamide,32,33 propafe-
none,33 or ibutilide,32 because none of these
agents have BB activity. Alternatively, synchro-
nized electrical cardioversion can be performed.
Amiodarone was once first line for WPW but
case reports of VF have altered the recommenda-
tion.32,33,79 Patients with AF and an anterograde
accessory pathway should be referred for catheter
ablation.33
Pregnancy
AF in pregnancy is rare and is often a marker of
structural heart disease such as mitral stenosis
or congenital heart disease, hyperthyroidism, elec-
trolyte abnormalities, or alcohol abuse. Echocardi-
ography and other investigations are mandatory to
distinguish these conditions from benign reasons
for AF related to increased volume in pregnancy.
Patients should be managed as a high-risk preg-
nancy, with combined care from cardiology, ob-
stetrics, and neonatology.
In the absence of instability, rate control is a
reasonable first-line therapy. Digoxin has a long
history of use in pregnancy. It crosses the
placenta but is not teratogenic and has few
adverse effects to the fetus. However, all rate-
control agents lack good data in pregnancy, and
are all categorized as C (benefits may outweigh
the risk), with the exception of atenolol (D: evi-
dence of risk). They should be used for as short
a time as possible.
Rhythm control may be necessary if hemody-
namic compromise is present.33 Electrical cardio-
version is considered safe but should be done in a
setting in which obstetrics and fetal monitoring are
available. Most antiarrhythmic agents are also
classified as C, with the exception of sotalol (B)
and amiodarone (D). If performed within 48 hours
the need for anticoagulation can be avoided
(vitamin K antagonists are teratogenic in the first
trimester, and may cause bleeding around the
time of delivery33,79).
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