Intern Emerg Med

DOI 10.1007/s11739-016-1580-x

CE - ORIGINAL

Guidelines on the management of atrial fibrillation

in the emergency department: a critical appraisal
Giorgio Costantino1 • Gian Marco Podda2 • Lorenzo Falsetti3 • Primiano Iannone4 •
Ana Lages5 • Alberto M. Marra6 • Maristella Masala7 • Olaug Marie Reiakvam5 •
Florentia Savva5 • Jan Schovanek5 • Sjoerd van Bree5 • Inês João da Silva Chora5 •
Graziella Privitera5 • Silvio Ragozzino5 • Matthias von Rotz5 • Lycke Woittiez5 •
Christopher Davidson8 • Nicola Montano1

Received: 4 August 2016 / Accepted: 19 November 2016

 SIMI 2016

Abstract Several guidelines often exist on the same topic,
sometimes offering divergent recommendations. For the
clinician, it can be difficult to understand the reasons for this
divergence and how to select the right recommendations.
The aim of this study is to compare different guidelines on
the management of atrial fibrillation (AF), and provide
practical and affordable advice on its management in the
acute setting. A PubMed search was performed in May 2014
to identify the three most recent and cited published guide-
lines on AF. During the 1-week school of the European
School of Internal Medicine, the attending residents were
divided in five working groups. The three selected guidelines
were compared with five specific questions. The guidelines
identified were: the European Society of Cardiology
guidelines on AF, the Canadian guidelines on emergency
department management of AF, and the American Heart
Association guidelines on AF. Twenty-one relevant sub-
questions were identified. For five of these, there was no
agreement between guidelines; for three, there was partial
agreement; for three data were not available (issue not cov-
ered by one of the guidelines), while for ten, there was
complete agreement. Evidence on the management of AF in
the acute setting is largely based on expert opinion rather
than clinical trials. While there is broad agreement on the
management of the haemodynamically unstable patient and
the use of drugs for rate-control strategy, there is less
agreement on drug therapy for rhythm control and no
agreement on several other topics.

Keywords Atrial fibrillation
Emergency department

A. Lages, O. M. Reiakvam, F. Savva, J. Schovanek, S. van Bree, I. J.
da Silva Chora, G. Privitera, S. Ragozzino, M. von Rotz, and L.
Guidelines
Evidence-based medicine
Critical appraisal
Woittiez are participants of the 22nd European Summer School of
Internal Medicine.
Introduction
Most of the references cited by the different guidelines can be found
in the Supplementary Appendix.
Evidence-based clinical practice guidelines (CPG) should
Electronic supplementary material The online version of this (1) define practical problems, and identify explicitly all
article (doi:10.1007/s11739-016-1580-x) contains supplementary possible decisions and outcomes; (2) evaluate and
material, which is available to authorized users.

& Giorgio Costantino 4

Dipartimento di Emergenza, Ospedale del Tigullio, ASL4
giorgic2@gmail.com Chiavarese, Lavagna, Genoa, Italy
5
1 The 22nd European Summer School of Internal Medicine,
Fondazione IRCCS Ca’ Granda, Ospedale Maggiore
Muravera, Cagliari, Italy
Policlinico, Dipartimento di Medicina Interna, Allergologia
6
Immunologia Clinica, Università degli Studi di Milano, Via IRCCS S.D.N., Naples, Italy
F. Sforza 34, Milan, Italy 7
Azienda Ospedaliera Universitaria AOU Sassari Medicina
2
Unità di Medicina 3, Dipartimento di medicina Interna, Interna, Sassari, Italy
ASST Santi Paolo e Carlo, Milan, Italy 8
European School of Internal Medicine, Muravera, Cagliari,
3
Medicina Interna Generale e Semintensiva, Azienda Italy
Ospedaliero-Universitaria ‘‘Ospedali Riuniti’’, Ancona, Italy

123

summarize the best evidence about the prevention, diag-
nosis, prognosis, therapy, potential harm, and cost-effec-
tiveness; and (3) identify aspects of decision-making, in
which the evidence must be integrated with individual
clinical experience [1]. Thus, CPG should provide useful
recommendations to guide busy physicians to best practice.
However, various pitfalls need to be stressed: the need to
keep CPG updated as the literature changes; potential
conflicts of interests; conflicts of prestige, bias in guideline
development, and grading by different scientific societies
on the same topic; and lack of representativeness of the
patients in everyday practice [2–4]. These are some of the
reasons that have led to the profusion of guidelines, often
with divergence between them.
For these reasons, we set up a working group during the
European Summer School of Internal Medicine, held over a
week in Sardinia in 2014. We decided to analyze as a case,
the guidelines on atrial fibrillation. We chose this topic for
the relevancy of the topic in clinical practice. We think,
however, that a similar approach could be used to compare
guidelines on different topics. The aim of the working
group was to examine the most recent and quoted guide-
lines on the management in the acute setting of atrial fib-
rillation (AF). We started from the general assumption that
internists should not create their own guidelines ex novo,
but they should critically appraise what already exists,
defining strength and weakness of the published recom-
mendations to use in the clinical practice.
Unfortunately, no reference standard method exists to
assess the best guidelines, so we decided to compare the
different guidelines, using clinical questions, to find issue
of convergence and divergence between them [5]. More-
over, we used the GRADE framework in a ‘‘backward
fashion’’ going from recommendation to evidence. Thus,
the aim of this study is twofold: (1) comparing the differ-
ence between guidelines, and (2) providing practical and
affordable advice on the management of atrial fibrillation
in the acute setting.
Methods
A PubMed search was performed in May 2014 to identify
the three most recent and cited published guidelines on AF.
The terms used for the search strategy were ‘‘atrial fibril-
lation’’ and limit ‘‘practice guidelines’’.
The comparison of the three selected guidelines was
done on five specific questions in the acute setting: (1)
When do you choose rate-control or rhythm-control
strategy? (2) When do you choose electrical or phar-
macological cardioversion? (3) In case of pharmacolog-
ical cardioversion, which drug should be used? (4) In the
case of rate-control strategy, which drug should be used?
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Intern Emerg Med
and (5) Considering the setting of atrial fibrillation car-
dioversion in patients without indication for long-term
anticoagulation, how would you manage anticoagulation
therapy?
The five questions were decided a priori, focusing on the
most relevant clinical question about AF in the ED. The 21
sub-questions were decided post hoc by each group for
explanatory clarity purpose.
During the 1-week school, the attending residents
were divided in five working groups. The reason for this
approach was both the practical organization of the work
and the reproducibility. Each person of the group reads
the guidelines, and constructed his/her own guideline
resume table. Then, the tables were compared and the
divergence was solved by discussion. Each group was
formed by a senior tutor (an Internal Medicine specialist)
and a variable number of students (from 5 to 7 Internal
Medicine residents and specialists). The group splits
every question into subheadings for which a conclusive
answer could be drawn. Then, they evaluated differences
and similarities between the selected guidelines and the
cited bibliography.
The agreement between the three guidelines was defined
as:
• No agreement When the three guidelines suggested
different therapeutic strategy or drugs of different
classes
• Agreement When the three guidelines suggested the
same therapeutic strategies or a similar strategy
(different drugs of the same class)
• Partial agreement When different guidelines agreed
with some differences (for example, agreement on a
drug, but no agreement regarding another drug)
• Not available When at least one of the guidelines did
not address the topic.
When there was agreement between guidelines, a rating
of the recommendations following the GRADE system was
given. Briefly, The GRADE system divides the strength of
the recommendations from the quality of the evidence that
should be explicitly reported. Therefore, unlike many other
rating systems, the GRADE system emphasizes that weak
recommendations in the face of high-quality evidence are
common because of factors other than the quality of evi-
dence influencing the strength of a recommendation. For
the same reason, it allows for strong recommendations
based on the evidence from observational studies.
A table was built to provide practical recommendations
about AF management when there was concordance
between the guidelines [6].
The work of the different groups continued after the end
of the school, and was read and approved by all the
participants.
Intern Emerg Med
Results
The guidelines identified through the PubMed search were:
European Society of Cardiology (ESC) guidelines on atrial
fibrillation (AF), the Canadian guidelines on Emergency
Department (ED) management of AF, and the American
Heart Association (AHA) guidelines on AF [7–9].
The three guidelines were published between 2010 and
2014. Supplementary Table a1 shows the different
modalities which they used to grade the recommendations.
Namely, the Canadian used the GRADE system (but no
information was available to assess the accuracy of this
system), the AHA used the AHA system. The ESC
guidelines use a method similar to AHA, but with slightly
different definitions. While the Canadian guidelines
explicitly focus on the acute management of AF, in the
other two guidelines, the information about acute man-
agement is found throughout the entire guideline.
The search strategy adopted by the three guidelines was
not very clear. The Canadian guideline states that ‘‘the
working groups undertook a review of the English lan-
guage literature, using MEDLINE or Cochrane library
searches and a critical appraisal of the evidence focusing
predominantly on the results of randomized clinical trials
and systematic reviews. In the absence of such data, rec-
ommendations were based on the results of large cohort
studies or smaller clinical studies’’. No data were available
about the terms and data of the search. The American
guideline stated that ‘‘an extensive evidence review,
focusing on 2006 to the present, was conducted through
October 2012, and selected other references through
February 2014. Searches were extended to studies, reviews,
and other evidence that were conducted in human subjects,
published in English, and accessible via PubMed,
EMBASE, Cochrane, Agency for Healthcare Research and
Quality Reports, and other selected databases relevant to
this guideline. Key search words included but were not
limited to the following: age, antiarrhythmic, atrial fibril-
lation, atrial remodeling, atrioventricular conduction, atri-
oventricular node, cardioversion, classification, clinical
trial, complications, concealed conduction, cost-effective-
ness, defibrillator, demographics, epidemiology, experi-
mental, heart failure, hemodynamics, human,
hyperthyroidism, hypothyroidism, meta-analysis, myocar-
dial infarction, pharmacology, postoperative, pregnancy,
pulmonary disease, quality of life, rate-control, rhythm
control, risks, sinus rhythm, symptoms, and tachycardia-
mediated cardiomyopathy. In addition, the committee
reviewed documents related to atrial fibrillation (AF) pre-
viously published by the ACC and AHA. References
selected and published in this document are representative
and not all-inclusive. Finally, the European one states that
‘‘experts in the field are selected and undertake a com-
prehensive review of the published evidence’’ without
giving more details on the method used to collect and
analyze the evidence.
Each guideline reports that a conflict of interest state-
ment should be present for every author; however, only the
AHA/ACC explicitly states that the writing committee
chair plus a minimum of 50% of the writing committee had
no relevant actual, potential, or perceived conflicts of
interest that may arise as a result of relationships with
industry and other entities. Finally, the Canadian Guideli-
nes state that the decision on each topic had to be done by a
secret vote and following discussion, an anonymous vote
was obtained in which a two-thirds majority was consid-
ered consensus. In the case of failing consensus, further
discussion was directed at areas of divergence of opinion
until consensus was reached. The other two guidelines do
not explicitly addressed this topic.
Twenty-one relevant sub-questions were identified. For
five of these, there is no agreement between guidelines; for
three, there is partial agreement; and for three, data are not
available (issue not covered by one of the guidelines),
while for ten, there is complete agreement.
Although most of the recommendations of the guideli-
nes were based on weak evidence or expert opinions, in
general, most of them give strong recommendations on the
selected topics.
Table 1 shows a detailed analysis about the agreement
between guidelines for each question considered with the
provisional GRADE-based opinion of the working group
about the most convincing answer, after considering pri-
mary evidence considered by the guidelines. See the Sup-
plementary Appendix for a more detailed analysis of the
comparison (Supplementary Appendix 1).
Table 2 summarizes the practical recommendations in
the management of AF according to the concordance
between guidelines.
Question #1: When do you choose rate-control or
rhythm-control strategy?
All three guidelines, considering survival as the main
outcome, were in agreement to restore rhythm control in
the haemodynamically unstable patient with an acute-onset
of non-valvular AF. However, despite this generalized
agreement, there is no reference to support this statement.
The consensus here is set on a strong recommendation with
low-quality evidence.
In contrast, there is no agreement on the preferred strat-
egy for the stable patient with an acute-onset of non-
valvular AF. The Canadian guidelines underline that the
choice is up to the patient and physician preference. Again,
this position is not supported by any type of reference or
evidence. The AHA guidelines state that the choice of
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 Table 1 Agreement between guidelines and provisional GRADE based recommendation of the working group
Questions Agreement Grade

123
Question 1: When do you choose rate control or rhythm control strategy?
Question 1a: In haemodynamically unstable patients affected by acute-onset non-valvular atrial Agreement on rhythm control Strong recommendation, low-
fibrillation is rhythm control preferable to a rate-control strategy? strategy quality evidence
Outcome: survival
Question 1b: In haemodynamically stable patients affected by acute-onset (less than 48 hours) non- No agreement
valvular atrial fibrillation for which patients rhythm control is preferable to a rate-control strategy ?
Question 1c: In haemodynamically unstable patients affected by acute-onset non-valvular atrial Not available (ESC not covered)
fibrillation and WPW syndrome is rhythm control preferable to a rate-control strategy?
Question 1d: In haemodynamically stable patients affected by acute-onset non-valvular atrial Not available (ESC not covered)
fibrillation and WPW syndrome is rhythm control preferable to a rate-control strategy?
Question 2: When do you choose electrical or pharmacological cardioversion?
Question 2a: In haemodynamically unstable patients affected by acute-onset non-valvular atrial Agreement on electrical Strong recommendation, low-
fibrillation is electrical cardioversion preferable to pharmacological cardioversion? cardioversion quality evidence
Outcome: survival
Question 2b: In haemodynamically unstable patients affected by acute-onset non-valvular atrial Agreement on electrical Strong recommendation, low-
fibrillation and WPW is electrical cardioversion preferable to pharmacological cardioversion? cardioversion quality evidence
Outcome: survival
Question 2c: In haemodynamically stable patients affected by acute-onset (less than 48 hours) non- No agreement
valvular atrial fibrillation is electrical cardioversion preferable to pharmacological cardioversion?
Question 2d: In haemodynamically stable patients affected by acute-onset non-valvular atrial Not available)
fibrillation and WPW syndrome is electrical cardioversion preferable to pharmacological (ESC not covered)
cardioversion?
Question 3: In case of pharmacological cardioversion which drug would you use?
Question 3a: In haemodynamically stable patients affected by acute-onset (less than 48 hours) non- Partial agreement: agreement on Weak recommendation, low
valvular atrial fibrillation and no structural heart disease which drug is preferable for Flecainide and Propafenone; less quality of evidence
pharmacological cardioversion? consensus regarding ibutilide Outcome: restoring sinus
rhythm
Question 3b: In haemodynamically stable patients affected by acute-onset (less than 48 hours) non- No agreement
valvular atrial fibrillation and structural heart disease which drug is preferable for pharmacological
cardioversion?
Question 3c: In haemodynamically stable patients affected by paroxysmal non-valvular atrial Agreement on pill-in-the-pocket Weak recommendation, low
fibrillation and no structural heart disease would you recommend the pill in the pocket approach with strategy quality of evidence
flecainide or propafenone? Outcomes: emergency room
visits, hospitalization,
quality of life
Question 4: In case of rate control strategy which drug would you use?
Question 4a: In patients affected by acute-onset non-valvular atrial fibrillation and no hypotension or Agreement on beta blockers or non- Strong recommendation, low
heart failure which therapy would you recommend in order to obtain rate control? dihydropyridine calcium channel quality of evidence
antagonists Outcome: rate control,
quality of life
Question 4b: In patients affected by acute-onset non-valvular atrial fibrillation with hypotension or Agreement on digitalis Strong recommendation, low
heart failure which drug would you recommend? quality of evidence
Outcome: rate control,
Intern Emerg Med

worsening of heart failure

 Table 1 continued
Questions Agreement Grade

Question 4c: In haemodynamically stable patients affected by acute-onset non-valvular atrial Partial agreement; agreement on Strong recommendation, low
fibrillation with WPW which drug would you recommend? class I drugs. Agreement against quality of evidence
calcium channel blockers, beta Outcomes: mortality (risk of
Intern Emerg Med

blockers, digitalis and adenosine major adverse events)

No agreement on amiodarone
(suggested by ESC, advice against
by AHA, use with caution by
Canadian)
Question 5: In the setting of atrial fibrillation cardioversion, how would you manage anticoagulation therapy?
Question 5a-1: In haemodynamically unstable patients affected by acute-onset non-valvular atrial No agreement
fibrillation undergoing to a rhythm control strategy, before the cardioversion would you recommend
for anticoagulation instead of no anticoagulation for the prevention of thromboembolic
complications?
Question 5a-2: In haemodynamically unstable patients affected by acute-onset non-valvular atrial Agreement on immediate need of the Strong recommendation, low
fibrillation undergoing to a rhythm control strategy, after the cardioversion would you recommend thromboembolic risk profile quality of evidence
for anticoagulation instead of no anticoagulation for the prevention of thromboembolic assessment and continuing/starting Outcome: stroke incidence
complications? For how long? of antithrombotic therapy based on
this profile
Question 5b-1: In haemodynamically stable patients affected by acute-onset (\48 h) non-valvular atrial No agreement before cardioversion
fibrillation undergoing to a rhythm control strategy, before the cardioversion would you recommend
for anticoagulation instead of no anticoagulation for the prevention of thromboembolic
complications?
Question 5b-2: In hemodynamically stable patients affected by acute-onset (\48 h) non-valvular atrial Partial agreement Strong recommendation, low
fibrillation undergoing to a rhythm control strategy, after the cardioversion would you recommend There is a general agreement on quality of evidence
for anticoagulation instead of no anticoagulation for the prevention of thromboembolic anticoagulant therapy after Outcome: stroke incidence
complications? cardioversion according to stroke
risk. No agreement on duration of
anticoagulation
Question 5c-1: In haemodynamically stable patients affected by acute-onset ([48 h) non-valvular atrial Agreement on oral anticoagulants Strong recommendation,
fibrillation undergoing to a rhythm control strategy, before the cardioversion would you recommend therapy for 3 weeks before moderate quality of
for anticoagulation instead of no anticoagulation for the prevention of thromboembolic cardioversion evidence
complications? Outcome: stroke incidence
Question 5c-2: In haemodynamically stable patients affected by acute-onset ([48 h) non-valvular atrial Agreement on oral anticoagulants Strong recommendation,
fibrillation undergoing to a rhythm control strategy, after the cardioversion would you recommend therapy for at least 4 weeks post moderate quality of
for anticoagulation instead of no anticoagulation for the prevention of thromboembolic cardioversion. After the 4 weeks of evidence
complications? anticoagulation with achievement Outcome: stroke incidence
of sinus rhythm there is a general
agreement on considering stroke
risk for the need of anticoagulation
Question 5d: In patients affected by acute-onset non-valvular atrial fibrillation can transesophageal Agreement on TEE-guided Strong recommendation, low
echocardiography modify antithrombotic strategy for the prevention of thromboembolic cardioversion as an alternative to quality of evidence
complications? anticoagulation prior to Outcome: stroke incidence
cardioversion

AF atrial fibrillation, AFL atrial flutter, COR class of recommendation, DCC direct-current cardioversion, OAC oral anticoagulants, ECG electrocardiogram, LOE level of evidence, TOE trans-
oesophageal echocardiogram, WPW Wolff–Parkinson–White

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 Table 2 Practical recommendations for acute AF management according to the agreement between guidelines
Treatment Dose Adverse effect/risk Main indications Contraindications

123
Electrical 150–200 joules biphasic-synchronized waveform Need sedation Haemodynamic instability
cardioversion
Drugs for cardioversion (intravenous route)
Ibutilide 1 mg i.v. over 10 min followed by 1 mg i.v. over Can cause prolongation of the QT interval and torsades de
10 min after waiting for 10 min can be pre- pointes; watch for abnormal T-U waves or QT prolongation.
treated with magnesium sulfate Will slow the ventricular rate
Procainamide 15–17 mg/kg IV over 60 min Hypotension
Propafenone 2 mg/kg i.v. over 10 min, May prolong QRS duration; will slightly slow the ventricular In haemodynamically stable patients Not suitable for
rate, but may inadvertently increase the ventricular rate due to affected by acute-onset (less than 48 h) patients with
conversion to atrial flutter and 1:1 conduction to the ventricles non-valvular atrial fibrillation and no marked structural
structural heart heart disease
In haemodynamically stable patients
affected by acute-onset non-valvular atrial
fibrillation with WPW
Flecainide 2 mg/kg i.v. over 10 min, or 200–300 mg p.o. May prolong QRS duration, and hence the QT interval; and may In haemodynamically stable patients Not suitable for
inadvertently increase the ventricular rate due to conversion affected by acute-onset (less than 48 h) patients with
to atrial flutter and 1:1 conduction to the ventricles non-valvular atrial fibrillation and no marked structural
structural heart heart disease
In haemodynamically stable patients
affected by acute-onset non-valvular atrial
fibrillation with WPW
Amiodarone 5 mg/kg i.v. over 1 h followed by 50 mg/h Phlebitis, hypotension. Will slow the ventricular rate. Delayed Patients with heart failure or structural heart
(ESC) or 150 mg in 10 min followed by 1 mg/ AF conversion to sinus rhythm disease
min for 6 h then oral doses or 0,5 mg/min for
18 h
Drugs for cardioversion (oral route); pill-in-the-pocket approach*
Propafenone 450–600 mg p.o May prolong QRS duration, and hence the QT interval; and may Not suitable for
inadvertently increase the ventricular rate due to conversion patients with
to atrial flutter and 1:1 conduction to the ventricles marked structural
heart disease
Flecainide 200–300 mg p.o. May prolong QRS duration, and hence the QT interval; and may Not suitable for
inadvertently increase the ventricular rate due to conversion patients with
to atrial flutter and 1:1 conduction to the ventricles marked structural
heart disease
Drugs for rate control (intravenous route)
Beta-blockers Heart failure, WPW
syndrome
Metoprolol 2.5–5.0 mg IV bolus over 2 min; up to 3 doses Hypotension, bradycardia In patients affected by acute-onset non-
tartrate valvular atrial fibrillation and no
hypotension or heart failure
Calcium channels blockers Heart failure, WPW
syndrome
Verapamil 0.075-0.15 mg/kg IV bolus over 2 min; may give Hypotension, bradycardia In patients affected by acute-onset non-
an additional 10.0 mg after 30 min if no valvular atrial fibrillation and no
response, then 0.005 mg/kg/min infusion hypotension or heart failure
Intern Emerg Med
 Table 2 continued
Treatment Dose Adverse effect/risk Main indications Contraindications

Diltiazem 0.25 mg/kg IV bolus over 2 min, then 5 15 mg/h Hypotension, bradycardia In patients affected by acute-onset non-
valvular atrial fibrillation and no
hypotension or heart failure
Intern Emerg Med

Others
Digoxin 0.25 mg IV with repeat dosing to a maximum of Bradycardia, digitalis toxicity patients affected by acute-onset non- WPW
1.5 mg over 24 h valvular atrial fibrillation with
hypotension or heart failure
Drugs for rate control (oral route)
Beta-blockers Heart failure, WPW
syndrome
Metoprolol 25–100 mg BID Hypotension, bradycardia In patients affected by acute-onset non-
tartrate valvular atrial fibrillation and no
hypotension or heart failure
Propranolol 10–40 mg TID or QID Hypotension, bradycardia In patients affected by acute-onset non-
valvular atrial fibrillation and no
hypotension or heart failure
Atenolol 25–100 mg QD Hypotension, bradycardia In patients affected by acute-onset non-
valvular atrial fibrillation and no
hypotension or heart failure
Calcium channels antagonists Heart failure, WPW
syndrome
Verapamil 180–480 mg QD Hypotension, bradycardia In patients affected by acute-onset non-
valvular atrial fibrillation and no
hypotension or heart failure
Diltiazem 120–360 mg QD Hypotension, bradycardia In patients affected by acute-onset non-
valvular atrial fibrillation and no
hypotension or heart failure
Others
Digoxin 0.125–0.25 mg QD Bradycardia, digitalis toxicity Patients affected by acute-onset non-
valvular atrial fibrillation with
hypotension or heart failure

Pill-in-the-pocket approach: for conversion of atrial fibrillation to sinus rhythm, oral flecainide or propafenone is administered in a single dose according to the weight of the patient. The dose of
flecainide is 300 mg if the patient weighed 70 kg or more and is 200 mg otherwise; the dose of propafenone is 600 mg if the patient weighed 70 kg or more and is 450 mg otherwise. Patients
who had been treated successfully in the hospital should take the drug 5 min after any subsequent onset of palpitations. After the ingestion of the drug, a resting state (in a supine or sitting
position) is recommended until the palpitations stop or at least 4 h had passed. Patients should be advised to contact the emergency room if their palpitations persist 6–8 h after the ingestion of
the drug, if they have symptoms that had not occurred during the previous arrhythmic episodes (e.g., dyspnea, presyncope, or syncope), or if they feel a marked increase in heart rate after
ingestion of the drug. Patients should not take more than one oral dose during a 24-h period. Patients should not be treated if they have one or more of the following findings:
electrocardiographic evidence of ventricular pre-excitation or bundle-branch block (QRS interval, [120 ms), ischemic heart disease, dilated or hypertrophic cardiomyopathy, a history of heart
failure, severe valvular heart disease, chronic or pulmonale, left ventricular dysfunction (ejection fraction, \50%), a long QT interval or the Brugada syndrome, the bradycardia–tachycardia
syndrome (resting heart rate, B50 beats per minute, or repetitive sinoatrial blocks during waking hours), documentation of the previous episodes of second- or third-degree atrioventricular
block, acute disease, very severe chronic diseases (e.g., muscular dystrophies or systemic collagen diseases), renal or hepatic insufficiency, previous hypokalemia (potassium level, \3 mmol
per liter), suspected or known pregnancy, a known intolerance of flecainide or current propafenone, or current prophylactic antiarrhythmic treatment [13]

123

rhythm control has to be limited to patients with persistent
symptomatic AF. However, they also point out the possi-
bility of a rhythm-control strategy in patients with difficulty
in achieving adequate rate-control, younger age, tachycar-
dia-mediated cardiomyopathy, first episode of AF, AF pre-
cipitated by an acute illness, and patient preference. The
references presented make this a strong recommendation,
however, with low-quality evidence. As for the ESC
guidelines, they recommend the pursuit of a rhythm-control
strategy in the following situations: (1) patients with
symptomatic (EHRA score [2) AF despite adequate rate
control, (2) patients with AF and AF-related heart failure
should be considered for improvement of symptoms, (3) as
the initial approach in young symptomatic patients in whom
catheter ablation treatment has not been ruled out, and (4)
patients with AF secondary to a trigger or substrate that has
been corrected (e.g., myocardial ischaemia and hyperthy-
roidism). The rate-control strategy should instead be the
initial approach in elderly patients with AF and minor
symptoms. The literature provided show discrepant levels of
evidence, from data derived from large non-randomized
studies to consensus opinion of the experts, with both strong
and weak recommendations. The outcomes considered were
survival, hospitalization rate, stroke reduction, incidence of
heart failure, and quality of life (QOL).
For haemodynamically unstable patients affected by
acute-onset non-valvular atrial fibrillation and Wolff
Parkinson White (WPW) syndrome, the recommended
strategy for both the Canadian and AHA guidelines is to
perform a rhythm-control strategy by means of an urgent
electrical cardioversion. There are no cited references in
either guidelines, but the final outcome is survival, making
this a strong recommendation with low-quality evidence.
The ESC guidelines do not cover this specific condition.
For haemodynamically stable WPW patients, once
again, the ESC guidelines do not cover this specific con-
dition, while Canadian and AHA guidelines agree on the
recommendation of a rhythm-control strategy using phar-
macological cardioversion with ibutilide or procainamide.
The final outcomes are survival, hospitalization, stroke
reduction, incidence of heart failure, and quality of life.
Both guidelines pinpoint that this as a strong recommen-
dation with low-quality evidence, and only the AHA
guidelines cite as a reference an old AHA guideline on
supraventricular dysrhythmias.
Question #2: When do you choose electrical or phar-
macological cardioversion?
The three guidelines agree that in haemodynamically
unstable patients, with or without WPW, affected by acute-
onset non-valvular AF, electrical cardioversion is prefer-
able to pharmacological cardioversion. The Consensus is
set on a strong recommendation, but the quality of evi-
dence is low.
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Intern Emerg Med
By contrast, there is no agreement on the treatment of
stable patients. The Canadian guidelines leave the decision
on individual considerations of the patient and the treating
physician, while the AHA guidelines recommend electrical
cardioversion for atrial flutter or for patients not responding
to drug therapy. The ESC guidelines do not give a specific
recommendation.
For the stable patient affected by WPW Canadian and
the AHA, guidelines suggest drug therapy (Procainamide
or Ibutilide), citing the previous guidelines on supraven-
tricular dysrhythmia, while ESC does not cover the topic.
Question #3: In case of pharmacological cardioversion,
which drug should be used?
There is a general consensus among the three guidelines
regarding the use of class IC (Flecainide and Propafenone)
as first-line choice for pharmacological cardioversion in the
acute non-valvular AF, of the haemodynamically
stable patient without structural heart disease. ACC/AHA
and Canadian guidelines also recommend the use of the
class III antidysrhythmic ibutilide (COR:I), whereas ESC
guidelines downgrade this drug to a lower class of rec-
ommendation (COR: IIb) due to its pro dysrhythmic
effects. Only the AHA/ACC guidelines recommend Dofe-
tilide (anti dysrhythmic class III), while the others do not
even mention this drug, perhaps, because AHA/ACC
guidelines were published later than ESC and Canadian
guidelines. Procainamide (antidysrhythmic class IA) is
recommended only by Canadian guidelines.
All these recommendations are supported by a high level
of evidence (LOE: A). However, it must be stressed that in
all the studies mentioned above, the primary end-point is
the success rate in conversion to sinus rhythm, and there
are no available data regarding other outcomes, such as
hospitalization, heart failure, stroke, or quality of life.
Interestingly, some of the references cited by Canadian
guidelines are case reports [10] or reviews [11, 12], thus
leaving the grade of evidence weak.
It is not possible to gather an explicit answer to the
question of haemodynamically stable patients affected by
acute-onset (less than 48 h) non-valvular AF and structural
heart disease. A specific strategy for patients with new-
onset non-valvular AF and coexisting structural heart dis-
ease is provided only by European guidelines. According to
this document, amiodarone is the drug of choice with a
strong grade of recommendation (COR:I LOR: A). The
primary end-point in the aforementioned studies is the rate
of sinus rhythm conversion. On the other hand, ACC/AHA
does not provide a clear indication for the management of
this kind of patient. The recommendation might be sought
considering the contraindications of antidysrhythmic IC
class drugs in patients with impaired cardiac function.
According to these criteria, the only drugs with I/A rec-
ommendation are Dofetilide and intravenous Ibutilide,
Intern Emerg Med
whereas Amiodarone has only a IIa/A indication. Inter-
estingly, Canadian guidelines do not recommend Amio-
darone for restoring sinus rhythm at all. The drugs of
choice in this document are Ibutilide and Procainamide. It
is worth mentioning that none of the studies underlying all
the aforementioned recommendations used hard end-point,
such as survival, hospitalization, stroke reduction, inci-
dence of dysrhythmia, heart failure, and quality of life.
There is a general agreement among the three guidelines
regarding the ‘‘pill-in-the-pocket approach’’, (PiP) which is
considered feasible, safe, and effective. This recommen-
dation is based on a single study conducted in Italy [13]. In
this study, the main endpoints are the number of ED visits,
hospital admissions, and quality of life. All of them are
improved by PiP. No patients had a transient ischemic
attack, stroke, or arterial embolism, during the follow-up
period. However, it is worth noting that this study evalu-
ated only patients without structural heart disease. For this
reason, it is not clear whether this approach is safe and
effective in patients with impairment of cardiac function. It
should also be stressed that no data are available with
regard to the effects of the PiP in terms of incidence of
heart failure and survival.
According to ESC guidelines, PiP should be used in
patients with a number of episodes ranging between once
per month and once per year, whereas the Canadian
guidelines suggest using this approach with a number of
AF recurrences between 2 and 6/year. Moreover, Canadian
guidelines emphasize that AF episodes should be longer
lasting, e.g., [4 h, with long intercurrent periods of sinus
rhythm between episodes. Finally, both AHA and Canadian
guidelines underline that adequate rate control needs to be
achieved, either by the association of beta-blockers to the
anti dysrhythmic drug, or treatment with an AV-nodal
blocking agent, to prevent 1:1 conducting atrial flutter.
Another interesting aspect concerns the drugs that are
considered contraindicated to treat AF.
The contraindication of class IC antidysrhythmic drugs
in patients with paroxysmal non-valvular AF and structural
heart disease is well acknowledged by all three guidelines.
Some concerns still exist regarding the use of Dronedarone
in patients affected by chronic heart failure (CHF). There is
a general consensus in considering Dronedarone harmful in
this clinical context in all three guidelines. Indeed, the
‘‘Antidysrhythmic Trial with Dronedarone in Moderate to
Severe CHF Evaluating Morbidity Decrease (ANDRO-
MEDA)’’ study reports a fivefold increase in mortality
(mainly due to worsening of heart failure) in patients
treated with Dronedarone with severe heart failure and left
ventricular systolic dysfunction [14]. However, the three
guidelines deal in a different way with this evidence in
their recommendation. ESC and AHA/ACC agree in stat-
ing that Dronedarone should not be used in NYHA class
III–IV patients or NYHA class II patients with recent (less
than 1 month) decompensation (COR: III LOE: B). On the
other hand, Canadian guidelines ban Dronedarone only in
patients with ejection fraction B35% and consider this
drug as a first choice in patients with structural heart dis-
ease but with ejection fraction C35%.
Question #4: In case of rate-control strategy, which
drug should be used?
Rate-control strategy is a very important aspect of the
management of AF. The purpose of rate control is to
improve symptoms, positively impact QOL, reduce mor-
bidity, minimize the possibility of tachycardiomyopathy,
and reduce hospitalization. The primary drugs used for
ventricular rate control are: beta-blockers, calcium channel
blockers, and digoxin. These agents obtain their action by
slowing atrioventricular nodal (AV) conduction and pro-
longing AV-nodal refractoriness. The selection of a
specific drug is made according to the patients’ symptoms,
the presence or absence of heart failure, and other
comorbidities.
In patients affected by acute-onset non-valvular AF, all
guidelines strongly recommend the use of beta-blockers
and calcium antagonists to obtain rate control, when
hypotension and heart failure are absent. On the other hand,
in the presence of hypotension or heart failure, all the
guidelines recommend the use of digitalis. Some differ-
ences exist on amiodarone, which is suggested by the ESC
guidelines, but not mentioned by the other two. Regarding
WPW syndrome, all guidelines advise against calcium
antagonist, digoxin, beta-blockers, and adenosine because
of the potential for degeneration to ventricular fibrillation
related to rapidly conducting anterograde accessory path-
ways. There are some differences about the drugs of choice
in this setting. The ESC guidelines suggest amiodarone,
together with class I drugs, while the AHA counsels against
amiodarone, and the Canadian suggest using it with cau-
tion, without references. All three guidelines suggest using
class I drugs.
Question #5: Considering the setting of atrial fibrilla-
tion cardioversion in patients without indication for long-
term anticoagulation, how would you manage anticoagu-
lation therapy?
The statements of the three guidelines on the manage-
ment of haemodynamically unstable patients undergoing a
rhythm-control strategy are based only on the opinions of
experts.
In the emergency setting, Canadian guidelines place a
high value on the immediate management of haemody-
namic instability, and recommend anticoagulation with
intravenous unfractionated heparin (UFH) or low-molecu-
lar-weight (LMWH) prior to cardioversion only in selected
high-risk patients (e.g., mechanical valve, rheumatic valve
disease, recent stroke, or transient ischemic attack), or if
123

the duration of AF/Atrial flutter (AFL) is C48 h, or
unknown. ACC/AHA guidelines state that initiation of
anticoagulation should not delay interventions to stabilize
the patient; however, they consider it reasonable to
administer heparin (intravenous bolus of UFH followed by
infusion, or LMWH) or one of the newer oral anticoagu-
lants. In the ESC guidelines, experts recommend the use of
heparin (intravenous UFH bolus followed by infusion, or
weight-adjusted therapeutic dose LMWH) prior to emer-
gency cardioversion.
About post-cardioversion, guidelines agree on the
immediate need for a thromboembolic risk profile assess-
ment and starting or continuing antithrombotic therapy
based on this profile. The risk of stroke should be deter-
mined by CHADS2 score according to the Canadian and
ESC guidelines, and by CHA2DS2-VASc score according
to the ACC/AHA.
The recommendations of the three guidelines for
haemodynamically stable patients affected by acute-onset
(\48 h) non-valvular AF undergoing a rhythm-control
strategy are based only on observational studies. There are
no randomized clinical trials (RCT) on the use of heparin
peri-cardioversion.
In patients with low risk of stroke, ACC/AHA and ESC
guidelines recommend heparin near cardioversion, while
Canadian guidelines suggest no anticoagulation; in high-
risk patients, Canadian guidelines suggest delaying car-
dioversion until after 3 weeks of anticoagulation.
After cardioversion, there is agreement in considering
anticoagulation according to patient’s risk factors.
Concerning the stable non-valvular AF patients
of [48 h onset undergoing a rhythm-control strategy, the
three guidelines base their recommendations largely on the
previous guidelines.
They recommend oral anticoagulant (OAC) therapy for
3 weeks before and at least 4 weeks post-cardioversion.
After the 4 weeks of anticoagulation with achievement of
sinus rhythm, there is a general agreement on considering
stroke risk for the need for long-term anticoagulation; in
detail, Canadian guidelines suggest that if sinus rhythm is
achieved and sustained for 4 weeks, the need for ongoing
antithrombotic therapy should be determined based on the
risk of stroke, and, in selected cases, expert consultation
may be required; the ESC guidelines consider not only the
risk of stroke, but also the risk of AF recurrence. The AHA
guidelines suggest that the anticoagulant therapy should be
driven only by the risk of stroke.
Regarding the efficacy of transesophageal echocardio-
graphy (TEE) to modify antithrombotic strategy for the
prevention of thromboembolic complications, the three
guidelines base their recommendations on the only pub-
lished RCT on this topic, and agree on using TEE prior to
cardioversion, and then proceeding with cardioversion if no
123
Intern Emerg Med
thrombus in left atrium is identified in patients with AF or
atrial flutter of C48 h or of unknown duration. Thus, TEE
is an alternative to anticoagulation prior to cardioversion.
Oral anticoagulation must be continued for a minimum of
4 weeks. Although the three guidelines refer to the same
trial, the class of recommendation is different: the Cana-
dian and AHA guidelines express a weaker recommenda-
tion than European guidelines.
Discussion
The aim of our study is twofold: (1) to assess the differ-
ences in guidelines on the same topic and (2) to help the
clinician to address common problems where there is
scanty evidence. Our study confirms the findings of a
previous systematic review of cardiovascular guidelines
that in several clinical conditions, different guidelines give
different indications [15]. In the case of acute AF, one of
the reasons for this may be the scanty evidence available
that leads to many recommendations based on expert
opinions rather than results of clinical trials. However,
most of the recommendations are defined as strong, sug-
gesting that the authors seem to think that there is sufficient
clinical agreement that no further studies are needed.
However, there are some striking differences between the
guidelines in the choice of drugs used in acute AF, with the
use of a drug by one guideline and cautioning against its
use by another, which suggests that expert opinion is not
unanimous. For this reason, the second aim of our work is
to build some practical advice for internists on how to
address acute AF in the ED setting, based on the answer to
our questions on which the guidelines were coherent.
Many limitations of our work should be acknowledged.
To our knowledge, although there are many scales for
comparing CGP, there is no reference standard. The
AGREE II quality assessment has been developed to assess
the methodological quality of CGP, but not the clinical
content [16]. Thus, we prefer a comparison of the relevant
clinical topics, referring then to the citations on which the
recommendations are based. The coherence between
guidelines does not mean that the issue addressed is cor-
rect. However, it is unlikely to be totally incorrect, in a
setting in which there is very little evidence to support
decision-making. While many AF guidelines exist, we
selected the three most recent ones at that time that were
produced by important societies that should be at least
representative of all guidelines on the topic.
Instead of publishing further new guidelines, our aim is
to test a different approach that is to critically compare
different guidelines also giving some practical advice for
the clinicians. We limit our evaluation exclusively to the
acute AF management in the ED setting, and we do not
Intern Emerg Med
address any other aspects of the management of this
condition.
It is important to note the different years of publications
of different guidelines: the ACC/AHA guidelines are more
recent than the Canadian and ESC guidelines (2014 versus
2011 and 2010/2012, respectively); this may explain some
differences between the guidelines, such as the use of the
non-vitamin K oral anticoagulants (NOACs) or the use of
CHADS2 or CHA2DS2-VASc to determine the risk of
stroke. Other differences, where they give divergent rec-
ommendations from the evidence of the same studies,
remain difficult to explain.
We have approached this analysis as Internists rather
than specialist cardiologists. The role of the internist is to
deal with complexity; this is true for clinical decision-
making for patients, critical appraisal of the literature, and,
in our opinion, also for wisely choosing guidelines rec-
ommendations. Since there is no reference method on
practically judging the most useful guidelines on a specific
topic, our aim is to explore whether a comparison of dif-
ferent guidelines can provide any unambiguous informa-
tion on the specific topic of atrial fibrillation, and what
implications such an analysis might have for other CGPs.
In conclusion, there is scanty evidence on the manage-
ment of AF in the acute setting. While there is broad
agreement on the management of the haemodynamically
unstable patient and the use of drugs for rate-control
strategy, there is less agreement on drug therapy for rhythm
control and no agreement on several other topics.
Acknowledgements 2014 ESIM school residents: Arjola Bano,
Sharry Kahlon, Demetra Tourva, Frini Karaolidou, Maibrit Loogna,
Louise Caroline Aaltonen, Jyrki Mustonen, Jenni Koskela, Jan
Reimer, Amr Abdin, Inga Tetruashvili, Hen Kayless, Maayan Sasson
Ben, Teresa Vanessa Fiorentino, Valentina Tommasi, Marta Zanon,
Anna Salina, Claire Den Hoedt, Tranheim Marte Kase, Joao Estevao,
Nicolay Tsarev, Sanja Dragasevic, Noel Lorenzo Villalba, Eric Pascal
Kuhn, Lia Jeker, Claudia Beerli, Imene Rachid, Ayse Bahar kele-
soglu, Pinar Yildirim, Demet Sekure Arslan, and Richard Frederich
De Butts. This research did not receive any specific grant from
funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Statement of human and animal rights This article does not con-
tain any studies with human participants or animals performed by any
of the authors.
Informed consent None.
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