Journal of Thrombosis and Haemostasis, 13 (Suppl. 1): S304–S312 DOI: 10.1111/jth.

12974

INVITED REVIEW

Postoperative atrial fibrillation in non-cardiac and cardiac

surgery: an overview
A . B E S S I S S O W , * ‡ J . K H A N , ‡ ¶ P . J . D E V E R E A U X , ‡ § J . A L V A R E Z - G A R C I A † and
P. ALONSO-COELLO§**
*Division of General Internal Medicine, McGill University Health Center, Montreal, QC; ‡Population Health Research Institute’s Perioperative
Medicine and Surgical Research Unit, Hamilton; ¶Department of Anesthesia, University of Toronto, Toronto; §Departments of Clinical
Epidemiology and Biostatistics and Medicine, McMaster University, Hamilton, ON, Canada; †Cardiology Department, Hospital de la Santa
Creu i Sant Pau, Universidad Autonoma de Barcelona; and **Iberoamerican Cochrane Center, Biomedical Research Institute (CIBERESP-IIB-
Sant Pau), Barcelona, Spain

To cite this article: Bessissow A, Khan J, Devereaux PJ, Alvarez-Garcia J, Alonso-Coello P. Postoperative atrial fibrillation in non-cardiac and
cardiac surgery: an overview. J Thromb Haemost 2015; 13 (Suppl. 1): S304–S12.

postoperative setting are variable and depend on the type

Summary. Postoperative atrial fibrillation (POAF) is the
most common perioperative cardiac arrhythmia. A major
risk factor for POAF is advanced age, both in non-car-
diac and cardiac surgery. Following non-cardiac surgery,
it is important to correct reversible conditions such as
electrolytes imbalances to prevent the occurrence of
POAF. Management of POAF consists of rate control
and therapeutic anticoagulation if POAF persists for
> 48 h and CHADS2 score > 2. After cardiac surgery,
POAF affects a larger amount of patients. In addition to
age, valve surgery carries the greatest risk for new AF.
Rate control is the mainstay therapy in these patients.
Prediction, prevention, and management of POAF should
be further studied.
Keywords: atrial fibrillation; cardiac surgery; general
surgery; postoperative period; review.
Introduction
Atrial fibrillation (AF) is the most common serious car-
diac arrhythmia in the surgical setting. The incidence of
postoperative atrial fibrillation (POAF) varies according
to the type of surgery. Atrial fibrillation develops in 3%
of unselected adults aged ≥ 45 years undergoing non-
cardiac surgery, but it is much higher (30%) in thoracic
surgery [1–5]. This rate is even more substantial after car-
diac surgery, going up to 40% [6]. Causes of AF in the
Correspondence: Pablo Alonso-Coello, Iberoamerican Cochrane Cen-
ter, Biomedical Research Institute (CIBERESP-IIB-Sant Pau), Barce-
lona, Spain.
Tel.: +34 93 553 78 14; fax: +34 93 553 78 09.
E-mail: palonso@santpau.cat
of surgery.
Atrial fibrillation engenders multiple effects on the car-
diopulmonary hemodynamics, tachyarrhythmia being the
most common presentation. The rapid irregular ventricu-
lar rate can result in insufficient coronary flow to com-
pensate myocardial oxygen demand, leading to
myocardial ischemia [7]. Furthermore, decreased diastolic
filling time and cardiac output are important physiologi-
cal consequences of tachyarrhythmias [8]. Less frequently,
AF presents as a bradyarrhythmia, which can lead to
decreased cardiac output in patients with fixed stroke vol-
ume. Lastly, loss of atrial contraction, mainly in patients
with hypertension and diastolic dysfunction, increases
pulmonary artery pressures [8].
All these effects on the cardiopulmonary hemodynam-
ics can lead to hypotension, heart failure, and myocardial
infarction. Accordingly, AF after surgery has been associ-
ated with worse outcomes including increased risk of
stroke, mortality, and length of hospital stay [6,9].
In this article, we will review the incidence, pathophysi-
ology, prognosis, prediction, prevention, and management
of POAF in non-cardiac and cardiac surgery.
New atrial fibrillation after non-cardiac surgery
Incidence and pathophysiology
New POAF occurs in about 3% of unselected patients
[1]. However, this estimate is most likely an underestima-
tion due to only a minority of patients being monitored
for arrhythmias after non-cardiac surgery. The patho-
physiology behind the development of POAF in non-car-
diac surgery is not well understood [3]. It is believed that,
in most cases, AF is provoked by the combination of
multiple mechanisms and factors. First, the activation of
the sympathetic system due to the stress of surgery

© 2015 International Society on Thrombosis and Haemostasis


increases heart rate and catecholamines release. Addition-
ally, clinical circumstances such as hypovolemia, intraop-
erative hypotension, anemia, trauma, and pain can also
affect the sympathetic activity [3]. Other mechanisms that
could trigger arrhythmia are electrophysiological distur-
bances and metabolic imbalances (e.g., hypoglycemia or
electrolytes disturbances). Hypoxia can also result in
arrhythmia due to pulmonary vein vasoconstriction and
increase right ventricular pressure and right atrial stretch.
Also, hypoxia can cause ischemia of the myocardial atria
cells, altering the cardiac conduction system. Another
mechanism thought to contribute to the development of
AF is hypervolemia. Hypervolemia increases intravascular
volume, which causes stretching of the right atrium [3].
Lastly, in cardiac surgery, POAF was correlated to ele-
vated inflammatory markers such as C-reactive protein
(CRP), white blood cells (WBC), and interleukins [10–14].
A similar process may occur in non-cardiac surgery.
Prognosis
Most patients developing AF after surgical intervention
convert to sinus rhythm spontaneously [9]. Many physi-
cians, hence, question the need to diagnose and treat this
apparently self-limited arrhythmia that usually does not
always result hemodynamic compromise and death.
However, evidence since the 1980s shows that POAF has
a poor prognosis, with an increased risk of postoperative
complication [15].
In the POISE trial (a 8351 patient randomized con-
trolled trial of a beta-blocker vs. placebo in patients
undergoing non-cardiac surgery), patients who developed
new clinically important perioperative AF were at a
higher risk of stroke within 30 days after surgery. After
adjustment for perioperative risk factors, POAF
remained an independent predictor of stroke within
30 days of surgery (OR 3.51; 95% CI 1.45–8.52) [4].
Also, in the majority of the cases, the stroke led to the
patients’ death or patients were left incapacitated or
with severe limitations in their ability to perform activi-
ties of daily living.
Long-term risk of complications is also present in
POAF. A recent cohort study assessed the long-term risk
of stroke in over 1.6 million patients who underwent non-
cardiac surgery [5]. After non-cardiac surgery, 0.78% of
patients developed POAF during the index admission
(mean follow-up period was 2.1 years). Among the
patients who developed POAF, the cumulative risk of
stroke at 1 year after discharge was 1.47% compared to
0.36% in those with no AF (HR 2.0; 95% CI 1.7–2.3).
The higher the CHADS2 score was the higher the 1-year
cumulative rate of stroke.
Besides stroke, patients with POAF have a higher risk
to develop other complications such as congestive heart
failure (relative risk [RR] 3.9; 95% CI 2.9–5.3), myocar-
dial infarction (RR 4.2; 95% CI 2.7–6.6), cardiac arrest
© 2015 International Society on Thrombosis and Haemostasis
Perioperative atrial fibrillation: an overview S305
(RR 8.0; 95% CI 3.9–16), bacterial pneumonia (RR 7.4;
95% CI 5.5–9.9), and increased hospital length of stay
(increase of 2.5 days; 95% CI 1.9–3.1 days) [15].
Prediction
Following non-cardiac surgery, AF usually occurs during
the first 4 days. Numerous studies have tried to identify
possible risk factors for POAF after non-cardiac surgery.
In 2004, Vaporciyan et al. [16] performed univariate and
multivariate analyses on 2588 patients undergoing tho-
racic surgery. Factors identified as predictors of POAF
included: age 60–69 (RR 4.49; 95% CI 2.79–7.22), age
≥ 70 years (RR 5.30; 95% CI 3.28–8.59), male sex (RR
1.72; 95% CI 1.29–2.28), history of congestive heart fail-
ure (RR 2.51; 95% CI 1.06–6.24), and history of arrhyth-
mia (RR 1.92; 95% CI 1.22–3.02). The most predictive
variable was pneumonectomy (RR 8.91; 95% CI
5.59–17.28). More recently, a similar study was performed
that included over 13 000 patients undergoing lung cancer
surgery [17]. Multivariate logistic regression demonstrated
that increased age, increased extent of the operation, male
sex, and stage II or greater tumor were predictors of
POAF.
Passman et al. [18] developed a prediction score for AF
after major non-cardiac surgery. Four independent pre-
dictors were included in the predictive score: male gender
(OR 1.95; 95% CI 1.16–3.30) (one point), age 55–74 years
(OR 4.88; 95% CI 1.69–14.13) (three points), age
≥ 75 years (OR 9.31; 95% CI 3.01–29.50) (four points),
and preoperative heart rate ≥ 72 beats/minute (OR 1.89;
95% CI 1.15–3.13) (one point). The score, with six cate-
gories and their corresponding risk, ranges from 0% to
54.6%. The model was deemed appropriate for all sub-
types of surgery, and its c-statistics varied from 0.65 to
0.73. However, the score was developed using the data of
only 856 patients from one single center and requires fur-
ther validation.
A recent systematic review evaluated whether preopera-
tive B-type natriuretic peptide (BNP) measurements are
independent predictor of POAF after thoracic surgery.
Over 700 patients from five observational studies were
included in the meta-analysis. An elevated preoperative
BNP measurement was associated with an increase risk
for POAF (OR 3.13; 95% CI 1.38–7.12) [19].
Prevention
Any clinical state that triggers POAF should be consid-
ered as a potential target. Therefore, avoiding electrolyte
imbalances, hypervolemia, hypovolemia, hypotension,
anemia, and pain may help prevent the development of
this arrhythmia.
Few medications have been studied as potential agents
to prevent perioperative AF. Devereaux et al. [4] con-
ducted a large randomized controlled trial, the POISE
S306 A. Bessissow et al
trial that included over 8000 patients undergoing major
non-cardiac surgery. Patients were randomized to meto-
prolol succinate or placebo. The primary end point was a
composite outcome of cardiovascular death, non-fatal
myocardial infarction, and non-fatal cardiac arrest at
30 days after surgery. Clinically significant new POAF
was recorded in 2.2% of patients in the metoprolol group
vs. 2.9% in the placebo group (HR 0.76; 95% CI
0.58–0.99). While this observation suggests that preopera-
tive metoprolol administration may prevent the develop-
ment of POAF, these data should not be viewed in
isolation, as this intervention also increased the risk of
mortality and stroke.
Statins, besides its lipid lowering properties, also have
an anti-inflammatory effect, and its role to prevent AF
has been suggested [20]. In a recent systematic review,
statin therapy prevented POAF (RR 0.53; 95% CI
0.30–0.94). Of the 16 trials included, however, only four
were non-cardiac surgery trials [21]. Therefore, with the
current evidence, it is unclear whether a statin can
prevent POAF in patients undergoing major non-cardiac
surgery.
Colchicine, an anti-inflammatory drug, that has showed
promise in preventing POAF in cardiac surgery is being
evaluated in a multicenter pilot [22]. The purpose of col-
chicine for prevention of perioperative atrial fibrillation in
patients undergoing thoracic surgery (COP-AF) pilot
study is to determine the feasibility of comparing colchi-
cine to placebo for the prevention of new AF in patients
undergoing thoracic surgery and establish a foundation
for a large, multicenter, clinical trial. Study completion
for COP-AF pilot study is projected for June 2015.
Management
A fundamental step in managing new POAF is determin-
ing the underlying cause of this arrhythmia. In most
cases, the resolution of the precipitating cause will be
enough. In patients with persistent AF, rate control is the
mainstay of the therapy. Previous studies have compared
rate control with rhythm control in patients newly diag-
nosed with AF. In 2002, the AFFIRM trial demonstrated
that rate control had fewer adverse outcomes and is pre-
ferred over rhythm control [23]. Studies addressing this
clinical question excluded perioperative AF. Despite the
exclusion of perioperative patients, current recommenda-
tions favor rate control over rhythm control [3].
In patients with new POAF, assessing whether the
patient is symptomatic or asymptomatic is crucial and
will guide management. At any point, if the patient is
symptomatic or hemodynamically unstable, one must
consider electrical or pharmacological cardioversion.
Intravenous amiodarone can be used for cardioversion
and physicians can use digoxin, metoprolol, or diltiazem
for rate control. In the asymptomatic patient, choosing
oral metoprolol, diltiazem, or digoxin is recommended
[3]. In patients with underlying coronary artery disease or
low ejection fraction a beta-blocker is preferred. A heart
rate between 80 and 100 beats per minute should be tar-
geted.
During the perioperative period, patients are considered
to be in a hypercoagulable state and at high risk of bleed-
ing. Initiating anticoagulation during this period should
be performed with caution. Most guidelines agree to
consider anticoagulation when POAF persists over 48 h
[24–26]. The 2014 AHA/ACC guidelines suggest the use
CHA2DS2-VASC score to assess the risk of stroke (and
the need for anticoagulation) and the HAS-BLED score
to determine the risk of bleeding [26]. Although none of
these scores have been validated in surgical patients, their
use in patients with postoperative AF seems reasonable if
AF persists over 48 h [3].
It is recommended to consider therapeutic anticoagula-
tion if the CHA2DS2-VASC score is ≥ 2. Once again,
assessing the risk of bleeding is also crucial. If the risk of
thromboembolism outweighs the risk of bleeding, antico-
agulation is recommended in these patients [3]. If the risk
of bleeding is substantial and the CHA2DS2-VASC score
is ≥ 2, aspirin may then be indicated. All of these recom-
mendations are based on low quality evidence.
Postoperative atrial fibrillation after cardiac surgery
Incidence and pathophysiology
AF is the most common arrhythmia that occurs after car-
diac surgery [27]. POAF has an incidence of 20% to
40%, depending on the type of procedure, with higher
rates after valvular surgery (30–50%) [28–30]. Combined
coronary artery bypass surgery (CABG) and valvular sur-
gery have the highest risk of POAF (60–80%) [31]. Dif-
ferences in incidence rates are likely related to patient
populations, pre-existing comorbidities, and distinct surgi-
cal stressors and insults on the myocardium. Further-
more, diverse methods of detection, surveillance, and
study methodologies also contribute to the reported vari-
ability.
POAF typically occurs on postoperative day 2, with
70% of cases occurring within the first four postoperative
days [32]. Melby et al. [33] conducted a time series analy-
sis on patients after bypass and valvular surgeries and
documented two postoperative periods where patients are
at highest risk of POAF. They proposed a trajectory
whereby the highest risk occurs immediately after surgery
with a second increase in risk occurring 48 h postopera-
tively. Despite the vast majority of cases occurring within
the first week after surgery, late onset POAF is underap-
preciated and occurs at a rate of 4% after a patient is
discharged from hospital [34]. While POAF is typically
self-limited with an average duration of 11–12 h and 80%
of cases self-resolving to normal sinus rhythm within 24 h
after initial onset [35], a substantial proportion of patients
© 2015 International Society on Thrombosis and Haemostasis

will experience a second episode [36]. If a recurrence
occurs, the majority will occur within 2 days of the first
episode [36].
Clinical manifestations of POAF do not appear to dif-
fer from the signs and symptoms of AF in the non-car-
diac or non-operative setting. Hemodynamic instability,
reduced cardiac output, and hypotension are all signs
indicative of POAF after cardiac surgery. However, the
diagnosis is made relatively quickly because cardiac surgi-
cal patients receive telemetry surveillance or serial electro-
cardiograms in the immediate postoperative period.
The pathophysiological pathways for developing POAF
after cardiac surgery continue to be an active area of
research, and it is probable that its development is multi-
factorial and influenced by patient, surgical, anesthetic,
and postoperative factors. Cardiac surgery is associated
with vast physiological disturbances such as vasoplegia,
systemic inflammation, excessive catecholamine release,
changes in sympathetic and parasympathetic tone, large
fluid shifts, and neurohumoral activation—all potential
stimuli for arrhythmia [28,37]. Moreover, the presence of
significant coronary lesions in the arteries supplying to the
atria is an independent predictor of AF following CABG
[38,39]. So, atrial ischemia per se could be an additional
factor involved in the pathophysiology of this arrhythmia.
It appears that the common mechanistic pathway in
POAF is atrial refractoriness and subsequent generation
of re-entry wavelets. Direct atrial injury from surgical
incisions and manipulation may contribute to abnormal
atrial conduction disturbances and refractoriness [6]. Fur-
thermore, studies have suggested that the atria remains
electrically active during cardiopulmonary bypass surgery
despite adequate cardioplegia, predisposing to ischemia
and thus, susceptibility to arrhythmias [40].
Prognosis
Postoperative AF after cardiac surgery is associated with
similar, yet different, complications than AF after non-
cardiac surgery or in the non-operative setting. POAF
after cardiac surgery causes a reduction in ventricular fill-
ing and atrial pooling, predisposing to intracardiac
thrombus formation. POAF increases the risk of stroke
by threefold after cardiac surgery [41]. Other direct conse-
quences of POAF include hypotension, pulmonary
edema, and pacemaker placement [42]. Complications
such as acute kidney injury, cardiac failure, intra-aortic
balloon pump use, and encephalopathy and infections
such as pneumonias, deep and superficial wound infec-
tions, urinary tract infections, endocarditis, mediastinitis,
and sepsis also appear to be associated with POAF—
although many of these associations are likely to be mere
correlations rather than causation [30,31,36,43,44]. How-
ever, POAF is directly associated with doubling in length
of stay in the intensive care unit and an increase in length
of hospital stay by 5 days [31,32]. Even when a patient
© 2015 International Society on Thrombosis and Haemostasis
Perioperative atrial fibrillation: an overview S307
with POAF is discharged, they have increased rates of re-
hospitalization [45]. Mortality is also increased with
POAF [43,46]—in a cohort of 1832 patients who under-
went CABG surgery, AF increased the in-hospital (0.5–
3.3%) [47] and long-term mortality [31,47].
Prediction
Numerous studies have attempted to elucidate risk factors
for the development of POAF after cardiac surgery.
Increasing age is a dominant predisposing factor across
all types of CABG, valvular, and combined cardiac sur-
geries [30,32,36,46,48]. Other patient and medical vari-
ables have also been associated with the development of
POAF such as race (Caucasians at higher risk than those
of African descent); male gender; obesity and metabolic
syndrome; chronic obstructive pulmonary disease; conges-
tive heart failure; a high EuroSCORE rating; preoperative
digoxin use; mitral valve disease; left atrial enlargement;
withdrawal of beta-blocker or angiotensin-converting
enzyme inhibitor (ACEi) postoperatively; and history of
AF [28,29,31,32,36,46,49]. In a large cohort of 3093
patients undergoing CABG surgeries, six variables were
associated with an increased risk of POAF—age, history
of AF, chronic obstructive pulmonary disease, valvular
surgery, and withdrawal of beta-blocker or ACEi postop-
eratively [36]. Preoperative and postoperative treatment
with ACEi and beta-blockers as well as potassium supple-
mentation and non-steroidal anti-inflammatory drugs
were associated with a decreased risk in the derivation
model. The area under the receiver operating curve for
the derivation cohort was 0.78 and 0.77 for the validation
cohort of 1564 patients [36].
Beyond patient characteristics, certain surgical factors
have been shown to be associated with POAF develop-
ment. Valve surgery substantially increases the risk and is
associated with an OR of 1.74 (95% CI 1.31–2.32) for
POAF [29,35,36]. Other intraoperative factors such as
cardiac venting through right superior pulmonary vein
and inotropic use for > 30 min after cardiopulmonary
bypass have also been identified as potential risk factors
[30]. Although certain studies have identified on-pump
bypass surgery as a risk factor for POAF, this finding
was not reproduced in the largest randomized trial of on
vs. off-pump CABG surgeries [31,50].
Additionally, several perioperative investigations have
demonstrated predictive capabilities to identify those at
risk of POAF. Blood measurements of electrolytes such
as hypokalemia and hypomagnesemia, as well as postop-
erative leukocytosis, are associated with POAF [10,51,52].
A preoperative brain natriuretic peptide is emerging as a
predictor of POAF with an OR of 3.8 (95% CI;
1.45–10.38) [53]. A less negative P-wave in lead aVR and
a more positive or more negative P-wave in lead V1
are predictive features on an electrocardiogram. Left
ventricular diastolic dysfunction on an echocardiogram or
S308 A. Bessissow et al
angiographic evidence of right coronary artery stenosis is
also predictors of POAF [54,55].
Prevention
Beta-adrenergic blockers Beta-adrenergic blockers are
the most studied intervention for the prevention of POAF
after cardiac surgery. The benefit of preoperative beta-
blockade likely relates to attenuation of sympathetic tone,
which has a direct effect on atrial refractoriness and
arrhythmia initiation [28]. A recent Cochrane systematic
review performed by Arsenault et al. [56] found 33 trials
(4698 patients) that demonstrated a significant reduction
in POAF with beta-blocker use (16.3%) compared to pla-
cebo (31.7%) (OR 0.33; 95% CI 0.26–0.43) [56]. The
most common beta-blocker used was propranolol and
approximately 82% of the trials started beta-blockade
postoperatively. While a large reduction in POAF was
detected with beta-blocker use, patients in the control
arms in the included trials often stopped non-study beta-
blockers to participate in the study. This may have led to
a withdrawal effect, which appears to be an independent
predictor of POAF development [36]. Burgess et al. iden-
tified this issue and separated studies into those that with-
drew non-study beta-blockers to those that continued
non-study beta-blockers in the control group [57]. Studies
that continued beta-blocker still had a significant reduc-
tion in POAF (OR 0.69; 95% CI 0.54–0.87), while there
was a larger effect in studies that withdrew beta-blockers
(OR 0.30; 95% CI 0.22–0.40). Nonetheless, the beta-
blockers preoperative use have been put forward as a
Class I recommendation (ACC/AHA/ESC) for the pre-
vention of POAF after cardiac surgery [58].
Non-dihydropyridine Calcium Channel Blockers The use
of non-dihydropyridine calcium channel blockers is rec-
ommended as an alternative if beta-blockers are poorly
tolerated or contraindicated. A meta-analysis of random-
ized controlled trials assessing the use of calcium channel
blockers to reduce supraventricular arrhythmias after car-
diac surgery indicated that non-dihydropyridine was asso-
ciated with a significant decrease in supraventricular
arrhythmias (OR 0.62; 95% CI 0.41–0.93) [59]. The use
of non-dihydropyridine calcium antagonists has also
received Class I recommendation for the treatment of
POAF in the Canadian guidelines [60].
Amiodarone Arsenault et al. [56] combined 33 trials
(5402 patients) and found a significant reduction in
POAF (OR 0.43; 95% CI 0.34–0.54) with amiodarone
use. Significant heterogeneity was found which likely
relates to diverse dosing regimens, use of loading doses,
oral vs. intravenous administration, and preoperative or
postoperative use. Apart from AF, amiodarone appears
to also reduce the occurrence of other atrial tachyarrhyth-
mias. A randomized trial of 601 patients found that an
oral amiodarone regimen started 6 days prior and contin-
ued 6 days after cardiac surgery was associated with sig-
nificant reduction of all atrial tachyarrhythmias (HR
0.52; 95% CI 0.34–0.69) [61]. Furthermore, the use of
amiodarone also suppressed the development of ventricu-
lar arrhythmias (OR 0.45; 95% CI 0.29–0.69) [56].
However, many of these trials included patients taking
beta-blockers perioperatively, and thus, the effects of ami-
odarone without concomitant use of beta-blockers are
not known. Furthermore, amiodarone use appears to be
associated with more episodes of bradycardia (OR 1.66;
95% CI 1.73–2.47) [56]. Preoperative amiodarone has
received a Class IIa recommendation (ACC/AHA/ESC)
for the prevention of POAF after cardiac surgery [58].
Sotalol Sotalol is an anti-arrhythmic that has been eval-
uated in several clinical trials for the reduction of POAF.
A Cochrane systematic review by Arsenault et al. [56]
found 11 trials, which indicated an overall benefit of sota-
lol (OR 0.34; 95% CI 0.26–0.43). The authors describe
that the majority of patients (54.5%) received sotalol
administration postoperatively. A prior meta-analysis by
Burgess et al. [57] found 14 trials on sotalol and with a
similar overall estimate (OR 0.37; 95% CI 0.29–0.48).
However, many of the trials included in these meta-analy-
ses provided beta-blockers instead of placebos to those in
the control group. An analysis of trials comparing sotalol
to beta-blockers indicated that sotalol provides additional
benefit over beta-blockade alone (OR 0.42; 95% CI 0.26–
0.65) [57]. Guidelines suggest the use sotalol for the
prevention of POAF after cardiac surgery (Class IIb
recommendation) (ACC/AHA/ESC) [58].
Colchicine Colchicine, an anti-inflammatory drug,
showed promise in preventing POAF. In the COPPS trial,
colchicine reduced the incidence of perioperative AF sig-
nificantly compared to placebo (12.0 vs. 22.0%; relative
risk reduction = 45%; 95% CI 34.0–94.0) [62]. Colchicine
also resulted in faster conversion to sinus rhythm (average
duration of perioperative AF was 3 ( 1.2) vs. 8 ( 2.5)
days).
Magnesium The frequent occurrence of hypomagnese-
mia after cardiac surgery and its pro-arrhythmia effect
prompted the use of magnesium for the prevention of
POAF after cardiac surgery [52]. Arsenault et al. [58]
identified 21 trials evaluating magnesium that demon-
strated a combined reduction in POAF (OR 0.55; 95%
CI 0.41–0.73). Despite this pooled estimate, significant
heterogeneity exists among studies. Differential dosing
regimens, timing, but also concomitant use with other
drugs may explain this heterogeneity—Burgess et al. [57]
separated trials that administered magnesium alone (OR
0.05; 95% CI 0.02–0.16) and found a smaller effect when
magnesium was given with a concomitant beta-blocker
(OR 0.83; 95% CI 0.60–1.16).
© 2015 International Society on Thrombosis and Haemostasis

Atrial pacing Atrial pacing above the patient’s intrinsic
heart rate appears to reduce POAF events by preventing
triggering events such as premature atrial contractions or
atrial refractoriness [63]. Arsenault et al. [56] showed a
significant reduction in POAF with atrial pacing (OR
0.47; 95% CI 0.36–0.61). However, there was significant
heterogeneity found between studies, likely due to the
various types of atrial pacing (e.g., right atrial, left atrial,
biatrial, bachmann’s). Right atrial pacing appears to be
the most effective site, while epicardial pacing may be
pro-arrhythmic [63, 64]. Potential for pro-arrhythmia and
difficulties for wide-scale application, given technical com-
plexities, limit the use of atrial pacing. Before atrial pac-
ing can be recommended, further large randomized trials
are needed to ensure efficacy and safety.
Other preventative medications Several other medications
have been evaluated for preventing POAF. Atorvastatin
given 7 days prior to cardiopulmonary bypass surgeries
was associated with a relative risk reduction of 39% in a
200 patient randomized controlled trial [65]. A meta-analy-
sis of 31 randomized controlled trials (1974 patients) found
a significant decrease in risk of POAF associated with ste-
roid use in cardiac surgery (OR 0.56; 95% CI 0.44–0.72)
and has been advocated for use to prevent POAF in car-
diac surgery in European guidelines (Class IIb) [24]. The
results of the Steroids In cardiac Surgery (SIRS) trial will
provide further evidence about the use of steroids in this
type of surgery [66,67]. While non-dihydropyridines signifi-
cantly reduce supraventricular tachycardias after cardiac
surgery (OR 0.62; 95% CI 0.41–0.93), their use has been
associated with increased atrioventricular blocks and low
output syndrome [28]. Further, conflicting evidence still
remains regarding the efficacy of polyunsaturated fatty
acids on preventing POAF [68,69].
Management
Similar to AF after non-cardiac surgery and in the non-
operative setting, the management of AF after cardiac
surgery is based upon clinical symptoms and hemody-
namic stability. If hemodynamic instability exists, electri-
cal cardioversion should be performed immediately (Class
I—ESC) [24]. For those without hemodynamic instability,
ventricular rate control is preferred (Class I—ESC) [24].
Beta-blockers, non-dihydropyridine calcium antagonist,
or amiodarone can be used, in that order, for rate control
order (Class I—CCS). Propafenone, flecainide, ibutilide,
amiodarone, and vernakalant appear to be effective
agents in chemical cardioversion—there is a paucity of
evidence to guide choice of anti-arrhythmic agent for
POAF after cardiac surgery; however, vernakalant has
been shown to be superior to amiodarone [70–74]. Ver-
nakalant is a novel atrial-selective antiarrhythmic and
has been studied specifically in the setting of POAF after
© 2015 International Society on Thrombosis and Haemostasis
Perioperative atrial fibrillation: an overview S309
cardiac surgery (Class IIb—ESC) [24,75]. Drug-induced
proarrhythmic effects must be considered prior to rhythm
control—elderly patients, previous myocardial infarctions,
and those with reduced ejection fractions are at particu-
larly high risk [42]. Similar to non-cardiac surgery,
administration of anticoagulation must be weighed in the
context of risk of stroke with the risk of perioperative
bleeding.
Disclosure of Conflict of Interests
P. J. Devereaux reports grants from Abbott Diagnostics,
Boehringer Ingelheim, Covidien, Octopharma, Roche
Diagnostics, and Stryker, outside the submitted work.
The other authors state that they have no conflict of
interest.
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