Published online: 2020-09-23

New-Onset Atrial Fibrillation in Sepsis:

A Narrative Review
Jesus Aibar, MD, PhD1,2 Sam Schulman, MD, PhD2,3

1 Internal Medicine Department, Hospital Clínic, IDIBAPS – University Address for correspondence Jesus Aibar, MD, PhD, Department of
of Barcelona, Spain Internal Medicine, Hospital Clinic, Villarroel 170, Barcelona 08036,
2 Department of Medicine, Thrombosis and Atherosclerosis Research Spain (e-mail: jaibar@clinic.cat).
Institute, McMaster University, Hamilton, Ontario, Canada
3 Department of Obstetrics and Gynecology, I.M. Sechenov First
Moscow State Medical University, Moscow, Russia

Semin Thromb Hemost

Abstract Atrial fibrillation (AF) is a frequently identified arrhythmia during the course of sepsis.
The aim of this narrative review is to assess the characteristics of patients with new-
onset AF related to sepsis and the risk of stroke and death, to understand if there is a
need for anticoagulation. We searched for studies on AF and sepsis on PubMed, the
Cochrane database, and Web of Science, and 17 studies were included. The mean

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incidence of new-onset AF in patients with sepsis was 20.6% (14.7% in retrospective
studies and 31.6% in prospective). Risk factors for new-onset AF included advanced age,
white race, male sex, obesity, history of cardiopulmonary disease, heart or respiratory
failure, and higher disease severity score. In-hospital mortality was higher in patients
with than in those without new-onset AF in 10 studies. In four studies the overall
intensive care unit and hospital mortality rates were comparable between patients
with and without new-onset AF, while three other studies did not provide mortality
data. One study reported on the in-hospital incidence of stroke, which was 2.6 versus
0.69% in patients with or without new-onset AF, respectively. Seven of the studies
provided follow-up data after discharge. In three studies, new-onset AF was associated
with excess mortality at 28 days, 1 year, and 5 years after discharge of 34, 21, and 3%
Keywords patients, respectively. In two studies, the mortality rate was comparable in patients
► atrial fibrillation with and without new-onset AF. Postdischarge stroke was reported in five studies,
► new-onset atrial whereof two studies had no events after 30 and 90 days, one study showed a
fibrillation nonsignificant increase in stroke, and two studies demonstrated a significant increase
► sepsis in risk of stroke after new-onset AF. The absolute risk increase was 0.6 to 1.6%. Large
► severe sepsis prospective studies are needed to better understand the need for anticoagulation after
► septic shock new-onset AF in sepsis.

Atrial fibrillation (AF) is a common heart rhythm disorder1 and
its prevalence increases with age.2 Prevalence of AF in adults
between 55 and 59 years is
0.7% and increases to 18% in adults
older than 85 years.3 AF frequently complicates the course of
critically ill patients,4,5 with an incidence ranging from 4 to 25%
in noncardio-surgical intensive care unit (ICU) patients6–10 to
32 to 50% in patients after cardiac surgery,11–13 and is the most
frequent arrhythmia in patients with sepsis.14 In ICU patients,
AF may be responsible for new heart failure and thromboem-
bolism15,16 and is an independent risk factor for ischemic stroke
and systemic embolism17 with fivefold higher risk than patients
in sinus rhythm (SR). Possible triggers for new-onset AF in this

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New-Onset Atrial Fibrillation in Sepsis Aibar, Schulman
setting may include systemic inflammation, higher levels of
hormones implicated in the neuroendocrine stress system,
autonomic dysfunction, fluid and electrolyte imbalance, adren-
ergic overstimulation, and ischemia.8
The sepsis-3 task force defined sepsis as “life-threatening
organ dysfunction caused by a dysregulated host response to
infection.”18 As part of the resulting multiorgan dysfunction,
the cardiovascular system can be impaired.19–21 Sepsis is an
important public health problem and the incidence of septic
syndromes is increasing mainly because of the aging popu-
lation and more comorbidities. Sepsis is an important cause
of mortality and critical illness worldwide.18 New-onset AF
that occurs in the setting of sepsis could be associated with
increased length of stay in ICU,8 long-term stroke risk, and
mortality risk.20,22–29 The risk of ischemic stroke among
patients with new-onset AF during sepsis seems to be higher
than in the general population with AF and higher than in
patients with sepsis who do not have new-onset AF.27
However, there is no evidence to support anticoagulant
treatment for stroke prevention in patients with new-onset
AF during sepsis.30,31 Therefore, the management of patients
who present with new-onset AF during sepsis is uncertain. It
is commonly perceived that new-onset AF is a transient
complication of sepsis, in the same way as happens after
cardiac surgery or after acute myocardial infarction.32 Clini-
cal practice guidelines are not helpful in this type of patients
because there are not enough data to make recommenda-
tions. Because of this, anticoagulant therapy is not normally
used in these patients. In the event that anticoagulation is
chosen, the recommended duration is also unclear.33 The aim
of this review is to assess the characteristics of patients with
new-onset AF related to sepsis and the risk of stroke and
death, to understand if there is a need for anticoagulation.
Methods
Search Strategy
With the purpose of providing a narrative review, we searched
PubMed, the Cochrane database, and the Web of Science,
including all records from 1965 through to 2019. MeSH—
Medical Subject Headings—and keyword terms used were AF,
new-onset AF, sepsis, severe sepsis, and septic shock. Only
articles published in English were considered for the review.
We reviewed the titles and abstracts of all the articles
obtained and included studies that described the incidence,
risk factors, and prognosis of new-onset AF in patients over
18 years with septic syndromes (sepsis, severe sepsis, or
septic shock). We also reviewed the bibliographic references
of all systematic reviews obtained to find possible studies
related to our search.
Results
According to our search criteria, 917 studies were obtained of
which 786 were excluded after reading the title and abstract.
Of the remaining 131 articles, 114 were not included after a
complete text review so that only 17 studies could be
incorporated in our review. ►Table 1 shows general charac-
Seminars in Thrombosis & Hemostasis
teristics of the included studies. Of those, 6 were prospective
and the remaining 11 were retrospective studies. The total
number of patients with septic syndromes in the different
studies was very varied, ranging between 27 and 138,772
patients. The mean incidence of new-onset AF in patients
with sepsis, severe sepsis, or septic shock was 20.6% (range:
1.9–47.7%), being higher in prospective (31.6%) than in
retrospective studies (14.7%).
Of the 17 articles included in the study, only 7 had follow-
up data after hospital discharge and ►Table 2 shows the main
characteristics, mortality, and risk of stroke in those studies.
The mean follow-up was 17 months (range: 1–60 months).
Discussion
Physiopathology and Risk Factors for New-Onset
Atrial Fibrillation in Sepsis
Improved understanding of risk factors for new-onset AF during
sepsis can provide insights in physiopathology and guide
clinical practice.4 Sepsis could be responsible for biventricular
dilatation with both diastolic and systolic dysfunction. Under-
lying cause of these dysfunctions can be related to circulating
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cytokines and cardio-depressant factors as tumor necrosis
factor-α and interleukin-1b.34–36 Furthermore, it is important
to note that these changes can occur even in the absence of
coronary artery disease. The ventricular dilatation associated
with use of high volumes of fluids for resuscitation recom-
mended in the patient with sepsis can lead to an increase in the
diastolic pressure of the left ventricle, causing in turn a dilata-
tion of the left atrium, thus providing ideal anatomical con-
ditions for appearance of AF.36 Moreover, ventricular
remodeling secondary to sepsis can decrease ventricular com-
pliance with associated changes in left atrial and pulmonary
hemodynamics.36,37 Aoki et al38 suggested that systemic in-
flammation in sepsis may induce an electrophysiological sub-
strate for AF, responsible for the high incidence of new-onset AF
in septic patients.38,39 However, more studies should be per-
formed to verify these proposed pathophysiological mecha-
nisms. Clinical risk factors associated with new-onset AF during
sepsis include demographics (age, sex, and race), comorbidities
(heart disease, obesity, diabetes, and hypertension), factors
related to acute disease (cardiac and respiratory failure, renal
failure, severity of illness, etc.), and echocardiographic findings
(►Table 1). Risk factors that have been consistently reported to
increase the risk of new-onset AF include advanced age, white
race, male sex, respiratory and cardiovascular diseases, cardiac
and respiratory failure, and those with increased severity of
illness. In 14 out of the 17 studies analyzed, older age was
reported as an independent risk factor for new-onset AF in
septic patients.22–29,40–45 In this sense, it is well known that
older age is a risk factor for AF not only in the general
population, but also in ICU patients.46 Regarding other classical
risk factors for AF47 like diabetes, hypertension, obesity, and
cardiovascular disease, 11 studies showed that some of those
were associated with new-onset AF in sepsis.23–27,29,41–45
However in five studies these classical risk factors were not
related with new-onset AF,20,28,29,40,48 thus underlining that
new-onset AF in patients with septic syndromes may also be
 New-Onset Atrial Fibrillation in Sepsis Aibar, Schulman

Table 1 Study characteristics, in-hospital mortality, and risk factors for new-onset atrial fibrillation

Author (ref) Study design Number New-onset In-hospital mortality: Mortality risk estimate: Risk factors for
of AF: n (%) new-onset AF versus new-onset AF versus new-onset AF
patients sinus rhythm sinus rhythm
Bosch et al22 Retrospective 9,528 233 (2.5) 39.1 vs. 20.1%; OR, 2.54; 95% CI, Age, SOFA score
p < 0.001 1.94–3.32
Steinberg et al20 Prospective 27 9 (33.3) 66.7 vs. 11.1%; HR, 4.4; 95% CI, SOFA score
p ¼ 0.024 1.07–18.20
Cheng et al45 Retrospective 68,324 1,286 (1.9) Patients were Patients were Age, heart failure, coronary heart
sepsis survivors sepsis survivors disease, HTN, COPD, respiratory
failure
Klein Prospective 1,782 418 (23.4) 29 vs. 14%; RR, 2.10; 95% CI, Age, male sex, white race, obesity,
Klouwenberg p < 0.001 1.61–2.73 malignancy, comorbidities,
et al23 APACHE score, cardiovascular, renal
and respiratory failure, use of
vasopressors or inotropes, renal
failure, highest FiO2, time since ICU
admission
Lewis et al24 Retrospective 131 20 (15.3) 53 vs. 31%; OR, 2.6; 95% CI, Age, heart failure, dyslipidemia,
p ¼ 0.024 0.83–8.05 albumin levels, respiratory
failure, BMI
Liu et al25 Retrospective 503 240 (47.7) 61.3 vs. 17.5%; OR, 3.3; 95% CI, Age, HTN, heart failure, CAD, CVD,
p < 0.001 1.54–7.13 left atrial diameter, high SOFA and
APACHE II scores, dopamine and
norepinephrine use

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Rajmadhangi50 Retrospective 370 33 (8.9) 75 vs. 65%; p ¼ 0.25 No data No data
Ferrera et al26 Prospective 507 52 (10.3) 48 vs. 25.6%; OR, 1.9; 95% CI, Age, chronic renal failure, COPD,
p < 0.05 1.01–4.11 heart failure, diabetes, septic
shock, acute renal failure, cardio-
megaly, pleural effusion, C-reactive
protein, left atrial diameter
Guenancia et al40 Prospective 66 29 (44) 24 vs. 19%; p ¼ 0.61 No data Age, longer QRS duration, markers
of heart failure (troponin and
NT-pro-BNP), lower LVEF
Seemann et al48 Prospective 71 23 (32.4) 42 vs. 48%; No data Length of catecholamine and
p ¼ 0.63 vasopressor use during shock, SAPS
II at ICU admission, renal SOFA
Walkey et al41 Retrospective 138,722 9,540 (6.9) Patients were Patients were Age, male sex, white race, comor-
sepsis survivors sepsis survivors bid conditions, acute organ failure
Walkey et al42 Retrospective 60,209 4,320 (7.2) No data No data Age, white race, COPD, diabetes,
ICU stay, right heart catheteriza-
tion, greater severity of acute
illness
Wells and Retrospective 465 132 (28.4) 72 vs. 57%; OR, 5.7; 95% CI, Age, male sex, white race, CAD,
Morris43 p < 0.001 3.8–8.6 COPD, diabetes mellitus
Walkey et al27 Retrospective 49,082 2,896 (6) 56.3 vs. 37.7%; RR, 1.07; 95% CI, Age, male sex, white race, heart
p < 0.001 1.04–1.11 failure, obesity, malignancy, stroke,
respiratory failure, hematologic
failure, renal failure, right heart
catheter, pulmonary or abdominal
source of infection
Meierhenrich Prospective 50 23 (46) 43.4vs. 22.2%; No data Age, HTN, SOFA score
et al44 p ¼ 0.14
Christian et al28 Retrospective 272 16 (5.9) 68.8 vs. 39.6%; No data Age, septic shock, right heart
p ¼ 0.034 catheterization
Salman et al29 Retrospective 81 25 (30.9) 64 vs. 36%; OR, 3.28; 95% CI, Age, history of paroxysmal AF,
p ¼ 0.018 1.12–9.57 higher severity of illness at ICU
admission (APS and APACHE III
scores)

Abbreviations: AF, atrial fibrillation; APACHE, acute physiology and chronic health evaluation; APS, acute physiology score; BMI, body mass index;
CAD, coronary artery disease; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; FiO2, fraction of
inspired oxygen; HR, hazard ratio; HTN, hypertension; ICU, intensive care unit; LVEF, left ventricle ejection fraction; NT-pro-BNP, N-terminal pro b-
type natriuretic peptide; OR, odds ratio; RR, risk ratio; SAPS, simplified acute physiology score; SOFA, sequential organ failure assessment; vs., versus.
Note: QRS duration refers to the duration of Q-, R-, and S-waves.

Seminars in Thrombosis & Hemostasis

New-Onset Atrial Fibrillation in Sepsis Aibar, Schulman

Table 2 Characteristics, mortality and risk of stroke in studies with follow-up

Author (ref) Study Patients, New-onset Follow-up Mortality: new-onset Stroke: new-onset Persistent or
design n AF, n (%) months AF vs. sinus rhythm AF vs. sinus rhythm recurrent AF
Klein Prospective 1,782 418 (23.4) 12 90 days: 47 vs. 30%, No data No data
Klouwenberg p < 0.001; 1 y: 61
et al23 vs. 40%, p < 0.001
Cheng Prospective 68,324 1,286 (1.9) 6 Patients were All ages: 3.1 vs. 1.5%; No data
et al45 sepsis survivors adjusted OR, 1.74; 95%
CI, 1.26–2.41
Guenancia Prospective 66 29 (44) 3 28 days: 22 vs. 28%, None of the patients No data
et al40 p ¼ 0.58); 90 days: 41 developed new stroke
vs. 43%, p ¼ 0.88) in the 90-day follow-up
Walkey Retrospective 138,722 9,540 (6.9) 60 5 y: 75 vs. 72%, 5 y: 5.3 vs. 4.7%, No data, except: within 5 y
et al41 p < 0.001; HR, 1.04; p < 0.001; HR, 1.22; of the sepsis hospitaliza-
95% CI, 1.01–1.07 95% CI, 1.15–1.47 tion, 55% of patients with
new AF obtained another
AF diagnosis, as compared
with 63.5% of patients
with prior AF and 15.5% of
patients with no AF
Walkey Retrospective 49,082 2,896 (5.9) 6 No data 2.0 vs. 1.3%; p ¼ 0.06; No data
et al27 HR, 1.51; 95% CI,
0.98–2.33
Meierhenrich Prospective 50 23 (46) 24 28 days: 39 vs. 22%, No data Recurrence rate of AF:
et al44 p ¼ 0.22; 60 days: 48 42.9%
vs. 26%, p ¼ 0.14

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Salman Retrospective 81 25 (30.9) 1 28 days: 72 vs. 38%, None of the patients No data
et al29 p ¼ 0.004 developed new stroke
in the 28-day follow-up.

Abbreviations: AF, atrial fibrillation; CI, confidence interval; HR, hazard ratio; OR, odds ratio; vs., versus; y, year(s).

initiated by elevated levels of pro-inflammatory cytokines by Morbidity and Mortality

activation of the catecholaminergic system, electrolyte alter-
ations, and alteration in volume status during sepsis.8,38,39
Regarding echocardiographic findings, Ferrera et al26 and Liu
et al25 reported that left atrial dimension was larger in patients
with new-onset AF than in those who remained in SR. Con-
versely, in the study of Guenancia et al,40 there were no differ-
ences in left atrial dimension among patients with new-onset
AF and those with SR, although new-onset AF patients had a
lower left ventricular ejection fraction than patients in SR.40
Wetterslev et al49 used three categories to classify the
risk factors for development of new-onset AF in adult
critically ill patients: (1) predisposing factors, (2) condi-
tion-related precipitating factors, and (3) treatment-related
precipitating factors. Main predisposing factors in this
narrative review were older age, male sex, white race,
obesity, hypertension, dyslipidemia, diabetes mellitus,
heart failure, coronary artery disease, chronic renal failure,
and chronic obstructive pulmonary disease. Regarding con-
dition-related precipitating factors, hypo/hypervolemia,
electrolyte alterations, elevated simplified acute physiology
score-II (SAPS-II), sequential organ failure assessment
(SOFA) score, acute physiology and chronic health evalua-
tion-II (APACHE II) score, need for highest fraction of
inspired oxygen (FiO2), left atrial diameter, and organ
failure (cardiovascular, renal, respiratory, or hematologic
failure) were the most frequent. Finally, as for treatment-
related precipitating factors, the ICU stay, mechanical
ventilation, renal replacement therapy, and the use of
inotropes, vasopressors, and right central venous catheter
were the most common risk factors for new-onset AF.
►Table 1 summarizes the results of the 17 studies regarding in-
hospital mortality and mortality risk estimates in new-onset AF
versus SR as well as identified risk factors. In-hospital mortality
in patients with new-onset AF and sepsis was described in 16
studies. In 10 studies, in-hospital mortality was higher in
patients with new-onset AF than in patients with
SR.20,22–29,43 In four studies,40,44,48,50 the overall ICU- and in-
hospital mortality rates were similar between patients with and
without new-onset AF and two studies were performed in
survivors after sepsis.41,45 Estimated odds ratio (OR) ranged
from 1.9 (95% confidence interval [CI], 1.01–4.11) to 5.7 (95% CI,
3.8–8.6) for in-hospital mortality. By pooling data from four
studies that provided information, the average ICU stay in
patients with new-onset AF was 7.7 days longer (mean, range:
3.4–13 days) compared with patients who did not develop
AF.23,28,29,44 Severity scores such as SAPS-II, SOFA, and APACHE
II, or the presence of any organ failure, were identified as
independent risk factors for new-onset AF in sepsis in up to
10 studies.20,22,23,25,27,29,41,42,44,48
Three studies reported higher mortality during postdi-
scharge follow-up in patients with sepsis and new-onset AF
versus SR at 28 days (72 vs. 38%, p ¼ 0.004),29 1 year (61 vs. 40%,
p < 0.001),23 and 5 years (75 vs. 72%, p < 0.001).41 In two studies,
the after-discharge mortality rate was similar in patients with
and without new-onset AF. One study was on sepsis survivors
and another study lacked data on mortality (►Table 2).
Stroke Risk
Only one study reported higher in-hospital frequency of
ischemic stroke in patients with compared with without

Seminars in Thrombosis & Hemostasis


new-onset AF (2.6 vs. 0.69%, respectively; OR, 2.70; 95% CI,
2.05–3.57).27 Postdischarge stroke incidence was reported in
five studies, two of which had no events after 30 and
90 days.29,40 One study showed a nonsignificant increase
in stroke after new-onset AF (2.0 vs. 1.3%; hazard ratio [HR],
1.51; 95% CI, 0.98–2.33).27 In two studies,41,45 new-onset AF
was associated with higher risk of ischemic stroke (OR, 1.74;
95% CI, 1.26–2.41; and HR, 1.22; 95% CI, 1.15–1.47
[►Table 2]). The risk was in one of those studies the highest
in patients aged 45–65 and less in patients older than
65 years (OR, 3.88; 95% CI, 1.69–8.89; and OR, 1.62; 95% CI,
1.14–2.3, respectively).45
Management
Modifiable Risk Factors
New-onset AF in sepsis has been associated with poor out-
comes and therefore identification and management of
modifiable risk factors should be of importance.22 In a
meta-analysis, Bosch et al4 reported that avoidance risk
factors such as dopamine,51 right heart catheterization,52
and high mean arterial pressure targets53 during septic shock
were associated with better prognosis. In addition, identify-
ing patients with nonmodifiable risk factors for new-onset
AF (age, male sex, white race, etc.) will allow for establishing
a high-risk profile for occurrence of this arrhythmia during
sepsis, and will alert the ICU team to avoid introduction of
additional risk factors. New large prospective studies may
provide more evidence regarding modifiable risk factors and
inform how to prevent the new-onset AF.
Prevention of New-Onset AF
There are no randomized controlled clinical trials on the
management of new-onset AF in patients with sepsis and
thus clinical practice recommendations are mainly based on
observational studies.25,54 New-onset AF could lead to wors-
ening of hemodynamic state during septic syndromes due to
negative cardiovascular effects, for example, rapid heart rate,
lack of atrial systole, and hormonal activation.25 This can
decrease the cardiac output, thereby destabilizing patients
with septic syndromes resulting in acute heart failure.25,55 It is
thus important to identify early the patients that are more
likely to have new-onset AF during septic syndromes,8 to
implement preventive measures. Electrolyte imbalances
should be amended, incorrect right heart catheter position
adjusted, myocardial ischemia treated, excessive volume
avoided, and use of vasopressors and inotropes optimized.
The effectiveness of pharmacologic prophylaxis for new-onset
AF after coronary artery bypass surgery has been evaluated in
several studies.56,57 In a meta-analysis,58 β-blockers reduced
the incidence of postoperative AF. Another meta-analysis
showed that amiodarone prevented AF in patients undergoing
cardiothoracic surgery, but without influence on the length of
stay or mortality.59 Magnesium administration was an effec-
tive prophylactic measure to prevent AF after cardiac surgery
in another meta-analysis.60 Moreover, the use of statins before
surgery in patients who underwent major lung or esophageal
resection was associated with lower incidence of new-onset AF
New-Onset Atrial Fibrillation in Sepsis Aibar, Schulman
in a prospective study.61 In patients with septic shock, Launey
et al62 reported that administration of low-dose hydrocorti-
sone was associated with a lower risk of developing AF during
the acute phase of septic shock (hydrocortisone group 16.8%,
nonhydrocortisone group 28.8%, p ¼ 0.40). Nevertheless, evi-
dence for the effect of possible preventive measures against
new-onset AF in sepsis patients is lacking and further research
is needed to make any recommendation in this respect.
Rate Control versus Rhythm Control
Notably, in the 17 studies we evaluated, only 2 described the
treatment initiated for the new-onset AF.25,44 Liu et al25
reported that β-blockers and amiodarone (36.7 and 33.3%,
respectively) were the most used medications in the 240
patients with new-onset AF and sepsis. Electrical cardiover-
sion was performed in only 3.3% of the patients. It was possible
to reverse 165 patients to SR. There was no difference
between electrical cardioversion and pharmacological thera-
pies regarding restoration of SR. However, failure to restore SR
seemed to be unfavorable with respect to hospital mortality
(OR, 4.50; 95% CI, 2.52–8.04; p < 0.01). In the study by Meier-
henrich et al,44 amiodarone (73%) and β-blockers (51%) were
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the most commonly used medications. Electrical cardiover-
sion was performed in 34.7% of patients. In 86.7% of patients
with sepsis and new-onset AF, the investigators achieved SR. In
this study, persistent AF, despite the efforts to convert to SR,
was associated with an increased ICU mortality of 71% in
contrast to 21% in successfully cardioverted patients
(p ¼ 0.015). Despite the results of these two studies, there
are no recommended protocols regarding the rate control
versus rhythm control treatment of new-onset AF and the
management is left to the discretion of the medical doctor
responsible for patient care. In nonseptic patients, rhythm
control had no advantage to rate control regarding neither
morbidity nor mortality.63,64
Anticoagulation
The 2019 American Heart Association, American College of
Cardiology, and Heart Rhythm Society guideline for the man-
agement of patients with AF recommends oral anticoagulation
for new-onset AF lasting longer than 48 hours for patients with
a CHA2DS2-VASc (Congestive heart failure, Hypertension, Age
 75 years (doubled), Diabetes mellitus, prior Stroke or tran-
sient ischemic attack or thromboembolism (doubled), Vascular
disease, Age 65 to 74 years, Sex category) score of 2 or greater in
the general population.65 In patients that develop AF of more
than 48 hours duration after cardiothoracic surgery, initiation
of anticoagulation is recommended similarly to nonsurgical
patients.66 It is currently unclear whether sepsis patients with
new-onset AF benefit from anticoagulation to prevent arterial
thromboembolic events. As described above, the incidence of
stroke during hospitalization for sepsis was reported in five
studies, two of which had no events after 30 and 90 days, one
study showed a nonsignificant increase in stroke and in two
studies new-onset AF was associated with increased risk of
stroke. Although no study evaluated the use of anticoagulants in
this setting, the best strategy to prevent ischemic stroke is
reasonably to administer an anticoagulant. In fact, none of the
Seminars in Thrombosis & Hemostasis
New-Onset Atrial Fibrillation in Sepsis Aibar, Schulman
17 studies included described the use of anticoagulant treat-
ment in these patients. Walkey et al reported in a retrospective
cohort study31 that among patients with AF during septic
syndromes, anticoagulation was not associated with a reduced
risk of ischemic stroke but resulted in increased incidence of
bleeding events. Kanji et al67 reported in a prospective cohort
study in medical and noncardiac surgical adult ICUs that anti-
coagulation was administered to 16% of patients with new-
onset AF while in the ICU. There were no patients with
documented ischemic stroke during ICU stay; however, 5
(9%) of 58 patients treated with anticoagulation had a bleeding
episode that required cessation of anticoagulation and transfu-
sion of at least one blood unit. Søgaard et al68 described in a
cohort study that warfarin treatment in patients with preex-
isting AF during sepsis was associated with higher bleeding
rates compared with patients with sepsis without AF or warfa-
rin (HR, 1.19; 95% CI, 1.00–1.41). There were no differences in
thromboembolic events (HR, 1.25; 95% CI, 0.89–1.76), but
mortality at 90 days after sepsis was significantly lower in
the warfarin group (HR, 0.64; 95% CI, 0.58–0.69). As such, it is
important to emphasize that decisions regarding anticoagulant
therapy are complex in septic patients because of the presence
of organ failures, coagulopathy or full blown disseminated
intravascular coagulation, need for invasive interventions,
and so forth—that may increase risks of bleeding and throm-
bosis.49 Therefore, the benefit and the risk of anticoagulant use
in new-onset AF in septic patients during the admission remain
largely unclear and untested.25 With respect to management
after discharge, we only found follow-up data in 5 of the 17
studies. There were no events reported in the two smallest
cohorts with only 1 to 3 months of follow-up.29,40 In the three
remaining studies, there was an increase in the incidence of
stroke that was borderline or statistically significant among
those with new-onset AF versus those that remained in SR
during the initial hospitalization.27,41,45 Notably, in the largest
study (> 138,000 patients) with the longest follow-up (5 years),
the absolute difference in risk was only 0.6%, or
0.1% per
year.45 This suggests that the bleeding risk associated with
anticoagulation would outweigh any benefit. Nevertheless, it is
not possible to exclude that certain subsets of patients would
benefit from at least a time-limited anticoagulant prophylaxis
against stroke, but the studies we reviewed do not provide
sufficient details for this kind of analysis.
Limitations
We did not perform a formal systematic review of the topic and
we did not search Scopus or Embase. However, our search in
Web of Science yielded only one eligible abstract in addition to
the records identified from PubMed. We did not perform a
meta-analysis of the results, but the heterogeneity between the
studies is obvious. This, together with the lack of randomized
controlled trials, makes the quality of any evidence very low.
Conclusion
New-onset AF is frequent in sepsis patients, and its incidence
increases with the severity of the condition (sepsis, severe
Seminars in Thrombosis & Hemostasis
sepsis, and septic shock). Various risk factors have been
associated with new-onset AF in sepsis patients. Classical
risk factors such as age, male sex, white race, hypertension,
diabetes, and cardiovascular disease were represented in
several studies, albeit not consistently, emphasizing that
new-onset AF in patients with sepsis may be triggered by
other factors including inflammatory cytokines, electrolyte
imbalances, use of inotropes and vasopressors, and an alter-
ation in volume status during sepsis. Multivariable analyses
have demonstrated that new-onset AF is independently
associated with mortality. Some mechanisms that can ex-
plain this association are that new-onset AF causes adverse
cardiovascular effects related to rapid heart rate, loss of atrial
systole, and neurohormonal activation. It is difficult to
establish if this association is causal or coincidental, because
new-onset AF may just be a marker of organ failure, which
leads to hospital mortality. With regard to prophylaxis
against stroke, there are no randomized clinical trials that
have studied the management of new-onset AF in patients
with sepsis and therefore any recommendations for man-
agement are based on observational studies. In conclusion,
based on our search of three scientific databases, there
Downloaded by: Cornell. Copyrighted material.
appears to be a need for large prospective cohort studies
to clarify the need for anticoagulation to prevent ischemic
stroke and to try and identify any subset of patients that may
derive net benefit from such a strategy.
Funding
This work was supported by a grant from Hospital Clinic,
IDIBAPS, and University of Barcelona (Estada Retribuïda
per ampliació d’estudis).
Conflict of Interest
Dr. Schulman reports research grants from Octapharma
and Boehringer-Ingelheim and honoraria from Alnylam,
Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daii-
chi-Sankyo, and Sanofi.
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