European Heart Journal: Acute Cardiovascular

Care
http://acc.sagepub.com/

Prognostic impact of atrial fibrillation in acute coronary syndromes: results from the ARIAM registry
Manuel Almendro-Delia, Mara Jos Valle-Caballero, Juan C Garcia-Rubira, Blanca Muoz-Calero, Angel
Garcia-Alcantara, Antonio Reina-Toral, Jos Bentez-Parejo, Rafael Hidalgo-Urbano and on behalf of the ARIAM
Andalucia Study Group
European Heart Journal: Acute Cardiovascular Care published online 17 December 2013
DOI: 10.1177/2048872613517370
The online version of this article can be found at:
http://acc.sagepub.com/content/early/2013/12/16/2048872613517370

Published by:
European Society of Cardiology

ESC Working Group on Acute Cardiac Care

and
http://www.sagepublications.com

Additional services and information for European Heart Journal: Acute Cardiovascular Care can be found at:
Email Alerts: http://acc.sagepub.com/cgi/alerts
Subscriptions: http://acc.sagepub.com/subscriptions
Reprints: http://www.sagepub.com/journalsReprints.nav
Permissions: http://www.sagepub.com/journalsPermissions.nav

>> OnlineFirst Version of Record - Dec 17, 2013

What is This?

Downloaded from acc.sagepub.com at HOSPITAL VIRGEN DE LA VICTORI on February 13, 2014

517370
research-article2013

ACC0010.1177/2048872613517370European Heart Journal: Acute Cardiovascular CareAlmendro-Delia et al.

EUROPEAN
SOCIETY OF
CARDIOLOGY

Original scientific paper

European Heart Journal: Acute Cardiovascular Care

201X, Vol XX(X) 18
The European Society of Cardiology 2013
Reprints and permissions:
sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/2048872613517370
acc.sagepub.com

Prognostic impact of atrial

fibrillation in acute coronary
syndromes: results from the
ARIAM registry

Manuel Almendro-Delia1,*, Mara Jos Valle-Caballero1,*, Juan C

Garcia-Rubira1, Blanca Muoz-Calero1, Angel Garcia-Alcantara2,
Antonio Reina-Toral3, Jos Bentez-Parejo4 and Rafael HidalgoUrbano1; on behalf of the ARIAM Andalucia Study Group

Abstract
Aims: The prognostic ability of atrial fibrillation (AF) in acute coronary syndromes (ACS) is unclear. Studies regarding
patient outcomes with respect to the timing of AF are scarce and conflicting. The present study aimed to determine the
frequency, predictors and impact on clinical outcome of AF in patients with ACS.
Methods: We analysed 39,237 consecutive patients with ACS included in the ARIAM registry between January /2001 and
December 2011. Patients with AF were compared with patients in sinus rhythm. We differentiate between new-onset
AF and previous AF cases to analyse mortality and other major adverse cardiac events (MACE) during hospitalization.
Results: Of the patients, 2851 (7.3%) developed AF; 1568 (55%) of these were new-onset AF and 1283 (45%) had
previous AF. The AF group had a higher risk profile at baseline and poorer clinical presentation at admission than
non-AF patients. Compared with previous AF patients, new-onset AF presented with fewer comorbidities, including
hypertension, diabetes, prior myocardial infarction, and chronic renal impairment. The inhospital mortality for newonset AF, previous AF, and non-AF patients were 14, 11.6, and 5.2%, respectively (new-onset AF unadjusted HR 2.19,
95% CI 1.92.53, p<0.001; adjusted HR 1.70, 95% CI 1.123.4, p<0.001). After propensity score analysis, only new-onset
AF persisted as an independent predictor for mortality (HR 1.62, 95% CI 1.092.89, p<0.001). Other MACE such as
reinfarction, malignant arrhythmias, and heart failure were also more frequent in new-onset AF patients than in previous
AF or non-AF patients.
Conclusions: These findings suggest that the presence of new-onset AF during ACS is associated with a significant
increase in mortality, even after adjusting for confounding variables.
Keywords
Acute coronary syndrome, atrial fibrillation, heart failure, myocardial infarction, propensity score, registry
Received: 12 September 2013; accepted: 28 November 2013

Introduction
Atrial fibrillation (AF) is the most common cardiac
arrhythmia observed in clinical practice and a frequent
complication of acute coronary syndromes (ACS), with an
incidence ranging between 5 and 23%.113 The prognostic
implication of AF in the ACS setting is unclear. Some
studies have found an association between AF and
increased morbidity and mortality,6,7,9,1419 whereas other
studies have failed to detect this association.1,8,20 The

1Virgen

Macarena University Hospital, Seville, Spain.

de la Victoria Hospital, Mlaga, Spain.
3Virgen de las Nieves Hospital, Granada, Spain.
4Coresoft, Mlaga, Spain.
*These authors contributed equally to this paper.
2Virgen

Corresponding author:
Manuel Almendro-Delia, Coronary Care Unit. Cardiology Department,
Virgen Macarena University Hospital, Avd Dr. Fedriani 3, 41071, Seville, Spain.
Email: almendrode@secardiologia.es

Downloaded from acc.sagepub.com at HOSPITAL VIRGEN DE LA VICTORI on February 13, 2014

European Heart Journal: Acute Cardiovascular Care XX(X)

majority of these findings were derived from studies using

unadjusted multivariate models210 or post-hoc analyses
of randomized control trials; 67,9,14,15,17,21 only few studies
differentiated between previous (PrAF) and new-onset AF
(NAF).1425
AF is frequently associated with heart failure (HF)
during ACS.1113,26 Thus, AF may be considered a surrogate marker of HF that is associated with increased
left ventricle filling pressure.11,13,2729 Current clinical
guidelines for treatment of AF during an ACS provide
recommendations based on limited evidence.29,30 The
efficacy of long-term antithrombotic and antiarrhythmic
drugs is unclear, especially in NAF that is resolved at
discharge.
This study aims to determine the incidence of AF in
ACS patients, identify risk factors for its development, and
determine if AF during ACS is an independent risk factor
for inhospital mortality.

Methods
ARIAM registry
The ARIAM Andalucia (Anlisis del Retraso en el
Infarto Agudo de Miocardio/Analysis of Delay in Acute
Myocardial Infarction) registry is a multicentre project
involving 44 medical centres with the goal of improving
the quality of treatment for patients with ischaemic heart
disease in Spain. The details of the registry have been previously published.31,32 In brief, data from patients admitted to coronary care units in Andalucia, Spain with the
diagnosis of ACS were collected from January 2001 to
December 2011. Case inclusion was prospective, although
data interpretation and the development of the study were
retrospective. The categorization and identification of
events and clinical variables were determined by individual investigators using the protocol definitions. The study
and this article followed the ethics and privacy guidelines
of the independent local ethics and research committees
related to the ARIAM project. The approval of ARIAM
primary investigators was obtained, and all of the patients
gave informed consent.

Study group
The study group consisted of patients with ACS who developed AF during hospitalization. AF was defined as an irregular rhythm with the absence of discrete atrial activation
(atrial fibrillation or flutter) recorded in a 12-lead ECG.29
We differentiated between those patients with previous
clear documentation or records of either paroxysmal, persistent, or permanent AF (PrAF), and those with new-onset
AF (NAF), which was defined as the absence of medical
records of AF but the development of arrhythmia, either at
admission or during hospitalization.

Variables
ST-segment elevation myocardial infarction (STEMI) was
defined based on the following criteria: acute ischaemic
symptoms and ST-segment elevation 2 mV in two contiguous precordial leads as well as 1 mV in inferior leads
or a presumed/new left bundle branch block on initial electrocardiogram. Non-ST-segment elevation myocardial
infarction (NSTEMI) was defined as the elevation of cardiac enzymes above the upper limit of normal in patients
with ischaemic symptoms but without persistent ST segment elevation or new left bundle branch block. Unstable
angina was defined as the presence of symptoms of angina
at rest, new-onset angina, or accelerated ischaemic symptoms with or without electrocardiographic changes but
without elevation of cardiac enzymes. Stroke was defined
as the occurrence of a new neurological deficit caused by
an ischaemic event with residual symptoms lasting for at
least 24 h after the onset of the ischaemic event. Cardiogenic
shock was defined as having clinical signs of pulmonary
congestion and impaired end-organ perfusion with persistent hypotension defined as a systolic blood pressure less
than 90 mmHg for more than 30 min or the need for vasopressor therapy to maintain a systolic pressure above 90
mmHg. Major and minor bleeding were defined according
to the TIMI definitions.33

Statistical analysis
Data are expressed as the meanstandard deviation for
quantitative normally distributed variables, median (interquartile range), or n (%). The differences between categorical variables were compared using Chi-squared or Fisher
exact tests and two-tailed Student t-test or MannWhitney
U-test for continuous variables, as appropriate. Stepwise
logistic regression was used to assess AF predictors.
A Cox proportional-hazards model was used to assess
predictors for inhospital mortality using the hazard ratio
(HR) with a 95% confidence interval (CI). Parsimonious
models were developed in a forward manner using predefined covariates. The model was adjusted to account for the
presence of malignant arrhythmias (either ventricular fibrillation (VF) and/or sustained ventricular tachycardia (SVT))
or cardiogenic shock, the two variables with the highest
statistical weight for hospital mortality as determined by
univariate analysis. The model was also adjusted for baseline characteristics related to mortality by univariate analysis (p<0.2), including age, diabetes mellitus, blood pressure,
renal impairment (creatinine clearance), previous myocardial infarction (MI), heart failure (Killip class), GRACE
risk score, mechanical complications of MI, and myocardial revascularization. KaplanMeier curves were also performed to examine outcomes based on AF status.
The propensity score model (PS) for the appearance of
AF was obtained by logistic regression using baseline

Downloaded from acc.sagepub.com at HOSPITAL VIRGEN DE LA VICTORI on February 13, 2014

Almendro-Delia et al.
Table 1. Baseline characteristics.
Characteristic

Non AF
(n=36,386)

Female
9305 (25.6)
Age (years)
63.812.6
Smoking
12,661 (35.6)
BMI 30 kg/m2)
3928 (11)
Diabetes
11,397 (32)
Hypertension
18,643 (52.5)
Previous MI
6355 (18)
Prior CHF
1508 (4.3)
Prior stroke
1903 (5.4)
AF history
1557 (4.4)
Peripheral arterial disease
1759 (5)
Renal impairment (CrCl
494 (1.4)
<60 ml/min)
Previous PCI
3079 (10)
Prior CV surgery
909 (2.9)
Clinical presentation at admission
VF
504 (1.5)
SVT
1170 (3.4)
3-grade AV block
1039 (3)
Systolic BP (mmHg)
11726
Heart rate (bpm)
8417
GRACE risk score
130 (108155)
LVEF (%)
50.613
Cardiac troponina
10,295 (59)
STEMI
22,004 (60.5)
Anterior MI
10,454 (39.6)
Killip class (%)
I
80
II
12
III
5
IV
3

AF (n=2851)

Previous AF
(n=1283)

New AF
(n=1568)

986 (34.6)
71.29.8
546 (1.7)
318 (11.5)
1097 (39.5)
1836 (66)
553 (20)
285 (10.4)
275 (10)
809 (29.4)
226 (8.2)
122 (4.4)

<0.001
<0.001
<0.001
0.520
<0.001
<0.001
0.01
<0.001
<0.001
<0.001
<0.001
<0.001

423 (34)
7110
225 (19)
192 (16)
477 (40)
842 (70.5)
239 (20.3)
141 (12)
139 (12)
1283 (100)
96 (8.1)
94 (8)

529 (35)
719.6
311 (21)
124 (8.4)
575 (39)
919 (62.3)
272 (18.5)
127 (8.7)
128 (8.7)

121 (8.2)
28 (1.9)

0.533
0.634
0.150
<0.001
0.614
<0.001
0.285
0.005
0.009
<0.001
0.927
<0.001

231 (9.3)
133 (5.4)

0.31
<0.001

139 (12)
75 (6.6)

82 (6.6)
47 (3.8)

<0.001
0.002

0.007
<0.001
0.55
0.13
<0.001
<0.001
<0.001
<0.001
<0.001
0.312

38 (3)
23 (2)
20 (2.3)
13032
9331
160 (136182)
45.314
293 (31.2)
540 (43.5)
326 (35)

58 (2.1)
445 (16.2)
88 (3.2)
11828
9426
161 (136181)
44.214
1009 (70.8)
1485 (52)
805 (38.5)
52
25
14
9

<0.001

55
27
12
6

20 (1.3)
422 (28)
60 (4)
10819
9519
162 (138183)
4314
196 (40)
945 (63)
444 (41)
50
24
16
10

<0.001
<0.001
0.01
<0.001
0.014
0.432
0.029
<0.001
<0.001
0.008

<0.001

Data are meanstandard deviation, n (%), or median (interquartile range). Categories do not add up to 100% for all variables due to missing values.
aCardiac troponin levels >5 times the upper limit of normal. Data from 20,228 patients with available and valid cardiac troponin values
AF, atrial fibrillation; AV, atrioventricular; BMI, body mass index; BP, blood pressure; CHF, chronic heart failure; CrCl, creatinine clearance; CV
surgery, cardiovascular surgery; LVEF, left ventricular ejection fraction; MI, myocardial infarction; PCI, percutaneous coronary intervention; RI, renal
impairment; SVT, sustained ventricular tachycardia; VF, ventricular fibrillation.

clinical characteristics as covariates.34 Nearest neighbour

PS matching was used in terms of Mahalanobis distance
(calliper 0.2). Goodness of fit was achieved if the standardized differences were 10%.35 A two-sided p-value <0.05
was considered statistically significant. The analyses were
performed using SPSS version 18.0 (SPSS, Chicago, IL,
USA) and R version 2.10.0 (The R Foundation for Statistical
Computing).

Results
This study included 39,237 patients. Among these, 2851
patients (7.3%) developed AF during hospitalization. Of
these, 1568 (55%) developed NAF and 1283 (45%)
developed PrAF. Of all of the included patients, 52%

STEMI and 48% were NSTE-ACS, with 41% NSTEMI

and 7% unstable angina.

Clinical data
The baseline characteristics are shown in Table 1. AF
patients were more likely to be female, older, and sicker
than those with sinus rhythm. At the time of admission, the
AF group had a higher incidence of malignant arrhythmias
(VF/SVT) and higher heart rates and plasma cardiac troponin levels than non-AF. Killip class at admission was
worse and the left ventricle ejection fraction (LVEF) was
lower in AF patients than in non-AF patients. Compared
with the PrAF group, the NAF patients presented with fewer
comorbidities but showed a worse clinical presentation at

Downloaded from acc.sagepub.com at HOSPITAL VIRGEN DE LA VICTORI on February 13, 2014

European Heart Journal: Acute Cardiovascular Care XX(X)

Table 2.Treatments.
Non AF
(n=36,386)
Pharmacological treatment (at discharge)
Aspirin
27,162 (78)
Clopidogrel
21,506 (61.7)
ACE Inhibitors
21,579 (67.5)
Beta-blockers
21,738 (68)
Digoxin
87 (0.3)
Diuretics
2545 (8)
GP inhibitorsa
7139 (26)
Inotropesa
2071 (5.9)
Aldosterone antagonistb
554/4395 (12.6)
Statinsb
2349/4395 (53.4)
Vitamin K antagonistsb
86/4395 (2)
Reperfusion treatmentc
Thrombolysis
12,711 (57.8)
pPCI
2607 (11.8)
No reperfusion
6691 (30.4)
PCI during hospitalization
15,092 (68.6)

AF (n=2851)

Previous AF
(n=1283)

New AF
(n=1 568)

2176 (78.8)
1753 (63.5)
1600 (65.5)
1273 (52.2)
131 (5.4)
566 (23.2)
449 (19.3)
512 (18.5)
88/433 (18.5)
209/433 (48.3)
86/433 (20)

0.26
0.06
0.05
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
0.039
<0.001

1141 (93)
1021 (84)
589 (48)
545 (45)
73 (6)
410 (41)
147 (15)
202 (16.5)
59 (12)
885 (84)
67 (25)

967 (67.2)
694 (48.2)
736 (51)
589 (41)
10 (1)
564 (45)
275 (22)
297 (21)
297 (21)
761 (59)
8 (9.2)

<0.001
<0.001
0.134
0.05
<0.001
0.05
<0.001
0.007
0.016
<0.001
0.002

804 (54.1)
194 (13.1)
487 (32.8)
975 (65.7)

0.006
0.16
0.04
0.02

239 (44)
112 (21)
189 (35)
351 (65)

565 (60)
82 (9)
298 (31)
624 (66)

<0.001
<0.001
0.002
0.687

Data are n (%). Categories do not add up to 100% for all variables due to missing values.
aDrugs used in the acute stage.
bData from 4828 patients.
cData from 20,403 patients with STEMI diagnosis.
ACE, angiotensin-converting enzyme; AF, atrial fibrillation; GP, glycoprotein; pPCI, primary percutaneous coronary intervention; STEMI, ST-elevation
myocardial infarction.

admission with a greater proportion of patients with STEMI

and anterior MI, a higher Killip class, and cardiac troponin
levels and lower LVEF, together with more ventricular
arrhythmias.

Pharmacological and reperfusion treatment

Table 2 summarizes the pharmacological treatment and
revascularization strategies during hospitalization. In general, the AF group was less likely to be treated with evidence-based therapies. Thrombolysis was applied less
frequently to AF patients diagnosed with STEMI than to
non-AF STEMI patients. During hospitalization, AF
patients as a group received less reperfusion, although in
the STEMI cohort, more AF patients received primary
percutaneous coronary intervention (pPCI) than the nonAF STEMI patients. Compared with PrAF patients, the
NAF group was less likely to receive antiplatelet agents,
statins, vitamin K antagonist, beta-blockers, and pPCI.
Thrombolysis was more frequently performed in the NAF
group than in the PrAF group, but NAF and PrAF patients
underwent similar numbers of PCI procedures during
hospitalization.

Predictors of AF
The predictor variables for AF development included age,
being female, prior history of AF, elevated heart rate at

Figure 1. Predictors of atrial fibrillation.

*, Every ten years increased; , Every 5 bpm increased; , Every 5 points

increased. AF, atrial fibrillation; HR, heart rate; LVEF, left ventricular
ejection fraction. C-statistic: 0.79 (0.72-0.86 95% CI; p<0.0001).

admission, and heart failure, whereas a better ejection fraction behaved as a protective factor (Figure 1).

Hospital outcomes
AF patients had a poorer prognosis, with a higher incidence
of malignant arrhythmias, reinfarction, ischaemic mitral
regurgitation, heart failure, cardiogenic shock, and inhospital mortality than non-AF patients. NAF patients had a
poorer outcome than PrAF patients (Table 3). There was no
difference in bleeding between AF and non-AF patients.
Table 4 summarizes the impact of AF on hospital mortality.
In the unadjusted analysis, both PrAF and NAF patients had
an approximately 2-fold increase in mortality compared with

Downloaded from acc.sagepub.com at HOSPITAL VIRGEN DE LA VICTORI on February 13, 2014

Almendro-Delia et al.
Table 3. Differences in outcomes in patients with and without atrial fibrillation during hospitalization.

Ventricular fibrillation
SVT
AV block
Asystolia
Reinfarction
Cardiac rupture
VSR
Ischaemic MR
Stroke
HF (KC 2)
Cardiogenic shock
Total bleeding (major and minor)
Total inhospital mortality
CCU stay (days)
Hospital stay (days)

Non AF
(n=36,386)

AF
(n=2851)

Previous AF
(n=1283)

New AF
(n=1568)

1165 (3.2)
1994 (5.5)
2119 (5.8)
542 (1.5)
532 (1.9)
93 (0.3)
45 (0.2)
67 (0.2)
99 (2.4)
8174 (22.6)
1473 (4.1)
587 (14.5)
1881(5.2)
1 (12)
2 (16)

147 (5.2)
565 (19.8)
259 (9.1)
99(3.5)
62 (2.2)
13 (0.5)
4 (0.1)
16 (0.6)
21 (2.9)
1590 (56)
396 (14)
90 (13)
365 (12.8)
2 (13)
3 (17)

<0.001
<0.001
0.02
<0.001
0.003
0.22
0.85
0.001
0.44
<0.001
<0.001
0.196
<0.001
<0.001
<0.001

51 (4)
62 (5)
19 (1.5)
40 (32)
18 (1.6)
5 (0.4)
1 (0.1)
8 (0.7)
6 (2.6)
648 (52)
156 (12,6)
32 (14)
144 (11.6)
1 (12)
3 (17)

95 (6.3)
500 (33.3)
103 (7)
55 (35)
44 (2.9)
8 (0.5)
3 (0.2)
8 (0.5)
14 (3)
881 (59)
231 (15.4)
35 (12)
210 (14)
1 (14)
4 (27)

0.01
<0.001
<0.001
0.531
0.009
0.750
0.472
0.558
0.765
0.001
0.035
0.434
0.001
<0.001
0.001

Data are n (%)or median (interquartile range). Categories do not add up to 100% for all variables due to missing values.
AF, atrial fibrilation; AV, atrioventricular; CCU, coronary care unit; HF, heart failure; KC, Killip class; MR, mitral regurgitation; SVT, sustained ventricular tachycardia; VSR, ventricular septal rupture.

Table 4. Predictors of mortality: multivariate analysis.

Unadjusted

Adjusted

PS cohort

HR

HR

HR

PrAF
NAF

1.89 (1.62.4)
2.19 (1.92.53)

<0.001
<0.001

1.70 (1.123.40)

<0.001

1.62 (1.092.89)

<0.001

Values are hazard ratios (95% confidence interval).

NAF, new atrial fibrillation; PrAF, previous atrial fibrillation; PS, propensity score.

non-AF patients; the increase was slightly more pronounced

for NAF patients (Supplementary Table S1, available online).
After adjustment, NAF but not PrAF remained an independent
predictor of mortality (Figure 2 and Supplementary Table S2).
By using PS matching, 1908 pairs of AF and non-AF patients
were matched with both groups balanced with respect to baseline characteristics (Supplementary Table S3). After matching,
only NAF remained as an independent predictor of inhospital
mortality, with a slight reduction in HR (Table 4 and
Supplementary Table S4).

Discussion
We have demonstrated an increased risk of mortality associated with the presence of AF in the setting of ACS. NAF
is associated with an almost 70% increase in mortality risk.
This increased risk was not demonstrated for PrAF after a
two well-conducted adjustment analyses. The results of
previous studies are conflicting regarding the prognostic
impact of AF types in MI.16,8,9 However, our results are
consistent with some previous reports.213
The predictors and significance of AF in the setting of
MI reviewed by Schmitt etal.11 are fairly consistent with

our findings. Schmitt etal. concluded that AF during MI

implied worse short- and long-term outcomes, independent
of MI treatment strategies. Two well-conducted meta-analyses focusing on the prognostic implication of AF during
MI have been published. The first one, by Jabre etal.,12
included 43 articles with a total of 278,854 MI patients.
Their analysis indicated that AF led to a 40% increase in the
risk of mortality in the setting of MI, even after adjustment
for the same variables as in our study, and concluded that
NAF and PrAF did not differ in mortality risk. The second
and most recent study, by Angeli etal.,13 was a meta-analysis of 24 studies comparing outcomes in patients with MI
and sinus rhythm with those observed for AF patients. In
their study, patients with AF had a 2-fold increased risk of
inhospital mortality and patients with clear evidence of
NAF had a 3-fold higher risk of mortality than sinus rhythm
patients, although the study did not adjust for the Killip
class, an important confounding variable.15,2628
It is important to note that in the meta-analysis by Jabre
etal.,12 the association between AF and mortality was similar for NAF and PrAF. These results persisted even after
adjusting for confounding variables such as heart failure
and revascularization, although only four of the 43 studies

Downloaded from acc.sagepub.com at HOSPITAL VIRGEN DE LA VICTORI on February 13, 2014

European Heart Journal: Acute Cardiovascular Care XX(X)

Figure 2. Kaplan Meier survival curves for inhospital mortality.

included in his work performed such important adjustments. These results are consistent with ours with respect
to risk ratios for NAF patients but differ in relation to PrAF
patients. To understand these conflicting results, we performed a PS analysis, demonstrating that only NAF persists as an independent predictor of inhospital mortality.
The association of PrAF with mortality found in the analysis of Jabre etal.12 is most likely explained by the inclusion
of studies that analysed long-term mortality and not only
inhospital outcomes, as we did in our study. NAF in the
setting of ACS reflects a greater ischaemic burden than
PrAF, as shown by the lower LVEF, larger infarct sizes,
and higher Killip class associated with NAF compared
with PrAF in our study. In contrast, PrAF is associated
with a worse clinical baseline profile than NAF due to the
existence of chronic heart disease.9,36 Along the same line
of reasoning, recent data from a large registry in Canada37
has showed that patient with prior history of AF receive
less evidence-based therapies and inhospital coronary
angiography compared to non-AF patients, similarly to our
results. As in our observational study, patients with prior
AF were older and sicker,37 and broadly differ to those
included in the work by Lopes etal.38 that examined pooled
data from 10 ACS trials, which includes more cases of
NAF and STEMI and probably less patients with significant comorbidities or those receiving warfarin, as is common in patients included in clinical trials compared with
those derived from registries.
The development of AF may worsen the prognosis of
ACS due to several factors. First, AF triggers some adverse
haemodynamic effects, including increased oxygen

consumption, loss of atrial contraction, and AV synchrony,

which lead to a decrease in effective cardiac output.7,9,1215,39
Secondly, irregular RR intervals can develop malignant
arrhythmias, as was observed in our cohort.1215,40 However,
the mechanism of AF-related mortality in ACS remains elusive; the association of AF with higher heart rates, lower
LVEF and an increased incidence of HF suggests that
haemodynamic impairment is a potential explanation as
well as increased adrenergic and neurohormonal
activation.9,12,13,21
The rate of cerebrovascular events in patients with any
type of AF in our study was quite low and not significantly
different from patients in sinus rhythm. This may have been
due to the relatively young age of patients enrolled in our
ACS registry, but we cannot rule out other reasons. The
current AF guidelines do not provide a better therapeutic
approach for treating AF during an ACS.2930 However,
European Society of Cardiology STEMI guidelines clearly
recommend optimized triple antithrombotic therapy for
patients with a clear indication of oral anticoagulation.31
The use of oral anticoagulants was quite low in our study,
below 30%, clearly not in line with clinical guidelines.2930
This finding may be due to the use of dual antiplatelet therapy, thereby avoiding the risk of bleeding associated with
triple therapy. Nonetheless, our data are consistent with
those of a Swedish registry (RIKS-HIA), in which longterm oral anticoagulation therapy was only given to 30% of
the patients with AF during an acute MI.41 Likewise, statin
use was quite low in our study. Danchin etal.42 have demonstrated that early statin therapy reduces the incidence of
AF during MI; thus, the mortality risk associated with AF

Downloaded from acc.sagepub.com at HOSPITAL VIRGEN DE LA VICTORI on February 13, 2014

Almendro-Delia et al.
in our study may be greater than expected due to the lack of
early use of statin.
Considering our results, there is sufficient evidence to
consider AF a mortality risk factor in the course of ACS.

Study limitations

Funding
This research received no specific grant from any funding agency
in the public, commercial, or not-for-profit sectors. However, the
Health Council of the Junta de Andalucia gives support to the virtual platform of the Registry.

References

Several limitations of the present investigation deserve discussion. First, the study population were derived from an
ACS-specific registry, not from an AF-specific registry.
The results should be considered only as hypothesis generating, and we cannot exclude the influence of other noncontrolled confounders in our conclusions. There is also
selection bias because we included only patients admitted
to coronary care units.
Secondly, data concerning the temporal relation between
the onset of AF and the appearance of complications were
not available, so we can establish an association but not a
causality relationship. Silent episodes of AF could not be
analysed in the sinus rhythm group. Furthermore, the
adjustment of variables that were not measured at baseline
(e.g. mechanical complications of MI and revascularization) in multivariable analysis, and comparison of outcomes
which might occur before or after AF (since its timing was
not known), should be interpreted with caution.
Thirdly, data concerning the causes of death were only
available for a minority of patients; thus, the causes of
death are not shown. Data concerning treatment strategies
used for AF as well as the timing, duration, and final outcome of AF episodes were not assessed.
Although rates of reperfusion were low in our registry,
the mortality numbers were similar to that reported in the
GRACE registry.18 In the final adjusted model, three-vessel
disease was not finally included, because in our study coronary angiography rates was low and this might influence
the results.

Conclusions
AF is not an infrequent event during ACS. The presence
of NAF is associated with nearly an 70% mortality
increase in MI patients. Our results suggest that the
appearance of NAF during ACS should not be considered
an isolated benign event but a severe complication with
prognosis implications. These results are hypothesis generating and the prognostic impact of treatment strategies
for NAF in MI patients must be assessed in future
studies.
ARIAM Andalucia Study Group
A list of investigators is given in the Appendix available online.

Conflict of interest
The authors declare that there is no conflict of interest.

1. Goldberg RJ, Seeley D, Becker RC, etal. Impact of atrial

fibrillation on the in-hospital and long-term survival of
patients with acute myocardial infarction: a community-wide
perspective. Am Heart J 1990; 119: 9961001.
2. Sakata K, Kurihara H, Iwamori K, etal. Clinical and prognostic significance of atrial fibrillation in acute myocardial
infarction. Am J Cardiol 1997; 80: 15221527.
3. Torres M, Rocha S, Marques J, etal. Impact of atrial fibrillation in acute coronary syndromes. Rev Port Cardiol 2008;
27: 14071418.
4. Cui K, Gu S, Ding YS, etal. Effects of atrial fibrillation/atrial flutter on the short and medium-term prognosis of patients with
acute myocardial infarction. J Interv Radiol 2008; 17: 594596.
5. Galcera TJ, Melgarejo MA, Garcia AA, etal. Incidence, clinical characteristics and prognostic significance of supraventricular tachyarrhythmias in acute myocardial infarction [in
Spanish]. Rev Esp Cardiol 1999; 52: 647655.
6. Lopes RD, Elliott LE, White HD, etal. Antithrombotic therapy and outcomes of patients with atrial fibrillation following primary percutaneous coronary intervention: results from
the APEX-AMI trial. Eur Heart J 2009; 30: 20192028.
7. Crenshaw BS, Ward SR, Granger CB, etal. Atrial fibrillation
in the setting of acute myocardial infarction: the GUSTO-I
experience: Global Utilization of Streptokinase and TPA for
Occluded Coronary Arteries. J Am Coll Cardiol 1997; 30:
406413.
8. Kinjo K, Sato H, Sato H, etal. Prognostic significance of
atrial fibrillation/atrial flutter in patients with acute myocardial infarction treated with percutaneous coronary intervention. Am J Cardiol 2003; 92: 11501154.
9. Pizzetti F, Turazza FM, Franzosi MG, etal. Incidence and
prognostic significance of atrial fibrillation in acute myocardial infarction: the GISSI-3 data. Heart 2001; 86: 527532.
10. Rathore SS, Berger AK, Weinfurt KP, etal. Acute myocardial
infarction complicated by atrial fibrillation in the elderly:
prevalence and outcomes. Circulation 2000; 101: 969974.
11. Schmitt J, Duray G, Gersch BJ, etal. Atrial fibrillation in
acute myocardial infarction: a systematic review of the incidence, clinical features and prognostic implications. Eur
Heart J 2009; 30: 10381045.
12. Jabre P, Roger VL, Murad MH, etal. Mortality associated
with atrial fibrillation in patients with myocardial infarction:
a systematic review and meta-analysis. Circulation 2011;
123: 15871593.
13. Angeli F, Reboldi G, Garofoli M, etal. Atrial fibrillation and
mortality in patients with acute myocardial infarction: a systematic overview and meta-analysis. Curr Cardiol Rep 2012;
14: 601610.
14. Behar S, Zahavi Z, Goldbourt U, etal. Long-term prognosis of patients with paroxysmal atrial fibrillation complicating acute myocardial infarction: SPRINT Study Group. Eur
Heart J 1992; 13: 4550.

Downloaded from acc.sagepub.com at HOSPITAL VIRGEN DE LA VICTORI on February 13, 2014

European Heart Journal: Acute Cardiovascular Care XX(X)

15. Eldar M, Canetti M, Rotstein Z, etal. Significance of paroxysmal atrial fibrillation complicating acute myocardial
infarction in the thrombolytic era: SPRINT and Thrombolytic
Survey Groups. Circulation 1998; 97: 965970.
16. Lehto M, Snapinn S, Dickstein K, etal. Prognostic risk of
atrial fibrillation in acute myocardial infarction complicated
by left ventricular dysfunction: the OPTIMAAL experience.
Eur Heart J 2005; 26: 350356.
17. Wong CK, White HD, Wilcox RG, etal. New atrial fibrillation after acute myocardial infarction independently predicts
death: the GUSTO-III experience. Am Heart J 2000; 140:
878885.
18. Mehta RH, Dabbous OH, Granger CB, etal. Comparison of
outcomes of patients with acute coronary syndromes with
and without atrial fibrillation. Am J Cardiol 2003; 92: 1031
1036.
19. Berton G, Cordiano R, Cucchini F, etal. Atrial fibrillation
during acute myocardial infarction: association with allcause mortality and sudden death after 7-year of follow-up.
Int J Clin Pract 2009; 63: 712721.
20. Asanin M, Perunicic J, Mrdovic I, etal. Prognostic significance of new atrial fibrillation and its relation to heart failure following acute myocardial infarction. Eur J Heart Fail
2005; 7: 671676.
21. Pedersen OD, Bagger H, Kober L, etal. The occurrence
and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction: TRACE Study Group:
TRAndolapril Cardiac Evaluation. Eur Heart J 1999; 20:
748754.
22. Saczynski JS, McManus D, Zhou Z, etal. Trends in atrial
fibrillation complicating acute myocardial infarction. Am J
Cardiol 2009; 104: 169174.
23. Trappolini M, Scorza A, Chillotti FM, etal. Prognostic

significance of atrial fibrillation in thrombolysed and non
thrombolysed patients. Minerva Cardioangiol 2006; 54:
471479.
24. Poi D, Hartford M, Kalrsson T, etal. Effect of new versus
known versus no atrial fibrillation on 30-day and 10-year
mortality in patients with acute coronary syndrome. Am J
Cardiol 2012; 110: 217221.
25. Lau DH, Huynh LT, Chew DP, etal. Prognostic impact of
types of atrial fibrillation in acute coronary syndromes. Am J
Cardiol 2009; 104: 13171323.
26. Cha YM, Redfield MM, Shen WK, etal. Atrial fibrillation
and ventricular dysfunction: a vicious electromechanical
cycle. Circulation 2004; 109: 28392843.
27. Ehrlich JR, Nattel S and Hohnloser SH. Atrial fibrillation
and congestive heart failure: specific considerations at the
intersection of two common and important cardiac disease
sets. J Cardiovasc Electrophysiol 2002; 13: 399405.
28. Wang TJ, Larson MG, Levy D, etal. Temporal relations
of atrial fibrillation and congestive heart failure and their
joint influence on mortality: the Framingham Heart Study.
Circulation 2003; 107: 29202925.

29. Camm AJ, Kirchhof P, Lip GYH, etal. Guidelines for the
management of atrial fibrillation: the Task Force for the
Management of Atrial Fibrillation of the European Society
of Cardiology (ESC). Eur Heart J 2010; 31: 23692429.
30. Steg PG, James SK, Atar D, etal. ESC Guidelines for the
management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33:
25692619.
31. lvarez Bueno M, Vera Almazn A, Rodrguez Garca

JJ, etal. Concept, development and objectives of project
ARIAM [in Spanish]. Med Intensiva 1999; 23: 273280.
32. Saturno PJ, Felices F, Segura J, etal. Reducing time delay in
the thrombolysis of myocardial infarction: an internal quality
improvement project. Am J Med Quality 2000; 15: 8593.
33. Chesebro JH, Knatterud G, Roberts R, etal. Thrombolysis
in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and
intravenous streptokinase. Clinical findings through hospital
discharge. Circulation 1987; 76: 142154.
34. Rubin DB. Estimating causal effects from large data sets
using propensity scores, Ann Intern Med 1997; 127: 757763.
35. DAgostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized
control group. Stat Med 1998; 17: 22652281.
36. Corradi D, Callegari S, Maestri R, etal. Structural remodeling in atrial fibrillation. Nat Clin Pract Cardiovasc Med
2008; 5: 782796.
37. Al Khdair D, Alshengeiti L, Elbarouni B, etal.; Global
Registry of Acute Coronary Events (GRACE/GRACE2) and
the Canadian Registry of Coronary Events (CANRACE)
Investigators. Management and outcome of acute coronary
syndrome patients in relation to prior history of atrial fibrillation. Can J Cardiol 2012; 28: 443449.
38. Lopes RD, Pieper KS, Horton JR, etal. Short- and long-term
outcomes following atrial fibrillation in patients with acute
coronary syndromes with or without ST-segment elevation.
Heart 2008; 94: 867873.
39. Waldecker B. Atrial fibrillation in myocardial infarction

complicated by heart failure: cause or consequence?. Eur
Heart J 1999; 20: 710712.
40. Sankaranarayanan R, James MA, Nuta B, etal. Does atrial
fibrillation beget ventricular fibrillation in patients with acute
myocardial infarction? Pacing Clin Electrophysiol 2008; 31:
16121619.
41. Stenestrand U, Lindback J and Wallentin L. Anticoagulation
therapy in atrial fibrillation in combination with acute myocardial infarction influences long-term outcome: a prospective cohort study from the Register of Information and
Knowledge About Swedish Heart Intensive Care Admissions
(RIKS-HIA) Circulation 2005; 112: 32253231.
42. Danchin N, Fauchier L, Marijon E, etal. Impact of early statin therapy on development of atrial fibrillation at the acute
stage of myocardial infarction: data from the FAST-MI register. Heart 2010; 96: 18091814.

Downloaded from acc.sagepub.com at HOSPITAL VIRGEN DE LA VICTORI on February 13, 2014