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Hellenic Society of Cardiology (2017) 58, 204e212

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ORIGINAL ARTICLE

Characteristics of coronary artery disease


among patients with atrial fibrillation
compared to patients with sinus rhythm
Lukas J. Motloch, MD, PhD a,*, Sara Reda, MD a,
Robert Larbig, MD a,b, Ariane Wolff, MD a,
Karolina A. Motloch, MD a,c, Bernhard Wernly, MD a,
Christina Granitz, MD a, Michael Lichtenauer, MD, PhD a,
Martin Wolny, PhD a, Uta C. Hoppe, MD a

a
Department of Internal Medicine II, Paracelsus Medical University Salzburg, Salzburg, Austria
b
Division of Electrophysiology, Department of Cardiovascular Medicine, University Hospital Muenster,
Muenster, Germany
c
Department of Ophthalmology, SALK/University Clinic, Paracelsus Medical University, Salzburg,
Austria

Received 22 August 2016; received in revised form 24 February 2017; accepted 3 March 2017
Available online 11 March 2017

KEYWORDS Abstract Background: With a high prevalence of coronary artery disease (CAD) among pa-
coronary artery tients with atrial fibrillation (AF), CAD is one of the main risk factors for AF. However, little
disease; is known about the characteristics of CAD in AF patients, especially whether a specific anatom-
atrial fibrillation; ical distribution of coronary artery stenoses might predispose an individual to AF via atrial
heart failure; ischemia remains speculative. To address this issue, we evaluated the potential associations
myocardial between angiographic characteristics of CAD and AF.
infarction; Methods: In this single-center retrospective analysis, 796 consecutive patients with confirmed
coronary artery CAD and AF (CAD-AF) and 785 patients with CAD and sinus rhythm (CAD-SR) were enrolled. Clin-
stenoses ical characteristics and angiographic findings were compared between groups in stable CAD
and during acute myocardial infarction (MI).
Results: Mitral valve disease and chronic heart failure were significantly more common in
CAD-AF than in CAD-SR. Clinical condition in CAD-AF was significantly more severe as indi-
cated by New York Heart Association/World Health Organization functional class. Left ven-
tricular ejection fraction was reduced in CAD-AF, reflecting the marked fraction of

* Correspondence to. Lukas J. Motloch, MD, PhD. Department of Internal Medicine II, Paracelsus Medical University Salzburg, Muellner
Hauptstr. 48, A-5020 Salzburg, Austria. Tel.: þ43 (0)662 4482-58870; fax: þ43 (0)662 4482-4111.
E-mail address: lukas.motloch@pmu.ac.at (L.J. Motloch).
Peer review under responsibility of Hellenic Society of Cardiology.

http://dx.doi.org/10.1016/j.hjc.2017.03.001
1109-9666/ª 2017 Hellenic Society of Cardiology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Coronary artery disease in atrial fibrillation 205

patients with ischemic cardiomyopathy. No association between anatomical characteristics


of CAD and AF was found. However, CAD-AF seemed to be associated with a higher CAD
severity (p Z 0.06). Additionally, CAD-AF with MI showed a significantly higher number of
diseased coronary vessels.
Conclusion: The anatomical distribution of coronary artery stenoses does not contribute
to AF in CAD patients. However, AF is linked to a higher CAD severity, which might predis-
pose individuals to AF by driving ischemic heart disease and changes in left ventricular
function.
ª 2017 Hellenic Society of Cardiology. Publishing services by Elsevier B.V. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
nd/4.0/).

1. Introduction 2. Methods

Atrial fibrillation (AF), the most common cardiac 2.1. Study participants
arrhythmia, is associated with a high risk of stroke, heart
failure, and hospitalization.1,2 AF is related to a variety of A flow diagram outlining the total number of patient re-
cardiovascular and other conditions, which have additive cords creened and how the final numbers of patients who
effects on the perpetuation of AF by promoting a substrate were included in the trial were obtained is presented in
that maintains AF. Coronary artery disease (CAD) is present Figure 1. To study a population that was investigated by
in >20% of patients with AF.3 In contrast to the high prev- similar clinical standards, all patients included in this study
alence of CAD in AF, the prevalence of AF in the total were admitted to the same university hospital with acute
population with CAD is relatively low. In the Coronary Ar- MI, percutaneous coronary intervention, or diagnostic cor-
tery Surgical Study (CASS), AF was present in only 0.6% of onary angiography between December 1999 and September
patients with angiographically documented CAD, although 2008. The study cohort comprised all 796 eligible consec-
the prevalence of intermittent AF was presumably some- utive patients with a confirmed diagnosis of AF and stable
what higher.4 CAD or acute MI (CAD-AF). To compare this group to a
Furthermore, AF occurs transiently in 6e10% of patients similar number of patients who were studied in the same
with acute myocardial infarction (MI). These patients are period of time, 785 patients were randomly chosen from
known to have a worse prognosis, primarily due to comor- the cohort of all 3680 eligible consecutive patients with
bidities such as heart failure. Since patients with severe confirmed sinus rhythm and stable CAD or MI (CAD-SR) using
CAD are very likely to have a reduced left ventricular
ejection fraction, heart failure is thought to be a cause of
AF in patients with MI. However, also in this population, in
addition to atrial stretching secondary to heart failure,
atrial ischemia is suggested to drive AF.5e7
Nevertheless, whether CAD per se predisposes patients
to AF via atrial ischemia and how AF interacts with coronary
artery perfusion are uncertain.8,9 Indeed, one might spec-
ulate that coronary macroangiopathy drives atrial ischemia
and, therefore, triggers atrial arrhythmias. The sinus nodal
artery arises from the proximal right coronary artery in
approximately 60% of patients and from the proximal left
circumflex artery in 40% of patients and supplies most of
the right atrium. The left atrial circumflex artery arises
from the proximal left circumflex artery and supplies most
of the left atrium.10 Consequently, in patients with CAD and
AF, angiographic localizations of coronary artery lesions
might correspond to the coronary arteries supplying the
atria.
However, in this population, the characteristics of cor-
onary artery stenoses have not yet been systematically
assessed. Therefore, whether specific anatomical distribu-
tions of coronary artery stenoses might promote AF remains
speculative. To address this issue, we compared the Figure 1 Flow diagram of patient screening protocol. The
angiographic characteristics of coronary artery lesions be- flow diagram presents the total number of patient records
tween CAD patients with AF and CAD patients with sinus screened and how the final numbers of included patients were
rhythm. obtained.
206 L.J. Motloch et al.

the PASW statistics 18 software (SPSS, Chicago, IL, USA; main coronary artery branches (right coronary artery, left
Figure 1). Furthermore, in both study groups, a subgroup anterior descending, or left circumflex coronary artery)
analysis was performed of the subpopulation with acute MI were defined as multiple stenoses. In this case, only the
(MI-AF vs. MI-SR). most proximal localization with an obstruction  70% of the
The AF of each eligible patient was classified into one of internal diameter was analyzed. A chronic total occlusion
three groups (first diagnosed, paroxysmal, persistent/per- was defined as TIMI 0 flow for >3 months.14 MI and differ-
manent),9 and information about clinical severity (New entiation of ST-elevation myocardial infarction (STEMI) or
York Heart Association/World Health Organization [NYHA/ non-STEMI were assessed according to the European
WHO] functional class), medication, and concomitant dis- guidelines.15
eases was obtained from the University Patient Database.
Furthermore, coronary angiography results of all patients 2.5. Statistical analysis
were analyzed. Inclusion criteria were the presence of at
least coronary one vessel disease on the coronary angio- Statistical analyses were performed using PASW Statistics
gram. Patients’ data were analyzed only if a complete data 18 software (SPSS). The results are given as
set including a conclusive coronary angiogram of all three mean  standard error of the mean. Differences between
coronary vessels, information about clinical severity groups and subgroups were evaluated by chi-square-testing
(NYHA/WHO functional class), medication, and concomi- for discrete variables and Student’s t test for continuous
tant diseases could be obtained from the university data- variables. The Mann-Whitney-U test was used to examine
base. Exclusion criteria were the history of a different ordinal data. Values of p < 0.05 were considered statisti-
supraventricular rhythm disorder than AF including sick cally significant.
sinus syndrome, atrial flutter, atrioventricular tachycardia,
and unclassified atrial tachycardia. If more than one coro-
nary angiogram was performed in a patient during the study 3. Results
period, only data from the first coronary evaluation were
included. 3.1. Baseline characteristics

2.2. Definition of AF A total of 796 patients with CAD and AF were analyzed and
compared to 785 patients with CAD and absent AF (SR). The
AF was defined as the presence of AF on an electrocardio- demographic variables of the individual groups with and
gram during the index hospitalization and/or as indicated without AF are shown in Table 1. Valve disease, chronic
by a diagnosis found in medical records, the hospital’s heart failure, and previous cardiac surgery were signifi-
database, or outpatient databases. Electrocardiographic AF cantly more common in the CAD-AF group. This observation
was defined as the presence of an irregular rhythm with was consistent for all causes of left heart failure. Further-
fibrillatory waves and no defined P-waves. Diagnoses and AF more, in cases of valvular disease, a strong association
classification were based on physician-assigned diagnoses in between mitral valve disease and AF was evident.
the medical records and/or the presence of corresponding
ICD-9-CM codes for AF (427.31) in the hospital discharge or 3.2. Left ventricular function in patients with CAD
outpatient databases.1 AF was sub-classified into newly and AF
diagnosed AF, paroxysmal AF, or chronic AF (persistent and
permanent).9 Cardiac function data were evaluated by ventriculography.
Expectedly, the mean left ventricular ejection fraction was
2.3. Left heart catheterization reduced in the CAD-AF group, reflecting the marked frac-
tion of patients with ischemic cardiomyopathy (Table 1).
Left ventricular ejection fraction was estimated via biplane
ventriculography as previously described.11 Coronary angi- 3.3. Results of coronary angiography in patients
ography was performed according to the Judkins with CAD-AF and CAD-SR
technique.12
CAD-AF showed a trend toward a higher CAD degree without
2.4. Definition of CAD reaching statistical significance (p Z 0.06), indicating more
severe CAD in CAD-AF (Table 2). To assess the distribution
CAD degree was classified as one-, two-, or three-vessel and characteristics of coronary artery stenoses in patients
disease. One-, two-, or three-vessel disease was diagnosed with AF compared to SR, we analyzed coronary angiogra-
when coronary angiography presented a reduction of 70% phies. The results are presented in Table 2. The distribution
of the internal diameter of the right coronary artery, left of stenoses, including the RCA, LAD, RCX, and smaller
anterior descending, or left circumflex system. A stenosis of branches of the coronary arteries, showed no significant
50% of the left main artery was considered a two-vessel differences in CAD-AF compared to CAD-SR (Table 2).
disease.13 Locations of coronary stenoses were established Furthermore, no significant difference in the percentage of
according to definitions of coronary artery segments as coronary artery stenoses was found in patients with AF
previously described.13 More than one stenosis of one of the compared to those with SR (Figure 2).
Coronary artery disease in atrial fibrillation 207

Table 1 Patient characteristics.


CAD-AF CAD-SR
(n Z 796) (n Z 785)
Characteristic n % or Mean  SEM n % or Mean  SEM
Age 796 70.2  0.3 785 63.8  0.4*
Male 578 72.6% 607 77.3%
Female 218 27.4% 178 22.7%
Atrial fibrillation
Type of AF
First diagnosed 167 21.0%
Paroxysmal 406 51.0%
Persistent or permanent 223 28.0%
NYHA classification
NYHA I 509 63.9% 621 79.1%x
NYHA II 143 18.0% 135 17.2%x
NYHA III 128 16.1% 27 3.4%x
NYHA IV 16 2.0% 2 0.3%x
Cardiac function
LVEF 648 61.6  0.7 575 67.4  0.6*
Patient history
Myocardial infarction 248 31.2% 245 31.2%
Arterial hypertension 549 69.0% 568 72.4%
Diabetes mellitus 218 27.4% 196 25.0%
Hyperlipoproteinemia 388 48.7% 479 61.0%#
History of coronary PTCA 205 25.8% 208 26.5%
History of coronary stenting 133 16.7% 148 18.9%
Mitral valve disease 111 13.9% 17 2.2%#
Mitral valve regurgitation 86 10.8% 17 2.2%#
Mitral valve stenosis 6 0.7% 0 0.0%#
Combined mitral valve disease 11 1.4% 0 0.0%#
History of mitral valve intervention 11 1.4% 0 0.0%#
Other valvular disease 172 21.6% 56 7.1%#
Pulmonary disease 93 11.7% 73 9.3%
Chronic heart failure 164 20.6% 63 8.0%#
Systolic heart failure 134 16.8% 58 7.4%#
Diastolic heart failure 29 3.6% 8 1.0%#
Dilatative cardiomyopathy 17 2.1% 4 0.5%#
Ischemic cardiomyopathy 152 19.1% 109 13.9%#
Hypertrophic cardiomyopathy 5 0.6% 3 0.4%
Previous heart surgery 214 26.9% 111 14.1%#
Pulmonary embolism 13 1.6% 9 1.1%
Myocarditis 2 0.3% 1 0.1%
Hyperthyroidism 53 6.7% 20 2.5%#
Medication
Cardioselective calcium antagonist 25 3.1% 3 0.4%#
Non-cardioselective calcium antagonist 115 14.4% 94 12.0%
Beta-blocker 688 86.4% 698 88.9%
Digitalis 304 38.2% 19 2.4%#
Amiodarone 82 10.3% 9 1.1% #
Sotalol 10 1.3% 0 0.0% #
Class I anti-arrhythmics 2 0.3% 0 0.0%
Diuretics 569 71.5% 469 59.7% #
Aldosteron-antagonists 164 20.6% 56 7.1% #
ACE-inhibitor/AT-1 antagonist 618 77.6% 572 72.9%
Statins 544 68.3% 654 33.3% #
ACE, angiotensin converting enzyme; AF, atrial fibrillation; AT, angiotensin; PTCA, percutaneous transluminal coronary angioplasty;
LVEF, left ventricular ejection fraction obtained by cardiac ventriculography; NYHA, New York Heart Association. *p < 0.05 vs. CAD-AF,
Student’s t-test; #p < 0.05 vs. CAD-AF, chi-square test; xp < 0.05 vs. CAD-AF, Mann-Whitney U-test
208 L.J. Motloch et al.

Table 2 Comparison of coronary angiography results in SR and AF


CAD-AF CAD-SR
Coronary angiography n % n %
Newly diagnosed CAD 356 44.7% 388 49.4%
One-vessel 218 27.4% 239 30.4% (p Z 0.06x)
Two-vessel 201 25.2% 209 26.6% (p Z 0.06x)
Three-vessel 377 47.3% 337 42.9% (p Z 0.06x)
LCA
Stenosis 81 10.2% 57 7.3%
LAD
Stenosis 416 52.3% 441 56.2%
Proximal 252 31.7% 283 36.1%
Middle 140 17.6% 137 17.5%
Distal 24 3.0% 21 2.7%
Chronic total occlusion 117 14.7% 116 14.8%
Proximal 64 8.0% 59 7.5%
Middle 37 4.6% 50 6.4%
Distal 16 2.0% 7 0.9%
RD-1
Stenosis 143 18.0% 152 19.4%
Chronic total occlusion 12 1.5% 7 0.9%
RD-2
Stenosis 8 1.0% 8 1.0%
Chronic total occlusion 0 0.0% 0 0.0%
RIMA
Stenosis 44 5.5% 29 3.7%
Chronic total occlusion 5 0.6% 6 0.8%
RCX
Stenosis 294 36.9% 283 36.1%
Proximal 196 24.6% 180 22.9%
Middle 73 9.2% 88 11.2%
Distal 25 3.1% 15 1.9%
Chronic total occlusion 80 10.1% 54 6.9%
Proximal 59 7.4% 37 4.7%
Middle 11 1.4% 13 1.7%
Distal 8 1.0% 4 0.5%
OB Marg-1
Stenosis 20 2.5% 35 4.5%
Chronic total occlusion 14 1.8% 8 1.0%
OB Marg-2
Stenosis 79 9.9% 60 7.6%
Chronic total occlusion 8 1.0% 9 1.1%
RCA
Stenosis 359 45.1% 344 43.8%
Proximal 221 27.8% 226 28.8%
Middle 92 11.6% 81 10.3%
Distal 46 5.8% 37 4.7%
Chronic total occlusion 123 15.5% 126 16.1%
Proximal 97 12.2% 93 11.8%
Middle 19 2.4% 23 2.9%
Distal 7 0.9% 10 1.3%
RPLS
Stenosis 13 1.6% 16 2.0%
Chronic total occlusion 5 0.6% 3 0.4%
RPDA
Stenosis 23 2.9% 26 3.3%
Chronic total occlusion 2 0.3% 2 0.3%
LCA, left coronary artery; RCA, right coronary artery; LAD, left anterior descending; RCX, circumflex coronary artery; RPLS, right
posterolateral segment; RPDA, artery of the posterior interventricular groove; RIMA, ramus intermedius; RD-1, first diagonal branch; RD-
2, second diagonal branch; OB Marg-1, first obtuse marginal; OB Marg-2, second obtuse marginal. xvs. CAD-AF, Mann-Whitney U-test
Coronary artery disease in atrial fibrillation 209

Table 3 AF in patients with acute myocardial infarction.


MI-AF MI-SR
Myocardial n % or n % or
infarction Mean  SEM Mean  SEM
Age 99 70.7  0.9 148 60.2  1.0 *
Male 70 70.7% 119 80.4%
Female 29 29.3% 29 19.6%
STEMI 49 49.5% 80 54.1%
NSTEMI 50 50.5% 68 45.9%
Cardiac function n Mean  SEM n Mean  SEM
LVEF 43 55.6  1.0 47 59.9  2.2
Coronary n % n %
angiography
One-vessel 23 23.3% 58 39.2%x
Two-vessel 35 35.4% 39 26.4%x
Three-vessel 41 41.4% 51 34.5%x
LCA
Stenosis 8 8.1% 5 3.4%
LAD
Stenosis 65 65.7% 92 62.2%
Proximal 43 43.4% 58 39.2%
Middle 20 20.2% 32 21.3%
Distal 2 2.0% 2 1.4%
RCX
Stenosis 42 42.4% 62 41.9%
Proximal 26 26.3% 35 23.6%
Middle 15 15.2% 26 17.6%
Distal 1 1.0% 1 0.7%
Figure 2 Degree of stenosis in AF compared to SR. Compar- RCA
ison of the degree of stenosis of the coronary arteries in CAD- Stenosis 55 55.6% 71 48.0%
AF and CAD-SR. A) Branches of the LCA and LAD. B) Branches of Proximal 38 38.4% 51 34.5%
the RCX. C) Branches of the RCA. LAD, left anterior descend- Middle 12 12.1% 17 11.5%
ing; LCA, left coronary artery; OB Marg-1, first obtuse marginal; Distal 5 5.1% 3 2.0%
OB Marg-2, second obtuse marginal; RCA, right coronary artery;
AF, atrial fibrillation; LAD, left anterior descending; LCA, left
RCX, circumflex coronary artery; RIMA, ramus intermedius;
coronary artery; LVEF, left ventricular ejection fraction ob-
RPDA, artery of the posterior interventricular groove; RPLS,
tained by cardiac ventriculography; RCA, right coronary artery;
right posterolateral segment; RD-1, first diagonal branch; RD-2, RCX, circumflex coronary artery. *p < 0.05 vs. patients with
second diagonal branch. *p < 0.05 vs. confirmed coronary ar- myocardial infarction and atrial fibrillation (MI-AF), Student’s t-
tery disease and atrial fibrillation, Student’s t-test. test; xp < 0.05 vs. MI-AF, Mann-Whitney U-test

3.4. AF and MI
association between atrial ischemia (sclerosis of the SA and
The demographic variables of the MI-AF and MI-SR groups AV nodal arteries) and postoperative AF.16 In dogs, occlu-
are shown in Table 3. The distribution of stenoses was sion of an atrial coronary artery increased the duration of
similar in MI-AF compared to MI-SR. Notably, the CAD-AF AF induced by burst pacing.17 Furthermore, in a previous
with acute MI group showed a significantly higher number study, stenosis of the RCA was shown to be a risk factor for
of diseased coronary vessels (Table 3). postoperative AF in patients undergoing coronary bypass
graft surgery.18 Of note, the studies described above were
4. Discussion performed in an experimental setting in animals or in a
different population of patients who underwent cardiac
In the present study, we systematically assessed the dis- surgery.16e18 Nevertheless, by analyzing first-time coronary
tribution and degree of coronary artery stenoses and their angiographs in AF patients compared to the cohort with
association with AF in CAD patients. clinically non-relevant CAD, Kralev and colleagues reported
The distribution of small vessels in the atria varies. Since a higher prevalence of RCA occlusions in patients under-
atrial branches divide from the proximal RCA or the prox- going coronary intervention.19 In our systematic analysis of
imal RCX, one might speculate atrial ischemia caused by coronary angiograms of a larger study cohort, we observed
proximal stenoses of these vessels to be associated with AF. no association between degree or localization of coronary
Indeed, in a cohort of 25 patients undergoing coronary ar- stenoses and AF, indicating that a more complex mecha-
tery bypass graft Kolvekar and colleagues described an nism might drive AF in CAD patients.
210 L.J. Motloch et al.

Davies and Pomerance, who performed studies on hearts were reported in the distributions of coronary artery steno-
from deceased patients with AF, described cases with ses. However, patients with AF presented with more severe
presumed atrial ischemia and no evidence of significant CAD, which was associated with a higher prevalence of
lesions of the major coronary arteries or intra-atrial ves- chronic heart failure and mitral valve insufficiency.28 Inter-
sels.20 They suggested that, in patients with CAD, prior left estingly, in CAD patients, CAD severity is known be associ-
ventricular failure is a major risk factor for AF.20 Similar ated with a worse outcome.29,30 Indeed, CAD may induce
findings were also observed in our cohort with CAD and AF. chronic heart failure by promoting decreased LV perfor-
In accordance with Davies and Pomerance, we observed no mance31 as well as an increased incidence of moderate or
differences between CAD-AF and CAD-SR regarding fre- severe mitral regurgitation.32 All of these mentioned cardiac
quency or severity of coronary stenoses of the proximal RCA pathologies are known to drive the incidence of AF. In
or the proximal RCX. Additionally, we found no significant accordance, they were more frequently present in our CAD-
differences in the locations of coronary artery stenoses in AF population. Therefore, one might speculate that not
AF regardless of any vessel compared to SR, implicating atrial ischemia but rather secondary consequences of
that AF occurrence might be independent of coronary ischemic heart disease like reduced LV performance or mitral
macroangiopathy distribution. However, in accordance with regurgitation might drive AF in CAD patients. However, this
speculations by Davies and Pomerance, patients with CAD speculation should be applied with caution.
and AF presented a higher prevalence of chronic heart Our data might also affect clinical practice. Since, in our
failure and mitral valve disease mainly caused by ischemic study, AF was linked to a higher number of diseased coro-
heart disease and/or mitral ring dilatation due to ischemic nary vessels, one might suggest that a closer rhythm
heart failure. Consequently, patients with AF presented a monitoring should be applied in patients with severe CAD.
higher NYHA classification. Of note, the early detection of AF in this population could
Given distinct cardiac pathomechanisms, we decided to affect the prevention of AF-associated complications like
further evaluate coronary angiograms in the subgroup of stroke, heart failure, and hospitalization. On the other
patients with acute MI. Indeed, AF is a known indicator of hand, since the prevalence of AF in our study was inde-
severe prognosis after acute MI, both in short- and long- pendent of the distribution of coronary stenoses, this
term follow-up.7,21e23 AF occurs transiently in 6e10% of observation might discount a higher risk of the incidence of
patients with MI, presumably due to atrial ischemia or atrial AF when angiographic localizations of coronary lesions
stretching secondary to MI complications such as heart correspond to the coronary arteries supplying the atria.
failure.5,24,25 Sakata and colleagues reported a higher
incidence of RCA infarcterelated lesions in patients with 5. Limitations
acute MI and the occurrence of AF in the first 24 hours after
the incident. Furthermore, decreased cardiac function was
Our study suffers from several limitations. The results ob-
observed in AF patients.26 Consequently, GUSTO-1 patients
tained retrospectively in a single-center should be
with AF at entry or after admission presented more
confirmed in a multicenter randomized prospective study.
extensive CAD and more impaired left ventricular function.
However, our data represent a real-life scenario since they
However, GUSTO-1 only weakly implicated right coronary
were obtained during daily clinical practice. In our popu-
artery involvement (suggesting territories at risk - including
lation, functional flow reserve was not determined. This
the sinoatrial node, atrioventricular node, and atria) in the
could promote an inaccurate assessment of the functional
pathogenesis of AF.5 Moreover, AF frequently occurred
significance of coronary stenosis. Therefore, to minimize
secondary to infarct complications.25 Interestingly, similar
this issue, in this study, only cases of stenosis with a
findings were reported by Kinjo and colleagues.23 In the
reduction  70% were defined as significant.33 In addition,
present study, after performing a systematical analysis of
regarding the percentage degree of occlusion, no signifi-
the distribution of the acute coronary events, we were not
cant differences between CAD-SR and CAD-AF were
able to find any associations between the localizations of
observed in our trial (Figure 2). Furthermore, our study did
acute occlusions in the proximal RCA or the proximal RCX.
not explore the impact of cardiac ischemia, which is
Furthermore, no additional differences were observed in
induced by coronary small-vessel disease. Indeed, coronary
the localizations of coronary artery stenoses when MI-AF
plaque distribution and coronary microangiopathy were
was compared to MI-SR, suggesting that the overall inci-
shown to occur independently of coronary large-vessel
dence of AF after MI might be independent of the
occlusions.34,35 Of note, in the Rotterdam Study, asymp-
anatomical distributions of acute coronary events. Howev-
tomatic atherosclerosis was shown to be associated with
er, in accordance with GUSTO-3 and the observations ob-
AF.36
tained by Kinjo and colleagues,23,25 patients in the MI-AF
group presented a significantly higher number of diseased
coronary vessels, indicating more severe CAD in this 6. Conclusion
subgroup.
Of note, this trend was also detected in the total CAD-AF Our findings suggest that, in patients with stable CAD or MI
population in our trial (p Z 0.06). This observation is undergoing coronary angiography, AF is not associated
consistent with previous studies, which explored CAD with the localization of coronary artery stenoses. Howev-
severity in patients with AF.19,27,28 Furthermore, our results er, CAD severity could drive ischemic heart disease and
are supported by a previous observation in patients with AF promote changes in LV performance, which might induce
on electrocardiograms obtained at the time of coronary AF. Further trials should investigate the impact of CAD in
angiography. Consistent with our results, no differences AF patients.
Coronary artery disease in atrial fibrillation 211

Conflict of interest 16. Kolvekar S, D’Souza A, Akhtar P, Reek C, Garratt C, Spyt T. Role
of atrial ischaemia in development of atrial fibrillation
following coronary artery bypass surgery. Eur J Cardiothorac
The authors declare no conflicts of interest. Surg. 1997;11:70e75.
17. Sinno H, Derakhchan K, Libersan D, Merhi Y, Leung TK, Nattel S.
Atrial ischemia promotes atrial fibrillation in dogs. Circulation.
2003;107:1930e1936.
References 18. Pehkonen E, Honkonen E, Makynen P, Kataja M, Tarkka M.
Stenosis of the right coronary artery and retrograde car-
1. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, dioplegia predispose patients to atrial fibrillation after coro-
et al. Prevalence of diagnosed atrial fibrillation in adults: na- nary artery bypass grafting. Thorac Cardiovasc Surg. 1998;46:
tional implications for rhythm management and stroke pre- 115e120.
vention: the AnTicoagulation and Risk Factors in Atrial 19. Kralev S, Schneider K, Lang S, Suselbeck T, Borggrefe M. Inci-
Fibrillation (ATRIA) Study. JAMA. 2001;285:2370e2375. dence and severity of coronary artery disease in patients with
2. Vardas P, Andrikopoulos G, Baroutsou B, Investigators Odyssey. atrial fibrillation undergoing first-time coronary angiography.
A greek prospective observational study of cardiovascular PLoS One. 2011;6:e24964.
morbidity and mortality in patients with atrial fibrillation. 20. Davies MJ, Pomerance A. Pathology of atrial fibrillation in man.
Hellenic J Cardiol. 2015;56:475e494. Br Heart J. 1972;34:520e525.
3. Nieuwlaat R, Capucci A, Camm AJ, Olsson SB, Andresen D, 21. Mehta RH, Dabbous OH, Granger CB, Kuznetsova P, Kline-
Davies DW, et al. Atrial fibrillation management: a prospective Rogers EM, Anderson Jr FA, et al. Comparison of outcomes of
survey in ESC member countries: the Euro Heart Survey on patients with acute coronary syndromes with and without
Atrial Fibrillation. Eur Heart J. 2005;26:2422e2434. atrial fibrillation. Am J Cardiol. 2003;92:1031e1036.
4. Cameron A, Schwartz MJ, Kronmal RA, Kosinski AS. Prevalence 22. Pizzetti F, Turazza FM, Franzosi MG, Barlera S, Ledda A,
and significance of atrial fibrillation in coronary artery disease Maggioni AP, et al. Incidence and prognostic significance of
(CASS Registry). Am J Cardiol. 1988;61:714e717. atrial fibrillation in acute myocardial infarction: the GISSI-3
5. Crenshaw BS, Ward SR, Granger CB, Stebbins AL, Topol EJ, data. Heart. 2001;86:527e532.
Califf RM. Atrial fibrillation in the setting of acute myocardial 23. Kinjo K, Sato H, Sato H, Ohnishi Y, Hishida E, Nakatani D, et al.
infarction: the GUSTO-I experience. Global Utilization of Prognostic significance of atrial fibrillation/atrial flutter in pa-
Streptokinase and TPA for Occluded Coronary Arteries. J Am tients with acute myocardial infarction treated with percuta-
Coll Cardiol. 1997;30:406e413. neous coronary intervention. Am J Cardiol. 2003;92:1150e1154.
6. Liberthson RR, Salisbury KW, Hutter Jr AM, DeSanctis RW. Atrial 24. Eldar M, Canetti M, Rotstein Z, Boyko V, Gottlieb S, Kaplinsky E,
tachyarrhythmias in acute myocardial infarction. Am J Med. et al. Significance of paroxysmal atrial fibrillation complicating
1976;60:956e960. acute myocardial infarction in the thrombolytic era. SPRINT
7. Foussas S. Acute coronary syndromes and atrial fibrillation. and Thrombolytic Survey Groups. Circulation. 1998;97:
Hellenic J Cardiol. 2016;57:141e142. 965e970.
8. Goette A, Bukowska A, Dobrev D, Pfeiffenberger J, 25. Wong CK, White HD, Wilcox RG, Criger DA, Califf RM, Topol EJ,
Morawietz H, Strugala D, et al. Acute atrial tachyarrhythmia et al. New atrial fibrillation after acute myocardial infarction
induces angiotensin II type 1 receptor-mediated oxidative independently predicts death: the GUSTO-III experience. Am
stress and microvascular flow abnormalities in the ventricles. Heart J. 2000;140:878e885.
Eur Heart J. 2009;30:1411e1420. 26. Sakata K, Kurihara H, Iwamori K, Maki A, Yoshino H,
9. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Yanagisawa A, et al. Clinical and prognostic significance of
Hohnloser SH, et al. 2012 focused update of the ESC Guidelines atrial fibrillation in acute myocardial infarction. Am J Cardiol.
for the management of atrial fibrillation: an update of the 2010 1997;80:1522e1527.
ESC Guidelines for the management of atrial fibrillation. 27. Nucifora G, Schuijf JD, Tops LF, van Werkhoven JM, Kajander S,
Developed with the special contribution of the European Heart Jukema JW, et al. Prevalence of coronary artery disease
Rhythm Association. Eur Heart J. 2012;33:2719e2747. assessed by multislice computed tomography coronary angi-
10. James TN. Anatomy of the coronary arteries in health and ography in patients with paroxysmal or persistent atrial fibril-
disease. Circulation. 1965;32:1020e1033. lation. Circ Cardiovasc Imaging. 2009;2:100e106.
11. Dodge HT, Sandler H, Ballew DW, Lord Jr JD. The use of biplane 28. Lokshyn S, Mewis C, Kuhlkamp V. Atrial fibrillation in coronary
angiocardigraphy for the measurement of left ventricular vol- artery disease. Int J Cardiol. 2000;72:133e136.
ume in man. Am Heart J. 1960;60:762e776. 29. Hammermeister KE, DeRouen TA, Dodge HT. Variables predic-
12. Judkins MP. Percutaneous transfemoral selective coronary tive of survival in patients with coronary disease. Selection by
arteriography. Radiol Clin North Am. 1968;6:467e492. univariate and multivariate analyses from the clinical, elec-
13. Ringqvist I, Fisher LD, Mock M, Davis KB, Wedel H, trocardiographic, exercise, arteriographic, and quantitative
Chaitman BR, et al. Prognostic value of angiographic indices of angiographic evaluations. Circulation. 1979;59:421e430.
coronary artery disease from the Coronary Artery Surgery 30. Nelson GR, Cohn PF, Gorlin R. Prognosis in medically-treated
Study (CASS). J Clin Invest. 1983;71:1854e1866. coronary artery disease: influence of ejection fraction
14. Suero JA, Marso SP, Jones PG, Laster SB, Huber KC, Giorgi LV, compared to other parameters. Circulation. 1975;52:408e412.
et al. Procedural outcomes and long-term survival among pa- 31. Moraski RE, Russell Jr RO, Smith MK, Rackley CE. Left ven-
tients undergoing percutaneous coronary intervention of a tricular function in patients with and without myocardial
chronic total occlusion in native coronary arteries: a 20-year infarction and one, two or three vessel coronary artery dis-
experience. J Am Coll Cardiol. 2001;38:409e414. ease. Am J Cardiol. 1975;35:1e10.
15. Steg PG, James SK, Atar D, Badano LP, Lundqvist CB, 32. Gahl K, Sutton R, Pearson M, Caspari P, Lairet A, McDonald L.
Borger MA, et al. ESC Guidelines for the management of acute Mitral regurgitation in coronary heart disease. Br Heart J.
myocardial infarction in patients presenting with ST-segment 1977;39:13e18.
elevation: The task force on the management of ST-segment 33. Tonino PA, Fearon WF, De Bruyne B, Oldroyd KG, Leesar MA,
elevation acute myocardial infarction of the European Soci- Ver Lee PN, et al. Angiographic versus functional severity of
ety of Cardiology (ESC). Eur Heart J. 2012. coronary artery stenoses in the FAME study fractional flow
212 L.J. Motloch et al.

reserve versus angiography in multivessel evaluation. J Am Coll lumen stenosis is highly correlated with atherosclerotic plaque
Cardiol. 2010;55:2816e2821. burden in humans: a histologic study of 723 coronary artery
34. Mosseri M, Yarom R, Gotsman MS, Hasin Y. Histologic evidence segments using nondecalcifying methodology. J Am Coll Car-
for small-vessel coronary artery disease in patients with angina diol. 1998;31:126e133.
pectoris and patent large coronary arteries. Circulation. 1986; 36. Heeringa J, van der Kuip DA, Hofman A, Kors JA, van Rooij FJ,
74:964e972. Lip GY, et al. Subclinical atherosclerosis and risk of atrial fibril-
35. Sangiorgi G, Rumberger JA, Severson A, Edwards WD, lation: the rotterdam study. Arch Intern Med. 2007;167:382e387.
Gregoire J, Fitzpatrick LA, et al. Arterial calcification and not