Introduction: Coronary slow flow phenomena (CSFP) are associated with endothelial and blood component abnormalities in coronary arteries. Asymmetric dimethylarginine (ADMA) can damage the endothelium of the heart or blood vessels in patients with non-valvular atrial fibrillation (NVAF), causing changes in levels of biological indicators. Our aim was to analyze the relationship between ADMA and CSFP in NVAF patients. Methods: We consecutively enrolled 134 patients diagnosed with NVAF and underwent coronary angiography, 50 control patients without a history of atrial fibrillation and with normal coronary angiographic flow were included at the same time. Based on the corrected TIMI frame count (CTFC), the NVAF patients were categorized into two groups, CTFC ≤27 frames and CTFC >27 frames. Plasma ADMA, P-selectin (p-sel), von Willebrand factor (vWF), D-dimer (D-Di), plasminogen activator inhibitor 1 (PAI-1), and nitric oxide (NO) were detected by ELISA in the different groups. Results: We found that plasma ADMA levels were significantly higher among NVAF patients in the CTFC >27 grade group compared with the control or CTFC ≤27 group. In addition, the levels of blood cells and endothelium-related biomarkers (NO, P-selectin, vWF, D-Di, and PAI-1) were significantly altered and correlated with ADMA levels. Multifactorial analysis showed that plasma ADMA (odd ratio [OR; 95% CI]: 1.65 [1.21–2.43], p < 0.001) and left atrial internal diameter (OR [95% CI]: 1.04 [1.02, 1.1], p < 0.001) could be used as independent risk factors for the development of CSFP in patients with NVAF. The ROC curves of ADMA can predict the development of CSFP in NVAF patients. The minimum diagnostic concentration for the development of CSFP in patients was 2.31 µmol/L. Conclusion: Our study demonstrated that CSFP in NVAF patients was associated with high levels of ADMA and left atrial internal diameter. Therefore, aggressive preoperative detection and evaluation of ADMA and left atrial internal diameter can help deal with the intraoperative presence of CSFP.

1.
Rahman
H
,
Demir
OM
,
Khan
F
,
Ryan
M
,
Ellis
H
,
Mills
MT
, et al
.
Physiological stratification of patients with angina due to coronary microvascular dysfunction
.
J Am Coll Cardiol
.
2020
;
75
(
20
):
2538
49
. .
2.
Zhu
Q
,
Wang
S
,
Huang
X
,
Zhao
C
,
Wang
Y
,
Li
X
, et al
.
Understanding the pathogenesis of coronary slow flow: recent advances
.
Trends Cardiovasc Med
.
2022
. .
3.
Wang
X
,
Geng
LL
,
Nie
SP
.
Coronary slow flow phenomenon: a local or systemic disease
.
Med Hypotheses
.
2010
;
75
(
3
):
334
7
. .
4.
Okawa
K
,
Miyoshi
T
,
Tsukuda
S
,
Hara
S
,
Matsuo
N
,
Nishibe
N
, et al
.
Differences in endothelial dysfunction induced by paroxysmal and persistent atrial fibrillation: insights from restoration of sinus rhythm by catheter ablation
.
Int J Cardiol
.
2017
;
244
:
180
5
. .
5.
Watson
T
,
Shantsila
E
,
Lip
GY
.
Mechanisms of thrombogenesis in atrial fibrillation: virchow's triad revisited
.
Lancet
.
2009
;
373
(
9658
):
155
66
. .
6.
Liu
H
,
Qu
X
,
Liang
Z
,
Chen
W
,
Xia
W
,
Song
Y
.
Variance of DDAH/PRMT/ADMA pathway in atrial fibrillation dogs
.
Biochem Biophys Res Commun
.
2008
;
377
(
3
):
884
8
. .
7.
Böger
RH
.
The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor
.
Cardiovasc Res
.
2003
;
59
(
4
):
824
33
. .
8.
Polovina
MM
,
Lip
GY
,
Potpara
TS
.
Endothelial (dys)function in lone atrial fibrillation
.
Curr Pharm Des
.
2015
;
21
(
5
):
622
45
. .
9.
Gibson
CM
,
Cannon
CP
,
Daley
WL
,
Dodge
JT
Jr
,
Alexander
B
Jr
,
Marble
SJ
, et al
.
TIMI frame count: a quantitative method of assessing coronary artery flow
.
Circulation
.
1996
;
93
(
5
):
879
88
. .
10.
Beltrame
JF
.
Defining the coronary slow flow phenomenon
.
Circ J
.
2012
;
76
(
4
):
818
20
. .
11.
Roshanravan
N
,
Shabestari
AN
,
Alamdari
NM
,
Ostadrahimi
A
,
Separham
A
,
Parvizi
R
, et al
.
A novel inflammatory signaling pathway in patients with slow coronary flow: NF-κB/IL-1β/nitric oxide
.
Cytokine
.
2021
;
143
:
155511
. .
12.
Lu
TM
,
Ding
YA
,
Lin
SJ
,
Lee
WS
,
Tai
HC
.
Plasma levels of asymmetrical dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention
.
Eur Heart J
.
2003
;
24
(
21
):
1912
9
. .
13.
Grobler
C
,
Maphumulo
SC
,
Grobbelaar
LM
,
Bredenkamp
JC
,
Laubscher
GJ
,
Lourens
PJ
, et al
.
Covid-19: the rollercoaster of fibrin(ogen), D-dimer, von Willebrand factor, P-selectin and their interactions with endothelial cells, platelets and erythrocytes
.
Int J Mol Sci
.
2020
;
21
(
14
):
5168
. .
14.
Gökçe
M
,
Kaplan
S
,
Tekelioğlu
Y
,
Erdoğan
T
,
Küçükosmanoğlu
M
.
Platelet function disorder in patients with coronary slow flow
.
Clin Cardiol
.
2005
;
28
(
3
):
145
8
. .
15.
Scridon
A
,
Girerd
N
,
Rugeri
L
,
Nonin-Babary
E
,
Chevalier
P
.
Progressive endothelial damage revealed by multilevel von Willebrand factor plasma concentrations in atrial fibrillation patients
.
Europace
.
2013
;
15
(
11
):
1562
6
. .
16.
Mondillo
S
,
Sabatini
L
,
Agricola
E
,
Ammaturo
T
,
Guerrini
F
,
Barbati
R
, et al
.
Correlation between left atrial size, prothrombotic state and markers of endothelial dysfunction in patients with lone chronic nonrheumatic atrial fibrillation
.
Int J Cardiol
.
2000
;
75
(
2–3
):
227
32
. .
17.
Lim
HS
,
Willoughby
SR
,
Schultz
C
,
Gan
C
,
Alasady
M
,
Lau
DH
, et al
.
Effect of atrial fibrillation on atrial thrombogenesis in humans: impact of rate and rhythm
.
J Am Coll Cardiol
.
2013
;
61
(
8
):
852
60
. .
18.
Xia
W
,
Wang
Y
,
Duan
T
,
Rong
Y
,
Chi
Y
,
Shao
Y
.
Asymmetric dimethylarginine predicts left atrial appendage thrombus in patients with non-valvular atrial fibrillation
.
Thromb Res
.
2015
;
136
(
6
):
1156
9
. .
19.
Chao
TF
,
Lu
TM
,
Lin
YJ
,
Tsao
HM
,
Chang
SL
,
Lo
LW
, et al
.
Plasma asymmetric dimethylarginine and adverse events in patients with atrial fibrillation referred for coronary angiogram
.
PLoS One
.
2013
;
8
:
e71675
. .
20.
Ozüyaman
B
,
Grau
M
,
Kelm
M
,
Merx
MW
,
Kleinbongard
P
.
Rbc NOS: regulatory mechanisms and therapeutic aspects
.
Trends Mol Med
.
2008
;
14
(
7
):
314
22
. .
21.
Camsarl
A
,
Pekdemir
H
,
Cicek
D
,
Polat
G
,
Akkus
MN
,
Döven
O
, et al
.
Endothelin-1 and nitric oxide concentrations and their response to exercise in patients with slow coronary flow
.
Circ J
.
2003
;
67
(
12
):
1022
8
. .
22.
Neubauer
K
,
Zieger
B
.
Endothelial cells and coagulation
.
Cell Tissue Res
.
2022
;
387
(
3
):
391
8
. .
23.
Dutta
U
,
Sinha
A
,
Demir
OM
,
Ellis
H
,
Rahman
H
,
Perera
D
.
Coronary slow flow is not diagnostic of microvascular dysfunction in patients with angina and unobstructed coronary arteries
.
J Am Heart Assoc
.
2023
;
12
(
1
):
e027664
. .
24.
Augustine
MS
,
Rogers
LK
.
Measurement of arginine metabolites: regulators of nitric oxide metabolism
.
Curr Protoc Toxicol
.
2013
;
58
(
1
). Unit 17.16. .
25.
Vischer
UM
.
von Willebrand factor, endothelial dysfunction, and cardiovascular disease
.
J Thromb Haemost
.
2006
;
4
(
6
):
1186
93
. .
26.
Smeets
M
,
Mourik
MJ
,
Niessen
H
,
Hordijk
PL
.
Stasis promotes erythrocyte adhesion to von Willebrand factor
.
Arterioscler Thromb Vasc Biol
.
2017
;
37
(
9
):
1618
27
. .
27.
Marín
F
,
Roldán
V
,
Climent
VE
,
Ibáñez
A
,
García
A
,
Marco
P
, et al
.
Plasma von Willebrand factor, soluble thrombomodulin, and fibrin D-dimer concentrations in acute onset non-rheumatic atrial fibrillation
.
Heart
.
2004
;
90
(
10
):
1162
6
. .
28.
Lip
GY
,
Conway
DS
.
Increased von Willebrand factor in the endocardium as a local predisposing factor for thrombogenesis in overloaded human atrial appendage
.
J Am Coll Cardiol
.
2001
;
38
(
7
):
2133
5
. .
29.
Tvaroška
I
,
Selvaraj
C
,
Koča
J
.
Selectins-the two dr. Jekyll and mr. Hyde faces of adhesion molecules-A review
.
Molecules
.
2020
;
25
(
12
):
2835
. .
30.
Blann
AD
,
Nadar
SK
,
Lip
GY
.
The adhesion molecule P-selectin and cardiovascular disease
.
Eur Heart J
.
2003
;
24
:
2166
79
. .
31.
Guo
L
,
Sun
G
,
Wang
G
,
Ning
W
,
Zhao
K
.
Soluble P-selectin promotes acute myocardial infarction onset but not severity
.
Mol Med Rep
.
2015
;
11
(
3
):
2027
33
. .
32.
Weitz
JI
,
Fredenburgh
JC
,
Eikelboom
JW
.
A test in context: D-dimer
.
J Am Coll Cardiol
.
2017
;
70
(
19
):
2411
20
. .
33.
Lominadze
D
,
Tsakadze
N
,
Sen
U
,
Falcone
JC
,
D'Souza
SE
.
Fibrinogen and fragment D-induced vascular constriction
.
Am J Physiol Heart Circ Physiol
.
2005
;
288
(
3
):
H1257
64
. .
34.
Wu
N
,
Chen
X
,
Cai
T
,
Wu
L
,
Xiang
Y
,
Zhang
M
, et al
.
Association of inflammatory and hemostatic markers with stroke and thromboembolic events in atrial fibrillation: a systematic review and meta-analysis
.
Can J Cardiol
.
2015
;
31
(
3
):
278
86
. .
35.
Altalhi
R
,
Pechlivani
N
,
Ajjan
RA
.
PAI-1 in diabetes: pathophysiology and role as a therapeutic target
.
Int J Mol Sci
.
2021
:
22
.
36.
Tilly
MJ
,
Geurts
S
,
Pezzullo
AM
,
Bramer
WM
,
de Groot
NMS
,
Kavousi
M
, et al
.
The association of coagulation and atrial fibrillation: a systematic review and meta-analysis
.
Europace
.
2023
;
25
(
1
):
28
39
. .
37.
Wijffels
MC
,
Kirchhof
CJ
,
Dorland
R
,
Allessie
MA
.
Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats
.
Circulation
.
1995
;
92
(
7
):
1954
68
. .
38.
Li
J
,
Wang
Y
,
Zhao
C
,
Zhu
Q
,
Li
G
,
Yang
J
, et al
.
Incremental value of three-dimensional echocardiography for evaluating left atrial function in patients with coronary slow flow phenomenon: a case control study
.
Cardiovasc Ultrasound
.
2020
;
18
(
1
):
6
. .
39.
Xing
Y
,
Chen
Y
,
Liu
Y
,
Kong
D
,
Yan
Y
,
Shu
X
, et al
.
Evaluation of left atrial volume and function in patients with coronary slow flow phenomenon using real-time three-dimensional echocardiography
.
Int J Cardiovasc Imaging
.
2019
;
35
(
12
):
2197
203
. .
You do not currently have access to this content.