Journal of Clinical Neuroscience 88 (2021) 213–218

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Journal of Clinical Neuroscience

journal homepage: www.elsevier.com/locate/jocn

Clinical study

BNP combined with echocardiographic parameters to predict the risk of

cardioembolic stroke
Meng Zhang, Yuan Wang, Jin Wei, Qing Peng, Xudong Pan ⇑, Aijun Ma ⇑
Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China

a r t i c l e i n f o a b s t r a c t

Article history: Background: Previous studies have found that BNP and some indicators of cardiac structure and function
Received 4 February 2021 are closely associated with atrial fibrillation, so we aim to investigate the potential role of BNP and
Accepted 4 April 2021 echocardiographic parameters to identify the acute ischemic stroke with atrial fibrillation patients
who have high risks of cardioembolic stroke based on it.
Methods: 436 AIS patients were divided into an AF group and non-AF group on the basis of the electro-
Keywords: cardiogram and Holter results. Then we compared vascular risk factors, laboratory test indicators, and
Atrial fibrillation
echocardiographic parameters among different groups.
Cardioembolic stroke
BNP
Results: AIS with AF group had significantly higher age, CHD, previous medication, creatinine, d-dimer,
LAD fibrinogen, CRP, BNP, LAD, LVDd, LVDs and lower cholesterol, triglyceride, LDL and ejection fraction than
the non-AF group (P < 0.05). Increased BNP, LAD, LVDd, LVDs and ejection fraction reduction were inde-
pendent risk factors to predict cardioembolic stroke. BNP and LAD could be the two most effective indi-
cators of the high risk of cardioembolic stroke. The area under the curve (AUC) of BNP and LAD were 0.791
[95%CI (0.743–0.838), p < 0.001), 0.786 [95%CI (0.739–0.833), p < 0.001]. The combined score we designed
improved the prediction effect of single-indicator. The AUC of it was 0.822 with a sensitivity of 69.5% and
specificity of 83.9%.There was an apparent positive correlation between BNP and LAD in AIS patients
(r = 0.327, P < 0.001).
Conclusion: BNP combined with echocardiographic parameters has outstanding value to predict the risk
of cardioembolic stroke, especially for BNP and LAD.
Ó 2021 Elsevier Ltd. All rights reserved.

1. Introduction ysmal atrial fibrillation without obvious clinical symptoms. As a

Cardioembolic stroke is defined as the ischemic stroke in which
a detached cardiogenic embolus causes a corresponding embolisa-
tion of the cerebral artery [1,2]. Atrial fibrillation related acute
ischemic stroke accounts for nearly 80% of the total cardioembolic
stroke and become the most essential risk factor of cardioembolic
stroke [3,4]. In comparison to other causes of stroke, atrial fibrilla-
tion related acute ischemic stroke tend to have an acute onset and
rapid progression, usually with severe and complicated clinical sit-
uations. Besides, it often predicts a poor prognosis, a higher mortal-
ity rate and recurrence rate, imposing enormous personal and
societal healthcare burdens [5,6]. Anticoagulation is recommended
for those patients in the absence of absolute contraindications [7].
Nevertheless, there is a high probability of a missed diagnosis of
atrial fibrillation due to the low detection rates of Holter monitor-
ing for clinicians, especially in patients with non-persistent parox-
⇑ Corresponding authors.
E-mail addresses: panxudong541@163.com (X. Pan), maaijun541@163.com (A. Ma).
result, those patients could not get timely and effective treatment
in secondary prevention [8,9].
Therefore, it is necessary for clinicians to search for immediate
and effective diagnostic indicators to identify AF in AIS patients.
Previous research has found that BNP and some indicators of car-
diac structure and function are closely related to atrial fibrillation
[10–14], our objective is to investigate the potential role of BNP
and echocardiographic parameters to identify the AIS with AF
patients who are high-risk to suffer from cardioembolic stroke
based on it.
2. Participants and Methods
2.1. Study population
436 AIS patients were enrolled in our research between Jun
2018 and Jun 2020 at the 61 Affiliated Hospital of Qingdao Univer-
sity. The AIS patients were divided into two groups (AF and non-AF
group) depending on the electrocardiogram and Holter results. Our

https://doi.org/10.1016/j.jocn.2021.04.002
0967-5868/Ó 2021 Elsevier Ltd. All rights reserved.
M. Zhang, Y. Wang, J. Wei et al. Journal of Clinical Neuroscience 88 (2021) 213–218

Table 1
Baseline demographics and clinical data of included AIS patients.

Variable All (n = 436) AF (n = 153) Non-AF (n = 283) P value

Age, years (median, IQR) 70.0(17.0) 74.0(16.0) 68.0(17.0) <0.001
Male (n, %) 271(62.2) 90.0(58.8) 181.0(64.0) 0.291
Premorbid mRS (median, IQR) 0.0(0.0) 0.0(0.0) 0.0(0.0) 0.535
Hypertension (n, %) 300(68.8) 106.0(69.3) 194.0(68.6) 0.875
Diabetes mellitus (n, %) 125(28.7) 37.0(24.2) 88.0(31.1) 0.128
CHD (n, %) 97(22.2) 50.0(32.7) 47.0(16.6) <0.001
Dyslipidemia (n, %) 60(13.8) 23.0(15.0) 37.0(13.1) 0.571
Previous TIA/stroke (n, %) 117(26.8) 47.0(30.7) 70.0(24.7) 0.178
Smoking (n, %) 150(34.4) 44.0(28.8) 106.0(37.5) 0.068
Alcoholism (n, %) 113(25.9) 41.0(26.8) 72.0(25.4) 0.758
Previous medication (n, %)
antiplatelete 129(29.6) 63.0(41.2) 66.0(23.3) <0.001
anticoagulant 25(5.7) 23.0(15.0) 2.0(0.7) <0.001
Admission NIHSS (median, IQR) 4.5(7.0) 5.0(12.0) 4.0(6.0) 0.053
Admission biochemistry (median, IQR)
fasting blood glucose, mmol/L 5.3(2.3) 5.5(1.8) 5.3(2.7) 0.690
cholesterol, mmol/L 4.1(1.5) 3.9(1.4) 4.3(1.5) 0.026
triglyceride, mmol/L 1.1(0.7) 1.0(0.5) 1.2(0.8) <0.001
LDL, mmol/L 2.4(1.2) 2.2(1.1) 2.5(1.2) 0.005
HDL, mmol/L 1.2(0.4) 1.2(0.4) 1.2(0.3) 0.265
BUN, mmol/L 5.2(2.2) 5.4(2.9) 5.1(2.1) 0.236
creatinine, mmol/L 88.0(20.7) 94.4(21.6) 87.0(18.0) 0.012
uric acid, mmol/L 304.0(127.1) 315.8(192.2) 299.0(114.0) 0.480
d-dimer, ng/mL 295.0(360.0) 430.0(540.0) 260.0(270.0) <0.001
fibrinogen, g/L 3.0(1.1) 3.2(1.5) 2.9(1.0) 0.017
CRP, mg/L 1.4(7.7) 6.5(17.9) 0.8(5.0) <0.001
BNP,pg/mL 89.5(231.0) 343.0(930.5) 62.0(123.0) <0.001
Echocardiography parameters (median, IQR)
LAD, mm 39.0(7.0) 43.0(9.0) 38.0(5.0) <0.001
LVDd, mm 46.0(5.0) 47.0(5.0) 45.0(5.0) 0.015
LVDs, mm 30.0(4.0) 31.0(4.0) 30.0(4.0) 0.014
ejection fraction, % 62.0(4.0) 61.0(5.0) 62.0(4.0) 0.001
Infarction location (n, %)
cortex 369.0(84.6) 131.0(85.6) 238.0(84.1) 0.674
brain stem 73.0(16.7) 23.0(15.0) 50.0(17.7) 0.482
cerebellum 48.0(11.0) 23(15.0) 25.0(8.8) 0.048
Discharge NIHSS (median, IQR) 4.0(7.0) 4.0(8.0) 4.0(6.0) 0.054
Discharge mRS (median, IQR) 2.5(3.0) 2.0(3.0) 2.0(3.0) 0.054

Abbreviations: SD, standard deviation; IQR, inter quartile range; AIS, acute ischemic stroke; AF, atrial fibrillation; mRS, modified Rankin Scale; CHD, coronary heart disease;
TIA, transient ischemic attack; NIHSS, National Institute of Health Stroke Scale; LDL, low density lipoprotein; HDL, high density lipoprotein; Bun, blood urea nitrogen; CRP, C-
reactive protein; BNP, brain natriuretic peptide; LAD, left atrial diameter; LVDd, left ventricular end-diastolic dimension; LVDs, left ventricular end-systolic dimension.

Fig. 1. Initial BNP value in the AIS with AF and Nan-AF groups(a): LAD in the AIS with AF and Non-AF EF groups(b); BNP, brain natriuretic peptide: LAD, left atrial diameter,
AIS, acute ischemic stroke; AF, atrial fibrillation; * denotes statistical signification by Mann-Whitney U test;***p<0.001.

diagnostic criteria of acute ischemic stroke were from the pub-
lished guideline [15]. AF was identified by a routine 12-leads elec-
trocardiogram or Holter (patients with a prior history of AF must
have electrocardiogram or Holter results). Diagnostic criteria for
atrial fibrillation: P wave disappeared and was replaced by F wave
of different size and shape. Atrial frequency ranged from 350 to
600 times /min. The R-R interval is definitely not homogeneous
[16]. If there was no previous history of AF or manifestations of
atrial fibrillation in electrocardiogram and Holter in participants,
they were assigned to the non-AF group. The patients diagnosed
with cardiac failure, severe infection, chronic inflammation,
autoimmune disease, malignant tumour, as well as severe hepatic
and renal insufficiency, were excluded. Data on the baseline demo-
graphics and clinical data were obtained from electronic medical
records. Stroke severity was assessed by the NIHSS score (National
Institutes of Health Stroke Scale), the functional status of patients

214
M. Zhang, Y. Wang, J. Wei et al. Journal of Clinical Neuroscience 88 (2021) 213–218

Table 2
Univariate analysis and multivariate analysis model for AIS with AF.

Univariate analysis Multivariate analysis

Odds ratio 95% CI P value Odds ratio 95% CI P value
BNP 1.002 1.001–1.002 <0.001 1.002 1.001–1.002 <0.001
LAD 1.255 1.189–1.325 <0.001 1.263 1.193–1.337 <0.001
LVDd 1.069 1.022–1.119 0.004 1.082 1.028–1.139 0.003
LVDs 1.068 1.017–1.120 0.008 1.081 1.025–1.141 0.004
Ejection fraction 0.939 0.902–0.977 0.002 0.942 0.904–0.983 0.005

Abbreviations: AIS, acute ischemic stroke; AF, atrial fibrillation; CI, confidence interval; CHD, coronary heart disease; LDL, low density lipoprotein; BNP, brain natriuretic
peptide; LAD, left atrial diameter; LVDd, left ventricular end-diastolic dimension; LVDs, left ventricular end-systolic dimension.

Table 3
Receiver operating characteristic analysis of BNP and echocardiographic parameters.

AUC Sensitivity (%) Specificity (%) 95% CI Cut-off value P-value

BNP 0.791 0.821 0.675 0.743–0.838 102.8 <0.001
LAD 0.786 0.721 0.755 0.739–0.833 39.5 <0.001
LVDd 0.573 0.544 0.602 0.513–0.632 46.5 0.001
LVDs 0.574 0.601 0.542 0.514–0.633 30.5 0.015
Ejection fraction 0.600 0.401 0.797 0.541–0.660 60.5 0.015
Combined score* 0.822 0.695 0.839 0.776–0.868 <0.001

Abbreviations: AUC, area under the curve; CI, confidence interval; BNP, brain natriuretic peptide; LAD, left atrial diameter; LDL, low density lipoprotein; LVDs, left ventricular
end-systolic dimension; LVDd, left ventricular end-diastolic dimension.
*BNP combined LAD.

between two groups were made using an independent t-test, Wil-

coxon (Mann-Whitney) test, Pearson v 2 test or Fisher0 s exact test
as appropriate. Receiver operating characteristic (ROC) curves were
applied to evaluate the role of BNP and echocardiographic param-
eters in identifying AIS with AF. Univariable and multivariable bin-
ary logistic regression analyses were put into use to determine the
prediction ability of those indicators. The relationship between
BNP and LAD was assessed using the Pearson correlation analysis.
All statistics were analysed by SPSS 26.0 software. P < 0.05 were
deemed statistically significant.

3. Results

3.1. Baseline characteristics

Fig. 2. Receiver-Operator Characteristic Curves for BNP and LAD to predict AIS with
AF; BNP, brain natriuretic peptide; LAD, left atrial diameter; AIS, acute ischemic
stroke: AF. atrial fibrillation.
was estimated by the modified Rankin scale (mRS) by two profes-
sional neurologists. Our research protocol was authorised by The
Ethical Committee of the Affiliated Hospital of Qingdao University.
Meanwhile, the ethical committee agreed with the dispensability
of the informed consent given the hospital-based observational
nature of our study.
2.2. Statistical analysis
For continuous variables, summary statistics are presented as
the mean ± SD or median (interquartile range). Categorical vari-
ables are presented as frequencies (percentages). Comparisons
215
Data on 436 AIS patients (153 AIS with AF and 283 AIS without
93 AF) were tabulated in Table 1. Their mean age was 70.0(17.0)
years. The levels of age, CHD (coronary heart disease), previous
medication, creatinine, d-dimer, fibrinogen, CRP (C-reactive pro-
tein), BNP (brain natriuretic peptide), LAD (left atrial diameter),
LVDd (left ventricular end-diastolic dimension), LVDs (left ventric-
ular end-systolic dimension) are higher in the AF group (P < 0.05).
Particularly, the BNP level was higher in the AF group compared
with the non-AF group, [343.0(930.5) versus. 62.0(123.0),
p < 0.001; Fig. 1a]. Likewise, a higher LAD level was presented in
patients with AF, which was also statistically significant [43.0
(9.0) versus. 38.0(5.0), p < 0.001; Fig. 1b]. The levels of cholesterol,
triglyceride, LDL and ejection fraction are lower in the AF group
(P < 0.05). Other clinical parameters in the two groups were not
statistically significant (P > 0.05).
3.2. Logistic regression analysis
BNP and echocardiographic parameters were incorporated into
logistic regression analysis. After adjusting for demographic char-
acteristics (gender, age) and clinical risk factors (hypertension, dia-
betes mellitus, CHD, dyslipidemia, smoking, alcoholism), we found
that the independent predictors of AIS with AF were BNP, LAD,
LVDd, LVDs, ejection fraction(Table 2). Patients with higher BNP
M. Zhang, Y. Wang, J. Wei et al. Journal of Clinical Neuroscience 88 (2021) 213–218

Table 4
Clinical data of AIS patients according to the BNP and LAD cut-off value.

Variable BNP(pg/mL) P value LAD(mm) P value

<102.8 102.8 <39.5 39.5
Age, years (median, IQR) 68.0(17.0) 74.0(15.0) <0.001 68.0(17.0) 72.0(15.0) 0.054
Male (n, %) 136.0(63.6) 121.0(59.6) 0.408 136.0(63.6) 109.0(64.1) 0.690
Hypertension (n, %) 142.0(66.4) 146.0(71.9) 0.219 142.0(66.4) 126.0(74.1) 0.094
Diabetes mellitus (n, %) 65.0(30.4) 55.0(27.1) 0.460 65.0(30.4) 53.0(31.2) 0.509
CHD (n, %) 33.0(15.4) 63(31.0) <0.001 33.0(15.4) 42(24.7) 0.499
AF (n, %) 24.0(11.2) 110.0(54.2) <0.001 24.0(11.2) 106.0(62.4) <0.001
Dyslipidemia (n, %) 31.0(14.5) 25.0(12.3) 0.516 31.0(14.5) 20.0(11.8) 0.391
Previous TIA/stoke (n, %) 49.0(22.9) 64.0(31.5) 0.048 49.0(22.9) 51.0(30.0) 0.284
Admission NIHSS (median, IQR) 4.0(6.0) 5.0(8.0) 0.037 4.0(6.0) 5.0(8.0) 0.091
LAD,mm (median, IQR) 37.0(5.0) 41.0(7.3) <0.001
BNP, pg/mL (median, IQR) 35.0(48.3) 217.9(684.9) <0.001
LVDd, mm (median, IQR) 45.0(6.0) 46.5(5.0) 0.010 45.0(6.0) 47.0(4.0) <0.001
LVDs, mm (median, IQR) 30.0(5.0) 31.0(4.0) 0.002 30.0(5.0) 31.0(5.0) <0.001
ejection fraction,% (median, IQR) 62.0(4.0) 62.0(4.0) 0.025 62.0(4.0) 62.0(4.0) 0.070

Abbreviations: CHD, coronary heart disease; AF, atrial fibrillation; TIA, transient ischemic attack; NIHSS, National Institute of Health Stroke Scale; BNP, brain natriuretic
peptide; LAD, left atrial diameter; LVDd, left ventricular end-diastolic dimension; LVDs, left ventricular end-systolic dimension.

and LAD had a 1.001-fold(95% CI1.001–1.002, p < 0.001, Table 3)
and 1.255-fold(95% CI 1.189–1.325, p < 0.001, Table 3) higher risk
of AIS with AF, respectively.
3.3. ROC analysis
3.4. Correlation between BNP and LAD
Besides, Spearman correlation analysis showed that there was
an apparent positive correlation between BNP and LAD in AIS
patients (r = 0.327, P < 0.001; Fig. 3).

The independent risk factors screened out by multivariate 4. Discussion

Logistic regression analysis were incorporated into the ROC analy-
sis (Table 3). It indicated that BNP and LAD both had higher predic-
tive value compared with other indicators. Especially, the area
under the curve (AUC) of BNP and LAD were 0.791 [95%CI
(0.743–0.838), p < 0.001), 0.786 [95%CI (0.739–0.833), p < 0.001],
respectively. The cut-off value was 102.8 pg/mL with a sensitivity
of 82.1% and specificity of 67.5% of BNP and 39.5 mm with a sensi-
tivity of 72.1% and specificity of 75.5% of LAD (Fig. 2, Table 4). The
data showed that although BNP was less specific to atrial fibrilla-
tion in acute ischemic patients than LAD, its sensitivity was higher.
We selected the indicators with an AUC>0.7 to be included in the
combined score. The combination of BNP with LAD improved the
predictive value of single-indicator. The AUC of it was 0.822 with
a sensitivity of 69.5% and specificity of 83.9%. Besides, we divided
our patients into two groups according to the cut-off value,
patients in BNP > 102.8 pg/mL group and LAD > 395 mm group
both had a higher incidence of AF (Table 4).
Fig. 3. Correlation between LAD and BNF in two acute ischemic groups; r
[spearman] = 0.327, p < 0.001.
216
Our research explored the role of BNP and echocardiographic
parameters in AIS patients with AF who had high risks of car-
dioembolic stroke. The results demonstrated that BNP and LAD
were the two most effective risk marker for the prediction of car-
dioembolic stroke.
Here are our main findings: (1) AIS with AF group had signifi-
cantly higher age, CHD, creatinine, d-dimer, fibrinogen, CRP, BNP,
LAD, LVDd, LVDs and lower LDL, cholesterol, triglyceride and ejec-
tion fraction than the non-AF group; (2) Increased BNP, LAD, LVDd,
LVDs and ejection fraction reduction were independent indictors to
predict cardioembolic stroke; (3) BNP and LAD could be the two
most effective predictors of the high risk of cardioembolic stroke;
(4) There was an apparent positive correlation between BNP and
LAD in AIS patients.
BNP is a neurohormone synthesised by the atrial and ventricu-
lar myocardium during cardiac diastole or synthesised and
released by the brain after acute ischemic stroke [17,18]. Previous
investigations have shown that BNP is a prediction indicator of
atrial fibrillation [19,20]and thromboembolic events [21–24],
especially for the cerebral embolism caused by atrial fibrillation
[25–31]. Some research indicated that the BNP levels were higher
in cerebral infarction complicated with atrial fibrillation group
compared with the non-AF group, which is consistent with our
findings [28,32,33]. Also, retrospective studies showed that plasma
BNP level was a significant predictor of functional outcome and
recurrence of the acute ischemic stroke in patients with nonvalvu-
lar atrial fibrillation [30,34]. Hiroshi et al. found that the BNP
threshold for predicting paroxysmal atrial fibrillation in ischemic
stroke patients was 52.4 mg/dL [35], which is lower than our
cut-off value, we hypothesised that the reason was that we
included more patients with persistent atrial fibrillation, which
might increase the plasma BNP levels to some extent. In addition,
BNP was also a risk factor for stroke, and the occurrence of stroke
was often accompanied by a higher BNP.
A meta-analysis of 22 clinical study from Njoku A et al. indi-
cated that the prevalence of atrial fibrillation and left atrial diam-
eter enlargement had a significantly positive correlation. It could
M. Zhang, Y. Wang, J. Wei et al.
be attributed to the decrease of the left atrial function because of
the left atrial diameter enlargement, which further promotes the
structural and electrical remodeling, making the atrial effective
refractory period and action potential conduction of atrial muscle
cell unified. Finally, atrial fibrillation occurs [36]. The left atrial
enlargement was also associated with embolism events [37–39].
Enlargement of the left atrium may contribute to stroke and
thrombosis by promoting endothelial injury [40], which is a severe
sign of atrial cardiomyopathy and coexists with atrial fibrillation
[41]. Atrial cardiomyopathy resulted from the left atrium fibrosis
finally leads to atrial fibrillation with time. Besides, the increase
of the left atrium diameter will lead to myocardial dysfunction,
hemodynamic changes and the production of inflammatory fac-
tors, exacerbating the rate of thrombosis. In our results, left ven-
tricular ejection fraction reduction was also an independent risk
factor of stroke with atrial fibrillation to imply a high risk of cardio-
genic stroke, which corroborated previous research [42]. We spec-
ulated that LVDd and LVDS could also be used as indicators of left
ventricular function to predict cardiogenic cerebral embolism to a
certain extent, which was consistent with our findings.
It must be admitted that our research had some limitations.
First, the number of enrolments is relatively insufficient to predict
the actual risk of cardioembolic stroke. Moreover, AIS with AF is
not all cardioembolic stroke, and it can not be excluded that the
real pathogenesis of very few AIS with AF should be attributed to
other etiologies caused by abnormal embolisation, tumour emboli-
sation, arterial dissection and non-stenosis large artery atheroscle-
rosis. Finally, given the hospital-based observational nature of our
study, further prospective studies need to be carried out to mea-
sure the real value of these indicators.
5. Conclusion
Our study found that BNP combined with echocardiographic
parameters has outstanding value to predict the risk of cardioem-
bolic stroke, especially for BNP and LAD, which will promote the
further screening of the high-risk populations and help clinicians
administer anticoagulant therapy as early as possible.
6. Declarations
Availability of data and materials
The data used to support the findings of this study are available
from the corresponding authors upon request.
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgements
This work was supported by the National Natural Science Founda-
tion of China [grant numbers: 81971111, 81771259].
Authors’ contributions
Meng Zhang analysed the patient data and was the major con-
tributors in writing the manuscript. Yuan Wang, Jin Wei and Qing
Peng were responsible for collecting data. Aijun Ma and Xudong
Pan provided financial support for research design and draft writ-
ing, and were responsible for draft revision. All authors read and
approved the final manuscript.
217
Journal of Clinical Neuroscience 88 (2021) 213–218
References
[1] Murtagh B, Smalling RW. Cardioembolic stroke. Curr Atheroscler Rep 2006;8
(4):310–6.
[2] Di TMR, Homma S. Mechanisms of cardioembolic stroke. Curr Cardiol Rep
2002;4(2):141–8.
[3] Khoo CW, Lip GY. Clinical outcomes of acute stroke patients with atrial
fibrillation. Expert Rev Cardiovasc Ther 2009;7(4):371–4.
[4] Schnabel RB, Haeusler KG, Healey JS, Freedman B, Boriani G, Brachmann J, et al.
Searching for Atrial Fibrillation Poststroke: A White Paper of the AF-SCREEN
International Collaboration. Circulation 2019;140(22):1834–50.
[5] Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G,
Baumgartner H, et al. Guidelines on the management of valvular heart
disease (version 2012). Eur Heart J 2012;33(19):2451–96.
[6] Kimura K, Minematsu K, Yamaguchi T, Collaboration JMSI, (J-MUSIC),. Atrial
fibrillation as a predictive factor for severe stroke and early death in 15,831
patients with acute ischaemic stroke. J Neurol Neurosurg Psychiatry 2005;76
(5):679–83.
[7] Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD,
et al. Guidelines for the prevention of stroke in patients with stroke and
transient ischemic attack: a guideline for healthcare professionals from the
American Heart Association/American Stroke Association. Stroke 2014;45
(7):2160–236.
[8] Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor
for stroke: the Framingham Study. Stroke 1991;22(8):983–8.
[9] Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to
prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern
Med 2007;146(12):857–67.
[10] Papageorgiou N, Providência R, Falconer D, Wongwarawipat T, Tousoulis D,
Lim WY, et al. Predictive Role of BNP/NT-proBNP in Non-Heart Failure Patients
Undergoing Catheter Ablation for Atrial Fibrillation: An Updated Systematic
Review. Curr Med Chem 2020;27(27):4469–78.
[11] Kishimoto I, Makino H, Ohata Y, Tamanaha T, Tochiya M, Kusano K, et al.
Impact of B-type natriuretic peptide (BNP) on development of atrial fibrillation
in people with Type 2 diabetes. Diabet Med 2016;33(8):1118–24.
[12] Danilo Menichelli Angela Sciacqua Roberto Cangemi Paola Andreozzi
Francesco Del Sole Francesco Violi et al. Atrial fibrillation pattern, left atrial
diameter and risk of cardiovascular events and mortality 75 3 2021 10.1111/
ijcp.v75.3 10.1111/ijcp.13771.
[13] Perlepe K, Sirimarco G, Strambo D, Eskandari A, Karagkiozi E, Vemmou A, et al.
Left atrial diameter thresholds and new incident atrial fibrillation in embolic
stroke of undetermined source. Eur J Intern Med 2020;75:30–4. https://doi.
org/10.1016/j.ejim.2020.01.002.
[14] Jin X, Pan J, Wu H., Xu D (2018) Are left ventricular ejection fraction and left
atrial diameter related to atrial fibrillation recurrence after catheter ablation?:
A meta-analysis. Medicine (Baltimore). https://doi.org/10.1097/
MD.0000000000010822.
[15] Chung J, Park SH, Kim N, Kim W, Park JH, Ko Y, et al. Trial of ORG 10172 in
Acute Stroke Treatment (TOAST) classification and vascular territory of
ischemic stroke lesions diagnosed by diffusion-weighted imaging. J Am
Heart Assoc 2014;3(4). https://doi.org/10.1161/JAHA.114.001119.
[16] Obeyesekere MN, Klein GJ. Application of the 2015 ACC/AHA/HRS guidelines
for risk stratification for sudden death in adult patients with asymptomatic
pre-excitation. J Cardiovasc Electrophysiol 2017;28(7):841–8.
[17] Rodriguez-Yanez M, Arias-Rivas S, Santamaria-Cadavid M, Sobrino T, Castillo J,
Blanco M. High pro-BNP levels predict the occurrence of atrial fibrillation after
cryptogenic stroke. Neurology 2013;81(5):444–7.
[18] Nakagawa K, Yamaguchi T, Seida M, Yamada S, Imae S, Tanaka Y, et al. Plasma
concentrations of brain natriuretic peptide in patients with acute ischemic
stroke. Cerebrovasc Dis 2005;19(3):157–64.
[19] Hijazi Z, Wallentin L, Siegbahn A, Andersson U, Christersson C, Ezekowitz J,
et al. N-terminal pro-B-type natriuretic peptide for risk assessment in patients
with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the
Prevention of Stroke in Subjects With Atrial Fibrillation). J Am Coll Cardiol
2013;61(22):2274–84.
[20] Schnabel RB, Larson MG, Yamamoto JF, Sullivan LM, Pencina MJ, Meigs JB, et al.
Relations of biomarkers of distinct pathophysiological pathways and atrial
fibrillation incidence in the community. Circulation 2010;121(2):200–7.
[21] Shimizu H, Murakami Y, Inoue S, Ohta Y, Nakamura K, Katoh H, et al. High
plasma brain natriuretic polypeptide level as a marker of risk for
thromboembolism in patients with nonvalvular atrial fibrillation. Stroke
2002;33(4):1005–10.
[22] Pant R, Patel M, Garcia-Sayan E, Wassouf M, D’Silva O, Kehoe RF, et al. Impact
of B-type natriuretic peptide level on the risk of left atrial appendage
thrombus in patients with nonvalvular atrial fibrillation: a prospective
study. Cardiovasc Ultrasound 2015;14(1). https://doi.org/10.1186/s12947-
016-0047-6.
[23] Harada M, Tabako S, Fujii Y, Takarada Y, Hayashi K, Ohara H, et al. Correlation
between plasma brain natriuretic peptide levels and left atrial appendage flow
velocity in patients with non-valvular atrial fibrillation and normal left
ventricular systolic function. J Echocardiogr 2018;16(2):72–80.
[24] Patton KK, Ellinor PT, Heckbert SR, Christenson RH, DeFilippi C, Gottdiener JS,
et al. N-terminal pro-B-type natriuretic peptide is a major predictor of the
development of atrial fibrillation: the Cardiovascular Health Study. Circulation
2009;120(18):1768–74.
M. Zhang, Y. Wang, J. Wei et al.
[25] Wasser K, Weber-Krüger M, Gröschel S, Uphaus T, Liman J, Hamann GF, et al.
Brain Natriuretic Peptide and Discovery of Atrial Fibrillation After Stroke: A
Subanalysis of the Find-AF Trial. Stroke 2020;51(2):395–401.
[26] Zecca B, Mandelli C, Maino A, Casiraghi C, Bolla G, Consonni D, et al. A
bioclinical pattern for the early diagnosis of cardioembolic stroke. Emerg Med
Int 2014;2014:1–7. https://doi.org/10.1155/2014/242171.
[27] Okada Y, Shibazaki K, Kimura K, Matsumoto N, Iguchi Y, Aoki J, et al. Brain
natriuretic peptide is a marker associated with thrombus in stroke patients
with atrial fibrillation. J Neurol Sci 2011;301(1-2):86–9. https://doi.org/
10.1016/j.jns.2010.10.017.
[28] Shibazaki K, Kimura K, Fujii S, Sakai K, Iguchi Y. Brain natriuretic peptide levels
as a predictor for new atrial fibrillation during hospitalisation in patients with
acute ischemic stroke. Am J Cardiol 2012;109(9):1303–7.
[29] Nigro N, Wildi K, Mueller C, Schuetz P, Mueller B, Fluri F, et al. BNP but Not s-
cTnln is associated with cardioembolic aetiology and predicts short and long
term prognosis after cerebrovascular events. PLoS ONE 2014;9(7):e102704.
https://doi.org/10.1371/journal.pone.0102704.
[30] Shibazaki K, Kimura K, Aoki J, Sakai K, Saji N, Uemura J. Brain natriuretic
peptide level on admission predicts recurrent stroke after discharge in stroke
survivors with atrial fibrillation. Clin Neurol Neurosurg 2014;127:25–9.
https://doi.org/10.1016/j.clineuro.2014.09.028.
[31] Chaudhuri JR, Sharma VK, Mridula KR, Balaraju B, Bandaru VCSS. Association of
plasma brain natriuretic peptide levels in acute ischemic stroke subtypes and
outcome. J Stroke Cerebrovasc Dis 2015;24(2):485–91.
[32] Wachter R, Lahno R, Haase B, Weber-Krüger M, Seegers J, Edelmann F, et al.
Natriuretic peptides for the detection of paroxysmal atrial fibrillation in
patients with cerebral ischemia–the Find-AF study. PLoS ONE 2012;7(4):
e34351. https://doi.org/10.1371/journal.pone.0034351.
[33] Fujii S, Shibazaki K, Kimura K, Sakai K, Aoki J. A simple score for predicting
paroxysmal atrial fibrillation in acute ischemic stroke. J Neurol Sci 2013;328
(1-2):83–6. https://doi.org/10.1016/j.jns.2013.02.025.
218
Journal of Clinical Neuroscience 88 (2021) 213–218
[34] Maruyama K, Uchiyama S, Shiga T, Iijima M, Ishizuka K, Hoshino T, et al. Brain
Natriuretic Peptide Is a Powerful Predictor of Outcome in Stroke Patients with
Atrial Fibrillation. Cerebrovasc Dis Extra 2017;7(1):35–43.
[35] Shiroto H, Tomita H, Hagii J, Metoki N, Fujita A, Kamada T, et al. Impact of
Atrial Natriuretic Peptide Value for Predicting Paroxysmal Atrial Fibrillation in
Ischemic Stroke Patients. J Stroke Cerebrovasc Dis 2017;26(4):772–8.
[36] Njoku A, Kannabhiran M, Arora R, Reddy P, Gopinathannair R, Lakkireddy D,
Dominic P (2018) Left atrial volume predicts atrial fibrillation recurrence after
radiofrequency ablation: a meta-analysis. Europace 20(1):33-42
[37] Frenkel D, D’Amato SA, Al-Kazaz M, Markowitz SM, Liu CF, Thomas G, et al.
Prevalence of Left Atrial Thrombus Detection by Transesophageal
Echocardiography: A Comparison of Continuous Non-Vitamin K Antagonist
Oral Anticoagulant Versus Warfarin Therapy in Patients Undergoing Catheter
Ablation for Atrial Fibrillation. JACC Clin Electrophysiol 2016;2(3):295–303.
[38] Calvo N, Mont L, Vidal B, Nadal M, Montserrat S, Andreu D, et al. Usefulness of
transoesophageal echocardiography before circumferential pulmonary vein
ablation in patients with atrial fibrillation: is it really mandatory?. Europace
2011;13(4):486–91.
[39] Yaghi S, Moon YP, Mora-McLaughlin C, Willey JZ, Cheung K, Di Tullio MR, et al.
Left atrial enlargement and stroke recurrence: the Northern Manhattan Stroke
Study. Stroke 2015;46(6):1488–93.
[40] Jordan K, Yaghi S, Poppas A, Chang AD, Mac Grory B, Cutting S, et al. Left Atrial
Volume Index Is Associated With Cardioembolic Stroke and Atrial Fibrillation
Detection After Embolic Stroke of Undetermined Source. Stroke 2019;50
(8):1997–2001.
_
[41] Uzie˛bło-Zyczkowska B, Krzesiński P, Jurek A, Kapłon-Cieślicka A, Gorczyca I,
Budnik M, et al. Left Ventricular Ejection Fraction Is Associated with the Risk of
Thrombus in the Left Atrial Appendage in Patients with Atrial Fibrillation.
Cardiovasc Ther 2020;2020:1–7. https://doi.org/10.1155/2020/3501749.
[42] Albertsen IE, Rasmussen LH, Overvad TF, Graungaard T, Larsen TB, Lip GYH.
Risk of stroke or systemic embolism in atrial fibrillation patients treated with
warfarin: a systematic review and meta-analysis. Stroke 2013;44(5):1329–36.