Acute Atrial Fibrillation During Onset of Stroke Indicates Higher Probability of Post-Stroke Death Outcomes

doi:10.21203/rs.3.rs-2015002/v1

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Acute Atrial Fibrillation During Onset of Stroke Indicates Higher Probability of Post-Stroke Death Outcomes

https://doi.org/10.21203/rs.3.rs-2015002/v1

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Patients with atrial fibrillation (AF) have a higher risk of ischemic stroke. However, it is still unknown whether acute atrial fibrillation (AAF) in the emergency department can affect the outcomes of acute ischemic stroke (AIS) patients. In this study, the risk and prognosis of AIS patients with AFF were assessed with a total of 706 identified patients, who were grouped based on their AF history. Logistic regression showed that age ≥ 73 (OR: 2.00; 95% CI: 1.18–3.37; p = 0.010), baseline NIHSS score (OR: 1.18; 95% CI: 1.15–1.22; p < 0.001), and AAF onset (OR: 1.87; 95% CI: 1.09–3.19; p = 0.022), were independent risk factors of severity of early neurological deficits in AIS. Baseline NIH Stroke Scale/Score (NIHSS) (OR: 1.11; 95% CI: 1.08 to 1.13; p < 0.001) and AAF onset (OR: 1.74; 95% CI: 1.01 to 2.98; p = 0.044) were independent predictors of the mortality. AAF in the emergency department was not only an independent risk factor for the severity of early AIS neurological deficits, but also an indicator of high probability of post-stroke death in 30 days.

Acute Atrial Fibrillation

Acute Ischemic Stroke

Emergency Department

Atrial fibrillation (AF) is the most common form of arrhythmia observed in the emergency department and is an important risk factor for acute ischemic stroke (AIS) ^1–2. It is estimated that 15% of strokes can be attributed to AF, and this proportion increases significantly with age ^3–4. AF-related ischemic stroke is generally more disabling and life-threatening than other types ⁵.

Acute atrial fibrillation (AAF) refers to the rapid, irregular, and recent chaotic atrial activity (with a time of onset generally < 48 h), including new-onset AF and paroxysmal AF, as well as cases of persistent or permanent AF with aggravated symptoms such as palpitation and dizziness caused by increased ventricular rates. In AIS patients with AF, the AF was diagnosed in 25–36.2% of the patients ^7–10 after the first stroke. The new onset of AF in patients with no prior history of AF, especially after cerebrovascular events (whether persistent or paroxysmal), indicates as increased risk of ischemic stroke and even stroke recurrence and adverse consequences ¹¹. In AIS patients with AF, the mean heart rate during an acute stroke has a J-curve correlation with stroke mortality. A comprehensive understanding of the relationship between AAF and AIS risk and prognosis will facilitate the management and treatment of AIS patients after clinical decision-making, including efforts to maintain cardiac records and the use of oral anticoagulant therapy to prevent stroke recurrence.

More than 70% of the AAF patients are initially treated in the emergency department, so emergency department physicians are gatekeepers for AAF management. Acute episodes of AF are common in patients with AIS however, few studies evaluate the risk and prognosis of such patients. The primary objective of this study was to assess the prevalence of AAF in patients with a AIS who entered the green channel for stroke in the emergency department for the first time and to explore the relationship between AAF onset and severity of early neurological deficits, and 30-day all-cause mortality after stroke in AIS patients.

2.2. Study design

This was a single-centered retrospective cohort study. This study includes data of patients admitted to the green emergency channel for stroke in Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine from December 2019 to December 2021. The flowchart is shown in Fig. 1.

The inclusion criteria of this study were as follows: (1) occurrence of AIS within last 24 h, (2) completion of 12-lead ECG in the emergency department, and (3) further hospitalization and treatment at the stroke center of the hospital. All patients were diagnosed with AAF by emergency physicians, while AIS was diagnosed and evaluated by neurologists.

The neurologist diagnosed AIS-related permanent focal neurological deficit and confirmed it using cranial computed tomography (CT) or magnetic resonance imaging (MRI). AAF was diagnosed by a physician in the emergency department using 12-lead ECG and past medical history. This study focused on patients with AIS who developed AAF, including new-onset AF, paroxysmal AF, and persistent or permanent AF with exacerbated symptoms such as palpitations and dizziness attributed to rapid ventricular rates.

This study extracted the following information from the medical records: demographic information, clinical symptoms, The National Institutes of Health Stroke Scale/Score (NIHSS), imaging information, emergency 12-lead ECG, previous medical history, and patient treatment. We assessed our patient for early neurological deficits using a 7-day NIHSS score. AIS patients with a 7-day NIHSS score ≥ 16 were defined as having moderate or severe stroke ^13–14. We evaluated the association of AAF onsets with the severity of early neurological deficits and verified whether they are associated with all-cause mortality within 30 days after the ischemic event.

2.3. Statistical analysis

Baseline category variables were listed as numbers (in percentage). Continuous variables with a normal baseline distribution were reported as the mean standard deviation (SD), while continuous variables with a non-normal distribution were reported as the median (interquartile range [IQR]). For a double sample with normal distribution, the analysis of variance was used to compare the continuous variables between the two groups. For those with non-normal distribution, the Wilcoxon rank-sum test was used. Categorical values were compared between the two groups using the χ² test or Fisher’s test.

Univariate analysis was used to analyze the relationship between statistically significant indexes (p < 0.05) and severity of early neurological deficits (7-day NIHSS score ≥ 16) and death within 30 days after stroke. Logistic regression was used to analyze the index in the univariate analysis (p < 0.05) and the independent risk factors for early neurological deficit severity (7-day NIHSS score ≥ 16) and 30-day mortality. A p < 0.05 was recognized as a statistically significant. The SPSS version 28.0 (SPSS Inc., Chicago, IL) was used for all statistical analyses conducted in this study.

A total of 706 AIS patients who entered the green channel for stroke in the emergency department from December 2019 to December 2021 were enrolled in this study. Patients were divided into two groups based on AAF episodes: AAF (142 cases) and No-AAF (564 cases). The ages of AIS patients without AAF were significantly lower than those with AAF (71.02 13.17 vs.80.32 9.47, p < 0.001). The patients’ age range was 74 years and the quartile age was 65 years, 73 years, and 84 years, respectively. The baseline NIHSS score was 16.09 ± 10.60 for AAF patients and 8.65 ± 8.39 for No-AAF patients (p < 0.001). A total of 64 AIS patients had AAF episodes while 81 patients had no AAF episodes with a 7-day NIHSS score ≥ 16 points (45.1% vs. 14.4%, p < 0.001). The 30-day mortality rate in AAF patients (30.3%) was significantly higher than that in No-AAF patients (10.1%), and there was a significant difference (p < 0.001) (Table 1).

Table 1

Baseline and clinical characteristic of the patients with AAF or No-AAF at the time of the ischemic stroke
Patient characteristic
Baseline
Age (mean ± SD)	80.32 (9.47)	71.02(13.17)	< 0.001
Male(%)	61 (43.0)	365 (64.8)	< 0.001
BMI (mean ± SD)	23.79(5.91)	24.00(3.67)	< 0.001
HbA1c (mean ± SD)	6.30(1.13)	6.53 (1.71)	0.001
TC (mean ± SD)	4.44 (1.11)	4.79(1.23)	0.263
TG (mean ± SD)	0.99 (0.49)	1.39(0.83)	< 0.001
HDL (mean ± SD)	1.31 (0.43)	1.20 (0.32)	0.001
LDL (mean ± SD)	2.48 (0.92)	2.81(0.99)	0.483
Baseline NIHSS (mean ± SD)	16.09 (10.60)	8.65(8.39)	< 0.001
AF history (%)	87(61.3)	96(17.1)	< 0.001
CAD (%)	21 ( 14.8)	53 (9.4)	0.062
HTN(%)	100(70.9)	394(71.4)	0.915
CI history (%)	35 (24.6)	120(21.3)	0.391
CH history (%)	6 ( 4.2)	14 ( 2.5)	0.265
DM history (%)	35 (24.6)	176 (31.3)	0.124
Clinical
IT (%)	28(19.7)	178(31.6)	0.005
DSA (%)	63(44.4)	137(24.5)	< 0.001
Outcome
7d NIHSS ≥ 16 (%)	64(45.1)	81(14.4)	< 0.001
Mortality (%)	43(30.3)	57(10.1)	< 0.001
SD, standard deviation; NIHSS, National Institutes of Health Stroke Scale; PAF, paroxysmal atrial fibrillation; CI history, history of cerebral infarction; CH history, history of cerebral hemorrhage; DM history, history of diabetes; IT, intravenous thrombolysis; DSA, digital subtraction angiography. p value < 0.05 was considered to be statistically significant.

Compared with no-AAF patients, the proportion of AAF patients receiving interventional thrombectomy was significantly increased (24.5% vs. 44.4%), and there was a significant statistical difference between the two groups (p < 0.001) (Table 1). The proportion of AIS patients without AAF onset receiving thrombolytic therapy was significantly higher than those who had AAF (31.6% vs. 19.7%, p = 0.005).

Logistic analysis showed that patients aged ≥ 73 years (OR: 2.00; 95% CI

: 1.18–3.37; p = 0.010) had a baseline NIHSS score (OR: 1.18; 95% CI 1.15–1.22; p < 0.001) and AAF (OR: 1.87; 95% CI 1.09–3.19; p = 0.022) as independent risk factors for early neurological deficits in stroke patients admitted to emergency department (Table 2). Baseline NIHSS score (OR: 1.11; 95% CI: 1.08–1.13; p < 0.001) and acute onset of atrial fibrillation (OR: 1.74; 95% CI: 1.01–2.98; p = 0.044) were independent indicative factors of 30-day mortality in patients with AIS. Age ≥ 84 years was associated with a 30-day mortality in patients with AIS (OR: 1.58; 95% CI: 0.94–2.64; p = 0.083), but there was no statistically significant difference across the study groups (Table 3).

Table 2

Adjusted odds ratio for the risk factors associated with 7 days NIHSS score (≥ 16)
	OR	95% Confidence Interval	p value
Age ≥ 73	2.00	1.18–3.37	0.01
AAF	1.87	1.09–3.19	0.022
Baseline NHISS	1.18	1.15–1.22	< 0.001

Table 3

Adjusted odds ratio for the risk factors associated with 30 days mortality with AAF or No-AAF
	OR	95% Confidence Interval	p value
Age ≥ 84	1.58	0.94–2.64	0.083
AAF	1.74	1.01–2.98	0.044
Baseline NHISS	1.11	1.08–1.13	< 0.001

In this study, 142 patients (20.11%) were diagnosed with AAF onset in the emergency department, of which 49 patients (34.51%) were new cases of AF onset. This study found that the age of AIS patients with AAF was significantly higher than that of patients without AAF. Age ≥ 73 years, baseline NIHSS score, and AAF episode were independent risk factors for early neurological deficits. Age ≥ 84 years was associated with, but not significantly different from the 30-day mortality in AIS patients. Baseline NIHSS scores and AAF episodes were independent risk factors for 30-day mortality in patients with acute stroke.

The risk of AF combined with AIS increases with age. The risk is about 6% in people over the age of 65 years, while it was 9% in people aged between 80–89 years ^[15–16]. A previous single-center study of 998 patients in Poland showed a significant increase in AIS in patients over 65 years of age with AF, compared to patients under 65 years (32.1%: 8.1%, p < 0.0001) ^[17]. Our results collaborate with the study in Poland, wherein were observed that the age of AIS patients without AAF was significantly lower than that of AIS patients with AAF. In addition, in this study, the age quartile was 65, 73, and 84 years, respectively, and it was found that age (≥ 73 years) was an independent risk factor for early neurological deficits. Age (≥ 84 years) is a risk factor for 30-day mortality in patients with acute stroke however, a larger sample size is needed to determine if the difference is statistically significant.

AF in patients with AIS is known to be associated with stroke severity and stroke outcomes compared with other stroke subtypes.

Clinically, we have found that the cause of about 20–30% of ischemic strokes is still unclear even after implementing all available diagnostic measures. Clinicians have long suspected an association between unexplained stroke, often referred to as an occult stroke, and asymptomatic AF. Occult strokes usually conceal occult paroxysmal AF, and these patients are more likely to miss the diagnosis. They are prone to thromboembolism and ischemic stroke without appropriate anticoagulant therapy ¹⁸.

On the one hand, acute cerebral ischemia can affect the control of cardiac autonomic rhythm and contribute to the occurrence of adverse cardiac events. On the other hand, the autonomic nervous system promotes the activation of inflammation and coagulation, leading to the occurrence of acute cerebrovascular events ^18–19. Approximately 2–6% of patients die from cardiac causes after acute ischemic stroke in the first few months. Necropsy studies have confirmed that ECG abnormalities could occur even in the presence of normal coronary arteries without acute ischemic changes, meaning that it was the neurological events rather than primary cardiac events that caused the abnormalities. ECG abnormalities are also common in stroke patients without primary heart disease ²⁰. According to the meta-analysis, in the sequential screening model, about one-third of patients were diagnosed with atrial fibrillation after stroke on ECG at admission (7.7% of 23.7%). Given the low cost and wide availability of ECG, ECG remains a key indicator for screening for stroke-induced atrial fibrillation ²¹. Our study was unique since it categorized patients in the emergency department for the presence of acute episodes of AF. According to the clinical results of AAF patients in the emergency department, 142 patients (20.11%) had paroxysmal AF, which was similar to other studies ¹⁸. Forty-nine of them (34.51%) had new onset of AF and denied any previous history of AF or coronary heart disease.

A retrospective analysis of a mode selection test (MOST) in 312 patients showed that patients with at least one atrial rate episode had a 2.5-fold increased risk of death or stroke [22]. In our study, the 30-day mortality of stroke patients with acute AF onset was significantly higher than in patients without acute episodes of AF (30.3% vs. 10.1%, p < 0.001). Based on this retrospective study, the results of this study seem to confirm that acute cerebral ischemia triggers the activation of AF, which can also predict the prognosis of stroke. AF may be the cause of ischemic stroke or the result of ischemic stroke.

This study evaluated these clinical indicators to validate the severity of early neurological deficits and the risk of 30-day mortality after stroke. Multivariate analysis suggested that age (≥ 73 years) to be one of the risk factors associated with the severity of early neurological deficits, NIHSS baseline score, and AAF onset. This table can be used for rapid individual clinical assessment of the extent of early neurological deficits in patients with AIS. Combined with clinical characteristics, it can provide a simple method to predict mortality in the acute stroke period. AAF and baseline NIHSS scores are powerful predictors of 30-day mortality.

This study has some limitations. First, it was a retrospective study, and the data recording was limited, as some patient information could not be reliably evaluated in some cases, such as the time of occurrence of AF and the duration of AF. The nature of the retrospective study can verify the clinical observations. Second, this is a single-center study that cannot reflect the overall situation of stroke patients in China, but it has the advantage that researchers can use unified criteria and evaluation methods, which is conducive to the consistency of the results.

Based on the clinical observations in this study, it can be concluded that acute episodes of AF are common in patients with AIS, which is associated with the severity of early neurological deficits and a 30-day after stroke mortality rate. Our findings reinforced the importance of AAF in assessing the risk and prognosis of acute ischemic stroke.

Acute Atrial Fibrillation，AAF

atrial fibrillation，AF

acute ischemic stroke，AIS

National Institute of Health Stroke Scale，NIHSS

All methods were carried out in accordance with relevant guidelines and regulations.

Ethical approval and consent to participate

Since this is the retrospective research, the need for informed consent was waived by Shanghai Sixth People's Hospital Ethic Committee. All experimental protocols were approved by Shanghai Sixth People's Hospital Ethic Committee. Ethics number: 2017-101-0（1）.

Funding

Fund Cardiovascular Multidisciplinary Integrated Research Fund（Z-2016-23-2101-47）, Construction of Shanghai Municipal Health Commission (201840099）.

Consent for publication:

Not applicable.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author upon reasonable request.

Submission declaration and verification

This manuscript has not been published previously, is not under consideration for publication elsewhere and this publication is approved by all authors and the responsible authorities where the work has been carried out. This manuscript will not be published elsewhere in the same form.

Conflict of interest

The authors report no conflict of interest.

Acknowledgment

We would like to thank all the patients.

Author contribution section:

Statement of authorship: All the authors have made substantial contributions to the conception, design of the work; or the acquisition, analysis, or interpretation of data for the work. They have participated in drafting the manuscript and approved the version to be published.

Jiamei Jiang: Data collection, data analysis, Writing – Original Draft, Visualization.

Yongxia Li: Data collection, data analysis, Writing – Original Draft

Jiangshan Deng: Data collection, data analysis

Xiaoguang Zhu and Qing Xu: Data collection, data analysis, Writing – Original Draft

QimingFeng: paper design，Methodology, Data Curation，Writing – Review & Editing..

Qin Gao: Conceptualization, data analysis, Writing Review and Editing. All authors interpreted data and approved the final draft of the manuscript.

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No competing interests reported.

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Acute Atrial Fibrillation During Onset of Stroke Indicates Higher Probability of Post-Stroke Death Outcomes

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1. Introduction

2. Materials And Methods

2.2. Study design

2.3. Statistical analysis

3. Results

4. Discussions

5. Conclusions

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