Although atrial fibrillation (AF)-associated acute ischemic stroke (AIS) is on the rise, is devastating, and life-threatening, there is limited data on the clinical course and in-hospital mortality of patients treated in the intensive care unit (ICU). This study aimed to describe the clinical course and factors associated with in-hospital mortality in AF-associated AIS patients admitted to the ICU.
This study was a retrospective analysis of a prospective nationwide multicenter cohort including non-valvular AF-AIS patients receiving ICU care admitted to 14 stroke centers in South Korea from 2017 to 2020. In-hospital outcomes, including in-hospital mortality and neurological deterioration (ND) have been described.
Amongst 2,487 AF-associated AIS patients, 259 (10.4%) were treated in the ICU. In-hospital mortality and ND occurred in 8.5% and 17.0% of the patients, respectively. Higher rates of initial National Institute for Health Stroke Scale scores, symptomatic steno-occlusive lesions, and CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age ≥75 [Doubled], Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular Disease, Age 65–74, Female) scores were found in those with in-hospital mortality. The CHA2DS2-VASc score after admission increased the risk of in-hospital mortality (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.00–2.18) were associated with in-hospital mortality. Antithrombotic use within 48 hours was related to decreased in-hospital mortality (OR, 0.26; 95% CI, 0.10–0.67).
ICU care in AF-associated AIS is common, and the establishment of optimal treatment strategies in the ICU may be needed.
Atrial fibrillation (AF) is a major risk factor for ischemic stroke, contributing to an incremental risk of more than five times [
Proper management in the intensive care unit (ICU) is known to improve outcomes in neurological diseases [
Understanding individual profiles and clinical courses may be required to establish optimal treatment strategies to enhance outcomes in AF-AIS patients in the ICU. In this study, we aimed to describe baseline characteristics and stroke information in AF-associated AIS patients treated in the ICU, compared to those who did not; further, the clinical parameters associated with in-hospital mortality using clinical data from a prospective nationwide multicenter AF cohort study were investigated.
Among AIS patients admitted to 14 stroke centers in Korea, the East Asian Ischemic Stroke Patients with Atrial Fibrillation Study (EAST-AF) Part II was used to provide risk stratification tools for assessing the risk of stroke recurrence by collecting clinical and neuroimaging characteristics potentially associated with clinical outcomes. The EAST-AF Part II prospectively enrolled patients with nonvalvular AF. These patients included those with priorly known AF and AF diagnosed after stroke upon routine electrocardiography, automatic electrocardiography monitoring or 24-hour Holter monitoring during their hospital stay. Clinical information and outcome data were derived from the Clinical Research Collaboration for Stroke in Korea (CRCS-K) registry [
A total of 15,353 patients admitted to the EAST-AF-Part II participating centers between October 26, 2017, and March 31, 2020, were screened. Amongst 2,690 non-valvular AF patients who provided informed consent, we included 2,489 patients who completed clinical and neuroimaging data from the prospective registry in this study (
Clinical data were obtained from the CRCS-K database, including records of intensive care during hospital stay. Information on sex, age, vascular risk factors including hypertension, diabetes, dyslipidemia, smoking status, history of stroke and coronary heart disease, and heart failure was further collected. Data on prior antithrombotic and premorbid functional statuses were also collected. Stroke information such as systolic and diastolic blood pressure, initial glucose level, initial National Institute for Health Stroke Scale (NIHSS) score, symptomatic steno-occlusive lesion (>50% stenosis or occlusion) [
The primary outcome was in-hospital mortality rate. Among the three discharge states, in-hospital mortality, transfer to other departments, and discharge, the occurrence of in-hospital mortality was analyzed. In-hospital mortality included patients with hopeless discharge. The occurrence of neurological deterioration (ND) was also assessed. ND was defined as any new neurological symptoms or signs worsening among patients with a total NIHSS score ≥2 or an increase in the NIHSS subscore of ≥1 for consciousness or motor function level, occurring during the hospital stay within 3 weeks of onset [
Baseline characteristics and stroke information of patients in the ICU were described as mean±standard deviation or median (interquartile range [IQR]), as appropriate. The discharge status and proportion of ND were described. Patients who received ICU care were further distinguished based on the occurrence of in-hospital mortality. We compared the baseline characteristics and stroke information between patients with and without in-hospital mortality. Clinical parameters that differed between the two groups were determined using the chi-square test or Fisher’s exact test for categorical variables and Student
Demographics and stroke information were described for patients receiving ICU care (
Comparing patients without in-hospital mortality among AF-associated stroke in the ICU, patients with in-hospital mortality were older, had higher CHA2DS2-VASc score, initial NIHSS score, proportion of symptomatic steno-occlusive lesions, and lower acute antithrombotic treatment within 48 hours (
In this retrospective analysis of a multicenter prospective cohort of AF-associated AIS patients, approximately one-tenth of the patients were managed in the ICU. The CHA2DS2-VASc score was associated with increased in-hospital mortality, whereas antithrombotic treatment within 48 h was related to low in-hospital mortality. ND and stroke progression, including brain swelling, were frequently observed in these patients. A decrease in the NIHSS score from admission to discharge was observed.
Several studies on AIS patients receiving ICU care have reported variable hospital mortality and functional outcomes [
Several clinical parameters have been associated with in-hospital mortality in patients with ICU-treated AF-associated AIS. The CHA2DS2-VASc score is a well-established risk stratification tool for stroke and thromboembolism in AF [
The lower risk of mortality in patients receiving acute antithrombotic treatment might be attributable to the preventive effect as well as selection bias. Acute antithrombotic therapy has been proven to reduce the risk of stroke recurrence and has been applied to AIS patients in current practice [
This study has several strengths. To our knowledge, this is the largest prospective AF cohort study in Asia, consisting of 14 nationwide stroke centers. This cohort represents the current clinical status and real-life practice of AF stroke management in Korea. As we collected data from a nationwide multicenter prospective cohort, we also attempted to reduce bias in the enrollment of participants. This cohort had a high outcome capture rate (3-month capture rate, 99%), on which this study could provide relatively accurate outcome information.
However, this study has several limitations. First, as decisions of ICU admission vary according to the centers’ policy in the indication, medical resources, and physicians’ opinions, the variable effect of the center or physician might be present. Detailed information on the indication for ICU admission and the time from onset to ICU admission were not available. Second, some patients with irreversible neurological damage with very severe stroke or underlying incurable progressive diseases, including malignancy, could have rejected ICU care, but resulted in in-hospital mortality and might not have been included in this study. Third, specific echocardiographic findings, such as left atrium diameter or cardiac markers, including brain natriuretic peptide or cardiac enzymes, were not included in the analysis. Further studies involving specific cardiac markers are warranted in the future.
In conclusion, ICU care is common in patients with AF-associated ischemic stroke. Initial stroke severity and CHA2DS2-VASc score increased the risk of in-hospital mortality whereas antithrombotic treatment was associated with decreased risk. To improve patient outcomes in AF-associated AIS, establishing optimal treatment strategies with upcoming high-level evidence may be required.
The study was reviewed and approved by the Institutional Review Boards of the participating centers (No. B-1705/396-306). Written informed consent was obtained from all patients.
No potential conflict of interest relevant to this article.
Conceptualization: BKK. Data curation: DYK, BKK. Formal analysis: DYK, BKK. Investigation: HGJ, CYP, JYK, BJK. Methodology: HGJ, CYP, JYK, BJK. Project administration: DYK, HJB, BKK. Resources: all authors. Software: all authors. Supervision: JK, JYK, MKH, HJB, BKK. Validation: JK. HGJ, CYP, JYK, BJK, MKH, HJB, BKK. Visualization: DYK, JK, CYP, HJB, BKK. Writing–original draft: DYK, CYP, HJB, BKK. Writing–review & editing: JK, CYP, JYK, BKK.
We would like to express our gratitude to the institutions that provided us with the opportunity to analyze the East Asian Ischemic Stroke Patients with Atrial Fibrillation Study (EAST-AF) and Clinical Research Collaboration for Stroke in Korea (CRCS-K) databases for this study.
Jun Yup Kim, MD; Jihoon Kang, MD, PhD; Beom Joon Kim, MD, PhD; Moon-Ku Han, MD, PhD; Hee-Joon Bae, MD, PhD (Seoul National University Bundang Hospital); Kang-Ho Choi, MD; Joon-Tae Kim, MD, PhD; Man-Seok Park, MD, PhD; Ki-Hyun Cho, MD, PhD (Chonnam National University Hospital); Kyu Sun Yum, MD; Dong Ick Shin, MD, PhD (Chungbuk National University Hospital); Dae-Hyun Kim, MD, PhD; Jae-Kwan Cha, MD, PhD (Dong-A University Hospital); Dong-Seok Gwak, MD; Wi-Sun Ryu, MD, PhD; Dong-Eog Kim, MD, PhD (Dongguk University Ilsan Hospital); Jong-Moo Park, MD, PhD (Uijeongbu Eulji Hospital); Yong Soo Kim, MD; Kyusik Kang, MD, PhD (Eulji General Hospital); Jae Guk Kim, MD; Soo Joo Lee, MD, PhD (Eulji University Hospital); Minwoo Lee, MD; Mi-Sun Oh, MD, PhD; Kyung-Ho Yu, MD, PhD; Byung-Chul Lee, MD, PhD (Hallym University Sacred Heart Hospital); Hong-Kyun Park, MD; Yong-Jin Cho, MD, PhD; Keun-Sik Hong, MD, PhD (Inje University Ilsan Paik Hospital); Chul-Hoo Kang, MD; Joong-Goo Kim, MD; Jay Chol Choi, MD, PhD (Jeju National University Hospital); Jang Seong Hwa, MD; Hyungjong Park, MD; Jeong-Ho Hong, MD, PhD; Sung-Il Sohn, MD, PhD (Keimyung University Dongsan Medical Center); Tai Hwan Park, MD, PhD; Sang-Soon Park, MD (Seoul Medical Center); Wook-Joo Kim, MD; Jee-Hyun Kwon, MD, PhD (Ulsan University Hospital); Kyung Bok Lee, MD, PhD (Soonchunhyang University Hospital); Kwon Doo Hyuk, MD; Jun Lee, MD, PhD (Yeungnam University Medical Center); Keon-Joo Lee, MD (Korea University Guro Hospital); Sang-Hwa Kee, MD, PhD; Chulho Kim, MD, PhD (Hallym University Chuncheon Sacred Heart Hospital); Hae-Bong Jeong, MD; Kwang Yeol Park, MD, PhD (Chung-Ang University Hospital); Ji Sung Lee, PhD (Asan Medical Center), Juneyoung Lee, PhD (Korea University)
Study population. ICU, intensive care unit.
Baseline characteristics of atrial fibrillation-associated acute ischemic stroke patients with intensive care management
Variable | Value (n=259) |
---|---|
Sex | |
Female | 128 (49.4) |
Male | 131 (50.6) |
Age (yr) | 78 (69–83) |
Onset to arrival | 87.0 (43.5–290.5) |
Vascular risk factor | |
Hypertension | 182 (70.3) |
Diabetes | 88 (34.0) |
Dyslipidemia | 72 (27.8) |
Current smoking | 36 (13.9) |
History of stroke | 56 (21.6) |
History of coronary heart disease | 42 (16.2) |
Heart failure | 35 (13.5) |
CHA2DS2-VASc score | 5.5±1.3 |
Prior antithrombotics | 112 (43.2) |
Premorbid mRS | 0 (0–1) |
Stroke information | |
Systolic BP (mmHg) | 151.3±27.9 |
Diastolic BP (mmHg) | 87.7± 19.0 |
Initial glucose (mg/dL) | 152.3±79.5 |
Initial NIHSS score | 14 (8–19) |
Symptomatic steno-occlusive lesion | 168 (64.9) |
Emergent revascularization therapy | 139 (53.7) |
Door to needle time (min) |
40.0 (27.0–53.0) |
Door to punture time (min) |
107.0 (76.0–142.5) |
Onset-to-reperfusion time (min) |
229.0 (187.5–295.0) |
Antithrombotics within 48 hours | 210 (81.1) |
Values are presented as number (%), median (interquartile range), or mean±standard deviation.
mRS, modified Rankin scale; BP, blood pressure; NIHSS, National Institutes of Health Stroke Scale.
Defined in 89 patients who underwent intravenous thrombolysis and an onset-to-arrival of <24 hours;
Defined in 99 patients who underwent endovascular treatment and an onset-to-arrival of <24 hours;
Defined in 79 patients who underwent endovascular treatment, with thrombolysis in cerebral infarction of ≥2a, and an onset-to-arrival of <24 hours.
In-hospital outcomes of atrial fibrillation-associated acute ischemic stroke patients treated in the intensive care unit
Outcome | Study population (n=259) |
---|---|
Discharge state | |
In-hospital mortality |
22 (8.5) |
Transfer to other departments | 59 (22.8) |
Discharge | 178 (68.7) |
Early neurological deterioration | 44 (17.0) |
Stroke recurrence | 6 (2.3) |
Ischemic recurrence | 5 (1.9) |
Hemorrhagic recurrence | 1 (0.4) |
Stroke progression | 27 (10.4) |
Brain swelling/IICP | 15 (5.8) |
Symptomatic hemorrhagic transformation | 6 (2.3) |
Others | 5 (1.9) |
mRS at discharge | 4 (2–5) |
Admission day | 15.4±19.0 |
Discharge NIHSS score | 6 (2–16) |
NIHSS score change | 3 (0–9) |
Values are presented as number (%), median (interquartile range), or mean±standard deviation.
IICP, increased intracranial pressure; mRS, modified Rankin scale; NIHSS, National Institute of Health Stroke Scale.
In-hospital mortality includes hopeless discharge.
Comparison of baseline characteristics and outcomes in atrial fibrillation-associated acute ischemic stroke patients treated in the intensive care unit according to in-hospital mortality
Variable | In-hospital mortality (+) (n=22) | In-hospital mortality (–) (n=237) | |
---|---|---|---|
Sex | 0.163 |
||
Female | 14 (63.6) | 114 (48.1) | |
Male | 8 (36.4) | 123 (51.9) | |
Age (yr) | 81 (76–86) | 78 (68–83) | 0.029 |
Onset to arrival | 101.0 (41.0–391.0) | 87.0 (44.0–277.0) | 0.810 |
Vascular risk factor | |||
Hypertension | 13 (59.1) | 169 (71.3) | 0.230 |
Diabetes | 11 (50.0) | 77 (32.5) | 0.097 |
Dyslipidemia | 4 (18.2) | 68 (28.7) | 0.455 |
Current smoking | 3 (13.6) | 33 (13.9) | 1.000 |
History of stroke | 4 (18.2) | 52 (21.9) | 0.793 |
History of coronary heart disease | 6 (27.3) | 36 (15.2) | 0.141 |
Heart failure | 1 (4.5) | 34 (14.3) | 0.328 |
CHA2DS2-VASc score | 6.1±1.3 | 5.4±1.3 | 0.022 |
Prior antithrombotics | 9 (47.4) | 103 (42.9) | 0.706 |
Premorbid mRS | 0 (0–2) | 0 (0–1) | 0.125 |
Stroke information | |||
Systolic BP (mmHg) | 155.5±29.8 | 150.9±27.8 | 0.462 |
Diastolic BP (mmHg) | 95.8±29.2 | 86.9±17.7 | 0.175 |
Initial glucose (mg/dL) | 170.5±62.0 | 150.6±80.8 | 0.264 |
Initial NIHSS score | 19 (14–24) | 14 (7–18) | 0.002 |
Symptomatic steno-occlusive lesion | 19 (86.4) | 149 (62.9) | 0.027 |
Emergent revascularization therapy | 10 (45.5) | 129 (54.4) | 0.419 |
Door to needle time (min)c) | 37.0 (35.0–45.5) | 40.5 (26.0–53.0) | 0.790 |
Door to punture time (min)d) | 108.0 (92.0–160.0) | 107.0 (75.0–142.0) | 0.484 |
Onset to reperfusion time (min)e) | 367.0 (269.5–423.0) | 226.0 (184.0–285.0) | 0.164 |
Antithrombotics within 48 hours | 11 (50.0) | 199 (84.0) | <0.001 |
Values are presented as number (%), median (interquartile range), or mean±standard deviation.
mRS, modified Rankin scale; BP, blood pressure; NIHSS, National Institutes of Health Stroke Scale.
Chi-square test;
Fisher’s exact test;
Defined in 89 patients who underwent intravenous thrombolysis and an onset-to-arrival of <24 hours;
Defined in 99 patients who underwent endovascular treatment and an onset-to-arrival of <24 hours;
Defined in 79 patients who underwent endovascular treatment, with thrombolysis in cerebral infarction of ≥2a, and an onset-to-arrival of <24 hours;
Indicates
Odds ratio of variables for associating in-hospital mortality in atrial fibrillation-associated acute ischemic stroke patients treated in the intensive care unit
Variable | Model | OR of variables |
OR of initial NIHSS score |
||
---|---|---|---|---|---|
OR (95% CI) | OR (95% CI) | ||||
CHA2DS2-VASc score (per 1 point increment) | Unadjusted | 1.52 (1.06–2.19) | 0.024 | ||
Adjusted with NIHSS | 1.48 (1.00–2.18) | 0.049 | 1.11 (1.04–1.18) | 0.002 | |
Symptomatic steno-occlusive lesion | Unadjusted | 3.74 (1.08–13.00) | 0.038 | ||
Adjusted with NIHSS | 2.72 (0.76–9.68) | 0.123 | 1.11 (1.04–1.18) | 0.003 | |
Antithrombotics within 48 hours | Unadjusted | 0.19 (0.08–0.47) | <0.001 | ||
Adjusted with NIHSS | 0.26 (0.10–0.67) | 0.005 | 1.10 (1.03–1.17) | 0.007 | |
Initial NIHSS score (per 1 point increment) | Unadjusted | 1.11 (1.05–1.19) | <0.001 |
OR, odds ratio; NIHSS, National Institute of Health Stroke Scale; CI, confidence interval.