論文ID: CJ-21-0937
Background: This study aimed to identify the association between long term functional outcomes and acute ischemic stroke (AIS) in patients with heart failure (HF) in Japan and whether 1-year event risks can be related to these patients.
Methods and Results: This was a prospective observational study, and 651 patients registered in the Tokyo Women’s Medical University Stroke Registry were classified into the HF and non-HF groups. Functional outcome at 1 year after stroke onset was defined as either good (modified Rankin Scale [mRS] score of 0–2) or poor (mRS score of 3–6). The primary outcome was a composite of major adverse cardiovascular events (MACE), including non-fatal stroke, non-fatal acute coronary syndrome, and vascular death. Patients with HF had a higher poor functional outcome rate at 1 year than those without HF (54.7% vs. 28.2%, P<0.001). Multivariate logistic regression analysis also demonstrated the prevalence of HF was an independent predictor of an mRS score of ≥3 at 1 year after stroke onset (odds ratio, 1.05; 95% confidence interval, 1.00–1.10; P=0.036). Furthermore, patients with HF tended to have a higher risk of MACE and all-cause mortality than those without HF.
Conclusions: AIS patients with HF were associated with poor functional outcome at the 1-year follow up. Further multicenter studies involving a larger number of patients are warranted to verify these results.
In Japan, stroke is the third leading cause of death after cancer and heart disease. Recently, stroke mortality has been declining;1 however, as a consequence, individuals are increasingly likely to live with their residual impairments, which can significantly impact their wellbeing.2 Moreover, residual impairments from stroke not only cause individual problems, but may also contribute to increased medical expenses and cause socioeconomic problems.
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In particular, chronic heart failure (HF) is widely known to affect stroke outcomes, with approximately 10–24% of all stroke patients reporting chronic HF.3 Previous studies have reported that stroke patients with HF have a 2-fold higher mortality rate than those without HF.4 Furthermore, HF is associated with a higher incidence of recurrent stroke5 and an increased risk of developing dementia, and is associated with worse short-term outcomes.6,7 Thus, these events may contribute to poor long-term outcomes in stroke patients with HF. However, few studies have reported the relationship between long-term outcomes assessed using the modified Rankin Scale (mRS) and stroke patients with HF.
This study aimed to identify the association between long-term functional outcomes and acute ischemic stroke (AIS) patients with HF in Japan and whether poor functional outcomes at 1-year follow up are evident.
The Tokyo Women’s Medical University Stroke Registry (https://upload.umin.ac.jp, UMIN000031913) is an ongoing prospective cohort study about AIS and transient ischemic attack. All patients provided written informed consent for their data to be included in our study and underwent brain magnetic resonance imaging or computed tomography scans. As such, the present cross-sectional study initially included 806 consecutive stroke patients registered between December 2013 and September 2019. After excluding 7 patients who met the exclusion criteria (e.g., those with stroke mimics as final diagnosis, or who enrolled >1 week after stroke onset), 82 patients with transient ischemic attacks, and 66 patients with a modified Rankin Scale (mRS) score ≥2 before stroke onset, a total of 651 AIS patients were included in the present analysis. All stroke cases were diagnosed by board-certified stroke neurologists based on neurological and radiological findings. Upon admission, neurological symptoms were assessed using the National Institutes of Health Stroke Scale (NIHSS) score. Patient data collected for this study were entered into a structured case report form, and included: demographic data, clinical symptoms during the qualifying event, medical history, medications, investigations (including blood tests, brain and cerebral artery imaging, and cardiac workup), management (medical treatment, revascularization procedure, and surgery), and the occurrence of clinical events after the qualifying event.
Risk FactorsPatients were diagnosed with hypertension if they had evidence of a systolic blood pressure ≥140 mmHg or a diastolic blood pressure ≥90 mmHg, or had received any antihypertensive medication. Diabetes mellitus was defined as having a fasting serum glucose level ≥126 mg/dL, a serum glucose level ≥200 mg/dL on 2 random measurements, or a glycated hemoglobin level ≥6.5%, or having received antidiabetic therapy (oral hypoglycemic agents or insulin). Dyslipidemia was diagnosed if the patient had a low-density lipoprotein cholesterol ≥140 mg/dL, had a total cholesterol ≥220 mg/dL, or had been treated with lipid-lowering agents. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula with the Japanese coefficient, and chronic kidney disease was defined as having an estimated glomerular filtration rate <60 mL/min/1.73 m2. Smoking status was defined on the basis of current use. Intracranial arterial stenosis ≥50% on magnetic resonance angiography, 3-dimensional computed tomography angiography, or digital subtraction angiography was considered a significant finding. Carotid artery ultrasonography findings were evaluated by trained neurologists, in which a stenosis ≥50% was defined as significant extracranial arterial stenosis.
Ischemic Stroke SubtypeIschemic stroke etiologies were classified into large artery atherosclerosis (LAA), cardioembolism (CE), small-vessel disease, other determined causes, and undetermined causes, according to the Trial of Org 10172 in Acute Stroke Treatment classification.8 Strokes of undetermined causes were further divided into embolic stroke of undetermined source, stroke with coexisting etiologies, and incomplete investigations. Furthermore, embolic stroke of undetermined source was diagnosed based on the criteria proposed by the Cryptogenic Stroke/ESUS International Working Group (i.e., non-lacunar stroke detected by brain computed tomography scans or magnetic resonance imaging, absence of extracranial or intracranial atherosclerosis in a finding of ≥50% luminal stenosis in the arteries supplying the ischemic area, no major-risk cardioembolic source of embolism or no other specific cause of stroke identified).9
Follow up and OutcomesFor follow-up visits, patients visited our center after 3 months, and thereafter, every year for 3 years after enrollment. As this study aimed to report the 1-year outcomes, findings from physical examinations, treatments, occurrences of clinical events, and mRS scores, were all recorded at each follow-up visit. If the patient could not be reached for follow up, a relative or caregiver was interviewed via telephone. The primary outcome of the study was a composite of major cardiovascular events (MACE), including non-fatal stroke (ischemic or hemorrhagic), non-fatal acute coronary syndrome, major peripheral artery disease, and vascular death. Specifically, vascular death was defined as fatal acute coronary artery disease, fatal stroke, and other causes of cardiovascular death. Meanwhile, secondary outcomes included recurrent ischemic stroke and all-cause mortality. Stroke-related functional outcomes were assessed using the mRS score at 1 year, and a poor functional outcome was characterized by an mRS score ≥3.
Definition of HFIn this study, the definition of pre-existing HF was having one of the following at enrollment: (1) a history of hospitalization for HF prior to enrollment; (2) heart disease-associated symptomatic HF (New York Heart Association class ≥2); or (3) LV dysfunction (ejection fraction <40%). History of hospitalization for HF was assessed by reviewing patient medical records. The New York Heart Association class was assessed by each attending physician based on their interpretation of the patient’s reported symptoms, medical history, and results from clinical tests on cardiac structure and function.
Statistical AnalysisThe statistical significance of the intergroup differences was assessed using the chi-squared test for categorical variables and the Student’s t-test or Mann-Whitney U-test for continuous variables. To identify poor functional outcome, we performed a multiple logistic regression analysis based on a forward stepwise method, with adjustments for age, sex, and the following other variables (P value <0.20) in univariate analysis: HF, hypertension, chronic kidney disease, coronary artery disease, atrial fibrillation, peripheral vascular disease, d-dimer, oral hypoglycemic agents or insulin use, and NIHSS. For all analyses, corresponding odds ratios and 95% confidence intervals were calculated, and a P value <0.05 was considered to be statistically significant. Event rates were estimated using the Kaplan-Meier method, and intergroup differences were assessed using the log-rank test. Cox proportional hazard regression models were also used to calculate age- and sex-adjusted hazard ratios with corresponding 95% CIs for the comparison of patients with and without HF. In addition, we further divided the patients based on the presence of CE and subsequently performed a subgroup analysis. The data of patients with no information at 1 year were censored at the time of the last available follow up. For a given outcome, the patients who died of causes other than the outcome had their data censored at the time of death. Events that occurred after 1 year of follow up were also excluded from the current analysis.
EthicsThe present study conformed to the ethical guidelines of the 1975 Declaration of Helsinki, which is in line with the Ethical Guidelines for Epidemiological Research by the Japanese government, and was approved by the ethics committee of the Tokyo Women’s Medical University Hospital (approval number: 2955-R2).
A comparison of patient characteristics between the HF and non-HF groups is shown in Table 1. The median NIHSS score (4 [interquartile range, 2–9] vs. 2 [interquartile range, 1–4], respectively; P<0.001) was higher in the HF group than in the non-HF group. Patients in the HF group more often presented with chronic kidney disease, coronary artery disease, atrial fibrillation, and peripheral vascular disease. The use of medical agents and antiplatelet agents was more frequently reported in the non-HF group than in the HF group, whereas anticoagulant agents were more frequently used in the HF group than in the non-HF group. Moreover, statins, calcium channel blockers, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers were more frequently used in patients with HF than in those without HF. Regarding stroke subtypes, CE was more frequent in patients with HF than in those without HF, whereas LAA and undetermined stroke were more frequent in patients with non-HF than in those with HF.
| Total (N=651) |
HF (N=94) |
Non-HF (N=557) |
P value | |
|---|---|---|---|---|
| Age, mean±SD | 70.4±13.3 | 72.9±13.7 | 69.8±13.2 | 0.022 |
| Males, n (%) | 394 (60.5) | 56 (59.6) | 338 (60.7) | 0.868 |
| Current smoking, n (%) | 120 (18.4) | 12 (12.8) | 108 (19.4) | 0.128 |
| Alcohol, n (%) | 43 (6.6) | 3 (3.1) | 40 (7.2) | 0.148 |
| Medical history, n (%) | ||||
| Hypertension | 485 (74.5) | 75 (79.8) | 410 (73.6) | 0.149 |
| Diabetes mellitus | 251 (38.6) | 42 (44.7) | 209 (37.5) | 0.192 |
| Hyperlipidemia | 308 (47.3) | 49 (52.1) | 259 (46.5) | 0.312 |
| Chronic kidney disease | 182 (27.9) | 53 (56.4) | 129 (23.2) | <0.001 |
| Coronary artery disease | 89 (13.7) | 35 (37.2) | 54 (9.7) | <0.001 |
| Atrial fibrillation | 145 (22.3) | 52 (55.3) | 93 (16.7) | <0.001 |
| Peripheral vascular disease | 36 (5.5) | 12 (12.8) | 24 (4.3) | 0.009 |
| Previous stroke | 113 (17.4) | 96 (17.2) | 17 (18.1) | 0.84 |
| Medications, n (%) | ||||
| Antiplatelet therapy | 194 (29.8) | 37 (39.4) | 157 (28.2) | 0.057 |
| Anticoagulant therapy | 89 (13.7) | 38 (40.4) | 51 (9.2) | <0.001 |
| Antiplatelet and anticoagulant combined therapy | 16 (2.5) | 6 (6.4) | 10 (1.8) | 0.024 |
| Antihypertension therapy | 408 (62.7) | 80 (85.1) | 328 (58.9) | <0.001 |
| β-blocker | 118 (18.1) | 32 (34.0) | 86 (15.4) | 0.323 |
| Calcium channel blocker | 266 (40.9) | 51 (54.3) | 215 (38.6) | 0.003 |
| ARB/ACEI | 268 (41.2) | 52 (55.3) | 216 (38.8) | 0.004 |
| Diuretic | 96 (14.7) | 10 (10.6) | 86 (15.4) | 0.001 |
| Hyperlipidemia therapy | 197 (30.3) | 41 (43.6) | 156 (28.0) | <0.004 |
| Statin | 188 (28.9) | 41(43.6) | 147 (26.4) | 0.001 |
| Oral hypoglycemic agent or insulin use | 187 (28.7) | 34 (36.2) | 153 (27.5) | 0.121 |
| NIHSS on admission, median (IQR) | 3 (1–5) | 4 (2–9) | 2 (1–4) | <0.001 |
| Stroke subtypes, n (%) | ||||
| Small-vessel occlusion | 149 (22.9) | 7 (7.4) | 142 (25.5) | 0.068 |
| Cardioembolism | 167 (25.7) | 62 (70) | 105 (18.9) | <0.001 |
| Large-artery atherosclerosis | 132 (20.3) | 12 (12.8) | 120 (22) | <0.001 |
| Undetermined | 167 (25.7) | 11 (11.7) | 156 (28) | 0.001 |
| Other | 36 (5.5) | 2 (2.1) | 34 (6.1) | 0.105 |
| Laboratory data | ||||
| D-dimer, μg/mL, median (IQR) | 0.9 (0.5–1.9) | 0.8 (0.5–1.5) | 1.9 (0.8–3.9) | <0.001 |
| BNP, pg/mL, median (IQR) | 60.8 (25.4–174.9) | 50.6 (23.0–130.0) | 280.3 (103.8–611.0) | <0.001 |
| LDL-c, mg/dL, mean±SD | 116.5±37.1 | 118.4±36.9 | 117.7±37.5 | 0.0023 |
| HDL-c, mg/dL, mean±SD | 50±22 | 55.9±17.7 | 51.9±16.8 | 0.050 |
| Triglycerides, mg/dL, mean±SD | 131.4±95.4 | 132.5±94.0 | 125.1±104.1 | 0.49 |
ARB, angiotensin II receptor blocker; ACEI, angiotensin-converting enzyme inhibitor; BNP, B-type natriuretic peptide; HDL-c, high-density lipoprotein cholesterol; HF, heart failure; IQR, interquartile range; LDL-c, low-density lipoprotein cholesterol; NIHSS, National Institute of Health Stroke Scale; SD, standard deviation.
A comparison of patients with and an mRS ≥3 and <3 at 1 year is shown in Table 2. On comparison, patients with an mRS ≥3 were older; had higher B-type natriuretic peptide levels, D-dimer levels, and NIHSS scores on admission; had a higher incidence of hypertension, chronic kidney disease, coronary artery disease, atrial fibrillation, peripheral vascular disease, and previous stroke; and tended to use medications (antithrombotic therapy, antihypertensive therapy, oral hypoglycemic agents, or insulin use), as compared to those with an mRS <3. Figure 1 shows the distribution of the mRS scores at the 1-year follow up. Patients with HF were also found to have a increased poor functional outcome rate at 1 year than those without HF (54.7% vs. 28.2%, P<0.001). Furthermore, multivariate logistic regression analysis (Table 3) found that the prevalence of HF was an independent predictor of an mRS score ≥3 at 1 year after stroke onset (odds ratio, 1.05; 95% confidence interval, 1.00–1.10; P=0.036).
| Total (N=634) |
mRS <3 (N=436) |
mRS ≥3 (N=198) |
P value | |
|---|---|---|---|---|
| Age, mean±SD | 70.2±12.6 | 67.6±12.9 | 75.7±12.1 | <0.001 |
| Males, n (%) | 385 (60.7) | 273 (62.6) | 112 (56.6) | 0.13 |
| Current smoking, n (%) | 118 18.6 | 89 (20.4) | 29 (14.6) | 0.075 |
| Alcohol, n (%) | 41 (6.5) | 33 (7.6) | 8 (4.0) | 0.079 |
| Medical history, n (%) | ||||
| Hypertension | 472 (74.4) | 314 (72.0) | 158 (80.0) | 0.040 |
| Diabetes mellitus | 247 (56.7) | 159 (36.4) | 88 (44.4) | 0.060 |
| Hyperlipidemia | 298 (47.0) | 212 (48.6) | 86 (43.4) | 0.22 |
| Chronic kidney disease | 177 (27.9) | 108 (24.8) | 69 (34.8) | 0.010 |
| Coronary artery disease | 87 (13.7) | 43 (9.9) | 44 (22.2) | <0.001 |
| Atrial fibrillation | 140 (22.1) | 78 (17.9) | 62 (31.3) | <0.001 |
| Peripheral vascular disease | 35 (5.5) | 13 (3.0) | 22 (11.1) | <0.001 |
| Previous stroke | 110 (17.4) | 64 (14.7) | 46 (23.2) | 0.010 |
| Medications, n (%) | ||||
| Antithrombotic therapy | 254 (40.1) | 158 (36.2) | 96 (49.2) | 0.002 |
| Antihypertensive therapy | 397 (62.6) | 252 (57.8) | 145 (73.2) | <0.001 |
| Statin use | 192 (30.3) | 130 (29.8) | 62 (31.3) | 0.67 |
| Oral hypoglycemic agent or insulin use | 184 (29.0) | 113 (26.0) | 71 (35.9) | 0.011 |
| Stroke subtypes, n (%) | ||||
| Small-vessel occlusion | 143 (22.6) | 116 (27.0) | 27 (13.2) | 0.001 |
| Cardioembolic | 162 (25.6) | 93 (21.6) | 69 (33.8) | 0.001 |
| Large-artery atherosclerosis | 129 (20.3) | 90 (20.9) | 39 (19.1) | 0.626 |
| Undetermined | 164 (25.9) | 114 (26.5) | 50 (24.5) | 0.811 |
| Other | 36 (5.7) | 17 (4.0) | 19 (9.3) | 0.033 |
| Laboratory data | ||||
| D-dimer, μg/mL, median (IQR) | 0.9 (0.5–1.9) | 0.7 (0.5–1.2) | 1.6 (0.8–4.1) | <0.001 |
| BNP, pg/mL, median (IQR) | 60.8 (25.4–174.9) | 49.3 (23.0–120.0) | 115.0 (44.3–291.3) | 0.018 |
| LDL-c, mg/dL, mean±SD | 111±41 | 117±37.0 | 117.7±37.5 | 0.26 |
| HDL-c, mg/dL, mean±SD | 50±22 | 56.1±17.6 | 53.5±17.7 | 0.09 |
| Triglycerides, mg/dL, mean±SD | 139±64 | 134.8±100.1 | 123.8±82.4 | 0.17 |
| NIHSS on admission, median (IQR) | 4 (1–5) | 3 (1–5) | 6 (3–10) | <0.001 |
Abbreviations as in Table 1.
Distributions of the mRS scores at 1-year follow up in patients with HF or with non-HF. HF, heart failure; mRS, modified Rankin Scale.
| Variables | OR | 95% CI | P value |
|---|---|---|---|
| Age | 1.01 | 1.00–1.01 | <0.001 |
| Heart failure | 1.05 | 1.00–1.10 | 0.036 |
| NIHSS on admission | 1.03 | 1.02–1.04 | <0.001 |
| D-dimer | 1.01 | 1.00–1.02 | 0.001 |
CI, confidence interval; NIHSS, National Institute of Health Stroke Scale; OR, odds ratio.
Among the 651 patients, 73 had at least one vascular event within1 year, resulting in an event rate of 11.2% (95% confidence interval, 11.1–21.1%). As shown in Figure 2 and Table 4, Kaplan-Meier survival analysis revealed that patients in the HF group tended to have a higher risk of MACE and all-cause mortality, although the differences were not statistically significant. Meanwhile, no differences were observed in the risk of recurrent ischemic stroke between patients in the HF and non-HF groups. Regarding the comparison of stroke subtype, Kaplan-Meier survival analysis revealed that there was no difference in the risk of MACE between CE patients with and without HF, whereas non-CE patients with HF had a higher risk of MACE than those without HF (Figure 3). The multivariable Cox proportional hazards regression model further showed that non-CE patients with HF had a significantly higher risk of MACE than those without HF (Table 5).
Kaplan-Meier curves for major cardiovascular events for the HF and non-HF groups. HF, heart failure.
| Event rate, n (%) | Log rank P value |
Adjusted HR (95% CI) |
P value | ||
|---|---|---|---|---|---|
| Non-HF (N=557) | HF (N=94) | ||||
| Primary outcome | |||||
| Major cardiovascular events | 58 (10.4) | 15 (15.6) | 0.110 | 1.59 (0.90–2.81) | 0.109 |
| Secondary outcome | |||||
| Ischemic stroke | 43 (7.7) | 8 (8.5) | 0.712 | 1.16 (0.54–2.46) | 0.705 |
| All cause death | 30 (5.4) | 10 (10.6) | 0.0438 | 1.97 (0.96–4.04) | 0.065 |
CI, confidence interval; HF, heart failure; HR, hazard ratio.
Kaplan-Meier curves for major cardiovascular event risks at 1-year for the HF and non-HF groups. (A) Patients with cardioembolism. (B) Patients with non-cardioembolism. HF, heart failure.
| Event rate, n (%/year) | Log rank P value |
Adjusted HR (95% CI) |
P value | ||
|---|---|---|---|---|---|
| Non-HF | HF | ||||
| Cardioembolism | (N=99) | (N=60) | |||
| Primary outcome | |||||
| Major cardiovascular events | 9 (9.1) | 6 (10.0) | 0.84 | 1.15 (0.41–3.23) | 0.80 |
| Secondary outcome | |||||
| Recurrent ischemic stroke | 7 (7.1) | 4 (6.7) | 0.94 | 1.01 (0.29–3.44) | 0.99 |
| All-cause death | 6 (6.1) | 7 (11.7) | 0.21 | 1.60 (0.52–4.84) | 0.40 |
| Non-cardioembolism | (N=458) | (N=34) | |||
| Primary outcome | |||||
| Major cardiovascular events | 49 (10.7) | 9 (26.5) | 0.008 | 2.52 (1.23–5.18) | 0.012 |
| Secondary outcome | |||||
| Recurrent ischemic stroke | 36 (7.9) | 4 (11.8) | 0.41 | 1.40 (0.50–3.97) | 0.52 |
| All-cause death | 24 (5.2) | 3 (8.8) | 0.35 | 1.64 (0.49–5.51) | 0.42 |
CI, confidence interval; HF, heart failure; HR, hazard ratio.
The present study demonstrated that HF was independently associated with poor functional outcome after ischemic stroke onset. Although the 1-year risk of MACE and all-cause mortality in stroke patients with HF tended to be higher than that in those without HF, the results were not significant, indicating an inconsistency with previous studies. However, in the stroke subgroup analysis of 1-year event risk, non-CE patients with HF had a higher risk of MACE than those without HF. To the best of our knowledge, previous studies have reported the relationship between various event risks and patients with HF, but few studies have demonstrated the relationship between HF and long-term functional outcomes in patients who have suffered an ischemic stroke.
In recent years, with the decline of stroke mortality rate, patients with post-stroke disabilities have increased. Therefore, predicting the degree of residual disability and the expected improvement in activities of daily living at an early stage is very important in long-term planning. In other words, it is more valuable to assess long-term functional outcomes than analyzing a diverse event that may not reflect the actual burden of disease in terms of impaired quality of life. Furthermore, defining disability is useful in clinical trials and is particularly informative for policymakers, given the huge medical expenses for disabilities in current societies.10 In contrast, assessing the occurrence of diverse events cannot be discounted entirely, because these events may require more frequent hospitalization. In addition, the hazards of bed rest during hospitalization have been well established, including immobility, accelerated bone loss, dehydration, malnutrition, delirium, sensory deprivation, isolation, shearing forces on the skin, and incontinence, all of which may be risk factors for declining physical function in the future.11,12
Several mechanisms are thought to underlie the poor functional outcomes of ischemic stroke in patients with HF. First, frailty commonly coexists with HF, as both conditions share predisposing pathophysiological abnormalities, including high comorbidity burden, aging, and hospitalizations, which all contribute to accelerated functional decline and sarcopenia. In fact, a study has reported that when presented together, frailty and HF were associated with worse clinical outcomes.13 Second, a previous study reported that the most common clinical presentations for AIS patients with HF were aphasia, visual field defects, and weakness,14 and these symptoms may directly affect subsequent activities of daily living. Third, chronic HF has been reported to adversely affect the physiological homeostasis of various organ systems in stroke patients, resulting in arterial and venous hemodynamic disturbances, worsening of cerebral tissue oxygenation, endothelial dysfunction, and proinflammatory and prothrombotic responses.15–18 Moreover, these deleterious effects may cause subsequent vascular events that may affect long-term functional outcomes. Our study also identified that non-CE patients with HF had a higher risk of MACE than those without HF. Additionally, HF in patients may be associated with underlying causes, including atherosclerotic coronary disease, hypertensive disease, and valvular disease, which are all related to a higher atherosclerotic burden19 and endothelial dysfunction.20 Regarding stroke subtypes, LAA patients with HF were more likely to have polyvascular disease (the presence of atherosclerosis in ≥2 arterial beds) than CE patients with HF. Previous studies also reported that the existence of polyvascular disease conferred a heightened risk of ischemic events.21,22 Therefore, non-CE patients including those with LAA and HF had a higher risk of MACE than those without HF.
Despite the findings of this study, certain limitations were noted. First, this study did not classify HF into 3 groups based on the percentage of the ejection fraction: HF with reduced ejection fraction, HF with preserved ejection fraction, and HF with mid-range ejection fraction.23 Second, this study was about the validity of the diagnosis of HF. Patients with undiagnosed HF may be missed because they do not undergo an extensive evaluation to diagnose HF. In contrast, most patients were diagnosed with HF by cardiologists; therefore, the positive predictive value of HF diagnosis was presumed to be high. Third, in logistic regression analysis, 11 patients were excluded because of missing d-dimer data. The exclusion of the data may affect the results. Fourth, this study adopted a relatively low number of adverse outcomes to investigate, which may be the reason for the differences with previous studies reporting a relationship between HF and recurrent ischemic stroke and all-cause mortality. Finally, this study was conducted in a single-center setting, and thus, further studies are needed to establish global applicability.
AIS patients with HF were associated with poor functional outcome at 1-year follow up. Moreover, non-CE patients with HF had a higher risk of 1-year MACE than those without HF. Further multicenter studies involving a larger number of patients are warranted to verify our results.
None.
K.K. reports lecture fees from Daiichi Sankyo, Kyowa Kirin, Bayer Inc., Sanofi, Nippon Boehringer Ingelheim, Takeda Pharmaceutical, Sumitomo Dainippon Pharma and Astellas Pharma, and research fundings from Daiichi Sankyo, Kyowa Kirin, Bayer Inc., Sanofi, Nippon Boehringer Ingelheim, Takeda Pharmaceutical, and Sumitomo Dainippon Pharma.
This study received no specific funding.
This study was approved by the ethics committee of the Tokyo Women’s Medical University Hospital (approval number: 2955-R2).
Deidentified participant data will not be shared.
