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*Only for medical professionals' reference In clinical practice, about one-third of ischemic strokes have undergone standard evaluation, and the exact cause cannot be found.
In 2014, researchers called this type of strokes embolic strokes of undetermined source (ESUS).
.
So, what diagnosis and treatment strategies should clinicians adopt in the face of ESUS patients? At the 24th National Neurology Academic Conference of the Chinese Medical Association, Professor Chen Huisheng from the Department of Neurology, General Hospital of the Northern Theater Command gave a wonderful report on "Diagnosis and Treatment Strategies for Unexplained Embolic Stroke"! Figure 1: Professor Chen Huisheng's report on the ESUS concept background Professor Chen Huisheng introduced that the central theory of the ESUS concept is that most cryptogenic strokes are embolism
.
Hart et al.
reported that the origin of emboli mainly includes various heart abnormalities, venous thrombosis passing through the open foramen ovale, and non-stenotic atherosclerosis
.
Two previous important studies, NAVIGATE ESUS and RE-SPECT ESUS trials, did not find that anticoagulation versus antiplatelet therapy can reduce the recurrence of ESUS stroke.
The reason may be that ESUS has not been further clinically divided
.
We should pay attention to the diagnosis and treatment of ESUS from two aspects: cardiogenic and arterial
.
Source of ESUS emboli: cardiogenic Professor Chen Huisheng introduced that cardiogenic factors mainly include 4 types, namely cryptogenic atrial fibrillation, atrial heart disease, undiagnosed myocardial infarction, and patent foramen ovale
.
Various factors have their own mechanisms, and there are also some unresolved problems in clinical practice
.
1.
Cryptogenic atrial fibrillation: The cryptogenic mechanism of ESUS is mainly considered to be subclinical atrial fibrillation.
These studies have shown that prolonged heart rhythm monitoring can detect 10%-20% of recent stroke patients with atrial fibrillation, and this The proportion increases with the extension of monitoring time, and the detection rate after 3 years of continuous monitoring is close to 30%
.
Clinical problems: The detection rate of atrial fibrillation is still low.
During the 3-year follow-up, 70% of patients failed to detect atrial fibrillation.
What is the cause of such a large proportion? Whether atrial fibrillation detected after ESUS is the cause of stroke is unclear
.
Will subclinical atrial fibrillation that last a few minutes in the clinic increase the risk of stroke a few months later? 2.
Atrial heart disease: atrial matrix abnormalities, such as atrial heart disease, atrial cardiomyopathy, atrial myopathy, even before atrial fibrillation, are the source of thromboembolism
.
The results of multiple studies suggest that there is a connection between left atrial dysfunction and ischemic stroke without atrial fibrillation.
Atrial heart disease is the closest to embolic stroke
.
For patients without atrial fibrillation, although anticoagulation therapy has not been proven to be superior to antiplatelet therapy, post-event analysis found that the P wave terminal potential (PTFV1) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in lead V1 increased.
Certain people with high or enlarged atria can benefit from anticoagulation
.
These findings suggest that atrial heart disease without atrial fibrillation may be a possible mechanism of ESUS, and anticoagulation therapy for this type of ESUS patients may be better than standard antiplatelet therapy
.
3.
Undiagnosed myocardial infarction In addition to unrecognized atrial abnormalities, intraventricular tissue disorders are also the cause of thromboembolism
.
Undiagnosed myocardial infarction can also cause myocardial scarring, which can induce thrombosis and subsequent cardiogenic embolism, leading to ischemic stroke
.
This type of heart disease requires anticoagulation therapy.
The COMPASS study found that for patients with clinically demonstrated coronary heart disease, anticoagulation therapy can reduce ischemic stroke more effectively than antiplatelet therapy alone
.
4.
Patent foramen ovale (PFO) A meta-analysis that included 5 randomized clinical trials showed that percutaneous PFO closure can reduce stroke recurrence in young patients with cryptogenic stroke and PFO
.
The pooled analysis of several randomized clinical trials supports the protective effect of anticoagulant therapy on patients with cryptogenic stroke and PFO, although the recently published RE-SPECT ESUS trial did not find the benefit of PFO patients
.
It is necessary to further explore the effect of anticoagulation therapy on special subgroups of patients, such as young patients with larger PFO
.
Source of ESUS emboli: Arterial non-stenotic large atherosclerosis mainly includes: atherosclerosis of the aortic arch, carotid artery, intracranial artery and other parts
.
The neutral results of NAVIGATE ESUS and RE-SPECT ESUS suggest that the effectiveness of anticoagulant therapy may be offset by other mechanisms in the ESUS population, the most important of which is high-risk, non-stenotic arteriosclerosis
.
Professor Chen Huisheng introduced that a large number of studies have focused on the carotid artery.
Many studies have found that the probability of non-stenotic atherosclerotic plaque on the ipsilateral side of cryptogenic cerebral infarction is higher than that on the opposite side
.
A meta-analysis, pooling 8 studies in 323 patients with unilateral anterior circulation ESUS stroke (assessed by MRA, CTA or ultrasound), found that the risk of developing high-risk carotid plaques on the same side of ESUS was 5.
5 times that of the contralateral side
.
The subgroup analysis of the NAVIGATE ESUS trial shows that there are indeed differences in the treatment effect: 1.
Patients with a left atrium diameter of more than 4.
6 cm (about 10%) can benefit from rivaroxaban; 2.
In intracranial non-stenotic arteriosclerosis Among the subgroups, the annual stroke recurrence of the rivaroxaban group vs.
aspirin group was 5.
8% vs.
3.
7%, no statistical difference, but the cross-analysis indicated that the antiplatelet therapy had a certain benefit trend; 3.
In the carotid atherosclerosis subgroup, both No difference between anticoagulation and antiplatelet therapy was found
.
This result may be limited by the timing of anticoagulation therapy, different treatments, and lack of intracranial imaging
.
Overlap of potential low-risk causes (PES) Professor Chen Huisheng said that the mechanisms of stroke are not isolated.
Many risk factors are shared.
Risk factors may coexist more than accidentally.
The coexistence mechanisms that cause thromboembolism have mutually promoting effects.
The existence of multiple PES may explain the failure of current clinical studies and the neutral results of the carotid artery subgroup of NAVIGAE ESUS
.
Figure 2: Research by Ntaios et al.
Figure 3: Research by Kamel et al.
Based on the exploratory analysis of NAVIGATE ESUS data, Ntaios et al.
found that 41% of ESUS populations have multiple PES, 15% of the population ≥ 3 PES, but Kamel et al.
found that 2.
4% of them also exist 2 Kind of PES (left atrium dilation ≥4.
7cm and ipsilateral neck plaque)
.
This contradictory result is probably due to the different number of PES types set in the two studies
.
In the Ntaios study, PES included 7 types (atrial heart disease, atrial fibrillation, arteriosclerosis, left ventricular dysfunction, valvular disease, PFO, and tumor), while Kamel's PES only included left atrial dilation ≥4.
7 cm or ipsilateral cervical plaques Block
.
Anti-board combined anticoagulation therapy-the second analysis of COMPASS research Professor Chen Huisheng introduced that the second analysis of COMPASS research aims to analyze the effect of anti-board combined anticoagulation therapy
.
The purpose of the COMPASS study: To analyze the correlation between low-dose rivaroxaban with or without aspirin and the occurrence of different types of ischemic stroke
.
The results of the COMPASS study suggest that for patients with systemic atherosclerosis, low-dose rivaroxaban plus aspirin can reduce the incidence of cardiogenic stroke and embolic stroke of unknown cause, but further verification is needed
.
Figure 4: Results of the second analysis of the COMPASS study.
Other important ongoing studies by ESUS.
ATTICUS trial: It evaluated the efficacy of anticoagulation therapy on ESUS patients with various cardiac abnormalities, including left atrial enlargement, PFO, or high-risk atrial fibrillation
.
ARCADIA trial (NCTO3192219): To evaluate the difference between anticoagulation vs.
antiplatelet in the ESUS population with atrial heart disease
.
NOAH and ARTESIA trial: compared the efficacy of anticoagulation vs.
antiplatelet in patients with subclinical atrial fibrillation
.
Summary: The article published by Hart et al.
in 2014 outlined a more simplified definition of ESUS.
Although it is still unable to guide treatment, it is still a practical diagnostic tool.
This function is more conducive to adopting more effective and precise treatment strategies to prevent stroke
.
ESUS treatment decision-making focuses on screening of potential causes and individualized evaluation, especially for the two most important causes of cardiac and arterial factors, and technical means are required.
Before this goal is achieved, there is still a lot of work to be done.
do
.
The neutral results of NAVIGATE-ESUS and RE SPECT-ESUS suggest that: on the one hand, the etiology of ESUS is heterogeneous (cardiogenic vs.
arterial); on the other hand, cardiogenic factors are not dominant
.
In 2014, researchers called this type of strokes embolic strokes of undetermined source (ESUS).
.
So, what diagnosis and treatment strategies should clinicians adopt in the face of ESUS patients? At the 24th National Neurology Academic Conference of the Chinese Medical Association, Professor Chen Huisheng from the Department of Neurology, General Hospital of the Northern Theater Command gave a wonderful report on "Diagnosis and Treatment Strategies for Unexplained Embolic Stroke"! Figure 1: Professor Chen Huisheng's report on the ESUS concept background Professor Chen Huisheng introduced that the central theory of the ESUS concept is that most cryptogenic strokes are embolism
.
Hart et al.
reported that the origin of emboli mainly includes various heart abnormalities, venous thrombosis passing through the open foramen ovale, and non-stenotic atherosclerosis
.
Two previous important studies, NAVIGATE ESUS and RE-SPECT ESUS trials, did not find that anticoagulation versus antiplatelet therapy can reduce the recurrence of ESUS stroke.
The reason may be that ESUS has not been further clinically divided
.
We should pay attention to the diagnosis and treatment of ESUS from two aspects: cardiogenic and arterial
.
Source of ESUS emboli: cardiogenic Professor Chen Huisheng introduced that cardiogenic factors mainly include 4 types, namely cryptogenic atrial fibrillation, atrial heart disease, undiagnosed myocardial infarction, and patent foramen ovale
.
Various factors have their own mechanisms, and there are also some unresolved problems in clinical practice
.
1.
Cryptogenic atrial fibrillation: The cryptogenic mechanism of ESUS is mainly considered to be subclinical atrial fibrillation.
These studies have shown that prolonged heart rhythm monitoring can detect 10%-20% of recent stroke patients with atrial fibrillation, and this The proportion increases with the extension of monitoring time, and the detection rate after 3 years of continuous monitoring is close to 30%
.
Clinical problems: The detection rate of atrial fibrillation is still low.
During the 3-year follow-up, 70% of patients failed to detect atrial fibrillation.
What is the cause of such a large proportion? Whether atrial fibrillation detected after ESUS is the cause of stroke is unclear
.
Will subclinical atrial fibrillation that last a few minutes in the clinic increase the risk of stroke a few months later? 2.
Atrial heart disease: atrial matrix abnormalities, such as atrial heart disease, atrial cardiomyopathy, atrial myopathy, even before atrial fibrillation, are the source of thromboembolism
.
The results of multiple studies suggest that there is a connection between left atrial dysfunction and ischemic stroke without atrial fibrillation.
Atrial heart disease is the closest to embolic stroke
.
For patients without atrial fibrillation, although anticoagulation therapy has not been proven to be superior to antiplatelet therapy, post-event analysis found that the P wave terminal potential (PTFV1) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in lead V1 increased.
Certain people with high or enlarged atria can benefit from anticoagulation
.
These findings suggest that atrial heart disease without atrial fibrillation may be a possible mechanism of ESUS, and anticoagulation therapy for this type of ESUS patients may be better than standard antiplatelet therapy
.
3.
Undiagnosed myocardial infarction In addition to unrecognized atrial abnormalities, intraventricular tissue disorders are also the cause of thromboembolism
.
Undiagnosed myocardial infarction can also cause myocardial scarring, which can induce thrombosis and subsequent cardiogenic embolism, leading to ischemic stroke
.
This type of heart disease requires anticoagulation therapy.
The COMPASS study found that for patients with clinically demonstrated coronary heart disease, anticoagulation therapy can reduce ischemic stroke more effectively than antiplatelet therapy alone
.
4.
Patent foramen ovale (PFO) A meta-analysis that included 5 randomized clinical trials showed that percutaneous PFO closure can reduce stroke recurrence in young patients with cryptogenic stroke and PFO
.
The pooled analysis of several randomized clinical trials supports the protective effect of anticoagulant therapy on patients with cryptogenic stroke and PFO, although the recently published RE-SPECT ESUS trial did not find the benefit of PFO patients
.
It is necessary to further explore the effect of anticoagulation therapy on special subgroups of patients, such as young patients with larger PFO
.
Source of ESUS emboli: Arterial non-stenotic large atherosclerosis mainly includes: atherosclerosis of the aortic arch, carotid artery, intracranial artery and other parts
.
The neutral results of NAVIGATE ESUS and RE-SPECT ESUS suggest that the effectiveness of anticoagulant therapy may be offset by other mechanisms in the ESUS population, the most important of which is high-risk, non-stenotic arteriosclerosis
.
Professor Chen Huisheng introduced that a large number of studies have focused on the carotid artery.
Many studies have found that the probability of non-stenotic atherosclerotic plaque on the ipsilateral side of cryptogenic cerebral infarction is higher than that on the opposite side
.
A meta-analysis, pooling 8 studies in 323 patients with unilateral anterior circulation ESUS stroke (assessed by MRA, CTA or ultrasound), found that the risk of developing high-risk carotid plaques on the same side of ESUS was 5.
5 times that of the contralateral side
.
The subgroup analysis of the NAVIGATE ESUS trial shows that there are indeed differences in the treatment effect: 1.
Patients with a left atrium diameter of more than 4.
6 cm (about 10%) can benefit from rivaroxaban; 2.
In intracranial non-stenotic arteriosclerosis Among the subgroups, the annual stroke recurrence of the rivaroxaban group vs.
aspirin group was 5.
8% vs.
3.
7%, no statistical difference, but the cross-analysis indicated that the antiplatelet therapy had a certain benefit trend; 3.
In the carotid atherosclerosis subgroup, both No difference between anticoagulation and antiplatelet therapy was found
.
This result may be limited by the timing of anticoagulation therapy, different treatments, and lack of intracranial imaging
.
Overlap of potential low-risk causes (PES) Professor Chen Huisheng said that the mechanisms of stroke are not isolated.
Many risk factors are shared.
Risk factors may coexist more than accidentally.
The coexistence mechanisms that cause thromboembolism have mutually promoting effects.
The existence of multiple PES may explain the failure of current clinical studies and the neutral results of the carotid artery subgroup of NAVIGAE ESUS
.
Figure 2: Research by Ntaios et al.
Figure 3: Research by Kamel et al.
Based on the exploratory analysis of NAVIGATE ESUS data, Ntaios et al.
found that 41% of ESUS populations have multiple PES, 15% of the population ≥ 3 PES, but Kamel et al.
found that 2.
4% of them also exist 2 Kind of PES (left atrium dilation ≥4.
7cm and ipsilateral neck plaque)
.
This contradictory result is probably due to the different number of PES types set in the two studies
.
In the Ntaios study, PES included 7 types (atrial heart disease, atrial fibrillation, arteriosclerosis, left ventricular dysfunction, valvular disease, PFO, and tumor), while Kamel's PES only included left atrial dilation ≥4.
7 cm or ipsilateral cervical plaques Block
.
Anti-board combined anticoagulation therapy-the second analysis of COMPASS research Professor Chen Huisheng introduced that the second analysis of COMPASS research aims to analyze the effect of anti-board combined anticoagulation therapy
.
The purpose of the COMPASS study: To analyze the correlation between low-dose rivaroxaban with or without aspirin and the occurrence of different types of ischemic stroke
.
The results of the COMPASS study suggest that for patients with systemic atherosclerosis, low-dose rivaroxaban plus aspirin can reduce the incidence of cardiogenic stroke and embolic stroke of unknown cause, but further verification is needed
.
Figure 4: Results of the second analysis of the COMPASS study.
Other important ongoing studies by ESUS.
ATTICUS trial: It evaluated the efficacy of anticoagulation therapy on ESUS patients with various cardiac abnormalities, including left atrial enlargement, PFO, or high-risk atrial fibrillation
.
ARCADIA trial (NCTO3192219): To evaluate the difference between anticoagulation vs.
antiplatelet in the ESUS population with atrial heart disease
.
NOAH and ARTESIA trial: compared the efficacy of anticoagulation vs.
antiplatelet in patients with subclinical atrial fibrillation
.
Summary: The article published by Hart et al.
in 2014 outlined a more simplified definition of ESUS.
Although it is still unable to guide treatment, it is still a practical diagnostic tool.
This function is more conducive to adopting more effective and precise treatment strategies to prevent stroke
.
ESUS treatment decision-making focuses on screening of potential causes and individualized evaluation, especially for the two most important causes of cardiac and arterial factors, and technical means are required.
Before this goal is achieved, there is still a lot of work to be done.
do
.
The neutral results of NAVIGATE-ESUS and RE SPECT-ESUS suggest that: on the one hand, the etiology of ESUS is heterogeneous (cardiogenic vs.
arterial); on the other hand, cardiogenic factors are not dominant
.
