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An illustration of MRI in the two patients who showed different types of new CMB locations. For each patient, the baseline GRE is on the left, and the follow-up GRE is on the right. Arrows indicate new CMBs on the follow-up scan. CMBs: cerebral microbleeds. GRE: T2 � -weighted gradient-recalled echo imaging.
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Objective:
Cerebral microbleeds (CMBs) are a magnetic resonance imaging (MRI) marker for cerebral small vessel disease. Existing CMBs and those that newly develop are associated with the risks of stroke incidence and recurrence. The purpose of the present study was to investigate the association of oral anticoagulant (OAC) use and the development...
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Background
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Citations
... Anticoagulation use has been associated with the appearance of microbleeds [22], although a recent prospective study suggests that this association is weaker in patients taking Fig. 2. B and C SWAN MRI sequence shows the appearance of multiple hemosiderin spots suggestive of microbleeds (red arrows). FLAIR indicates fluid attenuated inversion recovery; HARM, hyperintense acute reperfusion marker; MRI, magnetic resonance imaging; SWAN, susceptibility-weighted angiography direct oral anticoagulants, as in our case, than in those treated with Warfarin [23]. While we cannot rule out an additive effect of anticoagulation in the blooming of unilateral microbleeds in our patient, localization and timing suggest a close relationship between recent ischemic stroke, HARM, and cerebral microbleeds in this case, and it could be speculated that the increased risk of hemorrhagic transformation associated with HARM may be mediated by microbleeds appearances. ...
Background
Hyperintense Acute Reperfusion Marker (HARM) is a hyperintense subarachnoid signal on FLAIR MRI sequence caused by gadolinium contrast leakage into the subpial space. While, on FLAIR, HARM may mimic subarachnoid hemorrhage, it is differentiated from it on computed tomography (CT) and SWAN MRI sequences. Cerebral microbleeds are black, rounded spots on SWAN caused by blood-products deposition following red blood cell leakage from small cerebral vessels brain. Both microbleeds and HARM carry important prognostic implication as they are associated with blood-brain barrier disruption and an increased risk of intracerebral hemorrhage.
Case presentation
A 79-year-old man presented with aphasia and right hemiparesis due to ischemic stroke with left middle cerebral artery occlusion. Admission NIHSS score was 7, and he was successfully treated by intravenous thrombolysis and mechanical thrombectomy. On day 1, his clinical condition worsened, and he had an urgent gadolinium-enhanced MRI. There was no evidence of early recurrence, nor of hemorrhage on SWAN or on FLAIR. Left middle cerebral artery was permeable. The patient was anticoagulated for newly diagnosed atrial fibrillation, and a second MRI following a generalized tonic-clonic seizure showed multiple left hemispheric diffusion-weighted imaging (DWI) hyperintense spots and a left hemispheric sub-arachnoid hyperintensity on FLAIR, compatible with a subarachnoid hemorrhage. This diagnosis was excluded by SWAN MRI sequence and a normal cerebral CT the same day. The diagnosis of HARM was retained. At day 9, patient’s condition improved, and a control MRI did not show evidence of HARM. However, numerous microbleeds were detected in the left hemisphere only (ipsilateral with HARM and stroke).
Conclusions
This case highlights first of all the importance of differentiating HARM and subarachnoid hemorrhage, especially in an anticoagulated patient with clinical aggravation. Secondly, it is crucial to identify microbleeds and understand their pathophysiology, as they are associated with higher risk of hemorrhage and stroke recurrence in ischemic stroke patients. Finally, the mono-hemispheric appearance of microbleeds in this case suggests for the first time that, in some acute ischemic stroke patients, a relationship between HARM and cerebral microbleeds may exist.
... A total of 562 records were retrieved after the literature search (195 from PubMed and 367 from EMBASE). After the selection process, 17 articles 11,12,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] were included in the analysis (Supplementary material online, Figure S1). ...
... Nine studies were held in Asia, 11,[22][23][24][25][26][27][28]35 four in Europe, 12,31-33 and four were held in other countries. 21,29,30,34 Studies included were quite homogeneous in term of the proportion of women enrolled (ranging from 33% to 54% of the whole cohorts), the prevalence of key comorbidities, such as hypertension (ranging from 58% to 92%) and diabetes mellitus (17-39%), and follow-up times for studies that evaluated outcomes (range between 1.4 and 3.1 years). ...
... shows the main characteristics of the studies included. All the studies11,12,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] reported data about prevalence of CMBs in patients with AF, while eight reported data about ICH or IS according to the ...
Aims:
The aim of this study is to perform a systematic review and meta-analysis on the epidemiology of cerebral microbleeds (CMBs) and the risk of intracranial haemorrhage (ICH) and ischaemic stroke (IS) in patients with atrial fibrillation (AF).
Methods and results:
PubMed and EMBASE databases were systematically searched from inception to 6 March 2021. All studies reporting the prevalence of CMBs and incidence of ICH and IS in AF patients with and without CMBs were included. Meta-analysis was conducted using random-effect models; odds ratios (ORs), 95% confidence intervals (CIs), and prediction intervals (PIs) were calculated for each outcome. Subgroup analyses were performed according to the number and localization of CMBs. A total of 562 studies were retrieved, with 17 studies finally included in the meta-analysis. Prevalence of CMBs in AF population was estimated at 28.3% (95% CI: 23.8-33.4%). Individuals with CMBs showed a higher risk of ICH (OR: 3.04, 95% CI: 1.83-5.06, 95% PI 1.23-7.49) and IS (OR: 1.78, 95% CI: 1.26-2.49, 95% PI 1.10-2.87). Patients with ≥5 CMBs showed a higher risk of ICH. Metaregression showed how higher of prevalence of diabetes mellitus in AF cohort is associated with higher prevalence of CMBs.
Conclusions:
Cerebral microbleeds are common in patients with AF, found in almost one out of four subjects. Cerebral microbleeds were associated with both haemorrhagic and thromboembolic events in AF patients. Moreover, the risk of ICH increased consistently with the burden of CMBs. Cerebral microbleeds may represent an important overlooked risk factor for both ICH and IS in adults with AF.
Background:
An increased risk of intracranial hemorrhage (ICH) associated with statins has been reported; but data on the relationship between statin-use and cerebral microbleeds (CMBs) in patients with atrial fibrillation (AF), a population at high bleeding and cardiovascular risk are lacking.
Aims:
To explore the association between statin-use and blood lipid-levels with the prevalence and progression of CMBs in patients with atrial fibrillation with particular focus on anticoagulated patients.
Methods:
Data of Swiss-AF, a prospective cohort of patients with established AF were analyzed. Statin-use was assessed during baseline and throughout follow-up. Lipid values were measured at baseline. CMBs were assessed using magnetic resonance imagining (MRI) at baseline and at 2-years follow-up. Imaging data were centrally assessed by blinded investigators. Associations of statin-use and low-density lipoprotein (LDL) levels with CMB prevalence at baseline or CMB progression (at least one additional or new CMB on follow-up MRI at 2-years compared to baseline) were assessed using logistic regression models; the association with ICH was assessed using flexible parametric survival models. Models were adjusted for hypertension, smoking, body mass index, diabetes, stroke/transient ischemic attack, coronary heart disease, antiplatelet use, anticoagulant use and education.
Results:
Of the 1693 patients with CMB data at baseline MRI (mean±SD age 72.5±8.4y, 27.6% women, 90.1% on oral anticoagulants), 802 patients (47.4%) were statin users. The multivariable adjusted odds ratio (adjOR) for CMBs prevalence at baseline for statin users was 1.10 (95% CI, 0.83-1.45). AdjOR for 1 unit increase in LDL-levels was 0.95 (95% CI, 0.82-1.10). At 2-years, 1188 patients had follow-up MRI. CMBs progression was observed in 44 (8.0%) statin users and 47 (7.4%) non-statin users. Of these patients 64 (70.3%) developed a single new CMB, 14 (15.4%) developed 2 CMBs and 13 developed more than 3 CMBs. The multivariable adjOR for statin users was 1.09 (95% CI, 0.66-1.80). There was no association between LDL-levels and CMBs progression (adjOR 1.02, 95% CI, 0.79-1.32). At follow-up 14 (1.2%) statin users had ICH vs 16 (1.3%) non-users. The age and sex adjusted Hazard Ratio (adjHR) was 0.75 (95% CI, 0.36-1.55). Results remained robust in sensitivity analyses excluding participants without anticoagulants.
Conclusions:
In this prospective cohort of patients with AF, a population at increased hemorrhagic risk due to anticoagulation, the use of statins was not associated with an increased risk of CMBs.
Background and purpose:
Prospective studies on cerebral microbleeds (CMB) have departed from individuals who already have CMB at baseline. Therefore, main outcomes have usually been the composite of new lesions appearing on the follow-up among patients who already had CMB together with those who de novo developed CMB. Using the Atahualpa Project Cohort, we aimed to assess correlates of incident CMB in community-dwelling older adults free of CMB at baseline.
Methods:
Atahualpa residents aged ≥ 60 years received baseline clinical interviews and a brain MRI. Those who were free of CMB at baseline and received follow-up brain MRI at the end of the study were included. Multivariate logistic and Poisson regression models were fitted to assess the association and the incidence rate ratio (IRR) of incident CMB according to clinical and neuroimaging variables.
Results:
The mean age of 241 study participants was 65.6 ± 6.1 years (57% women). After 6.5 years of follow-up, 25 subjects (10.4%) developed incident CMB. A total of 37 CMB were noticed in these 25 patients. A parsimonious logistic regression model demonstrated an association between the Edmonton Frail Scale (EFS) and incident CMB (p = .043). Multivariate logistic regression models showed an association between WMH progression and incident CMB (p = .011). Using Poisson regression models, the IRR for WMH progression at follow-up was increased in subjects with incident CMB (p = .029).
Conclusions:
Study results show a significant relationship between the EFS, WMH progression, and incident CMB. This knowledge will allow the implementation of preventive policies to reduce incident CMB and its consequences.
Background
Cerebral microbleeds (CMBs) may have a differential impact on clinical outcome in stroke patients with atrial fibrillation (AF) treated with different types of oral anticoagulation (OAC).
Methods
Observational single-center study on AF-stroke-patients treated with OAC. Magnetic-resonance-imaging was performed to assess CMBs. Outcome measures consisted of recurrent ischemic stroke (IS), intracranial hemorrhage (ICH), death, and their combined analysis. Functional disability was assessed by mRS. Using adjusted logistic regression and Cox proportional-hazards models, we assessed the association of the presence of CMBs and OAC type (vitamin K antagonists [VKAs] vs. direct oral anticoagulants [DOACs]) with clinical outcome.
Results
Of 310 AF-stroke patients treated with OAC [DOACs: n = 234 (75%); VKAs: n = 76 (25%)], CMBs were present in 86 (28%) patients; of these, 66 (77%) received DOACs. In both groups, CMBs were associated with an increased risk for the composite outcome: VKAs: HR 3.654 [1.614; 8.277]; p = 0.002; DOACs: HR 2.230 [1.233; 4.034]; p = 0.008. Patients with CMBs had ~50% higher absolute rates of the composite outcome compared to the overall cohort, with a comparable ratio between treatment groups [VKAs 13/20(65%) vs. DOACs 19/66(29%); p < 0.01]. The VKA-group had a 2-fold higher IS [VKAs:4 (20%) vs. DOACs:6 (9%); p = 0.35] and a 10-fold higher ICH rate [VKAs: 3 (15%) vs. DOACs: 1 (1.5%); p = 0.038]. No significant interaction was observed between type of OAC and presence of CMBs. DOAC-patients showed a significantly better functional outcome (OR 0.40 [0.17; 0.94]; p = 0.04).
Conclusions
In AF-stroke patients treated with OAC, the presence of CMBs was associated with an unfavorable composite outcome for both VKAs and DOACs, with a higher risk for recurrent IS than for ICH. Strokes were numerically higher under VKAs and increased in the presence of CMBs.
Clinical trial registration
http://www.clinicaltrials.gov, Unique identifier: NCT03826927.
Atrial fibrillation (AF) is the most common clinical tachyarrhythmia, posing a significant burden to patients, physicians, and healthcare systems worldwide. With the advent of more effective rhythm control strategies, such as AF catheter ablation, an early rhythm control strategy is progressively demonstrating its superiority not only in symptoms control but also in prognostic terms, over a standard strategy (rate control, with rhythm control reserved only to patients with refractory symptoms). This review summarizes the different impacts exerted by AF on heart mechanics and systemic circulation, as well as on cerebral and coronary vascular beds, providing computational modeling-based hemodynamic insights in favor of pursuing sinus rhythm maintenance in AF patients.
