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Arterial Fibrillation (AF) is well-recognized as a cause for cryptogenic Acute Ischemic Stroke (AIS) and is associated with Silent Brain Infarction (SBI). However, the role of AF in the formation of lesions (SBIs) is less well established than its role in AIS and needs clarification.
The investigators hypothesize that continuous rhythm monitoring will yield a similar incidence of AF diagnosis in patients with SBI as compared to patients with cryptogenic AIS.
The primary objective is to assess the cumulative incidence of AF diagnosis at 24 months in patients with SBI.
Arterial Fibrillation (AF) is well-recognized as a cause for cryptogenic Acute Ischemic Stroke (AIS) and searched for in clinical practice. However, although AF is associated with Silent Brain Infarction (SBI), its role in the formation of these lesions is less well established and needs clarification. A multitude of clinical, laboratory, echocardiographic and electrocardiographic parameters are associated with AF. Although no single one of these parameters has sufficient specificity to rule-in AF, their combined use may nevertheless help to identify patients with SBI at highest risk for AF. The study is expected to provide evidence that long term monitoring in subjects with SBI yields similar rates of AF as in AIS patients.
Patients aged ≥65 years with a presumably silent brain lesion in a brain magnetic resonance imaging fulfilling inclusion criteria and consenting get a subcutaneous implantation of a cardiac monitor (Reveal LINQ). Data will be directly transferred to the treating physician by the Medtronic MyCareLink Patient Monitor. In case of a relevant arrhythmia, the respective study site will be informed by the staff of Inselspital. Relevant arrhythmias are defined as follows:
The expected results of the study would be supportive in introducing long term monitoring to the care pathway in subjects with SBI. Since SBI are more prevalent than AIS and current recommendations very restrictive, this would have a relevant impact on SBI management.
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| Measure | Description | Time Frame |
|---|---|---|
| Cumulative incidence of Arterial Fibrillation (AF) diagnosis over a median of 24 months | Only adjudicated events will be used for the analysis. An AF episode is defined as lasting more than 30 seconds. A diagnosis of atrial flutter will also be considered as a primary endpoint. | From day 0 to 24 months after inclusion |
| Measure | Description | Time Frame |
|---|---|---|
| Time to first diagnosis of AF (lasting ≥30 seconds; ≥6 minutes; ≥1 hour; ≥ 24 hour) | From day 0 to 24 months after inclusion | |
| Burden of AF | The burden of AF is defined as the amount of time (percentage) in AF during rhythm monitoring. AF burden will be calculated on a monthly basis. |
| Measure | Description | Time Frame |
|---|---|---|
| Time to first diagnosis of AF (lasting ≥30 seconds; ≥6 minutes; ≥1 hour; ≥ 24 hours) until battery depletion of Implantable Cardiac Monitor (ICM) (36-42 month). | From day 0 until battery depletion, expected to be 36 to 42 months | |
| Cumulative incidence of AF diagnosis until battery depletion of ICM |
Inclusion Criteria:
Age
≥ 65 years
≥ 50 years AND one the following:
Written informed Consent
Any clinically silent ischemic lesions of the brain parenchyma detected on neuroimaging defined according to established criteria as either:
Diffusion weighted imaging (DWI) positive lesions: Focus of restricted diffusion (high DWI signal and low apparent diffusion coefficient value) occurring in either white or gray matter, located in the cerebrum, cerebellum, or brain stem AND not satisfying the diagnostic criteria for multiple sclerosis OR
Cavitatory Lesions: ≥ 3 mm in size that follow cerebro-spinal fluid on all sequences that are slit or wedge shaped with an irregular margin AND NOT longitudinally aligned with perforating vessels or with a multiple, bilateral symmetrical distribution OR
T2 weighted (T2W) hyperintense/T1 weighted (T1W) hypointense lesions:
Exclusion Criteria:
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≥ 50 years
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Laurent Roten, PD Dr. med. | Contact | +41 31 632 52 63 | laurent.roten@insel.ch | |
| Thomas Meinel, Dr. med. | Contact | +41 76 49 28 545 | thomas.meinel@insel.ch |
| Name | Affiliation | Role |
|---|---|---|
| Laurent Roten, PD Dr. med. | Inselgruppe AG | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitätsspital Graz | Recruiting | Graz | Austria |
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| From day 0 to 24 months after inclusion |
| Time to composite of first diagnosis of AF, stroke and death. | From day 0 to 24 months after inclusion |
| Incidence of AF diagnosis according to Silent Brain Infarction (SBI) neuroradiological appearance (subcortical small vessel versus embolic pattern involving grey matter) and SBI fulfilling ESUS criteria versus lacunar type. | Embolic stroke of undetermined source (ESUS) | From day 0 to 24 months after inclusion |
| Start of oral anticoagulation therapy at 24 months. | At 24 months |
| Stroke at 24 months | At 24 months |
| Mortality at 24 months | At 24 months |
| Prevalence of other possible etiologies for SBI according to a modified TOAST-classification (large artery disease, small artery disease, other specific etiologies, unknown etiology, incomplete workup) | From day 0 to 24 months after inclusion |
| Incidence of new SBI at 24 months (only if sufficient funding can be obtained for repeat brain MRI at 24 months without contrast agent) | At 24 months |
| From day 0 to until battery depletion, expected to be 36 to 42 months |
| Charite Berlin | Not yet recruiting | Berlin | Germany |
|
| Centre hospitalier universitaire vaudois (CHUV) | Recruiting | Lausanne | Canton of Vaud | 1011 | Switzerland |
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| Kantonsspital Aarau | Active, not recruiting | Aarau | Switzerland |
| University Hospital Basel | Recruiting | Basel | 4031 | Switzerland |
|
| Inselspital Bern | Recruiting | Bern | 3010 | Switzerland |
|
| Kantonsspital St.Gallen | Recruiting | Sankt Gallen | 9007 | Switzerland |
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| Universitätsspital Zurich | Recruiting | Zurich | Switzerland |
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