Cerebral Protection in Transcatheter Left Atrial Appendage Occlusion

Study Overview
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Brief Summary
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The study aims to assess the effect of the use of neuroprotection in transcutaneous occlusion of the left atrial appendage in patients with atrial fibrillation on the risk of perioperative silent brain ischemia and associated cognitive impairment and depression.

Detailed Description
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Introduction: Left atrial appendage occlusion (LAAC) procedure is a method of preventing stroke in patients with atrial fibrillation who cannot use anticoagulants. The number of patients undergoing LAAC treatment tends to increase. LAAC procedures effectively reduce the number of strokes, with a significant reduction in the risk of bleeding compared to oral anticoagulants. However, although LAAC treatments alone have a low risk of perioperative stroke, some patients may experience incidents of silent brain ischemia (SBI). The distant effect of SBI may be cognitive deterioration, the onset of dementia syndromes, as well as depression. Purpose of the study: The study aims to assess the effect of the use of neuroprotection in transcutaneous occlusion of the left atrial appendage (LAAC) in patients with atrial fibrillation on the risk of perioperative SBI and associated cognitive impairment and depression. Methodology: The planned study is a prospective, multicentre, randomized, and double-blind intervention trial. Neuroprotection introduced from arterial access will be used in the LAAC treatment study group. In the control group, LAAC treatments will be performed without neuroprotection. Two hundred forty patients are planned to be enrolled with indications for stroke prevention due to atrial fibrillation. The analysis will include data obtained from DW MRI images, neurological evaluation results along with NIHSS-scale scores, results of cognitive evaluation tests (MoCA, COWAT, TMT A&B), and test of mood disorders (HADS Scale), as well as results of the EQ-5D-5L quality of life assessment questionnaire. It is planned to observe patients participating in the study for 24 months after LAAC procedure.

Official Title
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Cerebral Protection in Transcatheter Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation

Conditions
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Atrial Fibrillation, Silent Stroke, Cognitive Impairment, Depression

Intervention / Treatment
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* Procedure: LAAC procedure with the use of transcatheter cerebral protection system
* Procedure: LAAC procedure without the use of transcatheter cerebral protection system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 Years and older Subject able to provide signed informed consent. Documented permanent, persistent, or paroxysmal atrial fibrillation CHA2DS2VASc risk of stroke ≥2 At least one of the following criteria: Contraindications to the use of anticoagulants, HSBLED bleeding risk ≥3 Exclusion Criteria: Serious mental diseases, particularly: dementia syndrome of any etiology, schizophrenia,schizoaffective disorders, bipolar disorder History of ischemic stroke Chronic abuse of alcohol or any other psychoactive substances except for nicotine long-term therapy with benzodiazepines The use of antidepressants in 3 months prior inclusion. Previous infections of the central nervous system, including neuroborreliosis Parkinson's disease Huntington's chorea Creutzfeld-Jakob disease Pick's disease Significant atherosclerosis of the cephalic arteries (> 70% LCCA or the brachiocephalic trunk) Strictures, ectasias, dissection or aneurysms at the exit of the LCCA or the brachiocephalic trunk from the aorta and up to 3 cm above Advancement of vascular changes in DW MRI of the head, grade 3 on the Fazekas scale Presence of a thrombus or tumours of a different nature in the left atrium or its ear Presence of a thrombus in the left ventricle Left atrial appendage anatomy preventing the use of occluders to close the left atrium appendage The presence of mechanical heart valve prostheses The state after the operative closure of the defect in the atrial septum Condition after closing the defect in the interatrial septum with the use of occluders Active infective endocarditis Presence of devices and prostheses that prevent the performance of MRI (pacemakers, clips in the CNS) Status after oesophagal surgery Esophageal diverticula Esophageal varices> grade 3 Allergic to contrast agents A contraindication to use antiplatelet drugs Diagnosis of neoplastic disease with estimated survival beyond 1 year Clininally evident hypothyroidism and hyperthyroidism Klaustrofobia Pregnancy AIDS Participation in other drug research studies The presence of circumstances or any medical condition the Investigator considers problematic for subject inclusion, or test results that may couse problems to provide reliable, acurate to interpretation results

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LAAC with neuroprotection<br>Arm in which is used a transcatheter system to protect the cerebral circulation during the left atrial appendage closure procedures. | Procedure: LAAC procedure with the use of transcatheter cerebral protection system<br>* After aortography the cerebral protection system will be delivered to cerebral arteries through radial access before accessing the left atrium.<br>|
| Placebo Comparator: LAAC without neuroprotection<br>Arm in which the left atrial appendage closure procedures are performed without transcatheter cerebral protection. | Procedure: LAAC procedure without the use of transcatheter cerebral protection system<br>* Only the aortography through radial access will be done before accessing the left atrium.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in number of silent cerebral ischemia (SBI) foci | number of SBI foci in DW MRI of the brain | change in the period up to 24 months | 
| Change in volume of silent cerebral ischemia (SBI) foci | volume SBI foci in DW MRI of the brain | change in the period up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Deterioration of cognitive functions | Montreal Cognitive Assessment (MoCA) test (scoring 0-30; cut-off value <26) | prior to procedure, discharge (up to 5 days), 90 days, 12 months, 24 months | 
| Deterioration of cognitive functions | The Trail Making Test Part A and B for Dementia (TMT A&B) - incorrect values: for part A > 70 sec. and for part B> 273 sec. | prior to procedure, discharge (up to 5 days), 90 days, 12 months, 24 months | 
| Development of dementia | diagnosis made by a specialist neurologist | prior to procedure, discharge (up to 5 days), 90 days, 12 months, 24 months | 
| Occurrence of depressive disorders | Hemiltona depression scale - 0 to 50 point, the higher the score, the more severe the mood disorder | prior to procedure, discharge (up to 5 days), 90 days, 12 months, 24 months | 
| Presence of embolic material in the filters of the neuroprotection device |  | during LAAC procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cerebral protection, left atrial appendage occlusion, atrial fibrillation, silent brain ischemia, cognitive impairment, depression