Atrial Fibrillation and Characterization of Blood Platelet

Study Overview
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Brief Summary
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Arterial thromboembolism constitutes a major risk of atrial fibrillation (AF) requiring antithrombotic therapy. Platelets and microparticles (MPs) are important for hemostasis and thrombosis, their role during AF is not well known. The principal objective of this study is to compare morphologic, functional and proteomics characteristics of blood platelet between AF patients and healthy volunteers.

Detailed Description
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AF is associated with decreased quality of life and an increased risk of thromboembolic events. AF is the leading cause of embolic stroke. Identification of factors that may influence blood coagulability in these patients could better identify therapeutic targets to optimize anticoagulation. Platelets play a major role in the coagulation process, their study may provide valuable information. Moreover microparticles from platelet activation are known to have pathophysiological effects including effects on thrombosis and inhibition of fibrinolysis. It has also been shown that the microparticles have a role in endothelial dysfunction and generation of inflammatory condition which are associated with atrial fibrillation. Investigators propose in this project, a comparative study between AF patients and healthy volunteers. Complete characterization of platelet (morphology, platelet function, platelet proteome) and microparticles levels will be perform. Different site blood sampling (systemic or cardiac) will be done in patients during their ablation procedure. Patients will be followed during their hospitalisation.

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Device: Electrocardiogram (ECG)
* Biological: Blood sampling from the cephalic vein
* Biological: Blood sampling from the femoral vein
* Biological: First blood sampling from left atrium
* Procedure: Atrial stimulation
* Biological: Second blood sampling from left atrium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria: valid for all groups Age superior or equal to 18 years old, both genders. Patient affiliated or recipient of a social welfare regimen. Patient's write agreement for study participation after reading information note Inclusion Criteria: specific for groups Group 1: Volunteers without heart disease. Volunteers who never had AF and not in AF the day of inclusion. Group 2 Patient suffering of paroxysmal atrial fibrillation since at least 6 month and addressed for primo ablation of atrial fibrillation. Patient in sinus rhythm the day of inclusion. Group 3 Patient suffering of paroxysmal atrial fibrillation since at least 6 month and addressed for primo ablation of atrial fibrillation. Patient in atrial fibrillation the day of inclusion Group 4 Patient suffering of persistent atrial fibrillation since at least 6 month and addressed for primo ablation of atrial fibrillation. Patient in sinus rhythm the day of inclusion. Group 5 Patient suffering of persistent atrial fibrillation since at least 6 month and addressed for primo ablation of atrial fibrillation. Patient in atrial fibrillation the day of inclusion Exclusion Criteria: Age <18 years. Active smoker (> 10 cigarettes/days) Pregnant woman or breastfeeding women or not receiving effective contraception. Volunteer participating in another interventional study requiring taking drug. Volunteer having taken antinflammatory, platelet anti-aggregant or calcium-channel blocker drugs within 8 days prior to inclusion Valvular heart diseases. Chronic inflammatory diseases. Cardiovascular event or stroke within 3 month prior to inclusion Uncontrolled hypertension Chronic hepatic or renal diseases.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Volunteers | Device: Electrocardiogram (ECG)<br> <br> Biological: Blood sampling from the cephalic vein<br> <br> |
| Experimental: Group 2<br>Paroxysmal AF patients in sinus rhythm the day of inclusion | Biological: Blood sampling from the femoral vein<br>* Blood sampling will be done during radiofrequency ablation of AF procedure, after the introduction of catheter<br>Biological: First blood sampling from left atrium<br>* Blood sampling will be done during radiofrequency ablation of AF procedure, after transeptal punction<br>Procedure: Atrial stimulation<br>* Patients will receive atrial stimulation with the catheter positioned in the coronary sinus to induce AF<br>Biological: Second blood sampling from left atrium<br>* After 20min of continuous AF, a blood sampling from left atrium will be done<br>|
| Experimental: Group 3<br>Paroxysmal AF patients in atrial fibrillation the day of inclusion | Biological: Blood sampling from the femoral vein<br>* Blood sampling will be done during radiofrequency ablation of AF procedure, after the introduction of catheter<br>Biological: First blood sampling from left atrium<br>* Blood sampling will be done during radiofrequency ablation of AF procedure, after transeptal punction<br>|
| Experimental: Group 4<br>Persistent AF patients in sinus rhythm the day of inclusion | Biological: Blood sampling from the femoral vein<br>* Blood sampling will be done during radiofrequency ablation of AF procedure, after the introduction of catheter<br>Biological: First blood sampling from left atrium<br>* Blood sampling will be done during radiofrequency ablation of AF procedure, after transeptal punction<br>Procedure: Atrial stimulation<br>* Patients will receive atrial stimulation with the catheter positioned in the coronary sinus to induce AF<br>Biological: Second blood sampling from left atrium<br>* After 20min of continuous AF, a blood sampling from left atrium will be done<br>|
| Experimental: Group 5<br>Persistent AF patients in atrial fibrillation the day of inclusion | Biological: Blood sampling from the femoral vein<br>* Blood sampling will be done during radiofrequency ablation of AF procedure, after the introduction of catheter<br>Biological: First blood sampling from left atrium<br>* Blood sampling will be done during radiofrequency ablation of AF procedure, after transeptal punction<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of maximal aggregation level (expressed in aggregation percentage) after ex vivo stimulation by Adenosine Di-Phosphate (ADP), arachidonic acid, ristocetin, collagen and Thrombin Receptor Activating Peptide (TRAP-6mers) | Aggregation percentage is measured by the method of light transmission aggregometry | Day 1 | 
| Measure of maximal disaggregation level (expressed in disaggregation percentage) | Disaggregation percentage is measured by the method of light transmission aggregometry | Day 1 | 
| Measure of platelet volume mean |  | Day 1 | 
| Assessment of the Platelet morphology (shape change) |  | Day 1 | 
| Assessment of the modification of the membrane receptor expression modification |  | Day 1 | 
| Identification of platelet proteins differentially expressed between groups |  | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of Tissue Factor (TF) dependent microparticles level |  | Day 1 | 
| Measure of fibrinolytic microparticles level |  | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial fibrillation, blood platelet