Atrial Fibrillation Driver Study

Study Overview
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Brief Summary
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Atrial Fibrillation (AF) is an abnormal rhythm of the heart which is increasingly common and can be associated with serious consequences. We know that AF is associated with an increase in the scarring of the heart, the left atrium and it is thought that this scarring may be one of the drivers for this abnormal heart rhythm. The nature of this scarring in humans has been subject to limited study and generally only by indirect means such as cardiac MRI scans or measuring the voltage of the tissues. During cardiothoracic surgery, tissue from the left atrium is removed as a part of the procedure. This tissue is normally disposed of, but we would propose to consent patients to collect it to allow it to be analysed. Such analysis would examine the composition of the tissue, including the pattern of scarring, to allow us to gain a greater insight into the mechanisms of AF.

Detailed Description
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During cardiac surgery, a randomised trial has shown that surgical exclusion of the LAA at the time of cardiac surgery is associated with a 2.2% reduction in ischaemic stroke and systemic embolism. Therefore, surgical exclusion of the LAA, which in the latter study was most commonly achieved by excision, is a well-recognised part of routine surgical practice for patients with AF. During lung resections for malignancies, irrespective of a history of AF, along with the part of the lung being resected, the pulmonary vein and surrounding portion of the left atrium are also removed. These operations therefore provide tissue which is known to be of great importance in promoting and sustaining AF, but which is normally discarded. In the current study proposal, we will obtain this tissue and analyse it histologically. In the first instance, as a pilot study of up to 10 patients to assess the feasibility of such an analysis. This sample size is informed by our previous basic science studies of cardiac and lung fibrosis and will inform the design of a future full study. We aim to obtain samples from patients in sinus rhythm (thoracic surgical patients) and varying durations of AF (all surgical cases) to encompass tissues with different degrees of fibrosis. Design of research Up to 10 patients undergoing cardiothoracic surgery at University Hospital Southampton NHS Foundation Trust (UHS) will be recruited. In all cases, the patients would be undergoing surgery where the tissue being studied in the protocol would normally be removed. In the case of thoracic surgical patients, this would be those undergoing lung resections where an ostial pulmonary vein segment will be excised. Here the aim will be to have at least one patient with no history of atrial fibrillation, paroxysmal AF and persistent AF. Cardiac surgical patients included will be those where surgical left atrial exclusion will be performed as part of the procedure, in this case at least one patient with paroxysmal and one with persistent AF.

Official Title
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Atrial Fibrillation Driver Study - Pilot Project

Conditions
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Atrial Fibrillation, Fibrosis Myocardial

Intervention / Treatment
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* Procedure: Tissue excision as part of routine clinical care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide informed consent for study Male or female subjects between 18 and 100 years of age at the time of consent. Thoracic surgical patients either with or without a history of AF undergoing lung resection where an ostial pulmonary vein segment will be excised as part of this resection Cardiac surgical patients with a history of AF where surgical LAA exclusion is planned as part of the procedure Exclusion Criteria: Patient unable or unwilling to consent Patient not having ostial pulmonary vein or left atrial appendage tissue excised as part of routine clinical care.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cardiac Surgery<br>Patients undergoing cardiac surgery - left atrial appendage excision | Procedure: Tissue excision as part of routine clinical care<br>* Tissue excision<br>|
| Thoracic Surgery<br>Patients undergoing lung resection - ostial pulmonary vein tissue | Procedure: Tissue excision as part of routine clinical care<br>* Tissue excision<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological analysis | Immunohistochemistry, in situ hybridisation, electron microscopy, collagen cross-linking | 1 year | 
| Molecular analysis | genome sequencing, miRNA and RNA sequencing, culture, RT-PCR, flow cytometry and immunocytochemistry | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AF, Fibrosis