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Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation
Published on: February 26, 2013
Increased prothrombotic profile in the left atrial appendage of atrial fibrillation patients
Alexander Breitenstein1, Martina Glanzmann2, Volkmar Falk3
1Cardiology, University Heart Center, University Hospital Zurich, Switzerland; Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Center for Integrative Human Physiology (ZHIP), University of Zurich, Switzerland; Department of Electrophysiology, St. Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom.
Insights
Atrial fibrillation (AF) patients show increased prothrombotic and proinflammatory markers in left atrial appendage (LAA) endocardium compared to the right (RAA). This finding explains LAA clot formation and thromboembolic risks in AF.
Area of Science:
- Cardiovascular Biology
- Thrombosis Research
- Cellular and Molecular Medicine
Background:
- Atrial fibrillation (AF) increases thromboembolic event risk.
- Left atrial appendage (LAA) is a primary site for clot formation in AF.
- Mechanisms of LAA clot formation are poorly understood due to challenges in cell isolation and culture.
Purpose of the Study:
- To investigate the prothrombotic and proinflammatory profile of endocardial cells from LAA and RAA in AF patients.
- To establish a novel protocol for isolating and culturing atrial appendage endocardial cells.
Main Methods:
- Endocardial cells were isolated and cultured from LAA and RAA of AF patients undergoing cardiac surgery.
- Cells were stimulated with TNF-α to analyze prothrombotic and proinflammatory marker expression.
- Flow cytometry (FACS) was used to confirm cell purity and analyze marker expression.
Main Results:
- A novel protocol successfully isolated and cultured LAA endocardial cells with 98% purity.
- TNF-α stimulation significantly increased tissue factor (TF) and PAI-1 expression in LAA cells.
- VCAM-1 expression was significantly higher in LAA endocardial cells compared to RAA cells.
Conclusions:
- The LAA endocardium in AF patients exhibits a heightened prothrombotic and proinflammatory profile.
- This enhanced profile in LAA endocardium may explain its propensity for clot formation.
- Findings suggest novel therapeutic targets for preventing LAA-related thromboembolic complications in AF.
Background:
Atrial fibrillation (AF) is associated with an increased risk for thromboembolic events. While observational data demonstrated that the majority of clots are formed within the left atrial appendage, the mechanisms behind this finding remain unclear also due to the fact that vitro studies so far have been hampered by the inability to isolate and culture cells from the atrial appendages.
Methods:
Patients suffering from AF undergoing cardiac surgery were recruited for this study and endocardial cells from their left (LAA) and right atrial appendage (RAA) were isolated and cultured according to a novel established protocol. Once in culture, cells were stimulated with TNF-α (10 ng/mL) and the expression of prothrombotic as well as proinflammatory markers was analyzed.
Results:
FACS analysis confirmed a high purity (98%) of isolated LAA endocardial cells. TNF-α significantly increased tissue factor (TF) and PAI-1 expression (n=5; P<0.005), while TFPI remained unchanged. Similarly, expression of VCAM-1 was significantly higher in the LAA as compared to the RAA (n=5; P<0.0001).
Conclusion:
According to our newly established cell isolation protocol, this study reveals that in patients with AF, the endocardium of the LAA displays an increased prothrombotic and proinflammatory profile as compared to the RAA. This novel observation may constitute an important mechanism to explain the increased propensity of the LAA for clot formation, as well as the predominance of LAA-related thromboembolic complications in AF patients, and may have important implications for the development of novel treatment strategies.
