The Role of Epicardial Adipose Tissue Inflammation in Post-Operative Atrial Fibrillation

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Atrial fibrillation (AF) is the most common sustained heart rhythm disorder with significant associated morbidity including the risk of blood clots, stroke and heart failure alongside an increase in mortality. However, the precise causes of AF remain largely unknown. Recent studies suggest that generalised inflammation caused by circulating white blood cells may have a role in altering the properties of the heart to make it more susceptible to develop the abnormal electrical conduction of AF. Compelling data also shows that the layer of fat immediately surrounding the heart, known as epicardial adipose tissue (EAT), plays a key role in regulating the heart in health and disease. Putative roles of EAT in health include heat regulation, storage of energy and mechanical support to the heart. Given the proximity of EAT to the heart, it is also thought to be a critical link in mediating the effects of obesity on the heart. Hence, it has become a matter of intense medical interest to work out how and to what extent EAT can influence the heart tissue in disease states. EAT hosts a multitude of white blood cells which can produce inflammatory mediators that can easily pass into the heart. In turn, this can result in deleterious consequences such as inducing abnormal electrical impulses that may form the trigger for AF. Here, we propose to characterise the types of white blood cells and inflammatory mediators that play a role in the EAT-AF cascade in a cohort of patients undergoing open heart surgery. AF is the principal post-operative complication in patients undergoing heart surgery and carries specific additional short and long-term risks, including an elevated risk of stroke, death and increased length of hospitalisation with associated heightened health care costs. Hence, treatment strategies to reduce post-operative AF are of paramount importance.Our initial data indicates that a specific type of white blood cells (known as T cells) are elevated in patients who develop post-operative AF in addition to an elevation in markers characteristic of inflammation. In this project, we verify that the T cells identified in our initial analysis are responsible for the production of these elevated inflammatory markers. This will be performed in those patients who remain in normal heart rhythm post-operatively and those who develop AF (post-operative incidence of AF is in the order of 30-50%). Second, we will perform a detailed analysis of a host of inflammation markers to determine if they are increased in patients who develop new post-operative AF compared to patients who remain in normal heart rhythm post-operatively and those with longstanding AF. On identifying and verifying the specific immune parameters that are different we will aim to investigate their individual effect on the electrical properties of heart cells. Moreover, we will microscopically assess the heart tissue to look for abnormal immune cell infiltration into the heart itself. Finally, we will correlate these inflammatory and electrical alterations with detailed demographic and medical histories of patients. Ultimately, the project should form the basis of novel targets to reduce the incidence of post-operative AF.