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

心房颤动（AF）是最常见的持续性心律失常，具有显著的相关发病率，包括血栓、中风和心力衰竭的风险，以及死亡率的增加。然而，房颤的确切原因在很大程度上仍然未知。最近的研究表明，由循环白细胞引起的全身性炎症可能在改变心脏特性方面发挥作用，使其更容易发生心房纤颤的异常电传导。令人信服的数据还表明，心脏周围的脂肪层，即心外膜脂肪组织（EAT），在调节心脏健康和疾病方面起着关键作用。据推测，EAT在健康中的作用包括调节热量、储存能量和对心脏的机械支持。考虑到EAT离心脏很近，它也被认为是调节肥胖对心脏影响的关键环节。因此，研究EAT如何以及在多大程度上影响疾病状态下的心脏组织已成为医学关注的热点。EAT拥有大量的白细胞，这些白细胞可以产生很容易进入心脏的炎症介质。反过来，这可能导致有害的后果，如诱发异常的电脉冲，可能形成房颤的触发因素。在这里，我们建议在一组接受心脏手术的患者中描述在EAT-AF级联中起作用的白细胞和炎症介质的类型。房颤是心脏手术患者的主要术后并发症，具有特定的额外短期和长期风险，包括卒中、死亡风险升高、住院时间延长以及相关的医疗费用增加。因此，减少术后房颤的治疗策略至关重要。我们的初步数据表明，在发生术后房颤的患者中，除了炎症特征标志物的升高外，一种特定类型的白细胞（称为T细胞）也升高。在这个项目中，我们验证了在我们最初的分析中发现的T细胞是产生这些升高的炎症标志物的原因。这将适用于术后心律保持正常的患者和发生房颤的患者（房颤的术后发生率约为30-50%）。其次，我们将对一系列炎症标志物进行详细分析，以确定与术后保持正常心律的患者和长期房颤患者相比，新发房颤患者的炎症标志物是否增加。在识别和验证不同的特定免疫参数时，我们将旨在研究它们对心脏细胞电学特性的个体影响。此外，我们将在显微镜下评估心脏组织，以寻找异常的免疫细胞浸润到心脏本身。最后，我们将这些炎症和电改变与患者详细的人口统计和病史联系起来。最终，该项目应成为降低术后房颤发生率的新靶点的基础。

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.