STUDY OBJECTIVESPrimary objectiveThe primary objective of this study is to identify new imaging-derived biomarkers provided by modern imaging technologies, such as Cardiac Computed Tomography Angiography (CCTA), Delayed Enhancement MR Imaging (DE-MRI) or Speckle Tracking Echocardiography (STE), as well as haematological biomarkers, associated with the risk of intracavitary thrombosis in patients with AF, in order to identify the characteristics associated with an increased risk of cardio-embolic events.Secondary objectivesThis study also aims to evaluate the correlation between structural remodelling of the left and right atria and the amount of myocardial fibrosis of the left atrium by DE-MRI. We will determine the function of LA with EST, and will be performed automated quantification of atrial fibrosis. At the same time, volumetric assessment of epicardial adipose tissue will be performed in each patient undergoing CCTA and MRI. Besides this we will also look for identification of haematological biomarkers of predisposition for thrombosis and platelet aggregation. We will also evaluate the differences in these biomarkers in blood samples collected from a peripheral line and from the left atrium during interventional ablation procedures. Another important part of this study is to analyse the electrical remodelling of the atrium by three-dimensional electro-anatomic mapping system and to correlate these findings with the rate of thrombosis and with the level of local haematological markers. We will determine the rate of recurrence of AF, the rate of thromboembolic events and the rate of MACE, in every 3 months during the follow up.METHODSStudy designThis is a prospective, descriptive, cohort study and is composed of two major parts. In the first part of the study, laboratory tests and necessary interventions will be performed. The second part is represented by the follow-up of patients for 2 years and will contain the analysis of the data obtained during the first part of study. Before starting the study all patients will sign an informed consent. After evaluating eligibility for the screening process, patients who meet the inclusion criteria without exclusion criteria will be included in the study. All study procedures are in line with the principles in the Declaration of Helsinki. The study population will be comprised by minimal 50 patients. Each patient included in study need to be eligible to catheter ablation. The study population based on the degree of atrial remodelling (size, wall thickness and function) assessed with CCTA, will be divided in 2 groups. Patients with a mild atrial remodelling will be enrolled in the first group, while the second group will contain patients with moderate or severe atrial remodelling. Personal data of patients will be collected at the start of study. Anamnesis, physical examination, ECG, evaluation of risk factors and comorbidities will be performed in each case. Lab tests will include the level of leukocytes, hs-CRP, and the erythrocyte sedimentation rate. In each case we will exclude the presence of intracavitary thrombus using transthoracic and transesophageal echocardiography. The structure of atrial anatomy and the level of epicardial adipose tissue will be examined with echocardiography and CCTA. EST will be used for the assessment of cardiac function. Electrophysiological study will be performed in each patient included in the study and the images obtained with CCTA will be merged with the electrical map of the heart. After trans-septal puncture, but before pulmonary veins isolation, we will harvest blood from the left atrium to determine the level of pro-inflammatory and pro-coagulation factors. We will quantify the level of hs-CRP, IL-1,6, fibrinogen, tumour necrosis factor, the erythrocyte sedimentation rate, INR, PT, PT%. At the same time, we will harvest blood again to determine these factors but this time from the peripheral blood.The grade of atrial fibrosis will be assessed with DE-MRI. Upon discharge, we will re-perform a new ECG to confirm the success of cardioversion. All patients without atrial fibrillation at discharge will be followed for 2 years. Patients will be recalled for periodic investigations (anamnesis, physical examination, ECG, echocardiography) in the 3rd, 12th and 24th month and contacted by phone in the 6th and 9th month after cardioversion. At the last session (month 24), magnetic resonance, EST will be performed to assess the progression of atrial fibrosis and the changes in atrial function.INCLUSION AND EXCLUSION CRITERIAPatients are eligible if they had non-valvular paroxysmal or persistent AF. All patients need to be adults and to be able to read and understand the informed consent document. Also, only patients who have signed informed consent will be enrolled in the study.The study cannot be realized without imaging technics in consequence patients who present contraindications to imaging tests will be excluded from the study. These conditions are represented by claustrophobia, hypersensitivity to contrast agents (gadolinium, CT contrast agents), pregnancy, acute or chronic kidney failure (Stage 3a, 3b, 4, 5), and decompensated cirrhosis. Presence of metallic foreign bodies, cardiac rhythm device are contraindications for magnetic resonance imaging and therefore for the study. Patients receiving any drug that may affect the level of haematological markers will be excluded from the study. Terminally ill patients and those who may not adhere or may not complete follow up or do not have reliable information will be also excluded from the study.END-POINTSThe primary end point of the study is represented by the rate of thromboembolic events. Besides this, the rate of cardiovascular death, the rate of MACE and the rate of the AF recurrence will be determined.DATE STORAGE AND ANALYSES A dedicated database with the patient’s data and imaging tests will be created and handled with the utmost accuracy and confidentiality, only the staff involved in the research having access to this database. Imaging data stored in the database will undergo complex post-processing in the computational medicine laboratory, using computational simulations and advanced imaging techniques processing. The merging of images obtained with CT scanner with the electro anatomical map of the left atrium will be performed in real time during the catheter ablation procedure. The quantification of the left atrium fibrosis will be performed by a radiologist.The statistical analysis will be performed in the medical statistics laboratory of the Center of Advanced Research in Multimodal Cardiac Imaging of S.C. Cardio Med SRL.CONCLUSIONIn AF undergoing complex ablation procedures, the rate of recurrence and the cardioversion succession rate are influenced by several intra and extra-cardiac factors. Novel studies have shown that in addition to atrial stasis, many factors are involved in the appearance of intra-atrial thrombosis. Patients with positive history of atrial fibrillation have also an increased risk for stroke than those who never had atrial fibrillation. It is known that atrial fibrosis, inflammation and hypercoagubility have an important role in the appearance of intracavitary thrombosis but the exact mechanisms involved in this correlation has not been elucidated so far. This study will characterize new imaging-derived biomarkers to correlate the structural remodeling and fibrosis of the left and right atrium with the hematological parameters reflecting a high coagulability in the atria, in order identify new tools for predicting the risk of thromboembolic events in this group of patients.