Active clinical trials for "Atrial Fibrillation"

MIGAT will develop and transfer software tools to assist ablation therapy of cardiac arrhythmias. The scientific background and objectives of MIGAT differ between atrial and ventricular arrhythmias, because the knowledge on structure-function relationships and the definition of ablation targets are different. Hypothesis: The combination of body surface mapping and imaging will enable a comprehensive non-invasive assessment of cardiac arrhythmia mechanisms and localization, myocardial structural substrate, and cardiac anatomy, all of which should be of value to better define targets for ablation therapy. No software solution is currently available for multimodal data processing, fusion, and integration in 3-dimensional mapping systems to assist ablation. Because such a development requires a trans-disciplinary approach (cardiac electrophysiology, imaging, computer sciences), it is likely to emerge from an academic initiative. Objectives: MIGAT will gather resources from the Liryc Institute (L'Institut de Rythmologie et Modélisation Cardiaque), the Inria (Institut National de Recherche en Informatique et en Automatique) and the University Hospital of Bordeaux to develop a computer-based solution with high expected impact on the daily management of cardiac electrical disorders. The research program will benefit from the MUSIC (Magnetom Avanto, Siemens, Erlangen, Germany) equipment recently funded as part of the "Investissement d'Avenir" program, and combining state-of-the-art electrophysiology and magnetic resonance imaging technology. MIGAT will involve software engineers, computer science researchers, cardiologists, radiologists and clinical research personnel with the following objectives: Development of a multimodal data processing software to assist cardiac ablation Optimization and Validation of the software in terms of user experience Optimization and Validation of the software in terms of clinical performance Optimization of software quality compatible with subsequent device certification and randomized-controlled evaluation

The aim of this work is to study the prevalence of T-tubular system in left and right myocytes from patients in sinus rhythm and whether this is altered in paroxysmal and permanent atrial fibrillation. Furthermore, since current information is lacking on the key Ca2+-handling proteins RyR, NCX, and SERCA-2a from patients in Atrial Fibrillation (AF), it will be investigated whether a regulation of these proteins could be an underlying cause of the disease. Mitochondrial function will also studied. The investigators hypothesize that both structure of sarcolemma and localization of key Ca2+-handling proteins are altered in patients with atrial fibrillation compared with patients in sinus rhythm. The investigators hypothesize that mitochondrial function is altered in patients with atrial fibrillation compared with patients in sinus rhythm.

Investigators will assess the impact of treatments for atrial fibrillation on participant's thrombotic status

Background: The incidence of atrial fibrillation(AF) increases substantially with age and it is estimated that more than one third of AF patients are octogenarians. Direct oral anticoagulants (DOACs) were found favorable compared to warfarin with respect to efficacy and safety ( bleeding) across wide range of ages. Nevertheless, the rates of bleeding among elderly patients were shown to increase substantially with all anticoagulants. Dose-adjustments of DOAC are not universally performed among patients older than 80 years old and currently there is paucity of data regarding the actual drugs level among these patients. Accordingly, the investigators sought to investigate the drug levels of the different DOACs among "real world" octogenarians who receiving guideline-recommended dosage. Methods: A cross sectional, prospective study of 120 hospitalized and ambulatory patients who are treated with DOACs for AF. DOACs blood levels with be compared between octogenarians (n=70) and younger patient group ( age≤70 year-old; n=50).The cohort will include: 1)Sixty patients on APIXABAN: 40 octogenarians and 20 younger than 70 years, 2)Forty patients on RIVAROXABAN: 20 octogenarians and 20 younger than 70 years, and 3) Twenty patients treated with DABIGATRAN: 10 octogenarians and 10 younger than 70 years. DOACs Pharmacodynamic analysis will be performed using commercial kits for diluted thrombin time(DTT) and anti-factor Xa activity (AFXa). Drug level will be measured at steady state( through levels) and at Tmax after at least 4 days of complete adherence for DOAC consumption. Study End-Points:The study main objectives are: 1) DOACs levels in octogenarians in comparison to patients younger than 70 years and 2)percentage of patients, in each group, who have target DTT or AFXa ( predicted) at steady state. Potential significance of the study: The results of the study may provide new data on DOACs levels in octogenarians and thus would either support current recommendations or set the ground for further studies aim to optimize DOACs dosage in this vulnerable population.

Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. A novel technology was recently developed to allow an automatic points annotation when indirect parameters of lesion formation reach predefined target values. The aim of the study was to evaluate, in a prospective and multicenter study, the safety, efficiency and PVI effectiveness of a new ablation tracking tool (VISITAG; Biosense Webster) during paroxysmal AF ablation using a contact force sensing catheter.

"Left Atrial Appendage Occlusion and Biomarker Evaluation" (LABEL) is a single-center, prospective and observational study evaluating changes of the expression of biomarkers in eligible patients before and after percutaneous implantation of a left atrial appendage (LAA) occlusion device at mid-term follow-up.

Genomic studies on atrial fibrillation patients have identified polymorphisms in regions surrounding the PITX2 gene, suggesting it could be the locus responsible for atrial fibrillation. The PITX2 gene is essential for establishing the asymmetry between systemic and pulmonary blood flow, which is absolutely required for proper heart functions. In addition, PITX2 is required for the development the atrium myocardium. Investigators have performed transcriptomic analysis on left atrium tissues from atrial fibrillation patients and identify genes whose expression is altered in atrial fibrillation. Among affected genes, PITX2 expression is strongly decreased in the left atrium of atrial fibrillation patients. Moreover, investigators observed that the PITX2 promoter region is hypermethylated in atrial fibrillation patients. Interestingly, DNA methylation is a key actor of gene expression and directly regulates RNA transcription either by directly modulating transcription factor (TF) binding to gene promoters or by modifying local chromatin structures, therefore limiting access of TFs to DNA. These epigenetic modifications are reversible and therefore represent an interesting therapeutic target. Hence, many compounds that inhibit DNA methyl-transferase are currently tested in different disease models. Recently-designed hypomethylating molecules are available, such as the 5'azacytidine (Vidaza®, Celgen Inc.) or the 5-aza-2'-deoxycytidine (Decitabine) (Dacogen®, Janssen Cilag). Investigators have performed preliminary studies on the effect of Decitabine on DNA methylation and proper cardiac function recovering in a SHR model. Results indicate that the chronic delivery of Decitabine improves the arrhythmia profile by reducing tachyarrhythmia, fibrosis, as well as the oxidative stress in SHR left atrium submitted Acute Leukemia is a rare pathology with an incidence of 4 per 100,000 in France. Azacytidine, which is closely related to Decitabine, is commonly used for treating Acute Leukemia and possesses anti-neoplastic effect through multiple mechanisms, including direct cytotoxicity of blood cancer cells and DNA hypomethylation. The goal of this study is to evaluate the effects of azacytidine on arrhythmia and left atrium fibrosis as well, which are the two mains phenotypic manifestation of atrial fibrillation in humans. Investigators hypothesize that azacytidine decreases PITX2 promoter methylation and increases PITX2 expression. Hence, investigators expect to ameliorate the duration of atrium action potential and to observe a decrease of atrium fibrosis.

The optimal antithrombotic treatment for Coronary Heart disease (CHD) patients combined with Atrial Fibrillation (AF) is unresolved at present. Although the European and American guidelines have given a hand for us, there is absence of real-world data on the safety and efficacy of antithrombotic therapy in Asian populations. Only a few clinical trials are available to guide difficult decision on antithrombotic therapy in patients with combined AF and CHD，the investigators highlight the need for the rapid development of clinical trials to close the large gaps in evidence. This research aims to know the real-world use of antithrombotic treatment and clinical prognosis in Coronary Heart Disease patients complicated with Atrial Fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmias with a constantly growing prevalence. Two main techniques are used today to restore sinus rhythm: electrical cardioversion and radiofrequency ablation. Radiofrequency ablation has become a recognized and effective treatment of AF. Despite a relatively high success rate (about 80%), a substantial number of patients require a second procedure to obtain sinus rhythm. Many publications have led to the study of predictors of failure of this ablation factors (BMI, uncontrolled hypertension, size of the OG...) but to date no parameter is reliable and usable in daily practice. It is the same for electrical cardioversion. Despite a relatively high immediate success rate of approximately 80%, a significant number of patient relapse arrhythmia in short and long term. Many publications have led to the study of predictive factors of failure (seniority and type of AF, uncontrolled hypertension, size of the OG, mitral valve disease...) but so far the results are disappointing. In AF patients with heart disease underlying, it has been well demonstrated that the renin-angiotensin system (RAAS) was strongly activated. In addition, it is now well established that elevated plasma aldosterone as in primary hyperaldosteronism is associated with a significantly increased risk of occurrence of cardiovascular events. The high plasma concentrations were also highlighted in the acute phase of myocardial infarction, or heart failure and are associated with an increase in major cardiovascular event rate, especially arrhythmias. In some experimental models of heart failure, it has been demonstrated a suppression of the occurrence of spontaneous FA by an anti-aldosterone treatment. The arrhythmogenic effect of aldosterone has also been shown in animal models. All these results indicate a potential role of aldosterone in the genesis of an arrhythmogenic substrate and the FA. The hypothesis of this study is that aldosterone plasma levels in pre-reduced patients is predictive of recurrence risk of atrial fibrillation or other supraventricular tachycardias (flutter or atrial tachycardia) after FA reduction, either in using a radiofrequency ablation or via electrical cardioversion.

According to current guidelines for non-valvular atrial fibrillation treatment, the first line drugs are non-vitamin K oral anticoagulants (NOACs), which are preferred over vitamin K antagonists (VKAs). However, it is not clearly confirmed, how the success of NOACs approval trials (ROCKET-AF (rivaroxaban), RE-LY (dabigatran) and ARISTOTLE (apixaban) reflects on real-life clinical practice. The aim of this study is to assess treatment of AF patients with oral anticoagulants (OACs) in an academic and district hospital, with regard to inclusion/exclusion criteria used in the clinical trials.