Action of the Vidaza on the Atrial Fibrillation

Study Overview
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Brief Summary
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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.

Official Title
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Action of the Vidaza on the Atrial Fibrillation

Conditions
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Atrial Fibrillation, Acute Leukemia

Intervention / Treatment
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* Other: Effect of Vidaza treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old Patient with history of paroxysmal atrial fibrillation, and /or presenting a dilatation of the left atrium. Patient selected for a first Vidaza® treatment Non-opposition of the patient to participate in the study Exclusion Criteria: Age < 18 years old No paroxysmal atrial fibrillation Patients with previous history of Vidaza® treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Vidaza patients<br>This study will be performed on adults with Acute Myeloid Leukemia and atrial fibrillation. Only patients treated for the first time with vidaza® within an hospital hematology unit will be included. | Other: Effect of Vidaza treatment<br>* The goal of this study is to evaluate the effects of azacytidine on arrhythmia and left atrium fibrosis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of atrial arrhythmic events | Evolution of the atrial arrhythmic events observed in the inclusion, 6 months or 12 months (according to the frequency of follow-up of the atrial fibrillation) after the beginning of the cure by Holter-ECG. | Maximum 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of the morphology and the fibrosis atrial | Evolution of the morphology and the fibrosis atrial observed in the inclusion, 6 months or 12 months (according to the frequency of follow-up of the atrial fibrillation) after the beginning of the cure by transthoracic echocardiography. | Maximum 12 months |