Role and Interactions of Adenosine, Receptors, Methionine Cycle Nutritional, Metabolic and Genetic Determinants in the Onset of Atrial Fibrillation in Normal Heart (FACS)

Central Hospital, Nancy, France

Status: Unknown

Conditions: Atrial Fibrillation

Treatments: Other: Quantitative and qualitative nutritional evaluation; Biological: Blood sample; Genetic: Polymorphism analysis of genes related to adenosine metabolism and methionine cycle; Other: Quantification assay of adenosine and methionine cycle metabolites

Study type: Interventional

Funder types: Other

Identifiers

NCT02885740

2009-A01197-50

Details and patient eligibility

About

The purpose of this study is to analyze the association of atrial fibrillation onset in normal heart and:

• Genetic determinants (genes of receptors, enzymes involved in synthesis and degradation, genes of bioavailability of coenzymes and nutritional precursors)
• Metabolic determinants of adenosine and methionine cycles
• Nutritional determinants.

Secondary purposes are:

• Analysis of physiopathologic mechanisms of AF in normal hearts and adenosine metabolisms and its interaction with methionine metabolism, according to identified genetic determinants
• Analysis of blood markers of adenosine and methionine metabolites as phenotypic markers of detected polymorphisms
• Evaluate the role of adenosine receptors in AF onset

Full description

Atrial fibrillation (AF) is the most frequent arrhythmia and its causes are not well known. Experimental and clinical studies showed that activation of parasympathetic system can induce and maintain AF. Adenosine is a cardiovascular modulator with effects on vascular tonus and activation of nodal tissue through the activation of A1, A2A, A2B et A3 receptors. Intracellular production of adenosine is directly dependent (30%) on the hydrolysis of S-adenosylhomocysteine (SAH) by S-adenosylhomocysteine hydrolase in methionine cycle. Cellular production of adenosine depends on ratio SAH/S-adenosylmethionine (SAM) and modulates the expression of receptors. Other potential interactions between this 2 metabolisms in AF are: 1) ratio SAM/SAH influences epigenetic mechanisms that can modify the expression of candidate genes involved in synaptic transmission and potassium canals, 2) ratio SAM/SAH influences also the cellular production of homocysteine with effects on cellular polarization, 3) adenosine and homocysteine are factors involved in thrombophilia and potentially associated to thromboembolic complications of AF.

This study will evaluate the genetic (micro SNP-array) and adenosine and methionine metabolic determinants in the physiopathology of AF in normal hearts.

Perspectives of this study are the prevention of AF in normal hearts through a nutritional and metabolic approach in subjects having a multigenic predisposition.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Informed consent
• Affiliation to French social security plan

AF in normal heart:

• Atrial fibrillation in normal heart

Control:

• Junctional supraventricular tachycardia in normal heart

Normal heart: absence of macroscopic cardiomyopathy (echocardiography and normal ejection fraction)

Exclusion criteria

• Considerable consumption of coffee (> 50 mg/day, 15 cups/day)
• Actual administration of drugs interfering with adenosine metabolism: dipyridamole and methotrexate
• Actual administration interfering with methionine metabolism: folates, methotrexate and anticonvulsants
• Known renal insufficiency
• Known hypo- or hyperthyroidism
• Refusal or impossibility of informed consent
• Pregnant or breastfeeding women
• Person deprived of liberty
• Person under legal protection or not able to consent
• Person in emergency situation

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

Atrial fibrillation in normal heart

Experimental group

Description:

Patients having atrial fibrillation in normal heart

Treatment:

Other: Quantification assay of adenosine and methionine cycle metabolites

Biological: Blood sample

Genetic: Polymorphism analysis of genes related to adenosine metabolism and methionine cycle

Other: Quantitative and qualitative nutritional evaluation

Control

Active Comparator group

Description:

Patients having a junctional supraventricular tachycardia in normal heart

Treatment:

Other: Quantification assay of adenosine and methionine cycle metabolites

Biological: Blood sample

Genetic: Polymorphism analysis of genes related to adenosine metabolism and methionine cycle

Other: Quantitative and qualitative nutritional evaluation