Involvement of the Gut Microbiota in Calcified Aortic Stenosis

Involvement of the Gut Microbiota and Its Metabolites in the Pathophysiology of Calcified Aortic Stenosis

Calcific aortic stenosis (CAS) is a disease characterized by progressive calcification of the aortic valve, obstructing the passage of blood from the left ventricle into the general circulation. It is the most frequent cause of valve disease in the elderly. To date, no means of preventing the disease has been discovered, and the only treatment available is valve replacement during cardiac surgery, or percutaneous implantation of a valve prosthesis when the narrowing becomes severe and causes symptoms.

The intestinal flora or microbiota, the reservoir of all the microorganisms in the gut, is implicated in numerous diseases, particularly of the intestine. But to date, no study has established a link between CAS and microbiota. The intestinal microbiota acts through molecules produced by itself or the host and passing into the bloodstream. In the pathophysiology of CAS, the valve leaflets are breached and do not heal. These molecules can enter and have beneficial or deleterious effects, in particular promoting calcification of aortic valve cells.

Concrete objectives:

Improve understanding of calcific aortic stenosis in humans Study the composition of intestinal flora in patients with aortic stenosis and compare it with healthy subjects Study the molecules in the intestinal flora likely to be involved in the development of aortic stenosis in humans.

Inclusion Criteria:

• Group of patients with CAS:
• Calcified aortic stenosis diagnosed on a cardiac ultrasound or CT not older than 3 months
• Severe aortic stenosis: surgical indication based on symptoms and ultrasound data (high gradient aortic stenosis : Vmax> 4m/s, mean gradient > 40mmHg, area < 1cm², low flow low-gradient CAS: left ventricular ejection fraction (LVEF) < 40%, Vmax< 4m/s, mean gradient < 40mmHg, area < 1cm², paradoxical low-gradient CAS: LVEF > 55%, Vmax< 4m/s, mean gradient < 40mmHg, area < 1cm²)
• Moderate CAS: 3m/s <Vmax< 4m/s, 20mmHg < mean gradient < 40mmHg
• Mild CAS: 2,6m/s < Vmax < 2.9m/s, mean gradient < 20mmHg
• Aortic sclerosis: calcified remodeling of the aortic valve visible on ultrasound or CT.

Control group - free of CAS:

- No calcified aortic stenosis verified on a cardiac ultrasound or CT not older than 3 months

Exclusion Criteria:

• Treatment interfering with the composition of the intestinal microbiota: local or systemic corticosteroids within the last 3 months, antibiotics within the last 3 months, antiretrovirals, bile acid chelators (questran and colesevelam), HIV-targeted antiretroviral therapies, selective serotonin reuptake inhibitor-type antidepressants
• Clinical criteria: history of cholecystectomy, documented chronic liver disease in the patient, failure to fast on the day of the blood test, inflammatory bowel disease
• Patients requiring emergency intervention (myocardial infarction, acute aortic or mitral insufficiency, cardiogenic shock).
• AS of rheumatic origin, infective endocarditis.