SGLT2-MICRA: Expression of Sodium-glucose Co-transporter 2 in Human Heart

Sponsor

University Hospital, Strasbourg, France (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05830760

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the study is to evaluate the expression of Sodium Glucose Co-transporter 2 (SGLT2) in myocardium from patients with aortic stenosis. 2 groups of patients will be defined: Group A with diastolic heart failure and Group B without heart failure. The expression of SGLT2 will be measured on small myocardium specimens harvested during aortic valve replacement operation. This study should allow us to better understand the effect of glifozines in human heart failure.

Condition or Disease	Intervention/Treatment	Phase
Aortic Valve Stenosis	Biological: Myocardium biopsy	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Expression of Sodium Glucose Co-transporter2 in Myocardium From Patients With Aortic Valve Stenosis and With/Without Diastolic Heart Failure

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2025

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: patients with aortic valve stenosis with heart failure	Biological: Myocardium biopsy The expression of SGLT2 on small myocardium specimens harvested during aortic valve replacement operation in patients with aortic stenosis
Experimental: patients with aortic valve stenosis without heart failure	Biological: Myocardium biopsy The expression of SGLT2 on small myocardium specimens harvested during aortic valve replacement operation in patients with aortic stenosis

Arm

Intervention/Treatment

Experimental: patients with aortic valve stenosis with heart failure

Biological: Myocardium biopsy

The expression of SGLT2 on small myocardium specimens harvested during aortic valve replacement operation in patients with aortic stenosis

Experimental: patients with aortic valve stenosis without heart failure

Biological: Myocardium biopsy

The expression of SGLT2 on small myocardium specimens harvested during aortic valve replacement operation in patients with aortic stenosis

Outcome Measures

Primary Outcome Measures

To study the expression levels of SGLT2 in the myocardium of patients with surgical aortic stenosis [Day 0]
Measure of SGLT2 expression level by RT-PCR and
To study the SGLT2 tissue localization in the myocardium of patients with surgical aortic stenosis [Day 0]
SGLT2 expression level by immunofluorescence labeling

Secondary Outcome Measures

Comparison of SGLT2 expression levels between heart failure and non-heart failure patients. [Day 0]
SGLT2 expression levels between the 2 groups of patients
Assess oxidative stress [Day 0]
Pro-oxidant response (fluorescence level of the redox-sensitive fluorescent probe DHE)
Evaluate the pro-inflammatory response by analysing the expression level of tissue activation molecules VCAM-1, ICAM-1, MCP-1 [Day 0]
Pro-inflammatory response: (VCAM-1, ICAM-1, MCP-1). Expression level of tissue activation molecules VCAM-1, ICAM-1, MCP-1 by RT-PCR, Western blot analysis and immunofluorescence labeling
Evaluate the pro-fibrotic response [Day 0]
Pro-fibrotic response: TGF beta, Ang II, AT1R, ACE, collagen; MMP-2, MMP-9. Expression level of molecules involved in tissue remodeling TGF beta, Ang II, AT1R, ACE, collagen, MMP-2, MMP-9 by RT-PCR, Western blot analysis and immunofluorescence labeling
Evaluate the pro-senescent response [Day 0]
Pro-senescent response: SA-beta-galactosidase activity, p53, p21, P16. Determination of senescence-associated beta-galactosidase activity on cardiac muscle cryosections, and expression level of senescence mediators p53, p21, p16 by RT-PCR, Western blot analysis and immunofluorescence labeling
Evaluate the pro-thrombotic response [Day 0]
Pro-thrombotic response: tissue factor. Expression level of coagulation cascade activator, tissue factor by RT-PCR, Western blot analysis and immunofluorescence labeling
Evaluate endothelial dysfunction [Day 0]
Endothelial response: eNOS, NO, nitrotyrosine. Expression level of eNOS and nitrotyrosine by RT-PCR, Western blot analysis and immunofluorescence labeling and NO formation using the NO-sensitive fluorescent probe, DAF-FM on heart muscle cryosections

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

adults over 18 years-old
Patient with surgical aortic valve stenosis, with or without heart failure, in two equal-sized groups (40 subjects in each group)
Subjects affiliated with a social security health insurance plan
Subject able to understand the objectives and risks of the research and to give dated and signed informed consent

Exclusion Criteria:

Infective endocarditis in aortic stenosis
Severe coronary pathology associated with aortic stenosis
Impossible to give the subject informed information (subject in emergency situation, difficulties in understanding the subject, ...)
Subject under legal protection
Subject under guardianship or curatorship
Pregnancy and/or breastfeeding