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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Biological: Myocardium biopsy

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67098
    • Hopitaux Universitaires de Strasbourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of SGLT2 expression levels between heart failure and non-heart failure patients.	SGLT2 expression levels between the 2 groups of patients	Day 0
Assess oxidative stress	Pro-oxidant response (fluorescence level of the redox-sensitive fluorescent probe DHE)	Day 0
Evaluate the pro-inflammatory response by analysing the expression level of tissue activation molecules VCAM-1, ICAM-1, MCP-1	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	Day 0
Evaluate the pro-fibrotic response	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	Day 0
Evaluate the pro-senescent response	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	Day 0
Evaluate the pro-thrombotic response	Pro-thrombotic response: tissue factor. Expression level of coagulation cascade activator, tissue factor by RT-PCR, Western blot analysis and immunofluorescence labeling	Day 0
Evaluate endothelial dysfunction	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	Day 0

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: March 24, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 26, 2023

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: heart failure; aortic valve stenosis; myocardium; human heart; sodium glucose cotransporter 2
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Heart Failure; Aortic Valve Stenosis
• Other Study ID Numbers: 8774 (Duke legacy protocol number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No