Genetic Polymorphisms, Heart Failure
Conditions
Brief summary
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown further reductions in heart failure hospitalization, cardiovascular events, and mortality, especially for heart failure patients. The SGLT2 gene, also known as SLC5A2 (solute carrier family 5 member 2), is located on chromosome 16 and is responsible for encoding SGLT2. Several SLC5A2 mutations alter SGLT2 expression, membrane location, or transporter function. Several common genetic variations were found in the SLC5A2 gene that may affect the response to treatment with SGLT2 inhibitors.
Detailed description
Sodium-glucose cotransporter-2 inhibitors (SGLT-2i), which were first investigated and licensed for the treatment of diabetes, are now emerging as a promising class of drugs for the treatment of heart failure (HF), even in people without diabetes. Significant reductions in worsening heart failure or cardiovascular death were shown under treatment with dapagliflozin and empagliflozin in the trials of patients with heart failure. Several common genetic variations were found in the SLC5A2 gene that may affect the response to treatment with SGLT2 inhibitors. The most recent SLC5A2 Single Nucleotide Polymorphisms (SNPs) that reduce the risk of heart failure included two intronic SLC5A2 SNPs, s9934336, and rs3116150, both associated with the expression levels of the transporter. This study aims to detect the association between SLC5A2 single nucleotide polymorphisms and variability in response to SGLT2 Inhibitors as well as the association between cardiac biomarkers and non-coding RNA in patients with Heart Failure.
Interventions
10 mg of dapagliflozin or empagliflozin
Sponsors
University of Florida
National Heart Institute, Egypt
Beni-Suef University
October 6 University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Heart failure patients NYHA class II to III. * Heart failure patients with reduced left ventricular ejection fraction (LVEF) \< 45% or with preserved left ventricular ejection fraction (LVEF) \> 45% * Patients who will be candidate for add-on treatment with SGLT2. * Patients who will be able to sign informed consent to participate in the study.
Exclusion criteria
* Contraindications to SGLT2. * Significant coronary artery diseases (CAD), coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or valve surgery within 3 months. * Pregnant or breastfeeding women. * Patients with estimated glomerular filtration rates less than 30 mL/min/1.73 m2, as determined using the CKD-EPI equation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median / Mean of Left Ventricular End Diastolic Volumes among studied genetic polymorphisms | 6 months | Change in median / mean of Left Ventricular End Diastolic Volume (LVEDV) before and after drug administration |
| Median / Mean of Left Ventricular Ejection Fraction (LVEF) among studied genetic polymorphisms | 6 months | Change in median / mean of Left Ventricular Ejection Fraction (LVEF) before and after drug administration |
| Median / Mean of Left Ventricular End Systolic Volumes among studied genetic polymorphisms | 6 months | Change in median / mean of Left Ventricular End Systolic Volume (LVESV) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median / Mean of quality of life measure {Kansas City Cardiomyopathy Questionnaire (KCCQ-12)} among studied genetic polymorphisms | 6 months | Change in median / mean of Kansas City Cardiomyopathy Questionnaire (KCCQ-12) before and after drug administration |
Countries
United States
Contacts
Primary ContactAhmed Essam, MSc
Outcome results
None listed