Effect of Genetic Polymorphisms on the Clinical Response to SGLT2 Inhibitors in Heart Failure Patients

Effect of Genetic Polymorphisms on the Clinical Response to Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors in Prevention of Cardiac Remodeling and Fibrosis in Heart Failure Patients

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.

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.

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.