The Effect of Sodium Glucose Co-trnasportert Type 2 Inhibitors on Arterial Stiffness, Endothelial Glycocalyx Thickness , Left Atrial and Left Ventricular Deformation After Acute Myocardial Infarction

Acute myocardial infarction (MI) remains one of the leading causes of cardiovascular morbidity and mortality worldwide. It most commonly occurs due to acute coronary artery occlusion following rupture or erosion of an atherosclerotic plaque and subsequent thrombus formation. Despite significant advances in reperfusion strategies and guideline-directed pharmacological therapy, patients who survive MI remain at increased risk for adverse cardiovascular outcomes, including heart failure, recurrent myocardial infarction, stroke, and cardiovascular death. Therefore, additional therapeutic strategies that may improve vascular function, myocardial remodeling, and overall cardiovascular prognosis following MI are of considerable clinical interest.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have recently emerged as an important pharmacological class with significant cardiometabolic benefits. Large randomized clinical trials have demonstrated that SGLT2 inhibitors reduce the risk of hospitalization for heart failure and cardiovascular mortality in patients with type 2 diabetes mellitus and in patients with heart failure irrespective of diabetic status. The cardioprotective effects of these agents appear to extend beyond glycemic control and include improvements in myocardial energetics, vascular function, inflammation, and oxidative stress. Emerging evidence suggests that SGLT2 inhibitors may also exert beneficial effects on vascular stiffness, endothelial function, and myocardial remodeling. However, data regarding their potential impact on arterial stiffness, endothelial glycocalyx integrity, and myocardial deformation parameters in the early post-myocardial infarction setting remain limited.

The primary aim of the present study is to investigate the effect of empagliflozin administration (10 mg daily) on arterial stiffness, endothelial glycocalyx thickness, and myocardial deformation indices of the left ventricle and left atrium during a 12-month follow-up period in patients presenting with ST-segment elevation myocardial infarction (STEMI).

Secondary objectives include:

1. evaluation of the incidence of major adverse cardiovascular events (MACE), defined as cardiovascular death, recurrent myocardial infarction, and acute ischemic stroke;
2. investigation of the association between the occurrence of MACE and vascular and myocardial functional parameters, including indices of arterial stiffness, endothelial glycocalyx integrity, and myocardial strain measurements; and
3. assessment of oxidative stress burden through circulating biomarkers. This prospective observational study will include adult patients diagnosed with acute STEMI who are hospitalized in the Second University Cardiology Clinic of "Attikon" General Hospital. All participants will provide written informed consent prior to enrollment and will receive standard guideline-directed therapy for acute myocardial infarction according to the current European Society of Cardiology (ESC) guidelines.

Participants will be allocated into two groups. Group A will include patients receiving empagliflozin 10 mg once daily, initiated either at hospital discharge in patients with concomitant type 2 diabetes mellitus or in patients without diabetes who present with reduced left ventricular ejection fraction (LVEF <40%). Group B will serve as the control group and will not receive empagliflozin therapy. The anticipated sample size of the study is 80 patients, with approximately 40 participants in each group.

Exclusion criteria include chronic kidney disease with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m², active malignancy, autoimmune or autoinflammatory disorders, severe hepatic impairment, and pregnancy or breastfeeding.

Participants will undergo detailed evaluation at baseline and at 3, 6, and 12 months. Arterial stiffness will be assessed through measurement of carotid-femoral pulse wave velocity (cf-PWV) using the Complior SP system, which represents the gold standard non-invasive method for evaluating large-artery stiffness. In addition, 24-hour pulse wave analysis will be performed using the Mobil-O-Graph device to obtain central hemodynamic parameters.

Endothelial function will be evaluated through assessment of endothelial glycocalyx thickness in sublingual microvessels using Sidestream Dark Field (SDF) imaging with the GlycoCheck system. Glycocalyx integrity will be quantified by the Perfused Boundary Region (PBR) index, which reflects erythrocyte penetration into the glycocalyx layer and serves as a marker of endothelial barrier dysfunction.

Cardiac structure and function will be assessed using two-dimensional speckle-tracking echocardiography. Global longitudinal strain (GLS) of the left ventricle will be calculated using the standard 17-segment model from apical views, while left atrial strain will be measured to evaluate atrial reservoir and contractile function, providing sensitive markers of myocardial remodeling after infarction