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
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:
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
Introduction Acute myocardial infarction (MI) remains one of the leading causes of cardiovascular morbidity and mortality worldwide. It typically results from acute coronary artery occlusion caused by rupture or erosion of an atherosclerotic plaque followed by thrombus formation. Despite major advances in early reperfusion strategies and evidence-based pharmacological therapies, patients surviving MI remain at increased risk for adverse cardiovascular outcomes, including heart failure, recurrent myocardial infarction, and cardiovascular death.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors have recently emerged as a major therapeutic class with pleiotropic cardiometabolic benefits. Large randomized clinical trials have demonstrated that SGLT2 inhibitors significantly reduce the risk of hospitalization for heart failure and cardiovascular death in patients with type 2 diabetes mellitus as well as in patients with heart failure irrespective of diabetic status. These benefits 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 exert favorable effects on vascular stiffness, endothelial function, and myocardial remodeling. However, data regarding their impact on arterial stiffness, endothelial glycocalyx integrity, and myocardial deformation indices following acute ST-segment elevation myocardial infarction (STEMI) remain limited.
Understanding these effects may provide valuable mechanistic insights into the cardioprotective properties of SGLT2 inhibitors and help optimize post-MI management strategies.
Purpose of the Study 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 left atrial (LA) and left ventricular (LV) myocardial deformation during a 12-month follow-up period in patients with ST-segment elevation myocardial infarction (STEMI).
Secondary objectives of the study include:
Materials and Methods This prospective observational study will include adult patients diagnosed with acute ST-segment elevation myocardial infarction (STEMI) who are hospitalized at the Second University Cardiology Clinic of "Attikon" General Hospital.
Prior to participation, all individuals will provide written informed consent in accordance with the principles outlined in the Declaration of Helsinki.
A comprehensive clinical assessment will be performed for all participants, including detailed medical history, physical examination, and laboratory evaluation.
Participants will be allocated into two study groups:
Group A: Patients receiving empagliflozin 10 mg once daily, initiated either at hospital discharge due to the presence of type 2 diabetes mellitus, or without diabetes who exhibit reduced left ventricular ejection fraction (LVEF <40%).
Group B (Control Group): Patients who will not receive empagliflozin therapy. All participants will receive guideline-directed medical therapy for acute myocardial infarction according to the current European Society of Cardiology (ESC) guidelines.
The anticipated study population will consist of 80 patients, with 40 participants in each group.
Exclusion Criteria
The following conditions will constitute exclusion criteria:
Measurements All participants will undergo the following evaluations at baseline and at 3, 6, and 12 months following study enrollment.
Arterial Stiffness Arterial stiffness will be evaluated through the measurement of carotid-femoral pulse wave velocity (cf-PWV) using the Complior SP device (Alam Medical, Vincennes, France). Pulse wave velocity represents the gold-standard non-invasive method for assessing large-artery stiffness. Two pressure sensors will be placed over the carotid and femoral arteries to simultaneously record arterial pressure waveforms. The distance between the two recording sites will be measured using a standardized surface measurement technique. Pulse wave velocity will be calculated as the ratio between the measured arterial distance and the transit time between waveforms (expressed in m/s). Additionally, 24-hour ambulatory pulse wave analysis will be performed using the Mobil-O-Graph device (IEM GmbH) to obtain central hemodynamic parameters, including central systolic and diastolic blood pressure.
Endothelial Function Endothelial function will be assessed through evaluation of endothelial glycocalyx thickness in sublingual microvessels (diameter 5-25 μm) using Sidestream Dark Field (SDF) imaging with the GlycoCheck system (Microvascular Health Solutions Inc., Salt Lake City, Utah, USA). This non-invasive technique enables quantitative analysis of glycocalyx integrity by measuring the Perfused Boundary Region (PBR), which reflects the penetration depth of circulating erythrocytes into the glycocalyx layer. Increased PBR values indicate impaired glycocalyx barrier function and reduced glycocalyx thickness. The analysis is performed automatically by specialized software that evaluates thousands of microvascular segments, ensuring high reproducibility and minimizing operator-dependent variability.
Cardiac Deformation Cardiac deformation will be assessed using two-dimensional speckle-tracking echocardiography with dedicated analysis software (EchoPac PC 206, GE Healthcare, Horten, Norway). Global longitudinal strain (GLS) of the left ventricle will be calculated using the standard 17-segment LV model derived from apical four-chamber, two-chamber, and three-chamber views. GLS represents a sensitive marker of subclinical myocardial dysfunction and ventricular remodeling. Left atrial function will be evaluated through LA strain analysis, which provides information on atrial reservoir, conduit, and contractile function. LA reservoir strain will be calculated as the peak longitudinal strain during ventricular systole and reflects atrial compliance and reservoir capacity.
Oxidative stress burden Oxidative stress burden will be assessed by measuring circulating levels of malondialdehyde (MDA) and protein carbonyls (PCs), which are widely recognized biomarkers of lipid peroxidation and oxidative protein damage. MDA concentrations will be determined spectrophotometrically using a commercial lipid peroxidation colorimetric assay kit (Oxford Biomedical Research, Rochester Hills, MI) with a measurement range of 1-20 nmol/L. Protein carbonyl (PCs) levels will be quantified using spectrophotometric detection of 2,4-dinitrophenylhydrazine-derived carbonyl compounds.
Statistical Analysis Statistical analyses will be conducted using SPSS version 29 (IBM SPSS Statistics, Inc., Chicago, IL). Continuous variables will be expressed as mean ± standard deviation (SD) when normally distributed, as determined by the Kolmogorov-Smirnov and Shapiro-Wilk normality tests. Non-normally distributed variables will be appropriately transformed or presented as medians with interquartile ranges. Categorical variables will be presented as frequencies and percentages. Associations between continuous variables will be evaluated using Pearson or Spearman correlation coefficients, depending on the distribution of the data. Comparisons between categorical variables will be performed using Chi-square tests or Fisher's exact tests.vThe changes in the measured vascular and myocardial parameters will be assessed using repeated-measures analysis of variance (ANOVA), considering time points (baseline, 3 months, 6 months, and 12 months) as the within-subject factor and treatment group as the between-subject factor. When appropriate, Bonferroni post-hoc corrections will be applied.Violation of the sphericity assumption will be addressed using Greenhouse-Geisser or Huynh-Feldt corrections. All statistical tests will be two-tailed, and a p-value <0.05 will be considered statistically significant.
Inclusion Criteria:
Exclusion Criteria:
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