The main aim of this study is to holistically assess the cardiovascular and renal outcomes in HFpEF CKD patients with and without SGLT2 inhibition, with focus on the endothelial disfunction, MACE and mortality using clinical evaluation, flow mediated dilatation, carotid-femoral pulse wave velocity, intima-media thickness, echocardiographic parameters, NMR metabolomics and a series of novel biomarkers.
age>18 years;
ejection fraction > 40;
patients with CKD stage 3-4 (eGFR between 15-60 mL/min/1.73m2), with iSGLT2 recommendation, diabetic and non-diabetic;
age, sex and CKD stage 3 and 4 matched patients without iSGLT2 administration.
eGFR< 15 mL/min/1.73m2 or patients undergoing dialysis;
presence of congenital heart disease, decompensated cirrhosis, pregnancy and active malignancies;
coronary artery disease (including those with a history of acute coronary syndrome, angina pectoris, or prior coronary angiography or CT angiography demonstrating significant coronary artery lesions);
cardiac medical devices, namely metallic joint prostheses, cardiac stent or pacemakers;
Patients with CKD stages 3 and 4 (eGFR calculated by CKD-EPI) with HFpEF
Case-control
Prospective
Arterial stiffness
Diagnostic testArterial stiffness assessment will be performed by applanation tonometry with the patient being recumbent, 10 minutes before the measures were done. The carotid and femoral pulse will be acquired by applanation tonometry sequentially, allowing a single operator to acquire the measurement. The transit time from the R-wave of the simultaneously acquired electrocardiogram to the foot of the carotid and femoral pulse is measured. The difference acquired electrocardiogram to the foot of the carotid and femoral pulse is measured. The difference between these 2 transit times is divided by distances measured from the body surface to estimate the arterial path length in order to calculate carotid-femoral PWV.
Echocardiography
Diagnostic testEchocardiography will be performed on each patient at baseline; the measurements will be carried out according to the recommendations of the American Society of Echocardiography. Echocardiographic evaluation will provide information about cardiac anatomy (e.g. volumes, geometry, mass) and function (e.g. left ventricular function and wall motion, valvular function, right ventricular function, pulmonary artery pressure, pericardium).
Biomarkers determination
Other interventionNT-pro BNP, Syndecan-1, VCAM-1, Endoglin, NO and ADMA will be determined by specific enzyme linked immunosorbent assay (ELISA) kits.
NMR metabolomics and uremic toxins mapping
Other interventionThe aliquoted serum preserved at -80° C will be analysed by NMR using deuterated solvents (D2O, CDCl3, CD3OD, CD3CN), standards of metabolites and uremic toxins.
MACE
Composite CV outcome: time to first non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure or CV death
All-cause mortality
All-cause mortality
Composite renal outcome
Rapid progression of renal disease - defined as sustained annual decline of at least 5mL/min/1,73m2 in eGFR or a sustained drop of 25% or more in eGFR within 10 months
Changes in cardiac biomarkers
Blood levels of NT-pro BNP, Syndecan-1, VCAM-1, Endoglin, NO and ADMA will be measured at baseline and months 10 and 20. The outcome is defined as the change from baseline.
Changes in the NMR metabolomics and uremic toxins mapping
Blood levels of NMR metabolomics and uremic toxins will be measured at baseline and months 10 and 20. The outcome is defined as the change from baseline.
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Grigore T. Popa University of Medicine and Pharmacy
Lead sponsor
Dr. C.I. Parhon Hospital, Iasi
Collaborator
The Executive Agency for Higher Education, Research, Development and Innovation Funding
Collaborator
