Effect of Dapagliflozin on Metabolomics and Cardiac Mechanics in Chronic Kidney Disease

This is a 6-month interventional patient-oriented research study of sixty patients with chronic kidney disease (CKD) and evidence of subclinical heart failure with preserved ejection fraction (HFpEF) (estimated glomerular filtration rate \[eGFR\] 25-60 ml/min/1.73m2, absolute left ventricular longitudinal strain \[LVGLS\] \<18% or left atrial reservoir strain (LARS) \< 25% on 2D-speckle tracking echocardiography or meeting 3/5 of the American Society of Echocardiography criteria for diastolic dysfunction: septal e' \<7 cm/sec, lateral e'\<10 cm/sec, average E/e' ratio\>14, left atrial volume index \>34 mL/m2, or peak tricuspid regurgitation velocity \>2.8 m/sec), or peak VO2 Females: ≤ 18 mL/kg/min, peak VO2 Males: ≤ 20 mL/kg/min on cardiopulmonary exercise testing, or lack of augmentation of LVLS or LARS during exercise. Half of the patients will be randomized to receive dapagliflozin for six months as an add-on to standard of care (SOC). Metabolomic testing and cardiac and functional exercise testing will be done at baseline and at six months. The aim of the current study is to investigate whether SGLT2i-induced metabolomic changes are associated with improved cardiac and functional testing ascertained on 2D-speckle tracking echocardiography or cardiopulmonary functional testing at six months.