Empagliflozin Reduces Myocardial Extracellular Volume in Patients With Type 2 Diabetes and Coronary Artery Disease |
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| Authors: | Tamique Mason Otavio R. Coelho-Filho Subodh Verma Biswajit Chowdhury Fei Zuo Adrian Quan Kevin E. Thorpe Christopher Bonneau Hwee Teoh Richard E. Gilbert Lawrence A. Leiter Peter Jüni Bernard Zinman Michael Jerosch-Herold C. David Mazer Andrew T. Yan Kim A. Connelly |
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| Affiliation: | 1. Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael''s Hospital, Toronto, Ontario, Canada;2. Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada;3. Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, Brazil;4. Division of Cardiology, Department of Medicine, State University of Campinas, Campinas, Brazil;5. Department of Surgery, University of Toronto, Toronto, Ontario, Canada;6. Applied Health Research Centre, Li Ka Shing Knowledge Institute of St. Michael''s Hospital, Toronto, Ontario, Canada;7. Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada;8. Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute of St. Michael''s Hospital, Toronto, Ontario, Canada;9. Department of Medicine, University of Toronto, Toronto, Ontario, Canada;10. Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada;11. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada;12. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada;13. Heart and Vascular Center, Brigham and Women''s Hospital, Harvard Medical School, Boston, Massachusetts, USA;14. Department of Anesthesia, Li Ka Shing Knowledge Institute of St. Michael''s Hospital, Toronto, Ontario, Canada;15. Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada;p. Department of Physiology, University of Toronto, Toronto, Ontario, Canada;q. Division of Cardiology, Li Ka Shing Knowledge Institute of St. Michael''s Hospital, Toronto, Ontario, Canada |
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| Abstract: | ObjectivesThis study sought to evaluate the effects of empagliflozin on extracellular volume (ECV) in individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD).BackgroundEmpagliflozin has been shown to reduce left ventricular mass index (LVMi) in patients with T2DM and CAD. The effects on myocardial ECV are unknown.MethodsThis was a prespecified substudy of the EMPA-HEART (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes) CardioLink-6 trial in which 97 participants were randomized to receive empagliflozin 10 mg daily or placebo for 6 months. Data from 74 participants were included: 39 from the empagliflozin group and 35 from the placebo group. The main outcome was change in left ventricular ECV from baseline to 6 months determined by cardiac magnetic resonance (CMR). Other outcomes included change in LVMi, indexed intracellular compartment volume (iICV) and indexed extracellular compartment volume (iECV), and the fibrosis biomarkers soluble suppressor of tumorgenicity (sST2) and matrix metalloproteinase (MMP)-2.ResultsBaseline ECV was elevated in the empagliflozin group (29.6 ± 4.6%) and placebo group (30.6 ± 4.8%). Six months of empagliflozin therapy reduced ECV compared with placebo (adjusted difference: –1.40%; 95% confidence interval [CI]: –2.60 to –0.14%; p = 0.03). Empagliflozin therapy reduced iECV (adjusted difference: –1.5 ml/m2; 95% CI: –2.6 to –0.5 ml/m2; p = 0.006), with a trend toward reduction in iICV (adjusted difference: –1.7 ml/m2; 95% CI: –3.8 to 0.3 ml/m2; p = 0.09). Empagliflozin had no impact on MMP-2 or sST2.ConclusionsIn individuals with T2DM and CAD, 6 months of empagliflozin reduced ECV, iECV, and LVMi. No changes in MMP-2 and sST2 were seen. Further investigation into the mechanisms by which empagliflozin causes reverse remodeling is required. (Effects of Empagliflozin on Cardiac Structure in Patients With Type 2 Diabetes [EMPA-HEART]; NCT02998970) |
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| Keywords: | diabetes empagliflozin extracellular volume fraction LV remodeling SGLT2 inhibition T1 mapping CI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0055" }," $$" :[{" #name" :" text" ," _" :" confidence interval CMR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0065" }," $$" :[{" #name" :" text" ," _" :" cardiac magnetic resonance ECM" },{" #name" :" keyword" ," $" :{" id" :" kwrd0075" }," $$" :[{" #name" :" text" ," _" :" extracellular matrix ECV" },{" #name" :" keyword" ," $" :{" id" :" kwrd0085" }," $$" :[{" #name" :" text" ," _" :" extracellular volume iECV" },{" #name" :" keyword" ," $" :{" id" :" kwrd0105" }," $$" :[{" #name" :" text" ," _" :" indexed extracellular compartment volume iICV" },{" #name" :" keyword" ," $" :{" id" :" kwrd0115" }," $$" :[{" #name" :" text" ," _" :" indexed intracellular compartment volume LGE" },{" #name" :" keyword" ," $" :{" id" :" kwrd0125" }," $$" :[{" #name" :" text" ," _" :" late gadolinium enhancement LV" },{" #name" :" keyword" ," $" :{" id" :" kwrd0135" }," $$" :[{" #name" :" text" ," _" :" left ventricular LVMi" },{" #name" :" keyword" ," $" :{" id" :" kwrd0145" }," $$" :[{" #name" :" text" ," _" :" left ventricular mass indexed to body surface area MMP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0165" }," $$" :[{" #name" :" text" ," _" :" matrix metalloproteinase SGLT2" },{" #name" :" keyword" ," $" :{" id" :" kwrd0175" }," $$" :[{" #name" :" text" ," _" :" sodium-dependent glucose cotransporter 2 sST2" },{" #name" :" keyword" ," $" :{" id" :" kwrd0185" }," $$" :[{" #name" :" text" ," _" :" soluble suppressor of tumorigenicity-2 T2DM" },{" #name" :" keyword" ," $" :{" id" :" kwrd0195" }," $$" :[{" #name" :" text" ," _" :" type 2 diabetes mellitus |
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