Tamique Mason1, Otavio R Coelho-Filho2, Subodh Verma3, Biswajit Chowdhury4, Fei Zuo5, Adrian Quan4, Kevin E Thorpe6, Christopher Bonneau4, Hwee Teoh7, Richard E Gilbert8, Lawrence A Leiter9, Peter Jüni10, Bernard Zinman11, Michael Jerosch-Herold12, C David Mazer13, Andrew T Yan14, Kim A Connelly15. 1. Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. 2. Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, Brazil; Division of Cardiology, Department of Medicine, State University of Campinas, Campinas, Brazil. 3. Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada. 4. Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. 5. Applied Health Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. 6. Applied Health Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. 7. Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada; Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. 8. Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 9. Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada. 10. Applied Health Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. 11. Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. 12. Heart and Vascular Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 13. Department of Anesthesia, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada; Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada. 14. Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Cardiology, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. 15. Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada; Division of Cardiology, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. Electronic address: kim.connelly@unityhealth.to.
Abstract
OBJECTIVES: This 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). BACKGROUND:Empagliflozin has been shown to reduce left ventricular mass index (LVMi) in patients with T2DM and CAD. The effects on myocardial ECV are unknown. METHODS: This 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. RESULTS:Baseline 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. CONCLUSIONS: In 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).
RCT Entities:
OBJECTIVES: This 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). BACKGROUND:Empagliflozin has been shown to reduce left ventricular mass index (LVMi) in patients with T2DM and CAD. The effects on myocardial ECV are unknown. METHODS: This 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. RESULTS: Baseline 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. CONCLUSIONS: In 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).
Authors: Forrest N Gamble; M Rifqi Aufan; Oleg F Sharifov; Lamario J Williams; Shane Reighard; David A Calhoun; Himanshu Gupta; Louis J Dell'Italia; Thomas S Denney; Steven G Lloyd Journal: Physiol Meas Date: 2022-03-07 Impact factor: 2.688
Authors: Vasiliki Tsampasian; Ranu Baral; Rahul Chattopadhyay; Maciej Debski; Shruti S Joshi; Johannes Reinhold; Marc R Dweck; Pankaj Garg; Vassilios S Vassiliou Journal: Cardiol Res Pract Date: 2021-08-19 Impact factor: 1.866
Authors: Bradley Sarak; Subodh Verma; C David Mazer; Hwee Teoh; Adrian Quan; Richard E Gilbert; Shaun G Goodman; Karan Bami; Otávio R Coelho-Filho; Vineeta Ahooja; Djeven P Deva; Vinay Garg; Sumeet Gandhi; Kim A Connelly; Andrew T Yan Journal: Cardiovasc Diabetol Date: 2021-10-04 Impact factor: 9.951