Abstract
Background: Sodium-glucose co-transporter-2 inhibitors improve cardiac structure but most studies suggest no change in left ventricular (LV) systolic function at rest. Whether sodium-glucose co-transporter-2 inhibitors improve LV contractile reserve is unknown. We investigated the effect of empagliflozin on LV contractile reserve in patients with heart failure (HF) and reduced ejection fraction. Methods: Prespecified sub-study of the Empire HF trial, a double-blind, placebo-controlled, and randomized trial. Patients with LV ejection fraction (LVEF) ≤ 40% on guideline-directed HF therapy were randomized (1:1) to empagliflozin 10 mg or placebo for 12 weeks. The treatment effect on contractile reserve was assessed by low dose dobutamine stress echocardiography. Results: In total, 120 patients were included. The mean age was 68 (SD 10) years, 83% were male, and the mean LVEF was 38 (SD 10) %. Respectively 60 (100%) and 59 (98%) patients in the empagliflozin and placebo groups completed stress echocardiography. No statistically significant effect of empagliflozin was observed for the contractile reserve assessed by LV-GLS (adjusted mean absolute change, empagliflozin vs placebo, 0.7% [95% confidence interval {CI} –0.5 to 2.0, P = .25]) or LVEF (adjusted mean absolute change, empagliflozin vs placebo, 2.2% [95% CI –1.4 to 5.8, P = .22]) from baseline to 12 weeks. LV-GLS contractile reserve was associated with accelerometer-measured daily activity level (coefficient –24 accelerometer counts [95% CI –46 to –1.8, P = .03]). Conclusions: Empagliflozin for 12 weeks added to guideline-directed HF therapy did not improve LV contractile reserve in patients with HF and reduced ejection fraction.
Originalsprog | Engelsk |
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Tidsskrift | American Heart Journal |
Vol/bind | 250 |
Sider (fra-til) | 57-65 |
Antal sider | 9 |
ISSN | 0002-8703 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:This research was supported by The Danish Heart Foundation, Copenhagen, Denmark (grant numbers 17-R116-A7714-22076, 18-R124-A8573-22107); The Research Council at Herlev and Gentofte University Hospital, Herlev, Denmark (institutional research grant); The Research and Innovation Foundation of the Department of Cardiology (FUHAS, formerly FUKAP), Herlev and Gentofte University Hospital, Herlev, Denmark (institutional research grant); The A.P. Møller Foundation for the Advancement of Medical Science, Copenhagen, Denmark (grant number); The Capital Region of Denmark, Copenhagen, Denmark (grant number A6058). The manufacturer of empagliflozin had no role in any aspect of the study.
Funding Information:
The present study was conducted as part of the Empire HF trial which has been previously reported. 18 , 19 In brief, this was an investigator-initiated, double-blind, and placebo-controlled trial, investigating the short-term effects of empagliflozin in patients with stable, chronic HFrEF. No significant change in N-terminal pro-brain natriuretic peptide, the primary endpoint of the study, was observed. 19 The research protocol complies with the Declaration of Helsinki and the study was approved by an institutional review board (Danish National Committee on Health Research Ethics, number H-17010756). Written informed consent was obtained from all patients. The study was prospectively registered with ClinicalTrials.gov (NCT03198585). This research was supported by The Danish Heart Foundation, The Research Council and The Research and Innovation Foundation of the Department of Cardiology at Herlev and Gentofte University Hospital, The A.P. Møller Foundation for the Advancement of Medical Science, and The Capital Region of Denmark. The manufacturer of empagliflozin had no role in any aspect of the study. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper and its final contents.
Funding Information:
J.J. reports grants from The Research Council at Herlev and Gentofte University Hospital, Herlev, Denmark, grants from The Research and Innovation Foundation of the Department of Cardiology (FUHAS, formerly FUKAP), Herlev and Gentofte University Hospital, Herlev, Denmark, and grants from The A.P. Møller Foundation for the Advancement of Medical Science, Copenhagen, Denmark, during the conduct of the study; grants from the Danish Heart Foundation and personal fees from scientific advisory board from AstraZeneca and Boehringer Ingelheim, outside the submitted work. M.O. reports grants from The Steno Diabetes Center Odense, Odense, Denmark, during the conduct of the study. C.F.A. reports grants from The Research and Innovation Foundation of the Department of Cardiology (FUHAS, formerly FUKAP), Herlev and Gentofte University Hospital, Herlev, Denmark, outside the submitted work. J.H.L. has nothing to disclose. C.K. reports personal fees from scientific advisory panel and speaker fees from Boehringer Ingelheim, Merck, Sharp & Dohme, AstraZeneca, Amgen, Novartis, Novo Nordisk, and Shire, outside the submitted work. C.T. reports personal fees from scientific advisory board and speaker fees from Bayer and Orion Pharma outside the submitted work. M.A. has nothing to disclose. P.H.F. has nothing to disclose. M.K.E. has nothing to disclose. L.K. reports personal fees from speaker honorarium from Novartis, AstraZeneca, Novo Nordisk, and Boehringer Ingelheim, outside the submitted work. F.G. reports personal fees from scientific advisory panel and speaker fees from AstraZeneca, Boehringer Ingelheim, Abbott, Orion Pharma, Pfizer, and Novartis, and acting as an unpaid advisor for Corvia, outside the submitted work. J.F. has nothing to disclose. J.L.F. has nothing to disclose. J.E.M. reports grants from Abiomed Inc., personal fees from speaker honorarium from Novartis and Orion Pharma, outside the submitted work. M.S. reports grants from The Danish Heart Foundation, Copenhagen, Denmark, and from The Capital Region of Denmark, Copenhagen, Denmark, during the conduct of the study; personal fees from speaker honorarium and nonfinancial support (as the national lead investigator of the DAPA-HF trial) from AstraZeneca, personal fees from speaker honorarium from Novo Nordisk and Boehringer Ingelheim, outside the submitted work.
Publisher Copyright:
© 2022 The Author(s)