Does empagliflozin modulate the autonomic nervous system among individuals with type 2 diabetes and coronary artery disease? The EMPA-HEART CardioLink-6 Holter analysis

Vinay Garg; Subodh Verma; Kim A. Connelly; Andrew T. Yan; Aditya Sikand; Ankit Garg; Paul Dorian; Fei Zuo; Lawrence A. Leiter; Bernard Zinman; Peter Jüni; Atul Verma; Hwee Teoh; Adrian Quan; C. David Mazer; Andrew C.T. Ha

Metabolism Open (Sep 2020)

Does empagliflozin modulate the autonomic nervous system among individuals with type 2 diabetes and coronary artery disease? The EMPA-HEART CardioLink-6 Holter analysis

Vinay Garg,
Subodh Verma,
Kim A. Connelly,
Andrew T. Yan,
Aditya Sikand,
Ankit Garg,
Paul Dorian,
Fei Zuo,
Lawrence A. Leiter,
Bernard Zinman,
Peter Jüni,
Atul Verma,
Hwee Teoh,
Adrian Quan,
C. David Mazer,
Andrew C.T. Ha

Affiliations

Vinay Garg: Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
Subodh Verma: Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada; Corresponding author. at: Division of Cardiac Surgery, St. Michael’s Hospital, 30 Bond Street, Toronto, ON, Canada, M5B 1W8
Kim A. Connelly: Department of Medicine, University of Toronto, Toronto, ON, Canada; Division of Cardiology, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada
Andrew T. Yan: Department of Medicine, University of Toronto, Toronto, ON, Canada; Division of Cardiology, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada
Aditya Sikand: Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada
Ankit Garg: Department of Medicine, University of Toronto, Toronto, ON, Canada
Paul Dorian: Department of Medicine, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Division of Cardiology, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada
Fei Zuo: Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada
Lawrence A. Leiter: Department of Medicine, University of Toronto, Toronto, ON, Canada; Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada
Bernard Zinman: Department of Medicine, University of Toronto, Toronto, ON, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
Peter Jüni: Department of Medicine, University of Toronto, Toronto, ON, Canada; Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
Atul Verma: Department of Cardiology, Southlake Regional Health Centre, University of Toronto, Newmarket, ON, Canada
Hwee Teoh: Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada
Adrian Quan: Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada
C. David Mazer: Department of Physiology, University of Toronto, Toronto, ON, Canada; Department of Anesthesia, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada
Andrew C.T. Ha: Department of Medicine, University of Toronto, Toronto, ON, Canada; Peter Munk Cardiac Center, Toronto General Hospital, University Health Network, Toronto, ON, Canada

Journal volume & issue: Vol. 7
p. 100039

Abstract

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Context: We examined if empagliflozin was associated with modulation of cardiac autonomic tone among subjects with type 2 diabetes and stable coronary artery disease (CAD) relative to placebo. Methods: Using ambulatory 24-h Holter electrocardiographic data prospectively collected from a randomized trial, we compared changes in heart rate variability (HRV) parameters between empagliflozin- and placebo-assigned subjects over a follow-up period of 6 months. Measured HRV domains included: standard deviation (SD) of NN intervals (SDNN), SD of average NN intervals per 5-min (SDANN), root mean square of successive RR interval differences (RMSSD), % successive NN intervals differing >50 ms (ms) (pNN50), low frequency (LF), high frequency (HF) and the LF/HF ratio (LF:HF). Differences in HRV parameters between the 2 groups were compared with analysis of covariance (ANCOVA). Statistical measures of significance were reported as adjusted differences between the 2 groups and their corresponding 95% confidence intervals. Results: Sixty-six subjects completed 24-h Holter monitoring at baseline and 6-months. Over 6 months, the change in HRV was similar between subjects treated with empagliflozin vs. placebo for the following parameters: RMSSD -1.2 ms (-6.0 to 3.6 ms); pNN50 0.5% (-2.6 to 3.6%); VLF -907.8 ms2 (-2388.8 to 573.1 ms2); LF -341 ms2 (-878.7 to 196.7 ms2); HF -33.8 ms2 (-111.1 to 43.5 ms2); LF:HF -0.1 (-0.4 to 0.2). Subjects who received placebo experienced an increase in SDNN 18.6 ms (2.8–34.3 ms) and SDANN 20.2 ms (3.2–37.3 ms) relative to those treated with empagliflozin. Conclusion: Compared to placebo, empagliflozin did not result in changes in autonomic tone among individuals with type 2 diabetes and stable coronary artery disease.

Published in Metabolism Open

ISSN: 2589-9368 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Physiology; Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/metabolism-open

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