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      Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes

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          Abstract

          Background

          Type 2 diabetes mellitus (T2DM) greatly increases the risks of cardiovascular disease and heart failure. In particular, left ventricular diastolic dysfunction that develops from the early stages of T2DM is an important factor in the onset and exacerbation of heart failure. The effect of sodium-glucose cotransporter 2 inhibitors on left ventricular diastolic function has not been elucidated. We have performed the first prospective study on the effects of canagliflozin on left ventricular diastolic function in T2DM.

          Methods

          This study was performed to evaluate the effects of additional treatment with canagliflozin for 3 months on left ventricular diastolic function in patients with T2DM. A total of 38 patients with T2DM were consecutively recruited for this study. Left ventricular diastolic function was assessed by echocardiography. The primary study outcome was a change in the septal E/e′ as a parameter of left ventricular diastolic function.

          Results

          A total of 37 patients (25 males and 12 females) were included in the analysis. Mean age of participants was 64.2 ± 8.1 years (mean ± SD), mean duration of diabetes was 13.5 ± 8.1 years, and mean HbA1c was 7.9 ± 0.7%. Of the participants, 86.5% had hypertension, 100% had dyslipidemia, and 32.4% had cardiovascular disease. Canagliflozin significantly improved left ventricular diastolic function (septal E/e′ ratio 13.7 ± 3.5–12.1 ± 2.8, p = 0.001). Furthermore, among the various parameters that changed through the administration of canagliflozin, only changes in hemoglobin significantly correlated with changes in the septal E/e′ ratio ( p = 0.002). In multiple regression analysis, changes in hemoglobin were also revealed to be an independent predictive factor for changes in the septal E/e′ ratio.

          Conclusions

          This study showed for the first time that canagliflozin could improve left ventricular diastolic function within 3 months in patients with T2DM. The benefit was especially apparent in patients with substantially improved hemoglobin values.

          Trial registration UMIN Clinical Trials Registry UMIN000028141

          Electronic supplementary material

          The online version of this article (10.1186/s12933-018-0717-9) contains supplementary material, which is available to authorized users.

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          Most cited references44

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          Diabetes and cardiovascular disease. The Framingham study.

          W Kannel, D McGee (1979)
          Based on 20 years of surveillance of the Framingham cohort relating subsequent cardiovascular events to prior evidence of diabetes, a twofold to threefold increased risk of clinical atherosclerotic disease was reported. The relative impact was greatest for intermittent claudication (IC) and congestive heart failure (CHF) and least for coronary heart disease (CHD), which was, nevertheless, on an absolute scale the chief sequela. The relative impact was substantially greater for women than for men. For each of the cardiovascular diseases (CVD), morbidity and mortality were higher for diabetic women than for nondiabetic men. After adjustment for other associated risk factors, the relative impact of diabetes on CHD, IC, or stroke incidence was the same for women as for men; for CVD death and CHF, it was greater for women. Cardiovascular mortality was actually about as great for diabetic women as for diabetic men.
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            Irbesartan in patients with heart failure and preserved ejection fraction.

            Barry M. Massie, Peter E. Carson, John J McMurray … (2008)
            Approximately 50% of patients with heart failure have a left ventricular ejection fraction of at least 45%, but no therapies have been shown to improve the outcome of these patients. Therefore, we studied the effects of irbesartan in patients with this syndrome. We enrolled 4128 patients who were at least 60 years of age and had New York Heart Association class II, III, or IV heart failure and an ejection fraction of at least 45% and randomly assigned them to receive 300 mg of irbesartan or placebo per day. The primary composite outcome was death from any cause or hospitalization for a cardiovascular cause (heart failure, myocardial infarction, unstable angina, arrhythmia, or stroke). Secondary outcomes included death from heart failure or hospitalization for heart failure, death from any cause and from cardiovascular causes, and quality of life. During a mean follow-up of 49.5 months, the primary outcome occurred in 742 patients in the irbesartan group and 763 in the placebo group. Primary event rates in the irbesartan and placebo groups were 100.4 and 105.4 per 1000 patient-years, respectively (hazard ratio, 0.95; 95% confidence interval [CI], 0.86 to 1.05; P=0.35). Overall rates of death were 52.6 and 52.3 per 1000 patient-years, respectively (hazard ratio, 1.00; 95% CI, 0.88 to 1.14; P=0.98). Rates of hospitalization for cardiovascular causes that contributed to the primary outcome were 70.6 and 74.3 per 1000 patient-years, respectively (hazard ratio, 0.95; 95% CI, 0.85 to 1.08; P=0.44). There were no significant differences in the other prespecified outcomes. Irbesartan did not improve the outcomes of patients with heart failure and a preserved left ventricular ejection fraction. (ClinicalTrials.gov number, NCT00095238.) 2008 Massachusetts Medical Society
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              Influence of ejection fraction on outcomes and efficacy of spironolactone in patients with heart failure with preserved ejection fraction.

              Scott Solomon, Brian Claggett, Eldrin Lewis … (2016)
              While mineralocorticoid receptor antagonists (MRAs) have been shown to benefit patients with reduced left ventricular ejection fraction (LVEF), spironolactone did not reduce the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest in patients with heart failure with preserved ejection fraction (HFpEF) in the TOPCAT trial, which enrolled patients with LVEF of 45% or greater. We utilized data from TOPCAT to assess the relationship between LVEF as well as outcomes and efficacy of spironolactone.
              Article 0 comments Cited 196 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Daisuke Matsutani: daisuke19870116@yahoo.co.jp
                Masaya Sakamoto:
                ORCID: http://orcid.org/0000-0001-7839-0780
                m-sakamoto@umin.ac.jp
                Yosuke Kayama: aykayama9286@gmail.com
                Norihiko Takeda: ntakeda-tky@umin.ac.jp
                Ryuzo Horiuchi: horiuchi@shonai-mcoop.jp
                Kazunori Utsunomiya: kazu-utsunomiya@jikei.ac.jp
                Journal
                Journal ID (nlm-ta): Cardiovasc Diabetol
                Journal ID (iso-abbrev): Cardiovasc Diabetol
                Title: Cardiovascular Diabetology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1475-2840
                Publication date (Electronic): 22 May 2018
                Publication date PMC-release: 22 May 2018
                Publication date Collection: 2018
                Volume: 17
                Electronic Location Identifier: 73
                Affiliations
                [1 ]ISNI 0000 0001 0661 2073, GRID grid.411898.d, Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, , Jikei University School of Medicine, ; 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461 Japan
                [2 ]ISNI 0000 0001 0661 2073, GRID grid.411898.d, Department of Cardiology, , Jikei University School of Medicine, ; 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461 Japan
                [3 ]ISNI 0000 0001 2151 536X, GRID grid.26999.3d, Department of Cardiovascular Medicine, Graduate School of Medicine, , The University of Tokyo, ; 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8654 Japan
                [4 ]Department of Pathology, Tsuruoka Kyoritsu Hospital, 9-34, Fumizonomachi, Tsuruoka-shi, Yamagata 997-0816 Japan
                Author information
                http://orcid.org/0000-0001-7839-0780
                Article
                Publisher ID: 717
                DOI: 10.1186/s12933-018-0717-9
                PMC ID: 5963148
                PubMed ID: 29788955
                SO-VID: 5ff062cc-fd79-4196-af78-75c9a84b9f40
                Copyright © © The Author(s) 2018
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 21 March 2018
                Date accepted : 17 May 2018
                Categories
                Subject: Original Investigation
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: sodium-glucose cotransporter 2 inhibitors,left ventricular diastolic function,heart failure with preserved ejection fraction,autonomic function,type 2 diabetes mellitus
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: sodium-glucose cotransporter 2 inhibitors, left ventricular diastolic function, heart failure with preserved ejection fraction, autonomic function, type 2 diabetes mellitus

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