Journal of Cardiovascular Imaging

Korean Society of Echocardiography (한국심초음파학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors on Cardiac Imaging Parameters: A Systematic Review and Meta-analysis of Randomized Controlled Trials

  • Caitlin Fern Wee (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Yao Hao Teo (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Yao Neng Teo (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Nicholas LX Syn (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Ray Meng See (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Shariel Leong (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Alicia Swee Yan Yip (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Zhi Xian Ong (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Chi-Hang Lee (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Mark Yan-Yee Chan (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Kian-Keong Poh (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Ching-Ching Ong (Department of Diagnostic Imaging, National University Hospital) ;
  • Lynette LS Teo (Department of Diagnostic Imaging, National University Hospital) ;
  • Devinder Singh (Department of Cardiology, National University Heart Centre Singapore) ;
  • Benjamin YQ Tan (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Leonard LL Yeo (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • William KF Kong (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Tiong-Cheng Yeo (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Raymond CC Wong (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Ping Chai (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore) ;
  • Ching-Hui Sia (Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore)
  • Received : 2021.09.21
  • Accepted : 2022.05.14
  • Published : 2022.07.27
Download PDF
⟨ Previous Next ⟩

Abstract

Recent studies have shown that sodium/glucose cotransporter 2 (SGLT2) inhibitors might exert favourable changes on cardiac parameters as observed on cardiovascular imaging. We conducted a systematic review and meta-analysis to determine the effects of SGLT2 inhibitors on cardiac imaging parameters. Four electronic databases (PubMed, Embase, Cochrane, Scopus) were searched for studies in which the effects of SGLT2 inhibitors on cardiac imaging parameters were examined. Studies in which a population was administered SGLT2 inhibitors and analysed by echocardiography and/or cardiac magnetic resonance (CMR) imaging were included. Random-effects pair-wise meta-analysis models were utilized to summarize the studies. A total of 11 randomized controlled trials was included with a combined cohort of 910 patients. Comparing patients receiving SGLT2 inhibitors with subjects receiving placebo, the mean change in CMR-measured left ventricular mass (LVM) was -3.87 g (95% confidence interval [CI], -7.77 to 0.04), that in left ventricular end-systolic volume (LVESV) was -5.96 mL (95% CI, -10.52 to -1.41) for combined LVESV outcomes, that in left atrial volume index (LAVi) was -1.78 mL/m2 (95% CI, -3.01 to -0.55) for combined LAVi outcomes, and that in echocardiography-measured E/e' was -0.73 (95% CI, -1.43 to -0.03). Between-group differences were not observed in LVM and LVESV after indexation. The only between-group difference that persisted was for LAVi. Treatment with SGLT2 inhibitors resulted in reduction in LAVi and E/e' on imaging, indicating they might have an effect on outcomes associated with LV diastolic function.

Keywords

Acknowledgement

CS was supported by the Junior Academic Faculty Scheme of the National University of Singapore Yong Loo Lin School of Medicine.

References

  1. Blankstein R. Cardiology patient page. Introduction to noninvasive cardiac imaging. Circulation 2012;125:e267-71. https://doi.org/10.1161/CIRCULATIONAHA.110.017665
  2. Cavalcante JL, Lalude OO, Schoenhagen P, Lerakis S. Cardiovascular magnetic resonance imaging for structural and valvular heart disease interventions. JACC Cardiovasc Interv 2016;9:399-425. https://doi.org/10.1016/j.jcin.2015.11.031
  3. Shibayama K, Watanabe H. Clinical use of echocardiography in structural heart disease. Gen Thorac Cardiovasc Surg 2016;64:365-72. https://doi.org/10.1007/s11748-016-0649-9
  4. Teo YH, Teo YN, Syn NL, et al. Effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus: a systematic review and meta-analysis of randomized-controlled trials. J Am Heart Assoc 2021;10:e019463.
  5. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-28. https://doi.org/10.1056/NEJMoa1504720
  6. Lee MM, Brooksbank KJ, Wetherall K, et al. Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF). Circulation 2021;143:516-25. https://doi.org/10.1161/CIRCULATIONAHA.120.052186
  7. Verma S, Mazer CD, Yan AT, et al. Effect of empagliflozin on left ventricular mass in patients with type 2 diabetes mellitus and coronary artery disease: the EMPA-HEART CardioLink-6 randomized clinical trial. Circulation 2019;140:1693-702. https://doi.org/10.1161/CIRCULATIONAHA.119.042375
  8. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71.
  9. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.
  10. Schunemann H, Brozek J, Guyatt G, Oxman A. Handbook for Grading the Quality of Evidence and the Strength of Recommendations Using the GRADE Approach. [place unknown]: The GRADE Working Group; 2013.
  11. The Cochrane Collaboration. ReviewManager (RevMan). Version 5.4. London: The Cochrane Collaboration; 2020.
  12. Higgins JP, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane Handbook for Systematic Reviews of Interventions, 2nd ed. London: The Cochrane Collaboration; 2019.
  13. Furukawa TA, Barbui C, Cipriani A, Brambilla P, Watanabe N. Imputing missing standard deviations in meta-analyses can provide accurate results. J Clin Epidemiol 2006;59:7-10. https://doi.org/10.1016/j.jclinepi.2005.06.006
  14. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 2014;14:135.
  15. Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, et al. Randomized trial of empagliflozin in nondiabetic patients with heart failure and reduced ejection fraction. J Am Coll Cardiol 2021;77:243-55. https://doi.org/10.1016/j.jacc.2020.11.008
  16. Chaimani A, Caldwell DM, Li T, Higgins JPT, Salanti G. Chapter 11: Undertaking network meta-analyses. In: Higgins JPT, Thomas J, Chandler J, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions, Version 6.1. London: The Cochrane Collaboration; 2020.
  17. Brown AJ, Gandy S, McCrimmon R, Houston JG, Struthers AD, Lang CC. A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: the DAPA-LVH trial. Eur Heart J 2020;41:3421-32. https://doi.org/10.1093/eurheartj/ehaa419
  18. Oldgren J, Laurila S, Akerblom A, et al. Effects of 6weeks of treatment with dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes: a randomized, placebo-controlled, exploratory study. Diabetes Obes Metab 2021;23:1505-17. https://doi.org/10.1111/dom.14363
  19. Shim CY, Seo J, Cho I, et al. Randomized, controlled trial to evaluate the effect of dapagliflozin on left ventricular diastolic function in patients with type 2 diabetes mellitus: the IDDIA trial. Circulation 2021;143:510-2. https://doi.org/10.1161/CIRCULATIONAHA.120.051992
  20. Singh JS, Mordi IR, Vickneson K, et al. Dapagliflozin versus placebo on left ventricular remodeling in patients with diabetes and heart failure: the REFORM trial. Diabetes Care 2020;43:1356-9. https://doi.org/10.2337/dc19-2187
  21. de Boer RA, Nunez J, Kozlovski P, Wang Y, Proot P, Keefe D. Effects of the dual sodium-glucose linked transporter inhibitor, licogliflozin vs placebo or empagliflozin in patients with type 2 diabetes and heart failure. Br J Clin Pharmacol 2020;86:1346-56. https://doi.org/10.1111/bcp.14248
  22. Omar M, Jensen J, Ali M, et al. Associations of empagliflozin with left ventricular volumes, mass, and function in patients with heart failure and reduced ejection fraction: a substudy of the empire HF randomized clinical trial. JAMA Cardiol 2021;6:836-40. https://doi.org/10.1001/jamacardio.2020.6827
  23. Rau M, Thiele K, Hartmann NK, et al. Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study. Cardiovasc Diabetol 2021;20:6.
  24. Eickhoff MK, Olsen FJ, Frimodt-Moller M, et al. Effect of dapagliflozin on cardiac function in people with type 2 diabetes and albuminuria - a double blind randomized placebo-controlled crossover trial. J Diabetes Complications 2020;34:107590.
  25. Sattar N, McLaren J, Kristensen SL, Preiss D, McMurray JJ. SGLT2 Inhibition and cardiovascular events: why did EMPA-REG outcomes surprise and what were the likely mechanisms? Diabetologia 2016;59:1333-9. https://doi.org/10.1007/s00125-016-3956-x
  26. Chilton R, Tikkanen I, Cannon CP, et al. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab 2015;17:1180-93. https://doi.org/10.1111/dom.12572
  27. Ferrannini E, Mark M, Mayoux E. CV protection in the EMPA-REG OUTCOME trial: a "Thrifty Substrate" hypothesis. Diabetes Care 2016;39:1108-14. https://doi.org/10.2337/dc16-0330
  28. Iannantuoni F, M de Maranon A, Diaz-Morales N, et al. The SGLT2 inhibitor empagliflozin ameliorates the inflammatory profile in type 2 diabetic patients and promotes an antioxidant response in leukocytes. J Clin Med 2019;8:1814.
  29. Heerspink HJ, Perco P, Mulder S, et al. Canagliflozin reduces inflammation and fibrosis biomarkers: a potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease. Diabetologia 2019;62:1154-66. https://doi.org/10.1007/s00125-019-4859-4
  30. Leng W, Wu M, Pan H, et al. The SGLT2 inhibitor dapagliflozin attenuates the activity of ROS-NLRP3 inflammasome axis in steatohepatitis with diabetes mellitus. Ann Transl Med 2019;7:429.
  31. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392:1789-858. https://doi.org/10.1016/S0140-6736(18)32279-7
  32. Kane GC, Karon BL, Mahoney DW, et al. Progression of left ventricular diastolic dysfunction and risk of heart failure. JAMA 2011;306:856-63. https://doi.org/10.1001/jama.2011.1201
  33. Little WC, Oh JK. Echocardiographic evaluation of diastolic function can be used to guide clinical care. Circulation 2009;120:802-9. https://doi.org/10.1161/CIRCULATIONAHA.109.869602
  34. Tamura H, Watanabe T, Nishiyama S, et al. Increased left atrial volume index predicts a poor prognosis in patients with heart failure. J Card Fail 2011;17:210-6. https://doi.org/10.1016/j.cardfail.2010.10.006
  35. Hense HW, Gneiting B, Muscholl M, et al. The associations of body size and body composition with left ventricular mass: impacts for indexation in adults. J Am Coll Cardiol 1998;32:451-7. https://doi.org/10.1016/S0735-1097(98)00240-X
  36. Writing Committee Members, Yancy CW, Jessup M, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013;128:e240-327.
  37. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016;37:2129-200. https://doi.org/10.1093/eurheartj/ehw128
  38. Reis Filho JR, Cardoso JN, Cardoso CM, Pereira-Barretto AC. Reverse cardiac remodeling: a marker of better prognosis in heart failure. Arq Bras Cardiol 2015;104:502-6. https://doi.org/10.5935/abc.20150025