Effect of liraglutide on myocardial glucose uptake and blood flow in stable chronic heart failure patients: A double-blind, randomized, placebo-controlled LIVE sub-study

Journal of Nuclear Cardiology

Volumn 26, Issue 2, 2019, Pages 585-597

  Nielsen, Roni ^a   Jorsal, Anders ^a,b   Iversen, Peter ^a   Tolbod, Lars Poulsen ^a   Bouchelouche, Kirsten ^a   Sørensen, Jens ^a   Harms, Hendrik Johannes ^a   Flyvbjerg, Allan ^b   Tarnow, Lise ^c   Kistorp, Caroline ^d   Gustafsson, Ida ^e   Bøtker, Hans Erik ^a   Wiggers, Henrik ^a,b  

^a AARHUS UNIVERSITY HOSPITAL   (Denmark)

^b AARHUS UNIVERSITY   (Denmark)

^c STENO DIABETES CENTER   (Denmark)

^d GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^e HVIDOVRE HOSPITAL   (Denmark)

Author keywords

clinical studies; echocardiography; Heart failure; metabolism; nuclear cardiology and PET

Indexed keywords

FLUORODEOXYGLUCOSE F 18; GLUCOSE; HEMOGLOBIN A1C; LIRAGLUTIDE; OXYGEN 15;

ADENOSINE-INDUCED HYPEREMIA; AGED; ARTICLE; CARDIAC MUSCLE; CLINICAL OUTCOME; COMPARATIVE STUDY; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; EXERCISE TEST; FEMALE; FOLLOW UP; FORCED EXPIRATORY VOLUME; GLUCOSE BLOOD LEVEL; GLUCOSE TRANSPORT; HEART FAILURE; HEART LEFT VENTRICLE EJECTION FRACTION; HEART MUSCLE BLOOD FLOW; HEART MUSCLE PERFUSION; HEMOGLOBIN BLOOD LEVEL; HUMAN; INSULIN RESISTANCE; MAJOR CLINICAL STUDY; MALE; MYOCARDIAL PERFUSION RESERVE; ORAL GLUCOSE TOLERANCE TEST; PHARMACEUTICAL CARE; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; BLOOD FLOW VELOCITY; CHRONIC DISEASE; CORONARY ARTERY BLOOD FLOW; DENMARK; DIAGNOSTIC IMAGING; ECHOCARDIOGRAPHY; EPIDEMIOLOGY; GLUCOSE TOLERANCE TEST; HEART STROKE VOLUME; METABOLISM; MIDDLE AGED; ORAL DRUG ADMINISTRATION; PERFUSION;

ADMINISTRATION, ORAL; AGED; BLOOD FLOW VELOCITY; BLOOD GLUCOSE; CHRONIC DISEASE; CORONARY CIRCULATION; DENMARK; DOUBLE-BLIND METHOD; ECHOCARDIOGRAPHY; FEMALE; GLUCOSE TOLERANCE TEST; HEART FAILURE; HUMANS; LIRAGLUTIDE; MALE; MIDDLE AGED; MYOCARDIUM; PERFUSION; STROKE VOLUME;

EID: 85026772137     PISSN: 10713581     EISSN: 15326551     Source Type: Journal    
DOI: 10.1007/s12350-017-1000-2     Document Type: Article

References (35)

1. Egan JM, Meneilly GS, Habener JF, Elahi D. Glucagon-like peptide-1 augments insulin-mediated glucose uptake in the obese state. J Clin Endocrinol Metab. 2002;87:3768-73.
2. Bhashyam S, Fields AV, Patterson B, Testani JM, Chen L, Shen YT, et al. Glucagon-like peptide-1 increases myocardial glucose uptake via p38 MAP kinase mediated, nitric oxide dependent mechanisms in conscious dogs with dilated cardiomyopathy/clinical perspective,Circulation. Heart Fail. 2010;3:512-21.
3. Dokken BB, Hilwig WR, Teachey MK, Panchal RA, Hubner K, Allen D, et al. Glucagon-like peptide-1 (GLP-1) attenuates post-resuscitation myocardial microcirculatory dysfunction. Resuscitation. 2010;81:755-60.
4. Zhao T, Parikh P, Bhashyam S, Bolukoglu H, Poornima I, Shen YT, et al. Direct effects of glucagon-like peptide-1 on myocardial contractility and glucose uptake in normal and postischemic isolated rat hearts. J Pharmacol Exp Ther. 2006;317:1106-13.
5. Gejl M, Lerche S, Mengel A, Møller N, Bibby BM, Smidt K, et al. Influence of GLP-1 on myocardial glucose metabolism in healthy men during normo- or hypoglycemia. PLoS ONE. 2014;9:e83758.
6. Gejl M, Søndergaard HM, Stecher C, Bibby BM, Møller N, Bøtker HE, et al. Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes. J Clin Endocrinol Metab. 2012;97(7):E1165-9.
7. Lepore JJ, Olson E, Demopoulos L, Haws T, Fang Z, Barbour AM, et al. Effects of the novel long-acting GLP-1 agonist, albiglutide, on cardiac function, cardiac metabolism, and exercise capacity in patients with chronic heart failure and reduced ejection fraction. JACC. 2016;4(7):559-66.
8. Subaran SC, Sauder MA, Chai W, Jahn LA, Fowler DE, Aylor KW, et al. GLP-1 at physiological concentrations recruits skeletal and cardiac muscle microvasculature in healthy humans. Clin Sci (Lond). 2014;127(3):163-70.
9. Moberly SP, Mather KJ, Berwick ZC, Owen MK, Goodwill AG, Casalini ED, et al. Impaired cardiometabolic responses to glucagon-like peptide 1 in obesity and type 2 diabetes mellitus. Basic Res Cardiol. 2013;108(4):1-15.
10. Faber R, Zander M, Pena A, Michelsen MM, Mygind ND, Prescott E. Effect of the glucagon-like peptide-1 analogue liraglutide on coronary microvascular function in patients with type 2 diabetes - a randomized, single-blinded, cross-over pilot study. Cardiovasc Diabetol. 2015;14:41.
11. Jorsal A, Kistorp C, Holmager P, Tougaard RS, Nielsen R, Hänselmann A, et al. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE) - a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail. 2016;19(1):69-77.
12. Margulies KB, Hernandez AF, Redfield MM. Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: A randomized clinical trial. JAMA. 2016;316:500-8.
13. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-22.
14. Kofoed K, Carstensen S, Hove J, Freiberg J, Bangsgaard R, Holm S, et al. Low whole-body insulin sensitivity in patients with ischaemic heart disease is associated with impaired myocardial glucose uptake predictive of poor outcome after revascularisation. Eur J Nucl Med. 2002;29(8):991-8.
15. Majmudar MD, Murthy VL, Shah RV, Kolli S, Mousavi N, Foster C, et al. Quantification of coronary flow reserve in patients with ischaemic and non-ischaemic cardiomyopathy and its association with clinical outcomes. Eur Heart J. 2015;16(8):900-9.
16. Jorsal A, Wiggers H, Holmager P, Nilsson B, Nielsen R, Boesgaard TW, et al. A protocol for a randomised, double-blind, placebo-controlled study of the effect of LIraglutide on left VEntricular function in chronic heart failure patients with and without type 2 diabetes (The LIVE Study). BMJ Open. 2014;4:e004885.
17. Nielsen R, Nørrelund H, Kampmann U, Kim WY, Ringgaard S, Schär M, et al. Failing heart of patients with type 2 diabetes mellitus can adapt to extreme short-term increases in circulating lipids and does not display features of acute myocardial lipotoxicity. Circulation. 2013;6:845-52.
18. Wiggers H, Bøttcher M, Nielsen TT, Gjedde A, Bøtker HE. Measurement of myocardial glucose uptake in patients with ischemic cardiomyopathy: Application of a new quantitative method using regional tracer kinetic information. J Nucl Med. 1999;40:1292-300.
19. Harms H, Knaapen P, de Haan S, Halbmeijer R, Lammertsma A, Lubberink M. Automatic generation of absolute myocardial blood flow images using [15O]H2O and a clinical PET/CT scanner. Eur J Nucl Med Mol Imaging. 2011;38(5):930-9.
20. Rischpler C, Langwieser N, Souvatzoglou M, Batrice A, van Marwick S, Snajberk J, et al. PET/MRI early after myocardial infarction: Evaluation of viability with late gadolinium enhancement transmurality vs. 18F-FDG uptake. Eur Heart J. 2015;16:661-9.
21. Nielsen R, Jorsal A, Iversen P, Tolbod L, Bouchelouche K, Sørensen J, et al. Heart failure patients with prediabetes and newly diagnosed diabetes display abnormalities in myocardial metabolism. J Nucl Cardiol. 2016;. doi:10.1007/s12350-016-0622-0.
22. Knaapen P, Boellaard R, Götte MJW, Dijkmans PA, van Campen LMC, de Cock CC, et al. Perfusable tissue index as a potential marker of fibrosis in patients with idiopathic dilated cardiomyopathy. J Nucl Med. 2004;45(8):1299-304.
23. Marinho NVS, Keogh BE, Costa DC, Lammerstma AA, Ell PJ, Camici PG. Pathophysiology of chronic left ventricular dysfunction: New insights from the measurement of absolute myocardial blood flow and glucose utilization. Circulation. 1996;93:737-44.
24. Kaufmann PA, Gnecchi-Ruscone T, Yap JT, Rimoldi O, Camici PG. Assessment of the reproducibility of baseline and hyperemic myocardial blood flow measurements with 15O-labeled water and PET. J Nucl Med. 1999;40(11):1848-56.
25. Boudina S, Abel ED. Mitochondrial uncoupling: A key contributor to reduced cardiac efficiency in diabetes. Physiology. 2006;21:250-8.
26. Nikolaidis LA, Elahi D, Shen YT, Shannon RP. Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy. Am J Physiol. 2005;289:H2401-8.
27. Vyas AK, Yang KC, Woo D, Tzekov A, Kovacs A, Jay PY, et al. Exenatide improves glucose homeostasis and prolongs survival in a murine model of dilated cardiomyopathy. PLoS ONE. 2011;6(2):e17178.
28. Aravindhan K, Bao W, Harpel MR, Willette RN, Lepore JJ, Jucker BM. Cardioprotection resulting from glucagon-like peptide-1 administration involves shifting metabolic substrate utilization to increase energy efficiency in the rat heart. PLoS ONE. 2015;10(6):e0130894.
29. Egstrup M, Schou M, Gustafsson I, Kistorp CN, Hildebrandt PR, Tuxen CD. Oral glucose tolerance testing in an outpatient heart failure clinic reveals a high proportion of undiagnosed diabetic patients with an adverse prognosis. Eur J Heart Fail. 2011;13(3):319-26.
30. Lautamäki R, Airaksinen KEJ, Seppänen M, Toikka J, Luotolahti M, Ball E, et al. Rosiglitazone improves myocardial glucose uptake in patients with type 2 diabetes and coronary artery disease. Diabetes. 2005;54:2787-94.
31. Marathe CS, Rayner CK, Jones KL, Horowitz M. Relationships between gastric emptying, postprandial glycemia, and incretin hormones. Diabetes Care. 2013;36(5):1396-405.
32. Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M. Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor dependent and independent pathways. Circulation. 2008;117:2340-50.
33. Wang D, Luo P, Wang Y, Li W, Wang C, Sun D, et al. Glucagon-like peptide-1 protects against cardiac microvascular injury in diabetes via a cAMP/PKA/Rho-dependent mechanism. Diabetes. 2013;62:1697.
34. Ke J, Liu Y, Yang J, Lu R, Tian Q, Hou W, et al. Synergistic effects of metformin with liraglutide against endothelial dysfunction through GLP-1 receptor and PKA signalling pathway. Sci Rep. 2017;7:41085.
35. Bøttcher M, Refsgaard J, Gøtzsche O, Andreasen F, Toftegaard NT. Effect of carvedilol on microcirculatory and glucose metabolic regulation in patients with congestive heart failure secondary to ischemic cardiomyopathy. Am J Cardiol. 2002;89(12):1388-93.