Abstract
The clinical efficacy of glucagon-like peptide-1 (GLP-1) analogs in patients with acute myocardial infarction (AMI) is uncertain. The purpose of the present study was to evaluate the effects of the GLP-1 analog liraglutide on left ventricular (LV) remodeling in patients with AMI. We retrospectively evaluated the effects of liraglutide on LV remodeling assessed by cardiac magnetic resonance imaging (CMRI) in 15 patients with type 2 diabetes who were successfully treated with primary percutaneous coronary intervention (PCI) for AMI. Patients were divided into two groups based on their hypoglycemic medication: liraglutide use (group L; n = 6) or standard therapy (group S; n = 9). The CMRI findings in the early phase and at the 6-month follow-up were compared. At the 6-month follow-up, group S showed increases in LV end-diastolic (from 64 to 74 mL/m2, p = 0.08) and end-systolic (from 38 to 45 mL/m2, p = 0.13) volume indexes, whereas no such increase was observed in group L. The LV mass index (LVMI) was significantly smaller in group L than in group S at baseline (64 vs. 75 g/m2, p = 0.05) and at follow-up (56 vs. 78 g/m2, p = 0.009). Multivariate regression analysis showed that liraglutide use was an independent negative predictor of LVMI (β = −0.720, p = 0.003). In conclusion, liraglutide may be able to prevent the progression of LV remodeling and is associated with a lower LV mass in diabetic patients with AMI undergoing primary PCI.
Similar content being viewed by others
References
No authors listed (1983) Risk Stratification and Survival after Myocardial Infarction. N Engl J Med 309:331–336
Fieno DS, Hillenbrand HB, Rehwald WG, Harris KR, Decker RS, Parker MA, Klocke FJ, Kim RJ, Judd RM (2004) Infarct resorption, compensatory hypertrophy, and differing patterns of ventricular remodeling following myocardial infarctions of varying size. J Am Coll Cardiol 43:2124–2131
Keeley EC, Boura JA, Grines CL (2003) Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 361:13–20
Bolognese L, Neskovic AN, Parodi G, Cerisano G, Buonamici P, Santoro GM, Antoniucci D (2002) Left ventricular remodeling after primary coronary angioplasty: patterns of left ventricular dilation and long-term prognostic implications. Circulation 106:2351–2357
Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M (1998) Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 339:229–234
McGuire DK, Emanuelsson H, Granger CB, Magnus Ohman E, Moliterno DJ, White HD, Ardissino D, Box JW, Califf RM, Topol EJ (2000) Influence of diabetes mellitus on clinical outcomes across the spectrum of acute coronary syndromes. Findings from the GUSTO-IIb study. GUSTO IIb Investigators. Eur Heart J 21:1750–1758
Hausenloy DJ, Whittington HJ, Wynne AM, Begum SS, Theodorou L, Riksen N, Mocanu MM, Yellon DM (2013) Dipeptidyl peptidase-4 inhibitors and GLP-1 reduce myocardial infarct size in a glucose-dependent manner. Cardiovasc Diabetol 12:154
Wohlfart P, Linz W, Hübschle T, Linz D, Huber J, Hess S, Crowther D, Werner U, Ruetten H (2013) Cardioprotective effects of lixisenatide in rat myocardial ischemia-reperfusion injury studies. J Transl Med 11:84
Monji A, Mitsui T, Bando YK, Aoyama M, Shigeta T, Murohara T (2013) Glucagon-like peptide-1 receptor activation reverses cardiac remodeling via normalizing cardiac steatosis and oxidative stress in type 2 diabetes. Am J Physiol Heart Circ Physiol 305:H295–H304
Liu Q, Anderson C, Broyde A, Polizzi C, Fernandez R, Baron A, Parkes DG (2010) Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure. Cardiovasc Diabetol 9:76
Lønborg J, Kelbæk H, Vejlstrup N, Bøtker HE, Kim WY, Holmvang L, Jørgensen E, Helqvist S, Saunamäki K, Terkelsen CJ, Schoos MM, Køber L, Clemmensen P, Treiman M, Engstrøm T (2012) Exenatide reduces final infarct size in patients with ST-segment-elevation myocardial infarction and short-duration of ischemia. Circ Cardiovasc Interv 5:288–295
Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D, Shannon RP (2004) Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 109:962–965
Sokos GG, Bolukoglu H, German J, Hentosz T, Magovern GJ Jr, Maher TD, Dean DA, Bailey SH, Marrone G, Benckart DH, Elahi D, Shannon RP (2007) Effect of glucagon-like peptide-1 (GLP-1) on glycemic control and left ventricular function in patients undergoing coronary artery bypass grafting. Am J Cardiol 100:824–829
Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, Bundy J, Finn JP, Klocke FJ, Judd RM (1999) Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 100:1992–2002
Aletras AH, Tilak GS, Natanzon A, Hsu LY, Gonzalez FM, Hoyt RF Jr, Arai AE (2006) Retrospective determination of the area at risk for reperfused acute myocardial infarction with T2-weighted cardiac magnetic resonance imaging: histopathological and displacement encoding with stimulated echoes (DENSE) functional validations. Circulation 113:1865–1870
Kirschbaum SW, Baks T, Gronenschild EH, Aben JP, Weustink AC, Wielopolski PA, Krestin GP, de Feyter PJ, van Geuns RJ (2008) Addition of the long-axis information to short-axis contours reduces interstudy variability of left-ventricular analysis in cardiac magnetic resonance studies. Invest Radiol 43:1–6
Manning WJ, Atkinson DJ, Grossman W, Paulin S, Edelman RR (1991) First-pass nuclear magnetic resonance imaging studies using gadolinium-DTPA in patients with coronary artery disease. J Am Coll Cardiol 18:959–965
White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild CJ (1987) Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 76:44–51
Pfeffer MA, Braunwald E (1990) Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation 81:1161–1172
Lowes BD, Gill EA, Abraham WT, Larrain JR, Robertson AD, Bristow MR, Gilbert EM (1999) Effects of carvedilol on left ventricular mass, chamber geometry, and mitral regurgitation in chronic heart failure. Am J Cardiol 83:1201–1205
Pfeffer MA, Braunwald E, Moyé LA, Basta L, Brown EJ Jr, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC (1992) Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 327:669–677
Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Køber L, Maggioni AP, Solomon SD, Swedberg K, Van de Werf F, White H, Leimberger JD, Henis M, Edwards S, Zelenkofske S, Sellers MA, Califf RM, Valsartan in Acute Myocardial Infarction Trial Investigators (2003) Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 349:1893–1906
Hioki H, Motoki H, Izawa A, Kashima Y, Miura T, Ebisawa S, Tomita T, Miyashita Y, Koyama J, Ikeda U (2015) Impact of oral beta-blocker therapy on mortality after primary percutaneous coronary intervention for Killip class 1 myocardial infarction. Heart Vessels. doi:10.1007/s00380-015-0673-1
Schillaci G, Verdecchia P, Porcellati C, Cuccurullo O, Cosco C, Perticone F (2000) Continuous relation between left ventricular mass and cardiovascular risk in essential hypertension. Hypertension 35:580–586
Bhashyam S, Fields AV, Patterson B, Testani JM, Chen L, Shen YT, Shannon RP (2010) Glucagon-like peptide-1 increases myocardial glucose uptake via p38alpha MAP kinase-mediated, nitric oxide-dependent mechanisms in conscious dogs with dilated cardiomyopathy. Circ Heart Fail 3:512–521
Tamita K, Katayama M, Takagi T, Akasaka T, Yamamuro A, Kaji S, Morioka S, Kihara Y (2007) Impact of newly diagnosed abnormal glucose tolerance on long-term prognosis in patients with acute myocardial infarction. Circ J 71:834–841
Gierach J, Gierach M, Świątkiewicz I, Woźnicki M, Grześk G, Sukiennik A, Koziñski M, Kubica J (2014) Admission glucose and left ventricular systolic function in non-diabetic patients with acute myocardial infarction. Heart Vessels. doi:10.1007/s00380-014-0610-8
Lazzeri C, Valente S, Chiostri M, Attanà P, Mattesini A, Nesti M, Gensini GF (2014) Hyperglycemia, acute insulin resistance, and renal dysfunction in the early phase of ST-elevation myocardial infarction without previously known diabetes: impact on long-term prognosis. Heart Vessels 29:769–775
Shigeta T, Aoyama M, Bando YK, Monji A, Mitsui T, Takatsu M, Cheng XW, Okumura T, Hirashiki A, Nagata K, Murohara T (2012) Dipeptidyl peptidase-4 modulates left ventricular dysfunction in chronic heart failure via angiogenesis-dependent and -independent actions. Circulation 126:1838–1851
Fujiwara T, Yoshida M, Nakamura T, Sakakura K, Wada H, Arao K, Katayama T, Funayama H, Sugawara Y, Mitsuhashi T, Kakei M, Momomura SI, Ako J (2014) Dipeptidyl peptidase-4 inhibitors are associated with improved left ventricular diastolic function after acute myocardial infarction in diabetic patients. Heart Vessels (Epub ahead of print)
White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, Perez AT, Fleck PR, Mehta CR, Kupfer S, Wilson C, Cushman WC, Zannad F, EXAMINE Investigators (2013) Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 369:1327–1335
Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I, SAVOR-TIMI 53 Steering Committee and Investigators (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 369:1317–1326
Ayaori M, Iwakami N, Uto-Kondo H, Sato H, Sasaki M, Komatsu T, Iizuka M, Takiguchi S, Yakushiji E, Nakaya K, Yogo M, Ogura M, Takase B, Murakami T, Ikewaki K (2013) Dipeptidyl peptidase-4 inhibitors attenuate endothelial function as evaluated by flow-mediated vasodilatation in type 2 diabetic patients. J Am Heart Assoc 2:e003277
Monami M, Dicembrini I, Mannucci E (2014) Dipeptidyl peptidase-4 inhibitors and heart failure: a meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis 24:689–697
Scirica BM, Braunwald E, Raz I, Cavender MA, Morrow DA, Jarolim P, Udell JA, Mosenzon O, Im K, Umez-Eronini AA, Pollack PS, Hirshberg B, Frederich R, Lewis BS, McGuire DK, Davidson J, Steg PG, Bhatt DL, SAVOR-TIMI 53 Steering Committee and Investigators (2014) Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation 130:1579–1588
Nikolaidis LA, Elahi D, Shen YT, Shannon RP (2005) Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 289:H2401–H2408
Read PA, Hoole SP, White PA, Khan FZ, O’Sullivan M, West NE, Dutka DP (2011) A pilot study to assess whether glucagon-like peptide-1 protects the heart from ischemic dysfunction and attenuates stunning after coronary balloon occlusion in humans. Circ Cardiovasc Interv 4:266–272
Vanderheyden M, Bartunek J, Goethals M, Verstreken S, Lambeir AM, De Meester I, Scharpé S (2009) Dipeptidyl-peptidase IV and B-type natriuretic peptide. From bench to bedside. Clin Chem Lab Med 47:248–252
Jackson EK, Zhang M, Liu W, Mi Z (2007) Inhibition of renal dipeptidyl peptidase IV enhances peptide YY1-36-induced potentiation of angiotensin II-mediated renal vasoconstriction in spontaneously hypertensive rats. J Pharmacol Exp Ther 323:431–437
Oyama J, Node K (2014) Incretin therapy and heart failure. Circ J 78:819–824
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
None.
Rights and permissions
About this article
Cite this article
Nozue, T., Yamada, M., Tsunoda, T. et al. Effects of liraglutide, a glucagon-like peptide-1 analog, on left ventricular remodeling assessed by cardiac magnetic resonance imaging in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. Heart Vessels 31, 1239–1246 (2016). https://doi.org/10.1007/s00380-015-0734-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00380-015-0734-5