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22-11-2021 | Heart Failure

Prognostic impact of diabetes in chronic and acute heart failure

Authors: Stefano Ghio, Valentina Mercurio, Andrea Attanasio, Gaetano Asile, Carlo Gabriele Tocchetti, Stefania Paolillo

Published in: Heart Failure Reviews | Issue 3/2023

Abstract

A strong, bidirectional relationship exists between diabetes mellitus (DM) and heart failure (HF) and DM is responsible of the activation of several molecular and pathophysiological mechanisms that may, on the long term, damage the heart. However, the prognostic role of DM in the context of chronic and acute HF is still not yet defined and there are several gaps of evidence in the literature on this topic. These gaps are related to the wide phenotypic heterogeneity of patients with chronic and acute HF and to the concept that not all diabetic patients are the same, but there is the necessity to better characterize the disease and each single patient, also considering the role of other possible comorbidities. The aim of the present review is to summarize the pathophysiological mechanisms subtending the negative effect of DM in HF and analyze the available data exploring the prognostic impact of such comorbidity in both chronic and acute HF.

Bell DSH (2003) Heart failure: the frequent, forgotten, and often fatal complication of diabetes. Diabetes Care 26:2433–2441PubMedCrossRef

Aon MA, Tocchetti CG, Bhatt N, Paolocci N, Cortassa S (2015) Protective mechanisms of mitochondria and heart function in diabetes. Antioxid Redox Signal 22:1563–1586PubMedPubMedCentralCrossRef

Boyer JK, Thanigaraj S, Schechtman KB, Pérez JE (2004) Prevalence of ventricular diastolic dysfunction in asymptomatic, normotensive patients with diabetes mellitus. Am J Cardiol 93:870–875PubMedCrossRef

Carley AN, Severson DL (2005) Fatty acid metabolism is enhanced in type 2 diabetic hearts. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 1734:112–126CrossRef

Lopaschuk GD, Ussher JR, Folmes CDL, Jaswal JS, Stanley WC (2010) Myocardial fatty acid metabolism in health and disease. Physiol Rev 90:207–258PubMedCrossRef

Hue L, Taegtmeyer H (2009) The Randle cycle revisited: a new head for an old hat. American Journal of Physiology - Endocrinology and Metabolism 297:E578–E591PubMedPubMedCentralCrossRef

Harmancey R, Wilson CR, Taegtmeyer H (2008) Adaptation and maladaptation of the heart in obesity. Hypertension 52:181–187PubMedCrossRef

Tocchetti CG, Caceres V, Stanley BA et al (2012) GSH or palmitate preserves mitochondrial energetic/redox balance, preventing mechanical dysfunction in metabolically challenged myocytes/hearts from type 2 diabetic mice. Diabetes 61:3094–3105PubMedPubMedCentralCrossRef

Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820PubMedCrossRef

10.

Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625PubMedCrossRef

11.

Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070PubMedPubMedCentralCrossRef

12.

Negre-Salvayre A, Salvayre R, Augé N, Pamplona R, Portero-Otín M (2009) Hyperglycemia and glycation in diabetic complications. Antioxid Redox Signal 11:3071–3109PubMedCrossRef

13.

Ussher JR, Jaswal JS, Lopaschuk GD (2012) Pyridine nucleotide regulation of cardiac intermediary metabolism. Circulation Res c111:628–641

14.

Anderson EJ, Lustig ME, Boyle KE et al (2009) Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest 119:573–581PubMedPubMedCentralCrossRef

15.

Burgoyne JR, Oka SI, Ale-Agha N, Eaton P (2013) Hydrogen peroxide sensing and signaling by protein kinases in the cardiovascular system. Antioxid Redox Signal 18:1042–1052PubMedPubMedCentralCrossRef

16.

Maack C, O’Rourke B (2007) Excitation-contraction coupling and mitochondrial energetics. Basic Res Cardiol 102:369–392PubMedPubMedCentralCrossRef

17.

Harmancey R, Taegtmeyer H (2008) The complexities of diabetic cardiomyopathy: lessons from patients and animal models. Curr DiabRep 8:243–248

18.

Boudina S, Abel ED (2010) Diabetic cardiomyopathy, causes and effects. Rev Endocr Metab Disord 11:31–39PubMedPubMedCentralCrossRef

19.

Ishikawa T, Kajiwara H, Kurihara S (1999) Alterations in contractile properties and Ca2+ handling in streptozotocin-induced diabetic rat myocardium. Am J Physiol - Hear Circ Physiol 277:H2185–H2194CrossRef

20.

Netticadan T, Temsah RM, Kent A, Elimban V, Dhalla NS (2001) Depressed levels of Ca2+-cycling proteins may underlie sarcoplasmic reticulum dysfunction in the diabetic heart. Diabetes 50:2133–2138PubMedCrossRef

21.

Louch WE, Stokke MK, Sjaastad I, Christensen G, Sejersted OM (2012) No rest for the weary: diastolic calcium homeostasis in the normal and failing myocardium. Physiology 27:308–323PubMedCrossRef

22.

Bers DM (2006) Altered cardiac myocyte Ca regulation in heart failure. Physiology 21:380–387PubMedCrossRef

23.

Liu T, Brown DA, O’Rourke B (2010) Role of mitochondrial dysfunction in cardiac glycoside toxicity. J Mol Cell Cardiol 49:728–736PubMedPubMedCentralCrossRef

24.

Bugger H, Abel ED (2010) Mitochondria in the diabetic heart. Cardiovasc Res 88:229–420PubMedPubMedCentralCrossRef

25.

Nickel A, Löffler J, Maack C (2013) Myocardial energetics in heart failure. Basic Res Cardiol 108:358PubMedCrossRef

26.

Zhong Y, Ahmed S, Grupp IL, Matlib MA (2001) Altered SR protein expression associated with contractile dysfunction in diabetic rat hearts. Am J Physiol - Hear Circ Physiol 281:H1137–H1147CrossRef

27.

Trost SU, Belke DD, Bluhm WF, Meyer M, Swanson E, Dillmann WH (2002) Overexpression of the sarcoplasmic reticulum CA2+-ATPase improves myocardial contractility in diabetic cardiomyopathy. Diabetes 51:1166–1171PubMedCrossRef

28.

Vetter R, Rehfeld U, Reissfelder C et al (2002) Transgenic overexpression of the sarcoplasmic reticulum Ca2+ATPase improves reticular Ca2+ handling in normal and diabetic rat hearts. FASEB J 16:1657–1659PubMedCrossRef

29.

Francesco DR, Fabien D, Marc L et al (2013) Abstract 16277: hyperglycemia in congestive heart failure patients is associated to sympathetic overactivity (abstract). Circulation 128(suppl_22):A16277–A16277

30.

Mebazaa A, Gayat E, Lassus J, Meas T, Mueller C, Maggioni A, Peacock F, Spinar J, Harjola VP, van Kimmenade R, Pathak A, Mueller T, Tavazzi L, Disomma S, Metra M, Pascual-Figal D, Laribi S, Logeart D, Nouira S, Sato N, Parenica J, Deye N, Boukef R, Collet C, Van den Berghe G, Cohen-Solal A, Januzzi JL Jr (2013) GREAT Network. Association between elevated blood glucose and outcome in acute heart failure: results from an international observational cohort. J Am Coll Cardiol 61:820–829

31.

Seferović PM, Paulus WJ (2015) Clinical diabetic cardiomyopathy: a two-faced disease with restrictive and dilated phenotypes. Eur Heart J 36:1718–1727PubMedCrossRef

32.

Nieminen MS, Brutsaert D, Dickstein K, Drexler H, Follath F, Harjola VP, Hochadel M, Komajda M, Lassus J, Lopez-Sendon JL, Ponikowski P, Tavazzi L (2006) EuroHeart Survey Investigators; Heart Failure Association, European Society of Cardiology. EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population. Eur Heart J 27:2725–2736

33.

Fonarow GC, Heywood JT, Heidenreich PA, Lopatin M, Yancy CW, Scientific Advisory Committee ADHERE, Investigators. Temporal trends in clinical characteristics, treatments, and outcomes for heart failure hospitalizations, (2002) to 2004: findings from Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 2007(153):1021–1028

34.

Dauriz M, Mantovani A, Bonapace S, Verlato G, Zoppini G, Bonora E, Targher G (2017) Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis. Diabetes Care 40:1597–1605PubMedCrossRef

35.

MacDonald MR, Petrie MC, Varyani F, Ostergren J, Michelson EL, Young JB, Solomon SD, Granger CB, Swedberg K, Yusuf S, Pfeffer MA, McMurray JJ (2008) CHARM Investigators. Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J 29:1377–1385

36.

Johansson I, Dahlstrom U, Edner M, Nasman P, Ryden L, Norhammar A (2016) Prognostic implications of type 2 diabetes mellitus in ischemic and nonischemic heart failure. J Am Coll Cardiol 68:1404–1416PubMedCrossRef

37.

Domanski M, Krause-Steinrauf H, Deedwania P, Follmann D, Ghali JK, Gilbert E, Haffner S, Katz R, Lindenfeld J, Lowes BD, Martin W, McGrew F, Bristow MR (2003) BEST Investigators. The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial. J Am Coll Cardiol 42:914–922

38.

Dries DL, Sweitzer NK, Drazner MH, Stevenson LW, Gersh BJ (2001) Prognostic impact of diabetes mellitus in patients with heart failure according to the etiology of left ventricular systolic dysfunction. J Am Coll Cardiol 38:421–428PubMedCrossRef

39.

MacDonald MR, Jhund PS, Petrie MC, Lewsey JD, Hawkins NM, Bhagra S, Munoz N, Varyani F, Redpath A, Chalmers J, MacIntyre K, McMurray JJ (2008) Discordant short- and long-term outcomes associated with diabetes in patients with heart failure: importance of age and sex: a population study of 5.1 million people in Scotland. Circ Heart Fail 1:234–241

40.

Kristensen SL, Preiss D, Jhund PS, Squire I, Cardoso JS, Merkely B, Martinez F, Starling RC, Desai AS, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, McMurray JJ, Packer M (2016) PARADIGM-HF Investigators and Committees. Risk related to pre-diabetes mellitus and diabetes mellitus in heart failure with reduced ejection fraction: insights from prospective comparison of ARNI With ACEI to determine impact on global mortality and morbidity in heart failure trial. Circ Heart Fail 9:e002560

41.

Aune D, Schlesinger S, Neuenschwander M, Feng T, Janszky I, Norat T, Riboli E (2018) Diabetes mellitus, blood glucose and the risk of heart failure: a systematic review and meta-analysis of prospective studies. Nutr Metab Cardiovasc Dis 28:1081–1091PubMedCrossRef

42.

Pavlović A, Polovina M, Ristić A, Seferović JP, Veljić I, Simeunović D, Milinković I, Krljanac G, Ašanin M, Oštrić-Pavlović I, Seferović PM (2019) Long-term mortality is increased in patients with undetected prediabetes and type-2 diabetes hospitalized for worsening heart failure and reduced ejection fraction. Eur J Prev Cardiol 26:72–82PubMedCrossRef

43.

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 J Heart Fail 18:891–975

44.

Ghio S, Guazzi M, Scardovi AB, Klersy C, Clemenza F, Carluccio E, Temporelli PL, Rossi A, Faggiano P, Traversi E, Vriz O, Dini FL (2017) all investigators. Different correlates but similar prognostic implications for right ventricular dysfunction in heart failure patients with reduced or preserved ejection fraction. Eur J Heart Fail 19:873–879

45.

Ghio S, Klersy C, Carluccio E, Scardovi AB, Scelsi L, Falletta C, Rossi A, Faggiano P, Traversi E, Vriz O, Guazzi M, Dini FL, Targher G, Temporelli PL (2020) Pre-existing type 2 diabetes is associated with increased all-cause death independently of echocardiographic predictors of poor prognosis only in ischemic heart disease. Nutr Metab Cardiovasc Dis 30:2036–2040PubMedCrossRef

46.

Dauriz M, Mantovani A, Bonapace S, Verlato G, Zoppini G, Bonora E et al (2017) Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis. Diabetes Care 40:1597–1605PubMedCrossRef

47.

Paolillo S, Salvioni E, Perrone Filardi P et al (2020) MECKI score research group (see Appendix A). Long-term prognostic role of diabetes mellitus and glycemic control in heart failure patients with reduced ejection fraction: insights from the MECKI Score database. Int J Cardiol 317:103–110

48.

Agostoni P, Paolillo S, Mapelli M et al (2018) Multiparametric prognostic scores in chronic heart failure with reduced ejection fraction: a long-term comparison. Eur J Heart Fail 20:700–710PubMedCrossRef

49.

Kouwert IJ, Bakker EA, Cramer MJ, Snoek JA, Eijsvogels TM (2020) Comparison of MAGGIC and MECKI risk scores to predict mortality after cardiac rehabilitation among Dutch heart failure patients. Eur J Prev Cardiol 27:2126–2130PubMedCrossRef

50.

Chioncel O, Mebazaa A, Harjola VP et al (2017) Clinical phenotypes and outcome of patients hospitalized for acute heart failure: the ESC Heart Failure Long-Term Registry. Eur J Heart Fail 19:1242–1254PubMedCrossRef

51.

Teerlink JR, Felker GM, McMurray JJV et al (2016) Acute treatment with omecamtiv mecarbil to increase contractility in acute heart failure: the ATOMIC-AHF study. J Am Coll Cardiol 67:1444–1455PubMedCrossRef

52.

Teerlink JR, Cotter G, Davison BA et al (2013) Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet 381:29–39PubMedCrossRef

53.

Targher G, Dauriz M, Tavazzi L et al (2016) Prognostic impact of in-hospital hyperglycemia in hospitalized patients with acute heart failure: results of the IN-HF (Italian Network on Heart Failure) Outcome registry. Int J Cardiol 203:587–593PubMedCrossRef

54.

Oliva F, Mortara A, Cacciatore G et al (2012) Acute heart failure patient profiles, management and in-hospital outcome: results of the Italian Registry on Heart Failure Outcome. Eur J Heart Fail 14:1208–1217PubMedCrossRef

55.

Sarma S, Mentz RJ, Kwasny MJ, Fought AJ, Huffman M, Subacius H, Nodari S, Konstam M, Swedberg K, Maggioni AP, Zannad F, Bonow RO, Gheorghiade M (2013) EVEREST investigators. Association between diabetes mellitus and post-discharge outcomes in patients hospitalized with heart failure: findings from the EVEREST trial. Eur J Heart Fail 15:194–202

56.

Museedi AS, Alshami A, Douedi S et al (2021) Predictability of inpatient mortality of different comorbidities in both types of acute decompensated heart failure: analysis of national inpatient sample. Cardiol Res 12:29–36PubMedCrossRef

57.

Scrutinio D, Guida P, Passantino A et al (2018) Female gender and mortality risk in decompensated heart failure. Eur J Intern Med 51:34–40PubMedCrossRef

58.

Valente MA, Voors AA, Damman K, Van Veldhuisen DJ, Massie BM, O’Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Davison B, Cleland JG, Givertz MM, Bloomfield DM, Fiuzat M, Dittrich HC, Hillege HL (2014) Diuretic response in acute heart failure: clinical characteristics and prognostic significance. Eur Heart J 35:1284–1293PubMedCrossRef

59.

Damman K, Beusekamp JC, Boorsma EM, Swart HP, Smilde TDJ, Elvan A, van Eck JWM, Heerspink HJL, Voors AA (2020) Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF). Eur J Heart Fail 22:713–722PubMedCrossRef

60.

Tamaki S, Yamada T, Watanabe T et al (2021) Effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with diabetes hospitalized for acute decompensated heart failure: a prospective randomized controlled study. Circ Heart Fail 14(3):e007048

Title: Prognostic impact of diabetes in chronic and acute heart failure
Authors: Stefano Ghio
Valentina Mercurio
Andrea Attanasio
Gaetano Asile
Carlo Gabriele Tocchetti
Stefania Paolillo
Publication date: 22-11-2021
Publisher: Springer US
Keywords: Heart Failure
Acute Heart Failure
Chronic Heart Failure
Diabetes
Published in: Heart Failure Reviews / Issue 3/2023
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI: https://doi.org/10.1007/s10741-021-10193-8

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