Heart failure in patients with diabetic cardiomyopathy: features of pathogenesis and diagnosis

Prof. L.V. Zhuravlyova, as. prof. T.A. Rogachova, as. prof. N.V. Sokolnikova.

Kharkiv National Medical University

Currently, all over the world, type 2 diabetes mellitus and the heart failure are developing into an epidemic. In 1972, Shirley Rubler and colleagues defined cardiomyopathy, which was independent of atherosclerosis and hypertension, as diabetic cardiomyopathy. Recently, the so-called restrictive type has become more commonphenotype of diabetic cardiomyopathy: with the presence of diastolic dysfunction, with heart failure withpreserved systolic function of the left ventricle. New mechanisms for the development of heart failure in diabeticcardiomyopathy were also identified: microvascular endothelial dysfunction, leading to impaired vasodilationwith increased oxygen demand in the myocardium, and impaired free fatty acids metabolism, leading toimpaired adenosine triphosphoric acid synthesis in cardiomyocytes. Here we summarize the key questions byproviding an overview of current data.

Key Words: diabetes mellitus, heart failure, insulin resistance, diastolic dysfunction, diabetic cardiomyopathy, microvascular endothelial dysfunction, free fatty acids.

https://dx.doi.org/10.15407/internalmed2019.02.012

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For citing:

  1. Журавлева, Л.В. Сердечная недостаточность у больных диабетической кардиомиопатией: особенности патогенеза и диагностики / Л.В. Журавлева, Т.А. Рогачева, Н.В. Сокольникова // Східноєвропейський журнал внутрішньої та сімейної медицини. – 2019. – № 2. – С. 12-17. doi: 10.15407/internalmed2019.02.012.
  2. Zhuravlyova LV, Rogachova TA, Sokolnikova NV. [Heart Failure In Patients With Diabetic Cardiomyopathy: Pathogenesis, Diagnosis, Treatment]. Shidnoevr. z. vnutr. simejnoi med. 2019;2:12-17. doi: 10.15407/internalmed2019.02.012. Russian.

References:

1. Farmakis D, Stafylas P, Giamouzis G, Maniadakis N, Parissis J.The medical and socioeconomic burden of heart failure: a comparative delineation with cancer. Int J Cardiol.2016;203:279-281. DOI:10.1016/j.ijcard. 2015.10.172
https://doi.org/10.1016/j.ijcard.2015.10.172

2. Becher P, Fluschnik N, Blankenberg S, Westermann D. Challenging aspects of treatment strategies in heart failure with preserved ejection fraction: “Why did recent clinical trials fail?”. World J Cardiol. 2015;7:544. DOI:10.4330/wjc.v7.i9.544
https://doi.org/10.4330/wjc.v7.i9.544

3. Lombardi C, Spigoni V, Gorga E, Cas AD. Novel insight into the dangerous connection between diabetes and heart failure. Herz.2016;41:201-207. DOI:10.1007/s00059-016-4415-7
https://doi.org/10.1007/s00059-016-4415-7

4. Kristensen S, Mogensen U, Jhund P, Petrie MC, Preiss D, Win S, Køber L, McKelvie RS, Zile MR, Anand IS, Komajda M, Gottdiener JS, Carson PE, McMurray JJ. Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction: a report from the I-Preserve Trial (Irbesartan in Heart Failure With Preserved Ejection Fraction). Circulation. 2017;135:724-735. DOI:10.1161/circulationaha.116.024593
https://doi.org/10.1161/CIRCULATIONAHA.116.024593

5. Dei C, Fonarow G, Gheorghiade M, Butler J. Concomitant diabetes mellitus and heart failure. Curr Probl Cardiol.2015;40:7-43. DOI:10.1016/j.cpcardiol.2014.09.002
https://doi.org/10.1016/j.cpcardiol.2014.09.002

6. Seferovic P, Paulus W. Clinical diabetic cardiomyopathy: a two-faced disease with restrictive and dilated phenotypes. Eur Heart J. 2015;36:1718-1727.DOI:10.1093/eurheartj/ehv134
https://doi.org/10.1093/eurheartj/ehv134

7. Russo I, Frangogiannis N. Diabetes-associated cardiac fibrosis: cellular effectors, molecular mechanisms and therapeutic opportunities. J Mol Cell Cardiol.2016;90:84-93. DOI:10.1016/j.yjmcc. 2015.12.011
https://doi.org/10.1016/j.yjmcc.2015.12.011

8. Lambert R, Srodulski S, Peng X, Margulies KB, Despa F, Despa F Intracellular Na+ concentration is elevated in diabetic hearts due to enhanced Na+-glucose cotransport. J Am Heart Assoc.2015;4. DOI:10.1161/jaha.115.002183.
https://doi.org/10.1161/JAHA.115.002183

9. Pereira L, Ruiz-Hurtado G, Rueda A, Mercadier J, Benitah JP, Gómez AM. Calcium signaling in diabetic cardiomyocytes. Cell Calcium. 2014;56:372-380.DOI:10.1016/j.ceca.2014.08.004
https://doi.org/10.1016/j.ceca.2014.08.004

10. Bertero E, Maack C. Calcium signaling and reactive oxygen species in mitochondria. Circ Res. 2018;122:1460-1478. DOI:10.1161/circresaha.118.310082
https://doi.org/10.1161/CIRCRESAHA.118.310082

11. Bertero E, Roma L, Ameri P, Christoph Maack. Cardiac effects of SGLT2 inhibitors: the sodium hypothesis. Cardiovasc Res. 2018;114:12-18.DOI:10.1093/cvr/cvx149
https://doi.org/10.1093/cvr/cvx149

12. Gadde K, Martin C, Berthoud H, Steven B. Heymsfield Obesity: pathophysiology and managementю J Am Coll Cardiol. 2018;71:69-84. DOI:10.1016/j.jacc.2017.11.011
https://doi.org/10.1016/j.jacc.2017.11.011

13. Bertero E, Maack C. Metabolic remodeling in heart failure. Nat Rev Cardiol.2018. DOI:10.1038/s41569-018-0044-6
https://doi.org/10.1038/s41569-018-0044-6

14. Cadenas S. Mitochondrial uncoupling, ROS generation and cardioprotection. Biochim Biophys Acta. 2018;1859:940-950. DOI:10.1016/j.bbabio.2018.05.019
https://doi.org/10.1016/j.bbabio.2018.05.019

15. Bedi K, Snyder N, Brandimarto J, Aziz M, Mesaros C, Worth AJ, Wang LL, Javaheri A, Blair IA, Kenneth B, Eduardo MJ. Rame Evidence for intramyocardial disruption of lipid metabolism and increased myocardial ketone utilization in advanced human heart failure. Circulation 2016;133:706-716.DOI:10.1161/circulationaha.115.017545
https://doi.org/10.1161/CIRCULATIONAHA.115.017545

16. Taegtmeyer H, Beauloye C, Harmancey R, Hue L. Insulin resistance protects the heart from fuel overload in dysregulated metabolic states. Am J Physiol Heart Circ Physiol. 2013;305:1693-1697. DOI:10.1152/ajpheart.00854.2012
https://doi.org/10.1152/ajpheart.00854.2012

17. Lim S, Lam C, Segers V, Brutsaert DL, Gilles W. De KeulenaerCardiac endothelium-myocyte interaction: clinical opportunities for new heart failure therapies regardless of ejection fraction. Eur Heart J. 2015;36:2050-2060. DOI:10.1093/eurheartj/ehv132
https://doi.org/10.1093/eurheartj/ehv132

18. Eriksson L, Nystrom T. Antidiabetic agents and endothelial dysfunction-beyond glucose control. Basic Clin Pharmacol Toxicol.2015;117:15-25. DOI:10.1111/bcpt.12402
https://doi.org/10.1111/bcpt.12402

19. Ponikowski P, Voors A, Anker S, BuenoH, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola V, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH. ESC Scientific Document Group. 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.2016;18:891-975. https://doi.org/10.5603/kp.2016.0141.
https://doi.org/10.5603/KP.2016.0141

20. Kenny H, Abel E. Heart failure in type 2 diabetes mellitus. Circulation Research.2019;124(1):121-141. DOI:10.1161/circresaha.118.311371
https://doi.org/10.1161/CIRCRESAHA.118.311371

21. Holscher M, Bode C, Bugger H. Diabetic Cardiomyopathy: Does the Type of Diabetes Matter? Int J Mol Sci.2016;17(12):2136. DOI:10.3390/ijms17122136
https://doi.org/10.3390/ijms17122136

22. Jia G, Hill M, Sowers J. Diabetic Cardiomyopathy. An Update of Mechanisms Contributing to This Clinical Entity. Circulation Research.2018;122:624-638. DOI:10.1161/circresaha.117.311586
https://doi.org/10.1161/CIRCRESAHA.117.311586

23. Kuri L, Smail M, Qureshi M, Sydorenko V, Shmygol, Oz M, Singh J, Howarth FC. Calcium Signaling in the Ventricular Myocardium of the Goto-Kakizaki Type 2 Diabetic Rat. Journal of Diabetes Research.2018. DOI:10.1155/2018/2974304.
https://doi.org/10.1155/2018/2974304

24. Maack C, Lehrke M, Backs J, Heinzel FR, Hulot J, Marx N, Paulus W, Rossignol P, Taegtmeyer H, Bauersachs J, Bayes-Genis A, Brutsaert D, Bugger H, Clarke K, Cosentino F, De Keulenaer G, Cas AD, González A, Huelsmann M, Iaccarino G, Lunde IG, Lyon AR, Pollesello P, Rena G, Riksen NP, Rosano G, Staels G, van Laake LW, Wanner C, Farmakis D, Filippatos G, Ruschitzka F, Seferovic P, de Boer RA, Heymans S. Heart failure and diabetes: metabolic alterations and therapeutic interventions: a stateof-the-art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology. European Heart Journal.2018;39(48):4243-4254. DOI:10.1093/eurheartj/ehy596
https://doi.org/10.1093/eurheartj/ehy596

25. Gibb A, Hill B. Metabolic Coordination of Physiological and Pathological Cardiac Remodeling. Circulation Research.2018;123:107-128DOI:10.1161/circresaha.118.312017
https://doi.org/10.1161/CIRCRESAHA.118.312017

26. Lee W, Kim J. Diabetic cardiomyopathy: where we are and where we are going. Korean J Intern Med.2017;32(3):404-421. DOI:10.3904/kjim.2016.208
https://doi.org/10.3904/kjim.2016.208

27. Levelt E, Gulsin G. mechanisms in endocrinology: Diabetic cardiomyopathy: pathophysiology and potential metabolic interventions state of the art review. European Journal of Endocrinology.2018;178(4):127-139. DOI:10.1530/eje-17-0724
https://doi.org/10.1530/EJE-17-0724

28. Nakamura M, Sadoshima J. Cardiomyopathy in obesity, insulin resistance and diabetes. The Journal of Physiology.2019.DOI:10.1113/jp276747
https://doi.org/10.1113/JP276747

29. McHugh K, DeVore A, Wu J. Heart Failure With Preserved Ejection Fraction and Diabetes: JACC State-of-theArt Review. J Am Coll Cardiol.2019;73(5):602-611. DOI:10.1016/j.jchf.2018.12.017
https://doi.org/10.1016/j.jchf.2018.12.017

30. Lindman R. The Diabetic Heart Failure With Preserved Ejection Fraction Phenotype. Circulation. 2017;135:736-740. DOI:10.1161/circulationaha.116.025957
https://doi.org/10.1161/CIRCULATIONAHA.116.025957