Mechanisms of formation and progression of chronic heart failure on the background of type 2 diabetes mellitus

O.M. Hodlevska, Ya.Yu. Samburh, T.I. Mahdalits


Currently, cardiovascular diseases play a crucial role in the evolution of total mortality in Ukraine. Chronicheart failure is a complex clinical syndrome that, in recent decades, has been considered a global epidemic due to the increased incidence and prevalence. The prevalence of chronic heart failure increases with age and concomitant diseases such as hypertension, obesity, and type 2 diabetes. The pathophysiology of its development in the presence of type 2 diabetes mellitus is complex. Type 2 diabetes increases the risk of ischemic chronic heart failure due to the increased risk of coronary artery disease, as well as direct impact on the myocardium itself, leading to the structural and functional changes (diabetic cardiomyopathy). At the same time, endothelial dysfunction and microangiopathic processes are important for the development of diabetic cardiomyopathy. The manifestation and progression of heart dysfunction is accompanied by changes in the geometry and architecture of the myocardium, as well as an increase in the content of collagen and, as a result, fibrous tissue in the intercellular matrix, which can lead to cardiac remodeling and diastolic dysfunction. One of the important causes of heart failure, attention to which has recently been attracted, is cardiac dyssynchrony. Dyssynchrony is divided into electrical and mechanical. Electrical dyssynchrony is associated with slower conduction in the ventricles, which leads to a prolongation of QRS. Mechanical dyssynchrony is a mechanical discoordination, which is most often associated with simultaneous contraction and stretching in different segments of the left ventricle (LV), as well as with delays in time until peak contraction from one segment to another. LV synchronism has an important effect on the efficiency of LV functioning. Delayed electrical activation and a weaker link between arousal and contraction leads to a dispersion of regional mechanical activation, known as intraventricular dyssynchrony, which has a negative effect on cardiac activity. The lack of coordinated mechanical LV function leads to impaired LV inotropic function, abnormal relaxation, stretching of contracture segments, positive LV remodeling with progressive dilatation of the LV cavity, which, in turn, causes an increase in ventricular wall tension, aggravating the contractile function, and functional mitral regurgitation. Echocardiographic assessment of dyssynchrony is widely used because it is non-invasive, widely available and has no risks or side effects. The technique ranges from conventional Doppler echocardiography to more advanced tissue Doppler imaging. Recently, cardiac dyssynchrony against the background of fibrosis has been considered as one of the possible pathogenetic aspects of chronic heart failure progression. Additional studies are needed to find new pleiotropic effects of recommended drugs in the group of patients with a reduced left ventricular ejection fraction, and, possibly, a positive effect on patients with a preserved ejection fraction. Researches aimed at studying mechanisms responsible for the formation of fibrosis in patients with diabetes mellitus type 2 and, as a result, manifestation and progression of heart failure, studying myocardial remodeling, the use of biomarkers of pathophysiological determinants necessary for developing personalized therapeutic approaches in order to reduce fibrosis and prevent the development of heart failure are new directions in cardiology. Despite the significant advances in the treatment of chronic heart failure in recent years, this problem is still relevant. The article presents the latest literature analysis data, highlighting studies on the pathophysiological mechanisms involved in the formation, manifestation and progression of chronic heart failure in patients with type 2 diabetes mellitus.


chronic heart failure; diabetes mellitus; dyssynchrony


Маньковский Б.Н. Сахарный диабет 2 типа и сердечно-сосудистые осложнения: как снизить риск и не навредить пациенту? / Маньковский Б.Н. // Діабет. Ожиріння. Метаболічний синдром. — 2016. — № 1. — C. 39-51.

Сіренко Ю.М. Досвід лікування Ноліпрелом пацієнтів з артеріальною гіпертензією та цукровим діабетом 2-го типу в Україні (огляд досліджень) / Ю.М. Сіренко, О.Л. Рековець // Артеріальна гіпертензія. — 2016. — № 4. — С. 27-34.

Adameova A. Role of microangiopathy in diabetic cardiomyopathy / Adameova A., Dhalla N.S. // Heart Fail Rev. — 2014. — № 19. — С. 25-33.

American Heart Association Statistics Committee and Stroke Statistics Subcommittee: Executive summary: Heart di­sease and stroke statistics — 2010 update: A report from the American Heart Association / Lloyd Jones D., Adams R.J., Brown T.M. et al. // Circulation. — 2010. — № 121. — С. 948-954.

Benefits of cardiac resynchronization therapy for heart fai­lure patients with narrow QRS complexes and coexisting systolic asynchrony by echocardiography / Yu C.M., Chan Y.S., Zhang Q. та ін. // J. Am. Coll. Cardiol. — 2006. — № 48. — С. 2251-2257.

Boudina S. Diabetic cardiomyopathy revisited / Boudina S., Abel E.D. // Circulation. — 2007. — № 115. — С. 3213-23.

Cardiac Structure and Ventricular-Vascular Function in Persons with Heart Failure and Preserved Ejection Fraction from Olmsted County, Minnesota / Lam C.S.P., Roger Vr.L., Rodeheffer R.J. та ін. // Circulation. — 2011. — № 115. — Р. 1982-1990.

Comorbidity and Ventricular and Vascular Structure and Function in Heart Failure with Preserved Ejection Fraction / Cli­nical Perspective / Mohammed S.F., Borlaug B.A., Roger Vr.L. та ін. // Circ. Heart Fail. — 2012. — № 5. — С. 710-719.

Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction / Mohammed S.F., Hussain S., Mirzoyev S.A. та ін. // Circulation. — 2015. — № 131. — С. 550-559.

Correction of left ventricular asynchrony by coronary artery surgery / D.G. Gibson, R.A. Greenbaum, R.B. Pridie, M.H. Yacoub // Br. Heart J. — 1988. — № 59. — С. 304-308.

Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography / Mor-Avi V., Lang R.M., Badano L.P. та ін. // Eur. J. Echocardiogr. — 2011. — № 12. — С. 167-205.

Diabetes and all-cause and coronary heart disease mortality among US male physicians / Lotufo P.A., Gaziano J.M., Chae C.U. та ін. // Arch. Intern. Med. — 2001. — № 161. — С. 242-247.

Dorn G.W. Manipulating cardiac contractility in HF: Data from mice and men / Dorn G.W., Molkentin J.D. // Circulation. — 2004. — № 109. — С. 150-8.

Dyssynchrony by speckle-tracking echocardiography and response to cardiac resynchronization therapy: results of the speckle tracking and resynchronization (STAR) study / Tanaka H., Nesser H.J., Buck T. та ін. // Eur. Heart J. — 2010. — № 31. — С. 1690-1700.

Echocardiographic assessment of the inter-ventricular delay of activation and correlation to the QRS width in dilated cardiomyopathy / Rouleau F., Merheb M., Geffroy S. та ін. // Pacing Clin. Electrophysiol. — 2001. — № 24. — С. 1500-1506.

Effect of Intensive Versus Standard Blood Pressure Lowe­ring on Diastolic Function in Patients with Uncontrolled Hypertension and Diastolic Dysfunction / Solomon S.D., Verma A., Desai A. та ін. // Hypertension. — 2010. — № 55. — С. 241-248.

Electrical and mechanical dyssynchrony for prediction of cardiac events in patients with systolic heart failure / Cho G.Y., Kim H.K., Kim Y.J. та ін. // Heart. — 2010. — № 96. — С. 1029-1032.

Fang Z.Y. Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications / Fang Z.Y., Prins J.B., Marwick T.H. // Endocr. Rev. — 2004. — № 25. — С. 543-67.

Fauchier Interventricular and intraventricular dyssynchrony in idiopathic dilated cardiomyopathy: a prognostic study with Fourier phase analysis of radionuclide angioscintigraphy / L. Fauchier, O. Marie, D. Casset-Senon та ін. // J. Am. Coll. Cardiol. — 2002. — № 40. — С. 2022-2030.

Gorcsan J. 3rd. The contemporary role of echocardio­graphy in improving patient response to cardiac resynchronization therapy / Gorcsan J. 3rd, Marek J.J., Onishi T. // Curr. Cardiovasc. Imaging Rep. — 2012. — № 5. — С. 462-472.

Heart disease and stroke statistics 2014 update: a report from the American heart association / Go A.S., Mozaffarian D., Ro­ger V.L. та ін. // Circulation. — 2014. — № 129. — С. e28–e292.

Heart failure with preserved ejection fraction in the elderly: scope of the problem / Upadhya B., Taffet G.E., Cheng C.P., Kitzman D.W. // J. Mol. Cell. Cardiol. — 2015. — № 83. — С. 73-87.

High prevalence of systolic and diastolic asynchrony in patients with congestive heart failure and a normal QRS duration / Yu C.M., Lin H., Zhang Q. та ін. // Heart. — 2003. — № 89. — С. 54-60.

Impact of diastolic dysfunction on the development of heart failure in diabetic patients after acute myocardial infarction / Aronson D., Musallam A., Lessick J. та ін. // Circ. Heart Fail. — 2010. — № 3. — С. 125-31.

Insulin Resistance the Link between T2DM and CVD: Basic Mechanisms and Clinical Implications / Abdul-Ghani M.A., Jayyousi A., DeFronzo R.A. та ін. // J. Curr. Vasc. Pharmacol. — 2017.

Intra-left ventricular electromechanical asynchrony: A new independent predictor of severe cardiac events in heart failure patients / Bader H., Garrigue S., Lafitte S. та ін. // J. Am. Coll. Cardiol. — 2004. — № 43. — С. 248-256.

Kannel W.B., Hjortland M., Castelli W.P. Role of diabetes in congestive heart failure: the Framingham study / Kannel W.B., Hjortland M., Castelli W.P. // Am. J. Cardiol. — 1974. — № 34. — С. 29-34.

Left ventricular diastolic and systolic dyssynchrony and dysfunction in heart failure with preserved ejection fraction and a narrow QRS complex / Liu S., Guan Z., Jin X. та ін. // Int. J. Med. Sci. — 2018. — № 15. — С. 108-114.

Left ventricular diastolic filling in young persons with type 1 diabetes mellitus / Berková M., Opavský J., Berka Z. та ін. // Biomed. Pap. Med. Fac. Univ. Palacky Olomouc. Czech Repub. — 2003. — № 147. — С. 57-61.

Left ventricular dyssynchrony in patients with heart failure and preserved ejection fraction / Santos A.B., Kraigher-Krai­ner E., Bello N. та ін. // European Heart Journal. — 2014. — № 35. — С. 42-7.

Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy / Bax J.J., Blee­ker G.B., Marwick T.H. та ін. // J. Am. Coll. Cardiol. — 2004. — № 44. — С. 1834-1840.

Left ventricular systolic and diastolic dyssynchrony in co­ronary artery disease with preserved ejection fraction / Lee P.W., Zhang Q., Yip G.W. та ін. // Clin. Sci (Lond.). — 2009. — № 116. — С. 521-9.

Mechanical dyssynchrony assessed by tissue Doppler imaging is a powerful predictor of mortality in congestive heart failure with normal QRS duration / G.Y. Cho, J.K. Song, W.J. Park та ін. // J. Am. Coll. Cardiol. — 2005. — № 46. — С. 2237-2243.

Meta-analysis Global Group in Chronic Heart Failure (MAGGIC). The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis // Eur. Heart J. — 2012. — № 33. — С. 1750-7.

Myocardial Structure and Function Differ in Systolic and Diastolic Heart Failure / van Heerebeek L., Borbely A., Niessen H.W.M. та ін. // Circulation. — 2006. — № 113. — С. 1966-1973.

Myocardial reperfusion injury: looking beyond primary PCI / Fröhlich G.M., Meier P., White S.K., Yellon D.M. // European Heart Journal. — 2013. — № 34. — С. 1714-1724.

Myocardial viability testing and impact of revascula­rization on prognosis in patients with coronary artery disease and left ventricular dysfunction: a meta-analysis / K.C. Allman, L.J. Shaw, L.J. Shaw, J.E. Udelson // J. Am. Coll. Cardiol. — 2002. — № 39. — С. 1151-1158.

Myocardial viability testing and the effect of early intervention in patients with advanced left ventricular systolic dysfunction / K.G. Tarakji, R. Brunken, P.M. McCarthy та ін. // Circulation. — 2006. — № 113. — С. 230-237.

Novel speckle-tracking radial strain from routine black-and-white echocardiographic images to quantify dyssynchrony and predict response to cardiac resynchronization therapy / Suffoletto M.S., Dohi K., Cannesson M. та ін. // Circulation. — 2006. — № 113. — С. 960-968.

Intra-left ventricular electromechanical asynchrony. A new independent predictor of severe cardiac events in heart failure patients / Bader H., Garrigue S., Lafitte S. та ін. // J. Am. Coll. Cardiol. — 2004. — № 43. — С. 248-256.

Paulus W. A Novel Paradigm for Heart Failure with Preserved Ejection Fraction: Comorbidities Drive Myocardial Dysfunction and Remodeling Through Coronary Microvascular Endothelial Inflammation / Paulus W., Tschope C. // J. Am. Coll. Cardiol. — 2013. — № 62. — С. 263-271.

Ponikowski P., Voors A.A., Anker S.D., Bueno H., Cleland J.G., Coats A.J. 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 Jul 14. — 37(27). — 2129-200.

Prevalence and Significance of Alterations in Cardiac Structure and Function in Patients With Heart Failure and a Preserved Ejection Fraction / Zile M.R., Gottdiener J.S., Hetzel S.J. та ін. // Circulation. — 2011. — № 124. — С. 2491-2501.

Prevalence of mechanical dyssynchrony in patients with heart failure and preserved left ventricular function (a report from the Belgian Multicenter Registry on dyssynchrony / De Sutter J., Van de Veire N.R., Muyldermans L. та ін. // Am. J. Cardiol. — 2005. — № 96. — С. 1543-8.

Prevalence of systolic and diastolic dysfunction in patients with type 1 diabetes without known heart disease: the Thousand & 1 Study / Jensen M.T., Sogaard P., Andersen H.U. та ін. // Diabetologia. — 2014. — № 57. — С. 672-80.

Prevalence of ventricular diastolic dysfunction in asymptomatic, normotensive patients with diabetes mellitus / Boyer J.K., Thanigaraj S., Schechtman K.B., Pérez J.E. // Am. J. Cardiol. — 2004. — № 93. — С. 870-5.

Prognostic implications of prolonged QRS duration in patients with moderate and severe left ventricular systolic dysfunction / Silvet H., Amin J., Padmanabhan S. та ін. // Am. J. Cardiol. — 2001. — № 88. — С. 182-184.

Radionuclide viability testing: should it affect treatment strategy in patients with cardiomyopathy and significant coronary artery disease? / Bourque, E.J., Velazques S., Borges-Neto K.K. та ін. // Am. Heart J. — 2003. — № 145. — С. 758-767.

RAVE Study InvestigatorsPrevalence of echocardiographically detected ventricular asynchrony in patients with left ventricular systolic dysfunction / P.L. de Isla, J. Florit, M.A. Garcia-Fernandez та ін. // J. Am. Soc. Echocardiogr. — 2005. — № 18. — С. 850-859.

Real-time three-dimensional echocardiography: a novel technique to quantify global left ventricular mechanical dyssynchrony / Kapetanakis S., Kearney M.T., Siva A. та ін. // Circulation. — 2005. — № 112. — С. 992-1000.

Results of coronary artery surgery in patients with poor left ventricular dysfunction (CASS) / E. Alderman, L.D. Fisher, P. Litwi та ін. // Circulation. — 1983. — № 38. — С. 785-795.

Severe left ventricular dyssynchrony is associated with poor prognosis in patients with moderatesystolic heart failure undergoing coronary artery bypass grafting / Penicka M., Bartunek J., Lang O. та ін. // J. Am. Coll. Cardiol. — 2007. — № 50. — С. 1315-23.

Spragg D.D. Pathobiology of left ventricular dyssynchrony and resynchronization / Spragg D.D., Kass D.A. // Prog. Cardiovasc. Dis. — 2006. — № 49. — С. 26-41.

Suran D. Tissue Doppler imaging is a sensitive echocardiographic technique to detect subclinical systolic and diastolic dysfunction of both ventricles in type 1 diabetes mellitus / Suran D., Sinkovic A., Naji F. // BMC Cardiovasc. Disord. — 2016. — № 16. — С. 72.

Szelenyi Z., Fazakas A., Szenasi G. et al. The mechanism of reduced longitudinal left ventricular systolic function in hypertensive patients with normal ejection fraction / Szelenyi Z., Fazakas A., Szenasi G. та ін. // J. Hypertens. — 2015. — № 33. — С. 1962-69.

The perindopril in elderly people with chronic heart failure (PEP-CHF) study / Cleland J.G., Tendera M., Adamus J. та ін. // European. Heart Journal. — 2006. — № 27. — С. 2338-45.

Toedebusch R., Belenchia A., Pulakat L. Diabetic Cardiomyopathy: Impact of Biological Sex on Disease Development and Molecular Signatures / Toedebusch R., Belenchia A., Pulakat L. // Front Physiol. — 2018. — № 9. — С. 453.

Understanding the impact of hypoglycemia on the cardiovascular system / Davis I.C., Ahmadizadeh I., Randell J., Younk L. // Expert Rev. Endocrinol. Metab. — 2017. — № 12. — С. 21-33.

Copyright (c) 2019 EMERGENCY MEDICINE

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© Publishing House Zaslavsky, 1997-2020


   Seo анализ сайта