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Chronic Heart Failure in Rheumatoid Arthritis Patients (Part II): Difficulties of Diagnosis

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Rheumatoid arthritis (RA) is characterized by a twofold increase in morbidity and mortality due to chronic heart failure (CHF). At the same time, the prevalence of CHF among RA patients is significantly underestimated. The aim of the review was to analyze the results of the main studies on the features of the clinical presentation of heart failure (HF) in RA patients, the role of visualization techniques and biomarkers in the diagnosis of HF and preclinical dysfunction of the myocardium. HF in patients with RA is characterized by a predominance of HF with a preserved left ventricular ejection fraction (LVEF). The use of clinical diagnostic criteria in RA patients can lead to both over- or underdiagnosis of CHF. Systolic dysfunction estimated by LVEF is rare in RA and does not reflect the real frequency of myocardial dysfunction. Echocardiography (ECHO-CG) with tissue Doppler echocardiography (TDE) and visualization of myocardial deformation, magnetic resonance imaging (MRI) of the heart in RA patients revealed a high frequency of HF with preserved ejection fraction, left ventricular remodeling and hypertrophy, pre-clinical systolic and diastolic dysfunction. Determination of natriuretic peptides is useful for verifying the diagnosis of HF and estimating the prognosis in this cohort, despite the possible decrease in the sensitivity and specificity of these indicators in RA patients. The review discusses the advantages of MRI of the heart, including quantitative T1 and T2 regimens, in the diagnosis of myocarditis, myocardial fibrosis, and myocardial perfusion disorders in RA patients. In order to verify the diagnosis of heart failure and detect pre-clinical myocardial dysfunction in RA patients, the determination of natriuretic peptides concentration should become part of the routine examination, beginning with the debut of the disease, along with the collection of a cardiological history, physical examination, ECHO-CT with TDE, and visualization of myocardial deformation. Evaluation of the quantitative characteristics of tissue according to MRI of the heart could improve the diagnosis of myocardial damage.

About the Authors

D. S. Novikova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
MD, PhD, Leading Researcher, Rheumocardiology Laboratory

H. V. Udachkina
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
MD, Junior Researcher, Rheumocardiology Laboratory

I. G. Kirillova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
MD, Junior Researcher, Rheumocardiology Laboratory

T. V. Popkova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
MD, PhD, Leading Researcher, Systemic Rheumatic Diseases Laboratory


1. Novikova D.S., Kirillova I.G., Udachkina H.V., Popkova T.V. Chronic heart failure in rheumatoid arthritis patients (Part I): prevalence, etiology and pathogenesis. Rational Pharmacotherapy in Cardiology. 2018:5;703-10. (In Russ.). doi:10.20996/1819-6446-2018-14-5-703-710.

2. Ponikowski P., Voors A.A., Anker S.D. 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;37: 2129-200. doi:10.1093/eurheartj/ehw128.

3. Mareev V.Y., Fomin I.V., Ageev F.T. et al. Clinical guidelines. Chronic heart failure (CHF). Heart Failure Journal. 2017;18(1):3-40 (In Russ.) doi:10.18087/rhfj.2017.1.2346.

4. Davis III J.M., Roger V.L., Crowson C.S. et al. The presentation and outcome of heart failure in persons with rheumatoid arthritis differs from that of the general population. Arthritis Rheum. 2008;58(9): 2603-11. doi:10.1002/art.23798.

5. Bhatia G.S., Sosin M.D., Patel J.V. et al. Left ventricular systolic dysfunction in rheumatoid disease. An unrecognized burden? J Am Coll Cardiol. 2006;47(6):1169-74. doi:10.1016/j.jacc.2005.10.059.

6. Schau T., Gottwald M., Arbach O. et al. Increased prevalence of diastolic heart failure in patients with rheumatoid arthritis correlates with active disease, but not with treatment type. J Rheumatol. 2015;42(11):2029-37. doi:10.3899/jrheum.141647.

7. Greulich S., Mayr A., Kitterer D., Latus J. Advanced myocardial tissue characterization by a multi-component CMR protocol in patients with rheumatoid arthritis. Eur Radiol. 2017;27:4639-49. doi10.1007/s00330-017-4838-4.

8. Myasoedova E., Davis J.M. 3rd, Crowson C.S. et al. Brief report: rheumatoid arthritisis associated with left ventricular concentric remodeling: results of a population-based cross-sectional study. Arthritis Rheum. 2013;65(7):1713-8. doi:10.1002/art.37949.

9. Cioffi G., Ognibeni F., Dalbeni A. et al. High prevalence of occult heart disease in normotensive patients with rheumatoid arthritis. Clin Cardiol. 2018;41(6):736-43.

10. Cioffi G., Viapiana O., Ognibeni F. et al. Prevalence and factors associated with subclinical left ventricular systolic dysfunction evaluated by mid-wall mechanics in rheumatoid arthritis. Echocardiography. 2016;33(9):1290-9. doi:10.1111/echo.13186.

11. Cioffi G., Viapiana O., Ognibeni F. et al. Prevalence and factors related to inappropriately high left ventricular mass in patients with rheumatoid arthritis without overt cardiac disease. J Hypertens. 2015;33:2141-9. doi:10.1097/HJH.0000000000000669.

12. Myasoedova E., Crowson C.S., Nicola P.J. et al. The influence of rheumatoid arthritis disease characteristics on heart failure. J Rheumatol. 2011;38:1601-6. doi:10.3899/jrheum.100979.

13. Garza-García C., Sánchez-Santillán R., Orea-Tejeda A. et al. Risk factors for asymptomatic ventricular dysfunction in rheumatoid arthritis patients. ISRN Cardiol. 2013;2013:635439. doi:10.1155/2013/635439.

14. Kirillova I.G., Novikova D.S., Popkova T.V. et al. Left and right ventricular diastolic dysfunction in patients with early rheumatoid arthritis before prescribing disease-modifying antirheumatic therapy. Ter Arkhiv. 2015;87(5):16-23. (In Russ.) doi:10.17116/terarkh201587516-23.

15. Aslam F., Bandeali S.J., Khan N.A., Alam M. Diastolic dysfunction in rheumatoid arthritis: a metaanalysis and systematic review. Arthritis Care Res (Hoboken). 2013;65(4):534-43. doi:10.1002/acr.21861.

16. Corrao S., Argano C., Pistone G. et al. Rheumatoid arthritis affects left ventricular mass: Systematic review and meta-analysis. Eur J Intern Med. 2015;26(4):259-67. doi:10.1016/j.ejim. 2015.02.008.

17. Giles J.T., Malayeri A.A., Fernandes V. et al. Left ventricular structure and function by cardiac magnetic resonance imaging in rheumatoid arthritis. Arthritis Rheum. 2010;62(4):940-51. doi:10.1002/art.27349.

18. Midtbø H., Gerdts E., Kvien T.K. et al. Disease activity and left ventricular structure in patients with rheumatoid arthritis. Rheumatology (Oxford). 2015;54:511-9. doi:10.1093/rheumatology/ keu368.

19. Pascale V., Finelli R., Giannotti R. et al. Cardiac eccentric remodeling in patients with rheumatoid arthritis. Sci Rep. 2018;8(1):5867. doi:10.1038/s41598-018-24323-0.

20. Yazici D., Tokay S., Aydin S. et al. Echocardiographic evaluation of сardiac diastolic function in patients with rheumatoid arthritis: 5 years of follow-up. Clin Rheumatol. 2008;27(5):647-50. doi:10.1007/s10067-007-0820-x.

21. Arnab B., Biswadip G., Arindam P. et al. Anti-CCP antibody in patients with established rheumatoid arthritis: Does it predict adverse cardiovascular profile? J Cardiovasc Dis Res. 2013;4(2):102-6. doi:10.1016/j.jcdr.2012.09.003.

22. Dinh W., Futh R., Nickl W. et al. Elevated plasma levels of TNF-alpha and interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders. Cardiovasc Diabetol. 2009;8:58. doi:10.1186/1475-2840-8-58.

23. Novikova D.S., Popkova Т.V., Gerasimov А.N. et al. High heart rate as a potential risk factor for development of cardiovascular diseases in women with rheumatoid arthritis. Rational Pharmacotherapy in Cardiology. 2012;8(5):636-6. (In Russ.) doi: 10.20996/1819-6446-2012-8-5-636-646.

24. Davis J.M. 3rd, Lin G., Oh J.K. et al. Five-year changes in cardiac structure and function in patients with rheumatoid arthritis compared with the general population. Int J Cardiol. 2017;240:379-85. doi:10.1016/j.ijcard.2017.03.108.

25. Obradović-Tomasević B., Vujasinović-Stupar N., Tomasević R. The assessment of diastolic function in patients with rheumatoid arthritis. Med Pregl. 2009;62(11-12):522-8.

26. Mokotedi L., Gunter S., Robinson C. et al. The impact of different classification criteria sets on the estimated prevalence and associated risk factors of diastolic dysfunction in rheumatoid arthritis. Int J Rheumatol. 2017;2017:2323410. doi:10.1155/2017/2323410.

27. Midtbø H., Gerdts E., Kvien T.K. et al. The association of hypertension with asymptomatic cardiovascular organ damage in rheumatoid arthritis. Blood Pressure. 2016;25(5):298-304. doi:10.3109/08037051.2016.1172867.

28. Seyfeli E., Guler H., Akoglu S. et al. Right ventricular diastolic abnormalities in rheumatoid arthritis and its relationship with left ventricular and pulmonary involvement: a tissue Doppler echocardiographic study. Int J Cardiovasc Imaging. 2006;22:745-54. doi:10.1007/s10554-006-9096-5.

29. Liang K.P., Myasoedova E., Crowson C.S. et al. Increased prevalence of diastolic dysfunction in rheumatoid arthritis. Ann Rheum Dis. 2010;69(9):1665-70. doi:0.1136/ard.2009.124362.

30. Rexhepaj N., Bajraktari G., Berisha I. et al. Left and right ventricular diastolic functions in patients with rheumatoid arthritis without clinically evident cardiovascular disease. Int J Clin Pract. 2006;60(6):683-8. doi:10.1111/j.1368-5031.2006.00746.x.

31. Magda S.L., Mincu R.I., Florescu M. et al. The assessment of subclinical cardiovascular dysfunction in treated rheumatoid arthritis. Maedica (Buchar). 2016;11(4):267-76.

32. Maloberti A., Riva M., Tadic M. et al. Association between atrial, ventricular and vascular morphofunctional alterations in rheumatoid arthritis. High Blood Press Cardiovasc Prev. 2018;25(1):97-104. doi:10.1007/s40292-017-0246-8.

33. Benacka O., Benacka J., Blazicek P. et al. Speckle tracking can detect subclinical myocardial dysfunction in rheumatoid arthritis patients. Bratisl Med J. 2017;118(1)28-33. doi:10.4149/ BLL_2017_006.

34. Midtbø H., Semb A.G., Matre K. et al. Disease activity is associated with reduced left ventricular systolic myocardial function in patients with rheumatoid arthritis. Ann Rheum Dis. 2017;76(2):371-6. doi:10.1136/annrheumdis-2016-209223.

35. Cioffi G., Viapiana O., Ognibeni F. et al. Combined circumferential and longitudinal left ventricular systolic dysfunction in patients with rheumatoid arthritis without overt cardiac disease. J Am Soc Echocardiogr. 2016;29:689-98. doi:10.1016/j.echo.2016.01.004.

36. Gullo L., Rodríguez-Carrio J., Aragona C.O. et al. Subclinical impairment of myocardial and endothelial functionality in very early psoriatic and rheumatoid arthritis patients: association with vitamin D and inflammation. Atherosclerosis. 2018;271:214-22. doi:10.1016/j.atherosclerosis.2018.03.004.

37. Fine N.M., Crowson C.S., Lin G. et al. Evaluation of myocardial function in patients with rheumatoid arthritis using strain imaging by speckle-tracking echocardiography. Ann Rheum Dis. 2014;73(10):1833-9. doi:10.1136/annrheumdis-2013-203314.

38. Baktir A.O., Sarli B., Cebicci M.A. et al. Preclinical impairment of myocardial function in rheumatoid arthritis patients. Herz. 2015;40(4):669-74. doi:10.1007/s00059-014-4068-3.

39. Løgstrup B.B., Deibjerg L.K., Hedemann-Andersen A., Ellingsen T. Left ventricular function in treatment-naive early rheumatoid arthritis. Am J Cardiovasc Dis. 2014;4:79-86.

40. Venkateshvaran A., Sarajlic P., Lund L.H. et al. Impaired left atrial dynamics and its improvement by guided physical activity reveal left atrial strain as a novel early indicator of reversible cardiac dysfunction in rheumatoid arthritis. Eur J Prev Cardiol. 2018;25(10):1106-8. doi:10.1177/2047487318777775.

41. Solus J., Chung C., Oeser A. et al. Amino-terminal fragment of the prohormone brain-type natriuretic peptide in rheumatoid arthritis. Arthritis Rheum. 2008;58(9):2662-9. doi:10.1002/art.23796.

42. Wang T.J., Larson M.G., Levy D. et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med. 2004;350:655-63. doi:10.1056/NEJMoa031994.

43. Di Angelantonio E., Chowdhury R., Sarwar N. et al. B-type natriuretic peptides and cardiovascular risk: systematic review and meta-analysis of 40 prospective studies. Circulation. 2009;120:2177-87. doi:10.1161/CIRCULATIONAHA.109.884866.

44. Mirjafari H., Welsh P., Suzanne M. et al. N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and mortality risk in early inflammatory polyarthritis: results from the Norfolk Arthritis Registry (NOAR). Ann Rheum Dis. 2014;73:684-90.

45. Provan S., Angel K., Semb A. et al. NT-proBNP predicts mortality in patients with rheumatoid arthritis: results from 10-year follow-up of the EURIDISS study. Ann Rheum Dis. 2010;69:1946-50.

46. Breunig M., Kleinert S., Lehmann S. et al. Simple screening tools predict death and cardiovascular events in patients with rheumatic disease. Scand J Rheumatol. 2018;47(2):102-9. doi:10.1080/03009742.2017.1337924.

47. Tomáš L., Lazúrová I., Oetterová M. et al. Left ventricular morphology and function in patients with rheumatoid arthritis. Wien KlinWochenschr. 2013;125(9-10):233-8. doi:10.1007/s00508-013-0349-8.

48. Crowson C., Myasoedova E., Davis J. et al. Use of B-Type Natriuretic Peptide as a screening tool for left ventricular diastolic dysfunction in rheumatoid arthritis patients without clinical cardiovascular disease. Arthritis Care and Research. 2011;63(5):729-34.

49. Kirillova I.G., Novikova D.S., Popkova T.V. et al. N-terminal pro-brain natriuretic peptide levels and diastolic dysfunction in patients with early rheumatoid arthritis before the administration of diseasemodifying antirheumatic drugs. Ter Arkhiv. 2016;88(5):19-26. (In Russ.) doi:10.17116/terarkh201688519-26.

50. Yokoe I., Kobayashi H., Kobayashi Y. Impact of tocilizumab on N-terminal pro-brain natriuretic peptide levels in patients with active rheumatoid arthritis without cardiac symptoms. Scand J Rheumatolю 2018;28:1-7. doi:10.1080/03009742.2017.1418424.

51. Armstrong D.J., Gardiner P.V., O’Kane M.J. et al. Rheumatoid arthritis patients with active disease and no history of cardiac pathology have higher Brain Natriuretic Peptide (BNP) levels than patients with inactive disease or healthy control subjects. Ulster Med J. 2010;79(2):82-4.

52. Bradham W.S., Ormseth M.J., Oeser A. et al. Insulin resistance is associated with increased concentrations of NT-proBNP in rheumatoid arthritis: IL-6 as a potential mediator. Inflammation. 2014;37(3):801-8. doi:10.1007/s10753-013-9799-4.

53. Harney M.J., Timperley J., Daly C. et al. Brain natriuretic peptide is a potentially useful screening tool for the detection of cardiovascular disease in patients with rheumatoid arthritis. Ann Rheum Dis 2006;65:136. doi:10.1136/ard.2005.040634.

54. George J., Mackle G., Manoharan A. et al. High BNP levels in rheumatoid arthritis are related to inflammation but not to left ventricular abnormalities: A prospective case-control study. Int J Cardiol. 2014;172(1):e116-8. doi:10.1016/j.ijcard.2013.12.119.

55. Biskup M., Biskup W., Majdan M., Targońska-Stępniak B. Cardiovascular system changes in rheumatoid arthritis patients with continued low disease activity. Rheumatol Int. 2018;38(7):1207-15. doi:10.1007/s00296-018-4053-x.

56. Zoli A., Bosello S., Comerci G. et al. Preserved cardiorespiratory function and NT-proBNP levels before and during exercise in patients with recent onset of rheumatoid arthritis: the clinical challenge of stratifying the patient cardiovascular risks. Rheumatol Int. 2017;37(1):13-19. doi:10.1007/s00296-015-3390-2.

57. Provan S.A., Angel K., Odegård S. et al. The association between disease activity and NT-proBNP in 238 patients with rheumatoid arthritis: a 10-year longitudinal study. Arthritis Res Ther. 2008;10(3):R70. doi:10.1186/ar2442.

58. Targońska-Stępniak B., Majdan M. Amino-terminal pro-brain natriuretic peptide as a prognostic marker in patients with rheumatoid arthritis. Clin Rheumatol. 2011;30(1):61-9. doi:10.1007/s10067-010-1622-0.

59. Bernardes M., Vieira T.S., Martins M.J. et al. Myocardial perfusion in rheumatoid arthritis patients: associations with traditional risk factors and novel biomarkers. Biomed Res Int. 2017;2017:6509754. doi:10.1155/2017/6509754.

60. Oikonomou E., Vogiatzi G., Tsalamandris S. et al. Non-natriuretic peptide biomarkers in heart failure with preserved and reduced ejection fraction. Biomark Med. 2018;12(7):783-97. doi:10.2217/bmm-2017-0376.

61. Shi L.J., Liu C., Li J.H. et al. Elevated levels of soluble ST2 were associated with rheumatoid arthritis disease activity and ameliorated inflammation in synovial fibroblasts. Chin Med J (Engl). 2018;131(3):316-22. doi:10.4103/0366-6999.223847.

62. Shen J., Shang Q., Wong C.K. et al. IL-33 and soluble ST2 levels as novel predictors for remission and progression of carotid plaque in early rheumatoid arthritis: a prospective study. Semin Arthritis Rheum. 2015;45(1):18-27. doi:10.1016/j.semarthrit.2015.02.001.

63. Hong Y., Moon S.J., Joo Y.B. et al. Measurement of interleukin-33 (IL-33) and IL-33 receptors (sST2 and ST2L) in patients with rheumatoid arthritis. J Korean Med Sci. 2011;26(9):1132-9. doi:10.3346/jkms.2011.26.9.1132.

64. Hu Y., Yéléhé-Okouma M., Ea H.K. et al. Galectin-3: A key player in arthritis. Joint Bone Spine. 2017;84(1):15-20. doi:10.1016/j.jbspin.2016.02.029.

65. Sugiura T., Kamioka M., Yamanaka S. et al. Relationship between matrix metalloproteinase-3 serum level and pulmonary artery systolic pressure in patients with rheumatoid arthritis. Heart Vessels. 2018;33(2):191-7. doi:10.1007/s00380-017-1045-9.

66. Mavrogeni S.I., Kitas G.D., Dimitroulas T. et al. Cardiovascular magnetic resonance in rheumatology: Current status and recommendations for use. Int J Cardiol. 2016;217:135-48. doi:10.1016/j.ijcard.2016.04.158.

67. Fent G.J., Greenwood J.P., Plein S., Buch M.H. The role of non-invasive cardiovascular imaging in the assessment of cardiovascular risk in rheumatoid arthritis: where we are and where we need to be. Ann Rheum Dis. 2017;76(7):1169-75. doi:10.1136/annrheumdis-2016-209744.

68. Lagan J., Schmitt M., Miller C.A. et al. Clinical applications of multi-parametric CMR in myocarditis and systemic inflammatory diseases. Int J Cardiovasc Imaging. 2018;34:35-54.doi10.1007/s10554-017-1063-9.

69. Gester M., Peker E., Nagel E., Puntmann V.O. Deciphering cardiac involvement in systemic inflammatory diseases: noninvasive tissue characterisation using cardiac magnetic resonance is key to improved patients’ care. Expert Rev Cardiovasc Ther. 2016;14(11):1283-95. doi:10.1080/ 14779072.2016.1226130.

70. Holmström M., Koivuniemi R., Korpi K. et al. Cardiac magnetic resonance imaging reveals frequent myocardial involvement and dysfunction in active rheumatoid arthritis. Clin Exp Rheumatol. 2016;34(3):416-23.

71. Ntusi N.A.B., Piechnik S.K., Francis J.M. et al. Diffuse myocardial fibrosis and inflammation in rheumatoid arthritis: insights from CMR T1 mapping. JACC Cardiovasc Imaging. 2015;8(5):526-36. doi:10.1016/j.jcmg.2014.12.025.

72. Mavrogeni S., Bratis K., Sfendouraki E., Papadopoulou E., Kolovou G. Myopericarditis, as the first sign of rheumatoid arthritis relapse, evaluated by cardiac magnetic resonance. Inflamm Allergy Drug Targets. 2013;12(3):206-11.

73. Kobayashi H., Kobayashi Y., Yokoe I. et al. Magnetic resonance imaging-detected myocardial inflammation and fibrosis in rheumatoid arthritis: associations with disease characteristics and N-terminal pro-brain natriuretic peptide levels. Arthritis Care Res (Hoboken). 2017;69(9):1304-11. doi:10.1002/acr.23138.

74. Bradham W., Ormseth M.J., Elumogo C. et al. Absence of fibrosis and inflammation by cardiac magnetic resonance imaging in rheumatoid arthritis patients with low to moderate disease activity. J Rheumatol. 2018;45(8):1078-84. pii: jrheum.170770. doi:10.3899/jrheum.170770.

75. Geraldino-Pardilla L., Russo C., Sokolove J. Association of anti-citrullinated protein or peptide antibodies with left ventricular structure and function in rheumatoid arthritis. Rheumatology. 2017;56:534540. doi:10.1093/rheumatology/kew436.

76. Ntusi N.A.B., Francis J.M., Gumedze F. et al. Cardiovascular magnetic resonance characterization of myocardial and vascular function in rheumatoid arthritis patients. Hellenic J Cardiol. 2018. pii: S1109-9666(17)30493-1. doi:10.1016/j.hjc.2018.01.008.

For citation:

Novikova D.S., Udachkina H.V., Kirillova I.G., Popkova T.V. Chronic Heart Failure in Rheumatoid Arthritis Patients (Part II): Difficulties of Diagnosis. Rational Pharmacotherapy in Cardiology. 2018;14(6):870-878.

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