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open access

Vol 29, No 3 (2022)
Original Article
Submitted: 2019-11-01
Accepted: 2020-05-11
Published online: 2020-06-17
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Prevalence and prognostic relevance of myocardial inflammation and cardiotropic viruses in non-ischemic dilated cardiomyopathy

Ieva Kažukauskienė1, Vaida Baltrūnienė1, Artūras Jakubauskas2, Edvardas Žurauskas1, Vytė Valerija Maneikienė3, Dainius Daunoravičius4, Jelena Čelutkienė3, Kęstutis Ručinskas3, Virginija Grabauskienė13
DOI: 10.5603/CJ.a2020.0088
·
Pubmed: 32567670
·
Cardiol J 2022;29(3):441-453.
Affiliations
  1. Department of Pathology, Forensic Medicine and Pharmacology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
  2. Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
  3. Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
  4. Clinicus Vilnius, Lithuania

open access

Vol 29, No 3 (2022)
Original articles — Clinical cardiology
Submitted: 2019-11-01
Accepted: 2020-05-11
Published online: 2020-06-17

Abstract

Background: Non-ischemic dilated cardiomyopathy (DCM) is a heterogeneous disease with a spectrum of etiological factors. However, subsets of the disease are not well-characterized with respect to these factors. The aim of this study was to evaluate the prevalence of myocardial inflammation and cardiotropic viruses in DCM patients and their impact on clinical outcome.
Methods: Fifty-seven patients with DCM underwent endomyocardial biopsy between 2010 and 2013. Biopsies were analyzed by polymerase chain reaction (PCR) for the presence of cardiotropic viruses, and inflammatory cell infiltration was assessed by immunohistochemistry. During a 5-year follow-up, 27 (47%) patients reached the composite outcome measure: heart transplantation, left ventricle assist device implantation or cardiovascular-related death.
Results: Thirty-one (54%) patients had myocardial inflammation and cardiotropic viruses were detected in 29 (52%). The most frequent viruses were parvovirus B19 and human herpesvirus type-6. Four specific sub-groups were distinguished by PCR and immunohistochemistry: virus-positive (chronic) myocarditis, autoreactive inflammatory DCM, viral DCM, non-inflammatory DCM. The presence of a viral genome in myocardium or diagnosis of inflammatory DCM did not predict the outcome of composite outcome measures (p > 0.05). However, univariate Cox regression and survival function estimation revealed an association between inflammation by a high number of T-cells and poor prognosis.
Conclusions: This study has shown that two markers — cardiotropic viruses and myocardial inflammation — are prevalent among DCM patients. They are also helpful in identifying sub-groups of DCM. An increased number of T-lymphocytes in the myocardium is a predictor of poor mid-term and long-term prognosis.

Abstract

Background: Non-ischemic dilated cardiomyopathy (DCM) is a heterogeneous disease with a spectrum of etiological factors. However, subsets of the disease are not well-characterized with respect to these factors. The aim of this study was to evaluate the prevalence of myocardial inflammation and cardiotropic viruses in DCM patients and their impact on clinical outcome.
Methods: Fifty-seven patients with DCM underwent endomyocardial biopsy between 2010 and 2013. Biopsies were analyzed by polymerase chain reaction (PCR) for the presence of cardiotropic viruses, and inflammatory cell infiltration was assessed by immunohistochemistry. During a 5-year follow-up, 27 (47%) patients reached the composite outcome measure: heart transplantation, left ventricle assist device implantation or cardiovascular-related death.
Results: Thirty-one (54%) patients had myocardial inflammation and cardiotropic viruses were detected in 29 (52%). The most frequent viruses were parvovirus B19 and human herpesvirus type-6. Four specific sub-groups were distinguished by PCR and immunohistochemistry: virus-positive (chronic) myocarditis, autoreactive inflammatory DCM, viral DCM, non-inflammatory DCM. The presence of a viral genome in myocardium or diagnosis of inflammatory DCM did not predict the outcome of composite outcome measures (p > 0.05). However, univariate Cox regression and survival function estimation revealed an association between inflammation by a high number of T-cells and poor prognosis.
Conclusions: This study has shown that two markers — cardiotropic viruses and myocardial inflammation — are prevalent among DCM patients. They are also helpful in identifying sub-groups of DCM. An increased number of T-lymphocytes in the myocardium is a predictor of poor mid-term and long-term prognosis.

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Keywords

dilated cardiomyopathy, chronic heart failure, myocardial inflammation, viruses, prognosis

About this article
Title

Prevalence and prognostic relevance of myocardial inflammation and cardiotropic viruses in non-ischemic dilated cardiomyopathy

Journal

Cardiology Journal

Issue

Vol 29, No 3 (2022)

Article type

Original Article

Pages

441-453

Published online

2020-06-17

Page views

5701

Article views/downloads

1140

DOI

10.5603/CJ.a2020.0088

Pubmed

32567670

Bibliographic record

Cardiol J 2022;29(3):441-453.

Keywords

dilated cardiomyopathy
chronic heart failure
myocardial inflammation
viruses
prognosis

Authors

Ieva Kažukauskienė
Vaida Baltrūnienė
Artūras Jakubauskas
Edvardas Žurauskas
Vytė Valerija Maneikienė
Dainius Daunoravičius
Jelena Čelutkienė
Kęstutis Ručinskas
Virginija Grabauskienė

References (47)
  1. Caforio ALP, Pankuweit S, Arbustini E, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013; 34(33): 2636–2648.
    CrossRefPubMed
  2. Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2008; 29(2): 270–276.
    CrossRefPubMed
  3. Chambers DC, Cherikh WS, Goldfarb SB, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-fifth adult lung and heart-lung transplant report-2018; Focus theme: Multiorgan Transplantation. J Heart Lung Transplant. 2018; 37(10): 1169–1183.
    CrossRefPubMed
  4. Richardson P, McKenna W, Bristow M, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation. 1996; 93(5): 841–842.
    CrossRefPubMed
  5. Maisch B, Portig I, Ristic A, et al. Definition of inflammatory cardiomyopathy (myocarditis): on the way to consensus. A status report. Herz. 2000; 25(3): 200–209.
    CrossRefPubMed
  6. Pinto YM, Elliott PM, Arbustini E, et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J. 2016; 37(23): 1850–1858.
    CrossRefPubMed
  7. Cooper L, Baughman K, Feldman A, et al. The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease. J Am Coll Cardiol. 2007; 50(19): 1914–1931.
    CrossRef
  8. Caforio ALP, Calabrese F, Angelini A, et al. A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis. Eur Heart J. 2007; 28(11): 1326–1333.
    CrossRefPubMed
  9. Aretz HT, Billingham ME, Edwards WD, et al. Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol. 1987; 1(1): 3–14.
    PubMed
  10. Kühl U, Pauschinger M, Noutsias M, et al. High prevalence of viral genomes and multiple viral infections in the myocardium of adults with “idiopathic” left ventricular dysfunction. Circulation. 2005; 111(7): 887–893.
    CrossRefPubMed
  11. Mahrholdt H, Wagner A, Deluigi CC, et al. Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation. 2006; 114(15): 1581–1590.
    CrossRefPubMed
  12. Kindermann I, Kindermann M, Kandolf R, et al. Predictors of outcome in patients with suspected myocarditis. Circulation. 2008; 118(6): 639–648.
    CrossRefPubMed
  13. Van Linthout S, Tschöpe C. Viral myocarditis: a prime example for endomyocardial biopsy-guided diagnosis and therapy. Curr Opin Cardiol. 2018; 33(3): 325–333.
    CrossRefPubMed
  14. Cooper L. Myocarditis. N Engl J Med. 2009; 360(15): 1526–1538.
    CrossRef
  15. D'Ambrosio A, Patti G, Manzoli A, et al. The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy: a review. Heart. 2001; 85(5): 499–504.
    CrossRefPubMed
  16. Kühl U, Noutsias M, Seeberg B, et al. Immunohistological evidence for a chronic intramyocardial inflammatory process in dilated cardiomyopathy. Heart. 1996; 75(3): 295–300.
    CrossRefPubMed
  17. Hunt S, Baker D, Chin M, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. J Am Coll Cardiol. 2001; 38(7): 2101–2113.
    CrossRef
  18. Mueller KAL, Patzelt J, Sauter M, et al. Myocardial expression of the anaphylatoxin receptor C3aR is associated with cardiac inflammation and prognosis in patients with non-ischaemic heart failure. ESC Heart Fail. 2018; 5(5): 846–857.
    CrossRefPubMed
  19. Nakayama T, Sugano Y, Yokokawa T, et al. Clinical impact of the presence of macrophages in endomyocardial biopsies of patients with dilated cardiomyopathy. Eur J Heart Fail. 2017; 19(4): 490–498.
    CrossRefPubMed
  20. Escher F, Kühl U, Lassner D, et al. Presence of perforin in endomyocardial biopsies of patients with inflammatory cardiomyopathy predicts poor outcome. Eur J Heart Fail. 2014; 16(10): 1066–1072.
    CrossRefPubMed
  21. Katzmann JL, Schlattmann P, Rigopoulos AG, et al. Meta-analysis on the immunohistological detection of inflammatory cardiomyopathy in endomyocardial biopsies. Heart Fail Rev. 2020; 25(2): 277–294.
    CrossRefPubMed
  22. Henry WL, Gardin JM, Ware JH. Echocardiographic measurements in normal subjects from infancy to old age. Circulation. 1980; 62(5): 1054–1061.
    CrossRefPubMed
  23. Mestroni L, Maisch B, McKenna WJ, et al. Guidelines for the study of familial dilated cardiomyopathies. Collaborative Research Group of the European Human and Capital Mobility Project on Familial Dilated Cardiomyopathy. Eur Heart J. 1999; 20(2): 93–102.
    CrossRefPubMed
  24. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail. 2008; 10(10): 933–989.
    CrossRefPubMed
  25. McMurray JJV, Adamopoulos S, Anker SD, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012; 33(14): 1787–1847.
    CrossRefPubMed
  26. Baltrūnienė V, Bironaitė D, Kažukauskienė I, et al. The role of serum adiponectin for outcome prediction in patients with dilated cardiomyopathy and advanced heart failure. Biomed Res Int. 2017; 2017: 3818292.
    CrossRefPubMed
  27. Noutsias M, Seeberg B, Schultheiss HP, et al. Expression of cell adhesion molecules in dilated cardiomyopathy: evidence for endothelial activation in inflammatory cardiomyopathy. Circulation. 1999; 99(16): 2124–2131.
    CrossRefPubMed
  28. Allard A, Albinsson B, Wadell G. Rapid typing of human adenoviruses by a general PCR combined with restriction endonuclease analysis. J Clin Microbiol. 2001; 39(2): 498–505.
    CrossRefPubMed
  29. McIver CJ, Jacques CFH, Chow SSW, et al. Development of multiplex PCRs for detection of common viral pathogens and agents of congenital infections. J Clin Microbiol. 2005; 43(10): 5102–5110.
    CrossRefPubMed
  30. Palecek T, Kuchynka P, Hulinska D, et al. Presence of Borrelia burgdorferi in endomyocardial biopsies in patients with new-onset unexplained dilated cardiomyopathy. Med Microbiol Immunol. 2010; 199(2): 139–143.
    CrossRefPubMed
  31. Katzmann JL, Schlattmann P, Rigopoulos AG, et al. Meta-analysis on the immunohistological detection of inflammatory cardiomyopathy in endomyocardial biopsies. Heart Fail Rev. 2020; 25(2): 277–294.
    CrossRefPubMed
  32. Pankuweit S, Portig I, Eckhardt H, et al. Prevalence of viral genome in endomyocardial biopsies from patients with inflammatory heart muscle disease. Herz. 2000; 25(3): 221–226.
    CrossRefPubMed
  33. Verdonschot J, Hazebroek M, Merken J, et al. Relevance of cardiac parvovirus B19 in myocarditis and dilated cardiomyopathy: review of the literature. Eur J Heart Fail. 2016; 18(12): 1430–1441.
    CrossRefPubMed
  34. Maisch B, Richter A, Sandmöller A, et al. BMBF-Heart Failure Network. Inflammatory dilated cardiomyopathy (DCMI). Herz. 2005; 30(6): 535–544.
    CrossRefPubMed
  35. Kühl U, Pauschinger M, Seeberg B, et al. Viral persistence in the myocardium is associated with progressive cardiac dysfunction. Circulation. 2005; 112(13): 1965–1970.
    CrossRefPubMed
  36. Nowalany-Kozielska E, Kozieł M, Domal-Kwiatkowska D, et al. Clinical significance of viral genome persistence in the myocardium of patients with dilated cardiomyopathy. Intervirology. 2015; 58(6): 350–356.
    CrossRefPubMed
  37. Kuethe F, Sigusch HH, Hilbig K, et al. Detection of viral genome in the myocardium: lack of prognostic and functional relevance in patients with acute dilated cardiomyopathy. Am Heart J. 2007; 153(5): 850–858.
    CrossRefPubMed
  38. Lotze U, Egerer R, Glück B, et al. Low level myocardial parvovirus B19 persistence is a frequent finding in patients with heart disease but unrelated to ongoing myocardial injury. J Med Virol. 2010; 82(8): 1449–1457.
    CrossRefPubMed
  39. Schenk T, Enders M, Pollak S, et al. High prevalence of human parvovirus B19 DNA in myocardial autopsy samples from subjects without myocarditis or dilative cardiomyopathy. J Clin Microbiol. 2009; 47(1): 106–110.
    CrossRefPubMed
  40. Corcioli F, Zakrzewska K, Rinieri A, et al. Tissue persistence of parvovirus B19 genotypes in asymptomatic persons. J Med Virol. 2008; 80(11): 2005–2011.
    CrossRefPubMed
  41. Kawai C. From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future. Circulation. 1999; 99(8): 1091–1100.
    CrossRefPubMed
  42. Bajpai G, Schneider C, Wong N, et al. The human heart contains distinct macrophage subsets with divergent origins and functions. Nat Med. 2018; 24(8): 1234–1245.
    CrossRefPubMed
  43. Lavine KJ, Pinto AR, Epelman S, et al. The Macrophage in Cardiac Homeostasis and Disease: JACC Macrophage in CVD Series (Part 4). J Am Coll Cardiol. 2018; 72(18): 2213–2230.
    CrossRefPubMed
  44. Hilgendorf I, Gerhardt LMS, Tan TC, et al. Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium. Circ Res. 2014; 114(10): 1611–1622.
    CrossRefPubMed
  45. Steiner MK, Syrkina OL, Kolliputi N, et al. Interleukin-6 overexpression induces pulmonary hypertension. Circ Res. 2009; 104(2): 236–244.
    CrossRefPubMed
  46. Tschöpe C, Elsanhoury A, Schlieker S, et al. Immunosuppression in inflammatory cardiomyopathy and parvovirus B19 persistence. Eur J Heart Fail. 2019; 21(11): 1468–1469.
    CrossRefPubMed
  47. Bock CT, Klingel K, Kandolf R. Human parvovirus B19-associated myocarditis. N Engl J Med. 2010; 362(13): 1248–1249.
    CrossRefPubMed

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