Skip to main content

Advertisement

SpringerLink
Log in

New Advances and Ongoing Challenges in the Use of Biologic Agents in Cardiac Sarcoidosis and Other Inflammatory Cardiomyopathies

  • Heart Failure (W Tang, Section Editor)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Abstract

Purpose of review

Inflammatory cardiomyopathies encompass several different conditions revolving around inflammation. Experts, supported primarily by experience, have utilized immunosuppression as a treatment option to halt the inflammation and prevent the common end result of dilated cardiomyopathy. Very limited evidence exists to support a uniformed approach.

Recent findings

Standard immunosuppression protocols are typically used to treat inflammatory cardiomyopathies associated with systemic inflammatory diseases. However, specific features such as eosinophilic infiltration or fulminant course merit a more aggressive and targeted approach. As our understanding of inflammation continues to evolve, the more directed biologic agents have been more successfully used as alternatives to more traditional immunosuppression.

Summary

Subtyping inflammatory cardiomyopathies, including better immune-profiling, might aid more specific approaches. This review discusses the mechanisms of disease and new advances in the use of biologic agents in treatment of inflammatory cardiomyopathies, including cardiac sarcoidosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Trachtenberg BH, Hare JM. Inflammatory cardiomyopathic syndromes. Circ Res. 2017;121(7):803–18.

    Article  CAS  PubMed  Google Scholar 

  2. Caforio AP, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, 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):2636–48.

    Article  PubMed  Google Scholar 

  3. Imanaka-Yoshida K. Inflammation in myocardial disease: from myocarditis to dilated cardiomyopathy. Pathol Int. 2020;70(1):1–11.

    Article  PubMed  Google Scholar 

  4. •• Van Linthout S, Tschöpe C. The quest for antiinflammatory and immunomodulatory strategies in heart failure. Clin Pharmacol Ther. 2019;106(6):1198–208 An overview of inflammation immunobiology in heart failure.

    Article  PubMed  Google Scholar 

  5. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connell J, 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):841–2.

    Article  CAS  PubMed  Google Scholar 

  6. Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JJ, et al. Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol. 1987;1:3–14.

    CAS  PubMed  Google Scholar 

  7. Dominguez F, Kühl U, Pieske B, Garcia-Pavia P, Tschöpe C. Update on myocarditis and inflammatory cardiomyopathy: reemergence of endomyocardial biopsy. Rev. Esp Cardiol (Engl Ed). 2016;69(2):178–87.

    Article  PubMed  Google Scholar 

  8. Sagar S, Liu PP, Myocarditis CLT. Lancet. 2012;379:738–74.

    Article  PubMed  Google Scholar 

  9. Baughman RP, Wells A. Advanced sarcoidosis. Curr Opin Pulm Med. 2019;25(5):497–504.

    Article  CAS  PubMed  Google Scholar 

  10. Cooper LT Jr, Hare JM, Tazelaar HD, Edwards WD, Starling RC, Deng MC, et al. Usefulness of immunosuppression for giant cell myocarditis. Am J Cardiol. 2008;102(11):1535–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. De Luca G, Campochiaro C, Sartorelli S, Peretto G, Dagna L. Therapeutic strategies for virus-negative myocarditis: a comprehensive review. Eur J Intern Med. 2020;77:9–17.

    Article  PubMed  Google Scholar 

  12. Thompson W, Argáez C. Early biologic treatment versus conventional treatment for the management of Crohn’s disease: a review of comparative clinical effectiveness and cost-effectiveness. Canadian Agency for Drugs and Technologies in Health. 2019.

  13. Agostini C, Adami F, Semenzato G. New pathogenetic insights into the sarcoid granuloma. Curr Opin Rheumatol. 2000;12:71–6.

    Article  CAS  PubMed  Google Scholar 

  14. Terasaki F, Ukimura A, Tsukada B, Fujita S, Katashima T, Otsuka K, et al. Enhanced expression of type 1 helper T cell cytokines in the myocardium of active cardiac sarcoidosis. Circ J. 2008;72:1303–7.

    Article  PubMed  Google Scholar 

  15. Elwazir MY, Bois JP, Abou Ezzeddine OF, Chareonthaitawee P. Imaging and quantification of cardiac sarcoidosis. Semin Nucl Med. 2020 Jul;50(4):283–94.

    Article  PubMed  Google Scholar 

  16. Birnie DH. Cardiac sarcoidosis. Semin Respir Crit Care Med. 2020. https://doi.org/10.1055/s-0040-1,712,535 An overview of presentation, diagnosis, and management of cardiac sarcoidosis.

  17. Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) Trial. Circulation. 2003;107(25):3133–40.

    Article  CAS  PubMed  Google Scholar 

  18. Harper LJ, McCarthy M, Ribeiro Neto ML, Hachamovitch R, Pearson K, Bonanno B. Infliximab for refractory cardiac sarcoidosis. Am J Cardiol. 2019;124(10):1630–5.

    Article  CAS  PubMed  Google Scholar 

  19. Wijnen PA, Cremers JP, Nelemans PJ, Erckens RJ, Hoitsma E, Jansen TL, et al. Association of the TNF-α G-308A polymorphism with TNF-inhibitor response in sarcoidosis. Eur Respir J. 2014;43(6):1730–9.

    Article  CAS  PubMed  Google Scholar 

  20. Rosenthal DG, Parwani P, Murray TO, Petek BJ, Benn BS, De Marco T, et al. Long-term corticosteroid-sparing immunosuppression for cardiac sarcoidosis. J Am Heart Assoc. 2019;8(18):e010952.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Solomon DH, Rassen JA, Kuriya B, Chen L, Harrold LR, Graham DJ, et al. Heart failure risk among patients with rheumatoid arthritis starting a TNF antagonist. Ann Rheum Dis. 2013;72:1813–8.

    Article  CAS  PubMed  Google Scholar 

  22. Kudryavtsev I, Serebriakova M, Starshinova A, Zinchenko Y, Basantsova N, Malkova A, et al. Imbalance in B cell and T follicular helper cell subsets in pulmonary sarcoidosis. Sci Rep. 2020;10(1):1059.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bergantini L, d’Alessandro M, Cameli P, Vietri L, Vagaggini C, Perrone A. Effects of rituximab therapy on B cell differentiation and depletion. Clin Rheumatol. 2020;39(5):1415–21.

    Article  CAS  PubMed  Google Scholar 

  24. Sweiss NJ, Lower EE, Mirsaeidi M, Dudek S, Garcia JGN, Perkins D, et al. Rituximab in the treatment of refractory pulmonary sarcoidosis. Eur Respir J. 2014;43(5):1525–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Krause ML, Cooper LT, Chareonthaitawee P, Amin S. Successful use of rituximab in refractory cardiac sarcoidosis. Rheumatology (Oxford). 2016;55(1):189–91.

    Article  PubMed  Google Scholar 

  26. Cooper LT, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis--natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators. N Engl J Med. 1997;336(26):1860–6.

    Article  PubMed  Google Scholar 

  27. Okura Y, Dec GW, Hare JM, Kodama M, Berry GJ, Tazelaar HD, et al. A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis. J Am Coll Cardiol. 2003;41(2):322–9.

    Article  PubMed  Google Scholar 

  28. Toscano G, Tartaro P, Fedrigo M, Angelini A, Marcolongo R. Rituximab in recurrent idiopathic giant cell myocarditis after heart transplantation: a potential therapeutic approach. Transpl Int. 2014;27(5):e38–42.

    Article  CAS  PubMed  Google Scholar 

  29. Séguéla PE, Iriart X, Acar P, Montaudon M, Roudaut R, Thambo JB. Eosinophilic cardiac disease: molecular, clinical and imaging aspects. Arch Cardiovasc Dis. 2015;108(4):258–68.

    Article  PubMed  Google Scholar 

  30. Harish A, Schwartz SA. Targeted anti-IL-5 therapies and future therapeutics for hypereosinophilic syndrome and rare eosinophilic conditions. Clin Rev Allergy Immunol. 2020. https://doi.org/10.1007/s12016-019-08775-4 Online ahead of print.

  31. Khurana S, Brusselle GG, Bel EH, FitzGerald JM, Masoli M, Korn S, et al. Long-term safety and clinical benefit of mepolizumab in patients with the most severe eosinophilic asthma: the COSMEX Study. Clin Ther. 2019;41(10):2041–56.

    Article  CAS  PubMed  Google Scholar 

  32. Song T, Jones DM, Homsi Y. Therapeutic effect of anti-IL-5 on eosinophilic myocarditis with large pericardial effusion. BMJ Case Rep. 2017.

  33. Apte M, McGwin G Jr, Vilá LM, Kaslow RA, Alarcón GS, Reveille JD. Associated factors and impact of myocarditis in patients with SLE from LUMINA, a multiethnic US cohort. Rheumatology (Oxford). 2008;47(3):362–7.

    Article  CAS  PubMed  Google Scholar 

  34. Thomas G, Aubart FC, Chiche L, Haroche J, Hié M, Hervier B, et al. Lupus myocarditis: initial presentation and longterm outcomes in a multicentric series of 29 patients. J Rheumatol. 2017;44(1):24–32.

    Article  CAS  PubMed  Google Scholar 

  35. Bidani AK, Roberts JL, Schwartz MM, Lewis EJ. Immunopathology of cardiac lesions in fatal systemic lupus erythematosus. Am J Med. 1980;69(6):849–58.

    Article  CAS  PubMed  Google Scholar 

  36. Wang CR, Tsai YS, Li WT. Lupus myocarditis receiving the rituximab therapy-a monocentric retrospective study. Clin Rheumatol. 2018;37(6):1701–7.

    Article  PubMed  Google Scholar 

  37. Hurd ER. Extraarticular manifestations of rheumatoid arthritis. Sem Arthritis Rheum. 1979;8:151–76.

    Article  CAS  Google Scholar 

  38. Ikonomidis I, Lekakis JP, Nikolaou M, Paraskevaidis I, Andreadou I, Kaplanoglou T, et al. Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis. Circulation. 2008;117(20):2662–9.

    Article  CAS  PubMed  Google Scholar 

  39. Kuek A, Weerakoon A, Ahmed K, Ostör AJK. Adult-onset Still’s disease and myocarditis: successful treatment with intravenous immunoglobulin and maintenance of remission with etanercept. Rheumatology (Oxford). 2007;46(6):1043–4.

    Article  CAS  PubMed  Google Scholar 

  40. Savage E, Wazir T, Drake M, Cuthbert R, Wright G. Fulminant Myocarditis and Macrophage Activation Syndrome Secondary to Adult-onset still’s disease successfully treated with tocilizumab. Rheumatology (Oxford). 2014;53(7):1352–3.

    Article  PubMed  Google Scholar 

  41. Varnavas VC, Reinsch N, Perrey M, Nensa F, Schlosser T, Baba HA, et al. Recurrent lymphocytic myocarditis in a young male with ulcerative colitis. Eur J Med Res. 2014;19(1):11.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kim HK, Kim K, Jung SW, Mun HS, Cho JR, Lee N, et al. Successfully treated acute fulminant myocarditis induced by ulcerative colitis with extracorporeal life support and infliximab. J Cardiovasc Ultrasound. 2016;24(2):163–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Misra DP, Shenoy SN. Cardiac involvement in primary systemic vasculitis and potential drug therapies to reduce cardiovascular risk. Rheumatol Int. 2017;37(1):151–67.

    Article  CAS  PubMed  Google Scholar 

  44. Harada M, Yokouchi Y, Oharaseki T, Matsui K, Tobayama H, Tanaka N, et al. Histopathological characteristics of myocarditis in acute-phase Kawasaki disease. Histopathology. 2012;61(6):1156–67.

    Article  PubMed  Google Scholar 

  45. Munch A, Sundboll J, Hoyer S, Pareek M. Acute myocarditis in a patient with newly diagnosed granulomatosis with polyangiitis. Case Rep Cardiol. 2015;2015:134529.

    PubMed  PubMed Central  Google Scholar 

  46. Wang CR, Tsai YS, Tsai HW. Acute Myocarditis in Patients With Antineutrophil Cytoplasmic Antibody-positive microscopic polyangiitis and receiving rituximab therapy. J Rheumatol. 2019;46(12):1645–6.

    Article  PubMed  Google Scholar 

  47. Clifford A, Hoffman GS. Recent Advances in the medical management of Takayasu Arteritis: an update on use of biologic therapies. Curr Opin Rheumatol. 2014;26(1):7–15.

    Article  CAS  PubMed  Google Scholar 

  48. Lee Y, Schulte DJ, Shimada K, Chen S, Crother TR, Chiba N, et al. Interleukin-1β Is Crucial for the Induction of Coronary Artery Inflammation in a Mouse Model of Kawasaki disease. Circulation. 2012;125(12):1542–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk J3-4, Cleveland, OH, 44122, USA

    Ziad Taimeh MD & W. H. Wilson Tang MD

Authors
  1. Ziad Taimeh MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. H. Wilson Tang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ziad Taimeh MD.

Ethics declarations

Conflict of Interest

Ziad Taimeh and Wilson Tang declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Heart Failure

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Taimeh, Z., Tang, W.H.W. New Advances and Ongoing Challenges in the Use of Biologic Agents in Cardiac Sarcoidosis and Other Inflammatory Cardiomyopathies. Curr Treat Options Cardio Med 23, 39 (2021). https://doi.org/10.1007/s11936-021-00918-1

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11936-021-00918-1

Keywords

Search

Navigation