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Recurrent pericarditis: new and emerging therapeutic options

Key Points

  • Recurrent pericarditis is the most troublesome complication after an episode of acute pericarditis, and occurs in 20–50% of patients with pericarditis

  • Most cases of recurrent pericarditis are idiopathic, and the pathogenesis is presumed to be immune-mediated or autoinflammatory

  • The mainstay of treatment for recurrent pericarditis is high doses of anti-inflammatory therapy—usually aspirin or an NSAID (generally ibuprofen or indomethacin) plus colchicine

  • Second-line drugs are corticosteroids, to be used at low-to-moderate doses (such as prednisone 0.2–0.5 mg/kg per day or equivalent), plus colchicine

  • Triple combination therapy (aspirin or NSAID plus colchicine and corticosteroid) should be considered for patients with multiple recurrences

  • Additional options for patients with multiple (three or more) failures of conventional anti-inflammatory therapies include azathioprine, intravenous immunoglobulins, and anakinra, with pericardiectomy being a last resort

Abstract

Recurrent pericarditis is one of the most common and troublesome complications after an episode of pericarditis, and affects 20–50% of patients treated for pericarditis. In most of these patients, the pericarditis remains idiopathic, although an immune-mediated (either autoimmune or autoinflammatory) pathogenesis is often presumed. The mainstay of therapy for recurrences is aspirin or NSAIDs, with the adjunct of colchicine. Corticosteroids are a second-line option to be considered for specific indications, such as connective tissue disease or pregnancy; contraindications or intolerance to aspirin, NSAIDs, and/or colchicine; or insufficient response to these medications. Furthermore, corticosteroids can be added to NSAIDs and colchicine in patients with persistent symptoms. In patients who do not respond adequately to any of these conventional therapies, alternative treatment options include azathioprine, intravenous human immunoglobulins, and anakinra. An improved understanding of how recurrent pericarditis develops after an initiating event is critical to prevent this complication, and further research is needed into the pathogenesis of recurrences. We discuss the aetiology and diagnosis of recurrent pericarditis, and extensively review the treatment options for this condition.

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Figure 1: Mechanisms of action of emerging treatments for recurrent pericarditis.
Figure 2: Treatment levels for recurrent pericarditis.
Figure 3: Clinical trials of colchicine for the prevention of recurrent pericarditis.

References

  1. Imazio, M. et al. Colchicine in addition to conventional therapy for acute pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial. Circulation 112, 2012–2016 (2005).

    CAS  Article  Google Scholar 

  2. Imazio, M. et al. Colchicine as first-choice therapy for recurrent pericarditis: results of the CORE (COlchicine for REcurrent pericarditis) trial. Arch. Intern. Med. 165, 1987–1991 (2005).

    CAS  Article  Google Scholar 

  3. Imazio, M. et al. Colchicine for recurrent pericarditis (CORP): a randomized trial. Ann. Intern. Med. 155, 409–414 (2011).

    Article  Google Scholar 

  4. Imazio, M. et al. A randomized trial of colchicine for acute pericarditis. N. Engl. J. Med. 369, 1522–1528 (2013).

    CAS  Article  Google Scholar 

  5. Imazio, M. et al. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial. Lancet 383, 2232–2237 (2014).

    CAS  Article  Google Scholar 

  6. Artom, G. et al. Pretreatment with corticosteroids attenuates the efficacy of colchicine in preventing recurrent pericarditis: a multi-centre all-case analysis. Eur. Heart J. 26, 723–727 (2005).

    CAS  Article  Google Scholar 

  7. Imazio, M. et al. Management, risk factors, and outcomes in recurrent pericarditis. Am. J. Cardiol. 96, 736–739 (2005).

    Article  Google Scholar 

  8. Seferovic´, P. M. et al. Pericardial syndromes: an update after the ESC guidelines 2004. Heart Fail. Rev. 18, 255–266 (2013).

    Article  Google Scholar 

  9. Maisch, B., Rupp, H., Ristic, A. & Pankuweit, S. Pericardioscopy and epi- and pericardial biopsy—a new window to the heart improving etiological diagnoses and permitting targeted intrapericardial therapy. Heart Fail. Rev. 18, 317–328 (2013).

    Article  Google Scholar 

  10. LeWinter, M. M. Clinical practice. Acute pericarditis. N. Engl. J. Med. 371, 2410–2416 (2014).

    Article  Google Scholar 

  11. Brucato, A. et al. Recurrent pericarditis: infectious or autoimmune? Autoimmun. Rev. 8, 44–47 (2008).

    CAS  Article  Google Scholar 

  12. Cantarini, L. et al. Role of autoimmunity and autoinflammation in the pathogenesis of idiopathic recurrent pericarditis. Clin. Rev. Allergy Immunol. 44, 6–13 (2013).

    CAS  Article  Google Scholar 

  13. Imazio, M. Idiopathic recurrent pericarditis as an immune-mediated disease: current insights into pathogenesis and emerging treatment options. Expert Rev. Clin. Immunol. 11, 1487–1492 (2014).

    Article  Google Scholar 

  14. Imazio, M. et al. Antinuclear antibodies in recurrent idiopathic pericarditis: prevalence and clinical significance. Int. J. Cardiol. 136, 289–293 (2009).

    Article  Google Scholar 

  15. Caforio, A. L. et al. Anti-heart and anti-intercalated disk autoantibodies: evidence for autoimmunity in idiopathic recurrent acute pericarditis. Heart 96, 779–784 (2010).

    CAS  Article  Google Scholar 

  16. Imazio, M. Pericardial involvement in systemic inflammatory diseases. Heart 97, 1882–1892 (2011).

    Article  Google Scholar 

  17. Imazio, M., Hoit, B. D. Post-cardiac injury syndromes. An emerging cause of pericardial diseases. Int. J. Cardiol. 168, 648–652 (2013).

    Article  Google Scholar 

  18. Imazio, M., Adler, Y. Treatment with aspirin, NSAID, corticosteroids, and colchicine in acute and recurrent pericarditis. Heart Fail. Rev. 18, 355–360 (2013).

    CAS  Article  Google Scholar 

  19. Brucato, A., Brambilla, G. Recurrent idiopathic pericarditis: familial occurrence. Int. J. Cardiol. 102, 529 (2005).

  20. Soriano, A., Manna, R. Familial Mediterranean fever: new phenotypes. Autoimmun. Rev. 1, 31–37 (2012).

    Article  Google Scholar 

  21. Cantarini, L. et al. Clues to detect tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among patients with idiopathic recurrent acute pericarditis: results of a multicentre study. Clin. Res. Cardiol. 101, 525–531 (2012).

    CAS  Article  Google Scholar 

  22. Cantarini, L., Lucherini, O. M., Baldari, C. T., Laghi Pasini, F. & Galeazzi, M. Familial clustering of recurrent pericarditis may disclose tumour necrosis factor receptor-associated periodic syndrome. Clin. Exp. Rheumatol. 28, 405–407 (2010).

    PubMed  Google Scholar 

  23. Cantarini, L. et al. Idiopathic recurrent pericarditis refractory to colchicine treatment can reveal tumor necrosis factor receptor-associated periodic syndrome. Int. J. Immunopathol. Pharmacol. 22, 1051–1058 (2009).

    CAS  Article  Google Scholar 

  24. Maisch, B. Recurrent pericarditis: mysterious or not so mysterious? Eur. Heart J. 26, 631–633 (2005).

    Article  Google Scholar 

  25. Imazio, M. et al. Relation of acute pericardial disease to malignancy. Am. J. Cardiol. 95, 1393–1394 (2005).

    Article  Google Scholar 

  26. Imazio, M. et al. Medical therapy of pericardial diseases: part II: noninfectious pericarditis, pericardial effusion and constrictive pericarditis. J. Cardiovasc. Med. (Hagerstown) 11, 785–794 (2010).

    Google Scholar 

  27. Imazio, M. et al. Aetiological diagnosis in acute and recurrent pericarditis: when and how. J. Cardiovasc. Med. (Hagerstown) 10, 217–230 (2009).

    Article  Google Scholar 

  28. Seidenberg, P. H. & Haynes, J. Pericarditis: diagnosis, management, and return to play. Curr. Sports Med. Rep. 5, 74–79 (2006).

    Article  Google Scholar 

  29. Soler-Soler, J., Sagristà-Sauleda, J. & Permanyer-Miralda, G. Relapsing pericarditis. Heart 90, 1364–1368 (2004).

    Article  Google Scholar 

  30. Klein, A. L. et al. American Society of Echocardiography clinical recommendations for multimodality cardiovascular imaging of patients with pericardial disease: endorsed by the Society for Cardiovascular Magnetic Resonance and Society of Cardiovascular Computed Tomography. J. Am. Soc. Echocardiogr. 26, 965–1012.e15 (2013).

    Article  Google Scholar 

  31. Alraies, M. C. et al. Usefulness of cardiac magnetic resonance-guided management in patients with recurrent pericarditis. Am. J. Cardiol. 115, 542–547 (2014).

    Article  Google Scholar 

  32. Young, P. M. et al. MR imaging findings in 76 consecutive surgically proven cases of pericardial disease with CT and pathologic correlation. Int. J. Cardiovasc. Imaging 28, 1099–2010 (2012).

    Article  Google Scholar 

  33. Cremer, P. C. & Kwon, D. H. Multimodality imaging of pericardial disease. Curr. Cardiol. Rep. 17, 24 (2015).

    Article  Google Scholar 

  34. Imazio, M. & Gaita, F. Diagnosis and treatment of pericarditis. Heart 101, 1159–1168 (2015).

    CAS  Article  Google Scholar 

  35. Imazio, M. et al. Recurrent pain without objective evidence of disease in patients with previous idiopathic or viral acute pericarditis. Am. J. Cardiol. 94, 973–975 (2004).

    Article  Google Scholar 

  36. Horneffer, P. J. et al. The effective treatment of postpericardiotomy syndrome after cardiac operations. A randomized placebo-controlled trial. J. Thorac. Cardiovasc. Surg. 100, 292–296 (1990).

    CAS  PubMed  Google Scholar 

  37. Lotrionte, M. et al. International collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences. Am. Heart J. 160, 662–670 (2010).

    CAS  Article  Google Scholar 

  38. Imazio, M., Brucato, A., Trinchero, R., Spodick, D. & Adler, Y. Individualized therapy for pericarditis. Expert Rev. Cardiovasc. Ther. 7, 965–975 (2009).

    CAS  Article  Google Scholar 

  39. Maisch, B. et al. Guidelines on the diagnosis and management of pericardial diseases executive summary. Eur. Heart J. 25, 587–610 (2004).

    Article  Google Scholar 

  40. Imazio, M. et al. Prevalence of C-reactive protein elevation and time course of normalization in acute pericarditis: implications for the diagnosis, therapy, and prognosis of pericarditis. Circulation 123, 1092–1097 (2011).

    CAS  Article  Google Scholar 

  41. Imazio, M. et al. Corticosteroids for recurrent pericarditis: high versus low doses: a nonrandomized observation. Circulation 118, 667–671 (2008).

    CAS  Article  Google Scholar 

  42. Ristic´, A. D. et al. Pericardial disease in pregnancy. Herz 28, 209–215 (2003).

    Article  Google Scholar 

  43. Imazio, M. et al. Management of pericardial diseases during pregnancy. J. Cardiovasc. Med. (Hagerstown) 11, 557–562 (2010).

    Article  Google Scholar 

  44. Imazio, M. New clinical trials in acute and recurrent pericarditis. Curr. Cardiol. Rep. 17, 23 (2015).

    Article  Google Scholar 

  45. Rodríguez de la Serna, A., Guindo Soldevila, J., Martí Claramunt, V. & Bayés de Luna, A. Colchicine for recurrent pericarditis. Lancet 2, 1517 (1987).

    Article  Google Scholar 

  46. Adler, Y. et al. Colchicine treatment for recurrent pericarditis. A decade of experience. Circulation 97, 2183–2185 (1998).

    CAS  Article  Google Scholar 

  47. Imazio, M. Colchicine for pericarditis. Trends Cardiovasc. Med. 25, 129–136 (2015).

    CAS  Article  Google Scholar 

  48. Briasoulis, A. & Afonso, L. Prevention of pericarditis with colchicine: an updated meta-analysis. J. Cardiovasc. Med. (Hagerstown) 16, 144–147 (2015).

    Article  Google Scholar 

  49. Alabed, S., Cabello, J. B., Irving, G. J., Qintar, M. & Burls, A. Colchicine for pericarditis. Cochrane Database of Systematic Reviews, Issue 8. Art. No.: CD010652. http://dx.doi.org/10.1002/14651858.CD010652.pub2.

  50. Vianello, F. et al. Azathioprine in isolated recurrent pericarditis: a single centre experience. Int. J. Cardiol. 147, 477–478 (2011).

    Article  Google Scholar 

  51. Gelfand, E. W. Intravenous immune globulin in autoimmune and inflammatory diseases. N. Engl. J. Med. 367, 2015–2025 (2012).

    CAS  Article  Google Scholar 

  52. del Fresno, M. R. et al. Intravenous immunoglobulin therapy for refractory recurrent pericarditis. Pediatrics 134, e1441–e1446 (2014).

    Article  Google Scholar 

  53. Moretti, M. et al. Usefulness of high-dose intravenous human immunoglobulins treatment for refractory recurrent pericarditis. Am. J. Cardiol. 112, 1493–1498 (2013).

    CAS  Article  Google Scholar 

  54. Imazio, M. et al. Intravenous human immunoglobulins for refractory recurrent pericarditis. A systematic review of all published cases. J. Cardiovasc. Med. (Hagerstown) http://dx.doi.org/10.2459/JCM.0000000000000260.

  55. Grattagliano, I. et al. Novel therapeutics for the treatment of familial Mediterranean fever: from colchicine to biologics. Clin. Pharmacol. Ther. 95, 89–97 (2014).

    CAS  Article  Google Scholar 

  56. Mertens, M. & Singh, J. A. Anakinra for rheumatoid arthritis: a systematic review. J. Rheumatol. 36, 1118–1125 (2009).

    CAS  Article  Google Scholar 

  57. Picco, P. et al. Successful treatment of idiopathic recurrent pericarditis in children with interleukin-1β receptor antagonist (anakinra): an unrecognized autoinflammatory disease? Arthritis Rheum. 60, 264–268 (2009).

    CAS  Article  Google Scholar 

  58. Lazaros, G. et al. Anakinra for the management of resistant idiopathic recurrent pericarditis. Initial experience in 10 adult cases. Ann. Rheum. Dis. 73, 2215–2217 (2014).

    CAS  Article  Google Scholar 

  59. Lazaros, G. et al. Anakinra: an emerging option for refractory idiopathic recurrent pericarditis. A systematic review of published evidence. J. Cardiovasc. Med. (Hagerstown) http://dx.doi.org/10.2459/JCM.0000000000000266.

  60. Nieto González, J. C. et al. Idiopathic recurrent pericarditis treated successfully with tumour necrosis factor alpha blocking agents (anti-TNF-α). Clin. Exp. Rheumatol. 31, 776–778 (2013).

    PubMed  Google Scholar 

  61. Khandaker, M. H. et al. Pericardiectomy vs medical management in patients with relapsing pericarditis. Mayo Clin. Proc. 87, 1062–1070 (2012).

    Article  Google Scholar 

  62. Imazio, M. et al. Prognosis of idiopathic recurrent pericarditis as determined from previously published reports. Am. J. Cardiol. 100, 1026–1028 (2007).

    Article  Google Scholar 

  63. Imazio, M. et al. Risk of constrictive pericarditis after acute pericarditis. Circulation 124, 1270–1275 (2011).

    Article  Google Scholar 

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M.I. researched data and wrote the article. All the authors contributed substantially to discussion of its content, reviewing, and editing the manuscript before submission.

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Correspondence to Massimo Imazio.

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Imazio, M., Lazaros, G., Brucato, A. et al. Recurrent pericarditis: new and emerging therapeutic options. Nat Rev Cardiol 13, 99–105 (2016). https://doi.org/10.1038/nrcardio.2015.115

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