Myocarditis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-In-Chief: Varun Kumar, M.B.B.S.; Maliha Shakil, M.D. [2]

Overview

Symptomatic treatment is the mainstay of therapy for patients with viral myocarditis. Supportive therapy includes diuretics and inotropes for left ventricular failure. ACE inhibitor therapy may aid in left ventricular remodeling. Among patients with fulminant myocarditis, placement of either an intra-aortic balloon pump or a left ventricular assist device may be necessary as bridge to recovery. Administration of antimicrobial therapy is recommended for bacterial myocarditis. Immunosuppressive therapy may be effective in the management of giant cell myocarditis, autoimmune myocarditis, and eosinophilic myocarditis.

Medical Therapy

Lymphocytic/Viral Myocarditis

  • The mainstay of therapy for viral myocarditis is supportive care and standard management of CHF.
  • Animal studies have demonstrated better outcomes in viral myocarditis with the use of antiviral agents and interferon early in the course of infection prior to inoculation.[1][2] The use of antiviral therapy may be limited since patients with viral myocarditis are usually not seen in the early stages. However, it may be used in acute, fulminant myocarditis and in institutional outbreaks.[3] In a series, 6 months of beta interferon in patients with myocarditis secondary to enterovirus or adenovirus infection resulted in elimination of viral genomes in all patients and improvement of LV function in 68% of the patients.[4]
  • Immunotherapy was thought to be a treatment option for myocarditis as they suppress the activity of immunologic agents mediating myocardial inflammation. 2 randomized trials reported that there were no significant change in mortality rate with immunotherapy.[5][6] However, improvement in LV function was noted in patients with chronic inflammatory dilated cardiomyopathy.[5][7] The Heart Failure Society of America recommends against the routine use of immunosuppressive agents in treatment of myocarditis.[8]
  • Intravenous immunoglobulin (IVIG) is known to have both antiviral and immunologic properties. However, its use in treatment of myocarditis has not yet been established as of yet. In a small placebo-controlled trial, there was no significant differences in survival or improvement of LV ejection fraction among patients receiving IVIG or placebo at 6 and 12months.[9] Few case reports and series suggest improvement of cardiac function with use of IVIG in patients with myocarditis. A dramatic clinical improvement was noted in two children with fulminant myocarditis with 10 hour infusion of high-dose IVIG.[10][11][12][13]
  • In another series, a tendency towards improved 1 year survival among 21 children with myocarditis was demonstrated with the use of high-dose IVIG.[14] A recent multicentric nonconcurrent cohort study which analyzed 216 myocarditis patients reported that the IVIG did not affect survival rates, even in patients with extreme illness scores.[15] As illustrated above, a systematic review concluded that there are isufficient data from methodologically strong studies to recommend routine use of IVIG in patients with myocarditis and emphasized the need of future randomized studies that take into account the etiology of acute myocarditis.[16]
  • NSAIDs in myocarditis may actually worsen the condition as they inhibit the natural healing process, and may exacerbate the inflammatory process.[17]
  • NSAIDs have been associated with an increased risk of mortality in animal models of myocarditis and hence are not recommended.[17][18][19][20]
  • Temporary pacemaker insertion is indicated in patients with symptomatic bradycardia and/or heart block during the acute phase of myocarditis.
  • ICD implantation is not indicated during the acute phase of myocarditis.
  • Antiarrhythmic therapy can be useful in patients with symptomatic NSVT or sustained VT during the acute phase of myocarditis.

Giant Cell Myocarditis

Giant cell myocarditis is a rare form of myocarditis and is generally associated with a poor prognosis.[21] Immunosuppressive therapy directed at T-cells may be beneficial as T-cells mediate myocardial inflammation.[22] In a non-randomized series, 22 patients with giant cell myocarditis who were treated with corticosteroids and cyclosporine/azathioprine, survived for an average of 12.3 months. In contrast, those patients who were not treated with immunosuppressants survived for an average of 3 months.[21] Use of immunosuppressive therapy was further strengthened by a prospective, multicenter observational study which reported an improved survival of 6 years among patients receiving high dose steroids and cyclosporine with or without muromonab-CD3.[23] Of the 11 patients studied, two patients underwent cardiac transplantation early in the course of the study and one patient died. The study also reported that withdrawal of immunosuppression was associated with a recurrence of giant cell myocarditis in some patients which in some cases was fatal.

Cardiac transplantation is sometimes required to treat refractory giant cell myocarditis. However, the condition can recur in post-transplant patients. Recurrence of biopsy proven giant cell myocarditis between 3 weeks to 9 years was observed in 9 of 34 cardiac transplant patients.[21]

Eosinophilic Myocarditis

Eosinophilic myocarditis can occur secondary to hypersensitivity to drugs, parasitic infestation. or hypereosinophilic syndrome. The eosinophils which infiltrate the myocardium, degenerate leading to extracellular release of eosinophil granules which can contribute to death of myocytes.[24] Usage of immunosuppressants such as high dose steroids (after excluding infections) and removal of offending drug (in drug induced hypersensitivity) is known to be beneficial in treatment of eosinophilic myocarditis. Immunosuppressive therapy may be tapered gradually after 1 year if normal cardiac function and cardiac enzymes levels are restored.[25]

Autoimmune Myocarditis

Myocarditis can develop in autoimmune diseases such as celiac disease and sarcoidosis. Treatment with gluten-free diet and immunosuppressants in celiac disease improves cardiac function.[26] Corticosteroids are found to be beneficial in patients with sarcoidosis related myocarditis, particularly during initial stages of the disease before development of extensive fibrosis of myocardium.[27]

Treatment of Heart Failure

As heart failure in patients with myocarditis has poor prognosis, it is important to prevent progression or worsening of cardiac dysfunction.[28] These patients should be treated with low sodium intake, diuretics and ACE inhibitors. Few animal studies report that mortality rate is high with digoxin in comparison to beta blocker in viral myocarditi.s[29][30] Studies have also demonstrated that usage of carvedilol during recovery phase decreases expression of several histochemicals and subsequently myocardial inflammation and there by improving survival.[31] The beta-blockers should however be avoided in the acutely decompensating phase of illness. If heart failure or cardiogenic shock does not respond to medical therapy, circulatory support with an intraaortic balloon pump should be considered which could be used in fulminant myocarditis as a bridge to spontaneous recovery.[32][33] Implantation of ICD in severe heart failure should be deferred for several months to allow sufficient time for recovery of ventricular function. Following the initial circulatory stabilization, further treatment of cardiac dysfunction should follow current ACC/AHA recommendations.[34] Anticoagulation may be considered in patients with severe/chronic heart failure as they are at risk for developing thromboembolic complications.

For more information on heart failure treatment, click here

Treatment of Arrhythmia

Arrhythmias or conduction abnormalities can occur in patients with myocarditis. Treatment should be initiated only if arrhythmias are symptomatic or sustained. Caution should be observed while using antiarrhythmics as majority of these agents have negative inotropic property which may worsen heart failure. Regular monitoring with ECG is important as it enables early detection and treatment of asymptomatic yet life threatening arrhythmias.

Supraventricular tachycardia(SVT) can aggravate heart failure. Symptomatic and sustained SVT should be immediately converted electrically. While, patients with recurrent sustained SVT should be treated with antiarrhythmics and rate controlling agents. Implantation of ICD should be considered in patients with recurrent ventricular arrhythmia refractory to medical therapy. Myocarditis patients presenting with conduction abnormalities, particularly Mobitz type II and complete heart block require temporary pacemaker usually during the acute phase. Implantation of permanent pacemaker or ICD may be necessary in few patients.[35]

2006 ACC/AHA/ESC Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death - Myocarditis, Rheumatic Disease, and Endocarditis[36]

Class I
" 1. Temporary pacemaker insertion is indicated in patients with symptomatic bradycardia and/or heart block during the acute phase of myocarditis. (Level of Evidence: C)"
" 2. Acute aortic regurgitation associated with VT should be treated surgically unless otherwise contraindicated.(Level of Evidence: C)"
" 3. Acute endocarditis complicated by aortic or annular abscess and AV block should be treated surgically unless otherwise contraindicated. (Level of Evidence: C)"
Class III
"1.ICD implantation is not indicated during the acute phase of myocarditis. (Level of Evidence: C)"
Class IIa
"1. ICD implantation can be beneficial in patients with life-threatening ventricular arrhythmias who are not in the acute phase of myocarditis, as indicated in the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices[37] who are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year. (Level of Evidence: C)"
" 2. Antiarrhythmic therapy can be useful in patients with symptomatic NSVT or sustained VT during the acute phase of myocarditis. (Level of Evidence: C)"

References

  1. ↑ Kishimoto C, Crumpacker CS, Abelmann WH (1988). "Prevention of murine coxsackie B3 viral myocarditis and associated lymphoid organ atrophy with recombinant human leucocyte interferon alpha A/D". Cardiovasc Res. 22 (10): 732–8. PMID 2855719.
  2. ↑ Yamamoto N, Shibamori M, Ogura M, Seko Y, Kikuchi M (1998). "Effects of intranasal administration of recombinant murine interferon-gamma on murine acute myocarditis caused by encephalomyocarditis virus". Circulation. 97 (10): 1017–23. PMID 9529271.
  3. ↑ Ray CG, Icenogle TB, Minnich LL, Copeland JG, Grogan TM (1989). "The use of intravenous ribavirin to treat influenza virus-associated acute myocarditis". J Infect Dis. 159 (5): 829–36. PMID 2775346.
  4. ↑ Kühl U, Pauschinger M, Schwimmbeck PL, Seeberg B, Lober C, Noutsias M; et al. (2003). "Interferon-beta treatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction". Circulation. 107 (22): 2793–8. doi:10.1161/01.CIR.0000072766.67150.51. PMID 12771005. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  5. ↑ 5.0 5.1 Wojnicz R, Nowalany-Kozielska E, Wojciechowska C, Glanowska G, Wilczewski P, Niklewski T; et al. (2001). "Randomized, placebo-controlled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy: two-year follow-up results". Circulation. 104 (1): 39–45. PMID 11435335.
  6. ↑ Mason JW, O'Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME; et al. (1995). "A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators". N Engl J Med. 333 (5): 269–75. doi:10.1056/NEJM199508033330501. PMID 7596370.
  7. ↑ Frustaci A, Russo MA, Chimenti C (2009). "Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study". Eur Heart J. 30 (16): 1995–2002. doi:10.1093/eurheartj/ehp249. PMID 19556262. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  8. ↑
  9. ↑ McNamara DM, Holubkov R, Starling RC, Dec GW, Loh E, Torre-Amione G; et al. (2001). "Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy". Circulation. 103 (18): 2254–9. PMID 11342473.
  10. ↑ Shioji K, Matsuura Y, Iwase T, Kitaguchi S, Nakamura H, Yodoi J; et al. (2002). "Successful immunoglobulin treatment for fulminant myocarditis and serial analysis of serum thioredoxin: a case report". Circ J. 66 (10): 977–80. PMID 12381097.
  11. ↑ Takeda Y, Yasuda S, Miyazaki S, Daikoku S, Nakatani S, Nonogi H (1998). "High-dose immunoglobulin G therapy for fulminant myocarditis". Jpn Circ J. 62 (11): 871–2. PMID 9856608.
  12. ↑ McNamara DM, Rosenblum WD, Janosko KM, Trost MK, Villaneuva FS, Demetris AJ; et al. (1997). "Intravenous immune globulin in the therapy of myocarditis and acute cardiomyopathy". Circulation. 95 (11): 2476–8. PMID 9184576.
  13. ↑ Kim HS, Sohn S, Park JY, Seo JW (2004). "Fulminant myocarditis successfully treated with high-dose immunoglobulin". Int J Cardiol. 96 (3): 485–6. doi:10.1016/j.ijcard.2003.05.037. PMID 15301907. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  14. ↑ Drucker NA, Colan SD, Lewis AB, Beiser AS, Wessel DL, Takahashi M; et al. (1994). "Gamma-globulin treatment of acute myocarditis in the pediatric population". Circulation. 89 (1): 252–7. PMID 8281654.
  15. ↑ Klugman D, Berger JT, Sable CA, He J, Khandelwal SG, Slonim AD (2010). "Pediatric patients hospitalized with myocarditis: a multi-institutional analysis". Pediatr Cardiol. 31 (2): 222–8. doi:10.1007/s00246-009-9589-9. PMID 19936586.
  16. ↑ Robinson JL, Hartling L, Crumley E, Vandermeer B, Klassen TP (2005). "A systematic review of intravenous gamma globulin for therapy of acute myocarditis". BMC Cardiovasc Disord. 5 (1): 12. doi:10.1186/1471-2261-5-12. PMC 1173096. PMID 15932639. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  17. ↑ 17.0 17.1 Meune C, Spaulding C, Mahé I, Lebon P, Bergmann JF (2003). "Risks versus benefits of NSAIDs including aspirin in myocarditis: a review of the evidence from animal studies". Drug Saf. 26 (13): 975–81. PMID 14583071. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  18. ↑ Imazio M, Trinchero R (2008). "Myopericarditis: Etiology, management, and prognosis". Int J Cardiol. 127 (1): 17–26. doi:10.1016/j.ijcard.2007.10.053. PMID 18221804. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  19. ↑ Khatib R, Reyes MP, Smith F, Khatib G, Rezkalla S (1990). "Enhancement of coxsackievirus B4 virulence by indomethacin". J Lab Clin Med. 116 (1): 116–20. PMID 1695914.
  20. ↑ Rezkalla S, Khatib G, Khatib R (1986). "Coxsackievirus B3 murine myocarditis: deleterious effects of nonsteroidal anti-inflammatory agents". J Lab Clin Med. 107 (4): 393–5. PMID 2420912. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  21. ↑ 21.0 21.1 21.2 Cooper LT, Berry GJ, Shabetai R (1997). "Idiopathic giant-cell myocarditis--natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators". N Engl J Med. 336 (26): 1860–6. doi:10.1056/NEJM199706263362603. PMID 9197214.
  22. ↑ Menghini VV, Savcenko V, Olson LJ, Tazelaar HD, Dec GW, Kao A; et al. (1999). "Combined immunosuppression for the treatment of idiopathic giant cell myocarditis". Mayo Clin Proc. 74 (12): 1221–6. PMID 10593350.
  23. ↑ Cooper LT, Hare JM, Tazelaar HD, Edwards WD, Starling RC, Deng MC; et al. (2008). "Usefulness of immunosuppression for giant cell myocarditis". Am J Cardiol. 102 (11): 1535–9. doi:10.1016/j.amjcard.2008.07.041. PMC 2613862. PMID 19026310.
  24. ↑ Corradi D, Vaglio A, Maestri R, Legname V, Leonardi G, Bartoloni G; et al. (2004). "Eosinophilic myocarditis in a patient with idiopathic hypereosinophilic syndrome: insights into mechanisms of myocardial cell death". Hum Pathol. 35 (9): 1160–3. PMID 15343520. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  25. ↑ Cooper LT, Zehr KJ (2005). "Biventricular assist device placement and immunosuppression as therapy for necrotizing eosinophilic myocarditis". Nat Clin Pract Cardiovasc Med. 2 (10): 544–8. doi:10.1038/ncpcardio0322. PMID 16186853. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  26. ↑ Frustaci A, Cuoco L, Chimenti C, Pieroni M, Fioravanti G, Gentiloni N; et al. (2002). "Celiac disease associated with autoimmune myocarditis". Circulation. 105 (22): 2611–8. PMID 12045166.
  27. ↑ Kim JS, Judson MA, Donnino R, Gold M, Cooper LT, Prystowsky EN; et al. (2009). "Cardiac sarcoidosis". Am Heart J. 157 (1): 9–21. doi:10.1016/j.ahj.2008.09.009. PMID 19081391. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  28. ↑ Magnani JW, Danik HJ, Dec GW, DiSalvo TG (2006). "Survival in biopsy-proven myocarditis: a long-term retrospective analysis of the histopathologic, clinical, and hemodynamic predictors". Am Heart J. 151 (2): 463–70. doi:10.1016/j.ahj.2005.03.037. PMID 16442915. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  29. ↑ Tominaga M, Matsumori A, Okada I, Yamada T, Kawai C (1991). "Beta-blocker treatment of dilated cardiomyopathy. Beneficial effect of carteolol in mice". Circulation. 83 (6): 2021–8. PMID 1674900.
  30. ↑ Matsumori A, Igata H, Ono K, Iwasaki A, Miyamoto T, Nishio R; et al. (1999). "High doses of digitalis increase the myocardial production of proinflammatory cytokines and worsen myocardial injury in viral myocarditis: a possible mechanism of digitalis toxicity". Jpn Circ J. 63 (12): 934–40. PMID 10614837.
  31. ↑ Wang JF, Meissner A, Malek S, Chen Y, Ke Q, Zhang J; et al. (2005). "Propranolol ameliorates and epinephrine exacerbates progression of acute and chronic viral myocarditis". Am J Physiol Heart Circ Physiol. 289 (4): H1577–83. doi:10.1152/ajpheart.00258.2005. PMID 15923319. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  32. ↑ Rockman HA, Adamson RM, Dembitsky WP, Bonar JW, Jaski BE (1991). "Acute fulminant myocarditis: long-term follow-up after circulatory support with left ventricular assist device". Am Heart J. 121 (3 Pt 1): 922–6. PMID 2000764.
  33. ↑ Chen JM, Spanier TB, Gonzalez JJ, Marelli D, Flannery MA, Tector KA; et al. (1999). "Improved survival in patients with acute myocarditis using external pulsatile mechanical ventricular assistance". J Heart Lung Transplant. 18 (4): 351–7. PMID 10226900. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  34. ↑ Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG; et al. (2009). "2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation". Circulation. 119 (14): e391–479. doi:10.1161/CIRCULATIONAHA.109.192065. PMID 19324966. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  35. ↑ Cooper LT (2009). "Myocarditis". N Engl J Med. 360 (15): 1526–38. doi:10.1056/NEJMra0800028. PMID 19357408. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  36. ↑ European Heart Rhythm Association. Heart Rhythm Society. Zipes DP, Camm AJ, Borggrefe M, Buxton AE; et al. (2006). "ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death)". J Am Coll Cardiol. 48 (5): e247–346. doi:10.1016/j.jacc.2006.07.010. PMID 16949478. Unknown parameter |http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom= ignored (help)
  37. ↑ Gregoratos G, Abrams J, Epstein AE, Freedman RA, Hayes DL, Hlatky MA; et al. (2002). "ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines)". Circulation. 106 (16): 2145–61. PMID 12379588.


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