Myocarditis Organism-Specific Therapy 

Myocarditis Organism-Specific Therapy 

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General recommendations and organism-specific therapeutic regimens for myocarditis are provided below, including those for viral [1, 2, 3, 4] and bacterial organisms. [2, 3, 5] Special considerations are also discussed.

Most cases of myocarditis are post viral in origin [6, 7] ; therefore, supportive therapy is first-line treatment. [2]

Obtain hemodynamic stability with vasopressors and inotropic agents, if needed.

Use diuretics and vasodilators if high ventricular filling pressures are noted on echocardiography.

Consider a left ventricular assist device, transplantation, or both in patients with severe disease.

Once the patient is stabilized, follow the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the treatment of heart failure. [1] Angiotensin-converting enzyme inhibitors (ACEIs), beta-blockade, and an aldosterone antagonist are recommended if the patient has New York Heart Association (NYHA) grade III-IV symptoms). [3, 5]

Endomyocardial biopsy is the criterion standard for diagnosis of myocarditis. [2, 8, 9]

Historically, the Dallas criteria have been used for histologic diagnosis, although their utility is questioned.

Elevated troponin I (>0.1 ng/mL) is highly specific for the diagnosis of myocarditis; the creatine kinase–muscle-brain (CK-MB) fraction and the total creatine kinase (CK) level are not useful.

Echocardiography is recommended as the initial imaging test of choice in suspected myocarditis.

Cardiac magnetic resonance imaging (MRI) is useful to differentiate between myocarditis and other cardiomyopathies, as well as to target endomyocardial biopsy sites.

The classification of myocarditis based on etiology is shown in the chart below. [2, 8, 9]

Viral:

Human immunodeficiency virus (HIV):

Initiate antiretroviral therapy; for more information, see Antiretroviral Therapy for HIV Infection

Cytomegalovirus (CMV):

Induction therapy: Ganciclovir 5 mg/kg IV q12h for 7-14d

Maintenance therapy: Valganciclovir 900 mg PO q24h

Duration of therapy: Indefinite, but it may be stopped if the CD4 count is >100 for 6 months [10]

Borrelia burgdorferi:

First-degree atrioventricular (AV) block:

Doxycycline 100 mg PO q12h or

Amoxicillin 500 mg PO q8h or

Cefuroxime 500 mg PO q12h

Duration of therapy: 14-21d

Symptomatic, second- or third-degree AV block:

Ceftriaxone 2 g/day IV or

Cefotaxime 2 g IV q8h

Duration of therapy: 14-28 days [4]

Mycoplasma pneumoniae:

Doxycycline 100 mg PO q12h or

Azithromycin 500 mg PO q24h or

Levofloxacin 500 mg IV or PO q24h or

Moxifloxacin 400 mg PO q24h or

Erythromycin 250 mg PO q6h

Duration of therapy: 14-21d

Methicillin-resistant Staphylococcus aureus (MRSA):

Vancomycin 15-20 mg/kg/dose IV q8-12h (not to exceed 2 g/dose) (A-II) or

Daptomycin 6 mg/kg/dose IV once daily (A-I) for at least 2-6 weeks [11]

Corynebacterium diphtheriae:

Erythromycin 40 mg/kg/day PO/IV in divided doses for 14 days; not to exceed 2 g/day or

Penicillin G procaine 600,000 U IM for 14d; if weight < 10 kg, give 300,000 U/day [12]

Babesiosis:

Atovaquone 750 mg PO q12h plus azithromycin 500-1000 mg PO on day 1, then 250 mg once daily for 7-10d or

Clindamycin 300-600 mg IV q6h or 600 mg PO q8h plus quinine 650 mg PO q6-8h for 7-10 days

Clindamycin and quinine should be given for those with severe babesiosis [4]

Schistosoma mansoni, Schistosoma haematobium, Schistosoma intercalatum:

Praziquantel 20 mg/kg PO for 2 doses within 1 day [13, 14]

Trypanosoma cruzi:

Benznidazole 5-7 mg/kg/day PO in 2 divided doses for 60 days (investigational in the United States; available from the CDC)

Nifurtimox 8-10 mg/kg/day PO in 3 or 4 divided doses for 90 days [15]

Clinical therapeutic considerations for myocarditis scenarios  [2, 8, 9, 16]

See the acute myocarditis flow chart (first image below) and subacute myocarditis flow chart (second image below).

Forty percent of dilated cardiomyopathy patients not responding to treatment have myocarditis. [17, 18]

Ten percent of unexplained myocarditis cases are post viral in origin. [6, 7]

The prognosis depends on spontaneous complete resolution (acute fulminant myocarditis) or the development to dilated cardiomyopathy. [19, 20]

Inflammation has beneficial effects on clearing the viral particles; hence, immune suppression is not generally recommended. [21]

Infection with enterovirus and adenoviruses could be treated with 6 mIU interferon 3 times a week to reduce the viral load and improve ventricular function during an acute myocarditis episode. [9]

Studies investigating intravenous immunoglobulin (IVIG) therapy in adults with acute myocarditis and acute myopathy have failed to show any type of usefulness in treatment during an acute episode.

In patients with HIV infection, a long-term follow up (at 5 y) with echocardiogram has shown that 8% show dilated cardiomyopathy changes. [22] However, it is unknown if ACEIs and beta-blockers are effective in these patients.

Giant cell myocarditis is the only known cause of most fulminant heart failure with ventricular arrhythmias. [23, 24] Immunosuppression and mechanical cardiac support are recommended in this case and, possibly, cardiac transplantation, with a 20-25% recurrence rate post transplantation. Immunosuppression may have beneficial effects to some extent. [25]

Hypersensitivity-related myocarditis often manifests as infiltration with lymphocytes, histocytes, and eosinophil, and sometimes it results in sudden death from complications of myocarditis.

Myopericarditis with acute coronary syndrome is a potential complication. Treat inflammation with colchicine at 2 mg/day PO with stepwise dose reduction, which should improve pericarditis in 3 months; NSAIDs are contraindicated in this condition. [26, 27]

Syncope with ventricular arrhythmia and cardiac block should be treated with hospital admission with continuous echocardiogram monitoring and conservative management, similar to acute arrhythmias.

Cardiogenic shock may require mechanical ventilator support, extracorporal membrane oxygen therapy, and cardiac transplantation. [28, 29]

[Guideline] Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Jun 5. [Medline].

Magnani JW, Dec GW. Myocarditis: current trends in diagnosis and treatment. Circulation. 2006 Feb 14. 113(6):876-90. [Medline].

Knowlton KU, Oxman MN, Savoia MC. Myocarditis and pericarditis. Mandell, Douglas, and Bennett, eds. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Churchill Livingstone; 2009. Vol 1: Chapter 8.

[Guideline] Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1. 43(9):1089-134. [Medline].

[Guideline] Hunt SA, Abraham WT, Chin MH, et al. 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. 2009 Apr 14. 119(14):e391-479. [Medline].

Eshaghian S, Horwich TB, Fonarow GC. Relation of loop diuretic dose to mortality in advanced heart failure. Am J Cardiol. 2006 Jun 15. 97(12):1759-64. [Medline].

Gallager R, Luttik ML, Jaarsma T. Social Support and Self-care in Heart Failure. J Cardiovasc Nurs. 6:439-45. [Medline].

Schultz JC, Hilliard AA, Cooper LT Jr, Rihal CS. Diagnosis and treatment of viral myocarditis. Mayo Clin Proc. 2009 Nov. 84(11):1001-9. [Medline]. [Full Text].

Sagar S, Liu PP, Cooper LT Jr. Myocarditis. Lancet. 2012 Feb 25. 379(9817):738-47. [Medline].

Kimberlin DW, Lin CY, Sánchez PJ, et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr. 2003 Jul. 143(1):16-25. [Medline].

[Guideline] Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011 Feb 1. 52(3):285-92. [Medline].

[Guideline] Centers for Disease Control and Prevention. Diphtheria. Available at http://www.cdc.gov/diphtheria/clinicians.html. Accessed: Sept. 25, 2014.

[Guideline] Centers for Disease Control and Prevention. Schistosomiasis. Available at http://www.cdc.gov/parasites/schistosomiasis/health_professionals/index.html#tx. Accessed: Sept. 24, 2014.

[Guideline] World Health Organization. WHO-Preventive in human helminthiasis. Available at http://whqlibdoc.who.int/publications/2006/9241547103_eng.pdf. Accessed: Sept. 25, 2014.

[Guideline] Centers for Disease Control and Prevention. American Trypanosomiasis (also known as Chagas Disease). Available at http://www.cdc.gov/parasites/chagas/health_professionals/index.html. Accessed: Sept. 25, 2014.

Cooper LT Jr. Myocarditis. N Engl J Med. 2009 Apr 9. 360(15):1526-38. [Medline].

Sato Y, Yamada T, Matsumori A. Hepatitis C virus and cardiomyopathy. Matsumori A, ed. Cardiomyopathies and Heart Failure: Biomolecular, Infectious, and Immune Mechanisms. Boston, Mass: Kluwer Academic Publishers; Vol 92: 2519–25.

Matsumori A, Matoba Y, Sasayama S. Dilated cardiomyopathy associated with hepatitis C virus infection. Circulation. 1995 Nov 1. 92(9):2519-25. [Medline].

Domanski M, Norman J, Pitt B, Haigney M, Hanlon S, Peyster E. Diuretic use, progressive heart failure, and death in patients in the Studies Of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol. 2003 Aug 20. 42(4):705-8. [Medline].

Rogers HL, Marshall J, Bock J, et al. A randomized, controlled trial of the renal effects of ultrafiltration as compared to furosemide in patients with acute decompensated heart failure. J Card Fail. 2008 Feb. 14(1):1-5. [Medline].

Lieback E, Hardouin I, Meyer R, Bellach J, Hetzer R. Clinical value of echocardiographic tissue characterization in the diagnosis of myocarditis. Eur Heart J. 1996 Jan. 17(1):135-42. [Medline].

Pepi M, Marenzi GC, Agostoni PG, et al. Sustained cardiac diastolic changes elicited by ultrafiltration in patients with moderate congestive heart failure: pathophysiological correlates. Br Heart J. 1993 Aug. 70(2):135-40. [Medline]. [Full Text].

Costanzo MR, Guglin ME, Saltzberg MT, et al. Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol. 2007 Feb 13. 49(6):675-83. [Medline].

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Wojnicz R, Nowalany-Kozielska E, Wojciechowska C, et al. Randomized, placebo-controlled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy: two-year follow-up results. Circulation. 2001 Jul 3. 104(1):39-45. [Medline].

Griffiths PD, Hannington G, Booth JC. Coxsackie B virus infections and myocardial infarction. Results from a prospective, epidemiologically controlled study. Lancet. 1980 Jun 28. 1(8183):1387-9. [Medline].

Geri G, Wechsler B, Thi Huong du L, et al. Spectrum of cardiac lesions in Behçet disease: a series of 52 patients and review of the literature. Medicine (Baltimore). 2012 Jan. 91(1):25-34. [Medline].

Margari ZJ, Anastasiou-Nana MI, Terrovitis J, et al. Indium-111 monoclonal antimyosin cardiac scintigraphy in suspected acute myocarditis: evolution and diagnostic impact. Int J Cardiol. 2003 Aug. 90(2-3):239-45. [Medline].

Laissy JP, Messin B, Varenne O, et al. MRI of acute myocarditis: a comprehensive approach based on various imaging sequences. Chest. 2002 Nov. 122(5):1638-48. [Medline].

Harsha S Nagarajarao, MD Interventional, Structural Heart Disease, and Heart Failure Cardiologist, Jackson Cardiology Associates

Harsha S Nagarajarao, MD is a member of the following medical societies: American College of Cardiology, American Heart Association, American Society of Echocardiography, American Society of Transplantation, Society for Cardiac Angiography and Interventions

Disclosure: Nothing to disclose.

Archana Kedar, MBBS Instructor, Department of Medicine, Division of Digestive Diseases, University of Mississippi Medical Center

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Thomas E Herchline, MD Professor of Medicine, Wright State University, Boonshoft School of Medicine; Medical Consultant, Public Health, Dayton and Montgomery County (Ohio) Tuberculosis Clinic

Thomas E Herchline, MD is a member of the following medical societies: Alpha Omega Alpha, Infectious Diseases Society of America, Infectious Diseases Society of Ohio

Disclosure: Nothing to disclose.

Kelley Struble, DO, Fellow, Department of Infectious Diseases, University of Oklahoma College of Medicine

Kelley Struble, DO, is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Aamer Rehman, MRCP, MD, Fellow, Division of Cardiology, University of Louisville Medical Center for help with reviewing the article.

Disclosure: Nothing to disclose.

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