Acta Cardiologia Indonesiana (Vol 2 No. 2): 69-81 Current Diagnosis and Management of Myocarditis Windhi Dwijanarko, Hasanah Mumpuni, Bambang Irawan Department of Cardiology and Vascular Medicine Faculty of Medicine Universitas Gadjah Mada - Dr. Sardjito General Hospital, Yogyakarta, Indonesia ABSTRACT Myocarditis is an inflammation of the myocardium. The clinical presentations of myocarditis range from nonspecific systemic symptom such as fever, myalgias, palpitations, or exertional dyspnea, to severe hemodynamic derangement and sudden death. The wide variation of clinical manifestations has made the exact incidence of myocarditis difficult to determine. The prevalence of myocarditis based on autopsy data is ranging from 2 to 42%. Myocarditis has heterogeneous clinical presentation, ranging from mild chest pain or palpitations to cardiogenic shock and life-threatening ventricular arrhythmias. The diagnosis of myocarditis requires a high initial suspicion. Non-invasive techniques, such as cardiac magnetic resonance imaging, can be useful to diagnose and monitor of disease. The endomyocardial biopsy is the gold standard for definitive diagnosis of myocarditis and can identify the etiology of myocarditis. By endomyocardial biopsy, it can direct patients who can be managed by conventional therapy or who require specific treatment based on underlying etiology, such as antiviral or intravenous immunoglobulin infusion. Keywords: myocarditis; diagnosis; management Introduction progress to DCM and have a poor prognosis.2 Myocarditis is an inflammation of the The aim of the review is to inform the current myocardium. The clinical presentations of diagnosis and management of myocarditis. myocarditis range from nonspecific systemic symptom such as fever, myalgias, palpitations, Definition or exertional dyspnea, to severe hemodynamic Myocarditis refers to every inflammation in derangement and sudden death. The wide the myocardium. Inflammation can be occurred variation of clinical manifestations has made after any form of injury to the heart, including the exact incidence of myocarditis difficult to ischemia, mechanical trauma, and genetic determine. The use of endomyocardial biopsy cardiomyopathies. According to the Dallas criteria, has helped to understand the natural history of acute myocarditis is defined by lymphocytic myocarditis and to clarify the clinicopathological infiltrates in association with myocyte necrosis. 1 correlations. Borderline myocarditis is defined as inflammatory The prevalence of myocarditis based on infiltrates without evidence of myocyte necrosis.3 2 autopsy data is ranging from 2 to 42%. In Newer histologic criteria rely on cell-specific biopsy-proven myocarditis, the prevalence is immunoperoxidase stains for surface antigens ranging between 9 and 16% of adult patients such as anti-CD3, anti-CD4, anti-CD20, anti- suffering from idiopathic non-ischaemic dilated CD28, and antihuman leukocyte antigen. The cardiomyopathy (DCM). In most patients with criteria based on this type of staining has greater mild symptoms and minimal left ventricular sensitivity than the Dallas criteria and may have dysfunction, myocarditis subside spontaneously more prognostic value.4 without specific treatment. However, about 30% In the 2007 European Society of Cardiology of cases, in biopsy-proven myocarditis can (ESC) classifications of cardiomyopathies 69 Copyright©2013. Jurnal Perikanan (Journal of Fisheries Sciences) All Right Reserved Dwijanarko et al., 2016 and the 2013 ESC myocarditis Task Force histologically confirmed myocarditis with cardiac report, myocarditis is defined histologically as dysfunction.7 an inflammatory disease of the myocardium diagnosed by endomyocardial biopsy, Etiology based on histological, immunological, The etiology is large variety of infectious immunohistochemical and molecular findings agents, systemic diseases, drugs, and toxins to detect possible infectious causes.2,5,6 The term (table 1). Viral infections are the most important inflammatory cardiomyopathy may be used for Table 1. Causes of myocarditis classification Type Causes Specific 1. Infectious Bacterial Staphylococcus, Streptococcus, Pneumococcus, Meningococcus, myocarditis Gonococcus, Salmonella, Corynebacterium diphtheriae, Haemophilus influenzae, Mycobacterium (tuberculosis), Mycoplasma pneumoniae, Brucella Viral RNA viruses: Coxsackieviruses A and B, echoviruses, polioviruses, influenza A and B viruses, respiratory syncytial virus, mumps virus,measles virus, rubella virus, hepatitis C virus, dengue virus, yellow fever virus, Chikungunya virus, Junin virus, Lassa fever virus, rabies virus, human immunodeficiency virus-1 DNA viruses: adenoviruses, parvovirus B19, cytomegalovirus, human herpes virus-6, Epstein-Barr virus, varicella-zoster virus, herpessimplex virus, variola virus, vaccinia virus Spirochaetal Borrelia (Lyme disease), Leptospira (Weil disease) Fungal Aspergillus, Actinomyces, Blastomyces, Candida, Coccidioides, Cryptococcus, Histoplasma, Mucor-mycoses, Nocardia, Sporothrix Protozoal Trypanosoma cruzi (Chagas disease), Toxoplasma gondii, Entamoeba, Leishmania Parasitic Trichinella spiralis, Echinococcus granulosus, Taenia solium, Schistosoma Rickettsial Coxiella burnetii (Q fever), R. rickettsii (Rocky Mountain spotted fever), R. tsutsugamuschi 2. Immune- Allergens Tetanus toxoid, vaccines, serum sickness mediated Drugs: penicillin, cefaclor, colchicine, furosemide, isoniazid, lidocaine, myocarditis tetracycline, sulfonamides, phenytoin, phenylbutazone,methyldopa, thiazide diuretics, amitriptyline Alloantigens Heart transplant rejection Autoantigens Infection-negative lymphocytic, infection-negative giant cell. Autoimmune disorders:systemic lupus erythematosus, rheumatoid arthritis, Churg- Strausssyndrome, Kawasaki’s disease, inflammatory bowel disease, scleroderma, polymyositis, myasthenia gravis, insulin-dependent diabetesmellitus, thyrotoxicosis, sarcoidosis, Wegener’s granulomatosis, rheumatic heart disease (rheumatic fever) 3. Toxic Drugs Amphetamines, anthracyclines, cocaine, cyclophosphamide, ethanol, myocarditis fluorouracil, lithium, catecholamines, hemetine, interleukin-2,trastuzumab, clozapine Heavy metals Copper, iron, lead (rare, more commonly cause intramyocyte accumulation) Physical Radiation, electric shock, hypothermia, heat stroke agents Hormones Phaeochromocytoma, vitamins: beri–beri Miscellaneous Scorpion sting, snake, and spider bites, bee and wasp stings, carbon monoxide, inhalants, phosphorus, arsenic, sodium azide RNA, ribonucleic acid; DNA, deoxyribonucleic acid; HIV, human immunodeficiensy virus; CMV, cytomegalovirus; EBV, Epstein-Barr Virus; HSV, herpes simplex virus (Source: Caforio et al., 2013)2 70 Copyright©2013. Jurnal Perikanan (Journal of Fisheries Sciences) All Right Reserved Acta Cardiologia Indonesiana (Vol 2 No. 2): 69-81 Figure 1. Pathogenesis process of myocarditis (Source: Cooper, 2009)11 cause of myocarditis in North America and viral infection resulting in myocarditis andl Europe with genomes of enterovirus, adenovirus, eft ventricular dysfunction. It is often unclear influenza viruses, human herpes virus-6 (HHV-6), clinically whether the HIV virus itself, medications Epstein-Barr-virus, cytomegalovirus, hepatitis used for treatment, or myocardial coinfection C virus, and parvovirusB19 reported in the is responsible for the observed left ventricular myocardium of patients with myocarditis and systolic dysfunction due to myocarditis.9 DCM.2 In a multicenter study of 624 patients with In the myocarditis, if no viruses are identified biopsy-proven myocarditis (66%) or borderline in endomyocardial biopsy and other known myocarditis (34%), evidence of viral genome causes are excluded, lymphocytic and giant (adenovirus,enterovirus, and cytomegalovirus) cell myocarditis are presumed idiopathic or was detected in 38% of subjects’ endomyocardial autoimmune. Similarly, the diagnosis of idiopathic biopsies.8 Human immunodeficiency virus granulomatous myocarditis (cardiac sarcoidosis) (HIV) has been associated with cardiotropic requires negative stains for microorganisms. 71 Copyright©2013. Jurnal Perikanan (Journal of Fisheries Sciences) All Right Reserved Dwijanarko et al., 2016 Figure 2. Pathogenesis of myocarditis (Source: Blauwet & Cooper, 2010)13 Autoimmune myocarditis can be exclusively antibiotics, and antipsychotics, have been cardiac involvement or as a part of autoimmune associated with hypersensitivity myocarditis.12 disorders with extra-cardiac manifestations, such Eosinophilic myocarditis is characterized by a as in sarcoidosis, hypereosinophilic syndrome, largely eosinophilic infiltrate in the myocardium. It scleroderma, and systemic lupus erythematosus. may occur in association with systemic diseases, Autoimmune myocarditis is a primary antigen such as the hypereosinophilic syndrome, the responsible for progression from a self-limited viral Churg-Strauss syndrome, Löffler’s endomyocardial infection to subsequent autoimmune disease.10 fibrosis, cancer, and parasitic, helminthic, or The bacterial-induced myocarditis is far protozoal infections.12 Clinical manifestations less common than viral-induced myocarditis. of eosinophilic myocarditis include congestive Toxin-producing bacteria, including clostridium heart failure, endocardial and valvular fibrosis, and diphtheria, can cause severe myocardial and endocardial thrombi. A rare disorder, acute damage. Bacteremia from any source may result in necrotizing eosinophilic myocarditis is a progressive myocarditis. The most common