Aetiology
How to Treat – Myocarditis
Aetiology
THERE are many potential triggers, such as infections, drugs, toxic substances or autoimmune conditions. The majority of cases result from viral infection. Given that the vast majority of individuals exposed to cardiotropic viruses will not develop myocarditis, genetic predisposition may come into play. 3
The frequently identified viruses are adenovirus, parvovirus B19, human herpes virus, and enterovirus. 5 Viral aetiology varies depending on geographical location. Parvovirus B19 was present in EMB samples in the US and Germany, while hepatitis C virus was detected in serologic studies of myocarditis in Japan and the US. 6
Some cases have multiple-agent infections of the myocardium.
The spectrum of cardiotropic viruses has changed in the past decade, with parvovirus and herpes virus more commonly detected than enterovirus or adenovirus in the US. 10
Giant-cell myocarditis and cardiac sarcoidosis are rare but important causes of inflammatory cardiomyopathy. These cases are sometimes associated with a high frequency of ventricular arrhythmia and atrioventricular block. Early diagnosis and treatment initiation are crucial as they will determine prognosis. 6, 10 Giant-cell myocarditis is a rapidly progressive disease and frequently fatal, despite optimal medical care.
Box 1. Common causes of myocarditis Infectious causes
Viral
• Adenovirus
• Enterovirus— Coxsackie A virus— Coxsackie B virus
• Hepatitis C virus
• Herpes virus— Herpes virus 6— Epstein – Barr virus— Cytomegalovirus
• HIV
• Influenza A virus
• Parvovirus B19
Bacterial
• Corynebacterium diphtheria
• Mycobacterium
• Mycoplasma pneumoniae
• Pneumococcus
• Streptococcus— Streptococcus pneumoniae— Streptococcus pyogenes
• Staphylococcus
Fungal
• Actinomyces
• Aspergillus
• Candida
• Coccidioides
• Cryptococcus
• Histoplasma
• Nocardia
Protozoal
• Toxoplasma gondii
• Trypanosoma cruzi
Parasitic
• Schistosoma
• Visceral larva migrans
Spirochetal
• Borrelia burgdoferi
• Leptospira
• Trepanoma pallidum
Rickettsial
• Coxiella burnetti
• Rickettsia
Source: Pollack A, et al; Feldman A and McNamara D; and Kindermann I, et al. 7, 8, 9
Non-infectious causes
Immunological
• Churg – Strauss syndrome
• Giant cell myocarditis
• Insulin dependent diabetes mellitus
• Inflammatory bowel disease
• Kawasaki’ s disease
• Sarcoidosis
• Scleroderma
• SLE
• Thyrotoxicosis
• Wegener’ s granulomatosis
Hypersensitivity
• Cephalosporin
• Diuretics— Frusemide— Thiazides
• Penicillin
• Tetanus toxoid
• Tetracycline
• Tricyclic antidepressants
Toxins
• Amphetamines
• Anthracyclines
• Catecholamines
• Cocaine
• Interleukin-2
Coxsackie A virus |
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Hepatitis C virus |
Coxsackie B virus |
Enterovirus |
Parvovirus B19 |
Herpesvirus 6 |
Epstein – Barr virus |
Evolution of virus causes of myocarditis
Epstein – Barr virus illustration.
1948 1950s 1990s 2000 2007 Figure 1. Viral causes and evolution.
Pathogenesis |
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ANIMAL studies show that myocarditis, as a virus-induced autoimmune disease, is a progressive disease process with a sequence of three pathologically distinct phases. An initial insult from a viral infection or other forms of injury triggers the first phase of the disease in patients with or without genetic predisposition. 3, 12 Viraemia is followed by destruction of the myocytes, which activates |
the innate immune system, including natural killer cells, macrophages and T-lymphocytes. If the damage is extensive, heart failure develops, and the patient may present with fulminant heart failure. 13
An effective immune response is necessary for the elimination of the agent and may account for the full recovery of the disease. 12
The second phase develops as a consequence of autoimmunity in
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susceptible individuals and is caused by myocyte necrosis. The initial cellular and humoral immune responses may improve the outcome during the first phase; conversely, they are responsible for the deleterious effect during the next phase. 14 T-cells and antibodies are directed against some cardiac epitopes as cardiac autoantibodies through molecular mimicry, leading to a powerful inflammatory
14, 15 response.
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Progression from myocarditis to dilated cardiomyopathy in the third phase occurs in patients with histologically confirmed ongoing inflammation and extensive myocardial injury. 14 Autoimmune mechanisms and viral persistence significantly contribute to chronic cardiac inflammation. 3, 13
The presence of cardiac autoantibodies in myocarditis predicts the increased risk for the development
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of chronic dilated cardiomyopathy. 16 Although the molecular and cellular pathophysiology may differ between different aetiologies, cellular infiltration, oedema, necrosis and fibrotic scars in a later stage are common features.
The three phases of myocarditis may overlap one another chronologically, and multiple cycles of the disease can occur simultaneously. 12 cont’ d page 22
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VIRAL INFECTION |
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PHASE I Acute phase Viremia |
Innate immunity activated |
Virus-mediated myocardial damage |
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PHASE II Subacute phase Viral clearing |
Adaptive immunity activated |
Immunemediated myocardial damage |
Recovery phase Absence of virus |
PHASE III Chronic phase Low-grade viral persistence |
Cardiac remodelling |
Dilated cardiomyopathy |
3, 16, 17
Based on Caforio, et al; Kawai C, et al; Kearney, et al.
Figure 2. The pathogenetic mechanisms in viral myocarditis.
Source: Medical gallery of Blausen Medical 2014 bit. ly / 2qk0wOU
20 | Australian Doctor | 7 July 2017 www. australiandoctor. com. au