Viral Myocarditis

Question 1

What is myocarditis?

Answer 1

Inflammation of the heart muscle

Question 2

How is myocarditis classified?

Answer 2

Acute, subacute or chronic

Question 3

What two types of myocardium involvement may be present?

Answer 3

Myocardial involvement may be focal or diffuse

Question 4

How is diagnosis of myocarditis made?

Answer 4

Diagnostic criteria is based on histology, immunological and immunohistochemical findings in an endomyocardial biopsy specimen
- it does not consider the cause of the pathological finding

Question 5

How often is no etiology identified?

Answer 5

In approx 50% of patients with dilated cardiomyopathy no etiology is identified.

Question 6

What are the two possible classes of etiological agents in myocarditis?

Answer 6

1. Infectious

2. Non-infectious

Question 7

Are infectious or non-infectious causes of myocarditis more common?

Answer 7

Infectious = most common cause of myocarditis (of these viral = most common)

Question 8

What are the most frequently implicated cause of myocarditis in children?

Answer 8

Viruses

Question 9

What is acute myocarditis most often due to?

Answer 9

Viral infection

Question 10

What are the two possible outcomes following viral infection of myocardial cells?

Answer 10

1. Immune clearance - recovery (most common outcome)

2. Persistence / chronic infection and inflammatory process = chronic dilated cardiomyopathy = congestive heart failure

Question 11

What are the most common viruses implicated in myocarditis?

Answer 11

1. Enteroviruses = VERY COMMON e.g. Coxsackie B Virus
2. Adenoviruses
3. Parvovirus B19
4. Human Herpes Virus-6
5. Cytomegalovirus

Question 12

What other viruses are implicated in myocarditis?

Answer 12

HIV, Hepatitis C, Varicella-Zoster Virus, Epstein-Barr Virus, Influenza (low incidence in SA)

Question 13

What is the most common viral cause of myocarditis?

Answer 13

Coxsackie B Virus

Question 14

What are some of the predisposing factors to the development of viral myocarditis?

Answer 14

Immune status, malnutrition, age, exercise, pregnancy, genetic factors, environmental factors
Unknown factors also play a role

Question 15

What are the 3 steps in the pathogenesis of myocarditis?

Answer 15

1. Viral mediated myocardial damage
2. Immune mediated myocardial damage
3. Dilated cardiomyopathy due to myocardial remodeling

Question 16

How does direct viral destruction of cardiomyocytes occue?

Answer 16

1. Viral entry into the cell = active viral replication within the myocardium
2. Viral enzymes specifically cleave cellular proteins
3. Virus mediated cell toxicity and lysis

Question 17

What is significant about the immune response in myocarditis?

Answer 17

The immune response halts viral replication (important for viral clearance) BUT may also cause further damage to the myocardium (ineffective response - chronic myocarditis)

Question 18

What two types of immune mediated myocardial damage may be present?

Answer 18

1. Immune dysregulation triggered by the initial virus mediated myocardial damage
2. Myocardial damage due to lymphocytes and antibodies mimicking epitopes shared between the viral and cardiac antigen

Question 19

How does immune dysregulation cause myocardial damage?

Answer 19

(Occurs after a week(s) of the initial viral infection)

• A replication incompetent viral genome can persist for an extended period of time in the myocardium
• Viral persistence can lead to immune-mediated injury due to the constant presence of viral antigen driving the immune response

Question 20

How do lymphocytes and antibodies mimicking shared epitopes cause myocardial damage?

Answer 20

Molecular mimicry = auto-immune response

- Infiltration of T-lymphocytes in the cardiomyocytes = T-cell mediated myocardial injury / necrosis

Question 21

What are the causes of dilated cardiomyopathy due to myocardial remodeling?

Answer 21

1. Low grade persistent inflammatory process induced by cross-reacting antibodies with auto-antigens
2. Activation of T-cells and associated cytokines by intracellular cardiac proteins in response to virus mediated myocardial damage (cytokines suppress myocardial contractility)
3. Progressive myocardial damage and reparative fibrosis
4. Left ventricular dilation and cardiac dysfunction

Question 22

What happens during Phase I of myocarditis?

Answer 22

Virus infection and replication

innate immunity myocardial damage - virus-mediated myocarditis

Question 23

What happens during Phase II of myocarditis?

Answer 23

Incomplete viral clearance

anti-viral immunity - epitope spreading and molecular mimicry - auto-immunity - immune-mediated myocarditis

Question 24

What happens during Phase III of myocarditis?

Answer 24

Low grade viral persistence

cardiac remodeling - dilated cardiomyopathy

Question 25

What is the most common clinical presentation of viral myocarditis?

Answer 25

Viral myocarditis is often subclinical and self-limiting | = majority of patient are asymptomatic

Question 26

What does symptomatic viral myocarditis look like?

Answer 26

History (<1-2 week) of influenza-like symptoms | - fever, arthralgia and malaise / pharyngitis, tonsillitis, or upper respiratory tract infections of GIT symptoms

Question 27

What are common presenting complaints of viral myocarditis?

Answer 27

Palpitations, chest pain, syncope

Question 28

What are some of the clinical findings in viral myocarditis?

Answer 28

Clinical findings may be variable: - Acute heart failure = frequent presentation - Acute MI or tachyarrhythmia - Left ventricular systolic and/or diastolic dysfunction - Abnormalities in electrical activation

Question 29

How is diagnosis of viral myocarditis usually made?

Answer 29

Diagnosis is usually presumptive: based on patients history and clinical course

Question 30

What investigations can be done for viral myocarditis?

Answer 30

1. Blood Studies: FBC, CRP, cardiac enzymes (i.e. creatine kinase or cardiac troponins), serum cardiac auto-antibodies 2. CXR 3. ECG 4. Imaging studies (echo, cardiac angiogram, MRI)

Question 31

What is the preferred diagnostic test in viral myocarditis?

Answer 31

PCR

Question 32

What is the gold standard specimen?

Answer 32

Endomyocardial biopsy for detection of viral genome

Question 33

What tests can be used in making a presumptive diagnosis?

Answer 33

1. Specimen: blood, stool and respiratory secretions (for enterovirus secretions) - does not prove direct viral infection of the heart, symptoms prior to / at the time of diagnosis = is suggestive of the cause 2. PCR: positive viral result 3. Serology: positive IgM &/or a 4-fold raised IgG on paired sera

Question 34

What is the best management modality for myocarditis?

Answer 34

Early identification and treatment | Pitfall: majority are asymptomatic & self-limiting infection

Question 35

What is used to treat myocarditis?

Answer 35

1. Antiviral therapy 2. Immunoglobulin may be helpful 3. Supportive: standard heart failure treatment i.e. diuretics, beta-blockers, ACE-inhibitors, monitoring and treatment of arrhythmias etc.

Question 36

What should be done to prevent developing viral myocarditis?

Answer 36

Avoid exercise during active viral infection = may increase viral replication.