Myocarditis (derived from ‘myocardium’ = cardiac muscle, and -itis = inflammation) describes the inflammation of the muscular layer of the heart, the ‘myocardium’. The myocardium forms the majority of the atrial and ventricular wall thickness, with the pericardium superficial (surrounding the myocardium) and the endocardium deep (beneath the myocardium). The pericardium is formed of two layers (the visceral and parietal) with a potential cavity or ‘space’ that can fill with fluid i.e., blood (in pathological states), but exploring this is beyond the scope of this article.

Myocarditis can be acute or chronic. Acute myocarditis generally describes symptom onset and diagnosis <1 month, whereas chronic myocarditis is >1 month with evidence of a dilated heart, or a non-dilated heart with reduced wall motion¹.

The above picture was sourced from the URL: https://en.wikipedia.org/wiki/Idiopathic_giant-cell_myocarditis²

The above picture shows the three primary layers of the heart, from left to right and deep to superficial, the endocardium, the myocardium, and the pericardium. In myocarditis, the central, thick, muscular layer (the myocardium) is inflamed. From time to time, there can be an extension of the inflammation to also involve the pericardium causing myopericarditis.

Pathophysiology

As with any form of inflammation, inflammation of the myocardium can be caused by a variety of factors. This ranges from infection to immune-mediated, however, the most common causative agents worldwide are Trypanosoma cruzi^3,4 and diphtheria⁵ (the most common bacterial cause). In Europe, however, it is viral-induced myocarditis secondary to Coxsackievirus⁵. Other causative viruses include COVID-19, adenovirus, enterovirus, B19 parvovirus, HIV, EBV, HAV and HAC^5,6. The list below highlights other causes of myocarditis to be aware of^3,5-7:

Epidemiology

The Global Burden of Study Disease assessed the incidence of myocarditis, from the years 1990 to 2013, to be approximately 22 per 100 000 patients per annum. This does not differentiate between acute and chronic myocarditis, however⁸.

Risk Factors

Multiple different risk factors increase the risk of developing myocarditis. As we have seen in the causes of myocarditis, certain infections increase the risk. Similarly, the use of certain drugs, connective tissue disorders, and the peri/postpartum period have been shown to increase the risk. A list is shown below^{3, 5-7}:

• Infection: Trypanosoma cruzi (most common worldwide), diphtheria, coxsackievirus, COVID-19, adenovirus, enterovirus, B19 parvovirus, HIV, EBV, HAV and HAC
• Smallpox vaccine: interestingly, a study assessing 230 734 vaccines in smallpox-vaccine naïve US military personnel showed that myopericarditis occurred as an adverse event in every 12 819 vaccines⁹
• Systemic lupus erythematosus, scleroderma, sarcoidosis
• Peripartum and Postpartum women^10,11
• Medications/toxins: there are a variety of medicines that have been documented to cause hypersensitivity myocarditis. The more commonly known medicines/toxins include: alcohol, antiepileptics, cocaine, digoxin, penicillin, lithium, and thiazides

History, signs and symptoms

The signs and symptoms of myocarditis are varied, and there is often an overlap with other cardiac conditions, particularly pericarditis. Patients can present with symptoms of chest pain, shortness of breath, palpitations, extreme fatigue and syncope, and symptoms of a preceding viral illness owing to its most common cause in Europe.

Similarly, the use of illicit medicines/toxins outlined above, or exposure to the other risk factors aforementioned should prompt the clinician to consider myocarditis, especially when occurring in the context of cardiac symptoms.

Diagnosis and investigations

The diagnosis of myocarditis may not always be immediately apparent and can often be misdiagnosed in the acute phase, owing to the overlap of symptoms. For example, a systematic review identified that 33% of patients presenting with non-obstructive coronary arteries, initially diagnosed as a myocardial infarction (MI) were later identified as acute myocarditis¹².

Important first-line diagnostic tests, as with most cardiac conditions, include^5,13:

• 12-lead electrocardiogram (ECG) (classically widespread ST elevation or PR depression when myopericarditis)
• Echocardiogram
• Chest x-ray (CXR)
• Serum troponin-T / I (usually raised but static, not commonly dynamic like ACS)
• Serum Brain Natriuretic Peptide (BNP) / N-terminal pro-B-type natriuretic peptide (NT-Pro-BNP)

Other investigations to consider:

• Endomyocardial biopsy (gold standard – specialist-led)
• Cardiac angiography (if clinical uncertainty and concern for coronary ischaemia in the context of chest pain)
• Cardiac magnetic resonance imaging (MRI)
• Trypanosoma serology
• Autoimmune antibody screen

Treatment

In the U.K., the majority of myocarditis is viral, mild, and self-limiting. In an acute setting when the patient appears unwell, an A-E approach should be used as myocarditis can be associated with haemodynamic instability. It is important to remember, however, that often the haemodynamic instability is due to the severity of the underlying disease e.g. COVID-19, rather than pump failure due to myocarditis. 

There is no single curative treatment for myocarditis, and (as mentioned above), it is usually trivial and self-limiting. If there is a precipitating cause, treatment should be aimed at the cause, and at symptoms when there is evidence of heart failure, and/or haemodynamic instability. Suppose there is evidence of LVSD without haemodynamic compromise. In that case, additional treatment measures should include medicine optimisation for LVSD^5,14, i.e., angiotensin-converting enzyme inhibitors (ACEi’s), beta-blockers, loop diuretics, aldosterone antagonists, etc. (see our article on Heart Failure for more information). Other specialist measures may include methylprednisolone and immunosuppressants if there is evidence of fulminant myocarditis (FM) (incl. eosinophilic FM, giant-cell FM, lymphocytic FM, etc.)¹.

Haemodynamic instability

During the A-E assessment, if a patient is shown to have haemodynamic instability, more specialist interventions may be required in vasopressor/inotropic support, invasive monitoring, and early involvement of critical care^5,14. It is very rare, however, for myocarditis alone to require HDU/ICU support.

Remember that myocarditis can come as a package deal with pericarditis (myopericarditis), and the latter can be much more sinister due to the rapid rate that pericardial effusions can develop secondary to inflammation. This can lead to life-threatening complications such as cardiac tamponade. Therefore, although there is never a never and never an always in medicine if a patient is haemodynamically unstable, it is unlikely to be myocarditis alone; you should always think of other features such as pericarditis, sepsis, PE, etc.

References

1. Ammirati E, Frigerio M, Adler ED, Basso C, Birnie DH, Brambatti M, et al. Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy. Circulation: Heart Failure. 2020;13:e007405 [cited 2022 Jul 12]. Available from URL: https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.120.007405
2. Wikipedia. Idiopathic giant-cell myocarditis. 2015 [cited 2022 Jul 22]. Available from URL: https://en.wikipedia.org/wiki/Idiopathic_giant-cell_myocarditis
3. BMJ Best Practice. Myocarditis: History and exam. [cited 2022 Jul 12]. Available from URL: https://bestpractice.bmj.com/topics/en-gb/244/history-exam
4. Whitton JL, Feuer R. Myocarditis, microbes and autoimmunity. Autoimmunity. 2004 Aug;37(5):375-86.
5. Tidy C, Cox J. Myocarditis. Patient UK. 2017. [cited 2022 Jul 12]. Available from URL: https://patient.info/doctor/myocarditis-pro
6. Dennert R, Crijns HJ, Heymans S; Acute viral myocarditis. Eur Heart J. 2008 Jul 9.
7. Blauwet LA and Leslie TC. Myocarditis. Prog Cardiovasc Dis. 2010 Jan-Feb; 52(4): 274–288. [cited 2022 Jul 12]. Available from URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951175/
8. Global Burden of Disease Study C. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the global burden of disease study 2013.Lancet. 2015; 386:743–800. doi: 10.1016/S0140-6736(15)60692-4
9. Halsell JS, Riddle JR, Atwood JE, MD, et al. Myopericarditis Following Smallpox Vaccination Among Vaccinia-Naive US Military Personnel. AMA. 2003;289(24):3283-3289. [cited 2022 Jul 12]. Available from URL: [https://jamanetwork.com/journals/jama/fullarticle/196808]
10. Dec GW. Introduction to clinical myocarditis. In: Cooper LT, ed. Myocarditis: from bench to bedside. Totowa, NJ: Humana Press; 2003:257-81.
11. Pinney SP, Mancini DM. Myocarditis and specific cardiomyopathies – endocrine disease and alcohol. In: Fuster V, Alexander RW, O’Rourke FA, eds. Hurst’s the heart, 11th ed. New York, NY: McGraw-Hill; 2004:1949-74.
12. Pasupathy S, Air T, Dreyer RP, Tavella R, Beltrame JF. Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries.Circulation. 2015; 131:861–870. doi: 10.1161/CIRCULATIONAHA.114.011201
13. BMJ Best Practice. Myocarditis: Investigations. [cited 2022 Jul 12]. Available from URL: https://bestpractice.bmj.com/topics/en-gb/244/investigations
14. BMJ Best Practice. Myocarditis: Treatment algorithm. [cited 2022 Jul 12]. Available from URL:https://bestpractice.bmj.com/topics/en-gb/244/treatment-algorithm

Useful links

• Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy
• BMJ Best Practice: Myocarditis
• Patient UK: Myocarditis
• Life in the Fast Lane: Myocarditis
• RCEM Learning: Causes and Management of Myocarditis

Author: Dr Steven Scholfield (FY3)

Reviewed and edited by Dr Lucy Priestner (Cardiology ST4)