10th May 2025

Myocarditis

Background

Myocarditis is defined as inflammation of the myocardium in the absence of acute or chronic ischaemia. The diagnosis is suspected by classical clinical features and suggestive non-invasive investigation features. It is a clinical syndrome and the aetiology varies by infective, autoimmune and non-immune diseases. It is most commonly caused by viral processes, and unfortunately, the infectious agent is rarely identified. Mild forms usually resolve spontaneously or are treated conservatively, but more severe or late-diagnosed myocarditis can lead to end-stage heart failure (due to dilated cardiomyopathy) and fatal cardiac arrhythmias.

Epidemiology 

Myocarditis is likely underdiagnosed however, the number of UK hospital admissions is rising – 0.04% (36.5 per 100,000) of all hospital admissions in England between 1998 and 20172. The clinical features can be varied and frequently overlap and mimic other acute cardiac conditions, accounting for the variability in accurate diagnosis. 

It can affect all age groups, though the median age is slightly younger in men (33) compared to women (48) and there is a slightly higher prevalence in men than women (3:1).

There appears to be immunogenetic susceptibility in combination with an environmental trigger, e.g. infection, most commonly viral illness and patients are particularly susceptible if they have a viral co-infection.

It may present in acute, fulminant, subacute or chronic forms. Acute is diagnosed as less than one month between symptom onset and diagnosis. Fulminant is severe and associated with cardiogenic shock, often requiring inotropes or mechanical circulatory support. Subacute is considered to be either persistent or recurrent myocarditis, or healing myocarditis where there is evidence of previous myocardial inflammation. It is defined as between 1-3 months between symptoms onset and diagnosis. Chronic is diagnosed when symptoms persist for more than one month.

Aetiology 

Myocarditis is a result of inflammation of the heart which can result from several mechanisms, including direct toxic effects on the myocyte, production of a toxin and immunologically mediated cell damage.

Table 1: Aetiology of myocarditis, adapted from the ESC guidelines on heart failure

An accurate and in-depth history is important for suggesting the aetiology of myocarditis.

Viruses are the most common cause, accounting for around 50% of all cases and patients will often note a recent or concurrent illness associated with the onset of chest pain. In Western countries, enteroviruses (especially Coxsackie B) are the most common and usually mild and self-limiting, however, can be much more severe in neonates and young children. Recently myocarditis has become a well-recognised complication of COVID infections and there is growing evidence to suggest an association with the  COVID vaccination⁵.

Travel history can be helpful for those in which you suspect a parasitic cause or viruses less associated with the Western world, such as dengue or Zika virus.

Newly started drugs, including prescription, over-the-counter and recreational drugs, as well as recent vaccinations are important. Immunosuppressive medications are important for viruses which would not typically affect the immunocompetent.

Autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus and sarcoidosis are important to rule out. Myocarditis can (although uncommonly) be the first presentation of these disorders and around 7% of patients with myocarditis have an associated autoimmune disorder. Expanding your history taking and investigations to consider systemic symptoms (such as a history of fatigue, lymphadenopathy, ocular manifestations etc.) and a family history is therefore important. Sarcoidosis especially can present predominantly with cardiac manifestations.

Diagnosis

Patients typically present with a classical history of chest pain and on elucidating the history report recent or current infective symptoms, e.g. upper respiratory tract symptoms or recent fevers. The chest pain is often atypical, described as sharp or stabbing and may be positional if the pericardium is also involved (i.e. the pain is worse when lying flat). Some patients may be asymptomatic with only subclinical infection, or present late with symptoms of heart failure.

Troponin is frequently significantly and persistently raised and is often described as a “troponin leak”, although it can also be normal. Inflammatory markers are frequently raised, with CRP elevated in 80-90% of patients. PCR testing and IgG antibodies of common viral pathogens are recommended, although will frequently be negative.

ECG is frequently abnormal with non-specific ST- and T-wave changes, ventricular ectopics and AV conduction abnormalities. However diagnostic value is limited as the changes are neither specific nor sensitive enough alone for a definitive diagnosis.

Echocardiography is essential for ruling out any signs of heart failure due to myocarditis but do not make the diagnosis. Suggestive echocardiographic features of myocarditis are:

• New structural or functional abnormalities
• Regional wall motion abnormalities or global ventricular dysfunction without ventricular dilatation or with, generally mild, dilatation
• Increased wall thickness due to myocardial oedema
• Pericardial effusion
• Intracardiac thrombi, not explained by other conditions (e.g., coronary artery disease (CAD), acute coronary syndrome (ACS) or valvular heart disease).

Endomyocardial biopsy

This is indicated for those with progressive or persistent severe cardiac dysfunction and/ or life-threatening arrhythmias. The aim is to identify specific aetiology and treatment, e.g. giant cell myocarditis, eosinophilic myocarditis, sarcoidosis, and systemic inflammatory disorders. Histopathologically it is characterised by inflammatory cellular infiltrates with or without evidence of myocyte injury. Ideally, 5-7 samples are recommended – 3 for pathology, 2 for infections (PCR) and 2 for RNA viruses/ viral replications and therefore the type of infiltrate can be used to classify myocarditis:

• lymphocytic myocarditis: associated with pathogens, especially viral causes, as well as drugs, radiation and autoimmune disorders
• eosinophilic myocarditis: relatively uncommon, associated with parasitic infections, hypersensitivity reactions, eosinophilic inflammatory disorders and neoplastic processes
• Giant-cell myocarditis: frequently idiopathic, but also associated with autoimmune disorders such as thyroid disease or inflammatory bowel diseases
• granulomatous myocarditis: associated with sarcoidosis

However, biopsy provides many limitations, mostly due to its invasive nature and infrequent clinical use (often due to limited clinical centres that perform the procedure).

Cardiac MRI

Therefore more commonly cardiac magnetic resonance imaging (CMR) is used as a non-invasive alternative and the current European Society of Cardiology guidelines for acute and chronic heart failure consider CMR a useful method in patients with suspected myocarditis.

Cardiac MR findings suggestive of myocarditis:

• Oedema
• Inflammation and fibrosis detection
• Quantification and localisation through T1 and T2 mapping
• Extracellular volume assessment and late gadolinium enhancement (LGE)

ESC Working Up on Myocardial and Pericardial Diseases (2013) diagnostic criteria

As per ESC guidelines, myocarditis should be suspected if: 

•  ≥1 clinical presentation and ≥1 diagnostic criteria from different categories, in the absence of (1) angiographically detectable coronary artery disease (coronary stenosis ≥50%); 
• (2) known pre-existing cardiovascular disease or extra-cardiac causes that explain the symptoms (for instance, valve disease, congenital heart disease, hyperthyroidism, etc.)

These are summarised in the below table:

Table 2: Clinical Presentation and Diagnostic Criteria

Other investigations to consider:

• Coronary angiography or CT coronary angiography (CTCA)  to rule out coronary artery disease or ACS in those in which the clinical picture is unclear
• Cardiac PET, especially in those with suspected systemic autoimmune disease or cardiac sarcoidosis

Medical Management

In general, treatment is supportive and symptomatic. Patients are advised to avoid strenuous activity for at least six months, often following outpatient review with a Cardiologist and repeat echocardiogram. Treating the offending agent or infection is vital, and for those in which the agent can be removed entirely, e.g. alcohol, the recovery is very good. Non-steroidal anti-inflammatory drugs (NSAIDs), which are a mainstay of therapy in pericarditis, are not recommended in myocarditis due to their potential risk of worsening heart failure. 

For patients in which myocarditis has led to heart failure with reduced ejection fraction, they are treated as per heart failure with the four pillars of prognostic heart failure medications:

• Angiotensin‐converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) or an angiotensin receptor-neprilysin inhibitor (ARNi)
• β‐blocker
• Mineralocorticoid receptor antagonist (MRA)
• Sodium‐glucose cotransporter 2 inhibitor (SGLT2i).

Additionally, any symptomatic arrhythmias should be controlled. There is poor evidence of immunosuppressive therapy in patients with myocarditis, apart from those in specific cases (i.e. autoimmune diseases, especially sarcoidosis, giant cell myocarditis or autoimmune rheumatic diseases) so the use of steroids can be considered but the benefit is unproven outside of these cases. Multispecialty input may be required for patients in which the aetiology is complex, such as infectious diseases, rheumatology, immunology and respiratory medicine.

Complications

Generally, most people with myocarditis recover and inflammation spontaneously recovers with conservative treatment. Falling inflammatory markers and cardiac biomarkers are suggestive of recovery. Patients are recommended to follow up with a Cardiologist and CMR follow-up is recommended in patients with persistent dysfunction at echocardiography, arrhythmias or ECG abnormalities at this review.

It takes at least 3 months before CMR signs of oedema (secondary to inflammation in the acute phase/baseline) disappear. At 6 months, T1 or T2 signs of oedema should have disappeared if inflammation would be completely absent. Still, the absence of T1 or T2 oedema does not exclude chronic low-grade inflammation.

Yearly follow-up for at least 4 years, with an ECG and echocardiography, is recommended by the ESC as acute myocarditis may lead to dilated cardiomyopathy (DCM) in up to 20% of cases. In those with significantly impaired left ventricular ejection fraction (LVEF) at the time of hospital admission has been shown to be a poor prognostic marker. 

However, the prognosis can vary widely depending on aetiology, with giant-cell myocarditis being associated with the poorest prognosis, an approximately 90% rate of death or cardiac transplantation and a median survival of 5.5 months from symptom onset.