10th May 2025

Myocarditis and Cardiac Tumours

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.

Cardiac tumours

Epidemiology & aetiology

Cardiac tumours are classified as either benign or malignant. Over 90% of primary cardiac tumours are benign, with myxomas being predominant in adults and rhabdomyomas in children. Malignant tumours are most commonly sarcomas (65%) or lymphomas (25%). Cardiac metastases are much more common, and seen associated with melanomas, lymphoma, leukaemia, breast, lung or oesophageal primaries. 

Cardiac myxoma is the most common cardiac tumour overall, comprising 50% of tumours and occurs more commonly in women. It is most frequently diagnosed between the ages of 50-70 years old and 90% are left atrial, and 90% are solitary. They may be familial, associated as part of the Carney complex and therefore seen in younger patients. The Carney complex is an auto-dominant syndrome, comprising multiple and recurrent myxomas of the heart and skin, lentiginosis and endocrine dysfunction.

Sarcomas are more common in men and typically occur between the ages of 30-50 years old. Most rhabdomyomas (around half) are associated with tuberous sclerosis, an autosomal dominant disorder of neurofibromatous lesions, developmental delay and cutaneous lesions.

Diagnosis

The clinical presentation of intracavity masses is best described by Mahaim’s triad: obstruction; embolism; and constitutional symptoms. 

Obstruction

• Direct obstruction of blood flow due to mass effect, leading to syncope, especially prevalent with left atrial masses due to prolapse into the left ventricle during diastole. 
• May also cause acute congestive heart failure associated with pulmonary oedema or right ventricular heart failure.
• Valve dysfunction – either functional regurgitation or stenosis.
• If associated with atrial enlargement may lead to atrial arrhythmias such as atrial flutter or fibrillation.
• If associated with venous or ostial growth, superior or inferior vena cava syndrome may occur.

Embolism

• Due to the detachment of tumour fragments, particularly in myxomas and associated with tumour size. This may lead to any consequence of systemic emboli such as pulmonary emboli (PE), cerebral vascular accident (CVA), myocardial infarction (MI) or splenic or renal embolism.

Constitutional symptoms

• Most commonly associated with myxoma – fatigue, fever, weight loss, myalgia.
• Raynaud’s phenomenon and clubbing are associated with the release of cytokines. 

Note that cardiac masses with intramural growth (such as fibroma or cystic tumours of the atrioventricular node) frequently cause conduction disturbances and arrhythmias, including those leading to sudden cardiac death. These are much rarer and often diagnosed at autopsy and thus are much wider than necessary for this chapter.

Pericardial effusion is associated with both benign and malignant cardiac tumours, but haemorrhagic effusion is a typical manifestation of malignancies.

Additionally, some cardiac masses can be picked up incidentally at routine screening, due to being small and neither mobile nor friable.

In regards to diagnostic imaging, an echocardiogram is first line, with CMR and CT as complementary tools to further differentiate. Transthoracic echocardiogram is especially able to detect the presence of a cardiac mass but is usually limited in detecting pericardial infiltration and tissue composition. Therefore transoesophageal echocardiogram (TOE)11 is recommended for surgical assessment due to its better resolution for assessing the extent of the mass and its relationship to surrounding structures and attachments.

CMR is the best available non-invasive diagnostic tool for tissue characterisation (fibrosis, necrosis, calcification etc.) The heterogeneous tissue composition of cardiac myxomas can be visualised and appear isointense to hypointense compared with normal myocardium on T1 weighted sequences. 

CT is useful for assessing the involvement of the surrounding structures such as lung, pleural and mediastinum. Calcification is easily detectable which can be helpful in the detection of myxoma or fibroma. CMR and CT can differentiate haemorrhagic or serous pericardial effusions and can differentiate between thrombus and cardiac tumour. 

Finally, PET scan is used for staging where applicable. 

Prior to surgical intervention cytological evaluation of pericardial and/ or pleural fluid can be useful for diagnosis. However, preoperative sampling such as endomyocardial biopsy may not always be possible due to the risk of the procedure and so surgery is both diagnostic as well as part of treatment. Resected tumours are sent for histopathological analysis and some of the common features to know are as below:

• Myxoma: spindle or stellate cells, pseudovascular structure, myxoid matrix, dystrophic calcification haemorrhage 
• Sarcoma: myocardial infiltration, pleomorphism, necrosis, calcification 
• Myxoma: commonly in atria
• Sarcoma: left atrium (usually posterior wall or roof)

Management

All patients with cardiac tumours should be referred for consideration of surgical assessment. Even small or incidental benign cardiac tumours are considered for resection due to embolic risk. For right-sided and asymptomatic benign tumours they may not be resected but are still recommended for strict echocardiographic follow-up.

Cardiac tumours are usually resected through medial sternotomy and due to their friable nature recommended for minimal manipulation of the heart and radiotherapy is often carried out either before – to facilitate removal – and/ or after to prevent recurrences. Cardiac transplantation, or in the case of lung metastases combined heart and lung transplantation can be considered for appropriate patients. However, regarding extracardiac metastases, chemotherapy is the only therapeutic option.

Prognosis and complications

In regards to atrial myxomas, although they are histologically benign patients are at risk of death from obstruction, distal embolisation or arrhythmias. Dislodgement of tumour fragments can be a significant risk during surgery and to reduce this possibility manipulation of the heart is reduced to a minimum, however, survival following resection is excellent. Atrial myxomas may occasionally recur and thus long-term follow-up with echocardiography is recommended.

Cardiac sarcomas have a very poor prognosis, with a mean survival of about 9-11 months from diagnosis, improving to 24 months with complete resection. This is largely related to its association with tumour extension commonly into the epicardium, endocardium or intracavity as well as local spread to the pleural or mediastinum.

References

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