Myocarditis

Myocarditis is inflammation of the myocardium. It is most commonly caused by viral infection, though autoimmune disease, certain drugs and toxins, and hypersensitivity reactions also cause it. The clinical spectrum is highly variable, from subclinical disease detected only incidentally to fulminant heart failure and cardiogenic shock.

Diagnosis requires a high index of suspicion. Presenting features are frequently non specific, and a subset of patients deteriorates rapidly with life threatening disease.

Pathophysiology and aetiology

Viral infection triggers direct viral cytopathic injury to cardiomyocytes, followed by a host immune mediated inflammatory response. Causes include:

• coxsackievirus B, historically the most extensively studied cause
• parvovirus B19
• human herpesvirus 6
• adenovirus
• influenza
• SARS-CoV-2, increasingly recognised

In a proportion of patients the immune response continues beyond viral clearance. It contributes to ongoing myocardial injury and, in some cases, progression to chronic dilated cardiomyopathy.

Autoimmune and hypersensitivity related myocarditis reflects a primarily immune mediated rather than infective mechanism. This includes myocarditis associated with immune checkpoint inhibitor cancer therapy. It is an increasingly recognised and potentially fulminant cause requiring urgent recognition, given the growing use of these agents.

Presentation is highly variable, ranging from a mild, often subclinical illness with chest pain and mild breathlessness following a preceding viral prodrome, through to fulminant disease with acute severe heart failure, cardiogenic shock and life threatening arrhythmia, developing over hours to days.

A preceding or concurrent viral prodrome (fever, myalgia, upper respiratory or gastrointestinal symptoms) in the days to weeks before cardiac symptom onset is common though not universal.

Chest pain, when present, can mimic acute coronary syndrome. Careful clinical assessment is needed to distinguish the two, given differing management implications.

Palpitations and syncope, reflecting arrhythmia (which can range from isolated ectopy to life threatening ventricular arrhythmia or high grade atrioventricular block), together with symptoms and signs of heart failure (breathlessness, oedema, reduced exercise tolerance) in more significant disease, complete the range of typical presenting features.

Fulminant myocarditis presents with rapid onset severe heart failure and haemodynamic compromise within days of symptom onset. It is a critical presentation requiring immediate intensive cardiac and, frequently, mechanical circulatory support.

Paradoxically, survivors have a more favourable long term prognosis than those with the more insidious, less acute presentation. This reflects differing underlying immunopathological processes.

Troponin is typically elevated, reflecting myocardial injury. Electrocardiography frequently shows non specific ST segment and T wave changes, though it can occasionally mimic ST elevation myocardial infarction.

This is an important differential requiring careful clinical correlation. Where diagnostic uncertainty exists, perform urgent coronary angiography to exclude significant coronary artery disease.

Echocardiography assesses ventricular function and wall motion, which may show global or regional dysfunction. It also excludes other structural causes of the presenting symptoms.

Cardiac magnetic resonance imaging is increasingly the key non invasive diagnostic investigation. It uses established diagnostic criteria, assessing for myocardial oedema, hyperaemia and, particularly, late gadolinium enhancement in a characteristic non ischaemic, subepicardial or mid myocardial pattern. Sensitivity and specificity for identifying myocardial inflammation are high.

Endomyocardial biopsy remains the histological reference standard. Given its invasive nature, it is generally reserved for specific clinical scenarios:

• fulminant disease with haemodynamic compromise, where the result may directly influence urgent treatment decisions
• suspected giant cell myocarditis or cardiac sarcoidosis, both of which carry specific and different treatment implications requiring histological confirmation
• cases where the diagnosis remains uncertain despite full non invasive assessment

Viral serology and polymerase chain reaction testing on blood have limited clinical utility for confirming a specific causative virus. They do not reliably correlate with the presence of virus within the myocardium itself. They are not routinely required to guide acute management.

Assessment of overall cardiac function and exclusion of alternative diagnoses are more clinically relevant.

Management is predominantly supportive, following standard heart failure and arrhythmia management principles according to the severity of presentation, since no specific antiviral or targeted treatment has demonstrated consistent evidence of benefit for the common viral aetiologies.

Standard heart failure therapy is initiated according to standard heart failure guidelines once the patient is stable enough to tolerate these agents:

• an angiotensin converting enzyme inhibitor (or angiotensin receptor blocker where not tolerated)
• a beta blocker, introduced cautiously once haemodynamically stable
• a mineralocorticoid receptor antagonist

Diuretics are used for symptomatic fluid overload.

Fulminant myocarditis with cardiogenic shock requires management in an intensive or cardiac care unit. Give inotropic support (dobutamine, typically starting at 2.5 micrograms per kg per minute and titrated to haemodynamic response).

For the most severe presentations not responding adequately to pharmacological support, use mechanical circulatory support (intra-aortic balloon pump, or veno-arterial extracorporeal membrane oxygenation) as a bridge to recovery. In this specific fulminant presentation, the underlying inflammatory process, while acutely severe, frequently resolves substantially with adequate haemodynamic support.

Arrhythmia is managed according to standard protocols. Use temporary pacing for significant bradyarrhythmia or high grade atrioventricular block. Use standard antiarrhythmic therapy or, where indicated, consider an implantable cardioverter defibrillator for significant ventricular arrhythmia.

Device implantation decisions are generally deferred until the acute inflammatory phase has settled, given the potential for arrhythmia to resolve as myocarditis resolves.

Immunosuppression (corticosteroids, with additional agents such as azathioprine or ciclosporin in some protocols) is reserved for specific biopsy confirmed diagnoses where an immune mediated rather than viral mechanism is established. These are particularly giant cell myocarditis and cardiac sarcoidosis.

In giant cell myocarditis, aggressive combination immunosuppression is essential, given the otherwise poor prognosis of this specific entity.

Immunosuppression is not routinely used for presumed viral myocarditis. Evidence of benefit is inconsistent, and there is theoretical concern regarding impaired viral clearance in this broader population.

Immune checkpoint inhibitor associated myocarditis is an important and potentially fulminant cause requiring urgent recognition, given increasing use of these cancer therapies. Treat with immediate cessation of the causative agent together with high dose corticosteroids (methylprednisolone 1 g intravenously once daily for three days, followed by a prolonged oral taper).

Consider additional immunosuppression (mycophenolate, infliximab, or antithymocyte globulin in refractory cases) under specialist cardio-oncology guidance. Associated mortality is significant if not promptly and aggressively treated.

Restrict competitive sport and strenuous physical activity for a minimum of three to six months following diagnosis. This is standard advice, given evidence of increased arrhythmic risk during the active inflammatory phase. It is particularly relevant to exercise related sudden cardiac death in young athletes.

Return to activity is guided by resolution of symptoms, normalisation of cardiac biomarkers and ventricular function, and, where performed, resolution of inflammatory changes on follow up cardiac magnetic resonance imaging.

Long term follow up with serial echocardiography is important, given the risk of progression to chronic dilated cardiomyopathy in a proportion of patients. The risk is highest in those with persistent left ventricular dysfunction at the time of initial diagnosis.

Continue and titrate heart failure therapy according to standard chronic heart failure management principles in this group.