Acute Myocarditis (AM) is an inflammatory process of the myocardium with associated cardiac dysfunction and up to 30% of the AM patients progress to DCM which is associated with poor prognosis, death or heart transplant. AM should be diagnosed by established histopathological, immunological, and immunohistochemical criteria. It can be associated with any of the following conditions such as viral infections, autoimmune diseases, hypersensitivity/ hypereosinophilic syndromes and sarcoidosis, etc. After excluding all the known causes, a large and more important category of myocarditis is labeled as primary/idiopathic (possibly post viral) myocarditis.

Clinical symptoms may vary from asymptomatic patients to dyspnea, chest pain, heart attack, arrhythmias, or sudden cardiac death. The exact incidence of myocarditis is still not known as an endomyocardial biopsy (EMB) is the gold standard for the histological diagnosis

Pathogenic mechanisms:

AM is often a result of a viral infection that produces myocardial necrosis and triggers an immune response to eliminate the infectious agents (healed myocardium or DCM). Chronic myocardial injury may be caused by post-infectious immune or autoimmune process or develop by a persisting virus infection, responsible for persistent ventricular dysfunction. After a period around 3 months AM produces fibrosis and a permanent myocardium damage.

The sensitivity of cardiac biomarkers, ECG findings and echocardiography are nonspecific. Cardiac MRI could help us to the diagnosis of AM. For proper diagnosis and management of myocarditis, EMB should be performed in patients with acute cardiac deterioration of unknown etiology (more if there is a previous episode of fever) and in patients who are unresponsive to medical therapy. Histological findings have been proved to have prognostic implications (Dallas criteria for inflammation), and in several cases specific treatments can be added (if active virus still remains in myocardium thanks to check PCR virus in myocardium).

Imaging techniques:

-Echocardiography: remains the key method for analyzing ventricular function in AM. Findings are nonspecific, and include global ventricular dysfunction, impaired global longitudinal strain, regional wall motion abnormalities, or diastolic dysfunction.

-Cardiac magnetic resonance (cMRI): can help confirm the diagnosis of myocarditis, especially in the acute phase. Findings of CMR are compatible with myocardial inflammation if at least 2 Lake Louise criteria are met (sensitivity of 76% and specificity of 96%). These include:

• a) Regional or global myocardial signal intensity increase in T2-weighted edema images;
• b) an increased global myocardial early gadolinium enhancement ratio between myocardium and skeletal muscle in gadolinium-enhanced T1-weighted images, and
• c) at least 1 focal lesion with nonischemic regional distribution in inversion recovery-prepared gadolinium-enhanced T1-weighted images.

-EMB. Criteria of Inflammation:  The histology of inflammation in the myocardium will be by the qualitative Dallas criteria (presence of inflammatory infiltrates in the myocardium, >_14 leucocytes /mm2, with myocyte degeneration and necrosis of nonischemic cause) and the addition of immunohistochemical criteria > 7.0 CD3+ lymphocytes/mm2 (T cells are CD3 positive).

Treatment:

The basic treatment of myocarditis is the optimal care of heart failure and arrhythmias. Nonconventional and specific treatments depend on the result of the EMB, taking into account the patients’ symptoms and the disease course

–Conventional Treatment of Myocarditis: high doses of IVIg could be used as immunomodulatory effect (just in acute phase). Stable patients with systolic ventricular dysfunction should be treated with diuretics, renin angiotensin aldosterone system inhibitors, and beta-adrenergic blockade (after 1-2 weeks of the acute episode), avoid digoxin in early phases (risks of arrhythmias)

–ECMO support for myocarditis: In patients who develop progressive deterioration of cardiac pump function despite conventional treatment, extracorporeal membrane oxygenation (ECMO) may sometimes be needed as a bridge to recovery, in some cases a decompression LV should be needed

– Specific Treatments: In some patients, inflammation persists due to a post-infectious state or autoimmunity. In case of chronic myocarditis virus-negative patients (confirmed by EMB) the treatment with immunosuppressive agents are indicated (steroids and mycophenolate mofetil-MMF for 6 months):

Steroids: Methyl prednisolone 2mg/kg bolus and 1mg/k/d for 1 month, decreased progressively and doses of maintenance 0,2mg/k/d for 6 months + MMF (Cellcept): 20mg/k/12hr, max 750mg/12hr, levels between 2-4ng/ml: Orders powers as mycophenolic acid)

In case of persistence of virus in cardiac tissue without active inflammation, antiviral treatment will be administered, steroids should be given too if inflammatory data are obtained by EMB. Specific doses and treatments for each of the viruses are summarized in Table. CBC and hepatic profile should be controlled to avoid side effects of interferon during the follow-up.

Summary specific treatment of AM, depending EMB results (children > 1 year)

– Active inflammation + virus: steroids and antiviral treatment

– Active inflammation without virus: steroids and MMF

– Not inflammation + virus: antiviral treatment

– Not inflammation not virus: conventional HF treatment