Myocarditis represents the inflammatory reaction of the heart due to infectious, autoimmune or toxic causes. The process can be induced either by exogenous (bacteria, viruses or parasites) or endogenous (autoimmune diseases and toxins) pathogenic factors. All patients should receive standard heart failure care, while antiviral therapy has limited applicability.

Acute myocarditis represents one of the most challenging diagnoses in cardiology, as currently no diagnostic test can be considered a gold standard due to the insensitivity of traditional approaches. Modern techniques have improved the ability to diagnose specific pathogens in the myocardium, which increased interest in inflammatory heart diseases and improved our understanding of pathophysiology of myocarditis.

Laboratory work-up and imaging techniques

The initial evaluation of acute myocarditis must encompass detailed medical history and a thorough physical examination, searching for any potential features that may provide clues to its etiology. Additional laboratory and technical examinations should include an electrocardiogram (ECG), serum biomarkers, echocardiography, non-invasive imaging techniques and endomyocardial biopsy.

Despite its low sensitivity, the electrocardiogram (ECG) is widely used as a screening tool. In acute myocarditis, ECG may reveal sinus tachycardia with nonspecific ST-segment and T-wave abnormalities. Atrial or ventricular conduction delay with possible ventricular arrhythmias can also be noted in patients with inflammatory heart disease.

Serum cardiac biomarkers (creatine kinase and troponin) lack specificity, but may help to confirm the diagnosis of myocarditis; hence they are routinely measured in suspected cases. In acute myocarditis, increased levels of cardiac troponin are more commonly observed than increased levels of creatine kinase. Non-specific serum markers of inflammation (such as C-reactive protein) can also be elevated in myocarditis patients.

Echocardiography represents an important part of the initial diagnostic evaluation when evaluating a patient with myocarditis, serving to assess the function of the left heart ventricle, as well as to rule out other causes of heart failure (such as valvular, congenital and amyloid heart disease). Classic findings in myocarditis include global hypokinesis with or without pericardial effusion, although the echocardiographic features are often non-specific.

In recent years cardiovascular magnetic resonance imaging (MRI) has been recognized as a highly sensitive and specific tool for the diagnosis of myocarditis. This imaging technique has the unique potential to precisely visualize tissue changes, with a prospect to detect characteristic changes in myocaridtis – including interstitial and intracellular edema, hyperemia, capillary leakage and (in more severe cases) cellular necrosis and ensuing fibrosis.

Contrast-enhanced MRI can also play a significant role in discriminating myocarditis from myocardial infarction, which can aid in the evaluation of acute chest pain. In myocarditis, the infiltrates are usually located in the mid-wall and tend to spare subendocardial tissue, whereas the subendocardium is involved first in infarction. New contrast techniques using segmented inversion recovery gradient-echo pulse sequences and gadolinium enhancement can make even better distinction between diseased and normal myocardium.

Endomyocardial biopsy and Dallas criteria

Histologic examination of heart tissue is necessary to confirm the diagnosis of myocarditis, thus endomyocardial biopsy still represents one of the key diagnostic steps. Nevertheless, the applicability of endomyocardial biopsy is often hampered by sampling errors from patchy inflammatory infiltrates and inconsistency in observer interpretation.

The standard Dallas pathological criteria, which were published in 1986, served as the initial attempt to develop standardized diagnostic guidelines for the histopathological classification of myocarditis. The presence of an inflammatory infiltrate with or without necrosis under a light microscope was required for the histological diagnosis of myocarditis, but sampling error, low sensitivity and lack of prognostic value hindered the further use of these criteria.

Therefore, immunohistochemistry which allows quantification, identification and differentiation of inflammatory cells (using monoclonal antibodies) is gaining further acceptance in the diagnosis of myocarditis. A main criterion for immunohistological diagnosis of inflammatory cardiomyopathy is specified quantitatively as more than 14 infiltrating leukocytes per mm2 (preferably T-lymphocytes or activated T-cells).