By: Prof. Dr. Seyed Saeid Zamanieh Shahri, MD  and  Prof. Dr. Sonia Sayyedalhosseini, MD

Diagnostic Approaches in Myocarditis:

As discussed in the previous article, the exact cause of myocarditis remains unidentified in many cases. However, whenever an underlying cause can be established, it is most often related to an infectious process. Such infections—including viruses (the most common cause), bacteria, parasites, or fungi—may reach the heart muscle and initiate myocardial injury. As the infectious agent attempts to survive and replicate, the body’s immune system is activated to eliminate it. Although this immune response is essential for host defense, it may also trigger inflammation within the myocardium, ultimately impairing cardiac function. In addition, certain autoimmune diseases, such as systemic lupus erythematosus, may cause the immune system to mistakenly target cardiac tissue, resulting in myocardial inflammation and injury.

Cardiac MRI and the Lake Louise Criteria

   In recent years, cardiac magnetic resonance imaging (CMR) has become a cornerstone in the diagnosis of myocarditis. The Lake Louise Criteria state that imaging evidence of myocardial inflammation requires the presence of at least one marker of myocardial edema (such as elevated T2 relaxation time or increased T2-weighted signal intensity) together with at least one marker of myocardial injury or fibrosis (such as late gadolinium enhancement [LGE] or elevated T1 relaxation time/extracellular volume [ECV]).

   Recent studies have demonstrated that combining T1 and T2 mapping, LGE imaging, and feature-tracking strain analysis enhances both the sensitivity and specificity of CMR, improving differentiation between various forms of myocarditis and ischemic myocardial disease.

Endomyocardial Biopsy

   Endomyocardial biopsy (EMB) remains the only diagnostic modality capable of providing a definitive histopathological diagnosis. It is particularly valuable for identifying the specific type of inflammatory infiltrate (e.g., lymphocytic, eosinophilic, or granulomatous myocarditis), detecting viral genetic material within myocardial tissue using polymerase chain reaction (PCR), and diagnosing selected forms of myocarditis. Statements issued by the European Society of Cardiology (ESC) and more recent clinical guidelines recommend EMB in carefully selected patients with characteristic or high-risk clinical presentations.

Other Imaging Modalities

• Fluorodeoxyglucose positron emission tomography (FDG-PET): Used to evaluate active myocardial inflammation, particularly in selected cases of cardiac sarcoidosis or chronic inflammatory myocarditis.

• Cardiac computed tomography (CT) and coronary CT angiography: Primarily employed to exclude coronary artery disease in patients presenting with an infarct-like clinical syndrome.

Recent Advances in Technology and Innovation in Myocarditis

   Recent technological developments—particularly in advanced imaging and artificial intelligence—have substantially improved the understanding and diagnostic evaluation of myocarditis.

Next-Generation Cardiac MRI

Recent reviews of cardiac MRI indicate expanding applications of several advanced techniques, including:

• Quantitative T1 and T2 mapping for direct characterization of myocardial tissue properties.

• Extracellular volume (ECV) mapping as a quantitative indicator of extracellular expansion and myocardial fibrosis.

• Feature-tracking and strain analysis for detecting subtle abnormalities in myocardial motion and identifying subclinical ventricular dysfunction.

These techniques provide more accurate assessment of active inflammation, myocardial edema, and fibrosis, while improving differentiation between acute and chronic myocarditis and distinguishing myocarditis from other cardiomyopathies.

Radiomics and Artificial Intelligence in Cardiac MRI

   Radiomics refers to the extraction of a large number of quantitative imaging features and their integration into statistical or machine-learning models. Recent investigations have demonstrated that:

• Radiomic signatures derived from T1/T2 mapping and LGE images can differentiate myocardial inflammation from other patterns of myocardial injury, such as ischemic damage.

• Machine-learning algorithms are capable of analyzing complex combinations of imaging features and may achieve diagnostic performance for acute myocarditis that is comparable to, or in some settings approaches, expert human interpretation.

• The reproducibility of radiomic features obtained from T1 and T2 maps has been the focus of recent research, supporting their potential future role as diagnostic and prognostic biomarkers.