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

4) Risk Factors: Risk factors for myocarditis can be summarized along several axes. These factors are not necessarily direct causes, but they have been reported to correlate with disease occurrence or severity:

• Age and biological sex: In many reports, classic viral myocarditis is more common in young adults, whereas vaccine-associated myocarditis has been reported predominantly in adolescent and young adult males.

• Genetic and immune susceptibility: Certain genetic patterns and immune-response variations may influence inflammatory severity and the likelihood of progression to cardiomyopathy, although details are not yet fully clarified.

• Systemic autoimmune disease: Autoimmune conditions may predispose individuals to myocardial inflammation.

• Use of immune-modulating cancer therapies: These have been associated with a higher risk of drug-related myocarditis.

• Recent viral infection, particularly respiratory infections or coronavirus infection, which meta-analyses have associated with a significantly increased myocarditis risk compared with the pre-pandemic period.

A substantial portion of inter-individual variability in myocarditis likely reflects complex interactions among genes, environment, and immune status.

5) Signs and Symptoms: The clinical spectrum of myocarditis is very broad—from an asymptomatic course to acute heart failure and cardiogenic shock. Several clinical patterns may be described:

• “Infarct-like” presentation: Patients present with acute chest pain, ischemia-like ECG changes, and elevated troponin, yet coronary angiography shows no severe coronary stenosis. This infarct-mimicking pattern has been described in acute viral myocarditis and, in some cases, following COVID-19 vaccination.

• Predominantly arrhythmic presentation: In some patients, supraventricular or ventricular arrhythmias, conduction blocks, or even cardiac arrest are the first manifestations of myocardial inflammation; chest pain may not be prominent in this group.

• Heart failure–like presentation: Some patients present with dyspnea, fatigue, peripheral edema, orthopnea, and classic signs of heart failure. Echocardiography may show ventricular dilatation and reduced ejection fraction. This pattern is especially observed in subacute or chronic phases and in the context of progression toward dilated cardiomyopathy.

• General and nonspecific manifestations: Fever, myalgias, neurasthenic symptoms, palpitations, or vague chest discomfort may accompany myocarditis, particularly when occurring on the background of a systemic viral infection.

6) Complications: Myocarditis may lead to both short-term and long-term consequences:

• Acute heart failure and shock: Severe inflammation can acutely reduce myocardial contractility, lowering cardiac output and producing cardiogenic shock.

• Progression to dilated cardiomyopathy: In chronic myocarditis, adverse remodeling, fibrosis, and ventricular dilatation may lead to dilated cardiomyopathy and chronic heart failure.

• Serious arrhythmias and sudden death: Inflammatory injury and fibrosis may create a substrate for malignant arrhythmias, fibrillation, and sudden cardiac death.

• Reduced ventricular function and altered intracardiac flow may promote intraventricular thrombus formation and systemic embolic risk, especially in severely dilated, hypokinetic ventricles.

7) Diagnostic Approaches: Diagnosis of myocarditis relies on integrating clinical, electrocardiographic, laboratory, imaging, and sometimes histologic evidence.

• Clinical criteria and ECG: Consensus documents—such as statements by the European Society of Cardiology working groups—have proposed criteria for “clinically suspected myocarditis,” combining symptoms (chest pain, dyspnea, arrhythmia, syncope), ECG findings (waveform changes, conduction blocks, arrhythmias), and elevation of cardiac biomarkers (such as troponin).

• Biomarkers: Elevated cardiac troponin indicates myocardial injury and is observed in many cases of acute myocarditis. In addition, elevations may reflect ventricular functional involvement.

• Echocardiography: Echocardiography is a foundational tool for evaluating ventricular function, wall thickness, pericardial effusion, and regional or global motion abnormalities; however, echocardiographic patterns are not specific to myocarditis. To be continued next month…