General Information on Myocarditis

Myocarditis is a condition characterized by an inflammatory process affecting the myocardium that can be caused by infections, immune dysfunctions, exposure to toxins, or occur idiopathically. The clinical presentation is extremely variable, ranging from mild and asymptomatic forms to severe cases with heart failure, fatal arrhythmias, or progression to dilated cardiomyopathy.

Myocarditis is classified based on its etiology into:

• Infectious Myocarditis: viral, bacterial, fungal, parasitic.
• Immune-Mediated Myocarditis: autoimmune, drug hypersensitivity, post-infectious.
• Toxic Myocarditis: induced by cardiotoxic drugs, alcohol, drugs, heavy metals.
• Idiopathic Myocarditis: with no identifiable cause, often suspected to be of autoimmune origin or due to latent viral infections.

Epidemiology

Myocarditis represents a significant cause of both acute and chronic heart failure, with an estimated systemic incidence ranging between 1 and 10 cases per 100,000 inhabitants annually.
The viral form is the most common epidemiologically, with Coxsackievirus (B) and Parvovirus B19 as the predominant etiological agents. Prevalence varies significantly according to the specific etiology, with bacterial and parasitic forms showing a higher incidence in certain geographic regions.

Data suggest a higher incidence among young individuals, particularly those aged between 20 and 40 years, and a greater prevalence in populations with immune dysfunction. Idiopathic myocarditis has frequently been observed in patients with an autoimmune predisposition or following latent viral infections.

Pathophysiology

The pathophysiological mechanisms described below are common to all forms of myocarditis, regardless of their etiology.

Myocarditis is characterized by an inflammatory process affecting the myocardium, leading to direct cellular damage, cardiac dysfunction, and fibrotic remodeling. The pathogenic mechanism generally develops in three main phases:

1. Acute Phase: Initial Damage and Activation of the Innate Immune Response

Myocardial inflammation begins with a primary insult, which may stem from a viral, bacterial, or parasitic infection, toxin exposure, or an autoimmune process. The etiological agent affects the myocardium through three main mechanisms:

• Direct Cytotoxic Damage: some viruses, such as Coxsackievirus B, have a tropism for cardiomyocytes, inducing their destruction through cellular lysis.
• Activation of the Innate Immune System: myocardial damage releases Pattern Recognition Molecules (PRMs) that, by interacting with Toll-like receptors (TLR) on immune cells, trigger the production of pro-inflammatory interleukins (IL-1, IL-6, TNF-α).
• Vascular Damage: in some forms, involvement of the microvessels leads to ischemia and hypoxia of cardiac tissues.

2. Immune Phase: Amplification of the Inflammatory Response

In this phase, activation of the immune system leads to the recruitment of inflammatory cells into the myocardium. The effects may be transient or evolve into a persistent inflammatory response:

• Lymphocytic Infiltration: predominantly CD4+ and CD8+ T lymphocytes attack the damaged or infected cardiomyocytes.
• Cytokine Production: the high release of TNF-α, IL-1β, and IL-6 contributes to worsening myocardial damage.
• Mitochondrial Dysfunction: the release of free radicals amplifies cell death.
• Possible Autoimmune Activation: in some cases, the infection may trigger a persistent autoimmune response, leading to chronic myocarditis.

3. Chronic Phase: Remodeling and Possible Progression to Dilated Cardiomyopathy

In some patients, the inflammation completely resolves, while in others it persists, causing progressive ventricular dysfunction. The main elements characterizing the chronic phase are:

• Interstitial Fibrosis: replacement of necrotic cardiomyocytes with connective tissue.
• Extracellular Matrix Alterations: excessive collagen deposition that reduces ventricular compliance.
• Contractile Dysfunction: reduction in ejection fraction, evolving into dilated cardiomyopathy.

In the most severe cases, chronic myocardial damage may lead to progressive heart failure, malignant ventricular arrhythmias, and, in some cases, the need for a heart transplant.

Risk Factors and Prevention

The risk factors for developing myocarditis are multiple and vary according to the etiology of the condition. The main risk factors include:

• Genetic Predisposition: certain genetic variants can increase the myocardium's susceptibility to inflammatory events.
• Recent Infections: viral or bacterial infections, often preceding the onset of myocarditis, which trigger an intense immune response.
• Exposure to Toxins: the intake of cardiotoxic substances, such as certain drugs, alcohol, drugs, or heavy metals, represents a significant risk factor.
• Immune Dysfunctions: autoimmune conditions or alterations in the immune response may predispose individuals to the development of myocarditis.

Prevention is based on a multidisciplinary approach that includes:

• Timely Management of Infections: rapid identification and effective treatment of infections reduce the risk of myocardial inflammation.
• Continuous Clinical Monitoring: in at-risk patients, regular follow-up allows for the early detection of signs of myocarditis.
• Reduction of Toxin Exposure: adopting a healthy lifestyle and limiting the use of substances harmful to the heart.
• Education and Awareness: informing patients about the symptoms and the importance of early intervention to improve clinical outcomes.

References
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