Myocarditis refers to disorders characterized by an inflammatory process affecting the myocardium, which can be caused by infections, immune dysfunction, exposure to toxins, or may present in idiopathic form. The clinical presentation is extremely variable and ranges from mild, asymptomatic cases to severe forms with heart failure, fatal arrhythmias, or progression to dilated cardiomyopathy.
Myocarditis is classified according to its etiology into:
Immune-mediated myocarditis: autoimmune, drug hypersensitivity, post-infectious.
Toxic myocarditis: induced by cardiotoxic drugs, alcohol, recreational drugs, heavy metals.
Idiopathic myocarditis: 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 between 1 and 10 cases per 100,000 people per year.
The viral form is the most common epidemiologically, with Coxsackievirus (B) and Parvovirus B19 as predominant etiological agents. Prevalence varies significantly according to specific etiology, with bacterial and parasitic forms showing higher incidence in certain geographic regions.
Data suggest a higher incidence in younger individuals, particularly between 20 and 40 years of age, and greater prevalence in populations with immune dysfunction. Idiopathic myocarditis is frequently observed in patients with autoimmune predisposition or following latent viral infections.
Pathophysiology
The following pathophysiological mechanisms are common to all forms of myocarditis, regardless of etiology.
Myocarditis is characterized by an inflammatory process involving the myocardium, leading to direct cellular injury, cardiac dysfunction, and fibrotic remodeling. The pathogenetic mechanism generally develops in three main phases:
1. Acute phase: initial injury and activation of innate immunity
Myocardial inflammation begins with a primary insult, which may derive from viral, bacterial or parasitic infection, the action of toxins, or an autoimmune process. The etiological agent affects the myocardium through three main mechanisms:
Direct cytotoxic damage: some viruses, such as Coxsackievirus B, have tropism for cardiomyocytes and induce their destruction via cell lysis.
Activation of innate immunity: myocardial injury releases Pattern Recognition Molecules (PRMs), which interact with Toll-like receptors (TLR) on immune cells, triggering production of pro-inflammatory interleukins (IL-1, IL-6, TNF-α).
Vascular injury: in some forms, involvement of the microvasculature leads to ischemia and hypoxia of cardiac tissues.
2. Immune phase: amplification of inflammation
In this phase, activation of the immune system leads to recruitment of inflammatory cells into the myocardium. The effects may be transient or evolve into a persistent inflammatory response:
Lymphocytic infiltration: mainly CD4+ and CD8+ T lymphocytes attack damaged or infected cardiomyocytes.
Cytokine production: marked release of TNF-α, IL-1β, IL-6 further aggravates myocardial damage.
Mitochondrial dysfunction: release of free radicals amplifies cell death.
Possible autoimmune activation: in some cases, infection may trigger a persistent autoimmune response, leading to chronic myocarditis.
3. Chronic phase: remodeling and possible progression to dilated cardiomyopathy
In some patients, inflammation resolves completely, while in others it persists, causing progressive ventricular dysfunction. The main elements characterizing chronicity are:
Interstitial fibrosis: replacement of necrotic cardiomyocytes with connective tissue.
Contractile dysfunction: reduced ejection fraction, progressing towards dilated cardiomyopathy.
In the most severe cases, chronic myocardial damage can lead to progressive heart failure, malignant ventricular arrhythmias, and, in some cases, the need for heart transplantation.
Risk Factors and Prevention
The risk factors for developing myocarditis are numerous and vary depending on the disease’s etiology. 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, trigger an intense immune response.
Exposure to toxins: intake of cardiotoxic substances, such as some drugs, alcohol, recreational drugs, or heavy metals, is a significant risk factor.
Immune dysfunction: autoimmune conditions or alterations in immune response may predispose to the development of myocarditis.
Prevention is based on a multidisciplinary approach that includes:
Prompt management of infections: rapid identification and effective treatment of infections reduce the risk of myocardial inflammation.
Regular clinical monitoring: in at-risk patients, regular follow-up allows for early identification of possible signs of myocarditis.
Reduction of toxin exposure: adopting healthy lifestyles and limiting use of substances harmful to the heart.
Education and awareness: informing patients about symptoms and the importance of early intervention to improve clinical outcomes.
References
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Ammirati et al. Etiology and diagnosis of myocarditis. European Heart Journal. 42(8), 2020, 1023-1032.
Frustaci et al. Immune-mediated mechanisms in myocarditis. Cardiovascular Pathology. 30(1), 2020, 10-17.
Mavrogeni et al. Imaging in myocarditis: the role of CMR. Radiologia Medica. 125(5), 2022, 456-467.
Friedrich et al. Pathophysiology of myocarditis. European Journal of Radiology. 44(3), 2021, 1123-1131.
Sagar et al. Viral myocarditis: updates and perspectives. Circulation. 134(18), 2018, 1427-1435.
Caforio et al. Mechanisms of myocardial injury in myocarditis. Heart. 107(11), 2021, 765-772.
Imazio et al. Diagnostic approaches in myocarditis. Journal of the American College of Cardiology. 68(10), 2021, 1051-1062.
Ferreira et al. Impact of the inflammatory response in myocarditis. Cardiology. 150(4), 2020, 185-193.
Yilmaz et al. Risk factors in myocarditis: a review. Journal of Cardiovascular Medicine. 23(3), 2019, 144-151.
