The diagnosis and treatment points of myocarditis and the latest progress in treatment—an in-depth review

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Myocarditis is a non-ischemic inflammatory disease of the myocardium caused by viruses and various autoimmune diseases
.
The number of cases worldwide is about 1.
8 million cases per year, and the incidence rate is (1.
0 to 2.
2)/1 million
.
Symptoms of viral myocarditis are insidious and difficult to diagnose, and patients often present with nonspecific systemic symptoms in the early stages of the disease, including fever, muscle soreness, respiratory and gastrointestinal symptoms
.
This review discusses the latest overview
of the classification, diagnosis, clinical manifestations, and treatment of myocarditis.

classify

Myocarditis is classified in a variety of ways, and can be divided into infectious and non-infectious myocarditis according to its underlying pathogenesis
.

Noninfectious myocarditis is less common in general and includes toxic myocarditis (caused by drugs, toxins, or physical factors) and immune-mediated myocarditis, which in turn can be caused by allergens, allogens, or autoantigens (such as giant cell myocarditis or myocarditis associated with systemic autoimmune diseases
).

Infective myocarditis can be caused by several pathogens, and the prevalence varies from region to region
.
Areas with limited resources are associated with specific diseases, such as rheumatic diseases, American trypanosomiasis, HIV, and worm or bacterial infections
.
In Western countries, viruses are probably the most common cause of myocarditis (Table 1
).

Table 1 Several viruses that cause myocarditis (Note: Multiple viral infections may occur in about 27% of patients)

Clinical manifestations

According to the study, chest pain is the most common symptom of myocarditis (95%), followed by dyspnea (49%)
.
Other typical but nonspecific symptoms include fatigue, palpitations, and syncope
.
Precursor symptoms of fever, influenza-like, or gastrointestinal discomfort are present in 18% to 80% of patients
.

According to statements from the European Society of Cardiology and the American Heart Association, a diagnosis of myocarditis within 3 months of the onset of symptoms is defined as acute myocarditis
.

The main clinical features of acute myocarditis are three (usually manifested as one):

➤ Acute coronary syndrome-like manifestations, chest pain, changes in the ST/T waves of the electrocardiogram, overall or local left ventricle and / or right ventricular dysfunction, and possible elevation of troponin T or I;

➤ New or progressive heart failure, impaired systolic function of the left ventricle and/or right ventricle, possible non-specific ECG changes, atrioventricular or venous block, or ventricular arrhythmias;

➤ Sudden cardiac death, severely impaired left ventricular function, and cardiogenic shock (also known as fulminant myocarditis) requiring cardiac or mechanical circulatory support can be life-threatening
in the presence of severe arrhythmias and miscarriages.
Children and women are more susceptible to fulminant myocarditis
.

Patients with chronic myocarditis and chronic inflammatory cardiomyopathy usually have hemodynamically stable compared with patients with acute myocarditis, with only mild elevated plasma troponin levels, usually disproportionate to
the severity of left ventricular insufficiency.

diagnosis

Endocardial myocardial biopsy (EMB) is the "gold standard" for diagnosing viral myocarditis, but is underused in clinical practice; Diagnosis is usually a
combination of clinical findings, non-invasive biomarkers, and imaging features.

Transthoracic echocardiography (TTE) is usually the first-line imaging method for suspected myocarditis, especially when
hemodynamic instability is excluded using more accurate imaging modalities such as magnetic resonance imaging (CMR).
TTE plays an important role in ruling out heart failure or chest pain from other causes, but its diagnostic accuracy is limited due to the lack of specific echocardiographic findings
.
The most common manifestations are local ventricular wall motor abnormalities (often involving the lower or lower lateral wall), diastolic dysfunction with normal left ventricular ejection fraction (LVEF), and left ventricular systolic dysfunction
.
Features similar to hypertrophic, dilated, or restrictive cardiomyopathy may also be present
.

Recently, two-dimensional spot-tracking echocardiography has been used clinically as a tool for diagnosing and assessing prognosis in patients with suspected acute myocarditis
.

18 fluorine-labeled fluorodeoxyglucose PET (18F-FDG-PET) is more sensitive to the detection of metabolically active processes, including inflammation, and can be used in specific cases, such as patients with
CMR contraindications or suspected cardiac sarcoidosis.

Multi-row spiral CT coronary angiography (MDCT) and the recently introduced delayed enhancement-MDCT (DE-MDCT) can be used to distinguish ischemic and nonischemic cardiomyopathy, just like coronary angiography
.

CMR imaging is a non-invasive reference technique
for diagnosis and follow-up in patients with myocarditis.
CMR is based on the Lake Louise standard, which was first published in 2009, and the Lake Louise standard was updated in 2018 (Table 2) to improve sensitivity (87.
5%) and specificity (96.
2%)
for acute myocarditis after the standard modification, taking into account the increased sensitivity of T1 and T2 standards in detecting and quantifying myocardial fibrosis and edema.

Table 2 Update of CMR standards for myocardial inflammation

Note: EGE, early gadolinium enhancement; LGE, late delayed gadolinium enhancement; ECV, extracellular volume
.

Management of myocarditis

Patients with hemodynamically stable suspected myocarditis, even if mild or asymptomatic, should be admitted to hospital for clinical monitoring
.

In patients with chest pain, elevated troponin, and possible ischemic ECG changes, acute coronary syndrome
is excluded by invasive coronary angiography or computed tomography angiography.

β-blockers are often used to treat acute myocarditis or uncomplicated diseases, possibly because they have an anti-arrhythmic effect
.

The European Society of Cardiology recommends against the use of NSAIDs, especially acetylsalicylic acid
, in patients with acute myocarditis.

Patients should limit physical activity in the acute phase of myocarditis, as it may increase the risk
of sudden cardiac death.
Athletes should avoid competitive sports
for at least 3 months after the onset of myocarditis.

Antiviral and immunosuppressive therapy

There is currently no specific evidence-based treatment for myocarditis caused by the virus
.
The pathogenesis of myocarditis heart damage is often attributed to the autoimmune/superimmune response to viral infections, so immunomodulatory therapy is considered a potential treatment
.

Preliminary data suggest that interferon-β therapy can promote viral clearance in patients with enterovirus or adenoviral myocarditis and may improve ventricular function and survival, but further research
is needed before clinical application.

The causal role of human parvovirus B19 (B19V) in the pathogenesis of myocarditis remains controversial
.
Three potential strategies for treating B19V-associated myocarditis have been proposed and are being investigated: high-dose intravenous immunoglobulin, telbivudine (an antiviral nucleoside analogue primarily used for retroviral and hepatitis B virus infections), and immunosuppressive therapy
with prednisone and azathioprine.

References:

1.
Wang Tian,Liu Wenxiu,Wang Dan,Zhao Dechao.
Neutrophil extracellular trap and viral myocarditis[J].
Journal of Clinical and Pathology,2022,42(05):1247-1251.

2.
Sozzi FB, Gherbesi E, Faggiano A, et al.
Viral Myocarditis： Classification, Diagnosis, and Clinical Implications.
Front Cardiovasc Med.
2022 Jun 20; 9：908663.

3.
Ma Shuai, Yuan Xinyu.
2018 edition of "Expert Consensus on Cardiovascular Magnetic Resonance Examination of Non-ischemic Myocardial Inflammation".
CJCP, 2020, 5,35(05).