Hands on: Myocarditis diagnosis and treatment
Myocarditis is a disease characterized by a limited or diffuse inflammatory lesion of the myocardium. It is a challenging diagnosis because it has no specific clinical presentation and can often be confused with non-inflammatory myocardial disease.
The disease is essentially an inflammatory disease of the myocardial tissue, and the search for a possible etiology is based on myocardial biopsy, immunohistochemistry and molecular testing.
Although endomyocardial biopsy (EMB) is the current gold standard for the diagnosis of myocarditis and is currently the only method to find the cause. However, it is not widely used, thus leading to a lack of epidemiology of the disease and reducing the knowledge of its natural course.
The course of myocarditis can be self-limiting, recurrent or turn chronic, and it is currently the main cause of one third of dilated cardiomyopathies. Traditionally, the diagnostic criteria for myocarditis (Dallas criteria) have led to a relatively low detection rate of the disease, and it was thought to rarely cause heart failure and sudden cardiac death.
However, the current availability of highly sensitive immunohistochemical molecular biologic tools and noninvasive tests such as cardiac MRI have given physicians more opportunities to explore myocarditis.
Etiology
In North American and European countries, viral infections are the main cause of myocarditis. Minute virus B19 and HHV6 are among the most common. Autoimmune myocarditis is another cause, which may have only cardiac involvement or extracardiac clinical manifestations that accompany autoimmune disease. These include nodular disease, hypereosinophilic syndrome, scleroderma, and systemic lupus erythematosus.
Clinical manifestations
The clinical presentation of patients with myocarditis varies widely and is not specific. Most patients are young or have low-risk coronary artery disease with a prodromal upper respiratory tract infection or enteroviral infection, with or without fever, dyspnea, telangiectatic breathing, decreased myocardial function or exercise tolerance or heart failure, or chest pain.
Coronary angiography often indicates normal coronary arteries with or without elevated cTNI/cTNT. It can sometimes be associated with arrhythmias, including syncope and sudden death, subacute cardiac insufficiency, chronic heart failure, new-onset cardiac insufficiency, or cardiogenic shock, and may even cause pericarditis.
Fulminant myocarditis is often associated with viral infection within the first 4 weeks of onset, with significant cardiac insufficiency and hemodynamic instability, but the overall prognosis is good.
Examination
Electrocardiographic manifestations
Abnormal ECG presentations in patients with myocarditis are varied and hypersensitive. These include various types of spontaneous supraventricular and ventricular tachycardia or bradycardia, and abnormal P-Q segment depression or repolarization. In addition, there may be other signs: ST-segment arch-dorsal elevation, P-R depression, but not commonly pathologic Q waves. T-wave inversion after normal ST-T may also be present.
Echocardiography
Echocardiography can assess morphology and ventricular function but is not specific. It may be similar to dilated cardiomyopathy, and there may be pericardial effusion and abnormal ventricular wall segmental motion. Fulminant myocarditis is seen with a slightly thickened left ventricular wall with mild dilatation and severe hypokinesis.
Echocardiography can be used to rule out other non-inflammatory diseases that may cause cardiac impairment, such as valvular heart disease. In addition, it can be used to follow systolic function and changes in ventricular chamber size and thickness in patients with myocarditis after treatment.
Cardiac Magnetic Resonance Imaging
Cardiac MRI is the current non-invasive, radiation-free test for evaluating the structure and function of the heart. Combined with gadolinium contrast delayed intensification scans, it provides a comprehensive evaluation of the structural morphology of the heart, ventricular diastolic or systolic function, myocardial perfusion and myocardial activity.
T2-weighted images reveal edematous myocardial tissue, and gadolinium enhancement reveals congestion and capillary leakage in the early stages, while necrotic tissue and fibrosis are seen in the late stages.
According to the latest ESC guidelines, CMR may enhance the diagnostic basis for myocarditis before performing myocardial biopsy. CMR can be used as a follow-up tool in patients with myocarditis in whom no evidence of viral infection is found after EMB, but patients with myocarditis in whom evidence of viral infection is found at EMB need to undergo EMB again to ensure complete viral clearance.
Endomyocardial biopsy
EMB can confirm the diagnosis of myocarditis and suggest the cause of myocarditis and the type of inflammation, which can be helpful in determining the treatment and prognosis of myocarditis. The probability of complications is very low when myocardial biopsy is performed by an experienced team.
It can be used to identify other cardiac diseases that resemble the presentation of myocarditis (e.g. arrhythmogenic right ventricular cardiomyopathy, stress cardiomyopathy, perinatal cardiomyopathy, etc.).
Biomarkers
1. Inflammatory indicators
In patients with myocarditis, inflammatory markers such as ESR or CRP are not usually elevated, but instead are elevated in acute pericarditis.
2. Troponin and BNP
Elevated troponin does not distinguish ischemic cardiomyopathy, and normal does not exclude myocarditis, as do some cardiac hormones such as BNP.
3. Viral serology
Positive serologic evidence does not imply myocardial infection, except that circulating IgG antibodies to pro-cardiac viruses are extremely high in the general population with undetectable viruses.
Diagnosis
Suspected clinical manifestations of myocarditis.
(i) Acute chest pain with pseudo-ischemia.
② New onset of heart failure or worsening heart failure.
③ Palpitations and unexplained symptomatic arrhythmias, syncope or sudden cardiac death.
(iv) Cardiogenic shock.
Secondary features of the diagnosis in patients with clinically suspected myocarditis include
Temperature ≥38°C or evidence of respiratory infection or gastrointestinal infection with or without 30 days; perinatal period; previous suspected or confirmed myocarditis; personal or familial allergic asthma, other forms of extracardiac autoimmune disease; exposure to toxic substances; family history of DCM, myocarditis.
Laboratory diagnostic criteria.
(i) New abnormal changes on 12-lead ECG/Holter/load test.
② Elevated cardiomyocyte lysis markers cTnT/TnI.
③Cardiac imaging (echocardiography/CMR/contrast) shows abnormal cardiac structure and function.
④Tissue features typical of CMR in myocarditis: myocardial edema and delayed gadolinium enhancement (LGE).
Diagnostic criteria for suspected myocarditis: myocarditis should be suspected if there is ≥1 clinical manifestation and ≥1 laboratory diagnostic criteria met, no coronary arteriography, no underlying cardiac disease and no extracardiac disease that could explain the symptoms (e.g., valvular disease, congenital heart disease, hyperthyroidism, etc.).
The more conditions that meet the diagnostic criteria, the more likely it is. Asymptomatic patients with suspected myocarditis need to meet ≥2 laboratory diagnostic criteria. Patients with clinically suspected myocarditis are hospitalized for further observation and examination, and EMB should be performed to confirm the diagnosis after coronary angiography has ruled out coronary artery disease.
The 2013 ESC recommends endomyocardial myocardial biopsy in cases of clinically suspected myocarditis.EMB can confirm the diagnosis of myocarditis and suggest the etiology and type of inflammation of myocarditis, which can be helpful in the treatment and prognosis of myocarditis, and it can identify other cardiac diseases with similar myocarditis manifestations.
Summary
Clinical suspicion of myocarditis: those with ≥ 1 clinical manifestation and ≥ 1 abnormal ancillary test.
Those with ≥2 abnormalities in the ancillary tests if no clinical symptoms are present.
All should also exclude other diseases.
imaging suggestive of coronary artery disease (coronary stenosis >50%)
Previous history of heart disease (e.g., valvular disease, congenital heart disease).
If the patient is asymptomatic, then ≥2 abnormal ancillary tests should be met.
The latest ESC guidelines recommend EMB in all patients with clinically suspected myocarditis; the diagnosis of myocarditis is based on a confirmed diagnosis by EMB, including histology (Dallas criteria) and immunohistochemistry and PCR amplification to detect the pathogen.
It is the basis for safe treatment of immunosuppression in patients with myocarditis in which inflammatory immune-mediated disease is excluded.
EMB can confirm the diagnosis of specific myocarditis types (e.g., giant cell, eosinophilic, and sarcoidosis) and thus guide treatment options and prognosis.
EMB can improve the differential diagnosis and exclude arrhythmogenic right ventricular cardiomyopathy, stress cardiomyopathy, and perinatal cardiomyopathy.