What is Myocarditis?

Myocarditis refers to a disease with localized or diffuse inflammatory lesions of the myocardium as the main manifestation. According to the established Dallas standard, the histological evidence of myocardial infiltration is myocardial inflammatory cell infiltration, accompanied by degeneration and necrosis of adjacent myocardial cells. . In 1991, Lieberman classified myocarditis into fulminant myocarditis, acute myocarditis, chronic active myocarditis, and chronic persistent myocarditis according to the histological changes and clinical manifestations of myocardial biopsy. Myocarditis has a variety of clinical manifestations, ranging from asymptomatic to severe arrhythmia, acute cardiac insufficiency, cardiogenic shock, and even death. Endocardial myocardial tissue biopsy is the "gold standard" for the diagnosis of myocarditis. The treatment of myocarditis is mainly symptomatic support and treatment, mainly for the comprehensive treatment of shock, heart failure and arrhythmia, especially for patients with fulminant myocarditis.

Wepping

(Deputy Chief Physician) Review

Heart Failure Center, Fuwai Cardiovascular Hospital, Chinese Academy of Medical Sciences

Myocarditis refers to a disease with localized or diffuse inflammatory lesions of the myocardium as the main manifestation. According to the established Dallas standard, the histological evidence of myocardial infiltration is myocardial inflammatory cell infiltration, accompanied by degeneration and necrosis of adjacent myocardial cells. . In 1991, Lieberman classified myocarditis into fulminant myocarditis, acute myocarditis, chronic active myocarditis, and chronic persistent myocarditis according to the histological changes and clinical manifestations of myocardial biopsy. Myocarditis has a variety of clinical manifestations, ranging from asymptomatic to severe arrhythmia, acute cardiac insufficiency, cardiogenic shock, and even death. Endocardial myocardial tissue biopsy is the "gold standard" for the diagnosis of myocarditis. The treatment of myocarditis is mainly symptomatic support and treatment, mainly for the comprehensive treatment of shock, heart failure and arrhythmia, especially for patients with fulminant myocarditis.

English name

myocarditis

Visiting department

cardiology

Multiple groups

Young adults

Common locations

heart

Common causes

Infectious factors, autoimmune diseases, physical factors, chemical factors

Common symptoms

Chest pain, palpitations, myocardial infarction, cardiogenic shock

Contagious

no

Causes of myocarditis

Myocarditis is usually caused by common viral infection or immune response after viral infection. The etiology includes two types of infectious and non-infectious. Infectious factors include bacteria, fungi, protozoa, parasites, Borrelia, Rickettsia, and viruses. Non-infectious factors have the following aspects: (1) immune-mediated diseases (allergens, alloantigens, autoantigens); (2) toxicity (drugs, heavy metals, biotoxic substances, physical damage, etc.). The most common cause is a viral infection, and other factors are rare.

Pathophysiology of myocarditis

The pathophysiology of myocarditis is unclear. The rat enterovirus myocarditis model shows that viral myocarditis is divided into 3 stages.

First, the virus enters myocardial cells through specific receptors. Coxsackievirus B and adenoviruses enter myocardial cells through coxsackie and adenovirus receptors (CAR). Coxsackievirus specializes in decay acceleration factor (DAF) and adenoviruses. Integrins (v3 and v5) act as co-receptors. CAR expression was increased in patients with DCM undergoing heart transplantation. It is unclear whether increased expression of CAR is a risk factor for myocarditis.

The virus enters the acutely injured myocardial cells, which leads to myocardial necrosis through replication, intracellular antigen exposure, and host immune system activation. The acute phase of myocarditis lasts for several days and enters the second phase, which is characterized by autoimmune response, namely the subacute phase. This period lasts several weeks to several months and is characterized by virus-specific T lymphocyte activation, causing damage to target organs. Cytokines such as tumor necrosis factor, interleukin-1 (IL-1, IL-6), viral antibodies, and cardiac protein activate, accelerating damage to the heart muscle and its contractile function. In most patients with myocarditis, the myocardial damage is reduced by removing the virus through the immune response, and the left ventricular function is completely restored. In some patients, the autoimmune process does not depend on the presence of myocardial virus, which leads to myocardial remodeling to form DCM.

Persistent inflammation of the myocardium causes myocardial remodeling and eventually develops into DCM. The body's immunity results in the release of cytokines, causing an inflammatory response. Histamine increases susceptibility to autoimmune myocarditis in mice. The activation of cytokines such as transforming growth factor results in the SMAD cascade of intracellular signaling proteins, increased fibrosis factors, pathological fibrosis, myocardial remodeling, decreased cardiac function, and progressive heart failure.

Myocarditis disease manifestations

The clinical manifestations of myocarditis vary, mainly depending on the extent and severity of the lesions. A few can be completely asymptomatic. Mild patients can show non-specific symptoms such as fever, cough, and diarrhea. Severe patients can show severe arrhythmias, heart failure, and heart disease. Source shock and even death. Therefore, the possibility of diagnosing myocarditis based on clinical symptoms alone is low. According to the type of clinical manifestations, myocarditis is divided into mild, subclinical, occult progressive, acute dilated cardiomyopathy, atrioventricular block type, mimicking myocardial infarction and sudden death.

Myocarditis diagnosis

There is no uniform diagnostic standard for myocarditis in the world, and the diagnosis is often combined with clinical, laboratory tests and other related auxiliary tests. The 2013 European Heart Conference (ESC) first proposed the criteria for clinical diagnosis of myocarditis:

Clinical manifestations of myocarditis

1) Acute chest pain;

2) Newly occurring heart failure or heart failure symptoms within a few days to 3 months;

3) Palpitations, arrhythmia, syncope, or sudden cardiac death without obvious causes;

4) Unexplained cardiogenic shock;

Myocarditis auxiliary examination

1) ECG changes: ST-T changes, atrioventricular block, abnormal Q waves, supraventricular tachycardia, etc .;

2) Myocardial injury markers: increased troponin I or T;

3) Imaging examination (echocardiography or cardiac magnetic resonance) shows abnormal heart structure and function;

4) Cardiac magnetic resonance confirmed the histological characteristics of myocardium: T2WI showed myocardial edema and / or delayed enhanced scan of myocardium showed enhanced signals.

5) The diagnostic criteria for suspected myocarditis: those who have 1 clinical manifestations and auxiliary examinations 1 auxiliary examination abnormalities; if there are no clinical symptoms, they must meet 2 auxiliary examination abnormalities; all other diseases should be ruled out Patients with clinically suspected myocarditis are recommended to be admitted to the hospital for further observation and examination, and the diagnosis of endocardial myocardial tissue biopsy is confirmed.

Diagnosis of acute myocarditis

Exclusion diagnosis, after eliminating the cause and inducement, has one of the following conditions:

1) Unexplained elevation of troponin;

2) ECG shows acute myocardial injury;

3) Echocardiography or magnetic resonance (MRI) showed normal heart function.

4) Asymptomatic patients are classified as subacute myocarditis.

5) Acute myocarditis is diagnosed if it meets the criteria for subacute myocarditis and is accompanied by acute heart failure, chest pain, aura of syncope or syncope, and pericarditis.

6) Histological examination shows myocarditis, and the diagnosis can be confirmed regardless of symptoms.

Myocarditis laboratory test

Myocarditis biological markers

Although myocardial injury markers (such as troponin I or troponin T or creatine kinase isoenzymes) lack specificity, they help to diagnose myocarditis. In patients with acute myocarditis, the serum concentrations of troponin I or T are usually significantly higher than the serum concentrations of creatine kinase isoenzymes, and high concentrations of troponin T levels are of great value in assessing the prognosis. The initial troponin A high level of protein T indicates a poor prognosis.

Myocarditis etiology detection

Peripheral serum virus antibodies and PCR detection methods can be selected in combination with the clinic. When the clinical symptoms of the heart appear and the virus-specific IgG in the serum decreases, IgM and IgA increase, suggesting a high possibility of viral myocarditis. Studies have reported that some viral infections are associated with poor prognosis of myocarditis. However, because traditional pathogenic testing tends to reflect peripheral rather than heart-related infections, ESC did not recommend routine virus-related serological tests in 2013.

Electrocardiogram of myocarditis

Patients with myocarditis have a variety of abnormal ECG manifestations. The most common manifestations are ST-segment and / or T-wave changes, which can also be similar to acute myocardial infarction-like ST-segment changes, T-wave inversion, and pathological Q-waves, and serious symptoms can also occur. Arrhythmias (including supraventricular arrhythmias, atrioventricular block, etc.). The presence of left bundle branch block or pathological Q waves is associated with a high mortality rate in patients with myocarditis. In recent years, studies evaluating the prognostic value of ECG parameters in myocarditis have been reported. Prolonged QTc interval (> 440ms), abnormal QRS electrical axis, and ventricular premature beats are associated with poor clinical prognosis. Extended QRS interval (120ms) is an independent predictor of death in patients with myocarditis. Therefore, electrocardiogram is a simple and effective tool for stratification of risk index indicators in patients with myocarditis.

Myocarditis echocardiogram

Patients with myocarditis had no characteristic changes during echocardiography. However, echocardiography can assess ventricular cavity structure and function in patients with myocarditis. Patients with myocarditis are usually manifested as enlarged heart cavity, uneven myocardial echo, left ventricular thrombus, abnormal diastolic filling, and systolic function can be normal or decreased, segment or whole wall motion abnormal, pericardial effusion, etc. It is one of the important tools to identify the presence or absence of heart failure induced by other causes (such as valvular disease, restrictive cardiomyopathy, etc.). Some studies have evaluated the correlation between the parameters measured by echocardiography and prognosis, and found that patients with fulminant myocarditis usually show normal heart cavity size and increased ventricular septal thickness, and patients with acute myocarditis show enlarged left ventricle and normal ventricular septal thickness.

Myocarditis cardiac magnetic resonance

Cardiac magnetic resonance examination is a non-invasive and non-radiative examination method to evaluate the structure and function of the heart. Combined with the delayed contrast scan of gadolinium contrast, it can comprehensively evaluate the structure and shape of the heart, ventricular diastolic or systolic function, myocardial perfusion and myocardial activity. The initial stage of myocardial inflammation is manifested by increased membrane permeability of myocardial cells, intracellular and interstitial edema, and T2-weighted images in magnetic resonance examination are extremely sensitive to tissue edema. As a result, the edema tissue is normal and normal in the long T2 signal phenomenon. The tissues are clearly contrasted and show high signal, which can be used as a routine method to determine the acute phase of myocarditis. The histological basis for delayed enhancement in myocarditis patients is edema and necrosis of myocardial cells, infiltration of lymphocytes, and myocardial fibrosis. Among non-invasive inspection methods, its sensitivity and specificity are both high. The principle is that the radon contrast agent, as an extracellular contrast agent, cannot pass through the normal cell membrane and is rarely distributed in the interstitial tissue of normal myocardium. When myocarditis causes myocardial damage, the cell membrane of myocardial cells ruptures, so the radon contrast agent can pass through the damage. The myocardial cell membrane diffuses into the cardiomyocytes, and the interstitial edema between the cardiomyocytes and later myocardial fibrosis leads to an increase in the extracellular space, which causes the local contrast agent to condense, and presents a high signal during delayed intensive scanning. There is a sharp contrast with normal tissue. The American College of Cardiology Cardiovascular Intervention Journal (JACC) published a white paper on the application of cardiac magnetic resonance in myocarditis in 2009, and proposed three diagnostic criteria: (1) on T2 weighted images, local or whole heart myocardium Increased signal intensity indicates myocardial edema; (2) T1 weighted image ( is the contrast agent) of the whole heart myocardial enhanced early development; (3) enhanced scan, the myocardium showed delayed enhancement signal. The diagnosis is established when 2 or more of the above 3 conditions are met. Among them, the myocardial inflammation or myocardial injury caused by myocardial inflammation is mentioned in Article 3. If only one of the three criteria is met or none of them are met, but clinical evidence is highly suspected of myocarditis, the cardiac magnetic resonance should be reviewed 1 to 2 weeks after the initial examination. In addition, left heart failure and pericardial effusion are diagnosed as myocarditis Secondary evidence.

Endomyocardial biopsy of myocarditis

Endocardial myocardial tissue biopsy remains the "gold standard" for the diagnosis of myocarditis. According to the diagnostic criteria of Dallas histopathology, myocarditis is morphologically defined as infiltration of myocarditis cells with necrosis of adjacent myocardial cells. Critical myocarditis refers to myocardial inflammatory cell infiltration without cardiomyocyte injury or necrosis. Endocardial myocardial tissue biopsy is limited by the high variability in biopsy tissues between different patients and the inability of some biopsy tissues to detect non-cellular inflammatory processes. Therefore, immunohistochemistry is helpful for the diagnosis of myocarditis. According to the definition and classification of cardiomyopathy by the World Health Organization and the International Heart Association and Association Working Group, the results of immunohistochemistry of endocardial myocardial tissue biopsy show focal or diffuse monocyte infiltration is considered to be an inflammatory process. Includes enhanced expression of HLAII class molecular markers. Endocardial myocardial tissue biopsy can also be used to detect the virulence virus genome by molecular biological PCR detection. However, due to the influence of existing equipment and clinical experience, endocardial myocardial tissue biopsy has not yet been widely carried out clinically. However, if left ventricular or right ventricular endocardial biopsy is performed by an experienced interventionist, it must be relatively safe with relatively few complications (<1%). Studies have confirmed that endocardial myocardial tissue biopsy has not only diagnostic value but also prognostic value.

Myocarditis treatment

The treatment of myocarditis is usually adjuvant supportive therapy, especially viral myocarditis (self-limiting disease), which is mainly related to the clinical manifestations of the disease.

Myocarditis physical activity

Patients with acute myocarditis should avoid hypoxic exercise. The Coxsackie B3 viral myocarditis mouse model shows that continued high intensity exercise increases mortality and suppresses T lymphocyte activity. Myocarditis is one of the causes of sudden death of young athletes. The 36th meeting of Bethesda in 2005 pointed out that athletes with suspected myocarditis need to stop various competitive sports for more than 6 months. Left ventricular structure and function returned to normal, and can participate in training and competition when there is no arrhythmia. For patients with myocarditis and stable heart failure, it is recommended to participate in appropriate physical exercise.

Treatment of myocarditis heart failure

Can be divided into two aspects of medicine and / or mechanically assisted therapy. According to the current heart failure drug treatment plan, the following drugs should be selected according to the NYHA functional classification: receptor blockers, diuretics, ACEI, ARB, etc. For some patients, the condition continues to deteriorate even with the best medical treatment. The use of mechanical circulation assisted support or extracorporeal membrane oxygenation (ECMO) treatment provides a bridge for patient rehabilitation or heart transplantation. Even when the patient has a sudden onset of illness or is accompanied by severe clinical manifestations, after proactive and standardized treatment, there is still a good prognosis. Its survival rate can reach 60% to 80% and the heart function can return to normal.

Treatment of myocarditis arrhythmias

The treatment of arrhythmias includes etiology treatment, drug treatment and non-drug treatment. For patients with no subjective symptoms and a small number of ventricular arrhythmias, myocarditis should be actively treated, and anti-arrhythmic drugs may be temporarily omitted. Symptomatic or persistent arrhythmias should be treated according to guidelines issued by ACC / AHA and ESC in 2006. Symptomatic or persistent ventricular arrhythmias should be actively treated with amiodarone if necessary. When patients with myocarditis have severe atrioventricular block, glucocorticoid and isoproterenol can be used to increase the ventricular rate. If Asthma syndrome occurs, a pacemaker needs to be implanted to help the patient through the acute phase. In 2013, ESC recommended that implanted cardioverter defibrillator (ICD) should not be considered in the acute phase, and ESC guidelines should be followed for the treatment of arrhythmia after the acute phase.

Treatment of myocarditis arrhythmias

The treatment of arrhythmias includes etiology treatment, drug treatment and non-drug treatment. For patients with no subjective symptoms and a small number of ventricular arrhythmias, myocarditis should be actively treated, and anti-arrhythmic drugs may be temporarily omitted. Symptomatic or persistent arrhythmias should be treated according to guidelines issued by ACC / AHA and ESC in 2006. Symptomatic or persistent ventricular arrhythmias should be actively treated with amiodarone if necessary. When patients with myocarditis have severe atrioventricular block, glucocorticoid and isoproterenol can be used to increase the ventricular rate. If Asthma syndrome occurs, a pacemaker needs to be implanted to help the patient through the acute phase. In 2013, ESC recommended that implanted cardioverter defibrillator (ICD) should not be considered in the acute phase, and ESC guidelines should be followed for the treatment of arrhythmia after the acute phase.

Application of myocarditis immunomodulator

Intravenous immunoglobulin (IVIG) can directly clear the virus, neutralize antibodies, reduce the inflammatory response of the myocardium, and suppress the immune damage after viral infection. In adults with myocarditis, the use of IVIG has not been found to be beneficial. Studies on the treatment of pediatric patients have shown that high-dose immunoglobulin application can restore left ventricular function and improve survival.

Application of myocarditis immunosuppressants

The use of immunosuppressive agents in the treatment of myocarditis remains controversial. Routine use of immunosuppressants is not recommended. In recent years, literature and research have shown that patients with severe acute heart disease combined with cardiogenic shock, fatal arrhythmia (third-degree atrioventricular block, ventricular tachycardia) or myocardial biopsy have confirmed chronic autoimmune myocardial inflammatory response, should be Full and early application of glucocorticoids. Glucocorticoids have more adverse reactions and should be applied for a short course of treatment. For mild cases, it should not be used.

Myocarditis immunosorbent therapy

The purpose of immunoadsorption therapy is to adsorb inflammatory factors in the blood and remove anti-cardiomyocyte antibodies against a variety of cardiomyocyte proteins. There is evidence that immunoadsorption therapy can both improve cardiac function and reduce myocardial inflammatory lesions. The therapy is still under observation in a multicenter prospective randomized trial.

Antiviral treatment of myocarditis

Viral infection is common in the etiology of myocarditis, but most patients with myocarditis are diagnosed based on previous infections for several weeks, so the effectiveness in the implementation stage needs further study. For mouse models and a small number of patients with antiviral effects, antiviral therapy (virazole or interferon) can prevent myocarditis from turning into cardiomyopathy, reduce the severity of the disease and reduce the mortality rate. For patients with chronic dilated cardiomyopathy and viral infection, the application of interferon can inhibit the virus, assist, regulate immune function and improve left ventricular systolic function.

Myocarditis and other heart care treatments

Children with myocarditis should be given a low-fat, low-salt diet and limit physical activity to reduce the burden on the heart. Especially in acute phase of acute myocarditis and fulminant myocarditis, bed rest or physical activity should be restricted for at least 6 months until the left ventricular systolic function returns to normal. Normal cavity size and no arrhythmia. At the same time, creatine phosphate, fructose 1,6 diphosphate (FDP), coenzyme Q10, and vitamin C were given to protect myocardial cells.

Myocarditis prognosis

The prognosis of patients with myocarditis depends on clinical manifestations such as left ventricular dysfunction, pulmonary hypertension, persistently low blood pressure, increased heart rate, and changes in myocardial markers. Patients with acute myocarditis with a normal left ventricular ejection fraction have a better prognosis, most of which can heal without sequelae. Patients with fulminant viral myocarditis with normal hemodynamics have a good long-term prognosis, and patients with early intensive drug therapy and / or mechanical circulation support have a relatively good prognosis. The prognosis of patients with sarcomatoid disease or giant cell myocarditis depends on early immunosuppressive therapy or heart transplantation. Those who have not undergone heart transplantation have a 5-year survival rate of 39%.

There are many risk factors for prognosis in patients with myocarditis, including the following factors: syncope, increased NYHA cardiac function grade, certain biomarkers (fas, Fas ligand and IL-10 levels in serum), QRS interval on ECG Prolongation 120ms, right ventricular systolic dysfunction, increased pulmonary arterial pressure, absence of beta-blockers and endocardial myocardial tissue biopsy showed changes in immunohistochemical inflammatory characteristics.

In clinical work, all patients with myocarditis should be followed for a long time. The follow-up includes clinical evaluation, electrocardiogram and echocardiography, and cardiac magnetic resonance examination can be performed if necessary.