Recently, the Chinese guidelines for the clinical diagnosis and treatment of myocarditis in adults were officially released.
Guidelines state that myocarditis is an inflammatory disease of the myocardium caused by an infectious agent and/or other etiology, with myocardial inflammatory cell infiltration and/or non-ischemic necrosis.
The global incidence of myocarditis is about 10~22 cases per 100,000, and the statistics in China are still lacking.
Depending on pathology, etiology, and cytology, myocarditis can be classified into different categories, such as acute and chronic myocarditis, infectious and noninfectious myocarditis, lymphocytic, eosinophilic, and giant cell myocarditis.
For the diagnosis of myocarditis, guidelines recommend that myocarditis be diagnosed clinically after exclusion of other causes of myocardial disease, such as coronary atherosclerotic heart disease, valvular heart disease, hyperthyroidism, etc., with both clinical symptoms and signs in Table 1, new ECG changes (any of (1)(2)), markers of myocardial injury, and cardiac function and condensation abnormalities on echocardiography or magnetic resonance (any of (1)(2)).
Table 1 Clinical diagnostic criteria for myocarditis
| project | substance |
| (1) Clinical signs and symptoms | Cardiac manifestations such as severe fatigue, chest tightness, chest pain, palpitations, syncope, and lower limb edema appear within 1~3 weeks after infection (symptoms of upper respiratory tract and gastrointestinal tract infection); Cardiac enlargement, significantly decreased first apical heart sound, diastolic gallop rhythm, pericardial friction rub, etc |
| (2) New ECG changes | (1) New-onset sinus arrest, first- to third-degree atrioventricular block, sinus block, or bundle branch block. (2) Multisource/paired premature ventricular contractions, voluntary atrial or junctional tachycardia, sustained or non-sustained ventricular tachycardia, atrial or ventricular flutter or fibrillation. (3) The ST segment of more than two leads is horizontally or downward inclined to move downward≥ 0.01 mV or the ST segment is abnormally elevated or abnormally Q waves |
| (3) Elevated markers of myocardial injury | Elevated cardiac troponin, with or without elevated CK-MB |
| (4) UCG and CMR showed abnormal cardiac function and structure | (1) Unexplained structural and functional abnormalities of the left ventricle and/or right ventricle: abnormal systolic or diastolic function of the whole ventricle or abnormal movement of the local ventricular wall, with or without ventricular enlargement, increased wall thickness, pericardial effusion, intraventricular thrombosis. (2) Must be at least 1 T2-related sequence (T2-weighted imaging or T2 mapping) that can sensitively detect myocardial edema and at least 1 T1-related sequence (myocardial gadolinium delayed enhancement imaging, T1 mapping, extracellular volume score) that can reflect myocardial injury and fibrosis must be positive at the same time |
注：UCG：超声心动图；CMR：心脏磁共振成像；CK-MB：肌酸激酶同工酶。
The diagnostic algorithm for acute myocarditis is shown in the figure below:
Fig.1 Flowchart for the diagnosis of acute myocarditis
Endocardial biopsy: the gold standard for diagnosing myocarditis
Endocardial biopsy is the gold standard for diagnosing myocarditis, and cardiac magnetic resonance imaging (CMR) is the non-invasive "gold standard" for clinical diagnosis of myocarditis.
For patients with positive cardiac troponin, the above two are in good agreement, and guidelines recommend that magnetic resonance imaging be done before endocardial biopsy is performed, but magnetic resonance imaging cannot replace the role of endocardial biopsy in diagnosing myocarditis.
In addition, the prediction accuracy of advanced gadolinium-enhanced (LGE) technology of magnetic resonance for all-cause mortality and cardiogenic death in myocarditis is higher than that of cardiac troponin and CRP, and it is recommended to re-examine MRI one year after the recovery period of acute myocarditis.
Indications for endocardial biopsy are as follows:
(1) Patients who cannot be diagnosed after non-invasive examinations including magnetic resonance.
(2) Patients with fulminant myocarditis.
(3) Patients with acute severe myocarditis caused by immune checkpoint inhibitors.
(4) Patients with chronic inflammatory cardiomyopathy suspected of immune overactivation after heart transplantation.
(5) Patients with chronic active myocarditis or chronic inflammatory cardiomyopathy.
The relevant points to note are as follows:
Endometrial biopsy has a high diagnostic value for acute myocarditis 2~4 weeks after the onset of the disease.
The biopsy does not detect viral nucleic acid, and the possibility of viral myocarditis cannot be completely ruled out;
In patients with a long course of disease or severe symptoms or persistently high levels of cardiac troponin, biopsy to assess for the presence of ongoing myocardial inflammation is necessary;
Human leukocyte antigen DR (HLA-DR) is considered to be a hallmark of autoimmune myocarditis, and positive staining should be treated with immunosuppressive therapy, and positive myocardial CD3 and CD4 staining indicates chronic inflammatory cardiomyopathy caused by immune overactivation.
Onset of acute myocarditis within 30 days
Acute myocarditis is myocarditis that occurs within 30 days, and most patients have a history of fever, sore throat, diarrhea, etc., and often have symptoms such as chest tightness, vague pain in the precordial area, palpitations, fatigue, nausea and vomiting, and dizziness.
Troponin has a high sensitivity and specificity for diagnosing myocardial injury, but a normal cardiac troponin level does not completely exclude the possibility of acute myocarditis. Testing for BNP and NT-proBNP is recommended for patients with suspected cardiac insufficiency.
The prognosis of patients with acute myocarditis varies widely, with nearly 50% of patients recovering completely, 25% likely to develop chronic myocarditis, and some dying due to worsening of the condition.
Symptomatic chronic active myocarditis at 30 days ≥ onset
Chronic active myocarditis:
Acute myocarditis was diagnosed for more than 30 days, and the clinical symptoms persisted;
ECG may be normal/abnormal;
心肌肌钙蛋白升高,BNP/NT-proBNP正常/升高;
Echocardiography showed mildly enlarged ventricles, normal/slightly decreased left ventricular systolic activity, 50% < left ventricular ejection fraction <55%;
Magnetic resonance findings such as T2WI: linear hypointensity in the anterior, lateral, and inferior walls of the left ventricle;
LGE: multiple delayed enhancement of the left ventricular wall, mainly in the middle layer of myocardium and subadventitial distribution. Inflammatory cell infiltration and myocardial cell injury can be seen on endocardial tissue sections.
Chronic stable myocarditis Diagnosis of acute myocarditis has no obvious clinical symptoms for more than 30 days, cardiac troponin is normal, and BNP/NT-proBNP is normal/mildly elevated; The remaining radiographic findings are based on chronic active myocarditis. Inflammatory cell infiltration can still be observed on endocardial tissue sections, but no cardiomyocyte damage is present.
Chronic inflammatory cardiomyopathy Diagnosis of myocarditis for more than 30 days meets the clinical diagnostic criteria for dilated cardiomyopathy. Only inflammatory cell infiltrates can be observed on endocardial tissue sections.
Fig.2 Diagnostic flow chart of chronic myocarditis
Evidence for myocardial nutritional drugs is insufficient
The principle of myocarditis treatment is to reduce or control myocardial inflammation, effectively control arrhythmia and heart failure, and treat the cause accordingly to improve the prognosis.
All patients diagnosed with acute myocarditis should be admitted to the hospital for observation for at least 48 hours.
For patients with mild symptoms, i.e., patients with hemodynamic stability, normal cardiac function, and no arrhythmia, they can be discharged after the symptoms are stable and the cardiac troponin begins to decline, and they can be followed up after 2~4 weeks.
Consider trimetazidine as an adjuvant treatment for patients with acute myocarditis and chronic active myocarditis (II. a, B) with 35 mg bid trimetazidine extended-release tablets or 20 mg tid trimetazidine tablets; It is recommended to continue until the patient's symptoms resolve.
In patients with chronic stable myocarditis and chronic inflammatory cardiomyopathy, there is insufficient evidence for the effectiveness of trimetazidine, and its use can be considered for symptomatic relief (II. b, C).
Coenzyme Q10 is recommended in combination with trimetazidine for the adjuvant treatment of patients with acute myocarditis and chronic active myocarditis. Usage: Coenzyme Q10 capsules 20 mg tid; It is recommended to continue until the patient's symptoms resolve (II. b, B).
For patients with chronic stable myocarditis and chronic inflammatory cardiomyopathy, there is insufficient evidence for the efficacy of coenzyme Q10, and its application can be considered for symptomatic remission based on the patient's symptoms (II. b, C).
Limit heavy physical activity
For patients with acute myocarditis and chronic active myocarditis, regardless of their age, gender, clinical manifestations, occupation (athletes or non-athletes), regardless of the cause, it is recommended to limit strenuous physical activity within 3~6 months, not participate in heavy physical activities, and avoid emotional agitation and violent fluctuations (III., C).
According to the symptoms, the condition was assessed after 3~6 months, and the myocardial injury markers, inflammatory markers, UCG, CMR, Holter ECG, etc. were improved; If the indexes are normal, the CMR examination does not reveal new inflammatory infiltrates or the degree of myocardial fibrosis is aggravated, and the ambulatory ECG does not show frequent or complex ventricular arrhythmias, starting exercise or even competitive sports can be considered (I.,C); If there is any abnormality in the above indicators, continue to recommend exercise restriction and re-evaluate after 3~6 months according to symptoms.
For patients with various types of myocarditis who have residual myocardial scarring, cardiac insufficiency, frequent or complex ventricular arrhythmias such as magnetic resonance, cardiac ultrasound, and Holter electrocardiogram, it is not recommended to engage in strenuous sports or participate in heavy physical activity (III., C).
Patients with chronic stable myocarditis and chronic inflammatory cardiomyopathy who are negative for the above imaging and functional evaluations can participate in various sports and activities normally, but they need to consider regular evaluation of the above indicators, at least once a year (II. b, C).
Treatment of critically ill patients
1. Mechanical cycle support
For fulminant myocarditis that is hemodynamically unstable, with refractory heart failure or cardiogenic shock, life-supporting therapy such as mechanical circulatory support should be given as soon as possible (I.,C).
Early manifestations of shock, such as hypotension and increased heart rate, are preferentially treated with intra-aortic balloon counterpulsation (IABP). If adequate circulation is not restored, it should be combined with extracorporeal membrane oxygenation (ECMO) therapy (II. a, C).
When the patient presents with severe circulatory impairment or cardiac arrest at the onset of cardiopulmonary resuscitation, immediate initiation of ECMO plus IABP therapy is recommended (I.,A).
In addition to IABP and ECMO, percutaneous interventional microaxial flow pumps (e.g., the Impella system) alone or in combination with IABP/VA-ECMO have been used in recent years to shorten the duration of support and improve the long-term prognosis of cardiac insufficiency (II. a, C). The portable cardiopulmonary bypass system, as a biventricular assist system, also contributes to circulatory support in fulminant myocarditis (II. a, C).
Patients with tachypnea/distress, rapid respiratory rate, or respiratory depression, with or without oxygen desaturation, are given noninvasive mechanical ventilation (I.,C) immediately, and response is closely monitored, and if there is no improvement in clinical symptoms and oxygen saturation is persistently reduced, it is changed to invasive mechanical ventilation (I.,C) if necessary.
2. Immunotherapy
Patients are recommended to be given corticosteroids as early and in sufficient doses. During the follow-up period, discontinuation and adjustment of treatment were considered based on the patient's symptoms, cardiac function, cardiac troponin level, inflammatory factor level, degree of myocardial inflammation and edema shown by magnetic resonance or myocardial biopsy, and tolerance to the drug (I., A).
It is recommended to start gamma globulin intravenously infusion of 10~20 g per day as soon as possible after admission, and halve it to 5~10 g after 3~5 days of use, and continue to apply it for 3~5 days, with a total amount of about 2 g/kg (I.,A).
3. Antiviral therapy: Most antiviral drugs are non-specific and have uncertain efficacy, so they are not specifically recommended (III.,C).
4. Vasoactive drugs
Vasoactive drugs (III., C) are not used. However, it can be used briefly when mechanical circulatory support is not available, so that the average arterial pressure of the patient is maintained at 60~65 mmHg, the minimum perfusion of important organs is ensured, and the conditions are created for referral to a center with mechanical circulatory support conditions as soon as possible (I.,A).
5. Inotropes
Inotropes are not recommended in the acute phase (III., C) and may be considered in haemodynamically stable patients during the convalescent phase (II. a, C).
For patients treated with ECMO mechanical circulatory support alone, the use of levosimendan increases the success rate of ECMO device weaning (II. a, C).
Digitalis drugs are recommended to be used cautiously when necessary to control tachyventricular rate (II. b, C).
6. Renal replacement therapy
Continuous renal replacement therapy (I., C) may be used in patients with fulminant myocarditis and acute renal impairment.
7. Immunosorbent therapy
It may be considered in patients with persistently elevated inflammatory factors (II. a, B).
Viral myocarditis
Early antiviral therapy with interferon-β (II.a,C) is recommended.
For different viral infections, it is recommended to consult an infectious disease specialist to develop a targeted antiviral strategy (II. a, C).
The positive effects of astragalus preparation have a certain effect, and the positive effects of its oral granules and injection two dosage forms have been confirmed and supported by systematic reviews, and its combination with taurine has a better effect, and can be combined with Western medicine as a conventional adjuvant treatment (II. a, C).
Monotherapy such as Danhong and Shenmai and prescriptions such as Yinqiaosan and Shengmaisan can be tried as adjuvant treatment for viral myocarditis (II. b, C).
Traditional Chinese medicines, such as Codonopsis radix and Pueraria lobata, have the effect of reducing the expression of plasma inflammatory factors in myocarditis and improving cardiac function, and can be used for the early treatment of patients with myocarditis and heart failure (II. a, C).
For hemodynamically stable viral myocarditis, pulse glucocorticoids and immunoglobulin therapy are not recommended (III., C).
Immune-mediated acute myocarditis alone and chronic inflammatory cardiomyopathy
Treatment of this type of myocarditis is consistent with the treatment of the associated systemic disease, especially if myocarditis is the first manifestation of the associated systemic autoimmune disease (II. a, C).
Immune checkpoint inhibitor-associated myocarditis
Immune checkpoint inhibitor (ICI)-associated myocarditis has a high mortality rate, and once the diagnosis is confirmed, ICI therapy should be discontinued as soon as possible (I.,C); Second, intravenous high-dose glucocorticoids (I., C).
If high-dose corticosteroids do not respond well, the addition of mycophenolate, infliximab, antithymocyte globulin, or abatacept (I., C) may be considered.
If disease progresses, cardiac troponin is elevated, and cardiac conduction abnormalities are immediately transferred to an intensive care unit for mechanical circulatory respiratory support, and the indication for heart transplantation is evaluated as soon as possible.
嗜酸性粒细胞性心肌炎(EM)
Treatment should promptly identify and address the cause (II. a, C). Especially in allergy-related eosinophilic myocarditis, it is recommended to immediately discontinue the use of harmful substances (I., C) and at the same time use glucocorticoids (II. a, C).
Albendazole (0.8 g qd) and high-dose glucocorticoids in eosinophilic myocarditis associated with Toxoplasma candii infection (II. a, C); Imatinib is used in myeloproliferative variant hypereosinophilic syndrome (II. a, C).
Combination immunosuppressive therapy, including glucocorticoids and cyclophosphamide, azathioprine, or methotrexate, may be considered for the treatment of eosinophilic granulomatous disease with polyangiitis and HES-associated EM (II. a, C).
Giant cell myocarditis (GCM)
Giant cell myocarditis often presents with acute heart failure or cardiogenic shock and ventricular tachycardia or complete atrioventricular block.
For the treatment of patients with fulminant giant cell myocarditis, antithymocyte globulin combined with high-dose glucocorticoids is preferred (I., C); In addition to the above treatments, treatment with cyclosporine or tacrolimus is recommended.
Cyclosporine is treated with an initial dose of 150~300 micrograms/L for 3 months, followed by a dose of 100~150 micrograms/L to 12 months, usually maintained for >2 years, and a target plasma level of 80~100 ng/L (II. a, C).
or tacrolimus is treated with an initial dose of 10~15 μg/L for 6 months, followed by a dose reduction of 5~10 μg/L to 12 months. In the later stage of maintenance therapy, the dose reduction (cyclosporine 75~100 μg/L, tacrolimus 5~10 μg/L) can be considered according to the presence of recurrent symptoms and adverse drug reactions (II. a, C).
For patients who do not respond well to the above regimens, mycophenolate mofetil 1.5~2.0 mg/kg/d or azathioprine 1.0~2.0g/kg/d can be used in combination for treatment (II. a, C).
Cardiac sarcoidosis, myocarditis
Glucocorticoid therapy (II. a, C) is recommended, and the optimal dose of individualized glucocorticoids is determined in conjunction with assessment of response to treatment.
Methotrexate is often used as a second-line agent in refractory cases or in patients with glucocorticoid intolerance (II. b, C).
Other drugs used for the treatment of cardiac sarcoidosis include azathioprine, cyclophosphamide, infliximab, etc. (II. b, C).
SARS-CoV-2 感染疫苗相关心肌炎
It usually occurs within a few days of the second vaccination and is characterized by chest pain as the most common symptom and, rarely, fulminant myocarditis.
No specific treatment strategy has been established. In addition to glucocorticoids and immunoglobulins, the use of nonsteroidal anti-inflammatory drugs and colchicine is also effective.
Source: Cardiomyopathy Specialty Alliance of National Center for Cardiovascular Diseases, Cardiovascular Disease Precision Medicine Branch of China Association for the Promotion of International Exchange in Health Care. Guidelines for the clinical diagnosis and treatment of myocarditis in adults in China 2024[J]. Chinese Journal of Circulation, 2024, 39(6): 521-536. DOI: 10.3969/j.issn.1000-3614.2024.01.005
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