Guideline sources The following summarized guidelines for the evaluation and management of myocarditis are prepared by our editorial team based on guidelines from the Japanese Circulation Society (JCS 2023), the European Society of Cardiology (ESC 2022; 2013), the European Society of Cardiology (ESC/ESTRO/EHA/IC-OS 2022), the European Society of Medical Oncology (ESMO 2020), the American Heart Association (AHA 2020; 2016), the Single Hub and Access Point for Pediatric Rheumatology in Europe (SHARE initiative 2019), the American Heart Association (AHA/HRS/ACC 2018), the Canadian Cardiovascular Society (CCS 2017), the American Heart Association (AHA/ACC 2015), and the European Society of Cardiology (ESC/EACTS 2015). 1 2 3 4 5 6 7 8 9 10 11 12 Calculator Calculator Lake Louise criteria for magnetic NYHA functional classification f https://web.pathway.md/diseases/recnShGrKD6Fl8E3H 1/14 6/30/23, 1:06 AM Myocarditis Pathway Guidelines 1. Screening and diagnosis Diagnosis: As per JCS 2023 guidelines, suspect myocarditis in patients having common cold-like symptoms (respiratory symptoms, gastrointestinal symptoms) followed by signs and symptoms associated with HF or arrhythmias. B As per CCS 2017 guidelines, suspect myocarditis in the following clinical scenarios: cardiogenic shock due to LV systolic dysfunction (global or regional) with no apparent etiology acute or subacute development of LV systolic dysfunction (global or regional) with no apparent etiology evidence of myocardial damage not attributable to epicardial coronary artery disease or another cause. B 2. Diagnostic investigations History and physical examination: Assess the following in patients with suspected myocarditis: Situation Guidance Time of onset and course of symptoms History of present illness Skin rash (including insect bites) Past medical history History of medication, vaccination, and ingestion of harmful materials Recent travel history History of autoimmune disease Fever and tachycardia (as signs of infection) Physical examination Bradycardia or tachycardia (indicating arrhythmia) Low cardiac output (tachycardia, hypotension, cold extremities) Left-sided HF (hypoxemia, third or fourth heart sound, moist rales) Right-sided HF (jugular venous distention, hepatomegaly, peripheral edema). B Electrocardiogram: https://web.pathway.md/diseases/recnShGrKD6Fl8E3H 2/14 6/30/23, 1:06 AM Myocarditis Pathway As per JCS 2023 guidelines: Obtain a 12-lead ECG in all patients with suspected myocarditis based on signs and symptoms. B Obtain periodic 12-lead ECGs and 24-hour ECG monitoring in patients diagnosed with acute myocarditis. B As per AHA 2016 guidelines, obtain a 12-lead ECG in all patients with clinically suspected myocarditis. B As per ESC 2013 guidelines, obtain standard 12-lead ECG in all patients with clinically suspected myocarditis. E Transthoracic echocardiogram: As per JCS 2023 guidelines: Obtain a TTE for the diagnosis of acute myocarditis. B Monitor time-course changes in echocardiographic findings in acute myocarditis and assess fulminant changes and improvement of the pathological condition. B As per AHA 2016 guidelines, obtain a standard TTE in all patients with clinically suspected myocarditis. B As per ESC 2013 guidelines: Obtain a standard TTE at presentation of patients with clinically suspected myocarditis. E Repeat TTE during hospitalization in case of any worsening of hemodynamics. E Magnetic resonance imaging: As per JCS 2023 guidelines, obtain cardiac MRI for the diagnosis of myocarditis in patients with signs and symptoms suggestive of myocarditis and stable hemodynamics. A Show 2 more As per CCS 2017 guidelines, obtain cardiovascular MRI, where available and in the absence of contraindications, in all patients with HF and suspected myocarditis. A As per AHA 2016 guidelines, consider obtaining cardiovascular MRI for diagnosis in clinically stable patients with clinically suspected myocarditis. C As per ESC 2013 guidelines: Use the Lake-Louise criteria for cardiovascular MRI diagnosis of myocarditis. E Consider obtaining cardiovascular magnetic resonance before endomyocardial biopsy in clinically stable patients. Recognize that cardiovascular magnetic resonance does not replace endomyocardial biopsy in the diagnosis of myocarditis and should not delay endomyocardial biopsy in life-threatening presentations. E Nuclear imaging: do not obtain routine nuclear imaging in the diagnosis of myocarditis, with the possible exception of suspected cardiac sarcoidosis. D Laboratory tests, inflammatory markers: As per JCS 2023 guidelines, obtain WBC count with differential and CRP in all patients with clinically suspected myocarditis. B Consider repeating these tests in patients diagnosed with https://web.pathway.md/diseases/recnShGrKD6Fl8E3H 3/14 6/30/23, 1:06 AM Myocarditis Pathway myocarditis. B As per ESC 2013 guidelines, obtain ESR and CRP level measurement in all patients with clinically suspected myocarditis. E Laboratory tests, cardiac biomarkers: As per JCS 2023 guidelines: Obtain CK-MB and cardiac troponin in all patients with clinically suspected myocarditis. Monitor serial changes of CK-MB and cardiac troponin in patients diagnosed with myocarditis. B Obtain B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide in patients with myocarditis possibly accompanied by HF. B As per AHA 2016 guidelines, obtain cardiac troponin level measurement for diagnosis in patients with clinically suspected myocarditis. B As per ESC 2013 guidelines, obtain troponin level measurement in all patients with clinically suspected myocarditis. E Laboratory tests (metabolic panel): obtain liver and renal function tests, electrolytes, and lactate in patients with myocarditis possibly accompanied by HF. B Laboratory tests, serology: As per JCS 2023 guidelines: Obtain relevant autoantibodies in patients with myocarditis possibly accompanied by autoimmune disease. B Do not obtain routine viral serological tests to identify the causal virus in patients with myocarditis. D As per ESC 2013 guidelines: Obtain cardiac autoantibodies (preferably disease-specific), if possible and available, according to specific center expertise. E Do not obtain routine viral serology testing in patients with clinically suspected myocarditis. D 3. Diagnostic procedures Coronary angiography: consider obtaining selective coronary angiography in all patients with clinically suspected myocarditis. E Endomyocardial biopsy: As per JCS 2023 guidelines, perform an endomyocardial biopsy, if available, in patients with suspected acute myocarditis accompanied by acute HF, severe HF, cardiogenic shock, ventricular arrhythmias, or advanced AV block. B Show 2 more As per CCS 2017 guidelines, consider performing an endomyocardial biopsy in patients with HF presenting with any of the following characteristics: new-onset (< 2 weeks) of undetermined etiology with hemodynamic compromise https://web.pathway.md/diseases/recnShGrKD6Fl8E3H 4/14 6/30/23, 1:06 AM Myocarditis Pathway high-grade heart block recurrent ventricular arrhythmias unresponsive to medical therapy. C As per AHA 2016 guidelines, perform an endomyocardial biopsy in patients with clinically suspected, unexplained acute myocarditis requiring inotropic support or mechanical circulatory support and in patients with Mobitz type 2 second-degree or higher heart block, sustained or symptomatic VT, or failure to respond to guideline-based medical management within 1-2 weeks. B As per AHA 2016 guidelines, consider performing an endomyocardial biopsy in patients with suspected eosinophilic myocarditis. C As per ESC 2013 guidelines, consider performing an endomyocardial biopsy in all patients with clinically suspected myocarditis. E Show 3 more 4. Medical management Setting of care: As per JCS 2023 guidelines, consider hospitalizing patients with acute myocarditis and obtaining monitoring for at least 48 hours, even with stable hemodynamics or no HF symptoms. C As per ESC 2022 guidelines, refer patients with confirmed or clinically suspected acute myocarditis presenting with life-threatening ventricular arrhythmias to a specialized center. B As per AHA 2018 guidelines, refer patients with life-threatening VT or VF associated with confirmed or clinically suspected myocarditis to centers with mechanical hemodynamic support and advanced arrhythmia management. B As per CCS 2017 guidelines: Consider referring patients with suspected myocarditis to a center with experience and expertise in the assessment and management of myocarditis. B Consider referring patients with myocarditis associated with HF, progressive clinical deterioration, or end-organ dysfunction despite standard HF therapy urgently for evaluation/consideration for cardiac transplantation or mechanical circulatory support. B As per ESC 2013 guidelines, refer patients with a life-threatening presentation to specialized units with capability for hemodynamic monitoring, cardiac catheterization, and expertise in endomyocardial biopsy. E Management of fulminant myocarditis (inotropic support): Consider administering dobutamine or phosphodiesterase-3 for pump failure and pulmonary congestion. C Consider administering norepinephrine C or dopamine in patients with cardiogenic shock. C https://web.pathway.md/diseases/recnShGrKD6Fl8E3H 5/14 6/30/23, 1:06 AM Myocarditis Pathway Management of fulminant myocarditis (circulatory support): perform venoarterial ECMO in patients with cardiogenic shock or lethal arrhythmia. B Show 6 more Management of heart failure: As per JCS 2023 guidelines: Consider initiating guideline-directed medical therapy for HFrEF in patients with reduced LVEF (< 50%) early after onset. C Consider initiating guideline-directed medical therapy for HFrEF in patients with adequate LVEF ( 50%). C As per AHA 2016 guidelines, manage patients with HF caused by clinically suspected or confirmed myocarditis according to the current HF guidelines. B As per ESC 2013 guidelines: Manage ventricular dysfunction in line with current guidelines on HF. E Consider performing placement of mechanical cardiopulmonary assist device as a bridge to recovery or to heart transplantation in patients with hemodynamic instability. E Management of cardiac arrhythmias (general principles): manage arrhythmia outside the acute phase of myocarditis in line with current guidelines on arrhythmia and device implantation. E Management of cardiac arrhythmias (antiarrhythmic drugs): Consider initiating antiarrhythmic drugs, preferably amiodarone and -blockers, in patients with symptomatic non-sustained or sustained ventricular arrhythmias during the acute phase of myocarditis. C Consider initiating antiarrhythmic drugs in post-myocarditis patients with recurrent, symptomatic VT. C Management of cardiac arrhythmias (sedation): consider administering sedation to suppress sympathetic activity in an electrical storm. C Management of cardiac arrhythmias (cardiac pacing): perform temporary pacing in patients with unstable hemodynamics due to bradyarrhythmia. B Show 2 more Management of cardiac arrhythmias, ICD implantation: As per JCS 2023 guidelines: Decide on the indication of an implantable device (implantable cardioverter defibrillator, cardiac resynchronization therapy defibrillator) for sudden death prevention 3-6 months after the acute phase or later, based on the clinical course and the pathological assessment. B Consider placing a wearable cardioverter defibrillator to prevent sudden death in patients with a high risk of sudden cardiac death or complicating ventricular arrhythmia in the acute phase. C As per ESC 2022 guidelines: https://web.pathway.md/diseases/recnShGrKD6Fl8E3H 6/14 6/30/23, 1:06 AM Myocarditis Pathway Consider performing ICD placement before hospital discharge in patients with hemodynamically not-tolerated sustained VT or VF during the acute phase of myocarditis. C Consider performing ICD placement in patients with hemodynamically tolerated sustained monomorphic VT occurring in the chronic phase of myocarditis. C As per AHA 2016 guidelines, do not perform ICD placement in patients with recent-onset dilated cardiomyopathy and LVEF < 30% caused by clinically suspected or confirmed myocarditis in the absence of ventricular arrhythmias or syncope. D As per ESC 2013 guidelines, defer ICD implantation until resolution of the acute episode. E Management of cardiac arrhythmias (ECMO): perform venoarterial ECMO in patients with lethal arrhythmia (particularly electrical storm). B Management of cardiac arrhythmias (catheter ablation): Consider performing catheter ablation in specialized centers in post-myocarditis patients with recurrent, symptomatic sustained monomorphic VT or ICD shocks for sustained monomorphic VT, if antiarrhythmic drugs are ineffective, not tolerated, or not desired. C Consider performing catheter ablation as an alternative to ICD therapy, after discussion with the patient and provided that established endpoints have been reached, in patients with hemodynamically well-tolerated sustained monomorphic VT occurring in the chronic phase of myocarditis, preserved LV function, and a limited scar amenable to ablation. C Immunosuppressive therapy: As per JCS 2023 guidelines, do not initiate routine immunosuppressive therapy in patients with acute lymphocytic myocarditis. D Show 3 more As per CCS 2017 guidelines: Do not use general or specific immunological therapies directed toward myocarditis. D Consider initiating immunosuppressive therapy in subgroups of patients with myocarditis due to specific underlying etiologies, such as giant cell myocarditis, sarcoidosis, myocarditis due to systemic autoimmune disease, or biopsy-proven myocarditis with undetectable viral infection using PCR. C As per AHA 2016 guidelines: Initiate immunosuppressive therapy including calcineurin inhibitors and corticosteroids for the treatment of acute dilated cardiomyopathy caused by giant cell myocarditis. B Consider initiating IV corticosteroids, systemic immunosuppressants, or immunomodulatory agents in patients with biopsy-proven myocarditis believed to be caused by SLE, rheumatoid arthritis, or polyarteritis nodosa. C As per ESC 2013 guidelines, consider initiating immunosuppressive therapy, if not contraindicated, in patients with proven autoimmune (infection-negative) forms of myocarditis, including giant cell myocarditis, cardiac sarcoidosis, and myocarditis associated with known extra-cardiac autoimmune disease. E Show 3 more https://web.pathway.md/diseases/recnShGrKD6Fl8E3H 7/14 6/30/23, 1:06 AM Myocarditis Pathway Antiviral therapy: do not use antiviral therapy routinely in patients with myocarditis. D 5. Nonpharmacologic interventions Physical activity restrictions: As per JCS 2023 guidelines, consider advising refraining from intense exercise for 6 months after onset in patients with improved HF symptoms, cardiac enzymes, abnormal ECG, and image findings. C As per AHA 2016 guidelines, advise refraining from competitive sports for a minimum of 3-6 months in patients with HF caused by clinically suspected or confirmed myocarditis. B As per AHA 2015 guidelines, advise refraining from participation in competitive sports in athletes with probable or definite myocarditis while active inflammation is present. B As per ESC 2013 guidelines, advise restriction of physical activity during the acute phase of myocarditis and for at least 6 months in athletes and non-athletes. E 6. Surgical interventions Heart transplantation: Defer cardiac transplantation in the acute phase of myocarditis as recovery may occur. E Consider performing cardiac transplantation in the acute phase of myocarditis in hemodynamically unstable patients, including with giant cell myocarditis, when optimal pharmacological support and mechanical assistance failed to stabilize the patient. E 7. Specific circumstances Neonatal patients (evaluation): obtain an ECG and echocardiography to diagnose myocarditis in neonatal patients. B Show 2 more Neonatal patients (management): Consider initiating IgAnd immunosuppressive therapy in neonatal patients with myocarditis. C Perform venoarterial ECMO in neonatal patients with fulminant myocarditis. B Pediatric patients, evaluation: As per JCS 2023 guidelines, obtain cardiac enzymes, cardiac troponins, echocardiography, and cardiac MRI to diagnose myocarditis in pediatric patients. B Show 2 more As per AHA 2016 guidelines: Consider obtaining nasal swabs and stool specimens to evaluate for viruses as well as blood PCR in patients with suspected myocarditis. C https://web.pathway.md/diseases/recnShGrKD6Fl8E3H 8/14 6/30/23, 1:06 AM Myocarditis Pathway Consider performing an endomyocardial biopsy to guide further therapy in young patients with clinical signs of myocarditis failing to recover. C Pediatric patients, immunosuppressive therapy: As per JCS 2023 guidelines: Consider administering immunoglobulin therapy in pediatric patients with acute myocarditis. C Consider initiating immunosuppressive therapy in pediatric patients with acute myocarditis. C As per AHA 2016 guidelines: Consider administering IVIG in young patients with clinical or biopsy-proven myocarditis. C Do not use corticosteroids in pediatric patients with clinical signs of myocarditis. D Pediatric patients, advanced cardiac life support: As per JCS 2023 guidelines, initiate mechanical circulatory support in pediatric patients with fulminant myocarditis associated with cardiogenic shock or life-threatening arrhythmias. B As per AHA 2020 guidelines, consider referring pediatric patients with acute myocarditis presenting with arrhythmias, heart block, ST-segment changes, and/or low cardiac output early to ICU monitoring and therapy, given the high risk of cardiac arrest. B Show 2 more Pediatric patients (patients with vasculitides): consider obtaining an ECG and echocardiography to assess for myocarditis in patients with polyarteritis nodosa. C Show 2 more Patients with myopericarditis: obtain coronary angiography (according to clinical presentation and risk factor assessment) to rule out acute coronary syndromes in patients with pericarditis and suspected myocarditis. B Show 4 more Patients with giant cell myocarditis, immunosuppressive therapy: As per JCS 2023 guidelines, initiate combination immunosuppressive therapy in the early stages. B Show 3 more As per CCS 2017 guidelines, consider initiating immunosuppressive therapy in patients with giant cell myocarditis. C As per AHA 2016 guidelines, initiate immunosuppressive therapy including calcineurin inhibitors and corticosteroids for the treatment of acute dilated cardiomyopathy caused by giant cell myocarditis. B As per ESC 2013 guidelines, consider initiating immunosuppressive therapy in patients with giant cell myocarditis, unless contraindicated. E Patients with giant cell myocarditis, management of cardiac arrhythmia: As per JCS 2023 guidelines, place an ICD in patients with a history of cardiac arrest or sustained VT. B Show 6 more https://web.pathway.md/diseases/recnShGrKD6Fl8E3H 9/14 6/30/23, 1:06 AM Myocarditis Pathway As per HRS/ACC/AHA 2018 guidelines, consider placing an ICD and/or initiating antiarrhythmic medications in patients with giant cell myocarditis with VF or hemodynamically unstable VT treated according to guideline-directed medical therapy, if the expected meaningful survival is > 1 year. C Patients with giant cell myocarditis (heart transplantation): consider performing cardiac transplantation in the acute phase of myocarditis in hemodynamically unstable patients with giant cell myocarditis when optimal pharmacological support and mechanical assistance failed to stabilize the patient. E Patients with eosinophilic myocarditis: consider performing an endomyocardial biopsy in patients with suspected acute myocarditis accompanied by peripheral eosinophilia. C Show 3 more Patients with immune checkpoint inhibitor-induced myocarditis, evaluation: As per IC-OS/ESTRO/EHA/ESC 2022 guidelines, obtain cardiac troponin, ECG, and cardiovascular imaging (echocardiography and cardiac MRI) to diagnose immune checkpoint inhibitor-associated myocarditis. B Show 2 more As per ESMO 2020 guidelines: Obtain appropriate work-up (ECG, troponin, BNP or N-terminal pro-BNP, CRP, viral titer, echocardiogram with global longitudinal strain, cardiac MRI) for immune checkpoint inhibitor- associated cardiovascular toxicity, particularly myocarditis and other common differential diagnoses, in patients developing new cardiovascular symptoms or with incidentally detected arrhythmia, conduction abnormality on ECG, or LV systolic dysfunction on echocardiogram, while undergoing (or after recent completion) of immune checkpoint inhibitor therapy. B Consider performing an endomyocardial biopsy for diagnostic confirmation if the diagnosis is highly suspected with otherwise negative work-up. C Patients with immune checkpoint inhibitor-induced myocarditis, management: As per IC-OS/ESTRO/EHA/ESC 2022 guidelines, interrupt immune checkpoint inhibitor treatment in patients with confirmed immune checkpoint inhibitor-associated myocarditis. B Show 6 more As per ESMO 2020 guidelines, withhold further therapy with immune checkpoint inhibitors and initiate high-dose corticosteroids (methylprednisolone 1,000 mg/day, followed by oral prednisone 1 mg/kg/day) promptly in patients with either suspected or confirmed immune checkpoint inhibitor-associated myocarditis. Continue corticosteroids until resolution of symptoms and normalization of troponin, LV systolic function, and conduction abnormalities. B Show 3 more Patients with immune checkpoint inhibitor-induced myocarditis, restarting ICI therapy: As per IC-OS/ESTRO/EHA/ESC 2022 guidelines, arrange a multidisciplinary discussion before restarting immune checkpoint inhibitor treatment in selected patients with previous uncomplicated immune checkpoint inhibitor-associated myocarditis. B https://web.pathway.md/diseases/recnShGrKD6Fl8E3H 10/14 6/30/23, 1:06 AM Myocarditis Pathway As per ESMO 2020 guidelines, individualize the decision on restarting immune checkpoint inhibitor therapy in the absence of alternative available antineoplastic therapies with multidisciplinary discussion considering the cancer status, response to prior therapy, the severity of cardiotoxicity, regression of toxicity with immunosuppressive therapy, and patient preference after weighing the risks and benefits. Consider offering monotherapy with an anti-PD-L1 agent with very close surveillance for cardiotoxicity development if immune checkpoint inhibitor therapy needs to be restarted. B 8. Follow-up and surveillance Follow-up: As per JCS 2023 guidelines, consider obtaining long-term regular check-ups, including ECG and cardiac ultrasound, after the resolution of symptoms. C As per CCS 2017 guidelines, obtain clinical follow-up until resolution of myocarditis or until a chronic management plan is in place. B As per ESC 2013 guidelines, obtain monitoring with clinical assessment, ECG, and echocardiography in all patients with myocarditis. E Show 2 more Return to sport activities: Obtain a resting echocardiogram, 24-hour Holter monitoring, and an exercise ECG 3-6 months after the initial illness before returning to competitive sports in athletes initially presented with an acute clinical syndrome consistent with myocarditis. B Consider advising athletes to resume training and competition if all of the following criteria are met: ventricular systolic function has returned to the normal range serum markers of myocardial injury, inflammation, and HF have normalized clinically relevant arrhythmias, such as frequent or complex repetitive forms of ventricular or supraventricular ectopic activity, are absent on Holter monitoring and graded exercise ECGs. C Clinical findings Symptoms Past medical history Abdominal pain Cardiac sarcoidosis Arthralgia Eosinophilic granulomatosis with polyangiitis Chest pain Exposure to chemotherapy Chills Exposure to radiation therapy Diarrhea Granulomatosis with polyangiitis Exercise intolerance HF Fatigue https://web.pathway.md/diseases/recnShGrKD6Fl8E3H 11/14 6/30/23, 1:06 AM Myocarditis Pathway Fever Kawasaki disease Flu-like symptoms Polyarteritis nodosa Loss of appetite Rheumatoid arthritis Malaise SLE Myalgia Upper respiratory tract infection Nausea Vital signs Orthopnea Palpitations Bradycardia Shortness of breath Hypotension Skin rash Tachycardia Vomiting Integument exam Social history Cyanosis Alcohol consumption Hematological findings Cocaine use blood eosinophils Cardiac exam Imaging findings Cardiogenic shock Fourth heart sound Cardiomegaly Gallop rhythm Pericardial effusion Muffled heart sounds Regional wall motion abnormality Pericardial rub Pericarditis LVEF Third heart sound Lab findings CK-MB ESR serum BNP serum CRP serum LDH serum NT-proB-type natriuretic peptide serum troponin I serum troponin T ECG findings AV block Low voltages Prolonged QT interval St-segment changes St-segment elevation Ventricular arrhythmia https://web.pathway.md/diseases/recnShGrKD6Fl8E3H 12/14 6/30/23, 1:06 AM Myocarditis Pathway References 1. 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