Table 3.

Personalized treatment regimens for patients with myocarditis/inflammatory cardiomyopathy.

Treatment	Recommendation
Standard and/or supportive treatment
Standard HF medications (ACE-I/ARNI, beta-blocker, MRA, ivabradine, SGLT2-I, diuretic, etc.)	Management according to the current appropriate guidelines.
Therapy of end-stage or acute HF with hemodynamic compromise	Treatment in experienced intensive (cardiac) care unit. Advanced cardio-pulmonary support may be needed as a bridge to heart transplantation or recovery. If possible, referral for a heart transplant/LV assist device implantation should be deferred for at least 3–6 months.
Standard antiarrhythmic medications (i.e., amiodarone)	The management of arrhythmias should mainly be supportive, as in myocarditis, arrhythmias often diminish or disappear following the resolution of acute myocardial inflammation. Patients with life-threatening arrhythmias should be referred to experienced centers.
Nonsteroidal anti-inflammatory drugs (i.e., ibuprofen) and colchicine	Patients with mild myocarditis and predominant associated pericarditis (pericarditic chest pain, pericardial effusion, high C-reactive protein) with preserved or nearly preserved LV function. Potentially harmful in other groups, but data is lacking.
Anticoagulation	Patients with acute/fulminant myocarditis with reduced LVEF until resolution of the acute inflammatory phase may require anticoagulation. Patients with intracardiac thrombosis and peripheral embolization, particularly if biopsy-proven eosinophilic myocarditis.
Catheter ablation	No indication in acute myocarditis. If necessary, it may be considered in selected patients with drug-refractory or scar-related arrhythmias or arrhythmic storms (i.e., in giant cell myocarditis).
ICD/CRT	Indications for ICD/CRT implantation should be evaluated individually; however, urgent ICD implantation in primary SCD prevention is not recommended for patients with recent-onset myocarditis. The decision regarding ICD/CRT implantation should be deferred for at least 3–6 months. A wearable cardioverter defibrillator can provide protection as a bridge to ICD or transplant decision, or to recovery after immunosuppressive therapy, particularly in patients with high arrhythmic risk and/or severe left ventricular dysfunction.
Disease-specific treatment
Withdrawal of potential triggering factors (i.e., clozapine, immune-checkpoint inhibitors)	Myocardial damage induced by toxic substances or drugs may progress if treatment is not stopped immediately.
Anti-infectious treatment	Therapy (anti-viral, antibiotics, antifungal, antiparasitic) directed against specific infectious agents (i.e., HIV, HHV6, Parvovirus B19, Borrelia).
Immunosuppressive treatment in specific infectious-negative forms	Recommended for immune-mediated forms confirmed with EMB (and AHA if available). Giant-cell myocarditis: triple therapy with steroids, cyclosporin, azathioprine; Eosinophilic myocarditis: dual therapy with steroids and steroid-sparing drug (azathioprine, cyclosporine, or mycophenolate mofetil as alternatives); Cardiac sarcoidosis: dual therapy with steroids and steroid-sparing drug (azathioprine, cyclosporine, or mycophenolate mofetil as alternatives); Lymphocytic myocarditis: most commonly prednisone (starting from 1 mg/kg for 1 month and maintenance of 0.33 mg/kg for 5 months) with azathioprine (2 mg/kg for at least 6 months); cyclosporine or mycophenolate mofetil as alternatives; Specific disease-directed therapy (i.e., rituximab, methotrexate) if myocarditis occurs in the context of systemic inflammatory/autoimmune disease (i.e., GPA, lupus erythematosus)

ACE-I: angiotensin-converting enzyme inhibitors; ARNI: angiotensin receptor neprilysin inhibitor; AHA: anti-heart autoantibodies; CRT: cardiac resynchronization therapy; EMB: endomyocardial biopsy; HF: heart failure; HIV: human immunodeficiency virus; HHV6: human herpesvirus 6; GPA: granulomatosis with polyangiitis; ICD: implantable cardioverter defibrillator; LV: left ventricle; LVEF: left ventricle ejection fraction; MRA: mineralocorticoid receptor antagonists; SGLT2-I: sodium-glucose co-transporter-2; SCD: sudden cardiac death.