p.38 抽出テキスト

6.2.1.2 Fulminant myocarditis

Fulminant myocarditis is a rare and severe presentation of myocarditis and a cause of cardiogenic shock, and should be treated accordingly with inotropic or vasopressor support or, if needed, MCS (see Section 6.3).265 It is crucial to be aware of the condition and, when needed, to refer patients to tertiary referral centres that can institute temporary MCS and perform early EMB. Early EMB has been independently associated with a lower rate of death or HT/left ventricular assist device (LVAD) at 1 year.57 The timely communication of biopsy results is crucial. Specific subtypes of FM (e.g. biopsy-proven non-infectious forms) may respond to immunosuppressive therapy in addition to guideline-directed medical care.12,34 An ongoing trial is evaluating corticosteroids for FM (ClinicalTrials.gov Identifier: NCT05150704).

6.2.1.3 Acute myocarditis

Acute myocarditis has a high rate of spontaneous recovery, especially in uncomplicated cases. In cases of AM diagnosed by EMB, up to 50% of patients have spontaneous recovery and up to 25% may have a persistent stable cardiac dysfunction. Only 10%–25% have a progressive ventricular dysfunction, which could lead to end-stage DCM, HT, or death.9 Treatment of AM depends on severity and clinical presentation. Risk stratification of these patients is mandatory to assess the required level of care. The acute phase of viral myocarditis (e.g. induced by cytolytic enteroviruses) is characterized by intense virus replication and myocyte necrosis and usually lasts for only a few days.266 Thus, early antiviral therapy directed against an identified virus is a potential therapeutic avenue to stop the development of viral myocarditis. The evidence on clinical application of antiviral agents is limited, and antiviral treatments should be agreed upon with an infectious disease expert as part of the IMPS team.

Patients with AM show significant activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in the heart, thus it is a potential therapeutic target in the acute phase of myocarditis.267 Activation of NLRP3 functions as a rapid inducer of an inflammatory response through the production of IL-1β and IL-18. Theoretically, promising agents are anti-IL-1 agents (anakinra, rilonacept, canakinumab) and colchicine,267 although human data on the effect of such agents in myocarditis are still limited. In humans, the first evidence has been reported using anakinra, an IL-1 receptor antagonist (IL-1RA) that improved heart function in selected cases of AM refractory to standard treatment. However, in the ARAMIS trial, anakinra failed to demonstrate a benefit in patients with suspected AM without a specific aetiology (NCT03018834).268 The primary endpoint was the number of days alive free from any complication due to AM. The study had potential limitations related to the limited sample size, the inclusion of a low-risk population, and the short follow-up, but it proved that anakinra was safe in this setting. Regarding modulation of the immune response, further randomized studies are needed to assess treatment with intravenous immunoglobulins (IVIG) in AM for adults,269 since case series and retrospective analyses suggest a benefit in terms of transplant-free survival. Intravenous immunoglobulins are commonly prescribed in paediatric patients.269 In general, treatment of AM with corticosteroids is controversial, with the exception of ICI-induced myocarditis270 and EM.271

ICI-induced myocarditis 1st line therapy Withdraw ICI, reassess Non-severe: methylprednisolone 500–1000 mg/day × 3 days, then taper with oral prednisone

Severe: i.v. methylprednisolone 7–14 mg/kg/day × 3 days, then 1 mg/kg/day

2nd line therapy If no response in 24–48 h: mycophenolate mofetilb, ATGg abataceptl, alemtuzumabm 3rd line therapy Infliximabj or adalimumabk, rituximabi © ESC 2025

ATG, anti-thymocyte globulins; b.i.d., twice daily; CTLA-4, cytotoxic T-lymphocyte antigen 4; EM, eosinophilic myocarditis; ICI, immune checkpoint inhibitor; IgG, immunoglobulin; IL, interleukin; i.v., intravenous; IVIG, intravenous immunoglobulins; p.o., by mouth; s.c., subcutaneous; t.i.d., three times daily; TNF-α, tumour necrosis factor alpha. aAzathioprine (immunosuppressant purine analog): 1–2 mg/kg per day p.o. (typically 100–150 mg daily, in 1–2 divided doses, main target: lymphocytes). bMycophenolate mofetil (immunosuppressant that inhibits inosine monophosphate dehydrogenase, main target: lymphocytes): 500–1000 mg p.o. b.i.d. (total 1–2 g/day). cCyclosporine (calcineurin inhibitor that prevents IL-2 transcription in activated T-cells): ∼3–5 mg/kg/day p.o. (divided b.i.d.) adjusted to target trough levels ∼150–250 ng/mL. dMethotreaxate (antimetabolite that inhibits dihydrofolate reductase and other folate-dependent steps, reducing proliferation of active lymphocytes): 15–20 mg/week p.o. or s.c. (low-dose weekly, with folic acid supplementation). eIVIG (immunomodulatory therapy providing pooled IgG antibodies) = standard dose off-label 2 g/kg total dose, typically administered over 1 to 2 days; alternative dosing: 0.4 g/kg/day for 5 consecutive days (less commonly used in myocarditis but sometimes used in autoimmune settings). fPlasmapheresis (therapeutic plasma exchange that filters out and removes circulating autoantibodies, immune complexes, and inflammatory mediators) 3–5 sessions in 5–10 days. gAntithymocyte Globulin (ATG; polyclonal anti-T-lymphocyte antibody that causes profound T-cell depletion): ∼1 mg/kg i.v., often given daily for 3–5 days. hCyclophosphamide (cytotoxic alkylating agent that crosslinks DNA in rapidly dividing cells, main target: lymphocytes): 600 mg/m2 i.v. bolus on days 1, 15, and 30 (pulse therapy). iRituximab (monoclonal antibody against CD20 on B cells): 375 mg/m2 i.v. weekly × 4 doses (1 month). jInfliximab (monoclonal antibody against TNF-α): 5 mg/kg i.v. at weeks 0, 2, 6, then every ∼8 weeks (maintenance). kAdalimumab (anti-TNF-α fully human monoclonal antibody) 40 mg SC every week (or every 2 weeks, per clinical response). lAbatacept (CTLA-4 Ig fusion protein that binds CD80/86 on antigen-presenting cells, blocking the CD28 co-stimulatory signal required for full T-cell activation): 500 mg i.v. every 2 weeks × 5 doses (approximately 10 weeks). mAlemtuzumab (monoclonal antibody against CD52 on lymphocytes): 30 mg i.v. once (alternative: 15 mg i.v. daily for 2 days).

Main mechanisms of action:

• T-cell suppression (e.g., corticosteroids, cyclosporine, abatacept) • B-cell depletion (rituximab) • Cytokine inhibition (TNF-α blockers like infliximab, adalimumab) • DNA synthesis inhibition (azathioprine, mycophenolate, methotrexate) • Immunoglobulin replacement/modulation (IVIG) • Plasma filtration (plasmapheresis)

ESC Guidelines                                                                                                                                                                                          3989

Downloaded from academic.oup.com/eurheartj/article/46/40/3952/8234483 by guest on 07 October 2026