Immunosuppressive Treatment in Chronic Virus-Negative Inflammatory Cardiomyopathy

Inclusion Criteria:

1. Age ≥18 years

2. Medical therapy for HF for ≥3 months and <10 years according to current guidelinerecommendations

3. Persistent reduction of LVEF <50% on a routine echocardiographic evaluation (Simpson's biplane) not older than 1 month at time of inclusion

4. EMB with immunohistochemical evidence of lymphocytic myocarditis defined as ≥14leukocytes/mm2 including up to 4 monocytes/mm2 with the presence of CD3 positiveT-lymphocytes ≥7 cells/mm2 and increased MHC-II expression as approved by thehistopathology core lab

5. Absence of established cardiotropic virus infection in EMBs (i.e. enteroviruses,HHV-6, EBV, CMV, adenoviruses, parvovirus B19 >500 copies) as approved by thehistopathology core lab

6. Negative pregnancy test and the use of a highly effective contraceptive measure inwomen with child-bearing potential (according to CTFG recommendations)

7. Written informed consent.

Exclusion Criteria:

1. Histopathological (as approved by the histopathology core lab) and/ or clinicalevidence of acute lymphocytic myocarditis, sarcoidosis, GCM or eosinophilicmyocarditis,

2. Known systemic inflammatory disease,

3. Recent major surgery within <6 weeks, recent ICD implantation within <6 weeks orrecent CRT implantation within <3 months prior to,

4. Known coronary artery disease responsible for cardiac dysfunction (i.e., priormyocardial infarction, persistent stenosis ≥ 70%),

5. Pregnancy or lactation,

6. Contraindications to immunosuppressive treatment with MMF + corticosteroids,

7. Inability to provide informed consent.