CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine

Patients alive and free of any worsening features (clinical, arrhythmic burden and imaging outcome) AND that show at least one of the signs of improvements (IMAGING or ARRHYTMIC improvements).

Clinical worsening (at least one of the following): 1. cardiac death 2. hospitalization for worsening HF or arrhythmic events, 3. Sustained ventricular tachycardia (SVT). Worsening arrhythmic burden: 1. PVC burden increase of 50% on ECG ambulatory monitoring 2. Increase in NSVT of 30% compared with baseline 3. Any SVT.

Worsening imaging outcomes

1. Proportion of patients with LVEF reduction \>10%on echo/CMRI, 2. Proportion of patients with new areas of edema on CMRI or FDG-PET associated with an increase in the edema in the inflammatory lesion identified on baseline CMRI or FDG-PET. Improvement of imaging outcome: 1. Proportion of patients with a reduction in edema on CMRI or FDG without new areas of edema AND normal high sensitivity troponin. 2. Proportion of patients with disappearance of edema on CMRI OR NO FDG uptake on PET Improvement of arrhythmic outcome: 1\. Improvement of ARRHYTHMIC burden. Proportion of patients with a PVC burden reduction of 70% on the ECG ambulatory monitoring and no NSVT/SVT.

LVEF change on echocardiogram.

Absolute change at 6 months from randomization of the LVEF on echocardiogram. Patients not performing echocardiography due to death, heart transplantation (HTx) will be counted as -10 point in the LVEF.

LVEF change on CMRI

Absolute change at 6 months from randomization of the LVEF on CMRI when available. Patients not performing the CMRI due to death, HTx, LVAD implantation or device implantation after randomization will be counted as -10 point in the LVEF.

Evidence of dysfunction and/or dilation on CMRI

Proportion of patients with LVEF\<55% AND/OR LV dilation on 6-month CMRI (CMRI clips will be centrally reviewed) or not performing the CMRI due to death, HTx, LVAD implantation or device implantation after randomization (i.e. ICD).

Clinical secondary endpoints

Composite endpoint: (1) all-cause death or (2) HTx or (3) LVAD implantation, or (5) first rehospitalization due to HF or VA, or advanced atrioventricular (AV) block.

The primary aim of the REGISTRY is the proportion of patients with MCGV(+) Infl-CMP versus MCGV(-) Infl-CMP with more primary endpoints

We will measure the outcome of the patients in the registry as described in the TRIAL at the end of a minimum follow-up of 6 months. The co-primary aim of the registry will be to the identify baseline variables that are independently associated with the above-mentioned 6-month endpoints. The patients who enter the registry are expected to follow an even longer follow-up of 2 The Registry endpoints pooling together patients included in the trial and registry.

Differences in the results of in-vitro experiments between MCGV(+) vs. MCGV(-) Infl-CMP patients and between MCGV(+) Infl-CMP patients and family members of the probands with the negative cardiac phenotype (FMPNCP)

We will compare in-vitro experiments between MCGV(+) vs. Infl-CMP versus MCGV(-) Infl-CMP patients and between MCGV(+) Infl-CMP patients and family members of the probands with the negative cardiac phenotype (FMPNCP). Samples for the experiments will be from patients included in the trial and registry.