GEAM Study Aims At Assessing the Role of Genetic Testing in Patients with Arrhythmic Myocarditis.

Arrhythmic myocarditis is responsible for a significant proportion of out-of-hospital cardiac arrest and death in the young population. Although considered an uncommon feature, arrhythmias may present in myocarditis in both acute and chronic phase, leading to sudden cardiac death (SCD), especially in young males. Overall, the prevalence of undiagnosed myocarditis in post-mortem series ranges from 9% to 44%, involving 2% of infants, 5% of children, and 4-8% of athletes <40-year-old. Ventricular arrhythmias (VAs) are reported secondary to lymphocytic myocarditis. However, they are more commonly associated with giant cell myocarditis (GCM) and cardiac sarcoidosis (CS), with prevalence of 29% and 55%, respectively In addition, genetically-determined susceptibility might underlie arrhythmic myocarditis.

First, recent reports suggest that pathogenic variants in genes associated with nonischemic cardiomyopathies (NICM), hereby defined as cardiomyopathic gene variants (CGVs) are frequently found in patients with myocarditis proven by CMR and/or EMB, complicated by ventricular arrhythmias (VA). NICM constitute a heterogeneous group of diseases characterized by distinct structural and functional myocardial abnormalities in the absence of obstructive epicardial coronary artery disease. The main NICM overlapping with myocarditis are dilated (DCM) and arrhythmogenic cardiomyopathy (ACM).

Second, myocardial inflammation (M-Infl) has also been recently described in NICM complicated by arrhythmias. Preclinical data support a relevant role of M-Infl in the pathophysiology of AINICM, and its association with adverse outcomes.

Furthermore, there is a growing interest in transcriptomics in the setting of inflammatory and genetic cardiomyopathies. Cardiac transcriptome revealed specific subgroups of patients with early and overt DCM. In animal models of experimental autoimmune myocarditis, transcriptomics, transcriptomics allowed to depict the single-cell landscape of the cardiac immune cells in different phases of the disease. The addition of the cardiac transcriptome to the genotype and phenotype of patients increases the possibility for individualized medicine.

Inclusion criteria

Patients with ventricular arrhythmias (VA+) and without (VA-)

• Diagnosis of myocarditis proven by EMB (ESC criteria) and/or CMR (updated Lake Louise criteria)
• Age ≥ 10 years
• Baseline ECG telemonitoring
• Written informed consent Healthy controls
• Provided a negative known history of myocarditis
• The sample must have been biobanked as part of the study IMMUNORADAR

Exclusion criteria

Patients with ventricular arrhythmias (VA+) and without (VA-)

• Obstructive coronary artery disease, or lack of coronary angiography/computed tomography (CT) scan in patients >40 years.
• Absent informed consent.