Acute myocarditis associated with desmosomal gene variants

Myocarditis is an inflammatory disease of the myocardium caused by a variety of infectious and non-infectious (such as immune-mediated or toxic) triggers. Endomyocardial biopsy is considered the reference standard for myocarditis confirmation and further evaluation. However, this invasive procedure is performed only in a minority of patients with clinically suspected myocarditis and thus the aetiology of the disease remains often undetermined. Current recommendations don´t support genetic evaluations of subjects with acute or recurrent myocarditis. Nevertheless, there is increasing evidence about its possible utility in patients with myocarditis recurrencies or individuals with positive family history of the myocarditis, or positive history of cardiomyopathy, respectively sudden cardiac death.

In my opinion very interesting and clinically important study was recently published by Ammirati et al. in JACC: Heart failure. It was a retrospective, multi-center, international study, which aimed to ascertain the risk of death, ventricular arrhythmias, heart failure and recurrent myocarditis in patients with pathogenic or likely pathogenic desmosomal gene variants (DGV).

Three different subgroups with acute myocarditis were evaluated: 36 patients with proven DGV mutation, 25 individuals with absence of DGV mutation and 36 patients without genetic testing.

Patients with DGV mutation had significantly more often positive family history of arrhythmogenic right ventricle cardiomyopathy and sudden cardiac death. In this DGV positive group non-sustained ventricular tachycardia during in-hospital telemetry monitoring was more frequent and on cardiac magnetic resonance (CMR) septal and ring-like late gadolinium enhancement (LGE) were more common.  Kaplan-Meier curves estimated a risk of composite endpoint (death, ventricular fibrillation/ventricular tachycardia, acute heart failure and myocarditis recurrence) of 62.3% at 5 years in the group with DGV mutation, 17.5% in the group with absent DGV mutation and 5.3% in the group without genetic testing. The combined endpoint was mainly driven by myocarditis recurrence. The incidence rates (per 100 Patient-Years) of myocarditis recurrence were 20.84 for DGV positive group, 5.75 for DGV negative group and only 1.49 for group without genetic testing. In majority of all groups, CMR was performed during the follow-up. In DGV positive group LGE septal pattern was more common and the number of LGE segments was significantly higher in comparison with other two groups.
Authors conclude their study by the statement, that patients with acute myocarditis and DGV pathogenic or likely pathogenic mutation have a higher incidence of adverse cardiovascular events compared with patients without DGV mutation. 

Authors suggest possible red flags for indication of genetic testing of patients with acute myocarditis. These features are presence of positive family history, occurrence of non-sustained ventricular arrhythmias on in-hospital telemetry and the presence of ring-like or septal pattern on CMR.  Nevertheless, authors comment that further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with acute myocarditis who are considered low risk.