Acute Myocarditis Associated With Desmosomal Gene Variants

Area of Science:

• Cardiology
• Genetics
• Internal Medicine

Background:

• The cardiovascular risk associated with acute myocarditis (AM) in patients carrying desmosomal gene variants (DGV) is not well-established.
• Understanding this risk is crucial for patient management and prognostication.

Purpose of the Study:

• To determine the risk of major adverse cardiovascular events, including death, ventricular arrhythmias, recurrent myocarditis, and heart failure, in patients with AM and pathogenic or likely pathogenetic DGV.

Main Methods:

• A retrospective international study involving 97 patients with AM across 23 hospitals.
• Patients were categorized into three groups: AM with DGV (DGV[+]), AM with negative genetic testing (DGV[-]), and AM without genetic testing.
• Cardiac magnetic resonance (CMR) was used for diagnosis and reassessment of cardiac function and structure in 86 patients.

Main Results:

• Patients with AM and DGV (primarily DSP variants) showed a significantly higher 5-year incidence of the main endpoint (62.3%) compared to those without DGV (17.5%) or without genetic testing (5.3%) (P < 0.0001).
• This increased risk was primarily driven by myocarditis recurrence and ventricular arrhythmias.
• Follow-up CMR revealed more late gadolinium-enhanced segments in the DGV(+) AM group, indicating greater myocardial scarring.

Conclusions:

• Patients with AM and evidence of DGV experience a higher rate of adverse cardiovascular events than those with AM but without DGV.
• Further prospective research is warranted to evaluate the utility of genetic testing in refining risk stratification for AM patients, particularly those initially assessed as low-risk.