Infarct-like myocarditis in adolescents: Exploring genetic insights from diagnosis through follow-up

Abstract

Background: Myocarditis has traditionally been considered an acquired condition, but recent evidence suggests a genetic contribution, primarily in complicated cases. Data on pediatric uncomplicated or infarct-like myocarditis remain scarce. This study aimed to assess the prevalence of pathogenic or likely pathogenic (P/LP) variants in adolescents with infarct-like myocarditis and their association with clinical and imaging findings.

Methods: This prospective, multicenter study included 30 adolescents diagnosed with infarct-like myocarditis across five hospitals in Catalunya, Spain (2016-2024). Diagnosis was confirmed using the 2018 Lake Louise Criteria on cardiac magnetic resonance imaging (CMR). Follow-up CMR was performed at 12 months, and genetic testing was conducted using a next-generation sequencing panel targeting 174 genes associated with inherited cardiac diseases.

Results: P/LP variants in cardiomyopathy-associated genes were identified in 22.2 % of patients. Baseline CMR showed no significant differences in ventricular function or LGE extent, but a ring-like LGE pattern was significantly associated with genetic findings (p = 0.025), while septal involvement showed a p-value of 0.056. Over a median follow-up of 3 years (IQR 2-7), 9 patients (30 %) experienced recurrent myocarditis, more frequently in genetic-positive patients (66.7 % vs. 23.8 %). At 12 months, genetic-positive patients exhibited a greater LGE burden (p = 0.047) and persistent myocardial edema on T2-STIR (p = 0.009), suggesting ongoing myocardial remodeling.

Conclusions: The high prevalence of P/LP variants in infarct-like myocarditis highlights the need for genetic testing, particularly in patients with a ring-like LGE pattern or septal involvement. Persistent CMR abnormalities and symptomatic recurrences in genetic-positive cases support long-term monitoring, even in seemingly uncomplicated presentations.

Keywords: Adolescents; Cardiac magnetic resonance; Genetics; Infarct-like; Myocarditis.