Acute myocarditis and genetic testing: real-world practice before ESC guidance

Background Acute myocarditis (AM) may overlap with inherited cardiomyopathies, with genetic variants influencing susceptibility to injury and adverse remodeling. Genetic testing is increasingly integrated into AM evaluation, as recommended by recent ESC guidelines for high-risk groups. We aimed to determine the proportion of AM patients meeting ESC testing criteria and the gap between eligibility and testing performed. Methods We conducted a retrospective observational single-center study including all patients diagnosed with acute myocarditis (2017–2025). Clinical, laboratory, and imaging data were collected (Fig.1). Cardiac magnetic resonance (CMR) was reviewed using Lake Louise criteria, and late gadolinium enhancement (LGE) was categorized by pattern; septal and/or ring-like involvement were deemed significant. Genetic testing eligibility followed 2025 ESC recommendations. Endomyocardial biopsy (EMB) results were recorded when available. Results A total of 164 patients with AM were included (median age 40 years (IQR 24–55), 28% female). Nearly all patients were hospitalized (98%), and 12% had a complicated course, including cardiogenic shock (11%, n=18), ventricular arrhythmias (4.3%, n=7), complete AV block (3.7%, n=6), and cardiac arrest (3.1%, n=5) (Fig.2). Most cases represented first presentations (156, 95.1%), with 8 patients (4.9%) presenting with a recurrent episode. CMR was performed in 151 patients (92.1%). Significant LGE was present in 67 (40.8%), LV systolic dysfunction in 34 (20.7%), and biventricular dysfunction in 10 (6.1%). The pattern of LGE significantly influenced left ventricular functional recovery (p < 0.001) and the absence of significant LGE had a markedly higher likelihood of LVEF normalization than those with septal or ring-like patterns (OR = 8.36, 95% CI 2.26–30.96, p = 0.001). Of the 164 patients with AM, 77 (47%) met the 2025 ESC indications for genetic testing, yet only 5 (6.5% of eligible) underwent testing. Among the 5 patients who underwent genetic testing, 3 had negative results and 2 carried pathogenic variants (LMNA and MYBPC3). EMB was performed in 25 patients, with 17 confirming myocarditis. Conclusions Nearly half of AM patients in our pre-guideline cohort would have met the current ESC indications for genetic testing, yet very few underwent testing. These findings underscore the need to align practice with the newly released guidelines to improve detection of inherited risk and support appropriate patient and family management.