Myocarditis, defined as inflammation of myocardial tissue, is a rare disease in the pediatric population. Cardiovascular cardiac magnetic resonance (CMR) is a powerful tool for noninvasive assessment of myocardial inflammation as defined by the Lake Louise criteria, with a sensitivity of approximately 82% [1Banka P., Robinson J.D., Uppu S.C., e al. Cardiovascular magnetic resonance techniques and findings in children with myocarditis: a multicenter retro- spective study J Cardiovasc Magn Reson 2015 ;  17 : 1-8

Cliccare qui per andare alla sezione Riferimenti]. CMR allows tissue characterization of the myocardium, as well as accurate definition of ventricular volumes and function. Few prognostic factors have been associated with either normalization of function or progression to dilated cardiomyopathy in pediatric myocarditis. In the present study, we aimed to describe CMR findings in a large cohort of pediatric patients with acute myocarditis and to assess disease evolution. Our study received the proper ethical oversight [CNIL (Commission nationale de l’informatique et des libertés) declaration 2130271 v 0]. Sixty-eight children younger than 18 years of age with clinical myocarditis and positive acute-phase myocardial inflammation, as defined by the Lake Louise criteria [2Friedrich M.G., Sechtem U., Schulz-Menger J., e al. Cardiovascular magnetic resonance in myocarditis: a JACC white paper J Am Coll Cardiol 2009 ;  53 : 1475-1487 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti], underwent follow-up CMR during a 12-year period (from March 2007 to March 2019). The first follow-up CMR study was performed at a median of 5 months after the first examination (interquartile range: 1 to 6 months), and additional CMR studies were performed in 47% of the cohort (32 patients). Patient characteristics are presented in Table 1. Most of the cohort were males (73.5%) who presented with chest pain (68%) or new-onset heart failure (33%). Fever was found in 55% of the cohort. Full recovery from acute myocarditis, as defined by normalization of ventricular function [left ventricular ejection fraction (LVEF) >55%, right ventricular EF >54%], ventricular dimensions (LV end-diastolic volume index <104ml/m² for males, <95ml/m² for females, right ventricular end-diastolic volume index <108ml/m² for males, <94ml/m² females), regional wall function and tissue abnormalities [absent myocardial edema and late gadolinium enhancement (LGE)], was observed in 26% of the cohort (n ¼ 18). Fever at presentation was significantly more common in the patients who had full recovery (100% vs. 43%; P<0.01). Although baseline LV function was not different between those who had full recovery and those who did not, a non-significantly larger LV volume (79ml/m² vs. 89ml/m²) was found in those who did not recover. Concerning tissue characterization parameters, positive T2 (90% vs. 77%) and LGE (96% vs. 83%) were significantly more common in patients who did not recover. Early gadolinium enhancement followed the same pattern, without statistical significance. The prevalence of a sub-epicardial pattern of LGE was not different between groups (P ¼ 0.11), but other LGE patterns were more frequent in patients who did not recover (P ¼ 0.04). Conversely, acute-phase LGE extent did not differ between groups (4% vs. 3.9%; P ¼ 0.85). To the best of our knowledge, this was the largest multicenter pediatric study that assessed repeated CMR evaluation of acute myocarditis. In the present study, we confirmed the recent finding that LGE in the acute phase of myocarditis was not necessarily a marker of fibrosis. In our population, LGE disappeared completely in 26% of patients, which was higher than the 10% reported in adults [3Aquaro G.D., Ghebru Habtemicael Y., Camastra G., e al. Prognostic value of repeating cardiac magnetic resonance in patients with acute myocarditis J Am Coll Cardiol 2019 ;  74 : 2439-2448 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti]. This difference might translate to a higher healing ability of pediatric patients from tissue damage, as seen in other medical conditions. This complete healing of myocardial tissue abnormalities might be clinically relevant because residual fibrosis was associated with worse prognosis independently of LVEF [3Aquaro G.D., Ghebru Habtemicael Y., Camastra G., e al. Prognostic value of repeating cardiac magnetic resonance in patients with acute myocarditis J Am Coll Cardiol 2019 ;  74 : 2439-2448 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 4Yang F., Wang J., Li W., e al. The prognostic value of late gadolinium enhancement in myocarditis and clinically suspected myocarditis: systematic review and meta-analysis Eur Radiol 2020 ;  30 : 2616-2626 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti]. In our study, an LGE pattern other than sub-epicardial was associated with non-recovery. This result was concordant with a recent study by Aquaro et al. [5Aquaro G.D., Perfetti M., Camastra G., , e al. Cardiac M.R. with late gadolinium enhancement in acute myocarditis with preserved systolic function: ITAMY study J Am Coll Cardiol 2017 ;  70 : 1977-1987 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti], who demonstrated a worse prognosis in association with a mid-wall septal pattern of LGE compared with a sub-epicardial inferior-lateral pattern.

In conclusion, we found that fever at presentation was associated with full recovery from acute myocarditis, whereas specific acute-phase CMR findings (positive T2 criteria, LGE presence, and patterns other than sub-epicardial) were associated with its absence.