Risk stratification in myocarditis: retrospective application of the 2025 ESC Guidelines (GL) criteria in a large, well-characterized cohort with Inflammatory Myopericardial Disease (IMPD)

Introduction The 2025 ESC GL on Myocarditis propose a comprehensive approach to risk stratification in patients with IMPD. Risk classes application and long-term event rates evaluation remain unexplored. Purpose To assess long-term outcomes (death/Heart Transplant-HTx-/LVAD implant, Major Ventricular Arrhythmias-MVAs -:Sustained Ventricular Tachycardia -SVT- Ventricular Fibrillation, ICD interventions-, worsening Heart Failure-HF-) according to the new risk classification in myocarditis. Methods We retrospectively applied the 2025 ESC GL risk stratification criteria to a large, well-characterized registry population from a referral centre for myocarditis, with long-term follow-up. Results 285 patients (72.6% male, 34 [22–48] years) underwent baseline evaluation. According to the latest GL, 63.9% had definite (41.2% EMB-proven, 58.8% CMR-proven), 36.1% had possible myocarditis. 36.1% had pericardial involvement. 134 (47%) were classified as high risk: 23 required hemodynamic support (fulminant myocarditis-FM-), while 111 met high-risk criteria based on clinical features (electrical instability, HF; 70.3%) or imaging criteria (LVEF <40%/extensive Late Gadolinium Enhancement (LGE), 29.7%). 73 were at intermediate risk (17.8% due to clinical characteristics -Non-SVT, NYHA II; 82.2% due to imaging findings -LVEF 41–49%, LGE >1 segment), 78 (27.4%) were low risk. High-risk patients were older (p=0.003), had more severely impaired LV systolic function (p<0.001), and greater LV dilation (p<0.001). Follow-up data were available for 267 patients (median duration 54 [21–114] months). 14 (5.2%) died, 10 (3.7%) underwent HTx, and 1 received an LVAD. 24 (8.9%) experienced MVAs, and 21 (7.8%) developed worsening HF. Myocarditis recurrence occurred in 53 patients (19.9%). High-risk patients, compared with intermediate- and low-risk groups, more frequently reached the composite endpoint of death/HTx/LVAD (p=0.0496), MVAs (p=0.0017), and worsening HF (p=0.0011). Overall incidence and 1-, 5-, and 10-year event rates were significantly higher in the high-risk group for all outcomes. Within the high-risk category, sex and age did not influence outcomes. FM increased the risk of death/HTx/LVAD (p=0.009) and worsening HF (p<0.001). High-risk classification based solely on imaging criteria was associated with a lower risk of death/HTx/LVAD compared with high-risk clinical features (p=0.042), without significant differences in MVAs or worsening HF. In high-risk patients, 10-year event rates were 20.7% for death/HTx/LVAD, 21.5% for MVAs, and 17.7% for worsening HF. Myocarditis recurrency was more frequent in intermediate- and low-risk patients (p=0.0026), with 10-year rates of 46.7% and 42.6%, respectively. Conclusions In this large registry of myocarditis patients, retrospective application of the new risk classification showed good accuracy in identifying patients at higher risk of death/HTx/LVAD, MVAs, and worsening HF.