Independent predictors of dismal and favourable outcome in adult and paediatric myocarditis: data from the multicentric Italian Rare Biopsy-proven Myocarditis Registry

Abstract Background Diagnostic and prognostic features in adult and paediatric myocarditis are insufficiently characterized, and evidence supporting immunosuppression (IS) use in BP virus-negative myocarditis only comes from monocentric studies. Purpose To analyse diagnostic, therapeutic and prognostic features of biopsy-proven (BP) or clinically-suspected (CS) myocarditis patients from the first Italian multicentric myocarditis registry. Methods Retrospective (2000-2022) and prospective myocarditis patients were included, recruited in centre #1, centre #2, center #3 and centre #4. Predictors of death, heart transplantation (HTx) and/or disease relapse were assessed through multivariable regression models. Results We included 1458 patients, EMB was performed in 681 cases; lymphocytic myocarditis was the main histological type (89%), followed by eosinophilic (2.2%), giant cell (1.9%), and polymorphic (1.2%). Patients were aged 48 years (IQR 34-60), mainly Caucasian (95%), and male (68%). Compared to CS cases, BP cases were older at diagnosis (43 vs. 33 years) and more frequently had heart-failure (HF, 58% vs. 8) or arrhythmic (17% vs. 7%) presentation. BP patients indeed more frequently presented with HF (29% in III-IV NYHA class vs. 2%,) and less frequently with acute viral symptoms (22% vs. 45%). On baseline ECG, BP patients more frequently had left bundle branch block (LBBB, 9% vs. 2%), and lower echocardiographic LVEF (37% vs. 57%). IS was used in 237 BP virus-negative cases when clinically indicated. At 47 months median follow-up (IQR 17-94), 72 patients died and 34 underwent HTx; 140 patients had at least one myocarditis relapse. At follow-up, BP patients more frequently had LBBB persistence (5% vs. 1.9%) and low ECG voltages (4% vs 2.7%) than CS cases; even if LVEF was overall preserved, it was inferior in BP than CS cases (53% vs 61%). On multivariable regression analysis, overall baseline HF presentation (OR 3.72, 95%CI: 1.51-10.7) and lower EF (OR 1.02, 95%CI: 1.01-1.04) were independent predictors of death and relapse, respectively. Among BP patients, non-lymphocytic rare histological type was an independent predictor of relapse, HTx and/or death (OR 5.35, 95%CI: 1.94-14.8), while IS use was an independent predictor of good prognosis (OR 0.41, 95%CI: 0.20-0.81). Conclusions HF presentation, lower LVEF and rare non-lymphocytic histological types are independent predictors of death, HTx and/or relapse in myocarditis. For the first time, in a multicentre study IS use for BP virus-negative forms was identified as a favourable prognostic independent predictor.