Age-associated clinical patterns in paediatric myocarditis: left ventricular function as the key early risk stratifier

Abstract Background and Aims In myocarditis, early identification of high-risk patients is essential, robust prognostic markers are lacking. We aimed to identify early clinical risk stratifier at index hospitalization for major adverse cardiovascular events (MACE). Methods We analysed 725 paediatric patients with possible/definite myocarditis enrolled in the prospective multicentre MYKKE registry (2013–2024). MACE included mechanical circulatory support (MCS), heart transplantation, or death during initial admission. Model-based recursive partitioning (MOB) and bootstrap-based logistic regression with multiple imputation were applied for risk stratifier selection out of 20 baseline variables. The model was externally validated in the Swedish SWEDCON- cohort (n = 243). Discrimination was assessed by the area under the curve (AUC). Results Among 725 patients (median age 14.3 years [IQR 4.0–16.4]; 33% female), 88 (12.2%) experienced MACE (MCS 10.9%, transplantation 4.3%, death 2.2%). MOB identified left ventricular ejection fraction (LVEF) ≤ 39% as the only stable risk stratifier, delineating a “heart failure type” in younger children (1.9 years; LVEF 24%), and a “chest pain type” in adolescents with preserved LVEF (15.6 years; LVEF 59%). LVEF was confirmed as the sole robust risk stratifier (OR per 1% increase: 0.90 ; 95% CI 0.881-0.917; p < 0.01; AUC 0.90, 95% CI 0.896–0.903). In SWEDCON (7.4% MACE), discrimination was maintained (AUC 0.894, 95% CI 0.80–0.991). Conclusion Reduced LVEF at presentation was the only reproducible and externally validated risk stratifier of MACE during index hospitalization. Two age-associated clinical patterns were observed: a high-risk “heart failure type” in younger children and low-risk “chest pain type” in adolescents.