Neutrophil-to-lymphocyte ratio for risk stratification in acute myocarditis across the left ventricular ejection fraction spectrum

Aims: Acute myocarditis (AM) is a heterogeneous clinical condition. Several classification models have been proposed to predict adverse clinical outcomes, but risk stratification remains challenging, particularly for patients presenting with preserved left ventricular ejection fraction (LVEF). Neutrophil-to-lymphocyte ratio (NLR) is a useful tool for risk stratification in patients with AM. This study aimed to compare the predictive accuracy of available risk stratification models, including NLR, for identifying patients with AM at increased risk of adverse events. Methods and results: The study included 1150 patients with biopsy- or cardiac magnetic resonance (CMR)-proven AM from 10 hospitals in six countries. Baseline clinical, laboratory, echocardiographic and CMR data, and clinical outcomes, were collected. The population was divided into four groups based on published models of high-risk AM (complicated, fulminant, high-risk, and NLR ≥4). The primary outcome was all-cause mortality and heart transplantation. During a median follow-up of 228 weeks (interquartile range 114-339), 63 events occurred in 60 patients (5.2%) who experienced the primary outcome. NLR (area under the curve [AUC] 0.72) performed similarly to complicated (AUC 0.73) and high-risk definitions (AUC 0.73) for the prediction of adverse events, while the fulminant classification showed significantly inferior predictive accuracy (AUC 0.62, p = 0.02). Moreover, among patients with preserved LVEF (≥50%) at presentation, NLR showed superior prognostic value (AUC 0.73; complicated: 0.52, p = 0.001; high-risk: 0.52, p = 0.002). Multivariable analysis confirmed that each classification was independently associated with the primary outcome. However, the NLR model showed better predictive performance compared to the other models among patients with LVEF ≥50%. Conclusions: While traditional definitions of high-risk AM remain valuable, NLR ≥4 is a simple and cost-effective marker that aids in risk stratification. NLR ≥4 is particularly robust in patients with preserved LVEF, supporting its use across the LVEF spectrum.