Neutrophil-to-lymphocyte ratio independently predicts short- and long-term adverse outcomes in cardiac sarcoidosis

Background Cardiac sarcoidosis (CS) is characterized by myocardial and systemic inflammation and carries a substantial risk of arrhythmic events and death. While imaging and functional parameters are commonly used for risk stratification, the incremental prognostic value of systemic inflammatory markers remains unclear. Purpose To evaluate the association between neutrophil-to-lymphocyte ratio (NLR) and short- and long-term adverse events, and to compare its prognostic value with established clinical and imaging risk factors. Methods We analyzed 236 patients with CS from four tertiary centers. The primary endpoint was time to the first occurrence of death, ventricular tachycardia, appropriate implantable cardioverter defibrillator shock, or heart transplantation. The index date was defined as the first clinical manifestation in symptomatic patients or the first diagnostic imaging in asymptomatic individuals. Median follow-up was 5.4 years [IQR 3.4-8.2 years]. Multivariable Cox regression models were adjusted for age, sex, index year, cardiac magnetic resonance mass and left ventricular ejection fraction, beta-blocker therapy and steroid treatment variables, NT-proBNP, NYHA class, symptoms at onset, extracardiac PET uptake, and the overall PET impression. Results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). NLR was also analyzed as a continuous variable and subsequently modelled using restricted cubic splines with 3 degrees of freedom to explore non-linearity. Results Composite events occurred in 103 patients (43.6%). In univariable analysis, NLR showed a borderline linear association with outcome (HR per 1 unit increase 1.08, 95% CI 0.99-1.19). In multivariable analysis, NLR was independently associated with outcome (HR 1.18, 95% CI 1.03-1.27). When modelled using restricted cubic splines, NLR demonstrated a significant non-linear association with the composite outcomes (p=0.002). Using the cohort median NLR value (3.27) as the reference, lower NLR values were associated with a protective profile, whereas higher NLR values above the median were associated with progressively higher risk (Figure 1). Conclusion In this multicenter cohort of CS patients, NLR independently predicted adverse events beyond established clinical and imaging variables. Systemic inflammatory burden, as reflected by NLR, may represent a simple and widely available adjunct for risk stratification in this high-risk population.