Association of serial neutrophil-to-lymphocyte ratio trajectories with clinical risk profiles and one-year outcomes in patients with Takotsubo syndrome

BACKGROUND Takotsubo syndrome (TTS) is a heterogeneous acute cardiac syndrome associated with substantial early complications and adverse long-term outcomes. Although admission neutrophil-to-lymphocyte ratio (NLR) has been associated with outcomes in TTS, whether its temporal evolution identifies broader clinical vulnerability remains unclear. METHODS Consecutive adults with TTS diagnosed between January 2021 and January 2024 at three tertiary centres were retrospectively included. NLR was measured at admission and at 3-5 days. Using an NLR cutoff >5, patients were categorized as Stable Low NLR, Resolving NLR Elevation, or Persistent/Delayed NLR Elevation. The primary endpoint was time to first major adverse clinical event (MACE) within 1 year, defined as all-cause death, heart failure events, rehospitalization for symptomatic arrhythmia, stroke, or acute myocardial infarction. RESULTS Among 196 patients, 101 (51.5%) were Stable Low NLR, 51 (26.0%) Resolving NLR Elevation, and 44 (22.5%) Persistent/Delayed NLR Elevation. NLR at 3-5 days discriminated 1-year MACE better than admission NLR (AUC 0.834 vs 0.716; DeLong p = 0.0074). MACE occurred in 6.9%, 21.6%, and 62.8% across trajectories, respectively (p < 0.001). Compared with Stable Low NLR, Resolving NLR Elevation and Persistent/Delayed NLR Elevation trajectories were independently associated with MACE (HR 2.92, 95% CI 1.08-7.93; p = 0.035; and HR 10.26, 95% CI 4.15-25.37; p < 0.001). Adding NLR trajectory to a clinical model increased AUC from 0.823 to 0.886 (paired ROC p = 0.0156; likelihood-ratio p < 0.001). CONCLUSIONS Serial NLR trajectories were associated with 1-year outcomes in patients with TTS. Persistent/Delayed NLR Elevation identified a clinically vulnerable phenotype, likely reflecting broader systemic vulnerability rather than TTS-specific disease severity.