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.