Sex-stratified early biomarker model identifies lactate as the key predictor of in-hospital deterioration in acute heart failure

Introduction: Early identification of patients at risk for deterioration during hospitalization for acute heart failure (AHF) is essential for guiding intensive monitoring and advanced therapies. Biomarkers such as NT-proBNP and troponin I are routinely used, yet their comparative prognostic performance-particularly when stratified by sex-remains uncertain. Other emerging biomarkers, including lactate and the neutrophil-to-lymphocyte ratio (NLR), have also been linked to adverse outcomes, but their value relative to established cardiac markers has not been clearly defined. Methods: We conducted a retrospective cohort study using de-identified electronic medical records from 2010 to March 2025 at a tertiary care center. Patients aged ≥16 years with clinician-documented AHF and available admission biomarkers were eligible. The primary endpoint was a composite of in-hospital death, mechanical ventilation, extracorporeal membrane oxygenation (ECMO), or intra-aortic balloon pump (IABP). Broad and strict endpoints were examined in sensitivity analyses. Multivariable logistic regression models, sex-stratified analyses, and penalized regressions with bootstrap resampling were performed. Results: = 0.003) were significant in men, while no biomarker reached significance in women. NLR predicted outcomes in the non-HFrEF subgroup. Model performance was modest (AUC ∼0.71-0.73) but calibration was good. Findings remained consistent in winsorized and bootstrap sensitivity analyses. Conclusions: In this single-center AHF cohort, lactate emerged as the most consistent early biomarker associated with in-hospital deterioration, with stronger prognostic performance than the other evaluated cardiac markers. Sex-stratified and phenotype-specific findings (NT-proBNP and lactate in men, NLR in non-HFrEF) were exploratory and did not show significant sex-biomarker interaction. These results support incorporating lactate into early risk stratification and highlight the need for larger multicenter validation studies.