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 Among 143 eligible patients (81 men, 62 women), the primary endpoint occurred in 46.9%. In our cohort, women experienced a slightly higher crude rate of in-hospital deterioration compared with men (48.4% vs. 45.7%). Lactate was the most robust predictor across all models, with an odds ratio of 9.38 (95% CI 2.47–35.63; p = 0.001) per log10 increase and a clear dose–response (event rates 39.8%, 55.2%, and 85.7% across lactate strata ≤2, 2–4, and >4 mmol/L; p -trend = 0.002). In sex-stratified models, NT-proBNP (OR 2.87; p = 0.029) and lactate (OR 28.98; p = 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.