Inflammatory Phenotypes and Biomarker Trajectories During Hospitalization for Acute Heart Failure

Background: The clinical significance of inflammatory phenotypes and their temporal relationship with natriuretic peptide dynamics in acute heart failure (AHF) remain poorly defined. We investigated admission inflammatory phenotypes, in-hospital C-reactive protein (CRP) trajectories, and their relationship with N-terminal pro-B-type natriuretic peptide (NT-proBNP) dynamics. Methods: In this retrospective single-center cohort of 306 patients hospitalized for AHF, patients were stratified according to admission CRP (≤10 vs. >10 mg/L). Among patients with dual biomarker measurements (n = 147), a CRP-procalcitonin (PCT) concordance phenotype was evaluated. Serial CRP measurements were available in 65 patients, and NT-proBNP response (≥30% reduction) was assessed in 42 patients; because these repeat measurements were obtained at the treating physician's discretion, the corresponding subgroups were older and more severely ill than the full cohort and are treated as exploratory. Results: Elevated admission CRP (>10 mg/L) was associated with higher NT-proBNP levels (3621 vs. 1251 pg/mL, p < 0.001), more severe symptoms (New York Heart Association [NYHA] III-IV: 45.9% vs. 29.8%, p = 0.006), and greater PCT positivity (21.8% vs. 8.7%, p = 0.029), independent of left-ventricular ejection fraction; the association persisted after adjustment for age, sex, and ejection fraction (adjusted odds ratio 2.40, 95% CI 1.27-4.55). The biomarker-defined CRP+/PCT+ phenotype showed the greatest concurrent NT-proBNP burden and the highest prevalence of heart failure with preserved ejection fraction (HFpEF, 70.6%). Despite declining NT-proBNP, CRP increased during hospitalization in 69.2% of patients (median ΔCRP +5.9 mg/L, p < 0.001), and the two changes were uncorrelated, indicating divergent biomarker trajectories. Conclusions: Admission CRP identifies patients with a more severe concurrent inflammatory and hemodynamic profile, while combined CRP-PCT phenotyping further characterizes this profile. Divergent CRP and NT-proBNP trajectories suggest that inflammatory and hemodynamic changes follow distinct time courses during AHF hospitalization. Because no post-discharge outcomes were available, these findings describe concurrent associations rather than prognosis.