Serum Interleukin-8 Levels Identify Non-Atrial Fibrillation Patients at Risk for Catheterization-Confirmed Diastolic...

Left ventricular diastolic dysfunction (LVDD), confirmed by left heart catheterization, is the gold standard for diagnosing heart failure with preserved ejection fraction (HFpEF). However, current noninvasive diagnostic tools may fail to detect early-stage LVDD in patients without prior hospitalization for heart failure, delaying timely intervention. Given its role in inflammation and cardiovascular remodeling, serum interleukin-8 (IL-8) may serve as a potential biomarker for early detection. We conducted a retrospective cohort study that included patients who underwent diagnostic left heart catheterization between March 2020 and August 2024. In the discovery cohort (n = 1,014), we assessed the associations of 12 inflammatory cytokines with catheterization-confirmed LVDD via a highly sensitive flow cytometer. IL-8, the most strongly associated cytokine, was further evaluated in a separate prospective validation cohort (n = 248). Diagnostic performance was evaluated via the area under the receiver operating characteristic curve (AUC). IL-8 levels were significantly elevated in LVDD patients without atrial fibrillation compared with controls, with a 2.26-fold median increase (P < 0.001). In the discovery cohort (n = 1,014), IL-8 was independently associated with LVDD (adjusted odds ratio for highest vs. lowest quartile: 13.2 [95% CI: 6.5-26.7]). These findings were validated in an independent cohort. Combining IL-8 with B-type natriuretic peptide (BNP) and the E/e' ratio improved diagnostic accuracy, achieving an AUC of 0.79 (95% CI: 0.74-0.85). Serum IL-8 is an independent biomarker for diagnosing catheterization-confirmed LVDD in patients without atrial fibrillation. Its combination with traditional markers enhances diagnostic performance, offering a promising tool for early identification and potential risk stratification of HFpEF. Clinically, IL-8 testing may help identify patients with unexplained dyspnea who warrant closer monitoring or earlier therapeutic intervention.