Differential prognostic impact of interleukin-6 in acute heart failure with reduced versus preserved ejection fraction

Interleukin-6 (IL-6) plays a role in acute heart failure (AHF) and can predict death and re-hospitalization. However, the relationship between IL-6 levels and mortality, based on heart failure phenotype, remains unclear. This study aimed to clarify the association between IL-6 levels and mortality in patients with AHF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). A retrospective observational study was conducted on 371 AHF cases admitted to our institution. Patients were categorized into two groups based on IL-6 levels using Receiver Operating Characteristic (ROC) curve analysis: those with IL-6 below 29.0 pg/mL (N = 239) and those above 29.0 pg/mL (N = 132). Mortality rates were assessed for both HFrEF and HFpEF patients to determine the differential impact of IL-6. The average age was 71 years, with 60% male. Over a median follow-up of 222 days, 53 patients (14.8%) died. Kaplan-Meier analysis revealed a significantly higher mortality rate in patients with IL-6 levels above 29.0 pg/mL (P < 0.001). Elevated IL-6 levels were associated with increased mortality in both categories of left ventricular ejection fraction. In particular, among patients with HFrEF, those with elevated IL-6 levels exhibited a higher risk of death after 30 days (P = 0.017), while HFpEF patients with elevated IL-6 levels had a higher risk of death within 30 days (P = 0.002). Elevated IL-6 levels predicted higher all-cause mortality in both HFrEF and HFpEF patients. The effect of elevated IL-6 on mortality varies between short-term and long-term implications for HFrEF and HFpEF.