Abstract
BACKGROUND: Little is known about the predictive value of soluble AXL (sAXL) in heart failure (HF). This study aimed to describe the prognostic value of plasma sAXL in patients with symptomatic HF. METHODS: This is a multicentre observational prospective cohort study (Registration No. NCT03727828). Plasma sAXL were measured on admission. The primary endpoint is a composite of cardiovascular mortality and HF rehospitalization. Associations between plasma sAXL levels and clinical endpoints are described using Cox regression models and Kaplan-Meier methods. RESULTS: A total of 1030 symptomatic HF patients were enrolled in the study; the mean age (65% men) was 71 ± 12 years, with a median follow-up of 32 months (IQR: 26-41 months). The mean baseline sAXL levels were 20.03 ± 6.74 ng/mL. Plasma sAXL positively associated with NYHA classification and negatively associated with left ventricular ejection fraction (both P < 0.001). Cox regression showed that 1-SD increment of sAXL was associated with primary endpoint [HR (CI): 1.128 (1.024-1.242)], cardiovascular mortality [1.112 (1.032-1.198)], all-cause mortality [1.142 (1.057-1.234)], and HF rehospitalization [1.122 (1.030-1.224)] after adjustment for potential confounders including NT-proBNP. Kaplan-Meier curves revealed that patients with the highest sAXL levels were at the highest risk of primary endpoint events, cardiovascular mortality, and all-cause mortality (all P values < 0.001). Furthermore, both Kaplan-Meier method and Categorical analysis demonstrated that the combined use of sAXL and NT-proBNP were more likely to predict all-cause or cardiovascular mortality (both P < 0.001). Similar results were observed when separating patients with respect to left ventricular ejection fraction, namely, in HFrEF, HFmrEF, and HFpEF groups. CONCLUSIONS: Plasma sAXL concentrations are of great importance in predicting clinical outcomes in HF patients, independent of NT-proBNP, suggesting that sAXL is a promising prognostic marker for further study.