Estimating systemic fibrosis by combining galectin-3 and ST2 provides powerful risk stratification value for patients after acute decompensated heart failure

Background: Two fibrosis biomarkers, galectin-3 (Gal-3) and suppression of tumorigenicity 2 (ST2), provide prognostic value additive to natriuretic peptides and traditional risk factors in patients with heart failure (HF). However, it is to be investigated whether their combined measurement before discharge provides incremental risk stratification for patients after acute HF. Methods: A total of 344 patients with acute HF were analyzed with Gal-3, and ST2 measured. Patients were prospectively followed for 3.7 ± 1.3 years for deaths, and composite events (death/HF-related re-hospitalizations). Results: The levels of Gal-3 and ST2 were only slightly related (r = 0.20, p < 0.001). The medians of Gal-3 and ST2 were 18 ng/mL and 32.4 ng/mL, respectively. These biomarkers compensated each other and characterized patients with different risk factors. According to the cutoff at median values, patients were separated into four subgroups based on high and low Gal-3 (HG and LG, respectively) and ST2 levels (HS and LS, respectively). Kaplan-Meier survival curves showed that HGHS powerfully identified patients at risk of mortality (Log rank = = 21.27, p < 0.001). In multivariable analysis, combined log(Gal-3) and log(ST2) was an independent predictor. For composite events, Kaplan-Meier survival curves showed a lower event-free survival rate in the HGHS subgroup compared to others (Log rank = 34.62, p < 0.001; HGHS vs. HGLS, Log rank = 4.00, p = 0.045). In multivariable analysis, combined log(Gal-3) and log(ST2) was also an independent predictor. Conclusions: Combination of biomarkers involving heterogeneous fibrosis pathways may identify patients with high systemic fibrosis, providing powerful risk stratification value.