Zile MR, et al. - Researchers determined how biomarkers of extracellular matrix (ECM) homeostasis are influenced by sacubitril/valsartan and also examined the link between the rate of primary composite outcome (cardiovascular death or heart failure hospitalization) and these biomarkers. In 2,067 patients, a baseline evaluation of biomarkers was performed. In 1,776 patients, biomarkers were assessed at both baseline and 8 months after randomization. The evaluated biomarkers included aldosterone, soluble ST2 (sST2), tissue inhibitor of matrix metalloproteinase (TIMP)-1, matrix metalloproteinase (MMP)-2, MMP-9, Galectin-3 (Gal-3), N-terminal propeptide of collagen I (PINP), and N-terminal propeptide of collagen III (PIIINP). They assessed baseline biomarker values and changes from baseline to 8 months, associated with primary outcome. In HF with reduced ejection fraction, altered biomarkers related to profibrotic signaling were detected. A significant decrease in many of these biomarkers was induced by sacubitril/valsartan and these biomarkers displayed important prognostic value. Overall, a possible attenuation of profibrotic signaling by sacubitril/valsartan was suggested, which may lead to improved outcomes.