Pavo N, et al. - In 99 prospectively enrolled consecutive patients, researchers evaluated membrane granulocyte neprilysin (NEP) expression in heart failure with reduced ejection fraction (HFrEF). These patients had stable chronic HFrEF and have received optimal medical therapy (angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers), but not an angiotensin receptor-neprilysin inhibitor (ARNI). Using flow cytometry, they measured CD10 expression on peripheral leucocyte subsets. They also used a specific enzyme immunosorbent assay (SEB785Hu, USCN, China) to determine soluble NEP concentrations. The primary endpoint was all-cause mortality. Although ARNI therapy-induced NEP inhibition had beneficial impacts, an inverse association was seen between NEP expression on granulocytes and heart failure severity and mortality. B-type natriuretic peptide was inversely associated with plasma NEP activity in a mixed population of heart failure patients. Shed membrane NEP molecules possibly contributed to plasma NEP levels as a surrogate marker, as reflected by the observed positive correlation of granulocyte NEP expression with the soluble form of the enzyme (sNEP).