Januzzi Jr JL, Prescott MF, Butler J, et al. - Via a prospective study of 794 patients with heart failure with reduced ejection fraction (HFrEF) who initiated therapy with sacubitril-valsartan, researchers ascertained whether N-terminal pro–b-type natriuretic peptide (NT-proBNP) variances in patients with HFrEF treated with sacubitril-valsartan associated with variations in measures of cardiac volume and function. At 12 months, the variances in log₂–NT-proBNP concentration was related to variations in left ventricular ejection fraction (LVEF), LV end-systolic volume index (LVESVI), left atrial volume index (LAVI), and early diastolic filling velocity (E)/early diastolic mitral annular velocity (e'). At 12 months, LVEF rose from 28.2% to 37.8%, while LVEDVI reduced from 86.93 to 74.15 mL/m² and LVESVI reduced from 61.68 to 45.46 mL/m². LAVI and E/e′ ratio also diminished significantly. Hypotension, dizziness, hyperkalemia, and worsening kidney function were the most prevalent adverse events. In conclusion, in this exploratory study of patients with HFrEF treated with sacubitril-valsartan, a decrease in NT-proBNP concentration was weakly although significantly associated with betterments in markers of cardiac volume and function at 12 months. Moreover, the perceived reverse cardiac remodeling may give a mechanistic description of the influences of sacubitril-valsartan in patients with HFrEF.