Cardiac Biomarkers Response Under Angiotensin Receptor-Neprilysin Inhibitor: A Sub-Analysis of the Natrium-HF Study.

Aims Natriuretic peptides (NPs) are central to the diagnostic and therapeutic management of heart failure (HF), yet their short-term dynamics under sacubitril/valsartan (S/V) therapy and during acute volume changes remain incompletely characterized. We aimed to assess changes in circulating biomarkers and response to standardized acute intravascular volume expansion and diuretic treatment before and after S/V initiation.Methods We studied 229 ambulatory patients with HF with reduced ejection fraction receiving guideline-directed medical therapy who initiated S/V. Patients were evaluated at three outpatient visits: before S/V initiation and after 2 and 3 months of treatment. At each visit, participants underwent a standardized 9-hour protocol including volume infusion followed by diuretic administration. BNP, NT-proBNP, MR-proANP and neprilysin activity were measured serially alongside clinical assessment and natriuresis.Results Across visits, initiation of S/V was associated with lower concentrations of BNP (-8%, p = 0.009) and NT-proBNP (-35%, p < 0.001). During the acute protocol, both BNP and NT-proBNP increased significantly over time (timepoint effect p < 0.001), with parallel trajectories before and after S/V initiation and no visit-by-time interaction (p = 0.17 for BNP; p = 0.95 for NT-proBNP). Despite marked natriuresis and improvement in clinical signs following diuretic administration, BNP and NT-proBNP continued to rise during the 9-hour observation period.Conclusion In a controlled acute volume overload setting, BNP and NT-proBNP provide comparable information, but their short-term dynamics lag behind clinical decongestion. Routine serial NP measurements at very short time intervals are unlikely to add incremental clinical value in the early phase of acute HF.