Vexus Assessment and Natriuresis-guided Diuretic Therapy in Acute Heart Failure

This study evaluates whether natriuresis-guided diuretic therapy improves outcomes in patients with acute heart failure (AHF) and severe congestion. All patients hospitalized with AHF will be screened using Venous Excess Ultrasound (VExUS) and randomized 1:1 to either natriuresis-guided escalation of loop diuretics or standard care. The primary endpoint, evaluated in patients with VExUS grade 3 (severe congestion), is a hierarchical composite (win ratio) of 90-day mortality, 90-day rehospitalization, and hospital length of stay. Key secondary endpoints (hierarchical) include (1) difference in win ratio between patients with VExUS 3 versus VExUS 0-2 at hospital admission (assessed by interaction testing and statistically tested only if the primary endpoint is significant) and (2) win ratio (primary endpoint) tested among patients with VExUS 0-2 at hospital admission (statistically tested only if the first key seconday endpoint is significant). Exploratory endpoints include in-hospital clinical, hemodynamic, and biochemical outcomes (mortality, eGFR, NT-proBNP, NYHA class, VExUS score, natriuresis/diuresis, and patient-reported dyspnea), associations between congestion markers (VExUS, FibroScan, lung ultrasound, clinical score, and NT-proBNP), as well as quality of life at 90 days, GDMT optimization score at discharge, and long-term time to readmission and mortality assessed through registry linkage.