Abstract Heart failure (HF) affects nearly 6 million Americans annually, leading to nearly 1 million deaths and 1 million hospitalizations. Acute decompensated heart failure (ADHF) is a clinical syndrome of new or worsening signs and symptoms of HF, frequently resulting in hospitalization. Within 30 days of discharge, roughly one in four ADHF patients is rehospitalized and one in nine is dead. ADHF is most commonly caused by remodeling of the heart due to excessive retention of intravascular plasma volume making BV adjusting therapies, primarily diuretics, the most common treatments. However, their use is confounded by the inadequacy of the standard physical examination, high heterogeneity of patient physiology, and inaccuracy of standard care proxy tests for BV. Both over- and under-treatment pose significant risks highlighting the need for tools that enable precise individualization of care. Daxor’s BVA-100, provides 98% accurate quantitative measurement of total blood volume, plasma volume, and red blood cell volume, which it then compares to validated patient-specific norms to provide an accurate measure of intravascular blood volume composition and derangement. A recent retrospective propensity-matched control analysis demonstrated a 56% reduction in 30-day readmissions, an 82% reduction in 30-day mortality, and an 86% reduction in 365-day mortality for patients with HF and mixed– ejection fraction admitted for ADHF in whom inpatient care was guided by BVA assessments. Transitioning this initial success to clinical acceptance requires the performance of a large, multi-center prospective study comparing the efficacy and cost of standard care to that of a BVA guided treatment strategy, and the establishment of a proven, detailed treatment methodology across the diverse spectrum of ADHF patients. This proposed Phase I application consists of a proof-of-concept prospective, two-center, parallel design, interventional, single-blinded pilot study to compare the efficacy of standard care treatment decisions to those with accuracy enhanced by BVA-100. If this study demonstrates that treatment guided by BVA results in more effective achievement of patient-specific volume targets prior to discharge than care guided by standard care alone, Daxor will propose a subsequent larger multisite study (Phase II SBIR) to demonstrate readmission and mortality reduction over a 30-day and 90-day basis versus standard care, lower overall cost of care, and more effective triage of patients at admission and discharge to avoid unnecessary admissions/readmissions, while simultaneously guiding the development and validation of an HF-specific decision support algorithm.