Development and validation of precision blood volume diagnostic and decision support device for acute decompensated heart failure

摘要 心力衰竭（HF）每年影响近600万美国人，导致近100万人死亡和1 百万住院急性失代偿性心力衰竭（ADHF）是一种新发或恶化的临床综合征， HF的体征和症状，经常导致住院治疗。在出院后的30天内， 四名ADHF患者再次住院，九分之一的患者死亡。ADHF最常见的原因是 心脏由于血管内血浆容量的过度保留，使得BV调整治疗，主要是 利尿剂是最常见的治疗方法然而，标准的不足使它们的使用变得混乱 体格检查，患者生理学的高度异质性，以及标准护理代理测试的不准确性， BV.过度治疗和治疗不足都构成重大风险，突出表明需要能够精确 个性化护理。Daxor的BVA-100，提供98%准确的血液总量定量测量 体积、血浆体积和红细胞体积，然后将其与经验证的患者特异性标准进行比较 以提供血管内血容量组成和紊乱的精确测量。最近的一 回顾性倾向匹配对照分析显示，30天再入院率降低了56%， HF和混合型患者的30天死亡率降低82%，365天死亡率降低86%， 因ADHF入院的射血分数，住院治疗由BVA评估指导。把这个 临床接受的初步成功需要进行大型、多中心的前瞻性研究 比较标准治疗与BVA指导治疗策略的疗效和成本， 在不同的ADHF患者中建立一个经过验证的详细治疗方法。这 拟议的I期申请包括概念验证前瞻性、双中心、平行设计， 一项干预性、单盲、初步研究，旨在比较标准治疗决策与 BVA-100提高了准确性。如果这项研究表明，由BVA指导的治疗导致更多的 在出院前有效实现患者特定容量目标 Daxor将单独提出一项后续更大规模的多中心研究（第二阶段SBIR），以证明再入院率， 与标准护理相比，30天和90天内的死亡率降低，护理总成本降低，等等 在入院和出院时对病人进行有效的分流，以避免不必要的入院/再入院， 同时指导HF特定决策支持算法的开发和验证。

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.