Improving Diagnostic Accuracy for Acute Heart Failure

提高急性心力衰竭的诊断准确性

• 批准号: 10405617
• 负责人: SEAN PATRICK COLLINS
• 金额: $ 135.22万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10405617
• 关键词: Accident and Emergency department; Acute; Address; Affect; American; Antibiotics; Asthma; Biological; Biological Assay; Biological Markers; Bronchodilator Agents; Calibration; Cardiac; Chronic Obstructive Pulmonary Disease; Clinical; Clinical Data; Congestive Heart Failure; Data; Derivation procedure; Diagnosis; Diagnostic tests; Discrimination; Diuretics; Dyspnea; EFRAC; Emergency department visit; Enrollment; Frequencies; Future; Guidelines; Heart failure; Hospitalization; IV Fluid; Investigation; Knowledge; Left Ventricular Ejection Fraction; Logistic Models; Medicare; Modeling; Natriuretic Peptides; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Performance; Plasma; Pneumonia; Probability; Prognosis; Proteins; Proteomics; Recording of previous events; Reporting; Research Design; Sample Size; Sampling; Shortness of Breath; Signs and Symptoms; Specificity; Symptoms; Testing; Thoracic Radiography; Validation; Work; accurate diagnosis; adjudicate; adverse outcome; base; biomarker discovery; biomarker panel; circulating biomarkers; clinical diagnostics; clinical practice; cohort; cost; diagnosis standard; diagnostic accuracy; diagnostic strategy; health care service utilization; improved; mortality; novel; novel diagnostics; novel marker; performance tests; predictive modeling; preservation; prospective; protein biomarkers; recruit; respiratory

PROJECT SUMMARY/ABSTRACT Acute heart failure (HF) is highly morbid, lethal, and costly. It is a difficult diagnosis to make given its symptoms and signs overlap with other cardiac and non-cardiac conditions. In the emergency department (ED), misdiagnosis of acute HF is common and associated with adverse outcomes. Biomarker testing can facilitate accurate diagnosis; however, natriuretic peptides (NP) are the only guideline recommend biomarker of HF for diagnostic testing, and are better for ruling-out, rather than ruling-in, acute HF. Even with NP testing, in contemporary clinical practice misdiagnosis of acute HF still occurs in 10 to 45% of patients presenting to the ED with dyspnea. Clinical prediction models including multiple biomarkers hold promise for improving diagnostic accuracy. The few prior studies investigating a multiple biomarker approach for diagnosing acute HF were limited by constraint to highly correlated markers from known biologic pathways, relatively small sample sizes, lack of inclusion of all a priori selected biomarkers into a single model, and absence of validation cohorts. Our study design addresses these limitations. Recent advances in “omics” enable novel biomarker discovery on a larger scale and investigations less “biased” by existing knowledge. Thus, our overarching hypothesis is a multi-marker model incorporating novel proteins discovered with plasma proteomics improves diagnostic accuracy for acute HF. In preliminary work, we performed a proof of concept study utilizing plasma proteomics to discover a multi-marker panel of 21 biomarkers which improved diagnostic accuracy for acute HF beyond current clinical practice using clinical data and NP levels. Our promising preliminary data motivate broader discovery in a larger sample size with subsequent derivation and validation of a multi-marker model for diagnosing acute HF in independent samples of adequate size. Our specific aims are to: 1) expand the discovery cohort and refine the multi-marker panel of 21 biomarkers to improve diagnostic accuracy for acute HF, 2) derive a model for diagnosing acute HF incorporating the 21-biomarker panel, 3) test performance of the multi-marker model in a prospective validation cohort, and 4) assess the incremental value of the multi- marker model for diagnosing acute HF. In aim 1, existing plasma samples from 989 patients will be used to assay 925 proteins to discover a smaller set of novel biomarkers most strongly associated with an adjudicated acute HF diagnosis. In aim 2, we will utilize an existing prospective observational cohort, EMROC-AHF, to derive the multi-marker model in 1,000 patients who presented to the ED with acute dyspnea. In aim 3, from four EDs in Detroit, MI and Nashville, TN we will prospectively recruit a new sample of 1,000 patients presenting with acute dyspnea and adjudicate the presence of acute HF by cardiologist panel review. In aim 4, we will compare our multi-marker model against the current clinical approach for diagnosing acute HF using the cohorts for Aims 2 and 3. Given the burden of HF, the frequency of inaccurate diagnosis and its adverse consequences, we will address a significant unmet need by improving diagnostic accuracy for acute HF.

项目摘要/摘要 急性心力衰竭（HF）高度病态，致命和昂贵。出现症状是一个困难的诊断 并与其他心脏和非心脏条件重叠。在急诊室（ED）， 急性HF的误诊很常见，并且与不良结果有关。生物标志物测试可以促进 准确的诊断；但是，亚硝酸盐辣椒（NP）是HF的唯一指南推荐的生物标志物 诊断测试，更适合排除，而不是排除急性HF。即使进行NP测试， 急性HF的当代临床实践误诊仍发生在10％至45％的患者中 呼吸困难。包括多个生物标志物在内的临床预测模型有望改善 诊断准确性。少数先前研究了用于诊断急性HF的多种生物标志物方法 受到已知生物途径的高度相关标记的约束限制，样品相对较小 大小，缺乏所有先验选择的生物标志物中的所有模型，并且没有验证 同伙。我们的研究设计解决了这些局限性。 “ OMICS”的最新进展使小说生物标志物 大规模的发现和调查较少因现有知识而“偏见”。那，我们的总体 假设是一种编码血浆蛋白质组学发现的新型蛋白质的多标记模型，可改善 急性HF的诊断精度。在初步工作中，我们通过等离子体进行了概念研究证明 蛋白质组学可发现21个生物标志物的多标记面板，可提高急性诊断精度 HF使用临床数据和NP水平超出了当前的临床实践。我们承诺的初步数据动机 在更大的样本量中更广泛的发现，随后推导和验证多标记模型 在足够大小的独立样本中诊断急性HF。我们的具体目的是：1）扩展 发现队列并完善21个生物标志物的多标记面板，以提高急性诊断精度 HF，​​2）得出一种诊断急性HF的模型，该模型合并了21-Biomarker面板，3）测试性能 前瞻性验证队列中的多标记模型，以及4）评估多数的增量价值 诊断急性HF的标记模型。在AIM 1中，来自989名患者的现有血浆样本将用于 测定925蛋白，发现一组较小的新型生物标志物与裁决最密切相关的新型生物标志物 急性HF诊断。在AIM 2中，我们将利用现有的前瞻性观察队列EMROC-AHF来 在1,000例出现急性呼吸困难的患者中，推导了多标记模型。在AIM 3中，来自 底特律，密歇根州和田纳西州纳什维尔的四eds我们可能会招募1,000名患者的新样本 呈现急性呼吸困难，并通过心脏病专家小组审查调整急性HF的存在。在AIM 4中， 我们将比较我们的多标记模型与当前使用诊断急性HF的临床方法进行比较 AIM 2和3的队列鉴于HF的燃烧，诊断不准确的频率及其逆境的频率 后果，我们将通过提高急性HF的诊断准确性来满足重要的未满足需求。