Diagnosis of Heart Failure Status using Epidermal Metabolomics

使用表皮代谢组学诊断心力衰竭状态

• 批准号: 9794142
• 负责人: JAMES D BALEJA
• 金额: $ 25.82万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-26 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9794142
• 关键词: Affect; American; Biological; Biological Assay; Biological Markers; Blood; Blood flow; Cell physiology; Chronic Disease; Cities; Clinical; Clinical Data; Collection; Congestive; Data; Development; Diagnosis; Diffusion; Disease; Disease Management; Future; Genes; Genetic Risk; Goals; Hand; Health; Heart; Heart failure; Home environment; Human; Individual; Individual Differences; Kansas; Liquid substance; Measurable; Measurement; Measures; Metabolic; Metabolism; Methodology; Methods; Nuclear Magnetic Resonance; Outcome; Outpatients; Patient Care; Patients; Perfusion; Peripheral; Pilot Projects; Protocols documentation; Questionnaires; Research; Research Design; Saline; Sampling; Signs and Symptoms; Skin; Skin Cancer; Standardization; Symptoms; Testing; Time; Tissues; Variant; base; biomarker discovery; cardiac resynchronization therapy; clinical practice; design; heart function; imaging biomarker; improved; innovation; insight; left ventricular assist device; metabolic abnormality assessment; metabolic profile; metabolome; metabolomics; novel; patient stratification; programs; small molecule

Abstract Heart failure is the most expensive chronic disease affecting millions of Americans. While there are several clinical tests used to manage heart failure, these tests do not adequately track degrees of heart failure, are insufficiently quantitative, or require significant expertise. In particular, a biomarker of a key heart failure parameter, peripheral tissue perfusion and congestion, is lacking and sorely needed to help guide and stratify patient care. This application describes a novel, noninvasive method that samples the outermost epidermal layers of the palm that yields samples suitable for high-quality nuclear magnetic resonance (NMR)-based metabolomics. A cross-sectional pilot study provided preliminary data that there are significant differences in skin metabolites between the heart healthy and heart failure groups, supporting the central hypothesis that polar molecules in the outermost layers of the skin are sensitive predictors of the adequacy of blood flow. In the cross-sectional pilot study we noted individual differences unrelated to heart failure status, as manifested by greater variation in lactate between individuals than within an individual. To control for personal differences in epidermal profiles, we propose to measure lactate levels in individuals with advanced HF before and after placement of a left ventricular assist device (LVAD) or with cardiac resynchronization therapy (CRT) that dramatically augments tissue perfusion in HF patients. The aims proposed to test the central hypothesis are to (1) define the relationship of skin lactate levels with tissue perfusion in heart failure patients; and (2) to identify novel metabolic profiles in recuperating heart failure patients. The measurable outcomes will be the extent to which skin lactate and other metabolite levels correlate with symptom scores associated with heart function. The studies described in this application are the first to comprehensively determine the epidermal metabolome using NMR methods. If successful, this research could result in a new method of non-invasively assessing heart function and lays the groundwork for epidermal profiling to become part of clinical practice. More broadly, this study lays the groundwork for the use of epidermal metabolites to provide insight into any other disease that might manifest in the skin such as those associated with dry skin, cancer, or in-born errors of metabolism.

抽象的 心力衰竭是影响数百万美国人的最昂贵的慢性疾病。虽然有几个 用于管理心力衰竭的临床测试，这些测试不能充分跟踪心力衰竭程度，是 定量不足或需要大量专业知识。特别是关键心力衰竭的生物标志物 参数，外周组织灌注和充血，缺乏和迫切需要指导和分层 病人护理。该应用描述了一种新型无创方法，该方法采样了最外表皮 棕榈的层产生的样品适用于高质量的核磁共振（NMR） 代谢组学。一项横断面试点研究提供了初步数据，即在 心脏健康和心力衰竭组之间的皮肤代谢物，支持中心假设 皮肤最外层的极性分子是血流充足性的敏感预测指标。在 我们注意到的横断面试验研究指出了与心力衰竭状态无关的个体差异，如所示 通过比个体内部乳酸的变化更大。控制个人差异 在表皮曲线中，我们建议在先进HF之前和之后测量患有晚期HF的个体的乳酸水平 放置左心室辅助装置（LVAD）或心脏重新同步疗法（CRT）的放置 大大增加了HF患者的组织灌注。提议检验中心假设的目的是 （1）定义心力衰竭患者皮肤乳酸水平与组织灌注的关系； （2）确定 新的代谢特征在恢复心力衰竭患者中。可测量的结果将是 哪种皮肤乳酸和其他代谢物水平与与心脏功能相关的症状评分相关。 该应用中描述的研究是第一个全面确定表皮代谢组的研究 使用NMR方法。如果成功，这项研究可能会导致一种非侵入性评估的新方法 心脏功能并为表皮分析奠定了基础，以成为临床实践的一部分。更广泛地 这项研究为使用表皮代谢产物提供了对任何其他疾病的洞察力的基础 这可能体现在皮肤中，例如与皮肤干燥，癌症或新陈代谢的出生错误有关的皮肤。