Biological and Physiological Mechanisms of Symptom Clusters in Heart Failure (BIOMES-HF)

心力衰竭症状群的生物学和生理机制 (BIOMES-HF)

• 批准号: 10208572
• 负责人: Quin Eleanor Denfeld
• 金额: $ 50.15万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-23 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10208572
• 关键词: Acute; Address; Adult; Affective Symptoms; Age; Anxiety; Biological; Biological Markers; Body Weight decreased; Cardiovascular system; Chronic; Clinical; Coupled; Dyspnea; EFRAC; Elderly; Event; Failure; Fibrosis; Functional disorder; Gender; Growth; Heart failure; Heterogeneity; Hospitalization; Hospitals; Impairment; Inflammation; Insulin Resistance; Intervention; Knowledge; Light; Longitudinal Studies; Malignant Neoplasms; Measures; Mediating; Mediation; Mental Depression; Methods; Modeling; Myocardial; Nature; Outcome; Pain; Patient Outcomes Assessments; Patients; Phase; Phenotype; Physical activity; Physiological; Process; Pump; Quality of life; Research; Risk; Role; Skeletal Muscle; Sleep; Stress; Symptoms; Time; United States; associated symptom; base; biomarker panel; cognitive function; endothelial dysfunction; exhaustion; frailty; hemodynamics; hospital readmission; improved; individualized medicine; infancy; innovation; physical symptom; programs; symptom cluster; symptom management; symptom science; symptomatic improvement; therapy development; time use

PROJECT SUMMARY Symptom burden continues to be a significant problem for millions of adults living with heart failure (HF), the fastest growing cardiovascular condition in the U.S. Symptoms, which often co-occur or cluster together, are of utmost importance in HF because they predict quality of life and clinical events. There is considerable heterogeneity in symptoms in HF, however, that is particularly evident in the vulnerable transition period after a hospitalization for acute decompensated HF. While symptoms improve for some patients and they have longer periods of relative stability, others are plagued by enduring symptoms leading to poor outcomes, including rehospitalization. Given little-to-no association between hemodynamic markers (e.g. ejection fraction) and symptoms in HF, our clinical efforts to optimize hemodynamic stability during a hospitalization may not translate to improvement in symptoms post-hospitalization. Many studies have shown that HF is not just a hemodynamic, “pump failure” problem, but that it is a multifactorial, systemic condition involving processes such as inflammation, sympathetic dysregulation, and endothelial dysfunction. Based on research by our group and others, we propose that a multi-biomarker panel and the physical frailty phenotype that capture the multifaceted nature of HF might tell us more about symptoms in HF than our current objective markers. Therefore, the purpose of the proposed research is to 1) identify clusters of change in symptoms after a HF hospitalization and 2) quantify longitudinal associations between symptoms, biomarkers, and physical frailty. We will address the following aims through a gender- and age-balanced longitudinal study of 240 adults during the 6 month transition period after a hospitalization for acute decompensated HF: 1) identify clusters of change in physical symptoms among adults with heart failure, 2) quantify longitudinal associations between biomarkers and physical symptoms among adults with heart failure, and 3) quantify longitudinal associations between physical frailty and physical symptoms among adults with heart failure. We will use advanced quantitative modeling, including growth mixture modeling and longitudinal mediation modeling, to examine changes in symptoms, biomarkers, and physical frailty post-HF hospitalization and associations therein. This innovative study will advance HF symptom science by utilizing a multi-biomarker panel and the physical frailty phenotype that capture the multifaceted nature of HF, coupled with advanced quantitative modeling, to characterize heterogeneity and identify potential mechanisms of symptoms in HF. As a result, this research will inform the next phase of this program of research by pinpointing amenable targets for intervention to provide better, individualized treatment to improve symptom burden in HF.

项目摘要 症状负担仍然是数百万患有心力衰竭（HF）的成年人的一个重要问题， 在美国增长最快的心血管疾病的症状，往往共同发生或集群在一起，是 在HF中最重要，因为它们可预测生活质量和临床事件。有相当大 然而，HF中症状的异质性，在一次治疗后的脆弱过渡期尤其明显， 因急性失代偿性HF住院。虽然一些患者的症状有所改善， 在相对稳定的时期，其他人则受到导致不良结果的持久症状的困扰，包括 再次住院考虑到血流动力学标志物（例如射血分数）与 我们在住院期间优化血流动力学稳定性的临床努力可能不会 转化为住院后症状的改善。许多研究表明，HF不仅仅是一种 血液动力学，“泵故障”问题，但它是一个多因素，全身性疾病，涉及过程 例如炎症、交感神经失调和内皮功能障碍。根据我们小组的研究 和其他人，我们提出，一个多生物标志物面板和身体虚弱表型，捕捉 HF的多面性可能比我们目前的客观标志物更能告诉我们HF的症状。 因此，所提出的研究的目的是1）识别HF后症状变化的集群 住院和2）量化症状、生物标志物和身体虚弱之间的纵向关联。 我们将通过对240名成年人进行性别和年龄平衡的纵向研究， 急性失代偿性HF住院后6个月过渡期：1）确定变化簇 在患有心力衰竭的成年人的身体症状中，2）量化生物标志物之间的纵向关联 和身体症状，3）量化之间的纵向关联 成年心力衰竭患者的身体虚弱和身体症状。我们将使用先进的定量 模型，包括增长混合模型和纵向中介模型，以检查 HF住院后的症状、生物标志物和身体虚弱及其相关性。这一创新 一项研究将通过利用多生物标志物组和身体虚弱表型来推进HF症状科学 它捕捉了HF的多面性，再加上先进的定量建模， 异质性和识别HF症状的潜在机制。因此，这项研究将告知 这项研究计划的下一阶段，通过精确定位可接受的干预目标， 个体化治疗以改善HF的症状负担。