Cardiovascular reserve capacity in survivors of hematopoietic cell transplantation

造血细胞移植幸存者的心血管储备能力

• 批准号: 10092215
• 负责人: Saro Armenian
• 金额: $ 70.89万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10092215
• 关键词: Address; Adult; Age; Aging; Biological; Blood Vessels; Cancer Survivorship; Cardiac; Cardiology; Cardiomyopathies; Cardiopulmonary; Cardiotoxicity; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chronic; Clinical; Consensus; Data; Development; Ensure; Evidence based intervention; Exercise Physiology; Exercise Test; Functional disorder; Future; General Population; Goals; Gold; Health; Heart; Heart failure; Hematology; Hematopoietic Stem Cell Transplantation; Image; Impairment; Intervention; Knowledge; Late Effects; Lead; Longitudinal Studies; Lung; Measurable; Measures; Metabolic; Monitor; Morbidity - disease rate; Muscle; Musculoskeletal; Musculoskeletal System; Myocardial Infarction; Organ; Oxygen; Oxygen Consumption; Patient Self-Report; Patients; Physical Function; Physiological; Population; Prevention strategy; Pulmonology; Research; Research Design; Research Priority; Risk Assessment; Risk Factors; SF-36; Stem cell transplant; Survivors; System; Testing; Time; Transplant Recipients; Treatment Efficacy; Treatment-Related Cancer; United States National Institutes of Health; Vascular System; Vulnerable Populations; body system; cardiovascular disorder risk; cardiovascular health; clinically relevant; conditioning; early onset; evidence base; graft vs host disease; health related quality of life; hematopoietic cell transplantation; high risk; improved; improved outcome; mortality; multidisciplinary; novel diagnostics; optimal treatments; organ injury; premature; prevent; prospective; response; screening; sex; standard measure; symposium; therapy design; therapy development; time use; transplant centers; transplant survivor; virtual

Abstract There are currently 200,000 hematopoietic cell transplantation (HCT) survivors in the U.S today, a number that will exceed 500,000 by 2030. Despite improvements in overall survival, long-term HCT survivors remain at high risk for chronic health complications such as cardiovascular disease (CVD). Cardiovascular complications, such as myocardial infarction and cardiomyopathy/heart failure, are not only more common in HCT survivors, but they occur earlier than in the general population; in essence, HCT is associated with accelerated cardiovascular aging. However, as highlighted by the recent NIH HCT Late Effects Consensus Conference, the biological mechanisms underlying this problem remain unknown. Our overall hypothesis is that multiple sequential organ system and metabolic impairments sustained prior to, during, or after HCT accelerates depletion of cardiovascular physiologic reserves (cardiovascular reserve capacity), predisposing to early onset CVD. To test this hypothesis, we will measure cardiovascular reserve capacity in a group of HCT survivors over time. Peak oxygen consumption (VO2peak), as derived from cardiopulmonary exercise testing, is the gold standard measure of cardiovascular reserve capacity, because it represents the integrative efficiency with which multiple organ systems deliver and use oxygen for ATP resynthesis. Using a longitudinal study design, we will evaluate VO2peak at baseline (prior to HCT), 6 months, one year and two years post-HCT, allowing us to determine its trajectory over time. We will also determine the impact VO2peak on self-reported physical functioning, and identify populations at high risk for accelerated VO2peak decline after HCT (Aim 1). Importantly, we will use novel diagnostic strategies to define the organic-specific determinants of VO2peak and its impairment after HCT (Aim 2). By the end of our study, we will have: 1) established initial VO2peak in patients undergoing HCT and characterized its post-HCT trajectory over time, identifying patients at highest risk for decline after HCT; 2) informed the screening for subclinical CVD, using strategies that are readily applicable in the clinical setting; and 3) identified mechanisms by which organ-specific impairments, alone and in combination, contribute to abnormalities in VO2peak after HCT. This proposal builds on our previous successful research and will address important knowledge gaps about cardiovascular complications in HCT survivors. Information obtained from this proposal will support development of evidence-based interventions to decrease the risk of CVD after HCT. The growing population of long-term HCT survivors makes development of prevention strategies imperative, to ensure that these survivors live long and healthy lives well after completion of HCT.

抽象的 目前美国有 200,000 名造血细胞移植 (HCT) 幸存者，这个数字 到 2030 年，这一数字将超过 500,000 人。尽管总体生存率有所改善，但长期 HCT 幸存者仍处于较高水平 心血管疾病 (CVD) 等慢性健康并发症的风险。心血管并发症， 例如心肌梗死和心肌病/心力衰竭，不仅在 HCT 幸存者中更常见， 但它们发生的时间早于一般人群；本质上，HCT 与加速相关 心血管老化。然而，正如最近的 NIH HCT 迟发效应共识会议所强调的那样， 这一问题背后的生物学机制仍然未知。我们的总体假设是，多个 HCT 加速之前、期间或之后持续的器官系统和代谢损伤 心血管生理储备（心血管储备能力）耗竭，容易早发 化学气相沉积。为了检验这一假设，我们将测量一组 HCT 幸存者的心血管储备能力 随着时间的推移。峰值耗氧量（VO2peak）源自心肺运动测试，是黄金 心血管储备能力的标准衡量标准，因为它代表了心血管储备能力的综合效率 多个器官系统输送并使用氧气进行 ATP 再合成。采用纵向研究设计， 我们将在基线（HCT 之前）、HCT 后 6 个月、一年和两年评估 VO2peak，使我们能够 确定其随时间变化的轨迹。我们还将确定 VO2peak 对自我报告的身体状况的影响 功能，并确定 HCT 后 VO2peak 加速下降的高风险人群（目标 1）。重要的是， 我们将使用新颖的诊断策略来定义 VO2peak 及其损伤的有机特异性决定因素 HCT（目标 2）后。在我们的研究结束时，我们将：1）在接受治疗的患者中建立初始摄氧量峰值 HCT 并描述了 HCT 后随时间变化的轨迹，识别出 HCT 后病情恶化风险最高的患者 血细胞CT； 2）使用易于应用于临床的策略，为亚临床CVD的筛查提供信息 环境; 3）确定了器官特异性损伤（单独或组合）的机制， 导致 HCT 后 VO2peak 异常。该提案建立在我们之前成功的研究和 将解决 HCT 幸存者心血管并发症的重要知识差距。信息 从该提案中获得的成果将支持制定基于证据的干预措施，以降低风险 HCT 后的 CVD。长期 HCT 幸存者人口的不断增长促使预防工作的发展 战略势在必行，以确保这些幸存者在完成 HCT 后能够长久健康地生活。