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: 10558477
• 负责人: Saro Armenian
• 金额: $ 70.05万
• 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/10558477
• 关键词: Acceleration; Address; Adult; Age; Aging; Biological; Blood Vessels; Cancer Survivorship; Cardiac; Cardiology; Cardiomyopathies; Cardiopulmonary; Cardiotoxicity; Cardiovascular Diseases; Cardiovascular system; Cell Transplantation; Cessation of life; Chronic; Clinical; Consensus; Data; Development; Evidence based intervention; Exercise Physiology; Exercise Test; Functional disorder; Future; General Population; Goals; Health; Heart; Heart failure; Hematology; Hematopoietic; Image; Impairment; Intervention; Knowledge; Late Effects; 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; diagnostic strategy; early onset; evidence base; graft vs host disease; health related quality of life; hematopoietic cell transplantation; high risk; improved; improved outcome; longitudinal, prospective study; mortality; multidisciplinary; novel diagnostics; optimal treatments; organ injury; premature; prevent; response; screening; sex; standard measure; stem; symposium; therapy design; therapy development; 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 目前在美国有200,000个造血细胞移植（HCT）幸存者 到2030年将超过500,000。尽管总体生存率有所提高，但长期的HCT幸存者仍处于较高的状态 慢性健康并发症（例如心血管疾病（CVD））的风险。心血管并发症， 例如心肌梗塞和心肌病/心力衰竭，不仅在HCT幸存者中更常见 但是它们发生的时间比普通人群早。本质上，HCT与加速相关 心血管老化。但是，正如最近的NIH HCT后期效果共识会议所强调的那样 该问题的生物学机制仍然未知。我们的总体假设是多个 在HCT加速之前，期间或之后遭受的顺序器官系统和代谢障碍 心血管生理储量的耗竭（心血管储量容量），易于提早发作 CVD。为了检验这一假设，我们将测量一组HCT幸存者中的心血管储备能力 随着时间的推移。从心肺运动测试中得出的峰值氧消耗（VO2PEAK）是黄金 心血管储备容量的标准度量，因为它代表了综合效率 多个器官系统可输送和使用氧气进行ATP重新合成。使用纵向研究设计， 我们将在基线（HCT之前），6个月，一年和两年后评估VO2PEAK，使我们能够 随着时间的推移确定其轨迹。我们还将确定vo2peak对自我报告的物理的影响 功能，并确定HCT后VO2PEAK下降的高风险人群（AIM 1）。重要的是， 我们将使用新颖的诊断策略来定义VO2PEAK及其损害的有机特异性决定因素 HCT之后（AIM 2）。在研究结束时，我们将有：1）在接受的患者中确定了初始VO2PEAK HCT并表征了其HCT后的轨迹，随着时间的流逝，确定患者的风险最高。 HCT; 2）使用容易适用于临床的策略，告知了亚临床CVD的筛查 环境; 3）确定了单独和组合器官特异性损伤的机制 HCT后VO2PEAK的异常促成。这项建议是基于我们以前成功的研究和 将解决有关HCT幸存者中心血管并发症的重要知识差距。信息 从该提案中获得的将支持制定基于证据的干预措施，以降低 HCT之后的CVD。长期HCT幸存者的人口不断增长，使预防发展 必须采取策略，以确保这些幸存者在HCT完成后过着悠久的健康生活。