Shear-Induced Hemostatic Dysfunction and Bleeding in CF-VAD Patients

CF-VAD 患者中剪切引起的止血功能障碍和出血

• 批准号: 8888742
• 负责人: Bartley P GriffIth
• 金额: $ 54.27万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-20 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8888742
• 关键词: Adult; Adverse event; Affect; Annual Reports; Biocompatible; Biological; Biological Markers; Biomedical Engineering; Blood; Blood Coagulation Factor; Blood Platelets; Blood flow; Blood specimen; Cells; Characteristics; Clinical; Clinical Management; Data; Databases; Destinations; Device Designs; Device or Instrument Development; Devices; Diagnosis; Disease; Elements; Engineering; Environment; Event; Failure; Functional disorder; Goals; Heart Transplantation; Heart failure; Hematology; Hemorrhage; Hemostatic Agents; Hemostatic function; Implant; Infection; Injury; Interagency Registry for Mechanically Assisted Circulatory Support; Knowledge; Laboratories; Link; Liquid substance; Logistic Regressions; Measures; Mechanics; Medical; Modeling; Molecular; Molecular Profiling; Myocardial; Organ failure; Outcome; Patients; Physiological; Plasma; Quality of life; Recovery; Research; Risk; Series; Staging; Stratification; Structure; Survival Rate; Technology; Testing; Thrombosis; Time; Transplant Recipients; Ventricular; Weight; base; clinically significant; design; experience; hemodynamics; implantation; improved; indexing; next generation; novel; public health relevance; research study; shear stress; success; ventricular assist device

 DESCRIPTION (provided by applicant): Heart failure (HF) affects 5.1 million adult patients in the US. About 50% of people diagnosed with HF will die within 5 years. Ventricular assist device (VAD) therapy has evolved into a standard therapy for patients with advanced HF, not only as a bridge to myocardial recovery or cardiac transplantation but also as a destination therapy. The recent data suggest that approximately 85 and 75% of patients supported with continuous flow VADs (CF-VADs) will survive at 12 and 24 months, respectively. These survival rates are approaching those of heart transplant patients. However, bleeding has become a significant problem for the CF-VAD therapy. Thus it is critical to understand the bleeding risk of CF-VAD support and their underlying mechanistic origins. Given the potential of the CF-VAD therapy for end-stage HF patients and the need to reduce significant device associated complications, we propose to conduct a series of clinical, biological and bioengineering experiments to seek a better understanding of shear-induced hemostatic dysfunction (SIHD) and bleeding in HF patients supported with CF-VADs and their link to blood flow dynamics of CF-VADs and pre-existing hemostatic disorder of HF patients. Further we seek to uncover the underlying molecular mechanisms of SIHD for better medical management and to create a database of SIHD for VAD design refinements. Three specific aims of the proposed project are: (1) To determine temporal changes of biomarkers of SIHD in HF patients prior to and during CF-VAD support and to link these changes to post-implant bleeding events; (2) To model shear stress indices (SSI) of CF-VADs and link them to measured biomarkers of SIHD and Bleeding in CF- VAD patients with consideration of pre-existing hemostatic disorder and patient-specific SIHD sensitivity to SSI prior to receiving a CF-VAD; and (3) To elucidate underlying molecular mechanisms of SIHD associated with CF-VADs and to establish a database of biomarkers of SIHD for VAD design improvement. Altogether, a combination of clinical hematology, biological as well as bioengineering approaches will be used to derive the basic knowledge behind bleeding complications and to investigate the influence of device-specific non- physiological fluid dynamic characteristics like shear stress and exposure time on SIHD. The successful completion of this project will create a new knowledge of bleeding associated with CF-VADs. The new knowledge can be used by clinicians to refine bleeding risk stratification in patients for the improved quality of life and by engineers to develop less traumatic, next generation biocompatible VADs.

 描述（由适用提供）：心力衰竭（HF）在美国影响510万成人患者。大约50％的被诊断为HF的人将在5年内死亡。心室辅助装置（VAD）疗法已演变为晚期HF患者的标准疗法，不仅是心肌恢复或心脏移植的桥梁，而且还作为目的地疗法。最近的数据表明，大约85％和75％的持续流动VAD（CF-VAD）的患者将分别在12和24个月生存。这些存活率正在接近心脏移植患者的生存率。但是，出血已成为CF-VAD疗法的重要问题。了解CF-VAD支持的出血风险及其基本的机理起源至关重要。鉴于CF-VAD治疗对终末期HF患者的潜力以及减少与设备相关的并发症的需求，我们建议进行一系列临床，生物学和生物工程学实验，以寻求更好地了解剪切诱导的止血功能障碍（SIHD）（SIHD），并在CF-Flofds及其链接的HF患者中降低了CF-Flowics及其链接的患者的出血。 HF患者的止血疾病。此外，我们试图发现SIHD的基本分子机制，以更好地医疗管理，并为VAD设计改进创建SIHD数据库。拟议项目的三个具体目标是：（1）确定在CF-VAD支持之前和期间，HF患者中SIHD生物标志物的暂时变化，并将这些变化与植入后出血事件联系起来； （2）对CF-VADS的剪切应力指数（SSI）进行建模，并将其与CF-VAD患者的SIHD和出血的生物标志物联系起来，并在接受CF-VAD之前考虑了先前存在的止血和特异性SIHD敏感性； （3）阐明与CF-VAD相关的SIHD的基本分子机制，并建立SIHD生物标志物数据库以进行VAD设计改进。总之，将使用临床血液学，生物学和生物工程方法的结合来得出出血并发症背后的基本知识，并研究设备特异性非生理流体的影响 动态特征，例如剪切应力和SIHD的暴露时间。该项目的成功完成将创造与CF-VAD相关的出血的新知识。临床医生可以使用新知识来完善患者的出血风险分层，以提高生活质量，并通过工程师发展下一代生物相容性的VAD较少创伤。