Early Detection of Transthyretin Cardiac Amyloidosis: Defining a Novel Target for HFpEF Treatment and Prevention in Late Life

甲状腺素运载蛋白心脏淀粉样变性的早期检测:确定晚年 HFpEF 治疗和预防的新目标

基本信息

  • 批准号:
    10569547
  • 负责人:
  • 金额:
    $ 82.75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-03-01 至 2025-01-31
  • 项目状态:
    未结题

项目摘要

Project Abstract Heart failure (HF) with preserved ejection fraction (HFpEF) is a major public health concern that disproportionately affects the elderly and currently has no effective therapy. Accumulating evidence suggests that myocardial deposition of misfolded transthyretin proteins (ATTR) increases with age and is responsible for 13-18% of HFpEF in late life. ATTR cardiac amyloidosis (CA) is one of the most-deadly forms of HF with a median survival of 25-41 months. The diagnosis of ATTR-CA has commonly been delayed, often by several years, because of the need for invasive endocardial biopsy for diagnosis and lack of urgency due to limited therapeutic options. This has changed recently. ATTR CA can now be diagnosed non-invasively using 99mtechnetium pyrophosphate (99mTc-PYP) imaging, and recent therapeutic breakthroughs (e.g., tafamidis, inotersen, patisiran) have improved survival, alleviated symptoms, and reduced HF hospitalizations. However, lack of knowledge regarding the early changes in cardiac structure, function, and circulating biomarkers that reflect myocardial ATTR deposition, and their prognostic relevance in elderly persons free of HF are key barriers to effectively harnessing recent diagnostic and therapeutic breakthroughs to treat and prevent this important cause of HFpEF. Over the past 8 years, we have been building a unique database detailing longitudinal changes in cardiac structure and function over 5 years in >4,000 elderly participants (age 70-95 years) in the largely biracial Atherosclerosis Risk in Communities (ARIC) cohort study. We now aim to leverage this rich resource, in addition to serial clinical and circulating biomarker data over 25 years, to define the prevalence, predictors, and prognostic importance of incidentally detected late-life cardiac ATTR deposits. We will perform 99mTc-PYP SPECT imaging in 900 ARIC participants with either prevalent HFpEF (n=300) or asymptomatic cardiac remodeling/dysfunction (n=600). Our specific aims are to: 1) Define antecedent alterations in cardiac structure, function, and circulating biomarkers that discriminate late-life HFpEF with compared to without ATTR-CA. ; 2) Determine the predictors and prognostic relevance of ATTR-CA in elderly persons without HF but with cardiac remodeling/dysfunction; and 3) Define the extent to which novel candidate proteins and protein networks in mid- and late-life predict ATTR-CA in late-life. At the completion of this project, we will have defined the cardiac changes that antecede and predict HF from ATTR-CA, established the prognostic importance of asymptomatic ATTR-CA in late life, and identified novel circulating biomarkers of ATTR-CA. These findings will facilitate identification of persons at high risk to screen for ATTR-CA to facilitate HF treatment and, possibly, prevention. The results of these studies are likely to identify novel therapeutic targets to transform the management of ATTR-CA.
项目摘要

项目成果

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Sharmila Dorbala其他文献

Sharmila Dorbala的其他文献

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{{ truncateString('Sharmila Dorbala', 18)}}的其他基金

Interplay of Myocardial Fibrosis and Cardiac TTR Amyloid in Age Related Cardiac Remodeling in MESA-Multi-Ethnic Study of Atherosclerosis
MESA 动脉粥样硬化多种族研究中心肌纤维化和心脏 TTR 淀粉样蛋白在年龄相关心脏重塑中的相互作用
  • 批准号:
    10467374
  • 财政年份:
    2022
  • 资助金额:
    $ 82.75万
  • 项目类别:
Interplay of Myocardial Fibrosis and Cardiac TTR Amyloid in Age Related Cardiac Remodeling in MESA-Multi-Ethnic Study of Atherosclerosis
MESA 动脉粥样硬化多种族研究中心肌纤维化和心脏 TTR 淀粉样蛋白在年龄相关心脏重塑中的相互作用
  • 批准号:
    10589058
  • 财政年份:
    2022
  • 资助金额:
    $ 82.75万
  • 项目类别:
Mentoring Patient Oriented Research in Innovative Imaging and High-dimensional Data Approaches to Improve Outcomes in Cardiac Amyloidosis
指导创新成像和高维数据方法中以患者为导向的研究,以改善心脏淀粉样变性的治疗结果
  • 批准号:
    10191887
  • 财政年份:
    2021
  • 资助金额:
    $ 82.75万
  • 项目类别:
Mentoring Patient Oriented Research in Innovative Imaging and High-dimensional Data Approaches to Improve Outcomes in Cardiac Amyloidosis
指导创新成像和高维数据方法中以患者为导向的研究,以改善心脏淀粉样变性的治疗结果
  • 批准号:
    10397096
  • 财政年份:
    2021
  • 资助金额:
    $ 82.75万
  • 项目类别:
Mentoring Patient Oriented Research in Innovative Imaging and High-dimensional Data Approaches to Improve Outcomes in Cardiac Amyloidosis
指导创新成像和高维数据方法中以患者为导向的研究,以改善心脏淀粉样变性的治疗结果
  • 批准号:
    10627775
  • 财政年份:
    2021
  • 资助金额:
    $ 82.75万
  • 项目类别:
Early Detection of Transthyretin Cardiac Amyloidosis: Defining a Novel Target for HFpEF Treatment and Prevention in Late Life
甲状腺素运载蛋白心脏淀粉样变性的早期检测:确定晚年 HFpEF 治疗和预防的新目标
  • 批准号:
    10115113
  • 财政年份:
    2020
  • 资助金额:
    $ 82.75万
  • 项目类别:
Early Detection of Transthyretin Cardiac Amyloidosis: Defining a Novel Target for HFpEF Treatment and Prevention in Late Life
甲状腺素运载蛋白心脏淀粉样变性的早期检测:确定晚年 HFpEF 治疗和预防的新目标
  • 批准号:
    10333349
  • 财政年份:
    2020
  • 资助金额:
    $ 82.75万
  • 项目类别:
Molecular Imaging of Primary Amyloid Cardiomyopathy
原发性淀粉样心肌病的分子影像
  • 批准号:
    9124197
  • 财政年份:
    2016
  • 资助金额:
    $ 82.75万
  • 项目类别:
Prognostic Utility of Absolute Coronary Microvascular Function by PET/CT
PET/CT 绝对冠状动脉微血管功能的预后用途
  • 批准号:
    8080431
  • 财政年份:
    2009
  • 资助金额:
    $ 82.75万
  • 项目类别:
Prognostic Utility of Absolute Coronary Microvascular Function by PET/CT
PET/CT 绝对冠状动脉微血管功能的预后用途
  • 批准号:
    8267105
  • 财政年份:
    2009
  • 资助金额:
    $ 82.75万
  • 项目类别:

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