Developing a MRI-guided Disease-Modifying Therapy for Post Infarction Chronic Heart Failure

开发 MRI 引导的梗死后慢性心力衰竭疾病缓解疗法

基本信息

  • 批准号:
    9981537
  • 负责人:
  • 金额:
    $ 86.74万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-07-01 至 2022-06-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Re-establishment of blood flow (reperfusion) through coronary arteries has reduced immediate death from acute myocardial infarctions (MI). However, the long-term complications in the chronic phase of MI, particularly chronic heart failure (CHF) culminating in major adverse cardiovascular events (MACE: hospitalization or death), have become epidemic. Currently, ~2 million MI patients in the US are living with CHF and their 5-year survival rate is < 50%. An important and long-established predictor of chronic heart failure is the acute MI size; but reducing acute MI size is limited by time to reperfusion. Over the past two decades, advances in cardiac MRI (CMR) have established that persistent microvascular obstruction (PMO) is another independent predictor of CHF. PMO is an acute feature of MI where microvascular blood flow to the MI territory is lost despite reperfusion. PMOs are estimated to be present in >60% of all acute MIs. Notably, results from an international consortium recently reported that the presence of PMO carries a 4-fold greater risk for MACE than acute MI size in the chronic period. Accordingly, therapeutic targeting of PMOs holds great promise for patients otherwise at risk of developing CHF. Yet, currently available post MI medications are not specific to patients with PMO; and they have not shown any incremental benefit to the patients with PMO over other MI types. Furthermore, although a significant effort has been spent on preventing PMO from occurring, it has not yet been possible to consistently achieve this. These observations have led to recent emphatic calls for improved understandings of how PMOs drive adverse remodeling in the chronic phase of MI so that effective therapeutics may be developed. Using animal models of chronic MI, in this proposal we aim to demonstrate that (a) PMOs resolve into iron crystals, which play a central role in driving the adverse remodeling; and (b) chelation of iron from the heart with deferiprone can significantly reduce adverse remodeling. Aim 1 will develop a CMR approach for accurate quantification of iron within MI zones; Aim 2 will demonstrate the mechanism driving the adverse remodeling; and Aim 3 will show that reducing iron within MI reduces adverse remodeling. To address these Aims, this proposal brings together a group of experts in cardiac imaging (MRI and PET), macrophage biology, post infarction remodeling, iron-chelation therapy and chemistry. Successful completion of this proposal will significantly impact clinical care of MI patients as the proposed iron chelation therapy will be rapidly translatable owing to its established clinical profile for safety and efficacy in treating other cardiac iron disorders.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Rohan Dharmakumar其他文献

Rohan Dharmakumar的其他文献

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{{ truncateString('Rohan Dharmakumar', 18)}}的其他基金

Mechanistic Insights to A Translatable Therapy for Acute Reperfused Hemorrhagic Myocardial Infarctions
急性再灌注出血性心肌梗塞可转化疗法的机制见解
  • 批准号:
    10359807
  • 财政年份:
    2020
  • 资助金额:
    $ 86.74万
  • 项目类别:
Accurate, Needle-Free, MRI-based Detection of Ischemic Heart Disease without Contrast Agents
无需造影剂即可通过 MRI 进行准确、无针、基于 MRI 的缺血性心脏病检测
  • 批准号:
    10686342
  • 财政年份:
    2020
  • 资助金额:
    $ 86.74万
  • 项目类别:
Accurate, Needle-Free, MRI-based Detection of Ischemic Heart Disease without Contrast Agents
无需造影剂即可通过 MRI 进行准确、无针、基于 MRI 的缺血性心脏病检测
  • 批准号:
    9981378
  • 财政年份:
    2020
  • 资助金额:
    $ 86.74万
  • 项目类别:
Mechanistic Insights to A Translatable Therapy for Acute Reperfused Hemorrhagic Myocardial Infarctions
急性再灌注出血性心肌梗塞可转化疗法的机制见解
  • 批准号:
    10630055
  • 财政年份:
    2020
  • 资助金额:
    $ 86.74万
  • 项目类别:
Mechanistic Insights to A Translatable Therapy for Acute Reperfused Hemorrhagic Myocardial Infarctions
急性再灌注出血性心肌梗塞可转化疗法的机制见解
  • 批准号:
    9887771
  • 财政年份:
    2020
  • 资助金额:
    $ 86.74万
  • 项目类别:
Accurate, Needle-Free, MRI-based Detection of Ischemic Heart Disease without Contrast Agents
无需造影剂即可通过 MRI 进行准确、无针、基于 MRI 的缺血性心脏病检测
  • 批准号:
    10201743
  • 财政年份:
    2020
  • 资助金额:
    $ 86.74万
  • 项目类别:
Accurate, Needle-Free, MRI-based Detection of Ischemic Heart Disease without Contrast Agents
无需造影剂即可通过 MRI 进行准确、无针、基于 MRI 的缺血性心脏病检测
  • 批准号:
    10655692
  • 财政年份:
    2020
  • 资助金额:
    $ 86.74万
  • 项目类别:
Developing a MRI-guided Disease-Modifying Therapy for Post Infarction Chronic Heart Failure
开发 MRI 引导的梗死后慢性心力衰竭疾病缓解疗法
  • 批准号:
    9756228
  • 财政年份:
    2017
  • 资助金额:
    $ 86.74万
  • 项目类别:
4D SSFP MRI for Detecting Functionally Important Coronary Artery Stenosis at Rest
4D SSFP MRI 用于检测静息时具有重要功能的冠状动脉狭窄
  • 批准号:
    7837299
  • 财政年份:
    2009
  • 资助金额:
    $ 86.74万
  • 项目类别:
4D SSFP MRI for Detecting Functionally Important Coronary Artery Stenosis at Rest
4D SSFP MRI 用于检测静息时具有重要功能的冠状动脉狭窄
  • 批准号:
    8055423
  • 财政年份:
    2008
  • 资助金额:
    $ 86.74万
  • 项目类别:

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