Clinical and Metabolic Signature of Recovered Myocardium in Human Heart Failure

人类心力衰竭恢复心肌的临床和代谢特征

基本信息

  • 批准号:
    10066362
  • 负责人:
  • 金额:
    $ 38.13万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-12-09 至 2022-11-30
  • 项目状态:
    已结题

项目摘要

Clinical and Metabolic Signature of Recovered Myocardium in Human Heart Failure Summary: Remarkable improvements in myocardial structure and function have been reported in some advanced heart failure (HF) patients undergoing “mechanical unloading” induced by left ventricular assist devices (LVAD). Unlike other HF therapies, which have also been associated with significant myocardial improvement, this tractable and specific LVAD population provides us access to pre-treatment myocardial tissue from both responders and non- responders which has enabled us to start probing the “signature” of myocardium that has the potential to improve. Our central hypothesis is that refining this “signature” will lead to a rational therapeutic approach in severe HF and will reveal broader recovery principles applicable to all stages and severity of HF. Achieving and defining “response” in LVAD patients requires a battery of diagnostic and therapeutic protocols and, as shown in the real world of advanced HF multicenter registries, this is challenging. Thus, there is a critical need for a selection process that can reliably predict who will and who will not “respond” to LVAD therapy. This program will also enable us to develop such a predictive model in addition to our studies of the mechanisms driving myocardial recovery. First we will provide a clinically relevant ‘signature’ of failing hearts with the potential for recovery. Following a derivation- validation approach we will develop a myocardial recovery score using myocardial structural and/ or functional parameters together with clinical characteristics. This score will create a precise algorithm for selection of patients likely to recover prior to LVAD intervention, enrich the criteria for device explantation and sustained recovery following LVAD intervention and likely increase the real world incidence and sustainability of LVAD enabled recovery. Second, we hypothesized that specific metabolic adaptations drive myocardial recovery. Our preliminary data after examining myocardial tissue from normal donors and LVAD patients suggests a post- LVAD mismatch in glycolytic versus mitochondrial intermediates that might indicate increased flux through the cardioprotective pentose phosphate pathway. We have developed methodology and will employ novel and powerful in vivo metabolic flux studies using stable isotopes, mitochondrial respiratory measurements and additional metabolic assays to test this hypothesis. This project offers a rare opportunity to closely integrate clinical function, structure and in vivo mechanistic studies in human HF and recovery. The physiological insights derived are providing clinical characteristics and biomarkers that will impact our practice in advanced HF patients. They are also revealing novel biological insights that inform both our clinical and basic science understanding of myocardial recovery applicable to all stages and severity of HF.
心力衰竭患者心肌缺血的临床和代谢特征 总结: 在一些先进的心肌结构和功能的显着改善已被报道, 接受左心室辅助装置(LVAD)诱导的“机械卸载”的心力衰竭(HF)患者。 与其他HF治疗不同,这些治疗也与显著的心肌改善相关, 易于处理和特定的LVAD人群为我们提供了治疗前心肌组织, 反应者和无反应者,这使我们能够开始探测心肌的“签名”, 改进的潜力。我们的中心假设是,完善这一“签名”将导致一个合理的治疗 方法,并将揭示适用于所有阶段和严重程度的HF更广泛的恢复原则。 在LVAD患者中实现和定义“反应”需要一系列诊断和治疗 方案,并且如高级HF多中心登记研究的真实的世界所示,这是具有挑战性的。因此 是一个关键的需要,选择过程,可以可靠地预测谁会和谁不会“响应”左心室辅助装置 疗法该计划还将使我们能够开发这样一个预测模型,除了我们的研究, 驱动心肌恢复的机制。首先,我们将提供一个临床相关的'签名'衰竭的心脏 有恢复的潜力在推导-验证方法之后,我们将开发一个心肌 使用心肌结构和/或功能参数以及临床特征的恢复评分。 该评分将创建一个精确的算法,用于选择可能在LVAD干预前恢复的患者, 丰富了LVAD干预后器械恢复和持续恢复的标准, 增加LVAD启用恢复的真实的世界发生率和可持续性。其次,我们假设, 特定的代谢适应驱动心肌恢复。我们的初步数据,在检查心肌 来自正常供体和LVAD患者的组织提示LVAD后糖酵解与 线粒体中间体,可能表明通过心脏保护磷酸戊糖的流量增加 通路我们已经开发了方法,并将采用新的和强大的体内代谢通量研究 使用稳定同位素、线粒体呼吸测量和额外的代谢测定来测试这一点。 假说. 该项目提供了一个难得的机会,紧密结合临床功能,结构和体内 人类HF和恢复的机制研究。所得出的生理学见解为临床提供了 这些特征和生物标志物将影响我们在晚期HF患者中的实践。它们也揭示了 新的生物学见解,为我们对心肌恢复的临床和基础科学理解提供信息 适用于HF的所有阶段和严重程度。

项目成果

期刊论文数量(19)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Ryanodine Receptor Staining Identifies Viable Cardiomyocytes in Human and Rabbit Cardiac Tissue Slices.
  • DOI:
    10.3390/ijms241713514
  • 发表时间:
    2023-08-31
  • 期刊:
  • 影响因子:
    5.6
  • 作者:
    Pfeuffer, Ann-Katrin M.;Kuepfer, Linda K.;Shankar, Thirupura S.;Drakos, Stavros G.;Volk, Tilmann;Seidel, Thomas
  • 通讯作者:
    Seidel, Thomas
Outcomes of Asian-Americans Implanted With Left Ventricular Assist Devices: An Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Analysis.
  • DOI:
    10.1016/j.hlc.2019.11.017
  • 发表时间:
    2020-08
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Taleb I;Wever-Pinzon J;Wang W;Koliopoulou A;Dranow E;Yu T;Yin L;McKellar SH;Stehlik J;Fang JC;Wever-Pinzon O;Selzman CH;Drakos SG
  • 通讯作者:
    Drakos SG
Paramedic rhythm interpretation misclassification is associated with poor survival from out-of-hospital cardiac arrest.
护理人员心律解读错误分类与院外心脏骤停的生存率低有关。
  • DOI:
    10.1016/j.resuscitation.2021.12.016
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    6.5
  • 作者:
    Stoecklein,HHill;Pugh,Andrew;Johnson,MAustin;Tonna,JosephE;Stroud,Michael;Drakos,Stavros;Youngquist,ScottT
  • 通讯作者:
    Youngquist,ScottT
Heart waitlist survival in adults with an intra-aortic balloon pump relative to other Status 2, Status 1, and inotrope Status 3 patients.
与其他状态 2、状态 1 和正性肌力药物状态 3 患者相比,接受主动脉内球囊反搏的成人的心脏候补生存率。
The human heart contains distinct macrophage subsets with divergent origins and functions.
  • DOI:
    10.1038/s41591-018-0059-x
  • 发表时间:
    2018-08
  • 期刊:
  • 影响因子:
    82.9
  • 作者:
    Bajpai G;Schneider C;Wong N;Bredemeyer A;Hulsmans M;Nahrendorf M;Epelman S;Kreisel D;Liu Y;Itoh A;Shankar TS;Selzman CH;Drakos SG;Lavine KJ
  • 通讯作者:
    Lavine KJ
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Stavros George Drakos其他文献

COST EFFECTIVENESS ANALYSIS OF ECMO WITH ADJUNCT VENTRICULAR UNLOADING DEVICE COMPARED TO ECMO
  • DOI:
    10.1016/s0735-1097(24)04530-3
  • 发表时间:
    2024-04-02
  • 期刊:
  • 影响因子:
  • 作者:
    Kaan Raif;Stavros George Drakos;Craig H. Selzman;Joshua Horns;Joseph Tonna
  • 通讯作者:
    Joseph Tonna
SPHINGOLIPIDS AS POTENTIAL SURROGATES OF MYOCARDIAL RECOVERY IN LEFT VENTRICULAR ASSIST DEVICE PATIENTS
  • DOI:
    10.1016/s0735-1097(23)00741-6
  • 发表时间:
    2023-03-07
  • 期刊:
  • 影响因子:
  • 作者:
    Rana Hamouche;Sean Tatum;Elizabeth Dranow;Christos P. Kyriakopoulos;Thirupura Sundari Shankar;Joseph Visker;Jing Ling;Konstantinos Sideris;Craig H. Selzman;Abdallah G. Kfoury;Josef Stehlik;Rami Alharethi;James C. Fang;Sutip Navankasattusas;William Holland;Scott Summers;Stavros George Drakos;Eleni Tseliou
  • 通讯作者:
    Eleni Tseliou
IMPAIRED LIVER FUNCTION IS ASSOCIATED WITH HYPOTENSION AND ELEVATED RIGHT ATRIAL PRESSURE BUT NOT DEPRESSED CARDIAC INDEX IN CHRONIC HEART FAILURE
  • DOI:
    10.1016/s0735-1097(23)00919-1
  • 发表时间:
    2023-03-07
  • 期刊:
  • 影响因子:
  • 作者:
    Christos Kapelios;Eleni Tseliou;Rami Alharethi;Kevin Shah;Thomas Hanff;Christos P. Kyriakopoulos;Konstantinos Sideris;Iosif Taleb;Josef Stehlik;Spencer Carter;Abdallah G. Kfoury;William Caine;Craig H. Selzman;James C. Fang;Omar Wever-Pinzon;Stavros George Drakos
  • 通讯作者:
    Stavros George Drakos
Functional and Structural Myocardial Improvement after LVAD Therapy: The U-NOVA Reverse Remodeling Stages
  • DOI:
    10.1016/j.cardfail.2019.07.190
  • 发表时间:
    2019-08-01
  • 期刊:
  • 影响因子:
  • 作者:
    Shah Palak;Mitchell Psotka;Iosif Taleb;Rami Alharethi;Mortada A. Shams;Omar Wever-Pinzon;Michael Yin;Federica Latta;Josef Stehlik;James C. Fang;Ramesh Singh;Craig H. Selzman;Abdallah Kfoury;Stavros George Drakos
  • 通讯作者:
    Stavros George Drakos
HEALTH RELATED QUALITY OF LIFE AS PREDICTOR OF OUTCOMES IN HEART FAILURE WITH PRESERVED EJECTION FRACTION
  • DOI:
    10.1016/s0735-1097(23)01057-4
  • 发表时间:
    2023-03-07
  • 期刊:
  • 影响因子:
  • 作者:
    Konstantinos Sideris;Mingyuan Zhang;Alfonso F. Siu;Peter Wohlfahrt;Jincheng Shen;Christos P. Kyriakopoulos;Iosif Taleb;Omar Wever-Pinzon;Kevin Shah;Craig H. Selzman;Carlos Rodriguez Correa;Christos Kapelios;Lina M. Brinker;Rami Alharethi;Rachel Hess;Stavros George Drakos;Benjamin Adam Steinberg;Abdallah G. Kfoury;John A. Spertus;James C. Fang
  • 通讯作者:
    James C. Fang

Stavros George Drakos的其他文献

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{{ truncateString('Stavros George Drakos', 18)}}的其他基金

Mechanism of Eccentric Cardiomyocyte Hypertrophy Secondary to Mitral Regurgitation
二尖瓣反流继发偏心心肌细胞肥大的机制
  • 批准号:
    10565204
  • 财政年份:
    2023
  • 资助金额:
    $ 38.13万
  • 项目类别:
Perm1 is a Novel Regulator of Cardiac Energetics and Function
Perm1 是一种新型的心脏能量和功能调节剂
  • 批准号:
    10547828
  • 财政年份:
    2020
  • 资助金额:
    $ 38.13万
  • 项目类别:
Perm1 is a Novel Regulator of Cardiac Energetics and Function
Perm1 是一种新型的心脏能量和功能调节剂
  • 批准号:
    10631449
  • 财政年份:
    2020
  • 资助金额:
    $ 38.13万
  • 项目类别:
Perm1 is a Novel Regulator of Cardiac Energetics and Function
Perm1 是一种新型的心脏能量和功能调节剂
  • 批准号:
    10730363
  • 财政年份:
    2020
  • 资助金额:
    $ 38.13万
  • 项目类别:
Perm1 is a Novel Regulator of Cardiac Energetics and Function
Perm1 是一种新型的心脏能量和功能调节剂
  • 批准号:
    10523981
  • 财政年份:
    2020
  • 资助金额:
    $ 38.13万
  • 项目类别:
Understanding Myocardial Recovery in Diabetes and Heart Failure
了解糖尿病和心力衰竭的心肌恢复
  • 批准号:
    10426081
  • 财政年份:
    2020
  • 资助金额:
    $ 38.13万
  • 项目类别:
Perm1 is a Novel Regulator of Cardiac Energetics and Function
Perm1 是一种新型的心脏能量和功能调节剂
  • 批准号:
    10156104
  • 财政年份:
    2020
  • 资助金额:
    $ 38.13万
  • 项目类别:
Understanding Myocardial Recovery in Diabetes and Heart Failure
了解糖尿病和心力衰竭的心肌恢复
  • 批准号:
    10595643
  • 财政年份:
    2020
  • 资助金额:
    $ 38.13万
  • 项目类别:
Clinical and Metabolic Signature of Recovered Myocardium in Human Heart Failure
人类心力衰竭恢复心肌的临床和代谢特征
  • 批准号:
    9218590
  • 财政年份:
    2016
  • 资助金额:
    $ 38.13万
  • 项目类别:
Training in Cardiovascular Research
心血管研究培训
  • 批准号:
    10626716
  • 财政年份:
    1994
  • 资助金额:
    $ 38.13万
  • 项目类别:

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