Quantifying Left Ventricular Ejection Effectiveness

量化左心室射血效率

基本信息

项目摘要

DESCRIPTION (provided by applicant): Asynchronous left ventricular (LV) contraction is the most common cardiac abnormality and, if severe, impairs LV pump function, induces cardiac dilation and heart failure remodeling. Ventricular pacing usually increases contraction asynchrony and induces cardiac dilation even when contractility is normal. We hypothesize that LV contraction asynchrony reduces LV ejection efficiency, defined by the ratio of LV stroke work to myocardial O2 consumption (MVO2), by causing LV dilation without altering intrinsic contractility. We define LV ejection effectiveness as the synchrony of contraction of all contractile elements. Importantly, recent clinical trials of cardiac resynchronization therapy (CRT) in patients with dilated cardiomyopathy and prolonged QRS have shown that gated bi-ventricular pacing improves LV ejection pressure, decreases cardiac volumes and induces reverse remodeling in some but not all subjects. We hypothesize that all the beneficial effects of CRT come from its ability to improve LV contraction synchrony. We believe that these clinically opposite effects of pacing are explained by opposite changes in contraction synchrony. The relation between MVO2, LV ejection asynchrony and ejection effectiveness is unknown. We will develop a novel application of the assessment of LV ejection efficiency combining regional phase angle analysis with Fourier analysis of both phase angle and amplitude dispersion from echocardiographic data. We propose to quantify this asynchrony at the bedside in both animal and human models using tissue Doppler imaging (TDI). We have recently developed and validated a quantitative model to assess LV ejection effectiveness using regional phase angle analysis. However, this technique requires invasive monitoring and are not suitable for general clinical use. Importantly, we have also developed and validated quantitative methods of analyzing transthoracic echocardiographic LV images using TDI and acoustic quantification (AQ) algorithms. These powerful non-invasive tools allow us to define regional myocardial movement. Presently, there is no established method of analyzing these data to objectively quantify contraction asynchrony. We propose to couple our asynchrony analysis with our quantitative AQ and TDI techniques to create a clinically relevant tool to assess LV ejection effectiveness. We will use our established isolated perfused rabbit heart (Langendorf preparation) model to validate the relation between MVO2 and asynchronous LV contraction. We will use our intact anesthetized canine model under conditions of varying contraction asynchrony induced by selective pacing, mock CRT and regional ischemia and reperfusion to create an on-line TDI analysis algorithm. Finally, we shall study human subjects before and after CRT and non-CRT subjects to ascertain if we can predict which subjects will benefit from CRT and where in the ventricle CRT pacing would be optimal. Potentially, CRT could be used in subjects before they develop heart failure remodeling. We will test two related hypotheses. First, that increased global LV asynchrony induces parallel shifts in LV volume for a constant ejection pressure such that MVO2 increases as a function of the parallel shift of the LV end-systolic pressure-volume relation. Second, that LV ejection effectiveness, measured by AQ and TDI in both clinically relevant canine models of LV contraction asynchrony and humans with cardiac disease, can be quantified as both the sum of the amplitude-corrected phase angle dispersion among LV regions and as the cross correlation of amplitude-corrected phase angles. The ultimate goal of this proposal is to develop and validate an echocardiographic-based algorithm that quantifies LV ejection effectiveness by merging both power and synchrony of contraction into a common metric.
描述(由申请人提供): 左心室(LV)收缩不同步是最常见的心脏异常,如果严重,会损害LV泵功能,诱导心脏扩张和心力衰竭重塑。心室起搏通常会增加收缩力,甚至在收缩力正常时也会引起心脏扩张。我们假设,左心室收缩过度降低左心室射血效率,定义为左心室每搏功与心肌耗氧量(MVO 2)的比值,通过引起左心室扩张而不改变固有收缩力。我们将LV射血有效性定义为所有收缩成分收缩的同步性。重要的是,最近在扩张型心肌病和QRS延长患者中进行的心脏起搏治疗(CRT)的临床试验表明,门控双心室起搏可改善LV射血压,减少心脏容积,并在一些但不是所有受试者中诱导逆向重塑。我们假设CRT的所有有益作用都来自于其改善LV收缩同步性的能力。我们认为,这些临床上相反的影响起搏解释了相反的变化收缩同步。MVO 2、LV射血分数和射血效率之间的关系尚不清楚。我们将开发一种新的应用程序的LV射血效率的评估相结合的区域相位角分析与傅立叶分析的相位角和振幅离散从超声心动图数据。我们建议使用组织多普勒成像(TDI)在动物和人体模型中在床边量化这种疼痛。我们最近开发并验证了一个定量模型,以评估LV射血有效性,使用区域相角分析。然而,这种技术需要侵入性监测,不适合一般临床使用。重要的是,我们还开发和验证了定量方法,分析经胸超声心动图左室图像使用TDI和声学定量(AQ)算法。这些强大的非侵入性工具使我们能够定义局部心肌运动。目前,还没有建立分析这些数据的方法来客观地量化收缩率。我们建议将我们的定量AQ和TDI技术与我们的心血管分析相结合,以创建一个临床相关的工具来评估LV射血有效性。我们将使用我们建立的离体灌流兔心脏(Langendorf制备)模型来验证MVO 2与LV非同步收缩之间的关系。我们将使用我们完整的麻醉犬模型,在选择性起搏,模拟CRT和局部缺血和再灌注诱导的不同收缩能力的条件下,创建在线TDI分析算法。最后,我们将研究CRT前后的人类受试者和非CRT受试者,以确定我们是否可以预测哪些受试者将从CRT中受益以及心室中CRT起搏的最佳位置。CRT可能在受试者发生心力衰竭重塑之前用于受试者。我们将测试两个相关的假设。首先,对于恒定的射血压力,增加的整体LV收缩压诱导LV容积的平行移位,使得MVO 2作为LV收缩末期压力-容积关系的平行移位的函数而增加。第二,通过AQ和TDI在临床相关的LV收缩不稳定犬模型和患有心脏病的人中测量的LV射血有效性可以量化为LV区域之间的振幅校正相位角离散的总和以及振幅校正相位角的互相关。该提案的最终目标是开发和验证一种基于超声心动图的算法,该算法通过将收缩的功率和同步性合并为一个共同的度量标准来量化LV射血有效性。

项目成果

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MICHAEL R PINSKY其他文献

MICHAEL R PINSKY的其他文献

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{{ truncateString('MICHAEL R PINSKY', 18)}}的其他基金

Autonomous diagnosis and management of the critically ill during air transport (ADMIT)
航空运输中危重病人的自主诊断和管理(ADMIT)
  • 批准号:
    9912846
  • 财政年份:
    2019
  • 资助金额:
    $ 50.88万
  • 项目类别:
Autonomous diagnosis and management of the critically ill during air transport (ADMIT)
航空运输中危重病人的自主诊断和管理(ADMIT)
  • 批准号:
    10359812
  • 财政年份:
    2019
  • 资助金额:
    $ 50.88万
  • 项目类别:
Machine learning of physiological variables to predict diagnose and treat cardiorespiratory instability
机器学习生理变量来预测诊断和治疗心肺不稳定
  • 批准号:
    9029396
  • 财政年份:
    2016
  • 资助金额:
    $ 50.88万
  • 项目类别:
Quantifying Left Ventricular Ejection Effectiveness
量化左心室射血效率
  • 批准号:
    7142444
  • 财政年份:
    2004
  • 资助金额:
    $ 50.88万
  • 项目类别:
Quantifying Left Ventricular Ejection Effectiveness
量化左心室射血效率
  • 批准号:
    7280411
  • 财政年份:
    2004
  • 资助金额:
    $ 50.88万
  • 项目类别:
Quantifying Left Ventricular Ejection Effectiveness
量化左心室射血效率
  • 批准号:
    6937215
  • 财政年份:
    2004
  • 资助金额:
    $ 50.88万
  • 项目类别:
Heart-Lung Interactions & Cardiovascular Insufficiency
心肺相互作用
  • 批准号:
    6889992
  • 财政年份:
    2002
  • 资助金额:
    $ 50.88万
  • 项目类别:
Heart-Lung Interactions & Cardiovascular Insufficiency
心肺相互作用
  • 批准号:
    8078075
  • 财政年份:
    2002
  • 资助金额:
    $ 50.88万
  • 项目类别:
Heart-Lung Interactions & Cardiovascular Insufficiency
心肺相互作用
  • 批准号:
    6620534
  • 财政年份:
    2002
  • 资助金额:
    $ 50.88万
  • 项目类别:
Heart-Lung Interactions & Cardiovascular Insufficiency
心肺相互作用
  • 批准号:
    6418634
  • 财政年份:
    2002
  • 资助金额:
    $ 50.88万
  • 项目类别:
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