Quantifying Left Ventricular Ejection Effectiveness

量化左心室射血效率

• 批准号: 6937215
• 负责人: MICHAEL R PINSKY
• 金额: $ 47.72万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6937215
• 关键词: cardiovascular disorder epidemiology; cardiovascular disorder therapy; clinical research; congestive heart failure; disease /disorder model; dogs; electrocardiography; heart function; heart ventricle; human subject; laboratory rabbit; nonhuman therapy evaluation; pathologic process

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)： 左心室非同步收缩是最常见的心脏异常，如果严重，会损害左心室泵功能，导致心脏扩张和心力衰竭重塑。即使在收缩能力正常的情况下，心室起搏通常也会增加收缩的不同步性并导致心脏扩张。我们假设，通过在不改变固有收缩能力的情况下引起左心室扩张，左心室收缩不同步降低了左心室射血效率，该效率由左每搏做功与心肌耗氧量(MVO2)之比定义。我们将左室射血效率定义为所有收缩元素收缩的同步性。重要的是，最近对扩张型心肌病和QRS延长患者进行的心脏再同步治疗(CRT)的临床试验表明，门控双室起搏可以改善部分(但不是全部)受试者的左室射血压，减少心脏容量，并诱导反向重构。我们假设CRT的所有有益作用都来自于它改善左心室收缩同步性的能力。我们认为，起搏的这些临床上相反的效果可以通过收缩同步性的相反变化来解释。MVO2、LV射血不同步与射血效果之间的关系尚不清楚。我们将开发一种新的应用来评估左心室射血效率，结合区域相角分析和傅立叶分析相位角和幅度离散度从超声心动图数据。我们建议在动物和人类模型中使用组织多普勒成像(TDI)来量化床边的这种异步性。我们最近开发并验证了一个定量模型，使用区域相角分析来评估LV射血效果。然而，这项技术需要侵入性监测，不适合一般临床使用。重要的是，我们还开发并验证了使用TDI和声学定量(AQ)算法分析经胸超声心动图LV图像的定量方法。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，还没有既定的方法来分析这些数据来客观地量化收缩的不同步。我们建议将我们的异步性分析与我们的定量AQ和TDI技术结合起来，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兔心脏灌流模型(朗恩多夫制剂)来验证MVO2和异步性LV收缩之间的关系。我们将使用我们的完整麻醉犬模型，在选择性起搏、模拟CRT和局部缺血再灌注引起的不同收缩异步性条件下，创建一个在线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受益于CRT，以及CRT起搏在脑室的哪个部位将是最佳的。CRT有可能在受试者发生心力衰竭重塑之前用于他们。我们将检验两个相关的假设。首先，对于恒定的射血压力，增加的整体LV异步性导致LV容量的平行移动，使得MVO2作为LV收缩末期压力-容量关系的平行移动的函数而增加。其次，在临床相关的犬左室不同步收缩模型和人类心脏病模型中，通过AQ和TDI测量的左心室射血效率可以被量化为左室区域之间的幅度校正相角离散度之和和以及幅度校正相角的交叉相关。这项建议的最终目标是开发和验证一种基于超声心动图的算法，该算法通过将收缩功率和收缩同步性合并到一个共同的指标中来量化左心室射血效果。