Quantifying Left Ventricular Ejection Effectiveness

量化左心室射血效率

• 批准号: 7142444
• 负责人: MICHAEL R PINSKY
• 金额: $ 52.05万
• 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/7142444
• 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）： 异步左心室（LV）收缩是最常见的心脏异常，如果严重损害LV泵的功能，会诱导心脏扩张和心力衰竭重塑。心室起搏通常会增加收缩异步，即使收缩率正常，也会诱导心脏扩张。我们假设LV收缩异步可以降低LV射血效率，这是通过LV卒中工作与心肌O2消耗（MVO2）的比例来定义的，而不会导致LV扩张而不改变内在收缩力。我们将LV弹出效率定义为所有收缩元件收缩的同步。重要的是，最近对心肌病和延长QR的患者心脏重新同步治疗（CRT）的临床试验表明，封闭式双室腔内起搏会改善LV射出压力，降低心脏体积，并降低心脏量，并在某些受试者中诱导反向重塑。我们假设CRT的所有有益效应都来自改善LV收缩同步的能力。我们认为，起搏的这些临床相反的影响是通过收缩同步的相反变化来解释的。 MVO2，LV弹出异步和弹出效率之间的关系尚不清楚。我们将开发一种新的评估，从而将LV弹出效率与超声心动图数据的相角和振幅分散液的傅立叶分析结合在一起的LV弹出效率。我们建议使用组织多普勒成像（TDI）在动物和人类模型的床边量化这种异步。我们最近开发并验证了一个定量模型，以使用区域相角分析来评估LV弹性效果。但是，该技术需要侵入性监测，不适合一般临床使用。重要的是，我们还开发了并验证了使用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区域心肌运动。目前，尚无分析这些数据以客观量化收缩异步的方法。我们建议将我们的异步分析与定量AQ和TDI技术相结合，以创建一种临床相关的工具来评估LV射血效果。我们将使用已建立的孤立灌注兔心脏（Langendorf制剂）模型来验证MVO2和异步LV收缩之间的关系。我们将在选择性起搏，模拟CRT和区域缺血引起的不同收缩异步和再灌注的条件下使用完整的麻醉犬模型，以创建在线TDI分析算法。最后，我们将研究CRT和非CRT受试者之前和之后的人类受试者，以确定我们是否可以预测哪些受试者将从CRT中受益以及在心室CRT起搏中的位置将是最佳的。可能，CRT可以在受试者发展心力衰竭重塑之前使用。我们将检验两个相关的假设。首先，增加了整体LV异步诱导LV体积的平行移位，以达到恒定的弹出压力，从而使MVO2随着LV终端 - 音节压力量 - 量相关的平行移位而增加。其次，通过AQ和TDI在LV收缩异步和患有心脏疾病的人类的临床相关犬模型中通过AQ和TDI测量的LV弹出效率可以量化为LV区域之间振幅校正相位角分散体的总和振幅校正相角的相关性。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合并为共同度量来量化LV弹出效率。