Quantifying Left Ventricular Ejection Effectiveness

量化左心室射血效率

• 批准号: 6821586
• 负责人: MICHAEL R PINSKY
• 金额: $ 50.88万
• 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/6821586
• 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 (LV) 异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，引起心脏扩张和心力衰竭重塑。即使收缩力正常，心室起搏通常也会增加收缩异步性并引起心脏扩张。我们假设左心室收缩异步性会导致左心室扩张而不改变内在收缩力，从而降低左心室射血效率（由左心室每搏功与心肌耗氧量 (MVO2) 之比定义）。我们将左心室射血效率定义为所有收缩元件收缩的同步性。重要的是，最近对扩张型心肌病和 QRS 波延长患者进行心脏再同步治疗 (CRT) 的临床试验表明，门控双心室起搏可改善部分但并非所有受试者的左心室射血压、减少心脏容量并诱导逆重构。我们假设 CRT 的所有有益作用都来自其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、左心室射血异步性和射血有效性之间的关系尚不清楚。我们将开发一种评估左心室射血效率的新应用，将区域相位角分析与超声心动图数据的相位角和振幅离散度的傅立叶分析相结合。我们建议使用组织多普勒成像（TDI）在动物和人体模型的床边量化这种异步性。我们最近开发并验证了一个定量模型，使用区域相位角分析来评估左心室射血有效性。然而，该技术需要侵入性监测，不适合一般临床使用。重要的是，我们还开发并验证了使用 TDI 和声学量化 (AQ) 算法分析经胸超声心动图左心室图像的定量方法。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，还没有成熟的方法来分析这些数据以客观地量化收缩异步性。我们建议将异步分析与定量 AQ 和 TDI 技术结合起来，创建一个临床相关工具来评估 LV 射血有效性。我们将使用我们建立的离体灌注兔心脏（Langendorf 制备）模型来验证 MVO2 与异步左心室收缩之间的关系。我们将在选择性起搏、模拟 CRT 以及局部缺血和再灌注引起的不同收缩异步条件下使用完整的麻醉犬模型来创建在线 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 CRT 起搏的最佳位置。 CRT 可能可以在受试者发生心力衰竭重构之前使用。我们将检验两个相关的假设。首先，在射血压力恒定的情况下，左心室整体异步性的增加会引起左心室容量的平行移动，使得 MVO2 作为左心室收缩末期压力-容量关系的平行移动的函数而增加。其次，在左心室收缩异步的临床相关犬模型和患有心脏病的人类中通过 AQ 和 TDI 测量的左心室射血有效性可以量化为左心室区域之间幅度校正相位角离散度的总和以及幅度校正相位角的互相关性。该提案的最终目标是开发和验证基于超声心动图的算法，通过将收缩的功率和同步性合并到通用指标中来量化左室射血有效性。