Measuring Left Ventricular Dyssynchrony from ECG-gated Myocardial Perfusion SPECT

研究综述 心力衰竭(HF)在美国影响着500多万人，而且这个数字增加了 每年超过50万。急性失代偿性心衰占100多万住院人数 每年。2006年HF的直接和间接费用估计为296亿美元。我们的长期目标是 通过更准确地预测心力衰竭患者对心脏再同步化的反应改善其预后 治疗(CRT)和/或血运重建。CRT已被FDA批准用于治疗心力衰竭患者 对常规疗法无效。然而，选择接受CRT的患者中有20%-40%是基于 常规标准对CRT不起作用。超声心动图显示可以改善患者的选择 CRT，但它需要专业知识才能获得可靠的结果。前瞻试验表明，在“现实世界”下 目前可用的超声心动图技术不能用于CRT的常规预测 回应。我们的主要目标是预测心衰传导患者对CRT的反应。 心电紊乱和室壁不同步。它将通过改进的诊断和特征来实现 使用我们的新的定量多谐相位分析(MHPA)诊断左心室(LV)不同步 心电门控单光子发射计算机断层扫描(SPECT)心肌灌注成像研究 通过将这种对左室不同步的评估与我们已建立的心肌灌注定量相结合 以及同一项研究的可行性。这种综合量化也将被用来预测对 心力衰竭合并缺血性心肌病患者的血管重建是我们的次要目标。我们建议测量 来自心电门控SPECT MPI的LV不同步，因为1)它广泛可用，2)它高度可重复性， 3)它可以提供治疗心衰所需的额外的血流灌注/存活信息。 病人，不需要任何额外的程序。具体地说，在这项研究中，我们将1)发展左心室不同步 可模拟门控SPECT MPI研究的模拟工具，可模拟各种LV不同步模式，2) 开发MHPA并使用模拟工具进行优化，以确定以下各项的成像要求 准确的MHPA测量，3)定义和验证描述LV不同步和 开发这些指标的正常数据库，4)使用LV不同步量化与我们的 已建立的血流灌注/活性定量指标用于预测心衰患者对CRT的反应，以及5)使用 综合量化左心室不同步性、血流灌注和存活能力以预测对 心力衰竭合并缺血性心肌病患者的血运重建。完成这项研究后，我们会 为我们的阶段分析方法建立坚实的科学基础，从而支持一项大型临床试验 证明心电门控SPECT MPI与我们的左室不同步的综合量化的有效性， 对心衰患者的血流灌注、生存能力和预后的影响，从而促进其在临床上的广泛应用。

RESEARCH SUMMARY Heart failure (HF) affects more than 5 million people in the United States, and the number increases by more than 0.5 million every year. Acute decompensated HF accounts for over one million hospital admissions per year. The estimated direct and indirect cost for HF in 2006 is $29.6 billion. Our long-term objective is to improve the prognosis of HF patients by more accurately predicting their response to cardiac resynchronization therapy (CRT) and/or revascularization. CRT has been approved by FDA as a treatment of HF patients refractory to conventional therapy. However, 20-40% of the patients who selected for CRT based on the conventional criteria do not respond to CRT. Echocardiography has shown to improve patient selection for CRT, but it requires expertise to obtain reliable results. The PROSPECT trial has shown that under "real-world" conditions the current available echocardiographic techniques are not ready for routine prediction of CRT response. Our primary goal is to predict the response to CRT in patients with HF-induced conduction disturbances and ventricular dyssynchrony. It will be accomplished by improved diagnosis and characterization of left ventricular (LV) dyssynchrony using our novel, quantitative multi-harmonic phase analysis (MHPA) of ECG-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) study and by integrating this evaluation of LV dyssynchrony to our established quantification of myocardial perfusion and viability from the same study. This integrated quantification will also be used to predict the response to revascularization in HF patients with ischemic cardiomyopathy - our secondary goal. We propose to measure LV dyssynchrony from ECG-gated SPECT MPI, because 1) it is widely available, 2) it is highly reproducible, and 3) it can provide additional perfusion/viability information, which is needed for the management of the HF patient, without any additional procedure. Specifically, in this research we will 1) develop LV dyssynchrony simulation tools that can simulate gated SPECT MPI studies with a variety of LV dyssynchrony patters, 2) develop MHPA and optimize it by using the simulation tools to determine the imaging requirements for accurate MHPA measurements, 3) define and validate quantitative indices that describe LV dyssynchrony and development normal databases for these indices, 4) use the LV dyssynchrony quantification coupled with our established perfusion/viability quantification to predict the response to CRT in HF patients, and 5) use the integrated quantification of LV dyssynchrony, perfusion, and viability to predict the response to revascularization in HF patients with ischemic cardiomyopathy. Upon completion of this research, we will establish a strong scientific foundation for our phase analysis approach thus supporting a large clinical trial to prove the usefulness of ECG-gated SPECT MPI with our integrated quantification of LV dyssynchrony, perfusion, and viability in prognosis for HF patients and thus promoting widespread utilization clinically.