Measuring Left Ventricular Dyssynchrony from ECG-gated Myocardial Perfusion SPECT

描述(申请人提供)：心力衰竭(HF)在美国影响着500多万人，而且这个数字每年增加50多万。急性失代偿性心衰每年有100多万人入院。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脏再同步化治疗(CRT)和/或血管重建术的反应来改善心衰患者的预后。CRT已被FDA批准用于治疗常规治疗所不能及的心衰患者。然而，根据传统标准选择接受CRT的患者中，有20%-40%的患者对CRT没有反应。超声心动图已经证明可以改善CRT患者的选择，但它需要专业知识才能获得可靠的结果。PROCESS试验表明，在“真实世界”条件下，目前可用的超声心动图技术还不能用于CRT反应的常规预测。我们的主要目标是预测心衰引起的传导障碍和心室不同步患者对CRT的反应。它将通过使用我们新的心电门控单光子发射计算机断层扫描(SPECT)心肌灌注成像(MPI)研究的新的定量多谐相位分析(MHPA)来改进对左室(LV)不同步的诊断和表征，并通过将这种LV不同步的评估与我们根据同一研究建立的心肌灌注和存活的量化相结合来实现。这一综合量化方法也将用于预测心力衰竭合并缺血性心肌病患者对血管重建的反应，这是我们的次要目标。我们建议从心电门控SPECT MPI测量左室不同步，因为1)它广泛可用，2)高度重复性，3)它可以提供心力衰竭患者治疗所需的额外灌注/存活信息，而不需要任何额外的程序。具体地说，在这项研究中，我们将1)开发可以模拟各种左室不同步模式的门控SPECT MPI研究的左室不同步模拟工具；2)开发MHPA并通过使用模拟工具来确定准确测量MHPA的成像要求来优化它；3)定义和验证描述左室不同步的量化指标并为这些指标开发正常数据库；4)使用左室不同步量化与我们建立的灌注/存活量化相结合来预测心衰患者对CRT的反应；以及5)使用左室不同步、血流灌注和存活率的综合量化来预测心力衰竭患者对血运重建的反应。这项研究完成后，我们将为我们的时相分析方法奠定坚实的科学基础，从而支持一项大型临床试验，以证明心电门控SPECT MPI与我们对左室不同步、血流灌注和存活的综合量化在心力衰竭患者预后中的有用性，并促进临床的广泛应用。与公共健康相关：在美国，心力衰竭影响着500多万人，而且这个数字每年增加50多万。急性失代偿性心力衰竭每年有100多万人入院，2006年心力衰竭的直接和间接成本估计为296亿美元。本研究旨在为我们从常规的心电门控SPECT心肌灌注成像研究中对左心室不同步性、血流灌注和存活性的综合量化奠定坚实的科学基础，从而通过更准确地预测心力衰竭患者对心脏再同步治疗和/或血运重建的反应来改善心力衰竭患者的预后。

DESCRIPTION (provided by applicant): 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 patient's 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 promoting widespread utilization clinically. PUBLIC HEALTH RELEVANCE: Heart failure affects more than 5 million people in the United States, and the number increases by more than 0.5 million every year. Acute decompensated heart failure accounts for over one million hospital admissions per year, and the estimated direct and indirect cost for heart failure in 2006 is $29.6 billion. This research is to establish a strong scientific foundation for our integrated quantification of left ventricular dyssynchrony, perfusion, and viability from the conventional ECG-gated SPECT myocardial perfusion imaging studies to improve the prognosis of heart failure patients by more accurately predicting their response to cardiac resynchronization therapy and/or revascularization.