Measuring Left Ventricular Dyssynchrony from ECG-gated Myocardial Perfusion SPECT

描述（由申请人提供）：心力衰竭（HF）在美国影响着超过500万人，并且每年增加50多万人。急性失代偿性心衰每年有超过100万人住院。2006年氟化氢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他们对心脏再同步化治疗（CRT）和/或血运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难治性心衰患者。然而，根据常规标准选择CRT的患者中有20-40%对CRT没有反应。超声心动图显示可以改善患者对CRT的选择，但需要专业知识才能获得可靠的结果。PROSPECT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常规预测CRT反应。我们的主要目标是预测高频诱导的传导障碍和心室非同步化患者对CRT的反应。通过使用我们新颖的、定量的多谐相位分析（MHPA）的ecg门控单光子发射计算机断层扫描（SPECT）心肌灌注成像（MPI）研究来改进左心室（LV）非同步化的诊断和表征，并将这种左心室非同步化的评估与我们从同一研究中建立的心肌灌注和生存能力的量化相结合，来实现这一目标。这种综合量化也将用于预测合并缺血性心肌病的心衰患者对血运重建的反应——这是我们的次要目标。我们建议通过ecg门控SPECT MPI来测量左室不同步，因为1)它是广泛可用的，2)它是高度可重复性的，3)它可以提供额外的灌注/活力信息，这对于HF患者的管理是需要的，而不需要任何额外的程序。具体来说，在本研究中，我们将1)开发LV不同步模拟工具，可以模拟各种LV不同步模式的门控SPECT MPI研究，2)开发MHPA并通过使用模拟工具来优化它，以确定准确的MHPA测量的成像要求，3)定义和验证描述LV不同步的定量指标，并为这些指标开发正常数据库。4)使用左室非同步化量化结合我们建立的灌注/活力量化来预测心衰患者对CRT的反应；5)使用左室非同步化、灌注和活力的综合量化来预测心衰合并缺血性心肌病患者对血运重建的反应。在这项研究完成后，我们将为我们的相分析方法建立强大的科学基础，从而支持一项大型临床试验，以证明ecg门控SPECT MPI的有效性，通过我们对左室不同步化、灌注和心衰患者预后可行性的综合量化，并促进临床广泛应用。公共卫生相关性：心力衰竭在美国影响着超过500万人，并且每年增加50多万人。急性失代偿性心力衰竭每年导致100多万人住院，2006年心力衰竭的直接和间接费用估计为296亿美元。本研究旨在为我们从传统的ecg门控SPECT心肌灌注成像研究中对左室非同步化、灌注和活力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脏再同步化治疗和/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.