Improved Assessment of Coronary Flow Dysfunction Using Fundamental Fluid Dynamics

描述（由申请人提供）： 长期目标是改善冠状动脉介入治疗期间的诊断决策。心血管诊断知识的根本差距是，不存在将功能（压降-血流动力学）和解剖测量相结合以评估有或无微血管损伤的心外膜狭窄的单一终点。因此，需要组合的功能和解剖量化，基于该量化可以更准确地做出血管成形术或旁路手术的决定。目的是准确描述不同程度心外膜狭窄的微血管损伤。中心假设是，功能终点压降系数（CDPe）和病变流量系数（LFC）是一种结合功能（CDPe）和解剖学证据的额外且更全面的诊断终点，与用于病变冠状动脉临床评估的经验方法相比，将更好地评估临界狭窄。在强有力的初步数据的指导下，将通过追求三个特定目标来检验该假设：1）评估CDPe（功能终点）在独立区分伴随的心外膜和微血管功能障碍方面的有效性。工作假设是，在人类缺血性心脏病中，通过CDPe的截止值识别的诊断异常程度与可以从已建立的侵入性模式（例如IVUS、FFR和CFR）以及非侵入性模式（例如单光子发射计算机断层扫描（SPECT）和相对较新的正电子发射断层扫描（PET）技术）检测到的诊断异常程度相关; 2）评价结合功能（CDPe）和解剖学终点的LFC在独立区分伴随心外膜动脉和微血管疾病中的有效性。工作假设是，通过LFC临界值识别的诊断异常程度与可从已知模态（如IVUS、FFR、CFR、SPECT和PET）检测到的诊断异常程度相关; 3）确定显示动脉壁顺应性可变的年轻和高龄心脏冠状动脉之间CDPe和LFC值的差异。这里的工作假设是，与年轻心脏的动脉相比，由于非线性壁弹性的变化，老年心脏的动脉显示出较低的壁顺应性的效果，使我们能够描绘出我们发表的CDPe和LFC的数学公式的动脉顺应性效果。这项研究采用了一种创新的方法，结合功能和解剖终点，以更好地诊断，是基于基本的流体动力学原理。这项研究是有意义的，因为它有望消除临床决策过程中的“猜测”。

DESCRIPTION (provided by applicant): The long-term goal is to improve diagnostic decision making during coronary intervention. The fundamental gap of knowledge in cardiovascular diagnostics is that a single endpoint that combines functional (pressure drop-flow hemodynamics) and anatomic measurements to assess epicardial stenoses with or without microvascular impairment does not exist. Thus, there is a need for a combined functional and anatomical quantification upon which a decision for angio- plasty or bypass surgery can be made more accurately. The objective is to accurately delineate microvascular impairment from different degrees of epicardial stenoses. The central hypothesis is that the functional endpoint pressure drop coefficient (CDPe) and the lesion flow coefficient (LFC), an additional and more comprehensive diagnostic endpoint that combines functional (CDPe) and anatomical evidence, will better assess for critical stenosis than empirical methods used for clinical assessment of diseased coronary arteries. Guided by strong preliminary data, this hypothesis will be tested by pursuing three specific aims: 1) To assess the efficacy of CDPe, the functional endpoint, in distinguishing concomitant epicardial and microvascular dysfunc- tion independently. The working hypothesis is that, in human ischemic heart disease, the extent of diagnostic abnormalities identified by cut-off values of CDPe correlate well with those that can be detected from established invasive modalities such as IVUS, FFR, and CFR and with non- invasive modalities, such as single photon emission computed tomography (SPECT) and a rela- tively newer technique of positron emission tomography (PET); 2) To evaluate the effectiveness of LFC that combines functional (CDPe) and anatomical endpoints in distinguishing concomi- tant epicardial artery and microvascular diseases independently. The working hypothesis is that the extent of diagnostic abnormalities identified by cut-off values of LFC correlate well with those that can be detected from known modalities such as IVUS, FFR, CFR, SPECT and PET; 3) To establish the difference in CDPe and LFC values between the coronary arteries of younger and advanced age hearts showing variable arterial wall compliance. The working hypothesis here is that the arteries of older hearts show the effect of lower wall compliance due to the change in non-linear wall-elasticity as compared to the arteries of younger hearts, allowing us to delineate the arterial compliance effect of our published mathematical formulation of CDPe and LFC. This study incorporates an innovative approach of combining functional and anatomic endpoints for better diagnosis that are based on fundamental fluid dynamic principles. This research is sig- nificant because it is expected to remove the 'guesswork' from clinical decision-making process.