The state of energy in the right ventricle of patients with pulmonary arterial hypertension

项目总结/摘要 肺动脉高压（PAH）是一种进行性心肺疾病，死亡率高。在 在大多数情况下，PAH诱导的慢性压力超负荷导致右心室（RV）衰竭。右心 导管插入术（RHC）目前是PAH诊断和随访的金标准试验。此外，重复 在临床治疗期间发生不明原因临床恶化的患者应考虑RHC。 或随时间定期随访。然而，世界各地的许多中心并不定期进行RHC 在随访期间，由于各种潜在原因，包括其侵入性、成本或可用性。 我们最近开发了3D超声心动图粒子图像测速（Echo-PIV），它允许高- RV血流动力学的时间容积评估。结合标准3D散斑跟踪，3D Echo-PIV能够全面评估血流动力学和能量状态（心室动力学 能量/功和粘性能量耗散）。RV能量状态反映了结构和功能 PAH可能导致的RV变化。因此，它可以作为一个独立于负载的措施，以评估 右心室功能和监测PAH患者的疾病进展/消退。 该项目的总体假设是，在PAH患者的随访中，RV能量状态的变化：（1）反映 RHC衍生的肺动脉压的变化，以及（2）与患者临床 因此，它可以用于监测疾病的进展和消退。 鉴于在更晚期的疾病中，存在RV功能障碍，我们将收集一个前瞻性的，种族多样的 Cedars-Sinai Medical Center的210例受试者队列：70例RV功能正常的PAH患者，70例PAH患者 RV功能障碍患者和70名健康对照者。将实现以下具体目标： 特定目的1：研究3D Echo-PIV在表征RV中的4D血流动力学方面的准确性 使用4D Flow CMR作为参考标准，并评估PAH中3D Echo-PIV的试验/重复试验再现性。 具体目标2：确定非侵入性导出的RV能量状态与RHC之间的关系- 在随访PAH患者中导出参数，并测试RV能量状态的变化是否反映 伴有和不伴有RV功能障碍的PAH患者中RHC衍生肺动脉压的变化。 特定目的3：研究无创成像衍生RV能量状态用于监测的可行性 PAH患者的疾病进展/消退。 拟议研究的成功将确立3D Echo-PIV作为评估PAH患者的工具， 将：（1）确定无创RV成像和基于RHC的有创血流动力学之间的关系， (2)确定无创RV能量状态的变化是否反映了RHC衍生参数的变化 在PAH患者中，和（3）通过无创RV能量状态促进监测疾病进展/消退 代替侵入性RHC（当前临床金标准）。

PROJECT SUMMARY/ABSTRACT Pulmonary arterial hypertension (PAH) is a progressive cardiopulmonary disease with a high mortality rate. In most cases, PAH-induced chronic pressure overload leads to right ventricle (RV) failure. Right heart catheterization (RHC) is currently the gold standard test for PAH diagnosis and follow-up. Furthermore, repeated RHC should be considered in patients who experience unexplained clinical deterioration during their clinical course or for periodic follow-up over time. Yet many centers across the world do not routinely perform RHC during follow-up, for a variety of potential reasons, including its invasive nature, cost, or availability. We have recently developed 3D echocardiographic particle image velocimetry (Echo-PIV), which allows high- temporal volumetric assessment of RV hemodynamics. In combination with standard 3D speckle tracking, 3D Echo-PIV enables a comprehensive assessment of hemodynamics and energy state (ventricular kinetic energy/work and viscous energy dissipation) in the RV. The RV energy state reflects the structural and functional changes in the RV that may occur due to PAH. Thus, it can be used as a load-independent measure to assess RV function and monitor disease progression/regression in PAH patients. The project's global hypothesis is that in PAH patients' follow-up, changes in the RV energy state: (1) reflect changes in RHC-derived pulmonary arterial pressures, and (2) are associated with changes in patients' clinical status such that it can be used to monitor disease progression and regression. Given that in more advanced disease, RV dysfunction is present, we will gather a prospective, ethnically diverse cohort of 210 subjects at Cedars-Sinai Medical Center: 70 PAH patients with normal RV function, 70 PAH patients with RV dysfunction, and 70 healthy control subjects. The following Specific Aims will be accomplished: SPECIFIC AIM 1: Investigate the accuracy of 3D Echo-PIV in characterizing 4D flow hemodynamics in the RV using 4D Flow CMR as a reference standard and assess test/retest reproducibility of 3D Echo-PIV in PAH. SPECIFIC AIM 2: Determine the relationship between the noninvasively derived RV energy state and RHC- derived parameters in following up PAH patients and test whether changes in the RV energy state reflect changes in the RHC-derived pulmonary arterial pressures in PAH patients with and without RV dysfunction. SPECIFIC AIM 3: Investigate the feasibility of noninvasive imaging-derived RV energy state for monitoring disease progression/regression in PAH patients. The success of the proposed studies will establish 3D Echo-PIV as a tool for assessment of PAH patients and will: (1) determine the relationship between noninvasive RV imaging and invasive RHC-based hemodynamics, (2) establish whether changes in noninvasive RV energy state reflect changes in the RHC-derived parameters in PAH patients, and (3) facilitate monitoring of disease progression/regression by noninvasive RV energy state in lieu of invasive RHC (current clinical gold standard).