A non-invasive, automated platform for hemodynamic assessment of patients at risk of heart failure or pulmonary hypertension

项目摘要在美国，心力衰竭(HF)和心脏功能异常直接影响着600万人，是导致死亡的主要原因。早期干预是降低死亡率和发病率的关键，但早期诊断，特别是对于那些没有症状的疾病，是具有挑战性的。有效诊断和治疗心力衰竭及其伴发的肺动脉高压需要准确测量四项血流动力学参数，包括射血分数(EF)、心输出量(CO)、肺动脉压(PAP)和肺毛细血管楔压(PCWP)。目前，这些评估是通过超声心动图和心导管术相结合获得的，只能由经过专门培训的熟练医务人员进行。此外，心导管插入术是高度侵入性的，需要大量昂贵的资源，并且与患者的风险有关。对于一种精确的、非侵入性的、低成本的血流动力学测量工具的需求尚未得到满足，这种工具无需专门的培训即可操作，其精度与心导管和超声检查相当。这样的设备将使诊断更早、更安全、更负担得起，提高监测能力，更频繁地监测高危患者，并为临床医生指导治疗提供更好的临床决策支持。目前还没有非侵入性替代插管的方法，目前也没有同时测量EF、CO、PAP和PCWP的技术。Sensydia公司正在开发一种用于血流动力学测量的低成本、非侵入性“心脏性能系统”(CPS)，其目标是实现与黄金标准技术相当的准确性。CPS从一组易于使用的传感器获取并自动分析声学和心电信号，以准确测量EF、CO、PAP和PCWP。Sensydia已经为CPS开发了功能齐全的硬件和原型软件，使用专有算法来分析采集的信号。Sensydia已经获得了测量EF的510(K)许可；然而，需要进一步的算法开发和测试才能实现一个也可以以类似精度测量CO、PAP和PCWP的系统。在这个快速跟踪STTR项目的第一阶段，将使用Sensydia/匹兹堡大学医学中心(UPMC)团队获得的CPS和插管数据的现有培训数据集，进一步改进和测试PAP和PCWP算法，以满足临床使用的预期精度阈值，并将基于Bland-Altman偏差和一致性限制进行评估。与UPMC经验丰富的心脏病专家和麻醉师团队合作，CO、PAP和PCWP算法随后将在一个新的、独立的数据集中进行前瞻性验证，这些数据来自接受心导管置入术的患者。第二阶段将集中于展示在术前临床环境中常规使用的临床实用性和可行性。最后，将开发一个综合软件应用程序，用于根据AHA/ACC指南报告CPS数据和诊断，并在与UPMC医生进行的可用性研究中进行评估。

PROJECT SUMMARY Heart failure (HF) and abnormal heart function directly affects 6 million people in the U.S. and is a leading cause of death. Early intervention is key to reducing mortality and morbidity, yet early diagnosis, particularly for those with asymptomatic disease, is challenging. Effective diagnosis and management of HF and accompanying pulmonary hypertension (PH) requires accurate measurement of four hemodynamic parameters, including ejection fraction (EF), cardiac output (CO), pulmonary artery pressure (PAP), and pulmonary capillary wedge pressure (PCWP). Currently obtained by a combination of echocardiography and cardiac catheterization these assessments can only be performed by skilled medical personnel with specialized training. In addition, cardiac catheterization is highly invasive, requires significant expensive resources, and is associated with risks to the patient. There is an unmet need for an accurate, non-invasive, low cost hemodynamic measurement tool that can be operated without specialized training with accuracy equivalent to cardiac catheterization and sonography. Such a device would enable earlier, safer, and more affordable diagnosis, improved surveillance capabilities, more frequent monitoring of at-risk patients, and better clinical decision support for clinicians in guiding therapies. Non-invasive alternatives to catheterization are not currently available, and there are no technologies that currently exist for simultaneous measurement of EF, CO, PAP and PCWP. Sensydia Corporation is developing a low cost, non-invasive “Cardiac Performance System” (CPS) for hemodynamic measurement with the goal of achieving comparable accuracy to that of gold-standard techniques. CPS acquires and automatically analyzes acoustic and electrocardiogram signals from a set of easily applied sensors to accurately measure EF, CO, PAP, and PCWP. Sensydia has developed fully functioning hardware and prototype software for CPS that uses proprietary algorithms to analyze the acquired signals. Sensydia has been granted 510(k) clearance for measurement of EF; however, further algorithm development and testing are required to achieve a system that can also measure CO, PAP, and PCWP with similar accuracies. In Phase I of this Fast- Track STTR project, PAP and PCWP algorithms will be further refined and tested to meet desired thresholds of accuracy for clinical use using an existing training dataset of CPS and catheterization data obtained by the Sensydia/University of Pittsburgh Medical Center (UPMC) team and will be assessed based on Bland-Altman bias and limits of agreement. In collaboration with a team of experienced cardiologists and anesthesiologists at UPMC, the CO, PAP and PCWP algorithms will then be prospectively validated in a new, independent dataset from patients undergoing cardiac catheterization. Phase II will focus on demonstrating clinical utility and feasibility of routine use in a preoperative clinic setting. Finally, an integrated software application for reporting CPS data and diagnosis based on AHA/ACC guidelines will be developed and assessed in a useability study with UPMC physicians.