Assessing the Utility of Submaximal Cardiopulmonary Exercise Testing in Diagnosis and Treatment Management of Pulmonary Arterial Hypertension

摘要 肺动脉高压（PH）是一种以进行性呼吸困难/运动为特征的破坏性疾病 不耐受、右心衰竭，并具有发病和早期死亡的高风险。PH疾病进展 可能是迅速的，任何延误的诊断和治疗的PH可能会降低生存。鉴于其临床和 预后意义，早期和准确诊断PH，以便及时和最佳地建立 临床护理至关重要。虽然传统的最大/综合心肺运动 CPET测试（CPET）已在PH中得到验证，但其局限性阻碍了其在常规临床 评估和监测。我们的初步数据表明，特征性呼吸和肺部气体 即使在次极量运动期间，PH交换紊乱也变得明显。我们全面 一项概念验证研究（133例患者）支持我们的假设，即增加肺气体交换 标准化3分钟次极量运动试验（Shape iCPET）对标准超声心动图 PH证据（即RVSP >50 mmHg，疑似RV功能障碍）提高了PH检测的灵敏度 几乎40%。Shape iCPET系统结构紧凑，采用模式识别软件， 解释，使系统理想地适合广泛采用。本报告的总体目标 SBIR建议将Shape iCPET明确确立为一种工具，该工具：1）早期改善 检测PH;和2）提供了一种客观的基于证据的PH治疗疗效指标， 易于在学术和社区实践中使用。我们建立了一个由10个中心组成的学术联盟， 和社区PH中心的支持。具体目标1将评估 次极量心肺运动试验作为鉴别 肺动脉高压具体目标2将评估药物治疗诱导的 肺动脉高压严重程度和疾病状态的改善反映在生理学上， 对标准化次极量心肺运动试验的反应。我们假设形状 iCPET将被证明是传统临床指标的有效辅助手段，用于跟踪肺功能的变化。 随时间推移的血管功能和对旨在缓解PAH的治疗的反应。

Abstract Pulmonary hypertension (PH) is a devastating disease characterized by progressive dyspnea/exercise intolerance, right-heart failure, and carries a high risk of morbidity and early mortality. PH disease progression can be rapid, and any delay in the diagnosis and treatment of PH likely reduces survival. Given its clinical and prognostic significance, early and accurate diagnosis of PH to allow prompt and optimal establishment of clinical care is of critical importance. While traditional maximal/comprehensive cardiopulmonary exercise testing (CPET) has been validated in PH, it has limitations that have hindered its applicability to routine clinical assessment and monitoring. Our preliminary data suggest that the signature ventilatory and pulmonary gas exchange derangements of PH become apparent during even submaximal exercise. Our comprehensive proof-of-concept study (133 patients) supports our hypothesis that the addition of pulmonary gas exchange responses to a standardized 3-minute submaximal exercise test (Shape iCPET) to standard echocardiographic evidence of PH (i.e. RVSP >50 mmHg, suspicion of RV dysfunction) improves the sensitivity for PH detection by almost 40%. The Shape iCPET system is compact and utilizes pattern-recognition software that automates interpretation, making the system ideally suitable for widespread adoption. The overarching objective of this SBIR proposal is to categorically establish the Shape iCPET as a tool that: 1) improves early detection of PH; and 2) provides an objective evidence-based measure of PH therapy efficacy that can be easily used in academic and community practices. We have established a 10-center consortium of academic and community PH centers for this SBIR proposal. Specific Aim 1 will assess the clinical utility of submaximal cardiopulmonary exercise testing as a complementary tool for the identification of pulmonary hypertension. Specific Aim 2 will assess whether pharmacotherapy-induced improvements in pulmonary hypertension severity and disease status are reflected in the physiological responses to a standardized submaximal cardiopulmonary exercise test. We hypothesize that the Shape iCPET will prove to be an efficacious adjunct to traditional clinical metrics to track changes in pulmonary vascular function over time and responses to therapy aimed at alleviating PAH.