Cardiopulmonary Exercise Testing: Pulmonary Hypertension

（修订摘要）描述：肺动脉高压（PAH）是一种破坏性的、快速进展的肺血管疾病，通常影响21至40岁的年轻女性。未经治疗，中位生存时间为2.8年。只有肺移植才能缓解肺动脉高压。目前用于评估临床过程的方法要么是主观的，要么与症状和预期寿命没有很好的相关性。右心导管插入术被广泛用于测量疾病的严重程度和对治疗的反应，但重复的导管插入术会导致发病，并且是治疗中所需改变的潜在障碍。此外，导管插入术是在休息时进行的，而不是在运动时，当病人有症状时。相反，PI及其导师的初步数据显示，运动期间有氧功能和排便效率的无创测量与PAH患者的疾病严重程度和治疗反应密切相关。这对确定预后、选择治疗方法和决定肺移植的时机具有广泛的意义。该提案的广泛目标是定义无创评估PAH患者的最佳方法，并使用心肺运动试验（CPET）开发预后模型。具体目标是：1）将峰值运动耗氧量（峰值VOz）和其他CPET测量值确定为生存时间、是否需要肺动脉移植或因PAH症状住院的独立预测因素。2)使用CPET参数对具有NYHA II和III功能等级症状的患者以及6分钟步行距离为250-400 m 3的患者进行进一步细分）建立峰值VO 2和其他CPET测量值之间的关系，以跟踪对血管扩张剂的反应治疗。这项研究将有助于确定最有用的 做出关键临床决策时要遵循的参数，包括确定肺移植的需要和时机。在我们的大型PAH转诊诊所，我们将对72例PAH受试者（根据世界卫生组织的定义）进行CPET。我们将研究PAH的肺血管病变如何影响PAH的运动有氧能力和呼吸效率，以及这些重要的心肺血管功能反映如何与这些患者常规评价中使用的临床指标相关。我们的假设是基于这样一个概念，即CPET测量提供了客观的，定量的疾病严重程度和治疗反应的措施。因此，重要的治疗决策可以基于对运动的循环和排泄反应的客观测量，该提案将使PI能够参与结构化的分级职业发展计划，从而获得以患者为导向的心血管研究职业所需的技能。

(Revised Abstract) Description: Pulmonary arterial hypertension (PAH) is a devastating, rapidly progressive disease of the pulmonary vasculature that typically affects young women between the ages of 21 and 40. Untreated, the median survival time is 2.8 years. Only lung transplantation relieves the pulmonary hypertension. Methods currently used to assess the clinical course are either subjective or do not correlate well with symptoms and life expectancy. Right heart catheterization is widely-used to measure disease severity and response to therapy, but repeated catheterization causes morbidity and is a potential barrier to needed changes in therapy. Also, catheterization is performed at rest, not during exercise, when the patient is symptomatic. In contrast, preliminary data from the PI and his mentor show that noninvasive measures of aerobic function and ventilatory efficiency during exercise are closely related to disease severity and response to therapy in patients with PAH. This has broad implications for determining prognosis, selection of treatment, and making decisions on the timing of lung transplantation. The broad objectives of this proposal are to define optimal methods for noninvasively assessing patients with PAH, and to develop a prognostic model using cardiopulmonary exercise testing (CPET). The specific aims are: 1) To establish peak exercise oxygen consumption (peak VOz) and other CPET measurements as independent predictors of survival time, need for tung transplantation, or hospitalization for symptoms of PAH. 2) To use CPET parameters to further subclassify patients with NYHA II and III functional class symptoms, and patients with 6-minute walk distances of 250-400 m 3) To establish the relationship between peak VO2 and other CPET measurements in tracking the response to vasodilator therapy. This study will help determine the most useful parameter(s) to follow for making critical clinical decisions, including determining the need for and timing of lung transplantation. From our large PAH referral clinic, we will perform CPET in 72 human subjects with PAH, as defined by the World Health Organization. We will examine how the pulmonary vasculopathy of PAH affects exercise aerobic capacity and ventilatory efficiency in PAH, and how these important reflections of cardiac and pulmonary vascular function relate to clinical indices used in the conventional evaluation of these patients. Our hypotheses are based on the concept that CPET measurements provide objective, quantitative measures of disease severity and response to therapy. Therefore important therapeutic decisions can be based on objective measures of the circulatory and ventilatory responses to exercise, This proposal will enable the PI to participate in a structured, graded career development program leading to the acquisition of skills needed for a career in patient-oriented cardiovascular research.