Cardiopulmonary Exercise Testing: Pulmonary Hypertension

(修订摘要)描述：肺动脉高压(PAH)是一种破坏性的、进展迅速的肺血管疾病，通常影响21至40岁的年轻女性。未经治疗，中位生存期为2.8年。只有肺移植才能缓解肺动脉高压。目前用于评估临床病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。右心导管术被广泛用于衡量疾病的严重程度和对治疗的反应，但重复导尿术会导致发病率，并成为治疗所需改变的潜在障碍。此外，导尿术是在休息时进行的，而不是在运动时，当患者出现症状时。相比之下，来自PI和他的导师的初步数据显示，运动期间有氧功能和通风效率的非侵入性测量与PAH患者的疾病严重程度和治疗反应密切相关。这对判断预后、治疗方法的选择和肺移植时机的选择具有广泛的指导意义。这项建议的主要目标是确定无创评估PAH患者的最佳方法，并利用心肺运动试验(CPET)开发一个预后模型。具体目标是：1)建立峰值运动耗氧量(峰值VOZ)和其他CPET测量作为生存时间、是否需要进行肺移植或因PAH症状住院的独立预测指标。2)利用CPET参数对NYHA II、III功能分级症状和步行距离为250~400m 3的患者进行进一步分类，以建立峰值VO2与其他CPET指标之间的关系，以追踪血管扩张剂治疗的疗效。这项研究将有助于确定最有用的 参数(S)，以作出关键的临床决策，包括确定是否需要和时机的肺移植。从我们的大型PAH转诊诊所，我们将按照世界卫生组织的定义，对72名患有PAH的人类受试者进行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与这些患者常规评估中使用的临床指标之间的关系。我们的假设是基于这样一个概念，即CPET测量提供了疾病严重程度和治疗反应的客观、定量的衡量标准。因此，重要的治疗决策可以基于对运动的循环和换气反应的客观测量，这项建议将使PI能够参与结构化的、分级的职业发展计划，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.