BOSENTAN VS PLACEBO IN NYHA CLASS I/II SCLERODERMA PATIENTS WITH EXERCISE INDUCE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 肺动脉高压（PAH）是系统性硬化症（SSc）中常见且通常致命的肺部疾病。 多种药物已获批用于治疗硬皮病中的III/IV类PAH。波生坦是一种内皮素-1拮抗剂，在PAH患者的12周临床试验中显示出行走距离的显著改善（7）。对于偶然诊断为PAH（WHO功能I级）的无症状系统性硬化症患者的治疗仍存在争议。我们假设，无症状或症状轻微的系统性硬化症患者和静息肺动脉压正常的患者，经负荷多普勒超声心动图检查显示肺动脉收缩压异常升高，代表了已经患有肺血管疾病且有发生重度PAH风险的患者亚组。我们进一步假设，早期识别和治疗此类患者可能会延缓疾病的进展。 假设： 1. 负荷超声心动图通过检测系统性硬化症患者运动诱发的肺动脉高压来识别早期肺血管疾病 2. 波生坦治疗运动诱发的PAH将改善系统性硬化症患者的运动耐力。受试者将从运动试验异常的患者中招募，作为早期研究硬皮病运动超声心动图（IRB# 03-363）的一部分。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pulmonary hypertension (PAH) is a common and usually fatal form of lung disease in systemic sclerosis (SSc). Multiple drugs have been approved for the treatment of Class III/IV PAH in scleroderma. Bosentan is an endothelin-1 antagonist which showed significant improvement in distance walked during 12 week clinical trials in PAH patients (7). Therapy for asymptomatic systemic sclerosis patients diagnosed incidentally with PAH (WHO Functional Class I) remains controversial. We hypothesize that asymptomatic or minimally symptomatic patients with systemic sclerosis and normal resting pulmonary artery pressures who demonstrate an abnormal rise in pulmonary artery systolic pressure with stress Doppler echocardiography testing represent a subset of patients who already have pulmonary vascular disease and who are at risk for the development of severe PAH. We further hypothesize that early identification and treatment of such patients may retard the progression of that disease. Hypotheses: 1. Stress echocardiography identifies early pulmonary vascular disease by detecting exercise-induced pulmonary hypertension in patients with systemic sclerosis. 2. Treatment of exercise-induced PAH with Bosentan will lead to improved exercise endurance in patients with systemic sclerosis. Subjects will be recruited from those patients who have had an abnormal exercise test as part of an earlier study, Exercise Echocardiograms in Scleroderma (IRB# 03-363).