Saggar Rajeev, Khanna D, Shapiro S, Furst D E, Maranian P, Clements P, Abtin F, Dua Shiv, Belperio J, Saggar Rajan
Heart-Lung Institute, St. Joseph Hospital and Medical Center, Phoenix, Arizona, USA.
Arthritis Rheum. 2012 Dec;64(12):4072-7. doi: 10.1002/art.34614.
Exercise-induced pulmonary hypertension (ePH) may represent an early, clinically relevant phase in the spectrum of pulmonary vascular disease. The purpose of this pilot study was to describe the changes in hemodynamics and exercise capacity in patients with systemic sclerosis (SSc) spectrum-associated ePH treated with open-label daily ambrisentan.
Patients were treated with ambrisentan, 5 mg or 10 mg once daily, for 24 weeks. At baseline and 24 weeks, patients with SSc spectrum disorders exercised in a supine position, on a lower extremity cycle ergometer. All patients had normal hemodynamics at rest. We defined baseline ePH as a mean pulmonary artery pressure of >30 mm Hg with maximum exercise and a transpulmonary gradient (TPG) of >15 mm Hg. The primary end point was change in pulmonary vascular resistance (PVR) with exercise. Secondary end points included an improvement from baseline in 6-minute walking distance, health-related quality of life assessments, and cardiopulmonary hemodynamics.
Of the 12 enrolled patients, 11 completed the study. At 24 weeks there were improvements in mean exercise PVR (85.8 dynes × second/cm(5) ; P = 0.003) and mean distance covered during 6-minute walk (44.5 meters; P = 0.0007). Improvements were also observed in mean exercise cardiac output (1.4 liters/minute; P = 0.006), mean pulmonary artery pressure (-4.1 mm Hg; P = 0.02), and total pulmonary resistance (-93.0 dynes × seconds/cm(5) ; P = 0.0008). Three patients developed resting pulmonary arterial hypertension during the 24 weeks.
Exercise hemodynamics and exercise capacity in patients with SSc spectrum-associated ePH improved over 24 weeks with exposure to ambrisentan. Placebo-controlled studies are needed to confirm whether this is a drug-related effect and to determine optimal therapeutic regimens for patients with ePH.
运动诱发性肺动脉高压（ePH）可能是肺血管疾病谱中一个早期的、具有临床相关性的阶段。这项初步研究的目的是描述接受开放标签每日安立生坦治疗的系统性硬化症（SSc）谱系相关ePH患者的血流动力学和运动能力变化。
患者接受安立生坦治疗，5毫克或10毫克每日一次，共24周。在基线和24周时，患有SSc谱系疾病的患者在下肢周期测力计上仰卧位进行运动。所有患者静息时血流动力学正常。我们将基线ePH定义为最大运动时平均肺动脉压>30毫米汞柱且跨肺压差（TPG）>15毫米汞柱。主要终点是运动时肺血管阻力（PVR）的变化。次要终点包括6分钟步行距离较基线的改善、健康相关生活质量评估以及心肺血流动力学。
12名入组患者中，11名完成了研究。在24周时，平均运动PVR有所改善（85.8达因×秒/厘米⁵；P = 0.003），6分钟步行期间的平均行走距离也有所改善（44.5米；P = 0.0007）。平均运动心输出量（1.4升/分钟；P = 0.006）、平均肺动脉压（-4.1毫米汞柱；P = 0.0
