Department of Cardiac and Vascular Diseases, John Paul II Hospital, Jagiellonian University Medical College, Pradnicka Str 80, 31-202 Krakow, Poland.
Clin Rheumatol. 2012 Jan;31(1):99-104. doi: 10.1007/s10067-011-1792-4. Epub 2011 Jun 14.
Systemic sclerosis (SSc) is complicated by pulmonary hypertension and right ventricle (RV) failure in approximately 10% of the patients. Factors influencing the reactivity of pulmonary circulation to vasodilators are not established, while the examination of vasoreactivity is important in determining the treatment, because systemic administration of oral vasodilators can induce severe adverse events in nonresponders. The mechanism of RV failure in SSc is unclear and may result either from increased RV afterload or intrinsic myocardial disease. The aim of the study was to assess the reactivity of pulmonary circulation to inhaled nitric oxide (iNO) and to evaluate its influence on RV function in SSc patients with elevated right ventricle systolic pressure (RVSP). In 60 SSc patients aged 24-73 (58 females, two males; 33 patients with limited SSc and 27 with diffuse SSc), echocardiographic examination with tissue Doppler echocardiography (TDE) was performed. RV function was measured by systolic (S) and early diastolic (E) velocity of tricuspid annulus by TDE. In patients with RVSP >45 mmHg, the reactivity of pulmonary circulation was assessed by iNO test. High-resolution computerized tomography (HRCT) was performed to assess the extent of pulmonary fibrosis. Of 14 SSc subjects with elevated RVSP (13 females, one male; RVSP 47-62 mmHg), positive reaction to iNO was observed in five (RVSP decreased from 51.6 ± 3.7 to 32.24 ± 2.3 mmHg); nine patients were not reactive (RVSP 53.5 ± 5.7 mmHg before iNO vs. 49.6 ± 6.7 mmHg). RV systolic function was decreased in patients with elevated RVSP as compared to the patients with normal pulmonary pressure (S velocity 13.2 ± 1.3 vs. 14.4 ± 1.6 cm/s, respectively, p < 0.05). Significant increase of RV systolic function during iNO test was found in reactive patients only (S velocity before iNO 12.8 ± 1.2 cm/s, during iNO 14.5 ± 1.5 cm/s, p < 0.01). RVSP decrease strongly correlated with S velocity increase (r = 0.95, p < 0.0001). Response to iNO was found only in limited form of SSc; diffuse SSc patients showed no response. Pulmonary fibrosis on HRCT was more frequent in subjects nonreactive to iNO (67% of patients) than in the reactive group (40% of patients). The reactivity of pulmonary circulation to iNO in SSc patients with elevated RVSP was found predominantly in limited form of the disease. Pulmonary fibrosis typical for diffuse SSc was more frequent in nonreactive subjects. Elevated pulmonary pressure plays an important role in RV systolic dysfunction. Pulmonary pressure decrease during iNO test leads to the improvement of RV systolic function. Therapy for right-heart failure in reactive SSc patients should be directed, if possible, at the decrease in pulmonary resistance.
系统性硬化症（SSc）约有 10%的患者并发肺动脉高压和右心室（RV）衰竭。影响肺循环对血管扩张剂反应性的因素尚不清楚，而血管反应性的检查对于确定治疗方案很重要，因为全身性给予口服血管扩张剂可能会在无反应者中引起严重的不良反应。SSc 中 RV 衰竭的机制尚不清楚，可能是由于 RV 后负荷增加或固有心肌疾病所致。本研究旨在评估吸入一氧化氮（iNO）对肺动脉循环的反应性，并评估其对 SSc 患者 RVSP 升高时 RV 功能的影响。在 60 名年龄为 24-73 岁的 SSc 患者（58 名女性，2 名男性；33 名局限型 SSc 患者和 27 名弥漫型 SSc 患者）中，进行了超声心动图检查和组织多普勒超声心动图（TDE）检查。通过 TDE 测量三尖瓣环的收缩（S）和早期舒张（E）速度来评估 RV 功能。在 RVSP >45mmHg 的患者中，通过 iNO 试验评估肺循环的反应性。进行高分辨率计算机断层扫描（HRCT）以评估肺纤维化的程度。在 14 名 RVSP 升高的 SSc 患者（13 名女性，1 名男性；RVSP 47-62mmHg）中，5 名患者对 iNO 有阳性反应（RVSP 从 51.6±3.7mmHg 降至 32.24±2.3mmHg）；9 名患者无反应（RVSP 在吸入 iNO 之前为 53.5±5.7mmHg，吸入 iNO 后为 49.6±6.7mmHg）。与肺动脉压正常的患者相比，RVSP 升高的患者 RV 收缩功能降低（S 速度分别为 13.2±1.3cm/s 和 14.4±1.6cm/s，p<0.05）。仅在有反应的患者中发现 RV 收缩功能在 iNO 试验期间显著增加（吸入 iNO 前的 S 速度为 12.8±1.2cm/s，吸入 iNO 期间为 14.5±1.5cm/s，p<0.01）。RVSP 下降与 S 速度增加呈强烈相关性（r=0.95，p<0.0001）。仅在局限型 SSc 中发现对 iNO 的反应；弥漫型 SSc 患者无反应。对 iNO 无反应的患者 HRCT 显示肺纤维化更常见（67%的患者），而在有反应的患者中则较少见（40%的患者）。在 RVSP 升高的 SSc 患者中，对 iNO 的肺循环反应主要发生在局限型疾病中。弥漫型 SSc 中更常见的是典型的肺纤维化，对 iNO 无反应。升高的肺压在 RV 收缩功能障碍中起重要作用。iNO 试验期间肺压下降可改善 RV 收缩功能。如果可能的话，应针对反应性 SSc 患者的右心衰竭进行降低肺阻力的治疗。
