Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Pulm Circ. 2015 Mar;5(1):3-14. doi: 10.1086/679607.
Pulmonary arterial hypertension (PAH) results from severe remodeling of the distal lung vessels leading irremediably to death through right ventricular (RV) failure. PAH (Group 1 of the World Health Organization classification of pulmonary hypertension) can be idiopathic (IPAH) or associated with other disorders, such as connective tissue diseases. Prominent among the latter is systemic sclerosis (SSc), a heterogeneous disorder characterized by endothelium dysfunction, dysregulation of fibroblasts resulting in excessive collagen production, and immune abnormalities. For as-yet-unknown reasons, SSc-associated PAH (SSc-PAH) carries a significantly worse prognosis compared with any other form of PAH in Group 1, including IPAH. We have previously shown that patients with SSc-PAH have a median survival of only 3 years, compared with 8 years for IPAH, despite modern PAH therapy. Because death is principally due to RV failure, we speculated that RV adaptation to PAH differed between the two entities due to disparate pulmonary artery loading, perhaps from vessel stiffening, or intrinsic RV myocardial disease that might limit function and adaptation to high afterload. In SSc, RV function may also be impaired by inflammatory processes, excess fibrosis of the myocardium, or altered angiogenesis, which may all contribute to impaired contractile reserve exacerbating cardiopulmonary impedance mismatch. This is now suggested by recent findings from our group that demonstrate that, although pulmonary vascular load may be similar between patients with IPAH and those with SSc-PAH, the latter display reduced myocardial contractility as assessed by pressure-volume loop measurements. This review focuses on fundamental hemodynamic, structural, and functional differences in RV from patients with SSc-PAH compared with IPAH, which may account for survival discrepancies between the two populations. Possible underlying basic mechanisms are discussed.
肺动脉高压（PAH）是由远端肺血管严重重构引起的，最终会导致右心室（RV）衰竭而无法治愈。PAH（世界卫生组织肺动脉高压分类的第 1 组）可以是特发性的（IPAH）或与其他疾病相关，如结缔组织疾病。后者的突出代表是系统性硬化症（SSc），这是一种异质性疾病，其特征为内皮功能障碍、成纤维细胞失调导致胶原过度产生以及免疫异常。由于未知原因，SSc 相关的 PAH（SSc-PAH）与第 1 组中的任何其他形式的 PAH（包括 IPAH）相比，预后明显更差。我们之前已经表明，与 IPAH 相比，SSc-PAH 患者的中位生存时间仅为 3 年，尽管接受了现代 PAH 治疗。由于死亡主要是由于 RV 衰竭，我们推测两种实体的 RV 对 PAH 的适应不同，这是由于肺动脉加载的差异，可能是由于血管僵硬，或可能限制功能和对高后负荷的适应的 RV 心肌疾病。在 SSc 中，RV 功能也可能因炎症过程、心肌过度纤维化或血管生成改变而受损，这些都可能导致收缩储备受损，从而加剧心肺阻抗不匹配。这一点现在可以从我们小组的最新发现中得到证实，这些发现表明，尽管 IPAH 和 SSc-PAH 患者的肺血管负荷可能相似，但后者的压力-容积环测量显示心肌收缩力降低。这篇综述重点介绍了与 IPAH 相比，SSc-PAH 患者的 RV 在基本血流动力学、结构和功能方面的差异，这些差异可能是两种人群之间生存差异的原因。还讨论了可能的潜在基本机制。
