Université de Lille, UFR Médecine, Lille, France Département de Médecine Interne et Immunologie Clinique, CHRU Lille, Pôle Spécialités Médicales et Gérontologie, Lille Cedex, France Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), Lille Cedex, France LIRIC, INSERM UMR 995, EA2686, Lille, France.
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ann Rheum Dis. 2016 Aug;75(8):1457-65. doi: 10.1136/annrheumdis-2015-207336. Epub 2015 Aug 31.
Despite the wide use of the 6 min walk distance (6MWD), no study has ever assessed its validity as a surrogate marker for haemodynamics and predictor of outcome in isolated pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH). We designed this work to address this issue.
Treatment-naïve patients with SSc-PAH were prospectively included from two sources: the French PAH Network (a prospective epidemiological cohort) (n=83) and randomised clinical trials submitted for drug approval (Food and Drug Administration) (n=332). Correlations between absolute values of the 6MWD and haemodynamics at baseline, as well as between variations of 6MWD and haemodynamics during follow-up, were studied in both populations.
In the French cohort, baseline cardiac output (CO) (R(2)=0.19, p=0.001) and New York Heart Association class (R(2)=0.10, p<0.001) were significantly and independently correlated with baseline 6MWD in multivariate analysis. A significant, independent, but weaker, correlation with CO was also found in the Food and Drug Administration sample (R(2)=0.04, p<0.001). During follow-up, there was no association between the changes in 6MWD and haemodynamic parameters in patients under PAH-specific treatments.
In SSc-PAH, CO independently correlates with 6MWD at baseline, but accounts for a small amount of the variance of 6MWD in both study samples. This suggests that other non-haemodynamic factors could have an impact on the walk distance. Moreover, variations of 6MWD do not reflect changes in haemodynamics among treated patients. Our results suggest that 6MWD is not an accurate surrogate marker for haemodynamic severity, nor an appropriate outcome measure to assess changes in haemodynamics during follow-up in treated SSc-PAH.
尽管 6 分钟步行距离（6MWD）的应用非常广泛，但尚无研究评估其作为血流动力学替代标志物以及预测与系统性硬化症相关的孤立性肺动脉高压（SSc-PAH）的预后的有效性。我们设计了这项工作来解决这个问题。
从两个来源前瞻性纳入未经治疗的 SSc-PAH 患者：法国肺动脉高压网络（一项前瞻性流行病学队列研究）（n=83）和提交药物批准（美国食品和药物管理局）的随机临床试验（n=332）。在这两个群体中，研究了基线时 6MWD 的绝对值与血流动力学之间的相关性，以及随访期间 6MWD 的变化与血流动力学之间的相关性。
在法国队列中，多变量分析显示，基线时心输出量（CO）（R2=0.19，p=0.001）和纽约心脏协会（NYHA）分级（R2=0.10，p<0.001）与基线 6MWD 显著且独立相关。在 FDA 样本中也发现了与 CO 显著但较弱的独立相关性（R2=0.04，p<0.001）。在接受肺动脉高压特异性治疗的患者中，随访期间 6MWD 的变化与血流动力学参数之间没有关联。
在 SSc-PAH 中，CO 与基线时的 6MWD 独立相关，但在两个研究样本中，6MWD 的变异性仅占很小一部分。这表明其他非血流动力学因素可能会对步行距离产生影响。此外，6MWD 的变化并不能反映治疗患者的血流动力学变化。我们的研究结果表明，6MWD 不是血流动力学严重程度的准确替代标志物，也不是评估治疗后 SSc-PAH 随访期间血流动力学变化的合适指标。
