Sanges S1, Launay D1, Rhee RL2, Sitbon O3, Hachulla É1, Mouthon L4, Guillevin L4, Rottat L3, Montani D3, De Groote P5, Cottin V6, Magro P7, Prévot G8, Bauer F9, Bergot E10, Chabanne C11, Reynaud-Gaubert M12, Leroy S13, Canuet M14, Sanchez O15, Gut-Gobert C16, Dauphin C17, Pison C18, Boissin C19, Habib G20, Clerson P21, Conesa F21, Cordier JF22, Kawut SM2, Simonneau G3, Humbert M3.
Study of the validity of a 6 min walk test in pulmonary arterial hypertension
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) (R2=0.19, p=0.001) and New York Heart Association class (R2=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 (R2=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.
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Arterial Hypertension; Autoimmune Diseases; Outcomes research; Systemic Sclerosis