Background/Purpose

In pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc), no study has yet evaluated the correlation between the 6-minute walking test (6MWT) distance and the right-heart catheterization (RHC) hemodynamic data. This is an important matter, since the 6MWT is used as an outcome measure in SSc-PAH clinical trials, and can be biased by various comorbidities caused by the systemic disease. In this work, we assessed whether there is a correlation between the 6MWT and the RHC parameters at baseline and during follow-up, in SSc-PAH patients without extensive interstitial lung disease (ILD).

Methods

Patients with definite SSc (according to ACR 1987 and/or Leroy criteria), RHC-proven pre-capillary PAH and no extensive ILD on thoracic CT or pulmonary function tests (PFT) were included. Several data were collected regarding the clinical status (age, sex, BMI, NYHA class, SSc subtype), the 6WMT (total distance, heart rate and ΔHR, SaO₂ and ΔSaO₂, Borg score), the RHC (mRAP, mPAP, sPAP, dPAP, cardiac index (CI), PVR, TPR, stroke volume), the PFT and the transthoracic echocardiography, at baseline and during follow-up. The correlation of the 6MWT total distance with each hemodynamic parameter was studied, both at baseline and during follow-up, by linear regression.

Results

The statistical analysis was primarily conducted on a derivation cohort (83 patients from the French National SSc-PAH prospective network), and then confirmed on an independent validation cohort (329 patients from the FDA CTD-PAH register).

At baseline

In the derivation cohort, the univariate analysis showed that the 6MWT total distance was significantly correlated with all the RHC parameters, especially mPAP (p=0.005) and CI (p=0.0001), and with the NYHA class (p<0.0001). In multivariate analysis, the 6WMT total distance was significantly and independently correlated with the CI (R²=0.21, p=0.0002) and NYHA classes 3&4 (R²=0.12, p=0.002). In this regression model, the hemodynamic status explained only 21% of the distance walked during the test, suggesting the important weight of the confounding comorbidities. Those results were confirmed in the validation cohort, in which a significant, but weaker, correlation with the CI was also found (R²=0.08, p=0.0001).

During follow-up

In the univariate analysis conducted on the derivation cohort, the Δ6MWT total distance was non-significantly and weakly correlated with ΔmPAP (r = -0.20, p = 0.15) and with ΔPVR (r = -0.17, p = 0.22). Similar results were found on the validation cohort, but reached statistical significance (ΔmPAP : r = -0.20, p = 0.03 ; ΔPVR : r = -0.29, p= 0.008). There were no correlation between Δ6MWT total distance and ΔCI in both cohorts.

Conclusion

To our knowledge, this study is the first to prove a correlation between the baseline 6MWT total distance and the RHC hemodynamic parameters, in SSc-PAH patients without extensive ILD. As the CI explains only 8-21% of the distance, the weight of confounding comorbidities remains important in this test. During follow-up, a weak correlation persists between Δ6MWT and ΔmPAP, but not with ΔCI. These results question the relevance of the 6MWT as an outcome measure for SSc-PAH patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/relevance-of-the-6-minute-walking-test-in-assessing-the-severity-and-outcome-of-pulmonary-arterial-hypertension-associated-with-systemic-sclerosis-without-extensive-interstitial-lung-disease/