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A prospective study of the 6 min walk test as a surrogate marker for haemodynamics in two independent cohorts of treatment-naïve systemic sclerosis-associated pulmonary arterial hypertension
  1. Sébastien Sanges1,2,3,4,
  2. David Launay1,2,3,4,
  3. Rennie L Rhee5,
  4. Olivier Sitbon6,7,8,
  5. Éric Hachulla1,2,3,4,
  6. Luc Mouthon9,
  7. Loïc Guillevin9,
  8. Laurence Rottat6,7,8,
  9. David Montani6,7,8,
  10. Pascal De Groote1,10,
  11. Vincent Cottin11,
  12. Pascal Magro12,
  13. Grégoire Prévot13,
  14. Fabrice Bauer14,
  15. Emmanuel Bergot15,
  16. Céline Chabanne16,
  17. Martine Reynaud-Gaubert17,
  18. Sylvie Leroy18,
  19. Matthieu Canuet19,
  20. Olivier Sanchez20,
  21. Christophe Gut-Gobert21,
  22. Claire Dauphin22,
  23. Christophe Pison23,24,
  24. Clément Boissin25,
  25. Gilbert Habib26,
  26. Pierre Clerson27,
  27. François Conesa27,
  28. Jean-François Cordier10,
  29. Steven M Kawut5,
  30. Gerald Simonneau6,7,8,
  31. Marc Humbert6,7,8
  1. 1Université de Lille, UFR Médecine, Lille, France
  2. 2Département de Médecine Interne et Immunologie Clinique, CHRU Lille, Pôle Spécialités Médicales et Gérontologie, Lille Cedex, France
  3. 3Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), Lille Cedex, France
  4. 4LIRIC, INSERM UMR 995, EA2686, Lille, France
  5. 5Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
  6. 6Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France
  7. 7AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
  8. 8INSERM U999, Centre Chirurgical Marie-Lannelongue, LabEx LERMIT, Le Plessis-Robinson, France
  9. 9Service de Médecine Interne, Centre de Référence des Vascularites Nécrosantes et de la Sclérodermie Systémique, Université Paris Descartes, Hôpital Cochin, Paris, France
  10. 10Pôle Cardio-Vasculaire et Pulmonaire, Clinique de Cardiologie, CHRU de Lille, Lille, France
  11. 11Service de Pneumologie, Hospices Civils de Lyon, Centre de Compétence de l'Hypertension Pulmonaire, Centre de Référence des Maladies Pulmonaires Rares, Lyon, France
  12. 12Service de Pneumologie, Centre Hospitalier Régional Universitaire, Tours, France
  13. 13Pôle des Voies Respiratoires, Hôpital Larrey, Centre Hospitalier Universitaire, Toulouse, France
  14. 14Service de Cardiologie, Hôpital Charles Nicolle, Centre Hospitalier Universitaire, Rouen, France
  15. 15Service de Pneumologie, Centre Hospitalier Universitaire Côte-de-Nacre, Caen, France
  16. 16Service de Chirurgie Thoracique et Cardiovasculaire, Centre Hospitalier Universitaire Pontchaillou, Université de Rennes I, Rennes, France
  17. 17Service de Pneumologie, Centre Hospitalier Universitaire Nord, APHM, Université de la Méditerranée, Marseille, France
  18. 18Service de Pneumologie, Hôpital Pasteur, Centre Hospitalier Universitaire, Université de Nice Sophia Antipolis, Nice, France
  19. 19Service de Pneumologie, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France
  20. 20AP-HP, Service de Pneumologie et Soins Intensifs, Université Paris Descartes, Hôpital Européen Georges-Pompidou, INSERM UMR-S 1140, Paris, France
  21. 21Service de Médecine Interne et Pneumologie, Centre Hospitalier Universitaire La Cavale Blanche, Brest, France
  22. 22Service de Cardiologie et Maladies Vasculaires, Hôpital Gabriel Montpied, Centre Hospitalier Universitaire, Clermont-Ferrand, France
  23. 23Clinique Universitaire de Pneumologie, Centre Hospitalier Universitaire, Grenoble, France
  24. 24Université Joseph Fourier, Grenoble, France
  25. 25Service des Maladies Respiratoires, Hôpital Arnaud-de-Villeneuve, Centre Hospitalier Universitaire, Montpellier, France
  26. 26Service de Cardiologie, Hôpital de la Timone, Centre Hospitalier Universitaire, Marseille, France
  27. 27Soladis Clinical Studies, Biostatistics, Roubaix, France
  1. Correspondence to Professor David Launay, Service de Médecine Interne, Hôpital Claude-Huriez, CHRU Lille, Rue Michel Polonovski, LILLE Cedex F-59037, France; david.launay{at}


Objectives 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.

Methods 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.

Results 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.

Conclusions 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.

  • Systemic Sclerosis
  • Arterial Hypertension
  • Outcomes research
  • Autoimmune Diseases

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