Sébastien Sanges1, David Launay1, Rennie L Rhee2, Olivier Sitbon3, Éric Hachulla1, Luc Mouthon4, Loïc Guillevin4, Laurence Rottat3, David Montani3, Pascal De Groote5, Vincent Cottin6, Pascal Magro7, Grégoire Prévot8, Fabrice Bauer9, Emmanuel Bergot10, Céline Chabanne11, Martine Reynaud-Gaubert12, Sylvie Leroy13, Matthieu Canuet14, Olivier Sanchez15, Christophe Gut-Gobert16, Claire Dauphin17, Christophe Pison18, Clément Boissin19, Gilbert Habib20, Pierre Clerson21, François Conesa21, Jean-François Cordier22, Steven M Kawut2, Gerald Simonneau3, Marc Humbert3. 1. 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. 2. Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. 3. Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France INSERM U999, Centre Chirurgical Marie-Lannelongue, LabEx LERMIT, Le Plessis-Robinson, France. 4. Service de Médecine Interne, Centre de Référence des Vascularites Nécrosantes et de la Sclérodermie Systémique, Université Paris Descartes, Hôpital Cochin, Paris, France. 5. Université de Lille, UFR Médecine, Lille, France Pôle Cardio-Vasculaire et Pulmonaire, Clinique de Cardiologie, CHRU de Lille, Lille, France. 6. Service de Pneumologie, Hospices Civils de Lyon, Centre de Compétence de l'Hypertension Pulmonaire, Centre de Référence des Maladies Pulmonaires Rares, Lyon, France. 7. Service de Pneumologie, Centre Hospitalier Régional Universitaire, Tours, France. 8. Pôle des Voies Respiratoires, Hôpital Larrey, Centre Hospitalier Universitaire, Toulouse, France. 9. Service de Cardiologie, Hôpital Charles Nicolle, Centre Hospitalier Universitaire, Rouen, France. 10. Service de Pneumologie, Centre Hospitalier Universitaire Côte-de-Nacre, Caen, France. 11. Service de Chirurgie Thoracique et Cardiovasculaire, Centre Hospitalier Universitaire Pontchaillou, Université de Rennes I, Rennes, France. 12. Service de Pneumologie, Centre Hospitalier Universitaire Nord, APHM, Université de la Méditerranée, Marseille, France. 13. Service de Pneumologie, Hôpital Pasteur, Centre Hospitalier Universitaire, Université de Nice Sophia Antipolis, Nice, France. 14. Service de Pneumologie, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France. 15. AP-HP, Service de Pneumologie et Soins Intensifs, Université Paris Descartes, Hôpital Européen Georges-Pompidou, INSERM UMR-S 1140, Paris, France. 16. Service de Médecine Interne et Pneumologie, Centre Hospitalier Universitaire La Cavale Blanche, Brest, France. 17. Service de Cardiologie et Maladies Vasculaires, Hôpital Gabriel Montpied, Centre Hospitalier Universitaire, Clermont-Ferrand, France. 18. Clinique Universitaire de Pneumologie, Centre Hospitalier Universitaire, Grenoble, France Université Joseph Fourier, Grenoble, France. 19. Service des Maladies Respiratoires, Hôpital Arnaud-de-Villeneuve, Centre Hospitalier Universitaire, Montpellier, France. 20. Service de Cardiologie, Hôpital de la Timone, Centre Hospitalier Universitaire, Marseille, France. 21. Soladis Clinical Studies, Biostatistics, Roubaix, France. 22. Pôle Cardio-Vasculaire et Pulmonaire, Clinique de Cardiologie, CHRU de Lille, Lille, France.
Abstract
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) (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. 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
RCT Entities:
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) (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. 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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