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.
OBJECTIVE
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.
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.
Sébastien
S
Sanges
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.
David
D
Launay
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Rennie L
RL
Rhee
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.
Olivier
O
Sitbon
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.
Éric
É
Hachulla
Service de Médecine Interne, Centre de Référence des Vascularites Nécrosantes et de la Sclérodermie Systémique, Université Paris Descartes, Hôpital Cochin, Paris, France.
Luc
L
Mouthon
Service de Médecine Interne, Centre de Référence des Vascularites Nécrosantes et de la Sclérodermie Systémique, Université Paris Descartes, Hôpital Cochin, Paris, France.
Loïc
L
Guillevin
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.
Laurence
L
Rottat
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.
David
D
Montani
Université de Lille, UFR Médecine, Lille, France Pôle Cardio-Vasculaire et Pulmonaire, Clinique de Cardiologie, CHRU de Lille, Lille, France.
Pascal
P
De Groote
Service de Pneumologie, Hospices Civils de Lyon, Centre de Compétence de l'Hypertension Pulmonaire, Centre de Référence des Maladies Pulmonaires Rares, Lyon, France.
Vincent
V
Cottin
Service de Pneumologie, Centre Hospitalier Régional Universitaire, Tours, France.
Pascal
P
Magro
Pôle des Voies Respiratoires, Hôpital Larrey, Centre Hospitalier Universitaire, Toulouse, France.
Grégoire
G
Prévot
Service de Cardiologie, Hôpital Charles Nicolle, Centre Hospitalier Universitaire, Rouen, France.
Fabrice
F
Bauer
Service de Pneumologie, Centre Hospitalier Universitaire Côte-de-Nacre, Caen, France.
Emmanuel
E
Bergot
Service de Chirurgie Thoracique et Cardiovasculaire, Centre Hospitalier Universitaire Pontchaillou, Université de Rennes I, Rennes, France.
Céline
C
Chabanne
Service de Pneumologie, Centre Hospitalier Universitaire Nord, APHM, Université de la Méditerranée, Marseille, France.
Martine
M
Reynaud-Gaubert
Service de Pneumologie, Hôpital Pasteur, Centre Hospitalier Universitaire, Université de Nice Sophia Antipolis, Nice, France.
Sylvie
S
Leroy
Service de Pneumologie, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France.
Matthieu
M
Canuet
AP-HP, Service de Pneumologie et Soins Intensifs, Université Paris Descartes, Hôpital Européen Georges-Pompidou, INSERM UMR-S 1140, Paris, France.
Olivier
O
Sanchez
Service de Médecine Interne et Pneumologie, Centre Hospitalier Universitaire La Cavale Blanche, Brest, France.
Christophe
C
Gut-Gobert
Service de Cardiologie et Maladies Vasculaires, Hôpital Gabriel Montpied, Centre Hospitalier Universitaire, Clermont-Ferrand, France.
Claire
C
Dauphin
Clinique Universitaire de Pneumologie, Centre Hospitalier Universitaire, Grenoble, France Université Joseph Fourier, Grenoble, France.
Christophe
C
Pison
Service des Maladies Respiratoires, Hôpital Arnaud-de-Villeneuve, Centre Hospitalier Universitaire, Montpellier, France.
Clément
C
Boissin
Service de Cardiologie, Hôpital de la Timone, Centre Hospitalier Universitaire, Marseille, France.
Gilbert
G
Habib
Soladis Clinical Studies, Biostatistics, Roubaix, France.
Pierre
P
Clerson
Soladis Clinical Studies, Biostatistics, Roubaix, France.
François
F
Conesa
Pôle Cardio-Vasculaire et Pulmonaire, Clinique de Cardiologie, CHRU de Lille, Lille, France.
Jean-François
JF
Cordier
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Steven M
SM
Kawut
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.
Gerald
G
Simonneau
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.
Marc
M
Humbert
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D006328:Cardiac Catheterization; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results; D012595:Scleroderma, Systemic / Q000150:complications* / Q000453:epidemiology; D000070857:Walk Test / Q000379:methods*
D000959:Antihypertensive Agents
Arterial Hypertension; Autoimmune Diseases; Outcomes research; Systemic Sclerosis