A prospective study of the 6 min walk test as a surrogate marker for haemodynamics in two independent cohorts of treatment-naive systemic sclerosis-associated pulmonary arterial hypertension
Pascal de Groote
(1)
,
Vincent Cottin
(2, 3)
,
Pascal Magro
,
Gregoire Prevot
,
Fabrice Bauer
(4)
,
Emmanuel Bergot
(5)
,
Céline Chabanne
(6, 7)
,
Martine Reynaud-Gaubert
(8, 9)
,
Sylvie Leroy
(10)
,
Matthieu Canuet
(11)
,
Olivier Sanchez
(12)
,
Christophe Gut-Gobert
(13)
,
Claire Dauphin
(14)
,
Christophe Pison
(15, 16, 17)
,
Clement Boissin
,
Gilbert Habib
(18, 8)
,
Pierre Clerson
(19)
,
Francois Conesa
,
Jean-François Cordier
(20)
,
Steven M. Kawut
,
Gérald Simonneau
(21, 22, 23)
,
Marc Humbert
(21, 22, 23)
,
Sebastien Sanges
,
David Launay
(1, 24, 25)
,
Rennie L. Rhee
,
Olivier Sitbon
(21, 23, 22)
,
Eric Hachulla
(26)
,
Luc Mouthon
(27)
,
Loïc Guillevin
(27)
,
Laurence Rottat
,
David Montani
(21, 22, 23)
1
CHRU Lille -
Centre Hospitalier Régional Universitaire [CHU Lille]
2 UCBL - Université Claude Bernard Lyon 1
3 Service de Pneumologie
4 Service de Cardiologie [CHU Rouen]
5 Service de pneumologie [CHU Caen]
6 LTSI - Laboratoire Traitement du Signal et de l'Image
7 Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes]
8 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
9 Hôpital Nord [CHU - APHM]
10 NICE - Pneumo - Service de Pneumologie
11 Service de pneumologie (Strasbourg)
12 HEGP - Hôpital Européen Georges Pompidou [APHP]
13 DMIP - Brest - Département de Médecine Interne et Pneumologie [Brest]
14 Service Médecine Interne - site Gabriel-Montpied [CHU Clermont-Ferrand]
15 LBFA - Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée
16 EISBM - European Institute for Systems Biology and Medicine
17 Clinique de pneumologie
18 Service de cardiologie
19 Orgamétrie biostatistiques
20 Hôpital Louis Pradel [CHU - HCL]
21 DHU TORINO - Service de Pneumologie et Réanimation Respiratoire
22 HPPIT - Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique
23 UP11 - Université Paris-Sud - Paris 11
24 LIRIC - Lille Inflammation Research International Center - U 995
25 CREAK - Centre de référence des angiœdèmes à kinines
26 Service de médecine interne [Lille]
27 Service de médecine interne et centre de référence des maladies rares [CHU Cochin]
2 UCBL - Université Claude Bernard Lyon 1
3 Service de Pneumologie
4 Service de Cardiologie [CHU Rouen]
5 Service de pneumologie [CHU Caen]
6 LTSI - Laboratoire Traitement du Signal et de l'Image
7 Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes]
8 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
9 Hôpital Nord [CHU - APHM]
10 NICE - Pneumo - Service de Pneumologie
11 Service de pneumologie (Strasbourg)
12 HEGP - Hôpital Européen Georges Pompidou [APHP]
13 DMIP - Brest - Département de Médecine Interne et Pneumologie [Brest]
14 Service Médecine Interne - site Gabriel-Montpied [CHU Clermont-Ferrand]
15 LBFA - Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée
16 EISBM - European Institute for Systems Biology and Medicine
17 Clinique de pneumologie
18 Service de cardiologie
19 Orgamétrie biostatistiques
20 Hôpital Louis Pradel [CHU - HCL]
21 DHU TORINO - Service de Pneumologie et Réanimation Respiratoire
22 HPPIT - Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique
23 UP11 - Université Paris-Sud - Paris 11
24 LIRIC - Lille Inflammation Research International Center - U 995
25 CREAK - Centre de référence des angiœdèmes à kinines
26 Service de médecine interne [Lille]
27 Service de médecine interne et centre de référence des maladies rares [CHU Cochin]
Vincent Cottin
- Function : Author
- PersonId : 784269
- ORCID : 0000-0002-5591-0955
- IdRef : 166774731
Pascal Magro
- Function : Author
Gregoire Prevot
- Function : Author
Olivier Sanchez
- Function : Author
- PersonId : 958673
- ORCID : 0000-0003-1633-8391
- IdRef : 123454395
Christophe Pison
- Function : Author
- PersonId : 766182
- ORCID : 0000-0002-2152-6461
- IdRef : 066846692
Clement Boissin
- Function : Author
Gilbert Habib
- Function : Author
- PersonId : 757774
- ORCID : 0000-0003-3899-9983
- IdRef : 060822791
Francois Conesa
- Function : Author
Steven M. Kawut
- Function : Author
Marc Humbert
- Function : Author
- PersonId : 756837
- ORCID : 0000-0003-0703-2892
- IdRef : 071559426
Sebastien Sanges
- Function : Author
David Launay
- Function : Author
- PersonId : 760551
- ORCID : 0000-0003-1840-1817
- IdRef : 073349364
Rennie L. Rhee
- Function : Author
Eric Hachulla
- Function : Author
- PersonId : 1366882
- ORCID : 0000-0001-7432-847X
- IdRef : 031788866
Luc Mouthon
- Function : Author
- PersonId : 1330915
- ORCID : 0000-0002-9838-246X
- IdRef : 069140634
Loïc Guillevin
- Function : Author
- PersonId : 1171608
- ORCID : 0000-0001-6463-2160
- IdRef : 028285840
Laurence Rottat
- Function : Author
David Montani
- Function : Author
- PersonId : 765451
- ORCID : 0000-0002-9358-6922
- IdRef : 092632580
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-naive 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.
