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Schoindre, et al: Walking test in SSc
Personal non-commercial use only. The Journal of Rheumatology Copyright © 2009. All rights reserved.
Lack of Specificity of the 6-Minute Walk Test as an
Outcome Measure for Patients with Systemic Sclerosis
YOLAND SCHOINDRE, CHRISTOPHE MEUNE, ANH TUAN DINH-XUAN, JÉRÔME AVOUAC, ANDRÉ KAHAN,
and YANNICK ALLANORE
ABSTRACT. Objective. The 6-minute walk test (6MWT) is an important prognostic tool in various cardiovascu-
lar diseases and has been considered as a surrogate endpoint. However, conflicting results have been
reported in systemic sclerosis (SSc). Our objective was to evaluate the relationships of the 6-min
walking distance (6MWD) and organ damage in SSc.
Methods. Eighty-seven consecutive patients with SSc were included and prospectively investigated;
they underwent 6MWT in addition to conventional assessment of possible lung, heart, kidney, skin,
and muscle involvement, and disease activity scoring, severity, and quality of life determination.
Results. Twenty-six patients (30%) had an abnormal 6MWT and the mean 6MWD was 461.8 ±
103.0 m. When considering 6MWT as a binary variable — normal or abnormal — C-reactive pro-
tein (CRP) was the only independent variable associated with abnormal 6MWT. Considered as a
continuous variable, the 6MWD was associated with measures of lung involvement and inflamma-
tion, with the activity and severity of disease, and also with quality of life; nevertheless, calcinosis
was the only independent factor associated in multivariate analyses with a trend for an association
for CRP.
Conclusion. The 6MWD relates to broad factors in SSc and these results raise doubts about the
specificity of the 6MWD in this systemic disease, and its relevance to monitoring therapy. (First
Release June 1 2009; J Rheumatol 2009;36:1481–5; doi:10.3899/jrheum.081221)
Key Indexing Terms:
6-MINUTE WALK TEST EXERCISE TESTING
PULMONARY HYPERTENSION SYSTEMIC SCLEROSIS
From Université Paris Descartes, Service de Rhumatologie A,
Département de Cardiologie, and Service Physiologie et Explorations
Fonctionnelles, Hôpital Cochin, AP-HP, Paris, France.
Y. Schoindre, Fellow, Service de Rhumatologie A; C. Meune, MD, PhD,
Département de Cardiologie; A.T. Dinh-Xuan, MD, PhD, Service
Physiologie et Explorations Fonctionnelles; J. Avouac, MD; A. Kahan,
MD, PhD; Y. Allanore, MD, PhD, Université Paris Descartes, Service de
Rhumatologie A, Hôpital Cochin, AP-HP.
Address reprint requests to Dr. Y. Allanore, Service de Rhumatologie A,
Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France.
E-mail: yannick.allanore@cch.aphp.fr
Accepted for publication February 12, 2009.
Systemic sclerosis (SSc) is a heterogeneous connective tis-
sue disorder characterized by widespread vascular lesions
that culminates in fibrosis of the skin, vessels, and internal
organs. Pulmonary and cardiac involvements have emerged
as the leading causes of disease-related mortality
1
. In partic-
ular, pulmonary arterial hypertension (PAH) is a devastating
condition recognized as a major complication of SSc that is
responsible for excessive disability and mortality
2
.
Therefore, early detection and management of PAH, and
accurate methods of assessment of the efficacy of therapeu-
tics are required. Despite the availability of several new
drugs, outcome measures remain poorly defined and often
poorly validated in the domain of SSc-related PAH
(PAH-SSc)
3
.
The 6-minute walk test (6MWT) is a simple, safe, repro-
ducible test used in the evaluation of several moderate to
severe heart or lung diseases like primary PAH, idiopathic
pulmonary fibrosis (IPF), chronic obstructive pulmonary
disease, and congestive heart failure
4-6
. This test is the most
widely used as a primary outcome to assess therapeutic effi-
cacy in PAH clinical trials
1,7-10
and the only measure of
exercise capacity accepted by the U.S. Food and Drug
Administration. The 6MWT was shown to be an independ-
ent predictor of mortality and a reliable tool for the assess-
ment of exercise capacity in patients with idiopathic PAH.
However, the 6MWT is not yet validated in the specific sit-
uation of PAH related to connective tissue diseases (CTD),
particularly SSc. This is emphasized in the majority of stud-
ies, which included a majority of patients with idiopathic
PAH and small nested subgroups of patients with PAH relat-
ed to CTD. A recent metaanalysis of randomized controlled
trials from our group has shown that new oral PAH treat-
ments are less effective in improving exercise capacity in
subsets of patients with CTD than in other patients, with
nonsignificant effect sizes for exercise capacity. This point
raised the question of the real efficacy of these drugs and/or
the relevance of the 6MWT for the evaluation of treatment
effect in PAH-SSc
11
.
To date, no attempt has been made to investigate what is
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