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ORIGINAL ARTICLE

Can the Six-Minute Walk Test Predict Peak Oxygen Uptake


in Men With Heart Transplant?
Stéphane Doutreleau, MD, PhD, Paola Di Marco, MD, Samy Talha, MD, Anne Charloux, MD, PhD,
François Piquard, PhD, Bernard Geny, MD, PhD
ABSTRACT. Doutreleau S, Di Marco P, Talha S, Charloux sedentary subjects.3-7 This can be, in part, explained by both
A, Piquard F, Geny B. Can the six-minute walk test predict central and peripheral limitation, leading to a reduced quality
peak oxygen uptake in men with heart transplant? Arch Phys of life in patients with heart transplant.8-12 Thus, cardiac dia-
Med Rehabil 2009;90:51-7. stolic dysfunction6 and chronotropic insufficiency10,13 on the
one hand and muscular11,14 and endothelial dysfunction15 on
Objective: To determine whether the six-minute walk test the other hand appear to be the main limiting factors of exercise
(6MWT) might predict peak oxygen consumption (VO2peak) capacity after heart transplantation.
after heart transplantation. Standardized laboratory maximal exercise test with oxygen
Design: Case-control prospective study. uptake measurement can, noninvasively and objectively, quan-
Setting: Public hospital. tify this limitation by measuring VT and VO2peak. Thus, a
Participants: Patients with heart transplant (n⫽22) and maximal cardiopulmonary exercise test is considered a crite-
age-matched sedentary male subjects (n⫽13). rion standard, used in order to prescribe appropriate and indi-
Interventions: Not applicable. vidualized physical rehabilitation, allowing a complete assess-
Main Outcome Measures: Exercise performance using a ment of all systems involved in exercise performance.16
maximal exercise test, distance walked using the 6MWT, heart However, laboratory tests of maximal exercise performance
rate, and VO2peak. require sophisticated equipment and specially trained people.
Results: Compared with controls, exercise performance was They are costly and time-consuming. Furthermore, these tests
decreased in patients with heart transplant with less distance are not always well accepted, and some participants may have
ambulated (516⫾13m vs 592⫾13m; P⬍.001) and a decrease difficulties achieving a maximal exercise test.
in mean VO2peak (23.3⫾1.3 vs 29.6⫾1mL·min⫺1·kg⫺1; Therefore, easier modalities to assess exercise capacities
P⬍.001). Patients with heart transplant showed an increased have been developed. Particularly, the 6MWT is the most
resting heart rate, a response delayed both at the onset of popular and commonly used submaximal exercise test. Indeed,
exercise and during recovery. However, the patient’s heart rate it is easy to perform, is well tolerated, and better reflects daily
at the end of the 6MWT was similar to that obtained at the life activities of the subjects than other walk tests.17 The
ventilatory threshold. The formula did not predict measured 6MWT can predict functional change resulting from disease
V̇O2, with a weak correlation observed between the six-minute progression or therapeutic intervention, morbidity and mortal-
walk distance and both VO2peak (r⫽.53; P⬍.01) and ventila- ity in heart18 or lung disease,19 and capacity in older, healthy,
tory threshold (r⫽.53; P⬍.01) after heart transplantation. In- sedentary people.20 The 6MWT can also be used to assess
terestingly, when body weight was considered, correlations functional exercise performance across various subjects like
coefficient increased to .74 and .77, respectively (P⬍.001). young21 or older, sedentary people,22 patients with heart fail-
Conclusions: In heart transplant recipients, the 6MWT is a ure,18,23,24 and patients with a wide variety of pulmonary
safe, practical, and submaximal functional test. The distance- alterations.25,26
weight product can be used as an alternative method for as- The 6MWT performance has previously been shown to be
sessing the functional capacity after heart transplantation but reduced in kidney transplant recipients.27 Interestingly, a weak
cannot totally replace maximal V̇O2 determination. but significant correlation between the 6MWD and the
Key Words: Exercise; Functional residual capacity; Reha- VO2peak has been reported in patients with heart18,28,29 or lung
bilitation; Transplantation. failure.19 But curiously, whereas this test is commonly used in
© 2009 by the American Congress of Rehabilitation patients with heart failure needing cardiac transplantation,30
Medicine data on the 6MWT characteristics and usefulness in heart
transplant recipients are lacking.
LTHOUGH BOTH FUNCTIONAL status and exercise The main objective of the present investigation was therefore
A performance progressively increase during the first 2 years
1,2
after surgery, patients with heart transplant still present low
to determine whether the 6MWT could predict VO2peak in
patients with heart transplant. Other objectives were to deter-
activity level and exercise capacity compared with matched mine whether the 6MWT is a submaximal or a maximal exer-
cise test, and to compare the VO2peak predicted by formula
with the measured VO2peak after heart transplantation.

From the Physiology Institute, Medicine Faculty and Hospital, University Hospital List of Abbreviations
of Strasbourg, Strasbourg, France.
No commercial party having a direct financial interest in the results of the research 6MWD six-minute walk distance
supporting this article has or will confer a benefit on the authors or on any organi-
6MWT six-minute walk test
zation with which the authors are associated.
Reprint requests to Stéphane Doutreleau, MD, PhD, Service de Physiologie et SEM standard error of the mean
d’Explorations Fonctionnelles, 1 place de l’hôpital, 67000 Strasbourg, France, e-mail: V̇O2 oxygen uptake
stephane.doutreleau@chru-strasbourg.fr. VO2peak peak oxygen uptake
0003-9993/09/9001-00167$36.00/0 VT ventilatory threshold
doi:10.1016/j.apmr.2008.07.010

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52 WALK TEST AFTER HEART TRANSPLANTATION, Doutreleau

Table 1: Resting Clinical, Hemodynamic, and Echocardiographic calibrated track. Standardized encouragements were given ev-
Characteristics of Both the Control Subjects and the Subjects ery minute. Before the test, patients rested in a chair, located
With Heart Transplant
near the starting position, for 10 minutes. After 6 minutes, the
Characteristics Control (n⫽13) Heart Transplant (n⫽22) distance walked was recorded to the nearest meter. Results are
Age (y) 57.70⫾1.50 56.00⫾1.70 expressed as actual distance walked in meters.
Height (cm) 179.20⫾1.10 174.50⫾1.30 Heart rate (b.min⫺1) and pulse oxygen saturation (%) were
BMI, (kg.m⫺2) 25.80⫾0.50 26.00⫾0.70 continuously measured before the walk, during the test, and
Heart rate (b.min⫺1) 73.00⫾3.20 95.10⫾2.40* during the first 5 minutes of recovery by using a lightweight
Blood pressure (mmHg) pulse oximetera on the finger.
Systolic 125.00⫾2.30 143.00⫾2.80* A reference equation for healthy adults33 was used to com-
Diastolic 81.00⫾1.50 88.00⫾1.70† pute the percent predicted of 6MWD for individual adult pa-
EF (%) 65.00⫾3.00 64.00⫾2.00 tients with the following formula:
E/A ratio 1.55⫾0.08 1.49⫾0.09
6MWD (m) ⫽ [7.57 ⫻ height(cm)] ⫺ [1.76 ⫻ weight(kg)]
Abbreviations: BMI, body mass index; E/A, ratio of peak early (E) and
late (A) transmitral filling velocities; EF, ejection fraction. ⫺ [5.02 ⫻ age(y)] ⫺ 309
Differences between groups: *P⬍.001; †P⫽.01.
Predicted VO2peak from the 6MWT was calculated by using
the following formula from Cahalin et al:18

METHODS VO2peak (mL · min⫺1) ⫽ [0.03 ⫻ 6MWD (m) ⫹ 3.98]


Because the body weight of the patient directly affects the
Participants work/energy required to perform the walk, whereas it is of
The study was carried out between January 2005 and May minor importance during cycling exercise, we used the body
2006. During this period, the chirurgical team transplanted 8 weight-walking distance (body weight ⫻ walking distance)
patients. Eight heart transplant recipients were excluded: 3 product to assess the walking capacity of the subject (6-minute
refused to perform a maximal exercise test, and 5 were enrolled walk work ⫽ kg.m).34-36
in exercise rehabilitation or in sport. Twenty-two male seden- We also compared the 6MWD ⫻ body weight product to the
tary patients with heart transplant, at least 6 months since maximal workload (maximal power tolerated), the oxygen up-
transplant, in sinus rhythm, and clinically stable (free of rejec- take on the VT, and the VO2peak reached during the maximal
tion with no sign of heart failure and without cardiac allograft bicycle exercise test.
vasculopathy on the coronary arteriography) participated in the Maximal cardiopulmonary bicycle exercise test. All pa-
study. Thirteen healthy sedentary age-matched people served tients performed a symptom-limited exercise test in the upright
as controls. Patients with diabetes, pulmonary dysfunction, or position using an electronically braked bicycle ergometer.b The
conditions that might impair a successful completion of the protocol was the same for all patients, and after a warm-up on
6MWT or of the maximal exercise test, such as orthopedic or the bicycle for 3 minutes at 30W, exercise workload was
muscular problems, were excluded. All patients with heart trans- increased by 15W every minute. Exhaustion was defined as the
plant took their usual immunosuppressive therapy composed of inability to maintain the pedal frequency above 50rev/min
cyclosporine (189⫾12mg/d), prednisolone (6.9⫾0.8mg/d), and because of leg fatigue and/or dyspnea.
mycophenolate mofetil (909⫾170mg/d). All of them had a sys- Breath-by-breath V̇O2 (mL.min⫺1), carbon dioxide output
temic hypertension treated with angiotensin-converting enzyme (mL.min⫺1), and minute ventilation (L.min⫺1) were measured
inhibitor (n⫽15) and/or calcium antagonist (n⫽9), but none of throughout using a Vmax 229.c The system was calibrated
them took beta-blockers. before each test using known gas concentrations, and a 3-L
Clinical, hemodynamic, and echocardiographic characteris- calibrated syringe was used to ensure the accuracy of the
tics of the subjects are presented in table 1. Systolic and pneumotach.
diastolic left heart functions were obtained through the left Peak values of VO2 were averaged on the last 30 seconds of
ventricular ejection fraction and the mitral ratio of peak early the exercise test (VO2peak). The VT was manually determined
and late transmitral filling velocities, respectively, following by 2 blinded examiners, using the V-slope and ventilatory
the recommendations of the American Society of Echocardi- equivalents methods.37 The interobserver variability for VT
ography.31 All patients gave written informed consent, and the determination was 4.8⫾1.64%. VO2peak was compared with
study was approved by the hospital and university review board age/sex-adjusted peak oxygen uptake (peak % VO2).38
for human studies. Electrocardiographic activity was monitored continuously
using a standard 12-lead configuration,d and systemic arterial
Interventions blood pressure was registered every 2 minutes using a sphyg-
Both patients with heart transplant and control groups per- momanometer. Maximal exercise heart rate was defined as the
formed, 1 hour after a standardized meal, a 6MWT followed maximal value reach at the end of the test.
after a 2-hour resting period by a maximal upright bicycle
cardiopulmonary exercise test in a quiet air-conditioned room Statistical Analysis
(21°C). To avoid circadian variation, all exercise tests were Sigma-Stat Softwaree was used for statistical analysis. All
performed between 2 PM and 4 PM. data are presented as mean ⫾ standard error of the mean.
Differences between predicted V̇O2, 6MWD, and measured
Exercise Testing Protocol values were evaluated using paired t tests. For comparison of
Six-minute walk test. The 6MWT was coached by the chronotropic response between groups, a 2-way analysis of
same physicians, according to the American Thoracic Society variance with repeated measures was performed. When the F
recommendations.32 Briefly, patients were instructed to walk value indicated significant differences between means at dif-
the most distance possible in 6 minutes in a 13-m straight ferent time, a Student-Neman-Keuls test for multiple compar-

Arch Phys Med Rehabil Vol 90, January 2009


WALK TEST AFTER HEART TRANSPLANTATION, Doutreleau 53

isons was performed. A Pearson correlation analysis was used


to determine whether there was a significant association be-
tween the 6MWD and the 6-minute walk work with measured
VO2peak, maximal power tolerated, and VT. Correlation was
also determined between V̇O2 from predicted equations versus
the measured VO2peak. A P value less than .05 was considered
significant.
RESULTS
All 35 men completed the 6MWT and the cycle ergometry
with gas exchange. No complication occurred during both tests.
Resting Characteristics of the 2 Groups
The reason for cardiac transplantation was a dilated cardio-
myopathy for 14 and an ischemic cardiomyopathy for the other Fig 2. Chronotropic response at rest, exercise, and during the re-
covery period (R1 to R5). *P<.001 between heart transplant (black
8. The subjects were similar concerning their age and body point) and control groups (white point).
mass index. The delay between transplantation and the study
was 60.2⫾6.9 months, and the mean number of rejection
episodes was 1.3⫾0.2.
As expected, patients with heart transplant presented an 73.0⫾3.2b.min⫺1 and 123.4⫾3.0b.min⫺1 in the heart trans-
increased heart rate and blood pressure compared with control plant and control groups, respectively. Interestingly, despite
values. Both systolic and diastolic cardiac functions were in the reaching similar absolute values during exercise, the chrono-
normative range as inferred from the left ventricular ejection tropic response, calculated as peak heart rate minus resting
fraction and the mitral ratio of peak early and late transmitral heart rate, was significantly decreased in transplanted patients
filling velocities, respectively (see table 1). compared with the control group (28.4⫾2.9 and 50.4⫾2.8,
respectively; P⬍.001).
Distance Walked, Oxygen Saturation, and Heart Rate The peak heart rate reached during the 6MWT was similar to
Responses to the Six-Minute Walk Test the heart rate reached at the VT during the maximal exercise
The mean distance covered during the 6MWT was test, suggesting that the 6MWT is a submaximal test. It was
516.5⫾12.8m and 596.2⫾13.0m in patients with heart trans- significantly (P⬍.001) lower than the maximal heart rate (fig 3)
plant and control group, respectively (P⬍.001). When com- in both groups.
pared as a percentage of the predicted normative age-specific
and sex-specific values, patients with heart transplant presented Cardiorespiratory Responses to the Maximal Bicycle
with a significant (–14.7⫾2.5%; P⬍.001) reduction in the total Exercise Test
walk distance compared with the control group, which was in All patients also performed a maximal exercise test with an
normative range (– 0.2⫾2.2%) (fig 1). end-exercise respiratory exchange ratio of 1.16⫾0.03 and
Work for the 6MWT, calculated as the product of the walk 1.14⫾0.02 in the heart transplant and control groups, respec-
distance (m) ⫻ body weight (kg), was significantly reduced in tively. Patients stopped exercise because of leg fatigue (n⫽28)
patients with heart transplant compared with the control group or dyspnea (n⫽7). None of the exercise tests had to be termi-
(40,861.2⫾1883.1kg.m and 49,329.8⫾1447.8kg.m in patients nated prematurely because of an abnormal hemodynamic re-
with heart transplant and control group, respectively; P⫽.004). sponse. No subject had a ventilatory limitation. Ventilatory
Oxygen saturation remained unaltered throughout the walk reserves were 27.5⫾5.3% and 32.4⫾6.4% in heart transplant
and mean resting period and end-walking values were respec- and control subjects, respectively.
tively 97.3⫾0.2% and 97.2⫾0.1% in the 2 groups.
The chronotropic response is shown in figure 2. The heart
rate significantly increased during the walk test in the 2 groups
(P⬍.001). The mean resting and end-walking heart rate
values were 95.1⫾2.4b.min⫺1 and 123.5⫾2.8b.min⫺1 and

Fig 3. Comparison of heart rate measured at the end of the 6MWT


and during the incremental exercise test (IET) at the VT and at the
Fig 1. Distance walked in meters during the 6MWT in both control peak exercise both in the heart transplant (grey) and control groups
and heart transplant (HTx) groups. (white). Abbreviation: NS, not significant. *P<.001.

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54 WALK TEST AFTER HEART TRANSPLANTATION, Doutreleau

Table 2: Cycle Ergometry Gas Exchange Data on VT and at DISCUSSION


Peak Exercise
The main results of this study performed in heart transplant
Variables Controls (n⫽13) Heart Transplant (n⫽22) recipients are the following: (1) the 6MWT is a submaximal
VT test, safe, and easy to perform; (2) the VO2peak predicted by
Work (W) 116.3⫾8.5 92.7⫾3.9§ equations does not correspond well enough with the measured
V̇O2 VO2peak after heart transplantation; and (3) unlike the simple
mL.min⫺1.kg⫺1 17.9⫾0.7 15.7⫾0.6‡ distance walked, the weight-distance product (6-minute walk
% predicted 61.0⫾2.8 55.3⫾1.9 work) might be a useful approach of patients’ VO2peak after
VCO2 (mL.min⫺1) 1520.6⫾78.4 1179.3⫾63.9* heart transplantation.
SpO2 (%) 97.1⫾0.3 96.7⫾0.3
HR (beats.min⫺1) 126.1⫾4.3 128.8⫾2.3 Exercise Intolerance After Heart Transplantation
Peak exercise As expected, patients with heart transplant showed a tight
Work (W) 194.2⫾7.2 135.0⫾9.1† but significant reduction of their exercise capacity in both
Exercise time (min) 14.5⫾0.4 10.1⫾0.6† maximal bicycle exercise test (82.5⫾3.5% of the predicted
V̇O2 values) and 6MWT (88.7⫾2.5% of the predicted values) com-
mL.min⫺1.kg⫺1 29.6⫾1.0 23.3⫾1.3* pared with control values. After cardiac transplantation, central
% predicted 100.2⫾3.5 82.5⫾3.5* factors (cardiac diastolic dysfunction and cardiac denervation
VCO2 (mL.min⫺1) 2749.8⫾185.2 2130.1⫾144.6‡ resulting in chronotropic incompetence) and peripheral factors
V̇E (L.min⫺1) 94.2⫾15.5 79.3⫾4.4 such as endothelial and muscular dysfunctions (progressive
SpO2 (%) 96.7⫾0.3 96.1⫾0.5 reduction in muscular fibers, greater contribution of glycolytic
SBP (mmHg) 171.5⫾5.8 177.3⫾4.2 metabolism despite the oxidative one) likely contribute to the
DBP (mmHg) 85.1⫾3.6 93.7⫾2.1‡ reduced exercise capacity.4,10,39-42 The values of the VO2peak
HR (beats.min⫺1) 168.4⫾2.7 148.7⫾3.4† were greater than values found in the literature.1-3,6,7 Such a
difference could be explained, in part, by the inclusion of
Abbreviations: DBP, diastolic blood pressure; HR, heart rate; SBP, patients without cardiac allograft vasculopathy6 and only the
systolic blood pressure; SpO2, pulse oxygen saturation; V̇CO2, carbon
dioxide output; V̇E, minute ventilation. bicaval surgical technique.43
Differences between groups: *P⫽.002; †P⬍.001; ‡P⬍.05. In our well patients, it is unlikely that central factors have
played a significant limiting role. Indeed, both cardiac systolic
and diastolic functions were similar to those of control sub-
The heart transplant population presented with a moderate jects. The normative diastolic function in our population late
exercise capacity limitation compared with the age-matched after heart transplantation could probably be explained by the
control values (table 2). Overall, the mean VO2peak during inclusion of patients without cardiac allograft vasculopathy.6
cycle ergometry was 23.3⫾1mL.min⫺1.kg⫺1 at a mean work- Furthermore, although a reduced heart rate reserve was
load of 135.0⫾9.1W. This represented 82.5⫾3.5% of the pre- shown—mainly because of the increased resting heart rate
dicted maximal V̇O2. A similar reduction in other gas exchange secondary to the surgical cardiac denervation—no relationship
indexes was noted (see table 2). The VT was determined in all was observed in our patients with heart transplant between
patients and tended to occur earlier in heart transplant patients heart rate reserve and exercise capacity. This is not unexpected,
than in control groups. VT correlated with the measured because such a relationship has been previously observed
VO2peak (r⫽.64; P⬍.001) in both groups. mainly in highly trained patients with heart transplant, support-
ing that greater exercise intensity might be necessary to reveal
Relationship Between Six-Minute Walk Test the central limitation of exercise capacity after heart transplan-
and Measured Oxygen Uptake tation.3,10
There were relatively weak but significant correlations (fig Concerning peripheral factors, both vascular and muscular
4A) between 6MWD and measured VO2peak, VT, and maximal alterations are important to consider. Indeed, besides a possible
power in the 2 groups. influence of the amino acid taurine,41 muscular alterations
When body weight was considered, correlations between might be a result of a direct deleterious effect of deconditioning
6MWD ⫻ body weight product (6-minute walk work) and the and/or the immunosuppressive therapy. Thus, both glucocorti-
measured maximal power tolerated, VT, and VO2peak became coids and cyclosporine have been shown to damage the mus-
stronger (fig 4B). Thus, for example, 28% of the variance in cles of patients with heart transplant. Skeletal muscle dysfunc-
V̇O2 on VT was accounted for by the distance walked in 6 tion might also result from relative hypoxia secondary to
minutes in the heart transplant group, while 59% was ac- inadequate perfusion; thus, vascular dysfunction is related to
counted for when the 6-minute walk work calculation was exercise capacity reduction after heart transplantation.41,42,44
applied, representing an improvement of 31% in the variance
for the same patients. Similar improvements were noted for the Exercise Capacity Determination After
VO2peak and maximal power tolerated. Heart Transplantation
The maximal power tolerated estimated from performance To quantify the aerobic performance of patients with heart
on the 6MWT (see equation in fig 3) was 133.8⫾6.8W and did transplant, we used both a maximal exercise test and a walk
not differ significantly from the measured maximal power test. A maximal bicycle exercise test with oxygen uptake
tolerated (135⫾9W; P⫽.89). measurement is the best test used to identify the limiting factor
The V̇O2 predicted by the equation by Cahalin et al18 was of aerobic performance. This test measured the global and
significantly lower than the measured VO2peak (19.6⫾0.4 integrated response involved in exercise performance, includ-
vs 23.3⫾1mL.min ⫺1 .kg ⫺1 ; P⬍.001), with an SEM of ing the potential limitations observed in heart transplant recip-
3.4mL.min⫺1.kg⫺1. However, there was a moderate but signif- ients: cardiovascular system and muscle metabolism.
icant correlation between predicted and measured VO2peak Walk tests are typically administered as a means of evalu-
(r⫽.50; P⬍.02). ating functional status, monitoring treatment effectiveness, and

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WALK TEST AFTER HEART TRANSPLANTATION, Doutreleau 55

Fig 4. Relationship between


both distance walked during
6MWT (6MWD) (A, left) or dis-
tance walked during the
6MWD (m) multiplied by the
body weight (kg) (B, right),
with measured VO2peak, the
VT, and peak exercise work-
load (Wpeak) in subjects with
heart transplant.

establishing prognosis.17,45 Indeed, walking is the most com- remained in the sedentary predicted range. Indeed, healthy
mon, practical, and convenient form of exercise. Functional subjects have been shown to walk about 400 to 700m during
walk tests measure particularly the ability to undertake physi- the 6MWT, with the main predictors of the distance walked
cally demanding activities of daily living.17,46 Because most being sex, age, and height.21
activities of daily living are performed at submaximal levels of Second, we determined the heart rate response to the 6MWT
exertion, the distance walked may better reflect the functional in our patients with heart transplant. This parameter deserves
exercise level for daily physical activities. Thus, the 6MWT discussion after heart transplantation because patients pre-
has been shown to correlate well with formal measures of sented with a cardiac denervation secondary to the surgical
quality of life.47 Among walk tests, we chose the 6MWT procedure.9 Accordingly, their resting heart rate was increased
because it is easier to administer, is better tolerated, and better and, during exercise, cardiac denervation resulted primarily in a
reflects daily life activity than other walk tests.17 chronotropic incompetence characterized mainly by delays in the
heart rate response both at the beginning of exercise and during
Is the Six-Minute Walk Test a Submaximal or Maximal recovery. However, even if denervated, the transplanted heart
Test After Heart Transplantation? remains under hormonal control and thus, during exercise, its
This issue appeared controversial in previous studies be- increase is related to exercise intensity.4,8,48 Thus, the end exercise
cause authors proposed that the 6MWT corresponded either to heart rate is similar in patients with heart transplant and controls at
a submaximal21,48 or a maximal exercise test,22 mainly depend- the end of the 6MWT and, importantly, the heart rate of the
ing on the type of patients investigated. This is not surprising, patients with heart transplant at the end of the 6MWT was com-
because in people with an important exercise limitation factor, parable to that observed at the VT during the maximal exercise
the walking metabolic demand can approach their maximal test (124⫾3 and 129⫾2b.min⫺1, respectively in the heart trans-
capacity and walk speed. Conversely, when people do not have plant group) (see fig 4).
any important limiting factor, such as in sedentary people, the Thus, it appeared likely that the 6MWT was a submaximal
6MWD mainly depends on the walk speed (they cannot run) test in these patients with heart transplant.
with its sex, age, and weight dependence. In our patients with
heart transplant, several arguments suggest that the 6MWT was Can the Six-Minute Walk Test Predict Peak Oxygen
a submaximal test. Uptake After Heart Transplantation?
First, considering the values obtained in healthy subjects, the In heart failure with systolic dysfunction18 or in patients with
distance walked by our healthy patients with heart transplant end-stage lung diseases,19 the distance ambulated during the

Arch Phys Med Rehabil Vol 90, January 2009


56 WALK TEST AFTER HEART TRANSPLANTATION, Doutreleau

6MWT predicts the maximal oxygen consumption. Using the 5. Myers JL, Gullestad L, Bellin D, Ross H, Vagelos R, Fowler M.
heart failure prediction equation,18 we found higher values than Physical activity patterns and exercise performance in cardiac
predicted with an SEM of 3.4mL.min⫺1.kg⫺1. Our results are transplant recipients. J Cardiopulm Rehabil 2003;23:100-6.
similar to those reported recently in older patients with systolic 6. Schwaiblmair M, von Scheidt W, Uberfuhr P, Reichart B, Vo-
and diastolic heart failure, supporting the idea that such equations gelmeier C. Lung function and cardiopulmonary exercise perfor-
might not always be clinically useful.23 mance after heart transplantation: influence of cardiac allograft vas-
What about the direct determination of V̇O2 at the VT and at culopathy. Chest 1999;116:332-9.
the end of exercise (VO2peak)? Although positively correlated, the 7. Osada N, Chaitman BR, Donohue TJ, Wolford TL, Stelken AM,
relationship between the 6MWT distance and V̇O2 both at the VT Miller LW. Long-term cardiopulmonary exercise performance
and at peak were relatively weak. Thus, the distance walked after heart transplantation. Am J Cardiol 1997;79:451-6.
during the 6MWT did not predict V̇O2 after heart transplantation 8. Geny B, Charloux A, Lampert E, Lonsdorfer J, Haberey P, Pi-
accurately. quard F. Enhanced brain natriuretic peptide response to peak
However, the energy cost of walking depends on both
exercise in heart transplant recipients. J Appl Physiol 1998;85:
weight and walking speed,49 and the preferred minimum walk-
2270-6.
ing speed (to minimize the energy cost for walking) of healthy-
weight adults is higher than that of obese adults who prefer to 9. Geny B, Piquard F, Follenius M, et al. Role of cardiac innervation
walk more slowly.50 In fact, overweight persons expend much in atrial natriuretic peptide secretion in transplanted heart recipi-
more metabolic energy during walking than healthy-weight ents. Am J Physiol 1993;265:F112-8.
persons,50,51 and the distance walked during the 6MWT is 10. Richard R, Zoll J, Mettauer B, Piquard F, Geny B. Counterpoint:
weight-dependent. cardiac denervation does not play a major role in exercise limita-
Accordingly, the correlation between performance on timed tion after heart transplantation. J Appl Physiol 2008;104:560-2,
walking tests and VO2peak from a cycle test becomes stronger discussion 562-4.
if distance walked is multiplied by body weight (distance ⫻ 11. Lanfranconi F, Borrelli E, Ferri A, et al. Non invasive evaluation
weight ⫽ work of walking at horizontal level).34,36 To take into of skeletal muscle oxidative metabolism after heart transplant.
account this effect of weight on the distance walked by the Med Sci Sports Exerc 2006;38:1374-83.
patients, we compared the distance-weight product during the 12. Politi P, Piccinelli M, Poli PF, et al. Ten years of “extended” life:
6MWT and the patients’ V̇O2. Very interestingly, the significant quality of life among heart transplantation survivors. Transplan-
relationship between this parameter and V̇O2 at the VT and at peak tation 2004;78:257-63.
exercise was much stronger than that obtained with the 6MWD. 13. Schwaiblmair M, von Scheidt W, Uberfuhr P, et al. Functional
Such data increase the clinical relevance of the 6MWT in patients significance of cardiac reinnervation in heart transplant recipients.
with heart transplant and suggest that the distance walked multi- J Heart Lung Transplant 1999;18:838-45.
plied by the body weight might be used as a reasonable approach 14. Richard R, Verdier JC, Doutreleau S, Piquard F, Gény B, Rieu M.
to the patients’ VO2peak after heart transplantation. Exercise limitation in trained heart and kidney transplant recipi-
ents: central and peripheral limitations. J Heart Lung Transplant
Study Limitations 2005;24:1774-80.
15. Andreassen AK, Kvernebo K, Jørgensen B, Simonsen S, Kjekshus
This study has several limitations. We included only a low J, Gullestad L. Exercise capacity in heart transplant recipients:
number of men without cardiac allograft vasculopathy, late relation to impaired endothelium-dependent vasodilation of the
after heart transplantation. A greater number of all kinds of peripheral microcirculation. Am Heart J 1998;136:320-8.
patients are required to analyze the relation between the 6MWT 16. Vanhees L, Stevens A, Schepers D, Defoor J, Rademakers F,
and the maximal V̇O2. Fagard R. Determinants of the effects of physical training and of
the complications requiring resuscitation during exercise in pa-
CONCLUSIONS tients with cardiovascular disease. Eur J Cardiovasc Prev Rehabil
The 6MWT is a safe and practical test, easy to use in patients 2004;11:304-12.
with heart transplant. The heart rate response analysis support 17. Solway S, Brooks D, Lacasse Y, Thomas S. A qualitative system-
that this walk test is a submaximal test after heart transplanta- atic overview of the measurement properties of functional walk
tion. Like the equation, the use of the walking distance alone tests used in the cardiorespiratory domain. Chest 2001;119:256-70.
does not allow accurate prediction of the patients’ V̇O2. How- 18. Cahalin LP, Mathier M, Semigran M, Dec W, DiSalvo T. The
ever, the distance-weight product obtained during the 6MWT six-minute walk test predicts peak oxygen uptake and survival in
might be used as a clinically relevant approach to the patients’ patients with advanced heart failure. Chest 1996;110:325-32.
VO2peak after heart transplantation. This will allow a broader 19. Cahalin LP, Pappagianopoulos P, Prevost S, Wain J, Ginns L. The
use of exercise testing after heart transplantation and might relationship of the 6-min walk test to maximal oxygen consump-
help convince more patients to perform exercise training, the tion in transplant candidates with end-stage lung disease. Chest
beneficial effects of which have been largely demonstrated. 1995;108:452-9.
20. Newman AB, Simonsick E, Naydeck B, et al. Association of
References long-distance corridor walk performance with mortality, cardio-
1. Borrelli E, Pogliaghi S, Molinello A, Diciolla F, Maccherini M. vascular disease, mobility limitation, and disability. JAMA 2006;
Serial assessment of peak VO2 and VO2 kinetics early after heart 295:2018-26.
transplantation. Med Sci Sports Exerc 2003;35:1798-804. 21. Chetta A, Zanini A, Pisi G, et al. Reference values for the 6-min
2. Mandak JS, Aaronson KD, Mancini DM. Serial assessment of walk test in healthy subjects 20-50 years old. Respir Med 2006;
exercise capacity after heart transplantation. J Heart Lung Trans- 100:1573-8.
plant 1995;14:468-78. 22. Camarri B, Eastwood PR, Cecins NM, Thompson PJ, Jenkins S.
3. Braith RW, DG Edwards. Exercise following heart transplanta- Six minute walk distance in healthy subjects aged 55-75 years.
tion. Sports Med 2000;30:171-92. Respir Med 2006;100:658-65.
4. Marconi C, Marzorati M. Exercise after heart transplantation. Eur 23. Maldonado-Martin SP, Brubaker PH, Kaminsky LA, Moore BJ,
J Appl Physiol 2003;90:250-9. Stewart KP, Kitzman DW. The relationship of a 6-min walk to

Arch Phys Med Rehabil Vol 90, January 2009


WALK TEST AFTER HEART TRANSPLANTATION, Doutreleau 57

VO(2 peak) and VT in older heart failure patients. Med Sci Sports 39. Geny B, Saini J, Mettauer B, et al. Effect of short term endurance
Exerc 2006;38:1047-53. training on exercise capacity, hemodynamics and atrial natriuretic
24. Rostagno C, Olivo G, Comeglio M, et al. Prognostic value of peptide secretion in heart transplant recipients. Eur J Appl Physiol
6-minute walk corridor test in patients with mild to moderate heart 1996;73:259-66.
failure: comparison with other methods of functional evaluation. 40. Mettauer B, Lampert E, Petitjean P, et al. Persistent exercise
Eur J Heart Fail 2003;5:247-52. intolerance following cardiac transplantation despite normal oxy-
25. Oudiz RJ, Barst RJ, Hansen JE, et al. Cardiopulmonary exercise gen transport. Int J Sports Med 1996;17:277-86.
testing and six-minute walk correlations in pulmonary arterial 41. Geny B, Schaefer A, Epailly E, Thiranos JC, Richard R, Piquard
hypertension. Am J Cardiol 2006;97:123-6. F. Does decreased taurine participate in reduced exercise capacity
after heart transplantation? J Heart Lung Transplant 2006;25:
26. Provencher S, Chemla D, Herve P, Sitbon O, Humbert M, Simo-
997-8.
nneau G. Heart rate responses during the 6-minute walk test in
42. Schaefer A, Piquard F, Doutreleau S, et al. Reduced exercise
pulmonary arterial hypertension. Eur Respir J 2006;27:114-20.
capacity is associated with reduced nitric oxide production after
27. Riess KJ, Gourishankar S, Oreopoulos A, et al. Impaired arterial heart transplantation. J Thorac Cardiovasc Surg 2001;122:821-2.
compliance and aerobic endurance in kidney transplant recipients. 43. Leyh RG, Jahnke AW, Kraatz EG, Sievers HH. Cardiovascular
Transplantation 2006;82:920-3. dynamics and dimensions after bicaval and standard cardiac trans-
28. Ingle L, Goode K, Rigby AS, Cleland JG, Clark AL. Predicting plantation. Ann Thorac Surg 1995;59:1495-500.
peak oxygen uptake from 6-min walk test performance in male 44. Zoll J, N’Guessan B, Ribera F, et al. Preserved response of
patients with left ventricular systolic dysfunction. Eur J Heart Fail mitochondrial function to short-term endurance training in skeletal
2006;8:198-202. muscle of heart transplant recipients. J Am Coll Cardiol 2003;42:
29. Lipkin DP, Scriven AJ, Crake T, Poole-Wilson PA. Six minute 126-32.
walking test for assessing exercise capacity in chronic heart fail- 45. Enright PL. The six-minute walk test. Respir Care 2003;48:783-5.
ure. Br Med J (Clin Res Ed) 1986;292:653-5. 46. Guyatt GH, Sullivan M, Thompson P, et al. The 6-minute walk: a
30. Lewis ME, Newall C, Townend JN, Hill SL, Bonser RS. Incre- new measure of exercise capacity in patients with chronic heart
mental shuttle walk test in the assessment of patients for heart failure. Can Med Assoc J 1985;132:919-23.
transplantation. Heart 2001;86:183-7. 47. Guyatt GH, Townsend M, Keller J, Singer J, Nogradi S. Measur-
31. Schiller NB, Shah P, Crawford M, et al. Recommendations for ing functional status in chronic lung disease: conclusions from a
quantitation of the left ventricle by two-dimensional echocardiog- randomized control trial. Respir Med 1991;85:17-21; discussion
raphy. American Society of Echocardiography Committee on 33-7.
Standards, Subcommittee on Quantitation of Two-Dimensional 48. Geny B, Charloux A, Brandenberger G, Piquard F. Despite car-
diac denervation, atrial natriuretic peptides possess a cardiac sym-
Echocardiograms. J Am Soc Echocardiogr 1989;2:358-67.
pathoinhibitory effect after heart transplantation. J Thorac Cardio-
32. ATS statement: guidelines for the six-minute walk test. Am J
vasc Surg 2006;131:1417-8.
Respir Crit Care Med 2002;166:111-7.
49. Browning RC, Baker E, Herron JA, Kram R. Effects of obesity
33. Enright PL, Sherrill DL. Reference equations for the six-minute
and sex on the energetic cost and preferred speed of walking.
walk in healthy adults. Am J Respir Crit Care Med 1998;158:
J Appl Physiol 2006;100:390-8.
1384-7.
50. Melanson EL, Bell M, Knoll J, et al. Body mass index and sex
34. Carter R, Holiday D, Nwasuruba C, Stocks J, Grothues C, Tiep B.
influence the energy cost of walking at self-selected speeds [ab-
6-Minute walk work for assessment of functional capacity in
stract]. Med Sci Sports Exerc 2003;35:S183.
patients with COPD. Chest 2003;123:1408-15.
51. Foster GD, Wadden T, Kendrick Z, Letizia KA, Lander DP,
35. Arnardottir RH, Emtner M, Hedenstrom H, Larsson K, Boman G.
Conill AM. The energy cost of walking before and after signifi-
Peak exercise capacity estimated from incremental shuttle walking
cant weight loss. Med Sci Sports Exerc 1995;27:888-94.
test in patients with COPD: a methodological study. Respir Res
2006;7:127-33. Suppliers
36. Chuang ML, Lin IF, Wasserman K. The body weight-walking a. Oxypleth, Novametrix; Soma Technology Inc, 166 Highland Park
distance product as related to lung function, anaerobic threshold Dr, Wallingford, CT 06002.
and peak VO2 in COPD patients. Respir Med 2001;95:618-26. b. Medifit 1000 S; Planetenbaan 48, 3951 EK Maaren, The Nether-
37. Wasserman K, Stringer W, Casaburi R, Koike A, Cooper CB. lands.
Determination of the anaerobic threshold by gas exchange: bio- c. Sensormedics, 22705 Savi Ranch Pkwy, Yorba Linda, CA 92887.
chemical considerations, methodology and physiological effects. d. Cardiovit CS-200; Schiller, Altgasse 68, PO Box 1052, CH-6341
Z Kardiol 1994;83:1-12. Barr, Switzerland.
38. Hansen JE, Sue D, Wasserman K. Predicted values for clinical e. Version 3.1; Systat Software Inc, 501 Canal Blvd, Ste C, Point
exercise testing. Am Rev Respir Dis 1984;129:S49-55. Richmond, CA 94804.

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