Professional Documents
Culture Documents
ORIGINAL ARTICLE
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
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
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
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
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.