Six-minute walk test in pulmonary arterial hypertension

Rengin Demir, Mehmet Serdar Küçükoğlu, Rengin Demir, Mehmet Serdar Küçükoğlu

Abstract

Exercise intolerance is the main characteristic of pulmonary arterial hypertension (PAH). The six-minute walk test (6MWT) and cardiopulmonary exercise test are widely used in assessing exercise capacity of PAH patients. Six-minute walk distance (6MWD) has been specified as the main clinical outcome in PAH and has been used as the primary end-point in many studies conducted for new PAH treatments. Using 6MWD as the end-point in clinical studies has many advantages. 6MWT is an inexpensive, easily applicable, and repeatable standardized test that is well-tolerated by PAH patients. Moreover, it is a valid measure of symptomatic improvement. It is correlated with variables of maximal cardiopulmonary exercise test as a measure of submaximal exercise capacity and disease severity markers such as functional class and pulmonary hemodynamics. It is widely used in clinical practice together with other invasive and non-invasive disease markers in assessing disease progression and response to treatment. In addition, it has prognostic importance and is a good prognostic marker. On the other hand, there are limitations to the use of 6MWD as the primary end-point in PAH treatment. It has decreased sensitivity in individuals with less severe disease and high 6MWD at baseline and decreased adequacy in assessing the effects of treatment in patients who are still under PAH treatment. Despite the limitations, 6MWD plays a key role in the evaluation and management of PAH patients.

Conflict of interest statement

Conflict of interest: None declared.

References

    1. Guillevin L, Armstrong I, Aldrighetti R, Howard LS, Ryftenius H, Fischer A, et al. Understanding the impact of pulmonary arterial hypertension on patients’and careers’lives. Eur Respir Rev. 2013;22:535–42. [CrossRef]
    1. Kugukoglu MS, Bajkurt M. Pulmonary hypertension: diagnosis and clinical classification. Anatol J Cardiol. 2010;10(Supp 1):2–4. [CrossRef]
    1. Yurdakul S, Aytekin S. Diagnostic algorithms in pulmonary hypertension. Anatol J Cardiol. 2010;10(Supp 1):14–26. [CrossRef]
    1. Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010;122:156–63. [CrossRef]
    1. Can MM, Kaymaz C. Clinical end-points and surrogate markers of pulmonary arterial hypertension in the light of evidence-based treatment. Anatol J Cardiol. 2010;10(Supp 1):36–42. [CrossRef]
    1. McGoon M, Gutterman D, Steen V, Barst R, McCrory DC, Fortin TA, et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126(Suppl 1):14–34. [CrossRef]
    1. McLaughlin VV, Gaine SP, Howard LS, Leuchte HH, Mathier MA, Mehta S, et al. Treatment goals of pulmonary hypertension. J Am Coll Cardiol. 2013;62(Suppl 25):73–81. [CrossRef]
    1. McLaughlin VV, Badesch DB, Delcroix M, Fleming TR, Gaine SP, Galie N, et al. Endpoints and clinical trial design in pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(Suppl 1):97–107. [CrossRef]
    1. Rasekaba T, Lee AL, Naughton MT, Williams TJ, Holland AE. The six-minute walk test: a useful metric for the cardiopulmonary patient. Intern Med J. 2009;39:495–501. [CrossRef]
    1. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166:111–7. [CrossRef]
    1. Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009;34:1219–63. [CrossRef]
    1. McGoon MD, Benza RL, Escribano-Subios P, Jiang X, Miller DP, Peacock AJ, et al. Pulmonary arterial hypertension. Epidemiology and registries. J Am Coll Cardiol. 2013;62:51–9. [CrossRef]
    1. Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med. 2006;173:1023–30. [CrossRef]
    1. Degano B, Sitbon O, Savale L, Garcia G, O’Callaghan DS, Jais X, et al. Characterization of pulmonary arterial hypertension patients walking more than 450 m in 6 min at diagnosis. Chest. 2010;137:1297–303. [CrossRef]
    1. Miyamoto S, Nagaya N, Satoh T, Kyotani S, Sakamaki F, Fujita M, et al. Clinical correlates and prognostic significance of six minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2000;161:487–92. [CrossRef]
    1. Tokgozoglu L, Akdogan A, Okutucu S, Kaya EB, Aytemir K, Ozkutlu H. Two years of multidisciplinary diagnostic and therapeutic experience in patients with pulmonary arterial hypertension. Turk Kardiyol Dern Ars. 2009;37:378–93.
    1. Gungor H, Ertugay S, Ayik MF, Demir E, Engin C, Yagdi T, et al. Clinical and hemodynamic features of Eisenmenger syndrome patients at the time of first admission: a tertiary referral-center experience. Anatol J Cardiol. 2012;12:11–5.
    1. Okutucu S, Tokgozoglu L. Therapeutic algorithms in pulmonary hypertension in the light of current guidelines. Anatol J Cardiol. 2010;10(Supp 2):19–26. [CrossRef]
    1. Demir R, Kugukoglu MS. Evaluation of exercise capacity in pulmonary arterial hypertension. Turk Kardiyol Dern Ars. 2010;38:580–8.
    1. Simonneau G, Rubin LJ, Galie N, Barst RJ, Fleming TR, Frost AE, et al. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med. 2008;149:521–30. [CrossRef]
    1. Galie N, Humbert M, Vachiery JL, Vizza CD, Kneussl M, Manes A, et al. Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized double-blind, placebo-controlled study. J Am Coll Cardiol. 2002;39:1496–502. [CrossRef]
    1. Rubin LJ. The 6-minute walk test in pulmonary arterial hypertension: how far is enough? Am J Respir Crit Care Med. 2012;186:396–7. [CrossRef]
    1. Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996;334:296–301. [CrossRef]
    1. Provencher S, Sitbon O, Humbert M, Cabrol S, Jais X, Simonneau G. Long-term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension. Eur Heart J. 2006;27:589–95. [CrossRef]
    1. Barst RJ, Langleben D, Frost A, Horn EM, Oudiz R, Shapiro S, et al. Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med. 2004;169:441–7. [CrossRef]
    1. Badesch DB, Hill NS, Burgess G, Rubin LJ, Barst RJ, Galie N, et al. Sildenafil for pulmonary arterial hypertension associated with connective tissue disease. J Rheumatol. 2007;34:2417–22.
    1. Jing ZC, Yu ZX, Shen JY, Wu BX, Xu KF, Zhu XY, et al. Vardenafil in pulmonary arterial hypertension: a randomized double-blind, pla - cebo-controlled study. Am J Respir Crit Care Med. 2011;183:1723–9. [CrossRef]
    1. Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin LJ, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med. 2002;347:322–9. [CrossRef]
    1. Ghofrani HA, Morrell NW, Hooper MM, Olschewski H, Peacock AJ, Barst RJ, et al. Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy. Am J Respir Crit Care Med. 2010;182:1171–7. [CrossRef]
    1. McLaughlin VV, Oudiz RJ, Frost A, Tapson VF, Murali S, Channick RN, et al. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2006;174:1257–63. [CrossRef]
    1. Oudiz RJ, Schilz RJ, Barst RJ, Galie N, Rich S, Rubin LJ, et al. Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease. Chest. 2004;126:420–7. [CrossRef]
    1. Savarese G, Paolillo S, Costanzo P, D’Amore C, Cecere M, Losco T, et al. Do changes of 6-minute walk distance predict clinical events in patients with pulmonary arterial hypertension. A meta-analysis of 22 randomized trials. J Am Coll Cardiol. 2012;60:1192–201. [CrossRef]
    1. Galie N, Ghofrani AH. New horizons in pulmonary arterial hypertension therapies. Eur Respir Rev. 2013;22:503–14. [CrossRef]
    1. Simonneau G, Torbicki A, Hoeper MM, Delcroix M, Karlocai K, Galie N, et al. Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J. 2012;40:874–80. [CrossRef]
    1. Ghofrani HA, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013;369:330–40. [CrossRef]
    1. Hoeper MM, Barst RJ, Bourge RC, Feldman J, Frost AE, Galie N, et al. Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation. 2013;127:1128–38. [CrossRef]
    1. Vachiery JL, Yerly P, Huez S. How to detect disease progression in pulmonary arterial hypertension. Eur Respir Rev. 2012;123:40–7. [CrossRef]
    1. Benza RL, Miller DP, Gomberg-Maitland M, Frantz RP, Foreman AJ, Coffey CS, et al. Predicting survival in pulmonary arterial hypertension. Insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) Circulation. 2010;122:164–72. [CrossRef]
    1. Gaine S, Simonneau G. The need to move from 6-minute walk distance to outcome trials in pulmonary arterial hypertension. Eur Respir Rew. 2013;22:487–94. [CrossRef]
    1. Sitbon O, Humbert M, Nunes H, Parent F, Garcia G, Herve P, et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol. 2002;40:780–8. [CrossRef]
    1. Paciocco G, Martinez FJ, Bossone E, Pielsticker E, Gillespie B, Rubinfire M. Oxygen desaturation on the six-minute walk test and mortality in untreated primary pulmonary hypertension. Eur Respir J. 2001;17:647–52. [CrossRef]
    1. Macchia A, Marchioli R, Marfisi R, Scarano M, Levantesi G, Tavazzi L, et al. A meta-analysis of trials of pulmonary hypertension: a clinical condition looking for drugs and research methodology. Am Heart J. 2007;153:1037–47. [CrossRef]
    1. Fritz JS, Blair C, Qudiz RJ, Dufton C, Olschewski H, Despain D, et al. Baseline and follow-up 6-min walk distance and brain natriuretic peptide predict 2-year mortality in pulmonary arterial hypertension. Chest. 2013;143:315–23. [CrossRef]
    1. Groepenhoff H, Vonk-Noordegraaf, van de Veerdonk MC, Boonstra A, Westerhof N, Bogaard HJ. Prognostic relevance of changes in exercise test variables in pulmonary arterial hypertension. PLoS One. 2013;8:e72013. [CrossRef]
    1. Kempny A, Dimopoulos K, Alanso-Gonzalez R, Alvarez-Barredo M, Tutarel O, Uebing A, et al. Six-minute walk test distance and resting oxygen saturations but not functional class predict outcome in adult patients with Eisenmenger syndrome. Int J Cardiol. 2013;168:4784–9. [CrossRef]
    1. Wensel R, Francis DP, Meyer FJ, Opitz CF, Bruch L, Halank M, et al. Incremental prognostic value of cardiopulmonary exercise testing and resting haemodynamics in pulmonary arterial hypertension. Int J Cardiol. 2013;167:1193–8. [CrossRef]
    1. Benza RL, Gomberg-Maitland M, Naeije R, Arneson CP, Lang IM. Prognostic factors associated with increased survival in patients with pulmonary arterial hypertension treated with subcutaneous treprostinil in randomized, placebo-controlled trials. J Heart Lung Transplant. 2011;30:982–9. [CrossRef]
    1. Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005;353:2148–57. [CrossRef]
    1. Gabler NB, French B, Strom BL, Palevsky HI, Taichman DB, Kawut SM, et al. Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials. Circulation. 2012;126:349–56. [CrossRef]
    1. Rubin LJ, Galie N, Simonneau G, McLaughlin V. A paradigm shift in pulmonary arterial hypertension management. Eur Respir Rew. 2013;22:423–6. [CrossRef]
    1. Barst RJ, Oudiz RJ, Beardsworth A, Brundage BH, Simonneau G, Ghofrani HA, et al. Tadalafil monotherapy and as add-on to background bosentan in patients with pulmonary arterial hypertension. J Heart Lung Transplant. 2011;30:632–43. [CrossRef]
    1. Gilbert C, Brown MC, Cappelleri JC, Carlsson M, McKenna SP. Estimating a minimally important difference in pulmonary arterial hypertension following treatment with sildenafil. Chest. 2009;135:137–42. [CrossRef]
    1. Mathai SC, Puhan MA, Lam D, Wise RA. The minimal important difference in the 6-minute walk test for patients with pulmonary arterial hypertension. Am J Respir Crit Care Med. 2012;186:428–33. [CrossRef]
    1. Lee WT, Peacock AJ, Johnson MK. The role of percent predicted 6-min walk distance in pulmonary arterial hypertension. Eur Respir J. 2010;36:1294–301. [CrossRef]

Source: PubMed

3
Subscribe