nach oben

Erschienen in:

24.01.2018 | Original Paper

The 6MWT as a prognostic tool in pulmonary arterial hypertension: results from the COMPERA registry

verfasst von: Thomas A. Zelniker, Dörte Huscher, Anton Vonk-Noordegraaf, Ralf Ewert, Tobias J. Lange, Hans Klose, Daniel Dumitrescu, Michael Halank, Matthis Held, Henning Gall, David Pittrow, Marius M. Hoeper, Lutz Frankenstein

Erschienen in: Clinical Research in Cardiology | Ausgabe 6/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

In patients with pulmonary arterial hypertension, the 6-Minute Walk Test (6MWT) is recommended for risk stratification and follow-up by all guidelines. However, the prognostic value of the 6MWT has been discussed controversially. We sought to compare and validate all published 6MWT cut-off points.

Methods

From the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA)—registry we identified 2391 patients with pulmonary arterial hypertension who had at least one documented 6MWT measurement. A Medline search identified a total of 21 different threshold values for either single-point or change of 6MWT. All values were tested individually for prognostication of 1-year, 2-year and 3-year all-cause mortality.

Results

The highest positive likelihood ratio was a cut-off value < 165 ms, whereas the best negative likelihood ratio was found to be a threshold of 440 ms. Furthermore, improvement in 6MWT had considerably less predictive value on mortality and survival than deterioration. Moreover, absolute single-point values outperformed change values for both improvement and worsening.

Conclusion

Our data confirmed the prognostic relevance of the 6MWT and support the cut-off values stated in most recent guidelines. Furthermore, these results explain why changes in 6MWT did not correlate consistently with prognosis in previous studies.

Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M (2004) Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 43(12 Suppl S):13S-24S. https://doi.org/10.1016/j.jacc.2004.02.029 PubMedCrossRef

Hassoun PM, Mouthon L, Barbera JA, Eddahibi S, Flores SC, Grimminger F, Jones PL, Maitland ML, Michelakis ED, Morrell NW, Newman JH, Rabinovitch M, Schermuly R, Stenmark KR, Voelkel NF, Yuan JX, Humbert M (2009) Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol 54(1 Suppl):S10-19. https://doi.org/10.1016/j.jacc.2009.04.006 CrossRef

Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M (2015) 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J 46(4):903–975. https://doi.org/10.1183/13993003.01032-2015 CrossRefPubMed

Ewert R, Richter MJ, Steringer-Mascherbauer R, Grunig E, Lange TJ, Opitz CF, Warnke C, Ghofrani HA (2017) Intravenous treprostinil infusion via a fully implantable pump for pulmonary arterial hypertension. Clin Res Cardiol 106(10):776–783. https://doi.org/10.1007/s00392-017-1114-1 CrossRefPubMed

McLaughlin VV, Gaine SP, Howard LS, Leuchte HH, Mathier MA, Mehta S, Palazzini M, Park MH, Tapson VF, Sitbon O (2013) Treatment goals of pulmonary hypertension. J Am Coll Cardiol 62(25 Suppl):D73-81. https://doi.org/10.1016/j.jacc.2013.10.034 PubMedCrossRef

Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G, Guidelines ESCCfP (2009) Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 30(20):2493–2537. https://doi.org/10.1093/eurheartj/ehp297 CrossRefPubMed

McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J, American College of Cardiology Foundation Task Force on Expert Consensus D, American Heart A, American College of Chest P, American Thoracic Society I, Pulmonary Hypertension A (2009) ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol 53 (17):1573–1619. https://doi.org/10.1016/j.jacc.2009.01.004 CrossRefPubMed

Galie N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, Safdar Z, Shapiro S, White RJ, Chan M, Beardsworth A, Frumkin L, Barst RJ, Pulmonary Arterial H, Response to Tadalafil Study G (2009) Tadalafil therapy for pulmonary arterial hypertension. Circulation 119(22):2894–2903. https://doi.org/10.1161/CIRCULATIONAHA.108.839274 CrossRefPubMed

Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, Pulido T, Frost A, Roux S, Leconte I, Landzberg M, Simonneau G (2002) Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 346(12):896–903. https://doi.org/10.1056/NEJMoa012212 CrossRefPubMed

10.

Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A, Grimminger F, Kurzyna M, Simonneau G, Sildenafil Use in Pulmonary Arterial Hypertension Study G (2005) Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 353 (20):2148–2157. https://doi.org/10.1056/NEJMoa050010 CrossRefPubMed

11.

Galie N, Badesch D, Oudiz R, Simonneau G, McGoon MD, Keogh AM, Frost AE, Zwicke D, Naeije R, Shapiro S, Olschewski H, Rubin LJ (2005) Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol 46(3):529–535. https://doi.org/10.1016/j.jacc.2005.04.050 CrossRefPubMed

12.

Ghofrani HA, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, Keogh AM, Langleben D, Kilama MO, Fritsch A, Neuser D, Rubin LJ, Group P-S (2013) Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 369(4):330–340. https://doi.org/10.1056/NEJMoa1209655 CrossRefPubMed

13.

Fritz JS, Blair C, Oudiz RJ, Dufton C, Olschewski H, Despain D, Gillies H, Kawut SM (2013) Baseline and follow-up 6-min walk distance and brain natriuretic peptide predict 2-year mortality in pulmonary arterial hypertension. Chest 143(2):315–323. https://doi.org/10.1378/chest.12-0270 CrossRefPubMed

14.

Gaine S, Simonneau G (2013) The need to move from 6-minute walk distance to outcome trials in pulmonary arterial hypertension. Eur Respir Rev 22(130):487–494. https://doi.org/10.1183/09059180.00006213 CrossRefPubMed

15.

McLaughlin VV, Badesch DB, Delcroix M, Fleming TR, Gaine SP, Galie N, Gibbs JS, Kim NH, Oudiz RJ, Peacock A, Provencher S, Sitbon O, Tapson VF, Seeger W (2009) End points and clinical trial design in pulmonary arterial hypertension. J Am Coll Cardiol 54(1 Suppl):S97-107. https://doi.org/10.1016/j.jacc.2009.04.007 CrossRef

16.

Savarese G, Paolillo S, Costanzo P, D’Amore C, Cecere M, Losco T, Musella F, Gargiulo P, Marciano C, Perrone-Filardi P (2012) 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 60(13):1192–1201. https://doi.org/10.1016/j.jacc.2012.01.083 CrossRefPubMed

17.

Olsson KM, Delcroix M, Ghofrani HA, Tiede H, Huscher D, Speich R, Grunig E, Staehler G, Rosenkranz S, Halank M, Held M, Lange TJ, Behr J, Klose H, Claussen M, Ewert R, Opitz CF, Vizza CD, Scelsi L, Vonk-Noordegraaf A, Kaemmerer H, Gibbs JS, Coghlan G, Pepke-Zaba J, Schulz U, Gorenflo M, Pittrow D, Hoeper MM (2014) Anticoagulation and survival in pulmonary arterial hypertension: results from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA). Circulation 129(1):57–65. https://doi.org/10.1161/CIRCULATIONAHA.113.004526 CrossRefPubMed

18.

Hoeper MM, Huscher D, Pittrow D (2015) Incidence and prevalence of pulmonary arterial hypertension in Germany. Int J Cardiol 203:612–613. https://doi.org/10.1016/j.ijcard.2015.11.001 CrossRefPubMed

19.

Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, Langleben D, Manes A, Satoh T, Torres F, Wilkins MR, Badesch DB (2013) Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol 62(25 Suppl):D42-50. https://doi.org/10.1016/j.jacc.2013.10.032 PubMedCrossRef

20.

Pittrow D, Ghofrani HA, Opitz CF, Huscher D, Hoeper MM (2009) [International, prospective register for the documentation of first-line and maintenance therapy in patients with pulmonary hypertension (CompERA-XL)]. Dtsch Med Wochenschr 134(Suppl 5):S173–S175. https://doi.org/10.1055/s-0029-1225318 CrossRefPubMed

21.

Laboratories ATSCoPSfCPF (2002) ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 166(1):111–117. https://doi.org/10.1164/ajrccm.166.1.at1102 CrossRef

22.

Benza RL, Miller DP, Gomberg-Maitland M, Frantz RP, Foreman AJ, Coffey CS, Frost A, Barst RJ, Badesch DB, Elliott CG, Liou TG, McGoon MD (2010) Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation 122(2):164–172. https://doi.org/10.1161/CIRCULATIONAHA.109.898122 CrossRefPubMed

23.

Gilbert C, Brown MC, Cappelleri JC, Carlsson M, McKenna SP (2009) Estimating a minimally important difference in pulmonary arterial hypertension following treatment with sildenafil. Chest 135(1):137–142. https://doi.org/10.1378/chest.07-0275 CrossRefPubMed

24.

Gabler NB, French B, Strom BL, Palevsky HI, Taichman DB, Kawut SM, Halpern SD (2012) Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials. Circulation 126(3):349–356. https://doi.org/10.1161/CIRCULATIONAHA.112.105890 CrossRefPubMedPubMedCentral

25.

Mathai SC, Puhan MA, Lam D, Wise RA (2012) The minimal important difference in the 6-minute walk test for patients with pulmonary arterial hypertension. Am J Respir Crit Care Med 186(5):428–433. https://doi.org/10.1164/rccm.201203-0480OC CrossRefPubMedPubMedCentral

26.

Frost AE, Badesch DB, Miller DP, Benza RL, Meltzer LA, McGoon MD (2013) Evaluation of the predictive value of a clinical worsening definition using 2-year outcomes in patients with pulmonary arterial hypertension: a REVEAL Registry analysis. Chest 144(5):1521–1529. https://doi.org/10.1378/chest.12-3023 CrossRefPubMed

27.

McGee S (2002) Simplifying likelihood ratios. J Gen Intern Med 17(8):646–649CrossRefPubMed

28.

Galie N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, Badesch DB, McGoon MD, McLaughlin VV, Roecker EB, Gerber MJ, Dufton C, Wiens BL, Rubin LJ, Ambrisentan in Pulmonary Arterial Hypertension RD-BP-CMESG (2008) Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation 117 (23):3010–3019. https://doi.org/10.1161/CIRCULATIONAHA.107.742510 CrossRefPubMed

29.

Barst RJ, Langleben D, Frost A, Horn EM, Oudiz R, Shapiro S, McLaughlin V, Hill N, Tapson VF, Robbins IM, Zwicke D, Duncan B, Dixon RA, Frumkin LR, Group S-S (2004) Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med 169(4):441–447. https://doi.org/10.1164/rccm.200307-957OC CrossRefPubMed

30.

Farber HW, Miller DP, McGoon MD, Frost AE, Benton WW, Benza RL (2015) Predicting outcomes in pulmonary arterial hypertension based on the 6-minute walk distance. J Heart Lung Transplant 34(3):362–368. https://doi.org/10.1016/j.healun.2014.08.020 CrossRefPubMed

31.

Benza RL, Miller DP, Foreman AJ, Frost AE, Badesch DB, Benton WW, McGoon MD (2015) Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) analysis. J Heart Lung Transplant 34(3):356–361. https://doi.org/10.1016/j.healun.2014.09.016 CrossRefPubMed

32.

Tyndall AJ, Bannert B, Vonk M, Airo P, Cozzi F, Carreira PE, Bancel DF, Allanore Y, Muller-Ladner U, Distler O, Iannone F, Pellerito R, Pileckyte M, Miniati I, Ananieva L, Gurman AB, Damjanov N, Mueller A, Valentini G, Riemekasten G, Tikly M, Hummers L, Henriques MJ, Caramaschi P, Scheja A, Rozman B, Ton E, Kumanovics G, Coleiro B, Feierl E, Szucs G, Von Muhlen CA, Riccieri V, Novak S, Chizzolini C, Kotulska A, Denton C, Coelho PC, Kotter I, Simsek I, de la Pena Lefebvre PG, Hachulla E, Seibold JR, Rednic S, Stork J, Morovic-Vergles J, Walker UA (2010) Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 69(10):1809–1815. https://doi.org/10.1136/ard.2009.114264 CrossRefPubMed

33.

Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaici A, Weitzenblum E, Cordier JF, Chabot F, Dromer C, Pison C, Reynaud-Gaubert M, Haloun A, Laurent M, Hachulla E, Cottin V, Degano B, Jais X, Montani D, Souza R, Simonneau G (2010) Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 122(2):156–163. https://doi.org/10.1161/CIRCULATIONAHA.109.911818 CrossRefPubMed

34.

Lee WT, Peacock AJ, Johnson MK (2010) The role of per cent predicted 6-min walk distance in pulmonary arterial hypertension. Eur Respir J 36(6):1294–1301. https://doi.org/10.1183/09031936.00155009 CrossRefPubMed

35.

Frankenstein L, Remppis A, Graham J, Schellberg D, Sigg C, Nelles M, Katus HA, Zugck C (2008) Gender and age related predictive value of walk test in heart failure: do anthropometrics matter in clinical practice? Int J Cardiol 127(3):331–336. https://doi.org/10.1016/j.ijcard.2007.04.087 CrossRefPubMed

36.

Frankenstein L, Zugck C, Nelles M, Schellberg D, Katus H, Remppis A (2008) Sex-specific predictive power of 6-minute walk test in chronic heart failure is not enhanced using percent achieved of published reference equations. J Heart Lung Transplant 27(4):427–434. https://doi.org/10.1016/j.healun.2008.01.010 CrossRefPubMed

Titel: The 6MWT as a prognostic tool in pulmonary arterial hypertension: results from the COMPERA registry
verfasst von: Thomas A. Zelniker
Dörte Huscher
Anton Vonk-Noordegraaf
Ralf Ewert
Tobias J. Lange
Hans Klose
Daniel Dumitrescu
Michael Halank
Matthis Held
Henning Gall
David Pittrow
Marius M. Hoeper
Lutz Frankenstein
Publikationsdatum: 24.01.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Clinical Research in Cardiology / Ausgabe 6/2018
Print ISSN: 1861-0684
Elektronische ISSN: 1861-0692
DOI: https://doi.org/10.1007/s00392-018-1207-5

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

The 6MWT as a prognostic tool in pulmonary arterial hypertension: results from the COMPERA registry