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

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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.

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Acknowledgements

The authors are indebted to the COMPERA investigators.

Funding

This work was supported by the German Centre of Lung Research (DZL) and the Deutsche Forschungsgemeinschaft (Professor Hoeper, HO 1599/2-1). COMPERA is funded by unrestricted grants from Actelion Pharmaceuticals, Bayer and GSK. These companies were not involved in data analysis or the writing of this manuscript.

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Authors and Affiliations

  1. Department of Cardiology, Angiology, Pneumology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Thomas A. Zelniker & Lutz Frankenstein

  2. Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany

    Dörte Huscher

  3. Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands

    Anton Vonk-Noordegraaf

  4. Department of Internal Medicine, University of Greifswald, Greifswald, Germany

    Ralf Ewert

  5. Department of Internal Medicine II, Division of Pneumology, University Medical Center Regensburg, Regensburg, Germany

    Tobias J. Lange

  6. Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf, Center of Oncology, Hamburg, Germany

    Hans Klose

  7. Herzzentrum der Universität zu Köln, Klinik III für Innere Medizin, Cologne, Germany

    Daniel Dumitrescu

  8. Department of Internal Medicine I, Carl Gustav Carus University Hospital, Technical University of Dresden, Dresden, Germany

    Michael Halank

  9. Department of Internal Medicine, Respiratory Medicine and Cardiology, MissioClinic, Würzburg, Germany

    Matthis Held

  10. Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany

    Henning Gall

  11. Institute for Clinical Pharmacology, Medical Faculty, Technical University Dresden, Dresden, Germany

    David Pittrow

  12. Department of Respiratory Medicine, Hannover Medical School, 30623, Hannover, Germany

    Marius M. Hoeper

  13. German Centre of Lung Research (DZL/BREATHE), Hannover, Germany

    Marius M. Hoeper

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  1. Thomas A. Zelniker
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Correspondence to Thomas A. Zelniker.

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Conflict of interest

Dr. Zelniker has nothing to disclose. Dr. Huscher reports personal fees from Actelion Pharmaceuticals, Switzerland outside the submitted work. AVN reports speakers fees from actelion, and Bayer outside the submitted work. Dr. Ewert has nothing to disclose. Dr. Lange reports other from Compera-Registry, during the conduct of the study; grants, personal fees and non-financial support from Actelion, grants, personal fees and non-financial support from Bayer, grants and personal fees from GlaxoSmithKline, personal fees from Pfizer, personal fees from MSD, grants and personal fees from United Therapeutics, outside the submitted work. Dr. Klose reports grants and personal fees from Actelion, grants and personal fees from GSK, personal fees from Pfizer, grants and personal fees from Bayer, personal fees from MSD, personal fees from United Therapeutics, personal fees from OMT, outside the submitted work. Dr. Dumitrescu reports other from COMPERA-Registry, during the conduct of the study; grants, personal fees and non-financial support from Actelion Pharmaceuticals, personal fees from Bayer, personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Servier, outside the submitted work. Dr. Halank reports personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees and non-financial support from GlaxoSmithKline, personal fees from OMT, personal fees from MSD SHARP & DOHME, personal fees from Pfizer, outside the submitted work. Dr. Held reports grants from Actelion, honoraria for lectures from Actelion, Bayer Healthcare, Berlin Chemie, Boehringer Ingelheim, GSK, MSD, Novartis, Pfizer, honoraria for advisory board activities from Actelion, Bayer, Boehringer, GSK, MSD, outside the submitted work and partizipation in clinical trails of Actelion, Bayer, GSK, Pfizer, United Therapeutics. Dr. Gall has nothing to disclose. Dr. Pittrow reports personal fees from Actelion, personal fees from Bayer, personal fees from Pfizer, outside the submitted work. Dr. Hoeper reports personal fees from Actelion, personal fees from Bayer, personal fees from Gilead, personal fees from GSK, personal fees from MSD, personal fees from Pfizer, outside the submitted work. Dr. Frankenstein has nothing to disclose.

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Zelniker, T.A., Huscher, D., Vonk-Noordegraaf, A. et al. The 6MWT as a prognostic tool in pulmonary arterial hypertension: results from the COMPERA registry. Clin Res Cardiol 107, 460–470 (2018). https://doi.org/10.1007/s00392-018-1207-5

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