15 February 2020 by Martin Johnson

Effect of exercise training on 6 minute walking distance in severe precapillary pulmonary hypertension – results from a European multicenter randomized controlled trial

Objective: The benefits of exercise training on exercise capacity and quality of life in pulmonary hypertension (PH) have already been shown in several trials. Results of large multicentre studies are still lacking.

Methods: A specialised training program for patients with precapillary PH was implemented in 11 centers across 10 European countries. Patients were randomised in a training group or a sedentary control group. Patients of the training group performed a 10-30 days in-hospital training including interval ergometer training, dumbbell training, mental gait training and respiratory therapy. The training was continued at home until week 15. The primary outcome variable was change in 6-minute walking distance (6MWD) between baseline and 15 weeks in the two groups. Secondary outcome parameters included quality of life scores (SF-36 questionnaire) and peak oxygen consumption during cardiopulmonary exercise testing.

Results: Out of 129 patients who were enrolled, 116 (58 vs. 58) completed the study. Most participating centers implemented this specialised training program for PH for the first time and managed to adapt it to the local health care system. The primary endpoint mean 6MWD significantly improved in the training group vs. control-group by 34.1±8.3 m (p<0.0001). Also, secondary endpoints significantly improved in the training group. Significant improvements of the training group compared to the control group were found in the quality of life parameter mental health (p=0.004), WHO functional class (chi-square p=0.027) and peak oxygen
consumption (control-group corrected improvement 0.9±0.5 mL/min/kg, p=0.048). 

Conclusion: This is the first randomized, controlled multicenter study providing evidence of the feasibility of exercise training across ten European countries. Our study results provide
further multicenter evidence of the effect of exercise training programs for PH patients as an add-on therapy. Within this study, a standardized specialized training program with in-hospital
start for PH patients in different European countries was successfully established.

Key Contributors

Ekkehard Grünig, MD; Alison MacKenzie, MD; Andrew J. Peacock, MD; Christina Eichstaedt, PhD; Nicola Benjamin, MSc; Silvia Ulrich, MD; Stéphanie Saxer, MSc; Maurizio Bussotti, MD; Stefano Ghio, MD; Lina Gumbiene,MD; Eglė Palevičiūtė, MD; Elena Jurevičienė, MD; Antonio Cittadini, MD, PhD; Anna A. Stanziola, MD; Alberto M. Marra, MD; Gabor Kovacs, MD; Horst Olschewski, MD, PhD; Joan-Albert Barberà, MD, PhD; Isabel Blanco, MD, PhD; Martin Spruit, MD; Frits Fransen, MD; Anton Vonk Noordegraaf, MD, PhD; Abílio Reis, MD; Mário Santos, MD; Sofia Gonçalves Viamonte, MD; Heleen Demeyer, PhD; Marion Delcroix, MD, Ph; Eduardo Bossone, MD and Martin Johnson, MD Centre for Pulmonary Hypertension, Thoraxclinic at the University Hospital Heidelberg, Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany; Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom; Laboratory for Molecular Diagnostics, Institute of Human Genetics, Heidelberg University, Germany; Centre for Pulmonary Hypertension, University Hospital Zurich, Zurich, Switzerland; Cardiac Rehabilitation Department, IRCCS Maugeri Clinical Scientific Institutes, Milan, Italy; Competence Centre of Pulmonary Hypertension, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania; Faculty of Medicine, Vilnius University, Vilnius, Lithuania; Department of Cardiac Surgery, University Hospital Salerno, Salerno, Italy; Department of Cardiology, Antonio Carderelli Hospital, Naples, Italy; Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy; Department of Cardiovascular Imaging, IRCCS S.D.N., Naples, Italy; Department of Internal Medicine, Div. Pulmonology, Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; Hospital Clinic IDIBAPS, University of Barcelona, Barcelona and Biomedical Research Networking Center on Respiratory Diseases, Madrid, Spain; Department of Research and Education, CIRO, Horn, The Netherlands; Department of Pulmonology, VU University Medical Center Amsterdam, Amsterdam, Netherlands; Department of Internal Medicine, Hospital Geral de Santo António, Porto, Portugal; Centro de Rehabilitação do Norte, Porto, Portugal; Department of Pneumology, University Hospital Leuven, Leuven, Belgium

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