title: Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial.
abstract: OBJECTIVE
  The impact of exercise training on the right heart and pulmonary circulation has not yet been invasively assessed in patients with pulmonary hypertension (PH) and right heart failure. This prospective randomized controlled study investigates the effects of exercise training on peak VO2/kg, haemodynamics, and further clinically relevant parameters in PH patients.
  
  
  RESULTS
  Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thrombo-embolic PH (54% female, 56 ± 15 years, 84% World Health Organization functional class III/IV, 53% combination therapy) on stable disease-targeted medication were randomly assigned to a control and training group. Medication remained unchanged during the study period. Non-invasive assessments and right heart catheterization at rest and during exercise were performed at baseline and after 15 weeks. Primary endpoint was the change in peak VO2/kg. Secondary endpoints included changes in haemodynamics. For missing data, multiple imputation and responder analyses were performed. The study results showed a significant improvement of peak VO2/kg in the training group (difference from baseline to 15 weeks: training +3.1 ± 2.7 mL/min/kg equals +24.3% vs. control -0.2 ± 2.3 mL/min/kg equals +0.9%, P < 0.001). Cardiac index (CI) at rest and during exercise, mean pulmonary arterial pressure, pulmonary vascular resistance, 6 min walking distance, quality of life, and exercise capacity significantly improved by exercise training.
  
  
  CONCLUSIONS
  Low-dose exercise training at 4-7 days/week significantly improved peak VO2/kg, haemodynamics, and further clinically relevant parameters. The improvements of CI at rest and during exercise indicate that exercise training may improve the right ventricular function. Further, large multicentre trials are necessary to confirm these results.
authors.affiliation: Center for Pulmonary Hypertension Thoraxclinic, University Hospital Heidelberg, Amalienstrasse 5, Heidelberg D-69126, Germany nicola.ehlken@med.uni-heidelberg.de.
authors.forename: Nicola
authors.initials: N
authors.lastname: Ehlken
authors.affiliation: Center for Pulmonary Hypertension Thoraxclinic, University Hospital Heidelberg, Amalienstrasse 5, Heidelberg D-69126, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Lichtblau
authors.affiliation: Department of Pneumology, University of Hamburg, Hamburg, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Klose
authors.affiliation: Center for Pulmonary Hypertension Thoraxclinic, University Hospital Heidelberg, Amalienstrasse 5, Heidelberg D-69126, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Weidenhammer
authors.affiliation: Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Fischer
authors.affiliation: Rehabilitation Center Koenigstuhl, Heidelberg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Nechwatal
authors.affiliation: Rehabilitation Center Koenigstuhl, Heidelberg, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Uiker
authors.affiliation: Department of Pneumology, University of Dresden, Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Halank
authors.affiliation: Department of Pneumology, Hanover Medical School, Hanover, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Olsson
authors.affiliation: Department of Pneumology, University of Gießen, Gießen, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.affiliation: Department of Pneumology, University of Gießen, Gießen, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Gall
authors.affiliation: Department of Cardiology, Cologne, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Rosenkranz
authors.affiliation: Department of Pneumology, University of Homburg, Homburg, Germany.
authors.forename: Heinrike
authors.initials: H
authors.lastname: Wilkens
authors.affiliation: Department of Pneumology, University of Mainz, Mainz, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Mertens
authors.affiliation: Department of Pneumology, University of Leipzig, Leipzig, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Seyfarth
authors.affiliation: DRK Hospital-Westend, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Opitz
authors.affiliation: Clinic of Pulmonology, University Hospital Zurich, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ulrich
authors.affiliation: Center for Pulmonary Hypertension Thoraxclinic, University Hospital Heidelberg, Amalienstrasse 5, Heidelberg D-69126, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Egenlauf
authors.affiliation: Center for Pulmonary Hypertension Thoraxclinic, University Hospital Heidelberg, Amalienstrasse 5, Heidelberg D-69126, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Grünig
mesh_terms: D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism; D002302:Cardiac Output / Q000502:physiology; D002908:Chronic Disease; D005080:Exercise Test; D005081:Exercise Therapy / Q000379:methods*; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology / Q000534:rehabilitation*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism; D011446:Prospective Studies; D011669:Pulmonary Wedge Pressure / Q000502:physiology; D013923:Thromboembolism / Q000503:physiopathology / Q000534:rehabilitation*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000502:physiology; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology / Q000534:rehabilitation
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Cardiac index; Cardiac output; Cardiac rehabilitation; Pulmonary hypertension; Right heart catheterization