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

Eur Heart J. 2016 Jan 1;37(1):35-44. doi: 10.1093/eurheartj/ehv337. Epub 2015 Jul 31.


Aims: 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.

Methods and 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.

Conclusion: 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.

Keywords: Cardiac index; Cardiac output; Cardiac rehabilitation; Pulmonary hypertension; Right heart catheterization.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Analysis of Variance
  • Biomarkers / metabolism
  • Cardiac Output / physiology
  • Chronic Disease
  • Exercise Test
  • Exercise Therapy / methods*
  • Exercise Tolerance / physiology
  • Female
  • Heart Rate / physiology
  • Humans
  • Hypertension, Pulmonary / physiopathology
  • Hypertension, Pulmonary / rehabilitation*
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / metabolism
  • Oxygen Consumption / physiology
  • Peptide Fragments / metabolism
  • Prospective Studies
  • Pulmonary Wedge Pressure / physiology
  • Thromboembolism / physiopathology
  • Thromboembolism / rehabilitation*
  • Treatment Outcome
  • Vascular Resistance / physiology
  • Ventricular Dysfunction, Right / physiopathology
  • Ventricular Dysfunction, Right / rehabilitation


  • Biomarkers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain