Benefits of skeletal-muscle exercise training in pulmonary arterial hypertension: The WHOLEi+12 trial

Background: Pulmonary arterial hypertension is often associated with skeletal-muscle weakness. The purpose of this randomized controlled trial was to determine the effects of an 8-week intervention combining muscle resistance, aerobic and inspiratory pressure-load exercises on upper/lower-body muscle power and other functional variables in patients with this disease. Methods: Participants were allocated to a control (standard care) or intervention (exercise) group (n = 20 each, 45 +/- 12 and 46 +/- 11 years, 60% women and 10% patients with chronic thromboembolic pulmonary hypertension per group). The intervention included five, three and six supervised (inhospital) sessions/week of aerobic, resistance and inspiratory muscle training, respectively. The primary endpoint was peak muscle power during bench/leg press; secondary outcomes included N-terminal pro-brain natriuretic peptide levels, 6-min walking distance, five-repetition sit-to-stand test, maximal inspiratory pressure, cardiopulmonary exercise testing variables (e.g., peak oxygen uptake), health-related quality of life, physical activity levels, and safety. Results: Adherence to training sessions averaged 94 +/- 0.5% (aerobic), 98 +/- 0.3% (resistance) and 91 +/- 1% (inspiratory training). Analysis of variance showed a significant interaction (group x time) effect for leg/bench press (P < 0.001/P = 0.002), with both tests showing an improvement in the exercise group (P < 0.001) but not in controls (P > 0.1). We found a significant interaction effect (P < 0.001) for five-repetition sit-to-stand test, maximal inspiratory pressure and peak oxygen uptake (P < 0.001), indicating a training-induced improvement. No major adverse event was noted due to exercise. Conclusions: An 8-week exercise intervention including aerobic, resistance and specific inspiratory muscle training is safe for patients with pulmonary arterial hypertension and yields significant improvements in muscle power and other functional variables. (C) 2016 Elsevier Ireland Ltd. All rights reserved.