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

Abstract

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. 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. 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 × 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. 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.